Retreatment and Anti-tuberculosis Therapy Outcomes in Brazil Between 2015 and 2022: A Nationwide Study.

Background: Adherence to anti-tuberculosis treatment (ATT) in Brazil remains a challenge in achieving the goals set by the World Health Organization (WHO). Patients who are lost to follow-up during treatment pose a significant public health problem. This study aimed to investigate the factors associated with unfavorable ATT outcomes among those undergoing retreatment in Brazil. Methods: We conducted an observational study of patients aged ≥18 years with tuberculosis (TB) reported to the Brazilian National Notifiable Disease Information System between 2015 and 2022. Clinical and epidemiologic variables were compared between the study groups (new cases and retreatment). Regression models identified variables associated with unfavorable outcomes. Results: Among 743 823 reported TB cases in the study period, 555 632 cases were eligible, consisting of 462 061 new cases and 93 571 undergoing retreatments (44 642 recurrent and 48 929 retreatments after loss to follow-up [RLTFU]). RLTFU (odds ratio [OR], 3.96 [95% confidence interval {CI}, 3.83-4.1]) was a significant risk factor for any type of unfavorable ATT. Furthermore, RLTFU (OR, 4.93 [95% CI, 4.76-5.11]) was the main risk factor for subsequent LTFU. For death, aside from advanced age, living with HIV (OR, 6.28 [95% CI, 6.03-6.54]) was the top risk factor. Conclusions: Retreatment is a substantial risk factor for unfavorable ATT outcomes, especially after LTFU. The rates of treatment success in RLTFU are distant from the WHO End TB Strategy targets throughout Brazil. These findings underscore the need for targeted interventions to improve treatment adherence and outcomes in persons who experience RLTFU.

How does the age of control individuals hinder the identification of target genes for Huntington's disease?

Several studies have compared the transcriptome across various brain regions in Huntington's disease (HD) gene-positive and neurologically normal individuals to identify potential differentially expressed genes (DEGs) that could be pharmaceutical or prognostic targets for HD. Despite adhering to technical recommendations for optimal RNA-Seq analysis, none of the genes identified as upregulated in these studies have yet demonstrated success as prognostic or therapeutic targets for HD. Earlier studies included samples from neurologically normal individuals older than the HD gene-positive group. Considering the gradual transcriptional changes induced by aging in the brain, we posited that utilizing samples from older controls could result in the misidentification of DEGs. To validate our hypothesis, we reanalyzed 146 samples from this study, accessible on the SRA database, and employed Propensity Score Matching (PSM) to create a "virtual" control group with a statistically comparable age distribution to the HD gene-positive group. Our study underscores the adverse impact of using neurologically normal individuals over 75 as controls in gene differential expression analysis, resulting in false positives and negatives. We conclusively demonstrate that using such old controls leads to the misidentification of DEGs, detrimentally affecting the discovery of potential pharmaceutical and prognostic markers. This underscores the pivotal role of considering the age of control samples in RNA-Seq analysis and emphasizes its inclusion in evaluating best practices for such investigations. Although our primary focus is HD, our findings suggest that judiciously selecting age-appropriate control samples can significantly improve best practices in differential expression analysis.

Impact of Xpert MTB/RIF implementation in tuberculosis case detection and control in Brazil: a nationwide intervention time-series analysis (2011-2022).

Background: Since 2014, Brazil has gradually implemented the Xpert MTB/RIF (Xpert) test to enhance early tuberculosis (TB) and drug-resistant (DR-TB) detection and control, yet its nationwide impact remains underexplored. Our study conducts an intervention time-series analysis (ITSA) to evaluate how the Xpert's implementation has improved TB and DR-TB detection nationwide. Methods: 1,061,776 cases from Brazil's National TB Registry (2011-2022) were reviewed and ITSA (2011-2019) was used to gauge the impact of the Xpert's adoption on TB and DR-TB notification. Granger Causality and dynamic regression modelling determined if incorporating Xpert testing as an external regressor enhanced forecasting accuracy for Brazil's future TB trends. Findings: Xpert implementation resulted in a 9.7% increase in TB notification and substantial improvements in DR-TB (63.6%) and drug-susceptible TB (92.1%) detection compared to expected notifications if it had not been implemented. Xpert testing counts also presented a time-dependent relationship with DR-TB detection post-implementation, and improved predictions in forecasting models, which depicted a potential increase in TB and DR-TB detection in the next six years. Interpretation: This study underscores the critical role of Xpert's adoption in boosting TB and DR-TB detection in Brazil, reinforcing the case for its widespread use in disease control. Improvements in prediction accuracy resulting from integrating Xpert data are crucial for allocating resources and reducing the incidence of TB. By acknowledging Xpert's role in both disease control and improving predictions, we advocate for its expanded use and further research into advanced molecular diagnostics for effective TB and DR-TB control. Funding: FIOCRUZ.

