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BACKGROUND: Ankle foot orthoses are used to stabilize the ankle joint and aid toe clearance during stepping in persons after incomplete spinal cord injury. However, little is known about kinematics and kinetics of stepping with an orthosis during the transition from stance-to-swing and swing-to-stance. We intended to examine if an ankle foot orthosis impeded or facilitated optimal ankle, knee and hip joint kinematics, kinetics and spatiotemporal parameters during the transition phases of normal walking. METHODS: Fourteen healthy participants walked on a split-belt instrumented treadmill with and without a posterior leaf spring ankle foot orthosis at 1.2m/s. Three dimensional motion data and ground reaction forces were captured during 30-second trials of steady state walking. FINDINGS: During stance-to-swing, the orthosis significantly decreased hip extension [8.6 (5.5) to 6.7 (5.5) degrees, P=0.001], ankle plantarflexion [19.4 (5.7) to 12.0 (5.2) degrees, P<0.001] and plantarflexor power [0.18 (0.03) to 0.15 (0.03) watts/body weight, P<0.001]. During swing-to-stance, the orthosis significantly increased hip flexion [32.7 (4.7) to 35.6 (5.1) degrees, P=0.028] and ankle plantarflexion [8.4 (3.5) to 10.9 (4.7) degrees, P<0.001] and decreased loading rate [0.06 (0.01) to 0.05 (0.01) N/kg, P=0.018] and braking force [0.16 (0.02) to 0.15 (0.02) N/kg, P=0.013]. Double limb support time increased significantly with the orthosis [0.19 (0.02) to 0.22 (0.03) seconds, P<0.000]. INTERPRETATION: An ankle foot orthosis affected joint kinematics and kinetics during the transition from stance-to-swing and vice-versa. The use of orthosis to improve transition phase kinematics and kinetics in individuals with incomplete spinal cord injury warrants assessment. [ABSTRACT FROM AUTHOR]

Background: The efficacy of locomotor rehabilitation studies has largely been based on clinical measures of gait speed and walking performance. Although critical, gait speed does not fully capture the multidimensional benefits associated with walking recovery. The International Classification of Function, Disability and Health (ICF) model of rehabilitation emphasizes the role of personal and environmental factors in affecting quality of life and personal health status and advocates a broad approach in the assessment and treatment of people with disabling conditions.Objective: The purpose of this case report is to describe a multidimensional approach to outcome measurement reflecting the ICF model.Subject: The participant was a 59-year-old man with C7 American Spinal Injury Association impairment D tetraplegia, 16 months after injury.Intervention: The participant completed a 45-session, five days per week locomotor training program. Comprehensive evaluations were completed pre- and post-training targeting all elements of the ICF model.Outcomes: The participant achieved negligible increases in gait speed, but increased self-elected walking activity from 26 steps per day to 1273 steps per day. His assistive device changed from a platform to a rolling walker, representing a Walking Index for Spinal Cord Injury (WISCI) increase from 8/20 to 13/20. Qualitative interviews illustrated an attitudinal shift, leading to improved motivation, confidence, self-esteem, problem-solving, and increased activities/participation in the community. Ultimately, the participant was able to transition from nursing home placement to living independently.Conclusions: This case report emphasizes the need to move beyond traditional models for evaluation at the impairment and clinical level to examine the effects of interventions on independence, community integration, and quality of life. [ABSTRACT FROM AUTHOR]

Objective: Chronic kidney diseases (CKDs) characterized by progressive loss of kidney function impart significant burden on the patients. Besides physical disabilities, CKD affects the mental health and quality of life of the patients. Recent studies suggest the need for interdisciplinary patient-centric care in the management of CKD., Methods: The present study introduced patient-centric holistic integrative therapies (YNBLI) in a 64-year-old female diagnosed with CKD in 2021, who presented with breathlessness, fatigue, loss of appetite, and anxiety. She is a known case of type 2 diabetes, hypertension and osteoarthritis of knee. She was advised for dialysis by her nephrologists', however, she was reluctant to undergo dialysis due to anxiety about the side effects and lifelong dependency on dialysis. She initially underwent a 10-day YNBLI program at our inpatient setting followed by adhering to the home-based YNBLI for 16 weeks., Results: She showed significant improvement in the kidney function, hemoglobin levels, quality of life and symptoms with no adverse events. The improvements were consistent throughout the 16 weeks after discharge., Discussion: This study presents the effective use of patient-centric holistic integrative therapies (YNBLI) as an adjuvant in the management of CKD. Future studies are warranted to substantiate these findings., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Naturopathic medicine is a popular form of complementary and alternative medicine systems practiced worldwide. This study provides an overview of a typical inpatient yoga and naturopathy protocol followed in India. Naturopathic medicine is commonly used in the management of certain lifestyle-related disorders, such as diabetes mellitus, hypertension, obesity, cancer, musculoskeletal disorders, endocrine disorders, and neurological disorders. Moreover, naturopathic medicine integrates different lifestyle medicine practices, such as yoga, diet, acupuncture, hydrotherapy, and color therapy into its treatment plans. Moreover, India is one of the few countries that offer naturopathy treatments through inpatient hospitals. Although the clinical efficacy of naturopathic medicine practices in various pathological conditions has been confirmed, no studies have yet investigated the effectiveness of naturopathic medicines protocols in naturopathic inpatient settings. Naturopathic physicians use a set of philosophical principles when determining their therapeutic order and all therapies that upregulate physiological homeostasis., Competing Interests: • Conflicts of Interest: No conflict of interest., (© 2024 Journal of Lifestyle Medicine.)

