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Human African trypanosomiasis is among the World Health Organization's designated neglected tropical diseases. Repurposing strategies are often employed in academic drug discovery programs due to financial limitations, and in this instance, we used human kinase inhibitor chemotypes to identify substituted 4-aminoazaindoles, exemplified by 1 . Structure-activity and structure-property relationship analysis, informed by cheminformatics, identified 4s as a potent inhibitor of Trypanosoma brucei growth. While 4s appeared to be fast acting and cidal in the in vitro assays, it failed to cure a murine model of infection. Preliminary efforts to identify the potential mechanism of action of the series pointed to arginine kinase, though, as we demonstrate, this does not appear to be the sole target of our compounds. This comprehensive approach to drug discovery, encompassing cheminformatics, structure-potency and structure-property analysis, and pharmacophore identification, highlights our multipronged efforts to identify novel lead compounds for this deadly disease.

Introduction: Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a recent bariatric surgery technique, highly effective in terms of weight loss. Nevertheless, data regarding the impact of SADI-S at mid-long term (after >5 years of follow-up) are scarce. Objectives: To evaluate the effect of lengths of common intestinal loop on the evolution of patients with morbid obesity (MO), who undergo SADI-S. Materials and Methods: Descriptive study (case series), including patients with MO who underwent SADI-S procedure between January 2012 and December 2015 with at least 5 years of follow-up. Patients were classified as "Old-SADI-S" (OS) when length of the common alimentary loop was <2.5 m and "New-SADI-S" (NS) when length was >2.5 m. Clinical parameters and nutritional parameters were included. Results: Twenty-nine cases were included (17 OS; 12 NS), 86.2% women and mean age 46.7 ± 1 years. After 12 months, OS had significantly lower body mass index (29.7 ± 4.8 kg/m 2 versus 32.0 ± 5.1 kg/m 2 , P  = .01), without significant differences in the resolution of comorbidities. Nevertheless, OS group had severe malabsorptive complications requiring surgical conversion of OS to NS in 7 patients after 8 months. At 5 years of follow-up, no significant difference was seen between the two groups and resolution of comorbidities was maintained during this period of time. Conclusions: SADI-S is effective in terms of weight loss and resolution of comorbidities at 5 years of follow-up, regardless of the length of the common intestinal loop. However, a common intestinal loop <2.5 m was associated with severe malabsorptive complications that determined the surgical re-conversion in all cases.

Research on cave microorganisms has mainly focused on the microbial communities thriving on speleothems, rocks and sediments; however, drip water bacteria and calcite precipitation has received less attention. In this study, microbial communities of carbonate precipitates from drip waters in Nerja, a show cave close to the sea in southeastern Spain, were investigated. We observed a pronounced difference in the bacterial composition of the precipitates, depending on the galleries and halls. The most abundant phylum in the precipitates of the halls close to the cave entrance was Proteobacteria , due to the low depth of this sector, the direct influence of a garden on the top soil and the infiltration of waters into the cave, as well as the abundance of members of the order Hyphomicrobiales , dispersing from plant roots, and other Betaproteobacteria and Gammaproteobacteria , common soil inhabitants. The influence of marine aerosols explained the presence of Marinobacter, Idiomarina, Thalassobaculum, Altererythrobacter and other bacteria due to the short distance from the cave to the sea. Nineteen out of forty six genera identified in the cave have been reported to precipitate carbonate and likely have a role in mineral deposition., Competing Interests: The authors declare there are no competing interests., (©2022 Jurado et al.)

