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Objectives The aim of the study was to determine the aetiology and clinical predictors of peripheral lymphadenopathy in HIV-infected individuals during the antiretroviral ( ARV) era in a nontuberculosis endemic setting. Methods A multicentred, retrospective cohort study of peripheral lymph node biopsies in HIV-positive adults was carried out. A total of 107 charts were identified and reviewed for clinical features, lymphadenopathy size, and ARV use and duration. Biopsy results were categorized, and multivariate logistic regression determined independent predictors of lymphadenopathy aetiology. Results Evaluation of 107 peripheral lymph node biopsies revealed that 42.9% of peripheral lymphadenopathy was attributable to malignancy, 49.5% to reactive changes, and 7.5% to infections, with only 2.8% of all cases secondary to tuberculosis. Fevers, weight loss, ARV use, and lower viral loads are significantly associated with nonreactive lymphadenopathy. Conclusions Lymphadenopathy is likely to be reactive or malignant in nontuberculosis endemic regions. Readily available clinical features can aid clinicians in predicting the underlying aetiology, those at risk for malignancy, and who to biopsy. [ABSTRACT FROM AUTHOR]

Introduction: This study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early-stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well-established measures., Methods: For 291 older adults with healthy cognition or early mild cognitive impairment, Exploratory factor analyses were used to identify the factor structure of the NPE. Factor and total scores were examined for their psychometric properties and associations with AD risk biomarkers., Results: Composite scores from the novel cognitive and functional measures demonstrated better psychometric properties (distribution and test-retest reliability) and stronger associations with AD-related demographic, genetic, and brain risk markers than well-established measures, DISCUSSION: These novel measures have potential for use as primary cognitive and functional outcomes in early-stage AD clinical trials., Highlights: Well-established cognitive tests may not accurately detect subtle cognitive changes. No Practice Effect (NPE) and Computerized Functional Skills Assessment and Training are novel measures designed to have improved psychometric properties. NPE had Executive Function, Cognitive Control/Speed, and Episodic Memory domains. Novel measures had better psychometric properties compared to established measures. Significant associations with Alzheimer's disease biomarkers were found with novel measures., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

T cells mediate organ injury and repair. A proportion of unconventional kidney T cells called double-negative (DN) T cells (TCR + CD4 - CD8 - ), with anti-inflammatory properties, were previously demonstrated to protect from early injury in moderate experimental acute kidney injury (AKI). However, their role in repair after AKI has not been studied. We hypothesized that DN T cells mediate repair after severe AKI. C57B6 mice underwent severe (40 min) unilateral ischemia-reperfusion injury (IRI). Kidney DN T cells were studied by flow cytometry and compared with gold-standard anti-inflammatory CD4 + regulatory T cells (Tregs). In vitro effects of DN T cells and Tregs on renal tubular epithelial cell (RTEC) repair after injury were quantified with live-cell analysis. DN T cells, Tregs, CD4, or vehicle were adoptively transferred after severe AKI. Glomerular filtration rate (GFR) was measured using fluorescein isothiocyanate (FITC)-sinistrin. Fibrosis was assessed with Masson's trichrome staining. Profibrotic genes were measured with qRT-PCR. Percentages and the numbers of DN T cells substantially decreased during repair phase after severe AKI, as well as their activation and proliferation. Both DN T cells and Tregs accelerated RTEC cell repair in vitro. Post-AKI transfer of DN T cells reduced kidney fibrosis and improved GFR, as did Treg transfer. DN T cell transfer lowered transforming growth factor (TGF)β1 and α-smooth muscle actin (αSMA) expression. DN T cells reduced effector-memory CD4 + T cells and IL-17 expression. DN T cells undergo quantitative and phenotypical changes after severe AKI, accelerate RTEC repair in vitro as well as improve GFR and renal fibrosis in vivo. DN T cells have potential as immunotherapy to accelerate repair after AKI. NEW & NOTEWORTHY Double-negative (DN) T cells (CD4 - CD8 - ) are unconventional kidney T cells with regulatory abilities. Their role in repair from acute kidney injury (AKI) is unknown. Kidney DN T cell population decreased during repair after ischemic AKI, in contrast to regulatory T cells (Tregs) which increased. DN T cell administration accelerated tubular repair in vitro, while after severe in vivo ischemic injury reduced kidney fibrosis and increased glomerular filtration rate (GFR). DN T cell infusion is a potential therapeutic agent to improve outcome from severe AKI.

Objective: To assess how obesity, normal weight (NW) versus overweight/obese (OW/OB), impacts platelet-rich plasma's (PRP) effectiveness during in vitro fertilization and how obesity affects platelets during the menstrual cycle., Methods: Endometrial mean thickness (EMT), embryo implantation, and clinical pregnancy were assessed using a self-controlled retrospective study that enrolled 59 patients with two failed cycles and treated with autologous PRP (three-dose scheme). The NHANES dataset was used to assess platelet changes during the menstrual cycle, using the mean platelet volume to platelet count ratio (MPR) index. The COSINOR packages for R were used to determine rhythmicity., Results: PRP treatments significantly improved the EMT (2.5 ± 1.4 mm, P<0.001), unaffected by obesity. After the PRP treatment, one patient spontaneously became pregnant; therefore, 58 patients underwent embryo transfer (62 cycles), of which in 39 cycles the embryos implanted (63.9%). This was a significant improvement from their previous cycle (vs. 22.6%, P<0.001). Clinical pregnancy also improved with the PRP treatment over the previous cycle (57.4% vs. 16.1%, P<0.001). When stratified by obesity, there was an appreciable decrease in embryo implantation and clinical pregnancy rates for the OW/OB group; nevertheless, the PRP treatment significantly improved embryo implantation and clinical pregnancy (P<0.05). A rhythm was observed with the MPR index (P<0.05) only for the NW group, suggesting that the platelets normally fluctuate during the menstrual cycle., Conclusion: PRP improved embryo implantation and clinical pregnancy rates; however, these beneficial effects were attenuated by obesity. PRP presumptively promoted a change in the uterine environment to mimic the normal findings associated with normal-weight women., Competing Interests: None., (AJTR Copyright © 2024.)

Background: Neurofibromatosis type 1 (NF1) is one of the most common RASopathies predisposing affected patients to melanic lesions and benign tumors. NF1 is associated with considerable esthetic and functional burden negatively affecting the patient's quality of life (QoL). This study aims to assess the clinical features of NF1 patients and evaluate their impact on QoL. We identified NF1 patients from a public health database of a region in Spain. All patients underwent clinical and ophthalmological evaluation for NF1 features. We measured QoL using the Spanish version of the Skindex-29., Results: Forty patients fulfilled the NF1 National Institute of Health criteria when we recruited patients. The median age was 42.00 years (IQR 26.5 -53.75). The median total Skindex-29 score was 12.3 (IQR 5.9-22.4); (emotion: 15.0, IQR 5.0-37.5; symptoms 8.9, IQR 0.0-17.9 and functioning 8.3; IQR 0.5-18.3). Women and NF1 patients with lower educational levels were associated with poorer QoL scores. We identified itching and sleep troubles to influence NF1 patients' QoL negatively., Conclusion: NF1 considerably influences the psychological well-being of NF1 patients. We observed that female and low-educated patients scored higher on the emotional dimension of the Skindex-29 and could, therefore, be more at risk of depression. We also pointed out some "minor symptoms" that negatively impact NF1 patients' QoL such, as itching and sleep troubles which doctors could treat if sought by doctors., (© 2024. The Author(s).)

