Search

Objetivo. Detectar anomalías cromosómicas que afectan tanto el número de cromosomas como su estructura para definir la etiología de la enfermedad permitiéndole al clínico establecer posteriores planes de manejo y asesoramiento genético. Materiales y métodos. Para reconocer y detectar variaciones inusuales en la morfología cromosómica, se aplican distintas técnicas de cultivo celular y bandeo cromosómico. Entre ellas el laboratorio de citogenética de la Universidad Nacional presta el servicio de: Cariotipo convencional bandeo C y G, Cariotipo de alta resolución cromosómica con bandeo Q, G y R, Cariotipo para evaluación de fragilidad cromosómica del cromosoma X, Cariotipo para evaluación de fragilidad cromosómica en presencia de mitomicina C (MMC), Cariotipo para evaluación de estados leucémicos (cromosoma Philadelphia), Cariotipo de líquido amniótico. Resultados. Entre 2005 y 2013 se han atendido aproximadamente 3000 pacientes que gracias a los diagnósticos citogenéticos realizados por medio de técnicas citogenéticas convencionales y moleculares y a la unión con estrategias de prevención primordial y primaria (asesoría preconcepcional, diagnostico y tamizaje prenatal y neonatal), secundaria (diagnóstico oportuno) y terciaria (guías de manejo anticipatorio) se ha comprobado la mejora en la mortalidad, morbilidad, discapacidad, reducción en costos de aseguramiento y promoción de una mejoría en la calidad de vida de los pacientes, sus familias y los perfiles en salud de la comunidad. Conclusiones. El acceso a los servicios de análisis citogenético ha permitido detectar anomalías y desarrollar estrategias de manejo adecuadas para los pacientes atendidos y ha servido de base para la investigación y la enseñanza en la institución.

Background: A core feature of body dysmorphic disorder (BDD) is body image disturbance. Many with BDD misperceive and are dissatisfied with the sizes and shapes of body parts, but detailed quantification and analysis of this has not yet been performed. To address this gap, we applied Somatomap 3D, a digital avatar tool, to quantify body image disturbances by assessing body size estimation (BSE) accuracy and body dissatisfaction., Methods: Sixty-one adults (31 with BDD, 30 healthy controls) created avatars to reflect their perceived current body and ideal body by altering 23 body part sizes and lengths using Somatomap 3D. Physical measurements of corresponding body parts were recorded for comparison. BSE accuracy (current minus actual) and body dissatisfaction (ideal minus current) were compared between groups and in relation to BDD symptom severity using generalized estimating equations., Results: Individuals with BDD significantly over- and under-estimated certain body parts compared to healthy controls. Individuals with BDD overall desired significantly thinner body parts compared to healthy controls. Moreover, those with worse BSE accuracy had greater body dissatisfaction and poorer insight., Conclusion: In sum, this digital avatar tool revealed disturbances in body image in individuals with BDD that may have perceptual and cognitive/affective components., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Across the life sciences, an ongoing effort over the last 50 years has made data and methods more reproducible and transparent. This openness has led to transformative insights and vastly accelerated scientific progress 1,2 . For example, structural biology 3 and genomics 4,5 have undertaken systematic collection and publication of protein sequences and structures over the past half-century, and these data have led to scientific breakthroughs that were unthinkable when data collection first began (e.g. 6 ). We believe that neuroscience is poised to follow the same path, and that principles of open data and open science will transform our understanding of the nervous system in ways that are impossible to predict at the moment. To this end, new social structures along with active and open scientific communities are essential 7 to facilitate and expand the still limited adoption of open science practices in our field 8 . Unified by shared values of openness, we set out to organize a symposium for Open Data in Neuroscience (ODIN) to strengthen our community and facilitate transformative neuroscience research at large. In this report, we share what we learned during this first ODIN event. We also lay out plans for how to grow this movement, document emerging conversations, and propose a path toward a better and more transparent science of tomorrow.

We develop a data harmonization approach for C. elegans volumetric microscopy data, still or video, consisting of a standardized format, data pre-processing techniques, and a set of human-in-the-loop machine learning based analysis software tools. We unify a diverse collection of 118 whole-brain neural activity imaging datasets from 5 labs, storing these and accompanying tools in an online repository called WormID (wormid.org). We use this repository to train three existing automated cell identification algorithms to, for the first time, enable accuracy in neural identification that generalizes across labs, approaching human performance in some cases. We mine this repository to identify factors that influence the developmental positioning of neurons. To facilitate communal use of this repository, we created open-source software, code, web-based tools, and tutorials to explore and curate datasets for contribution to the scientific community. This repository provides a growing resource for experimentalists, theorists, and toolmakers to (a) study neuroanatomical organization and neural activity across diverse experimental paradigms, (b) develop and benchmark algorithms for automated neuron detection, segmentation, cell identification, tracking, and activity extraction, and (c) inform models of neurobiological development and function.

