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1.
EMBO J ; 41(22): e111952, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36314651

RESUMO

Aging is a major risk factor to develop neurodegenerative diseases and is associated with decreased buffering capacity of the proteostasis network. We investigated the significance of the unfolded protein response (UPR), a major signaling pathway activated to cope with endoplasmic reticulum (ER) stress, in the functional deterioration of the mammalian brain during aging. We report that genetic disruption of the ER stress sensor IRE1 accelerated age-related cognitive decline. In mouse models, overexpressing an active form of the UPR transcription factor XBP1 restored synaptic and cognitive function, in addition to reducing cell senescence. Proteomic profiling of hippocampal tissue showed that XBP1 expression significantly restore changes associated with aging, including factors involved in synaptic function and pathways linked to neurodegenerative diseases. The genes modified by XBP1 in the aged hippocampus where also altered. Collectively, our results demonstrate that strategies to manipulate the UPR in mammals may help sustain healthy brain aging.


Assuntos
Envelhecimento , Encéfalo , Proteínas Serina-Treonina Quinases , Resposta a Proteínas não Dobradas , Proteína 1 de Ligação a X-Box , Animais , Camundongos , Envelhecimento/genética , Encéfalo/metabolismo , Estresse do Retículo Endoplasmático/genética , Proteínas Serina-Treonina Quinases/genética , Proteômica , Transdução de Sinais/fisiologia , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
2.
Med Mycol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38936838

RESUMO

Candida auris is an emerging fungal pathogen responsible for healthcare associated infections and outbreaks with high mortality around the world. It readily colonizes the skin, nares, respiratory and urinary tract of hospitalized patients, and such colonization may lead to invasive Candida infection in susceptible patients. However, there is no recommended decolonization protocol for C. auris by international health authorities. The aim of this study is to evaluate the susceptibility of C. auris to commonly used synthetic and natural antiseptic products using an in vitro, broth microdilution assay. Synthetic antiseptics including chlorhexidine, povidone-iodine, and nystatin were shown to be fungicidal against C. auris. Among the natural antiseptics tested, tea tree oil and manuka oil were both fungicidal against C. auris at concentrations less than or equal to 1.25% (v/v). Manuka honey inhibited C. auris at 25% (v/v) concentrations. Among the commercial products tested, manuka body wash and mouthwash were fungicidal against C. auris at concentrations less than or equal to 0.39% (w/v) and 6.25% (v/v) of products as supplied for use, respectively, while tea tree body wash and MedihoneyTM wound gel demonstrated fungistatic properties. In conclusion, this study demonstrated good in vitro antifungal efficacy of tea tree oil, manuka oil, manuka honey, and commercially available antiseptic products containing these active ingredients. Future studies are warranted to evaluate the effectiveness of these antiseptic products in clinical settings.


Candida auris is an emerging superbug fungus that poses a serious threat to global public health. The excellent antifungal efficacy of natural antiseptics and their commercial hygiene products provide new insights into development of an alternative decolonization regimen against Candida auris.

3.
Mol Ther ; 31(7): 2240-2256, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37016577

RESUMO

Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol-requiring enzyme-1 (IRE1) operates as a central ER stress sensor, enabling the establishment of adaptive and repair programs through the control of the expression of the transcription factor X-box binding protein 1 (XBP1). To artificially enforce the adaptive capacity of the UPR in the AD brain, we developed strategies to express the active form of XBP1 in the brain. Overexpression of XBP1 in the nervous system using transgenic mice reduced the load of amyloid deposits and preserved synaptic and cognitive function. Moreover, local delivery of XBP1 into the hippocampus of an 5xFAD mice using adeno-associated vectors improved different AD features. XBP1 expression corrected a large proportion of the proteomic alterations observed in the AD model, restoring the levels of several synaptic proteins and factors involved in actin cytoskeleton regulation and axonal growth. Our results illustrate the therapeutic potential of targeting UPR-dependent gene expression programs as a strategy to ameliorate AD features and sustain synaptic function.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Estresse do Retículo Endoplasmático/genética , Camundongos Transgênicos , Proteômica , Proteostase/genética , Transdução de Sinais/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resposta a Proteínas não Dobradas/genética
4.
Emerg Infect Dis ; 29(1): 133-140, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36480674