T cells are important in the pathogenesis of acute kidney injury (AKI), and TCR + CD4 - CD8 - (double negative-DN) are T cells that have regulatory properties. However, there is limited information on DN T cells compared to traditional CD4 + and CD8 + cells. To elucidate the molecular signature and spatial dynamics of DN T cells during AKI, we performed single-cell RNA sequencing (scRNA-seq) on sorted murine DN, CD4 + , and CD8 + cells combined with spatial transcriptomic profiling of normal and post AKI mouse kidneys. scRNA-seq revealed distinct transcriptional profiles for DN, CD4 + , and CD8 + T cells of mouse kidneys with enrichment of Kcnq5, Klrb1c, Fcer1g, and Klre1 expression in DN T cells compared to CD4 + and CD8 + T cells in normal kidney tissue. We validated the expression of these four genes in mouse kidney DN, CD4 + and CD8 + T cells using RT-PCR and Kcnq5, Klrb1, and Fcer1g genes with the NIH human kidney precision medicine project (KPMP). Spatial transcriptomics in normal and ischemic mouse kidney tissue showed a localized cluster of T cells in the outer medulla expressing DN T cell genes including Fcer1g. These results provide a template for future studies in DN T as well as CD4 + and CD8 + cells in normal and diseased kidneys., (© 2023. The Author(s).)

Background/aim: Resistant triple-negative breast cancer (TNBC) is a subtype of this disease that is resistant to conventional chemotherapy agents. IFN-τ is a cytokine that has recently been shown to have immunoregulatory and antitumor effects. The present study aimed to examine the antiproliferative and apoptosis effects of IFN-τ in breast cancer cells and the antitumor effect in a murine tumor model of TNBC., Materials and Methods: Murine breast cancer 4T1 cells were cultured and treated with ovine IFN-τ and through MTT and Caspase-Glo 3/7 assays, viability and cell death were determined. In addition, the antitumor effect of IFN-τ was determined in a murine tumor model of TNBC., Results: Ovine IFN-τ showed a concentration-dependent antiproliferative effect on 4T1 murine breast cancer cells. Also, treatment of 4T1 cells with IFN-τ induced the activation of caspase 3 and 7, which is indicative of apoptotic cell death. Moreover, we detected an increase in the expression of type I interferon receptor (IFNAR1/2) in cells treated with IFN-. The intratumoral application of IFN-τ in mice inhibited tumor growth compared to the control non-treated group, and the effect was associated with the increased expression of GM-CSF., Conclusion: Ovine IFN-τ may be an effective immunotherapeutic cytokine for the treatment of TNBC., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The lateral hypothalamus (LH) plays a critical role in sensory integration to organize behavior responses. However, how projection-defined LH neuronal outputs dynamically transmit sensorimotor signals to major downstream targets to organize behavior is unknown. Here, using multi-fiber photometry, we show that three major LH neuronal outputs projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and lateral habenula (LHb) exhibit significant coherent activity in mice engaging sensory-evoked or self-initiated motor responses. Increased activity at LH axon terminals precedes movement initiation during active coping responses and the activity of serotonin neurons and dopamine neurons. The optogenetic activation of LH axon terminals in either of the DRN, VTA, or LHb was sufficient to increase motor initiation but had different effects on passive avoidance and sucrose consumption. Our findings support the complementary role of three projection-defined LH neuronal outputs in the transmission of sensorimotor signals to major downstream regions at movement onset., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Introduction: Thrombogenesis, a major cause of implantable cardiovascular device failure, can be addressed through the use of biodegradable polymers modified with anticoagulating moieties. This study introduces a novel polyester urethane urea (PEUU) functionalized with various anti-platelet deposition molecules for enhanced antiplatelet performance in regenerative cardiovascular devices. Methods: PEUU, synthesized from poly-caprolactone, 1,4-diisocyanatobutane, and putrescine, was chemically oxidized to introduce carboxyl groups, creating PEUU-COOH. This polymer was functionalized in situ with polyethyleneimine, 4-arm polyethylene glycol, seleno-L-cystine, heparin sodium, and fondaparinux. Functionalization was confirmed using Fourier-transformed infrared spectroscopy and X-ray photoelectron spectroscopy. Bio-compatibility and hemocompatibility were validated through metabolic activity and hemolysis assays. The anti-thrombotic activity was assessed using platelet aggregation, lactate dehydrogenase activation assays, and scanning electron microscopy surface imaging. The whole-blood clotting time quantification assay was employed to evaluate anticoagulation properties. Results: Results demonstrated high biocompatibility and hemocompatibility, with the most potent anti-thrombotic activity observed on pegylated surfaces. However, seleno-L-cystine and fondaparinux exhibited no anti-platelet activity. Discussion: The findings highlight the importance of balancing various factors and addressing challenges associated with different approaches when developing innovative surface modifications for cardiovascular devices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Rodríguez-Soto, Suárez Vargas, Ayala-Velásquez, Aragón-Rivera, Ostos, Cruz, Muñoz Camargo, Kim, D’Amore, Wagner and Briceño.)

Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery. These indices of recovery included increased glomerular filtration rate, diminution of kidney fibrosis, and reduction of kidney profibrotic gene expression. Amoxicillin was found to increase stool Alistipes, Odoribacter and Stomatobaculum species while significantly depleting Holdemanella and Anaeroplasma. Specifically, amoxicillin treatment reduced kidney CD4 + T cells, interleukin (IL)-17 + CD4 + T cells, and tumor necrosis factor-α double negative T cells while it increased CD8 + T cells and PD1 + CD8 + T cells. Amoxicillin also increased gut lamina propria CD4 + T cells while decreasing CD8 + T and IL-17 + CD4 + T cells. Amoxicillin did not accelerate repair in germ-free or CD8-deficient mice, demonstrating microbiome and CD8 + T lymphocytes dependence for amoxicillin protective effects. However, amoxicillin remained effective in CD4-deficient mice. Fecal microbiota transplantation from amoxicillin-treated to germ-free mice reduced kidney fibrosis and increased Foxp3 + CD8 + T cells. Amoxicillin pre-treatment protected mice against kidney bilateral ischemia reperfusion injury but not cisplatin-induced AKI. Thus, modification of gut bacteria with amoxicillin after severe ischemic AKI is a promising novel therapeutic approach to accelerate recovery of kidney function and mitigate the progression of AKI to chronic kidney disease., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: We analyzed the factors associated with vaccine uptake, vaccination intention, and reasons for vaccine hesitancy in Belize., Methods: We collected a nationally representative household survey of the population in Belize aged 15 years and older (September-October 2021). We compared potential correlates between vaccinated and unvaccinated people using Chi-square tests. Then, we performed logistic regression analysis to identify factors associated with vaccination uptake among all respondents and vaccination intention among the unvaccinated., Results: Our analysis included data from 1261 interviews. Nearly four out of every five people reported being vaccinated, having received at least one dose. Adolescents and young adults were more likely to be unvaccinated. Significant differences were observed for most behavioral variables. Among the 41.7% of the unvaccinated respondents who said they would probably not or definitely not get vaccinated, the primary reason for their hesitation was fear of side effects. Additionally, almost one third of the unvaccinated individuals expressed a lack of trust in vaccines. Factors associated with increased likelihood of vaccination were efficacy beliefs, self-efficacy and vaccine attitudes. People who believed it was easy to get a vaccine were over 23 times (OR 23.63 [95% CI: 14.21-39.27]) more likely to be vaccinated, while those who believed in vaccine safety were 2.57 times [OR 95% CI: 1.52-4.35] more likely to be vaccinated. Among the unvaccinated, factors associated with intention to get vaccinated were self-identifying as Garifuna and having clear efficacy beliefs., Conclusions: To our knowledge, this is the first study describing factors associated with COVID-19 vaccine uptake and vaccine hesitancy in Belize. Our findings revealed that accessibility has been the primary limitation in increasing vaccine coverage, and <7% of the eligible population have been strong vaccine deniers. To enhance vaccine uptake, targeted outreach efforts are necessary to address access barriers. Our results call for increased efforts improving self-efficacy, efficacy beliefs, and perceived norms., Competing Interests: 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. The opinions expressed in this publication are those of the authors and do not necessarily reflect the views of the Inter-American Development Bank, its Board of Directors, or the countries they represent. The authors report no conflicts of interest., (© 2023 The Authors.)

