Normal Function Research Articles

Associations between Sensitivity to Thyroid Hormones and Visceral Adiposity in Euthyroid Adults

Abstract Objectives The study aimed to explore the association between thyroid hormone (TH) sensitivity and obesity assessed by body mass index (BMI) and visceral adiposity index (VAI) in euthyroid adults. Methods This cross-sectional study used the thyroid feedback quantile-based index (TFQI), thyroid stimulating hormone index (TSHI), and thyrotrophic T4 resistance index (TT4RI) to indicate central TH sensitivity, and VAI to assess visceral obesity. Participants were categorized according to tertiles. We used logistic and linear regressions to explore the association stratified by sex. Results The study enrolled 5411 men and 5749 women with normal thyroid function. Men with the highest tertile of TT4RI had 1 kg/m2 higher BMI compared with men with the lowest tertile of TT4RI (P=0.001) after adjustment for age, hypertension, hyperlipidemia, diabetes, hyperuricemia, and renal function. There was no significant difference in BMI across tertiles of TFQI and TSHI in men, and TFQI, TSHI, and TT4RI in women after adjustment for other risk factors. TH sensitivity indices were positively related to VAI after adjustment for confounders in women but not in men. There were 1.21 (95%CI:1.02-1.44, P=0.03), 1.43 (95%CI: 1.20-1.70, P<0.001), and 1.47 (95%CI: 1.23 - 1.75, P<0.001) times higher odds of having high VAI among women in the highest TFQI, TSHI, and TT4RI tertiles respectively, compared to women in the lowest tertile. Conclusions Reduced central TH sensitivity was associated with increased visceral adiposity in women but not men. Our findings supplemented the evidence of the importance of TH sensitivity to metabolic disorders, especially among women.

Proposed Mechanisms of Cell Therapy for Alzheimer’s Disease

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches. The findings provide valuable insights into the applications of stem cell-based therapies and include the use of neural, glial, mesenchymal, embryonic, and induced pluripotent stem cells. We cover current studies on stem cell replacement therapy where cells can functionally integrate into neural networks, replace damaged neurons, and strengthen impaired synaptic circuits in the brain. We address the paracrine action of stem cells acting via secreted factors to induce neuroregeneration and modify inflammatory responses. We focus on the neuroprotective functions of exosomes as well as their neurogenic and synaptogenic effects. We look into the shuttling of mitochondria through tunneling nanotubes that enables the transfer of healthy mitochondria by restoring the normal functioning of damaged cells, improving their metabolism, and reducing the level of apoptosis.

ВПЛИВ ЕМОЦІЙНОГО СТАВЛЕННЯ В СІМ’Ї НА АДАПТИВНІ ВЗАЄМОСТОСУНКИ БАТЬКІВ ТА ДІТЕЙ СТАРШОГО ШКІЛЬНОГО ВІКУ

In the article we showed, that the family, as a small group, created for its members such conditions for emotional manifestations and satisfaction of emotional needs that enable a person to feel that he belonged to society. The family differs from other small groups in the diversity, depth and duration of the ties that unite its members. It is these characteristics of the family that make it indispensable in raising the younger generation, since they provide a long-lasting, deeply emotional and multifaceted influence on the formation of the child’s personality. We justified, that the child’s experience of his/her place in the family, the child’s interaction with the family as a whole and with its individual members was associated with the interpersonal relationships that existed in it. We proved, that the analysis of the “family-child” relationships was expressed by us in the assessment of the following orientations: interpersonal aspects of family interaction and the characteristics of communication of its members; the importance of personal criteria (motives, needs, self-awareness); attitudes, relationships of family members. Living in a family, a child accumulates a lot of experience in interpersonal relationships. Correctly or distortedly, he perceives how his parents treat him/her, as they avoid him/her, are dissatisfied with the child, recognize his/her autonomy, or infringe on him/her, how kindly they treat the child. Over time, children realize how loved and significant they are to their parents. Our researches show that a child’s body and his/her psyche feel a constant need for positive emotional support from parents. The nature of emotions greatly affects the child’s health, determines his/her vitality, attitudes to the world around a child. The influence of positive emotions reduces the child’s excitement, ensures the normal functioning of his/her body’s functional systems. It has been proven that under the conditions of long-term exposure to a traumatic nature, negative emotions inevitably are arisen in a child. This fact complicates the course of the child’s mental development: it makes it difficult to establish adaptive interpersonal relationships with others, prevents him/her from mastering new adaptive social roles, the development of communication skills and possibilities of interpersonal interaction. Adaptive family relationships between the family and the child’s side can shape the child’s positive outlook on the world and on himself/herself. However, these same officials, but with other psychological changes, can facilitate low self-esteem of children, distrust of others. In such a way, the emotional situation in the family directly flows into the adaptive mutual relationships between fathers and children of high school.

