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Evaluation of mechanical prosthetic valve function is based on echocardiography, but adequate assessment of leaflet motion is limited by acoustic shadowing. Cinefluoroscopy is a standard method to assess leaflet motion, while computed tomography (CT) has been suggested as an alternative. We sought to compare the feasibility of leaflet motion assessment by cinefluoroscopy vs. CT. In 35 prospectively enrolled patients, leaflet motion was assessed in 43 bileaflet mechanical prostheses (29 mitral and 14 aortic) by cinefluoroscopy and non-contrast CT. Assessment was considered feasible when the 'in profile' projection (with the radiographic beam parallel to both the valve ring plane and the tilting axis of discs) could be achieved. Overall feasibility of fluoroscopic assessment was 74% (mitral, 66% vs. aortic, 93%; p = 0.071), while feasibility of CT assessment was 100% (p = 0.003). Among prostheses with unfeasible fluoroscopic assessment, CT suggested an extreme C-arm angulation to achieve the "in profile" projection (RAO: 76.0 ± 5.8°, LAO: 122.7 ± 32.5°, CRA: 51.4 ± 16.0°, CAU: 57.0 ± 18.2°). Among prostheses with feasible assessment by both techniques, fluoroscopy and CT yielded similar opening and closing angles (intraclass correlation coefficient, 0.959–0.998) with lower irradiation with CT as compared with fluoroscopy (26.2[21.1–29.3] vs. 289[179–358] mGy, p < 0.001). While CT scan took 8.7 ± 0.5 s, fluoroscopy required 2.64 ± 1.56 min to achieve and record the "in profile" projection. Non-contrast CT provides a higher feasibility and a quicker evaluation of mechanical prosthetic valve leaflet motion with less irradiation than fluoroscopy, especially in mitral valve position. [ABSTRACT FROM AUTHOR]

Insomnia, and Excessive Daytime Sleepiness (EDS), a surrogate marker of Obstructive Sleep Apnea (OSA), are common sleep-related conditions among painful temporomandibular disorders (TMD) patients. OSA was found to increase the risk of chronic painful TMD. This prospective cohort study aims to determine the contribution of insomnia and EDS on acute to chronic painful TMD transition as well as its persistence when chronic pain is defined by: (i) duration (> 3 months), and (ii) dysfunction (Graded Chronic Pain Scale [GCPS II-IV]). From 456 patients recruited between 2015 to 2021, through four locations in Canada, 378 completed the follow-up. A diagnosis was obtained using the Research Diagnostic Criteria or the Diagnostic Criteria for TMD. Insomnia was assessed with the Insomnia Severity Scale (ISS), and OSA was assessed using the Epworth Sleepiness Scale (ESS) which measures EDS, both at baseline. Patients completed the GCPS form at baseline and 3-month follow-up. Borderline associations were found between EDS and the transition or persistence of chronic painful TMD when chronic pain was defined by pain duration (RR adjusted_duration = 1.11, P = 0.07) and dysfunction (RRadjusted_dysfunction =1.40, P = 0.051). Furthermore, EDS was specifically associated with persistent painful TMD when chronic pain was defined by pain duration (RR = 1.13, 95%CI: 1.00-1.26, P = 0.04). Insomnia was not related to the study outcomes (RRadjusted_duration = 0.94, P = 0.27, RRadjusted_dysfunction =1.00, P = 0.99). Results indicate that EDS contrary to insomnia predicted the persistence of chronic painful TMD at a 3-month follow-up. [ABSTRACT FROM AUTHOR]

The purpose of this conceptual paper is to explore the ways in which an analogy of integrative medicine levels of dysfunction could apply to organizational diagnosis to enhance practitioner understanding of the nature and depth of organizational dysfunction while preserving the collaborative and co-learning nature of the organization development (OD) process. This paper is to attempt to create greater specificity as OD practitioners look at the dysfunction in an organization when using Weisbord's diagnostic approach. By extending Weisbord's Six-Box Model to a seventh box, the external environment, the OD practitioner is able to focus more particularly on an area for intervention. Further, by extending the metaphor of diagnosis from the biomedical model to an integrative medicine model, organizations can gain insight into the gravity of their problems and more deeply embrace the nature of the required interventions. [ABSTRACT FROM AUTHOR]

Background: Although swallowing disorders can impact individuals of any age, some are unique to the elderly, and others are frequent. Some disorders, such as achalasia, are diagnosed by esophageal manometry studies, which assess lower esophageal sphincter (LES) pressure and relaxation, peristalsis in the esophageal body, and contraction wave characteristics. This research aimed to evaluate esophageal motility dysfunction in symptomatic patients and its relation to age. Methods: Conventional esophageal manometry was performed on 385 symptomatic patients who were divided into two groups; Group A (age < 65 years old) and Group B (age ≥ 65 years). The geriatric assessment for Group B included cognitive, functional, and clinical frailty scales (CFS). Additionally, a nutritional assessment was done for all patients. Results: About one-third of the patients (33%) had achalasia, in which manometric results were significantly higher in Group B (43.4%) than in Group A (28.7%) (P = 0.016). The resting lower esophageal sphincter (LES) pressure, as determined by manometry examination, was significantly lower in Group A than in Group B. In contrast, complete LES relaxation percentage and normal esophageal body peristalsis were significantly higher in Group A than in Group B. Patients who exhibited evidence of achalasia in the manometric study had a significantly increased risk of established malnutrition and functional impairment. Conclusions: Achalasia is a prevalent cause of dysphagia in elderly patients, placing them at risk of malnutrition and functional impairment. Thus, a multidisciplinary approach is vital when providing care for this population. [ABSTRACT FROM AUTHOR]

Background: Donor‐derived cell free DNA (dd‐cfDNA) and gene expression profiling (GEP) offer noninvasive alternatives to rejection surveillance after heart transplantation; however, there is little evidence on the paired use of GEP and dd‐cfDNA for rejection surveillance. Methods: A single center, retrospective analysis of adult heart transplant recipients. A GEP cohort, transplanted from January 1, 2015 through December 31, 2017 and eligible for rejection surveillance with GEP was compared to a paired testing cohort, transplanted July 1, 2018 through June 30, 2020, with surveillance from both dd‐cfDNA and GEP. The primary outcomes were survival and rejection‐free survival at 1 year post‐transplant. Results: In total 159 patients were included, 95 in the GEP and 64 in the paired testing group. There were no differences in baseline characteristics, except for less use of induction in the paired testing group (65.6%) compared to the GEP group (98.9%), P <.01. At 1‐year, there were no differences between the paired testing and GEP groups in survival (98.4% vs. 94.7%, P =.23) or rejection‐free survival (81.3% vs. 73.7% P =.28). Conclusions: Compared to post‐transplant rejection surveillance with GEP alone, pairing dd‐cfDNA and GEP testing was associated with similar survival and rejection‐free survival at 1 year while requiring significantly fewer biopsies. [ABSTRACT FROM AUTHOR]

