bluuebunny/crossref_metadata_2025 huggingface dataset:
Early amantadine treatment reduces the risk of death in patients with large hemisphere infarctions:a Chinese hospital-based study
Authors: Li Jie , Zhang Ping , Liu Yingying , Wu Simiao , Yi Xingyang , Zhang Shihong , Wang Chun , Liu Ming
Published: October 2021

Background

Amantadine hydrochloride is one of the most frequently prescribed drugs for patients with severe traumatic brain injury in restoring consciousness and accelerating the pace of functional recovery. However, there is a paucity of studies on the effectiveness of amantadine in patients with severe stroke especially large hemisphere infarction (LHI). The present study aimed to investigate whether amantadine treatment is associated with better clinical outcomes in conservatively treated LHI patients.

Methods

We retrospectively collected conservatively treated LHI patients according to inclusion/exclusion criteria. The patients were divided into two groups based on the treatment regimen, whether they did receive amantadine hydrochloride in addition to standard therapy (ST) or not. The primary outcomes were in-hospital death, 3-month mortality, and unfavorable outcome (defined as modified Rankin Scale score of 4 to 6). All outcomes were compared between the two groups before and after propensity score matching (PSM). Multivariate logistic regression was performed to identify the association between early amantadine hydrochloride treatment and clinical outcomes in LHI patients.

Results

Thirty-one LHI patients treated with amantadine combined with ST and 127 patients treated with ST were enrolled. Amantadine group had a shorter prehospital delay (median: 2 vs. 10 h), a higher baseline NIHSS score (21.71 ± 4.76 vs. 17.49 ± 5.84), and a higher rate of dominant hemisphere involvement (67.74% vs. 45.67%). After PSM, amantadine treatment significantly reduced the risk of in-hospital death (7.41% vs. 31.11%, p=0.019) and 3-month mortality (25.93% vs. 55.56%, p=0.008). Amantadine treatment yielded a significant decrease in death in-hospital (before PSM: OR 0.143, 95% CI 0.034 to 0.605; after PSM: OR 0.113, 95% CI 0.020 to 0.635) and 3-month mortality (before PSM: OR 0.214, 95% CI 0.077 to 0.598; after PSM: OR 0.176, 95% CI 0.053 to 0.586) in unmatched and matched multivariate analyses.

Conclusion

The results of our study provide initial evidence that early amantadine treatment was associated with a decrease in death in conservatively treated LHI patients. Considering the limitations of observational study, randomized controlled trials with a large sample size may help provide a clearer picture of the utility of amantadine in LHI patients.
Blast cells surviving acute myeloid leukemia induction therapy are in cycle with a signature of FOXM1 activity
Authors: Williams Mark S. , Basma Naseer J. , Amaral Fabio M. R. , Wiseman Daniel H. , Somervaille Tim C. P.
Published: October 2021

Background

Disease relapse remains common following treatment of acute myeloid leukemia (AML) and is due to chemoresistance of leukemia cells with disease repopulating potential. To date, attempts to define the characteristics of in vivo resistant blasts have focused on comparisons between leukemic cells at presentation and relapse. However, further treatment responses are often seen following relapse, suggesting that most blasts remain chemosensitive. We sought to characterise in vivo chemoresistant blasts by studying the transcriptional and genetic features of blasts from before and shortly after induction chemotherapy using paired samples from six patients with primary refractory AML.

Methods

Leukemic blasts were isolated by fluorescence-activated cell sorting. Fluorescence in situ hybridization (FISH), targeted genetic sequencing and detailed immunophenotypic analysis were used to confirm that sorted cells were leukemic. Sorted blasts were subjected to RNA sequencing. Lentiviral vectors expressing short hairpin RNAs were used to assess the effect of FOXM1 knockdown on colony forming capacity, proliferative capacity and apoptosis in cell lines, primary AML cells and CD34+ cells from healthy donors.

Results

Molecular genetic analysis revealed early clonal selection occurring after induction chemotherapy. Immunophenotypic characterisation found leukemia-associated immunophenotypes in all cases that persisted following treatment. Despite the genetic heterogeneity of the leukemias studied, transcriptional analysis found concerted changes in gene expression in resistant blasts. Remarkably, the gene expression signature suggested that post-chemotherapy blasts were more proliferative than those at presentation. Resistant blasts also appeared less differentiated and expressed leukemia stem cell (LSC) maintenance genes. However, the proportion of immunophenotypically defined LSCs appeared to decrease following treatment, with implications for the targeting of these cells on the basis of cell surface antigen expression. The refractory gene signature was highly enriched with targets of the transcription factor FOXM1. shRNA knockdown experiments demonstrated that the viability of primary AML cells, but not normal CD34+ cells, depended on FOXM1 expression.

