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1.
Contemp Clin Trials ; 118: 106808, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35644376

RESUMO

Asthma-related deaths, hospitalizations, and emergency visits are more numerous among low-income patients, yet management guidelines do not address this high-risk group's special needs. We recently demonstrated feasibility, acceptability, and preliminary evidence of effectiveness of two interventions to improve access to care, patient-provider communication, and asthma outcomes: 1) Clinic Intervention (CI): study staff facilitated patient preparations for office visits, attended visits, and afterwards confirmed patient understanding of physician recommendations, and 2) Home Visit (HV) by community health workers for care coordination and informing clinicians of home barriers to managing asthma. The current project, denominated "HAP3," combines these interventions for greater effectiveness, delivery of guideline-based asthma care, and asthma control for low-income patients recruited from 6 primary care and 3 asthma specialty practices. We assess whether patients of clinicians receiving guideline-relevant, real-time feedback on patient health and home status have better asthma outcomes. In a pragmatic factorial longitudinal trial, HAP3 enrolls 400 adults with uncontrolled asthma living in low-income urban neighborhoods. 100 participants will be randomized to each of four interventions: (1) CI, (2) CI with HVs, (3) CI and real-time feedback to asthma clinician of guideline-relevant elements of patients' current care, or (4) both (2) and (3). The outcomes are asthma control, quality of life, ED visits, hospitalizations, prednisone bursts, and intervention costs. The COVID-19 pandemic struck 6.5 months into recruitment. We describe study development, design, methodology, planned analysis, baseline findings and adaptions to achieve the original aims of improving patient-clinician communication and asthma outcomes despite the markedly changed pandemic environment.


Assuntos
Asma , Visita Domiciliar , Pandemias , Adulto , Asma/terapia , COVID-19/epidemiologia , Humanos , Pobreza , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Am J Manag Care ; 28(6): 262-268, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35738222

RESUMO

OBJECTIVES: Strategies to maintain hospital capacity during the COVID-19 pandemic included reducing hospital length of stay (LOS) for infected patients. We sought to evaluate the association between LOS and enrollment in the COVID Accelerated Care Pathway, which consisted of a hospital observation protocol and postdischarge automated text message-based monitoring. STUDY DESIGN: Retrospective matched cohort study of patients hospitalized from December 14, 2020, to January 31, 2021. METHODS: Participants were patients who presented to the emergency department with acute infection due to COVID-19, required hospitalization, and met pathway inclusion criteria. Participants were compared with a propensity score-matched cohort of patients with COVID-19 admitted to the same hospital during the 7 weeks preceding and following pathway implementation. RESULTS: There were 44 patients in the intervention group and 83 patients in the propensity score-matched cohort. The mean (SD) hospital LOS for patients in the intervention group was 1.7 (2.6) days compared with 3.9 (2.3) days for patients in the matched cohort (difference, -2.2 days; 95% CI, -3.3 to -1.1). In the intervention group, 2 patients (5%; 95% CI, 0%-15%) were rehospitalized within 14 days compared with 8 (10%; 95% CI, 4%-17%) in the matched cohort. CONCLUSIONS: Patients with COVID-19 who were managed through an accelerated hospital observation protocol and postdischarge monitoring service had reduced hospital LOS compared with patients receiving standard care. Hospital preparedness for future public health emergencies may involve the design of pathways that reduce the time that patients spend in the hospital, lower cost, and ensure continued recovery upon discharge.


