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1.
Appl Environ Microbiol ; 90(5): e0234923, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38597602

RESUMO

Piscine lactococcosis is a significant threat to cultured and wild fish populations worldwide. The disease typically presents as a per-acute to acute hemorrhagic septicemia causing high morbidity and mortality, recalcitrant to antimicrobial treatment or management interventions. Historically, the disease was attributed to the gram-positive pathogen Lactococcus garvieae. However, recent work has revealed three distinct lactococcosis-causing bacteria (LCB)-L. garvieae, L. petauri, and L. formosensis-which are phenotypically and genetically similar, leading to widespread misidentification. An update on our understanding of lactococcosis and improved methods for identification are urgently needed. To this end, we used representative isolates from each of the three LCB species to compare currently available and recently developed molecular and phenotypic typing assays, including whole-genome sequencing (WGS), end-point and quantitative PCR (qPCR) assays, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), API 20 Strep and Biolog systems, fatty acid methyl ester analysis (FAME), and Sensititre antimicrobial profiling. Apart from WGS, sequencing of the gyrB gene was the only method capable of consistent and accurate identification to the species and strain level. A qPCR assay based on a putative glycosyltransferase gene was also able to distinguish L. petauri from L. garvieae/formosensis. Biochemical tests and MALDI-TOF MS showed some species-specific patterns in sugar and fatty acid metabolism or protein profiles but should be complemented by additional analyses. The LCB demonstrated overlap in host and geographic range, but there were relevant differences in host specificity, regional prevalence, and antimicrobial susceptibility impacting disease treatment and prevention. IMPORTANCE: Lactococcosis affects a broad range of host species, including fish from cold, temperate, and warm freshwater or marine environments, as well as several terrestrial animals, including humans. As such, lactococcosis is a disease of concern for animal and ecosystem health. The disease is endemic in European and Asian aquaculture but is rapidly encroaching on ecologically and economically important fish populations across the Americas. Piscine lactococcosis is difficult to manage, with issues of vaccine escape, ineffective antimicrobial treatment, and the development of carrier fish or biofilms leading to recurrent outbreaks. Our understanding of the disease is also widely outdated. The accepted etiologic agent of lactococcosis is Lactococcus garvieae. However, historical misidentification has masked contributions from two additional species, L. petauri and L. formosensis, which are indistinguishable from L. garvieae by common diagnostic methods. This work is the first comprehensive characterization of all three agents and provides direct recommendations for species-specific diagnosis and management.


Assuntos
Doenças dos Peixes , Infecções por Bactérias Gram-Positivas , Lactococcus , Lactococcus/genética , Lactococcus/isolamento & purificação , Lactococcus/classificação , Animais , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/veterinária , Peixes/microbiologia , Sequenciamento Completo do Genoma , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
3.
Genet Med ; 26(3): 101035, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38059438

RESUMO

PURPOSE: Clinically ascertained variants are under-utilized in neurodevelopmental disorder research. We established the Brain Gene Registry (BGR) to coregister clinically identified variants in putative brain genes with participant phenotypes. Here, we report 179 genetic variants in the first 179 BGR registrants and analyze the proportion that were novel to ClinVar at the time of entry and those that were absent in other disease databases. METHODS: From 10 academically affiliated institutions, 179 individuals with 179 variants were enrolled into the BGR. Variants were cross-referenced for previous presence in ClinVar and for presence in 6 other genetic databases. RESULTS: Of 179 variants in 76 genes, 76 (42.5%) were novel to ClinVar, and 62 (34.6%) were absent from all databases analyzed. Of the 103 variants present in ClinVar, 37 (35.9%) were uncertain (ClinVar aggregate classification of variant of uncertain significance or conflicting classifications). For 5 variants, the aggregate ClinVar classification was inconsistent with the interpretation from the BGR site-provided classification. CONCLUSION: A significant proportion of clinical variants that are novel or uncertain are not shared, limiting the evidence base for new gene-disease relationships. Registration of paired clinical genetic test results with phenotype has the potential to advance knowledge of the relationships between genes and neurodevelopmental disorders.