Conclusions

We found that chemorefractory blasts from leukemias with varied genetic backgrounds expressed a common transcriptional program. In contrast to the notion that LSC quiescence confers resistance to chemotherapy we find that refractory blasts are both actively proliferating and enriched with LSC maintenance genes. Using primary patient material from a relevant clinical context we also provide further support for the role of FOXM1 in chemotherapy resistance, proliferation and stem cell function in AML.
Combined analysis of PTEN, HER2, and hormone receptors status: remodeling breast cancer risk profiling
Authors: Sajjadi Elham , Venetis Konstantinos , Piciotti Roberto , Gambini Donatella , Blundo Concetta , Runza Letterio , Ferrero Stefano , Guerini-Rocco Elena , Fusco Nicola
Published: October 2021

Background

Phosphatase and tensin homolog (PTEN) loss is associated with tumorigenesis, tumor progression, and therapy resistance in breast cancer. However, the clinical value of PTEN as a biomarker in these patients is controversial. We sought to determine whether the benefit of traditional biomarkers testing is improved by the analysis of PTEN status for the identification of high-risk breast cancer.

Methods

A cohort of 608 patients with breast cancer was included in this study. Based on the expression on the neoplastic cells compared to the normal internal controls by immunohistochemistry (IHC), cases were classified as PTEN-low (PTEN-L) or PTEN-retained (PTEN-WT). The former constituted the study group, while the latter the control group. Analysis of gene expression was performed on publicly available genomic data and included 4265 patients from the METABRIC and MSK cohorts retrieved from cBioPortal. The Shapiro-Wilk test was used to analyze the normal distributions of continuous variables. Relationships between PTEN status and the clinicopathologic and molecular features of the patient population were assessed using Fisher’s exact test or Chi-squared/Wilcoxon rank-sum test. Survival curves were built according to the Kaplan-Meier method.

Results

Alteration in PTEN status was significantly different at protein and gene levels, where the reduced protein expression was observed in 280/608 cases (46.1%) from our group, while genetic aberrations in only 315/4265 (7.4%) cases of the METABRIC and MSK cohorts. PTEN-L tumors were significantly enriched for hormone receptors (HR) and HER2 negativity (n = 48, 17.1%) compared to PTEN-WT tumors (n = 22, 6.7%; p = 0.0008). Lack of HR with or without HER2 overexpression/amplification was significantly associated with worse overall survival (OS) in PTEN-L but not in PTEN-WT breast cancers (p < .0001). Moreover, PTEN-L protein expression but not gene alterations was related to the outcome, in terms of both OS and disease-free survival (p = 0.002).

Conclusions

The combined analysis of PTEN, HER2, and HR status offers relevant information for a more precise risk assessment of patients with breast cancer.
Arrest and non-fatal suicide attempts among men: analysis of survey data from the National Survey on Drug Use and Health
Authors: Bryson William C. , Piel Jennifer , Thielke Stephen M.
Published: October 2021

Background

Studies have found an association between recent arrest and suicide attempts, but the population-level significance of this link has not been reported. We estimated the population attributable risk percent (PAR%) of self-reported non-fatal suicide attempts based on recent arrest in a national sample of adult men.

Methods

This study included men aged ≥18 who completed the 2008–2019 National Surveys on Drug Use and Health. The outcome measure was any non-fatal suicide attempts in the past year. The primary independent variable was any arrest in the past year. Major depression and substance use disorders were also included as independent variables for comparison. Descriptive statistics and multivariate logistic regression with postestimation marginal effects ascertained the PAR% of non-fatal suicide attempts for arrest, major depression, and substance use disorders, while controlling for sociodemographic covariates. All analyses applied survey weights. We disaggregated analyses by race/ethnicity.

Results

In the sample of 220,261 men, arrest accounted for 8.9% (99% CI 5.1 to 12.6%, p < 0.001) of non-fatal suicide attempts, while major depression accounted for 40.3% (99% CI 35.0 to 45.1%. p < 0.001) and substance use disorders for 24.1% (99% CI 17.6 to 30.2%, p < 0.001). After disaggregating by race/ethnicity, arrest accounted for 9.5% (99% CI 4.5 to 14.3%, p < 0.001) of suicide attempts among Non-Hispanic White men and fell short of statistical significance for Non-Hispanic Black men (10.2, 99% CI − 3.0 to 21.6%, p = 0.043) and Hispanic men (8.1, 99% CI − 0.5 to 15.9%, p = 0.016).

Conclusions

Arrest accounted for nearly one in eleven non-fatal suicide attempts in a national sample of American men, which is by extension about 50,000 suicide attempts per year. Results were similar for Non-Hispanic White, Non-Hispanic Black, and Hispanic men, although there were differences in prevalence of arrest and suicide attempts. Unlike major depression, arrest is an easily identifiable event, and the period after arrest might provide an opportunity to support mental health and coping.
Association between depression and antibiotic use: analysis of population-based National Health Insurance claims data
Authors: Lee Jong-Wook , Lee Hankil , Kang Hye-Young
Published: October 2021

Background

Frequent exposure to antibiotic treatments may increase the risk of antibiotic resistance, which may threaten the effectiveness of future antibiotic treatments. Thus, it is important to identify the preventable risks in terms of antibiotic use. This study assessed the association between major depressive disorder (MDD) and antibiotic use by comparing the likelihood and extent of antibiotic use between patients with and without MDD.

Methods

This retrospective cross-sectional study utilized the National Patients Sample data from the 2017 Health Insurance Review and Assessment Service. We analyzed 16,950 patients with MDD, defined as those with at least two claims records stating a primary diagnosis of MDD (International Classification of Diseases, 10th revision codes F32–33) and 67,800 patients without MDD (1:4 propensity-score matched control group). Antibiotic use was compared between the patients with and without MDD based on three variables: the presence of antibiotic prescriptions, total prescription days of antibiotics per year, and total medication costs of antibiotics per year.