High-grade gliomas are aggressive brain tumors with a poor prognosis despite conventional treatments such as surgery, radiation, and chemotherapy. Integrative oncology, combining conventional and complementary therapies, may offer additional benefits in managing these complex cases. We present a 68-year-old male farmer diagnosed with high-grade glioma in the left medial temporal lobe. The patient presented with severe headache, disturbed sleep, and anxiety, and experienced an episode of fever and seizure. He refused conventional radiation therapy due to concerns about side effects and opted for an integrative medicine protocol. This protocol included oncothermia, high-dose vitamin C therapy, hydrogen inhalation, ozone therapy, magnet therapy, fasting, acupuncture, pulsed electromagnetic field therapy, yoga therapy, hydrotherapy, biologicals, and dietary modifications. The patient underwent 12 sessions of oncothermia over 24 days, combined with other integrative therapies. MRI scans before and after treatment showed a reduction in tumor size from 3.6 x 2.9 x 2.5 cm to 3.4 x 2.7 x 2.5 cm, corresponding to a 12% decrease in volume. Hematological parameters (complete blood count, liver function test, kidney function test, C-reactive protein), cancer markers (carcinoembryonic antigen, lactate dehydrogenase), and mental health indices (quality of life, survival rate) also showed significant improvement. The patient experienced no adverse events and reported enhanced quality of life. This case report suggests that an integrative oncology approach, combining oncothermia and various complementary therapies, may be an effective treatment option for high-grade gliomas, particularly for patients intolerant to conventional therapies. Further research, including randomized controlled trials, is necessary to validate these findings and determine the specific contributions of each therapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nair et al.)

This study aimed to see the effect of oral supplementation of specific trace minerals mixture on the growth, immunity, and reproductive development of indigenous growing bull calves. Eighteen Sahiwal bull calves, with an average age of 6 months were chosen and divided into three groups. Group 1 was fed with a basal diet, Group 2 was provided with an additional specific trace mineral supplement to achieve a diet containing 70 ppm of Zn, 17.50 ppm of Cu, 65 ppm of Mn, and 1.75 ppm of Cr. Group 3 received a 25% extra supplement to achieve a diet containing 87.50 ppm of Zn, 21.87 ppm of Cu, 81.25 ppm of Mn, and 2.18 ppm of Cr. The experiment was carried out for a total of 180 days. According to the findings, there was no significant impact of specific trace minerals supplementation on the animals' body weight, morphometric parameters, dry matter intake, average daily gain, nutritional value, digestibility and nitrogen retention. However, higher levels of Zn, Cu, and Mn led to increased (p < 0.05) total retention, while Cr retention remained the same. Serum mineral concentrations of Zn, Cu, and Mn increased significantly (p < 0.05) in G2 and G3 compared to the G1 group while Ca, P, and Cr had no significant change. Blood plasma glucose, albumin, globulin, and total protein showed no significant differences. Plasma alkaline phosphatase activity improved significantly (p < 0.05) in G2 and G3 but alanine transaminase, aspartate aminotransferase, hemoglobin, hematocrit, and IGF-1 remained unchanged. Superoxide dismutase activity, ferric-reducing antioxidant power, and total immunoglobulin concentration increased significantly (p < 0.05) in G2 and G3 groups, however, catalase activity and IgG count did not change among the groups. Mineral-supplemented groups (G2 and G3) showed a significant change (p < 0.05) in testosterone production during the 120th and the 180th day of the trial. Scrotal circumference and temperature gradient of the scrotal surface did not show any significant change. Supplementing growing bull calves with specific trace minerals above the basal level (70, 17.50, 65 and 1.75 ppm of Zn, Cu, Mn and Cr) has no direct beneficial effect on the growth parameters but can have positive effects on their antioxidant status, immunity and reproductive development as the related blood parameters were positively affected., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Blood platelets are crucial to prevent excessive bleeding following injury to blood vessels. Platelets are crucial for the formation of clots and for clot strength. Platelet activation involves aggregation, attachment to fibrin and clot retraction. Most assays that address platelet function measure platelet aggregation, not clot retraction. Here, we describe a 96-well-based clot retraction assay that requires a relatively short runtime and small sample volume. The assay involves continuous optical density monitoring of platelet-rich plasma that is activated with thrombin. The data can be analyzed using time-series analytical tools to generate quantitative information about different phases of clot formation and clot retraction. The assay demonstrated good repeatability and reproducibility and was robust to different calcium concentrations. Impairment of platelet bioenergetics, actin polymerization, fibrin interaction, and signaling significantly affected clot retraction and was detected and showed good agreement with light transmission aggregometry, suggesting that clot retraction is predictive of platelet function. Using this microplate clot retraction assay, we showed a significant difference in platelets stored in autologous plasma compared with platelet additive solution after 7 days of room temperature storage.

