Embryotoxicity of serum from women smoking cocaine base paste (CBP)

OBJECTIVE: Using a mouse embryo bioassay, we examined the embryotoxic properties of serum obtained from eight women who had ingested cocaine base paste (CBP) for a period of 1-3 years. STUDY DESIGN: Two-cell stage mouse embryos were cultured in the presence of serum extracted from eight CBP-smoking or control women. After 48h, embryos were evaluated to determine their developmental stage and then processed by Tarkoswki's technique to determine the proportion of embryos with micronuclei, in order to establish the number of micronuclei/embryo. RESULTS: Serum from CBP patients diminished the percentage of embryos progressing to the compacted morula stage, while increasing the proportion of embryos with micronuclei and the corresponding micronuclei/embryo ratio. CONCLUSION: These findings provide the first experimental evidence of embryotoxic compounds in the serum of CBP-smoking women. This study highlights the reproductive risk of chronically ingested CBP and demonstrates the need for further studies.     

Premedication for tracheal intubation in neonates: confusion or controversy?

Tracheal intubation is performed frequently in the NICU and delivery room. This procedure is extremely distressing, painful, and has the potential for airway injury. Premedication with sedatives, analgesics, and muscle relaxants is standard practice for pediatric and adult intubation, yet the use of these drugs is not common for intubation in neonates. The risks and benefits of using premedications for intubating unstable newborns are hotly debated, although recent evidence shows that premedication for non-urgent or semi-urgent intubations is safer and more effective than awake intubations. This article reviews clinical practices reported in surveys on premedication for neonatal intubation, the physiological effects of laryngoscopy and intubation on awake neonates, as well as the clinical and physiological effects of different drug combinations used for intubation. A wide variety of drugs, either alone or in combination, have been used as premedication for elective intubation in neonates. Schematically, these studies have been of three main types: (a) studies comparing awake intubation versus those with sedation or analgesia, (b) studies comparing different premedication regimens comprising sedatives, analgesics, and anesthetics, and (c) case series of neonates in which some authors have reported their experience with a specific premedication regimen. The clinical benefits described in these studies and the need for pain control in neonates make the case for using appropriate premedication routinely for elective or semi-urgent intubations. Tracheal intubation without the use of analgesia or sedation should be performed only for urgent resuscitations in the delivery room or other life-threatening situations when intravenous access is unavailable.     

Resistance Exercise Training Improves Metabolic and Inflammatory Control in Adipose and Muscle Tissues in Mice Fed a High-Fat Diet

This study investigates whether ladder climbing (LC), as a model of resistance exercise, can reverse whole-body and skeletal muscle deleterious metabolic and inflammatory effects of high-fat (HF) diet-induced obesity in mice. To accomplish this, Swiss mice were fed for 17 weeks either standard chow (SC) or an HF diet and then randomly assigned to remain sedentary or to undergo 8 weeks of LC training with progressive increases in resistance weight. Prior to beginning the exercise intervention, HF-fed animals displayed a 47% increase in body weight (BW) and impaired ability to clear blood glucose during an insulin tolerance test (ITT) when compared to SC animals. However, 8 weeks of LC significantly reduced BW, adipocyte size, as well as glycemia under fasting and during the ITT in HF-fed rats. LC also increased the phosphorylation of Akt_Ser473 and AMPK_Thr172 and reduced tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL1-β) contents in the quadriceps muscles of HF-fed mice. Additionally, LC reduced the gene expression of inflammatory markers and attenuated HF-diet-induced NADPH oxidase subunit gp91phox in skeletal muscles. LC training was effective in reducing adiposity and the content of inflammatory mediators in skeletal muscle and improved whole-body glycemic control in mice fed an HF diet.     