Results

The adjusted odds ratio obtained by multivariate regression analysis for the presence of prescription of antibiotics was 1.31 (95% confidence interval [CI]: 1.25–1.36). In the negative binomial model, the number of prescription days was 1.25 times (95% CI: 1.23–1.28) higher in patients with MDD than in those without MDD. Generalized linear model analysis showed a 1.39-fold (95% CI: 1.36–1.43) higher cost of antibiotic prescription in patients with MDD than in those without MDD.

Conclusions

Our results suggest a potential association between MDD and the prescription of antibiotics, implying that patients with MDD are relatively vulnerable to infections. It is important to prevent as well as closely monitor the occurrence of infections when managing patients with MDD.
Risky motorcycle riding behaviour among young riders in Manipal, India
Authors: Sumit Kumar , Ross Veerle , Brijs Kris , Wets Geert , Ruiter Robert A. C.
Published: October 2021

Background

Motorcycles are one of the most commonly used transportation modes in low and middle-income countries. In India, motorized two-wheelers comprise 70% of the total vehicle population, and motorcycle users are considered the most vulnerable road users. It is essential to understand the risky riding behaviour and associated factors among the motorcyclists to develop evidence-based traffic safety programs targeting motorcycle riders. The purpose of the current study was two-fold. First, it aimed to determine the appropriate structure of a modified version of the MRBQ among young riders in Manipal, India. Second, it assessed to what extent MRBQ factors were associated with self-reported crash involvement and violations.

Methods

The motorcycle rider behaviour questionnaire (MRBQ) is a 43-item scale that assesses five aspects of risky motorcycle rider behaviour, i.e., violations, control errors, traffic errors, stunts, and protective equipment. The MRBQ, along with measures of socio-demographic variables and the number of motorcycle crashes, was filled out by 300 young motorcycle riders who were in the age group of 18–25 years and had been riding for at least the past three years (93% males, 92.3% students).

Results

Five factors emerged out of the MRBQ after an exploratory factor analysis: traffic errors, control errors, stunts, protective equipment, and violations. Cronbach’s alpha for these factors ranged from .66 to .82. Reports of performing stunts and committing violations were positively associated with self-reported near-crash experiences over the past three months. Riders reporting stunts, violations and using a motorcycle of 125-200 cc reported having received more fines in the last three months. These findings were confirmed in both univariate and multivariate binary logistic regression models.

Conclusion

The study assessed the factor structure of a modified version MRBQ and the extracted factors associations with self-reported crash involvement. The factor structure revealed in the current study is consistent with MRBQ factor structures found in other countries. However, the support for a relationship between MRBQ factors and self-reported crashes was less significant. The findings suggest that if replicated by future studies, local policymakers are advised to focus on the five MRBQ factors while planning future interventions to achieve a reduction in the number of road crashes among motorcyclists.
Patellar cartilage increase following ACL reconstruction with and without meniscal pathology: a two-year prospective MRI morphological study
Authors: Wang Xinyang , Bennell Kim L. , Wang Yuanyuan , Fortin Karine , Saxby David J. , Killen Bryce A. , Wrigley Tim V. , Cicuttini Flavia M. , Van Ginckel Ans , Lloyd David G. , Feller Julian A. , Vertullo Christopher J. , Whitehead Tim , Gallie Price , Bryant Adam L.
Published: October 2021

Background

Anterior cruciate ligament reconstruction (ACLR) together with concomitant meniscal injury are risk factors for the development of tibiofemoral (TF) osteoarthritis (OA), but the potential effect on the patellofemoral (PF) joint is unclear. The aim of this study was to: (i) investigate change in patellar cartilage morphology in individuals 2.5 to 4.5 years after ACLR with or without concomitant meniscal pathology and in healthy controls, and (ii) examine the association between baseline patellar cartilage defects and patellar cartilage volume change.

Methods

Thirty two isolated ACLR participants, 25 ACLR participants with combined meniscal pathology and nine healthy controls underwent knee magnetic resonance imaging (MRI) with 2-year intervals (baseline = 2.5 years post-ACLR). Patellar cartilage volume and cartilage defects were assessed from MRI using validated methods.

Results

Both ACLR groups showed patellar cartilage volume increased over 2 years (p < 0.05), and isolated ACLR group had greater annual percentage cartilage volume increase compared with controls (mean difference 3.6, 95% confidence interval (CI) 1.0, 6.3%, p = 0.008) and combined ACLR group (mean difference 2.2, 95% CI 0.2, 4.2%, p = 0.028). Patellar cartilage defects regressed in the isolated ACLR group over 2 years (p = 0.02; Z = − 2.33; r = 0.3). Baseline patellar cartilage defect score was positively associated with annual percentage cartilage volume increase (Regression coefficient B = 0.014; 95% CI 0.001, 0.027; p = 0.03) in the pooled ACLR participants.