Assuntos
COVID-19 , Assistência ao Convalescente , COVID-19/terapia , Estudos de Coortes , Serviço Hospitalar de Emergência , Hospitais , Humanos , Tempo de Internação , Pandemias , Alta do Paciente , Estudos Retrospectivos
3.
Commun Biol ; 5(1): 580, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35697829

RESUMO

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Creatinina , Nefropatias Diabéticas/genética , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular/genética , Humanos , Rim
5.
Foods ; 11(5)2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35267368

RESUMO

Eating behavior (EB) is a complex system influenced by many factors, but an undisputed role is played by the senses. In this work, we examined the effect of the sensory capacities on EB in 1152 Italian adult individuals. After administering a questionnaire on EB and assessing sensory performance through standard audiometric, olfactory, and taste tests, the prevalence of reduced sensory capacities (RSCs) and the correlation with selected risk factors were calculated. Regression models, structural equation modelling, and conditional recursive partitioning were used to investigate the relationship between variables. Around 70% of the subjects show reduced capacities in at least one sense, with taste being the most prevalent (55.21%). Male sex, aging, and low educational level are risk factors for RSCs. The increased number of senses with reduced capacities is a predictor of diminished food adventurousness and lower liking for vegetables, fish, and alcoholic beverages, while reduced capacities (RCs) in taste is a predictor of lower liking for alcoholic beverages and sweets. Overall, in addition to providing an overall picture of RSCs in Italian samples, our study reveals the association of RSCs with EB variables. This finding could have a relevant role in influencing individuals' dietary habits and, therefore, health status.

6.
Ann Intern Med ; 175(2): 179-190, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34781715

RESUMO

BACKGROUND: Although most patients with SARS-CoV-2 infection can be safely managed at home, the need for hospitalization can arise suddenly. OBJECTIVE: To determine whether enrollment in an automated remote monitoring service for community-dwelling adults with COVID-19 at home ("COVID Watch") was associated with improved mortality. DESIGN: Retrospective cohort analysis. SETTING: Mid-Atlantic academic health system in the United States. PARTICIPANTS: Outpatients who tested positive for SARS-CoV-2 between 23 March and 30 November 2020. INTERVENTION: The COVID Watch service consists of twice-daily, automated text message check-ins with an option to report worsening symptoms at any time. All escalations were managed 24 hours a day, 7 days a week by dedicated telemedicine clinicians. MEASUREMENTS: Thirty- and 60-day outcomes of patients enrolled in COVID Watch were compared with those of patients who were eligible to enroll but received usual care. The primary outcome was death at 30 days. Secondary outcomes included emergency department (ED) visits and hospitalizations. Treatment effects were estimated with propensity score-weighted risk adjustment models. RESULTS: A total of 3488 patients enrolled in COVID Watch and 4377 usual care control participants were compared with propensity score weighted models. At 30 days, COVID Watch patients had an odds ratio for death of 0.32 (95% CI, 0.12 to 0.72), with 1.8 fewer deaths per 1000 patients (CI, 0.5 to 3.1) (P = 0.005); at 60 days, the difference was 2.5 fewer deaths per 1000 patients (CI, 0.9 to 4.0) (P = 0.002). Patients in COVID Watch had more telemedicine encounters, ED visits, and hospitalizations and presented to the ED sooner (mean, 1.9 days sooner [CI, 0.9 to 2.9 days]; all P < 0.001). LIMITATION: Observational study with the potential for unobserved confounding. CONCLUSION: Enrollment of outpatients with COVID-19 in an automated remote monitoring service was associated with reduced mortality, potentially explained by more frequent telemedicine encounters and more frequent and earlier presentation to the ED. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.


Assuntos
COVID-19/terapia , Consulta Remota/métodos , Envio de Mensagens de Texto , Adulto , Idoso , COVID-19/mortalidade , Pesquisa Comparativa da Efetividade , Serviço Hospitalar de Emergência , Feminino , Serviços de Assistência Domiciliar , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia
7.
Drugs Context ; 102021.
Artigo em Inglês | MEDLINE | ID: mdl-34970321