Assuntos
Bases de Dados Genéticas , Variação Genética , Humanos , Variação Genética/genética , Testes Genéticos/métodos , Fenótipo , Encéfalo
4.
J Aging Health ; 36(5-6): 379-389, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37493607

RESUMO

ObjectivesAmong nursing home (NH) residents with Alzheimer's disease (AD) and AD-related dementias (AD/ADRD), racial/ethnic disparities in quality of care exist. However, little is known about quality of life (QoL). This study examines racial/ethnic differences in self-reported QoL among NH residents with AD/ADRD. Methods: Validated, in-person QoL surveys from 12,562 long-stay NH residents with AD/ADRD in Minnesota (2012-2015) were linked to Minimum Data Set assessments and facility characteristics. Hierarchical linear models assessed disparities in resident-reported mean QoL score (range, 0-100 points), adjusting for case-mix and facility factors. Results: Compared to White residents, racially/ethnically minoritized residents reported significantly lower total mean QoL scores (75.53 points vs. 80.34 points, p < .001). After adjustment for resident- and facility-level characteristics, significant racial/ethnic differences remained, with large disparities in food enjoyment, attention from staff, and engagement domains. Discussion: Policy changes and practice guidelines are needed to address racial/ethnic disparities in QoL of NH residents with AD/ADRD.


Assuntos
Doença de Alzheimer , Qualidade de Vida , Humanos , Fatores Raciais , Casas de Saúde , Instituições de Cuidados Especializados de Enfermagem
5.
Health Serv Res ; 59(2): e14263, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38145955

RESUMO

OBJECTIVE: The study aimed to assess whether individuals with Alzheimer's disease and related dementias (ADRD) experience restricted access to hospitals' high-volume preferred skilled nursing facility (SNF) partners. DATA SOURCES: The data source includes acute care hospital to SNF transitions identified using 100% Medicare Provider Analysis and Review files, 2017-2019. STUDY DESIGN: We model and compare the estimated effect of facility "preferredness" on SNF choice for patients with and without ADRD. We use conditional logistic regression with a 1:1 patient sample otherwise matched on demographic and encounter characteristics. DATA COLLECTION: Our matched sample included 58,190 patients, selected from a total observed population of 3,019,260 Medicare hospitalizations that resulted in an SNF transfer between 2017 and 2019. PRINCIPAL FINDINGS: Overall, patients with ADRD have a lower probability of being discharged to a preferred SNF (52.0% vs. 54.4%, p < 0.001). Choice model estimation using our matched sample suggests similarly that the marginal effect of preferredness on a patient choosing a proximate SNF is 2.4 percentage points lower for patients with ADRD compared with those without (p < 0.001). The differential effect of preferredness based on ADRD status increases when considering (a) the cumulative effect of multiple SNFs in close geographic proximity, (b) the magnitude of the strength of hospital-SNF relationship, and (c) comparing patients with more versus less advanced ADRD. CONCLUSIONS: Preferred relationships are significantly predictive of where a patient receives SNF care, but this effect is weaker for patients with ADRD. To the extent that these high-volume relationships are indicative of more targeted transitional care improvements from hospitals, ADRD patients may not be fully benefiting from these investments. Hospital leaders can leverage integrated care relationships to reduce SNFs' perceived need to engage in selection behavior (i.e., enhanced resource sharing and transparency in placement practices). Policy intervention may be needed to address selection behavior and to support hospitals in making systemic improvements that can better benefit all SNF partners (i.e., more robust information sharing systems).


Assuntos
Doença de Alzheimer , Cuidado Transicional , Idoso , Humanos , Estados Unidos , Instituições de Cuidados Especializados de Enfermagem , Doença de Alzheimer/terapia , Medicare , Alta do Paciente
6.
Microbiology (Reading) ; 169(11)2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37971493

