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Background: Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies. Methods: We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses. Results: Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D 2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling. Conclusions: TAAR1 agonists may be less efficacious than dopamine D 2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted. Registration: PROSPERO-ID: CRD42023451628.
There is a need for more effective treatments for psychosis, including schizophrenia. Psychosis is a collection of mental health symptoms, such as hearing voices, that can cause distress and impair functioning. These symptoms are thought to be caused by changes in a chemical messenger system in the brain called dopamine. Currently used antipsychotic medications target brain receptors that respond to dopamine. They are not effective in some people and can cause uncomfortable adverse events, such as weight gain and movement disorders, especially with long-term use. A new type of drug is the trace amine-associated receptor 1 (TAAR1) agonists. These drugs act on different brain receptors that can affect the activity of the dopamine system, but do not directly bind to dopamine receptors. We aimed to understand if TAAR1 agonists can reduce symptoms of psychosis, what adverse events they might have, and how they work. We did this by reviewing and collating all available evidence until November 2023. This is a "living" systematic review, so it will be regularly updated in the future. We looked at both human and animal studies investigating TAAR1 agonists. Human studies suggested that two TAAR1 agonists (namely, ulotaront or ralmitaront) might have little to no effect on reducing symptoms of psychosis compared to placebo in people with schizophrenia. They seemed to cause fewer adverse events than current antipsychotics. Data from animal studies suggested that TAAR1 agonists had some positive effects but potentially smaller than other antipsychotics. There were little to no data from both human and animal studies about how TAAR1 agonists actually work. From the current evidence we are uncertain about these results. With the ongoing development of new TAAR1 agonists, more evidence is needed to understand their potential role in the treatment of psychosis.
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Sharp-spined notothen (Trematomus pennellii) is an icefish endemic to the southern ocean. From the stomach of an individual, we identified the genomes of 51 microviruses (family Microviridae). The major capsid proteins of most of these share the closest similarities to those identified in other marine organisms.
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PURPOSE: Laparoscopic appendectomy for pediatric acute appendicitis is commonly performed by pediatric surgeons. A single incision approach has been investigated, but the lack of technical uniformity has resulted in conflicting data. We hypothesized that an initial single incision laparoscopic-assisted extracorporeal appendectomy (SILEA) approach is associated with similar complication rates as compared to the standard three-incision laparoscopic appendectomy (TILA). METHODS: Approximately 1300 laparoscopic appendectomies were retrospectively reviewed for acute appendicitis over a 5 year period. Patients were split into TILA or SILEA cohorts. Propensity score matching identified 102 matched cases in both cohorts. Case and control cohort comparisons were then analyzed. RESULTS: Successful SILEA was associated with no difference in post-operative complication rate. SILEA was associated with decreased postoperative narcotic dosage and shorter operative time than TILA. CONCLUSIONS: An initial SILEA approach is safe and associated with similar complication rates as TILA. Based on this data, the authors advocate adoption of the an initial SILEA approach for uncomplicated, freely mobile, acute appendicitis with seamless conversion to TILA if the appendix is not amendable to SILEA. LEVEL OF EVIDENCE: Level III.
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Apendicite , Laparoscopia , Ferida Cirúrgica , Humanos , Criança , Apendicectomia/métodos , Apendicite/cirurgia , Estudos Retrospectivos , Entorpecentes , Laparoscopia/métodos , Resultado do Tratamento , Doença Aguda , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Tempo de InternaçãoRESUMO
Fish papillomaviruses form a newly discovered group broadly recognized as the Secondpapillomavirinae subfamily. This study expands the documented genomes of the fish papillomaviruses from six to 16, including one from the Antarctic emerald notothen, seven from commercial market fishes, one from data mining of sea bream sequence data, and one from a western gull cloacal swab that is likely diet derived. The genomes of secondpapillomaviruses are â¼6 kilobasepairs (kb), which is substantially smaller than the â¼8 kb of terrestrial vertebrate papillomaviruses. Each genome encodes a clear homolog of the four canonical papillomavirus genes, E1, E2, L1, and L2. In addition, we identified open reading frames (ORFs) with short linear peptide motifs reminiscent of E6/E7 oncoproteins. Fish papillomaviruses are extremely diverse and phylogenetically distant from other papillomaviruses suggesting a model in which terrestrial vertebrate-infecting papillomaviruses arose after an evolutionary bottleneck event, possibly during the water-to-land transition.
