Chronic Disorder Research Articles

Myelodysplastic syndrome (MDS)/Myeloproliferative neoplasm (MPN) with loss of long arm of chromosome 5 (del 5q): Clinical case and treatment perspectives.

this clinical case report presents a patient diagnosed with a myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN), specifically myelofibrosis with a deletion of the long arm of chromosome 5 (del 5q), an exceedingly rare anomaly in chronic myeloproliferative disorders. We performed a thorough analysis of the patient’s clinical, laboratory, and molecular-genetic characteristics to evaluate their impact on prognosis, treatment decisions, and therapeutic outcomes. After excluding other genetic abnormalities, the patient was treated with lenalidomide and prednisolone, resulting in improved clinical and hematological parameters. These findings are consistent with previous studies and suggest the potential efficacy of lenalidomide in treating patients with MDS/MPN characterized by del 5q, especially when no additional genetic abnormalities are present.

The Role of Gut Microbiota as a Trigger for Exacerbations in Pulmonary Obstruction Disorder in General

Pulmonary diseases can be associated with the gastrointestinal (GI) system, particularly if an infection causes them. This relationship between organs is known as the gut-lung axis (GLA). Skin and mucosal surfaces are associated with microbiota (bacteria, fungi, viruses, macrophages, archaea, protists, helminths), which can trigger an immune response in GLA and serve a role in respiratory diseases. For instance, asthma can be inhibited by a specific antigen that is triggered by probiotics, the microorganisms found in the GI tract. Asthma incidence can be reduced by consuming fiber due to its ability to protect airways from infection. Pattern recognition receptors (PRRs) are the first immune component to identify microbial compounds in GI and lung epithelial cells. The PRRs then induce regulatory T-cell (T-reg) and Th-17 differentiation. Diet, antibiotics, and stress can all influence the structure and function of bacteria. This is known as dysbiosis. Lung microbiota can influence immune cell maturation and homeostasis. If the diversity of lung microbiota decreases, it will affect intestinal microbiota and may result in chronic respiratory disorders such as chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis. This literature review explained how the interactions between the intestines and lungs can affect humans’ health and well-being.

TRATAMENTO FARMACOLÓGICO DA ESQUIZOFRENIA: PASSADO, PRESENTE E FUTURO

Schizophrenia is a chronic and severe psychiatric disorder characterised by the manifestation of positive and negative symptoms and/or cognitive dysfunction. Treatment typically includes psychotherapy, sociotherapy and pharmacological therapy, which consists of the use of typical and atypical antipsychotic drugs, as well as dopaminergic system stabilisers. Although they do not provide a cure, these treatments can reduce the intensity and frequency of symptoms, resulting in improved quality of life and a quicker reintegration into social life. Thus, the aim of the present study was to conduct a narrative literature review on the clinical evolution of antipsychotic use throughout history, as well as to discuss potential new drugs that are still in clinical research. Studies have shown that typical antipsychotics are effective in treating positive symptoms but have no impact on negative symptoms and can even exacerbate or provoke them. Additionally, they produce highly limiting side effects, such as movement disorders. Atypical antipsychotics, on the other hand, are capable of reducing both positive and negative symptoms, and they also present fewer side effects related to the extrapyramidal motor system. However, they tend to cause metabolic disturbances. Conversely, dopaminergic system stabilisers also treat both positive and negative symptoms, with side effects that are generally better tolerated, along with a lower propensity to cause weight gain and motor disturbances. It is worth noting that many patients are unable to tolerate the various adverse reactions of the available antipsychotics. Moreover, some patients are or become refractory to their therapeutic effects. Consequently, there is currently a focus on developing new agents that have different pharmacological targets. Some of these potential new drugs have shown efficacy in refractory patients, representing a potential paradigm shift in the treatment of the disorder.

MGlu4R, mGlu7R, and mGlu8R allosteric modulation for treating acute and chronic neurodegenerative disorders.

