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1.
J Autism Dev Disord ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591436

RESUMO

Most children with autism spectrum disorder (ASD), in resource-limited settings (RLS), are diagnosed after the age of four. Our work confirmed and extended results of Pierce that eye tracking could discriminate between typically developing (TD) children and those with ASD. We demonstrated the initial 15 s was at least as discriminating as the entire video. We evaluated the GP-MCHAT-R, which combines the first 15 s of manually-coded gaze preference (GP) video with M-CHAT-R results on 73 TD children and 28 children with ASD, 36-99 months of age. The GP-MCHAT-R (AUC = 0.89 (95%CI: 0.82-0.95)), performed significantly better than the MCHAT-R (AUC = 0.78 (95%CI: 0.71-0.85)) and gaze preference (AUC = 0.76 (95%CI: 0.64-0.88)) alone. This tool may enable early screening for ASD in RLS.

2.
Am J Trop Med Hyg ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534741

RESUMO

Chagas disease is a neglected tropical disease that affects an estimated 300,000 people in the United States. This perspective piece reviews diagnostic challenges and proposes next steps to address these shortfalls.

3.
Int J Infect Dis ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33618005

RESUMO

BACKGROUND: Vertical transmission of Trypanosoma cruzi infection from mother to infant accounts for a growing proportion of new cases of Chagas disease. However, no systematic reviews of risk factors for T. cruzi vertical transmission have been performed. METHODS: We performed a systematic review of the literature in PubMed, LILACS, and Embase databases, following PRISMA guidelines. Studies were not excluded based on language, country of origin, or date of publication. RESULTS: Our literature review yielded 27 relevant studies examining a wide variety of risk factors, including maternal age, parasitic load, immunologic factors, vector exposure, and more. Several studies suggested that mothers with higher parasitic loads may have a greater risk of vertical transmission, and a meta-analysis of two studies found a significantly higher parasitic load among transmitting than non-transmitting mothers with T. cruzi infection. A second meta-analysis of ten studies demonstrated that maternal age was not significantly associated with vertical transmission risk. CONCLUSIONS: The current literature suggests that high maternal parasitic load may be a risk factor for congenital Chagas disease among infants of T. cruzi seropositive mothers. Given the considerable heterogeneity and risk of bias among current literature, additional studies are warranted to assess potential risk factors for vertical transmission of T. cruzi infection.

4.
Int Breastfeed J ; 16(1): 11, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468169

RESUMO

BACKGROUND: Substantial evidence exists surrounding the health risks of breast milk substitutes (BMS) in place of exclusive breastfeeding among infants < 6 months of age in resource-poor settings. Yet, mothers' experiences of selecting and purchasing BMS brands have not been well studied to date. This qualitative study explored the factors influencing BMS purchasing practices, along with the consequences of those decisions, in peri-urban Lima, Peru. METHODS: We conducted in-depth interviews (IDIs) with 29 mothers who had begun mixed-feeding their infants during the first 6 months of life. Interviews explored participants' reasons for initiating infant formula use and their experiences of selecting, purchasing, and providing BMS to their children. Audio recordings were transcribed, coded, and key themes and illustrative vignettes were identified. RESULTS: The primary reported reasons for initiating infant formula use included having received a recommendation for infant formula from a healthcare provider, concerns about an infant's weight gain, and the perception of insufficient breast milk. Mothers tended to initially purchase the BMS brand that had been recommended by a doctor, which was often more expensive than the alternatives. The costs of BMS, which escalated as infants grew, often disrupted the household economy and generated significant stress. While some mothers identified alternatives allowing them to continue purchasing the same brand, others chose to switch to less expensive products. Several mothers began to feed their infants follow-on formula or commercial milk, despite their awareness that such practices were not recommended for infants under 6 months of age. The approval of family members and the absence of an infant's immediate adverse reaction influenced mothers' decisions to continue purchasing these products. CONCLUSIONS: The high costs of BMS may deepen existing socio-economic vulnerabilities and generate new risks for infant health. The continued dedication of resources towards breastfeeding education and support is critical, and strategies would benefit from underscoring the long-term financial and health consequences of infant formula use, and from strengthening women's self-efficacy to refuse to initiate infant formula when recommended. In addition, health providers should be trained in counseling to help women to relactate or return to exclusive breastfeeding after cessation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33277433

