Field- and laboratory-based studies on correlates of Chlamydia trachomatis transmission by Musca sorbens: Determinants of fly-eye contact and investigations into fly carriage of elementary bodies.

Musca sorbens (Diptera: Muscidae) flies are thought to be vectors of the blinding eye disease trachoma, carrying the bacterium Chlamydia trachomatis (Ct) between the eyes of individuals. While their role as vectors has been convincingly demonstrated via randomised controlled trials in The Gambia, studies of fly-borne trachoma transmission remain scant and as such our understanding of their ability to transmit Ct remains poor. We examined fly-eye contact and caught eye-seeking flies from 494 individuals (79% aged ≤9 years) in Oromia, Ethiopia. Ct-carrying flies (harbouring Ct DNA) were found to cluster spatially in and nearby to households in which at least one resident had Ct infection. Fly-eye contact was positively associated with the presence of trachoma (disease), lower human body weight and increased human body temperature. Studies of laboratory-reared M. sorbens indicated that Ct is found both externally and internally following feeds to Ct culture, with scanning electron microscopy revealing how Ct bodies can cling to fly hairs (setae). Testing for Ct on field-caught M. sorbens found fly 'bodies' (thorax, wings and abdomen) to consistently test positive for Ct while legs and heads were infrequently Ct-positive. These studies strongly support the role of M. sorbens as vectors of trachoma and highlight the need for improved understanding of fly-borne trachoma transmission dynamics and vector competence.

First-trimester serum biomarkers in twin pregnancies and adverse obstetric outcomes-a single center cohort study.

PURPOSE: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies. METHODS: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used. RESULTS: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks. CONCLUSION: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended.

First-trimester uterine artery Doppler and hypertensive disorders in twin pregnancies: Use of twin versus singleton references.

OBJECTIVE: To determine the association of first-trimester uterine artery Doppler with hypertensive disorders of pregnancy in twin pregnancies. METHODS: This was a retrospective cohort study of twin pregnancies followed at the University Hospital Center of Central Lisbon, Portugal, between January 2010 and December 2022. First-trimester uterine artery pulsatility index (UtA-PI) was determined and compared between twin pregnancies (n = 454) and singleton pregnancies (n = 908), matched to maternal and pregnancy characteristics. Maternal characteristics and mean UtA-PI were analyzed for gestational age, birth weight, gestational hypertension, early- and late-onset pre-eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, and preterm birth. Univariable and multivariable logistic regression models were used. RESULTS: The mean first-trimester UtA-PI was significantly lower in dichorionic twins than in singletons (P < 0.001). To study hypertensive disorders of pregnancy in twins, 390 pregnancies were included: 311 (79.7%) dichorionic and 79 (20.3%) monochorionic twins. The observed rates of early- and late-onset pre-eclampsia, gestational hypertension, and HELLP syndrome were 1.0%, 4.4%, 7.4%, and 1.5%, respectively. We achieved a 100% detection rate for early-onset pre-eclampsia using the UtA-PI 90th centile for twins. However, when singleton references were considered, the detection rate decreased to 50%. UtA-PI at or above the 95th centile was associated with increased odds for preterm birth before 32 weeks (adjusted odds ratio 4.1, 95% confidence interval 1.0-16.7, P = 0.043). CONCLUSIONS: Unless other major risk factors for hypertensive disorders are present, women with low UtA-PI will probably not benefit from aspirin prophylaxis. Close monitoring of all twin pregnancies for hypertensive disorders is still recommended.

Higher risk of preterm twin delivery among shorter nulliparous women.

OBJECTIVE: To determine if maternal height in nulliparous women influences pregnancy results in twin pregnancies. MATERIAL AND METHODS: Retrospective cohort analysis evaluating twin pregnancies followed at Centro Hospitalar Universitário Lisboa Central, between 1995 and 2020. Of the 2900 pregnancies followed in that period, 886 nulliparous women with dichorionic twin pregnancies were selected. Two groups were considered: A - maternal height <163 cm (

Photodynamic therapy reduces cell viability, migration and triggers necroptosis in prostate tumor cells.

