bluuebunny/crossref_metadata_2025 huggingface dataset:
Commentary: Assessing the endocrine disrupting effects of chemicals on invertebrates in the European Union
Authors: Crane Mark , Dungey Steve , Lillicrap Adam , Thompson Helen , Weltje Lennart , Wheeler James R. , Lagadic Laurent
Published: April 2022

Evidence from both laboratory and field studies has shown that currently used synthetic and naturally occurring chemical substances may potentially disrupt invertebrate endocrine systems, although the extent of this in field populations remains unclear. Translating concerns about potential endocrine disrupting chemicals (EDCs) into practical and effective regulatory action is currently hampered by the breadth of invertebrate endocrinology when compared to the better understood vertebrate systems, a lack of fundamental knowledge about the endocrinology of many invertebrate groups, and the resulting uncertainty when making regulatory decisions. This commentary (i) outlines the breadth of invertebrate endocrine pathways for which European Union regulation of potential EDCs may be relevant; (ii) reviews the extent to which current knowledge meets regulatory requirements for invertebrates, including an assessment of the suitability of current invertebrate test guidelines for detecting endocrine modes of action; and (iii) proposes a roadmap towards the regulation of potential EDCs with greater confidence, based on the Adverse Outcome Pathway (AOP) concept and a focus on identifying Molecular Initiating Events (MIEs) within AOPs. We conclude there are no validated tools to determine any invertebrate endocrine mode of action in vitro or in vivo. However, there are commonly used invertebrate toxicity tests which might capture adverse effects that could potentially result from an endocrine mode of action but would not identify the causal mechanisms. Therefore, EU regulatory requirements for the identification of EDCs cannot currently be satisfied for invertebrates, either in general or for the specific invertebrates used in standard ecotoxicological studies. We propose that the most important research need is compilation of a comprehensive list of endocrine-related MIEs across invertebrate taxa via use of high-throughput ‘omics in combination with bioinformatics reverse engineered analyses. Although tractable, such an approach would require significant resource investment for development and implementation.
Antibiotic delivery evaluation against Mycobacterium fortuitum using nanofluids containing carbon nanotubes
Authors: Pargami Hamid Naderi , Siadat Seyed Davar , Amiri Vahid , Sheikhpour Mojgan
Published: April 2022

Background

Mycobacterium fortuitum (M. fortuitum) is a bacterium, which can cause infections in many anatomical regions of the body, including the skin, lymph nodes, and joints. This bacterium, which belongs to a group of bacteria known as nontuberculous mycobacteria, is regarded as an important nosocomial pathogen worldwide owing to its increasing antibiotic resistance. Recently, the antimicrobial effects of carbon nanotubes have been reported in numerous studies. These nanotubes can be very useful in drug delivery; besides, they exhibit unique properties against multidrug-resistant bacterial infections. This study aimed to investigate the antimicrobial effects of carboxyl-functionalized multi-walled carbon nanotubes (MWCNT-COOH) to reduce antibiotic resistance.

Methods

In this study, antibacterial effects of nanofluids containing functionalized MWCNTs at initial concentration of 2 mg/mL and serial dilutions of 54, 28.5, 14.25, 7.12, 3.5 µg/mL, antibiotics alone and combination of nanofluids with antibiotics were investigated.

Standard and resistant strains of M. fortuitum were obtained from the microbial bank of the Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran.

Results

It was observed that nanofluid containing MWCNT-COOH can exert antimicrobial effects on M. fortuitum and significantly reduce bacterial resistance to antibiotics including kanamycin and streptomycin. In the presence of antibiotics and nanofluids containing MWCNT-COOH at a dose of 28.5 µg/mL, no growth was observed.

Conclusion

One of the main antimicrobial mechanisms of MWCNT-COOH is penetration into the bacterial cell wall. In this study, by using the nanofluid containing MWCNT-COOH with increased stability, the antibiotic resistance of M. fortuitum was significantly reduced at lower dilutions compared to the antibiotic alone.
A case of esophageal neuromuscular choristoma
Authors: Zhao Wei , Zhu Xinying
Published: April 2022

Background

Neuromuscular choristoma (NMC) is a rare peripheral nerve lesion that is composed of ectopic mature muscle fibers and nerve fascicles, typically involving major nerve roots or trunks, such as the cranial nerves, brachial plexus, and sciatic nerves. The onset of NMC frequently occurs in the first decade of life. Here, we present the first documented case of a case of esophageal NMC in an adult patient.

Case presentation

A 46-year-old male patient presented in 2018 with a submucosal tumor of the esophagus. Upon presentation, the tumor was approximately 10 mm in diameter, covered by normal mucosa, and located in the left posterior wall of the esophagus in a position that was 30 cm from the incisor. The tumor was discovered incidentally during gastroscopic examination. In March 2021, endoscopic re-examination revealed no significant changes in the tumor. Endoscopic ultrasound revealed an oval hypoechoic mass with a homogeneous internal echo that originated from the muscularis propria with a maximum cross section of 13 mm × 6 mm. Resection was performed under gastroscopy. The resection specimen was 12 mm × 5 mm in size and was a well-demarcated, elastic, hard, and tough with a gray section. Histologically, the specimen consisted of an abundance of smooth muscle fiber bundles intercalated among nerve fibers, but without malignancy. Immunohistochemical examinations revealed positivity for S-100 protein, caldesmon, NSE and desmin, but negativity for CD117, DOG-1, HMB45, and Melan A. There was also aberrant nuclear localization of beta-catenin. Collectively, these findings led to a diagnosis of esophageal NMC.

