title: Amantadine and Modafinil as Neurostimulants Following Acute Stroke: A Retrospective Study of Intensive Care Unit Patients

text: BACKGROUND/OBJECTIVE: Neurostimulants may improve or accelerate cognitive and functional recovery after intracerebral hemorrhage (ICH), ischemic stroke (IS), or subarachnoid hemorrhage (SAH), but few studies have described their safety and effectiveness in the intensive care unit (ICU). The objective of this study was to describe amantadine and modafinil administration practices during acute stroke care starting in the ICU and to evaluate safety and effectiveness. METHODS: Consecutive adult ICU patients treated with amantadine and/or modafinil following acute non-traumatic IS, ICH, or SAH were evaluated. Neurostimulant administration data were extracted from the electronic medication administration record, including medication (amantadine, modafinil, or both), starting dose, time from stroke to initiation, and whether the neurostimulant was continued at hospital discharge. Patients were considered responders if they met two of three criteria within 9 days of neurostimulant initiation: increase in Glasgow coma scale (GCS) score ≥ 3 points from pre-treatment baseline, improved wakefulness or participation documented in caregiver notes, or clinical improvement documented in physical or occupational therapy notes. Potential confounders of the effectiveness assessment and adverse drug effects were also recorded. RESULTS: A total of 87 patients were evaluable during the 3.7-year study period, including 41 (47%) with ICH, 29 (33%) with IS, and 17 (20%) with SAH. The initial neurostimulant administered was amantadine in 71 (82%) patients, modafinil in 13 (15%), or both in 3 (3%) patients. Neurostimulants were initiated a median of 7 (4.25, 12.75) days post-stroke (range 1–27 days) for somnolence (77%), not following commands (32%), lack of eye opening (28%), or low GCS (17%). The most common starting dose was 100 mg twice daily for both amantadine (86%) and modafinil (54%). Of the 79 patients included in the effectiveness evaluation, 42 (53%) were considered responders, including 34/62 (55%) receiving amantadine monotherapy and 8/24 (33%) receiving both amantadine and modafinil at the time they met the definition of a responder. No patient receiving modafinil monotherapy was considered a responder. The median time from initiation to response was 3 (2, 5) days. Responders were more frequently discharged home or to acute rehabilitation compared to non-responders (90% vs 62%, p = 0.006). Among survivors, 63/72 (88%) were prescribed a neurostimulant at hospital discharge. The most common potential adverse drug effect was sleep disruption (16%). CONCLUSIONS: Neurostimulant administration during acute stroke care may improve wakefulness. Future controlled studies with a neurostimulant administration protocol, prospective evaluation, and discretely defined response and safety criteria are needed to confirm these encouraging findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-020-00986-4) contains supplementary material, which is available to authorized users.


title: Dynamical footprints enable detection of disease emergence

text: Developing methods for anticipating the emergence or reemergence of infectious diseases is both important and timely; however, traditional model-based approaches are stymied by uncertainty surrounding the underlying drivers. Here, we demonstrate an operational, mechanism-agnostic detection algorithm for disease (re-)emergence based on early warning signals (EWSs) derived from the theory of critical slowing down. Specifically, we used computer simulations to train a supervised learning algorithm to detect the dynamical footprints of (re-)emergence present in epidemiological data. Our algorithm was then challenged to forecast the slowly manifesting, spatially replicated reemergence of mumps in England in the mid-2000s and pertussis post-1980 in the United States. Our method successfully anticipated mumps reemergence 4 years in advance, during which time mitigation efforts could have been implemented. From 1980 onwards, our model identified resurgent states with increasing accuracy, leading to reliable classification starting in 1992. Additionally, we successfully applied the detection algorithm to 2 vector-transmitted case studies, namely, outbreaks of dengue serotypes in Puerto Rico and a rapidly unfolding outbreak of plague in 2017 in Madagascar. Taken together, these findings illustrate the power of theoretically informed machine learning techniques to develop early warning systems for the (re-)emergence of infectious diseases.


How the humanities can ameliorate China's health-care crisis


New York, USA


Correction to Lancet Infect Dis 2020; published online March 26. https://doi.org/10.1016/S1473-3099(20)30241-3


title: An immunoassay cassette with a handheld reader for HIV urine testing in point-of-care diagnostics

text: Currently, most HIV tests are performed with blood samples, or alternatively saliva samples are used for HIV testing. Simple HIV tests need to be performed in hospitals or other medical agencies instead of more invasive HIV blood tests. To enable point-of-care (POC) HIV diagnostics, based on a recently developed lateral flow strip for HIV urine testing, a microfluidic immunoassay cassette with a handheld optical reader is developed. Based on lateral flow strip with gold colloid reporter, the integrated immunoassay cassette can perform sample introduction, metering, discharging, applying and detection which simplifies HIV testing. An indicator is incorporated into the cassette to guide sample introduction based on color change, and further, the excess test sample is stored inside the sealed cassette to avoid any contamination. The low-cost handheld optical reader can provide a test result within a few seconds, which is useful for simple, sensitive and affordable HIV onsite detection. Instead of using normal white LEDs, a customized back light module embedded with green LEDs is adopted to illuminate the lateral flow strip with an appropriate working current to achieve optimal performance. Compared to the standard lateral flow strips using a benchtop reader, with the disposable immunoassay cassette assisted by the handheld optical reader, more convenient, easier-to-operate, and more affordable HIV urine testing can be achieved in POC diagnostics.


title: Rotavirus infection in children in Southeast Asia 2008–2018: disease burden, genotype distribution, seasonality, and vaccination

text: BACKGROUND: Rotaviruses (RVs) are recognized as a major cause of acute gastroenteritis (AGE) in infants and young children worldwide. Here we summarize the virology, disease burden, prevalence, distribution of genotypes and seasonality of RVs, and the current status of RV vaccination in Southeast Asia (Cambodia, Indonesia, Lao People’s Democratic Republic, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam) from 2008 to 2018. METHODS: Rotavirus infection in Children in Southeast Asia countries was assessed using data from Pubmed and Google Scholars. Most countries in Southeast Asia have not yet introduced national RV vaccination programs. We exclude Brunei Darussalam, and Timor Leste because there were no eligible studies identified during that time. RESULTS: According to the 2008–2018 RV surveillance data for Southeast Asia, 40.78% of all diarrheal disease in children were caused by RV infection, which is still a major cause of morbidity and mortality in children under 5 years old in Southeast Asia. Mortality was inversely related to socioeconomic status. The most predominant genotype distribution of RV changed from G1P[8] and G2P[4] into the rare and unusual genotypes G3P[8], G8P[8], and G9P[8]. Although the predominat strain has changed, but the seasonality of RV infection remains unchanged. One of the best strategies for decreasing the global burden of the disease is the development and implementation of effective vaccines. CONCLUSIONS: The most predominant genotype distribution of RV was changed time by time. Rotavirus vaccine is highly cost effective in Southeast Asian countries because the ratio between cost per disability-adjusted life years (DALY) averted and gross domestic product (GDP) per capita is less than one. These data are important for healthcare practitioners and officials to make appropriate policies and recommendations about RV vaccination.


Reply


title: Promoting best practice in nucleotide sequence data sharing

text: Today, Scientific Data is refining its standards for new submissions describing nucleic acid sequence data.


title: Prospective avenues for human population genomics and disease mapping in southern Africa

text: Population substructure within human populations is globally evident and a well-known confounding factor in many genetic studies. In contrast, admixture mapping exploits population stratification to detect genotype–phenotype correlations in admixed populations. Southern Africa has untapped potential for disease mapping of ancestry-specific disease risk alleles due to the distinct genetic diversity in its populations compared to other populations worldwide. This diversity contributes to a number of phenotypes, including ancestry-specific disease risk and response to pathogens. Although the 1000 Genomes Project significantly improved our understanding of genetic variation globally, southern African populations are still severely underrepresented in biomedical and human genetic studies due to insufficient large-scale publicly available data. In addition to a lack of genetic data in public repositories, existing software, algorithms and resources used for imputation and phasing of genotypic data (amongst others) are largely ineffective for populations with a complex genetic architecture such as that seen in southern Africa. This review article, therefore, aims to summarise the current limitations of conducting genetic studies on populations with a complex genetic architecture to identify potential areas for further research and development.


Pediatric Palliative Care: An Innovative Approach to Pediatric Care for Children With Life-Threatening Conditions


title: Comparative genomics of Streptococcus parauberis: new target for molecular identification of serotype III

text: ABSTRACT: This paper describes the predicted structure for the cps loci involved in capsule biosynthesis for Streptococcus parauberis serotypes III, IV, and V. Based on the specific serotype regions I, II, and III, a multiplex PCR protocol (mPCR) was designed to differentiate the main serotypes causing fish diseases. A real-time PCR method (qPCR) is also described to identify S. parauberis of serotype III in bacterial cultures and fish tissues. In silico and in vitro analyses revealed that both methods have a 100% specificity. The mPCR assay was optimized for the detection of S. parauberis strains of subtypes Ia (amplicon size 213 bp), subtypes Ib and Ic (both amplicon size 303 bp), serotype II (amplicon size 403 bp), and serotype III (amplicon size 130 bp) from bacterial cultures. The qPCR assay was optimized for the identification and quantification of S. parauberis serotype III strains in bacterial cultures and fish tissues. This assay achieved a sensitivity of 2.67 × 10(2) gene copies (equivalent to 3.8 × 10(−9) ng/μl) using pure bacterial cultures of S. parauberis serotype III and 1.76 × 10(2) gene copies in fish tissues experimentally and naturally infected with S. parauberis of the serotype III. The specificity and sensitivity of the protocols described in this study suggest that these methods could be used for diagnostic and/or epidemiological purposes in clinical diagnostic laboratories. KEY POINTS: • Structure of loci cps for S. parauberis of serotypes III, IV and V was described. • mPCR to differentiate S. parauberis serotypes causing disease in fish was optimized. • qPCR assay to quantify strains of S. parauberis serotype III in fish tissues. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-020-10683-z) contains supplementary material, which is available to authorized users.


