Functional Insufficiency Research Articles

Angiotensin II type 1 receptor-associated protein deletion combined with angiotensin II stimulation accelerates the development of diabetic kidney disease in mice on a C57BL/6 strain.

The progress in the research field of diabetic kidney disease (DKD) has been disturbed by the lack of reliable animal models. Angiotensin II (Ang II) type 1 receptor (AT1R)-associated protein (ATRAP) promotes internalization of AT1R and selectively inhibits pathological AT1R signaling. In this study, we investigated whether overactivation of the renin-angiotensin system (RAS) through a combination of ATRAP deletion with Ang II stimulation developed a progressive DKD model in C57BL/6 mice, which are resistant to the development of kidney injury. Eight-week-old male systemic ATRAP-knockout mice on the C57BL/6 strain (KO) and their littermate wild-type mice (Ctrl) were divided into five groups: 1) Ctrl, 2) Ctrl-streptozotocin (STZ), 3) KO-STZ, 4) Ctrl-STZ-Ang II, and 5) KO-STZ-Ang II. Ang II was administered for 6 weeks from 4 weeks after STZ administration. At 10 weeks after STZ administration, mice were euthanized to evaluate kidney injuries. Neither ATRAP deletion alone nor Ang II stimulation alone developed a progressive DKD model in STZ-induced diabetic C57BL/6 mice. However, a combination of ATRAP deletion with Ang II stimulation accelerated the development of DKD as manifested by overt albuminuria, glomerular hypertrophy, podocyte loss, mesangial expansion, kidney interstitial fibrosis and functional insufficiency, concomitant with increased angiotensinogen and AT1R expression in the kidneys. In STZ-induced diabetic C57BL/6 mice that are resistant to the development of kidney injury, the combination of ATRAP deletion and Ang II stimulation accelerates the development of DKD, which may be associated with intrarenal RAS overactivation.

Transcatheter mitral valve repair and its impact on reverse right ventricular remodelling

Abstract Introduction Transcatheter edge-to-edge repair (TEER) has been proven to reduce cardiovascular events in a particular subset of patients with severe mitral insufficiency (MR) and left ventricle dysfunction. Nevertheless, its short and long-term impact on the right ventricle (RV) remained to be determined. Our goal was to assess the effect of TEER on the RV and right chamber pressures. Methods Patients were consecutively enrolled from Nov 2018 to Jul 2022. Clinical, laboratory echocardiographic and procedural data were collected. Follow-up information of admissions for heart failure, New York Heart Association (NYHA) functional class and survival was collected. The data was analysed prior to and at 3 and 12 months after the procedure. RV dysfunction was defined as Tricuspid Annular Plane Systolic Excursion (TAPSE) < 17mm or S’ < 9cm/s. Changes between baseline and follow-up parameters were assessed using the paired t-test. Results A total of 46 patients were included. Average age was 77.28 ± 7.92 years and 30 were male (65.2%). Twelve patients were on NYHA class III (26.1%) and most had functional mitral insufficiency (25; 54.3%) and mild to moderate tricuspid insufficiency (36; 78.3%). All patients had severe mitral insufficiency (estimated regurgitant orifice area 41.28 ± 16.77mm; regurgitant volume 62 ± 28.96mL). Seventeen patients had diabetes (37.0%), 10 had coronary artery disease (21.7%), 23 had atrial fibrillation (50.0%) and 6 had chronic kidney disease (13.0%). At 3 months, mean right ventricular/right atrial gradient (RV/RAgrad) was significantly lower (37.26 ± 9.66 mmHg vs 30.81 ± 17.36 mmHg; p 0.017) as well as MR (2.98 ± 0.15 vs 1.67 ± 0.63; p < 0.001). There were no differences regarding severity of tricuspid regurgitation (TR) and RV and left ventricle (LV) function. At 1 year follow-up there was a marked improvement of RV/RAgrad (37.49 ± 10.87 mmHg vs 28.12 ± 10.13 mmHg; p 0.009), TAPSE (18.83 ± 4.22 mm vs 20.88 ± 3.08 mm; p 0.035), S’ (10.81 ± 4.00 cm/s vs 13.5 ± 1.97 cm/s, p 0.015) and MR severity (2.98 ± 0.15 vs 1.83 ± 0.71; p <0.001). Number of heart failure readmissions was also lower at 1 year follow-up post TEER (0.35 ± 0.80 vs 0.81 ± 0.87; p 0.032). Over a mean follow-up time of 1.72 ± 1.16 years, only 8.7% of patients died and 17.4% were readmitted due to heart failure. Conclusion TEER has a positive impact on right ventricle function and pressures. This effect was more prominent at 1 year follow-up and suggests reverse remodelling continues even after 3 months. Overall, patients with TEER had low rates of death and heart failure readmissions.

