Maternal depression and child development at 3 years of age: a longitudinal study in a Brazilian child development promotion program.

BACKGROUND: We tested the hypothesis that children of non-depressed mothers perform better in a developmental test at 3 years than children of depressed mothers. METHOD: Longitudinal analysis from a trial to assess the impact of a child development promotion program in 30 Brazilian municipalities. Mothers and children were appraised at first-year post-partum, 1 and 3 years after enrollment. Child development was assessed through the Ages and Stages Questionnaire (ASQ3) and maternal depression through the Edinburgh Postnatal Depression Scale (EPDS). Crude and adjusted beta coefficients were obtained by linear regression before and after multiple imputation. RESULTS: In total, 2098 mother/child dyads were included and 8.2% of the mothers had persistent depressive symptoms. There was a decrease in ASQ3 as the number of follow-ups with EPDS ≥ 10 increased (p for trend <0.001). In adjusted analysis, the direction of the association persisted but lost statistical significance. After multiple imputation, children from mothers with EPDS ≥ 10 in three follow-ups presented a decrease of about 14 points in ASQ3 (adjusted beta coefficient = -13.79; -22.59 to -5.00) (p for trend = 0.001). CONCLUSIONS: Identification of women at increased risk of depression should be among the primary health care sector priorities in maternal and child health in Brazil. IMPACT: In our population study, almost one in every ten women presented persistent depression symptoms across the first 3 years postpartum. In adjusted analysis there was a detrimental impact of persistent maternal depression on child development at 3 years of age. The persistent exposure to maternal depression across early childhood negatively influences children's development. Considering its prevalence, identification of women at increased risk of depression should be among the primary health care sector priorities in maternal and child health in Brazil.

Clinic-based evaluation of point-of-care dual HIV/syphilis rapid diagnostic tests at primary healthcare antenatal facilities in South Africa and Zambia.

BACKGROUND: Southern African countries have the largest global burden of HIV and syphilis, with a high prevalence among women of reproductive age. Although antenatal screening is standard of care, syphilis screening has generally lagged behind HIV screening. We aimed to evaluate the performance and operational characteristics of two commercial dual HIV/syphilis point-of-care tests (POCTs) for simultaneous maternal HIV/syphilis screening. METHODS: A clinic-based evaluation of dual HIV/syphilis POCTs (SD Bioline and Chembio) was conducted at five primary healthcare centres (PHCs) in South Africa and Zambia. POCT results using capillary fingerprick blood were compared to reference laboratory syphilis and HIV serological assays. RESULTS: Three thousand four hundred twelve consenting pregnant women aged ≥ 18 years were enrolled. The prevalence of treponemal antibody seropositivity and HIV infection ranged from 3.7 to 9.9% (n = 253) and 17.8 to 21.3% (n = 643), respectively. Pooled sensitivity for syphilis compared to the reference assay was 66.0% (95%CI 57.7-73.4) with SD Bioline and 67.9% (95%CI 58.2-76.3) with Chembio. Pooled specificity for syphilis was above 98% with both POCTs. The sensitivities of SD Bioline and Chembio assays were 78.0% (95%CI 68.6-85.7) and 81.0% (95%CI 71.9-88.2), respectively compared to an active syphilis case definition of treponemal test positive with a rapid plasma reagin titre of ≥ 8. The negative predictive values (NPVs) based on various prevalence estimates for syphilis with both assays ranged from 97 to 99%. The pooled sensitivity for HIV was 92.1% (95%CI 89.4-94.2) with SD Bioline; and 91.5% (95%CI 88.2-93.9) with Chembio. The pooled specificities for HIV were 97.2% (95%CI 94.8-98.5) with SD Bioline and 96.7% (95%CI 95.1-97.8) with Chembio. The NPV based on various prevalence estimates for HIV with both assays was approximately 98%. Most participating women (91%) preferred dual POCTs over two single POCTs for HIV and syphilis, and healthcare providers gave favourable feedback on the utility of both assays at PHC level. CONCLUSIONS: Based on the need to improve antenatal screening coverage for syphilis, dual HIV/syphilis POCTs could be effectively incorporated into antenatal testing algorithms to enhance efforts towards elimination of mother-to-child transmission of these infections.