In reproduction, mitochondria produce bioenergy, help to synthesize biomolecules, and support the ovaries, oogenesis, and preimplantation embryos, thereby facilitating healthy live births. However, the regulatory mechanism of mitochondria in oocytes and embryos during oogenesis and embryo development has not been clearly elucidated. The functional activity of mitochondria is crucial for determining the quality of oocytes and embryos; therefore, the underlying mechanism must be better understood. In this review, we summarize the specific role of mitochondria in reproduction in oocytes and embryos. We also briefly discuss the recovery of mitochondrial function in gametes and zygotes. First, we introduce the general characteristics of mitochondria in cells, including their roles in adenosine triphosphate and reactive oxygen species production, calcium homeostasis, and programmed cell death. Second, we present the unique characteristics of mitochondria in female reproduction, covering the bottleneck theory, mitochondrial shape, and mitochondrial metabolic pathways during oogenesis and preimplantation embryo development. Mitochondrial dysfunction is associated with ovarian aging, a diminished ovarian reserve, a poor ovarian response, and several reproduction problems in gametes and zygotes, such as aneuploidy and genetic disorders. Finally, we briefly describe which factors are involved in mitochondrial dysfunction and how mitochondrial function can be recovered in reproduction. We hope to provide a new viewpoint regarding factors that can overcome mitochondrial dysfunction in the field of reproductive medicine. [ABSTRACT FROM AUTHOR]

BACKGROUND: Shoulder disability is a common problem following neck dissection. Even if nerve structures are preserved, this may occur after the surgery. OBJECTIVE: The primary aim was to research changes in rotator cuff and scapular muscles strength, and scapular muscle endurance after neck dissection in patients with head and neck cancer. The secondary aim was to investigate the relationship between these changes and postoperative shoulder function. METHODS: This cross-sectional and prospective follow-up study included 14 patients who underwent neck dissection (9 unilateral and 5 bilateral). Evaluations were performed preoperatively and at 3 months postoperatively. Muscle strength measurements, including trapezius, serratus anterior, and rotator cuff muscles, were obtained using a handheld dynamometer. The scapular muscle endurance test was used for muscle endurance assessment. Postoperative shoulder function was evaluated using Constant-Murley shoulder score. RESULTS: A decrease in muscle strength and the scapular muscle endurance test was found at 3 months postoperatively, except for the subscapularis muscle strength (p < 0.05). There were moderate to strong correlations between Constant-Murley shoulder score and percentage changes in muscle strength and the scapular muscle endurance test, except for the upper trapezius muscle strength (p < 0.05). CONCLUSIONS: Muscle strength and scapular muscle endurance may reduce following neck dissection. These reductions are associated with postoperative shoulder function. Thus, muscle strength and endurance training may be beneficial for early postoperative rehabilitation in patients with head and neck cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value of pelvic floor ultrasound parameters in combination for pelvic floor dysfunction (PFD), and to explore the risk factors. Methods: Forty PFD patients treated from April2019to December 2020(case group) and another 40 healthy women (control group) were enrolled. Their clinical data were collected, and both groups received three‐dimensional (3D) ultrasound of the pelvic floor. The diagnostic value of pelvic floor ultrasound parameters for PFD was assessed by receiver operating characteristic (ROC) curves. The risk factors of PFD were evaluated by multivariate logistic regression analysis. Results: The area under the ROC curve (AUC), sensitivity, and specificity of the parameters in combination for predicting PFD were 0.851 [95% confidence interval (CI): 0.743–0.959], 0.901, and 0.812, respectively, indicating acceptable accuracy. Results of logistic regression analysis revealed that spontaneous delivery, lateral episiotomy/laceration, and large bladder neck rotation angle, posterior urethrovesical angle (PUA), bladder neck tilt angle, bladder neck distance (BND), levator hiatus area (LHA) (at anal contraction), R‐LHA and V‐LHA were risk factors for PFD (p < 0.05), while physical exercise was a protective factor (p < 0.05). ROC curve analysis revealed that the AUC, sensitivity, and specificity of the forest map model were 0.822 (95% CI: 0.759–0.885), 0.942, and 0.601, respectively, indicating acceptable accuracy of the model. Internal data validation of the model demonstrated consistence of the predicted occurrence of PFD with the actual one. Conclusions: Spontaneous delivery, lateral episiotomy/laceration, and large bladder neck rotation angle, PUA, bladder neck tilt angle, BND, LHA (at anal contraction), R‐LHA and V‐LHA were risk factors for PFD. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the commonest types of cancer in men worldwide. The primary treatment option for localized prostate cancer is radical prostatectomy. Unfortunately, a considerable proportion of men may experience long‐term post‐surgical sequelae is to determine the effect of nursing interventions on urinary, bowel, and sexual dysfunction among post‐radical prostatectomy patients. A quasi‐experimental (one group, pre‐test–post‐test) research design. We included 30 post‐radical prostatectomy patients in this study. Each patient was interviewed in five sessions. During these sessions, the information about the complications of RP, pelvic floor exercise training and sexual rehabilitation was given. International Consultation on Incontinence Questionnaire‐Urinary Incontinence‐Short Form (ICIQ‐UI‐SF), The Revised Faecal Incontinence Scale (RFIS) and Sexual Health Inventory for Men (SHIM) were used to evaluate the effect of nursing interventions. The study results demonstrate that the incidence of urinary and sexual dysfunction is high among patients post‐radical prostatectomy patients. Fortunately, urinary and sexual dysfunctions were improved post‐implementation of nursing intervention with statistically significant differences (p‐value <0.05). The incidence of faecal incontinence was 16.7% while it was 13.3% post‐nursing implementation with no statistically significant differences. Nursing intervention is effective in the management of urinary incontinence after radical prostatectomy within a short period time while the improvement in sexual dysfunction may need more time. [ABSTRACT FROM AUTHOR]

