Association of gene polymorphisms with body weight changes in prediabetic patients

Recent research has demonstrated that Type 2 Diabetes (T2D) risk is influenced by a number of common polymorphisms, including MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146. Knowledge of the association between these single nucleotide polymorphisms (SNPs) and body weight changes in different forms of prediabetes treatment is still limited. The aim of this study was to investigate the association of polymorphisms within the MC4R, PPARG, and TCF7L2 genes on the risk of carbohydrate metabolism disorders and body composition changes in overweight or obese patients with early carbohydrate metabolism disorders. From 327 patients, a subgroup of 81 prediabetic female patients (48.7 ± 14.8 years) of Eastern European descent participated in a 3-month study comprised of diet therapy or diet therapy accompanied with metformin treatment. Bioelectrical impedance analysis and genotyping of MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146 polymorphisms were performed. The MC4R CC and TCF7L2 TT genotypes were associated with increased risk of T2D (OR = 1.46, p = 0.05 and OR = 2.47, p = 0.006, respectively). PPARG CC homozygotes experienced increased weight loss; however, no additional improvements were experienced with the addition of metformin. MC4R TT homozygotes who took metformin alongside dietary intervention experienced increased weight loss and reductions in fat mass (p < 0.05). We have shown that the obesity-protective alleles (MC4R T and PPARG C) were positively associated with weight loss efficiency. Furthermore, we confirmed the previous association of the MC4R C and TCF7L2 T alleles with T2D risk. [Abstract copyright: © 2022. The Author(s).

Towards targeted colorectal cancer biopsy based on tissue morphology assessment by compression optical coherence elastography

Identifying the precise topography of cancer for targeted biopsy in colonoscopic examination is a challenge in current diagnostic practice. For the first time we demonstrate the use of compression optical coherence elastography (C-OCE) technology as a new functional OCT modality for differentiating between cancerous and non-cancerous tissues in colon and detecting their morphological features on the basis of measurement of tissue elastic properties. The method uses pre-determined stiffness values (Young’s modulus) to distinguish between different morphological structures of normal (mucosa and submucosa), benign tumor (adenoma) and malignant tumor tissue (including cancer cells, gland-like structures, cribriform gland-like structures, stromal fibers, extracellular mucin). After analyzing in excess of fifty tissue samples, a threshold stiffness value of 520 kPa was suggested above which areas of colorectal cancer were detected invariably. A high Pearson correlation (r =0.98; p &lt;0.05), and a negligible bias (0.22) by good agreement of the segmentation results of C-OCE and histological (reference standard) images was demonstrated, indicating the efficiency of C-OCE to identify the precise localization of colorectal cancer and the possibility to perform targeted biopsy. Furthermore, we demonstrated the ability of C-OCE to differentiate morphological subtypes of colorectal cancer – low-grade and high-grade colorectal adenocarcinomas, mucinous adenocarcinoma, and cribriform patterns. The obtained ex vivo results highlight prospects of C-OCE for high-level colon malignancy detection. The future endoscopic use of C-OCE will allow targeted biopsy sampling and simultaneous rapid analysis of the heterogeneous morphology of colon tumors