Functional Disabilities and Food Insufficiency During Pregnancy: Results from the Pregnancy Risk Assessment Monitoring System.

Background: Disability is a well-documented risk factor for food insecurity. However, prior literature has overlooked the possible connection between disability and food insecurity during the antenatal period. This study extends previous research by examining the relationship between those with any functional disabilities and food insufficiency during pregnancy among a sample of mothers. Methods: Data are from the Pregnancy Risk Assessment Monitoring System, 2019-2020 (N = 9084). The relationship between the number of self-reported functional disabilities and food insufficiency is examined using modified multivariable Poisson regression. Results: After adjusting for control variables, the results reveal that those with any functional disability have a significantly higher risk of food insufficiency during pregnancy (risk ratio [RR] = 1.464, 95% confidence interval [CI] = 1.201-1.785). Findings reveal that all types of functional disability are associated with a higher risk of food insufficiency, including difficulty seeing, difficulty hearing, difficulty walking, difficulty remembering, difficulty with self-care, and difficulty communicating. Finally, the findings revealed that respondents with two functional disabilities (RR = 1.473, 95% CI = 1.153-1.882) and three or more functional disabilities (RR = 1.974, 95% CI = 1.534-2.541) are significantly more likely to report food insufficiency compared with respondents with no disabilities. Conclusions: There is a significant positive association between reporting functional disabilities and food insufficiency. Expanding current public health programs, educating health care professionals, and implementing effective screening guidelines directed at pregnant women with disabilities may reduce the prevalence of food insufficiency and promote greater health equity.

Abstract P428: Angiotensin II Type 1 Receptor-associated Protein Deletion Combined With Angiotensin II Stimulation Exacerbates Diabetic Kidney Disease In C57BL/6 Mice

The progress in the research field of diabetic kidney disease (DKD) has been disturbed by the lack of reliable animal models. Angiotensin II (Ang II) type 1 receptor (AT1R)-associated protein (ATRAP) promotes internalization of AT1R and selectively inhibits pathological AT1R signaling. In this study, we investigated whether overactivation of the renin-angiotensin system (RAS) through a combination of ATRAP deletion with Ang II stimulation developed a progressive DKD model in C57BL/6 mice, which are resistant to the development of kidney injury. Eight-week-old male systemic ATRAP-knockout mice on the C57BL/6 strain (KO) and their littermate wild-type mice (Ctrl) were divided into five groups: 1) Ctrl, 2) Ctrl-streptozotocin (STZ), 3) KO-STZ, 4) Ctrl-STZ-Ang II, and 5) KO-STZ-Ang II. Ang II was administered for 6 weeks from 4 weeks after STZ administration. At 10 weeks after STZ administration, mice were euthanized to evaluate kidney injuries after measurements of systolic blood pressure (SBP) and urinary albumin excretion (UAE). Neither ATRAP deletion alone nor Ang II stimulation alone developed a progressive DKD model in STZ-induced diabetic C57BL/6 mice (UAE, Ctrl vs Ctrl-STZ vs KO-STZ vs Ctrl-STZ-Ang II: 10.6±2.0 vs 89.0±11.9 vs 69.1±15.0 vs 151.3±55.4 μg/day). However, a combination of ATRAP deletion with Ang II stimulation accelerated the development of DKD as manifested by overt albuminuria (UAE, KO-STZ-Ang II: 852.0±195.6 μg/day, p <0.001 vs Ctrl-STZ-Ang II), glomerular hypertrophy, podocyte loss, mesangial expansion, kidney interstitial fibrosis, and functional insufficiency, concomitant with increased angiotensinogen and AT1R expression in the kidneys. SBP levels were comparable between the Ctrl-STZ-Ang II and KO-STZ-Ang II groups (SBP, Ctrl-STZ-Ang II vs KO-STZ-Ang II: 144±4 vs 154±5 mmHg, p =0.363). In STZ-induced diabetic C57BL/6 mice, the combination of ATRAP deletion and Ang II stimulation accelerates the development of DKD by converting the C57BL/6 strain from being nephropathy-resistant to -susceptible, which may be associated with intrarenal RAS overactivation.

