bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Intracranial Extension of Craniofacial Dermoid Cysts
Authors: Overland Joseph , Hall Courtney , Holmes Anthony , Burge Jonathan
Published: January 2020

Background:

Dermoid cysts are benign lesions lined by keratinizing squamous epithelium that also contain epidermal adnexa (hair follicles, hair shafts, sebaceous glands, and both apocrine and eccrine sweat glands) and mesodermal derivatives (smooth muscle fibers, vascular stroma, nerves, and collagen fibers). Craniofacial dermoid cysts represent approximately 7 percent of all dermoids and have an incidence ranging between 0.03 and 0.14 percent.

Methods:

The authors conducted a single-center, consecutive, nonrandomized comparative case series over a 20-year period of all patients treated surgically for craniofacial dermoid at the Royal Children’s Hospital in Melbourne, Australia. Six hundred forty-seven patients had craniofacial dermoids and adequate information to be included in the study. The authors also conducted a thorough review of the literature using the MEDLINE and Embase databases.

Results:

Six hundred forty-seven patients amounted to 655 lesions in our case series. The age at surgery ranged from 2 months to 18 years, with an average age of 25.65 months. The depth of the lesions was stratified using a classification system, and the risk of intracranial extension was assessed using these data. Midline nasal lesions are established as high risk by other studies, but frontal, temporal, and occipital lesions were found to be as risky if not more risky for intracranial extension.

Conclusions:

Several classification systems for craniofacial dermoid cysts have used both broader anatomical locations and physical characteristics to group these lesions and identify those warranting preoperative imaging. The authors propose a system using more specific classification of anatomical location to assist in the prompt identification of high-risk lesions and facilitate sound preoperative planning.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Free Tissue Transfer with Distraction Osteogenesis and Masquelet Technique Is Effective for Limb Salvage in Patients with Gustilo Type IIIB Open Fractures
Authors: Abdou Salma A. , Stranix John T. , Daar David A. , Mehta Devan D. , McLaurin Toni , Tejwani Nirmal , Saadeh Pierre B. , Levine Jamie P. , Leucht Philipp , Thanik Vishal D.
Published: January 2020

Osteocutaneous reconstruction can be challenging because of concomitant injuries and limited donor sites. There is a paucity of data on limb salvage outcomes following combined soft-tissue reconstruction and bone transport or Masquelet procedures. The authors reviewed a consecutive series of open tibia fracture patients undergoing soft-tissue reconstruction with either distraction osteogenesis or Masquelet technique. Endpoints were perioperative flap complications and bone union. Fourteen patients with Gustilo type IIIB open tibia fractures were included. Half of the group received muscle flaps and the remaining half received fasciocutaneous flaps. Ten patients (71.4 percent) underwent distraction osteogenesis and the remaining patients underwent Masquelet technique. Average bone gap length was 65.7 ± 31.3 mm (range, 20 to 120 mm). In the bone transport group, the average external fixation duration was 245 days (range, 47 to 686 days). In the Masquelet group, the average duration of the first stage of this two-stage procedure (i.e., time from cement spacer placement to bone grafting) was 95 days (range, 42 to 181 days). Bone union rate, as determined by radiographic evidence, was 85.7 percent. There was one complete flap failure (7.1 percent). One patient underwent below-knee amputation after failing bone transport and developing chronic osteomyelitis and subsequent infected nonunion. Our case series demonstrates that nonosteocutaneous flap methods of limb reconstruction are a viable option in patients with segmental long bone defects, with a bone union rate of 85 percent and a limb salvage rate over 90 percent in patients with Gustilo type IIIB fractures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Antenatal Intracellular Concentrations of Tenofovir Diphosphate and Emtricitabine Triphosphate and Associations Between Tenofovir Diphosphate and Severe Adverse Pregnancy Outcomes: IMPAACT-PROMISE (1077BF) Trial
Authors: Aizire Jim , Brooks Kristina M. , Mirochnick Mark , Flynn Patricia M. , Butler Kevin , Kiser Jennifer J. , Siberry George K. , Fenton Terry , Cababasay Mae , Fowler Mary G. ,   for the PROMISE Study Team
Published: January 2020

Background:

In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, tenofovir disoproxil fumarate (TDF) use was associated with moderate or severe adverse pregnancy/neonatal outcomes. This study characterized tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations in dried blood spots (DBS) and assessed association between severe adverse pregnancy/neonatal outcomes and TFV-DP concentration.

Methods:

Retrospective case–control study of PROMISE trial arm-C women randomized to receive TDF, FTC, and ritonavir-boosted lopinavir (LPV/r), who took at least 1 dose of TDF + FTC and had week-4 postrandomization DBS drawn before delivery. Cases, defined as severe adverse pregnancy/neonatal outcomes (very preterm delivery before 34 weeks of gestation, stillbirth ≥20 weeks of gestation, or infant death before 14 days-of-age), were matched to controls (1:2 ratio) by site and gestational age at entry. Week 4 and week 8 DBS samples were assayed for TFV-DP and FTC-TP by liquid chromatography and tandem mass spectrometry. Associations were tested using Wilcoxon rank test and conditional logistic regression.