RESUMO

The Centers for Disease Control and Prevention recommends a COVID-19 vaccine booster dose for all persons >18 years of age. We analyzed data from the National Immunization Survey-Adult COVID Module collected during February 27-March 26, 2022 to assess COVID-19 booster dose vaccination coverage among adults. We used multivariable logistic regression analysis to assess factors associated with vaccination. COVID-19 booster dose coverage among fully vaccinated adults increased from 25.7% in November 2021 to 63.4% in March 2022. Coverage was lower among non-Hispanic Black (52.7%), and Hispanic (55.5%) than non-Hispanic White adults (67.7%). Coverage was 67.4% among essential healthcare personnel, 62.2% among adults who had a disability, and 69.9% among adults who had medical conditions. Booster dose coverage was not optimal, and disparities by race/ethnicity and other factors are apparent in coverage uptake. Tailored strategies are needed to educate the public and reduce disparities in COVID-19 vaccination coverage.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , Estados Unidos/epidemiologia , Cobertura Vacinal , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação
5.
MMWR Morb Mortal Wkly Rep ; 72(7): 190-198, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36795677

RESUMO

COVID-19 vaccine booster doses are safe and maintain protection after receipt of a primary vaccination series and reduce the risk for serious COVID-19-related outcomes, including emergency department visits, hospitalization, and death (1,2). CDC recommended an updated (bivalent) booster for adolescents aged 12-17 years and adults aged ≥18 years on September 1, 2022 (3). The bivalent booster is formulated to protect against the Omicron BA.4 and BA.5 subvariants of SARS-CoV-2 as well as the original (ancestral) strain (3). Based on data collected during October 30-December 31, 2022, from the National Immunization Survey-Child COVID Module (NIS-CCM) (4), among all adolescents aged 12-17 years who completed a primary series, 18.5% had received a bivalent booster dose, 52.0% had not yet received a bivalent booster but had parents open to booster vaccination for their child, 15.1% had not received a bivalent booster and had parents who were unsure about getting a booster vaccination for their child, and 14.4% had parents who were reluctant to seek booster vaccination for their child. Based on data collected during October 30-December 31, 2022, from the National Immunization Survey-Adult COVID Module (NIS-ACM) (4), 27.1% of adults who had completed a COVID-19 primary series had received a bivalent booster, 39.4% had not yet received a bivalent booster but were open to receiving booster vaccination, 12.4% had not yet received a bivalent booster and were unsure about getting a booster vaccination, and 21.1% were reluctant to receive a booster. Adolescents and adults in rural areas had a much lower primary series completion rate and up-to-date vaccination coverage. Bivalent booster coverage was lower among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) adolescents and adults compared with non-Hispanic White (White) adolescents and adults. Among adults who were open to receiving booster vaccination, 58.9% reported not having received a provider recommendation for booster vaccination, 16.9% had safety concerns, and 4.4% reported difficulty getting a booster vaccine. Among adolescents with parents who were open to getting a booster vaccination for their child, 32.4% had not received a provider recommendation for any COVID-19 vaccination, and 11.8% had parents who reported safety concerns. Although bivalent booster vaccination coverage among adults differed by factors such as income, health insurance status, and social vulnerability index (SVI), these factors were not associated with differences in reluctance to seek booster vaccination. Health care provider recommendations for COVID-19 vaccination; dissemination of information by trusted messengers about the continued risk for COVID-19-related illness and the benefits and safety of bivalent booster vaccination; and reducing barriers to vaccination could improve COVID-19 bivalent booster coverage among adolescents and adults.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Adulto , Estados Unidos/epidemiologia , Adolescente , Cobertura Vacinal , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação
6.
Clin Infect Dis ; 75(Suppl 2): S182-S192, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-35737951

RESUMO

The National Immunization Survey Adult COVID Module used a random-digit-dialed phone survey during 22 April 2021-29 January 2022 to quantify coronavirus disease 2019 (COVID-19) vaccination, intent, attitudes, and barriers by detailed race/ethnicity, interview language, and nativity. Foreign-born respondents overall and within racial/ethnic categories had higher vaccination coverage (80.9%), higher intent to be vaccinated (4.2%), and lower hesitancy toward COVID-19 vaccination (6.0%) than US-born respondents (72.6%, 2.9%, and 15.8%, respectively). Vaccination coverage was significantly lower for certain subcategories of national origin or heritage (eg, Jamaican [68.6%], Haitian [60.7%], Somali [49.0%] in weighted estimates). Respondents interviewed in Spanish had lower vaccination coverage than interviewees in English but higher intent to be vaccinated and lower reluctance. Collection and analysis of nativity, detailed race/ethnicity and language information allow identification of disparities among racial/ethnic subgroups. Vaccination programs could use such information to implement culturally and linguistically appropriate focused interventions among communities with lower vaccination coverage.