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Abstract Angiotensin II (AngII) causes endothelial dysfunction. Eucommia ulmoides extract (EUE) is documented to manipulate AngII, but its impact on cardiac microvascular endothelial cell (CMVEC) function remains unknown. This study determines the effects of EUE on AngII-treated CMVECs. CMVECs were treated with different concentrations of AngII or EUE alone and/or the p53 protein activator, WR-1065, before AngII treatment, followed by examinations of the apoptotic, migratory, proliferative, and angiogenic capacities and nitric oxide (NO), p53, von Willebrand factor (vWF), endothelin (ET)-1, endothelial NO synthase (eNOS), manganese superoxide dismutase (MnSOD), hypoxia-inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF) levels. AngII induced CMVEC dysfunction in a concentration-dependent manner. EUE enhanced the proliferative, migratory, and angiogenic capacities and NO, MnSOD, and eNOS levels but repressed apoptosis and vWF and ET-1 levels in AngII-induced dysfunctional CMVECs. Moreover, AngII increased p53 mRNA levels, p-p53 levels in the nucleus, and p53 protein levels in the cytoplasm and diminishes HIF-1α and VEGF levels in CMVECs; however, these effects were counteracted by EUE treatment. Moreover, WR-1065 abrogated the mitigating effects of EUE on AngII-induced CMVEC dysfunction by activating p53 and decreasing HIF-1α and VEGF expression. In conclusion, EUE attenuates AngII-induced CMVEC dysfunction by upregulating HIF-1α and VEGF levels via p53 inactivation.

Long noncoding RNAs (lncRNAs) increase in genomes of complex organisms and represent the largest group of RNA genes transcribed in mammalian cells. Previously considered only transcriptional noise, lncRNAs comprise a heterogeneous class of transcripts that are emerging as critical regulators of T cell-mediated immunity. Here we summarize the lncRNA expression landscape of different T cell subsets and highlight recent advances in the role of lncRNAs in regulating T cell differentiation, function and exhaustion during homeostasis and cancer. We discuss the different molecular mechanisms of lncRNAs and highlight lncRNAs that can serve as novel targets to modulate T cell function or to improve the response to cancer immunotherapies by modulating the immunosuppressive tumor microenvironment.

The current understanding of long COVID (LC) is still limited. This review highlights key findings regarding the role of gut microbiota, mitochondria, and the main pathophysiological aspects of LC revealed by clinical studies, related to the complex interplay between infection, intestinal dysbiosis, dysfunctional mitochondria, and systemic inflammation generated in a vicious circle, reflecting the molecular and cellular processes from the “leaky gut” to the “leaky electron transport chain (ETC)” into a quantum leap. The heterogeneity of LC has hindered progress in deciphering all the pathophysiological mechanisms, and therefore, the approach must be multidisciplinary, with a special focus not only on symptomatic management but also on addressing the underlying health problems of the patients. It is imperative to further assess and validate the effects of COVID-19 and LC on the gut microbiome and their relationship to infections with other viral agents or pathogens. Further studies are needed to better understand LC and expand the interdisciplinary points of view that are required to accurately diagnose and effectively treat this heterogeneous condition. Given the ability of SARS-CoV-2 to induce autoimmunity in susceptible patients, they should be monitored for symptoms of autoimmune disease after contracting the viral infection. One question remains open, namely, whether the various vaccines developed to end the pandemic will also induce autoimmunity. Recent data highlighted in this review have revealed that the persistence of SARS-CoV-2 and dysfunctional mitochondria in organs such as the heart and, to a lesser extent, the kidneys, liver, and lymph nodes, long after the organism has been able to clear the virus from the lungs, could be an explanation for LC.

ObjectiveInterpersonal dysfunction is an important marker of individual differences in personality and well-being. Existing research on interpersonal dysfunction focuses primarily on the problematic behaviors of individuals without considering how sensitivity to others' behavior impacts functioning. In this study, we test the structure and correlates of a model of relationship dysfunction that integrates the problems individuals bring to relationships with their sensitivities to others' behavior. We specifically examine the conjoint structure of interpersonal problems and sensitivities using a circumplex framework and associations between dimensions derived from this structure and personality, well-being, attachment, and response style variables.MethodWe evaluated competing measurement models and examined validity correlations of interpersonal problems and sensitivities in two samples (Study 1: N = 955; 79.2% women; Mage = 19.43; Study 2: N = 1,005; 72.1% women; Mage = 19.77).ResultsSix factors capturing general (nonspecific problems and sensitivities) and stylistic (warmth and dominance for both problems and sensitivities) variation in interpersonal dysfunction were empirically distinguishable and provided incremental information about external criteria.ConclusionsResults support problems and sensitivities as overlapping but distinct sources of information about interpersonal dysfunction, and they specifically suggest an integrative six-factor model with considerable potential for future research.

ObjectiveTo assess whether weakly recognized epitope variants induce anergy in HIV-1-specific CD8 T lymphocyte (CTL) clones as a mechanism of dysfunction.DesignHIV-1-specific CTL clones were exposed to suboptimally recognized epitope variants, and screened for anergy and other T-cell dysfunction markers, and subsequent capability to kill target cells bearing index epitope.MethodsIn addition to the optimally recognized index epitope, two suboptimally recognized epitope variants were selected based on titration curves for killing of peptide-labeled target cells by three HIV-1-specific CTL clones targeting the epitopes SLYNTVATL (Gag 77-85, A02-restricted), RPAEPVPLQL (Rev 66-75, B07-restricted), and KRWIIMGLNK (Gag 263-272, B27-restricted). Consequences of suboptimal stimulation were assessed by cytokine secretion, gene expression, and capacity to kill index epitope-labeled target cells upon rechallenge.ResultsSuboptimal recognition of epitope variants reduced cytokine production by CTL similarly to reduction in killing of target cells. Gene expression profiles after suboptimal stimulation demonstrated no patterns consistent with T-cell dysfunction due to anergy, exhaustion, or apoptosis. Preexposure of CTL to epitope variants had no discernable impact on their subsequent capacity to kill index epitope-bearing target cells.ConclusionOur data explore the hypothesis that poorly recognized epitope variants not only facilitate HIV-1 evasion of CTL recognition, but also induce CTL dysfunction through suboptimal signaling causing anergy. However, the results do not suggest that suboptimal signaling induces anergy (or exhaustion or apoptosis), indicating that the major role of CTL epitope variation is likely viral escape.

BackgroundKidney delayed graft function (kDGF) remains a challenging problem following simultaneous liver and kidney transplantation (SLKT) with a reported incidence up to 40%. Given the scarcity of renal allografts, it is crucial to minimize the development of kDGF among SLKT recipients to improve patient and graft outcomes. We sought to assess the role of preoperative recipient and donor/graft factors on developing kDGF among recipients of SLKT.MethodsA retrospective review of 194 patients who received SLKT in the period from January 2004 to March 2017 in a single center was performed to assess the effect of preoperative factors on the development of kDGF.ResultsKidney delayed graft function was observed in 95 patients (49%). Multivariate analysis revealed that donor history of hypertension, cold static preservation of kidney grafts [versus using hypothermic pulsatile machine perfusion (HPMP)], donor final creatinine, physiologic MELD, and duration of delay of kidney transplantation after liver transplantation were significant independent predictors for kDGF. kDGF is associated with worse graft function and patient and graft survival.ConclusionsKidney delayed graft function has detrimental effects on graft function and graft survival. Understanding the risks and combining careful perioperative patient management, proper recipient selection and donor matching, and graft preservation using HPMP would decrease kDGF among SLKT recipients.