RESUMO

Bacterial microcompartments (MCPs) are widespread protein-based organelles that play important roles in the global carbon cycle and in the physiology of diverse bacteria, including a number of pathogens. MCPs consist of metabolic enzymes encapsulated within a protein shell. The main roles of MCPs are to concentrate enzymes together with their substrates (to increase reaction rates) and to sequester harmful metabolic intermediates. Prior studies indicate that MCPs have a selectively permeable protein shell, but the mechanisms that allow selective transport across the shell are not fully understood. Here we examine transport across the shell of the choline utilization (Cut) MCP of Escherichia coli 536, which has not been studied before. The shell of the Cut MCP is unusual in consisting of one pentameric and four hexameric bacterial microcompartment (BMC) domain proteins. It lacks trimeric shell proteins, which are thought to be required for the transport of larger substrates and enzymatic cofactors. In addition, its four hexameric BMC domain proteins are very similar in amino acid sequence. This raises questions about how the Cut MCP mediates the selective transport of the substrate, products and cofactors of choline metabolism. In this report, site-directed mutagenesis is used to modify the central pores (the main transport channels) of all four Cut BMC hexamers to assess their transport roles. Our findings indicate that a single shell protein, CmcB, plays the major role in choline transport across the shell of the Cut MCP and that the electrostatic properties of the CmcB pore also impact choline transport. The implications of these findings with regard to the higher-order structure of MCPs are discussed.


Assuntos
Proteínas de Bactérias , Colina , Proteínas de Bactérias/metabolismo , Colina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Bactérias/metabolismo , Sequência de Aminoácidos , Organelas/metabolismo
7.
J Aquat Anim Health ; 35(3): 187-198, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37749801

RESUMO

OBJECTIVE: The first objective of the study aimed to detect the presence of Lactococcus petauri, L. garvieae, and L. formosensis in fish (n = 359) and environmental (n = 161) samples from four lakes near an affected fish farm in California during an outbreak in 2020. The second objective was to compare the virulence of the Lactococcus spp. in Rainbow Trout Oncorhynchus mykiss and Largemouth Bass Micropterus salmoides. METHODS: Standard bacterial culture methods were used to isolate Lactococcus spp. from brain and posterior kidney of sampled fish from the four lakes. Quantitative PCR (qPCR) was utilized to detect Lactococcus spp. DNA in fish tissues and environmental samples from the four lakes. Laboratory controlled challenges were conducted by injecting fish intracoelomically with representative isolates of L. petauri (n = 17), L. garvieae (n = 2), or L. formosensis (n = 4), and monitored for 14 days postchallenge (dpc). RESULT: Lactococcus garvieae was isolated from the brains of two Largemouth Bass in one of the lakes. Lactococcus spp. were detected in 14 fish (8 Bluegills Lepomis macrochirus and 6 Largemouth Bass) from 3 out of the 4 lakes using a qPCR assay. Of the collected environmental samples, all 4 lakes tested positive for Lactococcus spp. in the soil samples, while 2 of the 4 lakes tested positive in the water samples through qPCR. Challenged Largemouth Bass did not show any signs of infection postinjection throughout the challenge period. Rainbow Trout infected with L. petauri showed clinical signs within 3 dpc and presented a significantly higher cumulative mortality (62.4%; p < 0.0001) at 14 dpc when compared to L. garvieae (0%) and L. formosensis (7.5%) treatments. CONCLUSION: The study suggests that qPCR can be used for environmental DNA monitoring of Lactococcus spp. and demonstrates virulence diversity between the etiological agents of piscine lactococcosis.


Assuntos
Doenças dos Peixes , Infecções por Bactérias Gram-Positivas , Oncorhynchus mykiss , Animais , Virulência , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/veterinária , Infecções por Bactérias Gram-Positivas/microbiologia , Lagos , Lactococcus/genética , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/microbiologia
8.
Dis Aquat Organ ; 155: 147-158, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37706645