Assuntos
COVID-19 , Etnicidade , Adulto , Atitude , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Haiti , Humanos , Intenção , Inquéritos e Questionários , Estados Unidos , Vacinação , Cobertura Vacinal
7.
Am J Public Health ; 112(11): 1599-1610, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36223572

RESUMO

Objectives. To explore previous COVID-19 diagnosis and COVID-19 vaccination status among US essential worker groups. Methods. We analyzed the US Census Household Pulse Survey (May 26-July 5, 2021), a nationally representative sample of adults aged 18 years and older. We compared currently employed essential workers working outside the home with those working at home using adjusted prevalence ratios. We calculated proportion vaccinated and intention to be vaccinated, stratifying by essential worker and demographic groups for those who worked or volunteered outside the home since January 1, 2021. Results. The proportion of workers with previous COVID-19 diagnosis was highest among first responders (24.9%) working outside the home compared with workers who did not (13.3%). Workers in agriculture, forestry, fishing, and hunting had the lowest vaccination rates (67.5%) compared with all workers (77.8%). Those without health insurance were much less likely to be vaccinated across all worker groups. Conclusions. This study underscores the importance of improving surveillance to monitor COVID-19 and other infectious diseases among workers and identify and implement tailored risk mitigation strategies, including vaccination campaigns, for workplaces. (Am J Public Health. 2022;112(11):1599-1610. https://doi.org/10.2105/AJPH.2022.307010).


Assuntos
Vacinas contra a AIDS , COVID-19 , Vacinas contra Influenza , Vacinas contra Papillomavirus , Vacinas contra Vírus Sincicial Respiratório , Vacinas contra a SAIDS , Adulto , Vacina BCG , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Teste para COVID-19 , Vacinas contra COVID-19 , Vacina contra Difteria, Tétano e Coqueluche , Humanos , Intenção , Vacina contra Sarampo-Caxumba-Rubéola , Vacinação
8.
MMWR Morb Mortal Wkly Rep ; 71(23): 757-763, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35679179

RESUMO

Some racial and ethnic minority groups have experienced disproportionately higher rates of COVID-19-related illness and mortality (1,2). Vaccination is highly effective in preventing severe COVID-19 illness and death (3), and equitable vaccination can reduce COVID-19-related disparities. CDC analyzed data from the National Immunization Survey Adult COVID Module (NIS-ACM), a random-digit-dialed cellular telephone survey of adults aged ≥18 years, to assess disparities in COVID-19 vaccination coverage by race and ethnicity among U.S. adults during December 2020-November 2021. Asian and non-Hispanic White (White) adults had the highest ≥1-dose COVID-19 vaccination coverage by the end of April 2021 (69.6% and 59.0%, respectively); ≥1-dose coverage was lower among Hispanic (47.3%), non-Hispanic Black or African American (Black) (46.3%), Native Hawaiian or other Pacific Islander (NH/OPI) (45.9%), multiple or other race (42.6%), and American Indian or Alaska Native (AI/AN) (38.7%) adults. By the end of November 2021, national ≥1-dose COVID-19 vaccination coverage was similar for Black (78.2%), Hispanic (81.3%), NH/OPI (75.7%), and White adults (78.7%); however, coverage remained lower for AI/AN (61.8%) and multiple or other race (68.0%) adults. Booster doses of COVID-19 vaccine are now recommended for all adults (4), but disparities in booster dose coverage among the fully vaccinated have become apparent (5). Tailored efforts including community partnerships and trusted sources of information could be used to increase vaccination coverage among the groups with identified persistent disparities and can help achieve vaccination equity and prevent new disparities by race and ethnicity in booster dose coverage.


Assuntos
COVID-19 , Etnicidade , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Grupos Minoritários , Estados Unidos/epidemiologia , Vacinação , Cobertura Vacinal
9.
MMWR Morb Mortal Wkly Rep ; 71(43): 1366-1373, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36302226

