DNA barcoding and new records of Ornithodoros yumatensis from Central Mexico.

Bats represent the second order of mammals with the highest number of species worldwide with over 1,616 species, and almost 10% of them are recorded in Mexico. These mammals have a great diversity of ectoparasites, in particular soft ticks of the genus Ornithodoros. Desmodus rotundus is one of the bat species that has scarcely been studied in terms of tick species richness in Mexico, with three tick species reported in five of the 32 Mexican states. For this reason, the aim of the present work was to identify ticks associated with D. rotundus from Central Mexico. Fieldwork was undertaken in the municipality El Marqués, Ejido Atongo A, Querétaro, Mexico. Bats were captured using mist nets and were visually inspected for tick presence. The ectoparasites were identified morphologically and molecularly with the use of mitochondrial markers 16SrDNA and cytochrome oxidase subunit I (COI). A total of 30 D. rotundus (1 female, 29 males) were captured, from which 20 larvae identified as Ornithodoros yumatensis were recovered. Molecular analysis confirmed the presence of this species with identity values of 99-100% with sequences of this species from the southwestern US, and the Yucatán Peninsula, Mexico. This is the first report of ticks associated with bats for the state of Querétaro, providing the first sequences of the COI gene from Mexican populations of O. yumatensis and shows an increase in the distribution of this soft tick across Central Mexico.

Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy.

Children living in poverty experience excessive relapse and death from newly diagnosed acute lymphoblastic leukemia (ALL). The influence of household poverty and neighborhood social determinants on outcomes from chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory (r/r) leukemia is poorly described. We identified patients with r/r CD19+ ALL/lymphoblastic lymphoma treated on CD19-directed CAR T-cell clinical trials or with commercial tisagenlecleucel from 2012 to 2020. Socioeconomic status (SES) was proxied at the household level, with poverty exposure defined as Medicaid-only insurance. Low-neighborhood opportunity was defined by the Childhood Opportunity Index. Among 206 patients aged 1 to 29, 35.9% were exposed to household poverty, and 24.9% had low-neighborhood opportunity. Patients unexposed to household poverty or low-opportunity neighborhoods were more likely to receive CAR T-cell therapy with a high disease burden (>25%), a disease characteristic associated with inferior outcomes, as compared with less advantaged patients (38% vs 30%; 37% vs 26%). Complete remission (CR) rate was 93%, with no significant differences by household poverty (P = .334) or neighborhood opportunity (P = .504). In multivariate analysis, patients from low-opportunity neighborhoods experienced an increased hazard of relapse as compared with others (P = .006; adjusted hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.3-4.1). There was no difference in hazard of death (P = .545; adjusted HR, 1.2; 95% CI, 0.6-2.4). Among children who successfully receive CAR T-cell therapy, CR and overall survival are equitable regardless of proxied SES and neighborhood opportunity. Children from more advantaged households and neighborhoods receive CAR T-cell therapy with a higher disease burden. Investigation of multicenter outcomes and access disparities outside of clinical trial settings is warranted.

Results from a cross-sectional, observational study to assess inadequate pain relief in patients with knee and/or hip osteoarthritis in Mexico.

INTRODUCTION AND OBJECTIVES: There is limited data that characterizes osteoarthritis (OA) patients who experience moderate to severe pain despite analgesic treatment in Mexico. In this study, we estimate the real-world prevalence of inadequate pain relief (IPR) among individuals with knee and/or hip OA who have been prescribed analgesic therapy and characterize this patient population for each country separately. MATERIALS AND METHODS: This is a multinational, multi-site, cross-sectional, observational study. Participating physicians enrolled patients over 50 years of age with diagnosed knee and/or hip OA who had been prescribed topical and/or oral pain medication for at least 30 days prior to study visit, extracted data from their medical charts, and collected patient data using established questionnaires. RESULTS: 301 patients treated by 35 physicians in Mexico were enrolled in the study. More than half of the patients (53%) met the definition of IPR. Patients with IPR were significantly older (66.8 vs. 63.5 years, p=0.002) and were more likely to be obese (24.2% vs. 11.9%, p=0.006). Patients in the IPR group were more likely to report moderate/severe problems across all 5 dimensions of the EQ-5D and reported higher scores, indicating worse outcomes, on all three WOMAC subscales. Patients in the IPR group also reported reduced work productivity and greater treatment dissatisfaction compared to patients without IPR. DISCUSSION AND CONCLUSIONS: IPR is highly prevalent among individuals with knee and/or hip OA in Mexico. Patients with IPR experience decreased health-related quality of life HRQoL and work productivity, impaired function, and poor treatment satisfaction. Health care professionals need to be aware of the high prevalence of IPR, work toward improving OA patient management, and facilitate early intervention or changes in drug and other treatment modalities.

