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1.
Cell ; 167(2): 433-443.e14, 2016 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-27667685

RESUMO

While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcγRIII, and distinct Ab glycosylation patterns. Moreover, compared to Abs from Atb, Abs from Ltb drove enhanced phagolysosomal maturation, inflammasome activation, and, most importantly, macrophage killing of intracellular Mtb. Combined, these data point to a potential role for Fc-mediated Ab effector functions, tuned via differential glycosylation, in Mtb control.


Assuntos
Anticorpos Antibacterianos/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Humoral , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia , Adulto , Feminino , Glicosilação , Humanos , Fragmentos Fc das Imunoglobulinas/imunologia , Ativação de Macrófagos , Masculino , Pessoa de Meia-Idade , Polissacarídeos/imunologia , Análise Serial de Proteínas , Receptores de IgG/imunologia , Adulto Jovem
2.
Euro Surveill ; 28(46)2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37971660

RESUMO

We observed a rebound in consumption of antibacterials for systemic use (ATC J01) in the community sector in the European Union/European Economic Area during 2021 and 2022, after an observed decrease between 2019 and 2020. The rates in 2022 returned to pre-COVID-19-pandemic levels and were exceeded in 13 countries. Although these patterns could partly be a result of changes in disease transmission during the study period, it could also reflect a lost opportunity to strengthen and reinforce prudent antibiotic use.


Assuntos
Antibacterianos , COVID-19 , Humanos , Antibacterianos/uso terapêutico , Pandemias , União Europeia , Europa (Continente)/epidemiologia
3.
Clin Infect Dis ; 75(1): e909-e911, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34893827

RESUMO

During July-August 2021, a coronavirus disease 2019 (COVID-19) outbreak involving 21 residents (all fully vaccinated) and 10 staff (9 fully vaccinated) occurred in a Connecticut nursing home. The outbreak was likely initiated by a fully vaccinated staff member and propagated by fully vaccinated persons. Prior COVID-19 was protective among vaccinated residents.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/prevenção & controle , Connecticut/epidemiologia , Surtos de Doenças/prevenção & controle , Humanos , Casas de Saúde
4.
Surg Endosc ; 36(12): 9262-9272, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35254522

RESUMO

INTRODUCTION: A high proportion of colorectal surgery patients within an enhanced recovery pathway (ERP) do not experience complications but remain hospitalized mainly waiting for gastrointestinal (GI) recovery. Accurate identification of these patients may allow discharge prior to the return of GI function. Therefore, the objective of this study is to determine if tolerating clear fluid (CF) on postoperative day (POD) 0 was associated with uncomplicated return of GI function after laparoscopic colorectal surgery. METHODS: Pooled data from three prospective studies from a single specialist colorectal referral center were analyzed (2013-2019). The present study included adult patients that underwent elective laparoscopic colectomy without stoma. Postoperative GI symptoms were collected daily in all three datasets. The main exposure variable, whether CF diet was tolerated on POD0, was defined as patients drinking at least 300 mL of CF without any nausea, anti-emetics, or vomiting (CF+ vs CF-). The main outcome measure was time to GI-3 (tolerating solid diet and passage of gas or stools). RESULTS: A total of 221 patients were included in this study, including 69% CF+ and 31% CF-. The groups were similar in age, gender, and comorbidities, but the CF- patients were more likely to have surgery for inflammatory bowel disease. CF+ patients had faster time to GI-3 (mean 1.6d (SD 0.7) vs. 2.3d (SD 1.5), p < 0.001). The CF+ group also experienced fewer complications (19% vs. 35%, p = 0.009), shorter mean LOS (mean 3.6d (SD 2.9) vs. 6.2d (SD 9.4), p = 0.002), and were more likely to be discharged by the target LOS (66% vs. 50%, p = 0.024). CONCLUSION: Toleration of CF on POD0 was associated with faster return of GI function, fewer complications, and shorter LOS. This may be used as a criteria for potential discharge prior to full return of GI function after laparoscopic colectomy within an ERP.


