Design of an effective small expression tag to enhance GPCR production in E. coli-based cell-free and whole cell expression systems.

G protein-coupled receptors (GPCRs) play crucial roles in sensory, immune, and tumor metastasis processes, making them valuable targets for pharmacological and sensing applications in various industries. However, most GPCRs have low production yields in Escherichia coli (E. coli) expression systems. To overcome this limitation, we introduced AT10 tag, an effective fusion tag that could significantly enhance expression levels of various GPCRs in E. coli and its derived cell-free protein synthesis (CFPS) system. This AT10 tag consisted of an A/T-rich gene sequence designed via optimization of translation initiation rate. It is translated into a short peptide sequence of 10 amino acids at the N-terminus of GPCRs. Additionally, effector proteins could be utilized to suppress cytotoxicity caused by membrane protein expression, further boosting GPCR production in E. coli. Enhanced expression of various GPCRs using this AT10 tag is a promising approach for large-scale production of functional GPCRs in E. coli-based CFPS and whole cell systems, enabling their potential utilization across a wide range of industrial applications.

Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as "variant of concern" due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous variants of concern, the Omicron variant has 15 mutations on the receptor-binding domain of spike protein and the changes in the key amino acid residues of S protein can enhance the binding ability of the virus to hACE2, resulting in a significant increase in the infectivity of the Omicron variant. Therefore, there is still an urgent need for treatment and prevention of variants of concern, particularly for the Omicron variant. In this study, an in silico drug repurposing was conducted through the molecular docking of 2890 FDA-approved drugs against the mutant S protein of SARS-CoV-2 for Omicron variant. We discovered promising drug candidates for the inhibition of alarming Omicron variant such as quinestrol, adapalene, tamibarotene, and dihydrotachysterol. The stability of ligands complexed with the mutant S protein was confirmed using MD simulations. The lead compounds were further evaluated for their potential use and side effects based on the current literature. Particularly, adapalene, dihydrotachysterol, levocabastine and bexarotene came into prominence due to their non-interference with the normal physiological processes. Therefore, this study suggests that these approved drugs can be considered as drug candidates for further in vitro and in vivo studies to develop new treatment options for the Omicron variant of SARS-CoV-2.

Early signs of sleep-disordered breathing in healthy women predict carotid intima-media thickening after 10 years.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in women. The risk of CVD increases in women after menopause. The aim was to study how sleep parameters and cardiovascular risk factors in 46-year-old women predict future carotid intima-media thickness (IMT) 10 years after. METHODS: Prospective study of 92 healthy women, aged 46 years, were studied at baseline and at 10-year follow-up. Polysomnography for sleep and breathing; blood samples for cholesterol, glucose and follicle stimulating hormone; blood pressure (BP), weight and height measurements; questionnaires for background variables and vasomotor symptoms were carried out at both time points. Carotid ultrasound was scanned for IMT at 10-year follow-up. RESULTS: After adjusting for conventional risk factors, apnea-hypopnea index (AHI) during rapid-eye-movement (REM) sleep was the only parameter at baseline that predicted IMT 10 years after (IMT mean: ß 81.4 [95% CI, 14.0-148.8]; IMT max: ß 104.7 [95% CI, 15.4-194.1]). At 10-year follow-up, higher arousal index (IMT mean: ß 55.6 [95% CI, 19.5-91.8]; IMT max ß 59.9 [95% CI, 11.4-108.4]) and lower vasomotor symptoms (IMT max: ß -60.5 [95% CI, -119.0 to -2.0]) were associated with concurrent higher IMT. The conventional risk factors at baseline did not associate with future IMT but 10 years after higher concurrent HbA1c (IMT mean: ß 11.0 [95% CI, 3.4-18.5]; IMT max ß 14.0 [95% CI, 4.1-23.8]) and systolic BP (IMT mean: ß 2.4 [95% CI, 1.1-3.7]; IMT max: ß 2.7 [95% CI, 1.03 to 4.53]) were associated with higher IMT. CONCLUSIONS: In healthy 46-year-old women, AHI during REM sleep predicted IMT 10 years after. The conventional risk factors (HbA1c and BP) only associated with the concurrent IMT at 10-year follow-up.

Regional haemodynamic variables and perfusion index in the evaluation of sciatic nerve block: a prospective observational trial.

