bluuebunny/crossref_metadata_2025 huggingface dataset:
The necessity of gait evaluation on the 7th day after tap tests for the idiopathic normal pressure hydrocephalus patients
Authors: Oike Ryo , Inoue Yasuaki , Ota Yoshiaki , Sorimachi Takatoshi
Published: November 2023

Background

A tap test is established as an evaluation method to indicate shunt surgery for hydrocephalus, especially idiopathic normal pressure hydrocephalus (iNPH). The timing of gait assessment after the test is still controversial, while some studies reported the effectiveness of the gait evaluation up to 2nd day after tap tests. Our study explored whether the gait evaluation on the 7th day after a tap test is necessary.

Methods

We retrospectively evaluated 129 consecutive cases with possible iNPH who performed gait assessment on all 1st, 3rd, and 7th days after tap tests between May 2020 and February 2022. We reviewed the following items of the patients: age, sex, modified Rankin scale, iNPH grading scale, Mini-Mental State Evaluation (MMSE), and neurological imaging. The number of probable iNPH patients who improved their gait each day after the test was analyzed. We also assessed the number of definite iNPH patients and revealed the background characteristics of the patients who showed gait improvement on the 7th day after the tests.

Results

Of the 129 patients who met our inclusion criteria, 57 were judged as probable iNPH on the 1st day, 28 were new on the 3rd, and 23 were new on the 7th. The number of probable iNPH patients up to the 7th day after tests was significantly more extensive than that of those up to the 3rd (108 [83.7%] vs. 85 [65.9%]; 95% confidence interval [CI], p < 0.0001). The number of definite iNPH patients was also significantly more prominent when the evaluation after the tests was performed on all of the 1st, the 3rd, and the 7th days than just on the 1st (72 vs. 42; 95% CI, p = 0.00016) or both of the 1st and the 3rd (72 vs. 61; 95% CI, p = 0.00074). No statistically significant difference existed in the patients’ backgrounds except for the pre-tap test MMSE.

Conclusion

Gait evaluation on the 7th day after tap tests, in addition to the first few days, may reduce the number of iNPH patients who miss the opportunity of getting beneficial treatment.
Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR]
Authors: Fu Liang , Xiong Juan , Wang Haibo , Zhang Peize , Yang Qianting , Cai Yi , Wang Wenfei , Sun Feng , Zhang Xilin , Wang Zhaoqin , Chen Xinchun , Zhang Wenhong , Deng Guofang
Published: November 2023

Introduction

The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs).

Methods

Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients’ treatment regimens are initially based on drug resistance profiles and patient’s preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions.

Discussion

Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations.

Trail registration

Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021.
Regular gastroscopy and colonoscopy during the evaluation of urachal cancer: do we really need them?
Authors: Luo Ming-rui , Cai Tao-nong , Lu Jiang-li , Liu Zhen-hua , Guo Sheng-jie , Liu Zhuo-wei , Yao Kai , Qin Zi-ke , Ye Yun-lin
Published: November 2023

Purpose

Urachal cancer is similar to gastrointestinal adenocarcinoma in histology, and gastroscopy/colonoscopy is often administered during perioperative evaluation. However, gastroscopy and colonoscopy have corresponding disadvantages. This study discusses whether gastroscopy/colonoscopy is truly necessary for patients with urachal cancer.

Patients and methods

A total of 166 bladder adenocarcinoma cases diagnosed at Sun Yat-sen University Cancer Center were retrospectively reviewed and divided into two groups (urachal cancer and nonurachal cancer), and perioperative evaluations were retrieved.

Results

There were 78 patients with urachal cancer, the median age was 48 years, and 59 were male. Perioperative gastroscopy/colonoscopy revealed 5 intestinal polyps and 1 adenoma during these evaluations, and no primary gastrointestinal cancer was found. Meanwhile, preoperative imaging evaluation did not detect significant gastrointestinal lesions. For 88 patients with nonurachal cancer, including primary bladder adenocarcinoma and metastatic tumors from gastrointestinal cancer, the median age was 56 years, and 64 were male. Preoperative imaging evaluation demonstrated 36 cases of gastrointestinal lesions, and 32 were confirmed by gastroscopy/colonoscopy; the other 4 were negative. Another 4 cases of colon cancer were detected by regular colonoscopy for suspected primary bladder adenocarcinoma. In all, 35 cases of colon cancer and 1 case of gastric cancer were identified by endoscopic examination. The diagnostic consistency of imaging and gastrointestinal endoscopy was favorable (P < 0.001), and the negative predictive value and diagnostic efficiency of imaging were 96.9% and 94.6%, respectively.