Conclusions

NMC is extremely rare, especially esophageal NMC, and is very challenging to accurately diagnose prior to resection. It is important that we can differentiate NMC from other types of tumors.
Evaluation of screening tests for autoimmune gastritis in histopathologically confirmed Japanese patients, and re-evaluation of histopathological classification
Authors: Wada Yasuhiro , Nakajima Shigemi , Mori Naoko , Takemura Shizuki , Chatani Rena , Ohara Mariko , Fujii Makoto , Hasegawa Hiroshi , Hayafuji Kiyoyuki , Kushima Ryoji , Murakami Kazunari
Published: April 2022

Background

The aims of the present study are to evaluate non-invasive screening tests for autoimmune gastritis (AIG) and re-evaluate histopathological classification.

Methods

We screened candidates of AIG in JCHO Shiga Hospital between May 2012 and January 2020. The screening criteria were as follows: endoscopic O-p atrophy with Updated Kimura–Takemoto classification, 3 + pepsinogen (PG) test, low serum vitamin B12or elevated serum gastrin with positive anti-parietal cell (PC) or intrinsic factor antibodies. We evaluated the screening criteria in the patients who were histopathologically confirmed as AIG, and re-evaluated histopathological staging in clinical aspects.

Results

Twenty-two of 28 (78.6%) patients who met the screening criteria were histopathologically confirmed as AIG. Common clinical findings in the AIG patients were 10 × or greater anti-PC antibody, elevated serum gastrin greater than 172 pg/mL and endoscopic atrophy O-1 or greater. The areas under the curve of PG I, PG II and PG I/II ratio were 0.81, 0.29 and 0.98, respectively. Among histopathologically confirmed AIG patients, 4 and 18 patients were histopathologically classified into florid and end stages, respectively, while no patients into early stage. We could not find a significant difference between florid and end stages in the screening items studied.

Conclusions

Florid and end stages in histopathological classification are both advanced-stage AIG in clinical aspects. Our screening criteria without biopsy are applicable to screen clinically-advanced AIG with 78.6% positive predictive value. PG I and PG I/II ratio may be useful to screen AIG. However, we may need other criteria to screen early stage of AIG.
Nontuberculous mycobacterial skin and soft tissue infection in Hawaiʻi
Authors: Tokunaga Darcy S. , Siu Andrea M. , Lim Sian Yik
Published: April 2022

Background

Hawaiʻi has the highest nontuberculous mycobacterial (NTM) lung infection prevalence in the United States. Limited data regarding skin and soft tissue infections (SSTI) due to NTM in Hawaiʻi exists. This study describes patient demographics, clinical courses of infection, treatment patterns, and clinical outcomes of NTM SSTIs in Hawaiʻi.

Methods

A retrospective chart review (n = 50) of patients diagnosed and treated at Hawaiʻi Pacific Health facilities for NTM SSTIs between January 2010 and July 2021 was conducted. Patient demographics, clinical course, and treatment data were collected from electronic medical records.

Results

Half of the patient population consisted of females, and the average age of patients during infection was 49 years (SD = 25.6). The majority of cases (80%) were caused by rapidly growing mycobacteria (RGM), most commonly Mycobacterium abscessus. NTM SSTI by race were Asian (48%), White (28%), and Native Hawaiian and Other Pacific Islanders (16%). Almost all Asian patients with NTM SSTI were Filipino or Japanese. Diagnosis was frequently delayed. The average time to diagnosis was 116 days. Most patients achieved complete resolution (72%) following a prolonged course of antimicrobial treatment (mean = 196 days) with surgical debridement.

Conclusion

Increased awareness among physicians and the community of non-mycobacterial skin infections is essential in Hawaiʻi due to the high prevalence of NTM and the high percentage of predisposed populations. Increased awareness of NTM could reduce delayed diagnosis and improve patient care. Further studies are required to inform optimal treatment and diagnostic strategies, improve patient outcomes, and aid public health surveillance efforts.
Quality of life in children with cochlear implants in Kazakhstan
Authors: Zhumabayev Ruslan , Zhumabayeva Galiya , Kapanova Gulnara , Tulepbekova Nailya , Akhmetzhan Anuar , Grjibovski Andrej
Published: April 2022

Background

Although cochlear implantation (CI) has been performed in Kazakhstan since 2007 little is known about quality of life of patients after CI. The aim of this study was to assess the health-related quality of life (HRQoL) of Kazakhstani children after CI.

Methods

Altogether, 53 families with a child using a cochlear implant for at least 1 year participated in the study between July 20, 2019 and February 20, 2020 at the Audiological Сenter of Almaty, Kazakhstan. The parents/caregivers completed the “Children with Cochlear Implants: Parental Perspectives (CCIPP)” questionnaire.

Results

‘Well-being and happiness’ subdomain of the HRQoL yielded the highest ratings. ‘Communication’, ‘general functioning’, ‘self-reliance’, and ‘supporting the child’ subdomains each achieved significant (p < 0.01) associations with all HRQoL subdomains. There were positive correlations between language used by the parent who completed the questionnaire (Kazakh or Russian) and three HRQoL subdomains, including ‘well-being and happiness’, ‘supporting the child’ and ‘social relations’.