Humanized CD19-Targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-Naive and CAR-Exposed Children and Young Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia.

PURPOSE: CD19-targeted chimeric antigen receptor (CAR)-modified T cells demonstrate unprecedented responses in B-cell acute lymphoblastic leukemia (B-ALL); however, relapse remains a substantial challenge. Short CAR T-cell persistence contributes to this risk; therefore, strategies to improve persistence are needed. METHODS: We conducted a pilot clinical trial of a humanized CD19 CAR T-cell product (huCART19) in children and young adults with relapsed or refractory B-ALL (n = 72) or B-lymphoblastic lymphoma (n = 2), treated in two cohorts: with (retreatment, n = 33) or without (CAR-naive, n = 41) prior CAR exposure. Patients were monitored for toxicity, response, and persistence of huCART19. RESULTS: Seventy-four patients 1-29 years of age received huCART19. Cytokine release syndrome developed in 62 (84%) patients and was grade 4 in five (6.8%). Neurologic toxicities were reported in 29 (39%), three (4%) grade 3 or 4, and fully resolved in all cases. The overall response rate at 1 month after infusion was 98% (100% in B-ALL) in the CAR-naive cohort and 64% in the retreatment cohort. At 6 months, the probability of losing huCART19 persistence was 27% (95% CI, 14 to 41) for CAR-naive and 48% (95% CI, 30 to 64) for retreatment patients, whereas the incidence of B-cell recovery was 15% (95% CI, 6 to 28) and 58% (95% CI, 33 to 77), respectively. Relapse-free survival at 12 and 24 months, respectively, was 84% (95% CI, 72 to 97) and 74% (95% CI, 60 to 90) in CAR-naive and 74% (95% CI, 56 to 97) and 58% (95% CI, 37 to 90) in retreatment cohorts. CONCLUSION: HuCART19 achieved durable remissions with long-term persistence in children and young adults with relapsed or refractory B-ALL, including after failure of prior CAR T-cell therapy.

Neighborhood education status drives racial disparities in clinical outcomes in PPCM.

BACKGROUND: Peripartum cardiomyopathy (PPCM) disproportionately affects women of African ancestry. Additionally, clinical outcomes are worse in this subpopulation compared to White women with PPCM.  The extent to which socioeconomic parameters contribute to these racial disparities is not known. METHODS: We aimed to quantify the association between area-based proxies of socioeconomic status (SES) and clinical outcomes in PPCM, and to determine the potential contribution of these factors to racial disparities in outcomes. A retrospective cohort study was performed at the University of Pennsylvania Health System, a tertiary referral center serving a population with a high proportion of Black individuals. The cohort included 220 women with PPCM, 55% of whom were Black or African American. Available data included clinical and demographic characteristics as well as residential address georeferenced to US Census-derived block group measures of SES. Rates of sustained cardiac dysfunction (defined as persistent LVEF <50%, LVAD placement, transplant, or death) were compared by race and block group-level measures of SES, and a composite neighborhood concentrated disadvantage index (NDI). The contributions of area-based socioeconomic parameters to the association between race and sustained cardiac dysfunction were quantified. RESULTS: Black race and higher NDI were both independently associated with sustained cardiac dysfunction (relative risk [RR] 1.63, confidence interval [CI] 1.13-2.36; and RR 1.29, CI 1.08-1.53, respectively). Following multivariable adjustment, effect size for NDI remained statistically significant, but effect size for Black race did not. The impact of low neighborhood education on racial disparities in outcomes was stronger than that of low neighborhood income (explaining 45% and 0% of the association with black race, respectively). After multivariate adjustment, only low area-based education persisted as significantly correlating with sustained cardiac dysfunction (RR 1.49; CI 1.02-2.17). CONCLUSIONS: Both Black race and NDI independently associate with adverse outcomes in women with PPCM in a single center study. Of the specific components of NDI, neighborhood low education was most strongly associated with clinical outcome and partially explained differences in race. These results suggest interventions targeting social determinants of health in disadvantaged communities may help to mitigate outcome disparities.