Recognizing Patterns of Nature Contact Associated with Well-Being: An Exploratory Cluster Analysis.

Statement of Problem: Progressive urbanization has reduced human interactions with nature, raising concerns about its impact on mental well-being. Previous research has often focused on specific aspects of nature contact, neglecting its multifaceted dimensions and their effects on mental health, particularly in developing countries. Research Gap: There is a scarcity of studies exploring the comprehensive dimensions of nature contact, such as frequency, duration, intensity, and space naturalness, and their correlation with mental well-being in developing countries' urban settings. Purpose: This study aims to identify patterns of nature contact related to mental well-being in metropolitan areas of Brazil using exploratory cluster analysis, bridging the existing knowledge gap and informing targeted interventions to enhance mental health through nature contact. Method: An online survey collected data from 2136 participants in Brazil's metropolitan areas, focusing on their nature interaction patterns and mental health status using the Depression Anxiety and Stress Scale (DASS-21), hierarchical clustering with p-values via multiscale bootstrap resampling, and analysis of variance. Results and Conclusions: Three distinct groups were identified, showing varied patterns of nature contact and demographic profiles. Greater and more frequent nature contact was associated with lower levels of depression, anxiety, and stress. These findings suggest a beneficial relationship between nature contact and mental well-being. Practical Implications: The results underline the importance of urban planning and public health policies that facilitate access to natural spaces, highlighting socioeconomic factors as significant barriers to this access. Future Directions: Further research should explore causal relationships and consider the specific realities and challenges faced by residents of developing nations.

Pressure dynamics of the esophagogastric junction at rest and during inspiratory maneuvers after Nissen fundoplication.

Low sphincter pressure and inability of the crural diaphragm to elevate it at the esophagogastric junction are important pathophysiological mechanisms of gastroesophageal reflux disease (GERD). The object of this study was to depict how Nissen fundoplication changed the resting and inspiratory pressures of the anti-reflux barrier. We selected 14 patients (eight males; mean age 42.7 years; mean body mass index 27.8) for surgery. They answered symptoms questionnaires and underwent high-resolution manometry (HRM) before and 6 months after Nissen fundoplication. We used a standard manometric protocol (resting and liquid swallows) and assessment of esophagogastric junction (EGJ) pressure metrics during standardized forced inspiratory maneuvers against increasing loads (Threshold Maneuvers). We used the Wilcoxon test for comparison of pre and postoperative data. After fundoplication, heartburn and regurgitation scores diminished remarkably (from 4.5 and 2, respectively, to zero; P = 0.002 and P = 0.0005, respective medians). Also, the median expiratory EGJ pressure had a significant increase from 8.1 to 18.1 mmHg (P = 0.002), while mean respiratory pressure and EGJ contractility integral (EGJ-CI) increased without statistical significance (P = 0.064 and P = 0.06, respectively). Axial EGJ displacement was lower after fundoplication. The EGJ relaxation pressure (P = 0.001), the mean distal esophageal intrabolus pressure (P = 0.01) and the distal latency (P = 0.017) increased after fundoplication. There was a reduction in the contraction front velocity (P = 0.043). During evaluation with standardized inspiratory maneuvers, the inspiratory EGJ pressures (under loads of 12, 24, 36 and 48 cmH2O) were lower after surgery for all loads (median for load 12 cmH2O: 145.6 vs. 102.7 mmHg; P = 0.004). Fundoplication and hiatal closure increased the expiratory EGJ pressure and promoted a great GERD symptom relief. The surgery seemed to overcompensate a reduced EGJ mobility and inspiratory pressure.

How does the age of control individuals hinder the identification of target genes for Huntington’s disease?