RESUMO

Introduction: CDC estimates that influenza resulted in 9-41 million illnesses, 140,000-710,000 hospitalizations, and 12,000-52,000 deaths annually during 2010-2020. Persons from some racial and ethnic minority groups have historically experienced higher rates of severe influenza and had lower influenza vaccination coverage compared with non-Hispanic White (White) persons. This report examines influenza hospitalization and vaccination rates by race and ethnicity during a 12-13-year period (through the 2021-22 influenza season). Methods: Data from population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in selected states participating in the Influenza-Associated Hospitalization Surveillance Network (FluSurv-NET) from the 2009-10 through 2021-22 influenza seasons (excluding 2020-21) and influenza vaccination coverage data from the Behavioral Risk Factor Surveillance System (BRFSS) from the 2010-11 through 2021-22 influenza seasons were analyzed by race and ethnicity. Results: From 2009-10 through 2021-22, age-adjusted influenza hospitalization rates (hospitalizations per 100,000 population) were higher among non-Hispanic Black (Black) (rate ratio [RR] = 1.8), American Indian or Alaska Native (AI/AN; RR = 1.3), and Hispanic (RR = 1.2) adults, compared with the rate among White adults. During the 2021-22 season, influenza vaccination coverage was lower among Hispanic (37.9%), AI/AN (40.9%), Black (42.0%), and other/multiple race (42.6%) adults compared with that among White (53.9%) and non-Hispanic Asian (Asian) (54.2%) adults; coverage has been consistently higher among White and Asian adults compared with that among Black and Hispanic adults since the 2010-11 season. The disparity in vaccination coverage by race and ethnicity was present among those who reported having medical insurance, a personal health care provider, and a routine medical checkup in the past year. Conclusions and Implications for Public Health Practice: Racial and ethnic disparities in influenza disease severity and influenza vaccination coverage persist. Health care providers should assess patient vaccination status at all medical visits and offer (or provide a referral for) all recommended vaccines. Tailored programmatic efforts to provide influenza vaccination through nontraditional settings, along with national and community-level efforts to improve awareness of the importance of influenza vaccination in preventing illness, hospitalization, and death among racial and ethnic minority communities might help address health care access barriers and improve vaccine confidence, leading to decreases in disparities in influenza vaccination coverage and disease severity.


Assuntos
Vacinas contra Influenza , Influenza Humana , Adulto , Estados Unidos/epidemiologia , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Etnicidade , Estações do Ano , Cobertura Vacinal , Grupos Minoritários , Vacinação , Hospitalização , Sinais Vitais
10.
MMWR Morb Mortal Wkly Rep ; 71(5): 171-176, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35113846

RESUMO

Lesbian, gay, bisexual, and transgender (LGBT) populations have higher prevalences of health conditions associated with severe COVID-19 illness compared with non-LGBT populations (1). The potential for low vaccine confidence and coverage among LGBT populations is of concern because these persons historically experience challenges accessing, trusting, and receiving health care services (2). Data on COVID-19 vaccination among LGBT persons are limited, in part because of the lack of routine data collection on sexual orientation and gender identity at the national and state levels. During August 29-October 30, 2021, data from the National Immunization Survey Adult COVID Module (NIS-ACM) were analyzed to assess COVID-19 vaccination coverage and confidence in COVID-19 vaccines among LGBT adults aged ≥18 years. By sexual orientation, gay or lesbian adults reported higher vaccination coverage overall (85.4%) than did heterosexual adults (76.3%). By race/ethnicity, adult gay or lesbian non-Hispanic White men (94.1%) and women (88.5%), and Hispanic men (82.5%) reported higher vaccination coverage than that reported by non-Hispanic White heterosexual men (74.2%) and women (78. 6%). Among non-Hispanic Black adults, vaccination coverage was lower among gay or lesbian women (57.9%) and bisexual women (62.1%) than among heterosexual women (75.6%). Vaccination coverage was lowest among non-Hispanic Black LGBT persons across all categories of sexual orientation and gender identity. Among gay or lesbian adults and bisexual adults, vaccination coverage was lower among women (80.5% and 74.2%, respectively) than among men (88.9% and 81.7%, respectively). By gender identity, similar percentages of adults who identified as transgender or nonbinary and those who did not identify as transgender or nonbinary were vaccinated. Gay or lesbian adults and bisexual adults were more confident than were heterosexual adults in COVID-19 vaccine safety and protection; transgender or nonbinary adults were more confident in COVID-19 vaccine protection, but not safety, than were adults who did not identify as transgender or nonbinary. To prevent serious illness and death, it is important that all persons in the United States, including those in the LGBT community, stay up to date with recommended COVID-19 vaccinations.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Etnicidade/estatística & dados numéricos , Identidade de Gênero , Comportamento Sexual/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Cobertura Vacinal/estatística & dados numéricos , Adulto , COVID-19/prevenção & controle , Feminino , Heterossexualidade/psicologia , Humanos , Masculino , SARS-CoV-2/imunologia , Estados Unidos/epidemiologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-35476712

