Miracle-dz/UniFAR-FTUs huggingface dataset:
Adherence to antiretroviral therapy among people living with HIV/AIDS in northeastern Brazil: a cross-sectional study

ABSTRACT BACKGROUND: Nonadherence to antiretroviral therapy (ART) may lead to viral replication and development of antiretroviral resistance. OBJECTIVE: To identify the factors associated with nonadherence to ART among people living with the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA). DESIGN AND SETTING: Cross-sectional study in a tertiary-level hospital in northeastern Brazil. METHODS: Intake of less than 90% of the antiretroviral drugs prescribed in the last week prior to the interview was defined as nonadherence. Intake was evaluated using a questionnaire. Descriptive and multivariate analyses were conducted on the study population, with estimation of the respective odds ratios and 95% confidence intervals. RESULTS: The prevalence of nonadherence was 28.4%. Significant associations were found regarding the following variables: age less than 35 years, smoking, sedentary lifestyle, lack of medication and lack of knowledge regarding the patient’s HIV status, on the part of the patient’s partner or family. CONCLUSIONS: Encouragement of adherence to antiretroviral therapy is one of the fundamental pillars of treatment for HIV-infected patients. The high proportion of nonadherence (28.4%) and the predictive factors related to this indicate that it is necessary to improve patients’ adherence to antiretroviral therapy.
Response to mechanical loading in rat Achilles tendon healing is influenced by the microbiome

We have previously shown that changes in the microbiome influence how the healing tendon responds to different treatments. The aim of this study was to investigate if changes in the microbiome influence the response to mechanical loading during tendon healing. 90 Sprague-Dawley rats were used. Specific Opportunist and Pathogen Free (SOPF) rats were co-housed with Specific Pathogen Free (SPF) rats, carrying Staphylococcus aureus and other opportunistic microbes. After 6 weeks of co-housing, the SOPF rats were contaminated which was confirmed by Staphylococcus aureus growth. Clean SOPF rats were used as controls. The rats were randomized to full loading or partial unloading by Botox injections in their calf muscles followed by complete Achilles tendon transection. Eight days later, the healing tendons were tested mechanically. The results were analysed by a 2-way ANOVA with interaction between loading and contamination on peak force as the primary outcome and there was an interaction for both peak force (p = 0.049) and stiffness (p = 0.033). Furthermore, partial unloading had a profound effect on most outcome variables. In conclusion, the response to mechanical loading during tendon healing is influenced by changes in the microbiome. Studies aiming for clinical relevance should therefore consider the microbiome of laboratory animals.
Origanum majorana Essential Oil Triggers p38 MAPK-Mediated Protective Autophagy, Apoptosis, and Caspase-Dependent Cleavage of P70S6K in Colorectal Cancer Cells

Colorectal cancer (CRC) is the third most common type of cancer in terms of incidence and mortality worldwide. Here we have investigated the anti-colon cancer potential of Origanum majorana essential oil (OMEO) and its underlying mechanisms of action. We showed that OMEO significantly inhibited the cellular viability and colony growth of human HT-29 colorectal cancer cells. OMEO induced protective autophagy, associated with downregulation of the mTOR/p70S6K pathway, and activated caspase-8 and caspase-9-dependent apoptosis. Blockade of autophagy with 3-methyladenine (3-MA) and chloroquine (CQ), two autophagy inhibitors, potentiated the OMEO-induced apoptotic cell death. Inversely, inhibition of apoptosis with the pan-caspase inhibitor, Z-VAD-FMK, significantly reduced cell death, suggesting that apoptosis represents the main mechanism of OMEO-induced cell death. Mechanistically, we found that OMEO induces protective autophagy and apoptotic cells death via the activation of the p38 MAPK signaling pathway. Pharmacological inhibition of p38 MAPK by the p38 inhibitors SB 202190 and SB 203580 not only significantly decreased apoptotic cell death, but also reduced the autophagy level in OMEO treated HT-29 cells. Strikingly, we found that OMEO also induces p38 MAPK-mediated caspase-dependent cleavage of p70S6K, a protein reported to be overexpressed in colon cancer and associated with drug resistance. Our findings suggest that OMEO inhibits colon cancer through p38 MAPK-mediated protective autophagy and apoptosis associated with caspase-dependent cleavage of p70S6K. To the best of our knowledge, this study is the first to report on the implications of the p38 MAPK signaling pathway in targeting p70S6K to caspase cleavage.
A Frameshift Mutation in wcaJ Associated with Phage Resistance in Klebsiella pneumoniae

