bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and risk factors of fall-related injury among older adults in India: evidence from a cross-sectional observational study
Authors: Srivastava Shobhit , Muhammad T.
Published: March 2022

Background

Falls and related injuries in older ages have become a major public health problem. This study aims to identify the prevalence of self-reported fall-related injury and to describe risk factors associated with fall-related injury among older adults in India.

Method

The study used data from the "Building Knowledge Base on Population Ageing in India" (BKPAI), which was carried out in seven major states in India (2011). Bivariate and multivariable logistic regression analyses were conducted to examine the prevalence and risk factors of fall-related injury among older people.

Results

The study found that 3.6% of older adults had a fall-related injury. Older adults with walk difficulty had a significantly higher likelihood of reporting fall-related injuries in comparison to their counterparts [adjusted odds ratio (AOR):1.80; confidence interval (CI): 1.38–2.36]. Older adults who consumed alcohol had significantly higher odds of reporting fall-related injuries than those who did not consume alcohol [AOR: 1.97; CI: 1.31–2.97]. Poor self-rated health was another risk factor for fall-related injury [AOR: 1.24; CI: 1.05–1.61]. Further, older adults with dementia were 2.15 times significantly more likely to report fall-related injuries than older adults with no dementia [AOR: 2.15; CI: 1.03–5.05]. Also, older women compared to men were 98% significantly more likely to report fall-related injury [AOR: 1.98; CI: 1.43–2.75]. The odds of reporting fall-related injury was significantly higher among those who had a secondary level education compared to those with no education [AOR: 1.44; CI: 1.01–2.06].

Conclusions

Walking disabilities, alcohol consumption, poor self-rated health, dementia, and female gender were found to be the risk factors for fall-related injury among older adults. The results highlight the importance of improving physical as well as mental health of older individuals including dementia in terms of reducing the risk of experiencing fall-related injury.
68-year old man with progressive weakness and ventilator dependent respiratory failure: a case report of sporadic late onset nemaline myopathy
Authors: Kirupaharan Pradhab , Kramer Daniel , Gandler Alan , Kenyon Lawrence , Summer Ross
Published: March 2022

Background

Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy.

Case presentation

A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to our hospital, he was found to have elevated muscle specific enzymes, prompting evaluation for neuromuscular causes of respiratory failure. He was also found to have elevated HMG-CoA Reductase (HMGCR) antibodies. Ultimately, a right quadriceps muscle biopsy was performed and electron microscopy identified nemaline bodies within skeletal myofibers. Given the clinical course and other histopathologic findings, he was diagnosed with Sporadic late-onset nemaline myopathy (SLONM).

Conclusion

The diagnosis of neuromuscular disease in patients with ventilator dependent respiratory failure is challenging. A detailed history of a patient’s clinical course prior to hospitalization is key and may raise suspicion for underlying neuromuscular pathology. Further evaluation in non-critically ill patients may include pulmonary function, electromyography and confirmatory muscle biopsy. Sporadic late onset nemaline myopathy remains a rare disease entity which rarely presents with respiratory failure and lacks effective treatment.
A modified lung ultrasound score to evaluate short-term clinical outcomes of bronchopulmonary dysplasia
Authors: Sun Ying-Hua , Du Yang , Shen Jie-Ru , Ai Dan-Yang , Huang Xiang-Yuan , Diao Si-Hao , Lin Sam Bill , Zhang Rong , Yuan Lin , Yang Yi-Pei , He Li-Li , Qin Xiao-Jiao , Zhou Jian-Guo , Chen Chao
Published: March 2022

Background

Lung ultrasound (LUS) is a useful tool for assessing the severity of lung disease, without radiation exposure. However, there is little data on the practicality of LUS in assessing the severity of bronchopulmonary dysplasia (BPD) and evaluating short-term clinical outcomes. We adapted a LUS score to evaluate BPD severity and assess the reliability of mLUS score correlated with short-term clinical outcomes.

Methods

Prospective diagnostic accuracy study was designed to enroll preterm infants with gestational age < 34 weeks. Lung ultrasonography was performed at 36 weeks postmenstrual age. The diagnostic and predictive values of new modified lung ultrasound (mLUS) scores based on eight standard sections were compared with classic lung ultrasound (cLUS) scores.

Results

A total of 128 infants were enrolled in this cohort, including 30 without BPD; 31 with mild BPD; 23 with moderate BPD and 44 with severe BPD. The mLUS score was significantly correlated with the short-term clinical outcomes, superior to cLUS score. The mLUS score well correlated with moderate and severe BPD (AUC = 0.813, 95% CI 0.739–0.888) and severe BPD (AUC = 0.801, 95% CI 0.728–0.875), which were superior to cLUS score. The ROC analysis of mLUS score to evaluate the other short-term outcomes also showed significant superiority to cLUS score. The optimal cutoff points for mLUS score were 14 for moderate and severe BPD and 16 for severe BPD.

Conclusions

The mLUS score correlates significantly with short-term clinical outcomes and well evaluates these outcomes in preterm infants.
Understanding barriers to and strategies for medication adherence in COPD: a qualitative study
Authors: O’Toole Jacqueline , Krishnan Meera , Riekert Kristin , Eakin Michelle N.
Published: March 2022

Background

Medication adherence in chronic obstructive pulmonary disease (COPD) is low, though not enough is known about the factors that affect adherence in COPD. This study uses qualitative methods to understand the patient perspective on facilitators and barriers to medication adherence in COPD as well as patient-reported strategies for self-management of disease.