Prostate cancer is the most common cancer in American men, aside from skin cancer. As an alternative cancer treatment, photodynamic laser therapy (PDT) can be used to induce cell death. We evaluated the PDT effect, using methylene blue as a photosensitizer, in human prostate tumor cells (PC3). PC3 were subjected to four different conditions: DMEM (control); laser treatment (L-660 nm, 100 mW, 100 J.cm-2); methylene blue treatment (MB-25 µM, 30 min), and MB treatment followed by low-level red laser irradiation (MB-PDT). Groups were evaluated after 24 h. MB-PDT treatment reduced cell viability and migration. However, because MB-PDT did not significantly increase the levels of active caspase-3 and BCL-2, apoptosis was not the primary mode of cell death. MB-PDT, on the other hand, increased the acid compartment by 100% and the LC3 immunofluorescence (an autophagy marker) by 254%. Active MLKL level, a necroptosis marker, was higher in PC3 cells after MB-PDT treatment. Furthermore, MB-PDT resulted in oxidative stress due to a decrease in total antioxidant potential, catalase levels, and increased lipid peroxidation. According to these findings, MB-PDT therapy is effective at inducing oxidative stress and reducing PC3 cell viability. In such therapy, necroptosis is also an important mechanism of cell death triggered by autophagy.

Self-reported use of the paretic lower extremity of people with stroke: A reliability and validity study of the Lower-Extremity Motor Activity Log (LE-MAL) - Brazil.

BACKGROUND: Most measures to assess the lower extremity (LE) after a neurological injury assess the lower limb motor capacity in the laboratory or clinical settings as the lower-extremity motor subscale of Fugl Meyer Assessment (FMA-LE). The LE Motor Activity Log (LE-MAL) measures the use of paretic LE in real-life conditions, which for many researchers and stakeholders is considered an important goal of rehabilitation. OBJECTIVE: Investigate the reliability, validity, floor, and ceiling effects of the Brazilian version of the LE-MAL. METHODS: Cross-sectional study to examine the reliability and validity of LE-MAL in patients with chronic stroke. The translation and adaptation of LE-MAL was carried out for the Brazilian version. After this stage, to ensure the inter-rater reliability two raters (LCF, DBM) applied the translated version of LE-MAL in the 21 selected participants. Subsequently, the concurrent validity was calculated by the correlation with the FMA-LE. RESULTS: The translation and retro-translation of the LE-MAL was approved to the Brazilian context. A floor effect was not observed, and there was no ceiling effect for the LE-MAL total scores. The Inter-rater reliability ranged between 0.80 and 0.86. The Bland-Altman analysis showed difference of LE-MAL scores ranged from 0.8 to 1.6. The Cronbach's alpha coefficients for LE-MAL and subscales were high ranging between 0.86 and 0.80. There was a significant moderate correlation between the LE-MAL and FMA-LE (Pearson correlation 0.55 (p = .009)). CONCLUSION: The Brazilian version LE-MAL is valid and reliable to assess real-world use of the paretic LE of individuals with chronic stroke.

Left ventricular function by strain in uncomplicated malaria: a prospective study from the Brazilian Amazon.

