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Challenges of academic pediatric medicine: the American Pediatric Society and Society for Pediatric Research Virtual Chat Series
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Angiotensin-converting enzyme 2 activity in patients with chronic kidney disease
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BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a novel regulator of the renin–angiotensin system that counteracts the adverse effects of angiotensin II. In heart failure patients, elevated plasma ACE2 activity predicted adverse events and greater myocardial dysfunction. We aimed to describe plasma ACE2 activity and its clinical associations in patients with kidney disease. METHODS: Patients recruited from a single centre comprised of chronic kidney disease Stage III/IV (CKD), haemodialysis patients and kidney transplant recipients (KTRs). Plasma ACE2 enzyme activity was measured using a fluorescent substrate assay in plasma, collected at baseline and stored at −80°C. Linear regression was performed in both males and females separately to determine the covariates associated with log-transformed ACE2. RESULTS: The median (interquartile range) plasma ACE2 activity in pmol/mL/min was 15.9 (8.4–26.1) in CKD (n = 59), 9.2 (3.9–18.2) in haemodialysis (n = 100) and 13.1 (5.7–21.9) in KTR (n = 80; P < 0.01). In male haemodialysis patients, ACE2 activity was 12.1 (6.8–19.6) compared with 4.4 (2.5–10.3) in females (P < 0.01). Log-transformed ACE2 plasma activity was associated with post-haemodialysis systolic blood pressure in females [β-coefficient 0.04, 95% confidence interval (95% CI) 0.01–0.06, P = 0.006]. In males, log-transformed ACE2 plasma activity was associated with B-type natriuretic peptide (β-coefficient 0.39, 95% CI 0.19–0.60, P < 0.001). Plasma ACE2 activity was not associated with mortality. CONCLUSIONS: Plasma ACE2 activity is reduced in haemodialysis patients compared with CKD patients, and in female haemodialysis patients compared with male. The different associations of plasma ACE2 activity between male and female haemodialysis patients indicate that the role of ACE2 in cardiovascular disease may differ by gender.
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Lecythophora hoffmannii isolated from a case of canine osteomyelitis in Japan
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A 2-year-old spayed female mongrel dog showed claudication with abnormal ossification containing fungal cells detected by biopsy. The dog was treated with ketoconazole and itraconazole perorally for 5 months; however, the osteomyelitis became aggravated, and an amputation from the scapula was performed. The right superficial cervical lymph node became swollen 5 months after the operation. The lymph node contained PAS positive fungal elements and a portion of tissue produced mycelial fungal growth on potato dextrose agar supplemented with chloramphenicol. The culture was identified as Lecythophora hoffmannii based on morphology, physiology and 100% identity in the sequence of the D1/D2 domain of the large subunit ribosomal RNA gene of the fungal species in the GenBank database (accession number AB100627). In addition, the sequence from the present isolate was submitted as AB189164. The isolate showed resistance to antifungal agents, i.e., amphotericin B, 5-FC, fluconazole, itraconazole, miconazole and micafungin. The dog developed cachexia 2 months after the onset of lymphadenopathy, and was euthanized on the 459th day after onset of clinical symptoms. This was the first disseminated case of L. hoffmannii infection in Japan.
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Practical identification of eight medically important Trichosporon species by reverse line blot hybridization (RLB) assay and rolling circle amplification (RCA)
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We developed a reverse line blot (RLB) hybridization-, and rolling circle amplification (RCA)-based assays for the identification of Trichoporon species and evaluated them with 48 isolates that had been previously recognized as belonging to eight species (Trichosporon asahii, T. cutaneum, T. dermatis, T. domesticum, T. inkin, T. japonicum, T. jirovecii, and T. laibachii). Results were compared to those obtained with DNA sequencing of three rRNA gene loci, i.e., the internal transcribed spacer (ITS) region, D1/D2 domain of the 28S rRNA gene and intergenic spacer 1 (IGS1) region. Using species-specific, or group-specific probes targeted at the ITS region and the D1/D2 domain, the RLB assay permitted accurate species identification of all 48 isolates with 100% specificity. Species-specific RLB probes correctly assigned 45/48 (94%) of the isolates (six species) with the exception of T. dermatis and T. japonicum isolates which were not targeted by the assay. Identification of T. dermatis relied on a positive hybridization result with the group-specific probe hybridizing with T. dermatis and T. jirovecii and the absence of a signal with the T. jirovecii-specific probe. T. japonicum strains were first assigned to the T. asahii-T. japonicum group by hybridization with the two species group-specific probe and then as T. japonicum by the absence of signal with a T. asahii-specific probe. Twelve species-specific RCA probes targeting the eight species studied detected templates of all 48 Trichosporon isolates and an artificial template of T. asteroides, all with good specificity. Both RLB and RCA are potential alternatives to DNA sequencing for the identification of Trichosporon species. The RLB approach is suited for the batched simultaneous analysis of large numbers of isolates, while RCA is more appropriate for the immediate study of single isolates. Comparative costs are US$7 and US$2 per assay for the RLB and RCA methods, respectively.
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Insights from Parasite-Specific Serological Tools in Eco-Immunology
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Eco-immunology seeks evolutionary explanations for the tremendous variation in immune defense observed in nature. Assays to quantify immune phenotypes often are crucial to this endeavor. To this end, we suggest that more use could (and arguably should) be made of the veterinary and clinical serological toolbox. For example, measuring the magnitude and half-life of parasite-specific antibodies across a range of host taxa may provide new ways of testing theories in eco-immunology. Here, we suggest that antibody assays developed in veterinary and clinical immunology and epidemiology provide excellent tools—or at least excellent starting points for development of tools—for tests of such hypotheses. We review how such assays work and how they may be optimized for new questions and new systems in eco-immunology. We provide examples of the application of such tools to eco-immunological studies of seabirds and mammals, and suggest a decision-tree to aid development of assays. We expect that addition of such tools to the eco-immunological toolbox will promote progress in the field and help elucidate how immune systems function and why they vary in nature.
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Combining evolutionary information extracted from frequency profiles with sequence-based kernels for protein remote homology detection
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Motivation: Owing to its importance in both basic research (such as molecular evolution and protein attribute prediction) and practical application (such as timely modeling the 3D structures of proteins targeted for drug development), protein remote homology detection has attracted a great deal of interest. It is intriguing to note that the profile-based approach is promising and holds high potential in this regard. To further improve protein remote homology detection, a key step is how to find an optimal means to extract the evolutionary information into the profiles. Results: Here, we propose a novel approach, the so-called profile-based protein representation, to extract the evolutionary information via the frequency profiles. The latter can be calculated from the multiple sequence alignments generated by PSI-BLAST. Three top performing sequence-based kernels (SVM-Ngram, SVM-pairwise and SVM-LA) were combined with the profile-based protein representation. Various tests were conducted on a SCOP benchmark dataset that contains 54 families and 23 superfamilies. The results showed that the new approach is promising, and can obviously improve the performance of the three kernels. Furthermore, our approach can also provide useful insights for studying the features of proteins in various families. It has not escaped our notice that the current approach can be easily combined with the existing sequence-based methods so as to improve their performance as well. Availability and implementation: For users’ convenience, the source code of generating the profile-based proteins and the multiple kernel learning was also provided at http://bioinformatics.hitsz.edu.cn/main/∼binliu/remote/ Contact: bliu@insun.hit.edu.cn or bliu@gordonlifescience.org Supplementary information: Supplementary data are available at Bioinformatics online.
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Seroincidence of Influenza Among HIV-infected and HIV-uninfected Men During the 2009 H1N1 Influenza Pandemic, Bangkok, Thailand
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Among 368 Thai men who have sex with men with paired serum samples collected before and during the 2009 H1N1 influenza pandemic, we determined influenza A (H1N1)pdm09 seroconversion rates (≥4-fold rise in antibody titers by hemagglutination inhibition or microneutralization assays). Overall, 66 of 232 (28%) participants seroconverted after the first year of A(H1N1)pdm09 activity, and 83 of 234 (35%) participants seroconverted after the second year. Influenza A(H1N1)pdm09 seroconversion did not differ between human immunodeficiency virus (HIV)-infected (55 of 2157 [35%]) and HIV-uninfected (71 of 2211 [34%]) participants (P = .78). Influenza A(H1N1)pdm09 seroconversion occurred in approximately one third of our Thai study population and was similar among HIV-infected and HIV-uninfected participants.
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3,207 |
Influenza Circulation in United States Army Training Camps Before and During the 1918 Influenza Pandemic: Clues to Early Detection of Pandemic Viral Emergence
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Background. Surveillance for respiratory diseases in domestic National Army and National Guard training camps began after the United States’ entry into World War I, 17 months before the “Spanish influenza” pandemic appeared. Methods. Morbidity, mortality, and case-fatality data from 605 625 admissions and 18 258 deaths recorded for 7 diagnostic categories of respiratory diseases, including influenza and pneumonia, were examined over prepandemic and pandemic periods. Results. High pandemic influenza mortality was primarily due to increased incidence of, but not increased severity of, secondary bacterial pneumonias. Conclusions. Two prepandemic incidence peaks of probable influenza, in December 1917–January 1918 and in March–April 1918, differed markedly from the September–October 1918 pandemic onset peak in their clinical-epidemiologic features, and they may have been caused by seasonal or endemic viruses. Nevertheless, rising proportions of very low incidence postinfluenza bronchopneumonia (diagnosed at the time as influenza and bronchopneumonia) in early 1918 could have reflected circulation of the pandemic virus 5 months before it emerged in pandemic form. In this study, we discuss the possibility of detecting pandemic viruses before they emerge, by surveillance of special populations.