Phage therapy is a potential and promising avenue for controlling the emergence and spread of multidrug-resistant (MDR) Klebsiella pneumoniae, however, the rapid development of anti-phage resistance has been identified as an obstacle to the development of phage therapy. Little is known about the mechanism employed by MDR K. pneumoniae strains and how they protect themselves from lytic phage predation in vitro and in vivo. In this study, comparative genomic analysis shows undecaprenyl-phosphate glucose-1-phosphate transferase (WcaJ), the initial enzyme catalyzing the biosynthesis of colanic acid, is necessary for the adsorption of phage 117 (Podoviridae) to the host strain Kp36 to complete its lytic life cycle. In-frame deletion of wcaJ alone was sufficient to provide phage 117 resistance in the Kp36 wild-type strain. Complementation assays demonstrated the susceptibility of phage 117, and the mucoid phenotype could be restored in the resistant strain Kp36-117R by expressing the wild-type version of wcaJ. Remarkably, we found that bacterial mobile genetic elements (insA and insB) block phage 117 infections by disrupting the coding region of wcaJ, thus preventing phage adsorption to its phage receptor. Further, we revealed that the wcaJ mutation likely occurred spontaneously rather than adapted by phage 117 predation under unfavorable environments. Taken together, our results address a crucial evolutionary question around the mechanisms of phage–host interactions, increasing our current understandings of anti-phage defense mechanisms in this important MDR pathogen.
Lumbar Erector Spinae Plane Block as a Main Anesthetic Method for Hip Surgery in High Risk Elderly Patients: Initial Experience with a Magnetic Resonance Imaging.

Objective Since initial description by Forero for thoracic region, ultrasound guided erector spinae plane (ESP) block has experienced several surgeries for postoperative pain management, chronic pain or surgical anesthesia. Although ESP block has been reported to provide effective analgesia in the thoracic region, its effect in lumbar region still unclear. In this study we aimed to showed our successful experience with lumbar ESP block as a main anesthetic technique in fifteen high risk elderly patients undergoing hip surgery with mild propofol sedation. Materials and Methods In this observational study high risk elderly fifteen patients received lumbar ESP block as a main anesthetic technique with mild propofol sedation. 40 mL of local anesthetic mixture (20 mL bupivacaine 0.5%, 10 mL lidocaine 2%, and 10 mL normal saline) was administered between the erector spinae muscles and transverse process at the level of the 4th lumbar vertebra. Also we demonstrate magnetic resonance images and discuss the anatomic basis of lumbar ESP block. Results All patients' surgeries were completed without requirement for general anesthesia or local anesthesia infiltration of the surgical site. All patients' pain scores were <2/10 in the recovery room. Significant contrast spread was observed between the Th12 and L5 transverse process and erector spinae muscle and between multifidus muscle and iliocostal muscle at the L2-4 levels. Contrast material was observed at the anterior of the transverse process spreading to the paravertebral, foraminal and partially epidural area/spaces and also in the areas where the lumbar nerves enter the psoas muscle. Conclusion Lumbar ESP block when combined with mild sedoanalgesia provides adequate and safe anesthesia in high risk elderly patients undergoing hip surgery.
Parental use of 'cry it out' in infants: no adverse effects on attachment and behavioural development at 18 months.

