Trabajo interdisciplinario en las profesiones de la voz humana: retos, límites y proyecciones

El presente documento resume los principales aportes del conversatorio titulado "Trabajo interdisciplinario en las profesiones de la voz humana: retos, límites y proyecciones", organizado por Vocology Center el 18 de julio de 2023, que reunió a líderes y representantes de diversas agremiaciones relacionadas con la voz humana, incluyendo profesionales del ámbito clínico, artístico, rehabilitación vocal, voz ocupacional, pedagogía vocal y otras disciplinas afines. El propósito de este conversatorio fue promover un debate crítico sobre la naturaleza del trabajo interdisciplinario en el estudio de la voz humana. Se exploraron los desafíos que surgen al configurar equipos de trabajo que incluyan profesionales con diferentes enfoques y experticias en el abordaje de la voz, así como los límites inherentes a los diversos roles y funciones desempeñados por los profesionales especializados en este campo, junto con las cuestiones éticas emergentes en este proceso. Con un enfoque encaminado a fortalecer alianzas interdisciplinarias, el evento se centró en la búsqueda de una comunicación y colaboración más efectiva. Este documento marca un avance significativo en la comprensión y colaboración interdisciplinar en el cuidado de la voz humana.

This document summarizes the main contributions of the panel discussion titled "Interdisciplinary work in the human voice professions: challenges, limits and projections" organized by the Vocology Center on July 18, 2023. The event brought together leaders and representatives from various associations related to the human voice, including professionals from the clinical, artistic, vocal rehabilitation, occupational voice, vocal pedagogy, and other related disciplines. The purpose of this panel discussion was to promote a critical debate on the nature of interdisciplinary work in the study of the human voice. The discussion explored the challenges that emerge when teams that include professionals with different approaches and expertise address voice production, as well as the inherent boundaries of the various roles and functions performed by specialized professionals in this field, along with the emerging ethical issues in this process. With a focus on strengthening interdisciplinary collaborations, the event centered on seeking more effective communication and collaboration. This document represents a significant step forward in understanding and fostering interdisciplinary cooperation in the care of the human voice.

HARNet in deep learning approach-a systematic survey.

A comprehensive examination of human action recognition (HAR) methodologies situated at the convergence of deep learning and computer vision is the subject of this article. We examine the progression from handcrafted feature-based approaches to end-to-end learning, with a particular focus on the significance of large-scale datasets. By classifying research paradigms, such as temporal modelling and spatial features, our proposed taxonomy illuminates the merits and drawbacks of each. We specifically present HARNet, an architecture for Multi-Model Deep Learning that integrates recurrent and convolutional neural networks while utilizing attention mechanisms to improve accuracy and robustness. The VideoMAE v2 method ( https://github.com/OpenGVLab/VideoMAEv2 ) has been utilized as a case study to illustrate practical implementations and obstacles. For researchers and practitioners interested in gaining a comprehensive understanding of the most recent advancements in HAR as they relate to computer vision and deep learning, this survey is an invaluable resource.

Baltimore oral epidemiology, disease effects, and HIV evaluation study (BEEHIVE) study protocol: a prospective cohort study.

BACKGROUND: As antiretroviral therapy has become widely available and highly effective, HIV has evolved to a manageable, chronic disease. Despite this health advancement, people living with HIV (PLWH) are at an increased risk for age-related non-communicable diseases (NCDs) compared to HIV-uninfected individuals. Similarly, PLWH are at an increased risk for selected oral diseases. PLWH with a history of injecting drugs experience an even greater burden of disease than their counterparts. The overall objective of the Baltimore Oral Epidemiology, Disease Effects, and HIV Evaluation (BEEHIVE) study is to determine the combined effects of HIV infection and NCDs on oral health status. The specific aims of the study are to: (1) determine to what extent HIV status influences access to and utilization of oral health care services; (2) determine to what extent HIV status affects self-reported and clinical oral health status; (3) determine to what extent HIV status influences the progression of periodontitis; and (4) determine to what extent HIV status impacts the periodontitis-associated oral microbiome signature. METHODS: The BEEHIVE study uses a prospective cohort study design to collect data from participants at baseline and at a 24-month follow-up visit. Data are collected through questionnaire assessments, clinical examinations, and evaluation of oral microbiological samples to determine the drivers of oral disease among a high-risk population of PLWH with a history of injection drug use and prevalent comorbid NCDs. The established AIDS Linked to the Intravenous Experience (ALIVE) cohort serves as the source of participants for the BEEHIVE Study. DISCUSSION: Upon completion of the BEEHIVE study, the knowledge gained will be important in informing future clinical and preventive interventions that can be implemented into medical and dental practice to ultimately help eliminate long-standing oral health inequities that PLWH experience.