We hypothesized that adults with uncomplicated malaria have lower left ventricular contractile function compared to the general population and that this improves after antimalarial treatment. We examined uncomplicated malaria and the general population from the Western part of the Brazilian Amazon Basin. All persons underwent an echocardiographic examination and peripheral blood smears. Left ventricular function was assessed by speckle tracking analysis of global longitudinal strain (GLS). Logistic regression models were used to assess the association between malaria status (yes/no) and GLS and improvement in GLS by follow-up was assessed using a paired T-test. We enrolled 99 adults with uncomplicated malaria (mean age 40 years, 46% female) of whom 75 had Plasmodium vivax, 22 Plasmodium falciparum and two had both species [median 1595 (528 to 6585) parasites/mm3]. Seventy adults completed a follow-up examination after standard malaria treatment (median 31 days). We examined 486 from the general population (mean age 41 years, 63% female). In persons with malaria at baseline, GLS was lower compared to the general population (18.7% vs. 19.4%, P = 0.002) and GLS improved at follow-up (19.2%, P = 0.032). In multivariable models adjusted for clinical, socioeconomic and echocardiographic confounders, baseline GLS remained significantly associated with malaria status [odds ratio 2.45 (95%CI 1.00 to 7.25), P = 0.023 per 1% increase]. Parasite density was associated with worsening in GLS [+ 16% (+ 0% to + 34%), P = 0.047 per 1 unit increase in GLS]. Adults with uncomplicated malaria had lower GLS compared to the general population and this improved after completed antimalarial treatment. Our results suggest that malaria infection may affect left ventricular contractile function, however, further studies are needed to fully elucidate such a relationship.

Potential role of transthoracic echocardiography for screening LV systolic dysfunction in patients with a history of dengue infection. A cross-sectional and cohort study and review of the literature.

BACKGROUND: Dengue virus can affect the cardiovascular system and men may be at higher risk of severe complications than women. We hypothesized that clinical dengue virus (DENV) infection could induce myocardial alterations of the left ventricle (LV) and that these changes could be detected by transthoracic echocardiography. METHODOLOGY/PRINCIPAL FINDINGS: We examined individuals from Acre in the Amazon Basin of Brazil in 2020 as part of the Malaria Heart Study. By questionnaires we collected information on self-reported prior dengue infection. All individuals underwent transthoracic echocardiography, analysis of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). We included 521 persons (mean age 40±15 years, 39% men, 50% urban areas) of which 253 (49%) had a history of dengue infection. In multivariable models adjusted for clinical and sociodemographic data, a history of self-reported dengue was significantly associated with lower LVEF (ß = -2.37, P < 0.01) and lower GLS (ß = 1.08, P < 0.01) in men, whereas no significant associations were found in women (P > 0.05). In line with these findings, men with a history of dengue had higher rates of LV systolic dysfunction (LVEF < 50% = 20%; GLS < 16% = 17%) than those without a history of dengue (LVEF < 50% = 7%; GLS < 16% = 8%; P < 0.01 and 0.06, respectively). CONCLUSIONS/SIGNIFICANCE: The findings of this study suggest that a clinical infection by dengue virus could induce myocardial alterations, mainly in men and in the LV, which could be detected by conventional transthoracic echocardiography. Hence, these results highlight a potential role of echocardiography for screening LV dysfunction in participants with a history of dengue infection. Further larger studies are warranted to validate the findings of this study.

Is self-rated health associated with cardiovascular risk factors and disease in a low-income setting? A cross-sectional study from the Amazon Basin of Brazil.

OBJECTIVE: Prior studies have suggested that self-rated health may be a useful indicator of cardiovascular disease. Consequently, we aimed to assess the relationship between self-rated health, cardiovascular risk factors and subclinical cardiac disease in the Amazon Basin. DESIGN: Cross-sectional study. SETTING, PARTICIPANTS AND INTERVENTIONS: In participants from the Amazon Basin of Brazil we obtained self-rated health according to a Visual Analogue Scale, ranging from 0 (poor) to 100 (excellent). We performed questionnaires, physical examination and echocardiography. Logistic and linear regression models were applied to assess self-rated health, cardiac risk factors and cardiac disease by echocardiography. Multivariable models were mutually adjusted for other cardiovascular risk factors, clinical and socioeconomic data, and known cardiac disease. OUTCOME MEASURES: Cardiovascular risk factors and subclincial cardiac disease by echocardiography. RESULTS: A total of 574 participants (mean age 41 years, 61% female) provided information on self-rated health (mean 75±21 (IQR 60-90) points). Self-rated health (per 10-point increase) was negatively associated with hypertension (OR 0.87 (95% CI 0.78 to 0.97), p=0.01), hypercholesterolaemia (OR 0.89 (95%CI 0.80 to 0.99), p=0.04) and positively with healthy diet (OR 1.13 (95%CI 1.04 to 1.24), p=0.004). Sex modified these associations (p-interaction <0.05) such that higher self-rated health was associated with healthy diet and physical activity in men, and lower odds of hypertension and hypercholesterolaemia in women. No relationship was found with left ventricular ejection fraction <45% (OR 0.97 (95% CI 0.77 to 1.23), p=0.8), left ventricular hypertrophy (OR 0.97 (95% CI 0.76 to 1.24), p=0.81) or diastolic dysfunction (OR 1.09 (95% CI 0.85 to 1.40), p=0.51). CONCLUSION: Self-rated health was positively associated with health parameters in the Amazon Basin, but not with subclinical cardiac disease by echocardiography. Our findings are of hypothesis generating nature and future studies should aim to determine whether assessment of self-rated health may be useful for screening related to policy-making or lifestyle interventions. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04445103; Post-results.

