Imaging findings of primary adrenal tumors in pediatric patients

Apart from neuroblastomas, adrenal tumors are rarely seen in children. The most common adrenal tumors are adrenocortical carcinoma and pheochromocytoma. Adrenocortical carcinoma is usually a large heterogeneous, well-marginated mass with solid/cystic areas and calcifications, with poor prognosis. Most of the pheochromocytomas are benign tumors and usually show intense contrast enhancement, the pattern of which may be diffuse, mottled, or peripheral on computed tomography and magnetic resonance imaging. The purpose of this article is to evaluate primary nonneurogenic adrenal tumors

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Sperm DNA fragmentation: A new guideline for clinicians

Sperm DNA integrity is crucial for fertilization and development of healthy offspring. The spermatozoon undergoes extensive molecular remodeling of its nucleus during later phases of spermatogenesis, which imparts compaction and protects the genetic content. Testicular (defective maturation and abortive apoptosis) and post-testicular (oxidative stress) mechanisms are implicated in the etiology of sperm DNA fragmentation (SDF), which affects both natural and assisted reproduction. Several clinical and environmental factors are known to negatively impact sperm DNA integrity. An increasing number of reports emphasizes the direct relationship between sperm DNA damage and male infertility. Currently, several assays are available to assess sperm DNA damage, however, routine assessment of SDF in clinical practice is not recommended by professional organizations

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

SYMPTOM DIMENSIONS, SMOKING AND IMPULSIVENESS IN OBSESSIVE-COMPULSIVE DISORDER

Background: Obsessive-compulsive disorder (OCD) has distinct symptom dimensions with possibly subtle differences in the underlying neurobiology. One behavioral habit, smoking, has been widely investigated in psychiatric disorders, though received less attention in OCD. Here, we aimed to investigate the relationship between symptom dimensions and smoking behavior in OCD. Subjects and methods: OCD patients (n=167) with the symptom dimensions of washing, taboo thoughts and symmetry-countingrepeating- ordering (S+C+R+O) were questioned in terms of smoking status and assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Fagerström Test for Nicotine Dependence (FTND), Hamilton Depression Rating Scale-17 Items (HDRS-17), Beck Anxiety Inventory (BAI) and Barratt Impulsiveness Scale-11 (BIS 11). Results: Smoking status differed significantly among patients with distinct symptom dimensions (p=0.009).The ratio of smokers was the lowest in those with the washing (30%, N=12) and the highest in the S+C+R+O (68.2%, N=15) group. Those with taboo thoughts had a smoking ratio of 37.14% (N=39). In post hoc analysis, smoking ratio was significantly higher in the S+C+R+O group than in those with washing symptoms (p=0,004) and taboo thoughts (p=0,007) though it did not differ significantly between washers and taboo thought groups. The BIS-11 did not differ across symptom dimensions. Conclusions: OCD is a heterogeneous disorder in terms of smoking. Impulsiveness, which does not significantly vary across distinct symptom dimensions, cannot explain this heterogeneity. The severity of addiction does not differ in smokers with OCD across symptom dimensions

SYMPTOM DIMENSIONS, SMOKING AND IMPULSIVENESS IN OBSESSIVE-COMPULSIVE DISORDER

Background: Obsessive-compulsive disorder (OCD) has distinct symptom dimensions with possibly subtle differences in the underlying neurobiology. One behavioral habit, smoking, has been widely investigated in psychiatric disorders, though received less attention in OCD. Here, we aimed to investigate the relationship between symptom dimensions and smoking behavior in OCD. Subjects and methods: OCD patients (n=167) with the symptom dimensions of washing, taboo thoughts and symmetry-countingrepeating- ordering (S+C+R+O) were questioned in terms of smoking status and assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Fagerström Test for Nicotine Dependence (FTND), Hamilton Depression Rating Scale-17 Items (HDRS-17), Beck Anxiety Inventory (BAI) and Barratt Impulsiveness Scale-11 (BIS 11). Results: Smoking status differed significantly among patients with distinct symptom dimensions (p=0.009).The ratio of smokers was the lowest in those with the washing (30%, N=12) and the highest in the S+C+R+O (68.2%, N=15) group. Those with taboo thoughts had a smoking ratio of 37.14% (N=39). In post hoc analysis, smoking ratio was significantly higher in the S+C+R+O group than in those with washing symptoms (p=0,004) and taboo thoughts (p=0,007) though it did not differ significantly between washers and taboo thought groups. The BIS-11 did not differ across symptom dimensions. Conclusions: OCD is a heterogeneous disorder in terms of smoking. Impulsiveness, which does not significantly vary across distinct symptom dimensions, cannot explain this heterogeneity. The severity of addiction does not differ in smokers with OCD across symptom dimensions

Comparison of effects of bright light therapy alone or combined with fluoxetine on severity of depression, circadian rhythms, mood disturbance, and sleep quality, in patients with non-seasonal depression.

Purpose: To compare effects of bright light therapy (BLT) alone or combined with the selective serotonin reuptake inhibitor (SSRI) fluoxetine, on severity of depression, circadian rhythms, mood disturbance, and sleep quality, in patients with non-seasonal depression. Patients and methods: Drug-free patients who were administered 10,000 lux of BLT for 30 minutes for 7 days comprised the BLT group (n = 7), while patients who started fluoxetine as an add-on treatment day comprised the SSRI + BLT group (n = 8). The primary outcomes were severity of depression, measured using the Hamilton Depression Rating Scale (HAM-D) and the Beck Depression Inventory (BDI); chronotype, measured using the Morningness Eveningness Questionnaire (MEQ); mood disturbance, measured using the Profile of Mood States (POMS) survey; and sleep quality, measured using the Pittsburgh Sleep Quality Index (PSQI), before and after treatment in both groups. Results: All patients completed the study, and none reported obvious side effects. The mean onset age of depression was 26.1 years ± 5.3 years in the BLT group and 27 years ± 9.5 years in the SSRI + BLT group (P = 0.425). The number of past depressive episodes was 1.29 ± 0.76 in the BLT group, and 1.5 ± 0.8 in the SSRI + BLT group (P = 0.427). The difference between pre- and posttreatment scores revealed no significant difference between groups for the HAM-D scale, BDI, MEQ, POMS survey, and the PSQI. Conclusion: This study suggests that BLT is effective with respect to the severity of depression, circadian rhythms, mood disturbance, and sleep quality, in non-seasonal depression. However, there was no evidence in favor of adjunctive fluoxetine with BLT in the treatment of non-seasonal depression, for any of the rating scales used in our study