Broad-Spectrum Antibiotics and Risk of Graft-versus-Host Disease in Pediatric Patients Undergoing Transplantation for Acute Leukemia: Association of Carbapenem Use with the Risk of Acute Graft-versus-Host Disease

Variation in the gastrointestinal (GI) microbiota after hematopoietic cell transplantation (HCT) has been associated with acute graft-versus-host disease (aGVHD). Because antibiotics induce dysbiosis, we examined the association of broad-spectrum antibiotics with subsequent aGVHD risk in pediatric patients undergoing HCT for acute leukemia. We performed a retrospective analysis in a dataset merged from 2 sources: (1) the Center for International Blood and Marrow Transplant Research, an observational transplantation registry, and (2) the Pediatric Health Information Services, an administrative database from freestanding children's hospitals. We captured exposure to 3 classes of antibiotics used for empiric treatment of febrile neutropenia: (1) broad-spectrum cephalosporins, (2) antipseudomonal penicillins, and (3) carbapenems. The primary outcome was grade II-IV aGVHD; secondary outcomes were grade III-IV aGVHD and lower GI GVHD. The adjusted logistic regression model (full cohort) and time-to-event analysis (subcohort) included transplantation characteristics, GVHD risk factors, and adjunctive antibiotic exposures as covariates. The full cohort included 2550 patients at 36 centers; the subcohort included 1174 patients. In adjusted models, carbapenems were associated with an increased risk of grade II-IV aGVHD in the full cohort (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.02 to 1.51) and subcohort (sub hazard ratio [HR], 1.31; 95% CI, 0.99 to 1.72), as well as with an increased risk of grade III-IV aGVHD (subHR, 1.77; 95% CI, 1.25 to 2.52). Early carbapenem exposure (before day 0) especially impacted aGVHD risk. For antipseudomonal penicillins, the associations with aGVHD were in the direction of increased risk but were not statistically significant. There was no identified association between broad-spectrum cephalosporins and aGVHD. Carbapenems, more than other broad-spectrum antibiotics, should be used judiciously in pediatric HCT recipients to minimize aGVHD risk. Further research is needed to clarify the mechanism underlying this association.

Identification of Patient-Reported Outcome Phenotypes Among Oncology Patients With Palliative Care Needs.

PURPOSE: Despite evidence-based guidelines recommending early palliative care, it remains unclear how to identify and refer oncology patients, particularly in settings with constrained access to palliative care. We hypothesize that patient-reported outcome (PRO) data can be used to characterize patients with palliative care needs. To determine if PRO data can identify latent phenotypes that characterize indications for specialty palliative care referral. METHODS: We conducted a retrospective study of self-reported symptoms on the Edmonton Symptom Assessment System collected from solid tumor oncology patients (n = 745) referred to outpatient palliative care. Data were collected as part of routine clinical care from October 2012 to March 2018 at eight community and academic sites. We applied latent profile analysis to identify PRO phenotypes and examined the association of phenotypes with clinical and demographic characteristics using multinomial logistic regression. RESULTS: We identified four PRO phenotypes: (1) Low Symptoms (n = 295, 39.6%), (2) Moderate Pain/Fatigue + Mood (n = 180, 24.2%), (3) Moderate Pain/Fatigue + Appetite + Dyspnea (n = 201, 27.0%), and (4) High Symptoms (n = 69, 9.3%). In a secondary analysis of 421 patients, we found that two brief items assessing social and existential needs aligned with higher severity symptom and psychological distress phenotypes. CONCLUSION: Oncology patients referred to outpatient palliative care in a real-world setting can be differentiated into clinically meaningful phenotypes using brief, routinely collected PRO measures. Latent modeling provides a mechanism to use patient-reported data on a population level to identify distinct subgroups of patients with unmet palliative needs.

Cardiology Involvement in Patients with Breast Cancer Treated with Trastuzumab.

