Outcomes of childhood TB in countries with a universal BCG vaccination policy.

TB remains an important cause of childhood morbidity and mortality. Underdiagnosis, underreporting and limited data on the outcomes of childhood TB have led to an underestimation of its impact.This was a systematic review to characterise childhood TB outcomes. Studies reporting relevant epidemiological data on children between 0 and 14 years of age, with a particular focus on treatment outcomes, from countries with universal bacilli Calmette-Guérin (BCG) vaccination and conducted between 2000 and 2020 were selected. Random effects meta-analysis was performed in R software.We identified 1,806 references and included 35 articles. Among children with TB, the overall proportion of unfavourable outcomes was 19.5% (95% CI 14.4-25.8) and pooled case-fatality ratio was 6.1% (95% CI 4.3-8.4). The proportion of deaths observed among children between 0 and 4 years old was 6.6% (95% CI 4.9-8.7) and 4.6% (95% CI 3.1-6.9) in older children. TB and HIV co-infected children presented a case-fatality ratio of 15.1% (95% CI 7.9-27.0).Despite the efforts made in the last decades, treatment outcomes in childhood TB are still worrisome. Efforts to fill existing gaps and design health policies targeting vulnerable populations, such as children, should be intensified to tackle the global TB burden..

Spectrophotometric Analysis of Apical Extrusion of Sodium Hypochlorite using Different Irrigation Protocols in an Ex Vivo Model of Immature Teeth.

OBJECTIVE: To evaluate the effect of different agitation methods on apical extrusion of 1.5% sodium hypochlorite (NaOCl) in an ex vivo model of immature teeth. METHODS: Sixty extracted human inferior incisors were prepared to simulate immature teeth and embedded in an artificial root socket made of silicone impression material. The teeth were then divided into four groups: Conventional needle irrigation (CNI) alone, CNI supplemented with Ultrasonic Irrigant Activation (UIA), EasyClean (EC), or XP-endo Finisher (XPF). Extruded NaOCl was collected, reacted with m-cresol purple, and its absorbance values were measured. The data were statistically analyzed using One-way analysis of variance with a significance level of 5%. RESULTS: All groups showed apically extruded irrigating solution, and the mean volumes of extruded NaOCl did not differ significantly between any of the test groups (p⟩0.05). CONCLUSION: The activation of 1.5% NaOCL by UIA, EC, or XPF as supplementary to CNI does not promote greater apical extrusion when compared to CNI alone in simulated immature teeth.

[Clinical characteristics and follow-up of 60 patients with recent diagnosis of giant cell arteritis, NEWTON study]. / Caractéristiques et profils évolutifs des patients avec un diagnostic récent d'artérite à cellules géantes, étude NEWTON.

INTRODUCTION: The management of giant cell arteritis (GCA) has evolved with the arrival of tocilizumab (TCZ) and the use of PET/CT. Our objective is to describe the characteristics and followup of patients with recent diagnosis of GCA in current care. PATIENTS AND METHODS: The NEWTON cohort is a monocentric retrospective cohort based on data collected from 60 GCA patients diagnosed between 2017 and 2022 according to the ACR/EULAR 2022 criteria. RESULTS: The median age at diagnosis was 73 [68.75; 81] years old. At diagnosis, the main manifestations were unusual temporal headaches in 48 (80 %) and an inflammatory syndrome in 50 (83 %) patients. Temporal artery biopsy confirmed the diagnosis in 49/58 (84 %) patients. Doppler of the temporal arteries found a halo in 12/23 (52 %) patients. The PET/CT found hypermetabolism in 19/43 (44 %) patients. Prednisone was stopped in 17.5 [12.75; 24.25] months. During follow-up, 22 (37 %) patients received TCZ. At least one complication of corticosteroid therapy was observed in 22 (37 %) patients. After a median follow-up of 24 [12; 42] months, 25 (42 %) patients relapsed. At the end of the follow-up, 29 (48.3 %) patients were weaned from corticosteroid therapy and 15 (25 %) were on TCZ. CONCLUSION: Despite the increasing use of TCZ in the therapeutic arsenal and of the PET/CT in the imaging tools of GCA patients, relapses and complications of corticosteroid therapy remain frequent, observed in more than a third of patients.