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7 + mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target., (© 2023. Crown.)

Objectives: This study aims to determine what pathologic and clinical factors differentiate Brachyspira species that may be useful to clinicians and pathologists., Methods: We identified 21 studies of Brachyspira infection with individual patient information (n = 113) and conducted a pooled analysis comparing each species., Results: There were differences in the pathologic and clinical profiles of each Brachyspira species. Patients infected with Brachyspira pilosicoli infection were more likely to have diarrhea, fever, HIV, and immunocompromised conditions. Those patients infected with Brachyspira aalborgi were more likely to have lamina propria inflammation., Conclusions: Our novel data provide potential insights into the pathogenic mechanism(s) and the specific risk factor profile of Brachyspira species. This may be clinically useful when assessing and managing patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and objective Primary dysmenorrhea (PD) is one of the leading health issues among women. According to reports, nutrition/diet significantly affects the severity and course of PD. The present study aimed to evaluate the role of therapeutic fasting in alleviating the symptoms associated with PD, improving quality of life (QoL), and reducing absenteeism among young female adults with PD. Methods A total of 52 participants aged between 18 and 24 years were included in the study and randomly classified into two groups of 26 each. The study group (fasting group) was assigned to undergo a 10-day fasting regimen (≤500 kcal/day) while the control group was to follow a normal dietary routine. The severity of pain, associated distress symptoms, QoL, and sleep quality were measured at baseline and on the fifth day of the first, second, and third menstruation cycles after the intervention, using the Visual Analog Scale (VAS), Numerical Rating Scale (NRS), the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire, and Pittsburg Sleep Quality Index. We also recorded the rate of absenteeism among the study participants during menstruation cycles. Results We observed a significant reduction in pain (p<0.001), cramps (p=0.001), nausea/vomiting (p=0.02), dizziness (p=0.007), and mood changes (p=0.005) in the study group compared to the control group. The effects were persistent in most of the variables at the second and third follow-ups as well. The physical (p=0.005) and psychological (p<0.001) QoL significantly improved in the first month, and we observed a similar trend at the second (physical p=0.03; psychological p=0.001) and third follow-ups (psychological p=0.002) except for physical QoL, which was significant only at the second follow-up. The fasting group had significantly lower absenteeism compared to the controls during the first follow-up (p=0.001). Conclusion Therapeutic fasting may be considered a safe and effective option in the management of PD. Future trials should examine the long-term sustainability of the results., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Tewani et al.)