Background: There is a sparsity of knowledge of the specific mechanisms through which financial and non-financial incentives impact the performance of health teams. This study aims to address this knowledge gap by examining an in-kind incentives program for healthcare teams implemented in three districts in Belize (2012-2022) as part of the Salud Mesoamerica Initiative, which aimed to improve healthcare quality., Methods: We performed a qualitative study to understand the mechanisms through which the in-kind incentive program supported quality improvement in Belize. We conducted key informant interviews (April-June 2021) remotely on a sample of former and current healthcare workers from Belize's Ministry of Health and Wellness familiar with the program. We analyzed responses using qualitative content analysis. We used open coding to identify patterns and themes., Results: We conducted eight key informant interviews from a pool of thirty potential informants. Our analysis of the interviews yielded a total of 11 major themes with 27 subthemes. Most informants reported that in-kind incentives were not the primary motivation for improving their performance, though they did acknowledge that incentives had increased their attention on the quality of care provided. Conversely, we found that quarterly measurements and supportive supervision by national level authorities offered an external validation mechanism and instilled frontline staff with a sense of shared responsibility towards improving their performance. The majority of informants conveyed positive opinions about the in-kind incentives program., Conclusions: Our study contributes to the understanding of how in-kind incentives can enhance performance. We found that in-kind incentives created extrinsic motivation, leading to an increased focus on quality. Standardized measurements and supportive supervision improved intrinsic motivation and formed a stronger commitment to quality of care. Rather than focusing on tangible incentives, explicitly incorporating standardized measurements and supportive supervision in the routine work of the Ministry of Health could have longer lasting effects on quality improvement., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rios-Zertuche 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.)

Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next-generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body's innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

For more than 70 years, the countries of South America have been attempting to eliminate foot-and-mouth disease (FMD), but a regional strategy had not been established by all the affected countries until 1988. The Action Plan 1988-2009 of the Hemispheric Program for the Eradication of Foot-and-Mouth Disease (PHEFA 1988-2009) resulted in an FMD-free status in 88.4% of the bovine population of South America. However, countries of the Andean sub-region maintained an FMD endemic. In addition, sporadic outbreaks in vaccinated cattle populations have been reported in countries of the Southern Cone, endangering the disease-free status in these countries. Within this context, the PHEFA 2011-2020 was approved to eliminate FMD from the subcontinent, and this review describes the most important milestones during its execution. FMD in Ecuador and sporadic outbreaks in the Southern Cone sub-region were effectively eliminated. The outbreaks that occurred in Colombia in 2017 and 2018 were successfully controlled. The type C virus was removed from the vaccines in use in most countries, based on a risk assessment. This review also describes the progress made by the countries advancing toward official recognition as FMD-free in all their territories, with Bolivia, Brazil, and Peru leading the progressive suspension of vaccination to achieve FMD-free status without vaccination. Consequently, at the end of PHEFA 2011-2020, Venezuela was, and still is, the only country in the region whose control program has suffered setbacks, and no evidence has suggested that the transmission and infection of the bovine population have been eliminated. At the end of 2020, a new PHEFA Action Plan 2021-2025 was approved with a five-year horizon, to complete the eradication of the disease in the Americas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rivera, Sanchez-Vazquez, Pituco, Buzanovsky, Martini and Cosivi.)

Background and Purpose: High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere., Methods: We used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis-Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis., Results: Among 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032)., Conclusions: Our findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.

We sought to explore mental health and psychosocial impact among young people (18 to 24 years old) in Bogotá during the first months of the COVID-19 pandemic., Methods: We carried a cross sectional study using a web-based survey to assess mental health and personal impact among 18 to 24 years old living in Bogotá during the first 4 months of the 2020 COVID-19 pandemic lockdown. The depressive symptoms were measured with PHQ-8 and anxiety symptoms with (GAD-7). We also designed a questionnaire exploring changes in personal, family and social life., Results: Overall, 23% of the sample (n = 834) reported mild depressive symptoms (males 24% and females 23%); 29% reported moderate depressive symptoms (males 28%, females 30%); 22% moderate-severe symptoms (males 20%, females 23%) and 17% severe symptoms (males 15%, females 17%). Mild anxiety symptoms were reported by 29% of the sample (males 30%, females 29%); moderate anxiety symptoms by 29% (males 26%, females 30%); moderate-severe 18% (males 15%, females 20%) and severe anxiety by 6.0% (males 6.0% and females 6.0%). High symptoms of depression (PHQ-8 ≥ 10) were associated with being female, considering that the quarantine was stressful, having one member of the family losing their job, worsening of family relationships, decrease of physical activity and having a less nutritious diet. Having high anxiety symptoms (GAD-7 ≥ 10) were associated with sometimes not having enough money to buy food., Conclusions: The first months of the pandemic lockdown were associated with high depressive and anxiety symptoms among young persons living in Bogotá, Colombia. Increasing public health measures to provide support for young people is needed during lockdowns and it is necessary to further explore the long-term mental health impact due to personal, family and social changes brought by the COVID-19 pandemic., Competing Interests: Conflict of interest: The authors do not declare any conflict of interest related to this research., (© 2022 the Author(s), licensee AIMS Press.)

Vascular grafts (VGs) are medical devices intended to replace the function of a blood vessel. Available VGs in the market present low patency rates for small diameter applications setting the VG failure. This event arises from the inadequate response of the cells interacting with the biomaterial in the context of operative conditions generating chronic inflammation and a lack of regenerative signals where stenosis or aneurysms can occur. Tissue Engineered Vascular grafts (TEVGs) aim to induce the regeneration of the native vessel to overcome these limitations. Besides the biochemical stimuli, the biomaterial and the particular micro and macrostructure of the graft will determine the specific behavior under pulsatile pressure. The TEVG must support blood flow withstanding the exerted pressure, allowing the proper compliance required for the biomechanical stimulation needed for regeneration. Although the international standards outline the specific requirements to evaluate vascular grafts, the challenge remains in choosing the proper biomaterial and manufacturing TEVGs with good quality features to perform satisfactorily. In this review, we aim to recognize the best strategies to reach suitable mechanical properties in cell-free TEVGs according to the reported success of different approaches in clinical trials and pre-clinical trials.