RESUMO

The United States faces an opioid crisis with an unprecedented and increasing death rate from opioid overdose. Successfully reducing the rates of opioid use disorder (OUD) and overdose will require the engagement of frontline clinicians to prescribe opioids more safely and to build their capacity to treat patients with OUD using evidence-based approaches. The COVID-19 pandemic has created significant challenges for patients, clinicians and health systems and has been associated with increasing risks of overdoses and deaths. Herein, we review a multidisciplinary project designed to implement and evaluate clinic-based interventions in Oregon, USA, to improve pain management, opioid prescribing and treatment of OUD. The intervention, called Improving PaIn aNd OPiOId MaNagemenT in Primary Care (PINPOINT), combines practice facilitation, academic detailing and education through the Oregon ECHO Network. Implementation of PINPOINT has occurred across the Oregon Rural Practice-based Research Network and has involved 49 clinic sites to date. To evaluate the impact of the intervention, the research team created the Provider Results of Opioid Management and Prescribing Training (PROMPT), a dataset that links information from the state prescription drug monitoring program, all-payer claims database, emergency medical services, vital records and substance use disorder treatment system. The PROMPT dataset will allow evaluation of the impact of the intervention at both the clinician and clinic levels. Due to the constraints of the COVID-19 pandemic, elements of both implementation and evaluation required significant adaptations to continue to meet the original project goals.

8.
JCO Clin Cancer Inform ; 5: 1134-1140, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34767436

RESUMO

PURPOSE: Patients with cancer are at greater risk of developing severe symptoms from COVID-19 than the general population. We developed and tested an automated text-based remote symptom-monitoring program to facilitate early detection of worsening symptoms and rapid assessment for patients with cancer and suspected or confirmed COVID-19. METHODS: We conducted a feasibility study of Cancer COVID Watch, an automated COVID-19 symptom-monitoring program with oncology nurse practitioner (NP)-led triage among patients with cancer between April 23 and June 30, 2020. Twenty-six patients with cancer and suspected or confirmed COVID-19 were enrolled. Enrolled patients received twice daily automated text messages over 14 days that asked "How are you feeling compared to 12 hours ago? Better, worse, or the same?" and, if worse, "Is it harder than usual for you to breathe?" Patients who responded worse and yes were contacted within 1 hour by an oncology NP. RESULTS: Mean age of patients was 62.5 years. Seventeen (65%) were female, 10 (38%) Black, and 15 (58%) White. Twenty-five (96%) patients responded to ≥ 1 symptom check-in, and overall response rate was 78%. Four (15%) patients were escalated to the triage line: one was advised to present to the emergency department (ED), and three were managed in the outpatient setting. Median time from escalation to triage call was 11.5 minutes. Four (15%) patients presented to the ED without first escalating their care via our program. Participant satisfaction was high (Net Promoter Score: 100, n = 4). CONCLUSION: Implementation of an intensive remote symptom monitoring and rapid NP triage program for outpatients with cancer and suspected or confirmed COVID-19 infection is possible. Similar tools may facilitate more rapid triage for patients with cancer in future pandemics.


Assuntos
COVID-19 , Neoplasias , Envio de Mensagens de Texto , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias/diagnóstico , SARS-CoV-2 , Triagem
9.
Genes (Basel) ; 12(10)2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34680964

RESUMO

Pendred syndrome (PDS) is the most common form of syndromic Hearing Loss (HL), characterized by sensorineural HL, inner ear malformations, and goiter, with or without hypothyroidism. SLC26A4 is the major gene involved, even though ~50% of the patients carry only one pathogenic mutation. This study aims to define the molecular diagnosis for a cohort of 24 suspected-PDS patients characterized by a deep radiological and audiological evaluation. Whole-Exome Sequencing (WES), the analysis of twelve variants upstream of SLC26A4, constituting the "CEVA haplotype" and Multiplex Ligation Probe Amplification (MLPA) searching for deletions/duplications in SLC26A4 gene have been carried out. In five patients (20.8%) homozygous/compound heterozygous SLC26A4 mutations, or pathogenic mutation in trans with the CEVA haplotype have been identified, while five subjects (20.8%) resulted heterozygous for a single variant. In silico protein modeling supported the pathogenicity of the detected variants, suggesting an effect on the protein stabilization/function. Interestingly, we identified a genotype-phenotype correlation among those patients carrying SLC26A4 mutations, whose audiograms presented a characteristic slope at the medium and high frequencies, providing new insights into PDS. Finally, an interesting homozygous variant in MYO5C has been identified in one patient negative to SLC26A4 gene, suggesting the identification of a new HL candidate gene.