Anorexia nervosa is an often-severe psychiatric illness characterized by significantly low body weight, fear of gaining weight, and distorted body image. Multiple neuroimaging studies have shown abnormalities in cortical morphology, mostly associated with the starvation state. Investigations of white matter, while more limited in number, have suggested global and regional volume reductions, as well as abnormal diffusivity in multiple regions including the corpus callosum. Yet, no study has specifically examined thickness of the corpus callosum, a large white matter tract instrumental in the inter-hemispheric integration of sensory, motor, and cognitive information. We analyzed MRI data from 48 adolescents and adults with anorexia nervosa and 50 healthy controls, all girls/women, to compare corpus callosum thickness and examined relationships with body mass index (BMI), illness duration, and eating disorder symptoms (controlling for BMI). There were no significant group differences in corpus callosum thickness. In the anorexia nervosa group, severity of body shape concerns was significantly, positively correlated with callosal thickness in the rostrum, genu, rostral body, isthmus, and splenium. In addition, there were significant positive correlations between eating disorder-related obsessions and compulsions and thickness of the anterior midbody, rostral body, and splenium. There were no significant associations between callosal thickness and BMI or illness duration. In sum, those with AN with worse concerns about bodily appearance and worse eating disorder-related obsessive thought patterns and compulsive behaviours have regionally thicker corpus callosum, independent of current weight status. These findings provide important neurobiological links to key, specific eating disorder behavioural phenotypes., (© 2024. The Author(s).)

Mycetomas are endemic diseases in tropical and sub-tropical countries of Africa, Asia and America, mainly affecting rural populations living below the poverty line. We report a particular case of a mycetoma associated with pregnancy whose evolution was good, but at the cost of significant financial expenses. This was a 39-year-old woman who developed a fungal mycetoma due to Madurella mycetomatis from the ingunocrural region. The patient had to develop several previous pregnancies on this site of mycetoma, the outcome of which was favorable. The last pregnancy was accompanied by an aggravation of the mycetoma in the form of polyfistulized inflammatory swelling of the right inguino-crural region emitting black grains. Magnetic Resonance Imaging (MRI) of the region showed invasion of the adductor muscles at the level of the root of the thigh on its antero-internal side with no sign of pelvic extension or underlying bone lesion. The patient was treated by surgery associated with antifungal treatment. The evolution was favorable for pregnancy and mycetoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ndour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Optimal dietary intake of omega-3 long-chain polyunsaturated fatty acids (n3-LCPUFAs) is critical to human health across the lifespan. However, omega-3 index (O3I) determination is not routinely assessed due to complicated procedures for n3-LCPUFA analysis from the phospholipid (PL) fraction of erythrocytes. Herein, a high-throughput method for lipidomics based on multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry was applied to identify circulating PLs as surrogate biomarkers of O3I in two randomized placebo-controlled trials. An untargeted lipidomic data workflow using a subgroup analysis of serum extracts from sunflower oil versus high-dose fish oil (FO)-supplemented participants revealed that ingested n3-LCPUFAs were primarily distributed as their phosphatidylcholines (PCs) relative to other PL classes. In both high-dose FO (5.0 g/day) and EPA-only trials (3.0 g/day), PC (16:0_20:5) was the most responsive PL, whereas PC (16:0_22:6) was selective to DHA-only supplementation. We also demonstrated that the sum concentration of both these PCs in fasting serum or plasma samples was positively correlated to the O3I following FO (r = 0.708, P = 1.02 × 10 -11 , n = 69) and EPA- or DHA-only supplementation (r = 0.768, P = 1.01 × 10 -33 , n = 167). Overall, DHA was more effective in improving the O3I (ΔO3I = 4.90 ± 1.33%) compared to EPA (ΔO3I = 2.99 ± 1.19%) in young Canadian adults who had a poor nutritional status with an O3I (3.50 ± 0.68%) at baseline. Our method enables the rapid assessment of the O3I by directly measuring two circulating PC species in small volumes of blood, which may facilitate screening applications for population and precision health., Competing Interests: Conflict of interest S. M. P. reports grants or research contracts from the US National Dairy Council, Canadian Institutes for Health Research, Dairy Farmers of Canada, Roquette Freres, Ontario Centre of Innovation, Nestle Health Sciences, Myos, National Science and Engineering Research Council, and the US NIH during the conduct of the study; personal fees from Nestle Health Sciences, nonfinancial support from Enhanced Recovery, outside the submitted work. S. M. P. has patents licensed to Exerkine but reports no financial gains from any patent or related work. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Anorexia nervosa (AN) is characterized by low body weight, fear of gaining weight, and distorted body image. Anxiety may play a role in the formation and course of the illness, especially related to situations involving food, eating, weight, and body image. To understand distributed patterns and consistency of neural responses related to anxiety, we enrolled 25 female adolescents with AN and 22 non-clinical female adolescents with mild anxiety who underwent two fMRI sessions in which they saw personalized anxiety-provoking word stimuli and neutral words. Consistency in brain response patterns across trials was determined using a multivariate representational similarity analysis (RSA) approach within anxiety circuits and in a whole-brain voxel-wise searchlight analysis. In the AN group there was higher representational similarity for anxiety-provoking compared with neutral stimuli predominantly in prefrontal regions including the frontal pole, medial prefrontal cortex, dorsolateral prefrontal cortex, and medial orbitofrontal cortex, although no significant group differences. Severity of anxiety correlated with consistency of brain responses within anxiety circuits and in cortical and subcortical regions including the frontal pole, middle frontal gyrus, orbitofrontal cortex, thalamus, lateral occipital cortex, middle temporal gyrus, and cerebellum. Higher consistency of activation in those with more severe anxiety symptoms suggests the possibility of a greater degree of conditioned brain responses evoked by personally-relevant emotional stimuli. Anxiety elicited by disorder-related stimuli may activate stereotyped, previously-learned neural responses within- and outside of classical anxiety circuits. Results have implications for understanding consistent and automatic responding to environmental stimuli that may play a role in maintenance of AN., (© 2023. Springer Nature Limited.)