Neuroprotection, defined as safeguarding neurons from damage and death by inhibiting diverse pathological mechanisms, continues to be a promising approach for managing a range of central nervous system (CNS) disorders, including acute conditions such as ischemic stroke and traumatic brain injury (TBI) and chronic neurodegenerative diseases like Parkinson's disease (PD), Alzheimer's disease (AD), and multiple sclerosis (MS). These pathophysiological conditions involve excessive glutamatergic (Glu) transmission activity, which can lead to excitotoxicity. Inhibiting this excessive Glu transmission has been proposed as a potential therapeutic strategy for treating the CNS disorders mentioned. In particular, ligands of G protein-coupled receptors (GPCRs), including metabotropic glutamatergic receptors (mGluRs), have been recognized as promising options for inhibiting excessive Glu transmission. This review discusses the complex interactions of mGlu receptors with their subtypes, including the formation of homo- and heterodimers, which may vary in function and pharmacology depending on their protomer composition. Understanding these intricate details of mGlu receptor structure and function enhances researchers' ability to develop targeted pharmacological interventions, potentially offering new therapeutic avenues for neurological and psychiatric disorders. This review also summarizes the current knowledge of the neuroprotective potential of ligands targeting group III mGluRs in preclinical cellular (in vitro) and animal (in vivo) models of ischemic stroke, TBI, PD, AD, and MS. In recent years, experiments have shown that compounds, especially those activating mGlu4 or mGlu7 receptors, exhibit protective effects in experimental ischemia models. The discovery of allosteric ligands for specific mGluR subtypes has led to reports suggesting that group III mGluRs may be promising targets for neuroprotective therapy in PD (mGlu4R), TBI (mGlu7R), and MS (mGlu8R).

2D MoS2 plasmonic nanocavity based SERS platform for bilirubin detection

Although various methods can be used to detect bilirubin at the micromolar level, achieving reliable detection in the sub-nanomolar range remains challenging. Sensitivity at these ultralow levels is vital, as new evidence strongly associates bilirubin with chronic heart, lung, and neurological disorders. This accuracy is also essential for creating diagnostic protocols that can efficiently track bilirubin levels, assisting in managing related conditions. Such advancements will lead to enhanced diagnostic tools and methods, enabling more precise bilirubin monitoring in clinical environments. Here, the aforesaid blind-spot is addressed by utilizing surface enhanced Raman spectroscopy (SERS) as fingerprint technique to detect bilirubin concentrations as low as 0.1 nM. A plasmonically active 2D MoS2 based SERS substrate is formulated and optimized for single step SERS sensing of bilirubin. Plasmonic cavity based approach is utilized to circumvent the problem related to fluorescent background overwhelming the SERS signal. The 2D MoS2 based SERS platform shows threefold enhancement of scattering in comparison to the traditional gold nanoparticle on Si/SiO2 approach. The Raman signature of bilirubin is calibrated by taking citrate as a stable reference analyte and is shown to vary linearly with logarithmic concentration across the picomolar to micromolar range.

QbD Approach for the Development of Tea Tree Oil-Enhanced Microemulgel Loaded with Curcumin and Diclofenac for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis, a chronic autoimmune disorder affecting millions worldwide each year, poses a significant threat due to its potential for progressive joint damage and debilitating pain if left untreated. Topical anti-inflammatory and analgesic treatments offer localized relief with reduced systemic side effects compared to conventional oral therapies, making them a promising option for managing rheumatoid arthritis. Therefore, the current study endeavored to formulate a microemulsion gel formulation loaded with diclofenac and curcumin for topical administration in the management of rheumatoid arthritis, utilizing Tea tree oil. The ratio of surfactant and cosurfactant was 4:1, assessed by pseudoternary phase diagram on the basis of the maximum emulsification region. The microemulsion underwent optimization using a Central Composite Rotatable Design (CCRD) with constraints of minimum particle size, polydispersity index, and maximum transmittance. The Curcufenac-T microemulsion had a particle size, polydispersity index (PDI), and transmittance of 151.82 ± 15.9 nm, 0.287 ± 0.021, and -5.78 ± 0.26 mV, respectively. DSC analyses confirmed the stability and compatibility of diclofenac and curcumin within the formulation. The microemulsion was changed into gel form by incorporating 1% carbopol-934. Skin permeation analysis revealed that the percentage of diclofenac permeated at 0.5 h from Curcufenac-T microemugel and the conventional gel was 12.1% and 3.9%, respectively, while at 12 h, the rates were 82.6% and 34.2%, respectively. In vitro permeability demonstrated significant potential for the effective delivery of diclofenac and curcumin to targeted sites, compared to conventional gel. Therefore, it was deduced that the Tea tree oil integrated diclofenac and curcumin microemulsion gel could enhance the effectiveness of diclofenac and serve as a promising vehicle for rheumatoid arthritis treatment.