Methods

Semi-structured interviews were conducted with 30 individuals (n = 30). Transcripts were analyzed using iterative qualitative coding by 2 independent coders, and codes were categorized using thematic analysis.

Results

Challenges with adherence reported were gaps in understanding, forgetfulness of the patient, physician availability, cost navigation, and overcoming substance use. Most commonly, the financial burden of COPD medications caused patients to source other countries to obtain medications, rely on sample medications collected during doctors’ visits, and to alter medication dosage and frequency to extend the length of a prescription. Tools and resources reported by patients to support self-management of COPD included pharmacist assistance, physician office information, and community resources. Individuals further reported that the use of logs or diaries to track medication usage, visual or temporal cues to take medications, and support from family members were helpful in promoting adherence to their COPD medication regimen.

Conclusions

Medication adherence in individuals with COPD is affected by challenges with self-management of disease and financial burden of medications. However, patients reported multiple tools and resources to support adherence. Physician recognition of these factors impacting self-management, as well as awareness of strategies to promote adherence and manage disease, may improve patient outcomes.
Application of a new position in endoscopic combined intrarenal surgery: modified prone split-leg position
Authors: Wang Daming , Sun Hongliang , Xie Dongdong , Liu Zhiqi , Yu Dexin , Ding Demao
Published: March 2022

Background

Endoscopic combined intrarenal surgery (ECIRS) is well established as a minimally invasive procedure for the treatment of multiple urolithiasis. The position is the key to the perfect combination of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS). Galdakao-modified supine Valdivia (GMSV) and prone split-leg positions are widely used. However, both positions have their own advantages and disadvantages. This study aimed to evaluate the effect of ECIRS in the treatment of multiple urolithiasis in the modified prone split-leg position.

Patients and methods

A total of 96 patients with multiple urolithiasis underwent ECIRS in modified prone split-leg position from September 2017 to January 2021. Relevant demographic and clinical data were analysed retrospectively. Clinical outcomes, such as the stone free rate, complications and postoperative hospital stay were evaluated. The chi-square test was used to compare categorical variables and Student’s t test was applied for continuous variables of the treatment groups.

Results

The mean renal stone size was 32.5 ± 10.7 mm and renal stone surface area was 712.2 ± 264.8 mm2. The mean ureteral stones size was 24.8 ± 12.3 mm. The mean surgical time was 82.2 ± 38.3 min. The incidence of complications was 16.7%, and they were mainly grade 1 and grade 2. No complications occurred above grade 3. The stone was completely removed in 75 (78.1%) patients in a single operation. The risk factors affecting the stone-free rate of ECIRS were analysed, and only the number of involved calyces by stone was found to be significant (p = 0.01).

Conclusion

ECIRS is safe and effective in the treatment of multiple renal calculi or multiple renal calculi with ipsilateral ureteral calculi in the modified prone split-leg position. The modification of the prone split-leg position makes the retrograde operation more convenient, which is conducive to the combination of RIRS and PCNL.
Prevalence of prediabetes and associated factors in southwest iran: results from Hoveyzeh cohort study
Authors: Hashemi Seyed Jalal , Karandish Majid , Cheraghian Bahman , Azhdari Maryam
Published: March 2022

Background

Increasing trend of prediabetes and diabetes is a global public health issue. On the other hand, prediabetes can increase the risk of developing some non-communicable diseases, including type 2 diabetes, cardiovascular disease, hypertension, fatty liver disease, etc. Given that there are modifiable various risk factors for prediabetes, this cross-sectional study aimed to evaluate the prevalence of prediabetes and its risk factors among adults.

Methods

The present study included the baseline data from the Prospective Epidemiological Research Studies of the Iranian Adult and Neonates (PERSIAN), Hoveyzeh Cohort Study (N = 10,009). The demographic data, lifestyle habits, anthropometric data, and clinical and biochemical parameters were gathered. The odds ratio of prediabetes was assessed by logistic regression.

Results

The final analysis was conducted on 7629 participants. The prevalence of overweight (36.7%), obesity (37.5%), prediabetes (30.29%), abnormal high density lipoprotein (35.4%), cholesterol (33.8%) and triglyceride (39.7%), and HTN (21.3%) were common. In the adjusted analysis, there were higher odds of having prediabetes for overweight (OR = 1.9, 95% CI: (1.19, 3.03), p = 0.007), obesity (OR = 3.18, 95% CI: (1.99, 5.07), p < 0.001), waist circumstance (WC) (OR = 1.024, 95% CI: (1.002, 1.03), p < 0.001), hip circumstance (HC) (OR = 1.01, 95% CI: (1.003, 1.02), p = 0.008), older age (OR = 1.04, 95% CI: (1.04, 1.05), p < 0.001), hypertension (OR = 1.38, 95% CI: (1.21, 1.57), p < 0.001),), glutamic-pyruvic transaminase (OR = 1.013, 95% CI: (1.007, 1.019), p = 0.001), glutamic-oxaloacetic transaminase (OR = 1.01, 95% CI: (1.006, 1.013), p < 0.001), triglyceride = 150–199 mg/dl (OR = 1.32, 95% CI: (1.16, 1.51), p < 0.001), triglyceride ≥ 200 mg/dl (OR = 1.64 (95% CI: 1.44, 1.86), p < 0.001), cholesterol = 200- 239 mg/dl (OR = 1.33, 95% CI: (1.18, 1.49), p < 0.001), and cholesterol ≥ 240 mg/dl (OR = 2.04, 95% CI: (1.72, 2.42), p < 0.001) in general population.