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Evaluation of the Safety and Immunogenicity of a Candidate Pandemic Live Attenuated Influenza Vaccine (pLAIV) Against Influenza A(H7N9)
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Background. We evaluated a candidate A/Anhui/2013(H7N9) pandemic live attenuated influenza vaccine (pLAIV) in healthy adults, and assessed the ability of 1 or 2 doses to induce immune memory. Methods. Healthy subjects in 2 age groups (18–49 years and 50–70 years) with undetectable hemagglutination-inhibiting (HAI) antibody to H7N9 were enrolled. Younger subjects received either 1 or 2 intranasal doses of 10(7.0) fluorescent focus units of A/Anhui/1/2013 pLAIV, while older subjects received a single dose. All subjects received a single 30-µg dose of unadjuvanted, antigenically matched A/Shanghai2/2013(H7N9) pandemic inactivated influenza vaccine (pIIV) 12 weeks after their first dose of pLAIV. Results. Both vaccines were well tolerated. Serum HAI antibody responses were detected in 0 of 32 younger subjects and 1 of 17 older subjects after 1 dose of pLAIV and in 2 of 16 younger subjects after a second dose. Strong serum antibody responses were detected after a single subsequent dose of pIIV that was broadly reactive against H7 influenza viruses. Conclusions. An A(H7N9) pLAIV candidate was safe in both age groups. Priming with pLAIV resulted in responses to subsequent pIIV that exceeded those seen in naive subjects in previous reports. The A(H7N9) pLAIV induces strong immune memory that can be demonstrated by exposure to subsequent antigenic challenge. Clinical Trials Registration. NCT01995695 and NCT02274545.
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3,209 |
Outbreak of Variant Influenza A(H3N2) Virus in the United States
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Background. Variant influenza virus infections are rare but may have pandemic potential if person-to-person transmission is efficient. We describe the epidemiology of a multistate outbreak of an influenza A(H3N2) variant virus (H3N2v) first identified in 2011. Methods. We identified laboratory-confirmed cases of H3N2v and used a standard case report form to characterize illness and exposures. We considered illness to result from person-to-person H3N2v transmission if swine contact was not identified within 4 days prior to illness onset. Results. From 9 July to 7 September 2012, we identified 306 cases of H3N2v in 10 states. The median age of all patients was 7 years. Commonly reported signs and symptoms included fever (98%), cough (85%), and fatigue (83%). Sixteen patients (5.2%) were hospitalized, and 1 fatal case was identified. The majority of those infected reported agricultural fair attendance (93%) and/or contact with swine (95%) prior to illness. We identified 15 cases of possible person-to-person transmission of H3N2v. Viruses recovered from patients were 93%–100% identical and similar to viruses recovered from previous cases of H3N2v. All H3N2v viruses examined were susceptible to oseltamivir and zanamivir and resistant to adamantane antiviral medications. Conclusions. In a large outbreak of variant influenza, the majority of infected persons reported exposures, suggesting that swine contact at an agricultural fair was a risk for H3N2v infection. We identified limited person-to-person H3N2v virus transmission, but found no evidence of efficient or sustained person-to-person transmission. Fair managers and attendees should be aware of the risk of swine-to-human transmission of influenza viruses in these settings.
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3,210 |
Relative accuracy of social and medical determinants of suicide in electronic health records
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OBJECTIVE: This paper compares the accuracy of predicting suicide from Social Determinants of Health (SDoH) or history of illness. POPULATION STUDIED: 5 313 965 Veterans who at least had two primary care visits between 2008 and 2016. STUDY DESIGN: The dependent variable was suicide or intentional self‐injury. The independent variables were 10 495 International Classification of Disease (ICD) Version 9 codes, age, and gender. The ICD codes included 40 V‐codes used for measuring SDoH, such as family disruption, family history of substance abuse, lack of education, legal impediments, social isolation, unemployment, and homelessness. The sample was randomly divided into training (90 percent) and validation (10 percent) sets. Area under the receiver operating characteristic (AROC) was used to measure accuracy of predictions in the validation set. PRINCIPAL FINDINGS: Separate analyses were done for inpatient and outpatient codes; the results were similar. In the hospitalized group, the mean age was 67.2 years, and 92.1 percent were male. The mean number of medical diagnostic codes during the study period was 37; and 12.9 percent had at least one SDoH V‐code. At least one episode of suicide or intentional self‐injury occurred in 1.89 percent of cases. SDoH V‐codes, on average, elevated the risk of suicide or intentional self‐injury by 24‐fold (ranging from 4‐ to 86‐fold). An index of 40 SDoH codes predicted suicide or intentional self‐injury with an AROC of 0.64. An index of 10 445 medical diagnoses, without SDoH V‐codes, had AROC of 0.77. The combined SDoH and medical diagnoses codes also had AROC of 0.77. CONCLUSION: In predicting suicide or intentional self‐harm, SDoH V‐codes add negligible information beyond what is already available in medical diagnosis codes. IMPLICATIONS FOR PRACTICE: Policies that affect SDoH (eg, housing policies, resilience training) may not have an impact on suicide rates, if they do not change the underlying medical causes of SDoH.
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Prospects for detecting early warning signals in discrete event sequence data: Application to epidemiological incidence data
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Early warning signals (EWS) identify systems approaching a critical transition, where the system undergoes a sudden change in state. For example, monitoring changes in variance or autocorrelation offers a computationally inexpensive method which can be used in real-time to assess when an infectious disease transitions to elimination. EWS have a promising potential to not only be used to monitor infectious diseases, but also to inform control policies to aid disease elimination. Previously, potential EWS have been identified for prevalence data, however the prevalence of a disease is often not known directly. In this work we identify EWS for incidence data, the standard data type collected by the Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO). We show, through several examples, that EWS calculated on simulated incidence time series data exhibit vastly different behaviours to those previously studied on prevalence data. In particular, the variance displays a decreasing trend on the approach to disease elimination, contrary to that expected from critical slowing down theory; this could lead to unreliable indicators of elimination when calculated on real-world data. We derive analytical predictions which can be generalised for many epidemiological systems, and we support our theory with simulated studies of disease incidence. Additionally, we explore EWS calculated on the rate of incidence over time, a property which can be extracted directly from incidence data. We find that although incidence might not exhibit typical critical slowing down properties before a critical transition, the rate of incidence does, presenting a promising new data type for the application of statistical indicators.
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3,212 |
RNA Interference Targeted to the Conserved Dimerization Initiation Site (DIS) of HIV-1 Restricts Virus Escape Mutation
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Short hairpin RNAs (shRNA) targeting viral or cellular genes can effectively inhibit human immunodeficiency virus type 1 (HIV-1) replication. This inhibition, however, may induce mutations in the targeted gene, leading to rapid escape from the shRNA-induced inhibition. We generated a lymphoid cell line that stably expressed a 19-bp shRNA targeting a well-conserved dimerization initiation site (DIS) of HIV-1, which strongly inhibited viral replication, thereby delaying virus escape. Furthermore, treatment of HIV-1 infection with DIS- and vif-shRNA combination therapy resulted in superior anti-viral responses compared to vif-shRNA monotherapy. Continuous challenge with HIV-1, however, generated virus mutants that could overcome the RNA interference restriction. Such anti-genes may be promising tools for HIV-1 gene therapy for HIV/acquired immunodeficiency syndrome.
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3,213 |
High Viral Load and Respiratory Failure in Adults Hospitalized for Respiratory Syncytial Virus Infections
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A prospective study among adults hospitalized for polymerase chain reaction–confirmed respiratory syncytial virus infections (n = 123) showed frequent occurrence of lower respiratory-tract complications causing respiratory insufficiency (52.8%), requirement for assisted ventilation (16.3%), and intensive care unit admission/death (12.2%). High viral RNA concentration was detected at time of hospitalization, including in patients who presented later than 2 days of illness (day 1–2, 7.29 ± 1.47; day 3–4, 7.28 ± 1.41; day 5–8, 6.66 ± 1.87 log(10) copies/mL). RNA concentration was independently associated with risk of complications and respiratory insufficiency (adjusted odds ratio 1.40 per log(10) copies/mL increase, 95% confidence interval, 1.03–1.90; P = .034). Our data indicate the need and provide a basis for clinical research on antiviral therapy in this population.
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3,214 |
Endothelium-Derived Steroidogenic Factor Enhances Angiotensin II-Stimulated Aldosterone Release by Bovine Zona Glomerulosa Cells
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Endothelium-derived steroidogenic factor (EDSF) is an endothelial peptide that stimulates aldosterone release from bovine adrenal zona glomerulosa (ZG) cells. The regulation of aldosterone release by combinations of EDSF and angiotensin II (AII) or EDSF and ACTH was investigated. Endothelial cells (ECs) and EC-conditioned media (ECCM) increased aldosterone release from ZG cells, an activity attributed to EDSF. AII (10(−12) to 10(−8)m) and ACTH (10(−12) to 10(−9)m) also stimulated the release of aldosterone from ZG cells. The stimulation by AII, but not ACTH, was greatly enhanced when ZG cells were coincubated with ECs. AII was metabolized by ECs to peptides identified by mass spectrometry as angiotensin (1-7) and angiotensin IV. There was very little metabolism of AII by ZG cells. Neither of these two AII metabolites altered aldosterone release from ZG cells, so they could not account for the enhanced response with ECs. AII-induced aldosterone release from ZG cells was enhanced by ECCM but not cell-free conditioned medium. This enhanced response was not due to increased EDSF release from ECs by AII. The synergistic effect of EDSF and AII was apparent when AII was added during or after the generation of ECCM and not observed when the AII component of the enhancement was blocked by the AII antagonist, losartan. These studies indicate that EDSF enhances the steroidogenic effect of AII. In the adrenal gland, ECs are in close anatomical relationship with ZG cells and may sensitize ZG cells to the steroidogenic action of AII by releasing EDSF.
