Focused stimulation of dorsal versus ventral subthalamic nucleus enhances action-outcome learning in patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the clinical motor symptoms of Parkinson's disease, but may alter the ability to learn contingencies between stimuli, actions and outcomes. We investigated how stimulation of the functional subregions in the subthalamic nucleus (motor and cognitive regions) modulates stimulus-action-outcome learning in Parkinson's disease patients. Twelve Parkinson's disease patients with deep brain stimulation of the subthalamic nucleus completed a probabilistic stimulus-action-outcome task while undergoing ventral and dorsal subthalamic nucleus stimulation (within subjects, order counterbalanced). The task orthogonalized action choice and outcome valence, which created four action-outcome learning conditions: action-reward, inhibit-reward, action-punishment avoidance and inhibit-punishment avoidance. We compared the effects of deep brain stimulation on learning rates across these conditions as well as on computed Pavlovian learning biases. Dorsal stimulation was associated with higher overall learning proficiency relative to ventral subthalamic nucleus stimulation. Compared to ventral stimulation, stimulating the dorsal subthalamic nucleus led to a particular advantage in learning to inhibit action to produce desired outcomes (gain reward or avoid punishment) as well as better learning proficiency across all conditions providing reward opportunities. The Pavlovian reward bias was reduced with dorsal relative to ventral subthalamic nucleus stimulation, which was reflected by improved inhibit-reward learning. Our results show that focused stimulation in the dorsal compared to the ventral subthalamic nucleus is relatively more favourable for learning action-outcome contingencies and reduces the Pavlovian bias that could lead to reward-driven behaviour. Considering the effects of deep brain stimulation of the subthalamic nucleus on learning and behaviour could be important when optimizing stimulation parameters to avoid side effects like impulsive reward-driven behaviour.

The antiviral protein Shiftless blocks p-body formation during KSHV infection.

P-bodies (PB) are non-membranous foci involved in determining mRNA fate by affecting translation and mRNA decay. In this study, we identify the anti-viral factor SHFL as a potent disassembly factor of PB. We show that PBs remain sparse in the presence of SHFL even in the context of oxidative stress, a major trigger for PB induction. Mutational approaches revealed that SHFL RNA binding activity is not required for its PB disassembly function. However, we have identified a new region of SHFL which bridges two distant domains as responsible for PB disassembly. Furthermore, we show that SHFL ability to disrupt PB formation is directly linked to its anti-viral activity during KSHV infection. While WT SHFL efficiently restricts KSHV lytic cycle, PB disruption defective mutants no longer lead to reactivation defects. SHFL-mediated PB disassembly also leads to increased expression of key anti-viral cytokines, further expanding SHFL dependent anti-viral state. Taken together, our observations suggest a role of SHFL in PB disassembly, which could have important anti-viral consequences during infection.

PCL/PEO Polymer Membrane Prevents Biofouling in Wearable Detection Sensors.

Technological advances in biosensing offer extraordinary opportunities to transfer technologies from a laboratory setting to clinical point-of-care applications. Recent developments in the field have focused on electrochemical and optical biosensing platforms. Unfortunately, these platforms offer relatively poor sensitivity for most of the clinically relevant targets that can be measured on the skin. In addition, the non-specific adsorption of biomolecules (biofouling) has proven to be a limiting factor compromising the longevity and performance of these detection systems. Research from our laboratory seeks to capitalize on analyte selective properties of biomaterials to achieve enhanced analyte adsorption, enrichment, and detection. Our goal is to develop a functional membrane integrated into a microfluidic sampling interface and an electrochemical sensing unit. The membrane was manufactured from a blend of Polycaprolactone (PCL) and Polyethylene oxide (PEO) through a solvent casting evaporation method. A microfluidic flow cell was developed with a micropore array that allows liquid to exit from all pores simultaneously, thereby imitating human perspiration. The electrochemical sensing unit consisted of planar gold electrodes for the monitoring of nonspecific adsorption of proteins utilizing Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS). The solvent casting evaporation technique proved to be an effective method to produce membranes with the desired physical properties (surface properties and wettability profile) and a highly porous and interconnected structure. Permeability data from the membrane sandwiched in the flow cell showed excellent permeation and media transfer efficiency with uniform pore activation for both active and passive sweat rates. Biofouling experiments exhibited a decrease in the extent of biofouling of electrodes protected with the PCL/PEO membrane, corroborating the capacity of our material to mitigate the effects of biofouling.

Shiftless Restricts Viral Gene Expression and Influences RNA Granule Formation during Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.