Исходы оперативного лечения патологии щитовидной железы у детей

Background. In recent years there has been a tendency of increase in the proportion of nodular goiter and Graves’ disease in thyroid pathology in children, which necessitates a choice of rational tactics for treatment of these diseases. At present there is no optimal method of treatment for thyroid gland pathology, but one of the methods is surgery. Thyroid surgery due to the determination of the indications and choice of the optimal volume of the surgical intervention continues to be under debate as postoperative complications of surgical treatment of thyroid diseases in children are possible.Aim: to study the outcomes of surgical treatment for thyroid pathology in children, depending on the volume of operation.Materials and methods. This article presents the results of a survey of 77 children operated on in the period of 2002–2016 for Graves’ disease, single-node goiter, and multinodular goiter. The examination included the determination of the levels of ionized calcium and TSH, FT4, FT3 in the blood serum, the evaluation of the functional state of the pituitary-thyroid system, thyroid ultrasound examination, and examination by an otolaryngologist.Results. The incidence of adverse outcomes of surgical treatment in children with nodular goiter was 27%. Adverse outcomes were observed equally often after organ-preserving operations and after thyroidectomy, but they were of different structure. The frequency of postoperative complications after thyroidectomy performed on the nodular goiter was 27%. Complications presented as postsurgical hypoparathyroidism and vocal cord paresis. In children with nodular goiter, after thyroidectomy hypoparathyroidism occurred more frequently than paresis of the vocal folds. Symptomatic hypocalcemia was observed more frequently than the asymptomatic variant, and in most cases hypoparathyrodism was transient. Among children with a single-node goiter who underwent organ-preserving surgery on the thyroid gland postoperative complications such as hypoparathyroidism and paresis of the vocal folds were not identified. Adverse outcomes (disease recurrence, postoperative hypothyroidism) were observed equally often after hemithyrodectomy and node enucleation. But the risk of recurrence of nodular goiter was significantly more common in children after node enucleation than after hemithyroidectomy and postsurgical hypothyroidism was more common in children with nodular goiter after hemithyrodectomy than after node enucleation. The frequency of adverse outcomes of surgical treatment of Graves’ disease in children was 14%. Complications were presented by post-surgical hypoparathyroidism and vocal cord paresis. All complications occurred only after thyroidectomy. When compared adverse outcomes of thyroidectomy were equally common in both nodular goiter and Graves ‘disease, but persistent dysfunction in the form of permanent hypoparathyroidism and permanent vocal cord paresis were more common in Graves’ disease than in nodular goiter.Conclusion. The results obtained demonstrate the heterogeneity of surgical treatment outcomes structure which depends on the surgical intervention volume.Введение. В последние годы отмечается тенденция к росту доли узлового зоба и болезни Грейвса в структуре патологии щитовидной железы у детей, что определяет необходимость выбора рациональной тактики лечения этих заболеваний. Оптимального способа лечения данной патологии щитовидной железы на сегодняшний день не существует, но одним из методов лечения является хирургический. Остается дискуссионным вопрос хирургии щитовидной железы в связи с определением показаний и выбора оптимального объема оперативного вмешательства у детей, так как возможны послеоперационные осложнения.Цель исследования. Изучить исходы оперативного лечения патологии щитовидной железы у детей в зависимости от объема операции.Материал и методы. В статье приводятся сведения о результатах обследования 77 детей, оперированных в период 2002–2016 гг. по поводу болезни Грейвса, одноузлового и многоузлового зоба.Обследование включало определение значения ионизированного кальция в сыворотке крови, оценку функционального состояния гипофизарно-тиреоидной системы: исследовался сывороточный уровень тиреотропного гормона, свободного (св.) тироксина, св. трийодтиронина, проводились ультразвуковое исследование щитовидной железы, осмотр оториноларинголога.Результаты. Установлено, что частота неблагоприятных исходов оперативного лечения среди детей с узловым зобом составила 27%. Осложнения одинаково часто встречались как после органосохраняющих операций, так и после тиреоидэктомии, но отличались по своей структуре. Частота послеоперационных осложнений (послеоперационный гипопаратиреоз, парез голосовых складок) после тиреоидэктомии, выполненной по поводу узлового зоба, составила 27%. У детей с узловым зобом после тиреоидэктомии гипопаратиреоз возникал чаще, чем парез голосовых складок. Симптоматическая гипокальциемия отмечалась чаще, чем бессимптомная, и в абсолютном большинстве случаев гипопаратиреоз носил транзиторный характер.Среди детей с одноузловым зобом, которым проведена органосохраняющая операция на щитовидной железе таких послеоперационных осложнений, как гипопаратиреоз, парез голосовых складок, не выявлено. Неблагоприятные исходы (рецидив заболевания, послеоперационный гипотиреоз) одинаково часто встречались как после гемитиреоидэктомии, так и после энуклеации узла. Но риск развития рецидива узлового зоба достоверно чаще возникал у детей после проведенной энуклеации узла, чем после гемитиреоидэктомии, а послеоперационный гипотиреоз чаще возникал у детей с узловым зобом после гемитиреоидэктомии, чем после энуклеации узла.Частота неблагоприятных исходов оперативного лечения болезни Грейвса (послеоперационный гипопаратиреоз и парез голосовых складок) у детей составила 14%. Все осложнения возникли только после тиреоидэктомии.При сравнении неблагоприятных исходов тиреоидэктомии осложнения одинаково часто встречались как при узловом зобе, так и при болезни Грейвса. Но стойкие нарушения функции в виде перманентного гипопаратиреоза и перманентного пареза голосовых складок чаще встречались при болезни Грейвса, чем при узловом зобе. Полученные результаты позволяют сделать вывод о гетерогенности структуры исходов оперативного лечения, которая зависит от объема оперативного лечения

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Introducing an expanded CAG tract into the huntingtin gene causes a wide spectrum of ultrastructural defects in cultured human cells.

