Notes

[Development of classification conditions with regard to uveitis through the standardization of uveitis nomenclature (SUN) functioning group].
11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of.

We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021.

We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions.

11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable.

Open Science Framework, 10.17605/OSF.IO/NR7UV.
Open Science Framework, 10.17605/OSF.IO/NR7UV.
Endocrine disorders are common in patients with 22q11.2 deletion syndrome (22q11.2DS). This study aimed to elucidate the clinical manifestations of endocrine disorders, including parathyroid, thyroid and growth disorders, in Taiwanese patients with 22q11.2DS.

From 1994 to 2020, the medical records of 138 patients with 22q11.2DS diagnosed at a tertiary referral medical center in Taiwan were thoroughly reviewed retrospectively.

Hypocalcemia was detected in 57 of 135 patients (42%); 33 of 104 patients (32%) had hypoparathyroidism, and in 87% of them, hypocalcemia was detected before the age of one. Zoligratinib chemical structure Most patients had precipitating stressors during symptomatic hypocalcemic episodes. Eighteen of 29 patients had overt hypoparathyroidism at the last visit 11 had persistent hypoparathyroidism and the other seven had recurrent hypoparathyroidism. Four of 84 patients had thyroid disorders, including thyroid developmental anomalies in two, dyshormonogenesis in one and Graves' disease in one. Fifty of 126 patients (parathyroidism is a common endocrine disorder in patients with 22q11.2DS. It is prudent to assess parathyroid function at diagnosis and during follow-up, especially in the presence of stress, to prevent symptomatic hypocalcemia. Although thyroid disorders are not so common as hypoparathyroidism, screening of thyroid dysfunction is justified in these patients. Patients with 22q11.2DS demonstrate a retarded growth pattern with a tendency of catch-up and regular monitoring of growth is indicated.
The offspring of women with gestational diabetes mellitus (GDM) have a high predisposition to developing type 2 diabetes during childhood and adulthood. The aim of the study was to evaluate how GDM exposure in the second half of pregnancy contributes to hepatic glucose intolerance through a mouse model.

By creating a GDM mouse model, we tested glucose and insulin tolerance of offspring by intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT), and pyruvate tolerance test (PTT). In addition, we checked the expression of genes IGF2/H19, FoxO1, and DNMTs in the mouse liver by RT-qPCR. Pyrosequencing was used to detect the methylation status on IGF2/H19 differentially methylated regions (DMRs).
insulin stimulation experiments were performed to evaluate the effect of different insulin concentrations on HepG2 cells. Moreover, we detect the interaction between FoxO1 and DNMT3A by chromatin immunoprecipitation-quantitative PCR (Chip-qPCR) and knock-down experiments on HepG2 cells.

We fo demonstrated that the intrauterine hyperinsulinemia environment has increased hepatic FoxO1 levels and subsequently increased expression of DNMT3A and epigenetic alterations on IGF2/H19 DMRs. These findings provide potential molecular mechanisms responsible for glucose intolerance and insulin resistance in the first male generation of GDM mice.Progranulin (PGRN), a growth factor, is abundantly expressed in a broad range of tissues and cell types with pleiotropic functions including inflammation, neurodegeneration, and facilitating lysosome acidification. PGRN binds to TNF receptors (TNFR) and inhibits downstream inflammatory signaling pathways. TNFR is a well-known predictor of glomerular filtration rate (GFR) decline in a variety of diseases. Therefore, we measured circulating PGRN in addition to TNFR using an enzyme-linked immunosorbent assay and explored whether it predicted renal prognosis in 201 Japanese patients with type 2 diabetes. During a median follow-up of 7.6 years, 21 participants reached primary renal endpoint, which involves a decline of at least 57% in eGFR from baseline, or the onset of end-stage renal disease. Univariate Cox regression analysis revealed that classical renal measures (GFR and albuminuria), two TNF-related biomarkers (PGRN and TNFR), and BMI were associated with this outcome. Multivariate analysis demonstrated that high levels of PGRN [HR 2.50 (95%CI 2.47-2.52)] or TNFR1 [HR 5.38 (95%CI 5.26-5.50)] were associated with this outcome after adjusting for relevant covariates. The high levels of PGRN as well as TNFR1 were associated with a risk of primary renal outcome in patients with type 2 diabetes after adjusting for established risk factors.Pituitary adenomas (PAs), usually benign lesions, can sometimes present with "aggressive" features (rapid growth, local invasiveness, scarce response to conventional treatments). Despite the fact that a few genetic alterations have been associated to this clinical behavior, the role of epigenetic modifications, mainly methylation and miRNAs activity, is now opening new frontiers in this field. We evaluated the methylation profile of 21 PA (11 GH-omas, 10 nonfunctioning tumors-NFPAs) samples from TNS surgery and 5 normal pituitaries, collected at our neurosurgery between 2015 and 2017. DNA was extracted and sequenced, selecting 184,841 target regions. Moreover, methylation profiles were correlated with demographic, radiological, and clinicopathological features. NFPAs showed higher methylation levels vs. GH-omas, with 178 differentially methylated regions (DMRs) mainly consisting of noncoding and intronic sequences, and mostly localized in the open sea regions. We also found three hypermethylated genes (C7orf50, GNG7, and BAHCC1) involved in tumorigenesis processes and potentially influencing pituitary tumor pathophysiology. Among the clinicopathological features, only the maximum diameter resulted significantly higher in NFPAs. Our data provide further evidence of the complex epigenetic background of pituitary tumors. In line with the current literature, we confirmed a significant prevalence of hypermethylation in NFPAs vs. GH-omas, whose pathophysiological consequence is yet to be defined.
The impact of diabetes on reproductive function is still not clearly defined. This study aimed to evaluate accelerated ovarian aging in women with type 2 diabetes mellitus (T2DM) and its association with adverse lipid profile.