Context: One of the governing principles of naturopathic medicine is the concept of Unity of Disease and Unity of Cure (UDUC). Many naturopathic physicians and students find it challenging to provide a scientific basis for UDUC because conventionally every disease has varying etiologies., Objective: The review intended to explore the basis of UDUC, examining the available theoretical evidence around this fundamental tenet of naturopathic medicine, to promote its effective use when consulting new patients and planning the subsequent treatment., Design: The research team performed a narrative review by searching PubMed, PubMed central, Scopus, Google scholar databases, textbooks on naturopathy and websites of professional bodies representing naturopathic medicine. The search used the keywords 'Naturopathic Medicine', 'Naturopathy', 'Holism', 'Self-healing', 'Pyschosocial determinants and health', 'unity of disease and unity of cure', 'health and disease', 'Multi-model approach', 'whole-system practice' and 'Global naturopathic practice'., Setting: The review took place at Sant Hirdaram Medical College of Naturopathy and Yogic Sciences for women in Bhopal, Madhya Pradesh, India., Results: The present review provides a comprehensive overview of the scientific evidence behind UDUC under four layers: psychological factors, lifestyle factors, physiological alterations, and disease manifestation. The data presented in this review substantiate the presence of these four layers in the manifestation of various clinical conditions like musculoskeletal disorders, obstetric and gynecological disorders, cardiometabolic disorders, infectious disorders, and gastrointestinal disorders., Conclusions: It's very evident that the global naturopathic profession embraces traditional philosophies as the core of their practices. However, the field needs measures, such as the formulation of international working groups and the organization of continuous medical-education programs, congresses, and exchange programs, to facilitate crosstalk among practitioners from different parts of the world, which may assert the importance of philosophical tenets such as UDUC in clinical practice., (Copyright © 2023 InnoVision Professional Media Inc.)

Background: Functional dyspepsia is characterised by chronic symptoms of post-prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cells have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific phenotype was associated with FD., Objective: This study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology., Methods: We identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry using a surface marker antibody panel. We also analysed T cell populations in peripheral blood from 37 controls and 61 patients. Where available, we examined the number of duodenal eosinophils in patients and controls., Results: There was a shift in the duodenal T helper cell balance in FD patients compared to controls. For example, patients had increased duodenal mucosal Th2 populations in the effector (13.03 ± 16.11, 19.84 ± 15.51, p =0.038), central memory (23.75 ± 18.97, 37.52 ± 17.51, p =0.007) and effector memory (9.80±10.50 vs 20.53±14.15, p =0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, p =0.03) and effector memory (11.95±8.42 vs 18.44±15.63, p =0.027) subsets. Peripheral T cell populations were unchanged between FD and control., Conclusion: Our findings identify an association between lymphocyte populations and FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven., Competing Interests: Author GH received unrestricted educational support from Bayer Ptd, Ltd and the Falk Foundation. Research support was provided via the Princess Alexandra Hospital, Brisbane by GI Therapies Pty Limited, Takeda Development Center Asia, Pty Ltd, Eli Lilly Australia Pty Limited, F. Hoffmann-La Roche Limited, MedImmune Ltd Celgene Pty Limited, Celgene International II Sarl, Gilead Sciences Pty Limited, Quintiles Pty Limited, Vital Food Processors Ltd, Datapharm Australia Pty Ltd Commonwealth Laboratories, Pty Limited, Prometheus Laboratories, Falk GmbH and Co Kg, Nestle Pty Ltd, Mylan. Patent Holder: A biopsy device to take aseptic biopsies US 20150320407 A1. Author MV received grant/research Support: NIHR IBD clinical, LIVErNORTH Hepatology clinical. Author NP received advisory board fees from Abbvie, Allergan, Debiopharm International, Ferring, and Vifor Pharma and lecture fees from Allergan and Falk Pharma. Author MW received grant/research support: Prometheus Laboratories Inc Irritable bowel syndrome IBS Diagnostic, Commonwealth Diagnostics International biomarkers for FGIDs. Author NT received grant/research support: Rome Foundation; Abbott Pharmaceuticals; Datapharm; Pfizer; Salix irritable bowel syndrome; Prometheus Laboratories Inc irritable bowel syndrome IBS Diagnostic; Janssen constipation. Consultant/Advisory Boards: Allakos IBS, Adelphi Values functional dyspepsia patient reported outcome measures; Budesonide; GI therapies chronic constipation Rhythm IC; Allergens PLC; Napo Pharmaceutical; Outpost Medicine; Samsung Bioepis; Yuhan IBS; Synergy IBS; Theravance gastroparesis. Patent holder: Biomarkers of irritable bowel syndrome; Licensing Questionnaires Mayo Clinic Talley Bowel Disease Questionnaire—Mayo Dysphagia Questionnaire; Nestec European Patent Application No. 12735358.9; Singapore “Provisional” Patent NTU Ref: TD/129/17 “Microbiota Modulation of BDNF Tissue Repair Pathway. Author SK received grant/research support: Cancer Institute NSW Career Development Fellowship, National Health and Medical Research Council Project Grant, Commonwealth Diagnostics International biomarkers for FGIDs, Syntrix Biosystems contract research—drug delivery. Anatara Lifesciences Advisory Board/Funded research. Gossamer Bio Advisory Board/Funded research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Burns, Bruce, Minahan, Mathe, Fairlie, Cameron, Naudin, Nair, Potter, Irani, Bollipo, Foster, Gan, Shah, Koloski, Foster, Horvat, Veysey, Holtmann, Powell, Walker, Talley and Keely.)