Herpesviral infection reflects thousands of years of coevolution and the constant struggle between virus and host for control of cellular gene expression. During Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication, the virus rapidly seizes control of host gene expression machinery by triggering a massive RNA decay event via a virally encoded endoribonuclease, SOX. This virus takeover strategy decimates close to 80% of cellular transcripts, reallocating host resources toward viral replication. The host cell, however, is not entirely passive in this assault on RNA stability. A small pool of host transcripts that actively evade SOX cleavage has been identified over the years. One such "escapee," C19ORF66 (herein referred to as Shiftless [SHFL]), encodes a potent antiviral protein capable of restricting the replication of multiple DNA and RNA viruses and retroviruses, including KSHV. Here, we show that SHFL restricts KSHV replication by targeting the expression of critical viral early genes, including the master transactivator protein, KSHV ORF50, and thus subsequently the entire lytic gene cascade. Consistent with previous reports, we found that the SHFL interactome throughout KSHV infection is dominated by RNA-binding proteins that influence both translation and protein stability, including the viral protein ORF57, a crucial regulator of viral RNA fate. We next show that SHFL affects cytoplasmic RNA granule formation, triggering the disassembly of processing bodies. Taken together, our findings provide insights into the complex relationship between RNA stability, RNA granule formation, and the antiviral response to KSHV infection. IMPORTANCE In the past 5 years, SHFL has emerged as a novel and integral piece of the innate immune response to viral infection. SHFL has been reported to restrict the replication of multiple viruses, including several flaviviruses and the retrovirus HIV-1. However, to date, the mechanism(s) by which SHFL restricts DNA virus infection remains largely unknown. We have previously shown that following its escape from KSHV-induced RNA decay, SHFL acts as a potent antiviral factor, restricting nearly every stage of KSHV lytic replication. In this study, we set out to determine the mechanism by which SHFL restricts KSHV infection. We demonstrate that SHFL impacts all classes of KSHV genes and found that SHFL restricts the expression of several key early genes, including KSHV ORF50 and ORF57. We then mapped the interactome of SHFL during KSHV infection and found several host and viral RNA-binding proteins that all play crucial roles in regulating RNA stability and translation. Lastly, we found that SHFL expression influences RNA granule formation both outside and within the context of KSHV infection, highlighting its broader impact on global gene expression. Collectively, our findings highlight a novel relationship between a critical piece of the antiviral response to KSHV infection and the regulation of RNA-protein dynamics.

Effects of deep brain stimulation target on the activation and suppression of action impulses.

OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment to improve motor symptoms in Parkinson's disease (PD). The Globus Pallidus (GPi) and the Subthalamic Nucleus (STN) are the most targeted brain regions for stimulation and produce similar improvements in PD motor symptoms. However, our understanding of stimulation effects across targets on inhibitory action control processes is limited. We compared the effects of STN (n = 20) and GPi (n = 13) DBS on inhibitory control in PD patients. METHODS: We recruited PD patients undergoing DBS at the Vanderbilt Movement Disorders Clinic and measured their performance on an inhibitory action control task (Simon task) before surgery (optimally treated medication state) and after surgery in their optimally treated state (medication plus their DBS device turned on). RESULTS: DBS to both STN and GPi targets induced an increase in fast impulsive errors while simultaneously producing more proficient reactive suppression of interference from action impulses. CONCLUSIONS: Stimulation in GPi produced similar effects as STN DBS, indicating that stimulation to either target increases the initial susceptibility to act on strong action impulses while concomitantly improving the ability to suppress ongoing interference from activated impulses. SIGNIFICANCE: Action impulse control processes are similarly impacted by stimulating dissociable nodes in frontal-basal ganglia circuitry.

Outcomes of Endoscopic Carpal Tunnel Release Surgery With Home Guided Hand Therapy Versus No Hand Therapy: A Prospective Randomized Controlled Trial After Endoscopic Carpal Tunnel Release.