Conclusion

Parents/caregivers reported high quality of life in all HRQoL subdomains. Further research in this area with more detailed socio-demographic and medical history data is required to identify quality of life predictors in children after cochlear implantation.
Timing and pattern of growth faltering in children up-to 18 months of age and the associated feeding practices in an urban setting of Sri Lanka
Authors: Sithamparapillai K. , Samaranayake D. , Wickramasinghe V. P.
Published: April 2022

Background

Growth faltering is commonly encountered in breastfed infants during 4—6 months of age in low socioeconomic communities. The objective of this study was to describe the changes of growth indices with age, timing of growth faltering and its association with the feeding practices in children up-to 18 months of age.

Methods

A cross sectional descriptive study was conducted in 254 children aged 12 and 18 months attending an immunization clinic. Data on growth were extracted from the Child Health Development Record. Weight and length were measured using standard methods. Feeding practices were assessed using interviewer-administered questionnaire. A drop of > 0.25 in weight-for-age Standard Deviation Score (SDS) from birth SDS was defined as weight faltering.

Results

Weight faltering occurred at some point in 64.2% (n = 163) during first 18 months of life, and 78.5% of whom, had the onset ≤ 4 months of age. Majority (76.6%, n = 98) with weight for age faltering by 4 months remained so at 12 months (p = 0.497), while 29.7% (n = 38) had a weight-for-length below-2SD (p < 0.001). Prevalence of weight faltering was 50.4%, 46.1%, 48.4% and 48% at 4, 6, 9 and 12 months respectively. Exclusive breastfeeding was given at least until 4 months in 88% (n = 223) and up to 6 months in 60% (n = 153) while 92.9% (n = 236) were breastfed at 12 months, with 38.2% (n = 97) were breastfed on demand after six months. Complementary feeding (CF) was started before 6 months in 40.6% (n = 52) with early weight faltering, but only 20.3% received it with proper consistency. Breastfeeding throughout the night was significantly associated with current weight-for-length being < -1SD (OR = 1.89, CI, 1.04—3.45; p = 0.037).

Conclusions

Early growth faltering was found in this population with high exclusive breastfeeding rates and persisting growth faltering was associated with poor feeding practices. Therefore, timely individualized interventions need to be taken to improve long term growth.
Mindfulness-based stress reduction group training improves of sleep quality in postmenopausal women
Authors: Darehzereshki Samaneh , Dehghani Fahimeh , Enjezab Behnaz
Published: April 2022

Background and purpose

Sleep disorder is one of the most common problems during menopause, which affects different areas of people's lives. Today, mindfulness is one of the concepts that have attracted a lot of attention due to its desirable effects and low side effects. The present study was conducted to investigate the effect of mindfulness-based stress reduction (MBSR) group training on sleep quality of postmenopausal women.

Method

This is a quasi-experimental parallel study. The study involved 66 eligible postmenopausal women 45–60 years’ old (n = 33 in each group) during 2019–2020. The minimum score of women was 5 from Pittsburgh questionnaire. Eight sessions weekly (120-min/session) MBSR group training was conducted in the intervention group and menopausal health in the control group for two months. Pittsburgh Sleep Quality Questionnaire was used as a data collection tool. Descriptive statistics and nonparametric tests were utilized to analyze the data using SPSS software (version 25). The significance level < 0.05 was considered.

Results

Socio-demographic characteristics of participants were no statistically significant difference between the study groups before the intervention. The results showed that mean of overall quality of sleep score was before the intervention 10.21 ± 3.03, after the intervention 4.7 ± 2.45, and one month after the intervention 4.69 ± 2.4 respectively in intervention group (P < 0.001). While there was no significant change in the mean overall quality of sleep quality in the control group.

Conclusion

According to the results, MBSR group training is an effective strategy for improving the sleep quality of postmenopausal women. Therefore, could be used to improve the sleep quality of postmenopausal women by midwifery consultants in health centers.
Operative treatment outcomes of anterior sternoclavicular joint dislocation using two experimental methods - an acromioclavicular joint hook plate versus a locking plate: a retrospective study
Authors: Qu Yanzhen , Xie Xudong , Zhou Wu , Xia Tian , Cao Faqi , Mi Bobin , Xiong Yuan , Ye Zhewei , Liu Guohui
Published: April 2022

Background

We aimed to compare the intraoperative and early postoperative clinical outcomes of using an acromioclavicular joint hook plate (AJHP) versus a locking plate (LP) in the treatment of anterior sternoclavicular joint dislocation.

Methods

Seventeen patients with anterior sternoclavicular joint dislocation were retrospectively analyzed from May 2014 to September 2019. Six patients were surgically treated with an AJHP, and 11 were surgically treated with an LP. Five male and one female patients composed the AJHP group, and nine male and two female patients composed the LP group. The mean age of all patients was 49.5 years.

Results

Reduction and fixation were performed with AJHP or LP in all 17 patients. The mean operative blood loss, operative time, and length of incision in the AJHP group were significantly better than those in the LP group. Shoulder girdle movement of the AJHP group was significantly better than that of the LP group.