Conclusions

Hypertrophic response was evident in the patellar cartilage of ACLR participants with and without meniscal pathology. Surprisingly, the increase in patellar cartilage volume was more pronounced in those with isolated ACLR. Although cartilage defects stabilised in the majority of ACLR participants, the severity of patellar cartilage defects at baseline influenced the magnitude of the cartilage hypertrophic response over the subsequent ~ 2 years.
Coronal subluxation of the tibiofemoral joint before and after anterior cruciate ligament reconstruction
Authors: Li Ruibo , Yuan Xingyue , Fu Peng , Zhang Jianjun , Liu Yuehong
Published: October 2021

Background

Studies have shown that medial subluxation of the tibia occurs after anterior cruciate ligament (ACL) rupture. However, it is unclear whether anterior cruciate ligament reconstruction (ACLR) can correct tibial coronal subluxation.

Purpose

To determine whether the tibia is medially subluxated after ACL rupture, and whether ACLR can correct medial subluxation of the tibia.

Study design

Case series; Level of evidence, 4, Retrospective clinical study.

Methods

The distance of tibial coronal subluxation before and after ACLR surgery was measured in 48 patients with ACL rupture and meniscus injury. Tibiofemoral subluxation was defined as the perpendicular distance between the long axis of the tibia and a second parallel line originating at the most proximal aspect of the femoral intercondylar notch. To determine the long axis of the tibia, two circles separated by 5 cm were centered on the proximal tibia. The proximal circle is 5 cm from the tibial plateau, and the distal circle is 5 cm from the proximal circle. The line passing through the center of the two circles was considered the long axis of the proximal tibia. Care was taken to ensure that each patient lied on the back with their patellae facing upward, to minimize rotational variation among the radiographs. At the same time, 30 patients with simple meniscus injury who underwent arthroscopy during the same period were selected to determine the degree of tibiofemoral coronal subluxation as the baseline value. The changes before and after operation were compared, as well as the differences with the baseline data.

Result

The average follow-up period was 21.2 ± 5.8 months. The average distance of tibial coronal subluxation before ACLR was 5.5 ± 2.1 mm, which was significantly different from that of baseline group (7.3 ± 2.1 mm) (P < 0.001). The tibial subluxation after ACLR was 7.7 ± 2.6 mm, which was significantly different from that before operation (P < 0.001). There was no significant difference in the distance between postoperative tibial subluxation and baseline group (P = 0.472).

Conclusion

The tibia was coronally medially subluxated after ACL rupture. ACLR can correct the medial subluxation of tibia. This finding is helpful in the diagnosis of ACL rupture, and can be used to assess the imaging status of the tibiofemoral joint on the coronal plane during or after ACLR.
Transference of skills in robotic vs. laparoscopic simulation: a randomized controlled trial
Authors: Kanitra John J. , Khogali-Jakary Nashwa , Gambhir Sahil B. , Davis Alan T. , Hollis Michael , Moon Caroline , Gupta Rama , Haan Pamela S. , Anderson Cheryl , Collier Deborah , Henry David , Kavuturu Srinivas
Published: October 2021

Background

Elucidating how robotic skills are best obtained will enable surgeons to best develop future robotic training programs. We perform a randomized controlled trial to assess the performance of robotic compared to laparoscopic surgery, transference of pre-existing skills between the two modalities, and to assess the learning curve between the two using novice medical students.

Methods

Forty students were randomized into either Group A or B. Students practiced and were tested on a peg transfer task in either a laparoscopic simulator (LS) and robotic simulator (RS) in a pre-defined order. Performance, transference of skills and learning curve were assessed for each modality. Additionally, a fatigue questionnaire was issued.

Results

There was no significant difference between overall laparoscopic scores (219 ± 19) and robotic scores (227 ± 23) (p = 0.065). Prior laparoscopic skills performed significantly better on robotic testing (236 ± 12) than without laparoscopic skills (216 ± 28) (p = 0.008). There was no significant difference in scores between students with prior robotic skills (223 ± 16) than without robotic skills (215 ± 22) (p = 0.162). Students reported no difference in fatigue between RS and LS. The learning curve plateaus at similar times between both modalities.

Conclusion

Novice medical students with laparoscopic skills performed better on a RS test than students without laparoscopic training, suggesting a transference of skills from laparoscopic to robotic surgery. These results suggest laparoscopic training may be sufficient in general surgery residencies as the skills transfer to robotic if used post-residency.
Impact of mental imagery on enhancing surgical skills learning in novice’s surgeons: a pilot study
Authors: Souiki Tarik , Benzagmout Mohammed , Alami Badreeddine , Ibn Majdoub Karim , Toughrai Imane , Mazaz Khalid , Boujraf Saïd
Published: October 2021

Objective

Mental imagery (MI) has long been used in learning in both fields of sports and arts. However, it is restrictively applied in surgical training according to the medical literature. Few studies have evaluated its’ feasibility and usefulness. The aim of this study is to assess the impact of mental imagery on surgical skills learning among novice’s surgeons.

Material and methods

In this pilot prospective randomized comparative study; we recruited 17 residents and interns of surgery education curriculum. They were all included in their first semester of the curricula. Two groups were randomly designed. Group (a) including “Mental Imagery” volunteers (n = 9) which benefited from a mental imagery rehearsal exercise prior to physical practice, while the control group (b) (n = 8) didn’t underwent any MI process prior to surgery practice. Each participant of both groups was invited to perform an intestinal hand-sewn anastomosis on bovine intestine. Each procedure was evaluated and analyzed according to 14 qualitative criteria while each criterion was scored 0, 1 or 2 respectively assigned to the gesture was not acquired, gesture was performed with effort, or mastered gesture. The final score is 28 for those who master all 14 gestures. A non-parametric statistical comparison between the both studied groups was performed.

