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1.
Nat Immunol ; 12(10): 949-58, 2011 Sep 11.
Article in English | MEDLINE | ID: mdl-21909092

ABSTRACT

The transcription factor RORγt is required for the development of several innate lymphoid populations, such as lymphoid tissue-inducer cells (LTi cells) and cells that secrete interleukin 17 (IL-17) or IL-22. The progenitor cells as well as the developmental stages that lead to the emergence of RORγt(+) innate lymphoid cells (ILCs) remain undefined. Here we identify the chemokine receptor CXCR6 as an additional marker of the development of ILCs and show that common lymphoid progenitors lost B cell and T cell potential as they successively acquired expression of the integrin α(4)ß(7) and CXCR6. Whereas fetal RORγt(+) cells matured in the fetal liver environment, adult bone marrow-derived RORγt(+) ILCs matured outside the bone marrow, in a Notch2-dependent manner. Therefore, fetal and adult environments influence the differentiation of RORγt(+) cells differently.


Subject(s)
Fetus/immunology , Lymphocytes/immunology , Nuclear Receptor Subfamily 1, Group F, Member 3/physiology , Receptor, Notch2/physiology , Signal Transduction , Animals , Cell Differentiation , Cells, Cultured , DNA-Binding Proteins/physiology , Immunity, Innate , Integrins/physiology , Male , Mice , Mice, Inbred C57BL , Receptors, CXCR/physiology , Receptors, CXCR6
2.
Womens Stud Int Forum ; 101: 102822, 2023.
Article in English | MEDLINE | ID: mdl-39077555

ABSTRACT

Despite abortion being decriminalised in Victoria, Australia, access remains difficult, especially at later gestations. Institutions (i.e. health services) place restrictions on the availability of late abortions and/or require additional requirements to be satisfied (e.g. Hospital Termination Review Committee approval), as a consequence of local regulation (i.e. policies and processes determined at the institutional level). This paper reports on the results of 27 interviews with Victorian health professionals about late abortion processes and the operation of Termination Review Committees in Victorian health services, which were analysed thematically. The results reveal the operation of an 'institutional lottery' whereby patients' experiences in seeking late abortion services were variable and largely shaped by the institution(s) they found themselves in.

3.
AIDS Care ; 33(2): 172-179, 2021 02.
Article in English | MEDLINE | ID: mdl-31983231

ABSTRACT

An increase in new HIV infections among women in Kazakhstan has motivated efforts to improve access to comprehensive health services. This study estimates anxiety and depression frequency among women seeking HIV services. A cross-sectional survey was administered to women seen at the Almaty AIDS Center. Bivariable analyses (e.g., Chi-square, means with 95% confidence intervals) were performed to assess the relationship between anxiety (score of 10 or more on the Generalized Anxiety Disorder-7 Scale (GAD-7)), major depression (Patient Health Questionnaire 8 (PHQ-8)), and comorbid anxiety and major depression with sociodemographic characteristics, health functioning, and medication history. Of the 410 participants, 62 (15.1%) had a GAD-7 ≥ 10; 52 (12.7%) met major depression criteria; 35 (8.5%) met both criteria, and 79 (19.3%) met GAD-7, major depression, or both criteria. Women reporting depression or anxiety were more likely to lack food security (p < 0.01), not finish secondary school (p < 0.01), speak Russian at home (p < 0.01), perceive their health to be poor (p < 0.01), and report poorer physical and mental health functioning (p < 0.05). No medications approved for the treatment of anxiety or depression were reported. The considerable number of women reporting major depression and anxiety symptoms suggests a need for improving access to mental health care.