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 μmol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 μmol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P

Aim: to provide a literature review of the current data on various pathomechanisms of left ventricular (LV) remodeling in heart failure (HF) patients and their role in the development and progression of myocardial dysfunction. This paper is a first part of the review, devoted to the current state of pathophysiology of LV remodeling in HF. Material and methods. The thematic scientific papers, published during the last decade, constituted the study material. The research methodology involved bibliosemantic method and structural and logical analysis. Results and discussion. LV remodeling is the result of complex changes at the molecular, cellular and tissue levels, affecting the myocardial mass, geometry and performance, and ultimately leading to HF development and progression. LV systolic dysfunction occurs through the numerous mechanisms, including the defects in sarcomere function, abnormal excitation-contraction coupling and calcium homeostasis, ion channel dysfunction, mitochondrial and metabolic abnormalities, depressed cardiomyocytes survival signaling, redox pathobiology, inflammation and inadequate vasculogenesis. The term «LV diastolic dysfunction» covers the alterations in diastolic distensibility, filling or relaxation of the LV, regardless of whether LV (global) systolic function is normal or abnormal, and regardless of whether the patient has clinical manifestations of HF. The up-to-date pathophysiological paradigm of the development and progression of HF with LV diastolic dysfunction and preserved LV (global) systolic function considers systemic inflammation as a key pathomechanism of structural and functional changes of the myocardium, promoted by various cardiovascular and extracardiac conditions. In its turn, the systemic inflammation promotes endothelial dysfunction, contributing to multiple end-organ damage. Conclusion. The deepening one`s knowledge of various pathomechanisms of LV remodeling and related myocardial dysfunction in HF patients is an important prerequisite for identifying new perspectives on further fundamental research аnd more rational designing of future clinical trials.

Abstract Background Diaphragm fiber atrophy has been evidenced after short periods of mechanical ventilation (MV) and related to critical illness-associated diaphragm weakness. Atrophy is described as a decrease in diaphragm fiber cross-sectional area (CSA) in human diaphragm biopsy, but human samples are still difficult to obtain in clinics. In recent years, ultrasound has become a useful tool in intensive care to evaluate diaphragm anatomy. The present study aimed to evaluate the ability of diaphragm expiratory thickness (Tdi) measured by ultrasound to predict diaphragm atrophy, defined by a decrease in diaphragm fiber CSA obtained through diaphragm biopsy (the gold standard technique) in ventilated patients. Methods Diaphragm biopsies and diaphragm ultrasound were performed in ventilated donors and in control subjects. Demographic variables, comorbidities, severity on admission, treatment, laboratory test results and evolution variables were evaluated. Immunohistochemical analysis to determine CSA and ultrasound measurements of Tdi at end-expiration were performed, and median values of the control group were used as thresholds to determine agreement between them in further analysis. Sensitivity, specificity, and positive and negative predictive values of an ultrasound Tdi cutoff for detecting histologic atrophy were calculated. Agreement between two ultrasound observers was also assessed. Results Thirty-five ventilated organ donors and 5 ventilated controls were included, without differences in basic characteristics. CSA and Tdi were lower in donors than in controls. All donors presented lower CSA, but only 74% lower Tdi regarding control group thresholds. The cut-off value for lower diaphragm expiratory thickness (Tdi

Widespread use of fungicides in various spheres of human life leads to negative consequences for both humans and the environment. The article presents the results of a study of the acute effect of systemic fungicides of the chemical class triazoles on the content of macro- and microelements in kidney and liver rat tissues. The content of chemical elements was determined by inductively coupled plasma atomic emission spectrometry. The established changes in the content of macro- and microelements in the rat liver and kidney indicate tissue specificity of the fungicidal action. Under the influence of fungicide containing tebuconazole in amount of 250 g/dm3 or combined fungicide containing (tebuconazole, 125 g/dm3 + triadimefon, 100 g/dm3) the content of Potassium (K), Calcium (Ca), Chromium (Cr), Iron (Fe), Copper (Cu) and Zinc (Zn) increased sugnificantly (P

Acute peritonitis (AP) is among the most frequent and severe conditions in pediatric abdominal surgery. Due to development of antibiotic resistance and increasing number of atypical infectious and inflammatory diseases (IIDs), a lot of specialists suggest combined treatments for these patients which should include not only surgical and etiotropic approaches, as well as therapy aimed at correction of functional defects of immunity. Neutrophilic granulocytes (NGs) reepresent a unique population of cells of primary anti-infectious immune response. Functional NG defects in pediatric AP play a leading role in development, prevalence, severity of peritoneal inflammation, and response to the therapy. Special role is given to functionally significant NG subsets responsible for triggering and implementation of phagocytosis and microbicidal properties of NG in purulent lesions and inflammatory process in children. There is an urgent need for development of new approaches to targeted immunomodulatory therapy in order to correct the NG dysfunction. The aim of the present study was to arrange the programs of immunomodulatory therapy after surgical treatment of immunocompromised children with various forms of acute peritonitis followed by subsequent evaluation of its clinical and immunological efficacy. The study included 12 immunocompromised children aged 5-12 years with different clinical course of acute peritonitis. The study group 1 included patients with local nonrestricted AP; study group 2 involved children with diffuse AP. The comparison groups consisted of 6 children who received standard therapy, i.e., clinical comparison groups 1 and 2, matched for sex, age and diagnosis. A control group consisted of 18 conditionally healthy children at similar age. Clinical examination included collection of the patient’s history, complaints, objective examination and clinical course assessment of the underlying disease. Immunological study included determination of receptor, phagocytic and microbicidal activity of NCs; assessment of NC subpopulations by their numbers and phenotype using flow cytometry, i.e., the cells co-expressing CD64, CD16, CD32, CD11b, with testing density of these membrane receptors by the MFI approach. Targeted immunomodulatory therapy programs were applied for treatment of children with unrestricted local and diffuse AP, taking into account clinical features of AP, as well as changes in number and phenotype of NC subpopulations, and impairment of their effector function. The standards of postsurgical treatment in the children with various forms of AP included different courses of treatment with Imunofan (Hexapeptide – arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine; HP) using different schedules and duration. We have shown high clinical and immunological efficiency of these therapeutic programs. Thus, reversal of adequate NG functioning was observed, including positive rearrangements of negatively transformed functional NG subpopulations. In this respect, a positive clinical effect was noted in children with atypical AP with various clinical courses, i.e., absence of postsurgical complications, rapid regression of intoxication signs, normalization of body temperature, reduced volume of antibiotic therapy and shorter hospitalization terms.