Kynurenic Acid Levels and Kynurenine Aminotransferase I, II and III Activities in Ganglia, Heart and Liver of Snail Helix Pomatia.

Kynurenic acid (KYNA), a tryptophan metabolite along the kynurenine pathway, is an endogenous antagonist of glutamate ionotropic excitatory amino acid (EAA) receptors and the α7 nicotinic acetylcholine receptor (nAChR). The involvement of KYNA in various pathological conditions and during the aging process is significant. KYNA synthesis from L-kynurenine (L-KYN), through the action of several kynurenine aminotransferases (KATs), is present in the central nervous system (CNS) and periphery of mammals. We were interested in investigating the ability of the brain and peripheral organs of Helix pomatia snails to synthesize KYNA, in an in vitro study. In comparative studies between rat and snail, we looked for the synthesis of KYNA in the liver. We then looked for an effect of age on KYNA synthesis. Ten shell parameters of the Helix pomatia snail were used to establish an Age Rating Scale (ARS), i.e. body weight, shell weight, shell length, width and height, shell opening length and width, lip width, number of shell turns and external shell growth rings. An age of the snails was determined according to the ARS and the snails were divided into three groups, i.e. young, middle and old age. Homogenates of dissected regions, i.e. cerebral ganglia (CG), subpharyngeal ganglia (SG) consisting of pedal, visceral and pleural ganglia, heart and liver, were examined. KYNA was measured by high performance liquid chromatography (HPLC) and KAT activities were measured by an enzymatic method. With respect to ARS, an evaluation of the age of the snails between young (1-2 years), middle (5-7 years) and old (9-13 years) showed significant differences (p<0.001). Analysis of KYNA levels in different snail tissues, i.e. CG, SG, heart and liver, showed an occurrence in the low femtomolar range. Marked and significant increases of KYNA were found in the liver of middle and old age groups. In the SG, KYNA decreased significantly with age. There were no differences in KYNA levels between groups in CG and heart. The lowest KAT activity was found in CG and SG (5 pmol/mg/h), while in heart and liver the values were visibly higher (between 8 and 80 pmol/mg/h). Only in the liver, and exceptionally only for KAT I, the activity increased significantly with age, i.e. up to 14 years. No age-related changes in KAT I, II and III activities were found in CG and SG. Snail liver shows a different pattern of KAT activities compared to the rat liver. Regions of the CNS and periphery of the snail Helix pomatia are able to synthesize KYNA due to KAT activities. In the snail liver, KAT I activity increased with age. Notably, there was no age-related increase in KAT activities in the heart and especially in the CNS of Helix pomatia, indicating significant differences from mammals. A moderate KYNA metabolism in the Helix pomatia snail in the periods studied, up to 14 years, could be a physiological phenomenon that protects organs from possible functional insufficiency due to high KYNA levels, as has been suggested. It is reasonable to search for the factor(s) that could regulate the concentration of KYNA in the body of the snail.