Subject(s)
Anti-HIV Agents/therapeutic use , Anxiety/epidemiology , Depression/epidemiology , HIV Infections/drug therapy , HIV Infections/psychology , Adult , Anxiety/psychology , Anxiety Disorders/epidemiology , Anxiety Disorders/psychology , Cross-Sectional Studies , Depression/psychology , Female , HIV Infections/ethnology , Humans , Kazakhstan/epidemiology
4.
BMC Med Ethics ; 22(1): 149, 2021 11 12.
Article in English | MEDLINE | ID: mdl-34772412

ABSTRACT

BACKGROUND: Dealing with end of life is challenging for patients and health professionals alike. The situation becomes even more challenging when a patient requests a legally permitted medical service that a health professional is unable to provide due to a conflict of conscience. Such a scenario arises when Victorian health professionals, with a conscientious objection (CO) to voluntary assisted dying (VAD), are presented with patients who request VAD or merely ask about VAD. The Voluntary Assisted Dying Act 2017 (Vic) recognizes the inherent conflict of conscience that may arise for some health professionals when asked to provide VAD and responds by affording broad protection to conscientious objectors who wish to refuse to take part in the VAD process. METHODS: Seventeen semi-structured qualitative interviews were conducted with Victorian health professionals with a self-identified CO to VAD in the lead-up to the implementation of VAD in Victoria. Interviews explored how participants anticipated they would manage their CO in practice. Interviews were transcribed verbatim and analyzed thematically. RESULTS: Our results reveal that the way in which health professionals claimed they would approach CO conversations is variable and was dependant on the strength of their opposition to VAD. We categorized conscientious objectors according to their approach as either dissuasive non-referrers, passive non-referrers, facilitators or negotiators. Our study also explores the perceived difficulties of exercising one's CO as identified by our participants. CONCLUSION: The broad protection offered by the Voluntary Assisted Dying Act 2017 (Vic) encourages a range of behaviors from conscientious objectors, due to the minimal obligations imposed. In order to assist conscientious objectors, more policy, institutional guidance, and education needs to be available to conscientious objectors explicitly addressing how to effectively manage one's CO. Such guidance is imperative to ensuring that their moral integrity is preserved and that they are exercising their CO appropriately.


Subject(s)
Suicide, Assisted , Attitude of Health Personnel , Conscience , Health Personnel , Humans , Refusal to Treat , Victoria
5.
Pflugers Arch ; 472(2): 259-269, 2020 02.
Article in English | MEDLINE | ID: mdl-32025886

ABSTRACT

All living beings on earth are influenced by the circadian rhythm, the rising and the setting of the sun. The ubiquitous effect of exercise is widely believed to maximize health benefits but has not been formally investigated for cardiac responses in the exercise-induced circadian rhythms. We hypothesized that the exercise-related proteome is differentially influenced by circadian rhythm and analyzed the differences between the effects of morning and evening exercise. Twenty-four Sprague-Dawley rats were randomly divided into four groups (n = 6 per group): morning control, morning exercise, evening control, and evening exercise groups. The exercise groups were subjected to 12-week treadmill exercise (5 days/week) performed either during daytime or nighttime. After 12 weeks, the physiological characteristics (e.g., body weight, heart weight, visceral fat, and blood metabolites), cardiovascular capacity (ejection fraction (%) and fractional shortening (%)), circadian gene expression levels (clock, ball1, per1, per2, cry1, and cry2), and the proteomic data were obtained and subjected to univariate and multivariate analysis. The mRNA levels of per1 and cry2 increased in the evening group compared with those in the morning group. We also found that per2 decreased and cry2 increased in the evening exercise groups. The evening exercise groups showed more decreased triacylglycerides and increased blood insulin levels than the morning exercise group. The principal component analysis, partial least squares discriminant analysis, and orthogonal partial least squares discriminant analysis indicated that the circadian rhythm differently influenced the protein networks of the exercise groups. In the morning exercise group, the transcription-translation feedback loop (TTFL) (clock, per1, per2, cry1, and cry2) formed a protein-protein interaction network with Nme2, Hint1, Ddt, Ndufb8, Ldha, and Eef1a2. In contrast, the TTFL group appeared close to Maoa, Hist2h4, and Macrod1 in the evening exercise group. Interestingly, the evening exercise group decreased the mRNA level of per2 but not per1. Per1 and Per2 are known to transport Cry1 and Cry2 into the nucleus. Taken together, we summarized the characteristics of enriched proteins in the aspect of their molecular function, cellular component, and biological process. Our results might provide a better understanding of the circadian effect on exercise-related proteins.