Conclusion

The prevalence of prediabetes, overweight, obesity, HTN, and dyslipidemia was common. The greater chances of prediabetes were related to aging, overweight, obesity, HTN, higher liver enzymes, HC, abnormal WC, and dyslipidemia. It seems that practical interventions are necessary to prevent prediabetes.
Frontline physician burnout during the COVID-19 pandemic: national survey findings
Authors: Melnikow Joy , Padovani Andrew , Miller Marykate
Published: March 2022

Background

Physician burnout and wellbeing are an ongoing concern. Limited research has reported on the impact of the COVID 19 pandemic on burnout over time among U.S. physicians.

Methods

We surveyed U.S. frontline physicians at two time points (wave one in May–June 2020 and wave two in Dec 2020-Jan 2021) using a validated burnout measure. The survey was emailed to a national stratified random sample of family physicians, internists, hospitalists, intensivists, emergency medicine physicians, and infectious disease physicians. Burnout was assessed with the Professional Fulfillment Index Burnout Composite scale (PFI-BC). Responses were weighted to account for sample design and non-response bias. Random effects and quantile regression analyses were used to estimate change in conditional mean and median PFI-BC scores, adjusting for physician, geographic, and pandemic covariates.

Results

In the random effects regression, conditional mean burnout scores increased in the second wave among all respondents (difference 0.15 (CI: 0.24, 0.57)) and among respondents to both waves (balanced panel) (difference 0.21 (CI: − 0.42, 0.84)). Conditional burnout scores increased in wave 2 among all specialties except for Emergency medicine, with the largest increases among Hospitalists, 0.28 points (CI: − 0.19,0.76) among all respondents and 0.36 (CI: − 0.39,1.11) in the balanced panel, and primary care physicians, 0.21 (CI: − 0.23,0.66) among all respondents and 0.31 (CI: − 0.38,1.00) in the balanced panel. The conditional mean PFI-BC score among hospitalists increased from 1.10 (CI: 0.73,1.46) to 1.38 (CI: 1.02,1.74) in wave 2 in all respondents and from 1.49 (CI: 0.69,2.29) to 1.85 (CI: 1.24,2.46) in the balanced panel, near or above the 1.4 threshold indicating burnout. Findings from quantile regression were consistent with those from random effects.

Conclusions

Rates of physician burnout during the first year of the pandemic increased over time among four of five frontline specialties, with greatest increases among hospitalist and primary care respondents. Our findings, while not statistically significant, were consistent with worsening burnout; both the random effects and quantile regressions produced similar point estimates. Impacts of the ongoing pandemic on physician burnout warrant further research.
Addressing patient’s unmet social needs: disparities in access to social services in the United States from 1990 to 2014, a national times series study
Authors: Park Yoosun , Quinn James W. , Hurvitz Philip M. , Hirsch Jana A. , Goldsmith Jeff , Neckerman Kathryn M. , Lovasi Gina S. , Rundle Andrew G.
Published: March 2022

Background

To address patient’s unmet social needs and improve health outcomes, health systems have developed programs to refer patients in need to social service agencies. However, the capacity to respond to patient referrals varies tremendously across communities. This study assesses the emergence of disparities in spatial access to social services from 1990 to 2014.

Methods

Social service providers in the lower 48 continental U.S. states were identified annually from 1990 to 2014 from the National Establishment Times Series (NETS) database. The addresses of providers were linked in each year to 2010 US Census tract geometries. Time series analyses of annual counts of services per Km2 were conducted using Generalized Estimating Equations with tracts stratified into tertiles of 1990 population density, quartiles of 1990 poverty rate and quartiles of 1990 to 2010 change in median household income.

Results

Throughout the period, social service agencies/Km2 increased across tracts. For high population density tracts, in the top quartile of 1990 poverty rate, compared to tracts that experienced the steepest declines in median household income from 1990 to 2010, tracts that experienced the largest increases in income had more services (+ 1.53/Km2, 95% CI 1.23, 1.83) in 1990 and also experienced the steepest increases in services from 1990 to 2010: a 0.09 services/Km2/year greater increase (95% CI 0.07, 0.11). Similar results were observed for high poverty tracts in the middle third of population density, but not in tracts in the lowest third of population density, where there were very few providers.

Conclusion

From 1990 to 2014 a spatial mismatch emerged between the availability of social services and the expected need for social services as the population characteristics of neighborhoods changed. High poverty tracts that experienced further economic decline from 1990 to 2010, began the period with the lowest access to services and experienced the smallest increases in access to services. Access was highest and grew the fastest in high poverty tracts that experienced the largest increases in median household income. We theorize that agglomeration benefits and the marketization of welfare may explain the emergence of this spatial mismatch.
Procoagulant and anticoagulant plasma indicators in diabetic dogs showing increased antithrombin III levels in canine diabetes mellitus
Authors: Milczak Andrzej , Winiarczyk Dagmara , Winiarczyk Stanisław , Bochyńska Diana , Adaszek Łukasz , Winiarczyk Mateusz , Lechowski Roman
Published: March 2022

Background

Diabetes mellitus (DM) often leads to dangerous thromboembolic complications in humans. DM is also a relatively common endocrinopathy of dogs. There is scarce information regarding procoagulant and anticoagulant plasma indicators in this disease. The aim of the study was to evaluate the levels of the selected plasma haemostatic parameters in dogs suffering from diabetes. The study group consisted of 20 dogs meeting all the inclusion criteria, with fasting glycaemia exceeding 11.1 mmol/l. The control group consisted of 15 healthy dogs presented for routine examination. An evaluation of the prothrombin time (PT); and fibrinogen, D-dimer and antithrombin III (ATIII) levels was performed.