RESUMO

Western South America was one of the worldwide cradles of civilization. The well-known Inca Empire was the tip of the iceberg of an evolutionary process that started 11,000 to 14,000 years ago. Genetic data from 18 Peruvian populations reveal the following: 1) The between-population homogenization of the central southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward. Instead, longitudinal gene flow between the northern coast of Peru, Andes, and Amazonia accompanied cultural and socioeconomic interactions revealed by archeology. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower, and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia. 2) The genetic homogenization between the populations of the arid Andes is not only due to migrations during the Inca Empire or the subsequent colonial period. It started at least during the earlier expansion of the Wari Empire (600 to 1,000 years before present). 3) This demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest: in the Andes, a putative enhancer in HAND2-AS1 (heart and neural crest derivatives expressed 2 antisense RNA1, a noncoding gene related to cardiovascular function) and rs269868-C/Ser1067 in DUOX2 (dual oxidase 2, related to thyroid function and innate immunity) genes and, in the Amazon, the gene encoding for the CD45 protein, essential for antigen recognition by T and B lymphocytes in viral-host interaction.

6.
Vaccine ; 2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33349458

RESUMO

BACKGROUND: Maternal immunization has the potential to reduce both maternal and infant morbidity and mortality by protecting women from complications during pregnancy as well as conferring protection for babies who are too young to be vaccinated. Limited evidence is available about the drivers of maternal immunization in middle-income countries such as Peru. Vaccines against tetanus, diphtheria and influenza are recommended beginning in the second trimester in Peru; however, vaccination coverage has remained low in Peru compared to other countries in the region. As additional vaccines are recommended for administration in pregnancy, a better understanding of the perceptions and attitudes of pregnant women that influence vaccination are needed to design communication materials. METHODS: We conducted an exploratory qualitative study to understand the individual level factors influencing pregnant women's vaccine uptake. We interviewed pregnant women about their knowledge, perceptions and experiences with vaccination during pregnancy. Community health workers recruited women in a peri urban area of Peru in April 2018. RESULTS: Twelve women were interviewed, the majority of which had received vaccination during the current pregnancy. The most common reasons for vaccination were to protect the baby and because vaccines are effective. Concerns included vaccine safety during pregnancy and adverse effects on the unborn baby. Some women mentioned that because vaccines are given later in pregnancy, the unborn baby is stronger, so vaccines will not harm them. Women highlighted that the main reason for not being vaccinated was lack of information. They also noted that they were the decision-maker in whether or not they were vaccinated. Most women said that they trusted healthcare providers and that trust was linked to providing information through open communication. CONCLUSIONS: Overall, participants were supportive of maternal vaccination. They believed that vaccines were effective in protecting both their unborn baby and themselves. The main reason given for non-vaccination was lack of knowledge about vaccination in pregnancy. The strong desire expressed by study participants to get more information presents an opportunity for immunization programs to develop interventions that facilitate better information dissemination to pregnant women to increase vaccination uptake.