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2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC) Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS)
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3,216 |
Maternal Exposure to the Cannabinoid Agonist WIN 55,12,2 during Lactation Induces Lasting Behavioral and Synaptic Alterations in the Rat Adult Offspring of Both Sexes
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Consumption of cannabis during pregnancy and the lactation period is a rising public health concern (Scheyer et al., 2019). Exposure to synthetic or plant-derived cannabinoids via lactation disrupts the development of GABAergic neurons in the prefrontal cortex (PFC) and alters early-life behaviors (Scheyer et al., 2020b). Recently, additional data revealed that Δ9-tetrahydrocannabinol (THC) perinatal exposure via lactation causes lasting behavioral and neuronal consequences (Scheyer et al., 2020a). Here, the long-term effects in adult offspring of maternal exposure to the synthetic cannabinoid agonist WIN 55,12,2 are reported. The data demonstrate that rats exposed during lactation to WIN display social and motivational deficits at adulthood. These behavioral changes were paralleled by a specific loss of endocannabinoid-mediated long-term depression (eCB-LTD) in the PFC and nucleus accumbens (NAc), while other forms of synaptic plasticity remained intact. Thus, similarly to THC, perinatal WIN exposure via lactation induces behavioral and synaptic abnormalities lasting into adulthood.
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3,217 |
Influenza A(H1N1)v pandemic in the dialysis population: first wave results from an international survey
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Background. After the first cases of influenza A(H1N1)v in Mexico and the USA became public, Fresenius Medical Care established a case-based reporting of cases for all of its dialysis clinics located in Europe, Middle East, Africa and Latin America. This paper aims to describe mortality rates of patients on dialysis and to assess the risk profiles. Methods. The survey was developed in Lotus Notes with a secure browser-based form. The form was open to 602 Fresenius Medical Care clinics located in Europe, Middle East, Africa and Latin America. Results. As of 3 September 2009, 306 cases have been reported by 85 clinics located in Argentina, Chile, Brazil, UK and Spain. The mean age was 52.7 ± 17.7 years. The majority of cases (70.6%) were from 20- to 44-year-old and 45- to 64-year-old subgroups. Moreover, 35.3% had no associated comorbidity, 20.3% had two and 4.6% three comorbidities, with heart disease being the most frequent. Fever was the most common symptom, present in 94.4% of the cases, followed by cough (78.8%) and muscle and joint pain (69.3%). Eighty-seven percent were treated with antiviral agents, the majority with oseltamivir. One hundred and three patients (34%) were admitted to hospital because of influenza. Pneumonia was reported for 69 cases, out of which 52 patients belonged to a high-risk group. Mortality rate of all the patients (confirmed, probable and suspected cases) was around 5%. Conclusion. End-stage renal disease patients should be included in first ranks of the priority list for the influenza A (H1N1)v vaccine, as already advocated by some healthcare authorities.
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3,218 |
Direct imaging of pH1N1 2009 influenza virus replication in alveolar pneumocytes in fatal cases by transmission electron microscopy
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Human influenza virus pandemics constitute a major global public health issue. Although studies on autopsy specimens from the recent pandemic by the 2009 influenza A (H1N1) virus have revealed a broad spectrum of pathologic findings, direct electron microscopic studies of the lung tissue from influenza fatalities are few. In this study, we examined five well-preserved pulmonary necropsy specimens from fatal cases of laboratory-confirmed pH1N1 from India. The novel observations in comparison with earlier reports included direct imaging of influenza virus budding within dilated cisternae of pneumocytes, cell-free virus emerging from the cell membrane of a pneumocyte in the alveolar lumen, presence of polymorphonuclear cells with red blood cells as inflammatory exudates close to hyaline membranes and extensive cytoplasmic degeneration of epithelial cells of the alveolar lining. These observations are in consistent with the earlier findings and emphasize the possible role of this virus directly infecting cells of the lower respiratory tract as a key event in the rapid pathogenesis of pH1N1 disease process.
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3,219 |
Does Expert Opinion Trump Evidence?
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Corrigendum to: The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2
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3,221 |
Television exposure is related to fear of avian flu, an Ecological Study across 23 member states of the European Union
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Background: A pandemic outbreak of H5N1 avian influenza is believed to coincide with large-scale panic. Even without an outbreak fear of infection may be widespread. Mass media coverage of the risks of a pandemic may lead to higher levels of fear. Methods: An ecological study looked at data from 23 member states of the European Union and controlled for population size, level of education, age distribution and income and wealth. Results: When the findings for Cyprus were excluded each additional hour of average TV viewing was associated with a 15.6% increase in the proportion of people worrying about the virus. TV viewing explained 52% of the variance. Conclusion: Fear of a pandemic precedes any real pandemic and may have to be dealt with separately. Exposure to television is highly associated with worrying about the virus. This relationship merits further study.
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Remote Learning for Medical Students in Nigeria During a Pandemic
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3,223 |
Age-dependent carriage of alleles and haplotypes of Plasmodium falciparum sera5, eba-175, and csp in a region of intense malaria transmission in Uganda
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BACKGROUND: The development of malaria vaccines is constrained by genetic polymorphisms exhibited by Plasmodium falciparum antigens. The project the age-dependent distribution of alleles or haplotypes of three P. falciparum malaria vaccine candidates, Circumsporozoite Protein (csp), Erythrocyte Binding Antigen 175 (eba-175) and Serine Repeat Antigen 5 (sera5) in a region of intense malaria transmission in Uganda. METHODS: A cross-sectional study was carried out between August and November 2009 in which 250 study participants were selected from a population of 600. Finger prick blood samples were collected after informed consent from participants below 5 years, 5–10 years, and above 10 years of age. Blood was used for microscopy, RDT and dried blood spots. Plasmodium falciparum DNA was extracted by chelex method. Alleles of sera5 and eba-175 were determined by polymerase chain reaction (PCR) amplification followed by resolution of products by agarose gel electrophoresis. Allele calling was done using gel photographs from ethiduim bromide stained gels. Haplotypes of csp were identified by sequencing 63 PCR products using the P. falciparum 7G8 laboratory strain sequence as a reference. The data were analysed using SPSS 16, EQX for windows and Chi-square test was used to calculate associations (P-values), Excel was used to generate graphs. The BioEdit and NCBI blast software programs were used to analyse the sequences from which csp haplotypes map was constructed. RESULTS: Eba-175 FCR3 (48/178) and CAMP (16/178) alleles were observed, the FCR3 (24/67) allele being predominant among children aged below 5 years old while the CAMP (12/67) allele was predominant among older participants. Sera5 alleles ORI (6/204) and ORII (103/204) were observed in the population, ORII was more prevalent and was significantly associated with age (P values < 0.0001), parasite density (P-value < 0.0001) and clinical outcomes (P value = 0.018). There was marked csp diversity in the Th2/Th3 region. Out of 63 sequences, 16 conformed to the reference strain and one (1/16) was similar to a West African haplotype and the majority (14/16) of the haplotypes were unique to this study region. There was an age-dependent distribution of csp haplotypes with more haplotypes being harbored by children < 5-year of age, (10/16) compared to adults (2/16). Interestingly, the csp haplotype corresponding to 3D7 whose prototypical sequence is identical to the sequence of the leading malaria vaccine candidate RTS, S was not observed. CONCLUSION: This data suggest that the eba-175 FCR3 allele, sera5 ORII allele, and csp haplotypes are targets of host immunity and under immune selection pressure in Apac District. These molecules could provide alternative malaria vaccine candidates as sub-unit vaccines.
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3,224 |
Procalcitonin and lung ultrasound algorithm to diagnose severe pneumonia in critical paediatric patients (PROLUSP study). A randomised clinical trial
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BACKGROUND: Lung ultrasound (LUS) in combination with a biomarker has not yet been studied. We propose a clinical trial where the primary aims are: 1. To assess whether an algorithm with LUS and procalcitonin (PCT) may be useful for diagnosing bacterial pneumonia; 2. To analyse the sensitivity and specificity of LUS vs chest X-ray (CXR). METHODS/DESIGN: A 3-year clinical trial. Inclusion criteria: children younger than 18 years old with suspected pneumonia in a Paediatric Intensive Care Unit. Patients will be randomised into two groups: Experimental Group: LUS will be performed as first lung image. Control Group: CXR will be performed as first pulmonary image. Patients will be classified according to the image and the PCT: a) PCT < 1 ng/mL and LUS/CXR are not suggestive of bacterial pneumonia (BN), no antibiotic will be prescribed; b) LUS/CXR are suggestive of BN, regardless of the PCT, antibiotic therapy is recommended; c) LUS/CXR is not suggestive of BN and PCT > 1 ng/mL, antibiotic therapy is recommended. CONCLUSION: This algorithm will help us to diagnose bacterial pneumonia and to prescribe the correct antibiotic treatment. A reduction of antibiotics per patient, of the treatment length, and of the exposure to ionizing radiation and in costs is expected. TRIAL REGISTRATION: NCT04217980.
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18th Annual Meeting, Neurocritical Care Society September 22–25, 2020 Phoenix, Arizona
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3,226 |
Inhibition of overexpressed Kv3.4 augments HPV in endotoxemic mice
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BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is a reaction of the pulmonary vasculature upon hypoxia, diverting blood flow into ventilated areas to preserve oxygenation. It is impaired in endotoxemia or ARDS. Voltage gated potassium channels have been shown to play a key role in the regulation of HPV. The aim of the study was to identify a voltage gated potassium channel involved in dysregulated HPV during endotoxemia. METHODS: Lungs of male C57BL/6 mice with and without endotoxemia (n = 6 ea. group) were analyzed for Kv3.4 gene and protein expression. HPV was examined in isolated perfused lungs of mice with and without endotoxemia and with and without selective Kv3.4 blocker BDS-I (n = 7 ea. group). Pulmonary artery pressure (PAP) and pressure-flow curves were measured during normoxic (FiO(2) 0.21) and hypoxic (FiO(2) 0.01) ventilation. HPV was quantified as the increase in perfusion pressure in response to hypoxia in percent of baseline perfusion pressure (ΔPAP) in the presence and absence of BDS-I. RESULTS: Kv3.4 gene (3.2 ± 0.5-fold, p < 0.05) and protein (1.5 ± 0.1-fold p < 0.05) expression levels were increased in endotoxemic mouse lungs. Endotoxemia reduced HPV (∆PAP control: 121.2 ± 8.7% vs. LPS 19.5 ± 8.0%, means ± SEM) while inhibition of Kv3.4 with 50 nM BDS-I augmented HPV in endotoxemic but not in control lungs (∆PAP control BDS-I: 116.6 ± 16.0% vs. LPS BDS-I 84.4 ± 18.2%, means ± SEM). CONCLUSIONS: Kv3.4 gene and protein expressions are increased in endotoxemic mouse lungs. Selective inhibition of Kv3.4 augments HPV in lungs of endotoxemic mice, but not in lungs of control mice.