ВИТАМИН D ПРИ РАЗЛИЧНОЙ ВОЗРАСТ-АССОЦИИРОВАННОЙ ПАТОЛОГИИ У ДОЛГОЖИТЕЛЕЙ И БОЛЬНЫХ ИБС В СТАРЧЕСКОМ ВОЗРАСТЕ

Introduction. Vitamin D deficiency is associated with many pathological conditions. The elderly is at high risk of vitamin D deficiency due to their reduced ability to produce vitamin D precursors in the skin. Aim. To analyze 25-Hydroxycalciferol relationships with various clinical and laboratory parameters in centenarians and very elderly patients with coronary artery disease. Material and methods. This work was cross-sectional study. The study included 230 patients aged 76 to 99 years, hospitalized with the diagnosis of coronary heart disease. The concentration of 25-hydroxycalciferol was determined by immunochemiluminescent analysis. A 25-hydroxycalciferol level &lt;10 ng/mL was considered as severe vitamin D deficiency, 10-19 as deficiency, 20-29 as insufficiency, and ≥30 ng/mL as normal. Results and discussion. The mean 25-Hydroxycalciferol concentration was 14.9+10.2 ng/mL. Only 7.5% of patients had normal 25-Hydroxycalciferol level, 12.3% - insufficiency, 43.6% - deficiency, 36.6% - severe vitamin deficiency. In centenarians the mean concentration of vitamin D was 12.9+9.9 ng/ml, in patients &lt;90 years – 16.4+10.2 ng/ml (p=0.01). Significant positive correlations were registered between vitamin D level and hand grip strength measured by dynamometry (r=0.2; p=0.008) and the instrumental activity scale (r=0.1; p=0.03). The mean level of vitamin D in the group of patients with high risk of cognitive impairment was 11.2+5.8 ng/ml, with low risk of cognitive impairment – 20.8+18.5 ng/ml (p&lt;0.0001). Negative correlations were registered between 25-Hydroxycalciferol level and the Morse fall scale (r=-0.2, p=0.03). Significant direct correlation between serum uric acid and vitamin D was registered (r=0.3; p=0.001). No significant relationships were found between vitamin D levels and bone mineral density in various parts of the skeleton, with the exception of the T-score in the lumbar spine in centenarians (р=0.004). Conclusion. The study results indicate presence of various relationships between 25-Hydroxycalciferol blood concentration and various clinical and laboratory parameters in centenarians and very elderly patients with coronary artery disease and, above all, with functional insufficiency, cognitive impairment and hyperuricemia.

Diastolic Mitral Regurgitation as a Rare Cause of Acute Respiratory Failure Following Complete Atrioventricular Block

A 77-year-old male presented to the emergency department with dyspnea. A third-degree atrioventricular block was present in the electrocardiogram and an echocardiography showed a moderate mitral regurgitation with a diastolic functional insufficiency. Hemodynamic variations were assessed in the context of heart rhythm disturbances. (Level of Difficulty: Intermediate.)

Comparative morphometric characteristics of the dolichocolon decompensated stage

Introduction. Chronic constipation is one of the most actual problems in modern coloproctology and found in 14–16% of developed countries population. The causes of chronic constipation vary widely from functional to organic. The latter include dolichocolon, different variants of which occur in 16% cases.Aim: To give a morphological and quantitative characteristic of the decompensated stage of dolichocolon based on the morphogenesis of changes in comparison with the histologically normal colon.Material and Methods. Colon tissue samples from 16 people were used and divided into two groups. The first, control group, included 8 sectional cases of a morphologically normal colon wall. The second, the study group, was represented by surgical material from 8 patients with dolichocolon decompensated stage. Observation groups were comparable by sex and age.Results. In average, in patients with the decompensated dolichocolon stage, in comparison with the control group, statistically significantly (p ˂ 0.05), the thickness of the mucous and muscular membranes decreases by 1.07 and 2.26 times, respectively. The thickness of the submucosa increases by 1.17 times. However, the maximum and minimum values of this parameter change only by 1.35 times, while in the control group – by 7.21 times, as a consequence of the development of insufficiency of the evacuation-motor function of the colon which indicates the maximum smoothness of the colon wall, and is a consequence of its functional insufficiency. The specific proportion of neuro plexuses in the muscular membrane is 1.45 times higher than in the control group. However, the number of nerve cells decreases by 2.98 times, as a result of the development of insufficiency in the evacuation-motor function of the colon. The average area of lymphatic follicles decreases by 1.49 times, and secondary follicles disappear altogether, meaning the depletion of the compensatory-adaptive reactions of the lymphoid apparatus.Conclusion. Morphological and morphometric signs of irreversible changes, such as dystrophy, atrophy and sclerosis of all structural elements of the thick wall in the stage of decompensated dolichocolon, suggest surgical treatment, as well as prevention of the development of decompensation of the general condition of patients.

