bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect on deep brain stimulation of subthalamic nucleus and dopaminergic treatment in Parkinson disease
Authors: Lo Buono Viviana , Palmeri Rosanna , Stroscio Giuseppe , Corallo Francesco , Di Lorenzo Giuseppe , Sorbera Chiara , Ciurleo Rosella , Cimino Vincenzo , Bramanti Placido , Marino Silvia , Bonanno Lilla
Published: August 2020

Impulsivity is a frequent non-motor symptom in Parkinson disease (PD). It comprises psycho-behavioral alterations that negatively impact quality of life. Dopaminergic treatments underpin many impulsive controls disorders however, side effects, such as increased impulsivity, are described also after neurosurgical procedure of deep brain stimulation (DBS). We investigated the effect of deep brain stimulation on psycho-behavioral alterations and quality of life (QoL) in PD patients, analyzing, also, the role of dopaminergic therapies.

Twenty idiopathic PD patients with and 20 idiopathic PD patients without DBS were included in the study. All patient underwent to neuropsychological assessment for a screening of executive functions, impulsivity, anxiety and depressive symptoms and QoL.

Differences were found between DBS and no DBS groups and in term of dopaminergic therapies. The comparison between 2 groups showed a greater motor and attentional impulsivity in DBS patients. Moreover, this impulsivity worse QoL and interpersonal relationships. The combination of Levodopa and dopamine agonists exerted a great impact on impulsivity behavior.

The emergence of postoperative impulsivity seems to be a neurostimulator phenomenon related to the computational role of the subthalamic nucleus in modulation of behavior.
Accurate quantification of bacterial abundance in metagenomic DNAs accounting for variable DNA integrity levels
Authors: Manzari Caterina , Oranger Annarita , Fosso Bruno , Piancone Elisabetta , Pesole Graziano , D’Erchia Anna Maria
Published: August 2020

The quantification of the total microbial content in metagenomic samples is critical for investigating the interplay between the microbiome and its host, as well as for assessing the accuracy and precision of the relative microbial composition which can be strongly biased in low microbial biomass samples. In the present study, we demonstrate that digital droplet PCR (ddPCR) can provide accurate quantification of the total copy number of the 16S rRNA gene, the gene usually exploited for assessing total bacterial abundance in metagenomic DNA samples. Notably, using DNA templates with different integrity levels, as measured by the DNA integrity number (DIN), we demonstrated that 16S rRNA copy number quantification is strongly affected by DNA quality and determined a precise correlation between quantification underestimation and DNA degradation levels. Therefore, we propose an input DNA mass correction, according to the observed DIN value, which could prevent inaccurate quantification of 16S copy number in degraded metagenomic DNAs. Our results highlight that a preliminary evaluation of the metagenomic DNA integrity should be considered before performing metagenomic analyses of different samples, both for the assessment of the reliability of observed differential abundances in different conditions and to obtain significant functional insights.
Autoimmune Encephalitis Presenting with Malignant Catatonia in a 40-Year-Old Male Patient with Covid-19
Authors: Mulder Jan , Feresiadou Amalia , Fällmar David , Frithiof Robert , Virhammar Johan , Rasmusson Annica , Rostami Elham , Kumlien Eva , Cunningham Janet L.
Published: August 2020

Acute malignant catatonia with autonomic instability developed in a previously healthy man with PCR-verified SARS-CoV-2. CT and MRI were normal, EEG showed slowing and cerebrospinal fluid showed a subtle indication of inflammation. There were no signs of pathology in other organs.18F-FDG-PET conveyed high bilateral uptake in the striatum. While commercial tests were negative, immunohistochemical staining of mouse brain revealed anti-neuronal IgG antibodies against neuronal targets in the hippocampus, thalamus, striatum and cortex. Early treatment with plasmapheresis and corticosteroid reversed disease progression and may have prevented large-scale neurological damage. We are not aware of other types of encephalitis with such distinct pyramidal tract symptoms and raise the possibility that this may be a novel form of autoimmune encephalitis induced by infection with SARS-CoV-2.
The Impact of COVID-19 on Medical Practice: A Nationwide Survey of Dermatologists and Healthcare Providers
Authors: Shanshal Mohammed , Ahmed Hayder Saad , Asfoor Hayder , Salih Raad Ibrahim , Ali Shehab Ahmed , Aldabouni Yusif k.
Published: August 2020

Background

The COVID-19 pandemic has dramatically changed medical practice worldwide. It posed a significant impact on different health services, including dermatology.

Methods

A Cross-sectional observational study of 200 healthcare providers and 100 dermatologists (survey 1 and 2, respectively) were conducted.

Objectives

To determine the prevalence of occupational skin diseases among healthcare providers working amid the pandemic, and to demonstrate the outbreak’s impact on dermatology practice.

Results

Most healthcare providers (83%) reported hygiene-related hand dermatitis. The rates of PPE-related dermatoses were estimated to be 73%, including pressure injuries (51.9%), acne (33.1%), non-gloves contact dermatitis (29.9%), nonspecific rash (17.5%), urticaria (9.1%) and skin infections (3.2%). The emerging COVID-19-related cutaneous manifestations were recognized by 20% of surveyed dermatologists, including maculopapular rash (41.67%), urticaria (37.50%), chilblain (25%) and vasculitis (16.67). Telemedicine was provided by 73% of the dermatologists, and 89% reported minimal use of immunosuppressive drugs amid the pandemic.