Parathyroid Hormone and Osteocalcin as Criteria for Osteoporosis in Patients with Celiac Disease

Background: Osteoporosis is a disease that affects the entire skeletal system. It is characterized by the deterioration of the fine structural structure of the bone and the decline in bone mass, which ultimately leads to an increase in the bone's susceptibility to fracture. Celiac disease, often known as wheat allergy, is a single condition with numerous names. Celiac disease is a chronic autoimmune disorder that mostly affects the small intestine. It occurs when patients develop an intolerance to gluten, a protein found in foods including wheat, rye, and barley. Aim of the study: The objective of our study is to track the levels of osteocalcin and parathyroid hormone in the blood serum of patients diagnosed with celiac disease in Wasit Governorate, Iraq. We will be using Human Anti-Deamidated Gliadin Peptide IgG and IgA to diagnose celiac disease and evaluate the progress of bone health. Materials and methods: This study examined a total of 80 samples, consisting of 50 samples from individuals with celiac disease. The sample group included 19 males and 31 women. There are 30 control samples, with an equal number of samples for each sexes. Utilized an Enzyme-linked immunosorbent assay (ELISA) kit to quantify the levels of osteocalcin, parathyroid hormone, and Human Anti-Deamidated Gliadin Peptide IgG and IgA. Results: The study revealed that individuals with celiac disease had significantly higher levels of osteocalcin, parathyroid hormone, and Human Anti-Deamidated Gliadin Peptide IgG and IgA compared to the control group, with a statistical significance of p≤(0.05). Conclusion: The examined parameters serve as indicators of the development of health risks to the body and bone health in individuals with celiac disease.

Evaluation of the Relationship Between Bacterial Infection and Immunological Factors with Diabetic Foot Ulcer

Diabetes represent a chronic disorder that involve the decline in the levels of insulin produced by the pancreas due to many genetic and environmental factors. The disease involves the elevation of blood sugar in the circulation which may lead to vascular, neurological, ocular and renal complications. In addition, diabetic patients tend to develop ulceration due to wound infection swiftly in the lower limbs due to the reduce in the neurological sensation as well as to elevated sugar circulation which may greatly provoke wound infection and diabetic foot ulcerations. The current study aimed at isolation of the common causes of bacterial infection associated with diabetic foot ulcer as well as the assessment of IL-17 and IL-18 and in those patients and in control healthy group. The present study was conducted in Salah Aldeen province during the period from 1st of November 2023 to 15th of May 2024 and included 150 patients with diabetic foot infection who attended Salah-Alden Hospitals: (Tikrit Teaching Hospital, Balad General Hospital and private surgery clinics). Swabs and whole blood from patients with diabetic foot ulcer were taken and submitted to routine culture and identification of the causative bacterial infection followed by biochemical identification and antibiotics susceptibility test for the isolated microbe. The serum specimens from those positive bacterial isolates were submitted for IL17 and IL-18 ELISA assessment. IL-17, significant elevation P<0.05 of this cytokine was recorded in diabetic patients with foot ulcer with mean 21.94 pg/ml compared to control group. In the same way significant increase of IL-18 (P<0.05) was noted in diabetic patients with foot ulcer with mean 347.15 pg/ml in comparison to control group. In conclusion, diabetic foot ulceration is the result of in controlled elevation of blood glucose and bacterial infection with various pathogens can complicate the scenario, and the significant elevation of IL17 and IL18 in those patients can insight the role played by these cytokines in signaling the immune to recruit cellular and humoral response.

Detection of Prescribing Cascades in Multimorbid Older Patients Hospitalized with Acute Unselected Illness