EFFECTIVENESS AND SAFETY OF CHONDROGUARD THERAPY IN PATIENTS WITH ENDOCRINE PHENOTYPE OF OSTEOARTHRITIS

Objective. To evaluate the efficiency and safety of therapy with parenteral chondroitin sulfate (CS) Chondroguard®, CS-Bioactive© (Bioiberica S.A.U., Spain); ZAO “Sotex” PharmFirm, Russia) in patients with Stage II knee osteoarthritis (KOA), grade 1 knee functional insufficiency (FI), and type 2 diabetes mellitus (T2DM). Subjects and methods. A 50-day comparative pilot study involved 80 patients with Kellgren-Lawrence Stage II KOA, grade 1 FI, and T2DM, who were divided into 2 groups; Group 1 (a study group; n=40) received CS (Chondroguard®, 100 mg/ml, intramuscularly, every other day; the first three injections of 1 ml each; if they were well tolerated; starting from injection 4 of ml each; the treatment cycle was 25 injections for 50 days) and therapy for T2DM and its complications; Group 2 (a comparison group; n=40) took oral symptomatic slow acting drugs for osteoarthritis (SYSADOA) agents containing CS, glucosamine, unsaponifiable compounds of avocado and soybean, and therapy for T2DM and its complications. On study days 0 and 50, the investigators calculated in the patients the scores of the visual analogue scale (VAS), WOMAC index, the Lequesne index, those of the WHO and the Narango Therapy Safety Scales, assessed the parameters of the blood hormonal and metabolic profile, free radical oxidation (FRO), antioxidant system (AOS), and the levels of blood proinflammatory factors. Results. In Group 1, therapy with CS was well tolerated and was accompanied by a reduction in pain intensity on VAS at rest and in motion, in functional restrictions on the WOMAS index and the Lequesne index, as well аs by a decrease in blood proinflammatory markers (С-reactive protein, interleukin 6 and 1β, leptin, lipocalin-2), in the concentration of fasting and postprandial glucose, HbA1c, С-peptide, insulin-like growth factor-1, and in FRO-AOS activity (malondialdehyde, protein oxidative modification, superoxide dismutase) as compared with the indicators in Group 2. Conclusion. Chondroguard® was shown to be effective and safe in the combination therapy in patients with Stage II endocrine KOA phenotype, grade 1 FI, and T2DM.

DIAGNOSTIC ET FACTEURS PRONOSTIQUES DES OCCLUSIONS INTESTINALES AIGUES MECANIQUES DE L’ADULTE

Abstract Introduction: Acute intestinal obstruction is a syndrome whose prognosis depends on several factors. The aim of our study is to describe the diagnostic elements and prognostic factors of mechanical OIA in adults. Patients and methods: we carried out a retrospective study over a period of one year on mechanical acute intestinal obstruction in adults. The diagnostic assessment, etiologies and prognostic factors were studied. Results: Ninety-six (96) files were collected. ASP radiography was performed in 56 cases (58.3%) and contributed in 24.6% while abdominal CT was performed in 37 cases (38.4%) with a sensitivity of 89.2%. Etiologies were dominated by strangulated hernias in 30 cases (31.2%) and colon volvulus in 26 cases (27.1%). Intestinal necrosis was noted in 32.3% of cases. It was strongly correlated with a consultation delay of 6 hours in the event of strangulation with p=0.0021. Morbidity was 17.7% (n=17) dominated by parietal suppuration (n=13 or 76.4%). Severe ionic disorders, hypovolemia and functional renal insufficiency were factors of poor prognosis increasing the risk of intestinal necrosis and postoperative complications with p=0.03. Overall mortality was 8.3% (n=8). Conclusion: A time to consultation &gt;6 h, hydroelectrolyte disorders, strangulation and the existence of intestinal necrosis are factors of poor prognosis in mechanical OIA. Keywords: Acute intestinal obstruction, strangulated inguinal hernias, Flanges, intestinal necrosis

Interleukin-17 In Juvenile Idiopathic Arthritis

Joint diseases of childhood are an actual problem of pediatrics. Juvenile idiopathic arthritis (JIA) is a common chronic systemic inflammatory joint disease in children, the etiological factors of which remain not fully known. The disease can affect children of any age, it is characterized by a long progressive course, leading to the development of contractures and functional insufficiency, and thus the disability of children

