Medical Research Archives

IntroductionIndividuals with COPD can be classified according to their levels of physical activity (PA) and physical capacity (PC). The relationship between nutrition and body composition within these classifications remains unclear. ObjectivesTo compare the body composition and food intake of people with COPD and verify the associations. MethodsCross-sectional exploratory analysis study in which body composition and food intake were assessed in individuals with COPD. Classification was based on six-minute walk test (PC) and accelerometry(PA): Quadrant "can do, dont do" (I-preserved PC, low PA); quadrant "can do, do do" (II-preserved PC, preserved PA). Results72 individuals with COPD, 39 in quadrant I and 33 in quadrant II, with mean ages of (69 {+/-} 6) (67 {+/-} 7), respectively. Group I had a higher proportion of males, whereas group II had a higher proportion of females. A positive trend in skeletal muscle mass (p=0.011) (B= 2.883) and a negative trend in basal metabolic rate (p=0.010) (B=-0.092) for group I. ConclusionBrazilians with COPD classified in quadrants I and II showed similar results in terms of body composition and food intake. A positive trend in skeletal muscle mass was observed for the group I. These findings align with the pathophysiological model of COPD, in which the preservation of muscle mass and adequate protein intake support functional capacity and the maintenance of higher physical activity levels.

Background: Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of global mortality, with persistent lung inflammation contributing to disease progression. This inflammation is partly associated with reduced levels of histone deacetylase 2 (HDAC2). Previous studies suggest that Vitamin D may modulate HDAC2 levels. This study aimed to evaluate the effect of Vitamin D supplementation on HDAC2 expression in stable COPD patients. This experimental study aimed to evaluate the effect of vitamin D supplementation on HDAC2 expression in stable COPD patients at Jemursari Islamic Hospital. Methods: Five COPD patients received a daily dose of 5000 IU of Vitamin D for three months. Serum levels of 25(OH)D3 and HDAC2 were measured before and after the intervention. Results: Vitamin D supplementation resulted in a significant increase in both 25(OH)D and HDAC2 levels. Pulmonary function parameters showed an increasing trend, however, no statistically significant differences were observed. Conclusion: Vitamin D supplementation was associated with increased HDAC2 levels, suggesting a potential anti-inflammatory effect. However, no significant improvement in pulmonary function was observed. Further studies are needed to determine its clinical impact.

BackgroundBronchiectasis in adults often goes undiagnosed following the routine assessment. Cystic Fibrosis (CF) is usually diagnosed during childhood, but some cases are identified in adulthood when disease is mild. High-resolution computed tomography (HRCT) of chest may offer structural information that can indicate CF as an underlying etiology. ObjectiveTo compare the HRCT features of adult patients with CF and non-CF bronchiectasis and to determine the radiologic features that may be suggestive of CF. MethodsThis retrospective, analytical, cross-sectional study was carried out in Bangladesh Medical University after IRB clearance. Total 130 adults (12 with CF and 118 with non-CF bronchiectasis) of both sexes, whose bronchiectasis was confirmed by chest HRCT were included. Imaging findings were assessed based on Reid morphological classification, anatomical distribution and extent of spread within the lungs, and their association was tested using chi-square test with statistical significance of p<0.05. ResultsCystic bronchiectasis was more common in CF than non-CF patients (83.3% vs 29.7; p<0.001). Mixed central-peripheral extension had been found a considerable associated with CF (66.7% vs. 42.4; p=0.034). There was no statistically significant difference in right lung lobar distribution (p=0.540) but combined upper and lower lobe involvement on the left side was more common in CF patients (54.5%) than non-CF patients (21.3) (p=0.054). ConclusionAdult CF had unique chest HRCT imaging characteristics when compared to non-CF bronchiectasis, especially cystic morphology and mixed extension. Identification of such features could help physician in the early diagnosis and selection of treatment strategy.