Subject(s)
Adaptation, Physiological , Circadian Rhythm , Myocardium/metabolism , Physical Conditioning, Animal , Proteome/metabolism , Animals , Circadian Rhythm Signaling Peptides and Proteins/genetics , Circadian Rhythm Signaling Peptides and Proteins/metabolism , Heart/physiology , Male , Protein Interaction Maps , Proteome/genetics , Rats , Rats, Sprague-Dawley
6.
Adv Exp Med Biol ; 1147: 319-344, 2019.
Article in English | MEDLINE | ID: mdl-31147885

ABSTRACT

The muscular dystrophies are an heterogeneous group of inherited myopathies characterised by the progressive wasting of skeletal muscle tissue. Pericytes have been shown to make muscle in vitro and to contribute to skeletal muscle regeneration in several animal models, although recent data has shown this to be controversial. In fact, some pericyte subpopulations have been shown to contribute to fibrosis and adipose deposition in muscle. In this chapter, we explore the identity and the multifaceted role of pericytes in dystrophic muscle, potential therapeutic applications and the current need to overcome the hurdles of characterisation (both to identify pericyte subpopulations and track cell fate), to prevent deleterious differentiation towards myogenic-inhibiting subpopulations, and to improve cell proliferation and engraftment efficacy.


Subject(s)
Muscular Dystrophies , Pericytes , Animals , Cell Differentiation , Muscle Development , Muscle, Skeletal , Regeneration
7.
BMC Med Ethics ; 20(1): 11, 2019 01 31.
Article in English | MEDLINE | ID: mdl-30700292

ABSTRACT

BACKGROUND: In Victoria, Australia, the law regulating abortion was reformed in 2008, and a clause ('Section 8') was introduced requiring doctors with a conscientious objection to abortion to refer women to another provider. This study reports the views of abortion experts on the operation of Section 8 of the Abortion Law Reform Act in Victoria. METHODS: Nineteen semi-structured qualitative interviews were conducted with purposively selected Victorian abortion experts in 2015. Interviews explored the impact of abortion law reform on service provision, including the understanding and implementation of Section 8. Interviews were transcribed verbatim and analysed thematically. RESULTS: The majority of participants described Section 8 as a mechanism to protect women's right to abortion, rather than a mechanism to protect doctors' rights. All agreed that most doctors would not let moral or religious beliefs impact on their patients, and yet all could detail negative experiences related to Section 8. The negative experiences arose because doctors had: directly contravened the law by not referring; attempted to make women feel guilty; attempted to delay women's access; or claimed an objection for reasons other than conscience. Use or misuse of conscientious objection by Government telephone staff, pharmacists, institutions, and political groups was also reported. CONCLUSION: Some doctors are not complying with Section 8, with adverse effects on access to care for some women. Further research is needed to inform strategies for improving compliance with the law in order to facilitate timely access to abortion services.


Subject(s)
Abortion, Induced/ethics , Family Planning Services/ethics , Physicians/ethics , Refusal to Treat/ethics , Women's Rights/ethics , Abortion, Induced/legislation & jurisprudence , Adult , Attitude of Health Personnel , Conscience , Dissent and Disputes , Family Planning Services/legislation & jurisprudence , Female , Humans , Physicians/psychology , Pregnancy , Refusal to Treat/legislation & jurisprudence , Religion and Medicine , Social Stigma , Victoria , Women's Rights/legislation & jurisprudence
8.
J Antimicrob Chemother ; 72(4): 975-987, 2017 04 01.
Article in English | MEDLINE | ID: mdl-27999058