BACKGROUND: There is limited evidence regarding the impact of cardiology involvement in the care of cancer patients. OBJECTIVES: We evaluated the impact of cardiology involvement on guideline-adherent cardiovascular monitoring and risk factor management in breast cancer patients treated with trastuzumab. METHODS: In a single-center retrospective cohort study, we evaluated electronic health records from 1,047 breast cancer patients receiving trastuzumab between January 2009 and July 2018. A visit to a cardiology provider beginning from the 3 months prior to cancer therapy initiation until the last contact date defined cardiology involvement. Guideline-adherent monitoring, defined by echocardiography assessment within the 4 months prior to trastuzumab initiation and follow-up echocardiography at least every 4 months during therapy, was compared in patients with and without cardiology involvement prior to treatment initiation. Multivariable associations between cardiology involvement and time-varying risk factors blood pressure (BP) and body mass index (BMI) were assessed using generalized estimating equations. RESULTS: Cardiology involvement occurred in 293 (28%) patients. A higher proportion of patients with cardiology involvement prior to trastuzumab initiation had guideline-adherent monitoring (76.4% versus 60.1%, p=0.007). Cardiology involvement was associated with an average 1.5mmHg (95% CI -2.9,-0.1, p=0.035) lower systolic BP; which was more pronounced in those with hypertension (-2.7mmHg (95% CI -4.6,-0.7, p=0.007)). Cardiology involvement was associated with a lower BMI in patients with baseline BMI≥25 kg/m2 (mean difference; -0.5 (95% CI -1.0,-0.1, p=0.027)). CONCLUSIONS: Cardiology involvement in breast cancer patients treated with trastuzumab is associated with greater adherence to cardiovascular monitoring and modest improvements in risk factor control.

Intra-octahedral distortion on lamellar potassium niobate K4Nb6O17: a periodic DFT study of structural, electronic and vibrational properties.

Structural, electronic and spectroscopic properties of the anhydrous K4Nb6O17 niobate were investigated in the bulk phase using periodic density functional theory (DFT) calculations with global hybrid (B3LYP) and also including dispersion corrections (B3LYP-D3). The degree of native distortion of different niobium octahedra (here named [NbO6-x], or [NbO6]d) were quantified in terms of the effective coordination number (ECoN) and of other classical descriptors of local deformation and were correlated with the electronic structure. The effect of intrinsic deformation was also examined using the quantum theory of atoms in molecules and crystals (QTAIMC), density of states and charge analyses. The nature of the atom-atom interactions was classified by the ratio of the potential to the kinetic energy density at the bcp (3,-1): |V(rbcp)|/|G(rbcp)|, demonstrating that intraoctahedral Nb-O interactions are well characterized as "transit bond" (between the pure covalent and ionic chemical bonds). The vibrational spectra (infrared and Raman intensities) were fully characterized and discussed, correlating the frequencies with the intraoctahedral distortion.

Effect of Dexrazoxane on Left Ventricular Systolic Function and Treatment Outcomes in Patients With Acute Myeloid Leukemia: A Report From the Children's Oncology Group.

PURPOSE: To determine whether dexrazoxane provides effective cardioprotection during frontline treatment of pediatric acute myeloid leukemia (AML) without increasing relapse risk or noncardiac toxicities of the chemotherapy regimens. PATIENTS AND METHODS: This was a multicenter study of all pediatric patients with AML without high allelic ratio FLT3/ITD treated in the Children's Oncology Group trial AAML1031 between 2011 and 2016. Median follow-up was 3.5 years. Dexrazoxane was administered at the discretion of treating physicians and documented at each course. Ejection fraction (EF) and shortening fraction (SF) were recorded after each course and at regular intervals in follow-up. Per protocol, anthracyclines were to be withheld if there was evidence of left ventricular systolic dysfunction (LVSD) defined as SF < 28% or EF < 55%. Occurrence of LVSD, trends in EF and SF, 5-year event-free survival (EFS) and overall survival (OS), and treatment-related mortality (TRM) were compared by dexrazoxane exposure. RESULTS: A total of 1,014 patients were included in the analyses; 96 were exposed to dexrazoxane at every anthracycline course, and 918 were never exposed. Distributions of sex, age, race, presenting WBC count, risk group, treatment arm, and compliance with cardiac monitoring were similar for dexrazoxane-exposed and -unexposed patients. Dexrazoxane-exposed patients had significantly smaller EF and SF declines than unexposed patients across courses and a lower risk for LVSD (26.5% v 42.2%; hazard ratio, 0.55; 95% CI, 0.36 to 0.86; P = .009). Dexrazoxane-exposed patients had similar 5-year EFS (49.0% v 45.1%; P = .534) and OS (65.0% v 61.9%; P = .613) to those unexposed; however, there was a suggestion of lower TRM with dexrazoxane (5.7% v 12.7%; P = .068). CONCLUSION: Dexrazoxane preserved cardiac function without compromising EFS and OS or increasing noncardiac toxicities. Dexrazoxane should be considered for cardioprotection during frontline treatment of pediatric AML.

