bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic exposure of bisphenol S (BPS) affect hypothalamic-pituitary-testicular activities in adult male rats: possible in estrogenic mode of action
Authors: Ullah Hizb , Ullah Faizan , Rehman Owais , Jahan Sarwat , Afsar Tayyaba , Al-Disi Dara , Almajwal Ali , Razak Suhail
Published: March 2021

Background

The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats.

Methods

Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined.

Results

Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis.

Conclusion

These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.
Stable and Novel Quantitative Trait Loci (QTL) Confer Narrow Root Cone Angle in an Aerobic Rice (Oryza sativa L.) Production System
Authors: Vinarao Ricky , Proud Christopher , Zhang Xiaolu , Snell Peter , Fukai Shu , Mitchell Jaquie
Published: March 2021

Background

Aerobic rice production (AP) may be a solution to the looming water crisis by utilising less water compared to traditional flooded culture. As such, development of genotypes with narrow root cone angle (RCA) is considered a key AP adaptation trait as it could lead to deeper rooting and ensure water uptake at depth. Quantitative trait loci (QTL) and genes associated with rooting angle have been identified in rice, but usually in conventional transplanted systems or in upland and drought conditions. This study aimed to identify QTL associated with RCA in AP systems using a recombinant inbred line population derived from IRAT109.

Results

Four experiments conducted in glasshouse and aerobic field conditions revealed significant genotypic variation existed for RCA in the population. Single and multiple QTL models identified the presence of eight QTL distributed in chromosomes 1, 2, 3, 4, and 11. Combined, these QTL explained 36.7–51.2% of the genotypic variance in RCA present in the population. Two QTL, qRCA1.1 and qRCA1.3, were novel and may be new targets for improvement of RCA. Genotypes with higher number of favourable QTL alleles tended to have narrower RCA. qRCA4 was shown to be a major and stable QTL explaining up to 24.3% of the genotypic variation, and the presence of the target allele resulted in as much as 8.6° narrower RCA. Several genes related to abiotic stress stimulus response were found in the qRCA4 region.

Conclusion

Stable and novel genomic regions associated with RCA have been identified. Genotypes which had combinations of these QTL, resulted in a narrower RCA phenotype. Allele mining, gene cloning, and physiological dissection should aid in understanding the molecular function and mechanisms underlying RCA and these QTL. Ultimately, our work provides an opportunity for breeding programs to develop genotypes with narrow RCA and deep roots for improved adaptation in an AP system for sustainable rice production.
Genome-wide association analysis identified both RNA-seq and DNA variants associated to paratuberculosis in Canadian Holstein cattle ‘in vitro’ experimentally infected macrophages
Authors: Ariel Olivier , Brouard Jean-Simon , Marete Andrew , Miglior Filippo , Ibeagha-Awemu Eveline , Bissonnette Nathalie
Published: March 2021

Background

Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis, or Johne’s disease (JD), an incurable bovine disease. The evidence for susceptibility to MAP disease points to multiple interacting factors, including the genetic predisposition to a dysregulation of the immune system. The endemic situation in cattle populations can be in part explained by a genetic susceptibility to MAP infection. In order to identify the best genetic improvement strategy that will lead to a significant reduction of JD in the population, we need to understand the link between genetic variability and the biological systems that MAP targets in its assault to dominate macrophages. MAP survives in macrophages where it disseminates. We used next-generation RNA (RNA-Seq) sequencing to study of the transcriptome in response to MAP infection of the macrophages from cows that have been naturally infected and identified as positive for JD (JD (+); n = 22) or negative for JD (healthy/resistant, JD (−); n = 28). In addition to identifying genetic variants from RNA-seq data, SNP variants were also identified using the Bovine SNP50 DNA chip.

Results

The complementary strategy allowed the identification of 1,356,248 genetic variants, including 814,168 RNA-seq and 591,220 DNA chip variants. Annotation using SnpEff predicted that the 2435 RNA-seq genetic variants would produce high functional effect on known genes in comparison to the 33 DNA chip variants. Significant variants from JD(+/−) macrophages were identified by genome-wide association study and revealed two quantitative traits loci: BTA4 and 11 at (P < 5 × 10− 7). Using BovineMine, gene expression levels together with significant genomic variants revealed pathways that potentially influence JD susceptibility, notably the energy-dependent regulation of mTOR by LKB1-AMPK and the metabolism of lipids.

