Developmental beta-cell death orchestrates the islet's inflammatory milieu by regulating immune system crosstalk.

While pancreatic beta-cell proliferation has been extensively studied, the role of cell death during islet development remains incompletely understood. Using a genetic model of caspase inhibition in beta cells coupled with mathematical modeling, we here discover an onset of beta-cell death in juvenile zebrafish, which regulates beta-cell mass. Histologically, this beta-cell death is underestimated due to phagocytosis by resident macrophages.

LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype.

Background: The complex aetiology of type 1 diabetes (T1D), characterised by a detrimental cross-talk between the immune system and insulin-producing beta cells, has hindered the development of effective disease-modifying therapies. The discovery that the pharmacological activation of LRH-1/NR5A2 can reverse hyperglycaemia in mouse models of T1D by attenuating the autoimmune attack coupled to beta cell survival/regeneration prompted us to investigate whether immune tolerisation could be translated to individuals with T1D by LRH-1/NR5A2 activation and improve islet survival.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from individuals with and without T1D and derived into various immune cells, including macrophages and dendritic cells.

Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8 T cell activity and biomarker during the evolution of type 1 diabetes.

Aims/hypothesis: Surviving beta cells in type 1 diabetes respond to inflammation by upregulating programmed death-ligand 1 (PD-L1) to engage immune cell programmed death protein 1 (PD-1) and limit destruction by self-reactive immune cells. Extracellular vesicles (EVs) and their cargo can serve as biomarkers of beta cell health and contribute to islet intercellular communication. We hypothesised that the inflammatory milieu of type 1 diabetes increases PD-L1 in beta cell EV cargo and that EV PD-L1 may protect beta cells against immune-mediated cell death.

Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8+ T cell activity and biomarker during the evolution of Type 1 Diabetes.

Aims/hypothesis: Surviving beta cells in type 1 diabetes respond to inflammation by upregulating programmed death-ligand 1 (PD-L1) to engage immune cell programmed death-1 (PD-1) and limit destruction by self-reactive immune cells. Extracellular vesicles (EVs) and their cargo can serve as biomarkers of beta cell health and contribute to islet intercellular communication. We hypothesized that the inflammatory milieu of type 1 diabetes increases PD-L1 in beta cell EV cargo and that EV PD-L1 may protect beta cells against immune-mediated cell death.

PRAP study-partial versus radical adrenalectomy in hereditary pheochromocytomas.

Objective: Hereditary pheochromocytoma (hPCC) commonly develops bilaterally, causing adrenal insufficiency when standard treatment, radical adrenalectomy (RA), is performed. Partial adrenalectomy (PA) aims to preserve adrenal function, but with higher recurrence rates. This study compares outcomes of PA versus RA in hPCC.

Did we observe changes in obstetric interventions in SARS-CoV-2 infected pregnant women at the beginning of COVID-pandemic in Belgium? Results of a nationwide population-based study.

Background: Pregnant women are more vulnerable to the severe effects of COVID-19 compared to their non-pregnant peers. Early in the pandemic, there was a rise in cesarean deliveries and preterm births among infected pregnant women. This study aims to evaluate whether there were any changes in obstetric interventions during the first two waves of the pandemic in Belgium.

Defining Gestational Thyroid Dysfunction Through Modified Nonpregnancy Reference Intervals: An Individual Participant Meta-analysis.

Background: Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals.

Methods: We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy.

Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the Ca response to glucose supported by vitamin B6.

Coordination of cellular activity through Ca enables β cells to secrete precise quantities of insulin. To explore how the Ca response is orchestrated in space and time, we implement optogenetic systems to probe the role of individual β cells in the glucose response. By targeted β cell activation/inactivation in zebrafish, we reveal a hierarchy of cells, each with a different level of influence over islet-wide Ca dynamics.

Bax Inhibitor-1 preserves pancreatic β-cell proteostasis by limiting proinsulin misfolding and programmed cell death.