ABSTRACT

Background: Excessive use of antibiotics accelerates the acquisition/spread of antimicrobial resistance. A systematic review was conducted to identify the components of successful communication interventions targeted at the general public to improve antibiotic use. Methods: The databases MEDLINE, EMBASE, CINAHL, Web of Science and Cochrane Library were searched. Search terms were related to the population (public, community), intervention (campaign, mass media) and outcomes (antibiotic, antimicrobial resistance). References were screened for inclusion by one author with a random subset of 10% screened by a second author. No date restrictions were applied and only articles in the English language were considered. Studies had to have a control group or be an interrupted time-series. Outcomes had to measure change in antibiotic-related prescribing/consumption and/or the public's knowledge, attitudes or behaviour. Two reviewers assessed the quality of studies. Narrative synthesis was performed. Results: Fourteen studies were included with an estimated 74-75 million participants. Most studies were conducted in the United States or Europe and targeted both the general public and clinicians. Twelve of the studies measured changes in antibiotic prescribing. There was quite strong ( P < 0·05 to ≥ 0·01) to very strong ( P < 0·001) evidence that interventions that targeted prescribing for RTIs were associated with decreases in antibiotic prescribing; the majority of these studies reported reductions of greater than -14% with the largest effect size reaching -30%. Conclusion: Multi-faceted communication interventions that target both the general public and clinicians can reduce antibiotic prescribing in high-income countries but the sustainability of reductions in antibiotic prescribing is unclear.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Behavior Therapy/methods , Drug Resistance, Bacterial , Drug Utilization/standards , Health Communication/methods , Health Education/methods , Global Health , Humans
9.
PLoS Biol ; 12(6): e1001895, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24960609

ABSTRACT

The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD). Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT) in several models of Huntington's disease (HD). Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor ß-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished ß-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.


Subject(s)
Forkhead Transcription Factors/metabolism , Huntington Disease/etiology , Neurons/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Wnt/metabolism , Aged , Animals , Caenorhabditis elegans , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Cell Line , Female , Humans , Huntington Disease/metabolism , Male , Mice , Mice, Transgenic , Middle Aged , Oligonucleotide Array Sequence Analysis , Presenilin-1/metabolism , Receptor Protein-Tyrosine Kinases/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin Plasma Membrane Transport Proteins/metabolism , Wnt Signaling Pathway
10.
BMC Infect Dis ; 17(1): 534, 2017 08 02.
Article in English | MEDLINE | ID: mdl-28764660

ABSTRACT

BACKGROUND: In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. However, no clinical studies have evaluated the relationship between initial vancomycin exposure and emergence of hVISA. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a non-hVISA BSI at baseline. METHODS: This was a retrospective cohort study of patients with methicillin-resistant Staphylococcus aureus (MRSA) BSIs at Albany Medical Center Hospital (AMCH) between January 2005 and June 2009. The vancomycin AUC exposure variables on day 1 (AUC0-24h) and day 2 (AUC24-48h) were estimated using the maximal a posteriori probability (MAP) procedure in ADAPT 5. RESULTS: There were 238 unique episodes of MRSA BSIs during the study period, 119 of which met inclusion criteria. Overall, hVISA emerged in 7/119 (5.9%) of patients. All 7 cases of hVISA involved patients who did not achieve area under the curve over broth microdilution minimum inhibitory concentration (AUC0-24h/MICBMD) ratio of 521 or an AUC24-48h/MICBMD ratio of 650. No associations between other day 1 and day 2 AUC variables and emergence of hVISA were noted. CONCLUSIONS: Although more data are needed to draw definitive conclusions, these findings suggest that hVISA emergence among patients with non-hVISA MRSA BSIs at baseline may be partially explained by suboptimal exposure to vancomycin in the first 1 to 2 days of therapy. At a minimum, these findings support further study of the relationship between initial vancomycin exposure and hVISA emergence among patients with MRSA BSIs in a well-powered, multi-center, prospective trial.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Bacteremia/microbiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Vancomycin/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Area Under Curve , Bacteremia/drug therapy , Disk Diffusion Antimicrobial Tests , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Pilot Projects , Prospective Studies , Retrospective Studies , Staphylococcal Infections/drug therapy , Staphylococcus aureus/pathogenicity , Vancomycin/pharmacology , Vancomycin Resistance/drug effects
11.
Prenat Diagn ; 42(5): 535-541, 2022 05.
Article in English | MEDLINE | ID: mdl-35357014