BACKGROUND Leaving infant to cry it out has been the subject of discussion among researchers and parents. Nevertheless, there is paucity of empirical research investigating the association between leaving infant to cry it out and consequent crying duration and frequency, mother-infant attachment and behavioural development. METHODS The sample with complete longitudinal data comprised 178 infants and their caretakers. Parental use of 'leaving infant to cry out' and cry duration were assessed with maternal report at term, 3, 6 and 18 months, and frequency of crying was assessed at term, 3 and 18 months of age. Attachment was measured at 18 months using the strange situation procedure. Behavioural development of the infant was assessed with two observational measures and a parent-report questionnaire at 18 months. RESULTS The use of 'leaving infant to crying' was rare at term and increased over the next 18 months. 'Leaving infants to cry it out' at term was associated with a decrease in crying frequency at 3 months. Furthermore, leaving infants to cry it out a few times at term and often at 3 months was associated with shorter fuss/cry duration at 18 months of age. No adverse impacts of leaving infants to cry it out in the first 6 months on infant-mother attachment and behavioural development at 18 months were found. CONCLUSIONS Contemporary practice of some parents in the United Kingdom to occasionally or often 'leaving infant to cry it out' during the first 6 months was not associated with adverse behavioural development and attachment at 18 months. Increased use of 'leaving to cry it out' with age may indicate differential responding by parents related to infant self-regulation.
Prediction of Poor Responders to Neoadjuvant Chemotherapy in Patients with Osteosarcoma: Additive Value of Diffusion-Weighted MRI including Volumetric Analysis to Standard MRI at 3T

Objective To evaluate the added value of diffusion weighted image (DWI) including volumetric analysis to standard magnetic resonance imaging (MRI) for predicting poor responders to neoadjuvant chemotherapy in patients with osteosarcoma at 3-Tesla. Methods 3-Tesla Standard MRI and DWI in 17 patients were reviewed by two independent readers. Standard MRI was reviewed using a five-level-confidence score. Two-dimensional (2D) apparent diffusion coefficient (ADC)mean and 2D ADCminimum were measured from a single-section region of interest. An ADC histogram derived from whole-tumor volume was generated including 3D ADCmean, 3D ADCskewness, and 3D ADCkurtosis. The Mann-Whitney-U test, receiver operating characteristic curve with area under the curve (AUC) analysis, and multivariate logistic regression analysis were performed. Results There were 13 poor responders and 4 good responders. Statistical differences were found in posttreatment and percent change of both 2D ADCmean and 2D ADCminimum, posttreatment 3D ADCmean, and posttreatment 3D ADCskewness between two groups. The best predictors of poor responders were posttreatment 2D ADCmean and posttreatment 3D ADCskewness. Sensitivity and specificity of the 1st model (standard MRI alone), 2nd model (standard MRI+posttreatment 2D ADCmean), and 3rd model (standard MRI+posttreatment 2D ADCmean+posttreatment 3D ADCskewness) were 85% and 25%, 85% and 75%, and 85% and 100% for reader 1 and 77% and 25%, 77% and 50%, and 85% and 100% for reader 2, respectively. The AUC of the 1st, 2nd, and 3rd models were 0.548, 0.798, and 0.923 for reader 1 and 0.510, 0.635, and 0.923 for reader 2, respectively. Conclusion The addition of DWI including volumetric analysis to standard MRI improves the diagnostic accuracy for predicting poor responders to neoadjuvant chemotherapy in patients with osteosarcoma at 3-Tesla.
Flavin-Containing Monooxygenase 1 Catalyzes the Production of Taurine from Hypotaurine

Taurine is one of the most abundant amino acids in mammalian tissues. It is obtained from the diet and by de novo synthesis from cysteic acid or hypotaurine. Despite the discovery in 1954 that the oxygenation of hypotaurine produces taurine, the identification of an enzyme catalyzing this reaction has remained elusive. In large part, this is due to the incorrect assignment, in 1962, of the enzyme as an NAD-dependent hypotaurine dehydrogenase. For more than 55 years, the literature has continued to refer to this enzyme as such. Here we show, both in vivo and in vitro, that the enzyme that oxygenates hypotaurine to produce taurine is flavin-containing monooxygenase (FMO) 1. Metabolite analysis of the urine of Fmo1-null mice by 1H NMR spectroscopy revealed a buildup of hypotaurine and a deficit of taurine in comparison with the concentrations of these compounds in the urine of wild-type mice. In vitro assays confirmed that human FMO1 catalyzes the conversion of hypotaurine to taurine, utilizing either NADPH or NADH as cofactor. FMO1 has a wide substrate range and is best known as a xenobiotic- or drug-metabolizing enzyme. The identification that the endogenous molecule hypotaurine is a substrate for the FMO1-catalyzed production of taurine resolves a long-standing mystery. This finding should help establish the role FMO1 plays in a range of biologic processes in which taurine or its deficiency is implicated, including conjugation of bile acids, neurotransmitter, antioxidant and anti-inflammatory functions, and the pathogenesis of obesity and skeletal muscle disorders. SIGNIFICANCE STATEMENT The identity of the enzyme that catalyzes the biosynthesis of taurine from hypotaurine has remained elusive. Here we show, both in vivo and in vitro, that flavin-containing monooxygenase 1 catalyzes the oxygenation of hypotaurine to produce taurine.
Circulating lncRNA DANCR as a potential auxillary biomarker for the diagnosis and prognostic prediction of colorectal cancer