Conclusions

This article highlights the emergence of hygiene-related hand dermatitis and PPE-related dermatoses among healthcare providers working in the COVID-19 era. It also provides an appreciation of the major impact of COVID-19 on different aspects of dermatology practice in Iraq, and how the dermatologists adapt to these unfamiliar circumstances to meet the challenges.

Highlights

COVID-19 is associated with an ongoing emergence of occupational skin disease among healthcare providers

COVID-19 posed a significant impact on medical practice, including the epidemiology of diseases, the use of telemedicine, and modification of management plans

Dermatologists play a crucial role in recognizing the cutaneous manifestations associated with COVID-19 infection.
Detection of asymptomatic SARS-CoV-2 infections among healthcare workers: results from a large-scale screening program based on rapid serological testing
Authors: Carozzi Francesca Maria , Cusi Maria Grazia , Pistello Mauro , Galli Luisa , Bartoloni Alessandro , Anichini Gabriele , Azzari Chiara , Emdin Michele , Gandolfo Claudia , Maggi Fabrizio , Mantengoli Elisabetta , Moriondo Maria , Moscato Giovanna , Paganini Irene , Passino Claudio , Profili Francesco , Voller Fabio , Zappa Marco , Quattrone Filippo , Rossolini Gian Maria , Francesconi Paolo ,   SARS-CoV-2 serosurvey Tuscan working group
Published: August 2020

Objective

To evaluate the performance of two available rapid immunological tests for identification of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) antibodies and their subsequent application to a regional screening of health care workers (HCW) in Tuscany (Italy).

Design

measures of accuracy and HCW serological surveillance

Setting

6 major health facilities in Tuscany, Italy.

Participants

17,098 HCW of the Tuscany Region. Measures of accuracy were estimated to assess sensitivity in 176 hospitalized Covid-19 clinical subjects at least 14 days after a diagnostic PCR-positive assay result. Specificity was assessed in 295 sera biobanked in the pre-Covid-19 era in winter or summer 2013-14

Main outcome measures

Sensitivity and specificity, and 95% confidence intervals, were measured using two serological tests, named T-1 and T-2. Positive and Negative predictive values were estimated at different levels of prevalence. HCW of the health centers were tested using the serological tests, with a follow-up nasopharyngeal PCR-test swab in positive tested cases.

Results

Sensitivity was estimated as 99% (95%CI: 95%-100%) and 97% (95% CI: 90%-100%), whereas specificity was the 95% and 92%, for Test T-1 and T-2 respectively. In the historical samples IgM cross-reactions were detected in sera collected during the winter period, probably linked to other human coronaviruses. Out of the 17,098 tested, 3.1% have shown the presence of SARS-CoV-2 IgG antibodies, among them 6.8% were positive at PCR follow-up test on nasopharyngeal swabs.

Conclusion

Based on the low prevalence estimate observed in this survey, the use of serological test as a stand-alone test is not justified to assess the individual immunity status. Serological tests showed good performance and might be useful in an integrated surveillance, for identification of infected subjects and their contacts as required by the policy of contact tracing, with the aim to reduce the risk of dissemination, especially in health service facilities.
Genomic heterogeneity and clinical characterization of SARS-CoV-2 in Oregon
Authors: Dowdell Alexa K , Matlock Kevin , Robinson Fred L. , Weerasinghe Roshanthi , Rattray Rogan , Pukay Marina , Lathara Melvin , Harlan Anastacia , Ward Thomas R. , Campbell Mary , Urba Walter , Srinivasa Ganapati , Bifulco Carlo B. , Piening Brian D.
Published: August 2020

The first reported case of COVID-19 in the State of Oregon occurred in late February 2020, with subsequent outbreaks occurring in the populous Portland metro area but also with significant outbreaks in less-populous and rural areas. Here we report viral sequences from 188 patients across the hospitals and associated clinics in the Providence Health System in the State of Oregon dating back to the early days of the outbreak. We show a significant shift in dominant clade lineages over time in Oregon, with the rapid emergence and dominance of Spike D614G-positive variants. We also highlight significant diversity in SARS-CoV-2 sequences in Oregon, including a large number of rare mutations, indicative that these genomes could be utilized for outbreak tracing. Lastly, we show that SARS-CoV-2 genomic information may offer additional utility in combination with clinical covariates in the prediction of acute disease phenotypes.
Clinical course and severity outcome indicators among COVID-19 hospitalized patients in relation to comorbidities distribution: Mexican cohort
Authors:   COVID-19 Hospitalizations in Mexico, Carrillo Genny , Méndez-Domínguez Nina , Santos-Zaldivar Kassandra Desire , Rochel-Pérez Andrea , Azuela-Morales Mario , Cuevas-Koh Osman , Álvarez-Baeza Alberto
Published: August 2020

Introduction

COVID-19 affected worldwide, causing to date, around 500,000 deaths. In Mexico, by April 29, the general case fatality was 6.52%, with 11.1% confirmed case mortality and hospital recovery rate around 72%. Once hospitalized, the odds for recovery and hospital death rates depend mainly on the patients’ comorbidities and age. In Mexico, triage guidelines use algorithms and risk estimation tools for severity assessment and decision-making. The study’s objective is to analyze the underlying conditions of patients hospitalized for COVID-19 in Mexico concerning four severity outcomes.