Conclusion

In the present study, we succeeded in identifying genetic variants in regulatory pathways of the macrophages that may affect the susceptibility of cows that are healthy/resistant to MAP infection. RNA-seq provides an unprecedented opportunity to investigate gene expression and to link the genetic variations to biological pathways that MAP normally manipulate during the process of killing macrophages. A strategy incorporating functional markers into genetic selection may have a considerable impact in improving resistance to an incurable disease. Integrating the findings of this research into the conventional genetic selection program may allow faster and more lasting improvement in resistance to bovine paratuberculosis in dairy cattle.
microRNA-125b-5p is a promising novel plasma biomarker for alveolar echinococcosis in patients from the southern province of Qinghai
Authors: Deping Cao , Bofan Jiang , Yaogang Zhang , Mingquan Pang
Published: March 2021

Background

Alveolar echinococcosis (AE) is caused by parasitic infection by Echinococcus multilocularis. Its diagnosis is usually based on clinical symptoms, ultrasound, and other imaging methods. MicroRNAs (miRNAs) play important roles in disease processes and can exist in a highly stable cell-free form in body fluids. It is important to identify specific, sensitive diagnostic markers for early diagnosis and evaluation of AE. In this study, we examined hsa-miR-125b-5p as a potential plasma biomarker of E. multilocularis infection.

Methods

Plasma samples from patients with AE and healthy individuals were screened for the presence of five miRNAs using miRNA chips. We used quantitative polymerase chain reaction to measure miRNA expression levels in plasma and liver tissue samples from patients with AE.

Results

hsa-miR-125b-5p was stably upregulated in the plasma and liver tissue samples from patients with AE.

Conclusions

The results suggest that hsa-miR-125b-5p may be a promising biomarker for early, non-invasive diagnosis of AE.
The effects of physical activity on overall survival among advanced cancer patients: a systematic review and meta-analysis
Authors: Takemura Naomi , Chan Siu Ling , Smith Robert , Cheung Denise Shuk Ting , Lin Chia-Chin
Published: March 2021

Background

The survival rates of advanced cancer patients remain low despite clinical therapy advancements. However, physical activity showed promising effects in improving cancer outcomes. This review aimed to systematically evaluate and synthesize the effects on overall mortality of post-diagnosis physical activity in advanced cancer patients.

Methods

A systematic search of six English databases (PubMed, EMBASE, CINAHL, PsycINFO, The Cochrane Central Register of Controlled Trials, and SPORTDiscus) was conducted from their inception up to 3 February 2021. The association of physical activity with survival was evaluated by combining study-specific hazard ratios with random-effects meta-analysis models.

Results

Eleven studies were identified. Compared with the reference group, higher-level physical activity was not significantly associated with a lower risk of earlier mortality in advanced cancer patients (InHR = − 0.18, 95% CI, − 0.36 to 0.01). When separated by study type, a higher level of physical activity in non-randomised trials was significantly associated with reduced mortality risk (InHR = − 0.25, 95% CI: − 0.44, − 0.06). However, in randomised trials, engaging in exercise was not significantly associated with a lower mortality risk compared with the control group (InHR = 0.08, 95%CI: − 0.17, 0.32).

Conclusions

Discrepancies were uncovered in the effect of physical activity on overall survival in randomised and non-randomised trials. In non-randomised trials, a higher level of physical activity was significantly associated with a lower risk of mortality, whereas no significant effect on survival was observed during exercise interventions compared to the control in randomised trials. Considering the wider benefits of physical activity, exercise can still be recommended to improve outcomes for advanced cancer patients. Nevertheless, it might be too late for advanced cancer patients to start exercising for survival improvements, based on findings from randomised controlled trials.
Population-level indicators associated with hormonal contraception use: a register-based matched case–control study
Authors: Toffol Elena , Heikinheimo Oskari , But Anna , Latvala Antti , Partonen Timo , Haukka Jari
Published: March 2021

Background

Monitoring factors related to hormonal contraception (HC) use is essential to evaluating public health strategies and promoting access to contraception. We aimed to examine municipal social and health indicators of HC use at the population level, and to identify patterns of inequality across Finnish municipalities.

Methods

We identified all women (15–49 years) with a redeemed HC prescription in Finland in 2017 (n = 294,445), and a control group of non-users. Municipal social and health indicators at the population level were retrieved from the nationwide Statistics and Indicator Bank. Differences between the groups across 309 municipalities were calculated, and associations of municipal-specific proportions of HC users with municipal-specific indicators were studied using LASSO (Least Absolute Shrinkage and Selection Operator) models.

Results

Sociodemographic differences between HC users and non-users were non-homogenous across municipalities. Indicators positively associated with HC use included: larger population and higher proportions of population aged 16–24 years, of household-dwelling units with one person, of persons with higher education, and of divorces among those aged 25–64. Lower HC use was associated with higher proportions of Swedish-speaking population, of those aged 7–15 years, of young people not in education/training, and of household-dwelling units in overcrowded conditions. Lower HC use was also associated with indicators of outpatient and inpatient healthcare, and of municipal finances in welfare and healthcare.

Conclusions

Sociodemographic differences in relation to HC use exist across Finnish municipalities. Municipal indicators of social structure, health and welfare, and investment in and use of healthcare services are related to HC use.
Hypertension is associated with osteoporosis: a case-control study in Chinese postmenopausal women
Authors: Chai Hao , Ge Jirong , Li Li , Li Jianyang , Ye Yunjin
Published: March 2021

Background

Osteoporosis and cardiovascular disease (CVD) are age-related diseases. It is reported that patients with CVD have a higher risk of bone loss. This retrospective study sought to reveal the association between osteoporosis and CVD in Chinese women. Although epidemiological evidence has indicated a relationship between the two, clinical data in southeast China are lacking.