BACKGROUND: The most recent American Academy of Orthopaedic Surgeons Clinical Practice Guidelines found no high-quality evidence comparing home therapy to no therapy following carpal tunnel release surgery (CTRS). Therefore, this study's purpose is to compare the outcomes of patients receiving home therapy and patients receiving no therapy following endoscopic CTRS. METHODS: A single-blinded prospective randomized controlled trial was performed. Patients were randomized to receive home hand therapy or no therapy postoperatively. Patients were assessed at baseline, 2, 6, and 12 weeks postoperatively. Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores and Boston Carpal Tunnel Questionnaire (BCTQ) scores were evaluated as primary outcome measures. Grip strength, pinch strength, numerical pain rating scale (NRS), static 2-point discrimination, and hand circumference were also measured. RESULTS: Fifty patients were randomized to home therapy while 55 patients were randomized to no therapy. The QuickDASH, BCTQ functional status scale (FSS), and BCTQ symptom severity scale (SSS) improved over time in both treatment groups. As-treated and intention-to-treat analysis showed no difference in improvement of QuickDASH, BCTQ FSS, or BCTQ SSS between treatment groups. Additionally, there was no significant difference between treatment groups in grip strength, chuck and key strength, NRS, hand circumference, and static 2-point discrimination. CONCLUSIONS: This blinded, prospective randomized controlled study shows no significant difference in improvement of QuickDASH, BCTQ SSS, and BCTQ FSS scores between patients receiving no therapy and home therapy following endoscopic CTRS. Consideration should be given to releasing patients without supervised therapy in the postoperative setting. LEVEL OF EVIDENCE: Level II Therapeutic.

Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection.

Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity of mechanisms that differ from one virus to the next. These inhibitory strategies include the negative regulation of viral RNA stability, translation, and even the manipulation of RNA granule formation during viral infection. Even more surprisingly, SHFL is the first human protein found to directly inhibit the activity of the -1 programmed ribosomal frameshift, a translation recoding strategy utilized across nearly all domains of life and several human viruses. Recent literature has shown that SHFL expression also significantly impacts viral pathogenesis in mouse models, highlighting its in vivo efficacy. To help reconcile the many mechanisms by which SHFL restricts viral replication, we provide here a comprehensive review of this complex ISG, its influence over viral RNA fate, and the implications of its functions on the virus-host arms race for control of the cell.

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: Update of a living systematic review and meta-analysis.

BACKGROUND: Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic? METHODS AND FINDINGS: The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated. CONCLUSIONS: Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2. REVIEW PROTOCOL: Open Science Framework (https://osf.io/9ewys/).

Surgical timing for torsional ankle fractures is not associated with post-operative complications in patients with type II diabetes mellitus.

INTRODUCTION: Surgical stabilization of ankle fractures is one of the most commonly performed procedures in orthopedics, but these injuries can prove difficult to manage in patients with type II diabetes mellitus (DMII). The goal of this study is to determine if a correlation exists between surgical timing and complication rates among diabetic patients with ankle fractures. METHODS: This is a retrospective case-control study spanning from 2012 to 2019 including patients with DMII undergoing operative fixation for ankle fractures. The primary independent variable was surgical timing and the primary dependent variable was the rate of post-operative complications. RESULTS: The overall complication rate was 25.5% with 60% of these patients requiring repeat surgical intervention. The most common complication was superficial surgical-site infection. There was no significant difference in surgical timing between patients experiencing post-operative complication compared to those who did not. CONCLUSION: Among patients with DMII, we failed to show a correlation between surgical timing and post-operative complication.

Automated detection of electrocautery instrument in videos of open neck procedures using YOLOv3.

With the rapid development of deep learning approaches, tremendous progress has been made in computer- assisted analysis of minimally-invasive, videoscopic surgery. However, surgery through open incisions ("open surgery"), which constitutes a much larger portion of surgical procedures performed, is rarely investigated because of the difficulty in obtaining high-quality open surgical video footage. Automated detection of surgical instruments shows promise for evaluating surgical activities, and provides a foundation for quality/safety review, education, and identification of surgical performance. In this paper, we present results using YOLOv3 to successfully identify an electrocautery surgical instrument in a library of images derived from 22 open neck procedures (an 887-image training/validation set, and a 1149-image testing set) captured using a wearable surgical camera. We show that our method effectively detects the spatial bounds of the electrocautery pencil in still images and we further demonstrate the ability of our method to detect the location of this instrument in video footage. Our work serves as the first demonstration of open surgical instrument detection using first-person video footage from a wearable camera and sets the stage for further work in this field.Clinical Relevance- Detection of instrumentation in surgical video is the necessary first step towards automating surgical task identification and skills assessment, which will be useful for surgical quality improvement and training.