Materials and Methods

Retrospective cohort based on registries of all laboratory-confirmed patients with the COVID-19 infection that required hospitalization in Mexico. Independent variables were comorbidities and clinical manifestations.

Dependent variables were four possible severity outcomes

(a) pneumonia, (b) mechanical ventilation (c) intensive care unit, and (d) death; all of them were coded as binary Results: We included 69,334 hospitalizations of laboratory-confirmed and hospitalized patients to June 30, 2020. Patients were 55.29 years, and 62.61% were male. Hospital mortality among patients aged<15 was 9.11%, 51.99% of those aged >65 died. Male gender and increasing age predicted every severity outcome. Diabetes and hypertension predicted every severity outcome significantly. Obesity did not predict mortality, but CKD, respiratory diseases, cardiopathies were significant predictors.

Conclusion

Obesity increased the risk for pneumonia, mechanical ventilation, and intensive care admittance, but it was not a predictor of in-hospital death. Patients with respiratory diseases were less prone to develop pneumonia, to receive mechanical ventilation and intensive care unit assistance, but they were at higher risk of in-hospital death.
R3T (Rapid Research Response Team) One-step RT-qPCR kit for COVID-19 diagnostic using in-house enzymes
Authors: Takahashi Masateru , Tehseen Muhammad , Salunke Rahul , Takahashi Etsuko , Mfarrej Sara , Sobhy Mohamed A. , Alhamlan Fatimah S. , Hala Sharif , Mandujano Gerardo R. , Al-Qahtani Ahmed A. , Alofi Fadwa S. , Alsomali Afrah , Hashem Anwar M. , Khogeer Asim , Almontashiri Naif A. M. , Lee Jae Man , Mon Hiroaki , Sakashita Kosuke , Li Mo , Kusakabe Takahiro , Pain Arnab , Hamdan Samir M.
Published: August 2020

One-step RT-qPCR is the most widely applied method for COVID-19 diagnostics. Designing in-house one-step RT-qPCR kits is restricted by the patent-rights for the production of enzymes and the lack of information about the components of the commercial kits. Here, we provide a simple, economical, and powerful one-step RT-qPCR kit based on patent-free, specifically-tailored versions of Moloney Murine Leukemia Virus Reverse Transcriptase and Thermus aquaticus DNA polymerase termed the R3T (Rapid Research Response Team) One-step RT-qPCR. Our kit was routinely able to reliably detect as low as 10 copies of the synthetic RNAs of the SARS-CoV-2. More importantly, our kit successfully detected COVID-19 in clinical samples of broad viral titers with similar reliability and selectivity as that of the Invitrogen SuperScript™ III Platinum™ One-step RT-qPCR and TaqPath™ 1-Step RT-qPCR kits. Overall, our kit has shown robust performance in both of laboratory settings and the Saudi Ministry of Health-approved testing facility.
A multivariate geostatistical framework for combining multiple indices of abundance for disease vectors and reservoirs: A case study of rattiness in a low-income urban Brazilian community
Authors: Eyre Max T. , Carvalho-Pereira Ticiana S. A. , Souza Fábio N. , Khalil Hussein , Hacker Kathryn P. , Serrano Soledad , Taylor Joshua P. , Reis Mitermayer G. , Ko Albert I. , Begon Mike , Diggle Peter J. , Costa Federico , Giorgi Emanuele
Published: August 2020

A key requirement in studies of endemic vector-borne or zoonotic disease is an estimate of the spatial variation in vector or reservoir host abundance. For many vector species, multiple indices of abundance are available, but current approaches to choosing between or combining these indices do not fully exploit the potential inferential benefits that might accrue from modelling their joint spatial distribution. Here, we develop a class of multivariate generalized linear geostatistical models for multiple indices of abundance. We illustrate this novel methodology with a case study on Norway rats in a low-income urban Brazilian community, where rat abundance is a likely risk-factor for human leptospirosis. We combine three indices of rat abundance to draw predictive inferences on a spatially continuous latent process, rattiness, that acts as a proxy for abundance. We show how to explore the association between rattiness and spatially varying environmental factors, evaluate the relative importance of each of the three contributing indices, assess the presence of residual, unexplained spatial variation, and identify rattiness hotspots. The proposed methodology is applicable more generally as a tool for understanding the role of vector or reservoir host abundance in predicting spatial variation in the risk of human disease.
Evaluation of Serological SARS-CoV-2 Lateral Flow Assays for Rapid Point of Care Testing
Authors: Conklin Steven E. , Martin Kathryn , Manabe Yukari C , Schmidt Haley A , Miller Jernelle , Keruly Morgan , Klock Ethan , Kirby Charles S , Baker Owen R , Fernandez Reinaldo E , Eby Yolanda J , Hardick Justin , Shaw-Saliba Kathryn , Rothman Richard E , Caturegli Patrizio P , Redd Andrew R , Tobian Aaron AR , Bloch Evan M , Larman H Benjamin , Quinn Thomas C , Clarke William , Laeyendecker Oliver
Published: August 2020

Background

Rapid point-of-care tests (POCTs) for SARS-CoV-2-specific antibodies vary in performance. A critical need exists to perform head-to-head comparison of these assays.