Several studies have compared the transcriptome across various brain regions in Huntington’s disease (HD) gene-positive and neurologically normal individuals to identify potential differentially expressed genes (DEGs) that could be pharmaceutical or prognostic targets for HD. Despite adhering to technical recommendations for optimal RNA-Seq analysis, none of the genes identified as upregulated in these studies have yet demonstrated success as prognostic or therapeutic targets for HD. Earlier studies included samples from neurologically normal individuals older than the HD gene-positive group. Considering the gradual transcriptional changes induced by aging in the brain, we posited that utilizing samples from older controls could result in the misidentification of DEGs. To validate our hypothesis, we reanalyzed 146 samples from this study, accessible on the SRA database, and employed Propensity Score Matching (PSM) to create a “virtual” control group with a statistically comparable age distribution to the HD gene-positive group. Our study underscores the adverse impact of using neurologically normal individuals over 75 as controls in gene differential expression analysis, resulting in false positives and negatives. We conclusively demonstrate that using such old controls leads to the misidentification of DEGs, detrimentally affecting the discovery of potential pharmaceutical and prognostic markers. This underscores the pivotal role of considering the age of control samples in RNA-Seq analysis and emphasizes its inclusion in evaluating best practices for such investigations. Although our primary focus is HD, our findings suggest that judiciously selecting age-appropriate control samples can significantly improve best practices in differential expression analysis.

Comparison of Clinical and Pathological Staging in Patients with Head and Neck Cancer After Neck Dissection.

Introduction Clinical and pathological staging plays an important role on the prognosis of head and neck cancer (HNC) patients. Objective The present study aims to compare clinical and pathological T, N and overall staging in patients with HNC, to identify factors associated with these discrepancies, and to analyze and compare survival or disease-free survival in staging disagreements. Methods Retrospective cohort including every patient submitted to neck dissection from January 2010 to December 2020 in the department of Otorhinolaryngology of a tertiary hospital center. Results A total of 79 patients were analyzed; their mean age was 58.52 ± 13.15 years old and 88.9% were male. Assessing overall staging, discrepancies were noted in 53% (36.4% upstaging and 16.6% downstaging) and were significantly associated with clinical overall staging ( p = 0.006). Regarding T staging, differences were noted in 45.5% (30.3% upstaging and 15.2% downstaging) and were significantly associated with imaging modality ( p = 0.016), clinical T staging ( p = 0.049), and histology ( p = 0.017). Discrepancies in N staging were noted in 38% (25.3% upstaging and 12.7% downstaging) and were significantly associated with age ( p = 0.013), clinical N staging ( p < 0.001), and presence of extranodal invasion ( p < 0.001). Both in Overall, T, and N staging, the aforementioned disagreements were not associated with either higher mortality or higher disease relapse. Conclusion Overall, T, and N staging disagree in an important number of cases, and the overall stage can disagree in up to 53% of the cases. These disagreements do not seem to influence overall and disease-free survival.

Exosomes as a Nano-Carrier for Chemotherapeutics: A New Era of Oncology.

Despite the considerable advancements in oncology, cancer remains one of the leading causes of death worldwide. Drug resistance mechanisms acquired by cancer cells and inefficient drug delivery limit the therapeutic efficacy of available chemotherapeutics drugs. However, studies have demonstrated that nano-drug carriers (NDCs) can overcome these limitations. In this sense, exosomes emerge as potential candidates for NDCs. This is because exosomes have better organotropism, homing capacity, cellular uptake, and cargo release ability than synthetic NDCs. In addition, exosomes can serve as NDCs for both hydrophilic and hydrophobic chemotherapeutic drugs. Thus, this review aimed to summarize the latest advances in cell-free therapy, describing how the exosomes can contribute to each step of the carcinogenesis process and discussing how these nanosized vesicles could be explored as nano-drug carriers for chemotherapeutics.

Social and environmental determinants influencing injection drug use and HIV risk among two sister cities on the US-Mexico border: a comparative cross-sectional study, 2016-2018.

The economic, social, cultural and political milieus that influence injection drug-related HIV risk behaviors along the US-Mexico border in the previous decade have been studied comparing cities on an East-West axis. In an effort to inform interventions targeting factors beyond the individual level, we used a cross-sectional study design comparing people who inject drugs during 2016-2018, living on a North-South axis, in two cities-Ciudad Juárez, Chihuahua, Mexico and El Paso, Texas, USA-situated at the midpoint of the 2000 US-Mexico borderland stretch. We conceptualize injection drug use and its antecedents and consequences as influenced by factors operating at various levels of influence. Results of analysis comparing samples recruited from each border city indicated significant differences in demographic, socioeconomic, micro- and macro-level factors that affect risk. Similarities emerged in individual-level risk behaviors and some dynamics of risk at the drug use site most frequented to use drugs. In addition, analyses testing associations across samples indicated that different contextual factors such as characteristics of the drug use sites influenced syringe sharing. In this article, we reflect on the potential tailored interventions needed to target the context of HIV transmission risk among people who use drugs and reside in binational environment.

Predicting the body core temperature of recreational athletes at the end of a 10 km self-paced run under environmental heat stress.