RESUMO

Lactococcus petauri is an important emergent aquaculture pathogen in the USA. To better understand environmental conditions conducive to piscine lactococcosis and the susceptibility of fish species, laboratory-controlled challenges were used as models of infection. Rainbow trout Oncorhynchus mykiss maintained at 13 or 18°C were challenged by intracoelomic (ICe) injection with 101, 103 or 105 colony-forming units per fish (CFU fish-1) and monitored for 21 d. At 13°C, trout experienced mortalities of 7, 7 and 0%, and bacterial persistence of 0, 20 and 0% in survivors, respectively. When exposed to the same bacterial doses, trout maintained at 18°C experienced mortalities of 59, 84 and 91%, and bacterial persistence of 60, 66 and 0% in survivors, confirming a significant role of temperature in the pathogenesis of lactococcosis. Additionally, the susceptibility of rainbow trout, Chinook salmon Oncorhynchus tshawytscha, white sturgeon Acipenser transmontanus, Nile tilapia Oreochromis niloticus, and koi Cyprinus carpio to infection by L. petauri was compared using ICe challenges at 18°C. Trout and salmon experienced 96 and 56% cumulative mortality, respectively, and 17% of surviving salmon remained persistently infected. There were no mortalities in the other fish species, and no culturable bacteria recovered at the end of the challenge. However, when surviving fish were used in further cohabitation trials, naïve trout housed with previously exposed tilapia exhibited 6% mortality, demonstrating that non-salmonids can become sub-clinical carriers of this pathogen. The data obtained provide useful information regarding temperature-associated virulence, fish species susceptibility, and potential carrier transmission of L. petauri that can be used in the development of better management practices to protect against piscine lactococcosis.


Assuntos
Carpas , Ciclídeos , Oncorhynchus mykiss , Animais , Salmão , Temperatura , Virulência
10.
Front Cell Infect Microbiol ; 13: 1149032, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153143

RESUMO

Flavobacterial diseases, caused by bacteria in the order Flavobacteriales, are responsible for devastating losses in farmed and wild fish populations worldwide. The genera Flavobacterium (Family Flavobacteriaceae) and Chryseobacterium (Weeksellaceae) encompass the most well-known agents of fish disease in the order, but the full extent of piscine-pathogenic species within these diverse groups is unresolved, and likely underappreciated. To identify emerging agents of flavobacterial disease in US aquaculture, 183 presumptive Flavobacterium and Chryseobacterium isolates were collected from clinically affected fish representing 19 host types, from across six western states. Isolates were characterized by 16S rRNA gene sequencing and phylogenetic analysis using the gyrB gene. Antimicrobial susceptibility profiles were compared between representatives from each major phylogenetic clade. Of the isolates, 52 were identified as Chryseobacterium species and 131 as Flavobacterium. The majority of Chryseobacterium isolates fell into six clades (A-F) consisting of ≥ 5 fish isolates with ≥ 70% bootstrap support, and Flavobacterium into nine (A-I). Phylogenetic clades showed distinct patterns in antimicrobial susceptibility. Two Chryseobacterium clades (F & G), and four Flavobacterium clades (B, G-I) had comparably high minimal inhibitory concentrations (MICs) for 11/18 antimicrobials tested. Multiple clades in both genera exhibited MICs surpassing the established F. psychrophilum breakpoints for oxytetracycline and florfenicol, indicating potential resistance to two of the three antimicrobials approved for use in finfish aquaculture. Further work to investigate the virulence and antigenic diversity of these genetic groups will improve our understanding of flavobacterial disease, with applications for treatment and vaccination strategies.


Assuntos
Chryseobacterium , Doenças dos Peixes , Infecções por Flavobacteriaceae , Flavobacteriaceae , Animais , Estados Unidos , Flavobacterium/genética , Filogenia , RNA Ribossômico 16S/genética , Infecções por Flavobacteriaceae/veterinária , Infecções por Flavobacteriaceae/microbiologia , Flavobacteriaceae/genética , Peixes , Chryseobacterium/genética , Doenças dos Peixes/microbiologia
11.
Nat Food ; 4(1): 96-108, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-37118582

RESUMO

Organizations are increasingly committing to biodiversity protection targets with focus on 'nature-positive' outcomes, yet examples of how to feasibly achieve these targets are needed. Here we propose an approach to achieve nature-positive targets with respect to the embodied biodiversity impacts of an organization's food consumption. We quantify these impacts using a comprehensive database of life-cycle environmental impacts from food, and map exploratory strategies to meet defined targets structured according to a mitigation and conservation hierarchy. By considering the varying needs and values across the organization's internal community, we identify a range of targeted approaches towards mitigating impacts, which balance top-down and bottom-up actions to different degrees. Delivering ambitious nature-positive targets within current constraints will be challenging, particularly given the need to mitigate cumulative impacts. Our results evidence that however committed an organization is to being nature positive in its food provision, this is unachievable in the absence of systems change.


