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BioRxiv : the Preprint Server For... Jun 2024The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb...
UNLABELLED
The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb cysts that contribute to the overall architectural remodeling of lung tissue seen in the disease. Here we describe an additional histopathologic finding of epithelial desquamation in patients with IPF, wherein epithelial cells detach from the basement membrane of the distal bronchioles. To understand the mechanism driving this pathology, we performed spatial transcriptomics of the epithelial cells and spatial proteomics of the basement membrane of the distal bronchioles from IPF patients and patients with no prior history of lung disease. Our findings reveal a downregulation of cell junctional components, upregulation of epithelial-mesenchymal transition signatures and dysregulated basement membrane matrix in IPF distal bronchioles, facilitating epithelial desquamation. Further, functional assays identified regulation between Collagen IV in the matrix, and the junctional genes and , that is crucial for maintaining distal bronchiolar homeostasis. In IPF, this balanced regulation between matrix and cell-junctions is disrupted, leading to loss of epithelial adhesion, peribronchiolar fibrosis and epithelial desquamation. Overall, our study suggests that in IPF the interplay between the loss of cell junctions and a dysregulated matrix results in desquamation of distal bronchiolar epithelium and lung remodeling, exacerbating the disease.
ONE SENTENCE SUMMARY
Two-way regulation of cell junctional proteins and matrix proteins drives cellular desquamation and fibrosis in the distal bronchioles of patients with Idiopathic Pulmonary Fibrosis.
PubMed: 38948715
DOI: 10.1101/2024.06.17.599411 -
Frontiers in Veterinary Science 2024Synthesis and secretion of bile acids (BA) is a key physiological function of the liver. In pathological conditions like portosystemic shunt, hepatic insufficiency,...
Synthesis and secretion of bile acids (BA) is a key physiological function of the liver. In pathological conditions like portosystemic shunt, hepatic insufficiency, hepatitis, or cirrhosis BA metabolism and secretion are disturbed. Quantification of total serum BA is an established diagnostic method to assess the general liver function and allows early detection of abnormalities, liver disease progression and guidance of treatment decisions. To date, data on comparative BA profiles in dogs are limited. However, BA profiles might be even better diagnostic parameters than total BA concentrations. On this background, the present study analyzed and compared individual BA profiles in serum, plasma, urine, and feces of 10 healthy pups and 40 adult healthy dogs using ultra-high performance liquid chromatography coupled to electrospray ionization mass spectrometry. Sample preparation was performed by solid-phase extraction for serum, plasma, and urine samples or by protein precipitation with methanol for the feces samples. For each dog, 22 different BA, including unconjugated BA and their glycine and taurine conjugates, were analyzed. In general, there was a great interindividual variation for the concentrations of single BA, mostly exemplified by the fact that cholic acid (CA) was by far the most prominent BA in blood and urine samples of some of the dogs (adults and pups), while in others, CA was under the detection limit. There were no significant age-related differences in the BA profiles, but pups showed generally lower absolute BA concentrations in serum, plasma, and urine. Taurine-conjugated BA were predominant in the serum and plasma of both pups (68%) and adults (74-75%), while unconjugated BA were predominant in the urine and feces of pups (64 and 95%, respectively) and adults (68 and 99%, respectively). The primary BA chenodeoxycholic acid and taurocholic acid and the secondary BA deoxycholic acid and lithocholic acid were the most robust analytes for potential diagnostic purpose. In conclusion, this study reports simultaneous BA profiling in dog serum, plasma, urine, and feces and provides valuable diagnostic data for subsequent clinical studies in dogs with different kinds of liver diseases.
PubMed: 38948668
DOI: 10.3389/fvets.2024.1380920 -
Turkish Journal of Physical Medicine... Jun 2024This study explored the perceived impact of a smartphone app on awareness, knowledge, attitudes, help-seeking, behavior change, and intention to change an abnormal...