Background: Osteodystrophia fibrosa (ODF) is a metabolic disorder affecting the skeletal system, causing progressive loss of calcified bone mass and its replacement with fibrous tissue, which may be a sequel to primary or secondary hyperparathyroidism. This report intends to document the clinicopathological findings of ODF in a flock of young goats fed primarily on a wheat bran-rich diet., Case Description: In a flock of 50 stall-fed goats aged 1 to 2 years, seven were clinically presented with bilateral facial enlargement, leading to dyspnea and difficulty in prehension and mastication. Among the seven clinically affected goats, four died in 2 months., Findings/treatment and Outcome: The clinical examination revealed bilateral mandibular enlargement and limb deformities. On radiography, the maxilla and mandible had decreased radiopacity. Fine needle aspiration cytology (FNAC) from the affected bones showed occasional fibroblasts and individual osteoclasts clusters. On necropsy, the enlarged mandible revealed a meaty consistency. Undecalcified histological sections of the mandible showed severe osteopenia, multiple osteoclasts, Howship's lacunae, and extensive fibroplasia. Dietary corrective measures led to the prevention of ODF in the rest of the flock., Conclusion: Excessive wheat bran feeding in stallfed goats might have led to calcium and phosphorus imbalance, resulting in nutritional secondary hyperparathyroidism and subsequent skeletal deformities. FNAC of the affected bones, gross and histological findings provide a clinicopathological diagnosis of ODF., Competing Interests: Authors have no conflict of interest to declare.