RESUMO

A polyphasic taxonomic approach was used to characterize a Gram-stain-positive fermentative bacterium, designated strain CC-MHH1034T, isolated from a fermented vegetable residue. Cells of strain CC-MHH1034T were facultatively anaerobic, non-motile, and non-spore-forming rods, exhibiting positive catalase, oxidase and protease activities. Optimal growth occurred at 30 °Ð¡ and pH 6.0. Strain CC-MHH1034T shared the highest 16S rRNA gene sequence similarities with Agrilactobacillus composti (95.9 %) followed by Agrilactobacillus yilanensis (95.1 %) and established a distinct taxonomic lineage associated with these species. Highest orthologous average nucleotide identity (OrthoANI) values were recorded for strain CC-MHH1034T versus Agrilactobacillus (71.1-71.6 %, n=2) followed by Ligilactobacillus (66.5-66.8 %, n=2), Lactobacillus (64.1-65.8 %, n=4). The mean digital DNA-DNA hybridization (dDDH) value obtained for strain CC-MHH1034T against Agrilactobacillus was 19.2-19.5 % (n=2). The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids, four unidentified glycolipids, four unidentified phospholipids and one unidentified lipid. The major polyamine was sym-homospermidine and meso-diaminopimelic acid was detected as the cell-wall peptidoglycan. The dominating cellular fatty acids (>5 %) included C16 : 0, iso-C15 : 0, anteiso-C15 : 0 and C18 : 1 ω9c. Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits together with results of comparative 16S rRNA gene sequence, OrthoANI, dDDH, and the phylogenomic placement, strain CC-MHH1034T is considered to represent a novel species of the genus Agrilactobacillus, affiliated to the family Lactobacillaceae, for which the name Agrilactobacillus fermenti sp. nov. is proposed. The type strain is CC-MHH1034T (=BCRC 81220T=JCM 33476T).


Assuntos
Ácidos Graxos , Verduras , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
12.
Plant J ; 104(6): 1535-1550, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33048399

RESUMO

Heat stress occurring at reproductive stages can result in significant and permanent damage to crop yields. However, previous genetic studies in understanding heat stress response and signaling were performed mostly on seedling and plants at early vegetative stages. Here we identify, using a developmentally defined, gain-of-function genetic screen with approximately 18 000 Arabidopsis thaliana activation-tagged lines, a mutant that maintained productive seed set post-severe heat stress during flowering. Genome walking indicated this phenotype was caused by the insertion of 35S enhancers adjacent to a nuclear localized transcription factor AtMYB68. Subsequent overexpression analysis confirmed that AtMYB68 was responsible for the reproductive heat tolerance of the mutant. Furthermore, these transgenic Arabidopsis plants exhibited enhanced abscisic acid sensitivity at and post-germination, reduced transpirational water loss during a drought treatment, and enhanced seed yield under combined heat and drought stress during flowering. Ectopic expression of AtMYB68 in Brassica napus driven either by 35S or by heat-inducible promoter recapitulated the enhanced reproductive heat stress and drought tolerance phenotypes observed in the transgenic Arabidopsis. The improvement to heat stress is likely due to enhanced pollen viability observed in the transgenic plants. More importantly, the transgenic canola showed significant yield advantages over the non-transgenic controls in multiple locations, multiple season field trials under various drought and heat stress conditions. Together these results suggest that AtMYB68 regulate plant stress tolerance at the most important yield determining stage of plant development, and is an effective target for crop yield protection under current global climate volatility.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Fatores de Transcrição/fisiologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Brassica napus , Desidratação , Flores/crescimento & desenvolvimento , Mutação com Ganho de Função , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas , Reprodução , Termotolerância , Fatores de Transcrição/genética
13.
Haemophilia ; 27(6): 1022-1027, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34460979

RESUMO

INTRODUCTION: Congenital fibrinogen disorders (CFDs) are caused by mutations in fibrinogen-encoding genes, FGA, FGB, and FGG, which lead to quantitative or qualitative abnormalities of fibrinogen. Although the diagnosis of CFDs is based on antigenic and functional level of fibrinogen, few genotypes are clearly correlated with phenotype. METHODS: In this study, we investigated all of the referred patients diagnosed as CFDs in Taiwan's population between 1995 and 2020. Clinical features, laboratory data and genetic defects were analysed. Functional fibrinogen level was determined by the Clauss method. Antigenic fibrinogen was measured by an enzyme-linked immunosorbent assay. Fibrinogen genes were assessed for mutations by polymerase chain reaction and sequencing. RESULTS: A total of 18 patients from six unrelated families with CFDs were identified. One patient from a consanguineous family was diagnosed as afibrinogenemia type 1A with a novel homozygous frameshift mutation in FGB exon 4. The other five (83.3 %) index patients were all diagnosed as dysfibrinogenemia type 3A caused by two novel and one known mutation. Six (33.3 %) patients from three families had a novel mutation in FGB exon 8. The clinical features and laboratory data were highly variable among these patients with the same mutation. CONCLUSIONS: Three novel mutations of CFDs causing afibrinogenemia and dysfibrinogenemia were identified. The point mutation in FGB exon 8 is also a common mutation in Taiwan's population. Considerable phenotypic variability among the patients with an identical mutation was observed.