Assuntos
Bócio Nodular/genética , Perda Auditiva Neurossensorial/genética , Miosina Tipo V/genética , Transportadores de Sulfato/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Bócio Nodular/epidemiologia , Bócio Nodular/patologia , Haplótipos/genética , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/patologia , Humanos , Lactente , Masculino , Mutação , Sequenciamento Completo do Exoma , Adulto Jovem
10.
Genes (Basel) ; 12(7)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34356059

RESUMO

Hearing loss (HL) is the most frequent sensory disorder, affecting about 1-3 per 1000 live births, with more than half of the cases attributable to genetic causes. Despite the fact that many HL causative genes have already been identified, current genetic tests fail to provide a diagnosis for about 40% of the patients, suggesting that other causes still need to be discovered. Here, we describe a four-generation Italian family affected by autosomal dominant non-syndromic hearing loss (ADNSHL), in which exome sequencing revealed a likely pathogenic variant in NCOA3 (NM_181659.3, c.2909G>C, p.(Gly970Ala)), a gene recently described as a novel candidate for ADNSHL in a Brazilian family. A comparison between the two families highlighted a series of similarities: both the identified variants are missense, localized in exon 15 of the NCOA3 gene and lead to a similar clinical phenotype, with non-syndromic, sensorineural, bilateral, moderate to profound hearing loss, with a variable age of onset. Our findings (i.e., the identification of the second family reported globally with HL caused by a variant in NCOA3) further support the involvement of NCOA3 in the etiopathogenesis of ADNSHL, which should, thus, be considered as a new gene for autosomal dominant non-syndromic hearing loss.


Assuntos
Predisposição Genética para Doença/genética , Perda Auditiva/genética , Mutação , Coativador 3 de Receptor Nuclear/genética , Artrogripose , Brasil , Feminino , Genes Dominantes , Genótipo , Perda Auditiva Neurossensorial/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Itália , Masculino , Linhagem , Fenótipo
11.
Genes (Basel) ; 12(8)2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34440402

RESUMO

To date, the knowledge of the genetic determinants behind the modulation of hearing ability is relatively limited. To investigate this trait, we performed Genome-Wide Association Study (GWAS) meta-analysis using genotype and audiometric data (hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and pure-tone averages of thresholds at low, medium, and high frequencies) collected in nine cohorts from Europe, South-Eastern USA, Caucasus, and Central Asia, for an overall number of ~9000 subjects. Three hundred seventy-five genes across all nine analyses were tagged by single nucleotide polymorphisms (SNPs) reaching a suggestive p-value (p < 10-5). Amongst these, 15 were successfully replicated using a gene-based approach in the independent Italian Salus in the Apulia cohort (n = 1774) at the nominal significance threshold (p < 0.05). In addition, the expression level of the replicated genes was assessed in published human and mouse inner ear datasets. Considering expression patterns in humans and mice, eleven genes were considered particularly promising candidates for the hearing function: BNIP3L, ELP5, MAP3K20, MATN2, MTMR7, MYO1E, PCNT, R3HDM1, SLC9A9, TGFB2, and YTHDC2. These findings represent a further contribution to our understanding of the genetic basis of hearing function and its related diseases.