Results

Both groups of surgery students demonstrated equivalent age, sex ratio, laterality, and surgical experience. The mean overall score is significantly higher in the MI group (a) (17.78; SD = 2.42) compared to the control group (b) (10.63, SD = 2.85). However, advanced analysis of individual assessment items showed significant statistical difference between both groups only in 6 out of 14 assessed items.

Conclusion

Indeed, mental imagery will not be able to substitute the traditional learning of surgery for novice surgeons; it is an important approach for improving the technical skills acquisition and shortening the physical learning.
A multi-centre survey on hospital malnutrition: result of PNSI study
Authors: Poudineh Somayeh , Shayesteh Forough , Kermanchi Jamshid , Haghdoost Ali-Akbar , Torabi Parisa , Pasdar Yahya , Azimi-Nezhad Mohsen , Safarian Mohammad , Hajifaraji Majid , Eslami-Hasan-Abadi Saeed , Pournik Omid , Barkhidarian Bahareh , Norouzy Abdolreza
Published: October 2021

Background

Disease-related malnutrition is associated with adverse outcomes such as increased rates of morbidity and mortality, prolonged hospital stay, and extra costs of health care. This study was conducted to assess nutritional status among patients and to determine the risk factors for malnutrition in Iran university f.

Methods

Persian Nutritional Survey In Hospitals (PNSI) was a cross-sectional study that conducted in 20 university hospitals across Iran. All the patients with age range of 18 to 65 years, who were admitted or discharged, were assessed by subjective global assessment (SGA).

Results

In total, 2109 patients were evaluated for malnutrition. Mean values of age and body mass index were 44.68 ± 14.65 years and 25.44 ± 6.25 kg/m2, respectively. Malnutrition (SGA-B & C) was identified in 23.92% of the patients, 26.23 and 21% of whom were among the admitted and discharged patients, respectively. The highest prevalence of malnutrition was in burns (77.70%) and heart surgery (57.84%) patients. Multivariate analysis presented male gender (OR = 1.02, P < 0.00), malignant disease (OR = 1.40, P < 0.00), length of hospital stay (OR = 1.20, P < 0.00), and polypharmacy (OR = 1.06, P < 0.00) as independent risk factors for malnutrition. Malnutrition was not associated with age (P = 0.10).

Conclusion

This study provides an overall and comprehensive illustration of hospital malnutrition in Iran university hospitals, finding that one out of four patients were malnourished; thus, appropriate consideration and measures should be taken to this issue.
Long-term exposure to PM2.5 and cardiovascular disease incidence and mortality in an Eastern Mediterranean country: findings based on a 15-year cohort study
Authors: Jalali Soheila , Karbakhsh Mojgan , Momeni Mehdi , Taheri Marzieh , Amini Saeid , Mansourian Marjan , Sarrafzadegan Nizal
Published: October 2021

Background

Evidence concerning the impact of long-term exposure to fine Particulate Matter ≤2.5 μm (PM2.5) on Cardio-Vascular Diseases (CVDs) for those people subject to ambient air pollution in developing countries remains relatively scant. This study assessed the relationship of 15-year PM2.5 exposure with cardiovascular incidence and mortality rate in Isfahan province, Iran.

Methods

The cohort comprised 3081 participants over 35 years old who were free of CVDs. They were selected through multi-stage cluster sampling in Isfahan, Iran. PM2.5 exposure was determined separately for each individual via satellite-based spatiotemporal estimates according to their residential addresses. In this context, CVD is defined as either fatal and non-fatal Acute Myocardial Infarctions (AMI) or stroke and sudden cardiac death. The incidence risk for CVD and the ensuing mortality was calculated based on the average PM2.5 exposure within a study period of 15 years using the Cox proportional hazards frailty model upon adjusting individual risk factors. The mean annual rate of PM2.5 and the follow-up data of each residential area were combined.

Results

Mean three-year PM2·5 exposure for the cohort was measured at 45.28 μg/m3, ranging from 20.01 to 69.80 μg/m3. The median time period for conducting necessary follow-ups was 12.3 years for the whole population. Notably, 105 cardiovascular and 241 all-cause deaths occurred among 393,786 person-months (27 and 61 per 100,000 person-months, respectively). In well-adjusted models, 10 μg/m3 increase in PM2.5 corresponded to a 3% increase in the incidence rate of CVDs [0.95 CI = 1.016, 1.036] (in case of p = 0.000001 per 10 μg/m3 increase in PM2.5, the Hazard Ratio (HR) for AMI and Ischemic Heart Disease (IHD) was 1.031 [0.95 CI = 1.005, 1.057] and 1.028 [0.95 CI = 1.017, 1.039]), respectively. No consistent association was observed between PM2.5 concentration and fatal CVD (fatal AMI, fatal stroke, SCD (Sudden Cardiac Death)) and all-cause mortality.