OBJECTIVE: We determined whether regional haemodynamics and perfusion index (PI) could be reliable indicators of a successful sciatic nerve block (SNB). DESIGN: Prospective observational trial. SETTING: A tertiary teaching hospital in China from April 2020 to August 2020. PARTICIPANTS: We assessed 79 patients for eligibility to participate in this study. Nine patients were excluded for not meeting our inclusion criteria, and three patients were excluded due to missing measurements at all time points. INTERVENTIONS: The patients underwent SNB. Pulsed-wave Doppler and PI measurements were performed. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the diagnostic power of regional haemodynamic change and PI to predict successful SNB. The secondary outcome measure was the effect of SNB on the regional haemodynamics and PI in the lower extremity. RESULTS: We assessed 79 patients in this study and 67 patients available for the final analysis. The SNB was successful in 59 patients and failed in eight patients. There were no significant differences in demographic characteristics between the patients with successful and failed SNB. Starting from 10 min after SNB, the peak systolic velocity (PSV), end-diastolic velocity, time-averaged maximum velocity and time-averaged mean velocity of the anterior tibial artery and posterior tibial artery of patients in the successful SNB group were significantly higher than those in the failed SNB group (p<0.05). The PSV percentage increase at 10 min after SNB has great potential to predict the block success. The area under the receiver operating characteristic curve (AUC) values were 0.893 (95% CI 0.7809 to 1.000) and 0.880 (95% CI 0.7901 to 0.9699). The corresponding cut-off values were 19.22 and 35.88, respectively. The PI increased during 5-45 min intervals in patients with successful SNB. The AUC for the PI percentage increases at 10 min after SNB was 0.853 (95% CI 0.7035 to 1.000), with a cut-off value of 93.09. CONCLUSION: The regional haemodynamic variables, PSV and PI in particular, can be used as alternative indicators for clinicians to evaluate the success of SNB objectively and early. TRIAL REGISTRATION NUMBER: ChiCTR2000030772.

Effect of chicken manure and chemical fertilizer on the yield and qualities of white mugwort at dissimilar harvesting times.

One of the key components that affects soil productiveness, plant growth, and crop quality is fertilization. The effect of fertilizer, both organic and chemical, on the extremely acidic (pH 4.10) sandy loam soil chemical properties, yield, and quality of white mugwort grown were evaluated in this study. The field experiment arranged in a randomized complete block design, with four replications was conducted in Prachin Buri province, Thailand. There were six treatments, no fertilization (control), chemical fertilizer (25-7-7 + 46-0-0) applied at 187.50 (66.56 N:6.77 P2O5:6.77 K2O kg ha-1) kg ha-1 and applied at 375.00 (133.12 N:13.13 P2O5:13.13 K2O kg ha-1) kg ha-1, chicken manure applied at 3.36, 6.72, and 10.08 t ha-1. After harvesting, application of chicken manure tended to increase soil organic matter compared to the control, however, the application of chemical fertilizer did not show the same effect. The fresh weight of white mugwort increased with the rise in both fertilizer levels. Chicken manure application at 10.08 t ha-1 produced the highest fresh weight at all times. The level of accumulated nitrate was significantly greater when fertilizer rates increased. In addition, the total phenolic content of the white mugwort fertilized with chicken manure was higher than that fertilized with chemical fertilizer. However, there was no association between the DPPH radical scavenging capacity at harvesting times and different fertilization. Based on the results, chicken manure applied at 10.08 t ha-1 gave the best yield and higher total phenolic content of white mugwort, which was probably due to the improved soil organic matter.

Associations between illicit drug use in early adulthood and mortality: Findings from a National Birth Cohort.

Illicit drug use is known to be associated with premature mortality. Whether exposure to socioeconomic disadvantage and mental health problems in childhood help to explain this association, is unclear. We analysed data from 11,250 participants in the 1970 British Birth Cohort study. At 10-years of age, socioeconomic disadvantage (parental socioeconomic position, material disadvantage, family disruption) and mental health problems with antisocial behaviour, attention, and anxiety were reported by mothers and teachers. At 30-years of age, study members provided information on their illicit drug use, exposure to socioeconomic disadvantage and mental health problems. At 30-years, 19.2% of participants had used an illicit drug in the past year. Mortality was elevated for eight of the twelve drugs assessed. Family disruption, maternal, and teacher assessments of antisocial behaviour at 10-years were associated with illicit drug use at 30-years. There was, however, very little change in these associations when exposure to childhood socioeconomic disadvantage (% change in hazard ratios [HR] 0-10%) or mental health problems (0.4-11.9%) were added to the sex-adjusted model. Adding exposure to socioeconomic disadvantage (0.8-38.9%) and mental health problems (31.7-74.1%) in adulthood to the sex-adjusted model resulted in marked attenuation in HRs for all drugs. These findings imply that interventions which provide opportunities for education, employment and access to effective mental health treatments in early adulthood may help to reduce mortality among drug users.