Background: Recent research indicates prolonged fasting for more than 7 days is beneficial in priming the vitamin D metabolism. However, methodological limitations in previous studies, such as insufficient sample size and a lack of control group, limits its generalizability. The present study evaluated the impact of prolonged fasting (10 days) on vitamin D, vitamin B12, body mass index (BMI), weight, hemoglobin, vitality and quality of life (QoL) compared to a normal diet., Methods: This randomized control trial was conducted in an in-patient private yoga and naturopathy setting between February and April 2022. A total of 52 participants (mean age 51.57 ± 13.67 years) with varying medical conditions were randomized into a fasting group (FG) or a normal diet group (NDG) with 26 participants in each group. The FG was on a fasting diet (500 kCal/day) which included holy basil herbal tea, lemon honey water, and water (3 L). The NDG (1500 kCal/day) consumed a routine diet that included Indian bread, pulses, steamed rice, vegetable salads, and beverages., Results: The FG has shown significant increase in the Vitamin D levels ( P  = .003, d  = 0.475), vitality ( P  = .006, d  = 0.425), physical QoL ( P  < .001, d  = 0.549), psychological QoL ( P  = .002, d  = 0.488), and environmental QoL ( P  = .004, d  = 0.457) compared to NDG. No significant changes were observed in vitamin B12, weight, BMI, haemoglobin, and social QoL. A weak to moderate (ρ = 0.330-0.483) positive correlation was observed between vitality scores and QoL domains, whereas BMI scores showed an inverse correlation (ρ = -.280) with vitamin D levels., Conclusion: The results suggest that prolonged fasting for 10 days can improve vitamin D levels, improve vitality, and promote quality of life compared to a normal diet. Unlike previous studies, the FG does not differ from the NDG concerning weight and BMI. Nevertheless, fasting may be utilized as an effective tool to tackle vitamin D deficiency and associated health insufficiencies., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COPD overlap (ACO). Patients characterized with ACO have increased disease severity; however, the mechanisms driving this have not been widely studied., Objectives: This study sought to characterize the phenotypic and transcriptomic features of experimental ACO in mice induced by chronic house dust mite antigen and cigarette smoke exposure., Methods: Female BALB/c mice were chronically exposed to house dust mite antigen for 11 weeks to induce experimental asthma, cigarette smoke for 8 weeks to induce experimental COPD, or both concurrently to induce experimental ACO. Lung inflammation, structural changes, and lung function were assessed. RNA-sequencing was performed on separated airway and parenchyma lung tissues to assess transcriptional changes. Validation of a novel upstream driver SPI1 in experimental ACO was assessed using the pharmacological SPI1 inhibitor, DB2313., Results: Experimental ACO recapitulated features of both asthma and COPD, with mixed pulmonary eosinophilic/neutrophilic inflammation, small airway collagen deposition, and increased airway hyperresponsiveness. Transcriptomic analysis identified common and distinct dysregulated gene clusters in airway and parenchyma samples in experimental asthma, COPD, and ACO. Upstream driver analysis revealed increased expression of the transcription factor Spi1. Pharmacological inhibition of SPI1 using DB2313, reduced airway remodeling and airway hyperresponsiveness in experimental ACO., Conclusions: A new experimental model of ACO featuring chronic dual exposures to house dust mite and cigarette smoke mimics key disease features observed in patients with ACO and revealed novel disease mechanisms, including upregulation of SPI1, that are amenable to therapy., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Human colonic spirochetosis (CS) is usually due toBrachyspira pilosicolior Brachyspira aalborgiinfection. While traditionally considered to be commensal bacteria, there are scattered case reports and case series of gastrointestinal (GI) symptoms in CS and reports of colonic polyps with adherent spirochetes. We performed a systematic review and meta-analysis investigating the association between CS and GI symptoms and conditions including the irritable bowel syndrome (IBS) and colonic polyps. Following PRISMA 2020 guidelines, a systematic search of Medline, CINAHL, EMBASE, and Web of Science was performed using specific keywords for CS and GI disease. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Of 75 studies identified in the search, 8 case-control studies met the inclusion criteria for meta-analysis and 67 case series studies met the inclusion criteria for pooled prevalence analysis. CS was significantly associated with diarrhea (n = 141/127, cases/controls, OR: 4.19, 95% CI: 1.72-10.21, P = 0.002) and abdominal pain (n = 64/65, OR: 3.66, 95% CI: 1.43-9.35, P = 0.007). CS cases were significantly more likely to have Rome III-diagnosed IBS (n = 79/48, OR: 3.84, 95% CI: 1.44-10.20, P = 0.007), but not colonic polyps (n = 127/843, OR: 8.78, 95% CI: 0.75-103.36, P = 0.084). In conclusion, we found evidence of associations between CS and both diarrhea and IBS, but not colonic polyps. CS is likely underestimated due to suboptimal diagnostic methods and may be an overlooked risk factor for a subset of IBS patients with diarrhea., (© 2022 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background & Aims: Excessive shedding of apoptotic enterocytes into the intestinal lumen is observed in inflammatory bowel disease and is correlated with disease relapse. Based on their cytolytic capacity and surveillance behavior, we investigated whether intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) are actively involved in the shedding of enterocytes into the lumen., Methods: Intravital microscopy was performed on GFP γδ T cell reporter mice treated with intraperitoneal lipopolysaccharide (10 mg/kg) for 90 minutes to induce tumor necrosis factor-mediated apoptosis. Cell shedding in various knockout or transgenic mice in the presence or absence of blocking antibody was quantified by immunostaining for ZO-1 funnels and cleaved caspase-3 (CC3). Granzyme A and granzyme B release from ex vivo-stimulated γδ IELs was quantified by enzyme-linked immunosorbent assay. Immunostaining for γδ T cell receptor and CC3 was performed on duodenal and ileal biopsies from controls and patients with Crohn's disease., Results: Intravital microscopy of lipopolysaccharide-treated mice revealed that γδ IELs make extended contact with shedding enterocytes. These prolonged interactions require CD103 engagement by E-cadherin, and CD103 knockout or blockade significantly reduced lipopolysaccharide-induced shedding. Furthermore, we found that granzymes A and B, but not perforin, are required for cell shedding. These extracellular granzymes are released by γδ IELs both constitutively and after CD103/E-cadherin ligation. Moreover, we found that the frequency of γδ IEL localization to CC3-positive enterocytes is increased in Crohn's disease biopsies compared with healthy controls., Conclusions: Our results uncover a previously unrecognized role for γδ IELs in facilitating tumor necrosis factor-mediated shedding of apoptotic enterocytes via CD103-mediated extracellular granzyme release., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identifiable pathology. Psychological stress is a key factor associated with the onset of FD and locally acting hypothalamic-pituitary-adrenal (HPA) axis hormones have been implicated in GI motility and barrier dysfunction. Recent pre-clinical work has identified mechanistic pathways linking corticotropin-releasing hormone (CRH) with the innate epithelial immune protein NLRP6, an inflammasome that has been shown to regulate GI mucus secretion. We recruited twelve FD patients and twelve healthy individuals to examine whether dysregulation of hypothalamic-pituitary adrenal (HPA) axis hormones and altered NLRP6 pathways were evident in the duodenal mucosa. Protein expression was assessed by immunoblot and immunohistochemistry in D2 duodenal biopsies. Plasma HPA axis hormones were assayed by ELISA and enteroid and colorectal cancer cell line cultures were used to verify function. FD patients exhibited reduced duodenal CRH-receptor 2, compared to non-GI disease controls, indicating a dysregulation of duodenal HPA signalling. The loss of CRH-receptor 2 correlated with reduced NLRP6 expression and autophagy function, processes critical for maintaining goblet cell homeostasis. In accordance, duodenal goblet cell numbers and mucin exocytosis was reduced in FD patients compared to controls. In vitro studies demonstrated that CRH could reduce NLRP6 in duodenal spheroids and promote mucus secretion in the HT29-MTX-E12 cell line. In conclusion, FD patients exhibit defects in the NLRP6-autophagy axis with decreased goblet cell function that may drive symptoms of disease. These features correlated with loss of CRH receptor 2 and may be driven by dysregulation of HPA signalling in the duodenum of FD patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Calcium silicate-based cements or bioceramics have revolutionized and simplified pulp-capping procedures due to its versatility and accessibility., Aim: This study aimed to assess the shear bond strength (SBS) of a bioceramic material to composite resin at two aging periods and with three universal adhesives., Materials and Methods: Forty-eight samples of Biodentine with a height of 2 mm and internal diameter of 4 mm were prepared. After 12 min of mixing, 24 samples were randomly selected and divided into four subgroups: Group I: Single Bond Universal, Group II: Palfique Universal Bond, Group III: G-Premio BOND, and Group IV: Control. Composite resin was restored over Biodentine after the application of universal adhesives using a cylindrical plastic mold of 2 mm height and 2 mm internal diameter. This process was repeated 24 h after mixing on the remaining 24 samples of Biodentine. The universal testing machine was used to measure the SBS of the fractured specimens, followed by stereomicroscopic evaluation. One-way ANOVA test and Bonferroni post hoc test were used to statistically analyze the data., Results: Highest SBS values were observed in Group III at 12 min and 24 h of the setting of Biodentine., Conclusions: Compared to the 12-min group, SBS was higher at 24 h. Group III exhibited higher bond strength than other subgroups., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Conservative Dentistry.)