NEW FINDINGS: What is the central question of this study? The aim was to identify the factors predicting the body core temperature of athletes at the end of a 10 km self-paced run in a hot environment. What is the main finding and its importance? Hyperthermia in athletes subjected to self-paced running depends on several factors, highlighting the integrated control of core temperature during exercise under environmental heat stress. Five of the seven variables that significantly predicted core temperature are not invasive and, therefore, practical for use outside the laboratory environment: heart rate, sweat rate, wet-bulb globe temperature, running speed and maximal oxygen consumption. ABSTRACT: Measurement of body core temperature (Tcore ) is paramount to determining the thermoregulatory strain of athletes. However, standard measurement procedures of Tcore are not practical for extended use outside the laboratory environment. Therefore, determining the factors that predict Tcore during a self-paced run is crucial for creating more effective strategies to minimize the heat-induced impairment of endurance performance and reduce the occurrence of exertional heatstroke. The aim of this study was to identify the factors predicting Tcore values attained at the end of a 10 km time trial (end-Tcore ) under environmental heat stress. Initially, we extracted data obtained from 75 recordings of recreationally trained men and women. Next, we ran hierarchical multiple linear regression analyses to understand the predictive power of the following variables: wet-bulb globe temperature, average running speed, initial Tcore , body mass, differences between Tcore and skin temperature (Tskin ), sweat rate, maximal oxygen uptake, heart rate and change in body mass. Our data indicated that Tcore increased continuously during exercise, attaining 39.6 ± 0.5°C (mean ± SD) after 53.9 ± 7.5 min of treadmill running. This end-Tcore value was primarily predicted by heart rate, sweat rate, differences between Tcore and Tskin , wet-bulb globe temperature, initial Tcore , running speed and maximal oxygen uptake, in this order of importance (ß power values corresponded to 0.462, -0.395, 0.393, 0.327, 0.277, 0.244 and 0.228, respectively). In conclusion, several factors predict Tcore in athletes subjected to self-paced running under environmental heat stress. Moreover, considering the conditions investigated, heart rate and sweat rate, two practical (non-invasive) variables, have the highest predictive power.

Diagnosis of gynecologic malignancy after the treatment of presumed benign fibroid disease with interventional radiology procedures: a retrospective cohort study.

OBJECTIVE: To ascertain the finding of future diagnosis of malignancy in women who undergo nonsurgical treatment for uterine fibroid disease with interventional radiology (IR) procedures. DESIGN: Mixed-methods retrospective cohort study. SETTING: Two tertiary care academic hospitals in Boston, Massachusetts. PATIENT(S): A total of 491 women who underwent radiologic intervention for fibroids between 2006 and 2016. INTERVENTION(S): Uterine artery embolization or high-intensity focused ultrasound ablation. MAIN OUTCOME MEASURE(S): Subsequent surgical interventions and diagnosis of gynecologic malignancy after the IR procedure. RESULT(S): During the study period, 491 women underwent treatment of fibroids with IR procedures; follow-up information was available for 346 cases. The mean age was 45.3 ± 4.8 years, and 69.7% were between the ages of 40 and 49 years. Regarding ethnicity, 58.9% of patients were white, and 26.1% were black. The most common symptoms were abnormal uterine bleeding (87%), pelvic pressure (62.3%), and pelvic pain (60.9%). A total of 106 patients underwent subsequent surgical treatment of fibroids. Of the 346 patients who had follow-up, 4 (1.2%) were diagnosed with leiomyosarcoma after their interventional treatment for fibroids. An additional 2 cases of endometrial adenocarcinoma and 1 case of a premalignant lesion of the endometrium were noted. CONCLUSION(S): The proportion of patients who went on to be diagnosed with leiomyosarcoma after conservative IR treatments appears to be higher than previously reported. A thorough preprocedural workup and patient counseling regarding the possibility of underlying uterine malignancy should be undertaken.

Effects of Carbon Nanoparticles and Chromium Combined Exposure in Native (Ruditapes decussatus) and Invasive (Ruditapes philippinarum) Clams.