Results:

Of 447 PROMISE arm-C women, 33 met case definitions, and overall, 22 cases and 44 controls were analyzed. Median (interquartile range) concentrations of TFV-DP at weeks 4 and 8 were 706 (375–1023) fmol/punch and 806 (414–1265) fmol/punch, respectively. Odds ratio (95% confidence interval) for severe adverse pregnancy/neonatal outcome with natural log of TFV-DP concentrations as the predictor were 1.27 (0.74 to 2.18) and 1.74 (0.66 to 4.60) at weeks 4 and 8, respectively. Median (interquartile range) concentrations of FTC-TP at weeks 4 and 8 were 0.27 (0.05–0.36) pmol/punch and 0.29 (0.05–0.40) pmol/punch, respectively.

Conclusions:

TFV-DP concentrations in DBS appeared not to be associated with severe adverse pregnancy/neonatal outcomes, although sample size was limited.
Significance of Best Spirometry in the First Year After Bilateral Lung Transplantation: Association With 3-Year Outcomes
Authors: Mohanka Manish R. , Kanade Rohan , Garcia Heriberto , Mahan Luke , Bollineni Srinivas , Mullins Jessica , Joerns John , Kaza Vaidehi , Torres Fernando , Zhang Song , Banga Amit
Published: January 2020

Background.

Spirometry is the cornerstone of monitoring allograft function after lung transplantation (LT). We sought to determine the association of variables on best spirometry during the first year after bilateral LT with 3-year posttransplant survival.

Methods.

We reviewed charts of patients who survived at least 3 months after bilateral LT (n = 157; age ± SD: 54 ± 13 y, male:female = 91:66). Best spirometry was calculated as the average of 2 highest measurements at least 3 weeks apart during the first year. Airway obstruction was defined as forced expiratory volume in 1-second (FEV1)/forced vital capacity (FVC) ratio <0.7. Survival was compared based on the ventilatory defect and among groups based on the best FEV1 and FVC measurements (>80%, 60%–80%, and <60% predicted). Primary outcome was 3-year survival.

Results.

Overall, 3-year survival was 67% (n = 106). Obstructive defect was uncommon (7%) and did not have an association with 3-year survival (72% versus 67%, P = 0.7). Although one-half patients achieved an FVC>80% predicted (49%), 1 in 5 (19%) remained below 60% predicted. Irrespective of the type of ventilatory defect, survival worsened as the best FVC (% predicted) got lower (>80: 80.8%; 60–80: 63.3%; <60: 40%; P < 0.001). On multivariate logistic regression analysis, after adjusting for age, gender, transplant indication, and annual bronchoscopy findings, best FVC (% predicted) during the first year after LT was independently associated with 3-year survival.

Conclusions.

A significant proportion of bilateral LT patients do not achieve FVC>80% predicted. Although the type of ventilatory defect on best spirometry does not predict survival, failure to achieve FVC>80% predicted during the first year was independently associated with 3-year mortality.
LPS-induced Airway-centered Inflammation Leading to BOS-like Airway Remodeling Distinct From RAS-like Fibrosis in Rat Lung Transplantation
Authors: Takahagi Akihiro , Sato Masaaki , Chen-Yoshikawa Toyofumi F. , Miyamoto Ei , Saito Masao , Gochi Fumiaki , Hamaji Masatsugu , Yoshizawa Akihiko , Terasaki Yasuhiro , Urushiyama Hirokazu , Aoyama Akihiro , Sonobe Makoto , Date Hiroshi
Published: January 2020

Background.

Localization of inflammatory stimuli may direct lung allografts to different phenotypes of chronic dysfunction, such as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). We hypothesized that airway stimulation with lipopolysaccharide (LPS) in rats leads to airway-centered inflammation similar to human BOS.

Methods.

Rat left lung transplantation was conducted (donor: Brown Norway, recipient: Lewis). Allotransplant recipients received cyclosporine A (CsA) until postoperative day 56 with airway instillation of LPS (Allo-LPS, n = 8), phosphate buffered saline (Allo-PBS, n = 5) from days 35 to 46 (3 times a wk), or no further treatment (n = 4). Some allotransplant recipients received CsA until day 14 and were immunosuppression free after day 15 until day 56. Bronchial and pleural fibrosis were semiquantified; alveolar fibrosis was evaluated with a histological scale.

Results.

The Allo-LPS group had significantly increased International Society for Heart and Lung Transplantation rejection grades (grade A, P = 0.005; grade B, P = 0.004), bronchial obstructive proportion (0.34 ± 0.04% [Allo-LPS] versus 0.11 ± 0.04% [Allo-PBS], P = 0.006), and airway resistance (3.05 ± 1.78 cm H2O·s/mL [Allo-LPS] versus 0.83 ± 0.58 cm H2O·s/mL [Allo-PBS], P = 0.007) compared with other groups. Allotransplant recipients that underwent a short course of CsA developed RAS-like fibrosis involving the airways, alveoli, and pleura.

Conclusions.

Airway instillation of LPS in allografts under immunosuppression resulted in BOS-like airway-centered inflammation and fibrosis distinct from RAS-like diffuse fibrosis, which was induced by a shortened course of immunosuppression. We propose novel animal models for BOS and RAS after lung transplantation.
CXCL9 Predicts Severity at the Onset of Chronic Graft-versus-host Disease
Authors: Giesen Nicola , Schwarzbich Mark-Alexander , Dischinger Katharina , Becker Natalia , Hummel Manuela , Benner Axel , Radujkovic Aleksandar , Müller-Tidow Carsten , Dreger Peter , Luft Thomas
Published: January 2020

Background.