Metabolic syndrome following a first episode of psychosis: results of a 1-year longitudinal study conducted in metropolitan Lisbon,Portugal

ObjectiveWe aimed to assess the prevalence and course of metabolic syndrome (MetS) and the associated metabolic parameters during the year following a first episode pf psychosis (FEP).MethodsWe performed a 1-year longitudinal observation of 60 patients who experienced FEP. MetS was defined using the modified definition of the National Cholesterol Education Program Adult Treatment Panel III. We assessed the metabolic parameters and socio-demographic and psychopathological data for the participants.ResultsThe mean age of the participants was 27.1 years, and 33.3% of them were women. There was an increase in the prevalence of MetS from 6.7% to 11.7% during the year following the baseline assessment during the year following the baseline assessment (p = 0.250). There were also significant increases in the prevalences of abnormal triglyceride concentration, waist circumference, and high-density lipoprotein (HDL)-cholesterol concentration during this period. In addition, there was a considerable worsening of the metabolic profile of the participants. No baseline parameters were identified to be predictors of MetS over the 1-year follow-up period.ConclusionsWe can conclude that metabolic abnormalities are common in patients with FEP and that these rapidly worsen during the first year following the diagnosis of FEP. Studies on interventions are needed to reduce metabolic risk to cardiovascular diseases following the FEP.     

Emerging Biomarker-Guided Therapies in Prostate Cancer

Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and alpha-emitting radiation therapy, identifying their optimal sequencing remains a challenge. Progress in the understanding of the biology of prostate cancer has provided an opportunity for a more refined and personalized treatment selection process. With the advancement of molecular sequencing techniques, genomic precision through the identification of potential treatment targets and predictive biomarkers has been rapidly evolving. In this review, we discussed biomarker-driven treatments for advanced prostate cancer. First, we presented predictive biomarkers for established, global standard treatments for advanced diseases, such as chemotherapy and androgen receptor axis-targeted agents. We also discussed targeted agents with recent approval for special populations, such as poly ADP ribose polymerase (PARP) inhibitors in patients with metastatic castrate-resistant prostate cancer with homologous recombination repair-deficient tumors, pembrolizumab in patients with high levels of microsatellite instability or high tumor mutational burden, and prostate-specific membrane antigen (PSMA) directed radioligand theragnostic treatment for PSMA expressing tumors. Additionally, we discussed evolving treatments, such as cancer vaccines, chimeric antigen receptor T-cells (CAR-T), Bispecific T-cell engagers (BiTEs), other targeted agents such as AKT inhibitors, and various combination treatments. In summary, advances in molecular genetics have begun to propel personalized medicine forward in the management of advanced prostate cancer, allowing for a more precise, biomarker-driven treatment selection with the goal of improving overall efficacy.     

Baixa Concordância entre a Classificação da NYHA e as Variáveis do Teste de Exercício Cardiopulmonar em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida

BackgroundThe New York Heart Association (NYHA) functional classification is the most commonly used classification system for heart failure (HF), whereas cardiopulmonary exercise testing (CPET) is the gold standard for functional status evaluation in HF.ObjectiveThis study aimed to analyze correlation and concordance between NYHA classes and CPET variables.MethodsHF patients with clinical indication for CPET and ejection fraction (EF) < 50% were selected. Correlation (Spearman coefficient) and concordance (kappa) between NYHA classification and CPET-based classifications were analyzed. A p < 0.05 was accepted as significant.ResultsIn total, 244 patients were included. Mean age was 56 ± 14 years, and mean EF was 35.5% ± 10%. Distribution of patients according to NYHA classification was 31.2%% class I, 48.3% class II, 19.2% class III, and 1.3% class IV. Correlation (r) between NYHA and Weber classes was 0.489 (p < 0.001), and concordance was 0.231 (p < 0.001). Correlation (r) between NYHA and ventilatory classes (minute ventilation/carbon dioxide production [VE/VCO₂] slope) was 0.218 (p < 0.001), and concordance was 0.002 (p = 0.959). Spearman correlation between NYHA and CPET score classes was 0.223 (p = 0.004), and kappa concordance was 0.027 (p = 0.606).ConclusionThere was a moderate association between NYHA and Weber classes, although concordance was low. Ventilatory (VE/VCO₂slope) and CPET score classes had a weak association and a low concordance with NYHA classes.