Ethyl formate dilution in carbon dioxide for fumigation control of the brown marmorated stink bug Halyomorpha halys, Stål (Hemiptera: Pentatomidae).

BACKGROUND: The brown marmorated stink bug (BMSB), Halyomorpha halys, has caused significant agricultural damage to numerous hosts, so agricultural producers seek to limit its spread. Where established, BMSB can also cause substantial urban and commercial disturbance, as overwintering adults may seek refuge inside dwellings, covered spaces, vehicles, and consignments. Phytosanitary authorities are most concerned with the importation of 'hitchhiking' adults in this refugia, with certain countries requiring a quarantine treatment to mitigate risk. This study explores fumigation with ethyl formate, applied as 16.7% by mass dilution in carbon dioxide, for control of adult BMSB. RESULTS: The induction of diapause, to simulate overwintering physiology, resulted in 2- and 3-fold increases in the tolerance of adults toward this ethyl formate fumigation at 10 ± 0.5 °C ( x ¯ ± 2 s ) lasting for 8 and 12 h, respectively. However, a decreased tolerance (0.7-fold) of diapausing specimens was observed for a 4-h duration. Diapausing and nondiapausing adult BMSB can be controlled at the probit 9 level if the headspace concentration of ethyl formate, [EF], in the carbon dioxide mixture is maintained ≥7.68 mg L-1 for 12 h at 10 ± 0.5 °C ( x ¯ ± 2 s ). If the duration is shortened to 4 h, [EF] must be maintained ≥14.73 mg L-1 over the course of fumigation. CONCLUSION: The toxicity of ethyl formate in this mixture can be distinct for different physiological states of the same life stage, as evidenced by a ca. 3-fold increase in the Haber's z parameter for adult BMSB when in diapause. Respective to the physiological state of adults, this study identifies how the applied dose and/or treatment duration can be modulated (i.e. tuned) to ensure adequate toxicological efficacy toward BMSB infesting hosts or refuge at temperatures ca. >10 °C. Published 2022. This article is a U.S. Government work and is in the public domain in the USA.

Five nanometer size highly positive silver nanoparticles are bactericidal targeting cell wall and adherent fimbriae expression.

To tackle growing antibiotic resistance (AR) and hospital-acquired infections (HAIs), novel antimicrobials are warranted that are effective against HAIs and safer for human use. We hypothesize that small 5 nm size positively charged nanoparticles could specifically target bacterial cell wall and adherent fimbriae expression, serving as the next generation antibacterial agent. Herein we show highly positively charged, 5 nm amino-functionalized silver nanoparticles (NH2-AgNPs) were bactericidal; highly negatively charged, 45 nm citrate-functionalized AgNPs (Citrate-AgNPs) were nontoxic; and Ag+ ions were bacteriostatic forming honeycomb-like potentially resistant phenotype, at 10 µg Ag/mL in E. coli. Further, adherent fimbriae were expressed with Citrate-AgNPs (0.5-10 µg/mL), whereas NH2-AgNPs (0.5-10 µg/mL) or Ag+ ions (only at 10 µg/mL) inhibited fimbriae expression. Our results also showed no lipid peroxidation in human lung epithelial and dermal fibroblast cells upon NH2-AgNPs treatments, suggesting NH2-AgNPs as a biocompatible antibacterial candidate. Potent bactericidal effects demonstrated by biocompatible NH2-AgNPs and the lack of toxicity of Citrate-AgNPs lend credence to the hypothesis that small size, positively charged AgNPs may serve as a next-generation antibacterial agent, potentially addressing the rising HAIs and patient health and safety.

The ideal harvest time for seed production in maize (Zea mays L.) varieties of different maturity groups.

BACKGROUND: The correct time for harvesting is a key factor contributing to the production of high-quality maize seeds. We conducted field experiments to harvest seeds at 11 developmental stages for 3 years, to investigate seed vigor traits in three early maturity maize varieties and two late maturity varieties in one location. RESULTS: Significant correlations (r = 0.72 ~ 0.89) were found among six seed-related traits: standard germination (SG), accelerated aging germination (AAG), cold test germination (CTG), hundred-seed weight (HSW), seed moisture content (SMC), and ≥ 10 °C accumulated temperature from pollination to harvest (AT10). Analysis of variance showed that harvest stage, year, and variety had significant effects on all traits, and harvest stage displayed the greatest effect. The responses of SG, AAG, CTG, HSW and SMC to harvest stage fitted quadratic models, and AT10 fitted a linear model. From the quadratic models, an ideal harvest time (IHT, the final date to reach maximum SG, AAG, and CTG) could be calculated for each variety. The three early maturity varieties reached their IHT at 54.94-58.44 days after pollination (DAP); the two later maturity varieties reached IHT several days later (at 59.87-59.90 DAP). The early maturity varieties consistently required less AT10 to reach the IHT than the later maturity varieties. However, all of the varieties reached the IHT at similar SMC levels of about 35%. CONCLUSION: The later maturity varieties reached the IHT at later DAPs when they acquired more AT10 than the early maturity varieties but both reached it at similar SMC levels. © 2022 Society of Chemical Industry.