Desenlace de craniectomía descompresiva primaria y secundaria en pacientes con trauma craneoencefálico severo en la Clínica Universidad de La Sabana / Outcomes of Primary and Secondary Decompressive Craniectomy in Patients with Severe Traumatic Brain Injury at Clínica de la Universidad de La Sabana

RESUMEN Objetivos: El propósito de este estudio fue determinar el desenlace en el egreso y en el seguimiento a un año de los pacientes con trauma craneoencefálico severo sometidos a craniectomía descompresiva primaria y secundaria en la Clínica de la Universidad de La Sabana, en un periodo de cinco años. Pacientes y métodos: Se llevó a cabo una serie de casos retrospectiva de pacientes con trauma craneoencefálico severo sometidos a craniectomía descompresiva entre 2008 y 2013. Los desenlaces primarios fueron la sobrevida y el estado funcional medido por la escala de desenlace de Glasgow al momento del egreso hospitalario y al año de seguimiento. Como desenlaces secundarios se incluyeron el tiempo de latencia para la realización de la craniectomía, las complicaciones intra- y postoperatorias, días de hospitalización y estancia en la unidad de cuidados intensivos, tiempo de ventilación, resultados de la craneoplastia y causa de muerte. Resultados: Treinta y cinco pacientes con trauma craneoencefálico severo fueron sometidos a craniectomía descompresiva en el periodo de estudio, 29 primarias y 6 secundarias, con una latencia mediana de 5 horas y 57 horas, respectivamente. Se observó una sobrevida del 51,4 % de los pacientes, de los cuales 39 % presentó recuperación funcional satisfactoria en la escala de desenlace de Glasgow en el momento del egreso y al año. Conclusiones: En este grupo de pacientes sometidos a craniectomía descompresiva primaria o secundaria, junto con un manejo interdisciplinario y rehabilitación precoz, se presentaron desenlaces funcionales favorables en el seguimiento a largo plazo.

ABSTRACT Aim: The purpose of this study was to determine the outcome, at discharge and at one-year follow-up, of patients with severe traumatic brain injury undergoing primary and secondary decompressive craniectomy at Clinica Universidad de La Sabana, over a period of five years. Patients and methods: We conducted a retrospective case series of patients with severe traumatic brain injury undergoing decompressive craniectomy between 2008 and 2013. Te primary outcomes were survival and functional status, measured by the Glasgow Outcome Scale, both at discharge, and at the one year follow-up. Secondary outcomes included latency time for craniectomy, intra and postoperative complications, days of hospitalization and intensive care unit stay, ventilation time, cranioplasty results, and cause of death. Results: Thirty-five patients with severe traumatic brain injury underwent decompressive craniectomy in the study period, 29 of which were primary and 6, secondary, with a median latency of 5 hours and 57 hours, respectively. A survival of 51.4% of the patients was observed, of which 39% presented satisfactory functional recovery on the Glasgow outcome scale at the time of discharge and one year later. Conclusions: In this group of patients who underwent primary or secondary decompressive craniectomy, together with interdisciplinary management and early rehabilitation, favorable functional outcomes were found in the long-term follow-up.

Deep brain stimulation effects on verbal fluency dissociated by target and active contact location.

OBJECTIVE: Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but it can also disrupt verbal fluency with significant costs to quality of life. The current study investigated how variability of bilateral active electrode coordinates along the superior/inferior, anterior/posterior, and lateral/medial axes in the subthalamic nucleus (STN) or the globus pallidus interna (GPi) contribute to changes in verbal fluency. We predicted that electrode location in the left hemisphere would be linked to changes in fluency, especially in the STN. METHODS: Forty PD participants treated with bilateral DBS targeting STN (n = 23) or GPi (n = 17) completed verbal fluency testing in their optimally treated state before and after DBS therapy. Normalized atlas coordinates from left and right active electrode positions along superior/inferior, anterior/posterior, and lateral/medial axes were used to predict changes in fluency postoperatively, separately for patients with STN and GPi targets. RESULTS: Consistent with prior studies, fluency significantly declined pre- to postsurgery (in both DBS targets). In STN-DBS patients, electrode position along the inferior to superior axis in the left STN was a significant predictor of fluency changes; relatively more superior left active electrode was associated with the largest fluency declines in STN. Electrode coordinates in right STN or GPi (left or right) did not predict fluency changes. INTERPRETATION: We discuss these findings in light of putative mechanisms and potential clinical impact.

Fated for decay: RNA elements targeted by viral endonucleases.