Abstract Background Prescribing cascades (PCs) occur when a new medication is prescribed to treat an unrecognized side-effect of another medication. PCs represent an important but often underrecognized aspect of inappropriate prescribing in older people with multimorbidity and associated polypharmacy and can result in avoidable morbidity and mortality. Numerous PCs are described in the literature, however, there are no prospective studies describing PC prevalence in older people. Therefore, we aimed to investigate the prevalence of PCs in acutely hospitalized older adults. Methods We undertook a prospective observational study, including adults ≥65years with polypharmacy (≥5 daily drugs) and multimorbidity (≥3 chronic disorders). Prescription medication lists were examined for the co-prescription of 31 drug pairs according to two pre-defined PC lists– ThinkCasades1 and of the explicit cascades published by Doherty et al2. PCs were defined as ‘definite’, ‘probable’, ‘possible’, ‘uncertain’ or ‘indeterminate’ according to specific criteria. Results We obtained prospective data on 300 patients (56% female, mean age 80.4yrs SD 7.2). 233 drug pairs were prescribed in the sequence of drug A → drug B, these occurred in 43% (n=130) of patients. Of the 233 pairs, 38% (n=88) were probable or possible PCs and 62% (n=145) were uncertain. 45 patients (15%) had ≥1 possible or probable PCs. The most commonly identified probable/possible PCs were diuretic → overactive bladder medication and calcium channel blocker → diuretic. Patients with an identified PC experienced higher mean levels of polypharmacy than patients with no PCs (11.7, SD 4.0 vs 9.6, SD 3.1, T= -4.97, p <0.001). Conclusion In this first-ever study to report prospective prevalence of PCs, possible or probable PCs were significantly prevalent among acutely hospitalized multimorbid older patients and were associated with higher levels of polypharmacy.McCarthy LM, et al. Drgs & aging. 2022 Oct;39(10):829-40.Doherty AS, et al. Pharmacology research & perspectives. 2022 Oct;10(5): e01008.

Association between Inflammatory Markers and Psychometric Scores in Patients with Hidradenitis Suppurativa

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with a significant impact on the quality of life of affected patients. This study aimed to correlate serum inflammatory markers with specific tools assessing quality of life, emotional well-being, and loneliness, such as the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), and the UCLA Loneliness Scale. Methods: A pilot observational study including 37 patients with HS was conducted. Inflammatory serum markers, including C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR), were evaluated at baseline, 3 months, and 6 months later. Psychometric scores were also evaluated at the same study intervals. Results: DLQI was correlated with ESR at baseline (Spearman’s rho = 0.35, p = 0.03), indicating that poorer quality of life is associated with changes in this serum marker. Disease activity, as reflected by inflammatory markers, was associated with significant psychological burden. Specifically, a worse DLQI score was associated with higher ESR (estimate β = 0.14, 95% confidence interval [CI]: 0.05–0.22; p = 0.001) and higher CRP level (estimate β = 0.25, 95% CI: 0.02–0.48; p = 0.02). Similarly, a worse UCLA score was associated with higher ESR (estimate β = 0.11, 95% CI: 0.02–0.20, p = 0.01). Conclusions: Our study results underline the close relation between systemic inflammatory markers and clinical severity together with psychological burden in HS patients, as indicated by the significant association that was revealed between ESR/CRP and poorer psychometric scores. However, further research is warranted to validate these findings.

Stress triggers irritable bowel syndrome with diarrhea through a spermidine-mediated decline in type I interferon.

Irritable bowel syndrome with diarrhea (IBS-D) is a common and chronic gastrointestinal disorder that is characterized by abdominal discomfort and occasional diarrhea. The pathogenesis of IBS-D is thought to be related to a combination of factors, including psychological stress, abnormal muscle contractions, and inflammation and disorder of the gut microbiome. However, there is still a lack of comprehensive analysis of the logical regulatory correlation among these factors. In this study, we found that stress induced hyperproduction of xanthine and altered the abundance and metabolic characteristics of Lactobacillus murinus in the gut. Lactobacillus murinus-derived spermidine suppressed the basal expression of type I interferon (IFN)-α in plasmacytoid dendritic cells by inhibiting the K63-linked polyubiquitination of TRAF3. The reduction in IFN-α unrestricted the contractile function of colonic smooth muscle cells, resulting in an increase in bowel movement. Our findings provided a theoretical basis for the pathological mechanism of, and new drug targets for, stress-exposed IBS-D.

Chronic lymphoproliferative disorder of natural killer cells-related neurolymphomatosis with severe autonomic dysfunction: a case report

BackgroundChronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is a rare disease characterized by a persistent increase in NK cells in peripheral blood and is generally asymptomatic. If present, symptoms may include fatigue, B symptoms (fever, night sweats, and unintentional weight loss), autoimmune-associated diseases, splenomegaly, and infection due to neutropenia. Peripheral neuropathy, however, is uncommon with an incidence of 3%. Neurolymphomatosis is a neurological manifestation of non-Hodgkin lymphoma and leukemia in which neurotropic neoplastic cells infiltrate the nerves. Moreover, neurolymphomatosis caused by CLPD-NK is extremely rare, with even fewer cases of autonomic dysfunction. We report a case of neurolymphomatosis associated with CLPD-NK and developed autonomic dysfunction, including orthostatic hypotension and gastrointestinal symptoms.Case presentationThe patient was a 61-year-old male who was referred to our hospital for leukocytosis. He was diagnosed with CLPD-NK; however, was untreated since he had no hepatosplenomegaly, and other systemic symptoms. He later developed numbness in his lower extremities. Cerebral spinal fluid examination revealed a markedly elevated protein level of 140 mg/dL, and contrast-enhanced magnetic resonance imaging showed bilateral L4 and 5 nerve roots with enlargement and contrast effect. An immune-mediated polyradiculoneuropathy was suspected, and he was treated with intravenous methylprednisolone and immunoglobulin followed by oral prednisolone and cyclosporine. Although his symptoms were relieved by the immunotherapy, significant autonomic dysfunction, including intractable diarrhea, decreased sweating, and orthostatic hypotension, appeared. Additionally, tests for onconeuronal antibodies, ganglionic nicotinic acetylcholine receptor (gAChR) antibody, NF155, CNTN1, Caspr1 antibody, and anti-ganglioside antibodies were all negative. A sural nerve biopsy revealed lymphocytic infiltration, and immunohistochemical staining of lymphocytes confirmed the infiltration of NK and T cells. Therefore, a diagnosis of neurolymphomatosis caused by CLPD-NK was made, and chemotherapy led to partial symptom improvement.ConclusionsWe experienced a case of pathologically diagnosed neurolymphomatosis with autonomic dysfunction associated with CLPD-NK. In cases of subacute to chronic autonomic dysfunction, paraneoplastic neuropathy, amyloidosis, and autoimmune autonomic ganglionopathy are considered; however neurolymphomatosis caused by CLPD-NK, an important cause of autonomic dysfunction, is not. In difficult to make diagnosis, aggressive nerve biopsy is required.

Right Ventricular Longitudinal Strain-Related Indices in Acute Pulmonary Embolism.

Pulmonary embolism (PE) is correlated with serious morbidity and mortality. Efforts have been made to establish and validate mortality predictive scores based mainly on clinical parameters. Patients with PE and traditional indices of echocardiographic right ventricular (RV) dysfunction or pressure overload have a higher probability of a worse outcome. During the last two decades, studies regarding the use of two-dimensional speckle-tracking echocardiography (2DSTE) and its derived indices in the setting of acute PE have been conducted. In this comprehensive review of the literature, we aimed to summarize these studies. Safe conclusions and comparisons among the reviewed studies are prone to statistical errors, mainly because the studies published were heterogenous in design, different 2DSTE-derived parameters were tested, and different clinical outcomes were used as endpoints. Nonetheless, RV strain indices and, more commonly, regional longitudinal strain of the RV free wall have shown a promising correlation with mortality, assisting in the differential diagnosis between PE and other acute or chronic disorders.

Exploring Rheumatoid Arthritis: Unraveling Signaling Pathways, Advancing Management, and Charting Future Perspectives

Rheumatoid arthritis (RA) is a chronic autoimmune disorder in which inflammation occurs in the synovial joint and synovial membrane, and in severe condition, it leads to erosion of cartilage and bone. The etiology of RA is still indescribable; generally, RA is a multifactorial disease, wherein complex interactions between patients and different factors such as environmental, genetic, and epigenetic factors determine the overall risk of disease. RA is classified based on the stage of disease. Treatment for RA is still a challenge for doctors and researchers. Effective treatment for RA can be achieved by decreasing disease activity or reduction of RA to other patients using currently available treatment options. This article gives a comprehensive perspective of data regarding different signaling pathways involved in RA development, factors affecting RA, stages of RA, and other treatments of RA. This article also suggests future research perspectives that would be helpful for the development of RA treatment (medicine) with more efficacy, safety profiles, and lower financial costs.