Clinic-based evaluation of the dual Xpert CT/NG assay on the GeneXpert System for screening for extragenital chlamydial and gonococcal infections amongst men who have sex with men.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections have increased globally. Asymptomatic infections represent a significant risk of long-term complications. Men who have sex with men (MSM) are disproportionally affected, underscoring the need to offer screening programmes to this population. CT/NG Point of Care Testing (POCT) constitutes a strategic tool to improve the continuum of STI care, however extensive real-life evaluations amongst at risk populations are lacking. The aim of this study is to estimate the GeneXpert CT/NG assay performance and usability for CT and NG at genital and extragenital sites for screening amongst MSM. METHODS: This study was a multi-site sexual health clinic-based evaluation (Italy, Malta and Peru) with consecutive enrolment. A first void urine sample (divided in two aliquots), two oropharyngeal and two anorectal swabs were collected for each study participant. One specimen set (one for each anatomical site) was tested with the dual index test (Cepheid) at the clinics by the healthcare staff, the other set with FDA/CE approved Nucleic Acid Amplification Tests (NAATs) at the laboratory. Clinical sites and reference laboratories participated in an internal and external quality control programme. Sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values for each anatomical site were estimated using a meta-analytic approach. RESULTS: One thousand seven hundred two MSM were recruited across all clinical sites for a total of 5049 biological specimens. NG and CT were respectively detected in 274 and 287 of samples. Overall, the NG POCT sensitivity and specificity was 91.43% and 99.75% in urine (LR + 372.80, LR- 0.09), 89.68% and 99.55% in rectal specimens (LR + 197.30, LR- 0.10) and 75.87% and 98.77% at the pharynx respectively (LR + 61.94, LR- 0.24). The CT component of the POCT sensitivity was 84.82% and specificity 99.63% in urine (LR + 228.68, LR- 0.15), 78.07% and 99.19% respectively on rectal site (LR + 96.23, LR-0.22), 67.79% and 99.88% respectively at pharyngeal site (LR + 554.89, LR- 0.32). 95.95% of MSM reported to be willing to wait for POCT results and no provider reported difficulties in terms of performance or interpretation of the results of the Xpert CT/NG. CONCLUSION: Rapid turnaround time, ease of use and high acceptability make the Xpert CT/NG testing system a strategic tool for increasing testing frequency, reaching those not yet tested and offering the possibility of immediate treatment if needed. The assay showed good negative likelihood ratios and confirms its use to rule out CT/NG infections. Sensitivity varied across sites and pathogens. Periodic staff training at the testing sites should be mandatory.

Independent clinic-based evaluation of dual POCTs for screening for HIV and syphilis in men who have sex with men in Italy, Malta, Peru, and the United Kingdom.

INTRODUCTION: Globally, the incidence of HIV and syphilis can be reduced by the use of validated point of care tests (POCTs). As part of the WHO PRoSPeRo Network, we aimed to evaluate the performance, acceptability, and operational characteristics of two dual HIV/syphilis POCTs (Bioline HIV/Syphilis Duo (Abbott) and DPP® HIV-Syphilis assay (Chembio) for the screening of HIV and syphilis amongst men who have sex with men (MSM). METHOD AND ANALYSES: A cross sectional study of 2,577 MSM in Italy, Malta, Peru, and the United Kingdom (UK) presenting to seven clinic sites, were enrolled. Finger prick blood was collected to perform POCTs and results compared with standard laboratory investigations on venepuncture blood. Acceptability and operational characteristics were assessed using questionnaires. Diagnostic meta-analysis was used to combine data from the evaluation sites. RESULTS: Based on laboratory tests, 23.46% (n = 598/2549) of participants were confirmed HIV positive, and 35.88% of participants (n = 901/2511) were positive on treponemal reference testing. Of all participants showing evidence of antibodies to Treponema pallidum, 50.56% (n = 455/900) were Rapid Plasma Reagin (RPR) test reactive. Of HIV positive individuals, 60.62% (n = 354/584) had evidence of antibodies to T. pallidum, and of these 60.45% (n = 214/354) exhibited reactive RPR tests indicating probable (co)infection. For Bioline POCT, pooled sensitivities and specificities for HIV were 98.95% and 99.89% respectively, and for syphilis were 73.79% and 99.57%. For Chembio pooled sensitivities and specificities for HIV were 98.66% and 99.55%, and for syphilis were 78.60% and 99.48%. Both tests can detect greater than 90% of probable active syphilis cases, as defined by reactive RPR and treponemal test results. These dual POCTs were preferred by 74.77% (n = 1,926) of participants, due to their convenience, and the operational characteristics made them acceptable to health care providers (HCPs). CONCLUSIONS: Both the Bioline and the Chembio dual POCT for syphilis and HIV had acceptable performance, acceptability and operational characteristics amongst MSM in the PRoSPeRo network. These dual POCTs could serve as a strategic, more cost effective, patient and healthcare provider (HCP) friendly alternative to conventional testing; in clinical and other field settings, especially those in resource-limited settings.

