The non-pathogenic mycobacteria M. smegmatis and M. fortuitum induce rapid host cell apoptosis via a caspase-3 and TNF dependent pathway

<p>Abstract</p> <p>Background</p> <p>The HIV pandemic raised the potential for facultative-pathogenic mycobacterial species like, <it>Mycobacterium kansasii</it>, to cause disseminating disease in humans with immune deficiencies. In contrast, non-pathogenic mycobacterial species, like <it>M. smegmatis</it>, are not known to cause disseminating disease even in immunocompromised individuals. We hypothesized that this difference in phenotype could be explained by the strong induction of an innate immune response by the non-pathogenic mycobacterial species.</p> <p>Results</p> <p>A comparison of two rapid-growing, non-pathogenic species (<it>M. smegmatis </it>and <it>M. fortuitum</it>) with two facultative-pathogenic species (<it>M. kansasii </it>and <it>M. bovis </it>BCG) demonstrated that only the non-pathogenic bacteria induced strong apoptosis in human THP-1 cells and murine bone marrow-derived macrophages (BMDM) and dendritic cells (BMDD). The phospho-<it>myo</it>-inositol modification of lipoarabinomannan (PI-LAM) isolated from non-pathogenic species may be one of the cell wall components responsible for the pro-inflammatory activity of the whole bacteria. Indeed, PI-LAM induces high levels of apoptosis and IL-12 expression compared to the mannosyl modification of LAM isolated from facultative-pathogenic mycobacteria. The apoptosis induced by non-pathogenic <it>M. smegmatis </it>was dependent upon caspase-3 activation and TNF secretion. Consistently, BALB/c BMDM responded by secreting large amounts of TNF upon infection with non-pathogenic but not facultative-pathogenic mycobacteria. Interestingly, C57Bl/6 BMDM do not undergo apoptosis upon infection with non-pathogenic mycobacteria despite the fact that they still induce an increase in TNF secretion. This suggests that the host cell signaling pathways are different between these two mouse genotypes and that TNF is necessary but not sufficient to induce host cell apoptosis.</p> <p>Conclusion</p> <p>These results demonstrate a much stronger induction of the innate immune response by non-pathogenic versus facultative-pathogenic mycobacteria as measured by host cell apoptosis, IL-12 and TNF cytokine induction. These observations lend support to the hypothesis that the strong induction of the innate immune response is a major reason for the lack of pathogenicity in fast-growing mycobacteria.</p

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Development and characterisation of a Hybrid Soldering Alloy with AL2O3 Nanopracticles

In the field of soldering alloys lead free solder development and investigations have fellfield a great deal of advancement in the technical aspects, yet nanoparticle reinforcement of lead-free solder remains an open-ended field. This study has focused on developing a lead-free solder alloy enforced with nanoparticles and then proceeded to establish a thorough investigation of the solder’s basic and vital parameters from initial investigation of the solder’s thermal properties, mechanical strength properties, wetting abilities, and microstructural behavior analysis. On previously done studies from literature these tow base solder which the study focused on (Sn-3.0Ag-0.5Cu and Sn-9Zn ) were lacking in several aspects such as the mechanical strength and the density as well as few other. Yet due to the regular limitation in the research there remained the opportunity to reinforce these tow solders with various percentages of Al2O3 nanoparticles and record the behaviour and conduct the analysis needed on each composite. The percentages were 0.1, 0.3, and 0.5 % as well as the base solder containing 0.0% of nanoparticles addition. The parameters of each test conducted were listed with identical fabricating conditions and test rules so as to give a direct chance o compare between the behaviour of the tow solders. The Sn-3.0Ag-0.5Cu, for that the Sn-3.0Ag-0.5Cu-0.5Al2O3 recorded a melting temperature of 222.22°C, the same pattern of decrease in the melting temperature with the addition of the nanoparticle reinforcement was observed for the Sn-9Zn. The XRD as well as SEM analysis results showcased the existence of important IMC such as Cu6Sn5 indicating the reaction of the wetted solder. The microstructure and the IMC recorded a decrease as well in size and in clarity as well as magnitude of appearance. The maximum shear strength supported that both of the solders with the added 0.3% of Al2O3 reflected the highest shear strength and an encouraging result in regard to failure pattern. The lowest contact angle figure recorded was 37.82° and 41.39° for the Sn-3.0Ag-0.5Cu-0.3Al2O3 as well as for the Sn-9Zn-0.5Al2O3. All of these results have given a clear idea of the abilities of the reinforced soldering alloys and thus weather or not they are to be considered as a potential replacement for the currently excessively relied on lead free soldering alloys