Assuntos
Colectomia , Laparoscopia , Adulto , Humanos , Estudos Prospectivos , Tempo de Internação , Colectomia/efeitos adversos , Laparoscopia/efeitos adversos , Dieta , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica
5.
Clin Infect Dis ; 73(11): e4269-e4277, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-33175132

RESUMO

BACKGROUND: Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous hematopoietic stem cell transplantation (autoHCT) patients. METHODS: A randomized, single-blind, controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomized 1:1 to high-dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 weeks apart. Hemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2, and 6 months post-first dose. Evaluable primary outcomes were seroprotection (HI titer ≥40) and seroconversion (4-fold titer increase) rates and secondary outcomes were geometric mean titers (GMTs), GMT ratios (GMRs), adverse events, influenza-like illness (ILI), and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. RESULTS: Sixty-eight patients were enrolled (34/arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentages of patients achieving seroprotection were 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all P > .05), and 78.8% and 97.1% for influenza-B/Yamagata (P = .03), respectively. Seroconversion rates, GMTs and GMRs, and number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR, 4.3; 95% CI, 1.2-14.9; P = .02). CONCLUSIONS: High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either 2-dose vaccine schedules. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619000617167.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Anticorpos Antivirais , Austrália , Testes de Inibição da Hemaglutinação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Vacinação , Vacinas de Produtos Inativados
6.
Emerg Infect Dis ; 27(5): 1288-1295, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33900171

RESUMO

Nursing homes house populations that are highly vulnerable to coronavirus disease. Point prevalence surveys (PPSs) provide information on the severe acute respiratory syndrome coronavirus 2 infection status of staff and residents in nursing homes and enable isolation of infectious persons to halt disease spread. We collected 16 weeks of public health surveillance data on a subset of nursing homes (34/212) in Connecticut, USA. We fit a Poisson regression model to evaluate the association between incidence and time since serial PPS onset, adjusting for decreasing community incidence and other factors. Nursing homes conducted a combined total of 205 PPSs in staff and 232 PPSs in residents. PPS was associated with 41%-80% reduction in incidence rate in nursing homes. Our findings provide support for the use of repeated PPSs in nursing home staff and residents, combined with strong infection prevention measures such as cohorting, in contributing to outbreak control.


Assuntos
COVID-19 , SARS-CoV-2 , Connecticut/epidemiologia , Humanos , Casas de Saúde , Prevalência
7.
MMWR Morb Mortal Wkly Rep ; 70(11): 396-401, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33735160

RESUMO

Residents of long-term care facilities (LTCFs), particularly those in skilled nursing facilities (SNFs), have experienced disproportionately high levels of COVID-19-associated morbidity and mortality and were prioritized for early COVID-19 vaccination (1,2). However, this group was not included in COVID-19 vaccine clinical trials, and limited postauthorization vaccine effectiveness (VE) data are available for this critical population (3). It is not known how well COVID-19 vaccines protect SNF residents, who typically are more medically frail, are older, and have more underlying medical conditions than the general population (1). In addition, immunogenicity of the Pfizer-BioNTech vaccine was found to be lower in adults aged 65-85 years than in younger adults (4). Through the CDC Pharmacy Partnership for Long-Term Care Program, SNF residents and staff members in Connecticut began receiving the Pfizer-BioNTech COVID-19 vaccine on December 18, 2020 (5). Administration of the vaccine was conducted during several on-site pharmacy clinics. In late January 2021, the Connecticut Department of Public Health (CT DPH) identified two SNFs experiencing COVID-19 outbreaks among residents and staff members that occurred after each facility's first vaccination clinic. CT DPH, in partnership with CDC, performed electronic chart review in these facilities to obtain information on resident vaccination status and infection with SARS-CoV-2, the virus that causes COVID-19. Partial vaccination, defined as the period from >14 days after the first dose through 7 days after the second dose, had an estimated effectiveness of 63% (95% confidence interval [CI] = 33%-79%) against SARS-CoV-2 infection (regardless of symptoms) among residents within these SNFs. This is similar to estimated effectiveness for a single dose of the Pfizer-BioNTech COVID-19 vaccine in adults across a range of age groups in noncongregate settings (6) and suggests that to optimize vaccine impact among this population, high coverage with the complete 2-dose series should be recommended for SNF residents and staff members.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Surtos de Doenças/prevenção & controle , Instituições de Cuidados Especializados de Enfermagem , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Connecticut/epidemiologia , Feminino , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Hosp Pharm ; 56(6): 664-667, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34732919