Chronic graft-versus-host disease (cGVHD) represents a double-edged sword. In its nonsevere form, cGVHD associates with better control of the malignant disease, thus highlighting graft-versus-leukemia effects. However, severe cGVHD leads to debilitating morbidity and increased nonrelapse mortality. The prediction of severe cGVHD, in particular at disease onset, is therefore of high importance for ensuing clinical decisions and overall success of allogeneic stem cell transplantations. CXC-chemokine ligand 9 (CXCL9) is an interferon-inducible chemokine of the CXC family and is increased in cGVHD. Endothelial activation and stress index (EASIX) was shown to predict death after acute graft-versus-host disease. We explored CXCL9 and EASIX as predictors of severe cGVHD.

Methods.

Sera and clinical data of 480 patients were available who survived at least 6 months following allogeneic stem cell transplantation without steroid-refractory acute graft-versus-host disease and without early relapse. CXCL9 and EASIX were measured on day +100 and onset of cGVHD.

Results.

Development of nonsevere cGVHD was significantly associated with improved overall survival (hazard ratio 0.53, P < 0.001). CXCL9 serum levels at the onset of cGVHD predicted the development of severe cGVHD later on (hazard ratio 1.33, P = 0.02). In contrast, EASIX at the onset of cGVHD was not associated with cGVHD severity but was a significant independent risk factor for overall mortality and nonrelapse mortality.

Conclusions.

CXCL9 levels at the onset of cGVHD can help to predict severe courses of the disease and have potential for optimizing tailored administration of immunosuppressive therapy.
Nasal Pressure Injuries Due to Nasal Continuous Positive Airway Pressure Treatment in Newborns
Authors: Dai Tian , Lv Limin , Liu Xiaojuan , Chen Jin , Ye Yalan , Xu Lixuan
Published: January 2020

PURPOSE:

The purpose of this study was to calculate incidence, severity, and risk factors of nasal pressure injuries due to nasal continuous positive airway pressure (NCPAP) treatment in newborns.

DESIGN:

A prospective observational study.

SUBJECTS AND SETTING:

Newborns admitted between March 2017 and February 2018 to the neonatal intensive care unit of the First Affiliated Hospital of Xiamen University, Xiamen, China.

METHODS:

All newborns' noses were examined during NCPAP application. Every NCPAP-related nasal pressure injury including occurrence date, injury severity, outcomes, and pressure injury treatment methods was recorded. These data were collected twice a week by a research nurse. Nasal pressure injuries were classified using the National Pressure Ulcer Advisory Panel/European Pressure Ulcer Advisory Panel pressure injury classification system.

RESULTS:

During the study period, 429 newborns received NCPAP treatment via nasal prongs. Nasal pressure injuries were observed in 149 (34.7%); 99 (66.44%) were classified as Stage 1, 48 (32.31%) were Stage 2, and 2 (1.25%) cases were classified as deep tissue injury. The risk of nasal pressure injury was significantly higher when gestational age was less than 32 weeks (odds ratio [OR], 3.728; 95% confidence interval [CI], 1.18-11.77; P ≤ .025) and in those who received NCPAP treatment for more than 6 days (OR, 0.262; 95% CI, 0.087-0.787; P ≤ .017). The mean interval between the application of NCPAP and onset of nasal pressure injury was 4.72 days (SD, 4.78; range, 0-30 days).

CONCLUSIONS:

Nasal pressure injuries are a prevalent complication of NCPAP use, especially in preterm newborns. Our results identified a gestational age of less than 32 weeks and longer use of NCPAP are important factors associated with nasal pressure injuries. Methods to prevent the development of injuries such as the use of a prophylactic dressing along and replacement of binasal prongs with nasal masks are advocated.
Development of a Toileting and Containment Decision Support Tool
Authors: van Houten Paul , Newman Diane , Wijk Helle , Koehler Barbara , Costa Andrew , Hutt Edward
Published: January 2020

A multidisciplinary international expert panel was convened to provide input for a proposed decision support tool. This tool will assist health care professionals who are not specialized in incontinence care to assess individuals with urinary and/or fecal incontinence and recommend appropriate person-centered management options for the home care and ambulatory community settings. A targeted literature review was complemented by a series of interviews with experts in continence management, followed by a practitioner survey and rounds of expert opinion. A set of factors for assessment were defined, along with questions created to identify and quantify the factors. In addition, a range of lifestyle intervention, toileting and containment strategies were identified that were appropriate for the decision support tool. Future steps required to progress this work to a functioning tool are described.
Vertebrate palaeophysiology
Authors: Cubo Jorge , Huttenlocker Adam K.
Published: January 2020