Evaluation of the efficacy of insecticide-treated scarves to protect children from the trachoma vector Musca sorbens (Diptera: Muscidae): A phase II randomised controlled trial in Oromia, Ethiopia.

Background: The eye-seeking fly Musca sorbens can act as a vector for ocular Chlamydia trachomatis, causing trachoma, yet there has been very little research on control measures. We investigated whether insect repellent products, specifically insecticide-treated clothing, could provide personal protection to the user from eye-seeking flies. Methods: We first conducted a series of phase I laboratory studies to inform our choice of field intervention. We then conducted a phase II randomised controlled trial testing the efficacy of permethrin-treated scarves (PTS) in reducing fly-face contact in Oromia, Ethiopia. Children aged 4-10 years in full health and with no known adverse reactions to permethrin or other insecticides were allocated to either arm using restricted randomisation. Intervention arm children wore Insect Shield® versatile wraps (as PTS) for 28 days. The primary outcomes, fly-eye, -nose and -mouth contact, were assessed on the first day (0/30/60/180 minutes), on day 7 and on day 28. All participants present per timepoint were included in analyses. This trial was registered with ClinicalTrials.gov (NCT03813069). Findings: Participants were recruited to the field trial between 29/10/2019 and 01/11/2019, 58 were randomised to test or control arm. More fly (-eye, -nose and -mouth) contacts were observed in the PTS arm at baseline. After adjusting for baseline contact rates, across all timepoints there was a 35% decrease in fly-eye contacts in the PTS relative to control arm (rate ratio [RR] 0.65, 95% CI 0.52-0.83). Similar cross-timepoint reductions were seen for fly-nose and fly-mouth contacts (RR 0.69, 95% CI 0.51-0.92 and RR 0.79, 95% CI 0.62-1.01, respectively). All children were included on day 0. Two in the control arm were absent on day 7, one left the study and four were excluded from analysis at day 28. No adverse events occurred in the trial. Interpretation: Musca sorbens flies are sufficiently repelled by PTS to reduce fly-eye contacts for the wearer, thus possibly reducing the risk of trachoma transmission. Permethrin-treated scarves may therefore an alternative to insecticide space spraying for protection from these flies. Funding: Wellcome Trust.

Prevalence and Dynamic Changes in Lung Ultrasound Findings among Adults with Uncomplicated Malaria and Controls in the Amazon Basin, Brazil.