RESUMO

Background: Antimicrobial resistance is an increasingly serious threat to global public health. Antimicrobial stewardship programs need to identify inappropriate antibiotic use patterns and offer practical recommendations to prescribers and institutions. Urinary tract infection (UTI) is a common syndrome for which a standardized tool would be useful when treatment appropriateness is assessed. To date, few UTI treatment assessment tools have been published, and the available tools do not support appropriateness assessment against published guidelines, or consistent adjudication from one auditor to another. Objective: To develop a tool for auditing UTI antibiotic therapy that assesses treatment appropriateness based on guideline concordance, and with high inter-rater reliability. Methods: An audit tool was developed iteratively by the local antimicrobial stewardship team. Two auditors used the tool to adjudicate treatment appropriateness in a sample of UTI cases against local treatment guidelines. Inter-rater agreement was estimated with Cohen's kappa statistic. Results: The final design of the tool had individual sections for evaluating five aspects of treatment appropriateness, depending on the stage at which a patient was in his or her course of antibiotic therapy: diagnosis, empiric therapy, culture-directed therapy, route of antimicrobial administration, and duration of therapy. A total of 50 cases were assessed; among these, the two auditors agreed on 45 cases (90% agreement). The estimated kappa was 0.8. Conclusion: A unique tool with substantial inter-rater agreement was developed for assessing appropriateness of antimicrobial therapy in UTI. The process and design features that were outlined can be adapted by other antimicrobial stewardship programs to monitor antimicrobial use and improve quality of care.

9.
Hepatology ; 67(1): 260-272, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28370257

RESUMO

Two-dimensional shear wave elastography (2D-SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate-sized clinical trials. We aimed at running a larger-scale meta-analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D-SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D-SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D-SWE was 0.022-0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003-0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients. CONCLUSION: 2D-SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head-to-head comparison between 2D-SWE and other imaging modalities to establish disease-specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260-272).


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Bases de Dados Factuais , Progressão da Doença , Feminino , Seguimentos , Hepatite B Crônica/diagnóstico por imagem , Hepatite B Crônica/patologia , Hepatite C Crônica/diagnóstico por imagem , Hepatite C Crônica/patologia , Humanos , Imuno-Histoquímica , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Índice de Gravidade de Doença , Adulto Jovem
10.
MMWR Morb Mortal Wkly Rep ; 68(23): 519-523, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31194723

RESUMO

During May-October 2018, four patients from three states experienced sepsis after transfusion of apheresis platelets contaminated with Acinetobacter calcoaceticus-baumannii complex (ACBC) and Staphylococcus saprophyticus; one patient died. ACBC isolates from patients' blood, transfused platelet residuals, and two environmental samples were closely related by whole genome sequencing. S. saprophyticus isolates from two patients' blood, three transfused platelet residuals, and one hospital environmental sample formed two whole genome sequencing clusters. This whole genome sequencing analysis indicated a potential common source of bacterial contamination; investigation into the contamination source continues. All platelet donations were collected using apheresis cell separator machines and collection sets from the same manufacturer; two of three collection sets were from the same lot. One implicated platelet unit had been treated with pathogen-inactivation technology, and two had tested negative with a rapid bacterial detection device after negative primary culture. Because platelets are usually stored at room temperature, bacteria in contaminated platelet units can proliferate to clinically relevant levels by the time of transfusion. Clinicians should monitor for sepsis after platelet transfusions even after implementation of bacterial contamination mitigation strategies. Recognizing adverse transfusion reactions and reporting to the platelet supplier and hemovigilance systems is crucial for public health practitioners to detect and prevent sepsis associated with contaminated platelets.