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Peixes/virologia , Papillomaviridae/classificação , Animais , Regiões Antárticas , Evolução Biológica , Charadriiformes/virologia , DNA Viral , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Fases de Leitura Aberta , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/virologia , Filogenia , Análise de Sequência de DNAAssuntos
Doença Diverticular do Colo , Diverticulite , Fístula Intestinal , Procedimentos Cirúrgicos Robóticos , Fístula da Bexiga Urinária , Colectomia , Diverticulite/cirurgia , Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/cirurgia , Humanos , Fístula Intestinal/etiologia , Fístula Intestinal/cirurgiaRESUMO
BACKGROUND: Newly qualified nurses are known to experience a range of feelings and fears in the first transitional 12 months post-qualifying, with absence and turnover among potential outcomes. AIM: To evaluate the personal professional mentor role and scheme, a new pastoral support initiative, from the perspective of participating newly qualified nurses. METHODS: Newly qualified paediatric nurses (n=10), who had been assigned a personal professional mentor (an experienced nurse who worked elsewhere in their employing NHS Trust), completed a semi-structured interview. The data were analysed using thematic analysis. FINDINGS: The personal professional mentor counteracted some aspects of transition isolation for the newly qualified nurses. They were an independent, accessible, experienced confidant and a welcome new supportive role. CONCLUSION: Pairing experienced nurses with newly qualified nurses provided a new type of workplace support during transition. Inexpensive to set up and run, it is an easy addition to any portfolio of support strategies.
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Mentores , Enfermeiras e Enfermeiros , Criança , Humanos , Reorganização de Recursos HumanosRESUMO
Appendectomy is the standard of care in pregnant patients with acute appendicitis. The use of laparoscopy in pregnant patients with acute appendicitis is still debated, especially for patients in their third trimester. We present a case of a patient who safely underwent a laparoscopic appendectomy during early labor and subsequently delivered a healthy baby. In the correct situations and hands, laparoscopy can likely be safely used throughout pregnancy.
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Linezolid is a synthetic antibiotic that functions through the inhibition of bacterial protein synthesis by binding to ribosomal ribonucleic acid (rRNA). Deliverable in both intravenous and oral form, with a low level of resistance amongst Methicillin-resistant Staphylococcus aureus (MRSA) strains, it is recommended for a wide range of gram-positive infections. We present a case of a male patient who underwent endovascular abdominal aortic aneurysm repair complicated by abdominal sepsis due to bowel ischemia; several days after linezolid therapy was initiated, he presented with signs of lactic acidosis. After excluding other sources such as metabolic, hypoxia, or organ damage, the resulting lactic acidosis was determined to be a side effect of linezolid.
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INTRODUCTION: Native Americans have some of the worst health outcomes of any minority group in the USA, and are severely under-represented in the health professional workforce. From 2009 to 2015, partners from a tribal college in rural North Dakota and academic institutions in New York collaborated to create a program wherein non-Native health professionals traveled to the reservation to teach a summer course to Native students. This study assessed the impact of the program on both the Native students who took the course and the non-Native health professionals who taught the course. METHODS: Focus groups composed of former students in the program were held in Spirit Lake, North Dakota. Non-Native student teachers were surveyed using an online survey tool. Focus group data were analyzed using grounded theory methodology. Survey data were analyzed using descriptive statistics. RESULTS: Fifteen former students participated in the focus groups. Participants stated that their experiences in the course increased interest in health professions and knowledge of public health issues. Participants also described barriers to entering health professionals for Native students and the benefits of close interaction with non-Native individuals. Eighty-six percent (24/28) of former course teachers responded to the survey. Survey respondents stated their experiences in North Dakota increased their understanding of underserved populations and their interest in working in rural areas. CONCLUSION: This study assessed the successes and limitations of a collaborative, interprofessional immersion program in rural North Dakota. Similar programs may increase the number of Native Americans in health professions and increase non-Native health professional interest in and engagement with rural communities.