Association of macular microcirculation with renal function in Chinese non-diabetic patients with hypertension.

The aim of this study was to investigate the association of macular microcirculation with renal function and the feasibility of using macular microcirculatory parameters to monitor renal function in Chinese non-diabetic patients with hypertension. This case-control study included 62 non-diabetic patients with hypertension, including 31 with renal dysfunction (estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2) and 31 with normal renal function (eGFR ≥90 mL/min/1.73 m2). Age, sex and clinic blood pressure were matched between groups. Macular microcirculatory parameters of 124 eyes of the 62 patients were evaluated by optical coherence tomography (OCT) and OCT angiography (OCTA). In comparison with the patients with normal renal function, patients with renal dysfunction had lower macular superficial parafovea vessel density (18.6 vs. 19.4%, P = 0.029), macular cube average thickness (273.0 vs. 280.2 µm, P = 0.003), and average ganglion cell layer and inner plexiform layer (GCL-IPL) thickness (79.5 vs. 82.8 µm, P = 0.006), but similar macular central fovea vessel density and central fovea thickness (P ≥ 0.54). After adjustment for confounders, eGFR was significantly associated with macular superficial parafovea vessel density, cube average thickness and GCL-IPL thickness (P < 0.02). In detecting renal dysfunction, areas under the curve were 0.61, 0.66 and 0.65 for macular superficial parafovea vessel density, cube average thickness and GCL-IPL thickness. In non-diabetic patients with hypertension, macular superficial parafovea vessel density, cube average thickness and GCL-IPL thickness were significantly worse in patients with renal dysfunction than those with normal renal function. Using macular parameters to monitor renal function is feasible.

Piezo activity levels need to be tightly regulated to maintain normal morphology and function in pericardial nephrocytes.

Due to their position on glomerular capillaries, podocytes are continuously counteracting biomechanical filtration forces. Most therapeutic interventions known to generally slow or prevent the progression of chronic kidney disease appear to lower these biomechanical forces on podocytes, highlighting the critical need to better understand podocyte mechano-signalling pathways. Here we investigated whether the mechanotransducer Piezo is involved in a mechanosensation pathway in Drosophila nephrocytes, the podocyte homologue in the fly. Loss of function analysis in Piezo depleted nephrocytes reveal a severe morphological and functional phenotype. Further, pharmacological activation of endogenous Piezo with Yoda1 causes a significant increase of intracellular Ca++ upon exposure to a mechanical stimulus in nephrocytes, as well as filtration disturbances. Elevated Piezo expression levels also result in a severe nephrocyte phenotype. Interestingly, expression of Piezo which lacks mechanosensitive channel activity, does not result in a severe nephrocyte phenotype, suggesting the observed changes in Piezo wildtype overexpressing cells are caused by the mechanosensitive channel activity. Moreover, blocking Piezo activity using the tarantula toxin GsMTx4 reverses the phenotypes observed in nephrocytes overexpressing Piezo. Taken together, here we provide evidence that Piezo activity levels need to be tightly regulated to maintain normal pericardial nephrocyte morphology and function.

Epidemiological study of hospital acquired acute kidney injury in critically ill and its effect on the survival.