7.
Clin Infect Dis ; 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33367656

RESUMO

BACKGROUND: Vertical transmission of Trypanosoma cruzi infection accounts for a growing proportion of new cases of Chagas disease. Better risk stratification is needed to predict which women are more likely to transmit the infection. METHODS: This study enrolled women and their infants at the Percy Boland Women's Hospital in Santa Cruz, Bolivia. Pregnant women were screened for Chagas disease by rapid test and received confirmatory serology. Infants of seropositive mothers underwent diagnostic testing with quantitative polymerase chain reaction (qPCR). RESULTS: Among 5,828 enrolled women, 1,271 (21.8%) screened positive for Chagas disease. Older maternal age, family history of Chagas disease, home conditions, lower education level, and history of living in a rural area were significantly associated with higher adjusted odds of maternal infection. Of the 1,325 infants of seropositive mothers, 65 infants (4.9%) were diagnosed with congenital Chagas disease. Protective factors against transmission included Cesarean delivery (adjusted OR [aOR]: 0.60, 95% CI: 0.36-0.99) and family history of Chagas disease (aOR: 0.58, 95% CI: 0.34-0.99). Twins were significantly more likely to be congenitally infected than singleton births (OR: 3.32, 95% CI: 1.60-6.90). Among congenitally infected infants, 32.3% had low birth weight, and 30.8% required hospitalization after birth. CONCLUSIONS: Although improved access to screening and qPCR increased the number of infants diagnosed with congenital Chagas disease, many infants remain undiagnosed. A better understanding of risk factors and improved access to highly sensitive and specific diagnostic techniques for congenital Chagas disease may help improve regional initiatives to reduce disease burden.

8.
PLoS One ; 15(11): e0241600, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33151985

RESUMO

Pyrazinamide (PZA) susceptibility testing in Mycobacterium tuberculosis (Mtb) is a current area of development and PZA-resistant strains are increasingly prevalent. Previous studies have demonstrated that the detection of pyrazinoic acid (POA), the metabolite produced by the deamidation of PZA, is a good predictor for PZA resistance since a resistant strain would not convert PZA into POA at a critical required rate, whereas a susceptible strain will do, expelling POA to the extracellular environment at a certain rate, and allowing for quantification of this accumulated analyte. In order to quantify POA, an indirect competitive ELISA (icELISA) test using hyperimmune polyclonal rabbit serum against POA was developed: for this purpose, pure POA was first covalently linked to the highly immunogenic Keyhole Limpet Hemocyanine, and inoculated in rabbits. A construct made of bovine serum albumin (BSA) linked to pure POA and fixed at the bottom of wells was used as a competitor against spiked samples and liquid Mtb culture supernatants. When spiked samples (commercial POA alone) were analyzed, the half maximal inhibitory concentration (IC50) was 1.16 mg/mL, the limit of detection 200 µg/mL and the assay was specific (it did not detect PZA, IC50 > 20 mg/mL). However, culture supernatants (7H9-OADC-PANTA medium) disrupted the competition and a proper icELISA curve was not obtainable. We consider that, although we have shown that it is feasible to induce antibodies against POA, matrix effects could damage its analytical usefulness; multiple, upcoming ways to solve this obstacle are suggested.

9.
Plast Reconstr Surg ; 146(6): 1376-1380, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33234973

RESUMO

BACKGROUND: Although the benefits of gender-affirming surgery may be apparent to patients and providers, there remains a paucity of studies assessing the impact of these procedures. As an initial step, preoperative patient-reported outcomes using validated measures of depression, anxiety, and body image were used and compared to cisgender normative data. METHODS: Patients presenting for gender-affirming mastectomy were approached and surveyed using validated instruments measuring anxiety, depression, and body image. In addition, clinical data were collected from the medical record. Results were compared to published instrument norms in the general cisgender population. RESULTS: One hundred three patients completed the preoperative assessment; 70.3 percent and 66.3 percent of the cohort screened positive for mild to severe depression and anxiety, respectively. Only 25 percent and 29.8 percent of the cohort, respectively, had a previous diagnosis of depression and anxiety. The rates of depression and anxiety were significantly higher than those in cisgender normative data [mean Patient Health Questionnaire score, 2.7 (p < 0.0001); mean Generalized Anxiety Disorder Scale 7 score, 2.66 (p < 0.0001)]. Body Image Quality of Life Index and BREAST-Q scores were also significantly lower than those in cisgender normative data. CONCLUSIONS: Patients seeking gender-affirming mastectomy have a significant mental health burden that appears to be underdiagnosed. They further have significant challenges with body image compared with cisgender normative data. These findings signify dramatic mental health disparities in the preoperative transgender population and the need for ongoing prospective research of gender-affirming surgery.