Background Quality of Life (QoL) is a prognostic factor in heart failure (HF) of patients with acquired cardiac disease. The aim of this study was to determine the predictive value of QoL on outcomes in adults with congenital heart disease (ACHD) and HF. Methods and Results Quality of life of 196 adults with congenital heart disease with clinical heart failure (HF) (mean age: 44.3±13.8 years; 51% male; 56% with complex congenital heart disease; 47% New York Heart Association class III/IV) included in the prospective multicentric registry FRESH-ACHD (French Survey on Heart Failure-Adult with Congenital Heart Disease) was assessed using the 36-Item Short Form Survey (SF-36), a patient-reported survey. The primary end point was defined by all-cause death, HF-related hospitalization, heart transplantation, and mechanical circulatory support. At 12 months, 28 (14%) patients reached the combined end point. Patients with low quality of life experienced major adverse events more frequently (logrank P =0.013). On univariate analysis, lower score at physical functioning (hazard ratio [HR], 0.98 [95% CI, 0.97-0.99]; P =0.008), role limitations related to physical health (HR, 0.98 [95% CI, 0.97-0.99]; P =0.008), and general health dimensions of the SF-36 (HR, 0.97 [95% CI, 0.95-0.99]; P =0.002) were significantly predictive of cardiovascular events. However, after multivariable analysis, SF-36 dimensions were no longer significantly associated with the primary end point. Conclusions Patients with congenital heart disease with HF and poor quality of life experience severe events more frequently, making quality of life assessment and rehabilitation programs essential to alter their trajectory.

The neurophysiology of cells and tissues are monitored electrophysiologically and optically in diverse experiments and species, ranging from flies to humans. Understanding the brain requires integration of data across this diversity, and thus these data must be findable, accessible, interoperable, and reusable (FAIR). This requires a standard language for data and metadata that can coevolve with neuroscience. We describe design and implementation principles for a language for neurophysiology data. Our open-source software (Neurodata Without Borders, NWB) defines and modularizes the interdependent, yet separable, components of a data language. We demonstrate NWB's impact through unified description of neurophysiology data across diverse modalities and species. NWB exists in an ecosystem, which includes data management, analysis, visualization, and archive tools. Thus, the NWB data language enables reproduction, interchange, and reuse of diverse neurophysiology data. More broadly, the design principles of NWB are generally applicable to enhance discovery across biology through data FAIRness., Competing Interests: OR, AT, RL, SG, PB, IS, LN, KS, LF, KB No competing interests declared, BD BD is the Founder and CEO of CatalystNeuro, a software consulting company that works with neurophysiology labs to build state-of-the-art data management workflows. Much of this work involves converting data from lab-specific formats to the NWB standard, and enhancing analysis and visualization tools to read and write NWB data. As such, Dr. Dichter has a personal financial state in the success of the NWB standard, LN LN is a software engineer at MBF Bioscience, a for-profit biotech company that develops microscopy software and hardware, (© 2022, Rübel, Tritt, Ly et al.)