Assuntos
Audição/genética , Animais , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Itália , Masculino , Camundongos , Limiar Sensorial
12.
Hum Mol Genet ; 30(19): 1785-1796, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34059922

RESUMO

Non-Syndromic Hereditary Hearing Loss (NSHHL) is a genetically heterogeneous sensory disorder with about 120 genes already associated. Through exome sequencing (ES) and data aggregation, we identified a family with six affected individuals and one unrelated NSHHL patient with predicted-to-be deleterious missense variants in USP48. We also uncovered an eighth patient presenting unilateral cochlear nerve aplasia and a de novo splice variant in the same gene. USP48 encodes a ubiquitin carboxyl-terminal hydrolase under evolutionary constraint. Pathogenicity of the variants is supported by in vitro assays that showed that the mutated proteins are unable to hydrolyze tetra-ubiquitin. Correspondingly, three-dimensional representation of the protein containing the familial missense variant is situated in a loop that might influence the binding to ubiquitin. Consistent with a contribution of USP48 to auditory function, immunohistology showed that the encoded protein is expressed in the developing human inner ear, specifically in the spiral ganglion neurons, outer sulcus, interdental cells of the spiral limbus, stria vascularis, Reissner's membrane and in the transient Kolliker's organ that is essential for auditory development. Engineered zebrafish knocked-down for usp48, the USP48 ortholog, presented with a delayed development of primary motor neurons, less developed statoacoustic neurons innervating the ears, decreased swimming velocity and circling swimming behavior indicative of vestibular dysfunction and hearing impairment. Corroboratingly, acoustic startle response assays revealed a significant decrease of auditory response of zebrafish lacking usp48 at 600 and 800 Hz wavelengths. In conclusion, we describe a novel autosomal dominant NSHHL gene through a multipronged approach combining ES, animal modeling, immunohistology and molecular assays.


Assuntos
Perda Auditiva , Peixe-Zebra , Animais , Perda Auditiva/genética , Humanos , Hidrolases , Reflexo de Sobressalto , Ubiquitina , Proteases Específicas de Ubiquitina , Peixe-Zebra/genética
13.
Genes (Basel) ; 12(5)2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922566

RESUMO

To date, little is known about the role of olfactory receptor (OR) genes on smell performance. Thanks to the availability of whole-genome sequencing data of 802 samples, we identified 41 knockout (KO) OR genes (i.e., carriers of Loss of Function variants) and evaluated their effect on odor discrimination in 218 Italian individuals through recursive partitioning analysis. Furthermore, we checked the expression of these genes in human and mouse tissues using publicly available data and the presence of organ-related diseases in human KO (HKO) individuals for OR expressed in non-olfactory tissues (Fisher test). The recursive partitioning analysis showed that age and the high number (burden) of OR-KO genes impact the worsening of odor discrimination (p-value < 0.05). Human expression data showed that 33/41 OR genes are expressed in the olfactory system (OS) and 27 in other tissues. Sixty putative mouse homologs of the 41 humans ORs have been identified, 58 of which are expressed in the OS and 37 in other tissues. No association between OR-KO individuals and pathologies has been detected. In conclusion, our work highlights the role of the burden of OR-KO genes in worse odor discrimination.


Assuntos
Percepção Olfatória , Receptores Odorantes/genética , Olfato , Idoso , Animais , Feminino , Humanos , Mutação com Perda de Função , Masculino , Camundongos , Pessoa de Meia-Idade , Receptores Odorantes/metabolismo
14.
Eur J Hum Genet ; 29(8): 1272-1281, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33727708

RESUMO

Whole genome sequencing (WGS) allows the identification of human knockouts (HKOs), individuals in whom loss of function (LoF) variants disrupt both alleles of a given gene. HKOs are a valuable model for understanding the consequences of genes function loss. Naturally occurring biallelic LoF variants tend to be significantly enriched in "genetic isolates," making these populations specifically suited for HKO studies. In this work, a meticulous WGS data analysis combined with an in-depth phenotypic assessment of 947 individuals from three Italian genetic isolates led to the identification of ten biallelic LoF variants in ten OMIM genes associated with known autosomal recessive diseases. Notably, only a minority of the identified HKOs (C7, F12, and GPR68 genes) displayed the expected phenotype. For most of the genes, instead, (ACADSB, FANCL, GRK1, LGI4, MPO, PGAM2, and RP1L1), the carriers showed none or few of the signs and symptoms typically associated with the related diseases. Of particular interest is a case presenting with a FANCL biallelic LoF variant and a positive diepoxybutane test but lacking a full Fanconi anemia phenotypic spectrum. Identifying KO subjects displaying expected phenotypes suggests that the lack of correct genetic diagnoses may lead to inappropriate and delayed treatment. In contrast, the presence of HKOs with phenotypes deviating from the expected patterns underlines how LoF variants may be responsible for broader phenotypic spectra. Overall, these results highlight the importance of in-depth phenotypical characterization to understand the role of LoF variants and the advantage of studying these variants in genetic isolates.