Abstract Studies have shown that long non-coding RNAs (lncRNAs) play vital roles in the development of cancer, including colorectal cancer (CRC). Our purpose is to validate the diagnostic value of serum differentiation antagonizing non-protein coding RNA (DANCR) in CRC by focusing on its expression and clinical application. lncRNA expression profiles of CRC patients were obtained and analyzed by repurposing the publically available microarray data. Tissue or serum specimens were obtained from 40 patients with primary CRC, 10 patients with recurrent CRC, 40 patients with colorectal polyps, and 40 healthy controls. It was found that DANCR level in the CRC tissue and serum was significantly increased, and serum DANCR expression was decreased in post-operative patients as compared with that in pre-treatment patients and recurrent patients. In addition, serum DANCR expression was significantly correlated with different TNM stages. Correlation analysis of DANCR and other diagnostic indicators showed that the serum DANCR expression level was significantly correlated with CA199 but not with CEA in CRC patients. As for diagnostic efficiency by ROC analysis, the area under the curve (AUC) of serum DANCR was higher than that of CEA and CA199 in CRC group vs. colorectal polyp group. Simultaneous detection of DANCR, CEA and CA199 yielded the highest sensitivity and AUC as compared with either of them alone. Taken together, serum DANCR was up-regulated in CRC patients and high expression of DANCR may prove to be a potential biomarker for the diagnosis of CRC.
Using Nonstandardized Assessments to Evaluate Cognitive-Communication Abilities following Pediatric Traumatic Brain Injury

Abstract The subtle cognitive-communication challenges experienced by students with traumatic brain injury (TBI) are often missed, leaving these students with unmet needs in the school environment and increasing the likelihood for negative social, academic, and vocational outcomes. For children and adolescents with TBI, nonstandardized assessment offers several advantages over standardized assessment procedures, and may improve speech-language pathologists' ability to identify students who might benefit from intervention services. This article discusses curriculum-based assessment and discourse analysis specifically and uses case studies to demonstrate how these procedures can be used within the school environment. Nonstandardized assessment procedures are a valuable tool to measure a student's cognitive-communication abilities and the effects of intervention in real-world contexts.
Auditory steady‐state response at 20 Hz and 40 Hz in young typically developing children and children with autism spectrum disorder

The early detection of autistic tendencies in children is essential for providing proper care and education. The auditory steady‐state response (ASSR) provides a passive, non‐invasive technique for assessing neural synchrony at specific response frequencies in many mental disorders, including autism spectrum disorder (ASD), but few studies have investigated its use in young children. This study investigated the ASSR at 20 Hz and 40 Hz in typically developing (TD) children and children with ASD aged 5–7 years.
Commercial Formulation of Chlorpyrifos Alters Neurological Behaviors and Fertility

Pesticides are known to result in toxic insult. We aimed to evaluate Judo 40, the commercial formulation of chlorpyrifos on the neurological activities, fertility, and hormone levels of male rats. Male Wistar rats were treated orally with 1 mL of 20 or 50 mg/kg Judo 40. The doses were administered four times, twice a day. Sexual and exploratory behavior indices, fertility indices, serum androgen levels, blood acetylcholinesterase (BChE) levels, and neurological and muscular effects were evaluated. Serum testosterone and luteinizing hormone were significantly reduced in the rats receiving 50 mg/kg Judo 40. A reduction in viable implantation sites and live pups born were evident in the female rats mated with the male rats treated with the highest dose. Similarly, in the rats treated with the highest dose of Judo 40, a significant reduction in plasma BChE enzyme was observed. According to the results, prolonged Judo 40 exposure can cause impairment of the neurological alterations and sex hormones leading to impaired fertility. Therefore, chemical handlers should be educated on protection and risk minimization.
Rapid Release of Ca2+ from Endoplasmic Reticulum Mediated by Na+/Ca2+ Exchange