Crystal structure of human peptidylarginine deiminase type VI (PAD6) provides insights into its inactivity.

Human peptidylarginine deiminase isoform VI (PAD6), which is predominantly limited to cytoplasmic lattices in the mammalian oocytes in ovarian tissue, is essential for female fertility. It belongs to the peptidylarginine deiminase (PAD) enzyme family that catalyzes the conversion of arginine residues to citrulline in proteins. In contrast to other members of the family, recombinant PAD6 was previously found to be catalytically inactive. We sought to provide structural insight into the human homologue to shed light on this observation. We report here the first crystal structure of PAD6, determined at 1.7 Šresolution. PAD6 follows the same domain organization as other structurally known PAD isoenzymes. Further structural analysis and size-exclusion chromatography show that PAD6 behaves as a homodimer similar to PAD4. Differential scanning fluorimetry suggests that PAD6 does not coordinate Ca2+ which agrees with acidic residues found to coordinate Ca2+ in other PAD homologs not being conserved in PAD6. The crystal structure of PAD6 shows similarities with the inactive state of apo PAD2, in which the active site conformation is unsuitable for catalytic citrullination. The putative active site of PAD6 adopts a non-productive conformation that would not allow protein-substrate binding due to steric hindrance with rigid secondary structure elements. This observation is further supported by the lack of activity on the histone H3 and cytokeratin 5 substrates. These findings suggest a different mechanism for enzymatic activation compared with other PADs; alternatively, PAD6 may exert a non-enzymatic function in the cytoplasmic lattice of oocytes and early embryos.

Short-term Aronia melanocarpa extract supplementation improves cognitive performance: a randomized, double-blind, placebo-controlled cross-over study in healthy young adults.

PURPOSE: Evidence on the potential beneficial effects of anthocyanin-rich foods and supplements on cognitive performance is mainly based on acute or long-term studies in older adults. However, short-term studies focusing on a younger population are lacking. Therefore, short-term effects of Aronia melanocarpa extract (AME) supplementation on cognitive performance were investigated in healthy young adults. Potential underlying mechanisms were also addressed. METHODS: A randomized, double-blind, placebo-controlled cross-over study was performed involving 35 apparently healthy young adults. Participants consumed AME (180 mg anthocyanins/day) or a placebo for 1 week, separated by at least 2 weeks of wash-out. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Furthermore, arterial stiffness (carotid-to-femoral pulse wave velocity), retinal microvascular calibers (fundus photography), and serum brain-derived neurotrophic factor (BDNF) concentrations were measured at baseline and after 1 week. RESULTS: Participants had a mean age of 25 ± 4 years and an average BMI of 23.4 ± 2.7 kg/m2. Compliance was excellent and the study product was well-tolerated. As compared to placebo, movement time was significantly reduced by 4.8% within the five-choice reaction time test after 1 week of AME supplementation (intervention effect: - 12 ms; p < 0.05). Memory and executive function did however not change. Serum BDNF concentrations were significantly higher after AME supplementation as compared to placebo (+ 5.7%; intervention effect: 1.8 ng/mL; p < 0.05). However, arterial stiffness and retinal microvascular calibers were not affected. CONCLUSION: Short-term AME supplementation beneficially affected cognitive performance as attention and psychomotor speed improved. Serum BDNF concentrations were increased, but vascular function markers were not affected. CLINICAL TRIAL REGISTRATION: The study was registered on Clinical Trials under NCT03793777 on January 4th, 2019.