This study explored the perceived impact of a smartphone app on awareness, knowledge, attitudes, help-seeking, behavior change, and intention to change an abnormal posture of the neck while using smartphones among undergraduates addicted to smartphone use. This descriptive survey involved smartphone-addicted undergraduates recruited between February 2022 and July 2022. The self-administered questionnaires used for gathering the data were a smartphone addiction survey and a mobile app rating scale on app-specific query assessing changes in awareness, knowledge, attitude, intention to change, health-seeking, and behavior change. The questionnaire was completed by 316 participants (218 females, 98 males; mean: 20.7±2.6 years; range, 16 to 35 years). One hundred forty-two (44.9%) of the respondents strongly agreed that the app improved awareness, while 143 (45.3%) strongly agreed that the app improved knowledge about the significance of addressing abnormal posture of the neck while using smartphones. One hundred thirty-two (41.8%) were of the opinion that the app could change participant attitudes, and 135 (42.7%) agreed that the app could increase intentions toward improving abnormal posture of the neck. One hundred eighteen (37.3%) participants agreed that the app could promote help-seeking for abnormal posture of the neck. Respondents' age had a negative weak correlation with intention to treat (r=-0.191, p=0.001) and help-seeking (r=-0.199, p=0.0001). Most of the respondents in this study agreed that the CerviTech app could increase awareness, knowledge, attitude, intention to change, help-seeking, and behavior change of abnormal posture of the neck while using smartphones, with significant impact according to the age of the respondents regarding the intention to change and help-seeking behavior.
PubMed: 38948654
DOI: 10.5606/tftrd.2024.12392 -
Journal of Family Medicine and Primary... May 2024Systemic lupus erythematosus (SLE), the commonest type of lupus, is an autoimmune multisystemic disorder that can affect any organ system of the body, especially blood...
INTRODUCTION
Systemic lupus erythematosus (SLE), the commonest type of lupus, is an autoimmune multisystemic disorder that can affect any organ system of the body, especially blood vessels and connective tissues, causing widespread inflammation. Pediatric onset of SLE is a rare condition with more hematological involvement.
AIM
This study was undertaken to observe various hematological abnormalities and their association with various autoantibodies present in pediatric SLE in Eastern India.
METHODOLOGY
It was a single-centered, cross-sectional, observational, hospital-based study conducted in the Department of Pediatric Medicine in collaboration with the Department of Rheumatology in IPGME and R and SSKM Hospital, Kolkata. The duration of the study was 1.5 years, and a total of 30 children up to 12 years of age of either gender were enrolled. Study participants were evaluated for various parameters like demographic, hematological (anemia, neutropenia, leucopenia, lymphopenia, and thrombocytopenia), biochemical (CRP, Lactate dehydrogenase (LDH), and bilirubin), autoantibodies (anti-dsDNA, anti-Ro 52, and anti-Ribonucleoprotein [RNP]), and SLE related pathologies (Cutaneous, nephritis, serositis).
RESULTS
In the present study, most of the participants had arthritis, muscle pain (86.66%), and hematological involvement (80%). Among cytopenias, anemia was the commonest. dsDNA autoantibody was positive in most of the patients (83%), and about one-third suffered from autoimmune hemolytic anemia (AIHA). No association was observed between autoantibodies and various hematological manifestations.
CONCLUSION
It can be concluded from the present study that anemia is the most common cytopenia in pediatric SLE, but there is no association between autoantibodies and these cytopenias. However, study on larger population may give better results.
PubMed: 38948621
DOI: 10.4103/jfmpc.jfmpc_1583_23 -
Journal of Family Medicine and Primary... May 2024Polycystic ovary syndrome (PCOS) is a heterogeneous disorder and various phenotypes have been described. While most women with PCOS are obese, women who are lean also...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder and various phenotypes have been described. While most women with PCOS are obese, women who are lean also suffer from PCOS. Metabolic derangements often accompany this syndrome. Family physicians, being the first point of contact in the healthcare system, play a vital role in the early diagnosis and management of this condition through diet and lifestyle modifications. The present study was conducted at the Diet and Lifestyle Diseases Management Division of a Family Medicine Clinic.