Conclusions

Results from analyses suggest that the effect of PM2.5 on cardiovascular disease occurrence was stronger in the case of older people, smokers, and those with high blood pressure and diabetes. The final results revealed that long-term exposure to ambient PM2.5 with high concentrations positively correlated with IHD incidence and its major subtypes, except for mortality. The outcome accentuates the need for better air quality in many countries.
Geostatistical linkage of national demographic and health survey data: a case study of Tanzania
Authors: Yoo Eun-hye , Palermo Tia , Maluka Stephen
Published: October 2021

Background

When Service Provision Assessment (SPA) surveys on primary health service delivery are combined with the nationally representative household survey—Demographic and Health Survey (DHS), they can provide key information on the access, utilization, and equity of health service availability in low- and middle-income countries. However, existing linkage methods have been established only at aggregate levels due to known limitations of the survey datasets.

Methods

For the linkage of two data sets at a disaggregated level, we developed a geostatistical approach where SPA limitations are explicitly accounted for by identifying the sites where health facilities might be present but not included in SPA surveys. Using the knowledge gained from SPA surveys related to the contextual information around facilities and their spatial structure, we made an inference on the service environment of unsampled health facilities. The geostatistical linkage results on the availability of health service were validated using two criteria—prediction accuracy and classification error. We also assessed the effect of displacement of DHS clusters on the linkage results using simulation.

Results

The performance evaluation of the geostatistical linkage method, demonstrated using information on the general service readiness of sampled health facilities in Tanzania, showed that the proposed methods exceeded the performance of the existing methods in terms of both prediction accuracy and classification error. We also found that the geostatistical linkage methods are more robust than existing methods with respect to the displacement of DHS clusters.

Conclusions

The proposed geospatial approach minimizes the methodological issues and has potential to be used in various public health research applications where facility and population-based data need to be combined at fine spatial scale.
Estimating the potential impact of the Australian government’s reformulation targets on household sugar purchases
Authors: Coyle Daisy H. , Shahid Maria , Dunford Elizabeth K. , Louie Jimmy Chun Yu , Trieu Kathy , Marklund Matti , Neal Bruce , Wu Jason H. Y.
Published: October 2021

Background

Countries around the world are putting in place sugar reformulation targets for packaged foods to reduce excess sugar consumption. The Australian government released its voluntary sugar reformulation targets for nine food categories in 2020. We estimated the potential impact of these targets on household sugar purchases and examined differences by income. For comparison, we also modelled the potential impact of the UK sugar reduction targets on per capita sugar purchases as the UK has one of the most comprehensive sugar reduction strategies in the world.

Methods

Grocery purchase data from a nationally representative consumer panel (n=7,188) in Australia was linked with a large database (FoodSwitch) with product-specific sugar content information for packaged foods (n=25,261); both datasets were collected in 2018. Potential reductions in per capita sugar purchases were calculated overall and by food category. Differences in sugar reduction across income level were assessed by analysis of variance.

Results

In 2018, the total sugar acquired from packaged food and beverage purchases consumed at-home was 56.1 g/day per capita. Australia’s voluntary reformulation targets for sugar covered 2,471/25,261 (9.8%) unique products in the FoodSwitch dataset. Under the scenario that all food companies adhered to the voluntary targets, sugar purchases were estimated to be reduced by 0.9 g/day per capita, which represents a 1.5% reduction in sugar purchased from packaged foods. However, if Australia adopted the UK targets, over twice as many products would be covered (n=4,667), and this would result in a more than four times greater reduction in sugar purchases (4.1 g/day per capita). It was also estimated that if all food companies complied with Australia’s voluntary sugar targets, reductions to sugar would be slightly greater in low-income households compared with high-income households by 0.3 g/day (95%CI 0.2 - 0.4 g/day, p<0.001).

Conclusions

Sugar-reduction policies have the potential to substantially reduce population sugar consumption and may help to reduce health inequalities related to excess sugar consumption. However, the current reformulation targets in Australia are estimated to achieve only a small reduction to sugar intakes, particularly in comparison to the UK’s sugar reduction program.
Interleukin-6 mediates delirium-like phenotypes in a murine model of urinary tract infection
Authors: Rashid Mohammad Harun , Sparrow Nicklaus A. , Anwar Faizan , Guidry Gena , Covarrubias Ambart E. , Pang Haoming , Bogguri Chandrakumar , Karumanchi S. Ananth , Lahiri Shouri
Published: October 2021

Background

Urinary tract infection (UTI) is frequently implicated as a precipitant of delirium, which refers to an acute confusional state that is associated with high mortality, increased length of stay, and long-term cognitive decline. The pathogenesis of delirium is thought to involve cytokine-mediated neuronal dysfunction of the frontal cortex and hippocampus. We hypothesized that systemic IL-6 inhibition would mitigate delirium-like phenotypes in a mouse model of UTI.

Methods

C57/BL6 mice were randomized to either: (1) non-UTI control, (2) UTI, and (3) UTI + anti-IL-6 antibody. UTI was induced by transurethral inoculation of 1 × 108Escherichia coli. Frontal cortex and hippocampus-mediated behaviors were evaluated using functional testing and corresponding structural changes were evaluated via quantification of neuronal cleaved caspase-3 (CC3) by immunohistochemistry and western blot. IL-6 in the brain and plasma were evaluated using immunohistochemistry, ELISA, and RT-PCR.