Sudden onset anosmia and dysgeusia in two patients: An early sign of SARS-CoV-2 infection


Continuous positive airway pressure in children with severe pneumonia: a meta-analysis


title: An overview of management of intracranial hypertension in the intensive care unit

text: Intracranial hypertension (IH) is a clinical condition commonly encountered in the intensive care unit, which requires immediate treatment. The maintenance of normal intracranial pressure (ICP) and cerebral perfusion pressure in order to prevent secondary brain injury (SBI) is the central focus of management. SBI can be detected through clinical examination and invasive and non-invasive ICP monitoring. Progress in monitoring and understanding the pathophysiological mechanisms of IH allows the implementation of targeted interventions in order to improve the outcome of these patients. Initially, general prophylactic measures such as patient’s head elevation, fever control, adequate analgesia and sedation depth should be applied immediately to all patients with suspected IH. Based on specific indications and conditions, surgical resection of mass lesions and cerebrospinal fluid drainage should be considered as an initial treatment for lowering ICP. Hyperosmolar therapy (mannitol or hypertonic saline) represents the cornerstone of medical treatment of acute IH while hyperventilation should be limited to emergency management of life-threatening raised ICP. Therapeutic hypothermia could have a possible benefit on outcome. To control elevated ICP refractory to maximum standard medical and surgical treatment, at first, high-dose barbiturate administration and then decompressive craniectomy as a last step are recommended with unclear and probable benefit on outcomes, respectively. The therapeutic strategy should be based on a staircase approach and be individualized for each patient. Since most therapeutic interventions have an uncertain effect on neurological outcome and mortality, future research should focus on both studying the long-term benefits of current strategies and developing new ones.


title: Corneal donation for research versus for transplantation: A-year prospective study of acceptance rates in a French University Hospital

text: Fresh corneal donation is essential for basic and preclinical research, but more unknown to public and the medical teams than donation for transplantation: it may raise concerns. We prospectively compared the acceptance rates and the characteristics of targeted corneal donation for research versus donation for transplantation during one year. The Agence de la Biomédecine authorized us to procure fresh corneas targeted for research, only from the donors with medical contraindications for transplantation, in order not to increase grafts shortage. Three nurses from the hospital coordination team of Saint-Etienne University Hospital, obtained consent for research and transplantation in parallel, screening all intra-hospital deaths cases, following standard protocol to check no refusal from families, despite the French opt-out system. They contacted 127 families for research and 244 for transplantation, in 71% of cases by telephone. Consent was obtained in 62% of cases for research and 54% for transplantation (P = 0.135). The main contraindication for transplantation was the cognitive disorders (66%) followed by the blood cancers (8%). This new specific activity, providing new source of fresh corneas for research immediately usable without any eyebank storage steps, didn’t reduce the number of corneas procured for transplantation versus previous years (P = 0.998). Donors in the research group were 10 years older (P<0.001) without difference regarding endothelial cell quality (P = 0.071), allowing maximal clinical relevance for protocols using these fresh human scientific corneas provided by targeted donation.


title: Development of a competency profile for professionals involved in infectious disease preparedness and response in the air transport public health sector

text: BACKGROUND: Recent infectious disease outbreaks highlight the importance of competent professionals with expertise on public health preparedness and response at airports. The availability of a competency profile for this workforce supports efficient education and training. Although competency profiles for infectious disease control professionals are available, none addresses the complex airport environment. Therefore, the main aim of this study is to develop a competency profile for professionals involved in infectious disease preparedness and response at airports in order to stimulate and direct further education and training. METHODS: We developed the competency profile through the following steps: 1) extraction of competencies from relevant literature, 2) assessment of the profile in a national RAND modified Delphi study with an interdisciplinary expert group (n = 9) and 3) assessment of the profile in an international RAND modified Delphi study with an airport infectious disease management panel of ten European countries (n = 10). RESULTS: We systematically studied two competency profiles on infectious disease control and three air transport guidelines on event management, and extracted 61 relevant competencies for airports. The two RAND modified Delphi procedures further refined the profile, mainly by specifying a competency’s target group, the organizational level it should be present on, and the exact actions that should be mastered. The final profile, consisting of 59 competencies, covers the whole process from infectious disease preparedness, through the response phase and the recovery at airports. CONCLUSION: We designed a profile to support training and exercising the multidisciplinary group of professionals in infectious disease management in the airport setting, and which is ready for use in practice. The many adaptations and adjustments that were needed to develop this profile out of existing profiles and air transport guidelines suggest that other setting-specific profiles in infectious disease control are desirable.


title: THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation

text: Lipoprotein lipase (LPL) is upregulated in atherosclerotic lesions and it may promote the progression of atherosclerosis, but the mechanisms behind this process are not completely understood. We previously showed that the phosphorylation of Akt within THP-1 macrophages is increased in response to the lipid hydrolysis products generated by LPL from total lipoproteins. Notably, the free fatty acid (FFA) component was responsible for this effect. In the present study, we aimed to reveal more detail as to how the FFA component may affect Akt signalling. We show that the phosphorylation of Akt within THP-1 macrophages increases with total FFA concentration and that phosphorylation is elevated up to 18 hours. We further show that specifically the palmitoleate component of the total FFA affects Akt phosphorylation. This is tied with changes to the levels of select molecular species of phosphoinositides. We further show that the total FFA component, and specifically palmitoleate, reduces apolipoprotein A-I-mediated cholesterol efflux, and that the reduction can be reversed in the presence of the Akt inhibitor MK-2206. Overall, our data support a negative role for the FFA component of lipoprotein hydrolysis products generated by LPL, by impairing macrophage cholesterol efflux via Akt activation.


title: Knowledge, Attitudes, and Interactions with Chaplains and Nursing Staff Outcomes: A Survey Study

text: We conducted a cross-sectional survey of nursing staff (n = 51) in an academic hospital finding a significant inverse relationship between the frequency of chaplaincy interaction and perceived stress (r = − 0.27, p = 0.05). We also found a significant positive relationship between rated importance of having a chaplain at the hospital and secondary trauma (r = 0.30, p = 0.03). There was a significant positive relationship between religiosity and rated importance for having a chaplain (r = 0.30, p = 0.03) and rated helpfulness of chaplains (r = 0.32, p = 0.02). Similarly, there was a significant positive relationship between spirituality and average length of conversations with a chaplain, rated importance for having a chaplain, and helpfulness of chaplains (r = 0.32, p = 0.03; r = 0.44, p = 0.001; and r = 0.52, p = 0.0001, respectively). Interaction with chaplains is associated with decreased employee perceived stress for nursing staff who provide care for severely ill patients.


title: Association between racial discrimination and health-related quality of life and the impact of social relationships

text: PURPOSE: Interpersonal racial discrimination is associated with poor health. Social relationships may moderate the impact of discrimination and represent modifiable behaviors that can be targeted by public health interventions. We described citywide associations between self-reported racial discrimination and health-related quality of life among the overall New York City (NYC) adult residential population and by four main race/ethnicity groups and explored whether social relationships moderated health effects of discrimination. METHODS: We analyzed cross-sectional survey data from 2335 adults weighted to be representative of the NYC population. We measured exposures to lifetime interpersonal racial discrimination in nine domains using a modified version of the Experiences of Discrimination scale. We performed unadjusted and adjusted regression analyses on four self-rated health-related quality of life outcomes including general health, physical health, mental health, and limitations from physical or mental health. RESULTS: Overall, 47% [95% CI 44.5, 50.3] of respondents reported having experienced racial discrimination in at least one domain. In the overall population, significant associations with racial discrimination were noted in adjusted models for poor physical health, poor mental health, and limitations by poor physical and mental health. Among those exposed to racial discrimination, the risk of experiencing poor mental health was lower among those who had contact with family or friends outside their household at least once a week, compared with those who had less frequent social contact. CONCLUSION: This study provides evidence that social relationships may moderate the impact of racial discrimination on mental health and should be integrated into health promotion efforts.


title: Sodium–glucose cotransporter 2 inhibition suppresses HIF-1α-mediated metabolic switch from lipid oxidation to glycolysis in kidney tubule cells of diabetic mice

text: Inhibition of sodium–glucose cotransporter 2 (SGLT2) in the proximal tubule of the kidney has emerged as an effective antihyperglycemic treatment. The potential protective role of SGLT2 inhibition on diabetic kidney disease (DKD) and underlying mechanism, however, remains unknown. In this study, metabolic switch was examined using kidney samples from human with diabetes and streptozocin (STZ)-induced experimental mouse model of diabetes treated with or without SGLT2 inhibitor dapagliflozin. Results were further validated using primarily cultured proximal tubule epithelial cells. We found that DKD development and progression to renal fibrosis entailed profound changes in proximal tubule metabolism, characterized by a switch from fatty acid utilization to glycolysis and lipid accumulation, which is associated with the increased expression of HIF-1α. Diabetes-induced tubulointerstitial damage, such as macrophage infiltration and fibrosis, was significantly improved by dapagliflozin. Consistent with the effects of these beneficial interventions, the metabolic disorder was almost completely eliminated by dapagliflozin. The increased level of HIF-1α in renal proximal tubule was nearly nullified by dapagliflozin. Moreover, dapagliflozin protects against glucose-induced metabolic shift in PTCs via inhibiting HIF-1α. It suggests that SGLT2 inhibition is efficient in rectifying the metabolic disorder and may be a novel prevention and treatment strategy for kidney tubule in DKD.