Can structure predict function at individual level in the human connectome?

Several studies predicting Functional Connectivity (FC) from Structural Connectivity (SC) at individual level have been published in recent years, each promising increased performance and utility. We investigated three of these studies, analyzing whether the results truly represent a meaningful individual-level mapping from SC to FC. Using data from the Human Connectome Project shared accross the three studies, we constructed a predictor by averaging FC of training data and analyzed its performance in the same way. In each case, we found that group average FC is an equivalent or better predictor of individual FC than the predictive models in terms of raw prediction performance. Furthermore, we showed that additional analyses performed by the authors of the three studies, in which they attempt to show that their predicted FC has value beyond raw prediction performance, could also be reproduced using the group average FC predictor. This makes it unclear whether any of the three methods represent a meaningful individual-level predictive model. We conclude that either the methods are not appropriate for the data, that the sample size is too small, or that the data does not contain sufficient information to learn a mapping from SC to FC. We advise future individual-level studies to explicitly report results in comparison to the performance of the group average, and carefully demonstrate that their predictions contain meaningful individual-level information. Finally, we believe that investigating alternatives for the construction of SC and FC may improve the chances of developing a meaningful individual-level mapping from SC to FC.

Innovative direct introduction-ion mobility-mass spectrometry (DI-IM-MS) approach for fast and robust isomer-specific quantification in a complex matrix: Application to 2'-fucosyllactose (2'-FL) in breast milk.

Identification and specific quantification of isomers in a complex biological matrix by mass spectrometry alone is not an easy task due to their identical chemical formula and therefore their same mass-to-charge ratio (m/z). Here, the potential of direct introduction combined with ion mobility-mass spectrometry (DI-IM-MS) for rapid quantification of isomers as human milk oligosaccharides (HMOs) was investigated. Differences in HMO profiles between various analyzed breast milk samples were highlighted using the single ion mobility monitoring (SIM2) acquisition for high ion mobility resolution detection. Furthermore, the Se+ (secretor) or Se- (non-secretor) phenotype could be assigned to breast milk samples studied based on their HMO contents, especially on the response of 2'-fucosyllactose (2'-FL) and lacto-N-fucopentaose I (LNFP I). The possibility of quantifying a specific isomer in breast milk by DI-IM-MS was also investigated. The standard addition method allowed the determination of the 2'-FL despite the presence of other oligosaccharides, including 3-fucosyllactose (3-FL) isomer in breast milk. This proof-of-concept study demonstrated the high potential of such an approach for the rapid and convenient quantification of isomers in complex mixtures.

LILRB2 promotes immune escape in breast cancer cells via enhanced HLA-A degradation.

PURPOSE: Increased expression of leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) is associated with immune evasion in breast cancer (BC). The aim of this study to elucidate the role of LILRB2 in BC progression. METHODS: LILRB2 expression in tumor tissues was detected by immunohistochemical staining. Human leukocyte antigen A (HLA-A) expression in BC cells was detected by Western blotting, and HLA-A ubiquitination was detected by immunoprecipitation and histidine pulldown assay. An in-situ tumor model was established in nude BALB/c mice to verify the role of LILRB2 in immune escape. Finally, the functions and potential mechanisms of LILRB2 in BC progression were explored using in silico data. RESULTS: LILRB2 was upregulated in BC tissues and cells, and correlated positively with poor prognosis. LILRB2 promoted BC progression by downregulating HLA-A expression. Mechanistically, LILRB2 facilitates the ubiquitination and subsequent degradation of HLA-A by promoting the interaction between the ubiquitin ligase membrane-associated ring finger protein 9 (MARCH9) and HLA-A. In syngeneic graft mouse models, LILRB2-expressing BC cells evaded CD8 + T cells and inhibited the secretion of cytokines by the cytotoxic CD8 + T cells. CONCLUSION: LILRB2 downregulates HLA-A to promote immune evasion in BC cells and is a promising new target for BC treatment.

Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.

Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

BACKGROUND: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. OBJECTIVE: We aim to describe the RSC's plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. METHODS: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA's sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA's reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. RESULTS: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC's pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. CONCLUSIONS: The RSC extended its surveillance activities to meet more but not all of the mosaic framework's objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

Inpatient midwifery staffing levels and postpartum readmissions: a retrospective multicentre longitudinal study.

BACKGROUND: Preventing readmission to hospital after giving birth is a key priority, as rates have been rising along with associated costs. There are many contributing factors to readmission, and some are thought to be preventable. Nurse and midwife understaffing has been linked to deficits in care quality. This study explores the relationship between staffing levels and readmission rates in maternity settings. METHODS: We conducted a retrospective longitudinal study using routinely collected individual patient data in three maternity services in England from 2015 to 2020. Data on admissions, discharges and case-mix were extracted from hospital administration systems. Staffing and workload were calculated in Hours Per Patient day per shift in the first two 12-hour shifts of the index (birth) admission. Postpartum readmissions and staffing exposures for all birthing admissions were entered into a hierarchical multivariable logistic regression model to estimate the odds of readmission when staffing was below the mean level for the maternity service. RESULTS: 64 250 maternal admissions resulted in birth and 2903 mothers were readmitted within 30 days of discharge (4.5%). Absolute levels of staffing ranged between 2.3 and 4.1 individuals per midwife in the three services. Below average midwifery staffing was associated with higher rates of postpartum readmissions within 7 days of discharge (adjusted OR (aOR) 1.108, 95% CI 1.003 to 1.223). The effect was smaller and not statistically significant for readmissions within 30 days of discharge (aOR 1.080, 95% CI 0.994 to 1.174). Below average maternity assistant staffing was associated with lower rates of postpartum readmissions (7 days, aOR 0.957, 95% CI 0.867 to 1.057; 30 days aOR 0.965, 95% CI 0.887 to 1.049, both not statistically significant). CONCLUSION: We found evidence that lower than expected midwifery staffing levels is associated with more postpartum readmissions. The nature of the relationship requires further investigation including examining potential mediating factors and reasons for readmission in maternity populations.

Safety and pharmacokinetics of antifungal agent VT-1598 and its primary metabolite, VT-11134, in healthy adult subjects: phase 1, first-in-human, randomized, double-blind, placebo-controlled study of single-ascending oral doses of VT-1598.

VT-1598 is a novel fungal CYP51 inhibitor and 1-tetrazole-based antifungal drug candidate with improved selectivity minimizing off-target binding to and inhibition of human CYP450 enzymes. Data are presented from this first clinical study in the evaluation of the safety and pharmacokinetic (PK) of single ascending doses of 40, 80, 160, 320, and 640 mg VT-1598, comprising a 160 mg cohort in both fasting and fed states. Eight healthy adults per dose were randomized to receive either oral VT-1598 or placebo (3:1). Over the dose range, exposures were with relatively high variation. The maximum plasma concentrations (Cmax) for VT-1598 were 31.00-279.4 ng/ml and for its primary metabolite, VT-11134, were 27.80-108.8 ng/ml. The plasma area under the concentration-time curve to the last measurable concentration (AUC0-last) for VT-1598 were 116.1-4507 ng*h/ml, and for VT-11134 were 1140-7156 ng*h/ml. The dose proportionality was inconclusive based on the results of the power model. The peak concentration time (Tmax) was 4-5 h for VT-1598 and for VT-11134. Half-life was 103-126 h for VT-11134. After food intake, Cmax of VT-1598 increased by 44% (geometric mean ratio (GMR), 1.44; 90%CI [0.691, 2.19]) and AUC0-last by 126% (GMR, 2.26; 90%CI [1.09, 3.44]), while exposure of VT-11134 was decreased 23% for Cmax (GMR, 0.77; 90%CI [0.239, 1.31]) and unchanged for AUC0-last (GMR, 1.02; 90%CI [0.701, 1.33]). Neither VT-1598 nor VT-11134 were detected in urine. No serious adverse events (AEs) or AEs leading to early termination were observed. The safety and PK profiles of VT-1598 support its further clinical development.