As a common pollutant in the water environment, microcystin leucine arginine (MC-LR) can enter semen and damage the sperm in animals. However, the mechanism by which MC-LR damages human sperm is unclear. Therefore, human sperm samples were obtained from the Henan Provincial Sperm Bank and exposed to different concentrations (0, 1, 10, and 100 μg/L) of MC-LR for 1, 2, 4, and 6 h, to invegest the effects and potential mechanism of MC-LR on sperm. The results showed that MC-LR mainly accumulated in the neck and flagellum of human sperm. Compared to the control group, the sperm capacitation rate and motility were significantly decreased in the 100 μg/L group. After exposure of 100 μg/L of MC-LR, the central microtubule and microtubule doublet of sperm flagellum were blurred, asymmetrical, or even lost. Furthermore, the expression levels of flagellin DNAH17, SPEF2, SPAG16, SPAG6, and CFAP44 in human sperm were reduced. Also, the phosphorylation levels of CaMKKβ and AMPK can be inhibited by MC-LR. These findings revealed that MC-LR can induce functional and structural damage in human sperm, and the Ca2+/CaMKKβ/AMPK pathway may be involved in this process. This study will provide a basis for prevention and treatment of male fertility declines caused by MC-LR.

BackgroundChronic rhinosinusitis (CRS) is a clinical syndrome primarily characterized by long-term mucosal inflammation of the nasal cavity and sinuses. The pathogenesis of CRS is still unclear due to its high heterogeneity. A number of studies have recently focused on the sinonasal epithelium. Thus, there has been a quantum leap in awareness of the role of the sinonasal epithelium, which is now understood as an active functional organ rather than simply an inert mechanical barrier. Undoubtedly, epithelial dysfunction plays a vital role in the onset and development of CRS.ObjectiveIn this article, we discuss the potential contribution of sinonasal epithelium dysfunction to CRS pathogenesis and explore a few current and developing therapeutic options targeting the sinonasal epithelium.ResultsImpaired mucociliary clearance (MCC) and an abnormal sinonasal epithelial barrier are usually considered to be the main causative factors in CRS. Epithelial-derived bioactive substances, such as cytokines, exosomes, and complements, play a vital role in the regulation of innate and adaptive immunity and contribute to the pathophysiological alterations of CRS. The phenomena of epithelial–mesenchymal transition (EMT), mucosal remodeling, and autophagy observed in CRS offer some novel insights into the pathogenesis of this disease. In addition, existing treatment options targeting disorder of sinonasal epithelium can help to relieve the main symptoms associated with CRS to some extent.ConclusionThe presence of a normal epithelium is fundamental for maintaining homeostasis in the nasal and paranasal sinuses. Here, we describe various aspects of the sinonasal epithelium and highlight the contributions of epithelial dysfunction to CRS pathogenesis. Our review provides sound evidence of the need for in-depth study of the pathophysiological alterations of this disease and for the development of novel epithelium-targeting alternative treatments.

The synapse has consistently been considered a vulnerable and critical target within Alzheimer’s disease, and synapse loss is, to date, one of the main biological correlates of cognitive decline within Alzheimer’s disease. This occurs prior to neuronal loss with ample evidence that synaptic dysfunction precedes this, in support of the idea that synaptic failure is a crucial stage within disease pathogenesis. The two main pathological hallmarks of Alzheimer’s disease, abnormal aggregates of amyloid or tau proteins, have had demonstrable effects on synaptic physiology in animal and cellular models of Alzheimer’s disease. There is also growing evidence that these two proteins may have a synergistic effect on neurophysiological dysfunction. Here, we review some of the main findings of synaptic alterations in Alzheimer’s disease, and what we know from Alzheimer’s disease animal and cellular models. First, we briefly summarize some of the human evidence to suggest that synapses are altered, including how this relates to network activity. Subsequently, animal and cellular models of Alzheimer’s disease are considered, highlighting mouse models of amyloid and tau pathology and the role these proteins may play in synaptic dysfunction, either in isolation or examining how the two pathologies may interact in dysfunction. This specifically focuses on neurophysiological function and dysfunction observed within these animal models, typically measured using electrophysiology or calcium imaging. Following synaptic dysfunction and loss, it would be impossible to imagine that this would not alter oscillatory activity within the brain. Therefore, this review also discusses how this may underpin some of the aberrant oscillatory patterns seen in animal models of Alzheimer’s disease and human patients. Finally, an overview of some key directions and considerations in the field of synaptic dysfunction in Alzheimer’s disease is covered. This includes current therapeutics that are targeted specifically at synaptic dysfunction, but also methods that modulate activity to rescue aberrant oscillatory patterns. Other important future avenues of note in this field include the role of non-neuronal cell types such as astrocytes and microglia, and mechanisms of dysfunction independent of amyloid and tau in Alzheimer’s disease. The synapse will certainly continue to be an important target within Alzheimer’s disease for the foreseeable future.

Simple Summary: Hemato-poietic stem cell transplantation is associated with significant endothelial dysfunction, which may result in severe complications. Endothelial dysfunction induces the expression of multiple substances including, cell adhesion molecules, pro-inflammatory cytokines, and coagulation factors resulting in activation of the complement system, and promoting a procoagulant and proinflammatory state. The pathophysiological process that mediates the endothelial damage is not clearly understood and the aim of this study is a comprehensive review of the existing knowledge. Moreover, the levels of soluble molecules released in the systemic circulation as a result of endothelial damage may serve as biomarkers for the early diagnosis and the pre-emptive treatment of post-transplant syndromes. The review of the existing literature presented in detail shows that the ideal biomarker with sufficient sensitivity and specificity for the early diagnosis of post-transplant complications does not currently exist. Future studies should focus on the identification of novel biomarkers with sufficient specificity and sensitivity. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only therapy with a curative potential for a variety of malignant and non-malignant diseases. The major limitation of the procedure is the significant morbidity and mortality mainly associated with the development of graft versus host disease (GVHD) as well as with a series of complications related to endothelial injury, such as sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), transplant-associated thrombotic microangiopathy (TA-TMA), etc. Endothelial cells (ECs) are key players in the maintenance of vascular homeostasis and during allo-HSCT are confronted by multiple challenges, such as the toxicity from conditioning, the administration of calcineurin inhibitors, the immunosuppression associated infections, and the donor alloreactivity against host tissues. The early diagnosis of endothelial dysfunction syndromes is of paramount importance for the development of effective prophylactic and therapeutic strategies. There is an urgent need for the better understanding of the pathogenetic mechanisms as well as for the identification of novel biomarkers for the early diagnosis of endothelial damage. This review summarizes the current knowledge on the biology of the endothelial dysfunction syndromes after allo-HSCT, along with the respective therapeutic approaches, and discusses the strengths and weaknesses of possible biomarkers of endothelial damage and dysfunction. [ABSTRACT FROM AUTHOR]