10.
PLoS One ; 15(10): e0241067, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112923

RESUMO

Tuberculosis (TB) is a major global public health problem with high mortality and morbidity. In low-middle income countries (LMIC) a large number of respiratory symptomatic cases that require TB screening per year demands more accurate, fast and affordable testing for TB diagnostics. Sputum smear is the initial screening test in LMICs, however, its sensitivity is limited in patients with low sputum bacilli load. The same limitation is observed in the currently available molecular tests. We designed, standardized and evaluated an electrochemical biosensor that detects the highly specific DNA insertion element 6110 (IS6110). A PCR amplified DNA product is hybridized on the surface of the working electrode built on FTO-Glass with immobilized specific DNA probes, after which cyclic voltammetry is performed with an Ag/AgCl reference electrode and a platinum counter electrode. The response of the sensor was measured by the ratio (cathodic peak current of the hybridized sensor) / (cathodic peak current of the non-hybridized sensor). We tested the biosensor, using positive hybridization control sequences, genomic DNA extracted from M. tuberculosis strains and sputum of TB patients, and extracted DNA from the urine of healthy controls spiked with M. tuberculosis DNA. This biosensor was effective for the detection of M. tuberculosis DNA with a detection limit of 16 fM in sputum sample and 1 fM in spiked urine samples. The low cost and the relatively brief duration of the assay make this an important TB screening tool in the fight against tuberculosis.

11.
Sci Rep ; 10(1): 16395, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009443

RESUMO

Chagas disease is considered the most important parasitic disease in Latin America. The protozoan agent, Trypanosoma cruzi, comprises six genetic lineages, TcI-TcVI. Genotyping to link lineage(s) to severity of cardiomyopathy and gastrointestinal pathology is impeded by the sequestration and replication of T. cruzi in host tissues. We describe serology specific for TcI, the predominant lineage north of the Amazon, based on expression of recombinant trypomastigote small surface antigen (gTSSA-I) in the eukaryote Leishmania tarentolae, to allow realistic glycosylation and structure of the antigen. Sera from TcI-endemic regions recognised gTSSA-I (74/146; 50.7%), with no cross reaction with common components of gTSSA-II/V/VI recombinant antigen. Antigenicity was abolished by chemical (periodate) oxidation of gTSSA-I glycosylation but retained after heat-denaturation of conformation. Conversely, non-specific recognition of gTSSA-I by non-endemic malaria sera was abolished by heat-denaturation. TcI-specific serology facilitates investigation between lineage and diverse clinical presentations. Glycosylation cannot be ignored in the search for immunogenic antigens.

12.
Diabetes Res Clin Pract ; 170: 108494, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33058956

RESUMO

AIMS: To determine the predictive performance of well-known obesity markers: body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHtR), and total body fat percentage (TBF%), to identify incident cases of type 2 diabetes mellitus T2DM. METHODS: Secondary data analysis of the CRONICAS Cohort Study, conducted in 3 regions of Peru. Participants without T2DM at baseline were selected for analyses. The obesity markers were evaluated at the beginning of the study, and the development of T2DM was determined at 30 months of follow-up. The predictive performance of the markers was calculated using areas under the curve (AUC), and sensitivity and specificity of the best cutoff points were estimated. RESULTS: A total of 2510 participants with no diabetes at baseline, median age 54.1 years (inter-quartile range: 44.6 to 63.5), were included in the analysis. The cumulative incidence of T2DM at 30 months of follow-up was 4.7%. All the AUC studied for obesity markers and TBF% were poor. CONCLUSIONS: We found that obesity markers had a poor predictive performance (AUC) for the incidence of T2DM when used alone. The BMI, WC and WHtR had better performance for the incidence of T2DM relative to the WHR among women, and no differences in performance between obesity markers were found among men.