VT-1598 is a tetrazole antifungal with improved selectivity and demonstrated a high survival rate when murine infected with invasive aspergillosis, coccidiodomycosis, cryptococcosis, and candidiasis. We report a first-in-human study to evaluate safety and pharmacokinetics after an oral dose of VT-1598.

Global quantification of emerging and legacy per- and polyfluoroalkyl substances in indoor dust: Levels, profiles and human exposure.

This study investigated the occurrence and distribution of per- and polyfluoroalkyl substances (PFASs) in house dust samples from six regions across four continents. PFASs were detected in all indoor dust samples, with total median concentrations ranging from 17.3 to 197 ng/g. Among the thirty-one PFAS analytes, eight compounds, including emerging PFASs, exhibited high detection frequencies in house dust from all six locations. The levels of PFASs varied by region, with higher concentrations found in Adelaide (Australia), Tianjin (China), and Carbondale (United States, U.S.). Moreover, PFAS composition profiles also differed among regions. Dust from Australia and the U.S. contained high levels of 6:2 fluorotelomer phosphate ester (6:2 diPAP), while perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) were predominant in other regions. Furthermore, our results indicate that socioeconomic factors impact PFAS levels. The assessment of human exposure through dust ingestion and dermal contact indicates that toddlers may experience higher exposure levels than adults. However, the hazard quotients of PFASs for both toddlers and adults were below one, indicating significant health risks are unlikely. Our study highlights the widespread occurrence of PFASs in global indoor dust and the need for continued monitoring and regulation of these chemicals.

Impacts of decision support systems on cognition and performance for intelligence-gathering path planning.

Decision Support Systems (DSS) are tools designed to help operators make effective choices in workplace environments where discernment and critical thinking are required for effective performance. Path planning in military operations and general logistics both require individuals to make complex and time-sensitive decisions. However, these decisions can be complex and involve the synthesis of numerous tradeoffs for various paths with dynamically changing conditions. Intelligence collection can vary in difficulty, specifically in terms of the disparity between locations of interest and timing restrictions for when and how information can be collected. Furthermore, plans may need to be changed adaptively mid-operation, as new collection requirements appear, increasing task difficulty. We tested participants in a path planning decision-making exercise with scenarios of varying difficulty in a series of two experiments. In the first experiment, each map displayed two paths simultaneously, relating to two possible routes for the two available trucks. Participants selected the optimal path plan, representing the best solution across multiple routes. In the second experiment, each map displayed a single path, and participants selected the best two paths sequentially. In the first experiment, utilizing the DSS was predictive of adoption of more heuristic decision strategies, and that strategic approach yielded more optimal route selection. In the second experiment, there was a direct effect of the DSS on increased decision performance and a decrease in perceived task workload.

Discovery of a Novel Lidocaine Metabolite by Human Liver Microsome and Identification of Microbial Species Which Produces the Same Metabolite.

Preparation of drug metabolites at the milligram scale is essential for determining the structure and toxicity of drug metabolites. However, their preparation using recombinant proteins and human liver microsomes (HLM) is often difficult because of technical and ethical issues. Reproducing human drug metabolism in food-derived microorganisms may be useful for overcoming these challenges. In this study, we identified an unknown metabolite of the anaesthetic drug lidocaine, which is metabolised by HLM. By screening for lidocaine metabolic activity in five types of foods (blue cheese, shiitake mushroom, natto, yoghurt, and dry yeast), we found that bacteria isolated from natto reproduced the lidocaine metabolic reaction that occurs in HLM. A fraction containing the unknown lidocaine metabolite was prepared through mass cultivation of a Bacillus subtilis standard strain, ethyl acetate extraction, open column chromatography, and HPLC purification. We identified the unknown metabolite as 3-(2,6-dimethylphenyl)-1-ethyl-2-methyl-4-imidazolidinone using NMR. Our results showed that food-derived microorganisms can produce large amounts of human drug metabolites via large-scale cultivation. Additionally, food microorganisms that can reproduce drug metabolism in humans can be used to examine drug metabolites at a low cost and without ethical issues.