Methods

Performance of fifteen different lateral flow POCTs for the detection of SARS-CoV-2-specific antibodies was performed on a well characterized set of 100 samples. Of these, 40 samples from known SARS-CoV-2-infected, convalescent individuals (average of 45 days post symptom onset) were used to assess sensitivity. Sixty samples from the pre-pandemic era (negative control), that were known to have been infected with other respiratory viruses (rhinoviruses A, B, C and/or coronavirus 229E, HKU1, NL63 OC43) were used to assess specificity. The timing of seroconversion was assessed on five POCTs on a panel of 272 longitudinal samples from 47 patients of known time since symptom onset.

Results

For the assays that were evaluated, the sensitivity and specificity for any reactive band ranged from 55%-97% and 78%-100%, respectively. When assessing the performance of the IgM and the IgG bands alone, sensitivity and specificity ranged from 0%-88% and 80%-100% for IgM and 25%-95% and 90%-100% for IgG. Longitudinal testing revealed that median time post symptom onset to a positive result was 7 days (IQR 5.4, 9.8) for IgM and 8.2 days (IQR 6.3 to 11.3).

Conclusion

The testing performance varied widely among POCTs with most variation related to the sensitivity of the assays. The IgM band was most likely to misclassify pre-pandemic samples. The appearance of IgM and IgG bands occurred almost simultaneously.
Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity
Authors: Volz Erik , Hill Verity , McCrone John T. , Price Anna , Jorgensen David , O’Toole Áine , Southgate Joel , Johnson Robert , Jackson Ben , Nascimento Fabricia F. , Rey Sara M. , Nicholls Samuel M. , Colquhoun Rachel M. , da Silva Filipe Ana , Shepherd James , Pascall David J. , Shah Rajiv , Jesudason Natasha , Li Kathy , Jarrett Ruth , Pacchiarini Nicole , Bull Matthew , Geidelberg Lily , Siveroni Igor , Goodfellow Ian , Loman Nicholas J. , Pybus Oliver G. , Robertson David L. , Thomson Emma C. , Rambaut Andrew , Connor Thomas R.
Published: August 2020

Global dispersal and increasing frequency of the SARS-CoV-2 Spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of Spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large data set, well represented by both Spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.
Supervised beego, a traditional Chinese water-only fasting, ends up with reduced thrombosis risk without compromising hemostasis capacity
Authors: Fang Yixuan , Gu Yue , Zhao Chen , Lv Yaqi , Qian Jiawei , Zhu Lingjiang , Yuan Na , Zhang Suping , Wang Li , Li Mengli , Zhang Qing , Xu Li , Wei Wen , Li Lei , Ji Li , Gao Xueqin , Zhang Jingyi , Shen Yueping , Chen Zixing , Wang Guanghui , Dai Kesheng , Wang Jianrong
Published: August 2020

Beego is a traditional Chinese complete water-only fasting practice initially developed for spiritual purposes, later extending to physical fitness purposes. Beego notably includes a psychological induction component that includes meditation and abdominal breathing, light body exercise, and ends with a specific gradual refeeding program before returning to a normal diet. Beego has regained its popularity in recent decades in China as a strategy for helping people in subhealthy conditions or with metabolic syndrome, but we are unaware of any studies examining the biological effects of this practice. To address this, we here performed a longitudinal study of beego comprising fasting (7 and 14 day cohorts) and a 7-day programmed refeeding phase. In addition to detecting improvements in cardiovascular physiology and selective reduction of blood pressure in hypertensive subjects, we observed that beego decreased blood triacylglycerol (TG) selectively in TG-high subjects and increased cholesterol in all subjects during fasting; however, the cholesterol levels were normalized after completion of the refeeding program. Strikingly, beego reduced platelet formation, activation, aggregation, and degranulation, resulting in an alleviated thrombosis risk, yet maintained hemostasis by sustaining levels of coagulation factors and other hemostatic proteins. Mechanistically, we speculate that downregulation of G6B and MYL9 may influence the observed beego-mediated reduction in platelets. Fundamentally, our study supports that supervised beego reduces thrombosis risk without compromising hemostasis capacity. Moreover, our results support that beego under medical supervision can be implemented as noninvasive intervention for reducing thrombosis risk, and suggest several lines of intriguing inquiry for future studies about this fasting practice (http://www.chictr.org.cn/index.aspx, number, ChiCTR1900027451).
Estimating the reproductive numberR0of SARS-CoV-2 in the United States and eight European countries and implications for vaccination
Authors: Ke Ruian , Sanche Steven , Romero-Severson Ethan , Hengartner Nick
Published: August 2020

SARS-CoV-2 rapidly spread from a regional outbreak to a global pandemic in just a few months. Global research efforts have focused on developing effective vaccines against SARS-CoV-2 and the disease it causes, COVID-19. However, some of the basic epidemiological parameters, such as the exponential epidemic growth rate and the basic reproductive number,R0, across geographic areas are still not well quantified. Here, we developed and fit a mathematical model to case and death count data collected from the United States and eight European countries during the early epidemic period before broad control measures were implemented. Results show that the early epidemic grew exponentially at rates between 0.19-0.29/day (epidemic doubling times between 2.4-3.6 days). We discuss the current estimates of the mean serial interval, and argue that existing evidence suggests that the interval is between 6-8 days in the absence of active isolation efforts. Using parameters consistent with this range, we estimated the medianR0value to be 5.8 (confidence interval: 4.7-7.3) in the United States and between 3.6 and 6.1 in the eight European countries. This translates to herd immunity thresholds needed to stop transmission to be between 73% and 84%. We further analyze how vaccination schedules depends onR0, the duration of vaccine-induced immunity to SARS-CoV-2, and show that individual-level heterogeneity in vaccine induced immunity can significantly affect vaccination schedules.

