Search

Trachoma, caused by Chlamydia trachomatis , is the most common infectious blindness in the world and is present in indigenous Mayan from Chiapas (Mexico). Inflammatory genes are activated when suffering from trachoma, thus some polymorphisms could increase the susceptibility to develop irreversible blindness. This study aimed to evaluate the genetic risk of developing late-stage trachoma in Mayan ethnic groups. In a case-control study ( n = 51 vs n = 102, respectively), the following single-nucleotide polymorphisms (SNPs) in genes related to inflammation were analysed: HSD11B1 (rs11807619), HSD11B1 (rs932335), ABCG2 (rs2231142), SLCO1B1 (rs4149056), IL-10 (rs1800890), TNF (rs1800629), MMP2 (rs243865) and ACE. Three SNPs were associated with late-stage trachoma risk: (i) the T allele of rs11807619, (ii) the C allele of rs932335, which are linked to the HSD11B1 gene (OR = 22.5-27.3), particularly in men when adjusts for gender (OR = 16-16.7); and (iii) D allele of rs4340 in the ACE gene (OR = 5.2-5.3). In fact, significant linkage disequilibrium demonstrated association between ACE gene and HSD11B1 SNPs (r = 0.17-0.179; P = 0.0048-0.0073). Two SNPs HSD11B1 gene ( P = 0.013 vs 0.0039) and HSD11B1-ACE haplotypes showed association with late-stage trachoma in Mayan ethnic groups.

Midazolam (MDZ) is used for sedation in surgical procedures; its clinical effect is related to its receptor affinity and the dose administered. Therefore, a pharmacokinetic-pharmacodynamic (PK-PD) population model of MDZ in pediatric patients undergoing minor surgery is proposed. A descriptive, observational, prospective, and longitudinal, study that included patients of both sexes, aged 2-17 years, ASA I/II, who received MDZ in IV doses (0.05 mg/kg) before surgery. Three blood samples were randomly taken between 5-120 min; both sedation by the Bispectral Index Scale (BIS) and its adverse effects were recorded. The PK-PD relationship was determined using a nonlinear mixed-effects, bicompartmental first-order elimination model using Monolix Suite™. Concentrations and the BIS were fitted to the sigmoid Emax PK-PD population and sigmoid Emax PK/PD indirect binding models, obtaining drug concentrations at the effect site (biophase). The relationship of concentrations and BIS showed a clockwise hysteresis loop, probably indicating time-dependent protein binding. Of note, at half the dose used in pediatric patients, adequate sedation without adverse effects was demonstrated. Further PK-PD studies are needed to optimize dosing schedules and avoid overdosing or possible adverse effects.

This article describes a method for quantifying various cellular features (e.g., volume, curvature, total and sub-cellular fluorescence localization) of individual cells from sets of microscope images, and for tracking them over time-course microscopy experiments. One purposely defocused transmission image (sometimes referred to as bright-field or BF) is used to segment the image and locate each cell. Fluorescence images (one for each of the color channels or z-stacks to be analyzed) may be acquired by conventional wide-field epifluorescence or confocal microscopy. This method uses a set of R packages called rcell2. Relative to the original release of Rcell (Bush et al., 2012), the updated version bundles, into a single software suite, the image-processing capabilities of Cell-ID, offers new data analysis tools for cytometry, and relies on the widely used data analysis and visualization tools of the statistical programming framework R. © 2023 Wiley Periodicals LLC. Basic Protocol: Extracting quantitative information from single cells Support Protocol 1: Obtaining and installing Cell-ID and R Support Protocol 2: Preparing cells for imaging., (© 2023 Wiley Periodicals LLC.)

Whether age and sex influence the depth of sedation and the pharmacokinetics of midazolam is currently unknown. The influence of age and sex was investigated in 117 children (2 to 17 years) who required intravenous sedation for minor surgery (0.05 mg/kg). Plasma concentrations and sedation effects were simultaneously measured. The measured concentrations were analyzed using a two-compartment model with first-order elimination. Among the age ranges, significant differences were found ( p < 0.05) between the volume of distribution (Vd) of the first compartment (V1) and that of the second (V2). With respect to sex, differences in V2 were found between age groups. At the administered dose, in patients younger than 6 years, a profound sedative effect (40-60 BIS) was observed for up to 120 min, while in older children, the effect lasted only half as long. The differences found in the Vd and bispectral index (BIS) in patients younger than 6 years compared to older patients may be due to immature CYP3A activity and body fat content; furthermore, the Vd varies with age due to changes in body composition and protein binding. Patients younger than 6 years require intravenous (IV) doses <0.05 mg/kg of midazolam for deep sedation. Dosage adjustments according to age group are suggested.