13.
EClinicalMedicine ; 27: 100561, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33043286

RESUMO

Background: Norovirus (NV) causes acute gastroenteritis in infants. Humoral and fecal immunoglobulin A (IgA) responses have been correlated with protection against NV; however, the role of breast milk IgA against NV infection and associated diarrhea is still unknown. This study aimed to evaluate the protective role of NV-specific IgA (NV-IgA) in breast milk. Methods: Ninety-five breast milk samples collected from mothers enrolled in a 2016-2017 Peruvian birth cohort study were tested for total IgA and NV-IgA by ELISA using GII·4 variants and non-GII·4 genotype virus-like particles (VLPs). Breast milk samples were grouped according to the NV infection and diarrheal status of infants: NV positive with diarrhea (NV+D+, n=18); NV positive without diarrhea (NV+D-, n=37); and NV negative without diarrhea (NV-D-, n=40). The percent positivity and titer of NV-IgA were compared among groups. The cross-reactivity was estimated based on the correlation of ratio between NV-IgA against GII·4 variants and non-GII·4 genotype VLPs. Findings: NV-IgA had high positivity rates against different VLPs, especially against GII (89-100%). The NV+D- group had higher percent positivity (89% vs. 61%, p=0·03) and median titer (1:100 vs 1:50, p=0·03) of NV-IgA than the NV+D+ group against GI·1 VLPs. A relatively high correlation between different GII·4 variants (0·87) and low correlation between genogroups (0·23-0·37) were observed. Interpretation: Mothers with high positivity rates and titers of NV-IgA in breast milk had NV infected infants with reduced diarrheal symptoms. Antigenic relatedness to the genetic diversity of human norovirus was suggested.Funding National Institute of Allergy and Infectious Diseases, National Institute of Health: 1R01AI108695-01A1 and the Japan Society for the Promotion of Science (Fostering Joint International Research B):19KK0241.

14.
Aesthetic Plast Surg ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33063160

RESUMO

In this invited discussion, we applaud the authors of "Awareness of Facial Asymmetry and Its Impact on Postoperative Satisfaction of Rhinoplasty Patient" for their efforts to reinforce the importance of recognizing facial asymmetry preoperatively in the rhinoplasty patient. They can be applauded for translating this known key factor into data in the form of validated patient-reported outcomes tools. The study could be improved by better defining the asymmetry that the study patients had and investigating the symmetry of the surgical result. Furthermore, we provide suggestions for how to better counsel patients on facial asymmetry and its effects on their rhinoplasty result. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

15.
Am J Trop Med Hyg ; 103(6): 2581-2583, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32901595

RESUMO

Capacity building in public health is an urgent global priority. Recently, there has been an increasing emphasis on South-South and triangular cooperation. We describe our experience with a public health training collaboration between Peru and Bolivia, with Peru providing capacity building and expertise to Bolivia, while receiving supportive funding and training from the United States. This collaboration has led to a groundswell of research on clinically significant diseases, outreach to more than 800 scientists, several dozen publications, and the start of four institutional review boards. South-South and South-South-North collaborations should publish their experiences, and Northern funding organizations should consider funding such collaborations.