Differential temperature effects on photoperiodism in female voles: A possible explanation for declines in vole populations.

Many mammalian species use photoperiod as a predictive cue to time seasonal reproduction. In addition, metabolic effects on the reproductive axis may also influence seasonal timing, especially in female small, short-lived mammals. To get a better understanding of how annual cycling environmental cues impact reproductive function and plasticity in small, short-lived herbivores with different geographic origins, we investigated the mechanisms underlying integration of temperature in the photoperiodic-axis regulating female reproduction in a Northern vole species (tundra vole, Microtus oeconomus) and in a Southern vole species (common vole, Microtus arvalis). We show that photoperiod and temperature interact to determine appropriate physiological responses; there is species-dependent annual variation in the sensitivity to temperature for reproductive organ development. In common voles, temperature can overrule photoperiodical spring-programmed responses, with reproductive organ mass being higher at 10°C than at 21°C, whereas in autumn they are less sensitive to temperature. These findings are in line with our census data, showing an earlier onset of spring reproduction in cold springs, while reproductive offset in autumn is synchronized to photoperiod. The reproductive organs of tundra voles were relatively insensitive to temperature, whereas hypothalamic gene expression was generally upregulated at 10°C. Thus, both vole species use photoperiod, whereas only common voles use temperature as a cue to control spring reproduction, which indicates species-specific reproductive strategies. Due to global warming, spring reproduction in common voles will be delayed, perhaps resulting in shorter breeding seasons and thus declining populations, as observed throughout Europe.

Neuromuscular recruitment strategies of the vastus lateralis according to sex.

AIM: Despite males typically exhibiting greater muscle strength and fatigability than females, it remains unclear if there are sex-based differences in neuromuscular recruitment strategies e.g. recruitment and modulation of motor unit firing rate (MU FR) at normalized forces and during progressive increases in force. METHODS: The study includes 29 healthy male and 31 healthy female participants (18-35 years). Intramuscular electromyography (iEMG) was used to record individual motor unit potentials (MUPs) and near-fibre MUPs from the vastus lateralis (VL) during 10% and 25% maximum isometric voluntary contractions (MVC), and spike-triggered averaging was used to obtain motor unit number estimates (MUNE) of the VL. RESULTS: Males exhibited greater muscle strength (P < .001) and size (P < .001) than females, with no difference in force steadiness at 10% or 25% MVC. Females had 8.4% and 6.5% higher FR at 10% and 25% MVC, respectively (both P < .03), while the MUP area was 33% smaller in females at 10% MVC (P < .02) and 26% smaller at 25% MVC (P = .062). However, both sexes showed similar increases in MU size and FR when moving from low- to mid-level contractions. There were no sex differences in any near-fibre MUP parameters or in MUNE. CONCLUSION: In the vastus lateralis, females produce muscle force via different neuromuscular recruitment strategies to males which is characterized by smaller MUs discharging at higher rates. However, similar strategies are employed to increase force production from low- to mid-level contractions. These findings of similar proportional increases between sexes support the use of mixed sex cohorts in studies of this nature.

Are patients who return for 10-year follow-up after AIS surgery different from those who do not?

PURPOSE: To evaluate the impact of patients lost to follow-up on outcomes of surgery for adolescent idiopathic scoliosis (AIS) at 10-year postoperative. METHODS: Preoperative, 2-year, and 5-year postoperative demographic, radiographic, and SRS-22 data from a prospective multi-center registry were compared between patients with a 10-year follow-up visit versus those without. A second analysis utilized variables that were different between the groups, along with SRS scores, in a cohort of patients with preoperative, 2-, 5-, and 10-year postoperative SRS scores (complete cohort) to impute missing 10-year data (imputed cohort) utilizing Markov chain Monte Carlo simulation. RESULTS: 250 patients had 10-year follow-up (21%). Those with 10-year follow-up had a greater percentage of patients who underwent anterior procedures (p < 0.05). Radiographically, the groups were similar at all three time points. SRS-22 scores demonstrated slightly worse pain and function preoperatively and at 2 year in those lost to follow-up (effect size eta = 0.11-0.12), with no differences at 5 year. Imputed data analysis demonstrated similar trends over time in SRS-22 scores compared to the complete cohort for total score and all domains except pain. There was no significant difference in imputed versus complete 10-year SRS-22 scores (p > 0.05). CONCLUSION: This study identified early differences between patients with 10-year follow-up and those without, though effect sizes were small and non-existent at 5 years. SRS-22 scores at 10 year between the complete and imputed data sets did not differ. Clinically relevant outcomes of the subset who followed-up at 10 year are likely generalizable to the entire eligible AIS population.