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Educação Profissionalizante/métodos , Pessoal de Saúde/educação , Saúde Pública/educação , População Rural/estatística & dados numéricos , Adulto , Humanos , Relações Interprofissionais , Masculino , Área Carente de Assistência Médica , North Dakota , Avaliação de Programas e Projetos de Saúde , Serviços de Saúde Rural/organização & administraçãoRESUMO
The incidence of hepatocellular carcinoma (HCC) is rising sharply in the United States and deaths from HCC have increased at the highest rate of all cancers. Though Asians have the highest incidence of HCC of all ethnicities in the US, racial/ethnic minorities, including Asians, have worse survival from HCC. We sought to identify barriers to care in treatment of HCC among affected individuals in the NYC Chinese immigrant community. We held focus groups with Chinese immigrant patients in NYC with HCC. 29 individuals participated in the focus groups. We analyzed focus group data using grounded theory methodology. Barriers to care identified included insurance, money, time, language, residency status, and stigma. The impact of provider bias and culture were also discussed. Knowledge gathering with minority patients with HCC is essential for us to fully comprehend the barriers to healthcare experienced by this community. Future policy and intervention efforts must be founded in this reality.
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Povo Asiático/psicologia , Carcinoma Hepatocelular/etnologia , Emigrantes e Imigrantes/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Neoplasias Hepáticas/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Adulto , Idoso , Carcinoma Hepatocelular/terapia , Emigrantes e Imigrantes/psicologia , Feminino , Grupos Focais , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Cidade de Nova IorqueRESUMO
The Polyomaviridae is a diverse family of circular double-stranded DNA viruses. Polyomaviruses have been isolated from a wide array of animal hosts. An understanding of the evolutionary and ecological dynamics of these viruses is essential to understanding the pathogenicity of polyomaviruses. Using a high throughput sequencing approach, we identified a novel polyomavirus in an emerald notothen (Trematomus bernacchii) sampled in the Ross sea (Antarctica), expanding the known number of fish-associated polyomaviruses. Our analysis suggests that polyomaviruses belong to three main evolutionary clades; the first clade is made up of all recognized terrestrial polyomaviruses. The fish-associated polyomaviruses are not monophyletic, and belong to two divergent evolutionary lineages. The fish viruses provide evidence that the evolution of the key viral large T protein involves gain and loss of distinct domains.
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Evolução Molecular , Doenças dos Peixes/virologia , Infecções por Polyomavirus/veterinária , Polyomavirus/classificação , Polyomavirus/isolamento & purificação , Animais , Regiões Antárticas , Antígenos Virais de Tumores/química , Antígenos Virais de Tumores/genética , Perciformes/virologia , Filogenia , Polyomavirus/química , Polyomavirus/genética , Infecções por Polyomavirus/virologia , Domínios ProteicosAssuntos
Atitude do Pessoal de Saúde , Negro ou Afro-Americano , Serviços de Saúde do Indígena/organização & administração , Disparidades em Assistência à Saúde/organização & administração , Relações Médico-Paciente , Comunicação , Pessoal de Saúde , Humanos , Atenção Primária à Saúde/organização & administração , Estados UnidosRESUMO
Polyomaviruses are a family of DNA tumor viruses that are known to infect mammals and birds. To investigate the deeper evolutionary history of the family, we used a combination of viral metagenomics, bioinformatics, and structural modeling approaches to identify and characterize polyomavirus sequences associated with fish and arthropods. Analyses drawing upon the divergent new sequences indicate that polyomaviruses have been gradually co-evolving with their animal hosts for at least half a billion years. Phylogenetic analyses of individual polyomavirus genes suggest that some modern polyomavirus species arose after ancient recombination events involving distantly related polyomavirus lineages. The improved evolutionary model provides a useful platform for developing a more accurate taxonomic classification system for the viral family Polyomaviridae.