Significance

With the global efforts to develop vaccines for COVID-19, it is important to understand the contagiousness of the virus to design regional vaccination policy. To that end, we fit a mathematical model to data collected from the early epidemic period in the United States and eight European countries, estimating that the early epidemic doubles between 2.4-3.6 days. This suggests that SARS-CoV-2 is highly transmissible in the absence of strong control measures irrespective of heterogeneity in geographic and social settings. We estimated the median basic reproduction number,R0to be 5.8 (confidence interval: 4.7-7.3) in the United States and between 3.6 and 6.1 in the eight European countries. The herd immunity needed to stop transmission is high (between 73% and 84%).
Containing the Spread of Infectious Disease on College Campuses
Authors: Shah Mirai , Ferra Gabrielle , Fitzgerald Susan , Barreira Paul J. , Sabeti Pardis C. , Colubri Andres
Published: August 2020

College campuses are highly vulnerable to infectious disease outbreaks, and there is a pressing need to develop better strategies to mitigate their size and duration, particularly as educational institutions around the world reopen to in-person instruction during the COVID-19 pandemic. Towards addressing this need, we applied a stochastic compartmental model to quantify the impact of university-level responses to past mumps outbreaks in college campuses and used it to determine which control interventions are most effective. Mumps is a very relevant disease in such settings, given its airborne mode of transmission, high infectivity, and recurrence of outbreaks despite availability of a vaccine. Our model allows for stochastic variation in small populations, missing or unobserved case data, and changes in disease transmission rates post-intervention. We tested the model and assessed various interventions using data from the 2014 and 2016 mumps outbreaks at Ohio State University and Harvard University, respectively. Our results suggest that in order to decrease infectious disease incidence on their campuses, universities should apply diagnostic protocols that address false negatives from molecular tests, stricter quarantine policies, and effective awareness campaigns among their students and staff. However, one needs to be careful about the assumptions implicit in the model to ensure that the estimated parameters have a reasonable interpretation. This modeling approach could be applied to data from other outbreaks in college campuses and similar small-population settings.
Anuran assemblage changes along small-scale phytophysiognomies in natural Brazilian grasslands
Authors: Dalmolin Diego Anderson , Filho Volnei Mathies , Tozetti Alexandro Marques
Published: August 2020

We studied the species composition of frogs in two phytophysiognomies (grassland and forest) of a Ramsar site in southern Brazil. We aimed to assess the distribution of species on a small spatial scale and dissimilarities in community composition between grassland and forest habitats. The sampling of individuals was carried out through pitfall traps and active search in the areas around the traps. We evaluated the existence of these differences by using permutational multivariate analysis of variance and multivariate dispersion. We found 13 species belonging to six families. Leptodactylidae and Hylidae were the most representative families. The compositional dissimilarity was higher between the sampling sites from different phytophysiognomies than within the same phytophysiognomy, suggesting that forest and grassland drive anuran species composition differently. Also, the difference in anuran species composition between the sampling sites within the forest was considerably high. Based on our results, we could assume that the phytophysiognomies evaluated here offer quite different colonization opportunities for anurans, especially those related to microhabitat characteristics, such as microclimate variables.
Astroglia in lateral habenula is essential for antidepressant efficacy of light
Authors: Delcourte Sarah , Etievant Adeline , Rovera Renaud , Mor Damien , Cooper Howard M , Le Hiep D. , Williams April E. , Panda Satchidananda , Azmani Rihab , Raineteau Olivier , Coutanson Christine , Dkhissi-Benyahya Ouria , Haddjeri Nasser
Published: August 2020

Successful antidepressant (AD) treatments are still difficult to achieve. Recently, bright light stimulation (BLS) was shown effective in non-seasonal depression but its mode of action remains elusive. We demonstrate here, using a new mouse model of depression resistant to ADs including ketamine, that chemogenetic activation of lateral habenula (LHb) astroglia prevented the potentiating effect of BLS on the AD response. Additionally, the beneficial action of BLS was associated with upregulation of a specific part of the prefrontal cortex opioid system. These results show that improved behavioral outcome produced by BLS requires habenular astroglia and endogenous opioids as crucial buffer systems.
SK3-overexpression drives sex-dimorphic working and social memory impairment in mice
Authors: Campos Alline C , Scarante Franciele F , Martin Sabine , Lazzarini Marcio , Hermes Doris , De Souza-Silva Maria A , Pardo Luis A , Stühmer Walter , Del-Bel Elaine A
Published: August 2020