Assuntos
Frequência do Gene , Doenças Genéticas Inatas/genética , Mutação com Perda de Função , População/genética , Humanos , Itália , Isolamento Reprodutivo , Sequenciamento Completo do Genoma/estatística & dados numéricos
15.
J Int Adv Otol ; 17(1): 81-83, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33605226

RESUMO

This paper aims to present a third world case of Non-Syndromic sensorineural hearing loss (NSHL) due to a novel missense variant in COL11A1 gene, defined as DFNA37 non-syndromic hearing loss. The clinical features of a 6-year-old boy affected by a bilateral moderate to severe down-sloping sensorineural hearing loss are presented, as well as the genetic analysis, the latter identifying a heterozygous missense variation in the COL11A1 gene. In addition, in families with autosomal dominant transmission, COL11A1 gene should be considered in the genetic workup of the NSHL with prelingual onset.


Assuntos
Colágeno Tipo XI/genética , Perda Auditiva , Cesárea , Criança , Feminino , Perda Auditiva/genética , Humanos , Masculino , Mutação , Gravidez
17.
Biomedicines ; 10(1)2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-35052694

RESUMO

Hearing loss (HL) is the most common sensory impairment, and it is characterized by a high clinical/genetic heterogeneity. Here we report the identification of dual molecular diagnoses (i.e., mutations at two loci that lead to the expression of two Mendelian conditions) in a series of families affected by non-syndromic and syndromic HL. Eighty-two patients who displayed HL as a major clinical feature have been recruited during the last year. After an accurate clinical evaluation, individuals have been analyzed through whole-exome sequencing (WES). This protocol led to the identification of seven families characterized by the presence of a dual diagnosis. In particular, based on the clinical and genetic findings, patients have been classified into two groups: (a) patients with HL and distinct phenotypes not fitting in a known syndrome due to mutations at two loci (e.g., HL in association with Marfan syndrome) and (b) patients with two genes involved in HL phenotype (e.g., TMPRSS3 and MYH14). These data highlight for the first time the high prevalence of dual molecular diagnoses in HL patients and suggest that they should be considered especially for those cases that depart from the expected clinical manifestation or those characterized by a significant intra-familiar variability.

18.
Genes (Basel) ; 13(1)2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-35052345

RESUMO

Human personality (i.e., temperament and character) is a complex trait related to mental health, influenced by genetic and environmental factors. Despite the efforts performed during the past decades, its genetic background is only just beginning to be identified. With the aim of dissecting the genetic basis of temperament, we performed a Genome-Wide Association Study (GWAS) on Cloninger's Temperament and Character Inventory in 587 individuals belonging to different Italian genetic isolates. Data analysis led to the identification of four new genes associated with different temperament scales, such as Novelty Seeking (NS), Harm Avoidance (HA), and Reward Dependence (RD). In detail, we identified suggestive and significant associations between: MAGI2 (highest p-value = 9.14 × 10-8), a gene already associated with schizophrenia and depressive disorder, and the NS-Extravagance scale; CALCB (highest p-value = 4.34 × 10-6), a gene likely involved in the behavioral evolution from wild wolf to domestic dog, and the NS-Disorderliness scale; BTBD3 (highest p-value = 2.152 × 10-8), a gene already linked to obsessive-compulsive disorder, and the HA-Fatigability scale; PRKN (highest p-value = 8.27 × 10-9), a gene described for early onset Parkinson's disease, and the RD scale. Our work provides new relevant insights into the genetics of temperament, helping to elucidate the molecular basis of psychiatric disorders.