Conclusions

This study revealed that AJHP facilitated glenohumeral joint motion, reduced the risk of rupture of mediastinal structures, required a shorter incision, and had lesser blood loss and a shorter duration of operation compared with LP. However, some deficiencies require further improvement.
Efficacy of bisphosphonate therapy on postmenopausal osteoporotic women with and without diabetes: a prospective trial
Authors: Kim Jinyoung , Kim Kyoung Min , Lim Soo , Kang Moo-Il , Baek Ki-Hyun , Min Yong-Ki
Published: April 2022

Background

The co-occurrence of diabetes and osteoporosis is common in postmenopausal women. For the treatment of postmenopausal osteoporosis, current guidelines recommend initial treatment with bisphosphonates, but it is unclear whether bisphosphonates provide a similar degree of therapeutic efficacy in patients with diabetes. This study sought to compare the efficacy of monthly oral ibandronate for retaining bone mineral density (BMD) in diabetic and non-diabetic postmenopausal women with osteoporosis.

Methods

Postmenopausal osteoporotic women with or without diabetes were enrolled in this study from three hospitals in an open-label approach from 2018 to 2020. Each group of patients received oral ibandronate 150 mg once monthly for 1 year. BMD, trabecular bone score (TBS), serum C-terminal telopeptide of type I collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP) were evaluated prospectively. Treatment-emergent adverse events and changes in glucose metabolism during drug use were also monitored.

Results

Among the 120 study participants, 104 (86.7%) completed the study. Following 1 year of treatment, BMD increased by 3.41% vs. 3.71% in the lumbar spine, 1.30% vs. 1.18% in the femur neck, and 1.51% vs. 1.58% in the total hip in the non-diabetes and diabetes groups, respectively. There were no significant differences in BMD changes between the groups, and the differences in CTx or P1NP changes between groups were not significant. We did not observe any significant differences in baseline TBS values or the degree of change between before and after 1 year of ibandronate treatment in either group in this study. A total of 11 adverse events (9.2%) that recovered without sequelae occurred among the 120 included patients, and there was no significant difference in the frequency of adverse events between the groups (p = 0.862). The changes in fasting glucose and glycated hemoglobin levels between before and after treatment were not significant in the diabetic group.

Conclusions

Bisphosphonate therapy showed similar increases in BMD and decreases in CTx and P1NP of postmenopausal women with and without diabetes. Monthly oral ibandronate can be a safe and effective therapeutic option in postmenopausal osteoporosis patients with type 2 diabetes.

Trial registration

NCT number: NCT05266261, Date of registration: 04 March 2022.
Preferences for home care to enable home death among adult patients with cancer in late palliative phase – a grounded theory study
Authors: Nysæter Toril Merete , Olsson Cecilia , Sandsdalen Tuva , Wilde-Larsson Bodil , Hov Reidun , Larsson Maria
Published: April 2022

Background

The wish to be cared for and to die at home is common among people with end-stage cancer in the western world. However, home deaths are declining in many countries. The aim of this study was to explore the preferences for home care over time to enable home death among adult patients with cancer in the late palliative phase.

Methods

A qualitative method was applied according to grounded theory (Corbin & Strauss, 2008). Data was collected using individual interviews (n = 15) with nine adult patients. One to two follow up interviews were conducted with four patients. Sampling, data collection and constant comparative analysis were undertaken simultaneously.

Results

The findings are presented as a conceptual model of patients’ preferences for care to enable home death. The core category “Hope and trust to get the care I need to die at home” showed that the preference to die at home seemed stable over time and did not change with deterioration in health status and progression in illness. Five categories were related to the core category. The categories “being in the present”, “be safe and in charge” and “be seen and acknowledged” describe the patients’ preferences to live a meaningful life until death and be the same person as always. These preferences depended on the categories describing characteristics of healthcare personnel and the organisation of care: “reliable, compassionate and competent healthcare personnel” and “timely, predictive, continuous and adaptive organisation”.

Conclusion

An important preference over time was to be here and now and to live as meaningful a life as possible until death. Moreover, the patients preferred to retain control over their lives, to be autonomous and to be seen as the person they had always been. To achieve this, person-centred care provided by healthcare personnel with competence, skills and enough/ample time were required. In addition, home care needed to be organised in a way that ensured continuity and predictability. Systematic implementation of a person-centred care model and the use of advanced home care plans with continued re-evaluation for patients’ preferences of home care were proposed measures to enable home death.
Effects of bedside team-based learning on pediatric clinical practice in Chinese medical students
Authors: Gong Jie , Du Junfeng , Hao Jinjin , Li Lei
Published: April 2022

Background

Bedside teaching is a primary educational tool to improve the clinical practice of medical students. As a new medical pedagogical approach, team-based learning (TBL) is gradually being integrated into Chinese medical education programmes to promote clinical reasoning, knowledge application, teamwork and collaboration. The aim of this controlled study is to investigate the effects of TBL on pediatric bedside teaching in medical students.

Methods

Thirty medical students in pediatric clinical practice were randomly assigned to an intervention and a control group. Students in the intervention group exposed bedside teaching activity with TBL while students in the control group received traditional bedside teaching. Teaching for the two groups was conducted biweekly, and the same clinical cases were selected for both groups with the same instructors. After six months of clinical practice, the differences of learning outcomes between the two groups were compared through assessments by computer-based case simulations (CCS) and mini-Clinical Evaluation Exercise (mini-CEX). Student feedback following completion of bedside teaching was collected by questionnaire.