Predictive toxicological effects of Artemisia absinthium essential oil on hepatic stellate cells.

Medicinal plants are important worldwide, considering their properties for treating diseases; however, few studies have evaluated their toxicological potential. Among them, Artemisia absinthium is frequently used to treat liver diseases, because its essential oil has several popular therapeutic properties. Based on this information, in the present study, we investigated molecular connectors of physiological effects of the Artemisia absinthium essential oil on human hepatic stellate cell line, LX-2, to explore the potential toxicity of the plant on liver cells. LX-2 is a cellular model to investigate mechanisms of liver fibrosis; then, to analyze the essential oil effects LX-2 was cultured under different conditions, treated or not with the essential oil at 0.4 µg/µL for 24 h. Next, fluorescence microscopy analyses, gene expression measurements, and biochemical approaches revealed that the essential oil reduced pro-fibrogenic markers; however, disrupt lipid metabolism, and cause cellular stress, by the activation of cellular detoxification and pro-inflammatory processes. In conclusion, the hepatic stellate cells incubated with the essential oil present an antifibrotic potential, supporting its popular use; however, the combined results suggest that the essential oil of Artemisia absinthium should be used with caution.

Research progress on biodegradable polymeric platforms for targeting antibiotics to the bone.

The treatment of bone infections still involves systemic or local antibiotic therapy in high doses for prolonged periods. Current research focuses on the application of different drug delivery systems to the bone, aiming at a targeted local administration that will decrease the number of drugs used and their toxicity, compared to the systemic route. The gold standard in clinical practice is currently poly(methyl methacrylate) (PMMA) cement. The main drawback of PMMA, however, is that it is non-biodegradable, requiring a second follow-up surgery to remove the implant. Biodegradable delivery systems, on the other hand, are easily resorbable within the organism, and less invasive alternative with better patient compliance. Among biodegradable materials, natural and synthetic polymers are being studied as local drug delivery systems due to their excellent biocompatibility, sustained effect, and antibiotic release with high penetrability to infected bone and soft tissue. In this review, we focus on biodegradable polymeric platforms, such as micro- and nanoparticles, scaffolds, and hydrogels, as well as multi-delivery systems for targeting antibiotics to the bone. Additionally, we discuss the reported drug release profiles that provide important information about the systems' functionality.

The Effects of Different Exercise Training Types on Body Composition and Physical Performance in Older Adults with Sarcopenic Obesity: A Systematic Review and Meta-Analysis.

OBJECTIVES: To carry out a systematic review and meta-analysis to verify the effects of different exercise training types on body composition and physical performance in older adults with sarcopenic obesity (SO). DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Older adults (≥60 years). METHODS: Database searches were performed in MEDLINE (via PubMed), EMBASE, Cochrane Library, Web of Science, SCOPUS, and LILACS on January 10th, 2023. We included: randomized and/or controlled clinical trials; physical exercise as an intervention; analysis of body composition and/or muscle function; and sarcopenic obesity diagnosis. We used the Risk of Bias 2 tool and PEDro scale. The GRADE certainty of evidence was also performed. RESULTS: Fourteen studies were included in the systematic review and nine studies in the meta-analysis. A decrease in body fat (%) favoring the exercise group was identified (SMD: -0.34 [95% CI: -0.53 to -0.16]; p=0.0003) (GRADE: ⊕⊕⊕◯ Moderate). Only resistance training showed fat reduction (SMD: -0.27 [95% CI: -0.48 to -0.06]; p=0.01). Increases in upper (SMD: 0.41 [95% CI: 0.04 to 0.78]; p=0.03) (GRADE: ⊕⊕◯◯ Low) and lower (SMD: 0.80 [95% CI: 0.22 to 1.39]; p=0.007) (GRADE: ⊕⊕⊕⊕ High) limb strength was identified with exercise. Chair stand test showed increases with exercise (SMD: 0.73 [95% CI: 0.40 to 1.07]; p<0.0001) (GRADE: ⊕⊕⊕⊕ High), especially for resistance training (SMD: 0.62 [95% CI: 0.21 to 1.02]; p=0.003) and combined training (SMD: 0.99 [95% CI: 0.40 to 1.57]; p=0.0005). The PEDro scale for the studies in our review ranged from 3 to 8 (mean = 5.8 (1.6)), meaning fair methodological quality, and most studies were overall judged with at least low/some concerns in terms of risk of bias. CONCLUSION AND IMPLICATIONS: Overall, moderate to high certainty of evidence was found for body fat, lower limb strength, and chair stand test. On the other hand, low certainty of evidence was found for upper limb strength. Resistance, combined, and aerobic training evoked divergent results between the variables analyzed. Although promising, our results should be considered sparingly, but may guide additional exercise recommendations to improve specific health parameters in older adults with SO.