Assuntos
Personalidade/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Peptídeo Relacionado com Gene de Calcitonina/genética , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Guanilato Quinases/genética , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Ubiquitina-Proteína Ligases/genética , Adulto Jovem
19.
Genes (Basel) ; 11(11)2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33105617

RESUMO

Hearing loss (HL), both syndromic (SHL) and non-syndromic (NSHL), is the most common sensory disorder, affecting ~460 million people worldwide. More than 50% of the congenital/childhood cases are attributable to genetic causes, highlighting the importance of genetic testing in this class of disorders. Here we applied a multi-step strategy for the molecular diagnosis of HL in 125 patients, which included: (1) an accurate clinical evaluation, (2) the analysis of GJB2, GJB6, and MT-RNR1 genes, (3) the evaluation STRC-CATSPER2 and OTOA deletions via Multiplex Ligation Probe Amplification (MLPA), (4) Whole Exome Sequencing (WES) in patients negative to steps 2 and 3. Our approach led to the characterization of 50% of the NSHL cases, confirming both the relevant role of the GJB2 (20% of cases) and STRC deletions (6% of cases), and the high genetic heterogeneity of NSHL. Moreover, due to the genetic findings, 4% of apparent NSHL patients have been re-diagnosed as SHL. Finally, WES characterized 86% of SHL patients, supporting the role of already know disease-genes. Overall, our approach proved to be efficient in identifying the molecular cause of HL, providing essential information for the patients' future management.


Assuntos
Surdez/diagnóstico , Surdez/genética , Técnicas de Diagnóstico Molecular , Conexina 26/genética , Conexina 30/genética , DNA Mitocondrial/genética , Surdez/patologia , Testes Genéticos , Humanos , Itália , Sequenciamento Completo do Exoma
20.
J Perinat Neonatal Nurs ; 34(4): E23-E31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33079811

RESUMO

Adverse childhood experiences and trauma significantly impact physical and mental health. Increased maternal perinatal depression/anxiety, preterm labor, and low birth weight, as well as infant morbidity and mortality, are some examples of the impact of trauma on perinatal health. Trauma-informed care begins with knowledge about trauma, the ability to recognize signs of a trauma response, responding to patients effectively, and resisting retraumatization. As holistic providers, perinatal nurses can create safe care environments, establish collaborative patient relationships based on trust, demonstrate compassion, offer patients options when possible to support patient autonomy, and provide resources for trauma survivors. This can prevent or reduce the negative impact of trauma and improve the health and well-being of infants, mothers, and future generations. This clinical article outlines key strategies for implementation of patient-centered trauma-informed perinatal nursing care.


Assuntos
Experiências Adversas da Infância/prevenção & controle , Enfermagem Holística/métodos , Enfermagem Materno-Infantil/métodos , Enfermagem Neonatal/métodos , Complicações na Gravidez , Transtornos Relacionados a Trauma e Fatores de Estresse , Depressão Pós-Parto/complicações , Depressão Pós-Parto/enfermagem , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Efeitos Adversos de Longa Duração/enfermagem , Efeitos Adversos de Longa Duração/prevenção & controle , Saúde Mental , Trabalho de Parto Prematuro/enfermagem , Trabalho de Parto Prematuro/psicologia , Assistência Centrada no Paciente , Gravidez , Complicações na Gravidez/enfermagem , Complicações na Gravidez/psicologia , Transtornos Relacionados a Trauma e Fatores de Estresse/etiologia , Transtornos Relacionados a Trauma e Fatores de Estresse/enfermagem , Transtornos Relacionados a Trauma e Fatores de Estresse/prevenção & controle
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