Independent clinic-based evaluation of point-of-care testing for the screening of Chlamydia trachomatis, Neisseria gonorrhoea and Trichomonas vaginalis in women-at-risk in Australia, Guatemala, Morocco, and South Africa.

BACKGROUND: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa. METHODS: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs). RESULTS: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV. CONCLUSION: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries.

COVID-19 outbreaks surveillance through text mining applied to electronic health records.

BACKGROUND: The COVID-19 pandemic has caused significant disruptions to everyday life and has had social, political, and financial consequences that will persist for years. Several initiatives with intensive use of technology were quickly developed in this scenario. However, technologies that enhance epidemiological surveillance in contexts with low testing capacity and healthcare resources are scarce. Therefore, this study aims to address this gap by developing a data science model that uses routinely generated healthcare encounter records to detect possible new outbreaks early in real-time. METHODS: We defined an epidemiological indicator that is a proxy for suspected cases of COVID-19 using the health records of Emergency Care Unit (ECU) patients and text mining techniques. The open-field dataset comprises 2,760,862 medical records from nine ECUs, where each record has information about the patient's age, reported symptoms, and the time and date of admission. We also used a dataset where 1,026,804 cases of COVID-19 were officially confirmed. The records range from January 2020 to May 2022. Sample cross-correlation between two finite stochastic time series was used to evaluate the models. RESULTS: For patients with age 18 years, we find time-lag () = 72 days and cross-correlation () ~ 0.82, = 25 days and ~ 0.93, and = 17 days and ~ 0.88 for the first, second, and third waves, respectively. CONCLUSIONS: In conclusion, the developed model can aid in the early detection of signs of possible new COVID-19 outbreaks, weeks before traditional surveillance systems, thereby anticipating in initiating preventive and control actions in public health with a higher likelihood of success.

Fasting reduces satiety and increases hunger but does not affect the performance in resistance training.

Intermittent fasting (IF) has been suggested to reduce body fat percentage and improve non-communicable chronic diseases. However, little is known about resistance training (RT) and the subjective perception of hunger under fasted conditions. This study aimed to examine the effects of overnight fasting (12 h or 16 h fasting) on the maximum voluntary isometric contraction (MVIC) and countermovement jump (CMJ) performance in resistance-trained young male adults. In RT sessions, the maximum number of repetitions (MNR) and the total volume load (TVL) were evaluated in the back squat and leg press 45°. The volunteers performed all tests and the RT session in 3 different conditions: fed state, 12 and 16 hours of IF. The subjective perception of hunger was applied through an adapted visual analogue scale (adVAS). The results showed that strength and power variables did not change significantly: MVIC (p = 0.960), CMJ (p = 0.986), MNR back squat (p = 0.856), MNR leg press 45° (p = 0.998), TVL (p = 0.954). However, hunger was significantly greater after the 16-hour fasting (p = 0.001) compared to 12 hours of fasting and the fed state. Also, the desire to eat was greater after 16 hours (p = 0.001) compared to 12 hours of fasting and the fed state. This study indicates that IF for 12 or 16 hours does not significantly impair strength and power, but the longer the fasting duration, the greater are the hunger and desire to eat.

The current and future costs of colorectal cancer attributable to red and processed meat consumption in Brazil.