Objective: The aim of this study was to develop and evaluate the performance of artificial intelligence (AI) models that can identify safe and dangerous zones of dissection, and anatomical landmarks during laparoscopic cholecystectomy (LC)., Summary Background Data: Many adverse events during surgery occur due to errors in visual perception and judgment leading to misinterpretation of anatomy. Deep learning, a subfield of AI, can potentially be used to provide real-time guidance intraoperatively., Methods: Deep learning models were developed and trained to identify safe (Go) and dangerous (No-Go) zones of dissection, liver, gallbladder, and hepatocystic triangle during LC. Annotations were performed by 4 high-volume surgeons. AI predictions were evaluated using 10-fold cross-validation against annotations by expert surgeons. Primary outcomes were intersection- over-union (IOU) and F1 score (validated spatial correlation indices), and secondary outcomes were pixel-wise accuracy, sensitivity, specificity, ± standard deviation., Results: AI models were trained on 2627 random frames from 290 LC videos, procured from 37 countries, 136 institutions, and 153 surgeons. Mean IOU, F1 score, accuracy, sensitivity, and specificity for the AI to identify Go zones were 0.53 (±0.24), 0.70 (±0.28), 0.94 (±0.05), 0.69 (±0.20). and 0.94 (±0.03), respectively. For No-Go zones, these metrics were 0.71 (±0.29), 0.83 (±0.31), 0.95 (±0.06), 0.80 (±0.21), and 0.98 (±0.05), respectively. Mean IOU for identification of the liver, gallbladder, and hepatocystic triangle were: 0.86 (±0.12), 0.72 (±0.19), and 0.65 (±0.22), respectively., Conclusions: AI can be used to identify anatomy within the surgical field. This technology may eventually be used to provide real-time guidance and minimize the risk of adverse events., Competing Interests: Conflicts of Interest and Source of Funding: There were no sources of funding for this manuscript. D.A. is a consultant for Johnson & Johnson Institute, Verily Life Sciences, Worrell, and Mosaic Research Management. D.A. and A.N.W. have received grant funding from Olympus. A.O. has received honoraria for speaking and teaching from Medtronic, Ethicon, and Merck. A.A. is a consultant for Johnson & Johnson Institute. The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Double negative (DN) T cells, one of the least studied T lymphocyte subgroups, express T cell receptor αβ but lack CD4 and CD8 coreceptors. DN T cells are found in multiple organs including kidney, lung, heart, gastrointestinal tract, liver, genital tract, and central nervous system. DN T cells suppress inflammatory responses in different disease models including experimental acute kidney injury, and significant evidence supports an important role in the pathogenesis of systemic lupus erythematosus. However, little is known about these cells in other kidney diseases. Therefore, it is important to better understand different functions of DN T cells and their signaling pathways as promising therapeutic targets, particularly with the increasing application of T cell-directed therapy in humans. In this review, we aim to summarize studies performed on DN T cells in normal and diseased organs in the setting of different disease models with a focus on kidney., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Neurofibromatosis type 1 (NF1) predisposes to the development of dermal and plexiform neurofibromas and serum of NF1 patients stimulates neurofibroma proliferation in vitro. This study aimed to determine whether, in NF1 patients, serum levels of midkine (MK) and fibroblast growth factor 2 (FGF2) were associated with the number and/or type of neurofibromas. In addition, their concentrations were correlated with serum levels of dehydroepiandrosterone sulfate (DHEAS), a neurosteroid secreted by the peripheral nervous system. We performed a case control-study and measured, by ELISA assay, serum concentrations of MK, FGF2, and DHEAS in 20 NF1 patients and 30 controls. We found increased serum levels of MK and FGF2 in NF1 patients between 30 and 50 years old. Their concentrations were significantly higher in NF1 patients with plexiform neurofibromas than in controls (P=0.003 for MK and P=0.008 for FGF2). As an underlying hormonal regulation was suspected, DHEAS serum levels were measured but no difference was observed between patients and controls. We also observed a strong association between MK and FGF2 levels (P=0.0001) in NF1 patients and controls. In conclusion, we point out MK and FGF2 as biomarkers for plexiform neurofibroma in NF1 patients. As both growth factors are estrogen-responsive genes and neurofibromin is a co-repressor of estrogen receptor alpha activity, we suggest that the increased serum levels of MK and FGF2 observed in NF1 patients might be due to estradiol hypersensitivity., Competing Interests: None., (AJTR Copyright © 2022.)

The rapid evolution of fertilization proteins has generated remarkable diversity in molecular structure and function. Glycoproteins of vertebrate egg coats contain multiple zona pellucida (ZP)-N domains (1-6 copies) that facilitate multiple reproductive functions, including species-specific sperm recognition. In this report, we integrate phylogenetics and machine learning to investigate how ZP-N domains diversify in structure and function. The most C-terminal ZP-N domain of each paralog is associated with another domain type (ZP-C), which together form a "ZP module." All modular ZP-N domains are phylogenetically distinct from nonmodular or free ZP-N domains. Machine learning-based classification identifies eight residues that form a stabilizing network in modular ZP-N domains that is absent in free domains. Positive selection is identified in some free ZP-N domains. Our findings support that strong purifying selection has conserved an essential structural core in modular ZP-N domains, with the relaxation of this structural constraint allowing free N-terminal domains to functionally diversify., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

The process of gene duplication followed by gene loss or evolution of new functions has been studied extensively, yet the role gene duplication plays in the function and evolution of fertilization proteins is underappreciated. Gene duplication is observed in many fertilization protein families including Izumo, DCST, ZP, and the TFP superfamily. Molecules mediating fertilization are part of larger gene families expressed in a variety of tissues, but gene duplication followed by structural modifications has often facilitated their cooption into a fertilization function. Repeat expansions of functional domains within a gene also provide opportunities for the evolution of novel fertilization protein. ZP proteins with domain repeat expansions are linked to species-specificity in fertilization and TFP proteins that experienced domain duplications were coopted into a novel sperm function. This review outlines the importance of gene duplications and repeat domain expansions in the evolution of fertilization proteins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rivera and Swanson.)

Introduction: Armed conflicts affect territories rich in resources and biodiversity. As a result of the environmental damage caused by violent actions, the health of populations can be affected. Objectives: To assess the risks to human health due to environmental degradation associated with three violent actions in the context of the Colombian armed conflict: Pipeline bombing, informal mining with mercury, and spraying of illicit crops with glyphosate. Materials and methods: We conducted a quantitative evaluation of the risks to individual health associated with armed conflict activities using methodologies focused on the routes of pollutants dispersion, their concentrations in the environment, the exposure of the individuals, and the risks of carcinogenic and non-carcinogenic effects. Results: The risk assessment of the armed conflict-related actions under study evidenced intolerable carcinogenic risk and unacceptable non-carcinogenic risk due to the consumption of water and fish contaminated by polycyclic aromatic hydrocarbons (PAH), mercury, and glyphosate. Conclusions: The study reiterates the inextricable connections existing among the environment, society, and health, as well as the implications of environmental violence for the public health of vulnerable population groups and, in general, for the well-being of all living beings affected by the armed conflict.

