Comparative genomic analysis of Bacillus atrophaeus HAB-5 reveals genes associated with antimicrobial and plant growth-promoting activities.

Bacillus atrophaeus HAB-5 is a plant growth-promoting rhizobacterium (PGPR) that exhibits several biotechnological traits, such as enhancing plant growth, colonizing the rhizosphere, and engaging in biocontrol activities. In this study, we conducted whole-genome sequencing of B. atrophaeus HAB-5 using the single-molecule real-time (SMRT) sequencing platform by Pacific Biosciences (PacBio; United States), which has a circular chromosome with a total length of 4,083,597 bp and a G + C content of 44.21%. The comparative genomic analysis of B. atrophaeus HAB-5 with other strains, Bacillus amyloliquefaciens DSM7, B. atrophaeus SRCM101359, Bacillus velezensis FZB42, B. velezensis HAB-2, and Bacillus subtilis 168, revealed that these strains share 2,465 CDSs, while 599 CDSs are exclusive to the B. atrophaeus HAB-5 strain. Many gene clusters in the B. atrophaeus HAB-5 genome are associated with the production of antimicrobial lipopeptides and polypeptides. These gene clusters comprise distinct enzymes that encode three NRPs, two Transat-Pks, one terpene, one lanthipeptide, one T3PKS, one Ripp, and one thiopeptide. In addition to the likely IAA-producing genes (trpA, trpB, trpC, trpD, trpE, trpS, ywkB, miaA, and nadE), there are probable genes that produce volatile chemicals (acoA, acoB, acoR, acuB, and acuC). Moreover, HAB-5 contained genes linked to iron transportation (fbpA, fetB, feuC, feuB, feuA, and fecD), sulfur metabolism (cysC, sat, cysK, cysS, and sulP), phosphorus solubilization (ispH, pstA, pstC, pstS, pstB, gltP, and phoH), and nitrogen fixation (nif3-like, gltP, gltX, glnR, glnA, nadR, nirB, nirD, nasD, narl, narH, narJ, and nark). In conclusion, this study provides a comprehensive genomic analysis of B. atrophaeus HAB-5, pinpointing the genes and genomic regions linked to the antimicrobial properties of the strain. These findings advance our knowledge of the genetic basis of the antimicrobial properties of B. atrophaeus and imply that HAB-5 may employ a variety of commercial biopesticides and biofertilizers as a substitute strategy to increase agricultural output and manage a variety of plant diseases.

Exploring the Unknown: Appreciating the Challenges of Non-compaction Cardiomyopathy.

Left ventricular non-compaction cardiomyopathy (LVNC), or non-compaction cardiomyopathy (NCCM), is defined by pronounced left ventricular trabeculations and deep intertrabecular recesses connecting with the ventricular cavity. Patients with NCCM can be asymptomatic or have severe complications, including heart failure, arrhythmias, thromboembolism, and sudden cardiac death. Our case discusses a patient with shortness of breath who was found to have a newly decreased ejection fraction. The workup revealed non-ischemic cardiomyopathy and cardiac MRI showed hyper-trabeculations consistent with NCCM. The patient was started on oral anticoagulation and guideline-directed medical therapy (GDMT) and discharged with an event monitor. NCCM stands as a relatively rare and enigmatic condition, often veiled in ambiguity. The absence of standardized diagnostic and management protocols further complicates its clinical landscape. While echocardiography is the primary diagnostic tool, its tendency for under-diagnosis poses a significant challenge. Conversely, advanced imaging modalities like cardiac MRI may lead to instances of overdiagnosis. Treatment approaches are non-specific, incorporating GDMT, anticoagulation, implantable cardioverter-defibrillator placement, and genetic testing paired with counseling. Prioritizing genetic research is crucial to uncover tailored therapeutic interventions. Establishing consensus guidelines and refining diagnostic accuracy are pivotal steps toward mitigating the risks associated with under and over-diagnosis.

Handgrip strength and mortality in a cohort of kidney failure patients: Comparative analysis of different normalization methods.