Results

Except for ATIII activity, the haemostatic parameter differences were not statistically significant. High values of ATIII activity were observed in 90% of diabetic dogs. On average, the values amounted to 166.6% and were 31.4% higher than those in the control group. The ATIII activity in the diabetic group was significantly higher than that in the control group (p = 0.0004).

Conclusions

Here, we report elevated levels of ATIII in diabetic dogs. This finding may suggest the protective role of ATIII against potential thrombotic events. However, the exact role of ATIII in dog diabetes remains unclear.
Enhancing extracellular production of lipoxygenase in Escherichia coli by signal peptides and autolysis system
Authors: Pang Cuiping , Liu Song , Zhang Guoqiang , Zhou Jingwen , Du Guocheng , Li Jianghua
Published: March 2022

Background

Lipoxygenase (LOX) is a non-heme iron containing dioxygenase that is widely used to improve food quality and produce active drug intermediates and biodiesel. Escherichia coli is one of the most widely used host microorganisms for recombinant protein expression; however, its weak extracellular secretion ability precludes its effective production of recombinant proteins into the extracellular environment. To facilitate subsequent characterization and application of LOX, improving its secretion efficiency from E. coli is a major challenge that needs to be solved.

Results

Several strategies were adopted to improve the extracellular secretion of LOX based on the signal peptides and cell wall permeability of E. coli. Here, we studied the effect of signal peptides on LOX secretion, which increased the secretory capacity for LOX marginally. Although surfactants could increase the permeability of the cell membrane to promote LOX secretion, the extracellular LOX yield could not meet the requirements of industrialization production. Subsequently, an autolysis system was constructed in E. coli based on the bacteriophage lysis gene ΦX174-E to enhance the production of extracellular proteins. Thus, the extracellular production of LOX was achieved and the content of inclusion bodies in the cell was reduced by optimizing cell lysis conditions. The extracellular LOX yield reached 368 ± 1.4 U mL−1 in a 5-L bioreactor under optimized lysis conditions that is, an induction time and temperature, and arabinose concentration of 5 h, 25 °C, and 0.6 mM, respectively.

Conclusions

In this study, the different signal peptides and cell autolysis system were developed and characterized for extracellular LOX production in E. coli. Finally, the cell autolysis system presented a slight advantage on extracellular LOX yield, which also provides reference for other protein extracellular production.
MALAT1-related signaling pathways in colorectal cancer
Authors: Xu Wen-Wen , Jin Jin , Wu Xiao-yu , Ren Qing-Ling , Farzaneh Maryam
Published: March 2022

Colorectal cancer (CRC) is one of the most lethal and prevalent solid malignancies worldwide. There is a great need of accelerating the development and diagnosis of CRC. Long noncoding RNAs (lncRNA) as transcribed RNA molecules play an important role in every level of gene expression. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a highly conserved nucleus-restricted lncRNA that regulates genes at the transcriptional and post-transcriptional levels. High expression of MALAT1 is closely related to numerous human cancers. It is generally believed that MALAT1 expression is associated with CRC cell proliferation, tumorigenicity, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) plays a pivotal role in CRC pathogenesis. Therefore, MALAT1 can be a potent gene for cancer prediction and diagnosis. In this review, we will demonstrate signaling pathways associated with MALAT1 in CRC.
Microarray analysis of breast cancer gene expression profiling in response to 2-deoxyglucose, metformin, and glucose starvation
Authors: Aoun Rita , El Hadi Christopher , Tahtouh Roula , El Habre Rita , Hilal George
Published: March 2022

Background

Breast cancer (BC) is the most frequently diagnosed cancer in women. Altering glucose metabolism and its effects on cancer progression and treatment resistance is an emerging interest in BC research. For instance, combining chemotherapy with glucose-lowering drugs (2-deoxyglucose (2-DG), metformin (MET)) or glucose starvation (GS) has shown better outcomes than with chemotherapy alone. However, the genes and molecular mechanisms that govern the action of these glucose deprivation conditions have not been fully elucidated. Here, we investigated the differentially expressed genes in MCF-7 and MDA-MB-231 BC cell lines upon treatment with glucose-lowering drugs (2-DG, MET) and GS using microarray analysis to study the difference in biological functions between the glucose challenges and their effect on the vulnerability of BC cells.

Methods

MDA-MB-231 and MCF-7 cells were treated with 20 mM MET or 4 mM 2-DG for 48 h. GS was performed by gradually decreasing the glucose concentration in the culture medium to 0 g/L, in which the cells remained with fetal bovine serum for one week. Expression profiling was carried out using Affymetrix Human Clariom S microarrays. Differentially expressed genes were obtained from the Transcriptome Analysis Console and enriched using DAVID and R packages.