Reconstructive surgeries in the case of the knee joint osteoarthritis

Objective. To clarify the indications and volume of reconstructive surgeries under conditions of knee joint arthritis and to improve the methods of surgical correction of peri-articular deformations using an external rod fixator. Methods. During the last 10 years (2012‒2022), reconstructive surgeries were performed in 45 patients (49 joints). Indications for surgery were based on the study of pain and its localization, peri-articular deformation of the limb, ultrasound (USD) and X-ray examinations. Results. Indications for certain reconstructive surgical interventions on the knee joint are substantiated. The role of pathological changes of the meniscus in the development of knee joint arthritis has been determined. The positive clinical effect of paracapsular resection of the front part of the meniscus with hyperplastic growths of synovial tissue is shown. Deformation of the extremety (43 patients — with varus deformity, 2 — with valgus deformity) limited the function of the limb and caused pain. Surgical treatment in such cases were aimed at eliminating the deformation of the proximal part of the tibia. The types of osteotomies, the features of the author's rod external fixation device application, and the postoperative management of patients are presented. Due to external fixator, it is possible to perform, if necessary, angular correction of the limb axis during the period when the patient begins to walk with partial weight bearing, and the functional load of the limb makes it possible to achieve fusion of fragments within 3.5–4 months. A long-term positive clinical effect was obtained in 42 (93 %) patients. Conclusions. Indications for pathogenetic treatment should be based, first of all, on the identification of the source (or pathogenesis) of the pain syndrome, then on the analysis of the type and magnitude of peri-articular deformation of the limb, signs of functional insufficiency of the limb associated with it. In the third place, the X-ray signs should be analyzed. Elimination of angular peri-articular deformation of the limb has a positive effect on the course of knee arthritis, reduces pain, increases physical activity, and slows down the progression of cartilage destruction.

514 Incidence, Manifestation, Treatment and Outcomes related to Adrenal Insufficiency in Adult Burn Patients

Abstract Introduction In the setting of hypotension, serum cortisol levels are obtained to eliminate adrenal insufficiency as a contributing cause. Morbidity, prolonged length of intensive care unit and mechanical ventilator dependent days with higher mortality rates have been associated with adrenal insufficiency. The primary objective was to identify patient characteristics and treatment indications, approaches, and outcomes in adult burn – injured patients diagnosed with adrenal insufficiency. Methods This is a single center, five-year retrospective medical record review of adult patients aged 18 years and older admitted to the burn service were included. The data was analyzed using simple and correlational statistics to describe categorical data. Logistic regression, One-way ANOVA, and univariate analyses were conducted in Statistical Analysis System (SAS)® v 9.4. Results Sixty nine patients were included, 64% male, 51years old, with 27 % total body surface area, nearly half with smoke inhalation, and 32% mortality. Duration of hydrocortisone therapy in days, total dose in milligrams, duration of wean in days, and number of times therapy reinitiated were found to be (unadjusted) significantly related to intensive care length of stay, p = &amp;lt; 0.001. Hydrocortisone total dose in milligrams was found to be significantly related with increased vasopressor hours, p = 0.00927, p = 0.0163. Conclusions Hypotension, leading to shock, directly correlates with overall burn survivability. Functional adrenal insufficiency may result for shock and sepsis. Hypotension was the instigating factor for hydrocortisone therapy. Random cortisol levels were obtained in all patients included in the study, with an average of 14 mcg/dl which did not exclude adrenal insufficiency as a contributing cause. Applicability of Research to Practice This exploratory research will assist with formalizing a list of triggers for initiation of adrenal replacement therapy. These results are foundational in development of outcomes resulting from treatment with varying doses of hydrocortisone and lengths of therapy.

Molecular genetic features and clinical manifestations in Chinese familial cerebral cavernous malformation: from a novel KRIT1/CCM1 mutation (c.1119dupT) to an overall view.

Cerebral cavernous malformations (CCMs) are common vascular anomaly diseases in the central nervous system associated with seizures, cerebral microbleeds, or asymptomatic mostly. CCMs can be classified as sporadic or familial, with familial cerebral cavernous malformations (fCCMs) being the autosomal dominant manner with incomplete penetrance. Germline mutations of KRIT1, CCM2, and PDCD10 are associated with the pathogenesis of fCCMs. Till now, little is known about the fCCMs mutation spectrum in the Han Chinese population. In this study, we enrolled a large, aggregated family, 11/26 of the family members were diagnosed with CCMs by pathological or neuroradiological examination, with a high percentage (5/9) of focal spinal cord involvement. Genomic DNA sequencing verified a novel duplication mutation (c.1119dupT, p.L374Sfs*9) in exon 9 of the Krev interaction trapped 1 (KRIT1) gene. The mutation causes a frameshift and is predicted to generate a truncated KRIT1/CCM1 protein of 381 amino acids. All our findings confirm that c.1119dupT mutation of KRIT1 is associated with fCCMs, which enriched the CCM genes' mutational spectrum in the Chinese population and will be beneficial for deep insight into the pathogenesis of Chinese fCCMs. Additionally, with a retrospective study, we analyzed the molecular genetic features of Chinese fCCMs, most of the Chinese fCCMs variants are in the KRIT1 gene, and all these variants result in the functional deletion or insufficiency of the C-terminal FERM domain of the KRIT1 protein.