Although sex differences in memory tasks dependent on hippocampal function have been described in several species, including rodents and humans, the exact mechanisms involved remain debatable. The function of the small-conductance Ca2+-activated K+ channel type 3 has been associated with cognitive deficits, and its overexpression in male mice (T/T) induces shrinkage of the hippocampus. Here we describe that opposite to the observation in males, in female mice, SK3-induced-reduction in the volume of the hippocampal formation does not interfere with working and social memory performance. Male, but not female T/T mice showed decreased adult hippocampal neurogenesis and down-regulation of the expression of the genes related to Akt/mTOR and MAP kinase pathways. T/T male mice exhibit impaired estrogen and Neurogulin 1 signaling. An increased number of filopodia spines is observed in the dentate gyrus (DG). Our results suggest a fine-tune modulation of SK3 expression participates in the sex-dependent function of the hippocampus via estrogen signaling and neuroplasticity in the DG. Our results reinforce the importance of testing male and female mice while conducting experiments with transgenic mice.
Morphological and genomic shifts in mole-rat ‘queens’ increase fecundity but reduce skeletal integrity
Authors: Johnston Rachel A. , Vullioud Philippe , Thorley Jack , Kirveslahti Henry , Shen Leyao , Mukherjee Sayan , Karner Courtney , Clutton-Brock Tim , Tung Jenny
Published: August 2020

In some mammals and many social insects, highly cooperative societies are characterized by reproductive division of labor, in which breeders and nonbreeders become behaviorally and morphologically distinct. While differences in behavior and growth between breeders and nonbreeders have been extensively described, little is known of their molecular underpinnings. Here, we investigate the consequences of breeding for skeletal morphology and gene regulation in highly cooperative Damaraland mole-rats. By experimentally assigning breeding ‘queen’ status versus nonbreeder status to age-matched littermates, we confirm that queens experience vertebral growth that likely confers advantages to fecundity. However, they also up-regulate bone resorption pathways and show reductions in femoral mass, which predicts increased vulnerability to fracture. Together, our results show that, as in eusocial insects, reproductive division of labor in mole-rats leads to gene regulatory rewiring and extensive morphological plasticity. However, in mole-rats, concentrated reproduction is also accompanied by costs to bone strength.
Progressive Sperm Separation Using Parallelized, High-Throughput, Microchamber-based Microfluidics
Authors: Yaghoobi Mohammad , Azizi Morteza , Mokhtare Amir , Abbaspourrad Alireza
Published: August 2020

Motility is one of the most important factors in sperm migration toward egg. Therefore, sperm separation based on motility increases the chance of the best sperm selection in the process of infertility treatments. Unfortunately, it is now vastly done by conventional procedures which lack certain delicacy and precision and increase the risk of damage to sperm cells. Microfluidic systems, on the other hand, can sort sperm in a less intrusive way. However, microfluidic techniques have yet to receive widespread adoption in clinical settings, not only due to their relatively cumbersome operation, but also their extremely low outcome, leaving them inefficient in practice. Here we propose a microchamber-based microfluidic platform that can separate progressive motile sperm from nonviable sperm and debris as well as trapped nonprogressive sperm in the microchambers. Our platform is operated in a short period of time (<10 min) with an excellent degree of controllability, without any prior sample preparation. Our results show that the microchambers’ depth does not affect the residence time of motile sperm. Therefore, we are able to inspect high sample volumes (1 mL) within the same time. Furthermore, we maximize the concentration of the collected sperm by tuning the washing medium flow rate above the sperm rheotactic threshold. We foresee that our microfluidic platform may provide a facile solution for high-throughput, robust, and easy-to-modify for collection of progressive sperm needed for assisted reproductive technologies (ARTs).

Significance Statement

Assisted Reproductive Technologies require efficient, minimally invasive, and fast methods of sperm separation. Centrifugation methods used in clinics and biological research labs, fall short in these aspects as they are low-yield, intrusive to sperm’s DNA, and time consuming. We have developed a microchamber-based microfluidic platform for high-throughput separation of progressive motile sperm from undiluted raw semen samples. The method was further optimized to increase the concentration of collected samples. Higher concentration of collected samples combined with higher motility of the separated sperm compared to those in raw semen, make it a suitable choice in clinical applications, fertility diagnostics, and fundamental research.
Potential Hematotoxicity and Genotoxicity of Multi-Herbal Formulations in Albino Mice (Mus musculus)
Authors: Kehinde S. , Adebayo S. M. , Adesiyan A. L. , Kade E. A. , Gurpreet K.
Published: August 2020

The current increase in the use of multi-herbal remedies coupled with loose regulation on public access to these products underscore research efforts to evaluate their biochemical effect, noting that many of the herbal medicines lack scientific evidence to support their medicinal claims. Objective: We therefore investigated the potential genotoxicity and hematotoxicity of commonly consumed multi-herbal formulations (YoyoBitters™, Ogidiga™ and BabyOku™) in Lagos, Nigeria, in experimental mice. Methods: Fifty (50) adult female albino mice were randomly selected and distributed into 5 groups of 10 mice each. Two mL/kg body weight of distilled water were orally administered to the control groups while BabyOku™, YoyoBitters™ and Ogidiga™ herbal formulations were administered to the experimental groups at doses of 2 mL/kg body weights. Results: A dose- and tissue-dependent increase in induction of apoptotic DNA fragmentation was observed in the triherbal groups relative to control groups. Also, an increase in micronucleated polychromatic erythrocytes was formed in a dose-dependent manner in the multi-herbal groups when compared with the control groups. Conclusion: From our findings, multi-herbal formulations may possess hematotoxic and genotoxic potentials in mice.
Living in a changing world: effects of roads andPinusmonocultures on an anuran metacommunity in southern Brazil
Authors: Dalmolin Diego Anderson , Tozetti Alexandro Marques , Pereira Maria João Ramos
Published: August 2020