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Ethical Guidelines and Psychological Distress in a Pandemic
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3,228 |
Liver infusion tryptose (LIT): the best choice for growth, viability, and infectivity of Leishmania infantum parasites
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Leishmania spp. parasites have a complex biological cycle presenting basically two different morphological stages, the amastigote and promastigote forms. In vitro cultivation allows a more complete study of the biological aspects of these parasites, indicating better conditions for infection, immunoassay tests, drug evaluations, and vaccines. Thus, we evaluated the three most used culture media for Leishmania spp., Grace’s insect cell culture medium (Grace’s), liver infusion tryptose (LIT), and Schneider’s insect medium (Schneider’s), without supplementation or supplemented with fetal calf serum (FCS) and bovine serum albumin (Albumin) to evaluate the growth, viability, and infectivity of the L. infantum promastigotes. It was observed that promastigote forms have a better growth in LIT and Schneider’s with or without FCS when compared to that in Grace’s. The supplementation with albumin promoted greater viability of the parasites independent of the medium. For in vitro infection of J774.A1 macrophages using light microscopy and flow cytometry analyses, FCS-supplemented LIT and Grace’s promoted higher percentage of infected macrophages and parasite load compared with Schneider’s media. Taken together, our results demonstrated that the supplementation of LIT culture medium with FCS is the most suitable strategy to cultivate Leishmania infantum parasites enabling the maintenance of growth and infective parasites for research uses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00436-020-06893-z) contains supplementary material, which is available to authorized users.
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Mitteilungen der DGU
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Temporal trends of outcomes of neutropenic patients with ARDS enrolled in therapeutic clinical trials
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Self-management and HeAlth Promotion in Early-stage dementia with e-learning for carers (SHAPE): study protocol for a multi-centre randomised controlled trial
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BACKGROUND: With an increasing number of people with dementia worldwide and limited advancement in medical treatments, the call for new and cost-effective approaches is crucial. The utility of self-management has been proven in certain chronic conditions. However, very little work has been undertaken regarding self-management in people with dementia. METHODS: The SHAPE trial will include 372 people with mild to moderate dementia to evaluate the effectiveness and cost-effectiveness of an educational programme combining approaches of self-management, health promotion, and e-learning for care partners. The study is a multi-site, single-randomised, controlled, single-blinded trial with parallel arms. The intervention arm is compared with treatment as usual. The intervention comprises a 10-week course delivered as group sessions for the participants with dementia. The sessions are designed to develop self-management skills and to provide information on the nature of the condition and the development of healthy behaviours in a supportive learning environment. An e-learning course will be provided for care partners which covers similar and complementary material to that discussed in the group sessions for the participant with dementia. DISCUSSION: This trial will explore the effect of the SHAPE group intervention on people with mild to moderate dementia in terms of self-efficacy and improvement in key health and mental health outcomes and cost-effectiveness, along with carer stress and knowledge of dementia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04286139, registered prospectively February 26, 2020, https://clinicaltrials.gov/ct2/show/NCT04286139
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Influenza virus-flow from insects to humans as causative for influenza seasonality
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Virus biomass outweighs human biomass, and insects biomass outweighs human biomass. Insects are regularly habited by viruses as well as humans, humans are further inhabited via insects. A model of viral flow is described and specified to explain influenza virus seasonality, which, in temperate climate, usually evolves when insects have mostly disappeared. With this hypothesis a coherent description of regular seasonal influenza and other seasonal respiratory virus infections in temperate climates is possible. The incidence of influenza under different circumstances e.g. temperature, humidity, or tropical conditions and different aspects like synchronicity of infections or in respect to evolutionary conditions do sustain this hypothesis if the behaviour of insects is considered.
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Systems Science Approaches for Global Environmental Health Research: Enhancing Intervention Design and Implementation for Household Air Pollution (HAP) and Water, Sanitation, and Hygiene (WASH) Programs
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BACKGROUND: Two of the most important causes of global disease fall in the realm of environmental health: household air pollution (HAP) and poor water, sanitation, and hygiene (WASH) conditions. Interventions, such as clean cookstoves, household water treatment, and improved sanitation facilities, have great potential to yield reductions in disease burden. However, in recent trials and implementation efforts, interventions to improve HAP and WASH conditions have shown few of the desired health gains, raising fundamental questions about current approaches. OBJECTIVES: We describe how the failure to consider the complex systems that characterize diverse real-world conditions may doom promising new approaches prematurely. We provide examples of the application of systems approaches, including system dynamics, network analysis, and agent-based modeling, to the global environmental health priorities of HAP and WASH research and programs. Finally, we offer suggestions on how to approach systems science. METHODS: Systems science applied to environmental health can address major challenges by a) enhancing understanding of existing system structures and behaviors that accelerate or impede aims; b) developing understanding and agreement on a problem among stakeholders; and c) guiding intervention and policy formulation. When employed in participatory processes that engage study populations, policy makers, and implementers, systems science helps ensure that research is responsive to local priorities and reflect real-world conditions. Systems approaches also help interpret unexpected outcomes by revealing emergent properties of the system due to interactions among variables, yielding complex behaviors and sometimes counterintuitive results. DISCUSSION: Systems science offers powerful and underused tools to accelerate our ability to identify barriers and facilitators to success in environmental health interventions. This approach is especially useful in the context of implementation research because it explicitly accounts for the interaction of processes occurring at multiple scales, across social and environmental dimensions, with a particular emphasis on linkages and feedback among these processes. https://doi.org/10.1289/EHP7010
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Loss of dynamic regulation of G protein-coupled receptor kinase 2 by nitric oxide leads to cardiovascular dysfunction with aging
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Nitric oxide (NO) and S-nitrosothiol (SNO) are considered cardio- and vasoprotective substances. We now understand that one mechanism in which NO/SNOs provide cardiovascular protection is through their direct inhibition of cardiac G protein-coupled receptor (GPCR) kinase 2 (GRK2) activity via S-nitrosylation of GRK2 at cysteine 340 (C340). This maintains GPCR homeostasis, including β-adrenergic receptors, through curbing receptor GRK2-mediated desensitization. Previously, we have developed a knockin mouse (GRK2-C340S) where endogenous GRK2 is resistant to dynamic S-nitrosylation, which led to increased GRK2 desensitizing activity. This unchecked regulation of cardiac GRK2 activity resulted in significantly more myocardial damage after ischemic injury that was resistant to NO-mediated cardioprotection. Although young adult GRK2-C340S mice show no overt phenotype, we now report that as these mice age, they develop significant cardiovascular dysfunction due to the loss of SNO-mediated GRK2 regulation. This pathological phenotype is apparent as early as 12 mo of age and includes reduced cardiac function, increased cardiac perivascular fibrosis, and maladaptive cardiac hypertrophy, which are common maladies found in patients with cardiovascular disease (CVD). There are also vascular reactivity and aortic abnormalities present in these mice. Therefore, our data demonstrate that a chronic and global increase in GRK2 activity is sufficient to cause cardiovascular remodeling and dysfunction, likely due to GRK2’s desensitizing effects in several tissues. Because GRK2 levels have been reported to be elevated in elderly CVD patients, GRK2-C340 mice can give insight into the aged-molecular landscape leading to CVD. NEW & NOTEWORTHY Research on G protein-coupled receptor kinase 2 (GRK2) in the setting of cardiovascular aging is largely unknown despite its strong established functions in cardiovascular physiology and pathophysiology. This study uses a mouse model of chronic GRK2 overactivity to further investigate the consequences of long-term GRK2 on cardiac function and structure. We report for the first time that chronic GRK2 overactivity was able to cause cardiac dysfunction and remodeling independent of surgical intervention, highlighting the importance of GRK activity in aged-related heart disease.
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Sex differences in the structure and function of rat middle cerebral arteries
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Epidemiological studies demonstrate that there are sex differences in the incidence, prevalence, and outcomes of cerebrovascular disease (CVD). The present study compared the structure and composition of the middle cerebral artery (MCA), neurovascular coupling, and cerebrovascular function and cognition in young Sprague-Dawley (SD) rats. Wall thickness and the inner diameter of the MCA were smaller in females than males. Female MCA exhibited less vascular smooth muscle cells (VSMCs), diminished contractile capability, and more collagen in the media, and a thicker internal elastic lamina with fewer fenestrae compared with males. Female MCA had elevated myogenic tone, lower distensibility, and higher wall stress. The stress/strain curves shifted to the left in female vessels compared with males. The MCA of females failed to constrict compared with a decrease of 15.5 ± 1.9% in males when perfusion pressure was increased from 40 to 180 mmHg. Cerebral blood flow (CBF) rose by 57.4 ± 4.4 and 30.1 ± 3.1% in females and males, respectively, when perfusion pressure increased from 100 to 180 mmHg. The removal of endothelia did not alter the myogenic response in both sexes. Functional hyperemia responses to whisker-barrel stimulation and cognition examined with an eight-arm water maze were similar in both sexes. These results demonstrate that there are intrinsic structural differences in the MCA between sexes, which are associated with diminished myogenic response and CBF autoregulation in females. The structural differences do not alter neurovascular coupling and cognition at a young age; however, they might play a role in the development of CVD after menopause. NEW & NOTEWORTHY Using perfusion fixation of the middle cerebral artery (MCA) in calcium-free solution at physiological pressure and systematically randomly sampling the sections prepared from the same M2 segments of MCA, we found that there are structural differences that are associated with altered cerebral blood flow (CBF) autoregulation but not neurovascular coupling and cognition in young, healthy Sprague-Dawley (SD) rats. Understanding the intrinsic differences in cerebrovascular structure and function in males and females is essential to develop new pharmaceutical treatments for cerebrovascular disease (CVD).