OBJECTIVES: Reduced handgrip strength (HGS) is associated with adverse clinical outcomes. We analyzed and compared associations of HGS with mortality risk in dialysis patients, using different normalization methods of HGS. METHODS: HGS and clinical and laboratory parameters were measured in a cohort of 446 incident dialysis patients (median age 56 y, 62% men). The area under the receiver operating characteristic curve (AUROC) was used to compare different normalization methods of HGS as predictors of mortality: absolute HGS in kilograms; HGS normalized to height, weight, or body mass index; and HGS of a reference population of sex-matched controls (percentage of the mean HGS value [HGS%]). Multivariate linear regression analysis was used to assess HGS predictors. Competing risk regression analysis was used to evaluate 5-year all-cause mortality risk. Differences in survival time between HGS% tertiles were quantitated by analyzing the restricted mean survival time. RESULTS: The AUROC for HGS% was higher than the AUROCs for absolute or normalized HGS values. Compared with the high HGS% tertile, low HGS% (subdistribution hazard ratio [sHR] = 2.36; 95% CI, 1.19-3.70) and middle HGS% (sHR = 1.79; 95% CI, 1.12-2.74) tertiles were independently associated with higher all-cause mortality and those with high HGS% tertile survived on average 7.95 mo (95% CI, 3.61-12.28) and 18.99 mo (95% CI, 14.42-23.57) longer compared with middle and low HGS% tertile, respectively. CONCLUSIONS: HGS% was a strong predictor of all-cause mortality risk in incident dialysis patients and a better discriminator of survival than absolute HGS or HGS normalized to body size dimensions.

Epigenetic clocks indicate that kidney transplantation and not dialysis mitigate the effects of renal ageing.

BACKGROUND: Chronic kidney disease (CKD) is an age-related disease that displays multiple features of accelerated ageing. It is currently unclear whether the two treatment options for end-stage kidney disease (dialysis and kidney transplantation [KT]) ameliorate the accelerated uremic ageing process. METHODS: Data on clinical variables and blood DNA methylation (DNAm) from CKD stage G3-G5 patients were used to estimate biological age based on blood biomarkers (phenotypic age [PA], n = 333), skin autofluorescence (SAF age, n = 199) and DNAm (Horvath, Hannum and PhenoAge clocks, n = 47). In the DNAm cohort, we also measured the change in biological age 1 year after the KT or initiation of dialysis. Healthy subjects recruited from the general population were included as controls. RESULTS: All three DNAm clocks indicated an increased biological age in CKD G5. However, PA and SAF age tended to produce implausibly large estimates of biological age in CKD G5. By contrast, DNAm age was 4.9 years (p = 0.005) higher in the transplantation group and 5.9 years (p = 0.001) higher in the dialysis group compared to controls. This age acceleration was significantly reduced 1 year after KT, but not after 1 year of dialysis. CONCLUSIONS: Kidney failure patients displayed an increased biological age as estimated by DNAm clocks compared to population-based controls. Our results suggest that KT, but not dialysis, partially reduces the age acceleration.

COVID-19 promotes endothelial dysfunction and thrombogenicity: role of proinflammatory cytokines/SGLT2 prooxidant pathway.

BACKGROUND: COVID-19 is associated with an increased risk of cardiovascular complications. Although cytokines have a predominant role in endothelium damage, the precise molecular mechanisms are far from being elucidated. OBJECTIVES: The present study hypothesized that inflammation in patients with COVID-19 contributes to endothelial dysfunction through redox-sensitive SGLT2 overexpression and investigated the protective effect of SGLT2 inhibition by empagliflozin. METHODS: Human plasma samples were collected from patients with acute, subacute, and long COVID-19 (n = 100), patients with non-COVID-19 and cardiovascular risk factors (n = 50), and healthy volunteers (n = 25). Porcine coronary artery endothelial cells (ECs) were incubated with plasma (10%). Protein expression levels were determined using Western blot analyses and immunofluorescence staining, mRNA expression by quantitative reverse transcription-polymerase chain reaction, and the level of oxidative stress by dihydroethidium staining. Platelet adhesion, aggregation, and thrombin generation were determined. RESULTS: Increased plasma levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1 were observed in patients with COVID-19. Exposure of ECs to COVID-19 plasma with high cytokines levels induced redox-sensitive upregulation of SGLT2 expression via proinflammatory cytokines IL-1ß, IL-6, and tumor necrosis factor-α which, in turn, fueled endothelial dysfunction, senescence, NF-κB activation, inflammation, platelet adhesion and aggregation, von Willebrand factor secretion, and thrombin generation. The stimulatory effect of COVID-19 plasma was blunted by neutralizing antibodies against proinflammatory cytokines and empagliflozin. CONCLUSION: In patients with COVID-19, proinflammatory cytokines induced a redox-sensitive upregulation of SGLT2 expression in ECs, which in turn promoted endothelial injury, senescence, platelet adhesion, aggregation, and thrombin generation. SGLT2 inhibition with empagliflozin appeared as an attractive strategy to restore vascular homeostasis in COVID-19.