Studies have described the occurrence of nanoparticles (NPs) in aquatic ecosystems, with particular attention to the widely commercialized carbon nanotubes (CNTs). Their presence in the environment raises concerns, especially regarding their toxicity when co-occurring with other pollutants such as metals. In the present study, changes to the metabolic capacity, oxidative, and neurologic status were evaluated in the presence of carboxylated multi-walled CNTs and chromium (Cr(III)) using two of the most ecologically and economically relevant filter feeder organisms: the clam species Ruditapes decussatus and R. philippinarum. Results indicated that although Cr, either alone or in combination with CNTs, was found in a similar concentration level in both species, a species-specific Cr accumulation was observed, with higher values in R. decussatus in comparison with R. philippinarum. Inhibition of antioxidant defenses and neurotoxic effects were detected only in R. philippinarum. The interaction between contaminants seems to have no effect in terms of antioxidant enzyme activities and neuro status. Nevertheless, synergistic activation of responses to both contaminants may have altered the metabolic capacity of bivalves, particularly evident in R. decussatus. While both clams are tolerant to both contaminants (alone and together), they showed a relevant accumulation capacity, which may represent a possible contaminant transfer to humans.

Tendência temporal de mortalidade por câncer de cabeça e pescoço no Brasil entre os anos de 2000 e 2020 / Temporal trend of mortality from head and neck cancer in Brazil between 2000 and 2020 / Tendencia temporal en la mortalidad de la cabeza y el cáncer de cuello en Brasil entre 2000 y 2020

Analisar a tendência temporal de mortalidade por câncer de cabeça e pescoço no Brasil e em suas regiões geográficas entre os anos de 2000 a 2020. Métodos: Foram analisados os números de óbitos por neoplasias malignas de cabeça e pescoço (CID-10: C00-C14; C30-C32) disponibilizados no portal oficial do Ministério da Saúde do Brasil para o período, bem como os dados sobre população residente. O padrão temporal e geográfico foi analisado através da taxa de mortalidade padronizada por idade (TMPI) e avaliado em modelo de regressão por pontos de inflexão. Resultados: No Brasil, a TMPI permaneceu estável independente do sexo (AAPC: -0,3; IC95: -1,0-0,3) no período avaliado. O estudo das regiões brasileiras evidenciou crescimento médio da TMPI independente do sexo nas regiões Nordeste (AAPC: 2,8; IC95: 2,1-3,5) e Norte (AAPC: 1,3; IC95: 0,8-1,9), em oposição ao decréscimo anual médio no Sul (AAPC: -1,4; IC95: -2,7--0,3) e no Sudeste (AAPC: -1,5; IC95: -1,9--1,1). No Centro-Oeste, a TMPI também apresentou decréscimo anual médio no grupo feminino (AAPC: -1,8; IC95: -2,8--0,8), embora tenha permanecido estável no grupo masculino e independente do sexo. Considerações finais: A compreensão desses dados pode auxiliar o estudo e implementação de estratégias de enfrentamento para esse grupo de doenças de acordo com as necessidades específicas de cada grupo e região.

To analyze the temporal trend of mortality from head and neck cancer in Brazil and its geographical regions between the years 2000 to 2020. Methods: We analyzed the number of deaths due to malignant neoplasms of the head and neck (ICD- 10: C00-C14; C30-C32) available on the official portal of the Brazilian Ministry of Health for the period, as well as the data on resident population. The temporal and geographical pattern was analyzed using the standardized mortality rate by age (TMPI) and evaluated in an inflection point regression model. Results: In Brazil, TMPI remained stable independent of gender (AAPC: -0.3; IC95: -1.0-0.3) in the evaluated period. The study of the Brazilian regions showed average growth of the TMPI independent of sex in the Northeast (AAPC: 2.8; 95 CI: 2.1-3.5) and North (AAPC: 1.3; 95 CI: 0.8-1.9) regions, as opposed to the average annual decrease in the South (AAPC: -1.4; 95 CI: -2.7-0.3) and in the Southeast (AAPC: -1.5; 95 CI: -1.9-1.1). In the Midwest, the TMPI also showed an average annual decrease in the female group (AAPC: -1.8; IC95: -2.8­0.8), although it remained stable in the male group and independent of the sex. Final Considerations: Understanding this data can assist in the study and implementation of coping strategies for this group of diseases according to the specific needs of each group and region.

Análisis de la tendencia temporal de la mortalidad por cáncer de cabeza y cuello en Brasil y sus regiones geográficas entre los años 2000 y 2020. Métodos: Se analizó el número de muertes por neoplasias malignas de cabeza y cuello (CID-10: C00- C14; C30-C32), que se publicó en el portal oficial del Ministerio de Salud del Brasil para el período, así como en los datos sobre la población residente. El patrón temporal y geográfico se analizó a través de la tasa de mortalidad estandarizada por edad (TMPI) y se evaluó como modelo de regresión por puntos de inflexión. Resultados: En el Brasil, la TMPI se mantuvo estable, independiente del género (AAPC: -0,3; IC95: -1,0-0,3) en el período evaluado. El estudio de las regiones brasileñas mostró un crecimiento medio de la TMPI independiente de género en el noreste (APC: 2,8; IC95: 2,1-3,5) y en el norte (AAPC: 1,3; IC95: 0,8-1,9), frente a la disminución media anual en el sur (AAPC: -1,4; CI95: -2,7­0,3) y en el sudeste (AAPC: -1,5; IC95: -1,9-1,1). En el Medio Oeste, el IPM también mostró una disminución promedio anual en el grupo femenino (AAPC: -1,8; IC95: -2,8-0,8), aunque se mantuvo estable en el grupo independiente masculino y de género. Consideraciones finales: la comprensión de estos datos puede ayudar a estudiar y aplicar estrategias para tratar este grupo de enfermedades de acuerdo con las necesidades específicas de cada grupo y región.