Methods

In total, 2873 participants completed the baseline survey from January 2007 to October 2019, and 2039 were included in this retrospective study. We divided all subjects into an osteoporosis group and a non-osteoporosis group based on their bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) was used to examine BMD. The general information came from the questionnaire survey. Cardiovascular diseases were defined by asking participants at the first visit and checking relevant medical records if they had suffered from hypertension, coronary heart disease, or cerebral infarction.

Results

According to the criterion, the osteoporosis group had 678 subjects, and the non-osteoporosis group had 1361 subjects. Subjects in the osteoporosis group had a significantly higher prevalence of hypertension and coronary heart disease. Besides, the proportion of subjects who drank tea and drank milk were relatively higher in the osteoporosis group. The odds ratio (OR) for suffering from osteoporosis was high if the patients had hypertension.

Conclusions

This study indicated that Chinese postmenopausal women with osteoporosis had a higher prevalence of hypertension. Hypertension was significantly associated with osteoporosis.
Circumcision and its alternatives in Germany: an analysis of nationwide hospital routine data
Authors: Oetzmann von Sochaczewski Christina , Gödeke Jan , Muensterer Oliver J.
Published: March 2021

Background/purpose

Circumcisions are among the most frequent operations in children. Health service data on circumcision in the United States has documented an increase in neonatal circumcisions since 2012. We investigated whether a similar effect could be found in Germany, which does not endorse neonatal circumcision.

Methods

We analysed German routine administrative data for operations conducted on the preputium in order to analyse the frequency, age distribution, and time-trends in hospital-based procedures on a nationwide basis.

Results

There were 9418 [95% confidence interval (CI) 8860–10,029] procedures per year, of which 4977 (95% CI 4676–5337) were circumcisions. Age distributions were highly different between both circumcisions (van der Waerden’s χ² = 58.744,df = 4,P < 0.0001) and preputium-preserving operations (van der Waerden’s χ² = 58.481,df = 4,P < 0.0001). Circumcisions were more frequent in the first 5 years of life and above 15 years of age, whereas preputium-preserving procedures were preferred in the age groups between 5 and 14 years of age. The number of circumcisions and preputium-preserving operations decreased in absolute and relative numbers.

Conclusions

The increasing trend towards neonatal circumcision observed in the United States is absent in Germany. The majority of patients were operated after the first year of life and absolute and relative numbers of hospital-based procedures were decreasing. Other factors such as increasing use of steroids for the preferred non-operative treatment of phimosis may play a role. As operations in outpatients and office-based procedures were not covered, additional research is necessary to obtain a detailed picture of circumcision and its surgical alternatives in Germany.

Level of evidence

III.
The impact of Dual Eligible Special Need Plan regulations on healthcare utilization
Authors: Narain Kimberly Danae Cauley , Harwood Jessica , Mangione Carol , Duru O. Kenrik , Ettner Susan
Published: March 2021

Background

To determine if requiring Dual Eligible Special Need Plans (D-SNPs) to receive approval from the National Committee of Quality Assurance and contract with state Medicaid agencies impacts healthcare utilization.

Methods

We use a Multiple Interrupted Time Series to examine the association of D-SNP regulations with dichotomized measures of emergency room (ER) and hospital utilization. Our treatment group is elderly D-SNP enrollees. Our comparison group is near-elderly (ages 60–64) beneficiaries enrolled in Medicaid Managed Care plans (N = 360,405). We use segmented regression models to estimate changes in the time-trend and slope of the outcomes associated with D-SNP regulations, during the post-implementation (2012–2015) period, relative to the pre-implementation (2010–2011) period. Models include a treatment-status indicator, a monthly time-trend, indicators and splines for the post-period and the interactions between these variables. We conduct the following sensitivity analyses: (1) Re-estimating models stratified by state (2) Estimating models including interactions of D-SNP implementation variables with comorbidity count to assess for differential D-SNP regulation effects across comorbidity level. (3) Re-estimating the models stratifying by race/ethnicity and (4) Including a transition period (2012–2013) in the model.

Results

We do not find any statistically significant changes in ER or hospital utilization associated with D-SNP regulation implementation in the broad D-SNP population or among specific racial/ethnic groups; however, we do find a reduction in hospitalizations associated with D-SNP regulations in New Jersey (DD level = − 3.37%; p = 0.02)/(DD slope = − 0.23%; p = 0.01) and among individuals with higher, relative to lower levels of co-morbidity (DDD slope = − 0.06%; p = 0.01).

