Coexistence of D3R typical and atypical signaling in striatonigral neurons during dopaminergic denervation. Correlation with D3nf expression changes

Dopamine D₃R are widely expressed in basal ganglia where interact with D₁R. D₃R potentiate cAMP accumulation and GABA release stimulated by D₁R in striatonigral neurons through “atypical” signaling. During dopaminergic denervation, D₃R signaling changes to a “typical” in which antagonizes the effects of D₁R, the mechanisms of this switching are unknown. D₃nf splice variant regulates membrane anchorage and function of D₃R and decreases in denervation; thus, it is possible that D₃R signaling switching correlates with changes in D₃nf expression and increases of membranal D₃R that mask D₃R atypical effects. We performed experiments in unilaterally 6-hydroxydopamine lesioned rats and found a decrease in mRNA and protein of D₃nf, but not of D₃R in the denervated striatum. Proximity ligation assay showed that D₃R-D₃nf interaction decreased after denervation, whereas binding revealed an increased B_max in D₃R. The new D₃R antagonized cAMP accumulation and GABA release stimulated by D₁R; however, in the presence of N-Ethylmaleimide (NEM), to block G_i protein signaling, activation of D₃R produced its atypical signaling stimulating D₁R effects. Finally, we investigated if the typical and atypical effects of D₃R modulating GABA release are capable of influencing motor behavior. Injections of D₃R agonist into denervated nigra decreased D₁R agonist-induced turning behavior but potentiated it in the presence of NEM. Our data indicate the coexistence of D₃R typical and atypical signaling in striatonigral neurons during denervation that correlated with changes in the ratio of expression of D₃nf and D₃R isoforms. The coexistence of both atypical and typical signaling during denervation influences motor behavior.     

Acute Exposure to SiO2 Nanoparticles Affects Protein Synthesis in Bergmann Glia Cells

Neurotoxicity Research - Attractive due to an alleged high biocompatibility, silica nanoparticles have been widely used in the field of nanomedicine; however, their proven capacity to induce the...     

Obstetric and perinatal outcome in 200 infants conceived from vitrified oocytes

Cryopreservation of oocytes by vitrification is a promising new technique for assisted human reproduction. Any new technical development must be accompanied with data concerning obstetric and perinatal outcome. This study analysed the obstetric and perinatal outcomes in 165 pregnancies and 200 infants conceived following oocyte vitrification cycles in three assisted reproduction centres. The results indicate that the mean birth weight and the incidence of congenital anomalies are comparable to that of spontaneous conceptions in fertile women or infertile women undergoing in-vitro fertilization treatment. These preliminary findings may provide reassuring evidence that pregnancies and infants conceived following oocyte vitrification are not associated with increased risk of adverse obstetric and perinatal outcomes.     

Efficacy and renal toxicity of one daily dose of amikacin versus conventional dosage regime

This study assessed the efficacy and renal toxicity of one daily dose of amikacin versus several doses in infected full-term newborns. A clinical trial was conducted with 120 patients who were divided into two groups: group A (n = 60), infants who received amikacin 20 mg/kg/d in one dose; and group B (n = 60), infants who received amikacin 10 mg/kg/d every 12 hours. Both groups also received ampicillin 100 mg/kg/day. Blood levels of amikacin, urinary beta(2)-microglobulin (beta(2)-m), serum creatinine (SCr), and glomerular filtration rate (GFR) were measured in each patient. No significant difference was found in demographic characteristics as well as in their beta(2)-m, SCr, and GFR levels. Infection was resolved in 96% for infants of group A and 91% for group B ( P = 0.254). Renal toxicity was present in 20 versus 31.6%, respectively ( P = 0.211). In both groups no significant difference was found in peak amikacin levels, whereas trough levels were higher for group B ( P = 0.004). No significant difference was found in efficacy or renal toxicity in either group. We recommend using amikacin in one daily dose. It could diminish the manipulation of intravenous access, reducing the risk of nosocomial infections.     

Usefulness of the CAT,LCOPD, EQ-5D and COPDSS Scales in Understanding the Impact of Lung Disease in Patients with Alpha-1 Antitrypsin Deficiency

Alpha-1-antitrypsin deficiency (AATD) is an inherited disorder responsible for early onset emphysema associated with a significant impairment of health-related quality of life (HRQoL). Our aim was to assess the usefulness of different instruments to evaluate the HRQoL in patients with AATD compared to non-AATD COPD. Observational, cross-sectional study in which all patients filled out a series of questionnaires: the COPD severity score (COPDSS), the EuroQoL 5-Dimensions (EQ-5D), the Living with COPD (LCOPD) and the COPD Assessment Test (CAT).

A total of 96 patients were included, 35 with AATD (mean age 56.5 yrs, 57.1% male and mean FEV₁(%) 48.7% and 61 non-AATD COPD (70.3 yrs, 80.3% men and FEV₁(%) 47%. The questionnaire scores were similar, with a tendency towards worse scores in AATD for the EQ-5D (VAS) (64.8 (20.2) vs. 71.6 (17.1); p = 0.08). The correlations between the different scores and FEV1(%) were significant in both groups for COPDSS and LCOPD, but not for CAT and EQ-5D. In general, the correlations of scores with FEV₁(%) were stronger for AATD compared with non-AATD COPD patients: COPDSS r = ?0.570, p < 0.01 for AATD and r = ?0.260, p < 0.05 for COPD; LCOPD r = ?0.502, p < 0.001 for AATD and r = ?0.304, p < 0.05 for non-AATD COPD.

Patients with AATD have a similar degree of HRQoL impairment as older subjects with non-AATD COPD and showed a stronger correlation between HRQoL measurements and lung function impairment compared with non-AATD COPD. This may be related to the characteristics of the disease in these patients who are usually younger, with less co-morbidity and lower smoking consumption.     

Perception of risk and impact of the COVID-19 pandemic on patients with rheumatic diseases: a case–control study

Clinical Rheumatology - Risk perception of the COVID-19 pandemic may affect chronic disease outcomes among patients with rheumatic diseases (RD). To describe and compare the perception of risk and...     

Telenutrition: Changes in Professional Practice and in the Nutritional Assessments of Italian Dietitian Nutritionists in the COVID-19 Era

The COVID-19 pandemic has brought about various restrictions around the world, and its impact on healthcare has been enormous: RDNs have had to shift from in-person interactions with clients to telenutrition consultations, encountering obstacles. We designed the first survey to investigate the changes in RDN practices related to telenutrition provision after the onset of the pandemic through an online survey in Italy. Four hundred and thirty-six responses were analyzed. Before the pandemic, only 16% of Italian RDNs provided telenutrition; this percentage increased significantly up to 63% (p < 0.001). Among patients, the lack of interest in accessing telenutrition (30.9%) and the Internet (16.7%) were the most frequently reported barriers. Among RDNs, one of the main obstacles was their inability to conduct nutritional evaluation or monitoring activities (24.4%). Our survey indicated that increased adoption of telenutrition can be a valid, safe alternative to face-to-face visits. Telenutrition was mainly used by young RDNs (20–39 years) with fewer years of professional experience (0–20 years) and master’s degrees. Remote nutrition can enable RDNs to maintain normal workloads and provide patients with uninterrupted access to nutritional healthcare. It is important that RDNs using telemedicine resources possess the ability to provide high-quality, efficient, and secure services using evidence-based guidance.