Amphibians are undergoing global-scale declines due to the increased incidence of anthropogenic stressors. The loss of species with unique evolutionary histories and functional traits poses a serious risk to the maintenance of ecosystem functions in aquatic environments, already directly affected by several anthropogenic land-use changes. Here, we investigated the influence of anthropogenic stressors (roads andPinusmonocultures) on functional, phylogenetic and taxonomic composition and functional dispersion of an anuran metacommunity of 33 ponds in southern Brazil. We expected for the relative influence of anthropogenic stressors to vary according to the compositional facet, with a greater influence of these stressors on the functional and phylogenetic than on the taxonomic facet. We also expected traits related to habitat exploration (head shape and eye size and position) to be more influenced byPinusmonocultures, while the traits related to the dispersion and the physiological control of individuals (limb length and body mass) to be similarly influenced by roads andPinus. To evaluate this, we used PERMANOVA analyses for each of the compositional facets and anthropogenic stressor, and path models to verify all possible relationships between patterns of functional dispersion and anthropogenic stressors. We found that, while the distance from ponds toPinusmonocultures influences the phylogenetic composition, distance to roads influences the functional composition; distance to roads affects mostly the functional dispersion of the communities. These anthropogenic stressors affect the structure of anuran communities, even those formed by generalist species in terms of habitat use. There is a decline in diversity in communities located close toPinusand roads, leading to losses in the evolutionary history accumulated in these communities. The control of vehicle traffic during reproduction periods and the maintenance of areas with natural vegetation, particularly around ponds, may help mitigate the negative effects of anthropogenic stressors on anuran communities.
Neurovascular coupling and bilateral connectivity during NREM and REM sleep
Authors: Turner Kevin L. , Gheres Kyle W. , Proctor Elizabeth A. , Drew Patrick J.
Published: August 2020

Hemodynamic signals in the brain are used as surrogates of neural activity, but how these hemodynamic signals depend on arousal state is poorly understood. Here, we monitored neural activity and hemodynamic signals in un-anesthetized, head-fixed mice to understand how sleep and awake states impact cerebral hemodynamics. In parallel with electrophysiological recordings, we used intrinsic optical signal imaging to measure bilateral changes in cerebral hemoglobin ([HbT]), and two-photon laser scanning microscopy (2PLSM) to measure dilations of individual arterioles. We concurrently monitored body motion, whisker movement, muscle EMG, cortical LFP, and hippocampal LFP to classify the arousal state of the mouse into awake, NREM sleep, or REM sleep. We found that mice invariably fell asleep during imaging, and these sleep states were interspersed with periods of awake. During both NREM and REM sleep, mice showed large increases in [HbT] relative to the awake state, showing increase in hemoglobin and arteriole diameter two to five times larger than those seen in response to sensory stimulation. During NREM sleep, the amplitude of bilateral low-frequency oscillations in [HbT] increased markedly, and coherency between neural activity and hemodynamic signals was higher than the awake resting and REM states. Bilateral correlations in neural activity and [HbT] were highest during NREM sleep, and lowest in the awake state. Our results show that hemodynamic signals in the cortex are strongly modulated by arousal state, with hemodynamic changes during sleep being substantially larger than sensory-evoked responses. These results underscore the critical importance of behavioral monitoring during studies of spontaneous activity, as sleep-related hemodynamics dominate measures of neurovascular coupling and functional connectivity.
Impact of COVID-19 mitigation measures on the incidence of preterm birth: a national quasi-experimental study
Authors: Been Jasper V , Ochoa Lizbeth Burgos , Bertens Loes CM , Schoenmakers Sam , Steegers Eric AP , Reiss Irwin KM
Published: August 2020

Introduction

Preterm birth is the leading cause of child mortality globally, with many survivors experiencing long-term adverse consequences. Preliminary evidence suggests that preterm births dropped dramatically following implementation of policy measures aimed at mitigating the impact of the COVID-19 pandemic.

Methods

We undertook a national quasi-experimental difference-in-regression-discontinuity approach to study the impact of the COVID-19 mitigation measures implemented in the Netherlands in a stepwise fashion on 9, 15, and 23 March 2020 on the incidence of preterm birth. We used data from the neonatal dried blood spot screening programme (2010−2020) and cross-validated these against national perinatal registry data. Stratified analyses were conducted according to gestational age subgroups, and sensitivity analyses to assess robustness of the findings. We explored potential effect modification by neighbourhood socio-economic status.

Results

Data on 1,599,547 singleton newborns were available, including 56,720 post-implementation births. Consistent reductions in preterm birth were seen across various time windows surrounding implementation of the 9 March COVID-19 mitigation measures: ±2 months (n=531,823): odds ratio 0.77 (95% confidence interval 0.66–0.91), p=0.002; ±3 months (n=796,531): 0.85 (0.73–0.98), p=0.028; ±4 months (n=1,066,872): 0.84 (0.73–0.97), p=0.023. Decreases observed following the 15 March measures were of smaller magnitude and not statistically significant. No changes were observed after 23 March. Preterm birth reductions after 9 March were consistent across gestational age strata and robust in sensitivity analyses. They appeared confined to high-socioeconomic status neighbourhoods, but effect modification was not statistically significant.