Physiology is a functional branch of the biological sciences, searching for general rules by which explanatory hypotheses are tested using experimental procedures, whereas palaeontology is a historical science dealing with the study of unique events where conclusions are drawn from congruence among independent lines of evidence. Vertebrate palaeophysiology bridges these disciplines by using experimental data obtained from extant organisms to infer physiological traits of extinct ones and to reconstruct how they evolved. The goal of this theme issue is to understand functional innovations imprinted on modern vertebrate clades, and how to infer (or ‘retrodict’) physiological capacities in their ancient relativesa posteriori.As such, the present collection of papers deals with different aspects of a rapidly growing field to understand innovations in: phospho-calcic metabolism, acid–base homeostasis, thermometabolism, respiratory physiology, skeletal growth, palaeopathophysiology, genome size and metabolic rate, and it concludes with a historical perspective. Sometimes, the two components (physiological mechanism and palaeobiological inference) are proposed in separate papers. Other times, the two components are integrated in a single paper. In all cases, the approach was comparative, framed in a phylogenetic context, and included rigorous statistical methods that account for evolutionary patterns and processes.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
The evolution of mechanisms involved in vertebrate endothermy
Authors: Legendre Lucas J. , Davesne Donald
Published: January 2020

Endothermy, i.e. the endogenous production of metabolic heat, has evolved multiple times among vertebrates, and several strategies of heat production have been studied extensively by physiologists over the course of the twentieth century. The independent acquisition of endothermy by mammals and birds has been the subject of many hypotheses regarding their origin and associated evolutionary constraints. Many groups of vertebrates, however, are thought to possess other mechanisms of heat production, and alternative ways to regulate thermogenesis that are not always considered in the palaeontological literature. Here, we perform a review of the mechanisms involved in heat production, with a focus on cellular and molecular mechanisms, in a phylogenetic context encompassing the entire vertebrate diversity. We show that endothermy in mammals and birds is not as well defined as commonly assumed by evolutionary biologists and consists of a vast array of physiological strategies, many of which are currently unknown. We also describe strategies found in other vertebrates, which may not always be considered endothermy, but nonetheless correspond to a process of active thermogenesis. We conclude that endothermy is a highly plastic character in vertebrates and provides a guideline on terminology and occurrences of the different types of heat production in vertebrate evolution.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
Bone histology of varanopids (Synapsida) from Richards Spur, Oklahoma, sheds light on growth patterns and lifestyle in early terrestrial colonizers
Authors: Huttenlocker Adam K. , Shelton Christen D.
Published: January 2020

Varanopids were a group of small to medium-sized synapsids whose fossil record spans the Carboniferous through middle Permian. Although their phylogenetic relationships have received some interest in recent years, little is known about other aspects of their palaeobiology, including their skeletal growth, allometry and habitat preference. Here, we describe varanopid long bone histology based on a sample of well-preserved femora from the lower Permian Richards Spur fissure fill locality, Comanche County, Oklahoma, USA. The sample includes five femora from at least two varanopid taxa—
Mycterosaurus
and the large varanodontine
Varanops brevirostris
—and four additional mycterosaurine femora not diagnosed to genus. Prior work on femoral bone compactness provided a baseline to make lifestyle inferences and evaluate whether varanopids were ancestrally terrestrial. Moreover, the large availability of specimens spanning different sizes made possible an assessment of size-related ontogenetic histovariability. All specimens revealed moderately dense cortical bone tissues composed of sparsely vascularized parallel-fibred and lamellar bone with radially arranged rows of longitudinal canals (mostly simple), and many preserved regularly spaced growth marks (annuli and lines of arrested growth) as in modern varanids. We show that bone histology has the potential to explain how ballast was shed and the skeleton lightened for terrestrial mobility in ancestral synapsids and their basal amniote kin, as well as how adjustments in postnatal growth influenced the evolution of larger body sizes in the terrestrial frontier.

This article is part of the theme issue ‘Vertebrate palaeophysiology'.
The relationship between genome size and metabolic rate in extant vertebrates
Authors: Gardner Jacob D. , Laurin Michel , Organ Chris L.
Published: January 2020

Genome size has long been hypothesized to affect the metabolic rate in various groups of animals. The mechanism behind this proposed association is the nucleotypic effect, in which large nucleus and cell sizes influence cellular metabolism through surface area-to-volume ratios. Here, we provide a review of the recent literature on the relationship between genome size and metabolic rate. We also conduct an analysis using phylogenetic comparative methods and a large sample of extant vertebrates. We find no evidence that the effect of genome size improves upon models in explaining metabolic rate variation. Not surprisingly, our results show a strong positive relationship between metabolic rate and body mass, as well as a substantial difference in metabolic rate between endothermic and ectothermic vertebrates, controlling for body mass. The presence of endothermy can also explain elevated rate shifts in metabolic rate whereas genome size cannot. We further find no evidence for a punctuated model of evolution for metabolic rate. Our results do not rule out the possibility that genome size affects cellular physiology in some tissues, but they are consistent with previous research suggesting little support for a direct functional connection between genome size and basal metabolic rate in extant vertebrates.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
The closed eye harbors a unique microbiome in dry eye disease
Authors: Willis Kent A. , Postnikoff Cameron K. , Freeman Amelia B. , Rezonzew Gabriel , Nichols Kelly K. , Gaggar Amit , Lal Charitharth V.
Published: January 2020