Conclusions

These findings suggest that the impact of D-SNP regulations varies by state. Additionally, D-SNP regulations may be particularly effective in reducing hospital utilization among beneficiaries with high levels of co-morbidity.
Impact of seasonality and malaria control interventions on Anopheles density and species composition from three areas of Uganda with differing malaria endemicity
Authors: Mawejje Henry Ddumba , Kilama Maxwell , Kigozi Simon P. , Musiime Alex K. , Kamya Moses , Lines Jo , Lindsay Steven W. , Smith David , Dorsey Grant , Donnelly Martin J. , Staedke Sarah G.
Published: March 2021

Background

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. This study examined the changing pattern of Anopheles species in three areas of Uganda with markedly different transmission intensities and different levels of vector control.

Methods

From October 2011 to June 2016 mosquitoes were collected monthly using CDC light traps from 100 randomly selected households in three areas: Walukuba (low transmission), Kihihi (moderate transmission) and Nagongera (high transmission). LLINs were distributed in November 2013 in Walukuba and Nagongera and in June 2014 in Kihihi. IRS was implemented only in Nagongera, with three rounds of bendiocarb delivered between December 2014 and June 2015. Mosquito species were identified morphologically and by PCR (Polymerase Chain Reaction).

Results

In Walukuba, LLIN distribution was associated with a decline in Anopheles funestus vector density (0.07 vs 0.02 mosquitoes per house per night, density ratio [DR] 0.34, 95% CI: 0.18–0.65, p = 0.001), but not Anopheles gambiae sensu stricto (s.s.) nor Anopheles arabiensis. In Kihihi, over 98% of mosquitoes were An. gambiae s.s. and LLIN distribution was associated with a decline in An. gambiae s.s. vector density (4.00 vs 2.46, DR 0.68, 95% CI: 0.49–0.94, p = 0.02). In Nagongera, the combination of LLINs and multiple rounds of IRS was associated with almost complete elimination of An. gambiae s.s. (28.0 vs 0.17, DR 0.004, 95% CI: 0.002–0.009, p < 0.001), and An. funestus sensu lato (s.l.) (3.90 vs 0.006, DR 0.001, 95% CI: 0.0005–0.004, p < 0.001), with a less pronounced decline in An. arabiensis (9.18 vs 2.00, DR 0.15 95% CI: 0.07–0.33, p < 0.001).

Conclusions

LLIN distribution was associated with reductions in An. funestus s.l. in the lowest transmission site and An. gambiae s.s. in the moderate transmission site. In the highest transmission site, a combination of LLINs and multiple rounds of IRS was associated with the near collapse of An. gambiae s.s. and An. funestus s.l. Following IRS, An. arabiensis, a behaviourally resilient vector, became the predominant species, which may have implications for malaria vector control activities. Development of interventions targeted at outdoor biting remains a priority.
Hoots and harm reduction: a qualitative study identifying gaps in overdose prevention among women who smoke drugs
Authors: Bardwell Geoff , Austin Tamar , Maher Lisa , Boyd Jade
Published: March 2021

Background

Smoking or inhaling illicit drugs can lead to a variety of negative health outcomes, including overdose. However, most overdose prevention interventions, such as supervised consumption services (SCS), prohibit inhalation. In addition, women are underrepresented at SCS and are disproportionately impacted by socio-structural violence. This study examines women’s experiences smoking illicit drugs during an overdose epidemic, including their utilization of a women-only supervised inhalation site.

Methods

Qualitative research methods included on-site ethnographic observation and semi-structured interviews with 32 participants purposively recruited from the women-only site. Data were coded and analyzed using NVivo 12 and thematic analysis was informed by gendered and socio-structural understandings of violence.

Results

Participants had preferences for smoking drugs and these were shaped by their limited income, inability to inject, and perceptions of overdose risk. Participants expressed the need for services that attend to women’s specific experiences of gendered, race-based, and structural violence faced within and outside mixed-gender social service settings. Results indicate a need for sanctioned spaces that recognize polysubstance use and drug smoking, accommodated by the women-only SCS. The smoking environment further fostered a sociability where participants could engage in perceived harm reduction through sharing drugs with other women/those in need and were able to respond in the event of an overdose.

Conclusions

Findings demonstrate the ways in which gendered social and structural environments shape women’s daily experiences using drugs and the need for culturally appropriate interventions that recognize diverse modes of consumption while attending to overdose and violence. Women-only smoking spaces can provide temporary reprieve from some socio-structural harms and build collective capacity to practice harm reduction strategies, including overdose prevention. Women-specific SCS with attention to polysubstance use are needed as well as continued efforts to address the socio-structural harms experienced by women who smoke illicit drugs.
Does patient engagement affect IBD patients’ health-related quality of life? Findings from a cross-sectional study among people with inflammatory bowel diseases
Authors: Barello Serena , Guida Elena , Leone Salvatore , Previtali Enrica , Graffigna Guendalina
Published: March 2021

Background

Patients diagnosed with inflammatory bowel disease (IBD) are required to deal with the unpredictability of this clinical condition, which is associated with poorer health-related quality of life (HRQoL) compared to other clinical conditions. Patient engagement is currently demonstrated to relate with chronic patients’ HRQoL, but few studies have been conducted among this population.

