👤 Luiz Paulo Chaves

Obesity rates continue to rise in children and adolescents worldwide. The heritability of obesity is estimated to be 40-80 %. Genetic testing for monogenic causes of obesity in the clinical setting is increasing; however, how results of these tests affect family behaviors is unclear. The objective of this study was to understand caregiver intent to change family behaviors following genetic testing for obesity. The sample from this qualitative analysis derives from a larger study identifying mutations on the melanocortin 4 receptor (MC4R) pathway. Inclusion criteria included participation in the main study, aged 2-17 years, and a history of severe obesity and hyperphagia. Caregiver-child dyads were recruited to ensure equal representation of genetic results across racial/ethnic subgroups (Non-Hispanic White, Black, Hispanic). A third of participants in the main study enrolled in the sub-study. Structured caregiver interviews were analyzed using grounded theory. Twenty caregivers were female, 55 % White, 45 % Black, and 5 % Hispanic. Mean caregiver age was 42.3 ± 6.5 years and BMI 40.5 ± 7.9 kg/m Genetic testing for pediatric obesity, regardless of test outcome, motivates caregivers to move forward within the SoC Model or to remain in their current stage. These findings suggest that engaging caregivers to have their child with obesity tested for a genetic cause of obesity does not cause families to stop engaging in behavior change, unless the family was not ready to engage in behavior change prior to genetic testing. Show less

Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes. In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems. Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA ( Show less

Prostate cancer (PCa) is an immunologically cold tumor and the molecular processes that underlie this behavior are poorly understood. In this study, we investigated a primary cohort of intermediate-risk PCa ( Show less

The objective of this research was to evaluate the effectiveness of using LPL (Low power laser) to reduce pain, edema, and trismus after impacted lower third molar extraction. A split-mouth randomized triple-blind clinical trial was conducted at the Federal University of Ceará. For inclusion criteria, it was necessary that the patient presented a clear indication for removal of both lower third molars, in addition to both molars being in similar positions. The third molars (38 and 48) were randomly allocated to the test group that received the LPL application protocol, and to the placebo group that received a simulation of the protocol, making a total sample of 44 surgeries. Patients in the test group used an average of 50% of the amount of analgesics that was used by the placebo group, however, there was a statistically significant difference only on days four and five. Regarding trismus, the test group presented wide mouth openings, both at 48 hours and at 7 days after surgery compared to the placebo group, but without a statistically significant difference. For edema, we noted an equilibrium between the test group and the placebo group, but no measurement obtained a statistically significant difference. The use of LPL presented better pain and trismus indicators after complex extractions. The use of LPL is thus indicated as a complementary therapy to reduce postoperative discomfort caused by complex tooth extractions. Show less

Leptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5-12.4) and LH (12.3 ± 2.2 mUI/mL; reference: 1.7-8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss. The early diagnosis of monogenic forms of obesity can be of great interest since new treatments for these conditions are becoming available. Since BMI and leptin levels in patients with leptin receptor mutations are not significantly different from those found in randomly selected morbid obese patients, a careful medical history is mandatory to suspect this condition. Loss of leptin receptor function has been associated with infertility. However, our patients were able to conceive, emphasizing the need for genetic counselling in affected patients with this condition. Show less

Prostate cancers may reactivate a latent embryonic program called the epithelial-mesenchymal transition (EMT) during the development of metastatic disease. Through EMT, tumors can develop a mesenchymal phenotype similar to cancer stem cell traits that contributes to metastasis and variation in therapeutic responses. Some of the recurrent somatic mutations of prostate cancer affect EMT driver genes and effector transcription factors that induce the chromatin- and androgen-dependent epigenetic alterations that characterize castrate-resistant prostate cancer (CRPC). EMT regulators in prostate cancer comprise transcription factors ( Show less