Composite biomaterials are solids that contain two or more different materials, combining the properties of their components to restore or improve the function of tissues. In this study, we report the generation of electrospun matrices with osteoconductive properties and porosity using the combination of a biodegradable polyester, polylactic acid (PLA), and hydroxyapatite (HA). Additionally, we report the effects of modifying these matrices through plasma polymerization of pyrrole on the growth and osteogenic differentiation of rabbit bone marrow stem cells. Cells were isolated, seeded and cultured on biomaterials for periods between 7 and 28 days. The matrices we obtained were formed by nano and microfibers containing up to 35.7 wt% HA, presenting a variety of apparent pore sizes to allow for the passage of nutrients to bone cells. Scanning electron microscopy showed that the fibers were coated with polypyrrole doped with iodine, and MTT assay demonstrated this increased cell proliferation and significantly improved cell viability due to the adhesive properties of the polymer. Our results show that PLA/HA/Pyrrole/Iodine matrices are favorable for bone tissue engineering., (© 2021 Wiley Periodicals LLC.)

Pterin (Ptr) is a model photosensitizer that acts mainly through type I mechanism and is able to photoinduce the one-electron oxidation of purine and pyrimidine nucleobases. However, under anaerobic conditions Ptr reacts with thymine (T) to form photoadducts (Ptr-T) but does not lead to the photodegradation of guanine (G), which is the nucleobase with the lowest ionization potential. Accordingly, G is thermodynamically able to reduce the radicals of the other nucleobases and has been described in this sense as the "hole sink" of the DNA double helix. Here we analyze by steady-state and time-resolved studies the effect of G in the anaerobic photosensitization of T by Ptr, using nucleotides and oligonucleotides of different sequences. We demonstrated that G is able to reduce T radicals but does not prevent the formation of Ptr-T adducts. Our results suggest that after the encounter between the excited Ptr and T, and completion of the electron transfer step, part of the radicals escape from the solvent cage, to further react with other species. However, a proportion of radicals do not escape and evolve to photoadducts before separation. We provide new evidence that contributes to understand the photosensitizing properties of Ptr in the absence of O 2 , the mechanism of formation of photoadducts in the DNA and the protective role of G towards the photodamage in other nucleobases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Antimicrobial bacteria resistance is an important problem in children with recurrent urinary tract infections (rUTI), thus it is crucial to search for alternative therapies. Autologous bacterial lysates (ABL) may be a potential treatment for rUTI. Twenty-seven children with rUTI were evaluated for one year, urine and stool cultures were performed, 10 colonies of each culture were selected and those identified as Escherichia coli were characterized by serology. For patients who presented ≥10 5 UFC/mL, an ABL was manufactured and administered orally (1 mL/day) for a month. Twelve children were monitored for ≥1-year, 218 urine and 11 stool samples were analyzed. E. coli (80.5%) was the main bacteria isolated from urine and feces (72%). E. coli of classical urinary serotypes (UPEC), O25:H4, O75:HNM, and O9:HNM were identified in patients with persistent urinary infection (pUTI). In 54% of patients treated with ABL, the absence of bacteria was observed in urine samples after 3 months of treatment, 42% of these remained without UTI between 10-12 months. It was observed that the use of ABL controlled the infection for almost 1 year in more than 60% of the children. We consider it necessary to develop a polyvalent immunogen for the treatment and control of rUTI.

Introduction: Assessment of cognition and everyday function is essential in clinical trials for Alzheimer's disease (AD). Two novel measures of cognition (No Practice Effects (NPE) cognitive battery and Miami Computerized Functional Assessment Scale (CFAS)) were designed to have robust psychometric properties and reduced practice and ceiling effects. This study aims to evaluate if the NPE and CFAS demonstrate stronger psychometric properties and reduced practice effects compared with established measures, including the Preclinical Alzheimer Cognitive Composite (PACC), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Functional Activities Questionnaire (FAQ)., Methods: This parallel group, four-site study will randomize 320 cognitively intact adults aged 60 to 85 years to novel or well-established measures of cognition and function. All participants will receive assessments at baseline (week 0), 3-months, and 12-months, as well as a brain MRI scan and Apolipoprotein E genetic test at study entry. Analyses will determine psychometric properties of the NPE and CFAS, compare the sensitivity of measures to AD risk markers, and identify cognitive domains within the NPE., Discussion: Practice effects have been a major limitation of Alzheimer's disease clinical trials that typically assess cognitive changes over serial assessments. Detection of functional impairment in cognitively normal individuals with biomarkers for Alzheimer's disease requires instruments sensitive to very subtle functional changes. This study is intended to support the validation of two new composite measures, the NPE battery and the CFAS, which may advance clinical testing of interventions for individuals across the spectrum of early stage Alzheimer's disease., Trial Registration: NCT03900273., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: This systematic review summarises the existing evidence on the implementation of technology-based mental healthcare models in the primary care setting., Methods: A systematic search was conducted (MEDLINE, Embase, CENTRAL) in August 2019 and studies were selected according to predefined eligibility criteria. The main outcomes were clinical effectiveness, adherence to primary treatment and cost of implementation., Selection Criteria: Studies with an experimental or quasi-experimental design that evaluated the implementation of technology-based mental healthcare models were included., Results: Five articles met the inclusion criteria. The models included technological devices such as tablets, cellphones and computers, with programs and mobile apps that supported decision-making in the care pathway. These decisions took place at different times, from the universal screening phase to the follow-up of patients with specific conditions. In general, the studies showed a decrease in the reported symptoms. However, there was great heterogeneity in both the health conditions and the outcomes, which hindered a quantitative synthesis. The assessment of risk of bias showed low quality of evidence., Conclusion: There is not enough evidence to support the implementation of a technology-based mental healthcare model. High quality studies that focus on implementation and effectiveness outcomes are needed to evaluate the impact of technology-based mental healthcare models in the primary care setting., (Copyright © 2021. Published by Elsevier España, S.L.U.)

Foot-and-mouth disease (FMD) is a highly contagious animal disease caused by an RNA virus subdivided into seven serotypes that are unevenly distributed in Asia, Africa, and South America. Despite the challenges of controlling FMD, since 1996 there have been only two outbreaks attributed to serotype C, in Brazil and in Kenya, in 2004. This article describes the historical distribution and origins of serotype C and its disappearance. The serotype was first described in Europe in the 1920s, where it mainly affected pigs and cattle but as a less common cause of outbreaks than serotypes O and A. No serotype C outbreaks have been reported in Europe since vaccination stopped in 1990. FMD virus is presumed to have been introduced into South America from Europe in the nineteenth century, although whether serotype C evolved there or in Europe is not known. As in Europe, this serotype was less widely distributed and caused fewer outbreaks than serotypes O and A. Since 1994, serotype C had not been reported from South America until four small outbreaks were detected in the Amazon region in 2004. Elsewhere, serotype C was introduced to Asia, in the 1950s to the 1970s, persisting and evolving for several decades in the Indian subcontinent and for eighteen years in the Philippines. Serotype C virus also circulated in East Africa between 1957 and 2004. Many serotype C viruses from European and Kenyan outbreaks were closely related to vaccine strains, including the most recently recovered Kenyan isolate from 2004. International surveillance has not confirmed any serotype C cases, worldwide, for over 15 years, despite more than 2,000 clinical submissions per year to reference laboratories. Serology provides limited evidence for absence of this serotype, as unequivocal interpretation is hampered by incomplete intra-serotype specificity of immunoassays and the continued use of this serotype in vaccines. It is recommended to continue strengthening surveillance in regions of FMD endemicity, to stop vaccination against serotype C and to reduce working with the virus in laboratories, since inadvertent escape of virus during such activities is now the biggest risk for its reappearance in the field., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Endemic circulation of foot-and-mouth disease (FMD) in Africa and Asia poses a continuous risk to countries in Europe, North America, and Oceania which are free from the disease. Introductions of the disease into a free region have dramatic economic impacts, especially if they are not detected at an early stage and controlled rapidly. However, farmers and veterinarians have an obvious disincentive to report clinical signs that are consistent with FMD, due to the severe consequences of raising an official suspicion, such as farm-level quarantine. One way that the risk of late detection can be mitigated is offering non-discriminatory exclusion testing schemes for differential diagnostics, wherein veterinarians can submit samples without the involvement of the competent authority and without sanctions or costs for the farmer. This review considers the benefits and limitations of this approach to improve the early detection of FMD in free countries and gives an overview of the FMD testing schemes currently in use in selected countries in Europe and the Americas as well as in Australia., (Copyright © 2020 Eschbaumer, Vögtlin, Paton, Barnabei, Sanchez-Vazquez, Pituco, Rivera, O'Brien, Nfon, Brocchi, Bakkali Kassimi, Lefebvre, Navarro López, Maradei, Duffy, Loitsch, De Clercq, King, Zientara, Griot and Beer.)