Results

Our results showed that MDA-MB-231 cells were more responsive to glucose deprivation than MCF-7 cells. Endoplasmic reticulum stress response and cell cycle inhibition were detected after all three glucose deprivations in MDA-MB-231 cells and only under the metformin and GS conditions in MCF-7 cells. Induction of apoptosis and inhibition of DNA replication were observed with all three treatments in MDA-MB-231 cells and metformin-treated MCF-7 cells. Upregulation of cellular response to reactive oxygen species and inhibition of DNA repair mechanisms resulted after metformin and GS administration in MDA-MB-231 cell lines and metformin-treated MCF-7 cells. Autophagy was induced after 2-DG treatment in MDA-MB-231 cells and after metformin in MCF-7 cells. Finally, inhibition of DNA methylation were observed only with GS in MDA-MB-231 cells.

Conclusion

The procedure used to process cancer cells and analyze their expression data distinguishes our study from others. GS had the greatest effect on breast cancer cells compared to 2-DG and MET. Combining MET and GS could restrain both cell lines, making them more vulnerable to conventional chemotherapy.
SLC4A4 promotes prostate cancer progression in vivo and in vitro via AKT-mediated signalling pathway
Authors: Liu Zelin , Wang Qinghua , Zhai Guanzhong , Ke Shuai , Yu Xi , Guo Jia
Published: March 2022

Background

Prostate cancer (PCa) is the second leading cause of cancer-related male deaths worldwide. The purpose of this study was to investigate the effects of homo sapiens solute carrier family 4 member 4 (SLC4A4), which encodes the electrogenic Na+/HCO3− cotransporter isoform 1 (NBCe1), in the development and progression of PCa.

Methods

The expression levels of SLC4A4 in PCa and normal prostate tissues were evaluated by immunohistochemistry. The SLC4A4 knockdown cell model was structured by lentiviral infection, and the knockdown efficiency was validated by RT-qPCR and Western blotting. The effects of SLC4A4 knockdown on cell proliferation, apoptosis and cycle, migration, and invasion were detected by Celigo cell counting assay and CCK-8 assay, flow cytometry analysis, wound-healing, and Transwell assay, respectively. Tumor growth in nude mice was surveyed by in vivo imaging and Ki-67 staining. Furthermore, underlying mechanism of SLC4A4 silence induced inhibition of PCa progression was explored by human phospho-kinase array.

Results

Our results revealed that SLC4A4 expression was up-regulated in PCa tissues and human PCa cell lines. High expression of SLC4A4 in tumor specimens was significantly correlated with disease progression. SLC4A4 knockdown inhibited cell proliferation, migration and invasion, while facilitated apoptosis, which was also confirmed in vivo. Moreover, SLC4A4 promoted PCa progression through the AKT-mediated signalling pathway.

Conclusion

The results of this study indicated that SLC4A4 overexpression was closely associated with the progression of PCa; SLC4A4 knockdown suppressed PCa development in vitro and in vivo. SLC4A4 acts as a tumor promotor in PCa by regulating key components of the AKT pathway and may therefore act as a potential therapeutic target for PCa treatment.
The effect of the polycystic ovary syndrome and hypothyroidism on the risk of fibrocystic breast changes: a meta-analysis
Authors: Kohnepoushi Parisa , Dehghanbanadaki Hojat , Mohammadzedeh Pardis , Nikouei Maziar , Moradi Yousef
Published: March 2022

This meta-analysis aimed to determine the pooled association between polycystic ovary syndrome (PCOS), hypothyroidism, and fibrocystic breast changes. We searched important databases, including PubMed (Medline), Scopus, Web of Science, and Embase to retrieve all relevant studies published from 1990 to April 2021. The bias risk of selected articles was assessed based on the JBI checklist. Our search strategy yielded a total of 487 articles from the international databases. After screening their full-texts, 6 articles met the inclusion criteria and were considered for meta-analysis. The effect of PCOS on the incidence of fibrocystic breast changes was 2.49 (95% CI 1.85–3.34). Also, the effect of hypothyroidism on the incidence of fibrocystic breast changes was 1.90 (95% CI 0.92–3.93). The results showed that women with PCOS were at higher risks to develop fibrocystic breast changes.
Durability of three types of dual active ingredient long-lasting insecticidal net compared to a pyrethroid-only LLIN in Tanzania: methodology for a prospective cohort study nested in a cluster randomized controlled trial
Authors: Martin Jackline L. , Messenger Louisa A. , Mosha Franklin W. , Lukole Eliud , Mosha Jacklin F. , Kulkarni Manisha , Churcher Thomas S. , Sherrard-Smith Ellie , Manjurano Alphaxard , Protopopoff Natacha , Rowland Mark
Published: March 2022

Background

Progress achieved by long-lasting insecticidal nets (LLINs) against malaria is threatened by widespread selection of pyrethroid resistance among vector populations. LLINs with non-pyrethroid insecticides are urgently needed. This study aims to assess the insecticide and textile durability of three classes of dual-active ingredient (A.I.) LLINs using techniques derived from established WHO LLIN testing methods to set new standards of evaluation.