Assuntos
Afibrinogenemia , Fibrinogênio/genética , Afibrinogenemia/diagnóstico , Afibrinogenemia/genética , Homozigoto , Humanos , Mutação , Taiwan
14.
MMWR Morb Mortal Wkly Rep ; 70(39): 1365-1371, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34591826

RESUMO

Estimates from the 2019 American Community Survey (ACS) indicated that 15.2% of adults aged ≥18 years had at least one reported functional disability (1). Persons with disabilities are more likely than are those without disabilities to have chronic health conditions (2) and also face barriers to accessing health care (3). These and other health and social inequities have placed persons with disabilities at increased risk for COVID-19-related illness and death, yet they face unique barriers to receipt of vaccination (4,5). Although CDC encourages that considerations be made when expanding vaccine access to persons with disabilities,* few public health surveillance systems measure disability status. To describe COVID-19 vaccination status and intent, as well as perceived vaccine access among adults by disability status, data from the National Immunization Survey Adult COVID Module (NIS-ACM) were analyzed. Adults with a disability were less likely than were those without a disability to report having received ≥1 dose of COVID-19 vaccine (age-adjusted prevalence ratio [aPR] = 0.88; 95% confidence interval [CI] = 0.84-0.93) but more likely to report they would definitely get vaccinated (aPR = 1.86; 95% CI = 1.43-2.42). Among unvaccinated adults, those with a disability were more likely to report higher endorsement of vaccine as protection (aPR = 1.29; 95% CI = 1.16-1.44), yet more likely to report it would be or was difficult to get vaccinated than did adults without a disability (aPR = 2.69; 95% CI = 2.16-3.34). Reducing barriers to vaccine scheduling and making vaccination sites more accessible might improve vaccination rates among persons with disabilities.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Pessoas com Deficiência/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Vacinação/psicologia , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
15.
Cancer Causes Control ; 31(7): 691-702, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32436037

RESUMO

PURPOSE: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides free cervical cancer screening to low-income women. This study estimated the health benefits gained in terms of life years (LYs) saved and quality-adjusted life years (QALYs) gained if cervical cancer screening by the NBCCEDP increased to reach more eligible women. METHODS: Data from Surveillance, Epidemiology, and End Results, NBCCEDP, and Medical Expenditure Panel Surveys were used. LYs saved and QALYs gained/100,000 women were estimated using modeling methods. They were used to predict additional health benefits gained if screening by the NBCCEDP increased from 6.5% up to 10-25% of the eligible women. RESULTS: Overall, per 100,000 women screened by the NBCCEDP, 1,731 LYs were saved and 1,608 QALYs were gained. For white women, 1,926 LYs were saved and 1,780 QALYs were gained/100,000 women screened by the NBCCEDP. For black women, 1,506 LYs were saved and 1,300 QALYs were gained/100,000 women screened. If the proportion of eligible women screened by the NBCCEDP increased to 10-25%, the estimated health benefits would range from 6,626-34,896 LYs saved and 6,153-32,407 QALYs gained. CONCLUSIONS: The reported estimates emphasize the value of cervical cancer screening program by extending LE in low-income women. Further, it demonstrates that screening a higher percentage of eligible women in the NBCCEDP may yield more health benefits.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Estatísticos , Anos de Vida Ajustados por Qualidade de Vida , Sistema de Registros , Programa de SEER , Inquéritos e Questionários , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Adulto Jovem
16.
Int J Syst Evol Microbiol ; 70(4): 2602-2610, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32160142