Results

The CCS scores in the intervention group were significantly higher than that in the control group (p < 0.05). The mini-CEX results showed that clinical judgment and counseling skills of the intervention group were higher than those in the control group (p < 0.01). Medical interviewing skills and overall clinical competence in the intervention group were better than those in the control group (p < 0.05). In the questionnaire survey, students in the intervention group believed that bedside teaching activity with TBL could promote active learning ability, improve counseling skills and strengthen teamwork.

Conclusions

Application of TBL in bedside teaching not only enhanced clinical practice skills among medical students but also improved their clinical reasoning and counseling skills.
Correlation between the quality of nursing handover, job satisfaction, and group cohesion among psychiatric nurses
Authors: Wang Bin , Zou Guiyuan , Zheng Mei , Chen Chen , Teng Weiyu , Lu Qinghua
Published: April 2022

Background

Nursing handovers are a critical component of patient safety. Researchers have performed many primary studies in this field, mainly reporting findings from changes in nursing handover patterns. However, few quantitative studies have explored the factors that influence handover quality. Therefore, this study aimed to investigate the quality of handovers and explore the associations between handover quality, job satisfaction, and group cohesion among psychiatric nurses.

Methods

This cross-sectional study included 186 registered psychiatric nurses from a Chinese hospital, who responded to the Handover Evaluation Scale, McCloskey/Mueller Satisfaction Scale, and Group Cohesion Scale. Bootstrap analyses were used to evaluate the mediating effect between variables.

Results

The average item score for handover quality was (5.85 ± 1.14), and job satisfaction and group cohesion could predict the variance of handover quality. Job satisfaction could partially mediate between group cohesion and handover quality, and the value of the mediating effect was 45.77%.

Conclusion

The quality of psychiatric nursing handovers has enhanced space. Thus, hospital managers should take various measures to strengthen group cohesion and promote job satisfaction, both of which help improve the quality of psychiatric nursing handovers.
Jasmonates and Histone deacetylase 6 activate Arabidopsis genome-wide histone acetylation and methylation during the early acute stress response
Authors: Vincent Stacey A. , Kim Jong-Myong , Pérez-Salamó Imma , To Taiko Kim , Torii Chieko , Ishida Junko , Tanaka Maho , Endo Takaho A. , Bhat Prajwal , Devlin Paul F. , Seki Motoaki , Devoto Alessandra
Published: April 2022

Background

Jasmonates (JAs) mediate trade-off between responses to both biotic and abiotic stress and growth in plants. TheArabidopsis thalianaHISTONE DEACETYLASE 6 is part of the CORONATINE INSENSITIVE1 receptor complex, co-repressing the HDA6/COI1-dependent acetic acid-JA pathway that confers plant drought tolerance. The decrease in HDA6 binding to target DNA mirrors histone H4 acetylation (H4Ac) changes during JA-mediated drought response, and mutations in HDA6 also cause depletion in the constitutive repressive marker H3 lysine 27 trimethylation (H3K27me3). However, the genome-wide effect of HDA6 on H4Ac and much of the impact of JAs on histone modifications and chromatin remodelling remain elusive.

Results

We performed high-throughput ChIP-Seq on the HDA6 mutant,axe1-5, and wild-type plants with or without methyl jasmonate (MeJA) treatment to assess changes in active H4ac and repressive H3K27me3 histone markers. Transcriptional regulation was investigated in parallel by microarray analysis in the same conditions. MeJA- and HDA6-dependent histone modifications on genes for specialized metabolism; linolenic acid and phenylpropanoid pathways; and abiotic and biotic stress responses were identified. H4ac and H3K27me3 enrichment also differentially affects JAs and HDA6-mediated genome integrity and gene regulatory networks, substantiating the role of HDA6 interacting with specific families of transposable elements in planta and highlighting further specificity of action as well as novel targets of HDA6 in the context of JA signalling for abiotic and biotic stress responses.

Conclusions

The findings demonstrate functional overlap for MeJA and HDA6 in tuning plant developmental plasticity and response to stress at the histone modification level. MeJA and HDA6, nonetheless, maintain distinct activities on histone modifications to modulate genetic variability and to allow adaptation to environmental challenges.
Evaluation for clinical benefit of metformin in patients with idiopathic pulmonary fibrosis and type 2 diabetes mellitus: a national claims-based cohort analysis
Authors: Teague Taylor T. , Payne Stephanie R. , Kelly Bryan T. , Dempsey Timothy M. , McCoy Rozalina G. , Sangaralingham Lindsey R. , Limper Andrew H.
Published: April 2022

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high morbidity and limited treatment options. Type 2 diabetes mellitus (T2DM) is a common comorbid illness among patients with IPF and is often treated with metformin, the first-line agent in the management of T2DM. There is growing evidence demonstrating metformin’s anti-fibrotic properties; however, there is little real-world clinical data regarding its potential effectiveness in IPF. This study aims to evaluate the clinical benefit of metformin in patients with IPF and T2DM.

