Examination of pituitary adenylate cyclase-activating polypeptide in Parkinson’s disease focusing on correlations with motor symptoms

GeroScience - The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson’s disease (PD)...     

Body composition and newborn birthweight in pregnancies of adolescent and mature women

Teenage pregnancy has been associated with adverse effects for the mother and the newborn (NB). In order to compare body composition (BC) between adolescents (Ad) and mature women (MW) during pregnancy and to determine the difference in birthweight and perinatal morbidity, pregnant Ad (n = 40) and MW (n = 227) were studied. BC changes between the second and third trimesters were determined by multifrequency bioelectrical impedance analysis, and birthweight and NB morbidity were evaluated. During the second and third trimesters of the pregnancy, fat mass was lower in the Ad group [16 kg (13–19)] than in the MW group [22 kg (17–27)] (P < 0.01; median and quartiles 1–3). Fat‐free mass increased by 3.09 kg (2.29–4.20) and 2.20 kg (1.0–3.59) (P ≤ 0.01), and total body water increased by 2.77 L (0.84–4.49) vs. 2.04 L (0.55–3.89) (P = 0.36), in the Ad and MW groups, respectively (median and quartiles 1–3). Birthweight was not significantly different between NBs of Ad (3223 ± 399 g) and NBs of MW (3312 ± 427 g, P = 0.22). The youngest Ad (<18 year old, n = 8) had NB with lower birthweight than MW (3031 ± 503 g, P = 0.06). NBs of Ad mothers showed a non‐significant trend towards a higher rate of morbidity relative to the NBs of MW. In conclusion, the BC of Ad differs from that of MW during pregnancy. In addition, the NB infants of Ad mothers tended to have a lower birthweight than those from MW, a result that suggests that the Ad should be in strict prenatal control.     

Low Quality of Life,Falls, and Pre-Frailty are Associated with Depressive Symptoms in Virologically Suppressed PLWHIV in Salvador,Brazil

AIDS and Behavior - Depression is the leading cause of years lived with disability worldwide and PLWHIV present a higher risk of developing depressive symptoms. We aimed to evaluate depressive...     

Effects of hypocaloric diet and exercise training on inflammation and adipocyte lipolysis in obese postmenopausal women

The purpose of this study was to determine whether a hypocaloric diet with and without exercise training is effective in reducing plasma C-reactive protein, IL-6, TNFalpha, and their soluble receptors (sIL-6R, sTNFR1, and sTNFR2), and whether changes in these inflammatory markers are related to changes in regional lipolysis in obese (body mass index, 32.78 +/- 4.73) postmenopausal women (diet alone, n = 17; diet plus exercise, n = 17). All inflammatory markers were measured by an ELISA method. In vitro lipolysis was evaluated by measuring glycerol release using a one-step enzymatic fluorometric technique. Six months of diet and diet plus exercise decreased total and abdominal fat to a similar degree. Diet plus exercise, but not diet alone, decreased plasma levels of C-reactive protein, IL-6, sIL-6R, and sTNFR1 and increased basal and postreceptor stimulated lipolysis in both abdominal and gluteal regions. Changes in abdominal stimulated lipolysis correlated significantly with changes in plasma IL-6 (r = -0.39) and TNFR1 (r = -047). Thus, diet plus exercise training, but not diet alone, is effective in reducing chronic inflammation in obese postmenopausal women. In addition, modification of chronic inflammation is associated with changes in local adipose tissue metabolism in response to diet and exercise.     

Effects of aripiprazole on circadian prolactin secretion related to pharmacogenetics in healthy volunteers

Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic‐induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty‐one healthy volunteers receiving a 10‐mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro‐aripiprazole plasma concentrations were measured by HPLC‐MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin C_max and AUC_0‐12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen.     