BACKGROUND: Compelling evidence supports the association between red and processed meat consumption and increased risk of colorectal cancer. Herein, we estimated the current (2018) and future (2030) federal direct healthcare costs of colorectal cancer in the Brazilian Unified Health System attributable to red and processed meat consumption. Considering reduced red and processed meat consumption, we also projected attributable costs of colorectal cancer in 2040. METHODS: We retrieved information on red and processed meat consumption from two nationally representative dietary surveys, the Household Budget Survey 2008-2009 and 2017-2018; relative risks for colorectal cancer from a meta-analysis; direct healthcare costs of inpatient and outpatient procedures in adults ≥ 30 years with colorectal cancer (C18-C20) from 2008-2019 by sex. RESULTS: Attributable costs of colorectal cancer were calculated via comparative risk assessment, assuming a 10-year lag. In 2018, US$ 20.6 million (8.4%) of direct healthcare costs of colorectal cancer were attributable to red and processed meat consumption. In 2030, attributable costs will increase to US$ 86.6 million (19.3%). Counterfactual scenarios of reducing red and processed meat consumption in 2030 suggested that US$ 2.2 to 11.9 million and US$ 13 to 74 million could be saved in 2040, respectively. CONCLUSION: Red and processed meat consumption has an escalating economic impact on the Brazilian Unified Health System. Our findings support interventions and policies focused on primary prevention and cancer.

The future costs of cancer attributable to excess body weight in Brazil, 2030-2040.

BACKGROUND: Excess body weight (EBW), herein defined as body mass index (BMI) ≥25 kg/m2, is a well-known modifiable risk factor for cancer and a pivotal vector for growing healthcare costs. We estimated the future (2030) federal direct healthcare costs of cancer in the Brazilian Unified Health System (SUS) attributable to EBW. We also projected direct healthcare costs of cancer that could be potentially saved in 2040, considering counterfactual (alternative) scenarios of population-wide reductions in the BMI to be achievedin 2030. METHODS: We developed a macrosimulation model by sex using self-reported BMI data in adults ≥ 20 years who relied exclusively on the public health system from the Brazilian National Health Survey (PNS) 2019; relative risks for 12 types of cancer from the World Cancer Research Fund/American Institute Cancer Research (WCRF/AICR) meta-analysis; and nationwide registries of federal direct healthcare costs of inpatient and outpatient procedures in adults ≥30 years with cancer from 2008-2019. We calculated the attributable costs of cancer via comparative risk assessment, assuming a 10-year lag between exposure and outcome. We used the potential impact fraction (PIF) equation and the Monte Carlo simulation method to estimate the attributable costs and 95% uncertainty intervals, considering the theoretical-minimum-risk exposure and other counterfactual (alternative) scenarios of the EBW prevalence. We assessed the cancer costs attributable to EBW, multiplying PIF by the direct healthcare costs of cancer. RESULTS: In 2030, 2.4% or US$ 62.8 million in direct healthcare costs of cancer may be attributable to EBW. We projected potential savings of approximately US$ 10.3 to 26.6 million in 2040 by reducing the prevalence of EBW in 2030. CONCLUSIONS: We estimated high future costs of cancer attributable to EBW in Brazil. Our findings may support interventions and policies focused on the primary prevention of EBW and cancer.

Identification of pulmonary embolism: diagnostic accuracy of venous-phase dual-energy CT in comparison to pulmonary arteries CT angiography.

OBJECTIVES: To evaluate the diagnostic accuracy of venous-phase dual-energy computed tomography (VP-DECT) in the identification of PE compared with standard CT pulmonary angiography (CTPA). METHODS: This prospective IRB-approved study included 61 consecutive oncology patients (35 females, 26 males, mean age 66.91 years) examined by CTPA and VP-DECT. DECT data were post-processed on a SyngoVia workstation to obtain monoenergetic images (MEI+). The diagnosis of PE was based on the presence of any vascular perfusion defects. DECT images were evaluated independently by two radiologists (8 and 16 years of experience). A consensus reading of CTPA images (two senior radiologists, 18 and 24 years of experience) represented the reference for diagnosis. The diagnostic accuracy values of VP-DECT on a per-patient and per-lobe basis were assessed. Interobserver agreement was calculated using k-statistics. A value of p < 0.05 was considered statistically significant. RESULTS: Thirty of 61 patients (49.18%) were diagnosed with PE by CTPA, with 57/366 lobes being involved (15.57%). The sensitivity and specificity of the per-patient analysis of VP-DECT images were 90.0% (27/30) and 100% (31/31) respectively, for both readers. As concerns the per-lobe analysis, the sensitivity ranged from 100% for the right lower lobe to 50% for the left upper lobe for reader 1, and from 100% for the left upper lobe to 69.23% for the lingula for reader 2. The interobserver agreement ranged from 0.8671 (patients' analysis) to 0.6419 (lobes' analysis). CONCLUSION: VP-DECT could be considered an accurate imaging tool for diagnosing PE in a selected, high-prevalence population, compared with CTPA. KEY POINTS: • With regard to the patients' analysis, venous-phase DECT sensitivity and specificity in diagnosing pulmonary embolism were 90% and 100%, respectively, for both readers. • With regard to the lobes' analysis, the sensitivity ranged from 100 to 50%, for reader 1, and from 100 to 69.23%, for reader 2, respectively. • The sensitivity and specificity of lung perfusion maps obtained from venous DECT were 73.33% and 67.74% as concerns the patients' analysis and 71.92% and 75.72% as regards the lobes' analysis, respectively.