Assuntos
Biodiversidade , Objetivos
12.
J Fish Dis ; 46(6): 629-641, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36866813

RESUMO

The giant snakehead, Channa micropeltes, is an increasingly important economic freshwater fish in Thailand and other regions of Asia. Presently, giant snakehead are cultured under intensive aquaculture conditions, leading to high stress and conditions favouring disease. In this study, we reported a disease outbreak in farmed giant snakehead with a cumulative mortality of 52.5%, continuing for 2 months. The affected fish exhibited signs of lethargy, anorexia and haemorrhage of the skin and eyes. Further bacterial isolations revealed two different types of colonies on tryptic soy agar: small white, punctate colonies of gram-positive cocci and cream-coloured, round and convex colonies of rod-shaped gram-negative bacteria. Additional biochemical and species-specific PCR analysis based on 16S rRNA confirmed the isolates as Streptococcus iniae and Aeromonas veronii. Multilocus sequence analysis (MLSA) placed the S. iniae isolate into a large clade of strains from clinically infected fish worldwide. Gross necropsy findings showed liver congestion, pericarditis and white nodules in the kidney and liver. Histologically, the affected fish showed focal to multifocal granulomas with inflammatory cell infiltration in kidney and liver, enlarged blood vessels with mild congestion within the meninges of the brain and severe necrotizing and suppurative pericarditis with myocardial infarction. Antibiotic susceptibility tests revealed that S. iniae was sensitive to amoxicillin, erythromycin, enrofloxacin, oxytetracycline, doxycycline and resistant to sulfamethoxazole-trimethoprim, while the A. veronii was susceptible to erythromycin, enrofloxacin, oxytetracycline, doxycycline, sulfamethoxazole-trimethoprim and resistant to amoxicillin. Conclusively, our findings highlighted the natural concurrent bacterial infections in cultured giant snakehead, which support the implementation of appropriate treatment and control strategies.


Assuntos
Aeromonas , Doenças dos Peixes , Oxitetraciclina , Pericardite , Animais , Aeromonas veronii/genética , Streptococcus iniae/genética , Doxiciclina , Enrofloxacina , RNA Ribossômico 16S/genética , Doenças dos Peixes/microbiologia , Peixes/genética , Amoxicilina , Eritromicina , Sulfametoxazol , Trimetoprima , Tailândia , Aeromonas/genética
13.
J Am Geriatr Soc ; 71(6): 1963-1973, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36762760

RESUMO

BACKGROUND: Patients with complex behavioral and mental health conditions require significant transitional care coordination. It is unclear how skilled nursing facilities (SNFs) that serve these patients engage in care transfer with hospitals, specifically whether they experience discrepancies in the type of information shared by hospital partners and/or use different approaches to secure needed information. METHODS: Cross-sectional analysis of a national 2019-2020 SNF survey that collected information on transitional care practices with referring hospitals; respondents were directors of nursing services. We used chi-squared tests and descriptive statistics to characterize hospital information sharing practices experienced by facilities that accept complex patients (e.g., serious mental illness, substance use disorder, and/or medication assisted treatment), and to compare them to facilities that treat a less complex population. RESULTS: A total of 215 SNFs had sufficiently complete responses for inclusion in the analysis. Of these respondents, 57% accepted two or more types of patients with complex conditions of interest; these SNFs were more likely to be urban, for-profit, and serve more dual-eligible patients. SNFs accepting complex patients experience information sharing on par with other facilities, and are more likely to receive information on behavioral, social, mental, and functional status (25.41% vs. 12.90%; p = 0.023). These facilities are also more likely to consistently use electronic methods (e.g., an online portal, shared electronic health record [EHR] access) to retrieve information from partner hospitals. CONCLUSIONS: SNFs accepting complex patients demonstrate some evidence of enhanced information retrieval via electronically mediated pathways. Overall, information sharing remains underdeveloped in this care context. Policymakers should continue to prioritize widespread digital infrastructure that supports post-acute care delivery.