Supplementing Ca salts of soybean oil via low-moisture molasses-based blocks to improve reproductive performance and overall productivity of beef cows.

This experiment evaluated reproductive and productive responses of beef cows receiving self-fed low-moisture blocks (LMB) enriched or not with Ca salts of soybean oil (CSSO) throughout the breeding season. Non-pregnant, suckled multiparous Angus-influenced cows were assigned to a fixed-time artificial insemination (AI) protocol (day -10 to 0) followed by natural service (day 15-70). Cows were managed in 12 groups (46 ± 4 cows/group) maintained in individual pastures, and groups received LMB enriched with 25 % (as-fed basis) of CSSO or ground corn (CON) from day - 10 to 100. Both treatments were designed to yield a daily LMB intake of 0.454 kg/cow (as-fed basis). Cows receiving CSSO had greater (P < 0.01) mean concentrations of ω-6 fatty acids in plasma samples collected on days 0 and 55. Cows receiving CSSO had greater (P = 0.05) pregnancy rate to fixed-time AI (67.2 vs. 59.3 %), whereas final pregnancy rate did not differ (P = 0.92) between treatments. Pregnancy loss was less (P = 0.03) in CSSO cows (4.50 vs. 9.04 %), which also calved earlier during the calving season (treatment × week; P = 0.04). Weaning rate tended to be greater (P = 0.09) in CSSO (84.8 vs. 79.4 %), although calf weaning age and weight did not differ (P ≥ 0.72) between treatments. Kilos of calf weaned/cow exposed was greater (P = 0.04) in CSSO cows (234 vs. 215 kg). Therefore, supplementing CSSO to beef cows via LMB during the breeding season improved their reproductive and overall productivity during a cow-calf cycle.

Poly(DL-lactic acid) scaffolds as a bone targeting platform for the co-delivery of antimicrobial agents against S. aureus-C.albicans mixed biofilms.

New strategies for the treatment of polymicrobial bone infections are required. In this study, the co-delivery of two antimicrobials by poly(D,L-lactic acid) (PDLLA) scaffolds was investigated in a polymicrobial biofilm model. PDLLA scaffolds were prepared by solvent casting/particulate leaching methodology, incorporating minocycline and voriconazole as clinically relevant antimicrobial agents. The scaffolds presented a sponge-like appearance, suitable to support cell proliferation and drug release. Single- and dual-species biofilm models of Staphylococcus aureus and Candida albicans were developed and characterized. S. aureus presented a higher ability to form single-species biofilms, compared to C. albicans. Minocycline and voriconazole-loaded PDLLA scaffolds showed activity against S. aureus and C. albicans single- and dual-biofilms. Ultimately, the cytocompatibility/functional activity of PDLLA scaffolds observed in human MG-63 osteosarcoma cells unveil their potential as a next-generation co-delivery system for antimicrobial therapy in bone infections.

Using rumination and activity data for early detection of anaplasmosis disease in dairy heifer calves.