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A guide to human microbiome research: study design, sample collection, and bioinformatics analysis
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The purpose of this review is to provide medical researchers, especially those without a bioinformatics background, with an easy-to-understand summary of the concepts and technologies used in microbiome research. First, we define primary concepts such as microbiota, microbiome, and metagenome. Then, we discuss study design schemes, the methods of sample size calculation, and the methods for improving the reliability of research. We emphasize the importance of negative and positive controls in this section. Next, we discuss statistical analysis methods used in microbiome research, focusing on problems with multiple comparisons and ways to compare β-diversity between groups. Finally, we provide step-by-step pipelines for bioinformatics analysis. In summary, the meticulous study design is a key step to obtaining meaningful results, and appropriate statistical methods are important for accurate interpretation of microbiome data. The step-by-step pipelines provide researchers with insights into newly developed bioinformatics analysis methods.
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Public responses to the Salisbury Novichok incident: a cross-sectional survey of anxiety, anger, uncertainty, perceived risk and avoidance behaviour in the local community
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OBJECTIVES: Malicious incidents involving chemical agents sometimes trigger high public concern. We aimed to (1) identify levels of emotion, perceived risk and behaviour change with regard to visiting Salisbury, 1 month after three people were poisoned with a nerve agent; and (2) test whether factors including receipt of information, beliefs about personal exposure and trust in government were associated with these outcomes. DESIGN: A cross-sectional telephone survey of a random sample of Salisbury residents. SETTING: Conducted between 5 and 13 April 2018. PARTICIPANTS: 500 residents aged 18 or over. OUTCOME MEASURES: Self-reported anxiety, anger, uncertainty, perceived risk to self and avoidance of Salisbury. RESULTS: Any degree of anxiety, anger and uncertainty was reported by 40.6%, 29.8% and 30.6% of participants, respectively. For the majority, the level of emotion reported was mild. Only 7.0% met the criteria for high anxiety and 5.2% reported feeling any risk to their health, whereas 18.6% reported avoiding Salisbury. Factors associated with avoidance of Salisbury included being female, unable to rule out exposure for oneself or of loved ones, believing the incident was targeted against the general public, and lower trust in the government and responding agencies. Hearing a lot or a little about the recovery support (eg, financial packages), as opposed to nothing at all, and being satisfied with this information were associated with reduced avoidance. CONCLUSIONS: Although the March 2018 Salisbury incident had a relatively modest impact on emotion and risk perception in the community, the number who reported avoiding the city was notable. In this, and in future incidents, assuring people that contamination resulted from a targeted, rather than indiscriminate, incident; demonstrating that contamination is contained within specific areas; improving communication about any financial support; and promoting trust in responding agencies should help provide additional reassurance to the community.
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Residency redeployment during a pandemic: Lessons for balancing service and learning
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Teaching an educational simulation elective outside the simulation center
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Being a post-positivist is exhausting: The daunting commitment to an uncertain truth
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Modern day superheroes
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Multiple Traditional Chinese Medicine interventions for idiopathic pulmonary fibrosis: A protocol for systematic review and meta-analysis of overview
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BACKGROUND: The therapeutic strategies of idiopathic pulmonary fibrosis (IPF) tend to be comprehensive. Improving the major symptoms and quality of life (QoL) is as important as postponing the process of fibrosis. However, only pirfenidone and nintedanib conditionally recommended by guidelines and no definite proof indicate that they can significantly ameliorate the main symptoms and QoL of IPF sufferers. At present, multiple types of Traditional Chinese Medicine (TCM) interventions alone or in combination with conventional western medicine managements are widespreadly applied in IPF treatment, which seemingly have a promising clinical effect, especially in ameliorating the main symptoms and improving QoL. Subsequently, the number of relevant studies in systematic reviews(SRs) and meta-analyses of randomized controlled trials(RCTs) increased significantly. Hence, we plan to implement an overview to collect, evaluate, and summarize the results of these SRs. METHODS: An all-round literature retrieval will be conducted in 9 electronic databases, including PubMed, EMBASE, CINAHL, Cochrane Library, Epistemonikos, CNKI, CBM, Wanfang, and VIP. We will focus on the systematic review and meta-analysis of RCTs for multiple TCM interventions alone or in combination with routine western medicine measures in IPF treatment. The main outcomes we follow with interest include the improvement of major symptoms (cough, dyspnea) and QoL. Secondary outcomes will consist of minor symptoms improvement, clinical total effective rate, lung function, blood gas analysis, 6-minute walk text, adverse events, acute exacerbation, all-cause mortality, and IPF-related mortality. Two reviewers will independently select the SRs satisfactory with the enrolling criteria, extract key characteristics, and datas on predefined form, evaluate methodological quality by AMSTAR-2, ROBIS and PRISMA tools, and the quality of evidences adopting GRADE method. In case of any divergence will be reached an agreement by discussion or adjudicated by a third senior reviewer. We will perform a narrative synthesis of the proofs from SRs included. RESULTS: The findings of this overvew will be presented at relevant conferences and submitted for peer-review publication. CONCLUSIONS: We expect to obtain comprehensive and reliable evidence of IPF treated by diversified TCM interventions from the potential standard SRs, which may provide suggestions for future RCTs and SRs. REGISTRATION NUMBER: INPLASY 202080110
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Effect of traditional Chinese medicine injections on severe pneumonia: A protocol for systematic review and meta-analysis
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BACKGROUND: Traditional Chinese medicine injections (TCMJ) used in the treatment of severe pneumonia have been widely implemented in clinical practice, but their overall efficacy and safety remain unclear. This paper aims to evaluate the efficacy and safety of TCMJ in the treatment of severe pneumonia. METHODS: PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, and the Chongqing VIP Chinese Science and Technology Periodical Database were all searched for randomized controlled trials focusing on the administration of TCMJ for severe pneumonia. Two researchers independently screened titles, abstracts, full texts, and extracted relevant data. The RevMan 5.3 software (The Cochrane Collaboration, Software Update, Oxford, UK) and Stata 14 software (STATA Corporation, College Station, TX) were used for statistical analysis. RESULTS: This study summarizes the related randomized controlled trials to assess the effect and safety of TCMJ in the treatment of severe pneumonia. CONCLUSION: This article provides theoretical support for the clinical application of TCMJ in the treatment of severe pneumonia. PROSPERO REGISTRATION NUMBER: CRD42020185072
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Protective barrier enclosure during upper gastrointestinal endoscopy
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Human Cytomegalovirus Envelope Protein gpUL132 Regulates Infectious Virus Production through Formation of the Viral Assembly Compartment
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The human cytomegalovirus (HCMV) UL132 open reading frame encodes a 270-amino-acid type I envelope glycoprotein, gpUL132. The deletion of UL132 (ΔUL132) from the HCMV genome results in a pronounced deficit in virus yield, with an approximately 2-log decrease in the production of infectious virus compared to the wild-type (WT) virus. Characterization of the ΔUL132 mutant virus indicated that it was less infectious with a high particle-to-infectious unit ratio and an altered composition of virion proteins compared to the WT virus. In addition, the viral assembly compartment (AC) failed to form in cells infected with the ΔUL132 mutant virus. The expression of gpUL132 in trans rescued the defects in the morphogenesis of the AC in cells infected with the ΔUL132 mutant virus and in infectious virus production. Furthermore, using cell lines expressing chimeric proteins, we demonstrated that the cytosolic domain of gpUL132 was sufficient to rescue AC formation and WT levels of virus production. Progeny virions from ΔUL132-infected cells expressing the cytosolic domain of gpUL132 exhibited particle-to-infectious unit ratios similar to those of the WT virus. Together, our findings argue that gpUL132 is essential for HCMV AC formation and the efficient production of infectious particles, thus highlighting the importance of this envelope protein for the virus-induced reorganization of intracellular membranes and AC formation in the assembly of infectious virus.
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Recurrence rates suggest delayed identification of plantar ulceration for patients in diabetic foot remission
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INTRODUCTION: Foot ulcers are a common and costly complication of diabetes, and delays in treatment can result in impaired healing, infection, hospitalization, and lower extremity amputation. RESEARCH DESIGN AND METHODS: We aimed to determine whether patterns in plantar diabetic foot ulcer (DFU) recurrence coincided with typical intervals between routine preventive care appointments, which would suggest that delays exist between ulcer development and identification. We completed an analysis of existing data from two multicenter studies in 300 total participants. We analyzed unadjusted counts of DFU binned in weekly intervals and defined ‘exam periods’ as intervals from 2 to 4 weeks, from 6 to 8 weeks, within 1 week of 3 months and within 1 week of 6 months. We tested whether recurrence rates during exam periods were equivalent to rates outside exam periods. We estimated the delay between DFU development and DFU identification such that the rate of development would have been constant. RESULTS: During exam periods, a total of 43 DFUs were identified (43/86=50%) despite the fact that these periods represent only 23.5% of follow-up in aggregate. Accounting for censoring, the annualized incidence during exam periods was 0.68 DFU/year (CI 0.48 to 0.89) in contrast to 0.25 DFU/year (CI 0.18 to 0.32) outside exam periods (incidence ratio=2.8, CI 1.8 to 4.3). We estimated delays between DFU occurrence and identification to average 15.3 days (IQR 7.4–23.7 days). CONCLUSIONS: These findings have potential implications for practice, particularly related to the value of telehealth and in-home monitoring of patients in diabetic foot remission. Additionally, there are implications for study design, which should consider the impact of interval censoring and attempt to control for confounders related to frequency and timing of exams.
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Authors’ response
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Authors’ response
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Microsuffering: Lessons From a Pinky Finger
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A newly found handbook for developing vaccines during World War II in China: the legacy of global responses to crises
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Crop switching reduces agricultural losses from climate change in the United States by half under RCP 8.5
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A key strategy for agriculture to adapt to climate change is by switching crops and relocating crop production. We develop an approach to estimate the economic potential of crop reallocation using a Bayesian hierarchical model of yields. We apply the model to six crops in the United States, and show that it outperforms traditional empirical models under cross-validation. The fitted model parameters provide evidence of considerable existing climate adaptation across counties. If crop locations are held constant in the future, total agriculture profits for the six crops will drop by 31% for the temperature patterns of 2070 under RCP 8.5. When crop lands are reallocated to avoid yield decreases and take advantage of yield increases, half of these losses are avoided (16% loss), but 57% of counties are allocated crops different from those currently planted. Our results provide a framework for identifying crop adaptation opportunities, but suggest limits to their potential.