Background: The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) are used worldwide in adults. Until now, no adaptation for use in children has been proposed. Objective: The aim of this study was to present comprehensive and short‐form adaptations of Axis I and Axis II of the DC/TMD for adults that are appropriate for use with children in clinical and research settings. Methods: Global Delphi studies with experts in TMDs and in pain psychology identified ways of adapting the DC/TMD for children. Results: The proposed adaptation is suitable for children aged 6–9 years. Proposed changes in Axis I include (i) adapting the language of the Demographics and the Symptom Questionnaires to be developmentally appropriate for children, (ii) adding a general health questionnaire for children and one for their parents, (iii) replacing the TMD Pain Screener with the 3Q/TMD questionnaire and (iv) modifying the clinical examination protocol. Proposed changes in Axis II include (i) for the Graded Chronic Pain Scale, to be developmentally appropriate for children, (ii) adding anxiety and depression assessments that have been validated in children and (iii) adding three constructs (stress, catastrophising and sleep disorders) to assess psychosocial functioning in children. Conclusion: The recommended DC/TMD, including Axis I and Axis II, for children aged 6–9 years, is appropriate for use in clinical and research settings. This adapted the first version for children includes changes in Axis I and Axis II changes requiring reliability and validity testing in international settings. Official translations to different languages according to INfORM requirements will enable a worldwide dissemination and implementation. [ABSTRACT FROM AUTHOR]

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

When a girl experiences her first period, she starts a new phase of her life and becomes biologically capable of becoming a mother and giving birth to a child. Girls' hypothalamus-pituitary-ovary axis reaches "axial maturity" during puberty, when they are between the ages of 8 and 13 years old. Secondary biological features, including as growth, body-shape changes in females, breast growth, hair growth on the vulva, and hair growth on the axillary pits, are often observed during this era. The first menstruation, or menarche, is also commonly observed during this time. During the menstrual cycle, a woman's ability to conceive and give birth is at the core of her reproductive life. [ABSTRACT FROM AUTHOR]

Prenatal cardiac remodeling refers to in utero changes in the fetal heart that occur as a response to an adverse intrauterine environment. In this article, we will review the main mechanisms leading to cardiac remodeling and dysfunction, summarizing and describing the major pathological conditions that have been reported to be related to this in utero plastic adaptive process. We will also recap the current evidence regarding the persistence of fetal cardiac remodeling and dysfunction, both in infancy and later in adult life. Moreover, we will discuss primary, secondary, and tertiary preventive measures and future clinical and research aspects. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to elucidate the relationship between premature ventricular complexes (PVCs) and right ventricular (RV) dysfunction, and the effects of radiofrequency catheter ablation (RFCA) on RV function. Methods: A total of 110 patients (age, 50.8 ± 14.4 years; 30 men) without structural heart disease who had undergone RFCA for RV outflow tract (RVOT) PVCs were retrospectively included. RV function was assessed using fractional area change (FAC) and global longitudinal strain (GLS) before and after RFCA. Clinical data were compared between the RV dysfunction (n = 63) and preserved RV function (n = 47) groups. The relationship between PVC burden and RV function was analyzed. Change in RV function before and after RFCA was compared between patients with successful and failed RFCA. Results: PVC burden was significantly higher in the RV dysfunction group than in the preserved RV function group (p <.001). FAC and GLS were significantly worse in proportion to PVC burden (p <.001 and p <.001, respectively). The risk factor associated with RV dysfunction was PVC burden [odds ratio (95% confidence interval), 1.092 (1.052–1.134); p <.001]. Improvement in FAC (13.0 ± 8.7% and –2.5 ± 5.6%, respectively; p <.001) and GLS (–6.8 ± 5.7% and 2.1 ± 4.2%, respectively; p <.001) was significant in the patients with successful RFCA, compared to the patients in whom RFCA failed. Conclusions: Frequent RVOT PVCs are associated with RV dysfunction. RV dysfunction is reversible by successful RFCA. [ABSTRACT FROM AUTHOR]

Background: The DSM-5 introduced an alternative model of personality disorder (AMPD) that includes personality dysfunction plus maladaptive-range traits. This study clarifies relations of depression diagnoses and symptoms with AMPD personality pathology.Method: Two samples (Ns 402 and 601) of outpatients and community-dwelling adults completed four depression (criteria met for major depressive disorder and dysthymia; dysphoria and low well-being scales), ten trait (two scales for each of five domains-negative affectivity, detachment, disinhibition, antagonism, psychoticism), and eight dysfunction (four scales for each of two domains-self- and interpersonal pathology) measures. Diagnoses were made using a semi-structured interview; other measures were self-reports. We quantified cross-sectional relations between depression and personality pathology with correlation and multiple regression analyses.Results: Collectively (median R2; ps < 0.0001), the trait (0.46) and dysfunction (0.50) scales predicted the depression measures strongly, with most predictive power shared (0.41) between traits and dysfunction. However, trait and dysfunction scales altogether predicted depression (median R2 = 0.54) more strongly than either domain alone, ps < 0.0001. Participants with depression diagnoses showed elevations on all nonadaptive trait and personality dysfunction measures, particularly negative temperament/affectivity and self-pathology measures.Limitations: Generalization of findings to other populations (e.g., adolescents), settings (e.g., primary care), and measures (e.g., traditional personality disorder diagnoses) is uncertain. Cross-sectional analyses did not test changes over time or establish causality.Conclusions: The AMPD is highly relevant to depression. Assessment of personality pathology, including both personality dysfunction and maladaptive-range traits, stands to advance understanding of depression in adults. [ABSTRACT FROM AUTHOR]