Arthroscopic Hip Labral Reconstruction With Fresh Meniscal Allograft

The acetabular labrum is essential to maintaining the functional health of the hip joint through contributions to joint congruity, stability, and the negative pressure suction seal. Injury, overuse, long-standing developmental disorders, or failed primary labral repair can eventually lead to functional labral insufficiency requiring management via labral reconstruction. While numerous graft options exist for hip labral reconstruction, there is no current gold standard. The optimal graft should best mimic the native labrum with regard to geometry, structure, mechanical properties, and durability. This has led to the development of an arthroscopic technique for labral reconstruction with fresh meniscal allograft tissue.

Adolescent menstrual dysfunction as a marker of future disorders of women’s sexual and reproductive health

The literature review considers the health state in women of early reproductive age. This is related to the common factors of formation that arise in adolescence, and are clinically manifested in the reproductive age. Disorders of the reproductive system functioning in puberty often lead to infertility, obstetric complications and perinatal losses. Ghrelin is a factor in the pathogenesis of functional amenorrhea during weight loss. Its concentration has a negative correlation with body mass index and androgen levels in the female body. Excessive physical exertion is one of the causes of functional amenorrhea, because this pathology is associated with increased levels of β-endorphin and ghrelin, as well as extremely low concentrations of leptin. Recent researches have demonstrated the importance of hidden genetic reproductive polymorphisms in women with the above-mentioned risk factors for amenorrhea for the future impairment of fertility. That is why women without genetic polymorphisms are able to restore both menstrual and reproductive functions after eliminating the influence of risk factors. However, in patients with some types of genetic mutations, amenorrhea persists despite the normalization of body weight, disappearance of stress and/or reduction of physical exertion. Under conditions of war in Ukraine, there is an increase in the frequency of hypothalamic dysfunctions in women of active reproductive age with a decrease in body weight against the background of stress, head injuries, which gives the problem an extreme acuteness and urgency. An example of a clinical manifestation of functional gonadotropin insufficiency is a menstrual disorder with the formation of secondary amenorrhea in 35 % of cases. Stress-induced (psychogenic) amenorrhea is one of the most common causes of functional gonadotropin deficiency. Menstrual and sexual female dysfunction is a multifactorial disorder that impairs women’s fertility, leads to pregnancy loss, infertility, and abnormal gestation. Due to dysmetabolic disorders, violations of ovarian steroidogenesis with hypothalamic-pituitary imbalance, this problem becomes multidisciplinary.

Chronic endometritis and endometrial microsatellite instability: is there a connection?

Introduction One of the criteria of impaired DNA repair is microsatellite instability (MSI) resulting from functional insufficiency of the mismatched nucleotide repair (MMR) system, a complex of proteins (MLH-1, PMS- 2, MSH-2, MSH-6). No data on the study of MSI in chronic endometritis (CE) were found in the available literature.The aim of the study was to determine the structural features of microsatellite instability in the endometrium in female patients with chronic inflammation of the uterine mucosa.Materials and methods Group I consisted of 30 women with morphologically confirmed high-grade CE; Group II consisted of 30 patients with low-grade CE; Group III consisted of 30 women who sought pregnancy planning and had histologically unchanged endometrium. The degree of CE in patients in groups I and II was variable. We analyzed the expression levels of MLH-1-, MSH- 2-, MSH-6-, and PMS-2-proteins in the endometrium by estimating the staining area of nuclei and cytoplasm of the affected cells over the entire slice area. Nonparametric statistical methods with Mann-Whitney test were used. The value of probability of error was set at 0.05.Results There was a statistically significant decrease in the level of MMR protein expression in the endometrial samples from the Group I patients compared to the same indices in the Group II and III women. No statistically significant results were found when analyzing the level of MMR protein expression depending on the severity degree of CE.Discussion There was a statistically significant decrease in the expression level of the markers studied (MLH-1, PMS-2, MSH-2, MSH-6) in endometrial specimens from patients with low-activity CE compared to uterine mucosa biopsy specimens from highly active CE and mid-stage endometrial secretion phase specimens. The described morphological features of the uterine mucosa in patients with low-activity CE are consistent with the findings of other authors. The literature provides indications of structural features of MSI in pre-tumor and tumor processes in the uterine mucosa.Conclusion Endometrial samples with low activity and various degrees of CE show statistically significantly lower expression levels of MLH-1, PMS-2, MSH-2, MSH-6 when compared to biopsy specimens from highly active CE and normal endometrial samples, which may indicate pathogenetic heterogeneity in the development of inflammation in the endometrium.