Methods

This nationwide cohort study used de-identified administrative claims data from OptumLabs® Data Warehouse to identify 3599 adults with IPF and concomitant T2DM between January 1, 2014 and June 30, 2019. Two cohorts were created: a cohort treated with metformin (n = 1377) and a cohort not treated with metformin (n = 2222). A final 1:1 propensity score-matched cohort compared 1100 patients with IPF and T2DM receiving metformin to those with both diagnoses but not receiving metformin; matching accounted for age, sex, race/ethnicity, residence region, year, medications, oxygen use, smoking status, healthcare use, and comorbidities. Outcomes were all-cause mortality (primary) and hospitalizations (secondary).

Results

Among 2200 patients with IPF and T2DM included in this matched analysis, metformin therapy was associated with a reduction in all-cause mortality (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.36–0.58; p < 0.001) and hospitalizations (HR, 0.82; 95% CI, 0.72–0.93; p = 0.003) compared to patients not receiving metformin.

Conclusions

Among patients with IPF and T2DM, metformin therapy may be associated with improved clinical outcomes. However, further investigation with randomized clinical trials is necessary prior to metformin’s broad implementation in the clinical management of IPF.
“Many people have no idea”: a qualitative analysis of healthcare barriers among Yazidi refugees in the Midwestern United States
Authors: Rashoka Falah N. , Kelley Megan S. , Choi Jeong-Kyun , Garcia Marc A. , Chai Weiwen , Rashawka Hazim N.
Published: April 2022

Background

The COVID-19 pandemic has shed new light on inequities in healthcare access faced by immigrant and refugee communities. To address ongoing disparities, there is an urgent need for ecological approaches to better understand the barriers that hinder and resources that facilitate access to healthcare. This study investigates barriers to healthcare system access faced by Yazidi refugees in the Midwestern United States.

Methods

Informed by the Interpretative Phenomenological Approach, three focus group meetings with a community advisory board were conducted between September 2019 and January 2020. The nine-member focus group included social workers, healthcare providers, and members of the Yazidi community. Meeting recordings were transcribed into English, coded for themes, and validated.

Results

We describe themes related to specific barriers to healthcare access; analyze the influence of relational dynamics in the focus group; explore experiential themes related to healthcare access in the Yazidi community, and finally interpret our findings through a social-ecological lens.

Conclusion

Community agencies, healthcare organizations, policymakers, and other stakeholders must work together to develop strategies to reduce systemic barriers to equitable care. Community representation in priority-setting and decision-making is essential to ensure relevance, acceptability, and utilization of developed strategies.
Reprogramming the tumor microenvironment by genome editing for precision cancer therapy
Authors: Liu Ke , Cui Jia-Jia , Zhan Yan , Ouyang Qian-Ying , Lu Qi-Si , Yang Dong-Hua , Li Xiang-Ping , Yin Ji-Ye
Published: April 2022

The tumor microenvironment (TME) is essential for immune escape by tumor cells. It plays essential roles in tumor development and metastasis. The clinical outcomes of tumors are often closely related to individual differences in the patient TME. Therefore, reprogramming TME cells and their intercellular communication is an attractive and promising strategy for cancer therapy. TME cells consist of immune and nonimmune cells. These cells need to be manipulated precisely and safely to improve cancer therapy. Furthermore, it is encouraging that this field has rapidly developed in recent years with the advent and development of gene editing technologies. In this review, we briefly introduce gene editing technologies and systematically summarize their applications in the TME for precision cancer therapy, including the reprogramming of TME cells and their intercellular communication. TME cell reprogramming can regulate cell differentiation, proliferation, and function. Moreover, reprogramming the intercellular communication of TME cells can optimize immune infiltration and the specific recognition of tumor cells by immune cells. Thus, gene editing will pave the way for further breakthroughs in precision cancer therapy.
NKT-like (CD3 + CD56+) cells differ from T cells in expression level of cellular protective proteins and sensitivity to stimulation in the process of ageing
Authors: Kaszubowska Lucyna , Foerster Jerzy , Kmieć Zbigniew
Published: April 2022

Background

NKT-like cells are T lymphocytes coexpressing several NK cell-associated receptors. They are effector lymphocytes of innate and adaptive immunity, and their number increases with age. The study aimed to analyze the expression of cellular protective proteins, i.e. sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in NKT-like and T cells of the young (‘young’, 31 subjects, age range 19–24 years), seniors aged under 85 (‘old’; 30 subjects, age range 65–84 years) and seniors aged over 85 (‘oldest’, 24 subjects, age range 85–94 years). Both NKT-like and T cells were cultured for 48 h and stimulated with IL-2, LPS and PMA with ionomycin and compared with unstimulated control cells.

Results

The oldest seniors varied from the other age groups by significantly increased expression of SIRT1 and HSP70 in both NKT-like and T cells observed in both stimulated and nonstimulated cells. The analyzed lymphocyte populations of the oldest revealed not only the highest expression of these proteins but also insensitivity to all types of applied stimulation. When NKT-like cells were compared to T cells, higher expression of the studied protective proteins was observed in both stimulated and unstimulated NKT-like cells. Neither CD3 + CD56+ nor CD3+ cells revealed elevated expression of SOD2, and these cells responded to stimulation until very advanced age. T cells revealed higher sensitivity to stimulation with IL-2 regarding SIRT1 and HSP70 expression. NKT-like cells were more sensitive to stimulation with PMA and ionomycin concerning the expression of these proteins. IL-2 did not induce a significant increase in SOD2 expression in the studied age groups.