Objectives: This study aimed to assess the incidence, associated factors, and outcomes of atrial arrhythmias in adults with atrioventricular septal defect (AVSD)., Background: Data regarding atrial arrhythmias in adults with AVSD are particularly scarce., Methods: Data were analyzed from a multicentric cohort of adult patients with AVSD. Lifetime cumulative incidences of atrial arrhythmias were studied. Multiple logistic regression models were used to identify risk factors., Results: A total of 391 patients (61.6% women) were enrolled with a mean age of 36.3 ± 16.3 years and a mean follow-up of 17.3 ± 14.2 years after initial surgical repair. Overall, 98 patients (25.1%) developed at least 1 episode of atrial arrhythmia at a mean age of 39.2 ± 17.2 years. The mean ages of patients at first episode of intra-atrial re-entrant tachycardia (IART)/ focal atrial tachycardia (FAT) and atrial fibrillation were 33.7 ± 15.3 and 44.3 ± 16.5 years, respectively. The lifetime risks for developing atrial arrhythmia to ages 20, 40, and 60 years were 3.7%, 17.8%, and 55.3%, respectively. IART/FAT was the leading arrhythmia until the age of 45, then atrial fibrillation surpassed IART/FAT. Age (odds ratio [OR]: 1.4; 95% confidence interval [CI]: 1.2-1.6), number of cardiac surgeries (OR: 4.1; 95% CI: 2.5-6.9), left atrial dilatation (OR: 3.1; 95% CI: 1.4-6.8), right atrial dilatation (OR: 4.1; 95% CI: 1.7-10.3), and moderate or severe left atrioventricular valve regurgitation (OR: 3.7; 95% CI: 1.2-11.7) were independently associated with a higher risk of atrial arrhythmias, whereas the type of AVSD and the age at repair were not. The occurrence of atrial arrhythmias was associated with pacemaker implantation (41.8% vs. 8.5%; P < 0.001), heart failure (24.5% vs. 1.0%; P < 0.001), and cerebrovascular accidents (11.2% vs. 3.4%; P = 0.007)., Conclusions: The lifetime risk of atrial arrhythmias in patients with AVSD is considerable with more than half of patients developing ≥1 atrial arrhythmia by the age of 60 and is associated with a significant morbidity. The risk in partial/intermediate AVSD is as high as in complete AVSD and is not impacted by age at repair., Competing Interests: Funding Support and Author Disclosures The authors have received a research grant from the French Institute of Health and Medical Research and the Fédération Française de Cardiologie., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the diagnostic performances of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion., Background: PPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of 18 F-FDG PET/CT remains poorly studied in PPVE., Methods: A retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent 18 F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of 18 F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study., Results: A total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of 18 F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). 18 F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE., Conclusions: Using 18 F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes., Competing Interests: Funding Support and Author Disclosures Drs Venet, Jalal, and Thambo were supported by the French Government as part of the “Investments of the future” program managed by the National Research Agency (grant reference ANR-10-IAHU-04). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Body dysmorphic disorder (BDD) is characterized by preoccupations with misperceptions of one's physical appearance. Previous neuroimaging studies in BDD have yet to examine dynamic functional connectivity (FC) patterns between brain areas, necessary to capture changes in activity in response to stimuli and task conditions. We used Leading Eigenvector Dynamics Analysis to examine whole-brain dynamic FC from fMRI data during an own-face viewing task in 29 unmedicated adults with BDD with facial concerns and 30 healthy controls. The task involved two parts: (1) unconstrained, naturalistic viewing and (2) holding visual attention in the center of the image, to reduce scanning and fixation on perceived facial flaws. An FC state consisting of bilateral medial orbitofrontal cortex regions occurred significantly less often during the visual attention condition and afterward during the unconstrained face viewing in BDD participants, compared to the first unconstrained face viewing, a pattern that differed from controls. Moreover, the probability of this state during the second unconstrained face viewing was associated with severity of obsessions and compulsions and degree of poor insight in BDD, suggesting its clinical significance. These findings have implications for understanding the pathophysiology of own-face viewing in BDD and how it is affected by modification of viewing patterns, which may have implications for novel perceptual retraining treatment designs., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Noonan syndrome (NS) is a genetic disorder characterized by facial dysmorphism, congenital heart disease, and short stature. In very rare cases, patients with this syndrome have coronary disease. Their management and prognosis are currently unclear. We have described 4 cases of coronary aneurysms/coronary ectasia and 1 case of a single coronary artery in patients with adult Noonan syndrome, followed in a medical and surgical center of adult congenital heart disease. The average age was 49.4years old. The majority