Efficacy and Safety of Intravenous Iron Therapy for Treating Anaemia in Critically ill Adults: A Rapid Systematic Review With Meta-Analysis.

Our objective was to systematically evaluate the efficacy and safety of intravenous (IV) iron therapy for treating anaemia in critically ill adults (>16 years) admitted to intensive care or high dependency units. We excluded quasi-RCTs and other not truly randomised trials. We searched 7 electronic databases (including CENTRAL, MEDLINE, and Embase) using a pre-defined search strategy from inception to June 14, 2021. One reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane risk of bias (ROB) 1 and GRADE to assess the certainty of the evidence. We reported 3 comparisons across 1198 patients, in 8 RCTs: (1) IV iron vs control (7 RCTs, 748 participants); our primary outcome (hemoglobin (Hb) concentration at 10 to 30 days) was reported in 7 of the 8 included trials. There was evidence of an effect (very-low certainty) in favour of IV iron over control in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL [95%CI 0.23, 0.81], P = .0005). For the remaining outcomes there was no evidence of an effect in either direction (low certainty of evidence for Hb concentration at <10 days; very-low certainty of evidence for hospital duration, ICU duration, hospital readmission, infection, mortality; HRQoL outcomes were not GRADED). (2) IV iron + subcutaneous erythropoietin (EPO) vs control (2 RCTs, 104 participants); reported outcomes showed no evidence of effect in either direction, based on very-low certainty evidence (Hb concentration at 10-30 days, and <10 days, infection, mortality). (3) Hepcidin-guided treatment with IV iron or iron+ EPO vs standard care (1 RCT, 399 participants) reported evidence of an effect in favour of the intervention for 90-day mortality (low certainty of evidence), but no other group differences for the reported outcomes (low certainty evidence for Hb concentration at 10-30 days, hospital duration; HRQoL was not GRADED). The evidence across all comparisons was downgraded for high and unclear ROB for lack of blinding, incomplete outcome data, baseline imbalance, and imprecision around the estimate (wide CIs and small sample size). In conclusion, the current evidence continues to support further investigation into the role for iron therapy in increasing Hb in critically ill patients. Recent, small, trials have begun to focus on patient-centred outcomes but a large, well conducted, and adequately powered trial is needed to inform clinical practice.

Associations between family functioning during early to mid-childhood and weight status in childhood and adolescence: findings from a Quebec birth cohort.

BACKGROUND: Impaired family functioning has been associated with obesity in children and adolescents, but few longitudinal studies exist. We examined whether family functioning from early to mid-childhood is associated with overweight and obesity in later childhood and adolescence. METHODS: We examined data from the Quebec Longitudinal Study of Child Development (QLSCD), a birth cohort (N = 2120), collected between 1998 and 2011. Parent-reported family functioning was assessed at 4 time points between ages 0.5 and 8 years using the McMaster Family Assessment Device with established cut-offs for impaired family functioning. Participants were classified as having experienced: 1) early-childhood impaired functioning, 2) mid-childhood impaired functioning, 3) both early and mid-childhood impaired functioning, or 4) always healthy family functioning. Overweight and obesity were determined at 10- and 13-years using WHO criteria. Covariate adjusted multinomial logistic regressions were fitted to the data to examine associations between longitudinal family functioning groups (using the always healthy functioning as reference category) and the likelihood of having overweight and obesity (vs normal weight) at ages 10 (n = 1251) and 13 years (n = 1226). RESULTS: In the 10- and 13-year sub-samples, respectively 10.2% and 12.5% of participants had experienced both early and mid-childhood impaired family functioning. Participants in this group had an increased likelihood of having obesity (vs normal weight) at age 10 years [OR = 2.63 (95% CI: 1.36; 5.08)] and at age 13 years [OR = 1.94 (95% CI: 0.99; 3.80] compared to those in the always healthy functioning group. No associations were found for other family functioning categories or for overweight status. CONCLUSION: Approximately one in ten children experienced impaired family functioning throughout early and mid-childhood. Findings suggest a link between impaired functioning across childhood and the development of obesity at 10 years of age and possibly at 13 years of age.

Myopia progression from wearing first glasses to adult age: the DREAM Study.