Regression to the Mean Contributes to the Apparent Improvement in Glycemia 3.8 Years After Screening: The ELSA-Brasil Study

OBJECTIVEGlycemic regression is common in real-world settings, but the contribution of regression to the mean (RTM) has been little investigated. We aimed to estimate glycemic regression before and after adjusting for RTM in a free-living cohort of adults with newly ascertained diabetes and intermediate hyperglycemia (IH).RESEARCH DESIGN AND METHODSThe Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a cohort study of 15,105 adults screened between 2008 and 2010 with standardized oral glucose tolerance test and HbA_1c, repeated after 3.84 ± 0.42 years. After excluding those receiving medical treatment for diabetes, we calculated partial or complete regression before and after adjusting baseline values for RTM.RESULTSRegarding newly ascertained diabetes, partial or complete regression was seen in 49.4% (95% CI 45.2–53.7); after adjustment for RTM, in 20.2% (95% CI 12.1–28.3). Regarding IH, regression to normal levels was seen in 39.5% (95% CI 37.9–41.3) or in 23.7% (95% CI 22.6–24.3), depending on use of the World Health Organization (WHO) or the American Diabetes Association (ADA) definition, respectively; after adjustment, corresponding frequencies were 26.1% (95% CI 22.4–28.1) and 19.4% (95% CI 18.4–20.5). Adjustment for RTM reduced the number of cases detected at screening: 526 to 94 cases of diabetes, 3,118 to 1,986 cases of WHO-defined IH, and 6,182 to 5,711 cases of ADA-defined IH. Weight loss ≥2.6% was associated with greater regression from diabetes (relative risk 1.52, 95% CI 1.26–1.84) and IH (relative risk 1.30, 95% CI 1.17–1.45).CONCLUSIONSIn this quasi–real-world setting, regression from diabetes at ∼4 years was common, less so for IH. Regression was frequently explained by RTM but, in part, also related to improved weight loss and homeostasis over the follow-up.     

An Update on the Phenotype,Genotype and Neurobiology of ADCY5-Related Disease

Adenylyl cyclase 5 (ADCY5)-related phenotypes comprise an expanding disease continuum, but much remains to be understood about the underlying pathogenic mechanisms of the disease. ADCY5-related disease comprises a spectrum of hyperkinetic disorders involving chorea, myoclonus, and/or dystonia, often with paroxysmal exacerbations. Hypotonia, developmental delay, and intellectual disability may be present. The causative gene encodes adenylyl cyclase, the enzyme responsible for the conversion of adenosine triphosphate (ATP) to cyclic adenosine-3′,5′-monophosphate (cAMP). cAMP is a second messenger that exerts a wide variety of effects via several intracellular signaling pathways. ADCY5 is the most commonly expressed isoform of adenylyl cyclase in medium spiny neurons (MSNs) of the striatum, and it integrates and controls dopaminergic signaling. Through cAMP pathway, ADCY5 is a key regulator of the cortical and thalamic signaling that control initiation of voluntary movements and prevention of involuntary movements. Gain-of-function mutations in ADCY5 have been recently linked to a rare genetic disorder called ADCY5-related dyskinesia, where dysregulation of the cAMP pathway leads to reduced inhibitory activity and involuntary hyperkinetic movements. Here, we present an update on the neurobiology of ADCY5, together with a detailed overview of the reported clinical phenotypes and genotypes. Although a range of therapeutic approaches has been trialed, there are currently no disease-modifying treatments. Improved in vitro and in vivo laboratory models will no doubt increase our understanding of the pathogenesis of this rare genetic movement disorder, which will improve diagnosis, and also facilitate the development of precision medicine approaches for this, and other forms of hyperkinesia. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society     

Neutralisation of SARS-CoV-2 by anatomical embalming solutions

Teaching and learning anatomy by using human cadaveric specimens has been a foundation of medical and biomedical teaching for hundreds of years. Therefore, the majority of institutions that teach topographical anatomy rely on body donation programmes to provide specimens for both undergraduate and postgraduate teaching of gross anatomy. The COVID-19 pandemic has posed an unprecedented challenge to anatomy teaching because of the suspension of donor acceptance at most institutions. This was largely due to concerns about the potential transmissibility of the SARS-CoV-2 virus and the absence of data about the ability of embalming solutions to neutralise the virus. Twenty embalming solutions commonly used in institutions in the United Kingdom and Ireland were tested for their ability to neutralise SARS-CoV-2, using an established cytotoxicity assay. All embalming solutions tested neutralised SARS-CoV-2, with the majority of solutions being effective at high-working dilutions. These results suggest that successful embalming with the tested solutions can neutralise the SARS-CoV-2 virus, thereby facilitating the safe resumption of body donation programmes and cadaveric anatomy teaching.