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Deciphering and predicting CD4(+) T cell immunodominance of influenza virus hemagglutinin
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The importance of CD4(+) T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4(+) T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4(+) T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry–based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance.
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Authentic self-expression on social media is associated with greater subjective well-being
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Social media users face a tension between presenting themselves in an idealized or authentic way. Here, we explore how prioritizing one over the other impacts users’ well-being. We estimate the degree of self-idealized vs. authentic self-expression as the proximity between a user’s self-reported personality and the automated personality judgements made on the basis Facebook Likes and status updates. Analyzing data of 10,560 Facebook users, we find that individuals who are more authentic in their self-expression also report greater Life Satisfaction. This effect appears consistent across different personality profiles, countering the proposition that individuals with socially desirable personalities benefit from authentic self-expression more than others. We extend this finding in a pre-registered, longitudinal experiment, demonstrating the causal relationship between authentic posting and positive affect and mood on a within-person level. Our findings suggest that the extent to which social media use is related to well-being depends on how individuals use it.
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Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes
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Type 1 diabetes (T1D) has increased over the past half century and has now become the second most frequent autoimmune disease in childhood and one of major public health concern worldwide. Evidence suggests that modern lifestyles and rapid environmental changes are driving factors that underlie this increase. The integration of these two factors brings about changes in food intake. This, in turn, alters epigenetic regulations of the genome and intestinal microbiota composition, which may ultimately play a role in pathogenesis of T1D. Recent evidence shows that dysbiosis of the gut microbiota is closely associated with T1D and that a dietary intervention can influence epigenetic changes associated with this disease and may modify gene expression patterns through epigenetic mechanisms. In this review focus on how a diet can shape the gut microbiome, its effect on the epigenome in T1D, and the future of T1D management by microbiome therapy.
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People-centred surveillance: a narrative review of community-based surveillance among crisis-affected populations
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Outbreaks of disease in settings affected by crises grow rapidly due to late detection and weakened public health systems. Where surveillance is underfunctioning, community-based surveillance can contribute to rapid outbreak detection and response, a core capacity of the International Health Regulations. We reviewed articles describing the potential for community-based surveillance to detect diseases of epidemic potential, outbreaks, and mortality among populations affected by crises. Surveillance objectives have included the early warning of outbreaks, active case finding during outbreaks, case finding for eradication programmes, and mortality surveillance. Community-based surveillance can provide sensitive and timely detection, identify valid signals for diseases with salient symptoms, and provide continuity in remote areas during cycles of insecurity. Effectiveness appears to be mediated by operational requirements for continuous supervision of large community networks, verification of a large number of signals, and integration of community-based surveillance within the routine investigation and response infrastructure. Similar to all community health systems, community-based surveillance requires simple design, reliable supervision, and early and routine monitoring and evaluation to ensure data validity. Research priorities include the evaluation of syndromic case definitions, electronic data collection for community members, sentinel site designs, and statistical techniques to counterbalance false positive signals.
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Operative and Technical Modifications to the Coriolis(®) µ Air Sampler That Improve Sample Recovery and Biosafety During Microbiological Air Sampling
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Detecting infectious aerosols is central for gauging and countering airborne threats. In this regard, the Coriolis(®) µ cyclonic air sampler is a practical, commercial collector that can be used with various analysis methods to monitor pathogens in air. However, information on how to operate this unit under optimal sampling and biosafety conditions is limited. We investigated Coriolis performance in aerosol dispersal experiments with polystyrene microspheres and Bacillus globigii spores. We report inconsistent sample recovery from the collector cone due to loss of material when sampling continuously for more than 30 min. Introducing a new collector cone every 10 min improved this shortcoming. Moreover, we found that several surfaces on the device become contaminated during sampling. Adapting a high efficiency particulate air-filter system to the Coriolis prevented contamination without altering collection efficiency or tactical deployment. A Coriolis modified with these operative and technical improvements was used to collect aerosols carrying microspheres released inside a Biosafety Level-3 laboratory during simulations of microbiological spills and aerosol dispersals. In summary, we provide operative and technical solutions to the Coriolis that optimize microbiological air sampling and improve biosafety.
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Are long telomeres better than short? Relative contributions of genetically predicted telomere length to neoplastic and non-neoplastic disease risk and population health burden
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BACKGROUND: Mendelian Randomization (MR) studies exploiting single nucleotide polymorphisms (SNPs) predictive of leukocyte telomere length (LTL) have suggested that shorter genetically determined telomere length (gTL) is associated with increased risks of degenerative diseases, including cardiovascular and Alzheimer’s diseases, while longer gTL is associated with increased cancer risks. These varying directions of disease risk have long begged the question: when it comes to telomeres, is it better to be long or short? We propose to operationalize and answer this question by considering the relative impact of long gTL vs. short gTL on disease incidence and burden in a population. METHODS AND FINDINGS: We used odds ratios (OR) of disease associated with gTL from a recently published MR meta-analysis to approximate the relative contributions of gTL to the incidence and burden of neoplastic and non-neoplastic disease in a European population. We obtained incidence data of the 9 cancers associated with long gTL and 4 non-neoplastic diseases associated with short gTL from the Institute of Health Metrics (IHME). Incidence rates of individual cancers from SEER, a database of United States cancer records, were used to weight the ORs in order to align with the available IHME data. These data were used to estimate the excess incidences due to long vs. short gTL, expressed as per 100,000 persons per standard deviation (SD) change in gTL. To estimate the population disease burden, we used the Disability Adjusted Life Years (DALY) metric from the IHME, a measure of overall disease burden that accounts for both mortality and morbidity, and similarly calculated the excess DALY associated with long vs. short gTL. RESULTS: Our analysis shows that, despite the markedly larger ORs of neoplastic disease, the large incidence of degenerative diseases causes the excess incidence attributable to gTL to balance that of neoplastic diseases. Long gTL is associated with an excess incidence of 94.04 cases/100,000 persons/SD (45.49–168.84, 95%CI) from the 9 cancer, while short gTL is associated with an excess incidence of 121.49 cases/100,000 persons/SD (48.40–228.58, 95%CI) from the 4 non-neoplastic diseases. When considering disease burden using the DALY metric, long gTL is associated with an excess 1255.25 DALYs/100,000 persons/SD (662.71–2163.83, 95%CI) due to the 9 cancers, while short gTL is associated with an excess 1007.75 DALYs/100,000 persons/SD (411.63–1847.34, 95%CI) due to 4 non-neoplastic diseases. CONCLUSIONS: Our results show that genetically determined long and short telomere length are associated with disease risk and burden of approximately equal magnitude. These results provide quantitative estimates of the relative impact of genetically-predicted short vs. long TL in a human population, and provide evidence in support of the cancer-aging paradox, wherein human telomere length is balanced by opposing evolutionary forces acting to minimize both neoplastic and non-neoplastic diseases. Importantly, our results indicate that odds ratios alone can be misleading in different clinical scenarios, and disease risk should be assessed from both an individual and population level in order to draw appropriate conclusions about the risk factor’s role in human health.
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US primary care in 2029: A Delphi survey on the impact of machine learning
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OBJECTIVE: To solicit leading health informaticians’ predictions about the impact of AI/ML on primary care in the US in 2029. DESIGN: A three-round online modified Delphi poll. PARTICIPANTS: Twenty-nine leading health informaticians. METHODS: In September 2019, health informatics experts were selected by the research team, and invited to participate the Delphi poll. Participation in each round was anonymous, and panelists were given between 4–8 weeks to respond to each round. In Round 1 open-ended questions solicited forecasts on the impact of AI/ML on: (1) patient care, (2) access to care, (3) the primary care workforce, (4) technological breakthroughs, and (5) the long-future for primary care physicians. Responses were coded to produce itemized statements. In Round 2, participants were invited to rate their agreement with each item along 7-point Likert scales. Responses were analyzed for consensus which was set at a predetermined interquartile range of ≤ 1. In Round 3 items that did not reach consensus were redistributed. RESULTS: A total of 16 experts participated in Round 1 (16/29, 55%). Of these experts 13/16 (response rate, 81%), and 13/13 (response rate, 100%), responded to Rounds 2 and 3, respectively. As a result of developments in AI/ML by 2029 experts anticipated workplace changes including incursions into the disintermediation of physician expertise, and increased AI/ML training requirements for medical students. Informaticians also forecast that by 2029 AI/ML will increase diagnostic accuracy especially among those with limited access to experts, minorities and those with rare diseases. Expert panelists also predicted that AI/ML-tools would improve access to expert doctor knowledge. CONCLUSIONS: This study presents timely information on informaticians’ consensus views about the impact of AI/ML on US primary care in 2029. Preparation for the near-future of primary care will require improved levels of digital health literacy among patients and physicians.
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Influenza A virus co-opts ERI1 exonuclease bound to histone mRNA to promote viral transcription
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Cellular exonucleases involved in the processes that regulate RNA stability and quality control have been shown to restrict or to promote the multiplication cycle of numerous RNA viruses. Influenza A viruses are major human pathogens that are responsible for seasonal epidemics, but the interplay between viral proteins and cellular exonucleases has never been specifically studied. Here, using a stringent interactomics screening strategy and an siRNA-silencing approach, we identified eight cellular factors among a set of 75 cellular proteins carrying exo(ribo)nuclease activities or involved in RNA decay processes that support influenza A virus multiplication. We show that the exoribonuclease ERI1 interacts with the PB2, PB1 and NP components of the viral ribonucleoproteins and is required for viral mRNA transcription. More specifically, we demonstrate that the protein-protein interaction is RNA dependent and that both the RNA binding and exonuclease activities of ERI1 are required to promote influenza A virus transcription. Finally, we provide evidence that during infection, the SLBP protein and histone mRNAs co-purify with vRNPs alongside ERI1, indicating that ERI1 is most probably recruited when it is present in the histone pre-mRNA processing complex in the nucleus.