Copyright of Homo et Societas is the property of Jagiellonian University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Online Turkish Journal of Health Sciences (OTJHS) / Online Türk Sağlık Bilimleri Dergisi is the property of Oguz KARABAY and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Analysis of digestive system (DS) disorders in cosmonauts, participants in 83 missions on the Mir orbital station and ISS, showed that episodic DS problems were successfully cured with the help of onboard medications. A comparative assessment of space flight (SF) adversities and digestive disease risk factors resulted in drawing up a list of predictable digestive diseases that includes gastroesophageal reflux disease, irritable bowel syndrome, and functional dyspesia. Following the ensuing recommendations, the onboard medical kits have been modernized to include proton pump inhibitors, H2-histamine receptor antagonists, prokinetics of new classes, antibacterials, ursodesocholic acid preparations, and agents for the relief of symptoms of intestinal dysbacteriosis. A broad use of prefilled syringes is advisable. [ABSTRACT FROM AUTHOR]

Constipation afflicts many patients with Parkinson's disease (PD) and significantly impacts on patient quality of life. PD-related constipation is caused by intestinal dysfunction, but the etiology of this dysfunction in patients is unknown. One possible cause is neuron loss within the enteric nervous system (ENS) of the intestine. This review aims to 1) Critically evaluate the evidence for and against intestinal enteric neuron loss in PD patients, 2) Justify why PD-related constipation must be objectively measured, 3) Explore the potential link between loss of enteric neurons in the intestine and constipation in PD, 4) Provide potential explanations for disparities in the literature, and 5) Outline data and study design considerations to improve future research. Before the connection between intestinal enteric neuron loss and PD-related constipation can be confidently described, future research must use sufficiently large samples representative of the patient population (majority diagnosed with idiopathic PD for at least 5 years), implement a consistent neuronal quantification method and study design, including standardized patient recruitment criteria, objectively quantify intestinal dysfunctions, publish with a high degree of data transparency and account for potential PD heterogeneity. Further investigation into other potential influencers of PD-related constipation is also required, including changes in the function, connectivity, mitochondria and/or α-synuclein proteins of enteric neurons and their extrinsic innervation. The connection between enteric neuron loss and other PD-related gastrointestinal (GI) issues, including gastroparesis and dysphagia, as well as changes in nutrient absorption and the microbiome, should be explored in future research. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a common degenerative brain disorder of aging people which shares many clinical and pathological features with canine cognitive dysfunction (CCD). CCD is considered a naturally occurring model of human AD. Transcranial photobiomodulation (tPBMT) therapy, also known as transcranial laser therapy, entails delivering photons of near infrared to infrared light from the skin surface of the scalp to the underlying brain. Specific molecular cellular receptors, called chromophores, absorb this energy, and use it to initiate biological reactions with potential therapeutic benefit. Improvement in cognitive ability using tPBMT has been documented in rodent AD models and human clinical trials. The purposes of this review are to provide an overview of the suspected molecular mechanisms of action of tPBMT for treatment of cognitive decline and to propose potential application of this treatment modality for dogs affected by CCD.

Abstract Background In order to evaluate right ventricular (RV) systolic and diastolic dysfunctions in patients with type 2 diabetes mellitus (T2DM) with poor glycemic control by layer specific global longitudinal strain (GLS) and strain rate (GLSr). Methods 68 T2DM patients and 66 normal controls were enrolled for the present study. RV layer specific GLS (GLSEpi, GLSMid and GLSEndo represent the epimyocardial, middle layer and endomyocardial strains, respectively) and GLSr (GLSr-S, GLSr-E and GLSr-A represent the systole, early-diastole and late-diastole strain rate) were calculated by averaging each of the three regional peak systolic strains and strain rates along the entire RV free-wall (RVFW), entire RV free-wall and septal wall (RVFSW) on RV-focused view. Results The absolute values of RV layer specific GLS (GLSEpi, GLSMid and GLSEndo) in RVFW in T2DM patients were significantly lower than normal controls (P

The study forms a theoretical-methodological approach in management reduced to institutional adjustments taken as a tool for affecting economic objects in order to ensure their proper functioning. Institutional adjustments refers to targeted changes in regulations carried out by the subject of management in numerous alternative ways. The general focus of institutional adjustments can be limited to ensuring institutional well-being as one of the crucial functions of economic development, which is considered within achieving the greatest efficiency and the least functional disorder of institutions. The paper aims to extend the theoretical level of analysis by including institutional adjustments as a means of management in the set of methods for regulating the economy. The theory of economic policy and institutional theory applicable at the macro and other levels of management constitute the research methodology. The methods of comparative and taxonomic analysis, formal mathematical generalizations and functional analysis were used. The author develops a typology of institutional adjustments and reveals their substance according to the most important parameters of their identification. We also identify the models of functioning of the management object (institution) and describe the relevant modes of institutional adjustments, which links management impulses with the object’s state and its development objectives. Within the “efficiency – dysfunction” coordinates system, the characteristics of institutional adjustments are found. The study concludes that it is necessary to ensure institutional well-being that provides for the greatest efficiency of the institutions operating and the least disruption of their functions. The paper presents a formal condition of solving this task and positions it as an additional criterion in the contemporary theory of economic policy.

Despite recent advances in cancer therapy, anthracycline-based combination therapy remains the standardized first-line strategy and has been found to have effective antitumor actions. Anthracyclines are extremely cardiotoxic, which limits the use of these powerful chemotherapeutic agents. Although numerous studies have been conducted on the cardiotoxicity of anthracyclines, the precise mechanisms by which doxorubicin causes cardiomyocyte death and myocardial dysfunction remain incompletely understood. This review highlights recent updates in mechanisms and therapies involved in doxorubicin-induced cardiomyocyte death, including autophagy, ferroptosis, necroptosis, pyroptosis, and apoptosis, as well as mechanisms of cardiovascular dysfunction resulting in myocardial atrophy, defects in calcium handling, thrombosis, and cell senescence. We sought to uncover potential therapeutic approaches to manage anthracycline cardiotoxicity via manipulation of crucial targets involved in doxorubicin-induced cardiomyocyte death and dysfunction.

Background: In addition to intrahepatic angiogenesis, patients with cholestasis cirrhosis develop extrahepatic vasculature disorders and functional disturbances of multiple organ systems. Without effective intervention, these vascular disorders will eventually turn into multiple organs vascular syndromes, including the brain, lung and other organ systems. However, studies on the pathogenesis of vascular alterations among extrahepatic organ disturbances are still carried out separately, which hampered the successful translation of preclinical studies to the human setting and required further mechanistic insight into these complications. This study aims to investigate the relationship between extrahepatic angiogenesis and multiple organ impairment, and whether the vascular endothelial growth factor (VEGF) family members and their receptors are involved in this process. Methods: Pathological changes of the multiple organs were determined by histopathological and immunohistochemical staining in the established common bile duct ligation (CBDL) rats, and angiogenesis was estimated by microvessel density (MVD). Levels of the VEGF family members and their receptors in the serum and organ tissues were also measured by using enzyme-linked immunosorbent assays. Results: The MVD and VEGF family members and their receptors were significantly increased in CBDL rats with multiple organ injury, especially in the liver, lung and cerebral cortex. Meanwhile, we noticed moderate elevation of soluble receptor of the vascular endothelial growth factor-1 (sFlt-1) in the liver, lung, and cerebral cortex, whereas the levels of placental growth factor (PLGF) increased significantly. Conclusions: Extrahepatic angiogenesis may represent a common pathophysiological basis for multiple organ dysfunction and the sFlt-1/PLGF ratio could offer an avenue for further studies to target extrahepatic angiogenesis in cholestatic cirrhosis.