Methods

A cross-sectional study was conducted among 1176 IBD patients. Data were collected on participants’ HRQoL (SIBD-Q) and patient engagement (PHE-s®). Regression analysis was used to examine the effects of patient engagement on HRQoL.

Results

About the half of the sample (47%) reported a low patient engagement level. 30% of the sample reported a low level of HRQoL. Psycho-emotional functioning resulted to be the aspect of HRQoL most impacted in the 37% of the sample. The regression model showed that PHE-s® is significantly related to the SIBD-Q total score (B = .585;p < .001; R squared = .343) and to the subscales’ scores—systemic symptoms (B = .572;p < .001; R squared = .327), bowel symptoms (B = .482;p < .001; R squared = .232), social (B = .485;p < .001; R squared = .234) and psycho-emotional (B = .607;p < .001; R squared = .369) functioning.

Conclusions

Patients who are engaged in their IBD care pathway are more likely to report higher level of HRQoL, thus offering clues to potential therapeutic approaches to ameliorating IBD patients’ wellbeing. As this is a modifiable factor, screening for patient  health engagement levels, coupled with appropriate interventions, could improve care, and ultimately improve HRQoL outcomes among IBD patients.
The neonatal assessment manual score (NAME) for improving the clinical management of infants: a perspective validity study
Authors: Manzotti Andrea , Chiera Marco , Galli Matteo , Lombardi Erica , La Rocca Simona , Biasi Pamela , Esteves Jorge , Lista Gianluca , Cerritelli Francesco
Published: March 2021

Background and objectives

The Neonatal Assessment Manual scorE (NAME) was developed to assist in the clinical management of infants in the neonatal ward by assessing their body’s compliance and homogeneity. The present study begins its validation process.

Methods

An expert panel of neonatal intensive care unit (NICU) professionals investigated the NAME face and content validity. Content validity was assessed through the content validity index (CVI). Construct validity was assessed using data collected from 50 newborns hospitalized in the NICU of “Vittore Buzzi” Children Hospital of Milan, Italy. Kendall’s τ and ordinal logistic regressions were used to evaluate the correlation between the NAME scores and infants’ gestational age, birth weight, post-menstrual age, weight at the time of assessment, and a complexity index related to organic complications.

Results

The CVIs for compliance, homogeneity, and the whole scale were respectively 1, 0.9, and 0.95. Construct validity analysis showed significant positive correlations between the NAME and infants’ weight and age, and a negative correlation between the NAME and the complexity index (τ = − 0.31 [95% IC: − 0.47, − 0.12], p = 0.016 and OR = 0.56 [95% IC: 0.32, 0.94], p = 0.034 for categorical NAME; τ = − 0.32 [95% IC: − 0.48, − 0.14], p = 0.005 for numerical NAME).

Conclusions

The NAME was well accepted by NICU professionals in this study and it demonstrates good construct validity in discriminating the infant’s general condition. Future studies are needed to test the NAME reliability and predictive capacity.
Methylation of rRNA as a host defense against rampant group II intron retrotransposition
Authors: Waldern Justin M. , Smith Dorie , Piazza Carol Lyn , Bailey E. Jake , Schiraldi Nicholas J. , Nemati Reza , Fabris Dan , Belfort Marlene , Novikova Olga
Published: March 2021

Background

Group II introns are mobile retroelements, capable of invading new sites in DNA. They are self-splicing ribozymes that complex with an intron-encoded protein to form a ribonucleoprotein that targets DNA after splicing. These molecules can invade DNA site-specifically, through a process known as retrohoming, or can invade ectopic sites through retrotransposition. Retrotransposition, in particular, can be strongly influenced by both environmental and cellular factors.

Results

To investigate host factors that influence retrotransposition, we performed random insertional mutagenesis using the ISS1 transposon to generate a library of over 1000 mutants in Lactococcus lactis, the native host of the Ll.LtrB group II intron. By screening this library, we identified 92 mutants with increased retrotransposition frequencies (RTP-ups). We found that mutations in amino acid transport and metabolism tended to have increased retrotransposition frequencies. We further explored a subset of these RTP-up mutants, the most striking of which is a mutant in the ribosomal RNA methyltransferase rlmH, which exhibited a reproducible 20-fold increase in retrotransposition frequency. In vitro and in vivo experiments revealed that ribosomes in the rlmH mutant were defective in the m3Ψ modification and exhibited reduced binding to the intron RNA.

Conclusions

Taken together, our results reinforce the importance of the native host organism in regulating group II intron retrotransposition. In particular, the evidence from the rlmH mutant suggests a role for ribosome modification in limiting rampant retrotransposition.
Development of a novel, sensitive translational immunoassay to detect plasma glial fibrillary acidic protein (GFAP) after murine traumatic brain injury
Authors: Button Emily B. , Cheng Wai Hang , Barron Carlos , Cheung Honor , Bashir Asma , Cooper Jennifer , Gill Jasmine , Stukas Sophie , Baron David C. , Robert Jerome , Rowe Elyn M. , Cripton Peter A. , Wellington Cheryl L.
Published: March 2021

Background

Glial fibrillary acidic protein (GFAP) has emerged as a promising fluid biomarker for several neurological indications including traumatic brain injury (TBI), a leading cause of death and disability worldwide. In humans, serum or plasma GFAP levels can predict brain abnormalities including hemorrhage on computed tomography (CT) scans and magnetic resonance imaging (MRI). However, assays to quantify plasma or serum GFAP in preclinical models are not yet available.