PURPOSE: Data on myopia progression during its entire course are scarce. The aim of this study is to investigate myopia progression in Europeans as a function of age and degree of myopia from first prescription to final refractive error. METHODS: The Drentse Refractive Error and Myopia Study assessed data from a branch of opticians in the Netherlands from 1985 onwards in a retrospective study. First pair of glasses prescribed was defined as a spherical equivalent of refraction (SER) ≤-0.5 D to ≥-3.0 D. Subjects with prescriptions at an interval of at least 1 year were included in the analysis. RESULTS: A total of 2555 persons (57.3% female) met the inclusion criteria. Those with first prescription before the age of 10 years showed the strongest progression (-0.50 D; IQR: -0.75 to -0.19) and a significantly (p<0.001) more negative median final SER (-4.48 D; IQR: -5.37 to -3.42). All children who developed SER ≤-3 D at 10 years were highly myopic (SER ≤-6D) as adults, children who had SER between -1.5 D and -3 D at 10 years had 46.0% risk of high myopia, and children with SER between -0.5 D and -1.5 D had 32.6% risk of high myopia. Myopia progression diminished with age; all refractive categories stabilised after age 15 years except for SER ≤-5 D who progressed up to -0.25 D annually until age 21 years. CONCLUSION: Our trajectories of the natural course of myopia progression may serve as a guide for myopia management in European children. SER at 10 years is an important prognostic indicator and will help determine treatment intensity.

Changes in steering performance and muscle activity of the upper extremity according to the position of the spinner knob.

INTRODUCTION: A spinner knob attached to the steering wheel enables one-handed driving. However, changes in steering performance and muscle activity of the upper extremity based on the differences in the position of the knob are unknown. AIM: To quantify changes in steering performance and their muscle activity according to the position of the knob. METHOD: Twenty right-handed healthy men with a mean age of 30.9 years participated in the study. Steering operation (reaction time, accuracy, right-left balance and adaptability) as assessed by steering with both hands and left one-handed driving with the spinner knob at three positions (8, 10, and 12 o'clock) were evaluated using a driving simulator. Muscle activities of the left anterior deltoid, biceps brachii and long head of the triceps brachii during the simulated tasks were also recorded using a wireless surface electromyography. RESULTS: Muscle activity while steering with the knob at 8 o'clock was significantly lower than with the knob at 10 or 12 o'clock, and was equivalent to the steering performance and muscle activity when driving with both hands. On the other hand, muscle activity while driving with the knob at 10 o'clock was significantly higher than with the knob in the other positions. CONCLUSION: The present study provides basic data for determining the position of the spinner knob attached to the steering wheel when driving one-handed with the non-dominant left hand. Positioning of the knob at 8 o'clock can be recommended on the basis of steering performance and lower muscle activities.IMPLICATIONS FOR REHABILITATIONThe safe driving of an automobile requires the driver to have an adequate range of motion and advanced voluntary motor control of the upper and lower extremities.When steering with the bilateral hands becomes difficult and driving with one-hand is required, it is necessary to attach a spinner knob on the steering wheel.This study provides objective and valuable information for clinicians and therapists to determine the optimum position of the spinner knob.

Outcomes linked to eligibility for stem cell transplantation trials in diffuse cutaneous systemic sclerosis.

OBJECTIVES: The aim of this study was to explore outcomes in a cohort of dcSSc patients fulfilling eligibility criteria for stem cell transplantation (SCT) studies but receiving standard immunosuppression. METHODS: From a large single-centre dcSSc cohort (n = 636), patients were identified using the published SCT trials' inclusion criteria. Patients meeting the trials' exclusion criteria were excluded. RESULTS: Of the 227 eligible patients, 214 met the inclusion criteria for ASTIS (Autologous Stem Cell Transplantation International Scleroderma), 82 for SCOT (Scleroderma: Cyclophosphamide Or Transplantation) and 185 for the UPSIDE (UPfront autologous haematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) trial, and 66 were excluded based on age >65 years, low diffusing capacity of the lungs for carbon monoxide (DLco), pulmonary hypertension or creatinine clearance <40 ml/min. The mean follow-up time was 12 years (s.d. 7). Among the eligible patients, 103 (45.4%) died. Survival was 96% at 2 years, 88% at 5 years, 73% at 10 years and 43% at 20 years. Compared with this 'SCT-eligible' cohort, those patients who would have been excluded from SCT trials had a worse long-term survival (97% at 2 years, 77% at 5 years, 52% at 10 years and 15% at 20 years, log rank P < 0.001). Excluded patients also had a significantly worse long-term event-free survival. Hazard of death was higher in patients with higher age at onset [hazard ratio (HR) 1.05, P < 0.001], higher ESR at baseline (HR 1.01, P = 0.025) and males (HR 2.12, P = 0.008). CONCLUSION: SCT inclusion criteria identify patients with poor outcome despite current best practice treatment. Patients meeting the inclusion criteria for SCT but who would have been excluded from the trials because of age, pulmonary hypertension, poor kidney function or DLco <40% had worse outcomes.