In the intensive care unit (ICU), acute kidney injury (AKI) is the most common cause of morbidity and mortality. Hospital-acquired acute kidney injury (HAAKI) is AKI developing after 48h. We aimed to study the development of AKI and its associated risk factors. We conducted a longitudinal observational study. Inclusion criteria were patients > 18 years of age admitted to ICU. The primary outcome was the development of AKI as defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria. A total of 273 patients were included in the study. Out of 273, 44(16.11%) patients developed AKI. The mean age was 45.80(17.39) years, and 60.81% were males. The median acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores were 12(8-18) and 5(3-7), respectively. Diabetes mellitus (23.44%) and hypertension (23.81%) were predominant comorbidities. The risk factors associated with AKI were serum chloride level, colistin, invasive ventilation, positive end-expiratory pressure (PEEP), and fluid balance. The hospital mortality was significantly higher in patients with AKI (43.18%) as compared with no AKI (14.41%). Among the secondary outcomes, 7 (15.90%) patients required renal replacement therapy (RRT) during hospitalisation. The length of ICU stay was higher in patients with AKI 8(5-13) compared to no AKI 5(3-8). A total of 16.11% developed HAAKI, and mortality was 43.18%. Post 6 months follow-up of AKI patients, mortality was 23%. Among survivors none of the patients were on RRT.Patients admitted with normal kidney function can develop AKI. Hence, careful monitoring of ICU patients is necessary.

Dengue Cardiomyopathy Treatment Strategy Optimisation by Integrating Point-of-Care Ultrasound with VExUS

Dengue fever is an arthropod-borne viral disease that is widespread throughout the world. Herein, we report a case of dengue cardiomyopathy that was detected and treated to best effect using point-of-care ultrasound (POCUS) and the VExUS score. A 75-year-old lady with no known comorbidities presented with a 10-day history of fever, vomiting, loose stool, and poor appetite. Upon arrival, she was febrile and hypotensive. Bedside POCUS showed poor left ventricular systolic function, inferior vena cava measuring 2.27cm and VExUS grading of 2 to 3. Dengue serology IgM and IgG were positive and NT-proBNP raised at 12500pg/ml. Instead of fluid resuscitation, diuretic and inotropes were initiated along the line of cardiogenic shock secondary to dengue cardiomyopathy. Serial normal cardiac enzymes and electrocardiogram excluded acute coronary syndrome. She was discharged well, and repeated echocardiography one-month post discharge showed normal left ventricular systolic function with no clinical signs or symptoms of heart failure.

Natal factors influencing newborn's oral microbiome diversity.

The early microbiota of neonates is crucial for developing the postnatal immune system and establishing normal physiological, metabolic, and neurological functions. This study aimed to investigate the factors influencing the diversity of the neonatal oral microbiome, including mother-to-newborn microbial transmission. The study includes a prospective cohort comprising 73 mothers and 87 neonates and a retrospective cohort comprising 991 mothers and 1,121 neonates. Samples from the maternal cervix and neonatal gastric, bronchial, and oral cavities were analyzed using culture-based methods. Neonatal oral swab samples were also analyzed using16S rRNA gene sequencing to characterize microbial diversity and composition. Similar genera were detected in the neonatal gastric, bronchial, and oral samples, and the neonatal gastric culture was the most similar to the maternal cervical culture. In addition to mother-to-newborn microbial transmission, various natal factors including birth type, birth weight, delivery mode, maternal chorioamnionitis, maternal diabetes and the presence of microbes in other sites influenced neonatal oral microbiome diversity. Among these factors, the birth type was the most significant, and preterm neonates exhibited decreased oral microbiome diversity, with fewer beneficial bacteria and more pathogens. These findings could serve as a baseline for research on the establishment of the oral microbiota in preterm neonates and its health implications.