title: The Negative Implications of Being Tolerated: Tolerance From the Target’s Perspective

text: Intergroup toleration is a requirement for living with diversity and actively promoted by local, national, and international bodies. However, although psychological researchers have extensively considered the implications of being discriminated, little is known about the psychological consequences of being tolerated. In this article, we argue that beyond the freedoms implied by tolerance, being “merely” tolerated also implies social identity threats that compromise specific psychological needs (belongingness, esteem, control, certainty). We further consider the psychological consequences of being tolerated at the personal, interpersonal, and intergroup levels and consider factors that may moderate the impact of being tolerated for minority outcomes. Taken together, this work provides the first theoretical argument and overview of what it means to be tolerated by considering the negative implications of toleration in diverse nations.


title: How short is too short? A randomised controlled trial evaluating short-term existential behavioural therapy for informal caregivers of palliative patients

text: BACKGROUND: Informal caregivers of palliative patients show higher levels of depression and distress compared with the general population. Fegg’s (2013) existential behavioural therapy was shortened to two individual 1-h sessions (short-term existential behavioural therapy). AIM: Testing the effectiveness of sEBT on psychological symptoms of informal caregivers in comparison with active control. DESIGN: Randomised controlled trial. SETTING/PARTICIPANTS: Informal caregivers of palliative in-patients. METHODS: The primary outcome was depression; secondary outcomes were anxiety, subjective distress and minor mental disorders, positive and negative affect, satisfaction with life, quality of life and direct health care costs. General linear mixed models allow several measurements per participant and change over time. Reasons for declining the intervention were investigated by Rosenstock’s Health Belief Model. RESULTS: Overall inclusion rate was 41.0%. Data of 157 caregivers were available (63.1% females; mean age: 54.6 years, standard deviation (SD): 14.1); 127 participants were included in the main analysis. Participation in sEBT or active control was not significantly associated with post-treatment depression. Outcomes showed prevailingly significant association with time of investigation. Self-efficacy, scepticism of benefit of the intervention, belief of better coping alone and support by family and friends were significant factors in declining participation in the randomised controlled trial. CONCLUSION: Inclusion rate was tripled compared with a previously evaluated longer EBT group intervention. By shortening the intervention, inclusion rate was traded for effectiveness and the intervention could not impact caregivers’ psychological state. Early integration of sEBT and combination of individual and group setting and further study of the optimal length for caregiver interventions are suggested.


title: Making Sense of the World: Infant Learning From a Predictive Processing Perspective

text: For human infants, the first years after birth are a period of intense exploration—getting to understand their own competencies in interaction with a complex physical and social environment. In contemporary neuroscience, the predictive-processing framework has been proposed as a general working principle of the human brain, the optimization of predictions about the consequences of one’s own actions, and sensory inputs from the environment. However, the predictive-processing framework has rarely been applied to infancy research. We argue that a predictive-processing framework may provide a unifying perspective on several phenomena of infant development and learning that may seem unrelated at first sight. These phenomena include statistical learning principles, infants’ motor and proprioceptive learning, and infants’ basic understanding of their physical and social environment. We discuss how a predictive-processing perspective can advance the understanding of infants’ early learning processes in theory, research, and application.


title: The Association Between Adverse Child Health, Psychological, Educational and Social Outcomes, and Nondependent Parental Substance: A Rapid Evidence Assessment

text: BACKGROUND: Between 5% and 30% of children in high-income countries live with a substance misusing parent, the majority of which is below dependent levels. However, little is understood about the impact of nondependent parental substance misuse upon children. METHODS: We searched the international literature using rigorous systematic methods to identify studies examining parental substance misuse and adverse outcomes in children. The inclusion criteria were cross-sectional, longitudinal, case-control, and cohort studies; of children aged 0–18 years whose parents are high-risk substance misusers; reporting on their health, psychological, substance use, educational, and social outcomes. RESULTS: We identified 36 papers (from 33 unique studies), most of which were assessed as being of medium to high methodological quality (N= 28). Parental nondependent substance misuse was found to be associated with adversity in children, with strong evidence of an association with externalizing difficulties (N = 7 papers, all finding an association) and substance use (N = 23 papers, all finding an association) in adolescents and some evidence of adverse health outcomes in early childhood (N = 6/8 papers finding an association). There is less evidence of an association between parental substance misuse and adverse educational and social outcomes. The body of evidence was largest for parental alcohol misuse, with research examining the impact of parental illicit drug use being limited. CONCLUSION: Methodological limitations restrict our ability to make causal inference. Nonetheless, the prevalence of adverse outcomes in children whose parents are nondependent substance misusers highlights the need for practitioners to intervene with this population before a parent has developed substance dependency.


title: Image-Based Marker-Free Screening of GABA(A) Agonists, Antagonists, and Modulators

text: The ionotropic GABA(A) receptors represent the main target for different groups of widely used drugs having hypnotic and anxiolytic effects. So far, most approaches used to assess GABA activity involve invasive low -throughput electrophysiological techniques or rely on fluorescent dyes, preventing the ability to conduct noninvasive and thus nonperturbing screens. To address this limitation, we have developed an automated marker-free cell imaging method, based on digital holographic microscopy (DHM). This technology allows the automatically screening of compounds in multiple plates without having to label the cells or use special plates. This methodological approach was first validated by screening the GABA(A) receptor expressed in HEK cells using a selection of active compounds in agonist, antagonist, and modulator modes. Then, in a second blind screen of a library of 3041 compounds (mostly composed of natural products), 5 compounds having a specific agonist action on the GABA(A) receptor were identified. The hits validated from this unbiased screen were the natural products muscimol, neurosteroid alphaxalone, and three compounds belonging to the avermectin family, all known for having an agonistic effect on the GABA(A) receptor. The results obtained were exempt from false negatives (structurally similar unassigned hits), and false-positive hits were detected and discarded without the need for performing electrophysiological measurements. The outcome of the screen demonstrates the applicability of our screening by imaging method for the discovery of new chemical structures, particularly regarding chemicals interacting with the ionotropic GABA(A) receptor and more generally with any ligand-gated ion channels and transporters.


docid: fcgenwli

title: Transitioning from dental school


A lifesaving update for the dental team


The BDA; together


More than science


title: Oral healthcare workforce planning in post-Brexit Britain

text: The terms of the United Kingdom's (UK's) departure from the European Union (EU) are currently being negotiated. It is therefore uncertain exactly what effect they will have on planning the UK's oral healthcare workforce. Nevertheless, as 16% of dentists currently registered with the Genral Dental Council (GDC) have migrated to the UK from EU countries, this factor must be taken into consideration by workforce planners. However, it is far from being the only factor. This opinion piece therefore describes the current numbers of non-UK EU dentists and DCPs registered with the GDC and poses the question 'will they remain in the UK in the future'? It then comments on the current legislation on recognition of non-UK dental qualifications. It goes on to consider the Migration Advisory Committee's recommendation for dental practitioners, the oral healthcare needs of the population of the UK, who could address them and the implications for the Advancing Dental Care project


A plausible transmission mode


Redeployment to research?


A simple pleasure


Working group publishes rapid review for re-opening dental services


Progression of specialist trainees


Adopting an organised and cohesive team-based approach


'I am excited to start my career as a qualified dentist'


Another way for fractured jaws


Oral cancer patients


What will be viable for FDs?


Prescribing antibiotics for urgent dental care during the pandemic


DIY ultrasonic scaling


Webinar popularity


Orthodontic adjustments


title: Structural and molecular analyses of functional epitopes and escape mutants in Japanese encephalitis virus envelope protein domain III

text: The Japanese encephalitis virus (JEV) is one of the vector borne causes of encephalitis found in southeastern Asia. This positive single-stranded RNA virus is a member of the Flaviviridae family, which notably includes dengue, tick-borne, West Nile, Zika as well as yellow fever, and transmits to humans by infected mosquitos. The main site of interactions for antibodies against this virus is the envelope protein domain III (ED3). The present report investigates the time-dependent structural and conformational changes of JEV ED3 functional epitopes and escape mutants by computer simulations. The results indicate the presence of significant structural differences between the functional epitopes and the escape mutants. Mutation-induced structural/conformational instabilities of this type can decrease the antibody neutralization activity. Among the different escape mutants studied here, Ser40Lys/Asp41Arg appear to be most unstable, while Ser40Glu/Asp41Leu exhibit the lowest structural variations. The highest level of escape mutation observed in Ser40Lys is linked to the relatively higher values of root mean square deviation/fluctuation found in the molecular dynamics simulation of this protein. Secondary-structure deviations and depletion of H bonding are other contributing factors to the protein’s increased instability. Overall, the proteins with residue 41 mutations are found to be structurally more ordered than those with residue 40 mutations. The detailed time-based structural assessment of the mutant epitopes described here may contribute to the development of novel vaccines and antiviral drugs necessary to defend against future outbreaks of JEV escape mutants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12026-020-09130-y) contains supplementary material, which is available to authorized users.


title: Successful respiratory management of a Marshall-Smith syndrome patient with a tracheo-innominate artery fistula

text: BACKGROUND: Tracheo-innominate artery fistula (TIF) is a life-threatening complication of tracheostomy. We describe perioperative management for innominate artery transection in a case with TIF. CASE PRESENTATION: A 4-year-old Japanese female with Marshal-Smith syndrome presented for management of TIF. She underwent tracheostomy at the age of 3 months and an uncuffed tracheostomy tube was inserted. One month before admission to our hospital, intermittent tracheal bleeding, suggesting TIF, occurred. Although we considered to change to a cuffed endotracheal tube, craniofacial abnormality suggested difficult oral intubation, and there was a possibility of rebleeding. Finally, innominate artery transection was performed under total intravenous anesthesia without changing the tracheostomy tube. Surgery completed uneventfully and she received mechanical ventilation under sedation for a day, followed by weaning without complications. CONCLUSIONS: A cuffed tracheostomy tube should have been inserted before surgery for effective hemostasis against sudden bleeding from TIF even though conversion to oral intubation was difficult.