Prevalence of chronic non-cancer pain among military veterans: a systematic review and meta-analysis of observational studies.

INTRODUCTION: Chronic non-cancer pain is common among military veterans; however, the prevalence is uncertain. This information gap complicates policy decisions and resource planning to ensure veterans have access to healthcare services that align with their needs. METHODS: Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, we searched MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science from inception to 9 February 2023 for observational studies reporting the prevalence of chronic non-cancer pain among military veterans. We performed random-effects meta-analysis to pool pain prevalence data across studies and used the Grading of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence. RESULTS: Forty-two studies that included 14 305 129 veterans were eligible for review, of which 28 studies (n=5 011 634) contributed to our meta-analysis. Most studies (90%; 38 of 42) enrolled US veterans, the median of the mean age among study participants was 55 years (IQR 45-62) and 85% were male. The pooled prevalence of chronic non-cancer pain was 45%; however, we found evidence of a credible subgroup effect based on representativeness of the study population. Moderate certainty evidence found the prevalence of chronic pain among studies enrolling military veterans from the general population was 30% (95% CI 23% to 37%) compared with 51% (95% CI 38% to 64%) among military veterans sampled from populations with high rates of conditions associated with chronic pain (p=0.005). CONCLUSION: We found moderate certainty evidence that 3 in every 10 military veterans from the general population live with chronic non-cancer pain. These findings underscore the importance of ensuring access to evidence-based care for chronic pain for veterans, and the need for prevention and early management to reduce transition from acute to chronic pain. Further research, employing a standardised assessment of chronic pain, is needed to disaggregate meaningful subgroups; for example, the proportion of veterans living with moderate to severe pain compared with mild pain.

Qualitative Review of National Nutrition Surveillance Systems in the Eastern Mediterranean Region.

The World Food Conference in 1974 emphasized the significance of establishing global nutrition surveillance to monitor and address nutritional challenges effectively. However, many countries, especially in the EMRO region, continue to encounter substantial difficulties in regularly generating disaggregated data on nutrition. The current study aimed to review the existing nutrition surveillance systems in the region and to identify their strengths and weaknesses, as well as the challenges they face in functioning optimally. METHODS: This study focused on the functional nutrition surveillance systems in eight Arab countries; namely Kuwait, Morocco, Oman, Palestine, Saudi Arabia, Sudan, Syria, and Yemen. The study's analysis involved utilizing primary data collected from both published and unpublished reports. Additionally, a structured checklist was employed to gather information from all countries involved in the study. Furthermore, interviews were conducted with the EMRO offices to gain deeper insights into the challenges, if any, that these nutrition surveillance systems face in functioning optimally. RESULTS: All countries use health facilities as a basic source of data for their nutrition surveillance, some countries triangulate their nutrition surveillance reports with data from other sources of information such as community or school surveys. Identified nutrition surveillance approaches are closely split between those who operate in stable settings and use routine health information systems (Morocco, Saudi Arabia, Oman, and Kuwait) and other countries that operate in fragile settings; for example, Yemen, Syria, Palestine, and Sudan struggle to provide early warning reports for rapid nutritional responses. CONCLUSIONS: Nutrition surveillance systems that utilize existing health information systems are the most sustained in the EMRO region. However, by integrating data from multiple sources, such as health facilities, surveys, and population censuses, countries can provide a holistic view of the nutritional situation, enhance their response to any emergency, and can leverage the infrastructure and resources already in place for health data collection and reporting. Collaboration between countries in the region through sharing experiences and success stories is important in order to reach a standardized system that can be implemented in different settings.