Results

Compared to non-UTI control mice, mice with UTI demonstrated significantly greater impairments in frontal and hippocampus-mediated behaviors, specifically increased thigmotaxis in Open Field (p < 0.05) and reduced spontaneous alternations in Y-maze (p < 0.01), while treatment of UTI mice with systemic anti-IL-6 fully reversed these functional impairments. These behavioral impairments correlated with frontal and hippocampal neuronal CC3 changes, with significantly increased frontal and hippocampal CC3 in UTI mice compared to non-UTI controls (p < 0.0001), and full reversal of UTI-induced CC3 neuronal changes following treatment with systemic anti-IL-6 antibody (p < 0.0001). Plasma IL-6 was significantly elevated in UTI mice compared to non-UTI controls (p < 0.01) and there were positive and significant correlations between plasma IL-6 and frontal CC3 (r2 = 0.5087/p = 0.0028) and frontal IL-6 and CC3 (r2 = 0.2653,p < 0.0001).

Conclusions

These data provide evidence for a role for IL-6 in mediating delirium-like phenotypes in a mouse model of UTI. These findings provide pre-clinical justification for clinical investigations of IL-6 inhibitors to treat UTI-induced delirium.
Residues T48 and A49 in HIV-1 NL4-3 Nef are responsible for the counteraction of autophagy initiation, which prevents the ubiquitin-dependent degradation of Gag through autophagosomes
Authors: Castro-Gonzalez Sergio , Chen Yuexuan , Benjamin Jared , Shi Yuhang , Serra-Moreno Ruth
Published: October 2021

Background

Autophagy plays an important role as a cellular defense mechanism against intracellular pathogens, like viruses. Specifically, autophagy orchestrates the recruitment of specialized cargo, including viral components needed for replication, for lysosomal degradation. In addition to this primary role, the cleavage of viral structures facilitates their association with pattern recognition receptors and MHC-I/II complexes, which assists in the modulation of innate and adaptive immune responses against these pathogens. Importantly, whereas autophagy restricts the replicative capacity of human immunodeficiency virus type 1 (HIV-1), this virus has evolved the gene nef to circumvent this process through the inhibition of early and late stages of the autophagy cascade. Despite recent advances, many details of the mutual antagonism between HIV-1 and autophagy still remain unknown. Here, we uncover the genetic determinants that drive the autophagy-mediated restriction of HIV-1 as well as the counteraction imposed by Nef. Additionally, we also examine the implications of autophagy antagonism in HIV-1 infectivity.

Results

We found that sustained activation of autophagy potently inhibits HIV-1 replication through the degradation of HIV-1 Gag, and that this effect is more prominent for nef-deficient viruses. Gag re-localizes to autophagosomes where it interacts with the autophagosome markers LC3 and SQSTM1. Importantly, autophagy-mediated recognition and recruitment of Gag requires the myristoylation and ubiquitination of this virus protein, two post-translational modifications that are essential for Gag’s central role in virion assembly and budding. We also identified residues T48 and A49 in HIV-1 NL4-3 Nef as responsible for impairing the early stages of autophagy. Finally, a survey of pandemic HIV-1 transmitted/founder viruses revealed that these isolates are highly resistant to autophagy restriction.

Conclusions

This study provides evidence that autophagy antagonism is important for virus replication and suggests that the ability of Nef to counteract autophagy may have played an important role in mucosal transmission. Hence, disabling Nef in combination with the pharmacological manipulation of autophagy represents a promising strategy to prevent HIV spread.
Serum peptidome: diagnostic window into pathogenic processes following occupational exposure to carbon nanomaterials
Authors: Mostovenko Ekaterina , Dahm Matthew M. , Schubauer-Berigan Mary K. , Eye Tracy , Erdely Aaron , Young Tamara L. , Campen Matthew J. , Ottens Andrew K.
Published: October 2021

Background

Growing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals along with a significant release of bioactive peptides into the circulation, the augmented serum peptidome. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up.

Methods

Here, the serum peptidome was assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Studies employed a stratified design between High (> 0.5 µg/m3) and Low (< 0.1 µg/m3) inhalable CNT/F exposures in the industrial setting. Peptide biomarker model building and refinement employed linear regression and partial least squared discriminant analyses. Top-ranked peptides were then sequence identified and evaluated for pathological-relevance.

Results

In total, 41 peptides were found to be highly discriminatory after model building with a strong linear correlation to personal CNT/F exposure. The top-five peptide model offered ideal prediction with high accuracy (Q2 = 0.99916). Unsupervised validation affirmed 43.5% of the serum peptidomic variance was attributable to CNT/F exposure. Peptide sequence identification reveals a predominant association with vascular pathology. ARHGAP21, ADAM15 and PLPP3 peptides suggest heightened cardiovasculature permeability and F13A1, FBN1 and VWDE peptides infer a pro-thrombotic state among High CNT/F workers.

Conclusions

The serum peptidome affords a diagnostic window into sub-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring of systemic health risks.