Dry eye affects millions of individuals. In experimental models, dry eye disease is associated with T helper cell 17-mediated inflammation of the ocular surface that may cause persistent damage to the corneal epithelium. However, the initiating and perpetuating factors associated with chronic inflammation of the ocular surface remain unclear. The ocular microbiota alters ocular surface inflammation and may influence dry eye disease development and progression. Here, we collected serial samples of closed eye tears during a randomized clinical trial of a non-pharmaceutical dry eye therapy and used 16S rRNA metabarcoding to characterize the microbiome. We show the closed dry eye microbiome is distinct from the healthy closed eye microbiome. The ocular microbiome was described only recently, and this report implicates a distinct microbiome in ocular disease development. Our findings suggest an interplay between microbial commensals and inflammation on the ocular surface. This information may inform future studies of the pathophysiological mechanisms of dry eye disease.
Machine learning approaches for fracture risk assessment: a comparative analysis of genomic and phenotypic data in 5,130 older men
Authors: Wu Qing , Nasoz Fatma , Jung Jongyun , Bhattarai Bibek , Han Mira V
Published: January 2020

The study aims were to develop fracture prediction models by using machine learning approaches and genomic data, as well as to identify the best modeling approach for fracture prediction. The genomic data of Osteoporotic Fractures in Men, cohort Study (n= 5,130), was analyzed. After a comprehensive genotype imputation, genetic risk score (GRS) was calculated from 1,103 associated SNPs for each participant. Data were normalized and split into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and logistic regression were used to develop prediction models for major osteoporotic fractures separately, with GRS, bone density and other risk factors as predictors. For model training, the synthetic minority over-sampling technique was used to account for low fracture rate, and 10-fold cross-validation was employed for hyperparameters optimization. In the testing set, the area under the ROC curve (AUC) and accuracy were used to assess the model performance. The McNemar test was employed for pairwise comparisons to examine the accuracy difference between models. The results showed that the prediction performance of gradient boosting was the best, with AUC of 0.71 and an accuracy of 0.88, and the GRS ranked as the 7th most important variable in the model. The performance of random forest and neural network were also better than that of logistic regression. Pairwise comparisons showed that the accuracy difference between models was significant. This study suggested that improving fracture prediction can be achieved by incorporating genetic profiling and by utilizing the gradient boosting approach.
The ocrelizumab phase II extension trial suggests the potential to improve the risk:benefit balance in multiple sclerosis
Authors: Baker David , Pryce Gareth , James Louisa K. , Marta Monica , Schmierer Klaus
Published: January 2020

Objective

Ocrelizumab inhibits relapsing multiple sclerosis when administered every six months. Based on potential similar memory B cell depletion mechanisms with cladribine and alemtuzumab, we hypothesised that CD20-depletion of B cells by ocrelizumab may exhibit a duration of response exceeding the current licenced treatment interval.

Methods

Internet-located information from regulatory submissions and meeting reports relating to the unpublished open-label, phase II ocrelizumab extension trial (NCT00676715) were reviewed. This followed people (54-55/arm) with MS, who switched from placebo or interferon-beta to ocrelizumab for three 600mg treatment cycles (week 24, 48, 72) or people treated with ocrelizumab for four 600mg treatment cycles (week 0-72), followed by an 18 month treatment-free period.

Results

CD19+ B cells were rapidly depleted within 2 weeks and slow CD19+ B cell repopulation began about 6 months after the last infusion with median-repletion of over 15 months. The reduced annualized relapse rate during the published efficacy study appeared to be maintained in the extension study and there were no new T1 gadolinium-enhancing or T2 lesions detected in the treatment-free period. Importantly, within these extension cohorts, there appeared to be fewer adverse events and infections events.

Conclusions

Ocrelizumab appears to induce durable relapsing disease inhibition, within 3 treatment cycles Therefore, it may be possible to reduce the frequency of dosing to maintain efficacy, whilst limiting infection and other risks associated with continuous immunosuppression. Further studies are now clearly required to determine whether this data is robust, as few people seemed to complete the study.
Geographical Disparities in HIV Prevalence among Men Who Have Sex with Men and People Who Inject Drugs in Nigeria
Authors: Onovo Amobi , Kalaiwo Abiye , Katbi Moses , Ogorry Otse , Jaquet Antoine , Keiser Olivia
Published: January 2020

Background

Assessment of geographical heterogeneity of HIV among men who have sex with men (MSM) and people who inject drugs (PWID) can usefully inform targeted HIV prevention and care strategies. We aimed to measure HIV prevalence and identify hotspots of HIV infection among MSM and PWID in Nigeria.

Methods

We included all MSM and PWID accessing HIV testing services across seven prioritized states (Lagos, Nasarawa, Akwa Ibom, Cross Rivers, Rivers, Benue and the Federal Capital Territory) in three geographic regions (North Central, South South, South West) between Oct 1, 2016 and Sept 30, 2017. We extracted data from national testing registers, georeferenced all HIV test results aggregated at the level of Local Government Areas (LGAs), and calculated HIV prevalence. We calculated and compared HIV prevalence from our study to the integrated biological and behavioral surveillance survey (IBBSS) 2014 and used global spatial autocorrelation and hotspot analysis to highlight patterns of HIV infection, and to identify areas of significant clustering of HIV cases.

Findings

A positive HIV test was reported in 12.1% (95%CI 9.7-13.1) and 11.8% (95%CI 9.3-12.7) of the 26,423 MSMs and 9,474 PWIDs, respectively. Global spatial autocorrelation Moran’s I statistics revealed a clustered distribution of HIV infection among MSMs and PWIDs with a <5% and <1% likelihood that this clustered pattern could be due to chance respectively. Significant clusters of HIV infection (Getis-Ord-Gi* statistics) confined to the North Central, South-South regions were identified among MSM and PWID. Compared to the 2014 IBBSS our results suggest an increased HIV prevalence among PWID and a substantial decrease among MSM.