16.
Wellcome Open Res ; 5: 23, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32923686

RESUMO

Background: Three previous clinical trials have found that thermometry use reduced diabetic foot ulcers (DFUs) incidence four- to ten-fold among individuals with diabetes at high-risk of developing a DFU. However, these benefits depend on patient adherence to self-assessment. Therefore, novel approaches to improve self-management thermometry adherence are needed. Our objective was to compare incidence of DFUs in the thermometry plus mobile health (mHealth) reminders intervention arm vs. thermometry-only control arm. Methods: We conducted a randomized trial, enrolling adults with type 2 diabetes mellitus at risk of foot ulcers (risk groups 2 or 3) but without foot ulcers at the time of recruitment and allocating them to control (instruction to use a liquid crystal-based foot thermometer daily) or intervention (same instruction supplemented with text and voice messages with reminders to use the device and messages to promote foot care) groups and followed for 18 months. The primary outcome was time to occurrence of DFU. A process evaluation was also conducted. Results: A total of 172 patients (63% women, mean age 61 years) were enrolled; 86 to each study group. More patients enrolled in the intervention arm had a history of DFU (66% vs. 48%). Follow-up for the primary endpoint was complete for 158 of 172 participants (92%). DFU cumulative incidence was 24% (19 of 79) in the intervention arm and 11% (9 of 79) in the control arm. After adjusting for history of foot ulceration and study site, the Hazard Ratio (HR) for DFU was 1.44 (95% CI 0.65, 3.22). Adherence to ≥80% of daily temperature measurements was 87% (103 of 118) among the study participants who returned the logbook, with no difference between the intervention and control arms. Conclusions: This trial contributes to the evidence about the value of mHealth in preventing diabetes foot ulcers. Trial registration: ClinicalTrials.gov NCT02373592 (27/02/2015).

17.
Prim Care Diabetes ; 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32739222

RESUMO

OBJECTIVE: To describe and compare attitudes, lifestyle behaviors, and cardiometabolic risk factors between individuals with and without a relative with type 2 diabetes mellitus (T2DM) living in the same household. METHODS: A secondary analysis of baseline data from an implementation study in Peru was conducted. The outcomes were attitudes towards changing lifestyle behaviors (e.g. intentions towards losing weight, increasing physical activity, reducing salt consumption, etc), profiles of health lifestyle behaviors (e.g. daily smoking, heavy drinking, and physical activity), and cardiometabolic risk factors (e.g., overweight [body mass index ≥25 kg/m2] and hypertension); whereas the exposure was the presence of at least one relative with known diagnosis of T2DM living in the same household. Multilevel logistic mixed effect regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: A total of 2298 records, 1134 (49.4%) males, mean age 43.3 (SD: 17.2) years, were analyzed. There was no evidence of a difference in lifestyle-changing attitudes, smoking, alcohol drinking, physical activity levels, and hypertension between individuals with and without relatives with T2DM. Overweight was 63% more common among individuals having a relative with a T2DM in multivariable model (OR = 1.63; 95% CI: 1.03-2.61). CONCLUSIONS: Individuals with relatives with T2DM have higher probabilities of being overweight compared to those who did not have relatives with T2DM in the same household. The absence of differences on lifestyle-related attitudes and behaviors highlight the need of involving relatives of patients with T2DM on intervention strategies to further enhance diabetes prevention and management efforts.

18.
PLoS One ; 15(7): e0235643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735615

RESUMO

BACKGROUND: Pyrazinamide is an important drug against the latent stage of tuberculosis and is used in both first- and second-line treatment regimens. Pyrazinamide-susceptibility test usually takes a week to have a diagnosis to guide initial therapy, implying a delay in receiving appropriate therapy. The continued increase in multi-drug resistant tuberculosis and the prevalence of pyrazinamide resistance in several countries makes the development of assays for prompt identification of resistance necessary. The main cause of pyrazinamide resistance is the impairment of pyrazinamidase function attributed to mutations in the promoter and/or pncA coding gene. However, not all pncA mutations necessarily affect the pyrazinamidase function. OBJECTIVE: To develop a methodology to predict pyrazinamidase function from detected mutations in the pncA gene. METHODS: We measured the catalytic constant (kcat), KM, enzymatic efficiency, and enzymatic activity of 35 recombinant mutated pyrazinamidase and the wild type (Protein Data Bank ID = 3pl1). From all the 3D modeled structures, we extracted several predictors based on three categories: structural stability (estimated by normal mode analysis and molecular dynamics), physicochemical, and geometrical characteristics. We used a stepwise Akaike's information criterion forward multiple log-linear regression to model each kinetic parameter with each category of predictors. We also developed weighted models combining the three categories of predictive models for each kinetic parameter. We tested the robustness of the predictive ability of each model by 6-fold cross-validation against random models. RESULTS: The stability, physicochemical, and geometrical descriptors explained most of the variability (R2) of the kinetic parameters. Our models are best suited to predict kcat, efficiency, and activity based on the root-mean-square error of prediction of the 6-fold cross-validation. CONCLUSIONS: This study shows a quick approach to predict the pyrazinamidase function only from the pncA sequence when point mutations are present. This can be an important tool to detect pyrazinamide resistance.