Methods

A WHO Phase 3 active ingredients and textile durability study will be carried out within a cluster randomized controlled trial in 40 clusters in Misungwi district, Tanzania. The following treatments will be evaluated: (1) Interceptor®G2 combining chlorfenapyr and the pyrethroid alpha-cypermethrin, (2) Royal Guard® treated with pyriproxyfen and alpha-cypermethrin, (3) Olyset™ Plus which incorporates a synergist piperonyl butoxide and the pyrethroid permethrin, and (4) a reference standard alpha-cypermethrin only LLIN (Interceptor®). 750 nets will be followed in 5 clusters per intervention arm at 6, 12, 24 and 36 months post distribution for survivorship and hole index assessment. A second cohort of 1950 nets per net type will be identified in 10 clusters, of which 30 LLINs will be withdrawn for bio-efficacy and chemical analysis every 6 months up to 36 months and another 30 collected for experimental hut trials every year. Bio-efficacy will be assessed using cone bioassays and tunnel tests against susceptible and resistant laboratory strains of Anopheles gambiae sensu stricto. Efficacy of field-collected nets will be compared in six experimental huts. The main outcomes will be Anopheles mortality up to 72 h post exposure, blood feeding and egg maturation using ovary dissection to assess impact on fecundity.

Conclusions

Study findings will help develop bio-efficacy and physical durability criteria for partner A.I., in relation to the cRCT epidemiological and entomological outcomes, and refine preferred product characteristics of each class of LLIN. If suitable, the bioassay and hut outcomes will be fitted to transmission models to estimate correlation with cRCT outcomes.

Trial registration number: NCT03554616.
Effect of two types of shoulder prosthesis on the muscle forces using a generic multibody model for different arm motions
Authors: Weisse Bernhard , Lama Susan , Piskoty Gabor , Affolter Christian , Aiyangar Ameet K.
Published: March 2022

Background

This study aims to analyze the effects of a novel dual-bearing shoulder prosthesis and a conventional reverse shoulder prosthesis on the deltoid and rotator cuff muscle forces for four different arm motions. The dual-bearing prosthesis is a glenoid-sparing joint replacement with a moving center of rotation. It has been developed to treat rotator cuff arthropathy, providing an increased post-operative functionality.

Methods

A three-dimensional musculoskeletal OpenSim® model of an upper body, incorporating a natural gleno-humeral joint and a scapula-thoracic joint developed by Blana et al. (J Biomech 41: 1714-1721, 2008), was used as a reference for the natural shoulder. It was modified by integrating first a novel dual-bearing prosthesis, and second, a reverse shoulder prosthesis into the shoulder joint complex. Four different arm motions, namely abduction, scaption, internal and external rotation, were simulated using an inverse kinematics approach. For each of the three models, shoulder muscle forces and joint reaction forces were calculated with a 2 kg weight in the hand.

Results

In general, the maximal shoulder muscle force and joint reaction force values were in a similar range for both prosthesis models during all four motions. The maximal deltoid muscle forces in the model with the dual-bearing prosthesis were 18% lower for abduction and 3% higher for scaption compared to the natural shoulder. The maximal rotator cuff muscle forces in the model with the dual-bearing prosthesis were 36% lower for abduction and 1% higher for scaption compared to the natural shoulder. Although the maximal deltoid muscle forces in the model with the dual-bearing prosthesis in internal and external rotation were 52% and 64% higher, respectively, compared to the natural shoulder, the maximal rotator cuff muscle forces were 27% lower in both motions.

Conclusion

The study shows that the dual-bearing shoulder prosthesis is a feasible option for patients with rotator cuff tear and has a strong potential to be used as secondary as well as primary joint replacement. The study also demonstrates that computer simulations can help to guide the continued optimization of this particular design concept for successful clinical outcomes.
Near-roadway air pollution, immune cells and adipokines among obese young adults
Authors: Rahman Md Mostafijur , Liu Fei Fei , Eckel Sandrah P. , Sankaranarayanan Ishwarya , Shafiei-Jahani Pedram , Howard Emily , Baronikian Lilit , Sattler Fred , Lurmann Frederick W. , Allayee Hooman , Akbari Omid , McConnell Rob
Published: March 2022

Background

Air pollution has been associated with metabolic disease and obesity. Adipokines are potential mediators of these effects, but studies of air pollution-adipokine relationships are inconclusive. Macrophage and T cells in adipose tissue (AT) and blood modulate inflammation; however, the role of immune cells in air pollution-induced dysregulation of adipokines has not been studied. We examined the association between air pollution exposure and circulating and AT adipokine concentrations, and whether these relationships were modified by macrophage and T cell numbers in the blood and AT.

Methods

Fasting blood and abdominal subcutaneous AT biopsies were collected from 30 overweight/obese 18–26 year-old volunteers. Flow cytometry was used to quantify T effector (Teff, inflammatory) and regulatory (Treg, anti-inflammatory) lymphocytes and M1 [inflammatory] and M2 [anti-inflammatory]) macrophage cell number. Serum and AT leptin and adiponectin were measured using enzyme-linked immunosorbent assay (ELISA). Exposure to near-roadway air pollution (NRAP) from freeway and non-freeway vehicular sources and to regional particulate matter, nitrogen dioxide and ozone were estimated for the year prior to biopsy, based on participants’ residential addresses. Linear regression models were used to examine the association between air pollution exposures and adipokines and to evaluate effect modification by immune cell counts.

Results

An interquartile increase in non-freeway NRAP exposure during 1 year prior to biopsy was associated with higher leptin levels in both serum [31.7% (95% CI: 10.4, 52.9%)] and AT [19.4% (2.2, 36.6%)]. Non-freeway NRAP exposure effect estimates were greater among participants with greater than median Teff/Treg ratio and M1/M2 ratio in blood, and with greater M1 counts in AT. No adipokine associations with regional air pollutants were found.