title: Assessing the intestinal carriage rates of vancomycin-resistant enterococci (VRE) at a tertiary care hospital in Hungary

text: Excessive use of antibiotics contributes to the selection of resistant bacteria and intestinal colonization with multiresistant pathogens poses a risk factor for subsequent infections. The present study assessed vancomycin-resistant enterococci (VRE) carriage rates in patients admitted to our tertiary care hospital. Stool samples sent for routine culturing were screened with vancomycin containing solid or broth enrichment media. VRE isolates were identified with matrix-assisted laser desorption/ionization-time of flight mass spectrometry and antibiotic susceptibilities were tested by E-test. Vancomycin resistance genes were detected by polymerase chain reaction. Medical records of carriers were examined for suspected risk factors for colonization. Altogether 3025 stool specimens were analyzed. Solid media identified a VRE carriage rate of 2.2% while broth enrichment detected 5.8%. Seventy percent of the isolates were Enterococcus faecium. VanB genotype was detected in 38.2%, VanA in 37.3%, VanC1 in 22.6%, and VanC2 in 1.9%. All VRE were sensitive to linezolid, daptomycin, and tigecycline. Collective risk factors for carriage were diabetes, normal flora absence, Clostridioides difficile positivity, longer hospital stay, and advanced age. 78.5% of the carriers received antibiotic therapy which was metronidazole in most cases (47.3%). We recommend regular screening of risk groups such as patients with diabetes, history of recent hospitalization, or former C. difficile infection as an imperative step for preventing VRE dissemination.


Pandemie-Panik: Sollen sich die Patienten einmauern?: Etwas Realismus tut Not


title: In Bewegung bleiben …: Editorial

text: Bei aller Dringlichkeit der Corona-Pandemie und der erforderlichen Fokussierung unserer aktuellen Arbeit leiden Patienten weiterhin an den sog. großen „Volkskrankheiten“ wie koronare Herzerkrankung oder chronische Herzinsuffizienz. Sie müssen von uns weiterhin gut versorgt werden.


HZV: Engmaschige Kontrolle von COVID-19-Patienten: Neues Software-Modul


Pneumonie: CRB-65-Score mit neuem „Plus“


Nephritis signalisiert schweren Verlauf


title: Thinking Beyond HLH: Clinical Features of Patients with Concurrent Presentation of Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy

text: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune system activation driven mainly by high levels of interferon gamma. The clinical presentation of HLH can have considerable overlap with other inflammatory conditions. We present a cohort of patients with therapy refractory HLH referred to our center who were found to have a simultaneous presentation of complement-mediated thrombotic microangiopathy (TMA). Twenty-three patients had therapy refractory HLH (13 primary, 4 EVB-HLH, 6 HLH without known trigger). Sixteen (69.6%) met high-risk TMA criteria. Renal failure requiring renal replacement therapy, severe hypertension, serositis, and gastrointestinal bleeding were documented only in patients with HLH who had concomitant complement-mediated TMA. Patients with HLH and without TMA required ventilator support mainly due to CNS symptoms, while those with HLH and TMA had respiratory failure predominantly associated with pulmonary hypertension, a known presentation of pulmonary TMA. Ten patients received eculizumab for complement-mediated TMA management while being treated for HLH. All patients who received the complement blocker eculizumab in addition to the interferon gamma blocker emapalumab had complete resolution of their TMA and survived. Our observations suggest co-activation of both interferon and complement pathways as a potential culprit in the evolution of thrombotic microangiopathy in patients with inflammatory disorders like refractory HLH and may offer novel therapeutic approaches for these critically ill patients. TMA should be considered in children with HLH and multi-organ failure, as an early institution of a brief course of complement blocking therapy in addition to HLH-targeted therapy may improve clinical outcomes in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-020-00789-4) contains supplementary material, which is available to authorized users.


Schwerer Verlauf bei Adipösen


title: Universal access to essential health information: accelerating progress towards universal health coverage and other SDG health targets

text: The information that people need to protect and manage their own health and the health of those for whom they are responsible is a fundamental element of an effective people-centred healthcare system. Achieving universal health coverage (UHC) requires universal access to essential health information. While it was recently recognised by the World Medical Association, universal access to essential health information is not yet reflected in official monitoring of progress on UHC for the sustainable development goals (SDGs). In this paper, we outline key features that characterise universal access to essential health information and indicate how it is increasingly achievable. We highlight the growing evidence of the impact of wider access to practical and actionable information on health for the public, carers and frontline health workers and provide illustrative, evidence-based, examples of how increasing access to essential health information can accelerate the achievement of UHC and other health targets of the SDGs. The paper ends with an assessment of reasons why universal access to essential health information has not yet been achieved, and an associated call to action to key stakeholders—such as governments, multilaterals, funding bodies, policy-makers, health professionals and knowledge intermediaries—to explicitly recognise the foundational role of universal access to essential health information for achieving UHC and the rest of the health SDGs, to include it in the relevant SDG target and associated monitoring indicators, and to incorporate actions in their own policies and programmes to promote and enable this access.


Reply to Authors


title: Could Environment Affect the Mutation of H1N1 Influenza Virus?

text: H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact both on human health and social development. Though data on their complete genome sequences have recently been obtained, the evolution and mutation of A/H1N1 viruses remain unknown to this day. Among many drivers, the impact of environmental factors on mutation is a novel hypothesis worth studying. Here, a geographically disaggregated method was used to explore the relationship between environmental factors and mutation of A/H1N1 viruses from 2000–2019. All of the 11,721 geo-located cases were examined and the data was analysed of six environmental elements according to the time and location (latitude and longitude) of those cases. The main mutation value was obtained by comparing the sequence of the influenza virus strain with the earliest reported sequence. It was found that environmental factors systematically affect the mutation of A/H1N1 viruses. Minimum temperature displayed a nonlinear, rising association with mutation, with a maximum ~15 °C. The effects of precipitation and social development index (nighttime light) were more complex, while population density was linearly and positively correlated with mutation of A/H1N1 viruses. Our results provide novel insight into understanding the complex relationships between mutation of A/H1N1 viruses and environmental factors.


title: Perfectionism Profiles and Motivation to Exercise Based on Self-Determination Theory

text: This study complements extant variable-centered research that focus on the relationship between perfectionism and the autonomous and controlled motivation to exercise. A person-centered approach is used for identifying perfectionism profiles as well as analyzing inter-profile differences in terms of the six regulatory styles located on the autonomy-control continuum. A sample of 597 (M(age) = 22.08, SD = 3.33) Ecuadorian undergraduates enrolled in a sport science degree program was employed. Latent Profile Analysis based on two higher-order perfectionism dimensions, Perfectionistic Strivings (PS) and Perfectionistic Concerns (PC), supported a four-class solution: Non-Perfectionists (low PS and PC), Adaptive Perfectionists (high PS and low PC), Maladaptive Perfectionists (high PS and PC), and Moderate Perfectionists (moderate PS and PC). Adaptive Perfectionists obtained the highest means on Intrinsic, Integrated, and Identified regulations. However, these differences where only significant when compared with Moderate Perfectionists, and only in the case of Integrated regulation, in comparison with Non-Perfectionists. In contrast, Maladaptive Perfectionists obtained significantly higher scores on Introjected and External regulations as well as on Amotivation than the other three classes. Results are discussed in light of Self-Determination Theory.


title: Evolution of the Output–Workforce Relationship in Primary Care Facilities in China from 2009 to 2017

text: This study evaluates trends in workforce supply compared with those in the volume of service delivery (output) for basic clinical care (CC) and public health (PH) services from 2009 to 2017 in China. A cross-sectional survey (2018) was combined with retrospective data (2009–2017) from 785 primary care (PC) facilities in six provinces. Measures for the output of clinical care and of public health services were aggregated into a single (weighted) index for both service profiles. The output–workforce relationship was measured by its ratio. Latent class growth analysis and logistic regression analysis were applied to classify trajectories and determine associations with facility-level, geographic, and economic characteristics. From 2009 to 2017, the proportion of PC to overall healthcare workforce decreased from 24.25% to 18.57%; the proportion of PH to PC providers at PC facilities increased from 23.6% to 29.5%, while the proportion of PH output increased from 44.3% to 65.9%. Four trajectories of the output–workforce relationship were identified for CC, and five trajectories for PH services of which 85.3% of the facilities showed initially increasing and then slightly decreasing trends. Geographic characteristics impacted different trajectories. The PC workforce falls behind hospital workforce. The expansion in workload of PH services is unbalanced with that of workforce.


title: Workers’ Healthcare Assistance Model (WHAM): Development, Validation, and Assessment of Sustainable Return on Investment (S-ROI)

text: The present study aimed to present and validate the Worker´s Healthcare Assistance Model (WHAM), which includes an interdisciplinary approach to health risk management in search of integral and integrated health, considering economic sustainability. Through the integration of distinct methodological strategies, WHAM was developed in the period from 2011 to 2018, in a workers’ occupational health centre in the oil industry in Bahia, Brazil. The study included a sample of 965 workers, 91.7% of which were men, with a mean age of 44.9 years (age ranged from 23 to 73 years). The Kendall rank correlation coefficient and hierarchical multiple regression analysis were used for the validation of WHAM. The assessment of sustainable return on investment (S-ROI) was made using the WELLCAST ROI™ decision support tool, covering workers with heart disease and diabetes. WHAM can be considered an innovative healthcare model, as there is no available comparative model. WHAM is considered robust, with 86% health risk explanatory capacity and with an 85.5% S-ROI. It can be concluded that WHAM is a model capable of enhancing the level of workers’ health in companies, reducing costs for employers and improving the quality of life within the organization.