The association of psoriasis with composite dietary antioxidant index and its components: a cross-sectional study from the National Health and Nutrition Examination Survey

BackgroundPsoriasis is a chronic inflammatory skin disorder associated with various comorbidities. The role of nutrition and dietary antioxidants in psoriasis management has gained attention. The Composite Dietary Antioxidant Index (CDAI) quantifies overall dietary antioxidant intake, but its association with psoriasis remains unclear. This study aimed to investigate the association between the CDAI and psoriasis, as well as the relationship between individual components of CDAI and psoriasis risk.MethodsData from the US National Health and Nutrition Examination Survey (NHANES) were analyzed. Baseline characteristics, CDAI scores, and psoriasis status were assessed. Multivariable logistic regression and restricted cubic splines were employed to analyze the association.ResultsThe study included 23,311 participants, with 621 diagnosed with psoriasis. Higher CDAI scores were associated with a lower odds ratio (OR) of psoriasis occurrence (OR = 0.72, 95% CI 0.56–0.92, P = 0.009 in Model 3). Vitamin E intake exhibited an inverse correlation with psoriasis risk (OR = 0.76, 95% CI 0.60–0.96, P = 0.039 in Model 3). Other CDAI components did not show significant associations with psoriasis.ConclusionThis study demonstrates a significant inverse association between CDAI and psoriasis, indicating that higher dietary antioxidant intake is associated with a reduced risk of psoriasis. Specifically, higher vitamin E intake was associated with a lower likelihood of psoriasis. These findings underscore the potential role of dietary antioxidants in psoriasis management. Further research is warranted to elucidate the underlying mechanisms and explore targeted dietary interventions.

Regenerative capacity of alveolar type 2 cells is proportionally reduced following disease progression in idiopathic pulmonary fibrosis-derived organoid cultures.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that leads to respiratory failure and death due to irreversible scarring of the distal lung. While historically considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now recognized to play a central role in IPF pathophysiology. This study aimed to investigate the regenerative capacity of AT2 cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Lung tissues from 3 pneumothorax patients and 6 IPF patients (early and advanced stages) were obtained by VATS and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-EpCAM+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immuno-staining was used to confirm the presence of AT2 cells. FACS sorting yielded approximately 1% AT2 cells of the total cells in early IPF tissue, and the number decreased as the disease progressed, compared with 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller in size and fewer in number compared to those from pneumothorax patients. The colony-forming efficiency decreased as the disease progressed. In immuno-staining results, the IPF organoids showed lower expression of SFTPC compared to the pneumothorax group and contained KRT5+ cells. This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, and IPF AT2 cells inherently exhibit functional abnormalities and altered differentiation plasticity.

Correlates and predictors of symptom severity over time in people under investigation for postural orthostatic tachycardia syndrome (POTS).

Postural Orthostatic Tachycardia Syndrome (POTS) is a poorly understood chronic disorder characterised by an unexplained excessive increase in heartbeat upon standing. The aim of this study was to investigate psychosocial and physiological correlates and predictors of symptom severity over time in patients presenting with POTS-like symptoms. Longitudinal cohort study of patients under investigation for POTS ( n = 149). Patients completed questionnaires at one month pre-clinic appointment and 6 months later. Diagnosis, blood pressure (BP) and heart rate (HR) measures were collected from medical records. Data were analysed using hierarchical linear multiple regression. Orthostatic and small fibre neuropathy (SFN) symptoms remained stable over time and were significantly correlated with distress, cardiac anxiety, threatening views of the illness, and cognitive-behavioural responses to symptoms, but not with emotional reactivity or social support. Baseline psychosocial factors collectively explained 48% (F = 5.37, p < .001) of the variance in orthostatic symptoms, and 35% (F = 3.49, p < .001) of the variance of SFN symptoms at baseline, but a non-significant amount of variance in symptoms at 6 months when controlling for baseline symptoms. Haemodynamic measures explained a significant 4% (F = 3.37, p = .026) of variance of orthostatic symptoms at 6 months. Symptom burden in patients with suspected POTS remained high over 6 months. Psychosocial factors explained a large amount of the variance in symptoms at baseline. As symptoms did not change/improve over time, baseline symptoms accounted for most of the variance in symptoms at 6 months. An integrated approach addressing psychosocial factors alongside medical treatments may promote adjustment to the condition and lessen symptom burden for this group.