Graphical abstract
Zootherapeutic uses of animals excreta: the case of elephant dung and urine use in Sayaboury province, Laos
Authors: Dubost Jean-Marc , Kongchack Phommachack , Deharo Eric , Sysay Palamy , Her Chithdavone , Vichith Lamxay , Sébastien Duffillot , Krief Sabrina
Published: October 2021

Background

Despite a widespread aversion towards faeces and urine, animal excreta are used in traditional medicine in many countries since centuries, but records are scattered and few therapeutic uses have been accurately documented while in the current context of emerging zoonoses such records may be of major interest.

Methodology

In this study, we investigated the therapeutic uses that mahouts in Xayaboury province, Lao PDR make of elephant urine and faeces as well as of the brood chamber that beetles (Heliocopris dominus) fashion from elephant dung. Semi-structured interviews were conducted with mahouts on elephant diet, health problems and responses to disease, andwhether they use elephant products. Data were supplemented by interviews with traditional healers.

Results

Seven respondents reported the use of elephant urine in ethnoveterinary care for elephants and in human medicine in case of diabetes and otitis. 25 respondents reported therapeutic use of elephant faeces (EF) and elephant dung beetle brood chambers. The major indications are gastrointestinal and skin problems. Macerations or decoctions are drunk or used externally as a lotion. The mahouts attribute the therapeutic effectiveness of EFs to their content which includes the remains of many species from the elephant diet which they consider to be medicinal.

Discussion

The indications of these uses are consistent with pharmacological and clinical studies highlighting the properties of different animals’ urine and faeces and their curative potential tested in vivo. The acknowledgement by the mahouts of medicinal properties of elephant faecal bolus contrasts with the rare justifications of animal material use recorded in zootherapeutic studies, which falls within the symbolic domain. However, numerous studies highlight the preponderant role of the microbiota in physiological processes, raising the hypothesis of a curative action of EF, by rebalancing the user’s microbiota.

Conclusion

The therapeutic uses of EF preparations despite their possible curative properties are a potential source of zoonotic transmission from elephants to humans. In the current context of globalisation of trade which favours the emergence of zoonoses and in relation with the issue of One Health, it becomes crucial to further document the zootherapeutic practices to prevent emerging diseases. As elephants and local related ethnoethological knowledge are threatened, documenting them is urgent to contribute to their preservation.
Confrontment and solution to gonadotropin resistance and low oocyte retrieval in in vitro fertilization for type I BPES: a case series with review of literature
Authors: Yu Yiqi , Ji Mengxia , Xu Weihai , Zhang Ling , Qi Ming , Shu Jing
Published: October 2021

Background

FOXL2 mutations in human cause Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). While type II BPES solely features eyelid abnormality, type I BPES involves not only eyelid but also ovary, leading to primary ovarian insufficiency (POI) and female infertility. Current mainstream reproductive option for type I BPES is embryo or oocyte donation. Attempts on assisted reproductive technology (ART) aiming biological parenthood in this population were sparse and mostly unsuccessful.

Case presentation

Two Chinese type I BPES patients with low anti-müllerian hormone (AMH) and elevated follicle stimulating hormone (FSH) presented with primary infertility in their early 30s. Genetic studies confirmed two heterozygous duplication mutations that were never reported previously in East Asian populations. They received in vitro fertilization (IVF) treatment and both exhibited resistance to gonadotropin and difficulty in retrieving oocytes in repeated cycles. Doubled to quadrupled total gonadotropin doses were required to awaken follicular response. Patient 1 delivered a baby girl with the same eyelid phenotype and patient 2 had ongoing live intrauterine pregnancy at the time of manuscript submission.

Conclusions

This is the second reported live birth of biological offspring in type I BPES patients, and first success using IVF techniques. It confirmed that ART is difficult but feasible in type I BPES. It further alerts clinicians and genetic counsellors to type female BPES patients with caution in view of the precious and potentially narrowed reproductive window.
Cocultured porcine granulosa cells respond to excess non-esterified fatty acids during in vitro maturation
Authors: Shi Meihong , Sirard Marc-André
Published: October 2021

Background

Non-esterified fatty acids (NEFAs) are one of the main lipid components of follicular fluid at concentrations that depend on circulating levels. Elevated levels of NEFAs impair oocyte quality, development potential, and may subsequently influence the metabolism and reproductive fitness of offspring. Granulosa cells (GCs) are the follicular cells that are closely communicating with the oocyte. However, the responses of GCs exposed to high levels of NEFAs when cocultured with cumulus-oocyte complexes (COCs), and how they attenuate the negative effects of NEFAs on oocytes, are unclear.

Results

To better understand this protective effect, monolayers of porcine GCs were cocultured with COCs during in vitro maturation (IVM) in the presence of elevated levels of NEFAs. Genomic expression analysis was conducted to explore the responses of the GCs to the elevated levels of NEFAs. After limma algorithm analysis, 1,013 genes were differentially expressed between GCs cultured with and without elevated NEFAs. Among them, 438 genes were upregulated and 575 were downregulated. The differentially expressed genes were enriched in pathways related to metabolism, inflammation, and epithelial-mesenchymal transition.

Conclusions

The pathways and upstream regulators suggested that the cocultured GCs responded to the elevated NEFAs with (1) inhibition of the transition from granulosa to luteal cell, (2) interactions of metabolism change, anti-inflammation, mitochondrial function, and cell transition, (3) intercommunication with cocultured COCs of anti-inflammatory factors.