of them had both pulmonary stenosis and interauricular communication. None had symptoms of angina, at rest, or with stress. Only one patient who had any structural heart disease, had a thrombotic complication with chronic occlusion of the right coronary and anterior inter ventricular artery, fortuitous finding, with no ischemic signs to functional tests, treated only with anti-vitamin K. Finally, any deaths have also been reported in our series. Coronary artery diseases essentially coronary aneurysm/ectasia remain a rare condition in adult patients with NS. Evolution is unknown and complications such as coronary artery thrombosis do not necessarily require surgical treatment., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Critical access hospitals (CAHs) play an important role in providing access to care for many patients in rural communities. Prior studies have shown that these facilities are able to provide timely and quality care for patients who undergo various elective and emergency general surgical procedures. However, little is known about the quality and reimbursement of surgical care for patients undergoing surgery for hip fractures at CAHs compared with non-CAH facilities., Questions/purposes: Are there any differences in 90-day complications, readmissions, mortality, and Medicare payments between patients undergoing surgery for hip fractures at CAHs and those undergoing surgery at non-CAHs?, Methods: The 2005 to 2014 Medicare 100% Standard Analytical Files were queried using ICD-9 procedure codes to identify Medicare-eligible beneficiaries undergoing open reduction and internal fixation (79.15, 79.35, and 78.55), hemiarthroplasty (81.52), and THA (81.51) for isolated closed hip fractures. This database was selected because the claims capture inpatient diagnoses, procedures, charged amounts and paid claims, as well as hospital-level information of the care, of Medicare patients across the nation. Patients with concurrent fixation of an upper extremity, lower extremity, and/or polytrauma were excluded from the study to ensure an isolated cohort of hip fractures was captured. The study cohort was divided into two groups based on where the surgery took place: CAHs and non-CAHs. A 1:1 propensity score match, adjusting for baseline demographics (age, gender, Census Bureau-designated region, and Elixhauser comorbidity index), clinical characteristics (fixation type and time to surgery), and hospital characteristics (whether the hospital was located in a rural ZIP code, the average annual procedure volume of the operating facility, hospital bed size, hospital ownership and teaching status), was used to control for the presence of baseline differences in patients presenting at CAHs and those presenting at non-CAHs. A total of 1,467,482 patients with hip fractures were included, 29,058 of whom underwent surgery in a CAH. After propensity score matching, each cohort (CAH and non-CAH) contained 29,058 patients. Multivariate logistic regression analyses were used to assess for differences in 90-day complications, readmissions, and mortality between the two matched cohorts. As funding policies of CAHs are regulated by Medicare, an evaluation of costs-of-care (by using Medicare payments as a proxy) was conducted. Generalized linear regression modeling was used to assess the 90-day Medicare payments among patients undergoing surgery in a CAH, while controlling for differences in baseline demographics and clinical characteristics., Results: Patients undergoing surgery for hip fractures were less likely to experience many serious complications at a critical access hospital (CAH) than at a non-CAH. In particular, after controlling for patient demographics, hospital-level factors and procedural characteristics, patients treated at a CAH were less likely to experience: myocardial infarction (3% (916 of 29,058) versus 4% (1126 of 29,058); OR 0.80 [95% CI 0.74 to 0.88]; p < 0.001), sepsis (3% (765 of 29,058) versus 4% (1084 of 29,058); OR 0.69 [95% CI 0.63 to 0.78]; p < 0.001), acute renal failure (6% (1605 of 29,058) versus 8% (2353 of 29,058); OR 0.65 [95% CI 0.61 to 0.69]; p < 0.001), and Clostridium difficile infections (1% (367 of 29,058) versus 2% (473 of 29,058); OR 0.77 [95% CI 0.67 to 0.88]; p < 0.001) than undergoing surgery in a non-CAH. CAHs also had lower rates of all-cause 90-day readmissions (18% (5133 of 29,058) versus 20% (5931 of 29,058); OR 0.83 [95% CI 0.79 to 0.86]; p < 0.001) and 90-day mortality (4% (1273 of 29,058) versus 5% (1437 of 29,058); OR 0.88 [95% CI 0.82 to 0.95]; p = 0.001) than non-CAHs. Further, CAHs also had risk-adjusted lower 90-day Medicare payments than non-CAHs (USD 800, standard error 89; p < 0.001)., Conclusion: Patients who received hip fracture surgical care at CAHs had a lower risk of major medical and surgical complications than those who had surgery at non-CAHs, even though Medicare reimbursements were lower as well. Although there may be some degree of patient selection at CAHs, these facilities appear to provide high-value care to rural communities. These findings provide evidence for policymakers evaluating the impact of the CAH program and allocating funding resources, as well as for community members seeking emergent care at local CAH facilities., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that neither he or she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2020 by the Association of Bone and Joint Surgeons.)