Midazolam (MDZ) is a short-acting benzodiazepine that is widely used to induce and maintain general anesthesia during diagnostic and therapeutic procedures in pediatric patients due to its sedative properties. The aim of this study was to perform a systematic review without a meta-analysis to identify scientific articles and clinical assays concerning MDZ-induced sedation for a pediatric surgery approach. One hundred and twenty-eight results were obtained. After critical reading, 37 articles were eliminated, yielding 91 publications. Additional items were identified, and the final review was performed with a total of 106 publications. In conclusion, to use MDZ accurately, individual patient characteristics, the base disease state, comorbidities, the treatment burden and other drugs with possible pharmacological interactions or adverse reactions must be considered to avoid direct alterations in the pharmacokinetics and pharmacodynamics of MDZ to obtain the desired effects and avoid overdosing in the pediatric population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Primary screening with Human Papilloma Virus (HPV) testing was introduced in Colombia in 2014 for individuals between 30 and 65 years of age. When the result is positive, cytology triage is performed for colposcopy referral. The convenience of initiating HPV-DNA testing for screening at 25 years of age is currently a subject of discussion. Therefore, the objective of this health technology assessment (HTA) is to analyze the available evidence regarding safety, efficacy, cost-effectiveness, values and preferences, ethical dilemmas and considerations pertaining to the implementation of the HPV-DNA test as a cervical screening strategy in women under 30 years of age in the Colombian context., Domains to Be Assessed: Clinical efficacy and safety 1. Cumulative rate of cervical intraepithelial neoplasia (CIN) grade 2 or high-er after 2 screening rounds. 2. Cumulative rates of invasive cancer of the uterine cervix after 2 screening rounds. 3. Safety: referral to colposcopy. Cost-effectiveness Cost-effectiveness for Colombia. Other domains considered Ethical considerations associated with cervical screening in women under 30 years of age. Organizational and individual considerations. Barriers and facilitators pertaining to the implementation of cervical screening in women under 30 years of age in the Colombian context., Methods: Clinical efficacy and safety assessment A systematic literature search of systematic reviews and clinical trials was conducted in MEDLINE, Embase and CENTRAL. The body of evidence was rated using the GRADE approach. An interdisciplinary team was then convened to create a working group to review the retrieved evidence. This led to the discussion and construction of the conclusions following the guidelines of a formal consensus in accordance with the RAND/UCLA methodology. Economic study Systematic literature research of studies that had assessed cost-effectiveness for Colombia., Results: Clinical outcomes An integrative analysis of 5 randomized clinical trials that met the inclusion critera was performed. Compared with cytology, primary HPV-DNA testing in women under 30 years of age could be associated with a lower frequency of CIN+2 lesions during the first screening round (RR: 1.57; CI: 1.20 to 2.04; low evidence certainty), and a lower incidence of CIN+2 (RR: 0.67; CI: 0.48 to 0.92; low evidence certainty). Moreover, it is associated with a lower frequency of invasive carcinoma at the end of follow-up (RR: 0.19; CI: 0.07 to 0.53; high evidence certainty). Economic results From the financial point of view, the use of HPVDNA testing plus cytology-based triage starting at 25 years of age is perhaps the most cost-effective option for Colombia (incremental cost-effectiveness ratio, COP 8,820,980 in 2013). Other implications Two studies suggest that barriers to implementation attributable to intermediation, public unrest and geographic considerations could be overcome with the use of new screening technologies or strategies. It is important to consider administration and service provision alternatives in order to overcome some acceptability and access barriers. Any cervical screening program must take into consideration ethical principles of nonmaleficence, beneficence, autonomy and equity. Future studies should focus on analyzing new screening techniques with emphasis on the population under 30 years of age., Conclusions: The use of HPV-DNA testing as a screening strategy in women under 30 years of age is a potentially efficacious and cost-effective intervention for Colombia. Future studies should focus on analyzing new screening technologies, with emphasis on the population under 30 years of age.

Linear motifs are short protein subsequences that mediate protein interactions. Hundreds of motif classes including thousands of motif instances are known. Our theory estimates how many motif classes remain undiscovered. As commonly done, we describe motif classes as regular expressions specifying motif length and the allowed amino acids at each motif position. We measure motif specificity for a pair of motif classes by quantifying how many motif-discriminating positions prevent a protein subsequence from matching the two classes at once. We derive theorems for the maximal number of motif classes that can simultaneously maintain a certain number of motif-discriminating positions between all pairs of classes in the motif universe, for a given amino acid alphabet. We also calculate the fraction of all protein subsequences that would belong to a motif class if all potential motif classes came into existence. Naturally occurring pairs of motif classes present most often a single motif-discriminating position. This mild specificity maximizes the potential number of coexisting motif classes, the expansion of the motif universe due to amino acid modifications and the fraction of amino acid sequences that code for a motif instance. As a result, thousands of linear motif classes may remain undiscovered., Competing Interests: The authors have declared that no competing interests exist.

The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.0, has been completely redesigned and reimplemented with cutting-edge technology and now holds about six times more data (162 versus 24 entries and 242 versus 60 structural ensembles) and a broader representation of state of the art ensemble generation methods than the previous version. The database has a completely renewed graphical interface with an interactive feature viewer for region-based annotations, and provides a series of descriptors of the qualitative and quantitative properties of the ensembles. High quality of the data is guaranteed by a new submission process, which combines both automatic and manual evaluation steps. A team of biocurators integrate structured metadata describing the ensemble generation methodology, experimental constraints and conditions. A new search engine allows the user to build advanced queries and search all entry fields including cross-references to IDP-related resources such as DisProt, MobiDB, BMRB and SASBDB. We expect that the renewed PED will be useful for researchers interested in the atomic-level understanding of IDP function, and promote the rational, structure-based design of IDP-targeting drugs., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

We report the case of an 18-month-old boy who presented with caries in the upper central incisors associated with the use of propranolol solution for the treatment of an infantile hemangioma. This side effect of propranolol solution has not been reported before, and it may result from a sucrose-based excipient of the solution, or decreased salivation caused by beta-adrenergic antagonist effect of propranolol., (© 2010 Wiley Periodicals, Inc.)

Intestinal obstruction due to milk curds syndrome may present with a clinical picture and radiological findings which suggest the correct diagnosis. This type of intestinal obstruction usually affects neonates, previously healthy, with concentrated formula feeding. Surgical treatment may be avoided in some cases by the administration of Gastrografin enemas. Two patients with milk curd obstruction treatment in our Hospital, are presented.