Comparison of Clinical and Pathological Staging in Patients with Head and Neck Cancer After Neck Dissection

Abstract Introduction Clinical and pathological staging plays an important role on the prognosis of head and neck cancer (HNC) patients. Objective The present study aims to compare clinical and pathological T, N and overall staging in patients with HNC, to identify factors associated with these discrepancies, and to analyze and compare survival or disease-free survival in staging disagreements. Methods Retrospective cohort including every patient submitted to neck dissection from January 2010 to December 2020 in the department of Otorhinolaryngology of a tertiary hospital center. Results A total of 79 patients were analyzed; their mean age was 58.52 ± 13.15 years old and 88.9% were male. Assessing overall staging, discrepancies were noted in 53% (36.4% upstaging and 16.6% downstaging) and were significantly associated with clinical overall staging (p = 0.006). Regarding T staging, differences were noted in 45.5% (30.3% upstaging and 15.2% downstaging) and were significantly associated with imaging modality (p = 0.016), clinical T staging (p = 0.049), and histology (p = 0.017). Discrepancies in N staging were noted in 38% (25.3% upstaging and 12.7% downstaging) and were significantly associated with age (p = 0.013), clinical N staging (p < 0.001), and presence of extranodal invasion (p < 0.001). Both in Overall, T, and N staging, the aforementioned disagreements were not associated with either higher mortality or higher disease relapse. Conclusion Overall, T, and N staging disagree in an important number of cases, and the overall stage can disagree in up to 53% of the cases. These disagreements do not seem to influence overall and disease-free survival.

Exosomes as a nano-carrier for Chemotherapeutics: a new era of oncology

Despite the considerable advancements in oncology, cancer remains one of the leading causes of death worldwide. Drug resistance mechanisms acquired by cancer cells and inefficient drug delivery limit the therapeutic efficacy of available chemotherapeutics drugs. However, studies have demonstrated that nano-drug carriers (NDCs) can overcome these limitations. In this sense, exosomes emerge as potential candidates for NDCs. This is because exosomes have better organotropism, homing capacity, cellular uptake, and cargo release ability than synthetic NDCs. In addition, exosomes can serve as NDCs for both hydrophilic and hydrophobic chemotherapeutic drugs. Thus, this review aimed to summarize the latest advances in cell-free therapy, describing how the exosomes can contribute to each step of the carcinogenesis process and discussing how these nanosized vesicles could be explored as nano-drug carriers for chemotherapeutics.

Host-directed therapies in pulmonary tuberculosis: Updates on anti-inflammatory drugs.

Tuberculosis (TB) is a lethal disease and remains one of the top ten causes of mortality by an infectious disease worldwide. It can also result in significant morbidity related to persistent inflammation and tissue damage. Pulmonary TB treatment depends on the prolonged use of multiple drugs ranging from 6 months for drug-susceptible TB to 6-20 months in cases of multi-drug resistant disease, with limited patient tolerance resulting from side effects. Treatment success rates remain low and thus represent a barrier to TB control. Adjunct host-directed therapy (HDT) is an emerging strategy in TB treatment that aims to target the host immune response to Mycobacterium tuberculosis in addition to antimycobacterial drugs. Combined multi-drug treatment with HDT could potentially result in more effective therapies by shortening treatment duration, improving cure success rates and reducing residual tissue damage. This review explores the rationale and challenges to the development and implementation of HDTs through a succinct report of the medications that have completed or are currently being evaluated in ongoing clinical trials.

ACCURACY OF ELASTOGRAPHY IN THE ASSESSMENT OF REDUCTION IN LIVER STEATOSIS AND FIBROSIS IN THE EARLY POSTOPERATIVE PERIOD AFTER BARIATRIC SURGERY.