Assuntos
Amidoidrolases/metabolismo , Proteínas de Bactérias/metabolismo , Mycobacterium tuberculosis/enzimologia , Amidoidrolases/química , Amidoidrolases/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Clonagem Molecular , Cinética , Modelos Lineares , Simulação de Dinâmica Molecular , Mutagênese , Estabilidade Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação
19.
Sci Rep ; 10(1): 13944, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811861

RESUMO

An accurate urine test for diverse populations with active tuberculosis could be transformative for preventing TB deaths. Urinary liporabinomannan (LAM) testing has been previously restricted to HIV co-infected TB patients. In this study we evaluate urinary LAM in HIV negative, pediatric and adult, pulmonary and extrapulmonary tuberculosis patients. We measured 430 microbiologically confirmed pretreatment tuberculosis patients and controls from Peru, Guinea Bissau, Venezuela, Uganda and the United States using three monoclonal antibodies, MoAb1, CS35, and A194, which recognize distinct LAM epitopes, a one-sided immunoassay, and blinded cohorts. We evaluated sources of assay variability and comorbidities (HIV and diabetes). All antibodies successfully discriminated TB positive from TB negative patients. ROAUC from the average of three antibodies' responses was 0.90; 95% CI 0.87-0.93, 90% sensitivity, 73.5% specificity (80 pg/mL). MoAb1, recognizing the 5-methylthio-D-xylofuranose(MTX)-mannose(Man) cap epitope, performed the best, was less influenced by glycosuria and identified culture positive pediatric (N = 19) and extrapulmonary (N = 24) patients with high accuracy (ROAUC 0.87, 95% CI 0.77-0.98, 0.90 sensitivity 0.80 specificity at 80 pg/mL; ROAUC = 0.96, 95% CI 0.92-0.99, 96% sensitivity, 80% specificity at 82 pg/mL, respectively). The MoAb1 antibody, recognizing the MTX-Man cap epitope, is a novel analyte for active TB detection in pediatric and extrapulmonary disease.

20.
Aesthet Surg J ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32794545

RESUMO

BACKGROUND: Aesthetic surgery is a critical component of academic plastic surgery. As institutions are placing increased focus on aesthetic surgery, there is an opportunity to identify factors that facilitate the creation and maintenance of successful aesthetic plastic surgery programs. OBJECTIVES: The aim of this study was to conduct a national survey to evaluate the current state of academic aesthetic surgery and to identify factors that contribute to success. METHODS: A REDCap 122-question survey was developed and validated by members of the Academic Aesthetic Surgery Roundtable (AASR). The national survey was distributed to department chairs and division chiefs with active ACGME-approved plastic surgery programs (n = 92). Responses underwent Pearson's chi-squared, Wilcoxon rank-sum, and postselection inference analyses. AASR members convened to interpret data and identify best practices. RESULTS: Responses were received from 64 of 92 queries (69.6%). The multivariate analysis concluded traits associated with successful academic aesthetic surgery practices included the presence of aesthetic surgery-focused, full-time faculty whose overall practice includes >50% aesthetic surgery (P = 0.040) and nonphysician aesthetic practitioners who provide injection services (P = 0.025). In the univariate analysis, factors associated with strong aesthetic surgery training programs included resident participation in faculty aesthetic clinics (P = 0.034), aesthetic research (P = 0.006), and discounted resident aesthetic clinics (P < 0.001). CONCLUSIONS: The growth of academic aesthetic surgery practices represents a significant opportunity for advancement of resident training, departmental financial success, and diversification of faculty practices. By identifying and sharing best practices and strategies, academic aesthetic surgery practices can be further enhanced.

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