The prevalence of diabetes steadily increases worldwide mirroring the prevalence of obesity. Endoplasmic reticulum (ER) stress is activated in diabetes and contributes to β-cell dysfunction and apoptosis through the activation of a terminal unfolded protein response (UPR). Our results uncover a new role for Bax Inhibitor-One (BI-1), a negative regulator of inositol-requiring enzyme 1 (IRE1α) in preserving β-cell health against terminal UPR-induced apoptosis and pyroptosis in the context of supraphysiological loads of insulin production.

Fertility and sexual activity in patients with Triple A syndrome.

Objective: Triple A syndrome, caused by autosomal recessively inherited mutations in the gene is characterized by alacrima, achalasia, adrenal insufficiency, and neurological impairment. To the best of our knowledge, no patients of both sexes have been reported to have offspring. Our aim was to assess the causes of infertility in male patients with this multisystemic syndrome, and to present a female patient that spontaneously conceived a child.

Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis.

Background: Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death.

Methods: We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice.

Seven preoperative factors have strong predictive value for postoperative pneumonia in patients undergoing thoracoscopic lung cancer surgery.

Background: Postoperative pneumonia (POP) is a hospital acquired pneumonia that occurs >48 hours after tracheal intubation. The diagnosis of POP should be based on clinical and radiological findings within 30 days after surgery. It is a common complication after thoracoscopic surgery for lung cancer patients.

Gestation-suppressed serum TSH levels during early pregnancy are not associated with altered maternal and neonatal outcomes.

Objective: The aim of the study was to investigate the impact of suppressed serum TSH levels (sTSH) during early pregnancy on maternal and neonatal outcomes.

Methods: In this single-centre, retrospective cohort study 1081 women were screened at 11.8 ± 2.

Impact of thyroid hormone treatment on maternal pregnancy outcomes in women with subclinical hypothyroidism without TPOAb: a retrospective cross-sectional study.

Background: Evidence on the impact of thyroid hormone treatment (LT4) on maternal pregnancy outcomes in women with subclinical hypothyroidism (SCH) without thyroid peroxidase antibodies (TPOAb) positivity is scarce.

Methods: Single centre, cross-sectional study in 1460 women screened for TSH, free T4 and TPOAb at median 13 (11-17) weeks of gestation during the period 2013-2014. Exclusion criteria were twin- and assisted reproduction pregnancies, TPO positivity, overt thyroid dysfunction, and treatment with LT4 before screening.

Adipose tissue plasticity in pheochromocytoma patients suggests a role of the splicing machinery in human adipose browning.

Adipose tissue from pheochromocytoma patients acquires brown fat features, making it a valuable model for studying the mechanisms that control thermogenic adipose plasticity in humans. Transcriptomic analyses revealed a massive downregulation of splicing machinery components and splicing regulatory factors in browned adipose tissue from patients, with upregulation of a few genes encoding RNA-binding proteins potentially involved in splicing regulation. These changes were also observed in cell culture models of human brown adipocyte differentiation, confirming a potential involvement of splicing in the cell-autonomous control of adipose browning.

Why does the immune system destroy pancreatic β-cells but not α-cells in type 1 diabetes?

A perplexing feature of type 1 diabetes (T1D) is that the immune system destroys pancreatic β-cells but not neighbouring α-cells, even though both β-cells and α-cells are dysfunctional. Dysfunction, however, progresses to death only for β-cells. Recent findings indicate important differences between these two cell types.

PAI-BEL: a Belgian multicentre survey of primary adrenal insufficiency.

Objective: Primary adrenal insufficiency (PAI) is a rare disease with an increasing prevalence, which may be complicated by life-threatening adrenal crisis (AC). Good quality epidemiological data remain scarce. We performed a Belgian survey to describe the aetiology, clinical characteristics, treatment regimens, comorbidities and frequency of AC in PAI.

Incidence and clinical and microbiological features of invasive and probable invasive streptococcal group A infections in children and adults in the Brussels-Capital Region, 2005-2020.

Assess the incidence, risk factors, clinical and microbiological features, and outcome of both probable invasive and invasive group A Streptococcus (GAS) infections in children and adults in the BrusselsCapital Region between 2005 and 2020. A retrospective, multicentric study was performed in three university hospitals in Brussels. Patients were identified through the centralized laboratory information system.