BACKGROUND: Nonalcoholic hepatic steatosis is found in most obese patients and has a strong association with metabolic syndrome. The Roux-en-Y gastric bypass and the sleeve gastrectomy are the two techniques of bariatric surgery. Patients who underwent bariatric surgery have regression of nonalcoholic steatohepatitis due to a reduction in body mass index and changes in incretin hormones. AIMS: This study aimed to analyze the acuity of elastography in the regression of hepatic steatosis and fibrosis in obese patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy 2 months after surgery. METHODS: Patients in the preoperative period of bariatric surgery underwent an anthropometric evaluation and hepatic elastography to quantify fibrosis and hepatic steatosis. Two months after surgery, the same evaluation was performed again. RESULTS: All 17 patients who met the inclusion criteria participated in the study. Out of this, nine underwent sleeve gastrectomy, and eight underwent Roux-en-Y gastric bypass. The Roux-en-Y gastric bypass group had lower fibrosis levels postoperatively compared to preoperatively (p=0.029, p<0.05). As for steatosis, patients who underwent Roux-en-Y gastric bypass had lower postoperative values (p=0.01, p<0.05). There was also a reduction in fibrosis postoperatively in the sleeve gastrectomy group compared to preoperatively (p=0.037, p<0.05). CONCLUSIONS: Elastography accurately demonstrated decreased hepatic steatosis and fibrosis in the early postoperative period of bariatric surgery. Moreover, Roux-en-Y gastric bypass and sleeve gastrectomy are suitable surgical methods to improve hepatic steatosis and fibrosis within 2 months postoperatively.

Immunologic Biomarkers in Peripheral Blood of Persons With Tuberculosis and Advanced HIV.

Introduction: Tuberculosis (TB) is a common opportunistic infection among people living with HIV. Diagnostic tests such as culture, Xpert-MTB-RIF, and ULTRA have low sensitivity in paucibacillary TB disease; a blood biomarker could improve TB diagnostic capabilities. We assessed soluble factors to identify biomarkers associated with TB among persons with advanced HIV. Methods: A case-control (1:1) study was conducted, with participants from Rio de Janeiro and Manaus, Brazil. People living with HIV presenting with CD4 count ≤100 cells/mm3 were eligible to participate. Cases had culture-confirmed TB (N=15) (positive for Mycobacterium tuberculosis [Mtb]); controls had HIV-infection only (N=15). Study visits included baseline, month 2 and end of TB therapy, during which samples of peripheral blood were obtained. A panel containing 29 biomarkers including cytokines, chemokines and growth factors was utilized to assess candidate biomarkers using Luminex technology in cryopreserved EDTA plasma samples. We used neural network analysis, based on machine learning, to identify biomarkers (single or in combination) that best distinguished cases from controls. Additional multi-dimensional analyses provided detailed profiling of the systemic inflammatory environment in cases and controls. Results: Median CD4 count and HIV-1 RNA load values were similar between groups at all timepoints. Persons with TB had lower body mass index (BMI) (median=19.6, Interquartile Range [IQR]=18.6-22.3) than controls (23.7; IQR: 21.8 = 25.5, p=0.004). TB coinfection was also associated with increased frequency of other comorbidities. The overall profile of plasma cytokines, chemokines and growth factors were distinct between the study groups at all timepoints. Plasma concentrations of IL-15 and IL-10 were on average lower in TB cases than in controls. When used in combination, such markers were able to discriminate between TB cases and controls with the highest degree of accuracy at each study timepoint. Conclusion: Among persons with advanced HIV, plasma concentrations of IL-15 and IL-10 can be used in combination to identify TB disease regardless of time on anti-TB treatment.

Accuracy of elastography in the assessment of reduction in liver steatosis and fibrosis in the early postoperative period after bariatric surgery / Acuidade da elastografia na avaliação da redução da esteatose e fibrose hepáticas no pós-operatório precoce pós cirurgia bariátrica