Dynamics of anti-malarial antibodies in non-immune patients during and after a first and unique Plasmodium falciparum malaria episode.

BACKGROUND: Malaria is a major travel medicine issue. Retrospective confirmation of a malaria episode diagnosed in an endemic area can have relevant implications in transfusional medicine in Europe, where blood donors are excluded from donation on the basis of positive malaria serology. However, there is scarce evidence on the dynamics of anti-malarial antibodies after a first malaria episode in non-immune individuals. The first aim of this study was to describe the dynamics of anti-malarial antibodies in a first malaria episode in non-immune travellers. Secondary objectives were to assess the sensitivity of serology for a retrospective diagnosis in non-immune travellers diagnosed while abroad and to discuss the implications in transfusional medicine. METHODS: Retrospective analysis of the results of an indirect fluorescence antibody test (IFAT) for malaria available for patients with a first malaria episode by Plasmodium falciparum and admitted at the IRCCS Sacro Cuore Don Calabria hospital in a 14-year period. The antibody titres were collected at baseline and during further follow up visits. Epidemiological, demographic and laboratory test results (including full blood count and malaria parasite density) were anonymously recorded in a study specific electronic Case Report Form created with OpenClinica software. Statistical analysis was performed with SAS software version 9.4. RESULTS: Thirty-six patients were included. Among them, all but two were Europeans (one African and one American). Median length of fever before diagnosis was 2 days (IQR 1-3). Thirty-five patients had seroconversion between day 1 and day 4 from admission, and the titre showed a sharply rising titre, often to a very high level in a few days. Only a single patient remained negative in the first 5 days from admission, after which he was no more tested. Six patients were followed up for at least 2 months, and they all showed a decline in IFAT titre, tending to seroreversion (confirmed in one patient with the longest follow up, almost 4 years). CONCLUSIONS: Serology demonstrated reliable for retrospective diagnosis in non-immune travellers. The decline in the anti-malarial titre might be included in the screening algorithms of blood donors, but further studies are needed.

Bone marrow edema around the hip in non-traumatic pain: dual-energy CT vs MRI.

OBJECTIVES: To evaluate the diagnostic accuracy of dual-energy computed tomography (DECT) in identifying bone marrow edema (BME) around the hip joint in non-traumatic patients. METHODS: This prospective IRB-approved study was conducted between January 2019 and October 2019 and included 59 consecutive patients (18 males, 41 females; mean age 61.5 years, range 32-82) who were assessed by DECT and magnetic resonance imaging (MRI) within a 5-day period. Diagnostic accuracy values for diagnosing BME on a per-patient and on a per-partition-basis analysis were calculated for DECT images by two readers (R1 and R2, with 15 and 10 years of experience, respectively), using MRI as reference for diagnosis. Inter-observer agreements were calculated with k-statistics. A p value of < 0.05 was considered as statistically significant. RESULTS: MRI depicted BME in 44/59 patients (74.58%), with the involvement of 83/708 (11.72%) partitions. The sensitivity, specificity, and accuracy of R1 and R2 were 95.45% (42/44), 86.67% (13/15), and 93.22% (55/59) for R1, and 86.36% (38/44), 80.00% (12/15), and 84.75% (50/59) for R2. For both readers, the BME detection rate was higher in patients with severe edema (100%) in comparison to patients with mild edema (91.30% and 73.91%). In the partition-basis analysis, sensitivity, specificity, and accuracy ranges were 33.3 to 100%, 91.84 to 100%, and 88.14 to 100%, respectively. The inter-observer agreement for patients' analysis was substantial (k = 0.7065), whereas for partition analysis ranged from fair (k = 0.2976) to near-perfect (k = 1.000). CONCLUSION: DECT can accurately identify BME around the hip joint, in comparison to MRI. KEY POINTS: • DECT can accurately identify bone marrow edema around the hip joint in a cohort of non-traumatic patients. • The detection of bone marrow edema by means of DECT may help the radiologist to identify associated findings, including avascular necrosis of the femoral head and insufficiency or stress fractures. • In cases of patients suffering from groin pain with bone marrow edema identified by DECT, the concurrent reading of high-resolution conventional CT images may increase the confidence of diagnosis and/or reduce the reading time.