Occurrence of Treatment-Related Cardiotoxicity and Its Impact on Outcomes Among Children Treated in the AAML0531 Clinical Trial: A Report From the Children's Oncology Group.

PURPOSE: Late cardiotoxicity after pediatric acute myeloid leukemia therapy causes substantial morbidity and mortality. The impact of early-onset cardiotoxicity on treatment outcomes is less well understood. Thus, we evaluated the risk factors for incident early cardiotoxicity and the impacts of cardiotoxicity on event-free survival (EFS) and overall survival (OS). METHODS: Cardiotoxicity was ascertained through adverse event monitoring over the course of follow-up among 1,022 pediatric patients with acute myeloid leukemia treated in the Children's Oncology Group trial AAML0531. It was defined as grade 2 or higher left ventricular systolic dysfunction on the basis of Common Terminology Criteria for Adverse Events (version 3) definitions. RESULTS: Approximately 12% of patients experienced cardiotoxicity over a 5-year follow-up, with more than 70% of incident events occurring during on-protocol therapy. Documented cardiotoxicity during on-protocol therapy was significantly associated with subsequent off-protocol toxicity. Overall, the incidence was higher among noninfants and black patients, and in the setting of a bloodstream infection. Both EFS (hazard ratio [HR], 1.6; 95% CI, 1.2 to 2.1; P = .004) and OS (HR, 1.6; 95% CI, 1.2 to 2.2, P = .005) were significantly worse in patients with documented cardiotoxicity. Impacts on EFS were equivalent whether the incident cardiotoxicity event occurred in the absence (HR, 1.6; 95% CI, 1.1 to 2.2; P = .017) or presence of infection (HR, 1.6; 95% CI, 1.0 to 2.7; P = .069) compared with patients without documented cardiotoxicity. However, the reduction in OS was more pronounced for cardiotoxicity not associated with infection (HR, 1.7; 95% CI, 1.2 to 2.5; P = .004) than for infection-associated cardiotoxicity (HR, 1.3; 95% CI, 0.7 to 2.4; P = .387). CONCLUSION: Early treatment-related cardiotoxicity may be associated with decreased EFS and OS. Cardioprotective strategies are urgently needed to improve relapse risk and both short- and long-term mortality outcomes.

Níveis de flexibilidade e força muscular em mulheres praticantes e não praticantes de hidroginástica / Levels of fl exibility and muscle strength in women that are practicing and non-practicing of aqua-aerobics

O estudo se propôs comparar os níveis de fl exibilidade e força muscular em mulheres praticantes e não praticantes de hidroginástica da cidade de Guanambi/BA. Para isso, realizou-se uma pesquisa de campo de caráter quantitativo, descritivo e explicativo, composta por uma amostra de quarenta mulheres, sendo vinte mulheres praticantes e vinte mulheres não praticantes de hidroginástica, com a faixa etária dos 50 aos 77 anos de idades. A coleta dos dados foi através de três testes: "teste de sentar e alcançar", "teste de força de preensão manual" e "teste de levantar da cadeira em 30 segundos". Os dados foram tabulados e organizados no Programa da Microsoft Excel versão 2013. Em seguida, os resultados foram transpostos para a planilha do programa Graph Pad Prism 6, para comparar à média e o desvio padrão das variáveis (testes), utilizando o teste "t". Para análise estatística dos dados usou o programa Graph Pad Prism 6, que se atribui como nível de signifi cância valor de p<0,05. Após a análise dos dados notou-se que no "teste de sentar e alcançar", as praticantes de hidroginástica encontra-se na faixa recomendável e na baixa aptidão. Já no "teste de preensão manual direita e esquerda" foram classifi cadas como regular e fraca, e no "teste de levantar da cadeira em 30 segundos" encontram-se no valor de repetições recomendável....(AU)