Bovine anaplasmosis causes considerable economic losses in dairy cattle production systems worldwide, ranging from $300 million to $900 million annually. It is commonly detected through rectal temperature, blood smear microscopy, and packed cell volume (PCV). Such methodologies are laborious, costly, and difficult to systematically implement in large-scale operations. The objectives of this study were to evaluate (1) rumination and activity data collected by Hr-Tag sensors (SCR Engineers Ltd.) in heifer calves exposed to anaplasmosis; and (2) the predictive ability of recurrent neural networks in early identification of anaplasmosis. Additionally, we aimed to investigate the effect of time series length before disease diagnosis (5, 7, 10, or 12 consecutive days) on the predictive performance of recurrent neural networks, and how early anaplasmosis disease can be detected in dairy calves (5, 3, and 1 d in advance). Twenty-three heifer calves aged 119 ± 15 (mean ± SD) d and weighing 148 ± 20 kg of body weight were challenged with 2 × 107 erythrocytes infected with UFMG1 strain (GenBank no. EU676176) isolated from Anaplasma marginale. After inoculation, animals were monitored daily by assessing PCV. The lowest PCV value (14 ± 1.8%) and the finding of rickettsia on blood smears were used as a criterion to classify an animal as sick (d 0). Rumination and activity data were collected continuously and automatically at 2-h intervals, using SCR Heatime Hr-Tag collars. Two time series were built including last sequence of -5, -7, -10, or -12 d preceding d 0 or a sequence of 5, 7, 10, or 12 d randomly selected in a window from -50 to -15 d before d 0 to ensure a sequence of days in which PCV was considered normal (32 ± 2.4%). Long short-term memory was used as a predictive approach, and a leave-one-animal-out cross-validation (LOAOCV) was used to assess prediction quality. Anaplasmosis disease reduced 34 and 11% of rumination and activity, respectively. The accuracy, sensitivity, and specificity of long short-term memory in detecting anaplasmosis ranged from 87 to 98%, 83 to 100%, and 83 to 100%, respectively, using rumination data. For activity data, the accuracy, sensitivity, and specificity varied from 70 to 98%, 61 to 100%, and 74 to 100%, respectively. Predictive performance did not improve when combining rumination and activity. The use of longer time-series did not improve the performance of models to predict anaplasmosis. The accuracy and sensitivity in predicting anaplasmosis up to 3 d before clinical diagnosis (d 0) were greater than 80%, confirming the possibility for early identification of anaplasmosis disease. These findings indicate the great potential of wearable sensors in early identification of anaplasmosis diseases. This could positively affect the profitability of dairy farmers and animal welfare.

Discovery of serum biomarkers for diagnosis of tuberculosis by NMR metabolomics including cross-validation with a second cohort.

BACKGROUND: Tuberculosis (TB) is a disease with worldwide presence and a major cause of death in several developing countries. Current diagnostic methodologies often lack specificity and sensitivity, whereas a long time is needed to obtain a conclusive result. METHODS: In an effort to develop better diagnostic methods, this study aimed at the discovery of a biomarker signature for TB diagnosis using a Nuclear Magnetic Resonance based metabolomics approach. In this study, we acquired 1H NMR spectra of blood serum samples of groups of healthy subjects, individuals with latent TB and of patients with pulmonary and extra-pulmonary TB. The resulting data were treated with uni- and multivariate statistical analysis. RESULTS: Six metabolites (inosine, hypoxanthine, mannose, asparagine, aspartate and glutamate) were validated by an independent cohort, all of them related with metabolic processes described as associated with TB infection. CONCLUSION: The findings of the study are according with the WHO Target Product Profile recommendations for a triage test to rule-out active TB.

Left atrial ejection fraction is an indicator of left ventricular diastolic function.

Left atrial ejection fraction (LAEF) has been previously shown to accurately distinguish between patients with and without clearly defined left ventricle diastolic dysfunction (LVDD) by ASE/EACVI criteria, but indeterminate cases were excluded. We sought to determine if LAEF could accurately distinguish between normal, indeterminate and LVDD patients. A retrospective cohort of 125 patients who underwent transthoracic echocardiography was studied. Comprehensive echocardiographic study was performed with measurement of validated diastolic parameters. Subjects were assigned LVDF ASE/EACVI categories. ANOVA test was used to compare means between groups and binary logistic regression and ROC curves to assess diagnostic accuracy. Mean LAEF was statistically different between groups (p < 0.001): 56.3% ± 4.5 for normal patients, 50.2% ± 5.5 for indeterminate patients and 44% ± 8.5 for patients with LVDD. LAEF distinguished LVDD from patients without diastolic dysfunction (OR = 0.73, 95% CI 0.63-0.65, p < 0.001) and ROC curve reveals excellent discriminative power (AUC 0.91, 95% CI 0.84-0.97, p < 0.001). LAEF also distinguished indeterminate patients from LVDD (OR = 0.9, 95% CI 0.83-0.95, p < 0.001) and ROC curve revealed good discriminative power (AUC 0.72, 95% CI 0.62-0.82, p < 0.001). LAEF can accurately differentiate between normal, indeterminate and LVDD patients and could be considered as an additional parameter in the study of diastolic function.