Assuntos
Plaquetas/microbiologia , Transfusão de Plaquetas/efeitos adversos , Sepse/etiologia , Humanos , Masculino , Estados Unidos
11.
World J Surg ; 43(9): 2254-2261, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31101952

RESUMO

BACKGROUND: MRI performance in detecting pathologic complete response (pCR) post-neoadjuvant chemotherapy (NAC) in breast cancer has been previously explored. However, since tumor response varies by molecular subtype, it is plausible that imaging performance also varies. Therefore, we performed a literature review on subtype-specific MRI performance in detecting pCR post-NAC. METHODS: Two reviewers searched Cochrane, PubMed, and EMBASE for articles published between 2013 and 2018 that examined MRI performance in detecting pCR post-NAC. After filtering, ten primary research articles were included. Statistical metrics, such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were extracted per study for triple negative, HR+/HER2-, and HER2+ patients. RESULTS: Ten studies involving 2310 patients were included. In triple negative breast cancer, MRI showed NPV (58-100%) and PPV (72.7-94.7%) across 446 patients and sensitivity (45.5-100%) and specificity (49-94.4%) in 375 patients. In HR+/HER2- breast cancer patients, MRI showed NPV (29.4-100%) and PPV (21.4-95.1%) across 851 patients and sensitivity (43-100%) and specificity (45-93%) across 780 patients. In HER2+-enriched subtype, MRI showed NPV (62-94.6%) and PPV (34.9-72%) in 243 patients and sensitivity (36.2-83%) and specificity (47-90%) in 255 patients. CONCLUSION: MRI accuracy in detecting pCR post-NAC by subtype is not as consistent, nor as high, as individual studies suggest. Larger studies using standardized pCR definition with appropriate timing of surgery and MRI need to be conducted. This study has shown that MRI is in fact not an accurate prediction of pCR, and thus, clinicians may need to rely on other approaches such as biopsies of the tumor bed.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Receptor ErbB-2/análise
12.
BMC Nephrol ; 20(1): 376, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623557

RESUMO

BACKGROUND: Lipofuscin deposition is a characteristic manifestation of aging. There is very limited literature in humans and in animals describing these deposits in native kidneys. Overall, it is thought to be non-pathogenic and successful transplants from a donor with lipofuscin deposits have been reported. We present the case of a patient who underwent a kidney transplant and a for-cause biopsy post-transplantation incidentally revealed lipofuscin deposition. CASE PRESENTATION: A 48-year old gentleman with a past medical history of diabetes, hypertension, coronary artery disease, and ischemic and then hemorrhagic cardiovascular accident underwent a successful kidney transplant. His donor was an expanded criteria donor with no major past medical history. Post-transplant course was complicated by delayed graft function requiring one dialysis treatment for hyperkalemia. After that he had an uneventful course and achieved a baseline creatinine of 1.2 mg/dL, with no proteinuria. On a routine 19-month follow-up he was noted to have proteinuria and an antibody against the major-histocompatibility-complex class I-related chain A. A graft biopsy revealed acute antibody-mediated rejection and impressive lipofuscin deposition. He was subsequently treated with an antibody-mediated rejection protocol that included high dose steroids, Rituximab, plasmapheresis, and intravenous immunoglobulin, but responded poorly to this regimen. A 6-month follow up biopsy continued to show lipofuscin deposition, with similar microvascular injury scores and 12-months later his creatinine remained stable but his proteinuria worsened. Patient was struggling with recurrent infectious episodes requiring hospitalizations and thus no further diagnostic or therapeutic treatments were pursued. CONCLUSIONS: Lipofuscin deposition has been reported in solid organ transplants but the significance and cause are not well understood. Several physiologic and some pathologic causes to these deposits have been reported including age, diabetes, medications and a genetic syndrome. We propose that immunologic causes such as rejection in the presence of other risk factors could potentiate the oxidative stress leading to excessive lipofuscin deposition in kidney transplants. In the case of our patient, we conclude that these deposits were likely recipient-derived, and postulate that the cumulative burden of inflammation from rejection, and underlying medical conditions led to increased lipofuscin deposition. We speculate them to be an innocent bystander.


Assuntos
Aloenxertos/metabolismo , Rejeição de Enxerto/metabolismo , Rim/metabolismo , Lipofuscina/metabolismo , Aloenxertos/patologia , Biópsia , Rejeição de Enxerto/patologia , Humanos , Achados Incidentais , Rim/patologia , Transplante de Rim , Masculino , Microvasos/patologia , Pessoa de Meia-Idade
13.
Euro Surveill ; 24(45)2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31718744