BackgroundThe primary cause of death associated with opioids is opioid-induced respiratory depression (OIRD). Naloxone is used to reverse OIRD, but this drug is a competitive antagonist of {micro}-opioid receptor (MOR) and reverses analgesia, which limits its therapeutic use. Alternative non-opioid receptor antagonist-based approaches to OIRD treatment and prevention are needed. The aim of this study was to evaluate if setmelanotide (SET) is capable of reversing OIRD in a mouse model. MethodsC57BL/6J male and female mice and Sprague-Dawley rats were given IP morphine or fentanyl and then treated 15 min later with either SET or vehicle VEH (IP) in a random order. Breathing was recorded by barometric plethysmography, and pain sensitivity was measured by the tail-flick test. ResultsIn mice with OIRD, SET induced a 3-fold reduction of the apnea index, and decreased apnea duration as compared to the VEH treatment. SET increased respiratory rate and did not affect opioid-induced analgesia. Photostimulation of MC4R+ ChR2-expressing fibers in the parafacial region of MC4R-Cre mice elicited short-latency excitatory postsynaptic current in rostral ventral respiratory group (rVRG) pre-motoneurons projecting to the phrenic nucleus in the C3-C4 ventral horns of the spinal cord. Fentanyl inhibited the activity of rVRG neurons and SET reversed this effect. ConclusionsSET effectively treated OIRD by increasing respiratory rate and inducing a significant decrease in the number of apneas without decreasing analgesia.

BackgroundThoracic spine mobilization (TSM) has been proposed to influence autonomic nervous system (ANS) activity, yet evidence remains inconsistent and feasibility of standardised protocols is unclear. This study aimed to evaluate whether a randomized TSM protocol can be implemented successfully in healthy participants and to provide preliminary estimates of its effects on heart rate variability (HRV) and heart rate (HR). MethodsA randomized feasibility trial was conducted with healthy young adults receiving six manual therapy sessions consisting of rotational mobilizations above Th5 over 14 days. Feasibility outcomes included adherence, absence of unexpected adverse events (UAE), and practicality of autonomic data acquisition. Physiological outcomes comprised HRV parameters, high-frequency (HF), low-frequency/high-frequency ratio (LF/HF) and HR, analyzed using autoregressive (AR) and fast Fourier transform (FFT) methods. ResultsProcedural safety and methodological integrity were confirmed (no UAE; complete datasets), but feasibility was only partially achieved due to adherence shortfalls, higher attrition, and device-related delays. Physiologically, large effect sizes were observed in the intervention group: at evening assessment, HF_AR showed ES = 0.80 (p = .008); at morning assessment, HF_FFT ES = 0.72 (p = .016), HF_AR ES = 0.78 (p = .010), and LF/HF_AR ES = 0.70 (p = .021). HR remained unchanged. These findings suggest repeated TSM may modulate HRV, primarily through HF-related changes associated with vagal activity, while LF/HF interpretation remains controversial. ConclusionA randomized TSM protocol is safe and methodologically viable with logistical refinements. Preliminary evidence indicates potential vagal modulation, warranting larger trials with respiratory control, ECG-based HRV, multimodal ANS measures, and clinical populations to confirm efficacy and translational relevance.

Acidification of the oral environment has been implicated in the initiation and progression of oral pathologies including oral cancer, but how acidic environments modulate normal oral epithelial cell (OEC) responses to microbial ligands is not understood. This study examined the impact of acidic stress on OEC morphological, molecular, and functional responses to toll-like-receptor ligand engagement in vitro. OEC cultures were exposed to either normal (pH:=:8.0) or acidified growth media (pH:=:3.0) for 24 hours prior to machine-learning-guided morphological analysis and exposure to either toll-like receptor (TLR)5 (flagellin) or TLR2/TLR1 (Pam3CSK4) agonists. Multiplex gene expression technology was used to quantify the transcriptional responses of metabolic-and immune-related genes at 6 hours post-TLR agonist exposure. OEC-mediated production of transforming growth factor-beta (TGF-{beta}) was assessed by enzyme-linked immunosorbent assay at 2-, 6-, and 24-hours post-agonist exposure. Results showed that acid exposure induced significant changes to OEC morphology resembling epithelial-mesenchymal transition, the differential expression of n=197 metabolic-and n=43 immune-related genes and significantly increased OEC TGF-{beta}1 production. The results demonstrate that acid stress skews normal OECs towards pro-inflammatory and pro-oncogenic phenotypes when faced with concomitant microbial ligand challenge and provide key molecular clues to OEC survival strategies with potential implications for elucidating the early molecular events in the development of epithelial dysplasia. Article HighlightsO_LIAcute acid exposure reduces survival of OECs C_LIO_LIA subpopulation of OECs is resistant to acid-mediated cell loss and undergo morphometric changes consistent with epithelial-mesenchymal transition C_LIO_LIConcurrent acid stress and TLR stimulation modulates transcription of immune and metabolic genes in OECs C_LIO_LIAcid stress increases TGF-{beta}1 protein production of OECs following TLR agonist stimulation C_LI