The present study aimed to compare the levels of fl exibility and muscle strength in women from the city of Guanambi/Bahia, which were practicing and non-practicing of aqua-aerobics. For this, a fi eld research was done with 20 practicing and 20 non-practicing women of 50 to 77 years old. They were submitted to a "sit and reach test", "manual grip strength test" and "chair lift test in 30 seconds" and the quantitative, descriptive and explanatory data were obtained, transferred and tabulated in the Microsoft Excel 2013 software and in the Graph Pad Prism 6 software. The t test was used to compare the means and the standard deviations of the variables (tests) and a P value < 0.05 was considered to be statistically signifi cant. The results showed that practicing women were classifi ed in the group of recommendable range and low aptitude for the "sit-and-reach test". On the other hand, they were classifi ed as regular and weak for the "right and left hand grip test" and in the recommended repetition value for the "lift test of the chair in 30 seconds"....(AU)

Measuring herpes zoster disease burden in São Paulo, Brazil: a clinico-epidemiological single-center study.

OBJECTIVES: Herpes zoster is characterized by acute neuritis and post-herpetic neuralgia. Currently, data concerning the zoster-associated impact on quality of life and healthcare resource utilization in Brazil are scarce. This study measured the zoster-associated burden in a Brazilian population. METHODS: This was a prospective, observational, single-cohort study conducted in a primary hospital's emergency room in São Paulo, Brazil. Patients enrolled at various timepoints during a zoster episode were followed over 180 days. The Zoster Brief Pain Inventory and the Initial Zoster Impact Questionnaire assessed zoster-associated pain. The EuroQoL assessed the impact of herpes zoster and/or zoster-associated pain on quality of life. Healthcare resource utilization was assessed by patient-reported questionnaires. RESULTS: One-hundred forty-six zoster patients were enrolled [mean (SD) age of 69.9 (10.9) years]. Mean (SD) worst pain scores decreased from 5.3 (3.5) at baseline to 1.9 (3.0) 180 days following rash onset. Mean (SD) EuroQoL scores significantly decreased from 0.9 (0.2) before rash appearance to 0.7 (0.2) after rash onset (p<0.001), followed by gradual improvements in quality of life over 180 days, with pre-herpes zoster quality of life achieved at the end of the observation period. The majority of patients purchased prescription medications (89.7%) and required doctor's office visits (65.8%) for zoster episodes. CONCLUSIONS: Herpes zoster is associated with a significant disease burden, including zoster-associated pain, impaired quality of life and increased healthcare resource utilization in Brazil. These results support the implementation of early intervention and prevention programs such as vaccinations to reduce the herpes zoster-associated disease burden in Brazil.

Measuring herpes zoster disease burden in São Paulo, Brazil: a clinico-epidemiological single-center study

OBJECTIVES: Herpes zoster is characterized by acute neuritis and post-herpetic neuralgia. Currently, data concerning the zoster-associated impact on quality of life and healthcare resource utilization in Brazil are scarce. This study measured the zoster-associated burden in a Brazilian population. METHODS: This was a prospective, observational, single-cohort study conducted in a primary hospital's emergency room in São Paulo, Brazil. Patients enrolled at various timepoints during a zoster episode were followed over 180 days. The Zoster Brief Pain Inventory and the Initial Zoster Impact Questionnaire assessed zoster-associated pain. The EuroQoL assessed the impact of herpes zoster and/or zoster-associated pain on quality of life. Healthcare resource utilization was assessed by patient-reported questionnaires. RESULTS: One-hundred forty-six zoster patients were enrolled [mean (SD) age of 69.9 (10.9) years]. Mean (SD) worst pain scores decreased from 5.3 (3.5) at baseline to 1.9 (3.0) 180 days following rash onset. Mean (SD) EuroQoL scores significantly decreased from 0.9 (0.2) before rash appearance to 0.7 (0.2) after rash onset (p<0.001), followed by gradual improvements in quality of life over 180 days, with pre-herpes zoster quality of life achieved at the end of the observation period. The majority of patients purchased prescription medications (89.7%) and required doctor's office visits (65.8%) for zoster episodes. CONCLUSIONS: Herpes zoster is associated with a significant disease burden, including zoster-associated pain, impaired quality of life and increased healthcare resource utilization in Brazil. These results support the implementation of early intervention and prevention programs such as vaccinations to reduce the herpes zoster-associated disease burden in Brazil.