RESUMO

We compared 2019 influenza seasonality and vaccine effectiveness (VE) in four southern hemisphere countries: Australia, Chile, New Zealand and South Africa. Influenza seasons differed in timing, duration, intensity and predominant circulating viruses. VE estimates were also heterogeneous, with all-ages point estimates ranging from 7-70% (I2: 33%) for A(H1N1)pdm09, 4-57% (I2: 49%) for A(H3N2) and 29-66% (I2: 0%) for B. Caution should be applied when attempting to use southern hemisphere data to predict the northern hemisphere influenza season.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza B/genética , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Vacinação/estatística & dados numéricos , Potência de Vacina , Adolescente , Adulto , Austrália/epidemiologia , Criança , Chile/epidemiologia , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/imunologia , Vírus da Influenza B/isolamento & purificação , Vacinas contra Influenza/administração & dosagem , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Vigilância da População , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estações do Ano , Vigilância de Evento Sentinela , África do Sul/epidemiologia
14.
J Bacteriol ; 200(6)2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29311277

RESUMO

Septation in bacteria requires coordinated regulation of cell wall biosynthesis and hydrolysis enzymes so that new septal cross-wall can be appropriately constructed without compromising the integrity of the existing cell wall. Bacteria with different modes of growth and different types of cell wall require different regulators to mediate cell growth and division processes. Mycobacteria have both a cell wall structure and a mode of growth that are distinct from well-studied model organisms and use several different regulatory mechanisms. Here, using Mycobacterium smegmatis, we identify and characterize homologs of the conserved cell division regulators FtsL and FtsB, and show that they appear to function similarly to their homologs in Escherichia coli We identify a number of previously undescribed septally localized factors which could be involved in cell wall regulation. One of these, SepIVA, has a DivIVA domain, is required for mycobacterial septation, and is localized to the septum and the intracellular membrane domain. We propose that SepIVA is a regulator of cell wall precursor enzymes that contribute to construction of the septal cross-wall, similar to the putative elongation function of the other mycobacterial DivIVA homolog, Wag31.IMPORTANCE The enzymes that build bacterial cell walls are essential for cell survival but can cause cell lysis if misregulated; thus, their regulators are also essential. The number and nature of these regulators is likely to vary in bacteria that grow in different ways. The mycobacteria are a genus that have a cell wall whose composition and construction vary greatly from those of well-studied model organisms. In this work, we identify and characterize some of the proteins that regulate the mycobacterial cell wall. We find that some of these regulators appear to be functionally conserved with their structural homologs in evolutionarily distant species such as Escherichia coli, but other proteins have critical regulatory functions that may be unique to the actinomycetes.


Assuntos
Divisão Celular , Parede Celular/química , Parede Celular/genética , Mycobacterium smegmatis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Parede Celular/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mycobacterium smegmatis/química , Mycobacterium smegmatis/citologia , Mycobacterium smegmatis/metabolismo , Peptidoglicano/metabolismo , Ligação Proteica
15.
Biol Blood Marrow Transplant ; 24(7): 1490-1496, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29530766

RESUMO

Viral respiratory tract infection (vRTI) is a significant cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to assess the epidemiologic characteristics, risk factors, and outcomes of vRTI occurring in the period from conditioning to 100 days after allo-HSCT in the era of molecular testing. This study was a retrospective record review of patients who underwent allo-HSCT at Royal Melbourne Hospital between January 2010 and December 2015. Symptomatic patients were tested using respiratory multiplex polymerase chain reaction (PCR). Logistic regression and Kaplan-Meier analysis were used to identify risk factors for vRTI and the risk of death or intensive care unit (ICU) admission, respectively. A total of 382 patients were reviewed, and 65 episodes of vRTI were identified in 56 patients (14.7%). Rhinovirus accounted for the majority of infections (69.2%). The majority of episodes presented initially with upper respiratory tract infection (58.5%), with 28.9% of them progressing to lower respiratory tract infection. Eleven episodes (16.9%) were associated with ICU admission. There were no deaths directly due to vRTI. Previous autologous HSCT was associated with an increased risk of vRTI (odds ratio, 2.1; 95% confidence interval, 1.0 to 4.1). The risks of death (P = .47) or ICU admission (P = .65) were not significantly different by vRTI status. vRTI is common in the first 100 days after allo-HSCT and is associated with ICU admission.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Respiratórias/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Viroses/etiologia , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/patologia , Estudos Retrospectivos , Fatores de Risco , Viroses/patologia
16.
World J Surg ; 42(10): 3302-3311, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29696328