Spinal cord injury (SCI) is associated with cardiovascular deficits that affect cerebral blood flow, cerebral perfusion, and cerebrovascular control. While several studies use neuroimaging techniques such as functional magnetic resonance imaging (fMRI) to understand neuroplasticity following SCI, more work needs to be done to evaluate the cerebrovascular changes following SCI. Understanding these effects using neuroimaging is essential as these deficits also affect neurovascular coupling and how we interpret neuroplasticity measured based on neuroimaging. Hence, we conducted a pilot study in twelve healthy males and thirteen males with thoracolumbar SCI using functional near-infrared spectroscopy (fNIRS) to understand the effects of breath-holding induced hypercapnia on the hemodynamics of the sensorimotor cortex and prefrontal cortex (PFC) after SCI. Participants performed 30 seconds of regular breathing alternated by 15 seconds of breath-holding for 5 minutes. Compared to controls, the SCI group presented with a greater initial decrease in oxy-hemoglobin concentration change and a delayed subsequent increase in oxy-hemoglobin concentration change in response to hypercapnia at p<. Additionally, the net increase in oxy-hemoglobin concentration change following BH in the PFC was negatively correlated with the level of injury at p=0.005, where higher levels of injury were associated with a smaller increase in oxy-hemoglobin concentration following hypercapnia. These findings confirm that a) SCI, including lower levels of injury (below T6) are associated with cerebrovascular changes that are quantifiable using fNIRS, and b) fNIRS could be a robust tool to understand the neuroplastic and cerebrovascular changes in people with SCI.

Dental enamel, the hardest mineralised tissue in the human body, has proven to be an excellent source of ancient proteins, which have been found to survive within dental enamel for at least twenty million years. In archaeological and palaeontological contexts, the enamel proteome is generally considered to be rather small, consisting of about twelve proteins, most of which are unique to enamel. During amelogenesis these proteins undergo in vivo digestion by matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4) as well as serine phosphorylation by family with sequence similarity member 20-C (FAM20C) that alter their characteristics. Gaining knowledge of the previously understudied influence of amelogenesis on the archaeological human dental enamel proteome could benefit various palaeoproteomic analysis, especially in an human evolutionary context. Here we present archaeological dental enamel proteomes and explore protein cleavage patterns and sequence coverage to estimate the effects of in vivo digestion, as well as explore phosphorylation patterns. Additionally, we present a new marker based on phosphorylation to estimate genetic sex.