Phenylacetylglutamine and trimethylamine N-oxide: Two uremic players, different actions.

BACKGROUND: Chronic kidney disease (CKD) patients exhibit a heightened cardiovascular (CV) risk which may be partially explained by increased medial vascular calcification. Although gut-derived uremic toxin trimethylamine N-oxide (TMAO) is associated with calcium-phosphate deposition, studies investigating phenylacetylglutamine's (PAG) pro-calcifying potential are missing. METHODS: The effect of TMAO and PAG in vascular calcification was investigated using 120 kidney failure patients undergoing living-donor kidney transplantation (LD-KTx), in an observational, cross-sectional manner. Uremic toxin concentrations were related to coronary artery calcification (CAC) score, epigastric artery calcification score, and markers of established non-traditional risk factors that constitute to the 'perfect storm' that drives early vascular aging in this patient population. Vascular smooth muscle cells were incubated with TMAO or PAG to determine their calcifying effects in vitro and analyse associated pathways by which these toxins may promote vascular calcification. RESULTS: TMAO, but not PAG, was independently associated with CAC score after adjustment for CKD-related risk factors in kidney failure patients. Neither toxin was associated with epigastric artery calcification score; however, PAG was independently, positively associated with 8-hydroxydeoxyguanosine. Similarly, TMAO, but not PAG, promoted calcium-phosphate deposition in vitro, while both uremic solutes induced oxidative stress. CONCLUSIONS: In conclusion, our translational data confirm TMAO's pro-calcifying effects, but both toxins induced free radical production detrimental to vascular maintenance. Our findings suggest these gut-derived uremic toxins have different actions on the vessel wall and therapeutically targeting TMAO may help reduce CV-related mortality in CKD.

Impact of diarrhoea and acute respiratory infection on environmental enteric dysfunction and growth of malnourished children in Pakistan: a longitudinal cohort study.

Background: Diarrhoea and acute respiratory infections (ARI) are assumed to be major drivers of growth and likely contribute to environmental enteric dysfunction (EED), which is a precursor to childhood malnutrition. In the present study, we checked the correlation between diarrhoeal/ARI burden and EED using a novel duodenal histological index. Methods: Between November 2017 and July 2019, a total of 365 infants with weight-for-height Z scores (WHZ score) of <-2 were enrolled, and 51 infants with WHZ scores of >0 and height-for-age Z scores (HAZ scores) of >-1 were selected as age-matched healthy controls. Morbidity was assessed weekly and categorised as the total number of days with diarrhoea and acute respiratory infection (ARI) from enrolment until two years of age and was further divided into four quartiles in ascending order. Findings: The HAZ declined until two years of age regardless of morbidity burden, and WHZ and weight-for-age Z scores (WAZ scores) were at their lowest at six months. Sixty-three subjects who had a WHZ score <-2 and failed to respond to nutritional and educational interventions were further selected at 15 months to investigate their EED histological scores with endoscopy further. EED histological scores of the subjects were higher with increasing diarrhoeal frequency yet remained statistically insignificant (p = 0.810). Interpretation: There was not a clear correlation between diarrhoea and ARI frequency with growth faltering, however, children with the highest frequency of diarrhoea had the highest EED histological scores and growth faltering. Funding: Bill and Melinda Gates Foundation and The National Institutes of Health.

Elevated plasma phospholipid n-3 docosapentaenoic acid concentrations during hibernation.

Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in free-ranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alpha-linolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism.

Interleukin-6-to-Albumin Ratio as a Superior Predictor of Mortality in End-Stage Kidney Disease Patients.