RESUMO

BACKGROUND: In a previous study, we have shown that intermittent Pringle maneuver (IPM) might increase postoperative complications after hepatectomy for various indications. Complications which thought to be related to IPM were ascites, pleural effusion, wound infection and intra-abdominal collection. The aim of this study was to test the hypothesis that applying IPM during hepatectomy for hepatocellular carcinoma (HCC) could increase postoperative complications. METHODS: Between January 2013 and October 2016, eligible patients who received elective open hepatectomy for HCC were randomized to have IPM or no Pringle maneuver (NPM). Occurrence of various types of postoperative complications was specifically looked for. A routine postoperative day 5 abdominal ultrasound examination and chest X-ray were done to detect and grade any radiological ascites, pleural effusion and intra-abdominal collection. RESULTS: Fifty IPM and 50 NPM patients with histological proven HCC were recruited for final analysis. Demographics and operative parameters were comparable between the two groups. The postoperative complication rates were similar (IPM 36.0 vs. NPM 28.0%, P = 0.391). However, in the IPM group, more patients developed radiological posthepatectomy ascites (42.0 vs. 22.0%, P = 0.032) and pleural effusion (66.0 vs. 38.0%, P = 0.005). In patients with histologically proven cirrhosis, there were 28 IPM and 25 NPM patients. Again, there was no difference in postoperative complication rate but more radiological posthepatectomy ascites and pleural effusion in the IPM group. CONCLUSION: This trial was not able to detect a difference in postoperative complications whether IPM was applied or not, but use of IPM was associated with more subclinical ascites and pleural effusion. (ClinicalTrials.gov NCT01759901). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01759901.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Perda Sanguínea Cirúrgica/prevenção & controle , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Feminino , Hepatectomia/métodos , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Análise de Sobrevida , Resultado do Tratamento
17.
Australas J Dermatol ; 59(2): e106-e113, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28332195

RESUMO

BACKGROUND/OBJECTIVES: Renal transplant recipients (RTR) have both an excessive skin cancer incidence and a high mortality rate. In Australia RTR receive extensive public education on skin cancer and many undergo further education pre/post-transplant. This study examines whether RTR have sufficiently rigorous sun protection behaviour compared with the general population. METHODS: Altogether 179 RTR from two large Melbourne hospitals involving skin clinic teams in patient care were recruited to undergo cross-sectional telephone interviews. Comparisons were made with residents (25-69 years) surveyed using equivalent measures and methods in adjacent summers (2006-2007, n = 904; 2010-2011, n = 942) for regular population monitoring surveys. Multivariate analyses of weekend behaviour were adjusted for related ambient temperature records. RESULTS: RTR were more compliant with sun protection behaviour on the weekend prior to interview than the residents surveyed. For example, for 2006-2007 and 2010-2011, the odds ratio and confidence intervals (CI 95%) were respectively: used sunscreen: 2.0 (1.1-3.8) and 2.8 (1.4-5.3); wore a long-sleeved top: 4.5 (2.4-8.5) and 3.6 (1.9-7.0). RTR sunburn prevalence (5%) appeared similar to that of residents (odds ratios comparing 2006-2007 and 2010-2011 0.6 [95% CI, 0.2-1.6] and 0.7 [95% CI, 0.3-1.9]). Despite generally good sun protection behaviour, many RTR (47%) had skin cancers treated. CONCLUSION: The intensive education of RTR may have contributed to their better sun protection. Some RTR with excessive exposure to UV radiation introduction of may benefit from implementation of further photoprotection strategies. These findings may be particularly relevant to other RTR groups receiving education about sun protection.


Assuntos
Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Transplante de Rim , Neoplasias Cutâneas/prevenção & controle , Queimadura Solar/epidemiologia , Adulto , Idoso , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Prevalência , Roupa de Proteção/estatística & dados numéricos , Neoplasias Cutâneas/terapia , Protetores Solares/uso terapêutico , Adulto Jovem
18.
Euro Surveill ; 22(43)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29090681

RESUMO

In 2017, influenza seasonal activity was high in the southern hemisphere. We present interim influenza vaccine effectiveness (VE) estimates from Australia. Adjusted VE was low overall at 33% (95% confidence interval (CI): 17 to 46), 50% (95% CI: 8 to 74) for A(H1)pdm09, 10% (95% CI: -16 to 31) for A(H3) and 57% (95% CI: 41 to 69) for influenza B. For A(H3), VE was poorer for those vaccinated in the current and prior seasons.


Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Vigilância de Evento Sentinela , Potência de Vacina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Vacinas contra Influenza/imunologia , Influenza Humana/virologia , Laboratórios , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , RNA Viral/genética , Estações do Ano , Análise de Sequência de DNA , Vacinação/estatística & dados numéricos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Adulto Jovem
19.
Commun Dis Intell Q Rep ; 41(2): E150-E160, 2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28899310

RESUMO

As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System, the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 5,557 influenza positive samples during 2015. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties. In 2015, influenza B viruses predominated over influenza A(H1)pdm09 and A(H3) viruses, accounting for a total of 58% of all viruses analysed. The vast majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2015. However, phylogenetic analysis of a selection of viruses indicated that the majority of circulating A(H3) viruses were genetically distinct from the WHO recommended strain for 2015, resulting in an update to the recommended vaccine strain for the Southern Hemisphere for 2016. With an increasing predominance of B/Victoria lineage viruses over B/Yamagata lineage viruses through the course of 2015, WHO also updated the recommended influenza B strain in the trivalent influenza vaccine for 2016. Of more than 3,300 samples tested for resistance to the neuraminidase inhibitors oseltamivir and zanamivir, only 1 A(H1)pdm09 virus showed highly reduced inhibition by oseltamivir. The Centre undertook primary isolation of candidate vaccine viruses directly into eggs, and in 2015 a total of 45 viruses were successfully isolated in eggs.


Assuntos
Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza B/classificação , Influenza Humana/epidemiologia , Filogenia , África/epidemiologia , Relatórios Anuais como Assunto , Antígenos Virais/genética , Antivirais/uso terapêutico , Ásia/epidemiologia , Austrália/epidemiologia , Farmacorresistência Viral/genética , Genótipo , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/genética , Vírus da Influenza B/imunologia , Vírus da Influenza B/isolamento & purificação , Vacinas contra Influenza/administração & dosagem , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Oseltamivir/uso terapêutico , Organização Mundial da Saúde , Zanamivir/uso terapêutico
20.
J Shoulder Elbow Surg ; 26(5): 774-780, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28081996

RESUMO

BACKGROUND: Supraspinatus tendinopathy is one of the common causes of subacromial pain syndrome (SAPS) in overhead athletes. Changes in tendon vascularity have been reported in painful tendons; however, the prevalence and distribution have not been investigated in young overhead athletes. METHODS: We conducted a cross-sectional study of 47 overhead athletes (male, 31; female, 16) aged 18 to 36 years with SAPS for >3 months. A sonographer graded the severity of the tendinopathy and area of vascularization. Ultrasound imaging was used to measure supraspinatus tendon thickness, vascularity, and resting subacromial space. A self-written program was used to semiquantify the intensity of vascularity, expressed as the vascular index. RESULTS: The majority (87.2%) of the participants had signs of tendinopathy in the supraspinatus tendon, and 40 (85.1%) of the tendinopathic tendons had vascularity. The majority (66.0%) of the vascularized subjects presented with minimal increase in vascularity, and 19.1% had moderate to severe vascularization. Most (79.2%) of the vascularization was observed in the pericortical region. The vascular index was negatively correlated with the resting subacromial space in male athletes with a reduced subacromial space (ρ = -0.63; P = .038). CONCLUSION: Of overhead athletes with SAPS, 87.2% had supraspinatus tendinopathy with minimal to moderate vascularization, with the majority of vascularization occurring in the pericortical region. In male athletes with a reduced subacromial space, greater vascularity in the supraspinatus tendon was associated with a smaller resting subacromial space.


Assuntos
Traumatismos em Atletas/diagnóstico por imagem , Manguito Rotador/irrigação sanguínea , Dor de Ombro/diagnóstico por imagem , Tendinopatia/diagnóstico por imagem , Adolescente , Adulto , Atletas , Estudos Transversais , Feminino , Humanos , Masculino , Manguito Rotador/diagnóstico por imagem , Ultrassonografia , Adulto Jovem
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