Progress in application of medical absorbable haemostatic materials for haemostasis in orthopaedic surgery

The application progress of medical absorbable haemostatic material (MAHM) in hemostasis during orthoapedic surgery was reviewed, in order to provide reference for clinical hemostasis program. The domestic and foreign literature on the application of MAHM for hemostasis in orthopedic surgery was extensively reviewed and summarized. According to biocompatibility, MAHM can be divided into oxidized cellulose/oxidized regenerated cellulose materials, chitosan and its derivatives materials, starch materials, collagen and gelatin materials, and fibrin glue materials, etc., which can effectively reduce blood loss when used in orthopedic surgery for hemostasis. Each hemostatic material has different coagulation mechanism and suitable population. Oxidized cellulose/oxidized regenerated cellulose, chitosan and its derivatives, starch hemostatic material mainly stops bleeding by stimulating blood vessel contraction and gathering blood cells, which is suitable for people with abnormal coagulation function. Collagen, gelatin and fibrin glue hemostatic materials mainly affect the physiological coagulation mechanism of the human body to stop bleeding, suitable for people with normal coagulation function. Reasonable selection of MAHM can effectively reduce perioperative blood loss and reduce the risk of postoperative complications, but at present, single hemostatic material can not meet clinical needs, and a new composite hemostatic material with higher hemostatic efficiency needs to be developed.

Treatment of the terrible triad of the elbow by olecranon osteotomy: a retrospective cohort study

Background This study aims to evaluate the surgical techniques and outcomes of treating elbow dislocations with coronoid and radial head fractures, commonly referred to as the terrible triad of the elbow (TTE), through a single olecranon osteotomy. Methods A retrospective analysis was performed on 73 patients diagnosed with TTE between January 2015 and April 2022. The cohort included 44 men and 29 women, with an average age of 40.0 ± 15.1 years (range, 18–68 years). Among these patients, Mason Type I, II, and III fractures were identified in 11, 42, and 20 cases, respectively, while Morrey Type I, II, and III fractures were observed in 45, 23, and five cases, respectively. All patients underwent treatment via a single olecranon osteotomy. The average interval between injury and surgery was 5.6 ± 1.6 days (range, 3–8 days). Elbow function was assessed using the Mayo Elbow Performance Score (MEPS), pain was measured via the Visual Analogue Scale (VAS), and quality of life was evaluated using the SF-36 questionnaire. Results Patients were followed for 15 to 60 months (mean, 37.1 ± 13.3 months). All coronoid and radial head fractures achieved complete healing, with an average recovery time of 4.3 ± 1.1 months (range, 3–6 months). By the final follow-up, all patients had regained normal elbow function. The mean elbow flexion was 124.4° ± 9.2°, extension was 9.6° ± 6.5°, and the total range of flexion-extension was 114.8° ± 11.7°. Forearm pronation averaged 77.3° ± 4.8°, supination 79.2° ± 6.5°, and total forearm rotation 156.5° ± 8.4°. The mean MEPS was 89.3 ± 6.4, with 36 patients achieving excellent scores and 37 obtaining good scores. Preoperative VAS scores averaged 8.78 ± 1.11, which significantly dropped to 0.97 ± 0.83 at the final follow-up (p = 0.000). The SF-36 preoperative PCS and MCS scores were 45.77 ± 3.59 and 60.67 ± 3.91, respectively, with postoperative improvements to 93.85 ± 2.65 (p = 0.000) and 95.79 ± 3.11 (p = 0.000). Conclusion This retrospective analysis indicates that a single olecranon osteotomy could be a viable treatment option for TTE. However, additional research involving a control group is essential to substantiate the efficacy of this technique.