A new Luminex-based peptide assay to identify reactivity to baked, fermented, and whole milk.

BACKGROUND: The majority of children with cow's milk allergy (CMA) tolerate baked milk. However, reactivity to fermented milk products such as yogurt/cheese has not been previously evaluated. We sought to determine whether children with CMA could tolerate yogurt/cheese and whether a patient's IgE and IgG4-binding pattern to milk protein epitopes could distinguish clinical reactivity. METHODS: Four groups of reactivity were identified by Oral food challenge: baked milk reactive, fermented milk reactive, whole milk reactive, and outgrown. sIgE and sIgG4 binding to milk protein epitopes were assessed with a novel Luminex-based peptide assay (LPA). Using machine learning techniques, a model was developed to predict different degrees of CMA. RESULTS: The baked milk reactive patients demonstrated the highest degree of IgE epitope binding, which was followed sequentially by fermented milk reactive, whole milk reactive, and outgrown. Data were randomly divided into two groups with 75% of the data utilized for model development (n = 68) and 25% for testing (n = 21). All 68 children used for training were correctly classified with models using IgE and IgG4 epitopes. The average cross-validation accuracy was much higher for models using IgE plus IgG4 epitopes by LPA (84.8%), twice the performance of the serum component proteins assayed by UniCAP (41.9%). The performance of the model on "unseen data" was tested using the 21 withheld patients, and the accuracy of IgE was 86% (AUC = 0.89) while of IgE+IgG4 model was 81% (AUC = 0.94). CONCLUSION: Using a novel high-throughput LPA, we were able to distinguish the diversity of IgE/IgG4 binding to epitopes in the varying CMA phenotypes. LPA is a promising tool to predict correctly different degrees of CMA.

Forensic botany and forensic chemistry working together: application of plant DNA barcoding as a complement to forensic chemistry-a case study in Brazil.

Recently, Brazilian Federal Police used forensic chemistry and forensic botany techniques on a case. Two packets containing fragmented plant matter were seized and sent for forensic analysis. Forensic chemistry, the gold standard for evaluating plant material suspected to contain illicit substances, did not find illicit materials. Gas chromatography coupled mass spectrometry (GC-MS) identified thujone in the botanical material. Thujone is a chemical compound naturally found in many plant species, notably Artemisia absinthium. Because doubt remained, we next used plant DNA barcoding methods. Total DNA from plant tissue fragments was extracted and five different DNA regions were amplified, sequenced, and analyzed using plant DNA barcoding methods. Genetic analysis yielded 30 good quality sequences representing five taxa. Most specimens were identified as A. absinthium. Few studies focus on practical forensic applications of plant DNA barcoding methods using a case solved in a forensic laboratory with its difficulties and limitations. To the best of our knowledge, this is the first study to report an effective joint effort of forensic chemistry and botany techniques to assess plant material in Brazil. The availability of a new technical approach for the genetic sequencing of plant species will enhance many forensic investigations and inspire similar initiatives.

VDR polymorphisms influence immunological response in HIV-1+ individuals undergoing antiretroviral therapy.