Although the effect of hypoxia on p53 in human papillomavirus (HPV)-positive cancer cells has been studied for decades, the impact of p53 regulation on downstream targets and cellular adaptation processes during different periods under hypoxia remains elusive. Here, we show that, despite continuous repression of HPV16 E6/E7 oncogenes, p53 did not instantly recover but instead showed a biphasic regulation marked by further depletion within 24 h followed by an increase at 72 h. Of note, during E6/E7 oncogene suppression, lysosomal degradation antagonizes p53 reconstitution. Consequently, the transcription of p53 responsive genes associated with senescence (e.g., PML and YPEL3 ) cannot be upregulated. In contrast, downstream genes involved in autophagy (e.g., DRAM1 and BNIP3 ) were activated, allowing the evasion of senescence under hypoxic conditions. Hence, dynamic regulation of p53 along with its downstream network of responsive genes favors cellular adaptation and enhances cell survival, although the expression of the viral E6/E7 -oncogenes as drivers for proliferation remained inhibited under hypoxia.

The objective of this cross-sectional study was to determine the type of care that can be achieved and the epidemiological profile of patients attending the 3 public dental practices in the Haut-Sassandra region, in Côte d'Ivoire. The data collection concerned socio-demographic characteristics, reason for consultation, oral hygiene, dental condition, malocclusions and the availability of equipment for the performance of procedures. The 400 patients observed (51.5% male) were aged 16.0 to 86.0 years (mean=35.5 years; SD=13.1 years). The main reasons for consultation were pain (91.5%) and aesthetics (23.5%). Oral hygiene was insufficient for 36.8% of subjects. Oral conditions were malocclusions (12.8%), caries (98.7%) and edentulous (65.7%) with only 11.8% with prosthesis. The average DMFT index was 9.3. Only extractions and resin attached prostheses were possible in all 3 health facilities. Preventive dentistry (sealent, fluoridation), dentofacial orthopedics and implantology were not available in any dental practice. The most frequently performed acts were extractions (74.5%). The results of this study highlight the need for oral health planning with service equipment and awareness among populations who shouldn't wait until they are in pain to consult., Competing Interests: Conflict of interest: the authors declare no potential conflict of interests., (©Copyright: the Author(s), 2019.)

Background: In Côte d'Ivoire, maternal health service utilization indicators remain low despite improvements in health coverage and the availability of free health care for pregnant women. The objective of the study was to identify the determinants associated with the use of maternal health services in the department of Bloléquin, in western Côte d'Ivoire., Methods: We conducted a cross-sectional study with an analytical focus. The study sample size was 400 women. Study participants were selected through a two-stage cluster survey. The data were collected using a standardized questionnaire whose items concerned socio-demographic data, the different uses of maternal health services, namely childbirth assisted by a health professional, use of family planning, prenatal consultation and postnatal consultation. Logistic regression was used to investigate factors associated with the use of maternal health services. The significance of the statistical tests was set at 5%. The odds ratios and 95% confidence intervals were calculated and interpreted., Results: The results showed that women made less use of family planning services (OR = 0.4), prenatal consultation (OR = 0.2) and assisted childbirth (OR = 0.2) when they provided the funding for care themselves. Women with monthly incomes above $26.8 used family planning services 4 times more than those with lower incomes. Married women used prenatal consultations 3 times more often than unmarried women (CI 95%  = 1.4-7.3). Desiring pregnancy increased the use of post-natal consultations by 3 times (CI 95%  = 1.5-6.1)., Conclusion: Improving the use of maternal health services in western Côte d'Ivoire requires taking into account women's socio-cultural and economic challenges. In initiatives related to the financial empowerment of women, efforts must be made at the level of emotional considerations related to pregnancy.

A large body of evidence has linked unhealthy eating patterns with an alarming increase in obesity and chronic disease worldwide. However, existing methods of assessing dietary intake in nutritional epidemiology rely on food frequency questionnaires or dietary records that are prone to bias and selective reporting. Herein, metabolic phenotyping was performed on 42 healthy participants from the Diet and Gene Intervention (DIGEST) pilot study, a parallel two-arm randomized clinical trial that provided complete diets to all participants. Matching single-spot urine and fasting plasma specimens were collected at baseline, and then following two weeks of either a Prudent or Western diet with a weight-maintaining menu plan designed by a dietician. Targeted and nontargeted metabolite profiling was conducted using three complementary analytical platforms, where 80 plasma metabolites and 84 creatinine-normalized urinary metabolites were reliably measured (CV < 30%) in the majority of participants (>75%) after implementing a rigorous data workflow for metabolite authentication with stringent quality control. We classified a panel of metabolites with distinctive trajectories following two weeks of food provisions when using complementary univariate and multivariate statistical models. Unknown metabolites associated with contrasting dietary patterns were identified with high-resolution MS/MS, as well as co-elution after spiking with authentic standards if available. Overall, 3-methylhistidine and proline betaine concentrations increased in both plasma and urine samples after participants were assigned a Prudent diet ( q < 0.05) with a corresponding decrease in the Western diet group. Similarly, creatinine-normalized urinary imidazole propionate, hydroxypipecolic acid, dihydroxybenzoic acid, and enterolactone glucuronide, as well as plasma ketoleucine and ketovaline increased with a Prudent diet ( p < 0.05) after adjustments for age, sex, and BMI. In contrast, plasma myristic acid, linoelaidic acid, linoleic acid, α-linoleic acid, pentadecanoic acid, alanine, proline, carnitine, and deoxycarnitine, as well as urinary acesulfame K increased among participants following a Western diet. Most metabolites were also correlated ( r > ± 0.30, p < 0.05) to changes in the average intake of specific nutrients from self-reported diet records reflecting good adherence to assigned food provisions. Our study revealed robust biomarkers sensitive to short-term changes in habitual diet, which is needed for accurate monitoring of healthy eating patterns in free-living populations, and evidence-based public health policies for chronic disease prevention.