title: Digital Undergraduate Education in Dentistry: A Systematic Review

text: The aim of this systematic review was to investigate current penetration and educational quality enhancements from digitalization in the dental curriculum. Using a modified PICO strategy, the literature was searched using PubMed supplemented with a manual search to identify English-language articles published between 1994 and 2020 that reported the use of digital techniques in dental education. A total of 211 articles were identified by electronic search, of which 55 articles were selected for inclusion and supplemented with 27 additional publications retrieved by manual search, resulting in 82 studies that were included in the review. Publications were categorized into five areas of digital dental education: Web-based knowledge transfer and e-learning, digital surface mapping, dental simulator motor skills (including intraoral optical scanning), digital radiography, and surveys related to the penetration and acceptance of digital education. This review demonstrates that digitalization offers great potential to revolutionize dental education to help prepare future dentists for their daily practice. More interactive and intuitive e-learning possibilities will arise to stimulate an enjoyable and meaningful educational experience with 24/7 facilities. Augmented and virtual reality technology will likely play a dominant role in the future of dental education.


title: Kaizen–Kata, a Problem-Solving Approach to Public Service Health Care in Mexico. A Multiple-Case Study

text: Purpose: Mexico’s public hospitals are experiencing major operational problems which seriously affect the care of Mexican citizens. Some hospitals have initiated efforts to apply the Kaizen philosophy to improve this situation. Therefore, the purpose of this article is to analyze the methodological impact of Kaizen–Kata implementation in Mexican public hospitals that have tried to solve operational problems using this improvement approach. Design/Methodology/Approach: The service organization implemented Kaizen–Kata methodology in order to improve one operational problem-process in health care. A case-study approach was used in this research in order to understand the effects of the Kaizen–Kata methodology in solving problems in their operational procedures. Findings: Six specific drivers were identified when applying the Kaizen–Kata methodology. Furthermore, the impact on the levels of implementation of the Kaizen–Kata methodology in each of the improvement teams studied was also identified. Research Limitations: The main limitation of the research is that only three case-studies are presented thus it is not possible to generalize its results. Practical Implications (Where Possible): Other public hospitals can use this specific example as a working guide to solve the operational problems of health systems. Originality/Value: A methodology of continuous improvement in manufacturing was imported from the industry sector for application in an operational health care process. The Kaizen–Kata methodology contributed significantly to improving issues involving delays, customer complaints, process reworks and extra-cost, among other effects of operational problems.


title: Developments of Riboswitches and Toehold Switches for Molecular Detection—Biosensing and Molecular Diagnostics

text: Riboswitches and toehold switches are considered to have potential for implementation in various fields, i.e., biosensing, metabolic engineering, and molecular diagnostics. The specific binding, programmability, and manipulability of these RNA-based molecules enable their intensive deployments in molecular detection as biosensors for regulating gene expressions, tracking metabolites, or detecting RNA sequences of pathogenic microorganisms. In this review, we will focus on the development of riboswitches and toehold switches in biosensing and molecular diagnostics. This review introduces the operating principles and the notable design features of riboswitches as well as toehold switches. Moreover, we will describe the advances and future directions of riboswitches and toehold switches in biosensing and molecular diagnostics.


title: Recent advances in the understanding of trimeric autotransporter adhesins

text: Adhesion is the initial step in the infection process of gram-negative bacteria. It is usually followed by the formation of biofilms that serve as a hub for further spread of the infection. Type V secretion systems engage in this process by binding to components of the extracellular matrix, which is the first step in the infection process. At the same time they provide protection from the immune system by either binding components of the innate immune system or by establishing a physical layer against aggressors. Trimeric autotransporter adhesins (TAAs) are of particular interest in this family of proteins as they possess a unique structural composition which arises from constraints during translocation. The sequence of individual domains can vary dramatically while the overall structure can be very similar to one another. This patchwork approach allows researchers to draw conclusions of the underlying function of a specific domain in a structure-based approach which underscores the importance of solving structures of yet uncharacterized TAAs and their individual domains to estimate the full extent of functions of the protein a priori. Here, we describe recent advances in understanding the translocation process of TAAs and give an overview of structural motifs that are unique to this class of proteins. The role of BpaC in the infection process of Burkholderia pseudomallei is highlighted as an exceptional example of a TAA being at the centre of infection initiation.


docid: jewffjwj

title: Immunogenicity of trimeric autotransporter adhesins and their potential as vaccine targets

text: The current problem of increasing antibiotic resistance and the resurgence of numerous infections indicate the need for novel vaccination strategies more than ever. In vaccine development, the search for and the selection of adequate vaccine antigens is the first important step. In recent years, bacterial outer membrane proteins have become of major interest, as they are the main proteins interacting with the extracellular environment. Trimeric autotransporter adhesins (TAAs) are important virulence factors in many Gram-negative bacteria, are localised on the bacterial surface, and mediate the first adherence to host cells in the course of infection. One example is the Neisseria adhesin A (NadA), which is currently used as a subunit in a licensed vaccine against Neisseria meningitidis. Other TAAs that seem promising vaccine candidates are the Acinetobacter trimeric autotransporter (Ata), the Haemophilus influenzae adhesin (Hia), and TAAs of the genus Bartonella. Here, we review the suitability of various TAAs as vaccine candidates.


title: Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues

text: Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers. Several such compounds, including gemcitabine and cytarabine, are the go-to option in first-line treatments. However, these materials do have limitations and the development of next generation compounds remains a topic of significant interest and necessity. Herein, we discuss recent advances in the chemical synthesis and biological evaluation of nucleoside analogues as potential anticancer agents. Focus is paid to 4′-heteroatom substitution of the furanose oxygen, 2′-, 3′-, 4′- and 5′-position ring modifications and the development of new prodrug strategies for these materials.


title: Phenylpyrazalopyrimidines as Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, and Molecular Simulations

text: N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC(50) = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% and 79%, respectively, at a concentration of 50 µM after 96 h incubation. The compound showed modest inhibitory activity against c-Src (IC(50) = 60.4 µM), Btk (IC(50) = 90.5 µM), and Lck (IC(50) = 110 µM), while it showed no activity against Abl1, Akt1, Alk, Braf, Cdk2, and PKCa. In combination with target selection and kinase profiling assay, extensive theoretical studies were carried out to explore the selectivity behavior of compound 10. Specific interactions were also explored by examining the changing trends of interactions of tyrosine kinases with the phenylpyrazolopyrimidine derivative. The results showed good agreement with the experimental selectivity pattern among c-Src, Btk, and Lck.


Reply to the Comment by Dr. Cure on “Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade”


COVID-19 in Brazil: “So what?”


Anything But Routine


Offline: A global health crisis? No, something far worse


COVID-19: remaking the social contract


Society of Biological Psychiatry’s 75th Anniversary Meeting: A Guide to the Meeting That Wasn't


Society and the slow burn of inequality


Index of biochemical reviews


Oxidative stress in air pollution research


Celebrating Florence Nightingale's bicentenary


docid: tycjezou

title: Washing Away the Fear


docid: sbbkqirv

title: The Rapid Development of an Urgent Dental Care Hub in an Oral Surgery Unit—Key Learning Points


Hand touches on the surfaces of a healthcare waiting area


title: Factors Influencing Atypical Clinical Presentations during the 2017 Madagascar Pneumonic Plague Outbreak: A Prospective Cohort Study

text: In late 2017, Madagascar experienced a large urban outbreak of pneumonic plague, the largest outbreak to date this century. During the outbreak, there were widespread reports of plague patients presenting with atypical symptoms, such as prolonged duration of illness and upper respiratory tract symptoms. Reported mortality among plague cases was also substantially lower than that reported in the literature (25% versus 50% in treated patients). A prospective multicenter observational study was carried out to investigate potential reasons for these atypical presentations. Few subjects among our cohort had confirmed or probable plague, suggesting that, in part, there was overdiagnosis of plague cases by clinicians. However, 35% subjects reported using an antibiotic with anti-plague activity before hospital admission, whereas 55% had antibiotics with anti-plague activity detected in their serum at admission. Although there may have been overdiagnosis of plague by clinicians during the outbreak, the high frequency of community antibiotic may partly explain the relatively few culture-positive sputum samples during the outbreak. Community antibiotic use may have also altered the clinical presentation of plague patients. These issues make accurate detection of patients and the development of clinical case definitions and triage algorithms in urban pneumonic plague outbreaks difficult.


title: Caveolar communication with xenobiotic-stalled ribosomes compromises gut barrier integrity

text: In response to internal and external insults, the intestinal lining undergoes various types of epithelial adaptation or pathologic distress via stress-responsive eIF2α kinase signaling and subsequent cellular reprogramming. As a vital platform for growth factor-linked adaptive signaling, caveolae were evaluated for epithelial modulation of the insulted gut. Patients under ulcerative insult displayed enhanced expression of caveolin-1, the main structural component of caveolae, which was positively associated with expression of protein kinase R (PKR), the ribosomal stress-responsive eIF2α kinase. PKR-linked biological responses were simulated in experimental gut models of ribosome-inactivating stress using mice and Caenorhabditis elegans. Caveolar activation counteracted the expression of wound-protective epidermal growth factor receptor (EGFR) and its target genes, such as chemokines that were pivotal for epithelial integrity in the ribosome-inactivated gut. Mechanistic findings regarding ribosomal inactivation-associated disorders in the gut barrier provide crucial molecular evidence for detrimental caveolar actions against EGFR-mediated epithelial protection in patients with IBD.


Worldwide Experiences in Disaster Medicine Education


Minimizing Healthcare Worker Contamination Risk During Tracheostomy


In the aftermath: the legacy of measles in Samoa


La mascarilla (que tanto necesitamos es la que hubiéramos necesitado)()


What If They Threw A Pandemic And Nobody Came?