Mechanisms underlying the roles of leukocytes in the progression of cystic fibrosis

Recent advances in cystic fibrosis (CF) treatments have led to improved survival, with life expectancy for Australians living with CF at 57yo. As life expectancy improves, long-term cardiovascular disease risk factors (as for the general population) will become an issue in these patients. We hypothesized that increased leukocyte expression of vasoconstriction and pro-fibrotic mediators may contribute to CF severity in adults with CF. We recruited 13 adult and 24 pediatric healthy controls, and 53 adults and 9 children living with CF. Leukocyte expression/release of endothelin-1 (ET1) and members of the TGF-β/Smad signaling were measured by multifluorescence quantitative confocal microscopy, Western blotting, ELISA, and real-time quantitative polymerase chain reaction. The association between plasma ET1 levels and lung function was assessed. Leukocytes from adults living with CF expressed higher ET1 levels (p = 0.0033), and TGF-β (p = 0.0031); the phosphorylation ratio increased for Smad2/3 (p = 0.0136) but decreased for Smad1/5/8 (p = 0.0007), vs. control subjects. Plasma ET1 levels were significantly increased in adults with CF with FEV1<50% (p = 0.002) vs. controls, and adults with CF with normal lung function. The release of ET1 in adult plasma inversely correlated with CF severity (-0.609, p = 0.046). Our data indicates that upregulated ET1 and TGF-β/Smad signaling in leukocytes may contribute to CF severity, highlighting the need for further investigations into their impact on the clinical outcomes of people living with CF.

Adipocyte associated glucocorticoid signaling regulates normal fibroblast function which is lost in inflammatory arthritis.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Little is known about what regulates the homeostatic functions of fibroblasts. Here, we perform RNA sequencing and identify a gene expression program in healthy synovial fibroblasts characterized by enhanced fatty acid metabolism and lipid transport. We identify cortisol as the key driver of the healthy fibroblast phenotype and that depletion of adipocytes, which express high levels of Hsd11b1, results in loss of the healthy fibroblast phenotype in mouse synovium. Additionally, fibroblast-specific glucocorticoid receptor Nr3c1 deletion in vivo leads to worsened arthritis. Cortisol signaling in fibroblasts mitigates matrix remodeling induced by TNF and TGF-β1 in vitro, while stimulation with these cytokines represses cortisol signaling and adipogenesis. Together, these findings demonstrate the importance of adipocytes and cortisol signaling in driving the healthy synovial fibroblast state that is lost in disease.

Sympathetic transduction to blood pressure in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are more than twice as likely to die from a cardiovascular event than those with normal kidney function. Although CKD may increase resting sympathetic activity, quantification of resting sympathetic outflow alone does not account for the ensuing vasoconstriction, and blood pressure (BP) change (i.e., sympathetic transduction). Patients with CKD have been reported to exhibit elevated α-adrenergic receptor sensitivity, which may predispose this population to greater sympathetic transduction. We tested the hypothesis that patients with CKD have augmented sympathetic transduction to BP. In 16 patients with CKD, 17 bodyweight-matched (BWM) controls, and 11 lean controls of a similar age muscle sympathetic nerve activity (MSNA) and beat-to-beat BP were continuously recorded during quiet supine rest. Signal averaging was used to quantify changes in mean arterial pressure (MAP) and total vascular conductance (TVC) following spontaneous bursts of MSNA. Peak increases in MAP following MSNA bursts were not different among patients with CKD and the control groups (CKD: 2.3 ± 1.1mmHg; BWM controls: 2.1 ± 1.0mmHg; lean controls: 1.7 ± 0.9mmHg; P = 0.28). Likewise, nadir reductions in TVC following all bursts of MSNA were not different among patients with CKD and either control group (P = 0.69). Both patients with CKD and controls had graded increases in MAP and decreases in TVC with increasing burst size, which were not different among groups (all P > 0.05). In summary, these data indicate that patients with CKD do not have augmented sympathetic transduction to BP.

Chronic renal impairment predicts oncological outcomes in UTUC patients undergoing RNU.