Malaria patients are at risk of cardiopulmonary complications but diagnosis and management can be difficult in resource-limited settings. B-lines on lung ultrasound (LUS) mark changes in lung density; however, little is known about their role in malaria. We aimed to examine the prevalence of B-lines in adults with malaria at baseline and follow-up compared with controls in the Amazon Basin. We also examined the relationship between B-lines and left ventricular ejection fraction. We performed eight-zone LUS, echocardiography, and blood smears in 94 adults (mean age 40 years, 54% men) with uncomplicated malaria and 449 controls without heart failure, renal insufficiency or lung disease (mean age 41 years, 38% men). Examinations of adults with malaria were repeated after antimalarial treatment, corresponding to a median of 30 days (interquartile range [IQR] 27-39). Adults with malaria suffered from Plasmodium vivax (N = 70, median 2,823 [IQR 598-7,698] parasites/µL) or P. falciparum (N = 24, median 1,148 [IQR 480-3,128] parasites/µL). At baseline, adults with malaria more frequently had ≥ 3 B-lines (summed across eight zones) compared with controls (30% versus 2%, P value < 0.001), indicating higher lung density. When examinations were repeated, only 6% of adults with malaria had ≥ 3 B-lines at follow-up, which was significant lower compared with baseline (median reduction 3 B-line; P value < 0.001). B-lines were not significantly associated with left ventricular ejection fraction in adults with malaria. In conclusion, B-lines detected by LUS were more frequent in adults with uncomplicated malaria compared with controls and decreased after completed antimalarial treatment.

Prevalence of rheumatic heart disease in adults from the Brazilian Amazon Basin.

BACKGROUND: Rheumatic heart disease (RHD) continues to be a burden in low- and middle-income countries and prevalence estimates are lacking from South America. We aimed to determine the prevalence of RHD in the Brazilian Amazon Basin. METHODS: We examined a random sample of adults (≥18 years) from the general population, who underwent echocardiographic image acquisition by a medical doctor. All images were analyzed according to (i) the 2012 World Heart Federation criteria and (ii) a simplified algorithm for RHD from a previously validated risk score (categories: low-, medium-, high-risk) which involved assessment of the mitral valve (leaflet thickening and excessive motion, regurgitation jet length) and aortic valve (thickening and any regurgitation). RESULTS: A total of 488 adults were screened (mean age 40 ± 15 years, 38% men). The prevalence of RHD was 39/1000 adults (n = 17 definite and n = 2 borderline). Fourteen (74%) had pathological mitral regurgitation, four (21%) mitral stenosis, 0 (0%) pathological aortic regurgitation and six (32%) both mitral and aortic valve disease. None had a prior diagnosis of RHD, 10 (53%) had positive cardiac auscultation and two (11%) reported a history of rheumatic fever. The simplified algorithm identified four (21%) adults as low-risk, six (32%) as intermediate, and nine (47%) as high-risk. CONCLUSIONS: The prevalence of RHD was 39/1000 in adults from the Brazilian Amazon Basin, indicating the need for screening programs in remote areas. A simplified model was only able to categorize every second case of RHD as high-risk. External validation of simplified screening models to increase feasibility in clinical practice are encouraged.

Tropical diseases and risk of hypertension in the Amazon Basin: a cross-sectional study.

Although infectious diseases have been associated with cardiovascular conditions, little is known about tropical disease burden and hypertension. We hypothesized that a history of tropical infections was associated with hypertension. We examined participants from outpatient clinics in the Amazon Basin who were interviewed about prior exposure to tropical diseases, including dengue, malaria hospitalization, and leishmaniasis. Hypertension was defined as a prior physician diagnosis of hypertension, treatment with anti-hypertensive medication, or a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg. We used logistic regression models to examine the relationship between tropical infectious disease and hypertension. We included 556 participants (mean age 41 ± 15 years, 61% women) of whom 214 (38%) had hypertension and 354 (64%) had a history of tropical infectious disease. The distribution of tropical diseases was: dengue 270 (76%), malaria hospitalization 104 (29%) and leishmaniasis 48 (14%). Any prior tropical infection was significantly associated with prevalent hypertension (odds ratio 1.76 [95% CI 1.22-2.54], P = 0.003) and the association remained significant after adjusting for age, sex, body mass index, diabetes, hypercholesterolemia, socioeconomic status, smoking, vegetable intake and serum creatinine. Persons with a history of ≥2 tropical infections (n = 64) had the greatest risk of hypertension (odds ratio 2.04 [95% CI 1.15-3.63], P = 0.015). In adjusted models, prior infection with dengue was associated with hypertension (P = 0.006), but no associations were found with malaria hospitalization (P = 0.39) or leishmaniasis (P = 0.98). In conclusion, a history of tropical infectious disease was associated with hypertension. This finding supports the idea that pathogen burden may be related to cardiovascular conditions.

