PSICOFARMACOGENÉTICA

Psychiatric disorders are chronic, recurrent and are responsible for huge social and individual costs. Psychopharmacology is a growing field with and an increasing number and quality of drugs, which have improved treatment efficacy and decreased adverse effects. Pharmacogenetics is a relatively recent science that study genetics influence on drug response and adverse effects. In these review, we point to the major findings in psycopharmacogenetics and comment on the perspectives for the scientific community and clinicians in Brazil.Doenças psiquiátricas são patologias crônicas, recorrentes e promotoras de desarranjo e custo social extenso. A psicofarmacologia apresenta um número crescente de medicações eficazes e sua evolução acontece no sentido de aumentar a eficácia do tratamento de pacientes refratários, assim como reduzir os freqüentes efeitos colaterais associados com as medicações tradicionais. A farmacogenética é uma ciência relativamente recente que estuda as influências genéticas na resposta a droga e que pode vir a ser ferramenta essencial para o entendimento do funcionamento de drogas, assim como dos efeitos colaterais de medicações. Nessa revisão foram levantados os principais achados farmacogenéticos com antipsicóticos e antidepressivos e comentadas as perspectivas da farmacogenética na comunidade científica e clínica no Brasil

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D₂. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC): Neuronal Calcium Sensor-1 (NCS-1) and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D₂internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT) and PC12 cells stably overexpressing NCS-1 (PC12 Clone) with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment.</p> <p>Results</p> <p>We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol) or atypical (Clozapine and Risperidone) antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments.</p> <p>Conclusions</p> <p>Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.</p

Nursing diagnoses of newborns with sepsis in a Neonatal Intensive Care Unit

OBJECTIVES: to elaborate the Nursing Diagnoses of newborns with sepsis in a neonatal intensive care unit and characterize the profile of the neonates and their mothers.METHOD: a cross-sectional and quantitative study, with a sample of 41 neonates. A physical examination and consultation of the hospital records were undertaken, using an instrument. The elaboration of the Nursing Diagnoses followed a process of diagnostic inference and was based on the North American Nursing Diagnosis Association 2012-2014.RESULTS: the mothers were around 25 years old, had a low average number of pre-natal consultations, and various complications during the pregnancy; and the newborns were predominantly premature and with very low birth weights. Five Nursing Diagnoses predominated, and all the neonates presented Risk of Shock and Risk of fluid volume imbalance.CONCLUSION: the Nursing Diagnoses of the neonates with sepsis can guide the formulating of specific assistential plans. The study contributes to the generation of new knowledge and found various relationships between the Nursing Diagnoses and the variables selected in the characterization of the neonates, which deserve to be elucidated in greater detail based on further research on the issue

Parental experiences of homeschooling during the COVID-19 pandemic: differences between seven European countries and between children with and without mental health conditions

The aim of the present study was to examine parental experiences of homeschooling during the COVID-19 pandemic in families with or without a child with a mental health condition across Europe. The study included 6720 parents recruited through schools, patient organizations and social media platforms (2002 parents with a child with a mental health condition and 4718 without) from seven European countries: The United Kingdom (n=508), Sweden (n=1436), Spain (n=1491), Belgium (n=508), the Netherlands (n=324), Germany (n=1662) and Italy (n=794). Many parents reported negative effects of homeschooling for themselves and their child, and many found homeschooling to be of poor quality, with insufficient support from schools. In most countries, contact with teachers was limited, leaving parents with primary responsibility for managing homeschooling. Parents also reported increased levels of stress, worry, social isolation, and domestic conflict. A small number of parents reported increased parental alcohol/drug use. Some differences were found between countries and some negative experiences were more common in families with a child with a mental health condition. However, differences between countries and between families with and without a mental health condition were generally small, indicating that many parents across countries reported negative experiences. Some parents also reported positive experiences of homeschooling. The adverse effects of homeschooling will likely have a long-term impact and contribute to increased inequalities. Given that school closures may be less effective than other interventions, policymakers need to carefully consider the negative consequences of homeschooling during additional waves of the COVID-19 pandemic and future pandemics