Female patients with T2DM (n=964) and non-T2DM controls (n=263) aging from 18-80 years were included. Levels of circulating sex hormones were measured at the follicular phase in menstruating women. We analyzed the age-specific trends in the levels of sex hormones between T2DM and controls. The correlations of sex hormones with the lipid profile, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and triglycerides (TG) were also evaluated.

In the temporal trends analysis, LH and FSH both started to increase obviously approximately from the age of 45 years among patients with T2DM, and displayed peaks of LH and FSH among patients with T2DM aged between 61 and 65, both of which were obviously earlier than that iprofile in patients with T2DM. With an ever increasing number of female patients with T2DM diagnosed at younger ages, the accelerated ovarian aging and its adverse impacts in T2DM need to be carefully managed.
This study suggests that patients with T2DM have accelerated ovarian aging, and it is correlated with the occurrence of disturbed lipid profile in patients with T2DM. With an ever increasing number of female patients with T2DM diagnosed at younger ages, the accelerated ovarian aging and its adverse impacts in T2DM need to be carefully managed.The COVID-19 pandemic has adversely affected population mental health. Periods of psychological distress can induce menstrual dysfunction. We previously demonstrated a significant disruption in women's reproductive health during the first 6 months of the pandemic. The present study investigates longer-term reproductive and mental health disturbances. A cross-sectional online survey was completed by 1335 women of reproductive age in April 2021. It included validated standardized measures of depression (PHQ-9), anxiety (GAD-7) and sleep quality (PSQI). 581 (56%) of women reported an overall change in their menstrual cycle since the beginning of the pandemic. There was no change in median cycle length [28 days (28-30)] or days of menses [5 (4-5)], but there was a wider variability in minimum (p less then 0.0001) and maximum (p less then 0.0001) cycle length. There was a significant increase in heavy menstrual bleeding, painful periods and missed periods compared to pre-pandemic (all p less then 0.0001). 64% of women reported worsening pre-menstrual symptoms. Rates of severe depression, anxiety and poor sleep were more than double those from large scale representative community samples. Poor sleep quality was an independent predictor of overall change in menstrual cycle (OR=1.11, 95%CI 1.05-1.18), and missed periods (OR=1.11, 95%CI 1.03-1.19) during the pandemic. Increased anxiety was independently associated with a change from non-painful to painful periods (OR=1.06, 95%CI 1.01-1.11) and worsening of pre-menstrual symptoms (OR=1.06, 95%CI 1.01-1.07) during the pandemic. The COVID-19 pandemic continues to bear a significant impact on female reproductive health. Increased levels of psychological distress and poor sleep are associated with menstrual cycle disruption.
The relationship between pancreatic cancer (PC) and type 2 diabetes mellitus (T2DM) has long been widely recognized, but the interaction mechanisms are still unknown. This study was aimed to investigate the shared gene signatures and molecular processes between PC and T2DM.

The Gene Expression Omnibus (GEO) database was used to retrieve the RNA sequence and patient information of PC and T2DM. Weighted gene co-expression network analysis (WGCNA) was performed to discover a co-expression network associated with PC and T2DM. Enrichment analysis of shared genes present in PC and T2DM was performed by ClueGO software. These results were validated in the other four cohorts based on differential gene analysis. The predictive significance of S100A6 in PC was evaluated using univariate and multivariate Cox analyses, as well as Kaplan-Meier plots. The biological process of S100A6 enrichment in PC was detected using Gene Set Enrichment Analysis (GSEA). The involvement of S100A6 in the tumor immune microenvironment (TIME) was assessed by CIBERSORT.
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