Eliminating HCV: a marathon, not a sprint


Remembering Stephen Schwartz


Reviving the US CDC


Trial and error


Operational Considerations in Emergency Radiology


Reply: Comment on “From Air Pollution to the Anthropocene and Planetary Health. Implications for Clinicians, Researchers, and Society”


docid: wzzwvwrh

title: Comment on “From Air Pollution to the Anthropocene and Planetary Health. Implications for Clinicians, Researchers, and Society”


COVID-19: First Do No Harm


An Asymptomatic Patient with COVID-19


title: The new nurse manager survival guide, part II

text: Leading in a time of crisis


Caution Regarding Enclosures for Airway Procedures


Supporting your team during a global pandemic.


COVID-19 and changing social norms


title: Humor and sympathy in medical practice

text: Medical professionals seem to interpret their uses of humor very differently from those outside the medical profession. Nurses and physicians argue that humor is necessary for them to do their jobs well. Many (potential) patients are horrified that they could one day be the butt of their physician’s jokes. The purpose of this paper is to encourage the respectful use of humor in clinical prac-tice, so as to support its importance in medical practice, while simultaneously protecting against its potential abuse. I begin by examining two extremes of supporting or chastising the use of medical humor. I look at these views through the lenses of popular theories of humor to help explain their theoretical bases. In this second section, I explain the emotional aspect of humor as an embodied and embedded transformation of the world. This clarifies the role that humor plays in our daily lives, as well as why the ethical or unethical nature of its use is dependent on context. Third, I address the potential problems in the relationship between humor and clinical sympathy, and how this further affects the relationship between medical professionals and their patients. I conclude by arguing that humor can conflict with clinical sympathy, but this need not be the case. If medical professionals actively engage with clinical sympathy and focus on using humor in a way that is respectful towards their patients, then humor can continue to be a positive force in their lives while still providing the best care for their patients.


title: The effect of HIV status on the frequency and severity of acute respiratory illness

text: INTRODUCTION: Antiretroviral therapy has improved the health of people living with HIV (PLW-HIV), though less is known about how this impacts on acute respiratory illness. These illnesses are a common cause of ill health in the general population and any increase in their frequency or severity in PLW-HIV might have significant implications for health-related quality of life and the development of chronic respiratory disease. METHODS: In a prospective observational cohort study following PLW-HIV and HIV negative participants for 12 months with weekly documentation of any acute respiratory illness, we compared the frequency, severity and healthcare use associated with acute respiratory illnesses to determine whether PLW-HIV continue to have a greater frequency or severity of such illnesses despite antiretroviral therapy. RESULTS: We followed-up 136 HIV positive and 73 HIV negative participants for 12 months with weekly documentation of any new respiratory symptoms. We found that HIV status did not affect the frequency of acute respiratory illness: unadjusted incidence rates per person year of follow-up were 2.08 illnesses (95% CI 1.81–2.38) and 2.30 illnesses (1.94–2.70) in HIV positive and negative participants respectively, IRR 0.87 (0.70–1.07) p = 0.18. However, when acute respiratory illnesses occurred, PLW-HIV reported more severe symptoms (relative fold-change in symptom score 1.61 (1.28–2.02), p <0.001) and were more likely to seek healthcare advice (42% vs 18% of illnesses, odds ratio 3.32 (1.48–7.39), p = 0.003). After adjustment for differences in baseline characteristics, PLW-HIV still had higher symptom scores when unwell. CONCLUSIONS: HIV suppression with antiretroviral therapy reduces the frequency of acute respiratory illness to background levels, however when these occur, they are associated with more severe self-reported symptoms and greater healthcare utilisation. Exploration of the reasons for this greater severity of acute respiratory illness may allow targeted interventions to improve the health of people living with HIV. TRIAL REGISTRATION: ISRCTN registry (ISRCTN38386321).


docid: nuujqrvm

title: Viral delivery of tissue nonspecific alkaline phosphatase diminishes craniosynostosis in one of two FGFR2(C342Y/+) mouse models of Crouzon syndrome

text: Craniosynostosis is the premature fusion of cranial bones. The goal of this study was to determine if delivery of recombinant tissue nonspecific alkaline phosphatase (TNAP) could prevent or diminish the severity of craniosynostosis in a C57BL/6 FGFR2(C342Y/+) model of neonatal onset craniosynostosis or a BALB/c FGFR2(C342Y/+) model of postnatal onset craniosynostosis. Mice were injected with a lentivirus encoding a mineral targeted form of TNAP immediately after birth. Cranial bone fusion as well as cranial bone volume, mineral content and density were assessed by micro CT. Craniofacial shape was measured with calipers. Alkaline phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST) activity levels were measured in serum. Neonatal delivery of TNAP diminished craniosynostosis severity from 94% suture obliteration in vehicle treated mice to 67% suture obliteration in treated mice, p<0.02) and the incidence of malocclusion from 82.4% to 34.7% (p<0.03), with no effect on cranial bone in C57BL/6 FGFR2(C342Y/+) mice. In contrast, treatment with TNAP increased cranial bone volume (p< 0.01), density (p< 0.01) and mineral content (p< 0.01) as compared to vehicle treated controls, but had no effect on craniosynostosis or malocclusion in BALB/c FGFR2(C342Y/+) mice. These results indicate that postnatal recombinant TNAP enzyme therapy diminishes craniosynostosis severity in the C57BL/6 FGFR2(C342Y/+) neonatal onset mouse model of Crouzon syndrome, and that effects of exogenous TNAP are genetic background dependent.


docid: maqnvglz

title: Harnessing the potential of blood donation archives for influenza surveillance and control

text: Many blood donation services around the globe maintain large archives of serum and/or plasma specimens of blood donations which could potentially be used for serologic surveillance and risk assessment of influenza. Harnessing this potential requires robust evidence that the outcomes of influenza serology in plasma, which is rarely used, is consistent with that in serum, which is the conventional choice of specimens for influenza serology. We harvested EDTA-plasma specimens from the blood donation archives of Hong Kong Red Cross Transfusion Services, where EDTA is the type of anticoagulant used for plasma collection, compared their antibody titers and responses to that in serum. Influenza A/H1N1/California/7/2009 and A/H3N2/Victoria/208/2009 were the test strains. Our results showed that antibody titers in 609 matched serum/EDTA-plasma specimens (i.e. obtained from the same donor at the same time) had good agreement inferred by Intraclass Correlation Coefficient, the value of which was 0.82 (95% CI: 0.77–0.86) for hemagglutination inhibition assay and 0.95 (95% CI: 0.93–0.96) for microneutralization assay; seroconversion rates (based on hemagglutination inhibition titers) during the 2010 and 2011 influenza seasons in Hong Kong inferred from paired EDTA-plasma were similar to that inferred from paired sera. Our study provided the proof-of-concept that blood donation archives could be leveraged as a valuable source of longitudinal blood specimens for the surveillance, control and risk assessment of both pandemic and seasonal influenza.


title: Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma

text: BACKGROUND: A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma. METHODS: Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting the first cycle of IL-2. IL-2 (600,000 IU per kg via intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Responding patients received up to six IL-2 cycles. Patients assigned to IL-2 monotherapy who exhibited progression of melanoma after cycle 2 were allowed to crossover and receive SBRT and additional IL-2. Response Evaluation Criteria in Solid Tumors 1.1 criteria were applied to non-irradiated lesions for response assessment. RESULTS: 44 patients were included in the analysis. The ORR in the SBRT + IL-2 group was 54%: 21% complete response (CR), 33% partial response (PR), 21% stable disease (SD) and 25% progressive disease (PD). The ORR in patients receiving IL-2 monotherapy was 35%: 15% CR, 20% PR, 25% SD and 40% PD. Seven patients assigned to IL-2 subsequently received SBRT + IL-2. One CR and two PRs were observed in the crossover group. There was no difference in progression-free or overall survival (OS). At 5 years the OS was 26% in the SBRT + IL-2 group and 25% in the IL-2 monotherapy group. The disease control rate (DCR) was higher in the SBRT + IL-2 group (75% vs 60%, p=0.34). CONCLUSIONS: SBRT + IL-2 induced more objective responses with a higher DCR compared to IL-2 monotherapy in MM. IL-2 monotherapy resulted in a significantly higher ORR than anticipated. Some patients in the crossover group also achieved objective responses. TRIAL REGISTRATION NUMBER: NCT01416831.


title: To Petabytes and beyond: recent advances in probabilistic and signal processing algorithms and their application to metagenomics

text: As computational biologists continue to be inundated by ever increasing amounts of metagenomic data, the need for data analysis approaches that keep up with the pace of sequence archives has remained a challenge. In recent years, the accelerated pace of genomic data availability has been accompanied by the application of a wide array of highly efficient approaches from other fields to the field of metagenomics. For instance, sketching algorithms such as MinHash have seen a rapid and widespread adoption. These techniques handle increasingly large datasets with minimal sacrifices in quality for tasks such as sequence similarity calculations. Here, we briefly review the fundamentals of the most impactful probabilistic and signal processing algorithms. We also highlight more recent advances to augment previous reviews in these areas that have taken a broader approach. We then explore the application of these techniques to metagenomics, discuss their pros and cons, and speculate on their future directions.


