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This article, titled "Impact of assisted reproductive techniques on congenital heart disease: insights from a tertiary care centre and literature review," explores the correlation between assisted reproductive techniques (ART) and congenital heart disease (CHD). The study included a retrospective cohort of fetuses conceived spontaneously and through ART, and classified CHDs into different categories based on anatomical criteria and severity. The results showed that the prevalence of CHD was significantly higher in ART-conceived fetuses compared to spontaneous pregnancies, and severe CHD was more frequent in ART pregnancies. The study concludes that there is a relevant association between conception techniques and the type and severity of CHD among ART-conceived fetuses. [Extracted from the article]

This article, published in the journal Ultrasound in Obstetrics & Gynecology, describes a study conducted at two referral Fetal Medicine units to examine the sonographic features of the caudo-thalamic (CT) groove in the third trimester of pregnancy. The study included a cohort of normal fetuses who underwent 3D ultrasound of the fetal brain, and the results showed that the CT groove was consistently visible in the majority of cases. Additionally, the researchers found five cases with abnormal appearance of the groove, which suggests that abnormal findings at this level can be detected during antenatal brain ultrasound. The study provides valuable insights into fetal neurosonography and its potential for detecting abnormalities. [Extracted from the article]

Abstract: Aims: Glutamate decarboxylase (GAD) antibodies are the most widely used predictive marker for Type 1 diabetes, but many individuals currently found to be GAD antibody‐positive are unlikely to develop diabetes. We have shown previously that radioimmunoassays using N‐terminally truncated 35S‐GAD65(96–585) offer better disease specificity with similar sensitivity to full‐length 35S‐GAD65(1–585). To determine whether assay performance could be improved further, we evaluated a more radically truncated 35S‐GAD65(143–585) radiolabel. Methods: Samples from people with recent‐onset Type 1 diabetes (n = 157) and their first‐degree relatives (n = 745) from the Bart's–Oxford family study of childhood diabetes were measured for GAD antibodies using 35S‐labelled GAD65(143–585). These were screened previously using a local radioimmunoassay with 35S‐GAD65(1–585). A subset was also tested by enzyme‐linked immunosorbent assay (ELISA), which performs well in international workshops, but requires 10 times more serum. Results were compared with GAD antibody measurements using 35S‐GAD65(1–585) and 35S‐GAD65(96–585). Results: Sensitivity of GAD antibody measurement was maintained using 35S‐GAD65(143–585) compared with 35S‐GAD65(1–585) and 35S‐GAD65(96–585). Specificity for Type 1 diabetes was improved compared with 35S‐GAD65(1–585), but was similar to 35S‐GAD65(96–585). Relatives found to be GAD antibody‐positive using these truncated labels were at increased risk of diabetes progression within 15 years, compared with those positive for GAD(1–585) antibody only, and at similar risk to those found GAD antibody‐positive by ELISA. Conclusions: The first 142 amino acids of GAD65 do not contribute to epitopes recognized by Type 1 diabetes‐associated GAD antibodies. Low‐volume radioimmunoassays using N‐terminally truncated 35S‐GAD65 are more specific than those using full‐length GAD65 and offer practical alternatives to the GAD antibody ELISA for identifying children at increased risk of Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to investigate the role of systemic inflammation by means of the neutrophil‐to‐lymphocyte ratio (NLR) in men with erectile dysfunction (ED). Complete demographic, clinical, and laboratory data from 279 consecutive men with newly diagnosed ED were analyzed. Health‐significant comorbidities were scored with the Charlson Comorbidity Index (CCI). A complete blood count was requested for every man, and the NLR was calculated for every individual. Patients were invited to complete the IIEF questionnaire. Logistic regression models tested the odds (OR, 95% CI) of severe ED (defined as IIEF‐EF <11, according to Cappelleri's criteria) after adjusting for age, BMI, comorbidities (CCI >0), metabolic syndrome, NLR, cigarette smoking, and color duplex Doppler ultrasound parameters. Likewise, LNR values were also dichotomized according to the most informative cutoff predicting severe ED using the minimum p value approach. Median [IQR] age of included men was 51 [40–64] years. Of all, 87 (31%) men had severe ED. Men with severe ED were older (median [IQR] age: 61 [47–67] vs. 49 [39–58] years) and had a higher rate of CCI>0 [46/87 (53%) vs. 44/192 (23%) patients]. Thereof, NLR was dichotomized according to the most informative cutoff (NLR>3); patients with severe ED more frequently had NLR>3 as compared to all other ED patients [namely, 18/87 (21%) vs. 13/192 (7%)]. At multivariable logistic regression analysis, NLR>3.0 emerged as an independent predictor (OR [CI] 2.43 [1.06; 5.63]) of severe ED, after accounting for other clinical variables. A NLR>3 increased the risk of having severe ED in our cohort, boosting the already existing evidence linking systemic inflammation to ED. Moreover, this easily obtainable index can be clinically useful in better risk‐stratifying patients with ED. [ABSTRACT FROM AUTHOR]