This study aims to explore the relationship between pre-existing renal impairment and oncological outcomes in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU) using data from a multicentre international registry. Data on non-metastatic UTUC patients who underwent RNU were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry. Patients were categorised into normal pre-operative renal function and chronic renal impairment (CKD) groups, with CKD defined as an estimated glomerular filtration rate below 60 mL/kg/1.73m². Kaplan-Meier survival analysis was employed to investigate disease-free survival (DFS) and overall survival (OS). Multivariable Cox regression analysis was conducted to identify confounding variables. A total of 1393 patients diagnosed with UTUC who underwent RNU between 2014 and 2019 were analysed. 875 patients (62.4%) had normal renal function, whilst 528 patients (37.6%) had CKD prior to RNU. The two groups had similar proportions of bladder cancer history, comparable cardiovascular comorbidity, similar tumour stage, and comparable proportions receiving laparoscopic or robotic-assisted RNU. In multivariable cox regression analysis, CKD was found to be associated with inferior DFS (HR = 1.419; 95%CI = 1.060-1.898; p = 0.019). Upon multivariable analysis, pre-existing renal impairment and higher T stage (HR = 4.613; 95%CI = 1.829-4.712; p < 0.001) and the use of adjuvant chemotherapy (HR = 1.858; 95%CI = 1.229-2.807; p = 0.003) were also found to associate with worse DFS. Significant cardiovascular disease and higher T stage were associated with worse OS. Existing renal impairment at baseline did not have any significant associated with OS. In this multicentre registry, preoperative chronic renal impairment was identified as an independent predictor of inferior DFS in patients undergoing RNU for non-metastatic UTUC. Preoperative CKD could serve as a clinical predictor of poorer oncological outcomes.

Impaired Kidney Function and 10-Year Outcome After Percutaneous Coronary Intervention—Interaction with Age, Sex, Diabetic Status and Clinical Presentation

Background: Limited evidence exists regarding the association of chronic kidney disease (CKD) with long-term outcomes following percutaneous coronary intervention (PCI). We aimed to assess the association of CKD with 10-year outcome after PCI. Methods: This study included 5571 patients with coronary artery disease (CAD) undergoing PCI. Patients were categorized in groups according to the estimated glomerular filtration rate (eGFR) values: eGFR ≥ 90 mL/min/1.73 m2, (normal kidney function), 60 to &lt;90 mL/min/1.73 m2 (mild kidney impairment), 30 to &lt;60 mL/min/1.73 m2 (mild-to-moderate and moderate-to-severe kidney impairment) and &lt;30 mL/min/1.73 m2 (severe kidney impairment). The primary endpoint was all-cause mortality at 10 years. Results: All-cause deaths occurred in 155 patients (86.3%) with eGFR &lt; 30 mL/min/1.73 m2, 602 patients (59.1%) with eGFR 30 to &lt;60 mL/min/1.73 m2, 775 patients (31.3%) with eGFR 60 to &lt;90 mL/min/1.73 m2 and 220 patients (15.8%) with eGFR ≥ 90 mL/min/1.73 m2 (adjusted hazard ratio = 2.16, 95% confidence interval 1.84 to 2.54, p &lt; 0.001, for 30 mL/min/1.73 m2 decrement in the eGFR). There were CKD-by-age (Pint &lt; 0.001) and CKD–by-clinical presentation (Pint = 0.017) interactions showing a stronger association of CKD with mortality in younger patients and those presenting with acute coronary syndromes. The C statistic of the multivariable model for mortality increased from 0.748 [0.737–0.759] to 0.766 [0.755–0.777] (p &lt; 0.001) after the inclusion of eGFR in the model. Conclusions: In patients with CAD undergoing PCI, CKD was associated with higher mortality at 10 years compared with patients with preserved renal function. The association between CKD and mortality was stronger in patients of younger age and those presenting with acute coronary syndromes.

