Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by high levels of low-density lipoprotein-cholesterol (LDLc), associated to premature cardiovascular disease. The detection of the variants related to FH is important to improve the early diagnosis in probands / index-cases (ICs) and their relatives. We included ICs with FH and their relatives, living in a small region of Minas Gerais state-Brazil, which were classified according to Dutch Lipid Clinic Network Criteria (DLCNC) and submitted to sequencing of genes related to FH (LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, APOE, ABCG5 e ABCG8). In a total of 143 subjects (32 ICs and 111 relatives), eight variants were identified in 91 individuals. From these variants, five were in LDLR [p.(Asp224Asn), p.(Ser854Gly), p.(Cys34Arg), p.(Asp601His), deletion of exon15 in LDLR)], one in APOB [p.(Met499Val)], one in PCSK9 [p.(Arg237Trp)] and one in APOE [p.(Pro28Leu)] genes. The variants were detected in 100% of those subjects classified as definitive, 87% as probable and 69% as possible FH cases based on DLCNC. The LDLc level was higher in individuals with corneal arch and xanthomas or xanthelasmas, as well as in pathogenic or probably pathogenic variants carriers. This study showed higher frequency of LDLR gene variants compared to other genes related to LDL metabolism in individuals with FH in Minas Gerais - Brazil and the presence of FH in relatives without previous diagnosis. Our data reinforce the importance of molecular and clinical evaluation of FH relatives in order to early diagnosis the FH, as well as cardiovascular diseases prevention.Classical psychedelics are a group of drugs characterized by their activation of the serotonin-2A (5-hydroxytryptamine-2A; 5-HT2A) receptor and the unique hallucinogenic and mystical-type experiences that result. After a substantial period of restrictions limiting investigations into the therapeutic potential of psychedelics, a relatively recent recommencement of interest has sparked the burgeoning possibility for these drugs to play a part in the treatment of a wide array of psychopathologies. One of the most promising is in the study of addiction. Evidence has emerged that psychedelic agents may provide a novel avenue for the clinical treatment of patients dealing with substance use disorders (SUD). These serotonergic hallucinogens have displayed remarkable and enduring positive outcomes in this area, even when administered as one or two doses. The neural targets for these psychedelics are varied and underlie a complex mechanism of action-modulating multiple neural networks. It is believed that these agents allow for the reorganization of disordered neural pathways in the default mode network and attenuate maladaptive signaling in mesolimbic reward circuitry. The aim of this review is to examine the current standing of evidence regarding psychedelic psychopharmacology and to provide an overview of the use and effectiveness of these drugs in the treatment of SUD, alcohol use disorder, and for smoking cessation.Iron overload is the main cause of morbidity and mortality in β-thalassemia major patients, and cardiac iron overload is the most common reason for death in these transfusion-dependent patients. Hepcidin, a liver-derived peptide hormone, plays a key role in plasma iron levels regulation by controlling two main stages, digestive iron absorption in enterocytes, and iron recycling in macrophages. Although hepcidin is mainly secreted from hepatocytes in the liver, it is also synthesized from mononuclear cells consisting of monocytes and lymphocytes. Binding of this molecule to ferroportin, a specific cellular exporter of iron, leads to degradation of the ligand-receptor complex, which reduces the iron overload by lowering the amounts of iron released into the plasma. Likewise, the same mechanism has been proved to be true for lymphocyte-drived hepcidin. The expression levels of hepcidin mRNA were evaluated using quantitative real time PCR (qRT-PCR) in 50 β-thalassemia major patients, as well as 25 healthy volunteers as the group of control. There was a significantly positive correlation between the cardiac iron concentration, showed by higher T2 values, and hepcidin levels in the patients (p = 0.028; r = 0.311). However, hepcidin expression levels did not significantly correlate with ferritin and liver iron concentrations. Hepcidin can act as a beneficial marker to determine iron overload degrees, particularly in the heart, in β-thalassemia major patients and be used as a logical therapeutic agent for treatment of β-thalassemia disorders.Hearing loss (HL) is clinically and genetically heterogeneous disorder and is the most frequent occurring sensory deficit in humans. This study was conducted to decipher the genetic cause of HL occurring in two large consanguineous Pakistani families (GCNF-01, GCNF-03). Family history and pure tone audiometry of both families suggested prelingual HL, while the affected individuals of GCNF-01 also had low vision and balance problems, consistent with cardinal features of Usher syndrome type I (USH1). Exome sequencing followed by segregating analysis revealed a novel splice site variant (c.877-1G > A) of USH1C occurring with USH1 phenotype in family GCNF01. buy Ifenprodil While the affected individual of family GCNF-03 were homozygous for the c.716 T > A, p.(Val239Asp) previously reported pathogenic variant of SLC26A4. Both variants have very low frequencies in control database. In silico mutagenesis and 3-dimensional simulation analyses revealed that both variants have deleterious impact on the proteins folding and secondary structures. Our study expands the mutation spectrum of the HL genes and emphasizes the utility of exome sequencing coupled with bioinformatics tools for clinical genetic diagnosis, prognosis, and family counseling.Background Self-medication is a worldwide phenomenon of using medications without medical supervision. It is even more prevalent in low-income countries, where individuals seek community pharmacies because of accessibility and affordability. Although self-medication is associated with an increased risk of medication errors, few studies have been conducted to examine the quality of community pharmacy management towards self-medicating individuals of at-risk populations such as pregnant women. Objective We sought to investigate the quality of community pharmacies management of self-medication requests of tetracyclines for pregnant women. Setting The study was conducted in community pharmacies in Minya, Egypt. Methods A random sample of 150 community pharmacies was chosen from the urban areas of five districts of Minya, Egypt. To evaluate the actual practice, a simulated client was trained to visit pharmacies and purchase doxycycline for a pregnant woman. In a random subset of the sampled pharmacies (n = 100), interviews were conducted to evaluate pharmacy staff knowledge and attitudes regarding information gathering and dispensing practice.