METHODS
We conducted a retrospective analysis of the correlation between body mass index (BMI) and metabolic parameters in women diagnosed with PCOS. The case records of women with PCOS, diagnosed as per modified Rotterdam criteria and who attended the outpatient clinic from January 2020 to December 2022, were chosen. Data on BMI and metabolic parameters were retrieved and statistically analyzed.
RESULTS
Upon analysis of 51 case records, 25.49% of women were in the lean group and 74.51% were overweight or obese. Triglycerides/HDL ratio (1.91 ± 0.47 vs 3.97 ± 5.89) and Vitamin D levels (Median 14.12 vs 16.10 ng/ml) were abnormal in both the obese and the lean women groups. However, there was no significant difference between the groups. Other metabolic parameters were within normal ranges.
CONCLUSION
The present study indicates that metabolic derangements are associated with PCOS, irrespective of BMI. More robust studies in larger population samples are needed to elucidate the role of metabolic derangements and mainly insulin resistance in the pathophysiology of PCOS and its different phenotypes.
PubMed: 38948599
DOI: 10.4103/jfmpc.jfmpc_1425_23 -
Journal of Family Medicine and Primary... May 2024Diabetes mellitus is associated with carbohydrate, lipid and protein metabolism abnormalities. Uncontrolled hyperglycaemia can result in dysfunction of various organs...
BACKGROUND
Diabetes mellitus is associated with carbohydrate, lipid and protein metabolism abnormalities. Uncontrolled hyperglycaemia can result in dysfunction of various organs such as eyes, kidneys, nerves, and heart and blood vessels leading to long-term complications like nephropathy, neuropathy, retinopathy, stroke and ischaemia. The main objective of the study was to identify critical factors in Type 2 diabetes mellitus (Type 2 DM) with metabolic syndrome (mets) compared with Type 2 DM without mets and their association in the development of Type 2 DM to Type 2 DM with mets and cardiovascular complications. This can aid in improving the clinical management and the consequences of the disease.
MATERIALS AND METHODS
The present study was conducted in the Department of Biochemistry, a tertiary care centre in Northern India. All patients who were aged between 35 and 65 years of age were enrolled. Enrolled subjects were divided into three groups, Group I: 50 healthy people; Group II: 50 Type 2 DM without mets; and Group III: 50 Type 2 DM with mets. These patients were subjected to Anthropometric and biochemical parameter assessment.
RESULTS
On comparing Group III with control and Group II significant difference was observed in these parameters, that is, elevated TGs ( = 0.001), reduced high-density lipoprotein (HDL) level ( = 0.001), elevated high-sensitivity C-reactive protein (hs-CRP) (0.011), high serum insulin fasting ( = 0.010), weight ( = 0.021), waist circumference ( = 0.001) and BMI ( = 0.001). In the control group, head circumference was significantly lower compared to Group II ( = 0.001) and Group III ( = 0.001).
CONCLUSION
On the basis of observed observation, it has been suggested that low enzymatic activity with poor glycaemic control may further progress Type 2 DM into Type 2 DM with metabolic syndrome and cardiovascular complications. High hs-CRP concentration and high fasting insulin can be independent predictor of cardiovascular complications.
PubMed: 38948574
DOI: 10.4103/jfmpc.jfmpc_852_23 -
Journal of Family Medicine and Primary... May 2024Vaginal leiomyomas, originating from the anterior vaginal wall, are exceedingly uncommon, with only around 300 reported cases documented in the literature to date. We...
Vaginal leiomyomas, originating from the anterior vaginal wall, are exceedingly uncommon, with only around 300 reported cases documented in the literature to date. We present a rare case of a 50-year-old female who visited the outpatient department with complaints of abnormal uterine bleeding, and heaviness in abdomen with mass protrusion outside introitus since one year. Ultrasonography indicated adenomyosis of the uterus, with a suspected mass protruding through the posterior bladder or anterior vaginal wall. MRI imaging was conducted large polypoidal mass lesion is seen within the vaginal cavity two assymetrical round ends with close proximity to bladder and urethra with pedunculated submucosal uterine fibroid with adenomyotic changes . The provisional diagnosis of? vaginal leiomyoma along with pedunculated submucosal uterine fibroid with Adenomyosis made. Patient planned for Hysterectomy for submucosal leiomyoma with Adenomyosis and excision of vaginal mass via vaginal route. The size of vaginal mass was around size 5 * 6cm size enucleated, redundant vaginal wall excised and same sent for histopathology examination. The cut section of the vaginal mass showed whorled appearance .The Histopathology of vaginal mass showed Vaginal leiomyoma. Postoperative period was uneventful. The patient anatomy was restored and had no complaint of difficulty in urination and symptomatically improved.