Assuntos
Transferência de Pacientes , Cuidado Transicional , Humanos , Estados Unidos , Saúde Mental , Estudos Transversais , Disseminação de Informação , Instituições de Cuidados Especializados de Enfermagem , Alta do Paciente
14.
Gerontologist ; 63(9): 1437-1455, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36640128

RESUMO

BACKGROUND AND OBJECTIVES: Long-term services and supports in the United States are increasingly reliant on home- and community-based services (HCBS). Yet, little is known about the quality of HCBS. We conducted a scoping review of the peer-reviewed literature to summarize HCBS consumer, provider, and stakeholder satisfaction with services as a means of assessing quality. RESEARCH DESIGN AND METHODS: We searched PubMed, OVID-MEDLINE, and SCOPUS to identify articles published from 2000 to 2021 that reported on studies describing a U.S.-based study population. Articles were grouped into 3 categories: drivers of positive consumer satisfaction, drivers of negative consumer satisfaction, and provider and stakeholder perspectives on satisfaction. RESULTS: Our final sample included 27 articles. Positive perceptions of quality and reported satisfaction with services were driven by consistent, reliable, and respectful care providers, and adoption of person-centered models of service delivery. Mistreatment of consumers, staff turnover, training, service interruptions, and unmet functional needs were drivers of negative consumer perceptions of quality. Support for caregivers and emphasis on training were identified by providers and stakeholders as important for providing satisfactory services. DISCUSSION AND IMPLICATIONS: Multiple data challenges limit the ability to systematically evaluate HCBS program quality; however, studies examining single programs found that HCBS consumers are more satisfied and associate higher quality with easy-to-navigate programs and professional staff. Efforts to expand HCBS should also include requirements to systematically evaluate quality outcomes.


Assuntos
Serviços de Saúde Comunitária , Serviços de Assistência Domiciliar , Humanos , Estados Unidos , Medicaid , Cuidadores , Satisfação Pessoal
16.
JACC Basic Transl Sci ; 7(6): 608-625, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35818510

RESUMO

Duchenne muscular dystrophy (DMD) is a devastating disease affecting approximately 1 in every 3,500 male births worldwide. Multiple mutations in the dystrophin gene have been implicated as underlying causes of DMD. However, there remains no cure for patients with DMD, and cardiomyopathy has become the most common cause of death in the affected population. Extensive research is under way investigating molecular mechanisms that highlight potential therapeutic targets for the development of pharmacotherapy for DMD cardiomyopathy. In this paper, the authors perform a literature review reporting on recent ongoing efforts to identify novel therapeutic strategies to reduce, prevent, or reverse progression of cardiac dysfunction in DMD.

17.
Genet Med ; 24(9): 1899-1908, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35616647

RESUMO

PURPOSE: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not. METHODS: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. RESULTS: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants. CONCLUSION: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Transtorno Autístico/diagnóstico , Transtorno Autístico/genética , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética
18.
J Fish Dis ; 45(6): 847-859, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35306674

RESUMO

Piscine lactococcosis is an emergent bacterial disease that is associated with high economic losses in many farmed and wild aquatic species worldwide. Early and accurate detection of the causative agent of piscine lactococcosis is essential for management of the disease in fish farms. In this study, a TaqMan quantitative polymerase chain reaction (qPCR) targeting the 16S-23S rRNA internal transcribed spacer region was developed and validated. Validation of the qPCR was performed with DNA of previously typed L. petauri and L. garvieae recovered from different aquatic hosts from distinct geographical locations, closely related bacterial species and common pathogens in trout aquaculture. Further diagnostic sensitivity and specificity was investigated by screening of fish, water and faecal samples. The developed qPCR assay showed high specificity, sensitivity and accuracy in detection of L. petauri and L. garvieae with lack of signals from non-target pathogens, and in screening of rainbow trout (Oncorhynchus mykiss) posterior kidney and environmental samples. The detection limit of the qPCR was four amplicon copies. Moreover, the sensitivity of the qPCR assay was not affected by presence of non-target DNA from either fish or environmental samples. The robustness, specificity and sensitivity of the developed qPCR will facilitate fast and accurate diagnosis of piscine lactococcosis to establish appropriate control measures in fish farms and aquaria.