INTRODUCTION: In patients with chronic kidney disease (CKD), high interleukin-6 (IL-6) and low albumin circulating concentrations are associated with worse outcomes. We examined the IL-6-to-albumin ratio (IAR) as a predictor of risk of death in incident dialysis patients. METHODS: In 428 incident dialysis patients (median age 56 years, 62% men, 31% diabetes mellitus, 38% cardiovascular disease [CVD]), plasma IL-6 and albumin were measured at baseline to calculate IAR. We compared the discrimination of IAR with other risk factors for predicting 60-month mortality using receiver operating characteristic curve (ROC) and analyzed the association of IAR with mortality using Cox regression analysis. We divided patients into IAR tertiles and analyzed: (1) cumulative incidence of mortality and the association of IAR with mortality risk in Fine-Gray analysis, taking kidney transplantation as competing risk and (2) the restricted mean survival time (RMST) to 60-month mortality and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time. RESULTS: For all-cause mortality, the area under the ROC curve (AUC) for IAR was 0.700, which was greater than for IL-6 and albumin separately, while for CV mortality, the AUC for IAR (0.658) showed negligible improvement over IL-6 and albumin separately. In Cox regression analysis, IAR was significantly associated with all-cause mortality but not with CV mortality. Both high versus low and middle versus low tertiles of IAR associated with higher risk of all-cause mortality, subdistribution hazard ratio of 2.22 (95% CI 1.40-3.52) and 1.85 (95% CI 1.16-2.95), respectively, after adjusting for age, sex, diabetes mellitus, CVD, smoking, and estimated glomerular filtration rate. ∆RMST at 60 months showed significantly shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause mortality. CONCLUSIONS: Higher IAR was independently associated with significantly higher all-cause mortality risk in incident dialysis patients. These results suggest that IAR may provide useful prognostic information in patients with CKD.

Central obesity as assessed by conicity index and a-body shape index associates with cardiovascular risk factors and mortality in kidney failure patients.

Background: Anthropometric indices of central obesity, waist circumference (WC), conicity index (CI), and a-body shape index (ABSI), are prognostic indicators of cardiovascular (CV) risk. The association of CI and ABSI with other CV risk indices, markers of nutritional status and inflammation, and clinical outcomes in chronic kidney disease (CKD) stage 5 (CKD5) patients was investigated. Methods: In a cross-sectional study with longitudinal follow up of 203 clinically stable patients with CKD5 (median age 56 years; 68% males, 17% diabetics, 22% with CV disease, and 39% malnourished), we investigated CI and ABSI and their associations with atherogenic index of plasma (AIP), Framingham CV risk score (FRS), Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC), handgrip strength (HGS), high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). CV events (CVE) and all-cause mortality during up to 10-years follow up were analyzed by multivariate survival analysis of restricted mean survival time (RMST). Results: Chronic kidney disease patients with middle and highest CI and ABSI tertiles (indicating greater abdominal fat deposition), compared to those with the lowest CI and ABSI tertiles, tended to be older, more often men and diabetic, had significantly higher levels of hsCRP, IL-6, AIP, FRS, CAC and AVC scores. CI and ABSI were positively correlated with CAC, FRS, AIP, hsCRP and IL-6. Both CI and ABSI were negatively correlated with HGS. In age-weighted survival analysis, higher CI and ABSI were associated with higher risk of CVE (Wald test = 4.92, p = 0.027; Wald test = 4.95, p = 0.026, respectively) and all-cause mortality (Wald test = 5.24, p = 0.022; Wald test = 5.19, p = 0.023, respectively). In RMST analysis, low vs. high and middle tertiles of CI and ABSI associated with prolonged CVE-free time and death-free time, and these differences between groups increased over time. Conclusion: Abdominal fat deposit indices, CI and ABSI, predicted CV outcomes and all-cause mortality, and were significantly associated with the inflammatory status in CKD patients.

The effect of high-dose vitamin D supplementation on hepcidin-25 and erythropoiesis in patients with chronic kidney disease.