BackgroundIn the conflict-ridden Gaza Strip, burn injuries pose significant challenges for affected individuals. Often stemming from accidents involving generators and substandard gas cylinders, these burns can have profound physical and psychological impacts. Access to comprehensive medical care is limited in this context, making specialized burn treatment centers critical lifelines for those in need. This study seeks to explore the outcomes of rehabilitation and physiotherapy for post-surgical skin grafts in specialized burn treatment centers in Gaza, recognizing the crucial role such interventions play in improving the quality of life for burn survivors in this challenging environment. MethodsWe carried out a retrospective descriptive study of patients with post-surgical skin graft (SSG) scars subsequent to burns injury, and enrolled in the MSF post-op outpatient clinics in the Gaza Strip (Gaza City, Beit Lahia, and Khan Younis), between January 2018 and December 2020. Our analysis used five outcome measures to assess the effects of physiotherapy and post-surgical treatment: the reducibility score, which indicates the extent to which scars can be reduced in size or prominence; the Functional Activity for Burn (FAB) score, which evaluates the functional capabilities of patients following burn injury; the Vancouver Scar Scale (VSS), which assesses various aspects of scar appearance such as pigmentation, vascularity, pliability, and height; the Visual Analgesic Scale (VAS), which quantifies pain levels experienced by patients; and the itching score, which measures the severity of itching associated with scar formation ResultsA total of 177 patient records were examined, revealing that the majority of burn victims in Gaza were children under the age of 18 (n=136, 76.8%), with scalding from liquid burns being the primary cause (n=119, 67.6%). The outcomes of the physiotherapy program varied depending on the type of pressure therapy and insert material utilized. However, significant improvements were observed in various outcome measures following enrollment in the program. These improvements included reductions in pain scores (mean initial score: 5.3, SD: 2.5; mean final score: 1.4, SD: 1.8), itching (mean initial score: 3.7, SD: 2.7; mean final score: 2.7, SD: 2.2), scar pigmentation, vascularity, pliability, and height (mean initial VSS: 7.1, SD: 1.8; mean final VSS: 5.7, SD: 1.7). Moreover, treatment correlated with enhancements in overall function (mean initial score: 25.6, SD: 7.1; mean final score: 34.6, SD: 2.3) and a reduction in skin contracture (mean initial score: 2.3, SD: 1.4; mean final score: 0.8, SD: 0.9). ConclusionsOur findings underscore the important role of rehabilitation and physiotherapy in optimizing outcomes for post-surgical skin graft patients in conflict-affected regions like the Gaza Strip. Despite the challenging environment, MSFs clinic in Gaza has demonstrated the feasibility and effectiveness of delivering comprehensive care to burn survivors. Moving forward, further research is needed to refine and validate best practices in rehabilitation interventions tailored to the specific needs of patients in conflict zones, ensuring continued progress in enhancing the quality of care and quality of life for those affected by burn injuries.

The present study was aimed at evaluating the effects of the bioresonance (BR)-based device QDOME MINI PERSONAL, produced by the society QMED SWISS SA (Lugano, CH), on the viability and mitochondrial metabolic activity of cultured human umbilical venous endothelial cells (HUVEC). To this end, HUVEC were cultured under standard conditions and exposed for 24 h to an "active" or to a mock BR device, in resting conditions and during treatment with H2O2 at the concentration of 500 M, added at the beginning of the 24 h period. The personnel who performed the experiments, collected, and analysed the data was unaware of which device was "active" and which was mock. At the end of the culture, HUVEC were harvested and evaluated for viability and mitochondrial metabolic activity by means of the Trypan Blue exclusion and the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide reduction method, respectively. Under control conditions, viability and mitochondrial metabolic activity were not different in HUVEC exposed to the "active" or to the mock device. HUVEC viability, however, was significantly reduced by exposure to H2O2 in samples exposed to the mock device but not in those exposed to the "active" device. HUVEC mitochondrial metabolic activity was significantly reduced by exposure to H2O2 in both samples exposed to the "active" and to the mock device, however reduction was significantly less in samples exposed to the "active" device. In conclusion, exposure to the BR-based device QDOME MINI PERSONAL, produced by the society QMED SWISS SA (Lugano, CH), prevented the H2O2-induced reduction of viability and reduced the H2O2-induced impairment of mitochondrial metabolic activity in cultured HUVEC.

Pentosan polysulfate (PPS) is a semisynthetic sulfated polysaccharide that was approved by the United States Food and Drug Administration (FDA) for treatment of interstitial cystitis (IC). A 2018 study by our group described a vision-threatening macular toxicity associated with long-term use of PPS. However, given the relatively recent characterization of PPS maculopathy, we have limited knowledge of its pathophysiology. The present study therefore investigated the pathophysiology of PPS maculopathy in a cell culture model, assessing impacts of PPS exposure on morphology and mitochondrial function. We treated ARPE-19 cells with increasing doses of PPS and investigated both mitoprotective and cytoprotective mechanisms, mitochondrial reactive oxygen species production (ROS) and respiration, cellular structure, and retinal pigment epithelium (RPE) dysfunction through phagocytosis assays. We found that PPS increased mitochondrial superoxide accumulation and that increased doses of PPS impaired basal and maximal respiration in a Seahorse assay without the expected response of increases in the cellular energy sensor pAMPK. PPS exposure disrupted mitochondrial and cell protective mechanisms against ROS accumulation as assessed through examination of mitochondrial biogenesis markers PGC-1 and SIRT1 and autophagy markers LC3 and p62. PINK1 expression increased with increasing duration of exposure to PPS. Further, we found that PPS led to functional and structural changes to RPE cells, which exhibited an increase in cell aspect ratio and impaired phagocytosis with higher doses of PPS. Lastly, we found an increase in cell death in response to higher doses of PPS, evident through ethidium homodimer cell viability assays. Taken together, our study shows PPS exposure has profound effects on RPE viability and function through impairment of mitochondrial respiration and mito- and cyto-protective mechanisms and highlights mitochondrial insult as a potential focus of future PPS research.