Conclusions

The oldest seniors developed an adaptive stress response in both T and NKT-like cells regarding the expression of SIRT1 and HSP70, which was increased and insensitive to further stimulation in contrast to SOD2, which showed a more inducible pattern of expression. CD3 + CD56+ cells exhibited higher expression of cellular protective proteins than CD3+ cells in both stimulated and control, nonstimulated cells. NKT-like and T cells showed a distinct sensitivity to the applied stimulatory factors in the respective age groups.
Whole-genome sequencing and genetic characteristics of representative porcine reproductive and respiratory syndrome virus (PRRSV) isolates in Korea
Authors: Kim Seung-Chai , Moon Sung-Hyun , Jeong Chang-Gi , Park Gyeong-Seo , Park Ji-Young , Jeoung Hye-Young , Shin Go-Eun , Ko Mi-Kyeong , Kim Seoung-Hee , Lee Kyoung-Ki , Cho Ho-Seong , Kim Won-Il
Published: April 2022

Background

Porcine reproductive and respiratory syndrome virus (PRRSV) is a macrophage-tropic arterivirus with extremely high genetic and pathogenic heterogeneity that causes significant economic losses in the swine industry worldwide. PRRSV can be divided into two species [PRRSV1 (European) and PRRSV2 (North American)] and is usually diagnosed and genetically differentiated into several lineages based on the ORF5 gene, which constitutes only 5% of the whole genome. This study was conducted to achieve nonselective amplification and whole-genome sequencing (WGS) based on a simplified sequence-independent, single-primer amplification (SISPA) technique with next-generation sequencing (NGS), and to genetically characterize Korean PRRSV field isolates at the whole genome level.

Methods

The SISPA-NGS method coupled with a bioinformatics pipeline was utilized to retrieve full length PRRSV genomes of 19 representative Korean PRRSV strains by de novo assembly. Phylogenetic analysis, analysis of the insertion and deletion (INDEL) pattern of nonstructural protein 2 (NSP2), and recombination analysis were conducted.

Results

Nineteen complete PRRSV genomes were obtained with a high depth of coverage by the SISPA-NGS method. Korean PRRSV1 belonged to the Korean-specific subtype 1A and vaccine-related subtype 1C lineages, showing no evidence of recombination and divergent genetic heterogeneity with conserved NSP2 deletion patterns. Among Korean PRRSV2 isolates, modified live vaccine (MLV)-related lineage 5 viruses, lineage 1 viruses, and nation-specific Korean lineages (KOR A, B and C) could be identified. The NSP2 deletion pattern of the Korean lineages was consistent with that of the MN-184 strain (lineage 1), which indicates the common ancestor and independent evolution of Korean lineages. Multiple recombination signals were detected from Korean-lineage strains isolated in the 2010s, suggesting natural interlineage recombination between circulating KOR C and MLV strains. Interestingly, the Korean strain GGYC45 was identified as a recombinant KOR C and MLV strain harboring the KOR B ORF5 gene and might be the ancestor of currently circulating KOR B strains. Additionally, two novel lineage 1 recombinants of NADC30-like and NADC34-like viruses were detected.

Conclusion

Genome-wide analysis of Korean PRRSV isolates retrieved by the SISPA-NGS method and de novo assembly, revealed complex evolution and recombination in the field. Therefore, continuous surveillance of PRRSV at the whole genome level should be conducted, and new vaccine strategies for more efficient control of the virus are needed.
Breaking strength and bone microarchitecture in osteoporosis: a biomechanical approximation based on load tests in 104 human vertebrae from the cervical, thoracic, and lumbar spines of 13 body donors
Authors: Schröder Guido , Reichel Martin , Spiegel Sven , Schulze Marko , Götz Andreas , Bugaichuk Semjon , Andresen Julian Ramin , Kullen Claus Maximilian , Andresen Reimer , Schober Hans-Christof
Published: April 2022

Background

The purpose of the study was to investigate associations between biomechanical resilience (failure load, failure strength) and the microarchitecture of cancellous bone in the vertebrae of human cadavers with low bone density with or without vertebral fractures (VFx).

Methods

Spines were removed from 13 body donors (approval no. A 2017-0072) and analyzed in regard to bone mineral density (BMD), Hounsfield units (HU), and fracture count (Fx) with the aid of high-resolution CT images. This was followed by the puncture of cancellous bone in the vertebral bodies of C2 to L5 using a Jamshidi™ needle. The following parameters were determined on the micro-CT images: bone volume fraction (BVF), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), degree of anisotropy (DA), trabecular number (Tb.N), trabecular pattern factor (Tb.Pf), and connectivity density (Conn.D). The axial load behavior of 104 vertebral specimens (C5, C6, T7, T8, T9, T12, L1, L3) was investigated with a servohydraulic testing machine.