BACKGROUND: Hepcidin is considered to play a central role in the pathophysiology of renal anemia. Recent studies in healthy individuals have demonstrated a suppressive effect of vitamin D (VD) on the expression of hepcidin. In this post-hoc analysis based on a randomized controlled study, we evaluated the effect of supplementing chronic kidney disease (CKD) patients (stage G3-G4) with a high daily dose of native VD on serum levels of hepcidin-25, the hepcidin/ferritin ratio, as well as on markers of erythropoiesis. METHODS: Patients with CKD stage G3-G4 included in a double blind, randomized, placebo (PBO) controlled study with available hepcidin measurements were analyzed. Study subjects received either 8000 international units (IU) of cholecalciferol daily or PBO for 12 weeks. We evaluated the change in markers of hepcidin expression, erythropoiesis, and iron status from baseline to week 12 and compared the change between the groups. RESULTS: Eighty five patients completed the study. Calcitriol, but not 25-hydroxyvitamin D (25(OH) D), was inversely correlated with serum levels of hepcidin-25 (rho = -0,38; p = < 0, 01 and rho = -0,02; p = 0, 89, respectively) at baseline. Supplementation with VD significantly raised the serum concentration of serum 25(OH)D in the treatment group (from 54 (39-71) to 156 (120-190) nmol/L; p = < 0, 01)) but had no effect on any of the markers of hepcidin, erythropoiesis, or iron status in the entire cohort. However, we did observe an increase in hemoglobin (HB) levels and transferrin saturation (TSAT) as compared to the PBO group in a subgroup of patients with low baseline 25(OH)D levels (< 56 nmol/L). In contrast, in patients with high baseline 25(OH)D values (≥ 56 nmol/L), VD supplementation associated with a decrease in HB levels and TSAT (p = 0,056) within the VD group in addition to a decrease in hepcidin levels as compared to the PBO group. CONCLUSION: High-dose VD supplementation had no discernible effect on markers of hepcidin or erythropoiesis in the entire study cohort. However, in patients with low baseline 25(OH)D levels, high-dose VD supplementation associated with beneficial effects on erythropoiesis and iron availability. In contrast, in patients with elevated baseline 25(OH)D levels, high-dose VD supplementation resulted in a decrease in hepcidin levels, most likely due to a deterioration in iron status.

Decreasing incidence of knee arthroscopy in Sweden between 2002 and 2016: a nationwide register-based study.

BACKGROUND AND PURPOSE: Several randomized trials have demonstrated the lack of effect of arthroscopic lavage as treatment for knee osteoarthritis (OA). These results have in turn resulted in a change in Swedish guidelines and reimbursement. We aimed to investigate the use of knee arthroscopies in Sweden between 2002 and 2016. Patient demographics, regional differences, and the magnitude of patients with knee OA undergoing knee arthroscopy were also analyzed. PATIENTS AND METHODS: Trends in knee arthroscopy were investigated using the Swedish Hospital Discharge Register (SHDR) to conduct a nationwide register-based study including all adults (>18 years of age) undergoing any knee arthroscopy between 2002 and 2016. RESULTS: The total number of knee arthroscopies performed during the studied period was 241,055. The annual surgery rate declined in all age groups, for males and females as well as patients with knee OA. The incidence dropped from 247 to 155 per 105 inhabitants. Over 50% of arthroscopies were performed in metropolitan regions. CONCLUSION: We showed a dramatic decline in knee arthroscopy. There is variability in the surgery rate between males and females and among the regions of Sweden.

Low-Plasma Insulin-Like Growth Factor-1 Associates With Increased Mortality in Chronic Kidney Disease Patients With Reduced Muscle Strength.

OBJECTIVES: Chronic kidney disease (CKD) leads to metabolic and nutritional abnormalities including resistance to insulin-like growth factor-1 (IGF-1) action, and reduced muscle mass and strength. Low IGF-1 as well as low hand-grip muscle strength (HGS) are independent predictors of increased mortality in CKD patients. METHODS: In 685 patients (CKD Stage 3-5, median age 58 years; 62% men), baseline measurements of IGF-1, HGS, subjective global assessment (SGA), lean body mass index (LBMI), and metabolic and inflammatory biomarkers potentially linked to IGF-1 were analyzed in relation to mortality during 5 years of follow-up. We compared survival in 4 groups with high or low (cut-offs defined by receiver operating characteristic curve analysis) levels of IGF-1 and HGS. RESULTS: Patients with low IGF-1 were older; had lower BMI, HGS, and LBMI, were more likely to have diabetes, cardiovascular disease (CVD), and malnutrition (SGA >1); and had high-sensitivity C-reactive protein levels. During 5 years of follow-up, 208 patients died. The mortality rate was highest among patients with Low IGF-1 + Low HGS. In competing-risk regression analysis, Low IGF-1 + Low HGS was independently associated with 2.8 times higher all-cause mortality risk than Low IGF-1 + High HGS, after adjusting for Framingham's CVD risk score, presence of CVD, SGA, dialysis status, high-sensitivity C-reactive protein, albumin, LBMI, and sample time in freezer. CONCLUSION: Low IGF-1 was associated with increased all-cause mortality in patients who also had low HGS but not in those with high HGS, suggesting that the association of IGF-1 with survival in CKD patients depends on nutritional status.