A new study reveals the retinal circuit for encoding the types of light prominent at sunrise and sunset. The output of that circuit is conveyed to the brain's master circadian clock. Subconscious processing of sky color changes may therefore be the key stimulus for conveying morning and evening information to the circadian timing system in the brain., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Axicabtagene ciloleucel and tisagenlecleucel are 2 chimeric antigen receptor (CAR) T-cell immunotherapies targeting CD19 for the treatment of B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma. Two commonly recognized complications associated with CAR T-cell therapies are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS can occur in isolation or concomitantly with CRS following CAR T-cell therapy and may be due to disruption of the blood-brain barrier and the effects of elevated cytokine levels on the central nervous system. Presently, the optimum management of ICANS remains elusive, as there lacks consensus guidelines. The objective of this review is to provide a comprehensive summary of ICANS and strategies for prompt identification and management of patients presenting to the intensive care unit with this syndrome.

This study investigates the historical temporal trend and geographical distribution of the foot-and-mouth disease virus (FMDv) serotype C in South America; discussing the findings within the context of the actions and strategies carried out for the elimination of foot-and-mouth disease (FMD). This is the first time that such a comprehensive historical compilation has been carried out in the Region; hence, the study is intended as a reference and source of evidence about the presence/absence of FMDv serotype C in South America. Data on the occurrence of FMD were sourced from the Weekly Epidemiological Reports submitted by the countries to Pan American Foot-and-Mouth Disease Center (PANAFTOSA-PAHO/WHO) since 1972, and complemented with other sources of information from the 1968-1971 period. The temporal distribution was examined with local weighted regression (LOESS) to identify two temporal trends, that is, "smoothed" and "over-adjusted", utilising the time-series with the total number of cases per year, at Regional level. Thereafter the outbreaks were aggregated by decades and mapped by the first subnational administrative level. As a result, two major peaks of occurrence were identified, one in the 70s, with up to 1,193 outbreaks, and another in the 80s, with 380. Overall, the investigations show a clear regressive trend in the occurrence of serotype C, with a reduction in the number of outbreaks over-time, and with the subsequent reduction of affected locations. This study illustrates the contrast between the very limited presence over the last 20 years - with only one event in 2004 - and the epidemic situation in the 1970s and 1980s, and suggests that serotype C of FMDv is no longer present in the Region., (© 2018 Blackwell Verlag GmbH.)

Young Asian American women have high rates of depression and suicidality; however, few interventions address the urgent need for culturally informed care. Asian Women's Action for Resilience and Empowerment (AWARE) aims to be the first gender and culturally specific group psychotherapy intervention designed to improve mental and sexual health in Asian American women with trauma. This article specifically focuses on identifying the mechanisms of action that were responsible for improving mental health and well-being among those who participated in AWARE randomized controlled trial. Of the 435 women screened for the study, 63 Chinese, Korean, and Vietnamese women with histories of interpersonal violence were randomized into either the intervention (n = 32) or waitlist control groups (n = 31). Data from 16 posttrial focus group sessions were then thematically analyzed to explore the key themes and mechanisms of action of the AWARE intervention. Analysis revealed four cultural mechanisms that facilitated mental health improvements: psychoeducation on disempowering parenting, the reduction of mental illness-related stigma, community and relational building, and a heightened sense of empowerment. Results suggest that the AWARE intervention fosters Asian American women's well-being on an individual level and encourages social engagement through culturally salient messages. Women in the study were able to expand their social support network, engage in activism, and develop an empowered connection to their community. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Disruption of the circadian rhythms is a frequent preclinical and clinical manifestation of Alzheimer's disease. Furthermore, it has been suggested that shift work is a risk factor for Alzheimer's disease. Previously, we have reported association of intolerance to shift work (job-related exhaustion in shift workers) with a variant rs12506228A, which is situated close to melatonin receptor type 1A gene (MTNR1A) and linked to MTNR1A brain expression levels. Here, we studied association of that variant with clinical and neuropathological Alzheimer's disease in a Finnish whole-population cohort Vantaa 85+ (n = 512, participants over 85 years) and two follow-up cohorts. Rs12506228A was associated with clinical Alzheimer's disease (p = 0.000073). Analysis of post-mortem brain tissues showed association with higher amount of neurofibrillary tangles (p = 0.0039) and amyloid beta plaques (p = 0.0041). We then followed up the associations in two independent replication samples. Replication for the association with clinical Alzheimer's disease was detected in Kuopio 75+ (p = 0.012, n = 574), but not in the younger case-control sample (n = 651 + 669). While melatonin has been established in regulation of circadian rhythms, an independent role has been also shown for neuroprotection and specifically for anti-amyloidogenic effects. Indeed, in vitro, RNAi mediated silencing of MTNR1A increased the amyloidogenic processing of amyloid precursor protein (APP) in neurons, whereas overexpression decreased it. Our findings suggest variation close to MTNR1A as a shared genetic risk factor for intolerance to shift work and Alzheimer's disease in old age. The genetic associations are likely to be mediated by differences in MTNR1A expression, which, in turn, modulate APP metabolism.