Effect of Lacticaseibacillus rhamnosus IDCC 3201 on irritable bowel syndrome with constipation: a randomized, double-blind, and placebo-controlled trial

Irritable bowel syndrome is a chronic disorder affecting the gastrointestinal tract, negatively impacting patients’ quality of life. Here, we aimed to evaluate the effects of Lacticaseibacillus rhamnosus IDCC 3201 (RH 3201) on irritable bowel syndrome with constipation (IBS-C). In this randomised, double-blind, placebo-controlled trial, a total of 30 subjects with IBS-C were randomly assigned (1:1) to receive 8 weeks of probiotics administration or placebo. Concerning bowel activities, both irritant bowel movements and discomfort caused by constipation showed significant improvement with RH 3201 at 8 weeks. Symptoms including severity of abdominal bloating, frequency of abdominal bloating, and satisfaction of bowel habits based on the irritable bowel syndrome-severity scoring system also ameliorated in the probiotic group. Analysis of the fecal microbiome revealed that the abundance of Bacteroides cellulosilyticus and Akkermansia muciniphila was higher during the period of RH 3201 administration compared to the placebo. Untargeted metabolome analysis further suggested a correlation between specific metabolites, such as N-acetylornithine, xanthine, and 3-phenylpropionic acid, and the improvement of clinical symptoms. These results indicate that RH 3201 was effective in ameliorating IBS-C, potentially by enriching beneficial microbes and associated metabolites in the gut environment.

Prostaglandin E2 signaling through prostaglandin E receptor subtype 2 and Nurr1 induces fibroblast growth factor 23 production

Bone cells produce fibroblast growth factor 23 (FGF23), a hormone regulating renal phosphate and vitamin D homeostasis, and a paracrine factor produced in further tissues. Chronic kidney disease and cardiovascular disorders are associated with early elevations of plasma FGF23 levels associated with clinical outcomes. FGF23 production is dependent on many conditions including inflammation. Prostaglandin E2 (PGE2) is a major eicosanoid with a broad role in pain, inflammation, and fever. Moreover, it regulates renal blood flow, renin secretion, natriuresis as well as bone formation through prostaglandin E receptor 2 (EP2). Here, we studied the role of PGE2 and its signaling for the production of FGF23. Osteoblast-like UMR-106 cells were exposed to EP receptor agonists, antagonists or RNAi. Wild type and EP2 knockout mice were treated with stable EP2 agonist misoprostol. Fgf23 or Nurr1 gene expression was determined by quantitative real-time PCR, hormone and further blood parameters by enzyme-linked immunosorbent assay and colorimetric methods. PGE2 and EP2 agonists misoprostol and butaprost enhanced FGF23 production in UMR-106 cells, effects mediated by EP2 and transcription factor Nurr1. A single dose of misoprostol up-regulated bone Fgf23 expression and FGF23 serum levels in wild type mice with subtle effects on parameters of mineral metabolism only. Compared to wild type mice, the FGF23 effect of misoprostol was significantly lower in EP2-deficient mice. To conclude, PGE2 signaling through EP2 and Nurr1 induces FGF23 production. Given the broad physiological and pathophysiological implications of PGE2 signaling, this effect is likely of clinical relevance.

Comparative immunohistochemical expression of Beta catenin and CD163 between dysplastic / non-dysplastic oral lichen planus and lichenoid lesions (EX-VIVO STUDY)

BackgroundOral lichen planus is a well-known chronic inflammatory mucocutaneous disorder, which has clinical and histological presentation that mimics oral lichenoid reaction. According to the fifth edition of WHO, both conditions are considered as oral potentially malignant disorders. Recent studies on oral potential disorders documented deregulation of some signaling molecules related to the Wnt/β-catenin pathway. Therefore this study aimed to compare the immune expression of β-catenin & CD163 in dysplastic /non-dysplastic cases of Oral lichen planus & oral lichenoid lesion. In addition, a statistical correlation between both immune markers was done regardless of the type of the study group.MethodsFour study groups were designated as 2 groups of Oral lichen planus (one dysplastic & one non –dysplastic) and the other 2 groups were oral lichenoid lesions (one dysplastic & one non –dysplastic). Ten cases in each group were collected and investigated by immunohistochemistry. The area percent of beta catenin and also counting of m2 macrophages expressing + CD163 marker was calculated in the study groups.ResultsThe Statistical analysis highlighted a statistically significant difference between the studied groups. Moreover, Pearson correlation test reported a significant moderate positive correlation between beta catenin & CD163 expression in the studied cases.ConclusionOur findings supported new perceptions of the mechanism by which tumor associated macrophage specific β-catenin signaling promotes the aggressive behavior of oral potential malignant disorders.Clinical relevanceEvidence of the relationship between beta catenin and M2 macrophages (+ CD163) may enhance the development of macrophage-based strategies for treatment and improve the prognosis of such cases.