Prevalence and factors associated with coinfection of human papillomavirus and Chlamydia trachomatis in adolescents and young women.

BACKGROUND: Human papillomavirus and Chlamydia trachomatis share the same route of sexual transmission and possess similar risk factors, indicating that coinfection may act synergistically in the induction of epithelial cell abnormalities. OBJECTIVE: This study aimed to determine the prevalence of human papillomavirus and Chlamydia trachomatis in adolescents and young women and identify factors associated with coinfection. STUDY DESIGN: This cross-sectional study included 276 female participants, aged 15-24 years, who were sexually active. Interviews were conducted and cervical specimens were collected for cervical smears and molecular tests. All cervical specimens were tested for 27 human papillomavirus genotypes by polymerase chain reaction amplification and hybridization to a human papillomavirus linear array. Detection of Chlamydia trachomatis was performed by polymerase chain reaction using primers directed to the region encoding the cryptic plasmid. Bivariate and multivariate analyses were performed to evaluate the factors associated with coinfection with human papillomavirus and Chlamydia trachomatis. The odds ratio, the adjusted odds ratio, and the 95% confidence interval were calculated. RESULTS: The prevalence of infection by Chlamydia trachomatis and human papillomavirus was 9.1% (95% confidence interval, 5.61-12.4) and 47.1% (95% confidence interval, 41.0-53.2), respectively. The prevalence of coinfection with human papillomavirus and Chlamydia trachomatis was 5.8% (95% confidence interval, 3.3-9.2); coinfection with 1 human papillomavirus type was 3.3% (95% confidence interval, 1.5-6.1) and with multiple types was 2.5% (95% confidence interval, 1.0-5.2). The prevalence of cytological abnormalities was 12.3% (95% confidence interval, 8.6-16.79). Human papillomavirus infections of high oncogenic risk were more prevalent (85.4%). Factors independently associated with coinfection of human papillomavirus/Chlamydia trachomatis obtained by multivariate analysis were the initiation of sexual activity under 16 years of age with an an odds ratio of 4.9 (95% confidence interval, 1.0-23.63; P = .05) and cytological abnormalities with an odds ratio of 10.7 (95% confidence interval, 1.9-59.5; P = .01), which indicates there is risk for the detection of cytological abnormalities in adolescents and young women coinfected with human papillomavirus/Chlamydia trachomatis. CONCLUSION: The prevalence of coinfection among our study population was of a magnitude that warrants attention by public health services. Adolescents and young women should be monitored for Chlamydia trachomatis infection and vaccinated against human papillomavirus. The association between cytological abnormalities and coinfection with human papillomavirus and Chlamydia trachomatis indicates the potential synergistic role of these infections in carcinogenesis of the cervix.

Effects of a Workplace Intervention on Parent-Child Relationships.

This study tested whether effects of a workplace intervention, aimed at promoting employees' schedule control and supervisor support for personal and family life, had implications for parent-adolescent relationships; we also tested whether parent-child relationships differed as a function of how many intervention program sessions participants attended. Data came from a group randomized trial of a workplace intervention, delivered in the information technology division of a Fortune 500 company. Analyses focused on 125 parent-adolescent dyads that completed baseline and 12-month follow-up home interviews. Results revealed no main effects of the intervention, but children of employees who attended 75% or more program sessions reported more time with their parent and more parent education involvement compared to adolescents whose parents attended less than 75% of sessions, and they tended to report more time with parent and more parental solicitation of information about their experiences compared to adolescents whose parents were randomly assigned to the usual practice condition.

Comparison of Two Fluid Replacement Protocols During a 20-km Trail Running Race in the Heat.