Methods

We developed and validated a novel sensitive GFAP immunoassay assay for mouse plasma on the Meso Scale Discovery immunoassay platform and validated assay performance for robustness, precision, limits of quantification, dilutional linearity, parallelism, recovery, stability, selectivity, and pre-analytical factors. To provide proof-of-concept data for this assay as a translational research tool for TBI and Alzheimer’s disease (AD), plasma GFAP was measured in mice exposed to TBI using the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model and in APP/PS1 mice with normal or reduced levels of plasma high-density lipoprotein (HDL).

Results

We performed a partial validation of our novel assay and found its performance by the parameters studied was similar to assays used to quantify human GFAP in clinical neurotrauma blood specimens and to assays used to measure murine GFAP in tissues. Specifically, we demonstrated an intra-assay CV of 5.0%, an inter-assay CV of 7.2%, a lower limit of detection (LLOD) of 9.0 pg/mL, a lower limit of quantification (LLOQ) of 24.8 pg/mL, an upper limit of quantification (ULOQ) of at least 16,533.9 pg/mL, dilution linearity of calibrators from 20 to 200,000 pg/mL with 90–123% recovery, dilution linearity of plasma specimens up to 32-fold with 96–112% recovery, spike recovery of 67–100%, and excellent analyte stability in specimens exposed to up to 7 freeze-thaw cycles, 168 h at 4 °C, 24 h at room temperature (RT), or 30 days at − 20 °C. We also observed elevated plasma GFAP in mice 6 h after TBI and in aged APP/PS1 mice with plasma HDL deficiency. This assay also detects GFAP in serum.

Conclusions

This novel assay is a valuable translational tool that may help to provide insights into the mechanistic pathophysiology of TBI and AD.
A large-scale investigation of alcohol-based handrub (ABHR) volume: hand coverage correlations utilizing an innovative quantitative evaluation system
Authors: Voniatis Constantinos , Bánsághi Száva , Ferencz Andrea , Haidegger Tamás
Published: March 2021

Background

Current hand hygiene guidelines do not provide recommendations on a specific volume for the clinical hand rubbing procedure. According to recent studies volume should be adjusted in order to achieve complete coverage. However, hand size is a parameter that highly influences the hand coverage quality when using alcohol-based handrubs (ABHR). The purpose of this study was to establish a quantitative correlation between applied ABHR volume and achieved hand coverage.

Method

ABHR based hand hygiene events were evaluated utilizing a digital health device, the Semmelweis hand hygiene system with respect to coverage achieved on the skin surface. Medical students and surgical residents (N = 356) were randomly selected and given predetermined ABHR volumes. Additionally, hand sizes were calculated using specialized software developed for this purpose. Drying time, ABHR volume awareness, as well spillage awareness were documented for each hand hygiene event.

Results

Hand coverage achieved during a hand hygiene event strongly depends on the applied ABHR volume. At a 1 ml dose, the uncovered hand area was approximately 7.10%, at 2 ml it decreased to 1.68%, and at 3 ml it further decreased to 1.02%. The achieved coverage is strongly correlated to hand size, nevertheless, a 3 ml applied volume proved sufficient for most hand hygiene events (84%). When applying a lower amount of ABHR (1.5 ml), even people with smaller hands failed to cover their entire hand surface. Furthermore, a 3 ml volume requires more than the guideline prescribed 20–30 s to dry. In addition, results suggest that drying time is not only affected by hand size, but perhaps other factors may be involved as well (e.g., skin temperature and degree of hydration). ABHR volumes of 3.5 ml or more were inefficient, as the disinfectant spilled while the additional rubbing time did not improve hand coverage.

Conclusions

Hand sizes differ a lot among HCWs. After objectively measuring participants, the surface of the smallest hand was just over half compared to the largest hand (259 cm2 and 498 cm2, respectively). While a 3 ml ABHR volume is reasonable for medium-size hands, the need for an optimized volume of handrub for each individual is critical, as it offers several advantages. Not only it can ensure adequate hand hygiene quality, but also prevent unnecessary costs. Bluntly increasing the volume also increases spillage and therefore waste of disinfectant in the case of smaller hands. In addition, adherence could potentially decrease due to the required longer drying time, therefore, adjusting the dosage according to hand size may also increase the overall hand hygiene compliance.
Temporal trends, risk factors and outcomes of infections due to extended-spectrum β-lactamase producing Enterobacterales in Swiss solid organ transplant recipients between 2012 and 2018
Authors:   Swiss Transplant Cohort Study, Kohler Philipp , Wolfensberger Aline , Stampf Susanne , Brönnimann Andreas , Boggian Katia , van Delden Christian , Favre Melody , Hirzel Cédric , Khanna Nina , Kuster Stefan P. , Manuel Oriol , Neofytos Dionysios , Ragozzino Silvio , Schreiber Peter W. , Walti Laura , Mueller Nicolas J.
Published: March 2021

Background

The burden of antimicrobial resistance is high in solid organ transplant (SOT) recipients. Among Swiss SOT recipients, we assessed temporal trends of ESBL-producing Enterobacterales (ESBL-E), identified risk factors for ESBL-E, and assessed the impact of resistance on patient outcome.

