subtilis were engineered by using this system. Overall, we provide effective tools for genome editing and metabolic engineering of B. subtilis cell factories to produce various biochemicals. © 2020 Wiley Periodicals, Inc.Cushing's disease (CD) is characterised by excess production of adrenocorticotropic hormone (ACTH) by a pituitary corticotroph adenoma, which results in hypercortisolaemia. CD is extremely rare in the paediatric population, and few paediatric endocrinology centres have experience in diagnosing and treating this disease. The clinical presentation of hypercortisolaemia is variable, so proper and rapid diagnosis of CD is often challenging. The molecular pathogenesis of CD was largely unknown until recently. The latest research has revealed somatic mutations in the USP8 gene as the most common pathogenic molecular variants of this disease. Herein, we describe the current state of knowledge of paediatric CD epidemiology, molecular pathogenesis, clinical symptoms, and diagnostics.INTRODUCTION Patients with disorders/differences of sex differentiation/development (DSD) are exposed to mental and physical suffering. The aim of the study was to assess the mental state and the risk of psychological disorders in adult DSD patients in the Polish population, dependence of psychological disorders on therapeutic procedures and to identify groups of disorders which require particular psychological support. MATERIAL AND METHODS The study involved 59 patients with DSD (gonadal dysgenesis, androgen insensitivity syndrome, 5 alpha-reductase deficiency, ovotestis), and with the Y chromosome in the karyotype, aged 16-65 (mean 26), with registered female or male sex. The subjects completed the General Health Questionnaire (GHQ-28), which is used to assess the mental state of adults. Raw results were converted into sten scores using the norms for the Polish adult population. RESULTS A high risk of psychological problems was identified in 24% of the studied DSD patients. It was found that 26% of men and clitoris, as well as DSD patients without earlier corrective surgery of genital organs. DSD patients receiving sex hormone replacement therapy because of hypogonadism may be also at risk of mental problems. These patients require psychological support and an individual approach to their particular needs.Vertigo and balance disorders are common symptoms reported by approximately 15-20% of the adult population worldwide. For many years thyroid diseases have been suspected as the cause of vertigo by ENT physicians. Almost every patient hospitalised due to severe vertigo is investigated for thyroid disease as a suspected cause of acute vestibulopathy. The issue presented in this paper is related to a difficult and poorly understood relationship between autoimmune thyroid disease and peripheral vertigo.Diabetes mellitus is one the most frequent co-morbid conditions in patients with chronic kidney disease (CKD), frequently leading to chronic kidney failure. Progression of CKD accelerates several metabolic disorders, predominantly those related to abnormalities of carbohydrate metabolism. Patients with CKD are usually characterised by an insulin resistance additionally aggravated by several co-morbid conditions (for example chronic low-grade inflammation). Treatment with anti-diabetic medications in patients with CKD remains a challenge because, along with the disease progression, the dosing of several drugs needs to be adjusted to the reduced kidney function (especially those that are excreted intact with urine or as active metabolites). Progression of CKD also increases the risk of hypoglycaemia in patients treated with anti-diabetic drugs, and other adverse drug reactions may occur more frequently. Usefulness of the new generation drugs has not yet been verified in patients with advanced kidney disease (although some of them act through kidney-related mechanisms). The current position statement of the Polish Society of Nephrology Working Group provides practical recommendations for the diagnosis and treatment of type 2 diabetes mellitus in patients with CKD and reduced kidney function.BACKGROUND Adiponectin has been implicated to play a role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Many studies have assessed serum adiponectin concentrations in COPD patients. However, results from different reports were not consistent. To assess the association of serum adiponectin concentrations and COPD, a meta-analysis was performed. METHODS PubMed, Embase, Web of Science and Cochrane Library were searched for eligible studies. Data were extracted, and then standard mean differences (SMDs) and 95% confidence intervals (CI) were calculated. RESULTS Thirteen studies involving a total of 1131 cases and 689 controls were included in this meta-analysis. Combined data indicated that the serum adiponectin levels were higher in COPD patients than those in controls (SMD 1.09, 95% CI [0.73-1.45], P less then 0.001). In the subgroup analyses by disease period, there were similar results in stable COPD patients (SMD 0.77, 95% CI [0.47-1.07], p less then 0.001; I2 = 83.9%, P less then 0.001), AECOPD patients (SMD 2.51, 95% CI [0.71-4.30], P = 0.006; I2 = 95.2%, P less then 0.001) and mixed COPD patients (SMD 1.21, 95% CI [0.67-1.75], P less then 0.001). Furthermore, the serum adiponectin levels were higher in AECOPD patients than those in stable COPD patients (SMD 1.06, 95% CI [0.13-1.99], P = 0.026). CONCLUSIONS This meta-analysis indicates that patients with COPD have higher serum adiponectin concentration than healthy controls. © 2020 The Author(s).Aging-related illnesses are increasing and effective strategies to prevent and/or treat them are lacking. This is because of a poor understanding of therapeutic targets. Low-grade inflammation is often higher in older adults and remains a key risk factor of aging-related morbidities and mortalities. Emerging evidence indicates that abnormal (dysbiotic) gut microbiome and dysfunctional gut permeability (leaky gut) are linked with increased inflammation in older adults. https://www.selleckchem.com/products/pim447-lgh447.html However, currently available drugs do not treat aging-related microbiome dysbiosis and leaky gut, and little is known about the cellular and molecular processes that can be targeted to reduce leaky gut in older adults. Here, we demonstrated that metformin, a safe FDA approved antidiabetic drug, decreased leaky gut and inflammation in high-fat diet-fed older obese mice, by beneficially modulating the gut microbiota. In addition, metformin increased goblet cell mass and mucin production in the onese older gut, thereby decreasing leaky gut and inflammation.