Discussion

Our results suggest that NRAP may increase serum leptin levels in obese young adults, and this association may be promoted in a pro-inflammatory immune cell environment in blood and AT.
Novel multifunctional NIR-II aggregation-induced emission nanoparticles-assisted intraoperative identification and elimination of residual tumor
Authors: Qu Qiaojun , Zhang Zeyu , Guo Xiaoyong , Yang Junying , Cao Caiguang , Li Changjian , Zhang Hui , Xu Pengfei , Hu Zhenhua , Tian Jie
Published: March 2022

Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1–π–A–D2–R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes.

Graphic Abstract
PINK1/TAX1BP1-directed mitophagy attenuates vascular endothelial injury induced by copper oxide nanoparticles
Authors: Fan Yinzhen , Cheng Zhenli , Mao Lejiao , Xu Ge , Li Na , Zhang Mengling , Weng Ping , Zheng Lijun , Dong Xiaomei , Hu Siyao , Wang Bin , Qin Xia , Jiang Xuejun , Chen Chengzhi , Zhang Jun , Zou Zhen
Published: March 2022

Copper oxide nanoparticles (CuONPs) are widely used metal oxide NPs owing to their excellent physical–chemical properties. Circulation translocation of CuONPs after inhalation leads to vascular endothelial injury. Mitochondria, an important regulatory hub for maintaining cell functions, are signaling organelles in responses to NPs-induced injury. However, how mitochondrial dynamics (fission and fusion) and mitophagy (an autophagy process to degrade damaged mitochondria) are elaborately orchestrated to maintain mitochondrial homeostasis in CuONPs-induced vascular endothelial injury is still unclear. In this study, we demonstrated that CuONPs exposure disturbed mitochondrial dynamics through oxidative stress-dependent manner in vascular endothelial cells, as evidenced by the increase of mitochondrial fission and the accumulation of fragmented mitochondria. Inhibition of mitochondrial fission with Mdivi-1 aggravated CuONPs-induced mtROS production and cell death. Furthermore, we found that mitochondrial fission led to the activation of PINK1-mediated mitophagy, and pharmacological inhibition with wortmannin, chloroquine or genetical inhibition with siRNA-mediated knockdown of PINK1 profoundly repressed mitophagy, suggesting that the protective role of mitochondrial fission and PINK1-mediated mitophagy in CuONPs-induced toxicity. Intriguingly, we identified that TAX1BP1 was the primary receptor to link the ubiquitinated mitochondria with autophagosomes, since TAX1BP1 knockdown elevated mtROS production, decreased mitochondrial clearance and aggravated CuONPs-induced cells death. More importantly, we verified that urolithin A, a mitophagy activator, promoted mtROS clearance and the removal of damaged mitochondria induced by CuONPs exposure both in vitro and in vivo. Overall, our findings indicated that modulating mitophagy may be a therapeutic strategy for pathological vascular endothelial injury caused by NPs exposure.

Graphical Abstract
GSK-3β suppression upregulates Gli1 to alleviate osteogenesis inhibition in titanium nanoparticle-induced osteolysis
Authors: Wang Qing , Zhang Wei , Peng Xiaole , Tao Yunxia , Gu Ye , Li Wenming , Liang Xiaolong , Wang Liangliang , Wu Zerui , Wang Tianhao , Zhang Haifeng , Liu Xin , Xu Yaozeng , Liu Yu , Zhou Jun , Geng Dechun
Published: March 2022

Wear particle-induced periprosthetic osteolysis (PPO) have become a major reason of joint arthroplasty failure and secondary surgery following joint arthroplasty and thus pose a severe threat to global public health. Therefore, determining how to effectively suppress particle-induced PPO has become an urgent problem. The pathological mechanism involved in the PPO signaling cascade is still unclear. Recently, the interaction between osteogenic inhibition and wear particles at the implant biological interface, which has received increasing attention, has been revealed as an important factor in pathological process. Additionally, Hedgehog (Hh)-Gli1 is a crucial signaling cascade which was regulated by multiple factors in numerous physiological and pathological process. It was revealed to exert a crucial part during embryonic bone development and metabolism. However, whether Hh-Gli1 is involved in wear particle-induced osteogenic inhibition in PPO remains unknown. Our present study explored the mechanism by which the Hh-Gli1 signaling cascade regulates titanium (Ti) nanoparticle-induced osteolysis. We found that Hh-Gli1 signaling was dramatically downregulated upon Ti particle treatment. Mechanistically, glycogen synthesis kinase 3β (GSK-3β) activation was significantly increased in Ti particle-induced osteogenic inhibition via changes in GSK-3β phosphorylation level and was found to participate in the posttranslational modification and degradation of the key transcription factor Gli1, thus decreasing the accumulation of Gli1 and its translocation from the cytoplasm to the nucleus. Collectively, these findings suggest that the Hh-Gli1 signaling cascade utilizes a GSK3β-mediated mechanism and may serve as a rational new therapeutic target against nanoparticle-induced PPO.