RESUMO

A novel Gram-stain-positive, aerobic, motile with peritrichous flagella, rod-shaped bacterium, designated CC-MHH1044T, was isolated from a preserved vegetable sample. A polyphasic taxonomic approach was applied to the isolates in order to clarify its taxonomic position. Growth of the strain CC-MHH1044T occurred at 15-50 °C (optimum, 30 °C), pH 6.0-8.0 (optimum, pH 7.0) and with 0-2.0 % (w/v) NaCl (optimum, 1 %, w/v). The genome of strain CC-MHH1044T consisted of 8.5 Mb and the genomic DNA G+C content was 58.5 mol%. Comparison of the 16S rRNA gene sequences showed that CC-MHH1044T belonged to the genus Cohnella and showed a close relationship with the type strains of Cohnella damuensis (96.2 %) and Cohnella panacarvi (95.9 %), and lower sequence similarity to other species. Average nucleotide identity values calculated from whole-genome sequencing data proved that CC-MHH1044T represents a distinct Cohnella species. The dominant cellular fatty acids (>5 %) included iso-C14 : 0(7.4 %), iso-C15 : 0 (6.4 %), anteiso-C15 : 0(40.3 %), C16 : 0 (6.6 %) and iso-C16 : 0 (27.0 %). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified aminophospholipids, one unidentified phospholipid and glycolipid. The major polyamine was spermidine. The predominant isoprenoid quinone was menaqinone 7 (MK-7). Based on its distinct phylogenetic, phenotypic and chemotaxonomic traits, together with results of comparative 16S rRNA gene sequence, average nucleotide identity and digital DNA-DNA hybridization analyses, we conclude that strain CC-MHH1044T represents a novel member of the genus Cohnella, for which the name Cohnella fermenti sp. nov. is proposed. The type strain is CC-MHH1044T (=BCRC 81147T=JCM 32834T).


Assuntos
Bacillales/classificação , Fermentação , Alimentos Fermentados/microbiologia , Filogenia , Bacillales/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Microbiologia de Alimentos , Glicolipídeos/química , Naftóis/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Taiwan , Terpenos/química , Sequenciamento Completo do Genoma
17.
Molecules ; 24(8)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027193

RESUMO

The reducing and capping sites along with their local structure impact photo properties of the red bovine serum albumin-capped Au nanocluster (BSA-AuNC), however, they are hard to identify. We developped a workflow and relevant techniques using mass spectrometry (MS) to identify the reducing and capping sites of BSA-AuNCs involved in their formation and fluorescence. Digestion without disulfide cleavages yielded an Au core fraction exhibiting red fluorescence and [AunSm] ion signals and a non-core fraction exhibiting neither of them. The core fraction was identified to mainly be comprised of peptides containing cysteine residues. The fluorescence and [AunSm] signals were quenched by tris(2-carboxyethyl)phosphine, confirming that disulfide groups were required for nanocluster stabilization and fluorescence. By MS sequencing, the disulfide pairs, C75-C91/C90-C101 in domain IA, C315-C360/C359-C368 in domain IIB, and C513-C558/C557-C566 in domain IIIB, were identified to be main capping sites of red AuNCs. Peptides containing oxidized cysteines (sulfinic or cysteic acid) were identified as reducing sites mainly in the non-core fraction, suggesting that disulfide cleavages by oxidization and conformational changes contributed to the subsequent growth of nanoclusters at nearby intact disulfide pairs. This is the first report on precise identification of the reducing and capping sites of BSA-AuNCs.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Espectrometria de Massas , Peptídeos/química
18.
Int J Syst Evol Microbiol ; 68(1): 133-140, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29116039

RESUMO

A polyphasic approach was used to characterize an aerobic, Gram-stain-negative, rod-shaped bacterium (designed as strain CC-MHH0539T) isolated from the chopped tuber of taro (Colocasia esculanta) in Taiwan. Strain CC-MHH0539T was able to grow at 15-30 °C (optimum, 25 °C), at pH 6.0-9.0 (optimum, 7.0) and with 0-1 % (w/v) NaCl. Strain CC-MHH0539T showed highest 16S rRNA gene sequence similarity to Sphingomonas laterariae LNB2T (96.8 %), Sphingobium boeckii 469T (96.5 %), Sphingomonas faucium E62-3T (96.4 %) and Sphingosinicella vermicomposti YC7378T (96.2 %) and <96.1 % similarity to other sphingomonads. Strain CC-MHH0539T was found to cluster mainly with the clade that accommodated members of the genus Sphingomonas. The dominant cellular fatty acids were C16 : 0, C16 : 1ω5c, C14 : 0 2-OH, C16 : 1ω7c/C16 : 1ω6c and C18 : 1ω7c/C18 : 1ω6c. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, two sphingoglycolipids and two unidentified phospholipids were detected in strain CC-MHH0539T. The DNA G+C content was 69.5 mol%. The respiratory quinone system and predominant polyamine was ubiquinone 10 (Q-10) and sym-homospermidine, respectively, which is in line with Sphingomonas representatives. Based on the distinct phylogenetic, phenotypic and chemotaxonomic traits, strain CC-MHH0539T is considered to represent a novel species of the genus Sphingomonas, for which the name Sphingomonas colocasiae sp. nov. is proposed. The type strain is CC-MHH0539T (=BCRC 80933T=JCM 31229T).