PubMed: 38948554
DOI: 10.4103/jfmpc.jfmpc_1229_23 -
Frontiers in Endocrinology 2024Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and... (Review)
Review
Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and hypertension as individuals age. DR is a severe microvascular complication of both type I and type II diabetes mellitus and the leading cause of vision impairment. The critical approach to combatting and halting the advancement of DR lies in effectively managing blood glucose and blood pressure levels in diabetic patients; however, this is seldom achieved. Both human and animal studies have revealed the intricate nature of this condition involving various cell types and molecules. Aside from photocoagulation, the sole therapy targeting VEGF molecules in the retina to prevent abnormal blood vessel growth is intravitreal anti-VEGF therapy. However, a substantial portion of cases, approximately 30-40%, do not respond to this treatment. This review explores distinctive pathophysiological phenomena of DR and identifiable cell types and molecules that could be targeted to mitigate the chronic changes occurring in the retina due to diabetes mellitus. Addressing the significant research gap in this domain is imperative to broaden the treatment options available for managing DR effectively.
Topics: Humans; Diabetic Retinopathy; Animals; Molecular Targeted Therapy; Cell- and Tissue-Based Therapy; Vascular Endothelial Growth Factor A
PubMed: 38948520
DOI: 10.3389/fendo.2024.1416668 -
Journal of the Belgian Society of... 2024Contrast-enhanced FLAIR fat-suppressed (CE-FLAIR-FS) imaging can potentially increase the diagnostic accuracy of uveal diseases and ultimately provide better patient...
Contrast-enhanced FLAIR fat-suppressed (CE-FLAIR-FS) imaging can potentially increase the diagnostic accuracy of uveal diseases and ultimately provide better patient management. This study aimed to determine the diagnostic value of CE-FLAIR-FS imaging versus contrast-enhanced T1-weighted imaging (CE-T1WI) in the assessment of pediatric patients with uveitis. Twenty-one children with uveitis who underwent whole brain magnetic resonance imaging (MRI), including CE-FLAIR-FS and CE-T1WI, were retrospectively included in the study. We evaluated the presence of uveal tract contrast enhancement with thickening, vitreous humor signal abnormality, and accompanying brain abnormalities. The uveal enhancement intensity was assessed semiquantitatively as mild, moderate, and marked uveitis compared to CE-T1WI and CE-FLAIR-FS images. Panuveitis (61.9%) was the most frequent anatomic location, and most of them were idiopathic (47.6%). Of the 42 eyes with clinical uveitis, enhancement of the uveal tract was observed on CE-FLAIR-FS images in 21 eyes (50%), while in 5 eyes (11.9%) on CE-T1WI. The sensitivity of CE-FLAIR-FS in panuveitis was detected to be quite high (80.8%). The number of affected eyes and enhancement degree were found to be higher on CE-FLAIR-FS ( < 0.001). In assessing the severity of uveitis, CE-FLAIR-FS grades were significantly higher and more sensitive than CE-T1WI ( < 0.001, : -4.347). Three patients had vitreous abnormal signals on CE-FLAIR-FS images, but none on CE-T1WI. CE-FLAIR-FS plays a significant role in the diagnosis of pediatric uveitis, identifying the involvement and severity of the uveal inflammation and guiding the appropriate management. It would be beneficial to add it as a standard sequence to the routine MRI protocol for uveal pathologies.
PubMed: 38948498
DOI: 10.5334/jbsr.3565 -
Frontiers in Pharmacology 2024Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic...
Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD. High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1β in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot. The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors. Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.
PubMed: 38948463
DOI: 10.3389/fphar.2024.1294122