Although the role of high-risk human papillomaviruses (hrHPVs) as etiological agents in cancer development has been intensively studied during the last decades, there is still the necessity of understanding the impact of the HPV E6 and E7 oncogenes on host cells, ultimately leading to malignant transformation. Here, we used newly established immortalized human keratinocytes with a well-defined HPV16 E6E7 expression cassette to get a more complete and less biased overview of global changes induced by HPV16 by employing transcriptome sequencing (RNA-Seq) and stable isotope labeling by amino acids in cell culture (SILAC). This is the first study combining transcriptome and proteome data to characterize the impact of HPV oncogenes in human keratinocytes in comparison with their virus-negative counterparts. To enhance the informative value and accuracy of the RNA-Seq data, four different bioinformatic workflows were used. We identified potential novel upstream regulators (e.g., CNOT7, SPDEF, MITF, and PAX5) controlling distinct clusters of genes within the HPV-host cell network as well as distinct factors (e.g., CPPED1, LCP1, and TAGLN) with essential functions in cancer. Validated results in this study were compared to data sets from The Cancer Genome Atlas (TCGA), demonstrating that several identified factors were also differentially expressed in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and HPV-positive head and neck squamous cell carcinomas (HNSCs). This highly integrative approach allows the identification of novel HPV-induced cellular changes that are also reflected in cancer patients, providing a promising omics data set for future studies in both basic and translational research. IMPORTANCE Human papillomavirus (HPV)-associated cancers still remain a big health problem, especially in developing countries, despite the availability of prophylactic vaccines. Although HPV oncogenes have been intensively investigated for decades, a study applying recent advances in RNA-Seq and quantitative proteomic approaches to a precancerous model system with well-defined HPV oncogene expression alongside HPV-negative parental cells has been missing until now. Here, combined omics analyses reveal global changes caused by the viral oncogenes in a less biased way and allow the identification of novel factors and key cellular networks potentially promoting malignant transformation. In addition, this system also provides a basis for mechanistic research on novel key factors regulated by HPV oncogenes, especially those that are confirmed in vivo in cervical cancer as well as in head and neck cancer patient samples from TCGA data sets., (Copyright © 2019 Yang et al.)

Depression is a commonly occurring symptom in obsessive-compulsive disorder (OCD), and is associated with worse functional impairment, poorer quality of life, and poorer treatment response. Understanding the underlying neurochemical and connectivity-based brain mechanisms of this important symptom domain in OCD is necessary for development of novel, more globally effective treatments. To investigate biopsychological mechanisms of comorbid depression in OCD, we examined effective connectivity and neurochemical signatures in the pregenual anterior cingulate cortex (pACC), a structure known to be involved in both OCD and depression. Resting-state functional magnetic resonance imaging (fMRI) and 1 H magnetic resonance spectroscopy (MRS) data were obtained from participants with OCD (n=49) and healthy individuals of equivalent age and sex (n=25). Granger causality-based effective (directed) connectivity was used to define causal networks involving the right and left pACC. The interplay between fMRI connectivity, 1 H MRS and clinical data was explored by applying moderation and mediation analyses. We found that the causal influence of the right dorsal anterior midcingulate cortex (daMCC) on the right pACC was significantly lower in the OCD group and showed significant correlation with depressive symptom severity in the OCD group. Lower and moderate levels of glutamate (Glu) in the right pACC significantly moderated the interaction between right daMCC-pACC connectivity and depression severity. Our results suggest a biochemical-connectivity-psychological model of pACC dysfunction contributing to depression in OCD, particularly involving intracingulate connectivity and glutamate levels in the pACC. These findings have implications for potential molecular and network targets for treatment of this multi-faceted psychiatric condition.