Assuntos
Colocasia/microbiologia , Filogenia , Sphingomonas/classificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Espermidina/análogos & derivados , Espermidina/química , Sphingomonas/genética , Sphingomonas/isolamento & purificação , Taiwan , Ubiquinona/química
19.
Prev Med ; 106: 38-44, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28964854

RESUMO

This study aims to quantify the aggregate potential life-years (LYs) saved and healthcare cost-savings if the Healthy People 2020 objective were met to reduce invasive colorectal cancer (CRC) incidence by 15%. We identified patients (n=886,380) diagnosed with invasive CRC between 2001 and 2011 from a nationally representative cancer dataset. We stratified these patients by sex, race/ethnicity, and age. Using these data and data from the 2001-2011 U.S. life tables, we estimated a survival function for each CRC group and the corresponding reference group and computed per-person LYs saved. We estimated per-person annual healthcare cost-savings using the 2008-2012 Medical Expenditure Panel Survey. We calculated aggregate LYs saved and cost-savings by multiplying the reduced number of CRC patients by the per-person LYs saved and lifetime healthcare cost-savings, respectively. We estimated an aggregate of 84,569 and 64,924 LYs saved for men and women, respectively, accounting for healthcare cost-savings of $329.3 and $294.2 million (in 2013$), respectively. Per person, we estimated 6.3 potential LYs saved related to those who developed CRC for both men and women, and healthcare cost-savings of $24,000 for men and $28,000 for women. Non-Hispanic whites and those aged 60-64 had the highest aggregate potential LYs saved and cost-savings. Achieving the HP2020 objective of reducing invasive CRC incidence by 15% by year 2020 would potentially save nearly 150,000 life-years and $624 million on healthcare costs.


Assuntos
Neoplasias Colorretais/epidemiologia , Redução de Custos/estatística & dados numéricos , Programas Gente Saudável/economia , Anos de Vida Ajustados por Qualidade de Vida , Fatores Etários , Idoso , Neoplasias Colorretais/diagnóstico , Redução de Custos/economia , Feminino , Gastos em Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados Unidos
20.
Int J Syst Evol Microbiol ; 67(4): 956-962, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27959775

RESUMO

A novel amylolytic, nitrate-reducing and diazotrophic bacterium, designated strain CC-MHH0563T, isolated from a fermenter was assessed for its taxonomic status using a polyphasic approach. Cells of strain CC-MHH0563T were Gram-staining-negative, catalase- and oxidase-positive, mesophilic and aerobic cocci, which produced reddish nondiffusible pigments. Growth was observed at 15-37 °C (optimal 25 °C), pH 6.0-8.0 (optimal pH 7.0) and salinity of 0-3 % (w/v). Strain CC-MHH0563T showed highest pairwise 16S rRNA gene sequence similarity to members of the genera Cerasicoccus(89.3-89.5 %), Coraliomargarita (87.8 %), Pelagicoccus(85.8-86.4 %) and Puniceicoccus (87.9 %), and established a discrete taxonomic lineage during phylogenetic analysis. The major fatty acids found in strain CC-MHH0563T were C14 : 0, anteiso-C15 : 0, C16 : 0, C17 : 0, C18 : 0 and C18 : 1ω9c. The polar lipid profile consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, two unknown aminolipids and two unknown aminophospholipids. The polyamine pattern showed a predominance of spermidine and a minor amount of cadaverine. The DNA G+C content was 57.4 mol% and the predominant quinone system was menaquinone-7. The low 16S rRNA gene sequence similarity values (<90.0 %) and a distinct phylogenetic clustering clearly distinguished strain CC-MHH0563T from other representatives of the family Puniceicoccaceae. Based on the discrete phylogenetic, phenotypic and chemotaxonomic traits together with the results of comparative 16S rRNA gene sequence analysis, strain CC-MHH0563T is considered to represent a novel genus and species of the family Puniceicoccaceae, for which the name Ruficoccus amylovorans gen. nov., sp. nov. is proposed. The type strain of the type species is CC-MHH0563T (=BCRC 80918T=JCM 31066T).


Assuntos
Reatores Biológicos/microbiologia , Filogenia , Verrucomicrobia/classificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Nitratos/metabolismo , Fosfolipídeos/química , Poliaminas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Taiwan , Verrucomicrobia/genética , Verrucomicrobia/isolamento & purificação , Vitamina K 2/análogos & derivados , Vitamina K 2/química
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