High-frequency spinal cord stimulation (HF-SCS) has been established as an effective therapy for neuropathic pain. However, the analgesic mechanisms involved in HF-SCS remain to be clarified. In our study, adult rat neuropathic pain was induced by spinal nerve ligation. Two days after modeling, the rats were subjected to 4 hours of HF-SCS (motor threshold 50%, frequency 10,000 Hz, and pulse width 0.024 ms) in the dorsal horn of the spinal cord. The results revealed that the tactile allodynia of spinal nerve-injured rats was markedly alleviated by HF-SCS, and the effects were sustained for 3 hours after the stimulation had ceased. HF-SCS restored lysosomal function, increased the levels of lysosome-associated membrane protein 2 (LAMP2) and the mature form of cathepsin D (matu-CTSD), and alleviated the abnormally elevated levels of microtubule-associated protein 1A/B-light chain 3 (LC3)-II and sequestosome 1 (P62) in spinal nerve-injured rats. HF-SCS also mostly restored the immunoreactivity of LAMP2, which was localized in neurons in the superficial layers of the spinal dorsal horn in spinal nerve-injured rats. In addition, intraperitoneal administration of 15 mg/kg chloroquine for 60 minutes reversed the expression of the aforementioned proteins and shortened the timing of the analgesic effects of HF-SCS. These findings suggest that HF-SCS may exhibit long-lasting analgesic effects on neuropathic pain in rats through improving lysosomal dysfunction and alleviating autophagic flux. This study was approved by the Laboratory Animal Ethics Committee of China Medical University, Shenyang, China (approval No. 2017PS196K) on March 1, 2017.

Yuqiong Lin,1 Ying Xu,1 Xin Zheng,1 Jingwen Zhang,1 Junfeng Liu,1 Guotu Wu2 1Department of Basic Medical Science, Fujian Health College, Fuzhou, 350101, Fujian Province, People’s Republic of China; 2Department of Basic Medical Science, Fujian Medical University, Fuzhou, 350101, Fujian Province, People’s Republic of ChinaCorrespondence: Yuqiong LinDepartment of Basic Medical Science, Fujian Health College, No. 366 Jingxi Town, Fuzhou, 350101, Fujian Province, People’s Republic of ChinaEmail yuqiong90@sina.comBackground: Absolute or relative lack of insulin secretion caused by pancreatic β-cell dysfunction can lead to diabetes. Astragaloside IV (AS-IV), the main components of the traditional Chinese medicine Astragalus, has anti-oxidant, anti-inflammatory and anti-apoptotic properties, and exerts anti-diabetic pharmacological effects.Purpose: To explore whether AS-IV can protect the apoptosis and dysfunction of pancreatic β-cells induced by streptozotocin (STZ) and its underlying molecular mechanism.Methods: STZ-induced pancreatic β-cell line INS-1 was treated with different concentrations of AS-IV, then cell viability, apoptosis, oxidative stress and insulin secretion was assessed by CCK-8, TUNEL staining, Western blot, commercial kits and qRT-PCR, respectively. The expression of proteins involved in Sirtuin 1 (SIRT1)/p53 and Akt/glycogen synthase kinase-3 β (GSK3β)/nuclear factor E2-related factor 2 (Nrf2) signaling was measured by Western blot assay. Besides, Akt inhibitor MK-2206 and SIRT1 inhibitor EX-527 were used to co-treat STZ-induced INS-1 cells in the presence of AS-IV, and the above experiments were repeated.Results: AS-IV increased the cell viability of INS-1 cells induced by STZ. AS-IV also reduced the increase in apoptosis rate and reversed STZ-induced down-regulation of Bcl-2 and up-regulation of Bax and Cleaved caspase 3. In addition, AS-IV significantly reduced STZ-induced malondialdehyde upregulation and reduced superoxide dismutase and glutathione peroxidase levels. Furthermore, the use of AS-IV was found to increase the insulin secretion capacity of INS-1 cells with impaired function, along with the increase of the mRNA levels of insulin 1 and insulin 2. Mechanism studies further showed that MK-2206 and EX-527 reversed the protective effect of AS-IV against STZ-induced injury on INS-1 cells.Conclusion: AS-IV exerted cytoprotective effect on STZ-induced INS-1 cells through regulating SIRT1/p53 and Akt/GSK3β/Nrf2 signaling pathways. These findings are expected to provide new supplements to the molecular mechanism of AS-IV in the treatment of diabetes.Keywords: astragaloside IV, pancreatic β-cell, apoptosis, dysfunction, SIRT1/p53, Akt/GSK3β/Nrf2

Arthroscopic interventions are widely used to treat the consequences of the meniscus and anterior cruciate ligament (ACL) injuries. However, the long-term consequences of these surgeries are not always favorable and not in all cases allow to avoid the development of chronic pain and posttraumatic osteoarthritis.Objective: to evaluate the incidence of persistent postoperative pain and the persistence of functional disorders in patients undergoing arthroscopic interventions on the menisci and ACL.Material and methods. The study group consisted of 147 patients (60 women and 87 men, mean age 38.8±12.5 years) who underwent arthroscopic surgery on the knee joint (KJ) in the traumatology and orthopedic department of V.A. Nasonova Research Institute of Rheumatology in 2018– 2021. The condition of patients was assessed by telephone survey and/or online questionnaire. The pain and fatigue levels were assessed on numerical rating scale (NRS, 0–10), as well as the severity of functional disorders on the Lysholm scale (LS).Results and discussion. Moderate or intense knee pain and increased fatigue (≥4 according to NRS) were noted in 11.3% and 14.7% of respondents, respectively. The state of the KJ according to LS in 35.3% of patients was assessed as excellent (95–100 points), in 29.3% – as good (84–94 points), in 21.3% – as satisfactory (65–83 points) and 14.0% – as unsatisfactory (≤64 points).Conclusion. More than 10% of patients after arthroscopic operations on the knee joint experience moderate or severe pain and fatigue, satisfactory and unsatisfactory functional results are observed in 35.4% of cases.