INFLUENCE OF UROGENEITRAL INFECTION IN PREGNANT WOMEN ON THE UTERINE – FETOPLACENTARY COMPLEX

As reported by the World Health Organization (WHO), approximately 20 % of pregnant women globally are aff ected by an infection of the lower genital tract. Urogenital infection can result in complications during the onset and progression of pregnancy, as well as the postpartum period. These complications include placental dysfunction, premature birth, low birth weight, premature rupture of the fetal membranes, and postpartum endometritis. A marker of normal placental function is α2-fertility microglobulin (AFMG), the determination of which will refl ect the presence or absence of a uterine- fetoplacental complex violation during urogenital infection in pregnant women.The aim of the study is to reveal the infl uence of urogenital infection on the dysfunction of the uterine – fetoplacental complex in pregnant women.Materials and methods. A total of 75 pregnant women were examined, divided into two groups: the main group (MG) and the comparison group (CG). The MG consisted of 55 pregnant women, of whom 35 underwent local sanitation of the urogenital infection according to the identifi ed pathogen (Subgroup A) and 20 refused this procedure (Subgroup B). The CG consisted of 20 pregnant women without urogenital infection, as determined by bacterioscopic, bacteriological, and polymerase chain reaction (PCR) examinations. All pregnant women underwent determination of AFMG in blood serum via immunoenzymatic methodology. The statistical analysis was conducted using the MedStat software (serial number MS00019). The study was performed in accordance with the provisions of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committee of PFMU for all women who participated in this study. Statistical processing was performed using the MedStat program (serial number MS00019). The work is a part of the initiative research work of the Department of Obstetrics and Gynecology No. 1 of Poltava State Medical University «Pathogenetic role of endothelial dysfunction and genetic features in pathology during pregnancy and gynecological diseases» (state registration No. 0117U005253, term of implementation 2017-2023).Research results. The results of the study demonstrated that pregnant women with a urogenital infection had a history of chronic pyelonephritis 5.5 times more frequently (p = 0.03) and salpingo- oophoritis 10.2 times more frequently (p &lt; 0.001), which may be a source of latent infection. The most prevalent infectious agents among pregnant women were: The most prevalent microorganisms were Ureaplasma urealyticum (21.4 %), Candida fungi (19.04 %), Gardnerella vaginalis (11.9 %), and Toxoplasma gondii (11.9 %). The level of AFMG in pregnant women with urogenital infection was observed to be 4.3 times lower than in pregnant women with CG (p &lt; 0.001). The remediation of an infection of the lower genital tract during pregnancy has been observed to increase AFMG production by a factor of four (p &lt; 0.001). The level of AFMG in pregnant women of CG was 2.2 times higher than in pregnant womenof Subgroup A (p &lt; 0.004).Conclusions. It was demonstrated that urogenital infection in pregnant women has a considerable impact on the dysfunction of the utero- fetoplacental complex. It was also shown that local sanitation of the lower genital tract in these women, based on the identified pathogen, has a benefi cial eff ect on the placenta’s functioning. However, this approach does not fully address the issue of protein synthesis impairment.

Rescuable sleep and synaptogenesis phenotypes in a Drosophila model of O-GlcNAc transferase intellectual disability.

O-GlcNAcylation is an essential intracellular protein modification mediated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recently, missense mutations in OGT have been linked to intellectual disability, indicating that this modification is important for the development and functioning of the nervous system. However, the processes that are most sensitive to perturbations in O-GlcNAcylation remain to be identified. Here, we uncover quantifiable phenotypes in the fruit fly Drosophila melanogaster carrying a patient-derived OGT mutation in the catalytic domain. Hypo-O-GlcNAcylation leads to defects in synaptogenesis and reduced sleep stability. Both these phenotypes can be partially rescued by genetically or chemically targeting OGA, suggesting that a balance of OGT/OGA activity is required for normal neuronal development and function.

Clinical characteristics and prognosis of steroid-resistant nephrotic syndrome in children: a multi-center retrospective study.