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Diagnostic Infectious Diseases Testing Outside Clinics: A Global Systematic Review and Meta-analysis
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BACKGROUND: Most people around the world do not have access to facility-based diagnostic testing, and the gap in availability of diagnostic tests is a major public health challenge. Self-testing, self-sampling, and institutional testing outside conventional clinical settings are transforming infectious disease diagnostic testing in a wide range of low- and middle-income countries (LMICs). We examined the delivery models of infectious disease diagnostic testing outside clinics to assess the impact on test uptake and linkage to care. METHODS: We conducted a systematic review and meta-analysis, searching 6 databases and including original research manuscripts comparing testing outside clinics with conventional testing. The main outcomes were test uptake and linkage to care, delivery models, and adverse outcomes. Data from studies with similar interventions and outcomes within thematic areas of interest were pooled, and the quality of evidence was assessed using GRADE. This study was registered in PROSPERO (CRD42019140828). We identified 10 386 de-duplicated citations, and 76 studies were included. Data from 18 studies were pooled in meta-analyses. Studies focused on HIV (48 studies), chlamydia (8 studies), and multiple diseases (20 studies). HIV self-testing increased test uptake compared with facility-based testing (9 studies: pooled odds ratio [OR], 2.59; 95% CI, 1.06–6.29; moderate quality). Self-sampling for sexually transmitted infections increased test uptake compared with facility-based testing (7 studies: pooled OR, 1.74; 95% CI, 0.97–3.12; moderate quality). Conclusions. Testing outside of clinics increased test uptake without significant adverse outcomes. These testing approaches provide an opportunity to expand access and empower patients. Further implementation research, scale-up of effective service delivery models, and policies in LMIC settings are needed.
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Effectiveness and cost-effectiveness of a progressive, individualised walking and education programme for prevention of low back pain recurrence in adults: study protocol for the WalkBack randomised controlled trial
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INTRODUCTION: Low back pain (LBP) is recognised globally as a prevalent, costly and disabling condition. Recurrences are common and contribute to much of the burden of LBP. Current evidence favours exercise and education for prevention of LBP recurrence, but an optimal intervention has not yet been established. Walking is a simple, widely accessible, low-cost intervention that has yet to be evaluated. This randomised controlled trial (RCT) aims to establish the effectiveness and cost-effectiveness of a progressive and individualised walking and education programme (intervention) for the prevention of LBP recurrences in adults compared with no treatment (control). METHODS AND ANALYSIS: A pragmatic, two-armed RCT comparing walking and education (n=349) with a no treatment control group (n=349). Inclusion criteria are adults recovered from an episode of non-specific LBP within the last 6 months. Those allocated to the intervention group will receive six sessions (three face to face and three telephone delivered) with a trained physiotherapist to facilitate a progressive walking programme and education over a 6-month period. The primary outcome will be days to first recurrence of an episode of activity-limiting LBP. The secondary outcomes include days to recurrence of an episode of LBP, days to recurrence of an episode of LBP leading to care seeking, disability and quality of life measured at 3, 6, 9 and 12 months and costs associated with LBP recurrence. All participants will be followed up monthly for a minimum of 12 months. The primary intention-to-treat analysis will assess difference in survival curves (days to recurrence) using the log-rank statistic. The cost-effectiveness analysis will be conducted from the societal perspective. ETHICS AND DISSEMINATION: Approved by Macquarie University Human Research Ethics Committee (Reference: 5201949218164, May 2019). Findings will be disseminated through publication in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12619001134112.
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Akuter und chronischer Husten – gibt es etwas Neues?
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The most frequent cause of acute cough (lasting up to 3 weeks) or subacute cough (3–8 weeks) is a viral infection, which is mostly a self-limiting disease in otherwise healthy persons. Some herbal compounds, the antitussive dextromethorphan and ambroxol are effective for symptom relief. Antibiotics are ineffective and should not be used due to resistance development. If after appropriate diagnostic procedures the cause of chronic cough, i.e. cough lasting more than 8 weeks, cannot be attributed to a well-established respiratory disease, it meets the definition of a disease in its own right, chronic idiopathic (unexplained) cough (CIH). This is caused by hypersensitivity of the cough reflex. Thus, even weak low threshold stimuli, e.g. changing temperature, extensive speaking and odors can trigger the cough reflex. In the case of nonresponse to guideline-conform treatment the definition of chronic refractory cough is met.
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3,263 |
Preoperative opioid, sedative, and antidepressant use is associated with increased postoperative hospital costs in colorectal surgery
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BACKGROUND: Opioid (OPD), sedative (SDT), and antidepressant (ADM) prescribing has increased dramatically over the last 20 years. This study evaluated preoperative OPD, SDT, and ADM use on hospital costs in patients undergoing colorectal resection at a single institution. METHODS: This study was a retrospective record review. The local ACS-NSQIP database was queried for adult patients (age ≥ 18 years) undergoing open/laparoscopic, partial/total colectomy, or proctectomy from January 1, 2013 to December 31, 2016. Individual patient medical records were reviewed to determine preoperative OPD, SDT, and AD use. Hospital cost data from index admission were captured by the hospital cost accounting system and matched to NSQIP query-identified cases. All ACS-NSQIP categorical patient characteristic, operative risk, and outcome variables were compared in medication groups using chi-square tests or Fisher’s exact tests, and continuous variables were compared using Mann–Whitney U tests. RESULTS: A total of 1185 colorectal procedures were performed by 30 different surgeons. Of these, 27.6% patients took OPD, 18.5% SDT, and 27.8% ADM preoperatively. Patients taking OPD, SDT, and ADM were found to have increased mean total hospital costs (MTHC) compared to non-users (30.8 vs 23.6 for OPD, 31.6 vs 24.4 for SDT, and 30.7 vs 23.8 for ADM). OPD and SDT use were identified as independent risk factors for increased MTHC on multivariable analysis. CONCLUSION: Preoperative OPD and SDT use can be used to predict increased MTHC in patients undergoing colorectal resections.
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3,264 |
Less is more: critically ill status is not a carte blanche for unlimited antibiotic use
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3,265 |
Verfügbar: tetravalenter Grippe-Impfstoff
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3,266 |
British Association for the Study of Community Dentistry
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3,267 |
QQMedizin
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3,268 |
Column
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3,269 |
Royal Army Dental Corps to celebrate centenary in 2021
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3,270 |
Bio-fuel from PPE
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3,271 |
Teaching remote consultation
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3,272 |
Tijdelijk uit balans
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3,273 |
Redeployed as a district nurse
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3,274 |
medische coronaclaims
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3,275 |
Testing the limits of UDCs
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3,276 |
Dental tour all set to treat fishermen in Cornwall and Devon
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3,277 |
PE TER PAUL van Benthem
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3,278 |
Clinical features of 47 secondary hemophagocytic lymphohistiocytosis patients complicated with capillary leak syndrome
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The clinical features of patients with secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with capillary leak syndrome (CLS) remain controversial. The data of 259 sHLH patients were retrospectively analyzed. The clinical manifestations, laboratory findings, treatment, and prognosis of the CLS-sHLH group and non-CLS-sHLH group were compared. The levels of fibrinogen, albumin, and serum calcium in the CLS-sHLH group were lower than in the non-CLS-sHLH group, and serum triglycerides in the CLS-sHLH group were higher than in the non-CLS-sHLH group (P < 0.05). Univariate analysis showed that fibrinogen level was an independent prognostic factor in sHLH patients complicated with CLS. The median survival time was significantly shorter in patients with fibrinogen ≤ 1.3 g/L than in patients with fibrinogen > 1.3 g/L (P < 0.05). Patients with improved CLS conditions in the CLS-sHLH group had significantly increased albumin and serum calcium after treatment (P < 0.05); patients without improved conditions in the CLS-sHLH group also had significantly increased albumin after treatment (P < 0.05), but the serum calcium did not change significantly (P > 0.05). sHLH patients complicated with CLS had significantly worse prognosis than without CLS. Significant reduction in fibrinogen may be an independent prognostic factor for poor prognosis in sHLH patients complicated with CLS.
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3,279 |
Not entirely accurate
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3,280 |
Inbreng in het bestuur voor verpleeg- kundigen: Bestuursraad Martini Ziekenhuis uitgebreid
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3,281 |
Eddie Crouch is new BDA Chair
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3,282 |
Incidence of heparin-induced thrombocytopenia in patients with 2019 coronavirus disease()
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3,283 |
Olfactory dysfunction during COVID-19 pandemic()
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3,284 |
Re “The Elephant in the Operating Room”
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3,285 |
Cross-reactions between rheumatoid factor and IgM SARS-CoV-2()
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3,286 |
The body in isolation: The physical health impacts of incarceration in solitary confinement
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We examine how solitary confinement correlates with self-reported adverse physical health outcomes, and how such outcomes extend the understanding of the health disparities associated with incarceration. Using a mixed methods approach, we find that solitary confinement is associated not just with mental, but also with physical health problems. Given the disproportionate use of solitary among incarcerated people of color, these symptoms are most likely to affect those populations. Drawing from a random sample of prisoners (n = 106) in long-term solitary confinement in the Washington State Department of Corrections in 2017, we conducted semi-structured, in-depth interviews; Brief Psychiatric Rating Scale (BPRS) assessments; and systematic reviews of medical and disciplinary files for these subjects. We also conducted a paper survey of the entire long-term solitary confinement population (n = 225 respondents) and analyzed administrative data for the entire population of prisoners in the state in 2017 (n = 17,943). Results reflect qualitative content and descriptive statistical analysis. BPRS scores reflect clinically significant somatic concerns in 15% of sample. Objective specification of medical conditions is generally elusive, but that, itself, is a highly informative finding. Using subjective reports, we specify and analyze a range of physical symptoms experienced in solitary confinement: (1) skin irritations and weight fluctuation associated with the restrictive conditions of solitary confinement; (2) un-treated and mis-treated chronic conditions associated with the restrictive policies of solitary confinement; (3) musculoskeletal pain exacerbated by both restrictive conditions and policies. Administrative data analyses reveal disproportionate rates of racial/ethnic minorities in solitary confinement. This analysis raises the stakes for future studies to evaluate comparative prevalence of objective medical diagnoses and potential causal mechanisms for the physical symptoms specified here, and for understanding differential use of solitary confinement and its medically harmful sequelae.