Development of an automated sensor for in-situ continuous monitoring of streambed sediment height of a waterway.

The sedimentary processes play a major role in every aquatic ecosystem, however, there are few automated options for in-situ monitoring of sediment displacement in the streambed of waterways. We present an automated optical instrument for in-situ continuous monitoring of sediment deposition and erosion of the streambed that requires no calibration. With a production cost of 32€, power consumption of 300 µA in sleep mode, and capacity to monitor the bedform of a waterway, the sensor was developed to evaluate the sediment dynamics of coastal areas with a wide spatial and temporal resolution. The novel device is intended to be buried in the sand and uses 32 infrared channels to monitor the streambed sediment height. For testing purposes, a maximum measuring length of 160 mm and 5 mm resolution was chosen, but these values are scalable. Sensors can be built with different ranges and precision according to the needs of the fieldwork. A laboratory experiment was conducted to demonstrate the working principle of the instrument and its behaviour regarding the turbidity originated by suspended sediment and the settling and deposition of the suspended particles. The device was deployed for 119 days in an estuarine area and was able to detect patterns in the sediment deposition and resuspension during the tidal cycles. Also, abnormal events occurred during the experiment as floods and algae blooms. During these events, the sensor was able to record exceptional erosion and sediment deposition rates. The reported automated instrument can be broadly used in sedimentary studies or management and planning of fluvial and maritime infrastructures to provide real-time information about the changes in the bedform of the watersheds.

Insulin stimulates ß-alanine uptake in skeletal muscle cells in vitro.

We evaluated whether insulin could stimulate ß-alanine uptake by skeletal muscle cells in vitro. Mouse myoblasts (C2C12) (n = 3 wells per condition) were cultured with ß-alanine (350 or 700 µmol·L-1), with insulin (100 µU·mL-1) either added to the media or not. Insulin stimulated the ß-alanine uptake at the lower (350 µmol·L-1) but not higher (700 µmol·L-1) ß-alanine concentration in culture medium, indicating that transporter saturation might blunt the stimulatory effects of insulin.

Glass Ionomer Versus Self-adhesive Cement and the Clinical Performance of Zirconia Coping/Press-on Porcelain Crowns.

OBJECTIVE: This split-mouth clinical study investigated the effect of luting cement on the performance of veneered yttrium-stabilized tetragonal zirconia polycrystal (Y-TZP) zirconia crowns. METHODS AND MATERIALS: A total of 60 crowns prepared with Y-TZP coping and press-on porcelain were made with a split-mouth design in 30 participants. The crowns were cemented either with glass ionomer cement (GIC) (Meron, Voco) or with self-adhesive resin cement (Bifix-SE, Voco). The restorations were assessed immediately after treatment and after 6, 12, 24, 36, and 48 months using the modified United States Public Health Service criteria. The parameters analyzed were retention, color stability, marginal discoloration, marginal adaptation, surface roughness, anatomic form, and secondary caries. The differences between the groups were analyzed by the Fisher exact test in each period of evaluation. The survival rate was analyzed with the Kaplan-Meier and log-rank test (α=0.05). RESULTS: After 48 months, 20 participants attended the recall. During the period of evaluation, 1 crown cemented with glass ionomer cement and 1 crown cemented with resin cement lost retention. Color match, marginal discoloration and adaptation, surface roughness, and anatomic form did not change in any of the periods evaluated, and no secondary caries was observed. No significant differences were found between the 2 luting cements for any of the clinical parameters analyzed, nor for the survival rates during the study. CONCLUSIONS: The type of cement did not influence the performance of the crowns after 48 months of clinical use. Both cements resulted in adequate retention rates, aesthetic and functional outcomes, and biological response.