Methods

Data from the Swiss Transplant Cohort Study (STCS), a nationwide prospective cohort of SOT-recipients, were analysed. Temporal trends were described for ESBL-detection among Escherichia coli and non-Escherichia coli. In a nested case–control study, cases with ESBL-E infection were 1:1 matched (by time since transplantation, organ transplant, pathogen) to controls infected with non-ESBL-E. Factors associated with resistance and with unfavourable 30-day outcome (death, infection relapse, graft loss) were assessed.

Results

From 2012 to 2018, we identified 1′212 infection episodes caused by Enterobacterales in 1′074 patients, thereof 11.4% (138/1′212) caused by ESBL-E. The proportion of ESBL-production among Escherichia coli remained stable over time (p = 0.93) but increased for non-E. coli (p = 0.02) Enterobacterales. In the case–control study (n = 102), antibiotic pre-treatment was independently associated with ESBL-production (aOR = 2.6, 95%-CI: 1.0–6.8, p = 0.046). Unfavourable outcome occurred in 24/51 (47%) cases and 9/51 (18%) controls (p = 0.003). Appropriate empiric antibiotic therapy was the only modifiable factor associated with unfavourable outcome.

Conclusions

In Swiss SOT-recipients, proportion of infections with ESBL-producing non-E. coli Enterobacterales increased in recent years. Antibiotic pre-treatment represents a risk factor for ESBL-E. Improving appropriateness of empiric antibiotic treatment might be an important measure to reduce unfavourable outcome, which was observed in almost half of SOT-recipients with ESBL-E infections.
Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis
Authors: Jing Yingli , Yu Yan , Bai Fan , Wang Limiao , Yang Degang , Zhang Chao , Qin Chuan , Yang Mingliang , Zhang Dong , Zhu Yanbing , Li Jianjun , Chen Zhiguo
Published: March 2021

Background

Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect.

Results

FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI.

Conclusion

Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs.
Cancer Immunotherapy Update: FDA-Approved Checkpoint Inhibitors and Companion Diagnostics
Authors: Twomey Julianne D. , Zhang Baolin
Published: March 2021

Immune checkpoint inhibitors (ICIs) are considered a new standard-of-care across many cancer indications. This review provides an update on ICIs approved by the Food and Drug Administration (FDA), with focus on monoclonal antibodies that target the programmed cell death 1 (PD-1) or its ligand, PD-1 ligand 1 (PD-L1), including information on their clinical indications and associated companion diagnostics. The information is further discussed with strategies for identifying predictive biomarkers to guide the clinical use of PD-1/PD-L1-targeted therapies.
Cardiovascular Disease Risk Factors and Metabolic Morbidity in a Longitudinal Study of Congenital Adrenal Hyperplasia
Authors: Torky Ahmed , Sinaii Ninet , Jha Smita , Desai Jay , El-Maouche Diala , Mallappa Ashwini , Merke Deborah P
Published: March 2021

Context

Patients with congenital adrenal hyperplasia (CAH) are exposed to hyperandrogenism and supraphysiologic glucocorticoids, both of which can increase risk of metabolic morbidity.

Objective

Our aim was to evaluate cardiovascular and metabolic morbidity risk in a longitudinal study of patients with CAH spanning both childhood and adulthood.

Design and Setting

Patients with classic CAH followed for a minimum of 5 years during both childhood and adulthood (n = 57) at the National Institutes of Health were included and compared with the US general population using NHANES data.

Main outcome measures

Obesity, hypertension, insulin resistance, fasting hyperglycemia, and dyslipidemia.

Results

Compared to the US population, patients with CAH had higher (P < 0.001) prevalence of obesity, hypertension, insulin resistance, fasting hyperglycemia, and low high-density lipoprotein (HDL) during childhood and obesity (P = 0.024), hypertension (P<0.001), and insulin resistance (P < 0.001) during adulthood. In our cohort, obesity, hypertension, fasting hyperglycemia, and hypertriglyceridemia began prior to age 10. During childhood, increased mineralocorticoid dose was associated with hypertension (P = 0.0015) and low HDL (P = 0.0021). During adulthood, suppressed androstenedione was associated with hypertension (P = 0.002), and high low-density lipoprotein (P = 0.0039) whereas suppressed testosterone (P = 0.003) was associated with insulin resistance. Elevated 17-hydroxyprogesterone, possibly reflecting poor disease control, was protective against high cholesterol (P = 0.0049) in children. Children whose mothers were obese (maternal obesity) had increased risk of obesity during adulthood (P = 0.0021). Obesity, in turn, contributed to the development of hypertension, insulin resistance, and hypertriglyceridemia in adulthood.