Interpretation

This study identified geographical areas to prioritize for control of HIV infection among MSM and PWID, thus demonstrating that geographical information system technology is a useful tool to inform public health planning for interventions for epidemic control of HIV infection.

Funding

Data used for this study was collected from Key Population program in Nigeria through PEPFAR/USAID. OK was funded by the Swiss National Science Foundation (grant no 163878).
Basal forebrain rhythmicity is modulated by the exploration phase of novel environments
Authors: Santos-Pata Diogo , Verschure Paul FMJ
Published: January 2020

Acquaintance to novel environments requires the encoding of spatial memories and the processing of unfamiliar sensory information in the hippocampus. Cholinergic signaling promotes the stabilization of hippocampal long-term potentiation (LTP) and contributes to theta-gamma oscillations balance, which is known to be crucial for learning and memory. However, the oscillatory mechanisms by which cholinergic signals are conveyed to the hippocampus are still poorly defined. We analyzed local field potentials from the basal forebrain (BF), a major source of cholinergic projections to the hippocampus, while rats explored a novel environment, and compared the modulation of BF theta (4-10Hz) and gamma (40-80Hz) frequency bands at distinct stages of spatial exploration. We found that BF theta and gamma display learning stage-related rhythmicity and that theta-gamma coupling is stronger at the later stages of exploration, a phenomenon previously observed in the hippocampus. Overall, our results suggest that the BF-hippocampal cholinergic signaling is conveyed via the stereotypical oscillatory patterns found during mnemonic processes, which questions the origins of the learning-related rhythmic activity found in the hippocampus.

KEY-POINTS

Basal forebrain theta oscillations decrease their strength in function of exploration time, as observed in the hippocampus.

BF gamma ripples (bursting events) are longer after learning.

BF Theta-gamma coupling increases after initial spatial exploration, suggesting BF cross-frequency coupling relation to the learning stage.
Neuronal firing and waveform alterations through ictal recruitment in humans
Authors: Merricks Edward M. , Smith Elliot H. , Emerson Ronald G. , Bateman Lisa M. , McKhann Guy M. , Goodman Robert R. , Sheth Sameer A. , Greger Bradley , House Paul A. , Trevelyan Andrew J. , Schevon Catherine A.
Published: January 2020

Abstract

Clinical analyses of neuronal activity during seizures, invariably using extracellular recordings, is greatly hindered by various phenomena that are well established in animal studies: changes in local ionic concentration, changes in ionic conductance, and intense, hypersynchronous firing. The first two alter the action potential waveform, whereas the third increases the “noise”; all three factors confound attempts to detect and classify single neurons (units). To address these analytical difficulties, we developed a novel template-matching based spike sorting method, which enabled identification of 1,239 single units in 27 patients with intractable focal epilepsy, that were tracked throughout multiple seizures. These new analyses showed continued neuronal firing through the ictal transition, which was defined as a transient period of intense tonic firing consistent with previous descriptions of the ictal wavefront. After the ictal transition, neurons displayed increased spike duration (p< 0.001) and reduced spike amplitude (p< 0.001), in keeping with prior animal studies; units in non-recruited territories, by contrast, showed more stable waveforms. All units returned to their pre-ictal waveforms after seizure termination. Waveshape changes were stereotyped across seizures within patients. Our analyses of single neuron firing patterns, at the ictal wavefront, showed widespread intense activation, and commonly involving marked waveshape alteration. We conclude that the distinction between tissue that has been recruited to the seizure versus non-recruited territories is evident at the level of single neurons, and that increased waveform duration and decreased waveform amplitude are hallmarks of seizure invasion that could be used as defining characteristics of local recruitment.

SignificanceStatement

Animal studies consistently show marked changes in action potential waveform during epileptic discharges, but acquiring similar evidence in humans has proved difficult. Assessing neuronal involvement in ictal events is pivotal to understanding seizure dynamics and in defining clinical localization of epileptic pathology. Using a novel method to track neuronal firing, we analyzed microelectrode array recordings of spontaneously occurring human seizures, and here report two dichotomous activity patterns. In cortex that is recruited to the seizure, neuronal firing rates increase and waveforms become longer in duration and shorter in amplitude, while penumbral tissue shows stable action potentials, in keeping with the “dual territory” model of seizure dynamics.
5’ UTR variants in the quantitative trait geneHnrnph1support reduced 5’ UTR usage and hnRNP H protein as a molecular mechanism underlying reduced methamphetamine sensitivity
Authors: Ruan Qiu T. , Yazdani Neema , Reed Eric R. , Beierle Jacob A. , Peterson Lucy P. , Luttik Kimberly P. , Szumlinski Karen K. , Johnson William E. , Ash Peter E. A. , Wolozin Benjamin , Bryant Camron D.
Published: January 2020