The placenta is an important producer of hormones essential for fetal development. Insulin-like growth factor 1 (IGF1) is a hormone primarily produced in the placenta in utero and is an important regulator of various developmental pathways including those in heart and liver. Embryonic disruptions in these developmental pathways can lead to lifelong changes and are often associated with chronic disease. Further, the placenta has sex-specific impacts on offspring development in response to hormonal changes. Previous work has shown that altered expression of Igf1 in the placenta results in sexually dimorphic changes to placental and fetal developmental outcomes. Here, mice underwent placental-targeted CRISPR manipulation for overexpression or insufficiency of Igf1. At the time of euthanasia, heart and liver tissues were collected and weighed. This dataset presents the heart and liver mass of these postnatal mice. There was a significant increase in proportional heart mass in placental Igf1 overexpression adult female mice and a trending increase in proportional liver mass in placental Igf1 overexpression adult male mice. No significant changes in heart or liver mass were seen in placental Igf1 insufficiency mice. These data provide insight into the impact of placental IGF1 on long-term heart and liver development. VALUE OF THE DATAO_LIThere is significant evidence for the role of early genetic changes in influencing long-term health outcomes, as laid out by the Developmental Origins of Health and Disease (DOHaD) hypothesis [1]. According to this hypothesis, genetic factors may be critical in determining the timing and severity of chronic disease, with varying effects based on sex. Genetics of the placenta, which makes up the maternal-fetal interface, plays an important role in modulating exposures associated with the DOHaD hypothesis [2]. C_LIO_LIThe placenta provides essential hormones to the fetus during pregnancy [3]. Placental changes are associated with the development of chronic disease and metabolic changes [4,5]. Disruptions in placental functions have been linked to defects including congenital heart disease which affects approximately 40,000 babies each year in the United States [6,7]. The placenta is also linked to metabolic diseases later in life such as nonalcoholic fatty liver disease, a chronic liver disease which has increased in prevalence by over 50% from 1990 to 2019 [5,8,9]. C_LIO_LIInsulin-like growth factor 1 (IGF1) is a placentally produced factor that regulates pathways involved in fetal growth and development and has been shown to be critical in growth of the heart and liver [10-13]. Despite the importance of the placenta and IGF1 in heart and liver growth, specific links between placental Igf1 expression and developmental outcomes remain understudied. C_LIO_LIPlacental function is known to have sex-specific impacts on fetal growth [14]. Further, Igf1 expression in the placenta is linked to differences in offspring developmental outcomes by sex [15]. Placental Igf1 overexpression and insufficiency affect offspring in a sexually dimorphic manner. IGF1 is a hormone and interacts with sex hormones, likely contributing to sex differences in response to changes in Igf1 expression [16]. Further research, including the work done to produce this dataset, may help clarify the role of placenta Igf1 expression in fetal outcomes, specifically regarding sex differences. C_LIO_LIThe data presented in this paper provide insight into the effects of placental Insulin-like growth factor 1 overexpression and insufficiency on adult heart and liver mass. More research is needed to understand specific functional impacts on these organs. Further, understanding the effects of placental genetic changes may support the development of future treatments and therapies for placental insufficiencies. C_LI