Subject(s)
Heart Rate , Humans , Texas
12.
J Pediatr ; 166(1): 151-6, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25444525

ABSTRACT

OBJECTIVE: To identify children vaccinated following an alternative vaccine schedule using immunization information system data and determine the impact of alternative schedule use on vaccine coverage. STUDY DESIGN: Children born in New York State, outside New York City, between January 1, 2009 and August 14, 2011 were assessed for vaccination patterns consistent with use of an alternative schedule. Children who by 9 months of age had at least 3 vaccination visits recorded in the statewide mandatory immunization information system after 41 days of age were classified as either attempting to conform to the Centers for Disease Control and Prevention published recommended vaccination schedule or an alternative schedule. The number of vaccination visits and up-to-date status at age 9 months were compared between groups. RESULTS: Of the 222 628 children studied, the proportion of children following an alternative schedule was 25%. These children were significantly less likely to be up-to-date at age 9 months (15%) compared with those conforming to the routine schedule (90%, P < .05). Children following an alternative schedule on average had about 2 extra vaccine visits compared with children following a routine schedule (P < .05). CONCLUSIONS: Almost 1 in 4 children in this study appear to be intentionally deviating from the routine schedule. Intentional deviation leads to poor vaccination coverage leaving children vulnerable to infection and increasing the potential for vaccine-preventable disease outbreaks.


Subject(s)
Immunization Schedule , Vaccination/statistics & numerical data , Female , Humans , Infant , Male , New York , Patient Acceptance of Health Care , Safety , Treatment Refusal
13.
Stem Cells ; 32(2): 377-90, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24115267

ABSTRACT

Random epigenetic silencing of the X-chromosome in somatic tissues of female mammals equalizes the dosage of X-linked genes between the sexes. Unlike this form of X-inactivation that is essentially irreversible, the imprinted inactivation of the paternal X, which characterizes mouse extra-embryonic tissues, appears highly unstable in the trophoblast giant cells of the placenta. Here, we wished to determine whether such instability is already present in placental progenitor cells prior to differentiation toward lineage-specific cell types. To this end, we analyzed the behavior of a GFP transgene on the paternal X both in vivo and in trophoblast stem (TS) cells derived from the trophectoderm of XX(GFP) blastocysts. Using single-cell studies, we show that not only the GFP transgene but also a large number of endogenous genes on the paternal X are subject to orchestrated cycles of reactivation/de novo inactivation in placental progenitor cells. This reversal of silencing is associated with local losses of histone H3 lysine 27 trimethylation extending over several adjacent genes and with the topological relocation of the hypomethylated loci outside of the nuclear compartment of the inactive X. The "reactivated" state is maintained through several cell divisions. Our study suggests that this type of "metastable epigenetic" states may underlie the plasticity of TS cells and predispose specific genes to relaxed regulation in specific subtypes of placental cells.


Subject(s)
Dosage Compensation, Genetic , Genes, X-Linked , X Chromosome Inactivation/genetics , X Chromosome/genetics , Animals , Blastocyst/metabolism , Epigenesis, Genetic , Female , Humans , Mice , Placenta , Pregnancy , Stem Cells , Trophoblasts/metabolism
14.
AIDS Behav ; 19(7): 1298-304, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25294629

ABSTRACT

This study compares sexual risk behaviors among male and female migrant market vendors in Almaty, Kazakhstan. From the Barakholka Market, 209 male and 213 female market vendors were randomly recruited. Self-reported data were collected through standardized face-to-face interviews. Dry blood spot was used as specimen for syphilis testing. Propensity score stratification was used to estimate adjusted prevalence or rate ratios by gender. Compared to male migrant workers, females had lower HIV knowledge and were less likely to have multiple sexual partners. There was no evidence of a gender difference for prevalence of syphilis, condom use with unsteady partners, and safe sex communication between couples. Associations between mobility patterns and engagement in multiple sexual partnerships were stronger among women than men. Efforts should be made to mitigate the gender differential in HIV knowledge among migrants, especially women. Such efforts need to be implemented in both home and host countries.