We previously identified a 210 kb region on chromosome 11 (50.37-50.58 Mb, mm10) containing two protein-coding genes (Hnrnph1, Rufy1) that was necessary for reduced methamphetamine-induced locomotor activity in C57BL/6J congenic mice harboring DBA/2J polymorphisms. Gene editing of a small deletion in the first coding exon supportedHnrnph1as a quantitative trait gene. We have since shown thatHnrnph1mutants also exhibit reduced methamphetamine-induced reward, reinforcement, and dopamine release. However, the quantitative trait variants (QTVs) that modulateHnrnph1function at the molecular level are not known. Nine single nucleotide polymorphisms and seven indels distinguish C57BL/6J from DBA/2J withinHnrnph1, including four variants within the 5’ untranslated region(UTR). Here, we show that a 114 kb introgressed region containingHnrnph1andRufy1was sufficient to cause a decrease in MA-induced locomotor activity. Gene-level transcriptome analysis of striatal tissue from 114 kb congenics versusHnrnph1mutants identified a nearly perfect correlation of fold-change in expression for those differentially expressed genes that were common to both mouse lines, indicating functionally similar effects on the transcriptome and behavior. Exon-level analysis (including noncoding exons) revealed decreased 5’ UTR usage ofHnrnph1and immunoblot analysis identified a corresponding decrease in hnRNP H protein in 114 kb congenic mice. Molecular cloning of theHnrnph15’ UTR containing all four variants (but none of them individually) upstream of a reporter induced a decrease in reporter signal in both HEK293 and N2a cells, thus identifying a set of QTVs underlying molecular regulation ofHnrnph1.
Designing and implementing programmable depletion in sequencing libraries with DASHit
Authors: Dynerman David , Lyden Amy , Quan Jenai , Caldera Saharai , McGeever Aaron , Dimitrov Boris , King Ryan , Cirolia Giana , Tan Michelle , Sit Rene , van den Berge Maarten , Kerstjens Huib A. M. , Faiz Alen , Christenson Stephanie , Langelier Charles , DeRisi Joe , Crawford Emily
Published: January 2020

Since Next-Generation Sequencing produces reads uniformly subsampled from an input library, highly abundant sequences may mask interesting low abundance sequences. The DASH (Depleting Abundant Sequences by Hybridization) technique takes advantage of the programmability of CRISPR/Cas9 to deplete unwanted high-abundance sequences. Because desired depletion targets vary by sample type, here we describe DASHit, software that outputs an optimal DASH target set given a sequencing dataset, an updated DASH protocol, and show depletion results with DASHit-designed targets for three different species.
Calcium-independent lipid release from astrocytes modulates neuronal excitability
Authors: Wang Fushun , Bradshaw Heather B. , Pena Salvador , Jablonska Beata , Xavier Julia , Chittaranjan Siddharth , Gong Sheng , Li Baoman , Chandler-Militello Devin , Bekar Lane K. , Smith Nathan A.
Published: January 2020

An accumulating amount of data suggests that Ca2+-dependent gliotransmitter release plays a key role in the modulation of neuronal networks. Here, we tested the hypothesis that in response to agonist exposure, astrocytes release lipid modulators through activation of Ca2+-independent phospholipase A2(iPLA2) activity. We found that cultured rat astrocytes treated with selective ATP and glutamatergic agonists released arachidonic acid (AA) and/or its derivatives, including the endogenous cannabinoid 2-arachidonoyl-sn-glycerol (2AG) and prostaglandin E2 (PGE2). Surprisingly, the buffering of cytosolic Ca2+resulted in a sharp increase in agonist-induced lipid release by astrocytes. In addition, the astrocytic release of PGE2increased miniature excitatory postsynaptic potentials (mEPSPs) by inhibiting the opening of neuronal Kv channels in brain slices. This study provides the first evidence showing that a Ca2+-independent pathway regulates the release of PGE2from astrocytes and further demonstrates the functional role of astrocytic lipid release in the modulation of synaptic activity.

SIGNIFICANCE

Until now, most studies that implicate astrocytes in the modulation of synaptic activity have focused on Ca2+-dependent release of traditional gliotransmitters such as D-serine, ATP, and glutamate. Mobilization of intracellular stores of Ca2+occurs within a matter of seconds, but this novel Ca2+-independent lipid pathway in astrocytes could occur on a faster time scale and thus play a role in the rapid signaling processes involved in synaptic potentiation, attention, and neurovascular coupling.
The role of startle fluctuation and non-response startle reflex in tracking amygdala dynamics
Authors: Liu Mengting , Amey Rachel C. , Magerman Adam , Scott Matthew , Forbes Chad E.
Published: January 2020

The startle reflex is considered a sensitive defensive reaction to potential threats that manifests as a unique eye blink-like pattern in the EMG. Eye blink EMG has a bell-shaped potential when startle probes are elicited, that strongly corresponds to amygdala activity. Considering how amygdala activity fluctuates over time in response to emotional and self-threatening stimuli, observing startle eyeblink size fluctuation over time could provide a cost-effective, convenient, and less resource intensive means for examining amygdala activity over time. Yet based on current standards in the literature, often startle evoked eye blink EMG values do not exhibit activity 3SDs from the mean eyeblink response, thus these trials are typically excluded from startle analyses. It stands to reason, however, that these trials may still index amygdala activity in a meaningful way. Through investigating the association between startle eyeblink amplitude, corresponding ERP amplitude, and underlying neural activity, the current study provides evidence that startle amplitudes exhibit a linear relationship with proxies for amygdala activity, e.g., N100 amplitudes and regions heavily interconnected with the amygdala. Specifically, the startle reflex correlates to large amount of brain regions in N100 time window in addition to the N100 amplitude. Thus, both valid and otherwise traditionally non-valid startle reflex responses appear to index amygdala activity and should be included accordingly. This approach could help salvage large amounts of meaningful data traditionally excluded from studies interested in amygdala responses to various stimuli over time.
A practical staging atlas to study embryonic development ofOctopus vulgarisunder controlled laboratory conditions
Authors: Astrid Deryckere , Ruth Styfhals , Erica A.G. Vidal , Eduardo Almansa , Eve Seuntjens
Published: January 2020