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3,287 |
Behind the mask: demedicalising race and mental health in professional football
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3,288 |
Targeted Temperature Management for Treatment of Cardiac Arrest
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PURPOSE OF REVIEW: Cardiac arrest is a common condition associated with high mortality and a substantial risk of neurological injury among survivors. Targeted temperature management (TTM) is the only strategy shown to reduce the risk of neurologic disability cardiac arrest patients. In this article, we provide a comprehensive review of TTM with an emphasis on recent trials. RECENT FINDINGS: After early studies demonstrating the benefit of TTM in out-of-hospital cardiac arrest due to a shockable rhythm, newer studies have extended the benefit of TTM to patients with a nonshockable rhythm and in-hospital cardiac arrest. A target temperature of 33 °C was not superior to 36 °C, suggesting that a lenient targeted temperature may be appropriate especially for patients unable to tolerate lower temperatures. Although early initiation of TTM appears to be beneficial, the benefit of prehospital cooling has not been shown and use of intravenous cold saline in the prehospital setting may be harmful. SUMMARY: There is substantial risk of neurological injury in cardiac arrest survivors who remain comatose. TTM is an effective treatment that can lower the risk of neurological disability in such patients and ideally delivered as part of a comprehensive, goal-directed post-resuscitation management by a multidisciplinary team in a tertiary medical center.
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3,289 |
Introduction to SI: Homeownership and housing divide in China
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3,290 |
American Dairy Science Association® Journal of Dairy Science®, July 19–23 2016, Salt Lake City, UT
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3,291 |
Less daily oral hygiene is more in the ICU: yes
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3,292 |
Cocci Are in the Air
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The San Joaquin Valley in Central California is a semiarid region that is known to be highly endemic for coccidioidomycosis infections in high-risk groups. Coccidioidomycosis, also known as valley fever, is caused by the fungal spore Coccidioides, which can be found in the soil in arid and semiarid regions in the Southwest United States and parts of Central and South America. When soil is disturbed through excavation, agricultural activities, or with any other soil movement, these activities can release the fungal spores into air; people who are in close proximity can potentially inhale them. The purpose of this clinical case study is to address the need for coccidioidomycosis infection awareness and educate primary care providers to determine the diagnostic reasoning and process. A simple algorithm and template will aid them to accurately diagnose and treat patients with valley fever earlier in the disease process.
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3,293 |
Once-weekly vs. twice-weekly carfilzomib dosing in a subgroup of Japanese relapsed and refractory multiple myeloma patients from a randomized phase 3 trial (A.R.R.O.W.) and comparison with ENDEAVOR
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A.R.R.O.W. evaluated the superiority of once-weekly carfilzomib plus dexamethasone (Kd) 20/70 mg/m(2) vs. twice-weekly Kd 20/27 mg/m(2) based on progression-free survival (PFS) in relapsed and/or refractory multiple myeloma patients. Forty Japanese patients (once-weekly arm, n = 26; twice-weekly arm, n = 14) were randomized in A.R.R.O.W. In the Japanese subgroup of A.R.R.O.W., median PFS was 14.8 months (95% confidence interval [CI], 7.5–not evaluable [NE]) and 9.7 months (95% CI, 3.8–NE) in the once- and twice-weekly arms, respectively. The overall response rate (ORR) was 73.1% (19/26; 95% CI, 52.2–88.4) and 57.1% (8/14; 95% CI, 28.9–82.3) in each arm. The adverse events (AEs) incidence was 100% in both arms. Grade ≥ 3 AE incidence was 80.8% (21/26) and 78.6% (11/14) in each arm. Two fatal treatment-related AEs (acute lung injury and acute respiratory distress syndrome) occurred in the once-weekly arm. In exploratory unadjusted analyses of A.R.R.O.W. (once-weekly Kd 20/70 mg/m(2)) vs. ENDEAVOR (twice-weekly Kd 20/56 mg/m(2)), median PFS was 14.8 months vs. NE due to not yet being reached, and ORR was 73.1% (19/26) vs. 42.9% (3/7). In the Japanese subgroup, once-weekly Kd tended to improve ORR vs. twice-weekly Kd. Results from A.R.R.O.W. tended to be consistent with results from ENDEAVOR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12185-020-03013-6) contains supplementary material, which is available to authorized users.
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3,294 |
Diagnosis and Management of Lymphatic Disorders in Congenital Heart Disease
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PURPOSE OF REVIEW: Lymphatic disorders have received an increasing amount of attention over the last decade. Sparked primarily by improved imaging modalities and the dawn of lymphatic interventions, understanding, diagnostics, and treatment of lymphatic complications have undergone considerable improvements. Thus, the current review aims to summarize understanding, diagnostics, and treatment of lymphatic complications in individuals with congenital heart disease. RECENT FINDINGS: The altered hemodynamics of individuals with congenital heart disease has been found to profoundly affect morphology and function of the lymphatic system, rendering this population especially prone to the development of lymphatic complications such as chylous and serous effusions, protein-losing enteropathy and plastic bronchitis. SUMMARY: Although improved, a full understanding of the pathophysiology and targeted treatment for lymphatic complications is still wanting. Future research into pharmacological improvement of lymphatic function and continued implementation of lymphatic imaging and interventions may improve knowledge, treatment options, and outcome for affected individuals.
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3,295 |
The Effect of Low-Level Light Therapy on Capsaicin-Induced Peripheral and Central Sensitization in Healthy Volunteers: A Double-Blinded, Randomized, Sham-Controlled Trial
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INTRODUCTION: Several clinical trials have demonstrated that low-level light therapy (LLLT), a method of photobiomodulation, is an effective analgetic treatment. However, the mechanism of action has not yet been finally clarified. In particular, unanswered questions include whether it only affects peripheral or whether it also affects the spinal or supraspinal level. This study aimed to evaluate the effect of low-level light therapy on primary and secondary hyperalgesia in a human pain model. METHODS: This study was planned as a randomized, sham-controlled, and double-blinded trial with repeated measures within subject design. Capsaicin was applied on both forearms of ten healthy volunteers to induce peripheral and central sensitization. One forearm was treated with low-level light therapy; the other served as sham control. RESULTS: Low-level light therapy significantly increased the mechanical pain threshold, heat pain threshold, and decreased pain intensity. CONCLUSIONS: Our data indicate that low-level light therapy is effective at reducing the heat and mechanical pain threshold in a human pain model, pointing to a significant modulating effect on peripheral and central sensitization. These effects—especially in the absence of reported side effects—make low-level light therapy a promising tool in pain management. The application of low-level light therapy to treat chronic pain should be considered for further clinical trials.
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3,296 |
An intronic variant in BRAT1 creates a cryptic splice site, causing epileptic encephalopathy without prominent rigidity
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BRAT1-related neurodevelopmental disorders are characterized by heterogeneous phenotypes with varying levels of clinical severity. Since the discovery of BRAT1 variants as the molecular etiology of lethal neonatal rigidity and multifocal seizure syndrome (RMFSL, OMIM 614498), these variants have also been identified in patients with milder clinical forms including neurodevelopmental disorder with cerebellar atrophy and with or without seizures (NEDCAS, OMIM 618056), epilepsy of infancy with migrating focal seizures (EIMFS), and congenital ataxia (CA). This study aims to examine the consequences and pathogenicity of a novel homozygous splice site variant in BRAT1 in a patient presenting with migrating focal seizures since birth without prominent rigidity. The patient was born from a consanguineous marriage and has had seizures since the neonatal period. He presented with dysmorphic features, pontocerebellar hypoplasia, and migrating focal seizures. Despite supportive treatment, his symptoms rapidly progressed to intractable myoclonic seizures, bouts of apnea and bradycardia, and arrest of head growth, with no acquisition of developmental milestones. Clinical exome sequencing yielded a novel homozygous splice variant in BRAT1. Genetic analysis based on reverse transcription of the patient’s RNA followed by PCR amplifications performed on synthesized cDNA and Sanger sequencing was undertaken, and the functional effect of a BRAT1 variant on splicing machinery was demonstrated for the first time. The severe clinical presentation of migrating focal seizures and pontocerebellar hypoplasia in the absence of rigidity further expands the genotypic and phenotypic spectrum of BRAT1-related neurodevelopmental disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13760-020-01513-0) contains supplementary material, which is available to authorized users.
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3,297 |
International collaboration in Brazilian science: financing and impact
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The study of international collaborations can help in understanding the benefits of such relationships and aid in developing national financing policies. In this paper, the international collaboration of Brazilian scientists was studied using SciVal(®) and Incites(®) database, looking at its effect on the universities, financing agencies and different areas of knowledge and research topic clusters. Cluster and principal component analyses of scientometric data were carried out. While the results confirmed known knowledge that international collaboration increases impact, this study shows that Brazilian researchers are contributing to prominent research topics worldwide, in all areas of knowledge. This finding is contrary to several points of view that identify Brazil as a regional and not an international partner in science. Important also to note the impact of Brazilian authors in international collaboration that is well above the world mean. The collaboration of Brazil with foreign partners brings benefits for both sides, creating the opportunity of Brazilian research access to financing from international agencies. Increases in measures of impact are also seen for both sides. Foreign partners likewise benefit from higher impact factors in the same topic cluster, when collaborating with Brazilian partners. Publishing open access in high impact journals is fundamental for maintaining Brazilian science at the forefront. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11192-020-03728-7) contains supplementary material, which is available to authorized users.
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3,298 |
Lessons learned during my hand surgery career
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3,299 |
Safety of Remdesivir in Patients with Acute or Chronic Kidney Disease
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