Synergistic effect of serine protease inhibitors and a bothropic antivenom in reducing local hemorrhage and coagulopathy caused by Bothrops jararaca venom.

Snakebite accidents are a public health problem that affects the whole world, causing thousands of deaths and amputations each year. In Brazil, snakebite envenomations are caused mostly by snakes from the Bothrops genus. The local symptoms are characterized by pain, swelling, ecchymosis, and hemorrhages. Systemic disturbances can lead to necrosis and amputations. The present treatment consists of intravenous administration of bothropic antivenom, which is capable of reversing most of the systemic symptoms, while presenting limitations to treat the local effects, such as hemorrhage and to neutralize the snake venom serine protease (SVSP). In this context, we aimed to evaluate the activity of selective serine protease inhibitors (pepC and pepB) in combination with the bothropic antivenom in vivo. Further, we assessed their possible synergistic effect in the treatment of coagulopathy and hemorrhage induced by Bothrops jararaca venom. For this, we evaluated the in vivo activity in mouse models of local hemorrhage and a series of in vitro hemostasis assays. Our results showed that pepC and pepB, when combinated with the antivenom, increase its protective activity in vivo and decrease the hemostatic disturbances in vitro with high selectivity, possibly by inhibiting botropic proteases. These data suggest that the addition of serine protease inhibitor to the antivenom can improve its overall potential.

Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2.

The oral cavity, an essential part of the upper aerodigestive tract, is believed to play an important role in the pathogenicity and transmission of SARS-CoV-2. The identification of targeted antiviral mouth rinses to reduce salivary viral load would contribute to reducing the COVID-19 pandemic. While awaiting the results of significant clinical studies, which to date do not exist, the commercial availability of mouth rinses leads us to search among them for reagents that would have specific antiviral properties with respect to SARS-CoV-2. The challenges facing this target were examined for 7 reagents found in commercially available mouth rinses and listed on the ClinicalTrials.gov website: povidone-iodine, chlorhexidine, hydrogen peroxide, cyclodextrin, Citrox, cetylpyridinium chloride, and essential oils. Because SARS-CoV-2 is an enveloped virus, many reagents target the outer lipid membrane. Moreover, some of them can act on the capsid by denaturing proteins. Until now, there has been no scientific evidence to recommend mouth rinses with an anti-SARS-CoV-2 effect to control the viral load in the oral cavity. This critical review indicates that current knowledge of these reagents would likely improve trends in salivary viral load status. This finding is a strong sign to encourage clinical research for which quality protocols are already available in the literature.

Effectiveness of contact tracing and quarantine on reducing COVID-19 transmission: a retrospective cohort study.

OBJECTIVES: Contact tracing and quarantine are common measures used in the management of infectious disease outbreaks. However, few studies have measured their impact on the control of the COVID-19 pandemic. This study aimed to assess the effectiveness of those measures on reducing transmission of severe acute respiratory syndrome coronavirus 2 in a community setting. STUDY DESIGN: The study design is a retrospective cohort study. METHODS: A retrospective cohort study of COVID-19 cases notified in Eastern Porto from March 1st to April 30th, 2020 was performed. Intervention and control cohorts were defined based on whether cases were subjected to contact tracing and quarantine measures before the laboratory confirmation of disease. The number of secondary cases per index case and the proportion of cases with subsequent secondary cases were the primary outcomes. Secondary outcomes included the time from symptom onset to specimen collection and the number of close contacts. The analysis was stratified according to whether national lockdown measures had already been implemented. RESULTS: The intervention and control cohorts comprised 98 and 453 cases, respectively. No differences were observed concerning primary outcomes. The intervention group had a shorter time between symptom onset and specimen collection (median: 3 days, interquartile range [IQR]: 1-6, vs. median: 5 days, IQR: 2-7, P-value = 0.004) and fewer close contacts (median: 0, IQR: 0-2, vs. median: 2, IQR: 1-4, P-value<0.001). The stratified analysis returned similar results. CONCLUSION: Local public health measures were effective in reducing the time between symptom onset and laboratory diagnosis and the number of close contacts per case. No effect was apparent on secondary case figures, suggesting that further measures may be required.