Background: Fasting is being used as a therapeutic and cultural practice for millennia. There are numerous reports available on beneficial effects of fasting on various disease conditions. Despite the mounting evidence on fasting, little is known on its physiological effects in humans as most of the studies on physiological effects are done in animals., Methods: Twenty healthy female volunteers (mean age ± SD, 21.95 ± 2.52 years) participated in a 10-day fasting program, which has 1 preparatory day and 1 refeeding day (1,000 kcal) and 8 fasting days (500 kcal). All the participants consented to participate in the study. Blood parameters like complete blood count, renal function test, total iron binding capacity, lipid profile, liver profile, vitamins D and B12, thyroid function tests, glycated hemoglobin, and air blood gas test along with anthropometric measurements were taken on the first and last day., Results: All the parameters under the study have shown statistically significant changes (p < 0.05) except hemoglobin (p = 0.7) and non-high density lipoprotein (p = 0.32). Notable changes were the significant increase in vitamins D and B12 levels that signifies the homoeostatic potential of a fasting regimen., Conclusion: The result depicts the positive impact of fasting on various physiological parameters that warrants further studies on the safety of fasting in diverse diseases, especially the ones that have metabolic disarray as the root cause. Despite the limitation of the smaller sample size and lack of a control group, the results are encouraging to devise disease-specific fasting programs.

Rationale: Necroptosis, mediated by RIPK3 (receptor-interacting protein kinase 3) and MLKL (mixed lineage kinase domain-like), is a form of regulated necrosis that can drive tissue inflammation and destruction; however, its contribution to chronic obstructive pulmonary disease (COPD) pathogenesis is poorly understood. Objectives: To determine the role of necroptosis in COPD. Methods: Total and active (phosphorylated) RIPK3 and MLKL were measured in the lung tissue of patients with COPD and control subjects without COPD. Necroptosis-related mRNA and proteins as well as cell death were examined in lungs and pulmonary macrophages of mice with cigarette smoke (CS)-induced experimental COPD. The responses of Ripk3 -/- and Mlkl -/- mice to acute and chronic CS exposure were compared with those of wild-type mice. The combined inhibition of apoptosis (with the pan-caspase inhibitor quinoline-Val-Asp-difluorophenoxymethylketone [qVD-OPh]) and necroptosis (with deletion of Mlkl in mice) was assessed. Measurements and Main Results: The total MLKL protein in the epithelium and macrophages and the pRIPK3 and pMLKL in lung tissue were increased in patients with severe COPD compared with never-smokers or smoker control subjects without COPD. Necroptosis-related mRNA and protein levels were increased in the lungs and macrophages in CS-exposed mice and experimental COPD. Ripk3 or Mlkl deletion prevented airway inflammation upon acute CS exposure. Ripk3 deficiency reduced airway inflammation and remodeling as well as the development of emphysematous pathology after chronic CS exposure. Mlkl deletion and qVD-OPh treatment reduced chronic CS-induced airway inflammation, but only Mlkl deletion prevented airway remodeling and emphysema. Ripk3 or Mlkl deletion and qVD-OPh treatment reduced CS-induced lung-cell death. Conclusions: Necroptosis is induced by CS exposure and is increased in the lungs of patients with COPD and in experimental COPD. Inhibiting necroptosis attenuates CS-induced airway inflammation, airway remodeling, and emphysema. Targeted inhibition of necroptosis is a potential therapeutic strategy in COPD.

Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature-stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold-stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14-day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet-mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days. The results demonstrate that CSP have better preservation of contractile function, exhibiting retraction for up to 21 days in both AP and PAS and forming highly ordered fibrin scaffolds similar to those of fresh platelets. In contrast, RTP stored in AP showed impaired contractile function by Day 5 with no retraction after 10 days, whereas PAS-stored RTP retained contractile function for up to 21 days. Collectively, these findings support extended storage of CSP and suggest that storage in PAS can mitigate functional losses in RTP., (© 2021 AABB. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Disequilibrium syndrome is typically characterized by neurological manifestations that occur acutely posthemodialysis due to a significant drop in serum osmolality. We report a child with disequilibrium syndrome postrenal transplant and compare this presentation to previously reported cases.

In addition to their well characterized role in mediating IgE-dependent allergic diseases, aberrant accumulation and activation of mast cells (MCs) is associated with many non-allergic inflammatory diseases, whereby their activation is likely triggered by non-IgE stimuli (e.g., IL-33). Siglec-8 is an inhibitory receptor expressed on MCs and eosinophils that has been shown to inhibit IgE-mediated MC responses and reduce allergic inflammation upon ligation with a monoclonal antibody (mAb). Herein, we evaluated the effects of an anti-Siglec-8 mAb (anti-S8) in non-allergic disease models of experimental cigarette-smoke-induced chronic obstructive pulmonary disease and bleomycin-induced lung injury in Siglec-8 transgenic mice. Therapeutic treatment with anti-S8 inhibited MC activation and reduced recruitment of immune cells, airway inflammation, and lung fibrosis. Similarly, using a model of MC-dependent, IL-33-induced inflammation, anti-S8 treatment suppressed neutrophil influx, and cytokine production through MC inhibition. Transcriptomic profiling of MCs further demonstrated anti-S8-mediated downregulation of MC signaling pathways induced by IL-33, including TNF signaling via NF-κB. Collectively, these findings demonstrate that ligating Siglec-8 with an antibody reduces non-allergic inflammation and inhibits IgE-independent MC activation, supporting the evaluation of an anti-Siglec-8 mAb as a therapeutic approach in both allergic and non-allergic inflammatory diseases in which MCs play a role.

Background: Cold storage of platelets in plasma maintains hemostatic function and is an attractive alternative to room temperature platelets (RTPs). We have recently shown that functional differences between cold-stored platelets (CSPs) and RTPs after 5-day storage are associated with mitochondrial respiration and that CSPs in platelet (PLT) additive solution (PAS) can maintain hemostatic function for at least 15 days., Study Design and Methods: This study tested the hypothesis that cold storage in PAS preserves mitochondrial integrity by reducing PLT apoptosis. CSPs and RTPs in plasma or PAS were stored and assayed for up to 15 days for mitochondrial function and integrity, mitochondrial-associated mRNA transcript expression, apoptotic proteins, and apoptotic flow cytometry metrics., Results: CSP preserved mitochondria-associated mRNA comparable to baseline levels, improved mitochondrial respiration, and minimized depolarization to Day 15. Additionally, CSPs had minimal induction of caspases, preservation of plasma membrane integrity, and low expression of pro-apoptotic Bax. Storage in PAS appeared to be protective for RTPs in some parameters and enhanced the effects of CSPs., Conclusion: Mitochondrial function and molecular analyses defined CSP priming as distinctly different from the well-documented RTP storage lesion. While current blood bank storage at room temperature is limited to 5 to 7 days, refrigeration and storage in PAS for up to 15 days may represent an opportunity to enhance inventories and access to PLT hemostatic support for bleeding patients., (© 2020 AABB.)