Background: Congenital Zika virus (ZIKV) infection can be detected in both the presence and absence of microcephaly and manifests as a number of signs and symptoms that are detected clinically and by neuroimaging. However, to date, qualitative and quantitative measures for the purpose of diagnosis and prognosis are limited., Objectives: Main objectives of this study conducted on fetuses and infants with confirmed congenital Zika virus infection and detected brain abnormalities were (1) to assess the prevalence of microcephaly and the frequency of the anomalies that include a detailed description based on ultrasound and magnetic resonance imaging in fetuses and ultrasound, magnetic resonance imaging, and computed tomography imaging postnatally, (2) to provide quantitative measures of fetal and infant brain findings by magnetic resonance imaging with the use of volumetric analyses and diffusion-weighted imaging, and (3) to obtain additional information from placental and fetal histopathologic assessments and postnatal clinical evaluations., Study Design: This is a longitudinal cohort study of Zika virus-infected pregnancies from a single institution in Colombia. Clinical and imaging findings of patients with laboratory-confirmed Zika virus infection and fetal brain anomalies were the focus of this study. Patients underwent monthly fetal ultrasound scans, neurosonography, and a fetal magnetic resonance imaging. Postnatally, infant brain assessment was offered by the use of ultrasound imaging, magnetic resonance imaging, and/or computed tomography. Fetal head circumference measurements were compared with different reference ranges with <2 or <3 standard deviations below the mean for the diagnosis of microcephaly. Fetal and infant magnetic resonance imaging images were processed to obtain a quantitative brain volumetric assessment. Diffusion weighted imaging sequences were processed to assess brain microstructure. Anthropometric, neurologic, auditory, and visual assessments were performed postnatally. Histopathologic assessment was included if patients opted for pregnancy termination., Results: All women (n=214) had been referred for Zika virus symptoms during pregnancy that affected themselves or their partners or if fetal anomalies that are compatible with congenital Zika virus syndrome were detected. A total of 12 pregnant patients with laboratory confirmation of Zika virus infection were diagnosed with fetal brain malformations. Most common findings that were assessed by prenatal and postnatal imaging were brain volume loss (92%), calcifications (92%), callosal anomalies (100%), cortical malformations (89%), and ventriculomegaly (92%). Results from fetal brain volumetric assessment by magnetic resonance imaging showed that 1 of the most common findings associated with microcephaly was reduced supratentorial brain parenchyma and increased subarachnoid cerebrospinal fluid. Diffusion weighted imaging analyses of apparent diffusion coefficient values showed microstructural changes. Microcephaly was present in 33.3-58.3% of the cases at referral and was present at delivery in 55.6-77.8% of cases. At birth, most of the affected neonates (55.6-77.8%) had head circumference measurements >3 standard deviations below the mean. Postnatal imaging studies confirmed brain malformations that were detected prenatally. Auditory screening results were normal in 2 cases that were assessed. Visual screening showed different anomalies in 2 of the 3 cases that were examined. Pathologic results that were obtained from 2 of the 3 cases who opted for termination showed similar signs of abnormalities in the central nervous system and placental analyses, including brain microcalcifications., Conclusion: Congenital microcephaly is not an optimal screening method for congenital Zika virus syndrome, because it may not accompany other evident and preceding brain findings; microcephaly could be an endpoint of the disease that results from progressive changes that are related to brain volume loss. Long-term studies are needed to understand the clinical and developmental relevance of these findings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Patients with acute coronary syndrome complicated with high degree atrioventricular block still have a high mortality. A low percentage of these patients need a permanent pacemaker (PPM) but mortality and associated factors with the PPM implant in acute coronary syndrome patients are not known. We assess whether PPM implant is an independent variable in the mortality of acute coronary syndrome patients. Also, we explored the variables that remain independently associated with PPM implantation., Methods: This was an observational study on the Spanish ARIAM register. The inclusion period was from January 2001 to December 2011. This registry included all Andalusian acute coronary syndrome patients. Follow-up for global mortality was until November 2013., Results: We selected 27,608 cases. In 62 patients a PPM was implanted (0.024%). The mean age in PPM patients was 70.71±11.214 years versus 64.46±12.985 years in patients with no PPM. PPM implant was associated independently with age (odds ratio (OR) 1.031, 95% confidence interval (CI) 1.007-1.055), with left ventricular branch block (OR 6.622, 95% CI 2.439-18.181), with any arrhythmia at intensive care unit admission (OR 2.754, 95% CI 1.506-5.025) and with heart failure (OR 3.344, 95% CI 1.78-8.333). PPM implant was independently associated with mortality (OR 11.436, 95% CI 1.576-83.009). In propensity score analysis PPM implant was still associated with mortality (OR 5.79, 95% CI 3.27-25.63)., Conclusion: PPM implant is associated with mortality in the acute coronary syndrome population in the ARIAM registry. Advanced age, heart failure, arrhythmias and left ventricular branch block at intensive care unit admission were found associated factors with PPM implant in acute coronary syndrome patient.

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The goal of this study was to evaluate possible changes in the left myocardial performance of patients with cardiogenic shock (CS) during ascending levels of positive end-expiratory pressure (PEEP) using speckle-tracking echocardiography., Materials and Methods: This was an interventional clinical study performed on CS patients under mechanical ventilation. These patients underwent echocardiography after 15 to 30 minutes of progressive increases in PEEP zero end-expiratory pressure (ZEEP) (PEEP 5, PEEP 10, PEEP 15 cm H2O). We evaluated the changes caused by these increasing levels of PEEP on the E/E' ratio and the parameters of left ventricular systolic and diastolic functions, including longitudinal strain (S) and strain rate (SR). Analyses of mean values were carried out using analysis of variance., Results: A total of 65 CS patients were included. Their mean age was 68.58±14.61 years. Progressive increases in PEEP induced a significant decrease in the E/E' ratio (ZEEP=12.87±1.81; PEEP=5, 8.39±3.61; PEEP=10, 6.34±1.73; and PEEP=15, 7.10±0.37; P<0.0001). Although we did not find significant changes in left ventricular ejection fraction, a clear increase in left ventricular S and SR occurred (ZEEP=-13, 15±1.27; PEEP=5, -16.97±4.01; PEEP=10, -16.89±0.46; PEEP=15, -15.39±4.21; and ZEEP=-1.02±0.02; PEEP=5, -1.49±0.13; PEEP=10, -1.57±0.21; PEEP=15, -1.24±0.29, respectively; all values were significant)., Conclusions: Increasing levels of PEEP improve the left ventricular S and SR. PEEP levels could modify the performance of left ventricular fibers.

Background: Numerous historical descriptions of the Lesser Egyptian jerboa, Jaculus jaculus , a small bipedal mammal with elongate hindlimbs, make special note of their extraordinary leaping ability. We observed jerboa locomotion in a laboratory setting and performed inverse dynamics analysis to understand how this small rodent generates such impressive leaps. We combined kinematic data from video, kinetic data from a force platform, and morphometric data from dissections to calculate the relative contributions of each hindlimb muscle and tendon to the total movement., Results: Jerboas leapt in excess of 10 times their hip height. At the maximum recorded leap height (not the maximum observed leap height), peak moments for metatarso-phalangeal, ankle, knee, and hip joints were 13.1, 58.4, 65.1, and 66.9 Nmm, respectively. Muscles acting at the ankle joint contributed the most work (mean 231.6 mJ / kg Body Mass) to produce the energy of vertical leaping, while muscles acting at the metatarso-phalangeal joint produced the most stress (peak 317.1 kPa). The plantaris, digital flexors, and gastrocnemius tendons encountered peak stresses of 25.6, 19.1, and 6.0 MPa, respectively, transmitting the forces of their corresponding muscles (peak force 3.3, 2.0, and 3.8 N, respectively). Notably, we found that the mean elastic energy recovered in the primary tendons of both hindlimbs comprised on average only 4.4% of the energy of the associated leap., Conclusions: The limited use of tendon elastic energy storage in the jerboa parallels the morphologically similar heteromyid kangaroo rat, Dipodomys spectabilis . When compared to larger saltatory kangaroos and wallabies that sustain hopping over longer periods of time, these small saltatory rodents store and recover less elastic strain energy in their tendons. The large contribution of muscle work, rather than elastic strain energy, to the vertical leap suggests that the fitness benefit of rapid acceleration for predator avoidance dominated over the need to enhance locomotor economy in the evolutionary history of jerboas.