Breastfeeding provides health benefits in childhood, reducing the frequency of gastrointestinal and respiratory infections. Breastmilk (BM) is a rich source of bioactive molecules including extracellular vesicles (EVs), which exert immunomodulatory signalling in recipient cells, with cargo that is affected by maternal characteristics. Here we investigated the biophysical characteristics of BM-EVs from mothers with (asthmatic BM-EVs) or without asthma (control BM-EVs) and their effect on the release of cytokines from primary human hTERT-immortalized airway smooth muscle cells (hASMs) from asthmatic or non-asthmatic (control) donors. BM-EVs were isolated using size exclusion chromatography (N=5/group), characterized biophysically and by EV-specific protein markers. In addition, BM-EV were co-cultured (48h) with primary hASM cells from both non-asthmatic (control) and asthmatic donors to determine the effect on cytokine release. All participants were Caucasian and the BM was collected 12-15 weeks postpartum. BM-EVs showed the presence of intact and small-EVs ([~]100 nm). Asthmatic BM-EVs appeared to have a smaller average EV size (135.6 nm) vs. controls (148.3 nm, p=0.0613), but [~]5-fold higher concentration of both total (p=0.0014) and small EVs (p=0.0016). The expression of EV subtype protein expression was reduced in asthmatic BM-EVs vs. control BM-EVs: CD63 by 86% (p=0.0224), flotillin-1 by 40% (p=0.0196), CD9 by 24% (p=0.0646) and HSP70 by 69% (p=0.0873). Asthmatic BM-EVs co-cultured with hASMs from control donors decreased pro-inflammatory cytokine release: MCP-1 by 55% (p=0.0286), IL-6 by 45% (p=0.0801) and IL-2 by 32% (p=0.0970) vs. control-BM-EVs. Conversely, asthmatic BM-EVs co-cultured with hASMs from asthmatic donors increased secretion of anti-inflammatory cytokine IL-10 by 32% (p=0.0660), and IL-1Ra by 75% (p=0.0875), and pro-inflammatory IL-2 by 57% (p=0.0688) vs. control-BM-EVs. Internalization of control and asthmatic BM-EVs was confirmed by labelled EV uptake experiments. No detrimental effects on cell viability with BM-EV treatment were observed. In summary, asthmatic BM-EVs are smaller and enriched in BM, and exert differential effects on cytokine release in a BM-donor and recipient-cell specific manner. Given that BM can enter infant airways, the immunomodulatory effects of BM-EVs on hASMs warrants further investigation to delineate the under underlying mechanisms.

Intervertebral disc degeneration, a leading cause of low back pain with incompletely elucidated molecular mechanisms, was studied via integrated in vivo/vitro approaches. This study first reveals that lactic acid accelerates intervertebral disc degeneration by inducing cartilage endplate stem cells senescence and DNA damage, thereby activating the P16/P21/P53-centered senescence pathway. In a rat tail vertebra puncture-induced intervertebral disc degeneration model, degenerated discs exhibited increased lactic acid levels, narrowed intervertebral spaces, and disrupted nucleus pulposus structure (P<0.05). In vitro, 0/2/6/10 mM lactic acid dose-dependently suppressed cartilage endplate stem cells viability (10 mM group: 15.7% of the control), elevated intracellular reactive oxygen species (ROS, 2.8-fold relative to the control), induced G0 cell cycle arrest (10 mM group: 85.63%), reduced EdU-positive cells (8.62%), and increased {beta}-galactosidase-positive cells (10 mM group: 33.06%) and {gamma}-H2AX foci (all P<0.01).Molecularly, lactic acid significantly upregulated P16 (2.1-fold), P21 (3.1-fold), P53 (2.4-fold), and {gamma}-H2AX (1.8-fold). In vivo intervertebral disc injection confirmed a positive correlation between lactic acid concentration and intervertebral disc degeneration severity. This study clarifies lactic acids role in intervertebral disc degeneration via the "oxidative stress-cell cycle arrest-cellular senescence" axis, advancing understanding of intervertebral disc degeneration pathogenesis and providing a basis for targeted therapies against lactic acid metabolism.

Hydroxycarboxylic acid receptors (HCARs) are class A G-protein-coupled receptors that function as metabolic sensors. This receptor family includes three members (HCAR1, HCAR2, and HCAR3) expressed in metabolically active tissues and immune cells, where they link cellular metabolic status to physiological responses. This study aims to elucidate the evolutionary history of the most recently originated members of the HCAR gene family, namely HCAR2 and HCAR3, in primates. According to our phylogenetic analyses, the duplicative history of these genes involved multiple independent duplication events during ape evolution. Thus, most ape lineages possess independently originated duplicated copies, while non-ape primates retain the ancestral condition of a single-copy gene (HCAR2/3). Our analyses further indicate that this single-copy gene in non-ape primates is functionally equivalent to HCAR2, suggesting that the primary functional innovation in apes is associated with the physiological roles of HCAR3. Finally, gene expression analyses reveal that major divergence in tissue expression occurred after the initial duplication event that generated HCAR1 and the HCAR2/3 lineage, whereas HCAR2 and HCAR3 exhibit substantial overlap in their expression profiles. Thus, the more refined and context-dependent regulation of lipid metabolism that provides the HCAR3 receptor seems to have originated multiple times during the evolutionary history of apes.