Phototransduction in Drosophila is mediated by phospholipase C (PLC) and Ca2+-permeable TRP channels, but the function of endoplasmic reticulum (ER) Ca2+ stores in this important model for Ca2+ signaling remains obscure. We therefore expressed a low affinity Ca2+ indicator (ER-GCaMP6-150) in the ER, and measured its fluorescence both in dissociated ommatidia and in vivo from intact flies of both sexes. Phototransduction in Drosophila is mediated by phospholipase C (PLC) and Ca2+-permeable TRP channels, but the function of endoplasmic reticulum (ER) Ca2+ stores in this important model for Ca2+ signaling remains obscure. We therefore expressed a low affinity Ca2+ indicator (ER-GCaMP6-150) in the ER, and measured its fluorescence both in dissociated ommatidia and in vivo from intact flies of both sexes. Blue excitation light induced a rapid (tau ∼0.8 s), PLC-dependent decrease in fluorescence, representing depletion of ER Ca2+ stores, followed by a slower decay, typically reaching ∼50% of initial dark-adapted levels, with significant depletion occurring under natural levels of illumination. The ER stores refilled in the dark within 100–200 s. Both rapid and slow store depletion were largely unaffected in InsP3 receptor mutants, but were much reduced in trp mutants. Strikingly, rapid (but not slow) depletion of ER stores was blocked by removing external Na+ and in mutants of the Na+/Ca2+ exchanger, CalX, which we immuno-localized to ER membranes in addition to its established localization in the plasma membrane. Conversely, overexpression of calx greatly enhanced rapid depletion. These results indicate that rapid store depletion is mediated by Na+/Ca2+ exchange across the ER membrane induced by Na+ influx via the light-sensitive channels. Although too slow to be involved in channel activation, this Na+/Ca2+ exchange-dependent release explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors exposed to Ca2+-free solutions. SIGNIFICANCE STATEMENT Phototransduction in Drosophila is mediated by phospholipase C, which activates TRP cation channels by an unknown mechanism. Despite much speculation, it is unknown whether endoplasmic reticulum (ER) Ca2+ stores play any role. We therefore engineered flies expressing a genetically encoded Ca2+ indicator in the photoreceptor ER. Although NCX Na+/Ca2+ exchangers are classically believed to operate only at the plasma membrane, we demonstrate a rapid light-induced depletion of ER Ca2+ stores mediated by Na+/Ca2+ exchange across the ER membrane. This NCX-dependent release was too slow to be involved in channel activation, but explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors bathed in Ca2+-free solutions.
Simplification of Natural β-Carboline Alkaloids to Obtain Indole Derivatives as Potent Fungicides against Rice Sheath Blight

The increasing resistance of rice sheath blight caused by Rhizoctonia solani highlights the need for highly effective and environmentally benign agents. Natural β-carboline alkaloids were simplified to obtain a series of indole derivatives, and their fungicidal activity and preliminary mode of action against R. solani were also evaluated. The initial hit indole (7) displayed significant fungicidal activity with an EC50 value of 25.56 μg/mL, and was selected for further optimization. Importantly, compound 55, the most active compound, had an EC50 value of 0.62 μg/mL, and approximately 300-fold more potent than validamycin A (EC50 = 183.00 μg/mL). In vivo bioassay also demonstrated that compound 55 showed better fungicidal activities than validamycin A. Moreover, the mechanism studies revealed that compound 55 not only caused remarkable morphological and structural alterations of R. solani hyphae, but also induced the loss of mitochondrial membrane potential and interfered with DNA synthesis. Therefore, compound 55 showed superior fungicidal activity against R. solani, and the elucidated mode of action supported the potential application of compound 55 against rice sheath blight.