title: Remdesivir, the antiviral hope against SARS-CoV-2/ Remdesivir, la esperanza antiviral frente al SARS-CoV-2

text: On December 31, 2019 a pneumonia outbreak caused by a new coronavirus (SARS-CoV-2) was detected in the city of Wuhan (China) Due to the high capacity of diffusion and human infection it has become a new zoonotic pandemic The absence of a vaccine has determined the search for antiviral drugs with the capacity to inhibit the replication of the new virus Among them, remdesivir, an analogue of adenosine, is what seems to have a more promising future This drug has shown in vitro and in animals a high capacity to block infection and viral replication with attainable concentrations in human plasma Although all studies have been carried out with SARS-CoV and MERS-CoV, it seems that by virological and functional analogy, remdesivir is one of the few antiviral drugs with proven efficacy However, studies and clinical trials in humans are required to know the result of their application in them


title: Porcine parvovirus nonstructural protein NS1 activates NF-κB and it involves TLR2 signaling pathway

text: BACKGROUND: Porcine parvovirus (PPV) is a single-stranded DNA virus that causes porcine reproductive failure. It is of critical importance to study PPV pathogenesis for the prevention and control of the disease. NS1, a PPV non-structural protein, is participated in viral DNA replication, transcriptional regulation, and cytotoxicity. Our previous research showed that PPV can activate nuclear factor kappa B (NF-κB) signaling pathway and then up-regulate the expression of interleukin (IL)-6. OBJECTIVES: Herein, the purpose of this study is to determine whether the non-structural protein NS1 of PPV also has the same function. METHODS: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, western blot, immunofluorescence assay and small interfering RNA (siRNA) were used. RESULTS: Our findings demonstrated that PPV NS1 protein can up-regulate the expression levels of IL-6 and tumor necrosis factor-alpha in a dose-dependent manner. Moreover, PPV NS1 protein was found to induce the phosphorylation of IκBα, then leading to the phosphorylation and nuclear translocation of NF-κB. In addition, the NS1 protein activated the upstream pathways of NF-κB. Meanwhile, TLR2-siRNA assay showed TLR2 plays an important role in the activation of NF-κB signaling pathway induced by PPV-NS1. CONCLUSIONS: These findings indicated that PPV NS1 protein induced the up-regulated of IL-6 expression through activating the TLR2 and NF-κB signaling pathways. In conclusion, these findings provide a new avenue to study the innate immune mechanism of PPV infection.


A safe distance between doctor and patient


docid: auxhgbaq

title: Error in Methods


The year of the nurse and midwife 2020: activating the potential and power of nursing


Protecting the psychological well‐being of healthcare providers affected by the COVID‐19 outbreak: Implications for the psychological rescue work of international community


Changing the Paradigm of Surgical Research During a Pandemic


Wearing an N95 Respiratory Mask: An Unintended Exercise Benefit?


Potential Cost Savings With Low-Dose Abiraterone in the United States


title: Multicenter Evaluation of QIAstat-Dx Respiratory Panel V2 for Detection of Viral and Bacterial Respiratory Pathogens

text: QIAstat-Dx Respiratory Panel V2 (RP) is a novel molecular-method-based syndromic test for the simultaneous and rapid (∼70-min) detection of 18 viral and 3 bacterial pathogens causing respiratory infections. This report describes the first multicenter retrospective comparison of the performance of the QIAstat-Dx RP assay to the established ePlex Respiratory Pathogen Panel (RPP) assay, for which we used 287 respiratory samples from patients suspected with respiratory infections. The QIAstat-Dx RP assay detected 312 (92%) of the 338 respiratory targets that were detected by the ePlex RPP assay. Most of the discrepant results have been observed in the low-pathogen-load samples. In addition, the QIAstat-Dx RP assay detected 19 additional targets in 19 respiratory samples that were not detected by the ePlex RPP assay. Nine of these discordant targets were considered to represent true positives after discrepancy testing by a third method. The main advantage of the QIAstat-Dx system compared to other syndromic testing systems, including the ePlex RPP assay, is the ability to generate cycle threshold (C(T)) values, which could help with the interpretation of results. Taking the data together, this study showed good performance of the QIAstat-Dx RP assay in comparison to the ePlex RPP assay for the detection of respiratory pathogens. The QIAstat-Dx RP assay offers a new, rapid, and accurate sample-to-answer multiplex panel for the detection of the most common viral and bacterial respiratory pathogens and therefore has the potential to direct appropriate therapy and infection control precautions.


Stepping Forward: Urologists’ Efforts During the COVID-19 Outbreak in Singapore


Sars-Cov-2: Underestimated damage to nervous system


Radiotherapy in the time of the Coronavirus pandemic: when less is better


COVID-19 will not leave behind refugees and migrants


Patients with mental health disorders in the COVID-19 epidemic


2020 year of the nurse and midwife: Meeting new challenges


Authors' reply


Ebola virus disease in DR Congo


Redefining vulnerability in the era of COVID-19


A tale of two emergencies


Building bridges in Yemen


(18)F-Fluorodeoxyglucose Uptake in Patient With Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus Disease 2019) Referred to Positron Emission Tomography/Computed Tomography for NSCLC Restaging


The conference of the future today?


Editor's perspectives – April 2020


The first COVID-19 case in Afghanistan acquired from Iran


Rethinking online mental health services in China during the COVID-19 epidemic


title: Feline Leukemia/Sarcoma Viruses and Immunodeficiency

text: This chapter discusses the structure feline leukemia virus (FeLV) and pathogenesis of lymphomas and leukemias BY FeLV. FeLV is quite similar to the better-studied murine leukemia viruses in structure and genetic map. The virus particles bud from cytoplasmic membranes into either extracellular spaces or into vacuoles. FeLV has long been considered a typical noncytopathogenic, longlatency leukemia virus based on its behavior in fibroblasts in vitro. Recent evidence suggests that its in vivo behavior in critical target hemolymphatic tissues is as likely to be cytopathic as transforming. The type of FeLV-related disease that occurs and the disease-free interval probably are influenced by viral envelope proteins and glycoproteins and the consequences of proviral integration. FeLV subgroup specificity apparently determines when and what type of disease will occur. The ecotropic FeLV-A is the most frequent subgroup found in pet cats and is transmitted contagiously. Immunosuppression is the most frequent and the most devastating manifestation of FeLV viremia in clinical and experimental studies. It seems that multiple cell types and multiple processes are involved in the development of feline retrovirus-induced immunosuppression. Although no solid evidence is available for the malfunctioning of cat T helper cells because of the paucity of T-cell specific markers, the circumstantial evidence provided thus far indicates an impaired T helper function in FeLV-infected cats similar to that observed in humans infected with HIV. Studies on the pathogenesis of FeLV-induced immunosuppression might provide a valuable mode for a better understanding and means of control of human AIDS.


title: The evolving landscape around genome editing in agriculture: Many countries have exempted or move to exempt forms of genome editing from GMO regulation of crop plants

text: The EU and New Zealand are the only legislations where genome‐edited plants are considered and regulated as GMOs while many other countries move to exempt genome‐edited crops.[Image: see text]


title: SMaRT lncRNA controls translation of a G‐quadruplex‐containing mRNA antagonizing the DHX36 helicase

text: Guanine‐quadruplexes (G4) included in RNA molecules exert several functions in controlling gene expression at post‐transcriptional level; however, the molecular mechanisms of G4‐mediated regulation are still poorly understood. Here, we describe a regulatory circuitry operating in the early phases of murine muscle differentiation in which a long non‐coding RNA (SMaRT) base pairs with a G4‐containing mRNA (Mlx‐γ) and represses its translation by counteracting the activity of the DHX36 RNA helicase. The time‐restricted, specific effect of lnc‐SMaRT on the translation of Mlx‐γ isoform modulates the general subcellular localization of total MLX proteins, impacting on their transcriptional output and promoting proper myogenesis and mature myotube formation. Therefore, the circuitry made of lnc‐SMaRT, Mlx‐γ, and DHX36 not only plays an important role in the control of myogenesis but also unravels a molecular mechanism where G4 structures and G4 unwinding activities are regulated in living cells.


title: Use of Bronchoalveolar Lavage in Humans—Past Necessity and Future Imperative

text: Limited bronchoalveolar lavage (BAL) as an extension of fiberoptic bronchoscopy has permitted the recovery of airway-alveolar space cells and soluble substances in the extracellular lining fluid that have been used diagnostically and as research specimens in patients with a variety of lung diseases and in normal subjects for the study of lung host defenses. During the past three decades, use of BAL specimens has stimulated immunologic and cellular research of pulmonary diseases, which has provided significant insight into local host immunity, inflammation, fibrogenesis, asthma mechanisms, and infections. From this research new methods of antifibrotic therapy of interstitial pulmonary fibrosis, for example, have followed. Moreover, BAL applications have greatly enhanced professional interest in the field of pulmonary medicine. This review attempts to analyze the history and impact of BAL, appraise its current status, and assess its future usefulness. Understanding the immunopathogenesis of many lung diseases is predicated on obtaining in situ specimens from affected lung tissue and airways. BAL provides a direct sample that can be compared with an endobronchial or transbronchial biopsy tissue specimen and with cellular and immunologic components in the vascular circulation. Thus, the recovery of BAL fluid and its components involved directly with a disease process or continguous with interstitial tissue permits a much more detailed assessment of new cellular mediators and cytokines participating in the pathologic process. Furthermore, subjecting BAL cells to microarrays of DNA to discern what genes are activated will be one step closer to identifying intracellular processes involved or deranged. Identification of causative factors may solve questions of causation, so that preventive strategies or definitive therapy can be used.