Assuntos
Doenças dos Peixes , Oncorhynchus mykiss , Animais , DNA , Doenças dos Peixes/microbiologia , Lactococcus/genética , Oncorhynchus mykiss/microbiologia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética
19.
Transbound Emerg Dis ; 69(4): 2326-2343, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34328271

RESUMO

Lactococcus garvieae is an emergent bacterial pathogen of salmonid fish in North America that causes acute infections particularly at water temperatures above 15°C. During 2020, L. garvieae was detected in rainbow trout, Onchorhyncus mykiss, cultured in Southern California and the Eastern Sierras. Infected fish exhibited high mortalities and nonspecific clinical signs of lethargy, erratic swimming, dark skin pigmentation, and exophthalmia. Macroscopic changes included external and internal hemorrhages, mainly in the eyes, liver, coelomic fat, intestine, and brain. Histological examination revealed splenitis, branchitis, panophthalmitis, hepatitis, enteritis, and coelomitis, with variable degrees of tissue damage among evaluated fish. Pure colonies of L. garvieae were isolated from infected trout and specific PCR primers for L. garvieae confirmed the preliminary diagnosis. Multilocus sequence analysis showed that the strains recovered from diseased trout represent a novel genetic group. Isolates were able to form biofilms within 24 h that increased their resistance to disinfection by hydrogen peroxide. Laboratory challenge methods for inducing lactococcosis in steelhead trout, O. mykiss, were evaluated by intracoelomic injection with serial dilutions of L. garvieae. The median lethal dose 21 days post challenge was ∼20 colony-forming units/fish. Experimentally infected trout presented similar clinical signs, gross changes, and microscopic lesions as those with natural disease, fulfilling Koch's postulates and demonstrating the high virulence of the recovered strains.


Assuntos
Doenças dos Peixes , Infecções por Bactérias Gram-Positivas , Oncorhynchus mykiss , Animais , California/epidemiologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/veterinária , Lactococcus , Oncorhynchus mykiss/microbiologia
20.
J Am Med Dir Assoc ; 23(2): 214-219, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34958742

RESUMO

Long-term services and supports (LTSS), including care received at home and in residential settings such as nursing homes, are highly racially segregated; Black, Indigenous, and persons of color (BIPOC) users have less access to quality care and report poorer quality of life compared to their White counterparts. Systemic racism lies at the root of these disparities, manifesting via racially segregated care, low Medicaid reimbursement, and lack of livable wages for staff, along with other policies and processes that exacerbate disparities. We reviewed Medicaid reimbursement, pay-for-performance, public reporting of quality of care, and culture change in nursing homes and integrated home- and community-based service (HCBS) programs as possible mechanisms for addressing racial and ethnic disparities. We developed a set of recommendations for LTSS based on existing evidence, including (1) increase Medicaid and Medicare reimbursement rates, especially for providers serving high proportions of Medicaid-eligible and BIPOC older adults; (2) reconsider the design of pay-for-performance programs as they relate to providers who serve underserved groups; (3) include culturally sensitive measures, such as quality of life, in public reporting of quality of care, and develop and report health equity measures in outcomes of care for BIPOC individuals; (4) implement culture change so services are more person-centered and homelike, alongside improvements in staff wages and benefits in high-proportion BIPOC nursing homes; (5) expand access to Medicaid-waivered HCBS services; (6) adopt culturally appropriate HCBS practices, with special attention to family caregivers; (7) and increase promotion of integrated HCBS programs that can be targeted to BIPOC consumers, and implement models that value community health workers. Multipronged solutions may help diminish the role of systemic racism in existing racial disparities in LTSS, and these recommendations provide steps for action that are needed to reimagine how long-term care is delivered, especially for BIPOC populations.


Assuntos
Serviços de Assistência Domiciliar , Qualidade de Vida , Idoso , Serviços de Saúde Comunitária , Humanos , Assistência de Longa Duração , Medicaid , Medicare , Reembolso de Incentivo , Racismo Sistêmico , Estados Unidos
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