Modeling of neurodegenerative diseases in vitro holds great promise for biomedical research. Human cell lines harboring a mutations in disease-causing genes are thought to recapitulate early stages of the development an inherited disease. Modern genome-editing tools allow researchers to create isogenic cell clones with an identical genetic background providing an adequate "healthy" control for biomedical and pharmacological experiments. Here, we generated isogenic mutant cell clones with 150 CAG repeats in the first exon of the huntingtin (HTT) gene using the CRISPR/Cas9 system and performed ultrastructural and morphometric analyses of the internal organization of the mutant cells. Electron microscopy showed that deletion of three CAG triplets or an HTT gene knockout had no significant influence on the cell structure. The insertion of 150 CAG repeats led to substantial changes in quantitative and morphological parameters of mitochondria and increased the association of mitochondria with the smooth and rough endoplasmic reticulum while causing accumulation of small autolysosomes in the cytoplasm. Our data indicate for the first time that expansion of the CAG repeat tract in HTT introduced via the CRISPR/Cas9 technology into a human cell line initiates numerous ultrastructural defects that are typical for Huntington's disease

Outcomes of surgical treatment of thyroid disease in children

Background. In recent years there has been a tendency of increase in the proportion of nodular goiter and Graves’ disease in thyroid pathology in children, which necessitates a choice of rational tactics for treatment of these diseases. At present there is no optimal method of treatment for thyroid gland pathology, but one of the methods is surgery. Thyroid surgery due to the determination of the indications and choice of the optimal volume of the surgical intervention continues to be under debate as postoperative complications of surgical treatment of thyroid diseases in children are possible.Aim: to study the outcomes of surgical treatment for thyroid pathology in children, depending on the volume of operation.Materials and methods. This article presents the results of a survey of 77 children operated on in the period of 2002–2016 for Graves’ disease, single-node goiter, and multinodular goiter. The examination included the determination of the levels of ionized calcium and TSH, FT4, FT3 in the blood serum, the evaluation of the functional state of the pituitary-thyroid system, thyroid ultrasound examination, and examination by an otolaryngologist.Results. The incidence of adverse outcomes of surgical treatment in children with nodular goiter was 27%. Adverse outcomes were observed equally often after organ-preserving operations and after thyroidectomy, but they were of different structure. The frequency of postoperative complications after thyroidectomy performed on the nodular goiter was 27%. Complications presented as postsurgical hypoparathyroidism and vocal cord paresis. In children with nodular goiter, after thyroidectomy hypoparathyroidism occurred more frequently than paresis of the vocal folds. Symptomatic hypocalcemia was observed more frequently than the asymptomatic variant, and in most cases hypoparathyrodism was transient. Among children with a single-node goiter who underwent organ-preserving surgery on the thyroid gland postoperative complications such as hypoparathyroidism and paresis of the vocal folds were not identified. Adverse outcomes (disease recurrence, postoperative hypothyroidism) were observed equally often after hemithyrodectomy and node enucleation. But the risk of recurrence of nodular goiter was significantly more common in children after node enucleation than after hemithyroidectomy and postsurgical hypothyroidism was more common in children with nodular goiter after hemithyrodectomy than after node enucleation. The frequency of adverse outcomes of surgical treatment of Graves’ disease in children was 14%. Complications were presented by post-surgical hypoparathyroidism and vocal cord paresis. All complications occurred only after thyroidectomy. When compared adverse outcomes of thyroidectomy were equally common in both nodular goiter and Graves ‘disease, but persistent dysfunction in the form of permanent hypoparathyroidism and permanent vocal cord paresis were more common in Graves’ disease than in nodular goiter.Conclusion. The results obtained demonstrate the heterogeneity of surgical treatment outcomes structure which depends on the surgical intervention volume