Results

Individuals with more than 2 fractures had a significantly lower trabecular pattern factor (Tb.Pf), which also proved to be an important factor for a reduced failure load in the regression analysis with differences between the parts of the spine. The failure load (FL) and endplate sizes of normal vertebrae increased with progression in the craniocaudal direction, while the HU was reduced. Failure strength (FS) was significantly greater in the cervical spine than in the thoracic or lumbar spine (p < 0.001), independent of sex. BVF, Tb.Th, Tb.N, and Conn.D were significantly higher in the cervical spine than in the other spinal segments. In contrast, Tb.Sp and Tb.Pf were lowest in the cervical spine. BVF was correlated with FL (r = 0.600, p = 0.030) and FS (r = 0.763, p = 0.002). Microarchitectural changes were also detectable in the cervical spine at lower densities.

Conclusions

Due to the unique microarchitecture of the cervical vertebrae, fractures occur much later in this region than they do in the thoracic or lumbar spine.

Trial registration

Approval no. A 2017-0072.
Designing rare disease care pathways in the Republic of Ireland: a co-operative model
Authors: Ward A. J. , Murphy D. , Marron R. , McGrath V. , Bolz-Johnson M. , Cullen W. , Daly A. , Hardiman O. , Lawlor A. , Lynch S. A. , MacLachlan M. , McBrien J. , Ni Bhriain S. , O’Byrne J. J. , O’Connell S. M. , Turner J. , Treacy E. P.
Published: April 2022

Background

Rare diseases (RDs) are often complex, serious, chronic and multi-systemic conditions, associated with physical, sensory and intellectual disability. Patients require follow-up management from multiple medical specialists and health and social care professionals involving a high level of integrated care, service coordination and specified care pathways.

Methods and objectives

This pilot study aimed to explore the best approach for developing national RD care pathways in the Irish healthcare system in the context of a lack of agreed methodology. Irish clinical specialists and patient/lived experience experts were asked to map existing practice against evidence-based clinical practice guidelines (CPGs) and best practice recommendations from the European Reference Networks (ERNs) to develop optimal care pathways. The study focused on the more prevalent, multisystemic rare conditions that require multidisciplinary care, services, supports and therapeutic interventions.

Results

29 rare conditions were selected across 18 ERNs, for care pathway development. Multidisciplinary input from multiple specialisms was relevant for all pathways. A high level of engagement was experienced from clinical leads and patient organisations. CPGs were identified for 26 of the conditions. Nurse specialist, Psychology, Medical Social Work and Database Manager roles were deemed essential for all care pathways. Access to the therapeutic Health Service Professionals: Physiotherapy, Occupational Therapy, and Speech and Language Therapy were seen as key requirements for holistic care. Genetic counselling was highlighted as a core discipline in 27 pathways demonstrating the importance of access to Clinical Genetics services for many people with RDs.

Conclusions

This study proposes a methodology for Irish RD care pathway development, in collaboration with patient/service user advocates. Common RD patient needs and health care professional interventions across all pathways were identified. Key RD stakeholders have endorsed this national care pathway initiative. Future research focused on the implementation of such care pathways is a priority.
Characteristics of patients who received helicopter emergency medical services in Japan from 2012 to 2019: a retrospective analysis of data from Tochigi Prefecture
Authors: Wake Koji , Noguchi Takafumi , Hishinuma Hidekazu , Zaitsu Masayoshi , Kikuchi Jin , Uchida Masatoshi , Hayashi Kentaro , Machida Masanari , Houzumi Hajime , Hoshiyama Eisei , Takahashi Kyo , Kobashi Gen , Ono Kazuyuki
Published: April 2022

Background

Helicopter Emergency Medical Services (HEMS) has been in operation in Japan since 2001, allowing patients almost anywhere in the nation to receive on-scene emergency treatment from physicians. However, there is insufficient literature on the characteristics of the patients who use Japanese HEMS. Thus, this study aimed to investigate the overall characteristics of patients receiving HEMS care within a single prefecture in Japan.

Methods

We retrospectively analyzed the data of 5163 patients—in Tochigi Prefecture—who received HEMS care from 2012 to 2019. Descriptive statistics were used to analyze the following aspects of care: diagnosis, severity, background characteristics, geographical and environmental variables, immediate pre-hospital intervention, transportation type, and short-term clinical outcomes.

Results

Among 7370 HEMS requests received during the study period, treatment was provided to 5163 patients (1.8 cases per day; 3489 men [67.6%]). Nearly 55% (n = 2856) of patients were aged above 60 years. Age peaks were observed at 0–9 years and 60–69 years. The median distance from the base hospital to the site was 26.7 km. The age-standardized rate of HEMS treatment was 30.3 patients per 100,000 people. Cases of trauma and cardiovascular diseases were the most common (65.3%). Most individuals aged 0–9 years and 60–69 years had neurological disease (seizures accounted for 80.5% of this group) and cardiovascular disease, respectively. The number of patients was similar across all four seasons. After immediate pre-hospital intervention, 81.6% of patients receiving HEMS care were transferred by the helicopter ambulance (53.4% and 28.2% to the base hospital and to other hospitals, respectively). Overall, 56.6% of patients receiving HEMS care were transferred to the base hospital, and the short-term recovery rate was above 75%. Intravenous drip and oxygen administration were the most common pre-hospital interventions (93.1% and 72.7%, respectively).

Conclusions

This study is the first to describe the overall characteristics of HEMS patients using comprehensive data of all HEMS patients in one prefecture in Japan. Further research using both local- and national-level data is needed to accelerate the understanding of the benefits of HEMS.