Graphical Abstract
GelMA/PEGDA microneedles patch loaded with HUVECs-derived exosomes and Tazarotene promote diabetic wound healing
Authors: Yuan Meng , Liu Kun , Jiang Tao , Li Shengbo , Chen Jing , Wu Zihan , Li Wenqing , Tan Rongzhi , Wei Wenying , Yang Xiaofan , Dai Honglian , Chen Zhenbing
Published: March 2022

Clinical work and research on diabetic wound repair remain challenging globally. Although various conventional wound dressings have been continuously developed, the efficacy is unsatisfactory. The effect of drug delivery is limited by the depth of penetration. The sustained release of biomolecules from biological wound dressings is a promising treatment approach to wound healing. An assortment of cell-derived exosomes (exos) have been proved to be instrumental in tissue regeneration, and researchers are dedicated to developing biomolecules carriers with unique properties. Herein, we reported a methacrylate gelatin (GelMA) microneedles (MNs) patch to achieve transdermal and controlled release of exos and tazarotene. Our MNs patch comprising GelMA/PEGDA hydrogel has distinctive biological features that maintain the biological activity of exos and drugs in vitro. Additionally, its unique physical structure prevents it from being tightly attached to the skin of the wound, it promotes cell migration, angiogenesis by slowly releasing exos and tazarotene in the deep layer of the skin. The full-thickness cutaneous wound on a diabetic mouse model was carried out to demonstrate the therapeutic effects of GelMA/PEGDA@T + exos MNs patch. As a result, our GelMA/PEGDA@T + exos MNs patch presents a potentially valuable method for repairing diabetic wound in clinical applications.

Graphic Abstract
Triamcinolone acetonide-loaded nanoparticles encapsulated by CD90+ MCSs-derived microvesicles drive anti-inflammatory properties and promote cartilage regeneration after osteoarthritis
Authors: Li Yuanlong , Tu Qingqiang , Xie Dongmei , Chen Shurui , Gao Kai , Xu Xiaochun , Zhang Ziji , Mei Xifan
Published: March 2022

Background

Osteoarthritis (OA) is a highly prevalent human degenerative joint disorder that has long plagued patients. Glucocorticoid injection into the intra-articular (IA) cavity provides potential short-term analgesia and anti-inflammatory effects, but long-term IA injections cause loss of cartilage. Synovial mesenchymal stem cells (MSCs) reportedly promote cartilage proliferation and increase cartilage content.

Methods

CD90+ MCS-derived micro-vesicle (CD90@MV)-coated nanoparticle (CD90@NP) was developed. CD90+ MCSs were extracted from human synovial tissue. Cytochalasin B (CB) relaxed the interaction between the cytoskeleton and the cell membranes of the CD90+ MCSs, stimulating CD90@MV secretion. Poly (lactic-co-glycolic acid) (PLGA) nanoparticle was coated with CD90@MV, and a model glucocorticoid, triamcinolone acetonide (TA), was encapsulated in the CD90@NP (T-CD90@NP). The chondroprotective effect of T-CD90@NP was validated in rabbit and rat OA models.

Results

The CD90@MV membrane proteins were similar to that of CD90+ MCSs, indicating that CD90@MV bio-activity was similar to the cartilage proliferation-inducing CD90+ MCSs. CD90@NP binding to injured primary cartilage cells was significantly stronger than to erythrocyte membrane-coated nanoparticles (RNP). In the rabbit OA model, the long-term IA treatment with T-CD90@NP showed significantly enhanced repair of damaged cartilage compared to TA and CD90+ MCS treatments. In the rat OA model, the short-term IA treatment with T-CD90@NP showed effective anti-inflammatory ability similar to that of TA treatment. Moreover, the long-term IA treatment with T-CD90@NP induced cartilage to restart the cell cycle and reduced cartilage apoptosis. T-CD90@NP promoted the regeneration of chondrocytes, reduced apoptosis via the FOXO pathway, and influenced type 2 macrophage polarization to regulate inflammation through IL-10.

Conclusion

This study confirmed that T-CD90@NP promoted chondrocyte proliferation and anti-inflammation, improving the effects of a clinical glucocorticoid treatment plan.

Graphical Abstract
The impact of the work environment on the health-related quality of life of Licensed Practical Nurses: a cross-sectional survey in four work environments
Authors: Phillips Leah Adeline , de Los Santos Nyla , Ntanda Henry , Jackson Jennifer
Published: March 2022

Background

Nurses are known to have negative health outcomes related to their work. While it is acknowledged that nursing work is associated with things like back injuries and burnout, there is limited evidence as to what factors in the work environment contribute to these issues.

Purpose

The aims of this study were to assess how Licensed Practical Nurses (LPNs) report their Health-related quality of life (HRQoL), and how nurses’ health is impacted by their work environment.

Methods

These data used for analysis comes from a cross-sectional survey administered online to all LPNs in Alberta (2018). The survey collected data on the following variables: participant’s demographics, the SF-36 HRQoL, Practice Environment Scale of the Nursing Work Index (PES-NW) and the CD-RISC measure of resilience. The beta distribution was used to model HRQoL outcomes. In instances where optimal health (score of ‘1’) was observed then an extended version of beta distribution (called one—inflated beta) was applied.

Results

4,425 LPNs responded to the survey. LPNs (mean age: 40) report lower scores on each SF-36 subscale than the general Canadian population aged 35–44. LPNs who work ‘causal’ had better physical health, (OR 1.21, CI 1.11–1.32, p = 0.000), and mental health (OR 1.22, CI 1.12–1.30, p = 0.000) than LPNs who work full time, even after controlling for resilience. LPNs’ views on the adequacy of staffing and resources in their workplaces have an influence across all dimensions of health.

Conclusion

This study suggests that improvements in the work environment could positively impact health outcomes and that adequate resourcing could support the nursing workforce.