Conclusions

The vast majority of gastrointestinal cancer cases can be identified by assessment of the patient’s clinical symptoms, meticulous physical examination, and imaging evaluation. We recommend that gastroscopy/colonoscopy only be applied to patients with urachal cancer when the above examinations are positive.
Comparing vaccination coverage before and during COVID-19 pandemic in children under one year in the health district of commune V in Bamako, Mali
Authors: Diallo Mountaga , Dicko Ilo , Dembélé Samou , Konaté Brahima , Doumbia Cheick Oumar , Sanogo Ibrahim , Togola Ousmane Boua , Konaté Drissa , Sangaré Moussa , Thiam Hawa , Coulibaly Yaya Ibrahim , Diawara Sory Ibrahim , Toloba Yacouba , Coulibaly Adama Balla , Diakité Mahamadou , Doumbia Seydou
Published: November 2023

Introduction

Although an essential frontline service in the prevention of child morbidity and mortality, there are indications that routine vaccinations have been disrupted during the COVID-19 pandemic. The present study aimed to compare vaccination coverage before COVID-19 in Mali in 2019 and during COVID-19 in 2020.

Objective

To compare vaccination coverages before COVID-19 in Mali in 2019 and during COVID-19 in 2020.

Design

Cross-sectional study.

Setting and participants

We collected routine immunization data from 2019 to 2020 of children under one year in the health district of Commune V in Bamako which includes twelve community health centers (CSCom).

Results

Considering all vaccines together, coverage in 2019 was higher than in 2020 (88.7% vs. 71,6%) (p < 10− 3, Fig. 1). In 2020, low proportions of children vaccinated were observed in May (51.1%) two months after the first COVID-19 case in Mali on March 25, 2020. For all vaccines, the mean number of children vaccinated was significantly higher in 2019 (before COVID-19) as compared to 2020 (during COVID-19) (p < 0.05). However, in September and October 2019 BCG vaccine coverage was lower in 2019 as compared to 2020 (p < 10− 3).

Conclusion

COVID-19 pandemic has affected routine childhood vaccine coverage in Commune V of Bamako, particularly in May 2020. Therefore, new strategies are needed to improve vaccine coverage in young children below 1.
Coping strategies among adolescents and young adults living with HIV/AIDS in Accra-Ghana
Authors: Dake Selom , Bonful Harriet Affran , Ganu Vincent , Puplampu Peter , Asamoah Alexander , Arthur Hannah Ama , Mwintuu Linus , Asampong Emmanuel , Kretchy Irene A. , Anum Adote
Published: November 2023

Background

Living with HIV/AIDS is remarkably stressful and has an adverse effect on one’s physical and mental health. In Sub-Saharan Africa, the introduction of highly active anti-retroviral therapy has led to an increased number of children with perinatal acquired HIV who are living into adolescence and adulthood. Developing strategies to cope with HIV becomes imperative, especially among these adolescents. The study determined the factors that influence coping strategies among adolescents living with HIV.

Methods

An analytic cross-sectional design was used. A total of 154 adolescents aged 10–19 years living with HIV were systematically sampled at the Fevers Unit of Korle Bu Teaching Hospital from June to December, 2021. The adolescent version of the KidCope tool was used to assess the choice of coping strategies. Stata 16 was used to determine associations between independent variables and the coping strategies identified. Only variables that were significant at p = 0.1 or less in the crude model were used to run the adjusted regression model. The level of significance was set at p = 0.05 with a 95% confidence interval.

Results

The mean age of participants was 19.2 ± 0.45 years with 51.9% (80/154) of participants being males. A majority, 57.1% of the participants employed positive coping strategies with 87.0% (135/154) using cognitive restructuring strategy. In an adjusted linear regression model, participants coping strategies were significantly associated with their educational level (p = 0.04) and presence of both parents as caregivers (p = 0.02).

Conclusion

Participants largely adopted positive coping strategies in managing the disease. Factors that influenced the choice of coping strategies were higher levels of education and the presence of both parents as caregivers. The importance of a good social support structure and pursuing further education needs to be emphasized in counselling adolescents living with HIV as it promotes the choice of positive coping strategies.
Physical and mental health of informal caregivers before and during the COVID-19 pandemic in the United States
Authors: Ngamasana Emery L , Zarwell Meagan , Gunn Laura H
Published: November 2023

Background

Informal caregiving, a common form of social support, can be a chronic stressor with health consequences for caregivers. It is unclear how varying restrictions during the COVID-19 pandemic affected caregivers’ physical and mental health. This study explores pre-post March 2020 differences in reported days of poor physical and mental health among informal caregivers.

Methods

Data from the 2019/2020 Behavioral Risk Factor Surveillance System survey were used to match, via propensity scores, informal caregivers who provided care during COVID-19 restrictions to those who provided care before the pandemic. Negative binomial weighted regression models estimated incidence rate ratios (IRRs) and differences by demographics of reporting days of poor physical and mental health. A sensitivity analysis including multiple imputation was also performed.

Results

The sample included 9,240 informal caregivers, of whom 861 provided care during the COVID-19 pandemic. The incidence rate for days of poor physical health was 26% lower (p = 0.001) for those who provided care during the COVID-19 pandemic, though the incidence rates for days of poor mental health were not statistically different between groups. Informal caregivers with low educational attainment experienced significantly higher IRRs for days of poor physical and mental health. Younger informal caregivers had a significantly lower IRR for days of poor physical health, but higher IRR for days of poor mental health.