Anatomical double-bundle anterior cruciate ligament reconstruction moderately improved tegner scores over the long-term: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To assess the effects of anatomical double-bundle (DB) versus single-bundle (SB) for anterior cruciate ligament (ACL) reconstruction in skeletally mature patients with ACL injuries. METHODS: MEDLINE, EMBASE, and CENTRAL were searched from inception to February 7, 2022 were screened for randomized controlled trials. The Anatomic Anterior Cruciate Ligament Reconstruction Checklist was used to categorize studies as anatomic. A random-effects meta-analysis was conducted, with pooled results being summarized using mean difference (MD). Risk of Bias (RoB) was assessed using the RoB 2.0 tool. Certainty of evidence was rated using GRADE. RESULTS: A search of 1371 unique articles yielded eight eligible trials, representing 735 patients (360 DB, 375 SB) with mean (SD) age of 28.5 (2.86) years and follow-up of 52.1 (36.2) months. Most trials had moderate to low RoB. Overall, DB was not significantly better than SB on Lysholm scores (MD = 0.52, 95% CI, - 1.80-2.85, p = 0.66; moderate certainty) or subjective International Knee Documentation Committee (IKDC) scores (MD = - 0.40, 95% CI, - 4.35-3.55, p = 0.84; moderate certainty). Tegner scores were significantly higher in SB than DB in the intermediate term (MD = - 0.72, 95% CI, - 1.10 to - 0.34, p = 0.0002; high certainty), while significantly higher in DB relative to SB in the long-term (MD = 0.52, 95% CI, 0.02-1.03, p = 0.04; high certainty). CONCLUSION: DB ACL reconstruction significantly improves Tegner scores relative to SB ACL reconstruction over the long-term (t ≥ 5 years). Intermediate term Tegner scores favour SB reconstruction. In both durations, there was no clinically significant difference based on the pre-specified minimal clinically important difference of 1.0 point. There were also no significant differences in IKDC or Lysholm scores. Surgeons should consider anatomical DB ACL reconstruction as a result of long-term improvement in patient-reported outcomes. LEVEL OF EVIDENCE: I.

Characteristics-Based Framework of Effective Automated Monitoring Parameters in Construction Projects.

The construction industry is moving toward digitalization, and technologies support various construction processes. In the automated construction progress monitoring domain, several modern progress measurement techniques have been introduced. However, a hesitant attitude has been observed toward its adoption. Researchers have highlighted lack of theoretical understanding of effectual implementation is one of the significant reasons. This study aims to analyze general technological parameters related to automated monitoring technologies and devise a theoretical-based conceptual framework explaining the aspects affecting the adequate operation of automated monitoring. The study has been executed by following a systematic inline process for the identification of effective parameters, which include a structured literature review, semi-structured interviews, pilot survey, questionnaire survey, and structural equation modeling (SEM)-based mathematical model. A refined conceptual framework has been devised with 21 effective parameters under five significant categories, i.e., "Target Object," "Technical," "External Interference," "Occlusions," and "Sensing." A knowledge framework has been established by adopting the SEM technique, which is designed on the characteristics-based theme. This conceptual framework provides the theoretical base for practitioners toward the conceptual understanding of automated monitoring processes related to technological parameters that affect the outcomes. This study is unique as it focused on the general criteria or parameters that affect the performance or outcomes of the digital monitoring process and is easily understandable by the user or operator.

Research Priorities Among Canadian Military Veterans Living With Chronic Pain: A Cross-Sectional Survey.