This study investigated the factors influencing the prognosis of children with steroid-resistant nephrotic syndrome (SRNS) in patients from the Guangxi region. We retrospectively analyzed clinical and pathological data of 279 patients with SRNS from six tertiary hospitals in Guangxi. Clinical data were compared between initial (I-SRNS) and secondary (S-SRNS) steroid resistance subgroups and Cox regression analysis was used to determine risk factors for chronic kidney disease (CKD) and CKD stage 5 (CKD5) in patients with SRNS. The median age of onset was 54 months. Thirty-three patients had extra-kidney manifestations. Fifty-two, 24, 57, 33, and 41 patients had hypertension, acute kidney injury, vitamin D deficiency, high intraocular pressure, and dwarfism, respectively. One hundred eighty-two and 92 patients had I-SRNS and S-SRNS, respectively. There were significant differences in sex, ethnicity, family history, incidence of hematuria, clinical classification, efficacy of immune agents, and prognosis between groups (P < 0.05). Among the 279 cases of SRNS, 239 had normal kidney function, 37 developed CKD, and 16 had CKD5. An increase in serum creatinine level (HR = 1.003) was significantly associated with CKD in children with SRNS, and effective immunosuppressant therapy decreased the CKD risk (HR = 0.168). Patients with increased serum creatinine levels (HR = 1.003) and acute kidney injury (HR = 4.829) were more likely to progress to CKD5. Children with S-SRNS showed a higher response to immunosuppressants than those with I-SRNS. Effective immunosuppressant therapy was found to protect against CKD, whereas increased acute kidney injury was an independent risk factor for CKD5.

Fibin is a crucial mitochondrial regulatory gene in skeletal muscle development.

Fin bud initiation factor homolog (Fibin) is a secreted protein that is relatively conserved among species. It is closely related to fin bud development and can regulate a variety of cellular processes. In our previous high-throughput chromosome conformation capture (Hi-C) study of pig embryonic muscle development, it was found that Fibin has high expression and activity during the development of pig primary muscle fibers. Therefore, we speculated Fibin participated in myogenesis severely. Specific deletion of Fibin in mouse skeletal muscle resulted in abnormal primary muscle fiber development during the embryonic period and a substantial decrease in skeletal muscle mass in adulthood. In vitro, knocking out Fibin in C2C12 cells promoted cell proliferation; however, after myogenic induction, cells lacking Fibin had almost no ability to differentiate into myotubes. During myogenic differentiation, loss of Fibin disrupts the normal function of mitochondria and impairs oxidative phosphorylation, resulting in decrease of NADH and FADH in the electron transport chain. Transmission electron microscopy also showed that mitochondrial morphology of Fibin-deficient C2C12 was impaired. In conclusion, our research has unveiled a novel mechanism of myogenesis regulation in mitochondrial function and potential target Fibin, and improved understanding of a broad range of mitochondrial muscle diseases.

Association of Preserved Ratio Impaired Spirometry (PRISm) with All-Cause Mortality: A Longitudinal Cohort Study.

Numerous studies indicate that preserved ratio impaired spirometry (PRISm) is associated with adverse clinical outcomes. However, the impact of PRISm severity, particularly about FVC, on mortality risk remains unclear. To determine whether PRISm was associated with mortality and to identify specific groups with particularly increased mortality rates. This retrospective study enrolled individuals older than 40 years who underwent comprehensive health screening at the Center for Health Promotion, Samsung Medical Center, between 2003 and 2020. PRISm was characterized by FEV1/FVC ≥ 0.7 and FEV1 <80% of predicted values. Participants were classified into three groups: normal lung function, PRISm with normal FVC, and PRISm with low FVC (FVC <80% predicted). We compared all-cause mortality rates using the Kaplan-Meier method and the Cox proportional hazard ratio model. Among 106,458 individuals, 86,208 exhibited normal lung function, while 6,249 had PRISm with normal FVC, and 14,001 had PRISm with low FVC. Over a median follow-up of 10.1 years, 2,219 participants succumbed. Individuals with PRISm experienced a higher cumulative mortality rate compared to those with normal lung function (39 vs. 16 per 10,000 person-years; adjusted HR 1.43, 95% CI 1.31-1.56). The fully-adjusted HRs for all-cause mortality in PRISm with normal and low FVC were 1.25 (95% CI 1.03-1.52) and 1.47 (95% CI 1.33-1.62) relative to those with normal lung function, respectively. PRISm is associated with an increased risk of death, particularly when accompanied by low FVC.