For over a decade, studies of messenger RNA regulation have revealed an unprecedented level of connectivity between the RNA pool and global gene expression. These connections are underpinned by a vast array of RNA elements that coordinate RNA-protein and RNA-RNA interactions, each directing mRNA fate from transcription to translation. Consequently, viruses have evolved an arsenal of strategies to target these RNA features and ultimately take control of the pathways they influence, and these strategies contribute to the global shutdown of the host gene expression machinery known as "Host Shutoff". This takeover of the host cell is mechanistically orchestrated by a number of non-homologous virally encoded endoribonucleases. Recent large-scale screens estimate that over 70 % of the host transcriptome is decimated by the expression of these viral nucleases. While this takeover strategy seems extraordinarily well conserved, each viral endonuclease has evolved to target distinct mRNA elements. Herein, we will explore each of these RNA structures/sequence features that render messenger RNA susceptible or resistant to viral endonuclease cleavage. By further understanding these targeting and escape mechanisms we will continue to unravel untold depths of cellular RNA regulation that further underscores the integral relationship between RNA fate and the fate of the cell.

Subthalamic Nucleus Subregion Stimulation Modulates Inhibitory Control.

Patients with Parkinson's disease (PD) often experience reductions in the proficiency to inhibit actions. The motor symptoms of PD can be effectively treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN), a key structure in the frontal-striatal network that may be directly involved in regulating inhibitory control. However, the precise role of the STN in stopping control is unclear. The STN consists of functional subterritories linked to dissociable cortical networks, although the boundaries of the subregions are still under debate. We investigated whether stimulating the dorsal and ventral subregions of the STN would show dissociable effects on ability to stop. We studied 12 PD patients with STN DBS. Patients with two adjacent contacts positioned within the bounds of the dorsal and ventral STN completed two testing sessions (OFF medication) with low amplitude stimulation (0.4 mA) at either the dorsal or ventral contacts bilaterally, while performing the stop task. Ventral, but not dorsal, DBS improved stopping latencies. Go reactions were similar between dorsal and ventral DBS STN. Stimulation in the ventral, but not dorsal, subregion of the STN improved stopping speed, confirming the involvement of the STN in stopping control and supporting the STN functional subregions.

Bacterial versus non-bacterial infections: a methodology to support use-case-driven product development of diagnostics.

Acute febrile illness (AFI) is one of the most common reasons for seeking medical care in low-income and middle-income countries. Bacterial infections account for a relatively small proportion of AFIs; however, in the absence of a simple diagnostic test to guide clinical decisions, healthcare professionals often presume that a non-malarial febrile illness is bacterial in origin, potentially resulting in inappropriate antibiotic use. An accurate differential diagnostic tool for AFIs is thus essential, to both limit antibiotic use to bacterial infections and address the antimicrobial resistance crisis that is emerging globally, without resorting to multiple or complex pathogen-specific assays. The Biomarker for Fever-Diagnostic (BFF-Dx) study is one of the largest fever biomarker studies ever undertaken. We collected samples and classified disease aetiology in more than 1900 individuals, distributed among enrolment centres in three countries on two continents. Identical protocols were followed at each study site, and the same analyses were conducted in each setting, enabling like-with-like comparisons to be made among the large sample set generated. The BFF-Dx methodology can act as a model for other researchers, facilitating wider utility of the work in the future. The established sample collection is now accessible to researchers and companies and will facilitate the development of future fever-related diagnostic tests. Here, we outline the methodology used to determine the sample populations and to differentiate bacterial versus non-bacterial AFIs. Future publications will set out in more detail the study's demographics, the causes of fever identified and the performance of selected biomarkers.

Two new species of Megarthrus (Coleoptera, Staphylinidae, Proteininae) from Mexican Cloud Forests.

Two new species of Megarthrus are described from cloud forests of the Mexican state of Veracruz: M. cavianae Rodríguez, Navarrete-Heredia Arriaga-Varela sp. nov., and Chiapas:  M. chiapas Cuccodoro sp. nov. They differ from the two hitherto known Mexican species M. altivagans Bernhauer, 1929, and M. alatorreorum Rodríguez Navarrete-Heredia, 2015, both from temperate forests of the Transmexican Volcanic Belt, by having synapomorphic features of the M. inaequalis-supergroup of species. This lineage includes all the Central and South American members of the genus, with the inclusion of these species, the distribution of the group is extend by more than 5 degree of latitude to the North. Within this lineage, the two new species share a very peculiar morphology of the male abdominal sternite VIII found elsewhere in the genus only in M. flavosignatus Bierig, 1940, and M. zunilensis Sharp, 1887, with which they form the M. zunilensis-group of species defined here.