INTRODUCTION: Chronic pain is a debilitating problem that disproportionately affects military veterans. We completed a qualitative study that identified 20 research priorities of Canadian veterans living with chronic noncancer pain. The aim of this study was to establish the generalizability of these priorities. MATERIALS AND METHODS: From January to March 2021, we emailed a 45-item survey to a list of Canadian veterans living with chronic noncancer pain that asked about the relative importance of 20 research priorities. RESULTS: Overall, 313 of 701 Canadian military veterans living with chronic noncancer pain returned a completed survey (45% response rate). All 20 research priorities listed in the survey were endorsed by ≥75% of respondents, and four received ≥95% endorsement: (1) optimizing chronic pain management after release from the military; (2) establishing the effectiveness of self-care; and (3) identifying and (4) treating mental illness among veterans living with chronic pain. One research priority differed significantly by gender; 50% more females than males rated improving chronic pain care while in the military as important (99% vs. 49%, P < .001). CONCLUSIONS: Our survey established research priorities among Canadian veterans living with chronic noncancer pain. These findings should be considered by granting agencies when formulating calls for proposals and by researchers who wish to undertake research that will address the needs of military veterans living with chronic pain.

Subsurface groundwater aquifer mapping and quality characterization in Matiari district, Sindh, Pakistan.

Groundwater, is an alternative resource, is used as a supplement for irrigation as well as drinking purposes in Pakistan. This paper aims to determine the quantum and quality of groundwater in Matiari district of Sindh, Pakistan, through Electrical Resistivity Survey (ERS). The ERS was conducted at 52 location points using the ABEM Terrameter SAS 4000. The quantity of good quality groundwater has also been evaluated with ArcGIS interpolation techniques, i.e., the maximum percentage of fresh groundwater is 34% the marginal fresh groundwater 43% at the depth of with few patches of saline groundwater aquifers. Moreover, at 50-m depth, the percentage of fresh groundwater reduces to 21% and the marginal has increased to 48%. However, groundwater below the depth from 50 to 100 m was found only 8% fresh groundwater, 29% marginal, 49% salt water, and 14% high salt water. Analysis of groundwater samples for quality showed a good agreement with the quality obtained from VES results. In addition, a socio-economic survey of 55 tube well owners were conducted through interviews related to groundwater suitability and usage. According to the survey, about 62% of respondents are using good quality groundwater; however, 36% consuming the marginal and the remaining 2% are utilizing the hazardous quality of groundwater. The consumer satisfaction survey showed most farmers (89%) were satisfied with the groundwater usage, while 11% were unsatisfied due to poor-quality groundwater. The crop productivity could be enhanced through awareness and conjunctive use of marginal quality groundwater with the canal water.

Barriers and facilitators to exclusive breastfeeding in rural Pakistan: a qualitative exploratory study.

BACKGROUND: Exclusive breastfeeding (EBF) of children until six months of age is considered one of the most critical interventions in tackling childhood undernutrition. EBF rates are suboptimal in Pakistan, particularly in rural areas where child undernutrition is most prevalent. This study aimed to explore barriers to EBF in a rural context of Pakistan. METHODS: The study was conducted in the rural district Matiari of Sindh, Pakistan, during Jan-March 2020. We used a qualitative exploratory study design and conducted 36 focus group discussions (FGDs). Participants were purposively selected mothers who had not practiced EBF during their previous childbirth, their spouses and mothers-in-law, and lady health workers (LHWs) serving in the study catchment. FGDs were audio-recorded, transcribed, and translated into English from the local language and analysed using thematic content analysis. RESULTS: Barriers to EBF included low awareness and cultural practices of prelacteal feeds, insufficient breast milk production, undernutrition of mothers, mothers' occupation as fieldworkers, less birth spacing, low awareness about the correct technique of breastfeeding, maternal and child ailments, abnormal breasts, and influence of in-laws to start top-up feeds. Several facilitators were identified: family support, appropriate maternal diet, maternal awareness, and support in the neighborhood. CONCLUSION: Barriers to EBF are multifaceted in rural areas, and interventions aiming to improve adherence to EBFshould be multipronged. Awareness-raising alone might not be sufficient, and other interventions should be designed to address the barriers of maternal malnutrition, insufficient milk production, and socio-cultural practices. In addition, safe alternatives to breast milk may be necessary if breastfeeding is truly not feasible. Lack of breast milk substitutes is particularly challenging for poor rural women who cannot afford infant formula milk.