AimThe mammalian tracheal epithelium is composed by different cell types unevenly distributed along the proximal-distal axis. Nevertheless, variations in expression and function of ion channels and transporters participating in fluid absorption and secretion had never been studied separately in proximal and distal sections of the mouse trachea. In this work, we aim to characterize basal and stimulated absorption and secretion of fluid obtained from proximal and distal trachea from the same animal. MethodsUssing chamber experiments were performed using a custom-made tissue slider that allowed the mounting small tracheal sections, where response to agonists and blockers was recorded. The role of the NKCC1 co-transporter was studied using the Slc12a2-/- mouse. A genetically tomato-induced mouse model was used to assess co-expression of NKCC1 and ASCL3 by immunofluorescence. Animals were instilled with different interleukins (ILs) to determine changes in absorption, secretion and mucus properties. ResultsProximal trachea didnt participate in sodium absorption but exhibited higher cAMP- and succinate-induced anion secretion than the distal section. NBCe1-dependent bicarbonate and TMEM16A-driven chloride secretion was significantly higher in the distal section. NKCC1+ cells were found in the submucosal glands (SMGs) and abundant patches of NKCC1+ cells in the distal region. Isolated NKCC1+ cells co-expressing ASCL3 were also detected. ILs treatment changed the electrophysiological properties of the distal but not the proximal trachea. ConclusionsOur experiments determined that the mouse trachea organizes its functions differentially in the proximal and distal sections, based in the functional distribution of channels, transporters and receptors. While the distal trachea drastically changed its responses to agonists inducing anion secretion the proximal trachea was unperturbed by the action of ILs.

BackgroundThe COVID-19 pandemic significantly disrupted healthcare services globally, particularly in low-resource settings. This study explores the impact of the pandemic on physiotherapy services in Nepal. MethodsA cross-sectional study was conducted. Qualitative data were collected through semi-structured interviews with 12 physiotherapists, while quantitative data were gathered from an onsite survey of 29 health facilities at six different districts of Province III of Nepal. Inductive thematic analysis approach was used to analyze the qualitative data, and descriptive statistics were used for the closed ended questions. ResultsThe findings were categorized into sub-themes under two major themes: i) Pandemic effect on physiotherapy services and patient care and ii) Adaptation, innovation and collaboration. The study revealed a significant disruption in physiotherapy services with a notable decline in patient flow and service availability. Most patients, especially those with disabilities and post-operative needs, experienced worsening conditions due to limited access to care. There was an increased recognition of the role of physiotherapy in acute respiratory care and post-COVID-19 recovery. Tele-rehabilitation was explored as an alternative care method but faced challenges in implementation. More than half (62.07%) of the centers reported uninterrupted physiotherapy services, whereas almost one third (31.03%) experienced service suspension. Most centers (89.7%) had personal protective equipment available, and majority (86.2%) of the physiotherapists worked in multidisciplinary team: fever clinics, triage, emergency care, respiratory physical therapy, and nursing and administrative support were among the expanded roles. Several centers (37.9%) used virtual care with telephone consultation serving as the primary modality. Virtual service was mostly absent in centers where in-person services persisted. ConclusionThe COVID-19 pandemic significantly impacted physiotherapy services in Nepal, leading to service disruptions and compromised patient care. It highlighted the need to further incorporate physiotherapy into the healthcare system and enhance rehabilitation services to improve continued patient care.