Lopez, RM, Casa, DJ, Jensen, K, Stearns, RL, DeMartini, JK, Pagnotta, KD, Roti, MW, Armstrong, LE, and Maresh, CM. Comparison of two fluid replacement protocols during a 20-km trail running race in the heat. J Strength Cond Res 30(9): 2609-2616, 2016-Proper hydration is imperative for athletes striving for peak performance and safety, however, the effectiveness of various fluid replacement strategies in the field setting is unknown. The purpose of this study was to investigate how two hydration protocols affect physiological responses and performance during a 20-km trail running race. A randomized, counter-balanced, crossover design was used in a field setting (mean ± SD: WBGT 28.3 ± 1.9° C). Well-trained male (n = 8) and female (n = 5) runners (39 ± 14 years; 175 ± 9 cm; 67.5 ± 11.1 kg; 13.4 ± 4.6% BF) completed two 20-km trail races (5 × 4-km loop) with different water hydration protocols: (a) ad libitum (AL) consumption and (b) individualized rehydration (IR). Data were analyzed using repeated measures ANOVA. Paired t-tests compared pre-race-post-race measures. Main outcome variables were race time, heart rate (HR), gastrointestinal temperature (TGI), fluid consumed, percent body mass loss (BML), and urine osmolality (Uosm). Race times between groups were similar. There was a significant condition × time interaction (p = 0.048) for HR, but TGI was similar between conditions. Subjects replaced 30 ± 14% of their water losses in AL and 64 ± 16% of their losses in IR (p < 0.001). Ad libitum trial experienced greater BML (-2.6 ± 0.5%) compared with IR (-1.3 ± 0.5%; p < 0.001). Pre-race to post-race Uosm differences existed between AL (-273 ± 146 mOsm) and IR (-145 ± 215 mOsm, p = 0.032). In IR, runners drank twice as much fluid than AL during the 20-km race, leading to > 2% BML in AL. Ad libitum drinking resulted in 1.3% greater BML over the 20-km race, which resulted in no thermoregulatory or performance differences from IR.

Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence.

Non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are routinely used to treat HIV-1 infection, yet their mechanism of action remains unclear despite intensive investigation. In this study, we developed complementary single-molecule fluorescence and ensemble fluorescence anisotropy approaches to discover how NNRTIs modulate the intra-molecular conformational changes and inter-molecular dynamics of RT-template/primer (T/P) and RT-T/P-dNTP complexes. We found that NNRTI binding to RT induces opening of the fingers and thumb subdomains, which increases the dynamic sliding motion of the enzyme on the T/P and reduces dNTP binding affinity. Further, efavirenz promotes formation of the E138-K101 salt bridge between the p51 and p66 subunits of RT, which contributes to opening of the thumb/fingers subdomains. Engineering a more polar salt bridge between p51 and p66 resulted in even greater increases in the thumb/fingers opening, RT sliding, dNTP binding disruption and in vitro and in vivo RT inhibition than were observed with wild-type RT. We also observed that K103N, a clinically relevant NNRTI resistance mutation, does not prevent binding between efavirenz and RT-T/P but instead allows formation of a stable and productive RT-T/P-dNTP complex, possibly through disruption of the E138-K101 salt bridge. Collectively, these data describe unique structure-activity-resistance relationships that could be exploited for drug development.

Unilateral thalamic deep brain stimulation in essential tremor demonstrates long-term ipsilateral effects.

INTRODUCTION: Deep Brain Stimulation (DBS) of thalamus in essential tremor (ET) is effective for the treatment of contralateral tremors. Bilateral DBS controls tremors on both sides but is associated with increased morbidity and risks. We evaluated if unilateral surgery had ipsilateral benefits on tremors and thus could be a potentially safer alternative to bilateral DBS. METHODS: Medication refractory ET patients undergoing unilateral thalamic DBS were included and longitudinally followed. Tremor rating scale was used to record total motor, arm tremor and activities of daily living (ADL) scores at baseline, six months and at last visit (three or more years after surgery). Postoperative scores were recorded with DBS turned OFF and ON. RESULTS: Twenty-two patients with a mean follow-up 3.4 ± 0.14 years were enrolled. When baseline scores were compared to scores with the DBS turned ON, significant improvements were noted in total tremor (40%), ADL (67%) and arm tremor scores both on the ipsilateral and the contralateral side at six months and at the last visit of follow-up (all p < 0.05). Ipsilateral arm tremor (∼56%) improvements were milder compared to the contralateral side (∼73%) tremors. CONCLUSION: Unilateral thalamic DBS in ET demonstrates significant long-term benefits for ipsilateral arm tremors and can be offered to higher risk and to select patients.