Conclusion

In this national quasi-experimental study, initial implementation of COVID-19 mitigation measures was associated with a 15-23% drop in preterm births in the following months, in agreement with preliminary observations in other countries. It is now of pivotal importance that integration of comparable data from across the globe is undertaken to further substantiate these findings and start exploring the underlying mechanisms.
Role of Flipped Classroom Method in Short and Long Term Retention in Anatomy
Authors: Kasat Payal Arvind , Deshmukh Vishwajit , Muthiyan Gayatri , Gugapriya T.S. , Tarnekar Aaditya , Sontakke Bharat , Sorte Smita
Published: August 2020

Introduction

Medical education is changing towards more flexible, effective, active and student-centered teaching strategies that reduces the limitations of traditional methods of education. Recently, the flipped classroom method has been suggested to support this transition. However, research on the use of flipped classroom method in medical education is at its early stage and little is known about its effect on students learning in relation to short and long-term retention of the topics.

Aims

The present paper aims to study the comparative effect of traditional and flipped classroom method on short-term and long-term memories of first MBBS students in Anatomy with the aid of technology to promote learning.

Materials and methods

50 first year MBBS students were subjected to traditional and flipped classroom module separately. Immediate assessments were done at the completion of the module. Followed by a gap of 2 months, the students were again assessed on the content taught in the module as a part of formative assessment. The data so obtained was compared and analyzed statistically.

Result

The assessment scores showed differences between the two methods of teaching in short as well as long term. The flipped classroom method was observed to have significant long-term retention which was evident by assessment scores.

Conclusion

The study concludes that flipped classroom method serves as an advantageous tool and motivating factor for effective learning, understanding and retention of conceptual and factual anatomical content.
Respiratory viral infections by Non-influenza viruses are associated with more adverse clinical outcome in patients with underlying liver disease: a single centre laboratory based study
Authors: Gupta Ekta , Padhi Abhishek , Agarwal Kavita , Ramachandran Krithiga , Agarwal Reshu , Rao Pasupuleti Samba Siva , Bhattacharyya Debajyoti , Maiwall Rakhi , Sarin Shiv Kumar
Published: August 2020

Background

Respiratory viral infections are an important cause of acute respiratory tract infections. They are caused by both Influenza and non influenza viruses. Respiratory viral infections are known to be associated with severe clinical outcome especially in the critically ill. A constant surveillance is needed for early etiological identification which can help in timely and appropriate management and will further help in prevention of indiscriminate use of antibiotics in patients with viral etiology.

Methods

In this retrospective study, clinical records of all adult liver disease patients with clinically confirmed ARI, whose request for respiratory viral testing were received in the virology laboratory during September 2016 - March 2019 were reviewed. Respiratory viruses were identified by real time PCR on FilmArray 2.0 instrument (BioFire Diagnostics, Utah, USA) using Respiratory panel as per the manufacturer’s instructions.

Results

Of the 603 patients of liver disease with clinically confirmed influenza like illness, over all incidence of respiratory viral infection was 24.3% (n= 147). Infections by non-influenza viruses (87, 59.1%) were more than influenza group of viruses. Mortality was higher in non influenza group (43, 49.4%) as compared to influenza (24, 40%) [p=0.015] being maximum in Rhinovirus, 22 (32.8%). Two peaks were observed in both influenza and non influenza groups, first in the months of January and February and the other one in August and October.

Conclusion

With the emergence of SARS-CoV-2 it has now become imperative for a constant surveillance of the non influenza viruses for early etiological identification of the respiratory viral infection for proper and timely management in the critically ill.

Highlights

Patients with liver cirrhosis having Respiratory viral infections have a poor outcome in terms of morbidity and mortality.

Mortality associated with non influenza viruses (NIV) is more as compared to influenza virus infections.

COVID-19 pandemic and higher mortality in NIVs warrants a constant monitoring of respiratory viral infections.
Genome-wide association and Mendelian randomization analysis prioritizes bioactive metabolites with putative causal effects on common diseases
Authors: Qin Youwen , Méric Guillaume , Long Tao , Watrous Jeramie D. , Burgess Stephen , Havulinna Aki S. , Ritchie Scott C. , Brożyńska Marta , Jousilahti Pekka , Perola Markus , Lahti Leo , Niiranen Teemu , Cheng Susan , Salomaa Veikko , Jain Mohit , Inouye Michael
Published: August 2020

Bioactive metabolites are central to numerous pathways and disease pathophysiology, yet many bioactive metabolites are still uncharacterized. Here, we quantified bioactive metabolites using untargeted LC-MS plasma metabolomics in two large cohorts (combined N≈9,300) and utilized genome-wide association analysis and Mendelian randomization to uncover genetic loci with roles in bioactive metabolism and prioritize metabolite features for more in-depth characterization. We identified 118 loci associated with levels of 2,319 distinct metabolite features which replicated across cohorts and reached study-wide significance in meta-analysis. Of these loci, 39 were previously not known to be associated with blood metabolites. Loci harboring SLCO1B1 and UGT1A were highly pleiotropic, accounting for >40% of all associations. Two-sample Mendelian randomization found 46 causal effects of 31 metabolite features on at least one of five common diseases. Of these, 15, including leukotriene D4, had protective effects on both coronary heart disease and primary sclerosing cholangitis. We further assessed the association between baseline metabolite features and incident coronary heart disease using 16 years of follow-up health records. This study characterizes the genetic landscape of bioactive metabolite features and their putative causal effects on disease.