Frequency of Electrocardiographic Alterations and Pericardial Effusion in Patients With Uncomplicated Malaria.

Studies have proposed that malaria may lead to electrocardiographic (ECG) changes and pericardial inflammation. We aimed to investigate the frequency of ECG alterations, determined by ECG and Holter monitoring, and pericardial effusion in patients with malaria infection. We performed a prospective observational study of adult patients with uncomplicated malaria in Amazonas, Brazil. Peripheral blood smears, ECG, and bedside echocardiography were conducted before antimalarial treatment and repeated at follow-up after completed treatment. We evaluated the diagnostic value of PR-segment depression, PR-segment elevation, and Spodick's sign for detecting pericardial effusion. A subset of patients underwent Holter monitoring at baseline. Among 98 cases of uncomplicated malaria (55% men; mean age 40 years; median parasite density 1,774/µl), 75 had Plasmodium vivax, 22 Plasmodium falciparum, and 1 had mixed infection. At baseline, 17% (n = 17) had PR-segment depression, 12% (n = 12) PR-segment elevation, 3% (n = 2) Spodick's sign, and the prevalence of pericardial effusion was 9% (n = 9). ECG alterations had sensitivities of 22% to 89% and specificities of 88% to 100% for detecting pericardial effusion at baseline. PR-segment depression had the best accuracy (sensitivity 89%, specificity 90%). Of the 25 patients, 4 patients who did not have pericardial effusion, displayed nonsustained ventricular tachycardia, determined by Holter monitoring (median duration 43 hours). Follow-up examination data were obtained for 71 patients (median 31 days), for whom PR-segment depression, elevation, and pericardial effusion had reduced significantly (p <0.05). In conclusion, our findings suggest that ECG alterations may be useful to detect pericardial effusion in malaria and that these findings decrease after completed antimalarial treatment.

Mapping and characterizing areas with high levels of malaria in pregnancy in Brazil: A spatiotemporal analysis.

Background: Malaria in pregnancy (MiP) is a public health problem in the Brazilian Amazon region that requires special attention due to associated serious adverse consequences, such as low birth weight, increased prematurity and spontaneous abortion rates. In Brazil, there have been no comprehensive epidemiological studies of MiP. In this study, we aimed to explore the spatial and spatiotemporal patterns of MiP in Brazil and epidemiologically characterize this population of pregnant women over a period of 15 years. Methods: We performed a national-scale ecological analysis using a Bayesian space-time hierarchical model to estimate the incidence rates of MiP between 1 January 2004 and 31 December 2018. We mapped the high-incidence clusters among pregnant women aged 10-49 years old using a Poisson model, and we characterized the population based on data from the Epidemiological Surveillance Information System for Malaria (SIVEP-Malaria). Findings: We consolidated the data of 61,833 women with MiP in Brazil. Our results showed a reduction of 50·1% (95% CI: 47·3 to 52·9) in the number of malaria cases over the period analysed, with Plasmodium vivax malaria having the highest incidence. MiP was widely distributed throughout the Amazon region, and spatial and spatiotemporal analyses revealed statistically significant clusters in some municipalities of Amazonas, Acre, Rondônia and Pará. In addition, we observed that younger pregnant women had a higher risk of infection, and the administration of appropriate treatment requires more attention. Interpretation: This nationwide study provides robust evidence that, despite the reduction in the number of MiP cases in the country, it remains a serious public health problem, especially for young pregnant women. Our analyses highlight focus areas for strengthening interventions to control and eliminate MiP. Funding: FAPESP and CNPq - Brazil.

Shaping Exploration: How Does the Constraint-Induced Movement Therapy Helps Patients Finding a New Movement Solution.