Subject(s)
HIV Infections/prevention & control , Health Knowledge, Attitudes, Practice , Risk-Taking , Sexual Behavior , Transients and Migrants/psychology , Adult , Condoms/statistics & numerical data , Cross-Sectional Studies , Female , Gender Identity , HIV Infections/epidemiology , Humans , Kazakhstan/epidemiology , Male , Prevalence , Propensity Score , Sexual Partners , Socioeconomic Factors , Syphilis/epidemiology , Transients and Migrants/statistics & numerical data
15.
Inj Prev ; 21(e1): e109-12, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24966211

ABSTRACT

Traffic fatalities in Kazakhstan increased from 15 to more than 30 per 100 000 between 2001 and 2006. Mortality remains high compared with developed nations. Safety-restraint laws have been enacted, but little data exist regarding usage of seatbelts, particularly among children and passengers. This cross-sectional study surveyed medical university students about attitudes and behaviours regarding seatbelt and child safety-restraint usage. Seatbelts are widely used in the front seat (81%) but not in the back seat (79% 'never' or 'rarely' use a seatbelt in the back seat). Fewer than half reported 'always' or 'almost always' providing restraint for children under 7 years and 24% reported children secure the seatbelts themselves. Safety in the back seat merits attention. Adults generally do not buckle in the back seat despite a law requiring seatbelt use. Promotion of child safety restraints should be prioritised in prevention education for physicians and the community.


Subject(s)
Accidents, Traffic/prevention & control , Child Restraint Systems/statistics & numerical data , Health Knowledge, Attitudes, Practice , Seat Belts/statistics & numerical data , Students, Medical/psychology , Adolescent , Adult , Automobile Driving/legislation & jurisprudence , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Kazakhstan , Male , Safety , Schools, Medical , Young Adult
16.
South Med J ; 108(9): 567-73, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26332483

ABSTRACT

OBJECTIVES: The objectives of this study were to quantify the incidence of hepatitis B virus (HBV) vaccine nonresponse and identify clinical characteristics associated with vaccine nonresponse. METHODS: A retrospective cohort study was conducted among patients undergoing hemodialysis (HD) receiving the HBV vaccine. Study inclusion criteria were age 18 years and older, receipt of HD treatment for ≥ 1 month, receipt of ≥ 1 dose of HBV vaccine, availability of anti-HB surface antibody (anti-HBs) laboratory values ≥ 2 weeks after last HBV vaccine, and prevaccine anti-HBs value <10 mIU/mL. Clinical data were abstracted from patients' medical records. The outcome of interest was vaccine nonresponse, defined as anti-HBs values <10 IU/mL. Multivariate regression was used to determine variables independently associated with vaccine nonresponse. Kaplan-Meier estimates were constructed for determining HBV vaccine response retention. RESULTS: Of the 119 patients evaluated, nonresponse was observed in 58%. Mean age at first vaccination for vaccine responders and nonresponders was 58.8 ± 16.5 and 65.9 ± 14.1 (P = 0.01), respectively. Variables independently associated with nonresponse were age 58 years and older (adjusted relative risk, 95% confidence interval 1.62, 1.06-2.46; P = 0.02) and body mass index ≥ 36.4 kg/m(2) (adjusted relative risk, 95% confidence interval 1.66, 1.34-2.07; P < 0.01). Among the 50 patients who achieved an initial vaccine response, 26% were not able to maintain vaccine response upon subsequent anti-HBs measurement. The probability of retaining vaccine response over time was significantly modified by body mass index ≥ 25 kg/m(2). CONCLUSIONS: The frequency of nonresponse to the HBV vaccine was high among patients undergoing HD. The clinical covariates most predictive of vaccine nonresponse were advanced age at the time of vaccination and excess body weight.


