Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment.

Early life is a period of considerable plasticity and vulnerability and insults during that period can disrupt the homeostatic equilibrium of the developing organism, resulting in adverse developmental programming and enhanced susceptibility to disease. Fetal exposure to prenatal stress can impede optimum brain development and deranged mother's hypothalamic-pituitary-adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring's stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment.

In-hospital screening for diabetes mellitus with HbA1c in an internal medicine department was not useful; a prospective pilot study.

BACKGROUND: Screening inpatients for diabetes mellitus may be a good opportunity to detect undiagnosed cases and several studies have demonstrated the feasibility and usefulness of this practice. HbA1c has been suggested as the method of choice due to the effects of acute illness on glucose. The aim of this study was to evaluate a screening protocol based on HbA1c to identify inpatients with undiagnosed diabetes mellitus in an internal medicine department. METHODS: We conducted a prospective study of all admissions in the internal medicine department of a 412-bed community hospital in Greece during a 6-month period. Candidates for screening based on the American Diabetes Association's recommendations were screened with HbA1c. Patients with very poor health status and patients with conditions that may interfere with HbA1c measurement or interpretation were excluded. RESULTS: Of 463 patients (median age 74) only a small proportion (14.9%) were candidates for screening with HbA1c. Known diabetes mellitus, a low admission glucose, severe anemia or blood loss and poor health status were the most common reasons of exclusion. Among the 55 screened patients, 7 had diabetes (based on HbA1c ≥ 6.5%). However, in only 1 of them HbA1c was above target considering the patients' health status. Categorical agreement (no diabetes, prediabetes, diabetes) between morning glucose and HbA1c was low. However, the concordance between a morning glucose < 125 mg/dl and HbA1c < 6.5% was > 90%. CONCLUSIONS: In settings similar to ours (very elderly patients, high rate of conditions that confound the use of HbA1c and high rate of patients with poor health status), untargeted screening of inpatients with HbA1c is unlikely to be cost-effective. A morning glucose during hospitalization may be a better first step for screening.

Atypical Presentation of IgA Nephropathy Mimicking Acute Pyelonephritis.

BACKGROUND: IgA glomerulonephritis may present with hematuria, flank pain, and fever. This clinical presentation may be easily confused with acute pyelonephritis. CASE REPORT: We present the case of a 25-year-old female with a typical clinical presentation for acute pyelonephritis (high fever, left flank pain, left costovertebral angle tenderness, hematuria, elevated inflammatory markers, and a hypoenhancing region in the left kidney on contrast-enhanced computed tomography). However, urine and blood cultures were both negative, the serum creatinine was elevated, and the urinalysis revealed significant proteinuria and dysmorphic red blood cells. A kidney biopsy confirmed a diagnosis of IgA nephropathy. She was treated with a combination of lisinopril and methylprednisolone, with good response. CONCLUSION: Gross hematuria, especially in the absence of pyuria or bacteriuria, should raise the suspicion for underlying IgA nephropathy, even if the rest of the clinical presentation is typical for a urinary tract infection. The presence of significant proteinuria, red blood cell casts, and dysmorphic red blood cells are useful clues suggesting glomerular disease.