Cognitive-behavioral therapy (CBT) is effective for pediatric obsessive-compulsive disorder (OCD), but non-response is common. Brain glutamate (Glu) signaling may contribute to OCD pathophysiology and moderate CBT outcomes. We assessed whether Glu measured with magnetic resonance spectroscopy (MRS) was associated with OCD and/or CBT response. Youths aged 7-17 years with DSM-IV OCD and typically developing controls underwent 3 T proton echo-planar spectroscopic imaging (PEPSI) MRS scans of pregenual anterior cingulate cortex (pACC) and ventral posterior cingulate cortex (vPCC)-regions possibly affected by OCD-at baseline. Controls returned for re-scan after 8 weeks. OCD youth-in a randomized rater-blinded trial-were re-scanned after 12-14 weeks of CBT or after 8 weeks of minimal-contact waitlist; waitlist participants underwent a third scan after crossover to 12-14 weeks of CBT. Forty-nine children with OCD (mean age 12.2±2.9 years) and 29 controls (13.2±2.2 years) provided at least one MRS scan. At baseline, Glu did not differ significantly between OCD and controls in pACC or vPCC. Within controls, Glu was stable from scan-to-scan. Within OCD subjects, a treatment-by-scan interaction (p=0.034) was observed, driven by pACC Glu dropping 19.5% from scan-to-scan for patients randomized to CBT, with minor increases (3.8%) for waitlist participants. The combined OCD participants (CBT-only plus waitlist-CBT) also showed a 16.2% (p=0.004) post-CBT decrease in pACC Glu. In the combined OCD group, within vPCC, lower pre-CBT Glu predicted greater post-CBT improvement in symptoms (CY-BOCS; r=0.81, p=0.00025). Glu may be involved in the pathophysiology of OCD and may moderate response to CBT.

Background: Galectin-7 (Gal-7) is negatively regulated in cervical cancer, and appears to be a link between the apoptotic response triggered by cancer and the anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited., Methods: Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer, we ectopically re-expressed it in the HeLa and SiHa cervical cancer cell lines, and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Differences between samples were assessed with the Kruskall-Wallis, Dunn's Multiple Comparison and T tests. Kaplan-Meier and log-rank tests were used to determine overall survival., Results: Gal-7 was constantly downregulated in our meta-analysis (p < 0.0001). Tumors with combined high Gal-7 and low galectin-1 expression (p = 0.0001) presented significantly better prognoses (p = 0.005). In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio (p < 0.05) and their xenografts displayed strong growth retardation (p < 0.001). Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments (FDR < 0.05 %). Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity, and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples., Conclusions: Gal-7 re-expression affects the regulation of molecular networks in cervical cancer that are involved in diverse cancer hallmarks, such as metabolism, growth control, invasion and evasion of apoptosis. The effect of Gal-7 extends to the microenvironment, where networks involved in its configuration and in immune surveillance are particularly affected.

Key Points: At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca(2+) entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid postsynaptic Ca(2+) signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics. This component can amount up to 20% of the EPSC, and this fraction is maintained even at the high frequencies sometimes encountered in sensory processing. Modelling based on our biophysical characterization of T-type calcium channels in Purkinje cells suggests that the brief spine EPSCs cause the activated T-type channels to deactivate rather than inactivate, enabling repetitive activation., Abstract: In the cerebellum, sensory information is conveyed to Purkinje cells (PC) via the granule cell/parallel fibre (PF) pathway. Plasticity at the PF-PC synapse is considered to be a mechanism of information storage in motor learning. The induction of synaptic plasticity in the cerebellum and elsewhere usually involves intracellular Ca(2+) signals. Unusually, postsynaptic Ca(2+) signalling in PF-PC spines does not involve ionotropic glutamatergic receptors because postsynaptic NMDA receptors are absent and the AMPA receptors are Ca(2+) -impermeable; postsynaptic voltage-gated Ca(2+) channels therefore constitute the sole rapid Ca(2+) signalling mechanism. Low-threshold activated T-type calcium channels are present at the synapse, although their contribution to PF-PC synaptic responses is unknown. Taking advantage of 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide, a selective T-type channel antagonist, we show in the mouse that inhibition of these channels reduces PF-PC excitatory postsynaptic currents and excitatory postsynaptic potentials by 15-20%. This contribution was preserved during sparse input and repetitive activity. We characterized the biophysical properties of native T-type channels in young animals and modelled their activation during simulated dendritic excitatory postsynaptic potential waveforms. The comparison of modelled and observed synaptic responses suggests that T-type channels only activate in spines that are strongly depolarized by their synaptic input, a process requiring a high spine neck resistance. This brief and local activation ensures that T-type channels rapidly deactivate, thereby limiting inactivation during repetitive synaptic activity. T-type channels are therefore ideally situated to provide synaptic Ca(2+) entry at PF-PC spines., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)