Subject(s)
Hepatitis B Vaccines , Renal Dialysis , Age Factors , Aged , Female , Hepatitis B/prevention & control , Hepatitis B Antibodies/immunology , Hepatitis B Vaccines/immunology , Humans , Incidence , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Male , Middle Aged , Multivariate Analysis , Obesity/epidemiology , Retrospective Studies
17.
Clin Infect Dis ; 59(5): 666-75, 2014 Sep 01.
Article in English | MEDLINE | ID: mdl-24867791

ABSTRACT

BACKGROUND: Contemporary vancomycin dosing schemes are designed to achieve an area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio of ≥400. However, scant clinical data exist to support this target and available data relied on pharmacokinetic formulas based on daily vancomycin dose and estimated renal function (demographic pharmacokinetic model) to estimate AUCs. METHODS: A cohort study of hospitalized, adult, nondialysis patients with methicillin-resistant Staphylococcus aureus bloodstream infections treated with vancomycin was performed to quantitatively evaluate the relationship between vancomycin exposure and outcomes. Bayesian techniques were used to estimate vancomycin exposure profile for day 1 and 2 of therapy for each patient based on their dosing schedule and collected concentrations. Classification and Regression Tree (CART) analysis was used to identify day 1 and 2 exposure thresholds associated with an increased risk of failure. Failure was defined as 30-day mortality, bacteremia was ≥7 days, or recurrence. RESULTS: During the study period, 123 cases met criteria. Failure was uniformly less pronounced (approximately 20% less in absolute value) in patients who achieved the CART-derived day 1 and 2 thresholds for AUC/MIC by broth microdilution and AUC/MIC by Etest. In the multivariate analyses, all risk ratios were approximately 0.5 for all CART-derived AUC/MIC exposure thresholds, indicating that achievement of CART-derived AUC/MIC exposure thresholds was associated with a 2-fold decrease in failure. CONCLUSIONS: These findings establish the critical importance of daily AUC/MIC ratios during the first 2 days of therapy. As with all observational studies, these findings should be interpreted cautiously and validated in a multicenter randomized trial before adoption into practice.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacteremia/drug therapy , Bacteremia/microbiology , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Vancomycin/administration & dosage , Area Under Curve , Bayes Theorem , Cohort Studies , Female , Genotype , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Phenotype , Retrospective Studies , Treatment Failure
18.
PLoS Pathog ; 8(3): e1002555, 2012.
Article in English | MEDLINE | ID: mdl-22396644

ABSTRACT

Microbial pathogens have developed efficient strategies to compromise host immune responses. Cryptococcus neoformans is a facultative intracellular pathogen, recognised as the most common cause of systemic fungal infections leading to severe meningoencephalitis, mainly in immunocompromised patients. This yeast is characterized by a polysaccharide capsule, which inhibits its phagocytosis. Whereas phagocytosis escape and macrophage intracellular survival have been intensively studied, extracellular survival of this yeast and restraint of host innate immune response are still poorly understood. In this study, we have investigated whether C. neoformans affected macrophage cell viability and whether NF-κB (nuclear factor-κB), a key regulator of cell growth, apoptosis and inflammation, was involved. Using wild-type (WT) as well as mutant strains of C. neoformans for the pathogen side, and WT and mutant cell lines with altered NF-κB activity or signalling as well as primary macrophages for the host side, we show that C. neoformans manipulated NF-κB-mediated signalling in a unique way to regulate macrophage cell fate and viability. On the one hand, serotype A strains reduced macrophage proliferation in a capsule-independent fashion. This growth decrease, which required a critical dosage of NF-κB activity, was caused by cell cycle disruption and aneuploidy, relying on fungal-induced modification of expression of several cell cycle checkpoint regulators in S and G2/M phases. On the other hand, C. neoformans infection induced macrophage apoptosis in a capsule-dependent manner with a differential requirement of the classical and alternative NF-κB signalling pathways, the latter one being essential. Together, these findings shed new light on fungal strategies to subvert host response through uncoupling of NF-κB activity in pathogen-controlled apoptosis and impairment of cell cycle progression. They also provide the first demonstration of induction of aneuploidy by a fungal pathogen, which may have wider implications for human health as aneuploidy is proposed to promote tumourigenesis.