In reply to the Letter to the Editor “Leadership to improve consistency in echocardiography date”


title: Immunolocalization of Disorganized Muscle Protein-1 in Different Life Stages of Human Lymphatic Filariid, Brugia malayi

text: PURPOSE: We recently identified disorganized muscle protein-1 of Brugia malayi (DIM-1bm) as a vaccine candidate for human lymphatic filariasis. The present study was aimed at investigating the localization of DIM-1bm in the life-stages of B. malayi to identify the tissue target of vaccine action. METHODS: Recombinant DIM-1bm (rDIM-1bm) was prepared and antibodies were raised in BALB/c mice. Immunoblots of SDS-PAGE resolved B. malayi infective 3rd stage larvae (L(3)) and adult worm antigens and rDIM-1bm were prepared and reacted with anti-rDIM-1bm sera. Sections of adult female worms and whole-mount preparations of L(3) and microfilariae (mf) were stained by immunofluorescence using rDIM-1bm antibodies and Alexa Fluor 488 labeled secondary antibodies, and examined under a confocal microscope. RESULTS: Immunofluorescence staining showed that DIM-1bm is localized mainly in the subcuticular muscle layer in the L(3) and the adult worms; no fluorescent signal could be detected in mf. CONCLUSION: The localization of DIM-1bm in the parasites’ muscle layer suggests that the immunoprophylactic efficacy of DIM-1 is evidently due to immobilization of the parasite and its subsequent immune elimination.


title: Human genetics and malaria resistance

text: Malaria has been the pre-eminent cause of early mortality in many parts of the world throughout much of the last five thousand years and, as a result, it is the strongest force for selective pressure on the human genome yet described. Around one third of the variability in the risk of severe and complicated malaria is now explained by additive host genetic effects. Many individual variants have been identified that are associated with malaria protection, but the most important all relate to the structure or function of red blood cells. They include the classical polymorphisms that cause sickle cell trait, α-thalassaemia, G6PD deficiency, and the major red cell blood group variants. More recently however, with improving technology and experimental design, others have been identified that include the Dantu blood group variant, polymorphisms in the red cell membrane protein ATP2B4, and several variants related to the immune response. Characterising how these genes confer their effects could eventually inform novel therapeutic approaches to combat malaria. Nevertheless, all together, only a small proportion of the heritable component of malaria resistance can be explained by the variants described so far, underscoring its complex genetic architecture and the need for continued research.


title: The role of diagnostic laparoscopy for trauma at a high-volume level one center

text: BACKGROUND: The role of minimally invasive surgery in trauma has continued to evolve over the past 20 years. Diagnostic laparoscopy (DL) has become increasingly utilized for the diagnosis and management of both blunt and penetrating injuries. OBJECTIVE: While the safety and feasibility of laparoscopy has been established for penetrating thoracoabdominal trauma, it remains a controversial tool for other injury patterns due to the concern for complications and missed injuries. We sought to examine the role of laparoscopy for the initial management of traumatic injuries at our urban Level 1 trauma center. METHODS: All trauma patients who underwent DL for blunt or penetrating trauma between 2009 and 2018 were retrospectively reviewed. Demographic data, indications for DL, injuries identified, rate of conversion to open surgery, and outcomes were evaluated. RESULTS: A total of 316 patients were included in the cohort. The mean age was 34.9 years old (± 13.7), mean GCS 14 (± 3), and median ISS 10 (4–18). A total of 110/316 patients (35%) sustained blunt injury and 206/316 patients (65%) sustained penetrating injury. Indications for DL included evaluation for peritoneal violation (152/316, 48%), free fluid without evidence of solid organ injury (52/316, 16%), evaluation of bowel injury (42/316, 13%), and evaluation for diaphragmatic injury (35/316, 11%). Of all DLs, 178/316 (56%) were negative for injury requiring intervention, which was 58% of blunt cases and 55% of penetrating cases. There were no missed injuries noted. Average hospital length of stay was significantly shorter for patients that underwent DL vs conversion to open exploration (2.2 days vs. 4.5 days, p < 0.05). CONCLUSION: In this single institution, retrospective study, the high volume of cases appears to show that DL is a reliable tool for detecting injury and avoiding potential negative or non-therapeutic laparotomies. However, when injuries were present, the high rate of conversion to open exploration suggests that its utility for therapeutic intervention warrants further study.


title: Accuracy of a multiparametric score based on pulse wave analysis for prediction of fluid responsiveness: ancillary analysis of an observational study

text: PURPOSE: The pressure recording analytical method (PRAM) monitor is a non-invasive pulse contour cardiac output (CO) device that cannot be considered interchangeable with the gold standard for CO estimation. It, however, generates additional hemodynamic indices that need to be evaluated. Our objective was to investigate the performance of a multiparametric predictive score based on a combination of several parameters generated by the PRAM monitor to predict fluid responsiveness. METHODS: Secondary analysis of a prospective observational study from April 2016 to December 2017 in two French teaching hospitals. We included critically ill patients who were monitored by esophageal Doppler monitoring and an invasive arterial line, and received a 250–500 mL crystalloid fluid challenge. The main outcome measure was the predictive score discrimination evaluated by the area under the receiver operating characteristics curve. RESULTS: The three baseline PRAM-derived parameters associated with fluid responsiveness in univariate analysis were pulse pressure variation, cardiac cycle efficiency, and arterial elastance (P < 0.01, P = 0.03, and P < 0.01, respectively). The median [interquartile range] predictive score, calculated after discretization of these parameters according to their optimal threshold value was 3 [2–3] in fluid responders and 1 [1–2] in fluid non-responders, respectively (P < 0.001). The area under the curve of the predictive score was 0.807 (95% confidence interval, 0.662 to 0.909; P < 0.001). CONCLUSION: A multiparametric score combining three parameters generated by the PRAM monitor can predict fluid responsiveness with good positive and negative predictive values in intensive care unit patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12630-020-01736-y) contains supplementary material, which is available to authorized users.


title: Outcomes of Paraesophageal Hernia Repair: Analysis of the Veterans Affairs Surgical Quality Improvement Program Database

text: BACKGROUND: While there have been many outcome studies on paraesophageal hernia repair in the civilian population, there is sparse recent data on the veteran population. This study analyzes the mortality and morbidities of veterans who underwent paraesophageal hernia repair in the Veterans Affairs Surgical Quality Improvement Program database. METHODS: Veterans who underwent paraesophageal hernia repair from 2010 to 2017 were identified using Current Procedural Terminology codes. Multivariable analysis was used to compare laparoscopic and open, including abdominal and thoracic approaches, groups. The outcomes were postoperative complications and mortality. RESULTS: There were 1607 patients in the laparoscopic group and 366 in the open group, with 84.1% men and mean age of 61 years. Gender and body mass index did not influence the type of surgical approach. The mortality rates at 30 and 180 days were 0.5% and 0.7%, respectively. Postoperative complications, including reintubation (2.2%), pneumonia (2.0%), intubation > 48 h (2.0%), and sepsis (2.0%) were higher in the open group (15.9% versus 7.2%, p < 0.001). The laparoscopic group had a significantly shorter length of stay (4.3 versus 9.6 days, p < 0.001) and a lower percentage of return to surgery within 30 days (3.9% versus 8.2%, p < 0.001) than the open group. The ratio of open versus laparoscopic paraesophageal hernia repairs varied significantly by different Veterans Integrated Services Network regions. CONCLUSIONS: Veterans undergoing laparoscopic paraesophageal hernia repair experience similar outcomes as patients in the private sector. Veterans who underwent laparoscopic paraesophageal hernia repair had significantly less complications compared to an open approach even after adjusting for patient comorbidities and demographics. The difference in open versus laparoscopic practices between various regions requires further investigation.


Transformation of medical education in uncertainty


Our new feature: Narrative Medicine


COVID-19 and the Urology Match: Perspectives and a Call to Action


Addendum to: Risk Stratification and PPE Use in Pediatric Endoscopy During the COVID-19 Outbreak: A Single-Center Protocol.


title: Long-range movements coupled with heterogeneous incubation period sustain dog rabies at the national scale in Africa

text: Dog-transmitted rabies is responsible for more than 98% of human cases worldwide, remaining a persistent problem in developing countries. Mass vaccination targets predominantly major cities, often compromising disease control due to re-introductions. Previous work suggested that areas neighboring cities may behave as the source of these re-introductions. To evaluate this hypothesis, we introduce a spatially explicit metapopulation model for rabies diffusion in Central African Republic. Calibrated on epidemiological data for the capital city, Bangui, the model predicts that long-range movements are essential for continuous re-introductions of rabies-exposed dogs across settlements, eased by the large fluctuations of the incubation period. Bangui’s neighborhood, instead, would not be enough to self-sustain the epidemic, contrary to previous expectations. Our findings suggest that restricting long-range travels may be very efficient in limiting rabies persistence in a large and fragmented dog population. Our framework can be applied to other geographical contexts where dog rabies is endemic.


title: Measles outbreak amplified in a pediatric ward: Lyantonde District, Uganda, August 2017

text: BACKGROUND: Measles is a highly infectious viral disease. In August 2017, Lyantonde District, Uganda reported a measles outbreak to Uganda Ministry of Health. We investigated the outbreak to assess the scope, factors facilitating transmission, and recommend control measures. METHODS: We defined a probable case as sudden onset of fever and generalized rash in a resident of Lyantonde, Lwengo, or Rakai Districts from 1 June-30 September 2017, plus ≥1 of the following: coryza, conjunctivitis, or cough. A confirmed case was a probable case with serum positivity of measles-specific IgM. We conducted a neighborhood- and age-matched case-control study to identified exposure factors, and used conditional logistic regression to analyze the data. We estimated vaccine effectiveness and vaccination coverage. RESULTS: We identified 81 cases (75 probable, 6 confirmed); 4 patients (4.9%) died. In the case-control study, 47% of case-patients and 2.3% of controls were hospitalized at Lyantonde Hospital pediatric department for non-measles conditions 7–21 days before case-patient’s onset (OR(adj) = 34, 95%CI: 5.1–225). Estimated vaccine effectiveness was 95% (95%CI: 75–99%) and vaccination coverage was 76% (95%CI: 68–82%). During the outbreak, an “isolation” ward was established inside the general pediatric ward where there was mixing of both measles and non-measles patients. CONCLUSIONS: This outbreak was amplified by nosocomial transmission and facilitated by low vaccination coverage. We recommended moving the isolation ward outside of the building, supplemental vaccination, and vaccinating pediatric patients during measles outbreaks.