Despite the relative success of constraint-induced movement therapy in the recovery of injury-/trauma-related populations, the mechanisms by which it promotes its results are still unknown. From a dynamical systems approach, we investigated whether the induced exploratory patterns within and between trials during an exercise in Shaping (the therapy's practice) could shed light on this process. We analyzed data from four chronic spinal-cord injury patients during a task of placing and removing their feet from a step. We assessed the within and between trial dynamics through recurrent quantification analyses and task-space analyses, respectively. From our results, individuals found movement patterns directed to modulate foot height (to accomplish the task). Additionally, when the task was manipulated (increasing step height), individuals increased coupling and coupling variability in the ankle, hip, and knee over trials. This pattern of findings is in consonance with the idea of Shaping inducing exploration of different movements. Such exploration might be an important factor affording the positive changes observed in the literature.

Whole genome sequencing reveals large deletions and other loss of function mutations in Mycobacterium tuberculosis drug resistance genes.

Drug resistance in Mycobacterium tuberculosis, the causative agent of tuberculosis disease, arises from genetic mutations in genes coding for drug-targets or drug-converting enzymes. SNPs linked to drug resistance have been extensively studied and form the basis of molecular diagnostics and sequencing-based resistance profiling. However, alternative forms of functional variation such as large deletions and other loss of function (LOF) mutations have received much less attention, but if incorporated into diagnostics they are likely to improve their predictive performance. Our work aimed to characterize the contribution of LOF mutations found in 42 established drug resistance genes linked to 19 anti-tuberculous drugs across 32689 sequenced clinical isolates. The analysed LOF mutations included large deletions (n=586), frameshifts (n=4764) and premature stop codons (n=826). We found LOF mutations in genes strongly linked to pyrazinamide (pncA), isoniazid (katG), capreomycin (tlyA), streptomycin (e.g. gid) and ethionamide (ethA, mshA) (P<10-5), but also in some loci linked to drugs where relatively less phenotypic data is available [e.g. cycloserine, delaminid, bedaquiline, para-aminosalicylic acid (PAS), and clofazimine]. This study reports that large deletions (median size 1115 bp) account for a significant portion of resistance variants found for PAS (+7.1% of phenotypic resistance percentage explained), pyrazinamide (+3.5%) and streptomycin (+2.6%) drugs, and can be used to improve the prediction of cryptic resistance. Overall, our work highlights the importance of including LOF mutations (e.g. large deletions) in predicting genotypic drug resistance, thereby informing tuberculosis infection control and clinical decision-making.

Reference values for left ventricular dimensions, systolic and diastolic function: a study from the Amazon Basin of Brazil.

Country- and ethnicity-specific reference values for echocardiographic parameters are necessary for decision making. No prior studies have examined reference values in adults from the Amazon Basin of Brazil. We performed echocardiographic examinations in 290 healthy adults (mean age 37 ± 14 years, 40% male) from the Brazilian Amazon. Left ventricular (LV) dimensions and volumes were obtained and indexed to body surface area. We also assessed systolic (LV ejection fraction [LVEF] and global longitudinal strain [GLS]) and diastolic function. LV dimensions and volumes were larger in males compared to females, but after indexation only volumes remained larger (P < 0.001 for all). Parameters of systolic function, were significantly greater in females (LVEF 50 to 68%, GLS - 17 to - 24%) than in males (LVEF 50 to 67%, GLS - 15 to - 23%, P < 0.05). Upper limits of normality for cardiac dimensions (indexed and non-indexed) were markedly higher compared to contemporary guidelines (American Society of Echocardiography) and the Brazilian subgroup in the World Alliance Society of Echocardiography (WASE). Lower limit of normality for LVEF (both sex 50%) and upper limit of normality for the left atrial volume index (LAVI) (male: 31 mL/m2, female: 25 mL/m2) were within normal range but slightly lower compared to guidelines and the WASE study. Other diastolic parameters, including E/A-ratio, E/e' ratio and peak tricuspid regurgitation velocity were compatible with present recommendations. Normal reference ranges of echocardiographic parameters in healthy adults from the Brazilian Amazon Basin may be different compared to international guidelines and data from other regions of Brazil. This applies specifically for LVEF and LAVI.