Clinical features of chronic pancreatitis in Helicobacter pylori-infected patients

Helicobacter pylori infection (Hp) in patients with chronic pancreatitis (CP) is analyzed in this article. A comparative assessment of the clinical manifestations of the disease in Hp-infected and non-infected patients is carried out. Peculiarities of pain, dyspeptic syndromes, and palpation data are revealed.&#x0D; 96 patients with CP were examined, including 58 (60.4%) women and 38 (39.6%) men from 16 to 75. In addition to patients with CP, 30 patients with chronic gastritis, duodenitis, gastric ulcer, or duodenal ulcer without clinical, biochemical, or sonographic signs of pancreatic disease were examined (as a comparison group). The control group consisted of 30 healthy individuals.&#x0D; In patients with CP, the Hp infection rate is higher than in patients with acid-related disorders of the gastroduodenal zone. It is equal to 86.5%.&#x0D; Pain in the epigastrium, in its right half, and in the right hypochondrium is more typical for CP patients infected with Hp than for non-infected patients. Full belt pain irradiation is more frequent in Hp-infected patients. Constant, intense pain occurs in these patients both before and after meals. The intensity of pain in CP patients infected with Hp is higher than in non-infected patients. In the case of Hp infection, pancreatic pain is more clearly stopped by antisecretory drugs and less clearly by antispasmodics and hunger. In non-infected patients, pain relief is preferably achieved through hunger and antispasmodic drugs.&#x0D; The severity of dyspeptic manifestations, symptoms associated with functional pancreatic insufficiency, is higher in CP patients infected with Hp than in non-infected patients.&#x0D; It is proven that the clinical manifestations of functional pancreatic insufficiency are more severe in infected patients.

Comparative morphometric characteristics of the dolichocolon decompensated stage

Introduction. Chronic constipation is one of the most actual problems in modern coloproctology and found in 14-16% of developed countries population. The causes of chronic constipation vary widely from functional to organic. The latter include dolichocolon, different variants of which occur in 16% cases.Aim. To give a morphological and quantitative characteristic of the decompensated stage of dolichocolon based on the morphogenesis of changes in comparison with the histologically normal colon.Material and Methods. Colon tissue samples from 16 people were used and divided into two groups. The first, control group, included 8 sectional cases of a morphologically normal colon wall. The second, the study group, was represented by surgical material from 8 patients with dolichocolon decompensated stage. Observation groups were comparable by sex and age.Results. In average, in patients with the decompensated dolichocolon stage, in comparison with the control group, statistically significantly (p ˂ 0.05), the thickness of the mucous and muscular membranes decreases by 1.07 and 2.26 times, respectively. The thickness of the submucosa increases by 1.17 times. However, the maximum and minimum values of this parameter change only by 1.35 times, while in the control group – by 7.21 times, as a consequence of the development of insufficiency of the evacuation-motor function of the colon which indicates the maximum smoothness of the colon wall, and is a consequence of its functional insufficiency. The specific proportion of neuro plexuses in the muscular membrane is 1.45 times higher than in the control group. However, the number of nerve cells decreases by 2.98 times, as a result of the development of insufficiency in the evacuation-motor function of the colon. The average area of lymphatic follicles decreases by 1.49 times, and secondary follicles disappear altogether, meaning the depletion of the compensatory-adaptive reactions of the lymphoid apparatus.Conclusion. Morphological and morphometric signs of irreversible changes, such as dystrophy, atrophy and sclerosis of all structural elements of the thick wall in the stage of decompensated dolichocolon, suggest surgical treatment, as well as prevention of the development of decompensation of the general condition of patients.

Operation technique or secondary sequelae of functional tricuspid valve insufficiency: what is decisive for the course after 5 years?

Operation technique or secondary sequelae of functional tricuspid valve insufficiency: what is decisive for the course after 5 years?