Conclusion

Patients with CAH develop metabolic morbidity at a young age associated with treatment-related and familial factors. Judicious use of glucocorticoid and mineralocorticoid is warranted.
How can medical schools combat declining mental health amongst their students during the COVID-19 quarantine period?
Authors: Subhaskaran Kajani , Young Francesca Naomi
Published: March 2021

doi: https://doi.org/10.12669/pjms.37.3.4321

How to cite this:Subhaskaran K, Young FN. How can medical schools combat declining mental health amongst their students during the COVID-19 quarantine period?. Pak J Med Sci. 2021;37(3):926. doi: https://doi.org/10.12669/pjms.37.3.4321
Impact of COVID-19 lockdown and social distancing policies on small businesses in south-eastern Nigeria: whither the stimulus packages?
Authors: Iwuoha Victor Chidubem , Aniche Ernest Toochi , Ezirim Gerald Ekenedirichukwu , Alumona Ikenna Mike , Obiorji Josephine Nneka
Published: March 2021

This article examines the specific or sub-sectoral effects of COVID-19 lockdown measures on small business units, thus departing from previous studies which only focused on general effects. Based on qualitative and cross-sectional survey methods, the article depicts a cross-sectoral disparity in the patronage level and income stream of customers of small businesses found on the streets of south-eastern Nigeria. The article identifies the gap in the policy interventions meant to cushion the negative impacts of COVID-19 lockdown and social distancing policies on small businesses. Hence, state policy interventions have not had the cushioning impact on small businesses in south-eastern Nigeria. A pro-poor approach towards the review of the policy interventions is highly imperative.
What does Rachel Carson have to do with family sociology and family policies? Ecological imaginaries, relational ontologies, and crossing social imaginaries
Authors: Doucet Andrea
Published: March 2021

In the past decade, multiple compounding crises – ecological, racial injustices, ‘care crises’ and multiple recent crises related to the COVID-19 pandemic – have reinforced the powerful role of critical and social policy researchers to push back against ‘fake news’, ‘alternative facts’, and a post-truth era that denigrates science and evidence-based research. These new realities can pose challenges for social scientists who work within relational, ontological, non-representational, new materialist, performative, decolonising, or ecological ‘turns’ in social theory and epistemologies. This article’s overarching question is: How does one work within non-representational research paradigms while also attempting to hold onto representational, authoritative and convincing versions of truth, evidence, facts and data? Informed by my research on feminist philosopher and epistemologist Lorraine Code’s 40-year trajectory of writing about knowledge making and ecological social imaginaries, I navigate these dilemmas by calling on an unexpected ally to family sociology and family policy: the late American environmentalist Rachel Carson. Extending Code’s case study of Carson, I argue for an approach that combines (1) ecological relational ontologies, (2) the ethics and politics of knowledge making, (3) crossing social imaginaries of knowledge making and (4) a reconfigured view of knowledge makers as working towards just and cohabitable worlds.
Theorising anti-racism in health and social care
Authors: Choonara Esme
Published: March 2021

The emergence of the Black Lives Matter movement in 2020 in the context of a COVID-19 pandemic that was already disproportionally impacting on the lives of people from black, Asian and other minority ethnicities in the UK and the US has provoked scrutiny of how racism impacts on all areas of our lives. This article will examine some competing theories of racism, and ask what theoretical tools we need to successfully confront racism in health and social care. In particular, it will scrutinise the different levels at which racism operates – individual, institutional and structural – and ask how these are related. Furthermore, it will argue against theories that see racism as a product of whiteness per se or ‘white supremacy’, insisting instead that racism should be understood as firmly bound to the functioning and perpetuation of capitalism.
Stable, precisely controlled, and switchable thulium-doped fiber laser based on cascaded mode interference filters
Authors: Qin Qi , Yan Fengping , Liu Yan , Guo Ying , Li Ting , Guan Biao , Han Wenguo , Bai Zhuoya , Suo Yuping , Zhou Hong , Feng Ting
Published: March 2021

This research experimentally demonstrates a switchable, single-wavelength, thulium-doped fiber laser based on the cascading of a multimode–single-mode–multimode (MSM) fiber filter and a two-mode fiber (TMF) filter. When the MSM fiber filter suffers from bending, the blue-shift of the output spectrum can be obtained. A switchable lasing wavelength output is realized by bending the MSM fiber filter to cover different channels of the TMF filter. The output wavelength can be switched from 1982.54 to 1938.81 nm with an optical signal-to-noise ratio of higher than 40 dB. The wavelength interval of the switchable output is an integral multiple of the wavelength interval of the TMF filter. The stability of the output wavelength was tested within 60 min, and the wavelength shift and output power fluctuation were found to be less than 0.01 nm and 0.31 dB, respectively, which demonstrates a stable output performance.