Microscopy detection and molecular characterisation of Giardia duodenalis infection in outpatients seeking medical care in Egypt.

Introduction: Giardiosis remains one of the most prevalent enteric parasitic infections globally. Earlier molecular-based studies conducted in Egypt have primarily focused on paediatric clinical populations and most were based on single genotyping markers. As a result, there is limited information on the frequency and genetic diversity of G. duodenalis infections in individuals of all age groups. Methods: Individual stool samples (n = 460) from outpatients seeking medical care were collected during January-December 2021 in Kafr El-Sheikh governorate, northern Egypt. Initial screening for the presence of G. duodenalis was conducted by coprological examination. Microscopy-positive samples were further confirmed by real-time PCR. A multilocus sequence typing approach targeted amplification of the glutamate dehydrogenase (gdh), beta-giardin (bg), and triose phosphate isomerase (tpi) genes was used for genotyping purposes. A standardised epidemiological questionnaire was used to gather basic sociodemographic and clinical features of the recruited patients. Results: Giardia duodenalis cysts were observed in 5.4% (25/460, 95% CI: 3.6-7.9) of the stool samples examined by conventional microscopy. The infection was more frequent in children under the age of 10 years and in individuals presenting with diarrhoea but without reaching statistical significance. Stool samples collected during the winter period were more likely to harbour G. duodenalis. All 25 microscopy-positive samples were confirmed by real-time PCR, but genotyping data was only available for 56.0% (14/25) of the isolates. Sequence analyses revealed the presence of assemblages A (78.6%, 11/14) and B (21.4%, 3/14). All assemblage A isolates were identified as sub-assemblage AII, whereas the three assemblage B sequences belonged to the sub-assemblage BIII. Patients with giardiosis presenting with diarrhoea were more frequently infected by the assemblage A of the parasite. Conclusion: This is one of the largest epidemiological studies evaluating G. duodenalis infection in individuals of all age groups in Egypt. Our molecular data suggest that G. duodenalis infections in the surveyed population are primarily of anthropic origin. However, because assemblages A and B are zoonotic, some of the infections identified can have an animal origin. Additional investigations targeting animal (domestic and free-living) and environmental (water) samples are warranted to better understand the epidemiology of giardiosis in Egypt.

Markerless motion capture provides repeatable gait outcomes in patients with knee osteoarthritis.

Motion analysis has seen minimal adoption for orthopaedic clinical assessments. Markerless motion capture solutions, namely Theia3D, address limitations of previous methods and provide gait outcomes that are robust to clothing choice and repeatable in healthy adults. Repeatability in orthopaedic populations has not been investigated and is important for clinical utility and adoption. The purpose of this study was to evaluate the repeatability of Theia3D for gait analysis in a knee osteoarthritis population. Ten orthopaedic patients with knee osteoarthritis underwent gait analysis on three visits, with an average of 8 days between. Participants were recorded during one-minute overground walking trials at self-selected typical and fast speeds by 8 synchronized video cameras. Video data were processed using Theia3D. Intraclass correlations were used to examine the repeatability of temporal distance metrics as well as segment lengths of the underlying kinematic model. Inter-trial and inter-session variability of lower extremity joint angles were estimated for each point of the gait cycle. Intraclass correlations were greater than 0.98 for all temporal distance metrics for both speeds. Lower body segment lengths had intraclass correlations above 0.90. Participant average joint angle waveforms displayed consistent patterns between visits. The average inter-trial and inter-session variability in joint angles across speeds were 1.17 and 1.45 degrees, respectively. The variability in joint angles between visits was less than typically reported for marker-based methods. Gait outcomes measured with Theia3D were highly repeatable in patients with knee osteoarthritis providing further validation for its use in clinical assessment and longitudinal studies.