ABSTRACT BACKGROUND: Nonalcoholic hepatic steatosis is found in most obese patients and has a strong association with metabolic syndrome. The Roux-en-Y gastric bypass and the sleeve gastrectomy are the two techniques of bariatric surgery. Patients who underwent bariatric surgery have regression of nonalcoholic steatohepatitis due to a reduction in body mass index and changes in incretin hormones. AIMS: This study aimed to analyze the acuity of elastography in the regression of hepatic steatosis and fibrosis in obese patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy 2 months after surgery. METHODS: Patients in the preoperative period of bariatric surgery underwent an anthropometric evaluation and hepatic elastography to quantify fibrosis and hepatic steatosis. Two months after surgery, the same evaluation was performed again. RESULTS: All 17 patients who met the inclusion criteria participated in the study. Out of this, nine underwent sleeve gastrectomy, and eight underwent Roux-en-Y gastric bypass. The Roux-en-Y gastric bypass group had lower fibrosis levels postoperatively compared to preoperatively (p=0.029, p<0.05). As for steatosis, patients who underwent Roux-en-Y gastric bypass had lower postoperative values (p=0.01, p<0.05). There was also a reduction in fibrosis postoperatively in the sleeve gastrectomy group compared to preoperatively (p=0.037, p<0.05). CONCLUSIONS: Elastography accurately demonstrated decreased hepatic steatosis and fibrosis in the early postoperative period of bariatric surgery. Moreover, Roux-en-Y gastric bypass and sleeve gastrectomy are suitable surgical methods to improve hepatic steatosis and fibrosis within 2 months postoperatively.

RESUMO RACIONAL: A esteatose hepática não alcoólica é encontrada na maioria dos pacientes com obesidade e tem forte associação com a síndrome metabólica. O bypass gástrico em Y de Roux e a gastrectomia vertical são as duas técnicas de cirurgia bariátrica. Pacientes que são submetidos a cirurgia bariátrica tem regressão da esteatose hepática não alcoólica devido a redução do índice de massa corpórea e mudanças dos hormônios incretínicos. OBJETIVOS: analisar a acuidade da elastografia na regressão da esteatose e fibrose hepáticas em pacientes obesos submetidos a bypass gástrico em Y de Roux e gastrectomia vertical dois meses após a cirurgia. MÉTODOS: Pacientes em pré-operatório de cirurgia bariátrica foram submetidos a avaliação antropométrica e elastografia hepática para quantificação de fibrose e esteatose hepática. Dois meses após a cirurgia, a mesma avaliação foi realizada novamente. RESULTADOS: Dezessete pacientes preencheram todos os critérios de inclusão no estudo. Nove foram submetidos a gastrectomia vertical e 8 a bypass gástrico em Y de Roux. O grupo bypass gástrico em Y de Roux apresentou níveis de fibrose mais baixos no pós-operatório em comparação com o pré-operatório, (p=0,029, p<0,05). Quanto à esteatose, os pacientes que realizaram bypass gástrico em Y de Roux apresentaram valores menores no pós-operatório (p=0,01, p<0,05). No grupo gastrectomia vertical, também houve redução da fibrose no pós-operatório em relação ao pré-operatório (p=0,037, p<0,05). CONCLUSÕES: A elastografia mostrou acuidade para demonstrar diminuição da esteatose e fibrose hepáticas, no pós-operatório precoce de cirurgia bariátrica. Além disso, bypass gástrico em Y de Roux e gastrectomia vertical são métodos cirúrgicos adequados para melhorar a esteatose e fibrose hepática em um período de 2 meses de pós-operatório.

Relationship between upper limb physical performance tests and muscle strength of scapular, shoulder and spine stabilizers: A cross-sectional study.

INTRODUCTION: Performance tests of the upper limb have been frequently used in the evaluation of individuals to identify risk of injury and to determine improvement in physical performance. Understanding the variables related to the performance of the tests is important for better applicability and interpretation of test results. The aim of this cross-sectional study was to investige the correlation between isometric strength of scapular, shoulder and spine muscles with physical performance test of upper limb in men and women. EXPERIMENTAL: Forty-nine healthy and physically conditioned individuals, men (n = 24) (22,7 ± 3,2 years; 74,6 ± 8,1 Kg; 176,7 ± 7,1 cm) women (n = 25) (23 ± 2,7 years; 61,5 ± 9,1 Kg; 163,2 ± 5,6 cm), were evaluated for shoulder abductor isometric strength (S-ABD); Middle (MT) and lower (LT) trapezium; lateral shoulder rotators (S-LR); flexors (T-FLEX), lateral incliners (T-INCL), and trunk extenders (T-EXT). Evaluation of upper limb physical performance was carried out by Upper Quarter Y Balance test (YBT-UQ) and Chain upper extremity stability test (CKC-UEST). Pearson's test (r values) p ≤ 0.05 was used to analyze the correlation. RESULTS: The results reveal strong correlations between S-ABD and CKC-UEST in male group; and strong correlations in female group between S-ABD strength with CKC-UEST; and S-LR with all YBT-UQ directions and score and between T-EXT strength with CKC-UEST. CONCLUSION: Therefore, strength of shoulder and spine stabilizers influences performance in upper limb tests, but with different correlations as to sex. To improve test performance, it may be important to increase the strength of the shoulder and spine muscles.