Protein-coding genes in trypanosomes occur in polycistronic transcription units (PTUs). How RNA polymerase II (Pol II) initiates transcription of PTUs has not been resolved; the current model favors chromatin modifications inducing transcription rather than sequence-specific promoters. Here, we uncover core promoters by functional characterization of Pol II peaks identified by chromatin immunoprecipitation sequencing (ChIP-seq). Two distinct promoters are located between divergent PTUs, each driving unidirectional transcription. Detailed analysis identifies a 75-bp promoter that is necessary and sufficient to drive full reporter expression and contains functional motifs. Analysis of further promoters suggests transcription initiation is regulated and promoters are either focused or dispersed. In contrast to the previous model of unregulated and promoter-independent transcription initiation, we find that sequence-specific promoters determine the initiation of Pol II transcription of protein-coding genes PTUs. These findings in Trypanosoma brucei suggest that in addition of chromatin modifications, promoter motifs-based regulation of gene expression is deeply conserved among eukaryotes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background:  COVID-19 pandemic has been challenging for health services and systems around the world, including Peru.  A viable alternative in the telemedicine field to guarantee patient nutritional care is telenutrition. Telenutrition involves the interactive use of electronic information and telecommunications technologies to implement the nutrition care process with patients at a remote location. Information regarding the experience with this methodology and its potential effect on patients' nutritional goals, does not exist in Peru. The aim of the study was to report the effect of the evaluation type (telenutrition vs. in-person) on weight, body mass index (BMI), waist circumference (WC) and relative fat mass (RFM) in overweight and obese adult patients.  Methods:  This retrospective study included 100 eligible patients in a single nutritional center, from January 2019 to March 2021. Telenutrition and in-person continuous variables were compared with independent sample t-test or U Mann-Whitney test. Results:  There were significant differences in weight, BMI, WC and RFM by the end of follow-up period, in both evaluation modalities. Patients on the telenutrition group had a mean decrease of 6.80 ± 4.87 cm in WC, whereas the mean difference observed for the in-person group was 6.74 ± 4.55 cm. There were no significant differences in the changes of any anthropometric parameters when comparing both systems. Reductions were observed in weight (5.93 ± 3.88 kg vs. 4.92 ± 3.29 kg), BMI (2.23 ± 1.39 kg/ m2 vs. 1.83 ± 1.23 kg/ m2), WC (6.80 ± 4.87 cm vs. 6.74 ± 4.55 cm) and RFM (2.43 ± 1.78 vs. 2.63 ± 1.73) in telenutrition and in-person evaluation, respectively by the end of the follow-up period.  Conclusions:  Telenutrition may be regarded as an alternative to in-person evaluation offering anthropometric changes and nutritional goals similar to those reported through the in-person modality, in overweight and obese adult people., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Castrillón Liñan C et al.)

Background:  COVID-19 pandemic has been challenging for health services and systems around the world, including Peru.  A viable alternative in the telemedicine field to guarantee patient nutritional care is telenutrition. Telenutrition involves the interactive use of electronic information and telecommunications technologies to implement the nutrition care process with patients at a remote location. Information regarding the experience with this methodology and its potential effect on patients' nutritional goals, does not exist in Peru. The aim of the study was to report the effect of the evaluation type (telenutrition vs. in-person) on anthropometric parameters weight, body mass index (BMI), waist circumference (WC) and relative fat mass (RFM) in overweight and obese adult patients.  Methods:  This retrospective study included 100 eligible patients in a single nutritional center, from January 2019 to March 2021.  Results:  There was a significant difference in weight, BMI, WC and RFM at the end of the three-month follow-up period, in both evaluation modalities. Patients on the telenutrition group had a mean decrease of 6.80 ± 4.87 cm in their WC, whereas the mean difference observed for the in-person group was 6.74 ± 4.55 cm. There were no statistically significant differences in the changes of any anthropometric parameters when comparing both systems. Reductions were observed in weight (5.93 ± 3.88 kg vs. 4.92 ± 3.29 kg), BMI (2.23 ± 1.39 kg/ m2 vs. 1.83 ± 1.23 kg/ m2), WC (6.80 ± 4.87 cm vs. 6.74 ± 4.55 cm) and RFM (2.43 ± 1.78 vs. 2.63 ± 1.73) in telenutrition and in-person evaluation, respectively.  Conclusions:  Telenutrition may be regarded as an alternative to in-person evaluation offering anthropometric changes and nutritional goals similar to those reported through the in-person modality, in overweight and obese adult people., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Castrillón Liñan C et al.)