Obsessive-compulsive disorder (OCD) is a polygenic neuropsychiatric disorder characterized by repetitive thoughts and behaviors that cause distress. The pathogenic repeat expansion [GGGGCC] n found at the C9orf72 locus is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), and has also been documented in patients with psychosis and schizophrenia. Furthermore, obsessions and compulsions have been identified in patients diagnosed with ALS and/or FTD and carrying the pathogenic repeat expansion. Here, we performed genetic screening for the C9orf72 repeat expansion on 573 patients diagnosed with OCD. None of the patients were found to carry the expansion. The results show that patients with OCD do not commonly carry the pathogenic repeat expansion and therefore should not be routinely screened. OCD and psychotic patients who do test positive for the C9orf72, however, should be closely observed for the later development of FTD and ALS., (Published by Elsevier B.V.)

Background: The hemangiopericytoma is an uncommon vascular tumour. We report a case of interest because of its rarity, size and location., Case Report: We present the case of a 63-year-old woman who consulted for abdominal pain. TAC, MRI and arteriography showed a pelvic mass occupying Douglas' space, displacing the uterus, bladder and sigma, with vascularisation relative to the inferior mesenteric artery and both hypogastric arteries. The vascularity of the tumour itself was selectively embolised before the mass was resected. There were no intra- or postoperative complications. Pathology confirmed the diagnosis of hemangiopericitoma. The patient is being monitored as an outpatient, with no signs of recurrence to date., Discussion: The hemangiopericytoma is a tumour of the pericyte cells so it can occur in any location. The pelvic location is exceptional. The tumour may appear as nonspecific abdominal pain, show signs of compression of adjacent organs or occasionally be associated with paraneoplastic syndromes. The diagnosis is suspected via CT and angiography findings, but confirmation is only made by analysing the surgical specimen. The treatment of choice is surgery, in some cases after preoperative embolisation of the vascularisation of the mass. There is no agreement on chemo/radiotherapy as the primary treatment for hemangiopericytoma, although adjuvant radiation therapy has been found to improve local control and reduce recurrences. The prognosis is good if complete resection is achieved, with five- and 10-year survival rates between 70 and 80%, depending on the series.

Objective: To describe the clinical outcomes of patients undergoing serial observation for vestibular schwannoma (VS) and identify factors that may predict tumor growth or hearing loss., Study Design: Retrospective review., Methods: A retrospective review was conducted of patients seen at a tertiary care medical center between 2002 and 2013 with an International Classification of Diseases-9 diagnosis code of 225.1. Patients electing observation as initial management, with at least two documented imaging results, were included. Exclusion criteria comprised bilateral VS, diagnosis of neurofibromatosis type 2, and neoplasms other than VS. Decline in serviceable hearing, tumor growth, and changes in management strategy were recorded. Survival analysis to assess median time to outcomes and multiple logistic regression analyses were performed., Results: A total of 94 patients met inclusion criteria. While undergoing observation, 22.3% of patients underwent a change in management strategy to microsurgical excision or stereotactic radiotherapy. For patients with initial serviceable hearing, 24.3% observed a decline to a nonserviceable level. No significant clinical factors were identified to predict changes in hearing. Survival analysis revealed that an estimated 69.1% of patients electing observation as initial management continued to do so at 5 years. Imbalance or disequilibrium at presentation was found to be associated with an increased adjusted odds ratio (OR) (OR 2.96; 95% confidence interval, 1.03-8.50; P = 0.04) for tumor growth., Conclusion: Serial observation of VS is a viable treatment strategy for selected patients, with two-thirds of patients electing to continue this management option after 5 years. Disequilibrium as a presenting symptom may be associated with subsequent tumor growth., Level of Evidence: 4., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Several disorders might require vaginal reconstruction, such as congenital abnormalities, injury, or cancer. Reconstructive techniques for which non-vaginal tissue is used can be associated with complications. We assessed the use of engineered vaginal organs in four patients with vaginal aplasia caused by Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)., Methods: We invited to participate four consecutive patients who presented over a 3-year period with congenital vaginal aplasia due to MRKHS. Patients were aged 13-18 years. We obtained a vulvar biopsy of autologous tissue from every patient. We cultured, expanded, and seeded epithelial and muscle cells onto biodegradable scaffolds. The organs were constructed and allowed to mature in an incubator in a facility approved for human-tissue manufacturing. We used a perineal approach to surgically implant these organs. We recorded history, physical examination, vaginoscopy, serial tissue biopsies, MRIs, and self-administered Female Sexual Function Index questionnaire results for all patients, with a follow-up of up to 8 years., Findings: We noted no long-term postoperative surgical complications. Yearly serial biopsies showed a tri-layered structure, consisting of an epithelial cell-lined lumen surrounded by matrix and muscle, with expected components of vaginal tissue present. Immunohistochemical analysis confirmed the presence of phenotypically normal smooth muscle and epithelia. The MRIs, which showed the extent of the vaginal aplasia before surgery, showed the engineered organs and the absence of abnormalities after surgery, which was confirmed with yearly vaginoscopy. A validated self-administered Female Sexual Function Index questionnaire showed variables in the normal range in all areas tested, such as desire, arousal, lubrication, orgasm, satisfaction, and painless intercourse., Interpretation: Vaginal organs, engineered from the patient's own cells and implanted, showed normal structural and functional variables with a follow-up of up to 8 years. These technologies could be useful in patients requiring vaginal reconstruction., Funding: Wake Forest University and Hospital Infantil de México Federico Gómez., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: The objective of this study was to review the collective experience and utility of FDG-PET scans (FDG-PET) in the detection of systemic metastases in patients with stage III melanoma., Methods: A systematic search for relevant studies published between 1990 and 2012 was performed. We included English language studies that evaluated melanoma patients with stage III disease, with at least 10 patients per study, and collected statistical data to assess FDG-PET utility in the detection of distant metastases. The SIGN tool was used to evaluate methodological quality and a meta-analysis was performed using Stata statistical software to quantify the clinical utility of FDG-PET., Results: The systematic search yielded 9 studies eligible for inclusion in quantitative analyses with a total of 623 patients. The overall sensitivity of FDG-PET in detecting systemic metastases was 89.42% (95% CI: 65.07-97.46), and specificity was 88.78% (95% CI: 77.04-94.91). The pooled positive likelihood ratio was 7.97 (95% CI: 3.58-17.71) and the negative likelihood ratio was 0.12 (95% CI: 0.03-0.47). The area under the summary receiver operating curve (SROC) was 0.94 (95% CI: 0.92-0.96) and the diagnostic odds ratio (DOR) was 66.84 (95% CI: 10.66-418.89). A change in stage and/or management was noted in 22% (126/573) of patients when FDG-PET was utilized., Conclusions: Our findings indicate that FDG-PET may be useful in detecting distant metastases in patients with stage III melanoma. For this highly selected group of patients, FDG-PET has a high sensitivity, specificity and performance, frequently leading to a change in treatment plan., (Copyright © 2014 Elsevier Ltd. All rights reserved.)