Evolución y secuelas cognitivas en un paciente con encefalopatía por VIH/SIDA con tratamiento antirretroviral / Evolution and cognitive consequences in a patient with HIV/AIDS encephalopathy with antiretroviral treatment

El VIH/SIDA es una enfermedad neurotrópica que afecta al sistema nervioso central y dependiendo de la fase clínica de la enfermedad genera deterioro neurológico, psiquiátrico y neuropsicológico en grado variable. Se describe el caso de un paciente que presentó un cuadro de deterioro cognitivo severo (demencia SIDA) con posterior mejoría de signos y síntomas, y establecimiento posterior de secuelas neuropsicológicas después de un año de su diagnóstico. Se comparó una evaluación neuropsicológica en etapa de deterioro cognitivo severo con otra de seguimiento, realizada un año después de iniciar el tratamiento antirretroviral. Se presentan las características clínicas del paciente utilizando el estudio de caso como herramienta metodológica y sobre la base de un procedimiento clínico y psicométrico.

HIV/AIDS is a neurotropic disease that affects the central nervous system and depending on the clinical phase of the disease generates neurological, psychiatric and neuropsychological impairment to varying degrees. The case of a patient who presented severe cognitive impairment (AIDS dementia) is described with subsequent remission of signs and symptoms, and establishment of neuropsychological sequelae after one year of diagnosis. A neuropsychological evaluation in stage of severe cognitive impairment was compared with another follow-up one year after initiating antiretroviral treatment. The clinical characteristics of the patient are presented using the case study as a methodological tool and based on a clinical and psychometric procedure.

Stealing the Show: KSHV Hijacks Host RNA Regulatory Pathways to Promote Infection.

Kaposi's sarcoma-associated herpesvirus (KSHV) induces life-long infections and has evolved many ways to exert extensive control over its host's transcriptional and post-transcriptional machinery to gain better access to resources and dampened immune sensing. The hallmark of this takeover is how KSHV reshapes RNA fate both to control expression of its own gene but also that of its host. From the nucleus to the cytoplasm, control of RNA expression, localization, and decay is a process that is carefully tuned by a multitude of factors and that can adapt or react to rapid changes in the environment. Intriguingly, it appears that KSHV has found ways to co-opt each of these pathways for its own benefit. Here we provide a comprehensive review of recent work in this area and in particular recent advances on the post-transcriptional modifications front. Overall, this review highlights the myriad of ways KSHV uses to control RNA fate and gathers novel insights gained from the past decade of research at the interface of RNA biology and the field of KSHV research.

Comparative performance study of three Ebola rapid diagnostic tests in Guinea.

BACKGROUND: The 2014/15 Ebola outbreak in West Africa resulted in 11,000 deaths and massive strain on local health systems, and the ongoing outbreak in Democratic Republic of Congo has afflicted more than 3000 people. Accurate, rapid Ebola diagnostics suitable for field deployment would enable prompt identification and effective response to future outbreaks, yet remain largely unavailable. The purpose of this study was to assess the accuracy of three novel rapid diagnostic tests (RDTs): an Ebola, an Ebola-Malaria, and a Fever Panel test that includes Ebola, all from a single manufacturer. METHODS: We evaluated the three RDTs in 109 Ebola-positive and 96 Ebola-negative stored serum samples collected during the outbreak in Guinea in 2014/15, and tested by real-time polymerase chain reaction (RT-PCR). Sensitivity, specificity, and overall percent agreement were calculated for each RDT using RT-PCR as a reference standard, stratified by Ct value ranges. RESULTS: All tests performed with high accuracy on samples with low Ct value (high viral load). The Fever Panel test performed with the highest accuracy, with a sensitivity of 89.9% and specificity of 90.6%. The Ebola and Ebola-Malaria tests performed comparably to each other: sensitivity was 77.1 and 78% respectively, and specificity was 91.7% for the Ebola test and 95.8% for the Ebola-Malaria test. CONCLUSIONS: This study evaluated the accuracy of three novel rapid diagnostic tests for Ebola. The tests may have significant public health relevance, particularly the Fever Panel test, which detects seven pathogens including Ebola. Given limitations to the study resulting from uncertain sample quality, further evaluation is warranted. All tests performed with highest accuracy on samples with low Ct value (high viral load), and the data presented here suggests that these RDTs may be useful for point-of-care diagnosis of cases in the context of an outbreak. Restrictions to their use in non-severe Ebola cases or for longitudinal monitoring, when viral loads are lower, may be appropriate. Highlighting the challenge in developing and evaluating Ebola RDTs, there were concerns regarding sample integrity and reference testing, and there is a need for additional research to validate these assays.