Outcome of infants with 10 min Apgar scores of 0-1 in a low-resource setting.

BACKGROUND: In high-resource settings, postponing the interruption of cardiopulmonary resuscitation from 10 to 20 min after birth has been recently suggested, but data from low-resource settings are lacking. We investigated the outcome of newborns with Apgar scores of 0-1 at 10 min of resuscitative efforts in a low-resource setting. METHODS: This observational substudy from the NeoSupra trial included all 49 late preterm/full-term newborns with Apgar scores of 0-1 at 10 min of resuscitation. The study was carried out at Mulago National Referral Hospital (Kampala, Uganda) between May 2018 and August 2019. Outcome measures were mortality and hypoxic-ischaemic encephalopathy in the first week of life. All resuscitations were video recorded and daily reviewed by trial researchers. RESULTS: Median duration of resuscitation was 32 min (IQR 17-37). Advanced resuscitation was provided to 21/49 neonates (43%). Overall, 48 neonates (98%) died within 2 days of life (44 in the delivery room, three on the first day and one on the second day) and one survived at 1 week with severe hypoxic-ischaemic encephalopathy. CONCLUSION: Our study adds information from a low-resource setting to the recent evidence from high-resource settings about prolonging the resuscitation in infants with Apgar scores of 0-1 at 10 min. The vast majority died in the delivery room despite prolonged resuscitative efforts. We confirm that duration of resuscitation should be tailored to the setting, while the focus in low-resource settings should be improving the quality of antenatal and immediately after birth care.

Apresentação atípica de síndrome de hiper-IgM ligada ao X simulando doença inflamatória intestinal / Atypical presentation of X-linked hyper-IgM syndrome simulating inflammatory bowel disease

Relatamos o caso de um paciente do sexo masculino, que iniciou quadro de úlceras em trato gastrointestinal, associado a febre recorrente e diarreia com muco e sangue aos 10 meses de vida, suspeitado inicialmente de doença inflamatória intestinal, no entanto, não apresentou melhora do quadro com terapia imunossupressora, sendo realizada investigação para erro inato da imunidade. Nos exames laboratoriais, apresentou níveis baixos de IgG e IgA e níveis elevados de IgM e neutropenia persistente. Diante disso, foi realizado teste genético que confirmou diagnóstico de síndrome de hiper-IgM ligada ao X. Os erros inatos da imunidade podem se manifestar com doenças do trato gastrointestinal, de forma relativamente frequente, devendo entrar como diagnóstico diferencial de diarreia crônica. Inclusa nesse grupo de doenças, as síndromes de hiper-IgM constituem um grupo heterogêneo de doenças, possuindo em comum níveis significativamente baixos ou ausentes de IgG e IgA e níveis normais ou elevados de IgM, o que predispõe a infecções e febre recorrente; além de outras alterações laboratoriais, como neutropenia, que pode estar associada a úlceras no trato gastrointestinal e proctite, simulando apresentação clínica de doença inflamatória intestinal. Para o paciente relatado, foi iniciada terapia com imunoglobulinas de forma periódica, além de antibioticoprofilaxia para infecções, evoluindo com resposta clínica satisfatória. O artigo possui objetivo principal de alertar para o diagnóstico diferencial de erros inatos da imunidade diante do quadro apresentado, visando o diagnóstico precoce e a instituição da terapia adequada.

We report the case of a male patient, who started with ulcers in the gastrointestinal tract, associated with recurrent fever and diarrhea with mucus and blood at 10 months of life, initially suspected of inflammatory bowel disease, however, he did not improve the condition with immunosuppressive therapy, being investigated for inborn error of immunity. In laboratory tests, he had low levels of IgG and IgA and high levels of IgM and persistent neutropenia. Therefore, a genetic test was performed and confirmed the diagnosis of X-linked hyper IgM syndrome. Inborn errors of immunity can manifest relatively frequently with diseases of the gastrointestinal tract, and should be included as a differential diagnosis of chronic diarrhea. Included in this group of diseases, hyper-IgM syndromes constitute a heterogeneous group of diseases, having in common significantly low or absent levels of IgG and IgA and normal or high levels of IgM, which predispose to infections and recurrent fever; in addition to other laboratory alterations, such as neutropenia, which may be associated with ulcers in the gastrointestinal tract and proctitis, simulating the clinical presentation of inflammatory bowel disease. For the reported patient, therapy with immunoglobulins was started periodically, in addition to antibiotic prophylaxis for infections, evolving with a satisfactory clinical response. The main objective of the article is to alert to the differential diagnosis of inborn errors of immunity in view of the presented condition, aiming at early diagnosis and the institution of adequate therapy.