Objective: The purpose of this study was to evaluate the nasal septum and the depth of posterior palatal arch in the different facial vertical patterns using cone-beam computed tomography (CBCT)., Materials and Methods: A total of 143 CBCTs were analysed (53 normodivergents, 26 hypodivergents, and 64 hyperdivergents) using the software Real Scan 2.2. On the coronal view, the following measurements were taken, palatal interalveolar length (PIL), palatal arch depth (PAD), maxillopalatal arch angle (MPAA), septal vertical length (SVL), deviated septal length (DSL), and deviated septal curve angle (DSCA). Using the program Stata v16.0, we obtained the mean, standard deviation and median values. The identification of significant differences between facial biotypes was performed using the one-way ANOVA test and H of Kruskal-Wallis test, considering a significance level of 0.05., Results: The hypodivergent group got the highest PIL and MPAA (49.6mm and 118.1° respectively), with statistically significant differences (P<0.05) between this group and the hyperdivergent group. Statistically significant differences were found by gender for the SNMeGo, PFH, AFH, and the relationship between the facial heights, where the males had the highest values. Additionally, PIL and SVL also had the highest values for males (48.8mm and 63.6mm respectively)., Conclusions: Patients presenting with greater hyperdivergence have shorter interalveolar distances and smaller maxillopalatal arch angles., (Copyright © 2021 CEO. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Evaluate the height, thickness and cortical density of the palatal bone of adults with different vertical facial patterns using Cone-Beam Computed Tomography (CBCT)., Methods: This study analyzed 75 CBCTs of patients between 18 and 35 years old (45 men and 30 women). The CBCTs were classified into three groups based on their facial pattern: normodivergent, hypodivergent and hyperdivergent as determined from lateral cephalograms synthesized from the CBCTs. The height, cortical thickness and cortical density of the palatal bone were measured at 4, 8, 12, 16 and 20mm posterior to the incisive foramen, and at 3, 6 and 9mm lateral to the midpalatal suture. ANOVA with Tukey post-hoc tests were used for analysis of the data, at significance level of p< 0.05., Results: The hypodivergent pattern had a significant difference and the greatest height and cortical thickness of the palatal bone, followed by the hyperdivergent and the normodivergent patterns. No significant differences were found in minimum and maximum values of cortical density., Conclusion: The palatal bone is a favorable anatomical area to install different orthodontic temporary anchorage devices (TADs), where individuals with the hypodivergent vertical facial pattern have a higher height and cortical thickness of the palatal bone, followed by the hyperdivergent pattern and finally the normodivergent pattern. No significant differences in the cortical density of the palatal bone in the three facial patterns were found.

Functional defects in growth hormone (GH) secretion and its efficacy as a complementary treatment have been suggested for fibromyalgia. This study investigated the efficacy and safety of low-dose GH as an add-on therapy in patients with both severe FM and low insulin-like growth factor 1 levels. A total of 120 patients were enrolled in a multicenter, placebo-controlled study for 18 months. They were randomly assigned to receive either 0.006 mg/kg/day of GH subcutaneously (group A, n=60) or placebo (group B, n=60) for 6 months (blind phase). The placebo arm was switched to GH treatment from month 6 to month 12 (open phase), and a follow-up period after GH discontinuation was performed until month 18. Standard treatment for fibromyalgia (selective serotonin re-uptake inhibitors, opioids, and amitriptyline) was maintained throughout the study. Number and intensity of tender points, Fibromyalgia Impact Questionnaire (FIQ) with its subscales, and EuroQol 5 dimensions test (EQ5D) with visual analogue scale (VAS) were assessed at different time points. At the end of the study, 53% of group A patients obtained fewer than 11 positive tender points, vs 33% of group B patients (P<.05). 39.1% vs 22.4% reached more than 50% improvement in VAS (P<.05). Group A patients showed significantly improved FIQ scores (P=.01) compared with group B. Although GH discontinuation worsened all scores in both groups during follow-up, impairment in pain perception was less pronounced in the GH-treated group (P=.05). In this largest and longest placebo-controlled trial performed in FM (NCT00933686), addition of GH to the standard treatment is effective in reducing pain, showing sustained action over time., (Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)