Aims: To describe the in vitro characteristics and antidiabetic in vivo efficacy of the novel glucagon-like peptide-1 receptor agonist (GLP-1RA) GL0034., Materials and Methods: Glucagon-like peptide-1 receptor (GLP-1R) kinetic binding parameters, cyclic adenosine monophosphate (cAMP) signalling, endocytosis and recycling were measured using HEK293 and INS-1832/3 cells expressing human GLP-1R. Insulin secretion was measured in vitro using INS-1832/3 cells, mouse islets and human islets. Chronic administration studies to evaluate weight loss and glycaemic effects were performed in db/db and diet-induced obese mice., Results: Compared to the leading GLP-1RA semaglutide, GL0034 showed increased binding affinity and potency-driven bias in favour of cAMP over GLP-1R endocytosis and β-arrestin-2 recruitment. Insulin secretory responses were similar for both ligands. GL0034 (6 nmol/kg) led to at least as much weight loss and lowering of blood glucose as did semaglutide at a higher dose (14 nmol/kg)., Conclusions: GL0034 is a G protein-biased agonist that shows powerful antidiabetic effects in mice, and may serve as a promising new GLP-1RA for obese patients with type 2 diabetes., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To evaluate the ability of ladarixin (LDX, 400 mg twice-daily for three cycles of 14 days on/14 days off), an inhibitor of the CXCR1/2 chemokine receptors, to maintain C-peptide production in adult patients with newly diagnosed type 1 diabetes., Materials and Methods: A double-blind, randomized (2:1), placebo-controlled study was conducted in 45 males and 31 females (aged 18-46 years) within 100 days of the first insulin administration. The primary endpoint was the area under the curve (AUC) for C-peptide in response to a 2-hour mixed meal tolerance test (AUC [0-120 min] ) at week 13 ± 1. Secondary endpoints included C-peptide AUC (15-120 min) , HbA1c, daily insulin requirement, severe hypoglycaemic events (SHE), the proportion of subjects achieving HbA1c less than 7.0% without SHE and maintaining a residual beta cell function. Follow-up assessments were scheduled at weeks 13 ± 1, 26 ± 2 and 52 ± 2., Results: In total, 26/26 (100%, placebo) and 49/50 (98%, LDX) patients completed week 13. The mean change from baseline to week 13 in C-peptide AUC (0-120 min) was -0.144 ± 0.449 nmol/L with placebo and 0.003 ± .322 nmol/L with LDX. The difference was not significant (0.149 nmol/L, 95% CI -0.04 to 0.33; P = .122). At week 26, the proportion of patients with HbA1c less than 7.0% without SHE was transiently higher in the LDX group (81% vs. 54%, P = .024). Otherwise, no significant secondary endpoint differences were noted. Transient metabolic benefit was seen at week 26 in favour of the LDX group in the prespecified subpopulation with fasting C-peptide less than the median value at screening., Conclusions: In newly diagnosed patients with type 1 diabetes, short-term LDX treatment had no appreciable effect on preserving residual beta cell function., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To investigate the effect of kisspeptin on glucose-stimulated insulin secretion and appetite in humans., Materials and Methods: In 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m -2 ), we compared the effects of 1 nmol kg -1 h -1 kisspeptin versus vehicle administration on glucose-stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose-stimulated insulin secretion in vitro in human pancreatic islets and a human β-cell line (EndoC-βH1 cells)., Results: Kisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose-stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men., Conclusions: Collectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin-based therapies for reproductive and potentially metabolic conditions., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)