Análisis retrospectivo de las características y utilización de los recursos de salud en pacientes con cáncer de próstata resistente a la castración metastásico tratados con Enzalutamida o Acetato de Abiraterona en Colombia / Retrospective Analysis of the Characteristics and Utilization of Health Resources in Patients with Castration Resistant Prostate Cancer Treated with Enzalutamide or Abiraterone Acetate in Colombia

Objetivo Describir las características demográficas, clínicas, los recursos de salud utilizados y los costos directos del tratamiento del cáncer de próstata resistente a la castración metastásico (CPRCm), tratados con enzalutamida o acetato de abiraterona en Colombia. Métodos Mediante un estudio de corte transversal se analizaron datos de utilización de servicios de una EPS (entidad promotora de salud) colombiana. Para ello, se identificaron los pacientes que durante el 1 de julio de 2016 y 30 de junio de 2017 (fecha índice) presentaron registro de uso de enzalutamida o acetato de abiraterona y se confirmaron sus antecedentes de castración química o quirúrgica (6 meses previos a la fecha índice). Se establecieron las frecuencias de uso de servicios en dicha población y se extrajo el consumo reportado asociado a consultas (urgencias, consulta externa), procedimientos y medicamentos en el periodo de análisis. Los costos se organizaron por categorías y se reportaron en pesos colombianos (COP) 2016. Resultados se identificaron 161 pacientes con CPRCm con edad media de 77 años, se determinó que el departamento colombiano con más población de CPRCm en esta cohorte fue el Valle del Cauca, que 98,1% de los pacientes pertenecen al régimen contributivo y que 1,9% al subsidiado. El cálculo de la supervivencia con el índice de comorbilidad de Charlson mostró que esos pacientes tendrían una tasa de supervivencia de 0% a 10 años. Las comorbilidades más frecuentes encontradas fueron hipertensión, diabetes mellitus, insuficiencia renal y otras patologías tumorales relacionadas. El costo total de manejo de un paciente con CPRCm, que recibe de manera continua durante 12 meses abiraterona o enzalutamida es promedio $131.942.292 COP año. Esa cifra incluye tanto el uso de servicios como el consumo de medicamentos, y ese último representa cerca del 90% del costo. Conclusiones los pacientes con cáncer en estadio metastásico se caracterizan por presentar alta demanda de medicamentos, laboratorios, imágenes diagnósticas, visitas ambulatorias e ingresos hospitalarios. Debido a que es una muestra pequeña de pacientes, se requiere desarrollar una valoración posterior que permita corroborar los hallazgos encontrados en este estudio retrospectivo.

Objective describe the demographic, clinical characteristics, the health resources utilization and the direct costs of patients with metastatic castration-resistant prostate cancer (CPRCm) treated with Enzalutamide or Abiraterone Acetate in Colombia. Methods Through a descriptive retrospective analysis through the database of a Colombian health insurer, patients were identified who, during July 1st, 2016 and June 30th, 2017 (index date) were dispensed with enzalutamide or abiraterone acetate, medical history of chemical or surgical castration was confirmed (6 months prior to the index date). The frequencies of use of services in this population were established and the reported consumption associated with consultations (emergencies, outpatient consultation), procedures and medications in the period of analysis were extracted. The costs were organized by categories and were reported according to Colombian pesos (COP) 2016. Results In a cohort of 161 patients with CPRCm with an average age of 77 years, it was determined that Valle del Cauca is the Colombian department with the largest CPRCm population in this cohort. 98.1% of the patients belong to the contributory regimen and 1.9% to the subsidized. The calculation of the patient's survival with the Charlson Comorbidity Index (CCI) showed a 0% survival rate at 10 years and most frequent comorbidities were hypertension, diabetes mellitus, renal failure and other related tumor pathologies. The total cost of managing a patient with CPRCm, who receives continuous abiraterone or enzalutamide for 12 months on average is $ 131,942,292 COP per year, this figure includes both the use of services and the consumption of medications; the latter represents ∼90% of cost. onclusions These patients were characterized by being large demander of health services, namely, medicines, laboratories, images, outpatient visits and inpatient admission. Due to it is a small sample of patients, is necessary to develop a posterior evaluation to corroborate the findings found in this retrospective analysis.