Subject(s)
Apoptosis/physiology , Cell Cycle Checkpoints/genetics , Chromosomal Instability , Cryptococcus neoformans/pathogenicity , Macrophages/microbiology , NF-kappa B/genetics , Aneuploidy , Animals , Cell Line , Cell Proliferation , Cell Survival , Cryptococcosis/immunology , Cryptococcosis/metabolism , Cryptococcus neoformans/immunology , Cryptococcus neoformans/metabolism , Gene Expression Regulation , Host-Pathogen Interactions , Immune Evasion , Mice , Mice, Inbred Strains , Mice, Transgenic , NF-kappa B/metabolism , Signal Transduction
19.
J Pediatr ; 165(1): 129-33, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24795202

ABSTRACT

OBJECTIVE: To compare medical, religious, and personal belief immunization exemption rates between private and public schools in US. STUDY DESIGN: Exemption rates were calculated using the Centers for Disease Control and Prevention School Immunization Assessment Surveys for the 2009-2010 school year excluding states with incomplete survey data. Standardized exemption rates weighted on enrollments in public and private schools were calculated. Differences in exemption rates between public and private schools were tested using Wilcoxon signed rank test. RESULTS: The overall state exemption rate was higher in US private than public schools, 4.25% (SD 4.27) vs 1.91% (1.67), P = .0001 and private schools had higher exemption rates for all types of exemptions; medical 0.58% (0.71) vs 0.34% (0.34) respectively (P = .0004), religious 2.09% (3.14) vs 0.83% (1.05) respectively (P = .0001), and personal belief 6.10% (4.12) vs 2.79% (1.57), respectively (P = .006). Overall exemption rates were significantly higher in states that allowed personal belief exemptions. CONCLUSIONS: Exemption rates were significantly higher in US private than in public schools. Children attending private schools may be at higher risk of vaccine-preventable diseases than public school children.


Subject(s)
Health Policy , Immunization/standards , Private Sector/standards , Public Sector/standards , Schools/standards , Vaccination/standards , Attitude to Health , Child , Humans , Religion and Medicine , School Admission Criteria , United States
20.
AIDS Behav ; 18 Suppl 3: 305-15, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23709253

ABSTRACT

Prevention and treatment of injection drug use remains a public health concern. We used data from the 2005 Centers for Disease Control and prevention National HIV Behavioral Surveillance system to assess substance abuse treatment utilization, risk behaviors, and recruitment processes in a respondent driven sample of suburban injectors. Twelve service utilization and injection risk variables were analyzed using latent class analysis. Three latent classes were identified: low use, low risk; low use, high risk; and high use, moderate/high risk. In multivariate analysis, annual income <$15,000 (adjusted odds ratio (aOR) = 8.19 [95 % confidence interval (CI), 3.83-17.51]) and self-reported hepatitis C virus infection (aOR = 4.32, 95 % CI (1.84-10.17)) were significantly associated with class membership. Homophily, a measure of preferential recruitment showed that injectors with recent treatment utilization appear a more cohesive group than out-of-treatment injectors. Preferentially reaching injection drug users with high risk behaviors and no recent drug treatment history via respondent driven sampling will require future research.


Subject(s)
Drug Users/statistics & numerical data , HIV Infections/prevention & control , Patient Selection , Risk-Taking , Substance Abuse Treatment Centers/statistics & numerical data , Substance-Related Disorders/therapy , Adult , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Humans , Interviews as Topic , Male , Middle Aged , Multivariate Analysis , Needle Sharing , New York/epidemiology , Substance Abuse, Intravenous/epidemiology , Substance-Related Disorders/complications , Urban Population/statistics & numerical data , Young Adult
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