Global healthcare is targeting patient-centred care, as it leads to better health outcomes and higher level of patient satisfaction. Patient-centred communication, is an important part of patient-centred care because it focuses on involving patients in their care. Recent surveys both nationally and globally have shown that patients are not involved enough in their own healthcare decisions. This problem is especially common among the elderly with chronic conditions. This study aimed to describe patient-healthcare professional interactions, expectations, and satisfaction in physiotherapy within an understudied context, thereby providing important, specific data on ICE dynamics and satisfaction in the specific setting. Cross-sectional study of participants in scheduled consultations was conducted. Two government physiotherapy centres, seven private physiotherapy centres and two trust centres with physiotherapy facilities in Gujarat, India. 232 patients (from various public and private physiotherapy clinics) participated in the study. Patients' ideas, concerns, expectations (ICE) and satisfaction were explored. Almost 88% of patients reported their thoughts and explanations about their symptoms during the consultation. Most patients described not having any concerns about the diagnosis/treatment, and more than two-third of patients consulting PTs expected explanation for their symptoms. Almost 90% patients were satisfied with the consultation. The study revealed that while most patients conveyed their thoughts during consultations, very few expressed their concerns. Overall, patients were satisfied with their consultations.

High-frequency repetitive magnetic stimulation (rMS) has emerged as a non-invasive technique capable of modulating cellular signaling pathways, including those involved in inflammation and oxidative stress. Our previous work demonstrated that high-frequency rMS modulated p62/SQSTM1 expression. Given the intricate link between p62 and autophagy, we hypothesized that high-frequency rMS might influence autophagic processes in macrophages. This study investigated the effects of a single high-frequency rMS treatment on autophagy and inflammation in THP-1-derived macrophages. The results showed that 10 Hz rMS decreased autophagy, evidenced by a reduction in LC3-II expression, quantified by Western blot, and a decrease in autophagic flux, assessed by flow cytometry following bafilomycin A1 treatment. Immunofluorescence assays were used to evaluate the number of LC3-positive and LysoTracker-positive puncta. Furthermore, rMS treatment attenuated lipopolysaccharide-induced inflammation and M1 polarization in THP-1-derived macrophages, as demonstrated by the downregulation of genes encoding pro-inflammatory cytokines (IL-1{beta}, IL-6, TNF-) and M1 polarization markers (IL-23 and CCR7). These findings suggest that high-frequency rMS exerts a regulatory effect on autophagy and inflammation in macrophages, providing a novel approach for the treatment of inflammatory and autophagy-related diseases.

BackgroundThe effects of dexamethasone during in vitro human osteogenesis present a complex picture. On one side, dexamethasone promotes the osteogenic differentiation of human bone marrow mesenchymal stromal cells (BMSCs) by downregulating SOX9. On the other side, it simultaneously promotes adipogenesis through the upregulation of PPARG. The regulation of SOX9 and PPARG levels appears to be mediated by the transactivation function of the glucocorticoid receptor (GR), suggesting an indirect effect of dexamethasone on SOX9 downregulation. This study aims to determine whether PPAR-{gamma} affects the expression levels of SOX9, as suggested by several studies. MethodsHuman BMSCs were isolated from bone marrow and cultured in different osteogenic induction media containing 10 or 100 nM dexamethasone. Undifferentiated cells were used as control. Cells were treated either with a pharmacological PPAR-{gamma} inhibitor (T0070907) or with a PPARG-targeting siRNA. Differentiation markers or PPAR-{gamma} target genes were analysed by RT-qPCR. Mineral deposition was assessed by Alizarin Red staining. Two-way ANOVA followed by a Sidak multiple comparison test was used to compare the effects of treatments. ResultsPharmacological inhibition of PPAR-{gamma} had a mild effect on the expression of PPAR-{gamma} target genes but hindered adipocyte formation. Neither RUNX2 nor SOX9 expression were affected by T0070907. siRNA treatment successfully downregulated PPARG expression, as well as that of PPAR-{gamma} target genes LPL, LPAR1, and ADIPOQ. Contrary to expectations, RUNX2 was significantly downregulated by the PPARG-siRNA treatment during osteogenic differentiation both in the absence and presence of dexamethasone, while SOX9 levels were downregulated in undifferentiated cells. Overall, Alizarin Red staining analysis showed no change in mineralization levels when PPARG expression or activity was inhibited. ConclusionsUnderstanding how dexamethasone regulates human BMSC differentiation is crucial to refine current in vitro models. These results suggest that PPAR-{gamma} is not involved in SOX9 or RUNX2 repression during in vitro osteogenic differentiation of human cells.