Background

Octopus vulgarishas been an iconic cephalopod species for neurobiology research as well as for cephalopod aquaculture. It is one of the most intelligent and well-studied invertebrates, possessing both long- and short-term memory and the striking ability to perform complex cognitive tasks. Nevertheless, how the common octopus developed these uncommon features remains enigmatic.O. vulgarisfemales spawn thousands of small eggs and remain with their clutch during their entire development, cleaning, venting and protecting the eggs. In fact, eggs incubated without females usually do not develop normally, mainly due to biological contamination (fungi, bacteria, etc.). This high level of parental care might have hampered laboratory research on the embryonic development of this intriguing cephalopod.

Results

Here, we present a completely parameter-controlled artificial seawater standalone egg incubation system that replaces maternal care and allows successful embryonic development of a small-egged octopus species until hatching in a laboratory environment. We also provide a practical and detailed 1 staging atlas based on bright-field and light sheet fluorescence microscopy imaging for precise monitoring of embryonic development. The atlas has a comparative section to benchmark stages to the different scales published by Naef (1928), Arnold (1965) and Boletzky (2016). Finally, we provide methods to monitor health and wellbeing of embryos during organogenesis.

Conclusion

Besides introducing the study ofO. vulgarisembryonic development to a wider community, this work can be a high-quality reference for comparative evolutionary developmental biology.
Comparison of cellular Na+assays by flow fluorometry with ANG-2 and flame emission: Pitfalls in using ionophores for calibrating fluorescent probes
Authors: Yurinskaya Valentina E. , Aksenov Nikolay D. , Moshkov Alexey V. , Goryachaya Tatyana S. , Vereninov Alexey A.
Published: January 2020

Monovalent ions, sodium in particular, are involved in fundamental cell functions, such as water balance and electric processes, intra- and intercellular signaling, cell movement, pH regulation and metabolite transport into and out of cells. Fluorescent probes are indispensable tools for monitoring intracellular sodium levels in single living cells in heterogeneous cell populations and tissues. Since the fluorescence of sodium-sensitive dyes in cells is significantly different from that in an aqueous solution, the fluorescence signal is calibratedin situby changing the concentration of extracellular sodium in the presence of ionophores, making the membrane permeable to sodium and equilibrating its intra- and extracellular concentrations. The reliability of this calibration method has not been well studied. Here, we compare the determinations of the intracellular sodium concentration by flame emission photometry and flow cytometry using the Na+-sensitive probe Asante Natrium Green-2 (ANG). The intracellular Na+concentration was altered using known ionophores or, alternatively, by blocking the sodium pump with ouabain or by causing cell apoptosis with staurosporine. The use of U937 cells cultured in suspension allowed the fluorometry of single cells by flow cytometry and flame emission analysis of samples checked for uniform cell populations. It is revealed that the ANG fluorescence of cells treated with ionophores is approximately two times lower than that in cells with the same Na+concentration but not treated with ionophores. Although the mechanism is still unknown, this effect should be taken into account when a quantitative assessment of the concentration of intracellular sodium is required. Sodium sensitive fluorescent dyes are widely used at present, and the problem is practically significant.
Germination response of invasive plants to soil burial depth and litter accumulation is species specific
Authors: Sonkoly Judit , Valkó Orsolya , Balogh Nóra , Godó Laura , Kelemen András , Kiss Réka , Miglécz Tamás , Tóth Edina , Tóth Katalin , Tóthmérész Béla , Török Péter
Published: January 2020

Questions

Plant invasions are considered among the biggest threats to biodiversity worldwide. In a full-factorial greenhouse experiment we analysed the effect of soil burial depth and litter cover on the germination of invasive plants. We hypothesised that (i) burial depth and litter cover affect the germination of the studied species, (ii) the effects of burial and litter cover interact with each other, and (iii) the effects are species-specific, but dependent on seed size.

Methods

We tested the germination and seedling growth of 11 herbaceous invasive species in a full-factorial experiment using four levels of seed burial depths and litter cover. We analysed the effect of burial, litter cover, and their interactions on germination, seedling length and biomass across species and at the species level.

Results

Soil burial depth and litter cover had a significant effect on the germination of the studied species, but there were considerable differences between species. We observed a general trend of species with bigger seeds being not or less seriously affected by soil burial and litter cover than smaller-seeded species. Correlations between seed weight and effect sizes mostly confirmed this general trend, but not in the case of soil burial.

Conclusions

Our findings confirmed that seed size is a major driver of species’ response to litter cover and to the combined effects of litter cover and soil burial, but there is no general trend regarding the response to soil burial depth. Despite its very small seeds the germination ofCynodon dactylonwas not affected by soil burial. The germination ofAmbrosia artemisiifoliawas hampered by both soil burial and litter cover despite its relatively large seeds. Thus, specific information on species’ response to burial depth and litter accumulation is crucial when planning management or restoration in areas threatened by plant invasions.