Vitamin D exerts an immuno-modulatory activity on several immune system cells through the vitamin D receptor (VDR). Herein, we verified that age and a therapeutic regimen containing protease inhibitors are associated with failures in antiretroviral therapies (ARVs). In addition, we assessed whether a VDR SNP (rs11568820: C allele and CC genotype) and GC (rs2228570-rs11568820) allelic combinations are associated with immunological failure (p < 0.05). Our findings suggest a possible role of VDR SNPs on immunological failure in HIV-1+ individuals undergoing regular ARVs.

Contributions of the Left and the Right Hemispheres on Language-Induced Grip Force Modulation of the Left Hand in Unimanual Tasks.

Background andObjectives: Language-induced grip force modulation (LGFM) can be used to better understand the link between language and motor functions as an expression of embodied language. However, the contribution of each brain hemisphere to LGFM is still unclear. Using six different action verbs as stimuli, this study evaluated the grip force modulation of the left hand in a unimanual task to characterize the left and right hemispheres' contributions. Materials and Methods: Left-hand LGFM of 20 healthy and consistently right-handed subjects was evaluated using the verbs "to write", "to hold", "to pull" (left-lateralized central processing actions), "to draw", "to tie", and "to drive" (bihemispheric central processing actions) as linguistic stimuli. The time between the word onset and the first interval of statistical significance regarding the baseline (here as reaction time, RT) was also measured. Results: The six verbs produced LGFM. The modulation intensity was similar for the six verbs, but the RT was variable. The verbs "to draw", "to tie", and "to drive", whose central processing of the described action is bihemispheric, showed a longer RT compared to the other verbs. Conclusions: The possibility of a given manual action being performed by the left hand in consistent right-handers does not interfere with the occurrence of LGFM when the descriptor verb of this action is used as a linguistic stimulus, even if the possibility is remote. Therefore, LGFM seems to mainly rely on the left hemisphere, while a greater activation of the right hemisphere in action processing appears to slow the increase in LGFM intensity.

Dendritic Cell-Based Immunotherapies to Fight HIV: How Far from a Success Story? A Systematic Review and Meta-Analysis.

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.

Association of CD209 and CD209L polymorphisms with tuberculosis infection in a Northeastern Brazilian population.

Tuberculosis (TB) caused by Mycobacterium tuberculosis, is major cause of morbidity and mortality worldwide. So far, many candidate genes have been investigated for their possible association with TB. Dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) and Liver/lymph node-specific intercellular adhesion molecule-grabbing non-integrin (L-SIGN), encoded by CD209 and CD209L genes respectively, are known for binding to M. tuberculosis on human dendritic cells and macrophages. We screened 4 single nucleotide polymorphisms (SNPs) in the promoter region of CD209, namely -939G>A (rs735240), -871A>G (rs735239), -336A>G (rs4804803) and -139G>A (rs2287886) and tandem repeat polymorphisms in exon 4 of CD209 and CD209L genes looking for association with TB in a Northeastern Brazilian population (295 subjects, 131 TB patients and 164 healthy controls). The -139G>A and -939G>A SNPs were associated with susceptibility to TB, and in particular with pulmonary and extra-pulmonary forms respectively. The -871A>G and -336A>G SNPs were associated, the first with protection to both pulmonary and extra-pulmonary TB, the latter only with the pulmonary form. An association between GGAG haplotype and protection to TB infection was also found. Also tandem repeat polymorphism in CD209L exon 4 was associated with TB infection. This study provides evidence of an association between CD209 and CD209L polymorphisms and TB development in a Brazilian population, suggesting that variations in these genes may influence the protection and susceptibility to infection caused by M. tuberculosis.

The importance of insufficient national data on sexual and reproductive health and rights in international databases.

Looking at SRHR as an isolated set of elements, as is the current practice, does not do justice to the needs and rights of people and communities and may be one of the reasons why challenges remain in the attainment of SRHR for all. SRHR Infographic snapshots were developed for all 194 WHO Member States and included 120 indicators covering a broad range of policy, health systems and service delivery interventions. The snapshots were created using data less than 10 years old publicly available in data repositories maintained by international and global agencies. Data availability was not consistent across countries with low and lower-middle income countries having higher data availability (71%) compared to high income countries (40%). SRHR data that is easily accessible and consistently reported can improve accountability and opportunities for learning to improve people-centred approaches to accelerate the attainment of SRHR for all.