Review on the Al2O3 nanoparticle reinforcement effect on thermal and mechanical properties of SAC alloys

This paper presents a short summery on the effect of the addition and doping of Sn-Ag-Cu or commonly known as SAC alloys with Aluminum oxide (Al2O3) nanoparticles. The paper introduce initially the background of the lead free solders as well as establish the concept of nanoparticle reinforcement composite lead free solder alloys. Then a short summery on the effect of the two nanoparticle reinforcement on the sac solder in the sections of Thermal properties and mechanical properties is presented. For instance some reported with Sn-0.3Ag-0.7Cu (SAC0307) when alloyed with 0.12 Al2O3 it showed an improved shear force of thermal cycling when it came to the mode of ductile fracture in comparison to the original alloy which possess a mode of fracture that presented a mixture between ductile and brittle

Development and Characterization of a Hybrid Solder Alloy on a Copper Substrate

The study of the composite solders alloy can be divided into few major sections, which are the metallurgical study, the physical properties such as density and wetting angle, thermal properties, and finally the mechanical properties

An Innovative Approach to Developing a 3D Virtual Map Creator using an Ultrasonic Sensor Array

Human shifted their focus towards robots once realizing that the robots may serve for the human development with the increased complexity of the living structures and the rapid revolutions in field such as manufacturing and civil structures. This paper investigates the development of a mobile robot that utilizes ultrasonic sensors to obtain distance readings and utilize it to draw 3D map of its surrounding. The robot is designed to perform within narrow spaced as well as rough terrain environment such as underground piping structure or underground wiring networks. The chosen wheeled platform is capable of maneuvering through the rough surfaces, guided by a specially designed obstacle navigation strategy using ultrasonic sensors. The mounting of the 3D mapping sensors presented in this paper is a new and innovative approach that resolves many of the problems encountered through previous proposed designs of 3D ultrasonic mappers. The 3D mapping sensors obtain data that creates a 2D map along with the position localization data to create a 3D form. The results obtained from extensive work on developing the vehicle as well as testing of the control and 3D mapping algorithm is presented in this paper

Autism Spectrum Disorder Diagnostic Criteria Changes and Impacts on the Diagnostic Scales-Utility of the 2nd and 3rd Versions of the Gilliam Autism Rating Scale (GARS)

There is joint agreement among professionals internationally on the importance of diagnosing autism spectrum disorders (ASD) in the early stages of the emergence of symptoms. Criteria changes for the diagnosis of ASD need updated versions of the scale to make the diagnosis feasible. This study aimed to evaluate the level of overlap between two different versions of the Gilliam Autism Rating Scale (GARS-2 and GARS-3), which have been updated based on changes in DSM-IV and DSM-5 on a Kurdish sample of individuals at risk of having ASD and Intellectual Disability, referred to the Bahoz center in the Kurdistan Region of Iraq. A group of 148 cases with ASD and developmental disabilities (DD) was evaluated using the 2nd and 3rd versions of the GARS scale to understand the level of cases that confirm an ASD diagnosis in both scales. Ninety-six individuals (65%) scored about the cut-off score for being diagnosed with ASD based on the GARS-2, and 137 individuals (93%) scored above the cut-off score based on the GARS-3. Moreover, keeping updated and meeting the changing demand of standardization and cultural suitability of the updating scales is a challenge. This challenge is due to the shortage of infrastructure sources and lack of established professionals in low- and middle-income countries (LMICs). Findings indicated that GARS-3, updated based on the DSM-5, tends to diagnose children with accompanying diagnoses and different levels of symptoms severity of ASD at different age levels. Further studies are needed to help professionals and policymakers in low- and middle-income countries understand the updated versions of the available scales and depend on the older version, which must be considered cautiously