Hypothalamic neuronal activation in non-human primates drives naturalistic goal-directed eating behavior.

Maladaptive feeding behavior is the primary cause of modern obesity. While the causal influence of the lateral hypothalamic area (LHA) on eating behavior has been established in rodents, there is currently no primate-based evidence available on naturalistic eating behaviors. We investigated the role of LHA GABAergic (LHAGABA) neurons in eating using chemogenetics in three macaques. LHAGABA neuron activation significantly increased naturalistic goal-directed behaviors and food motivation, predominantly for palatable food. Positron emission tomography and magnetic resonance spectroscopy validated chemogenetic activation. Resting-state functional magnetic resonance imaging revealed that the functional connectivity (FC) between the LHA and frontal areas was increased, while the FC between the frontal cortices was decreased after LHAGABA neuron activation. Thus, our study elucidates the role of LHAGABA neurons in eating and obesity therapeutics for primates and humans.

Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer.

Due to the limitations of autologous chimeric antigen receptor (CAR)-T cells, alternative sources of cellular immunotherapy, including CAR macrophages, are emerging for solid tumors. Human induced pluripotent stem cells (iPSCs) offer an unlimited source for immune cell generation. Here, we develop human iPSC-derived CAR macrophages targeting prostate stem cell antigen (PSCA) (CAR-iMacs), which express membrane-bound interleukin (IL)-15 and truncated epidermal growth factor receptor (EGFR) for immune cell activation and a suicide switch, respectively. These allogeneic CAR-iMacs exhibit strong antitumor activity against human pancreatic solid tumors in vitro and in vivo, leading to reduced tumor burden and improved survival in a pancreatic cancer mouse model. CAR-iMacs appear safe and do not exhibit signs of cytokine release syndrome or other in vivo toxicities. We optimized the cryopreservation of CAR-iMac progenitors that remain functional upon thawing, providing an off-the-shelf, allogeneic cell product that can be developed into CAR-iMacs. Overall, our preclinical data strongly support the potential clinical translation of this human iPSC-derived platform for solid tumors, including pancreatic cancer.

Microplastics suspended in dust from different indoor environments in Barranquilla, Colombia: predominant microparticles?

Considering that microplastics (MPs) are classified as ubiquitous pollutants, that air quality affects human health, and that people remain indoors most of the time, the need has arisen to evaluate the exposure to MPs within the suspended dust in indoor environments. With this objective, the present study carried out passive sampling to analyze the precipitation of microparticles in some indoor residential environments (2 apartments) and workplaces (an office, a pastry shop, a gift shop, and a paint shop) in Barranquilla, Colombia. The quantification and physical characterization of microparticles were carried out under a stereomicroscope, and the chemical characterization was carried out by infrared microspectroscopy (µFTIR). The highest average concentration of MPs in the apartments was found in the air-conditioned rooms (1.1×104 MPs/m2/day), and concerning the workplaces, the gift shop and the paint shop were the spaces with a higher proportion of MPs (6.0-6.1×103 MPs/m2/day), with polyesters being the main synthetic polymers, but being semi-synthetic particles the predominant among the samples. Regarding its morphology, fibers were the most abundant shape (>90%), grouping mainly in the 1000-5000 µm range, while the few fragments found were mostly grouped below 50 µm. Exposure by inhalation of MPs in adults was estimated between 1.7×102 - 1.6×103 MPs/kg/day, while by ingestion it ranged between 1.3×103 -1.2×104 MPs/kg/day. On the other hand, within our research, a significant presence of non-plastic microparticles was found, which reached up to 69% in analyzed samples, corresponding mainly to cotton and cellulose, so we suggest that these should also be included in future studies that aim to estimate potential health implications from exposure to suspended micropollutants.