Conclusions

This study contends that the physical and mental health burden associated with informal caregiving in a period of great uncertainty may be heightened among certain populations. Policymakers should consider expanding access to resources through institutional mechanisms for informal caregivers, who may be likely to incur a higher physical and mental health burden during public health emergencies, especially those identified as higher risk.
Association between environmental factors and dengue incidence in Lao People’s Democratic Republic: a nationwide time-series study
Authors: Sugeno Masumi , Kawazu Erin C. , Kim Hyun , Banouvong Virasack , Pehlivan Nazife , Gilfillan Daniel , Kim Ho , Kim Yoonhee
Published: November 2023

Background

Dengue fever is a vector-borne disease of global public health concern, with an increasing number of cases and a widening area of endemicity in recent years. Meteorological factors influence dengue transmission. This study aimed to estimate the association between meteorological factors (i.e., temperature and rainfall) and dengue incidence and the effect of altitude on this association in the Lao People’s Democratic Republic (Lao PDR).

Methods

We used weekly dengue incidence and meteorological data, including temperature and rainfall, from 18 jurisdictions in Lao PDR from 2015 to 2019. A two-stage distributed lag nonlinear model with a quasi-Poisson distribution was used to account for the nonlinear and delayed associations between dengue incidence and meteorological variables, adjusting for long-term time trends and autocorrelation.

Results

A total of 55,561 cases were reported in Lao PDR from 2015 to 2019. The cumulative relative risk for the 90th percentile of weekly mean temperature (29 °C) over 22 weeks was estimated at 4.21 (95% confidence interval: 2.00–8.84), relative to the 25th percentile (24 °C). The cumulative relative risk for the weekly total rainfall over 12 weeks peaked at 82 mm (relative risk = 1.76, 95% confidence interval: 0.91–3.40) relative to no rain. However, the risk decreased significantly when heavy rain exceeded 200 mm. We found no evidence that altitude modified these associations.

Conclusions

We found a lagged nonlinear relationship between meteorological factors and dengue incidence in Lao PDR. These findings can be used to develop climate-based early warning systems and provide insights for improving vector control in the country.
Factors associated with early failure of the femoral neck system (FNS) in patients with femoral neck fractures
Authors: Chen L , Jiang JB , Ma H , Duan X , Chen JL
Published: November 2023

Background

Femoral neck system (FNS) is a new type of internal fixation system which has been widely used for treating femoral neck fractures (FNFs).Compared with other internal fixation methods, FNS is minimally invasive and stable, and often achieves satisfactory short-term efficacy.Early failure of FNS (EFFNS) is not uncommon, however, there are few literatures and reports on factors associated with EFFNS.This study aimed to survey the prevalence and risk factors of EFFNS.

Methods

We retrospectively analysed 62 patients with FNFs and underwent FNS fixation between 2019 and 2021. Demographic data, clinical characteristics, radiographic features and treatment process were described. Multifactor logistic regression analysis was used to analyse the different influencing factors.

Results

Out of the 62 FNFs patients, 10 patients (16.1%) developed EFFNS, including 6 cases of severe femoral neck shortening, 2 cases of screw-out, 1 case of avascular necrosis of the femoral head and 1 case of nonunion. In the failure group, all patients were younger than 65 years old, which was significantly higher than 59.6% in the healing group (P = 0.012). There were no significant differences in sex(P = 0.490), BMI (P = 0.709), injured side (P = 0.312), injury mechanism (P = 0.617), reduction method(P = 0.570),femoral neck-shaft angle(P = 0.545), Pauwels classification (P = 0.564) and Garden classification (P = 0.195). Moreover, we not found that Garden classification (P = 0.464) and age (P = 0.128) were statistically significant risk factors for EFFNS at multivariate analysis.

Conclusion

In this study, sex, BMI, injury side, injury mechanism, reduction method, Pauwels angle, femoral neck-shift angle, Pauwels classification and Garden classification were excluded as EFFNS risk factors. Moreover, our study demonstrated that age and Garden classification were not significant risk factors at multivariate analysis.

Trial registration

ChiCTR, ChiCTR2100051360. Registered on 21 September, 2021. https://www.chictr.org.cn/index.aspx.
What is the association between gender and self-perceived health status when controlling for disease-specific conditions? A retrospective data analysis of pre- and post-operative EQ-5D-5L differences in total hip and knee arthroplasty
Authors: Bischof Anja Y. , Steinbeck Viktoria , Kuklinski David , Marques Carlos J. , Bohlen Karina , Westphal Karl C. , Lampe Frank , Geissler Alexander
Published: November 2023

Background

The self-perceived health status of patients undergoing total hip and knee arthroplasty (THA and TKA) might differ post-operatively due to gender, age, or comorbidities. Patient-reported outcome measures (PROMs) such as the EQ-5D-5L measure the self-perceived health status. This study investigates whether the index score of the EQ-5D-5L is a valid tool for interpreting gender differences in outcomes for patients undergoing THA and TKA.

Methods

Routine and PROM-data of elective primary THA or TKA patients in two German hospitals between 2016 and 2018 were analyzed. Univariate analysis with Pearson’s chi-square was conducted to identify control variables for gender. To quantify the association between gender and the EQ-5D-5L dimensions, a cumulative odds ordinal logistic regression with proportional odds was conducted.

Results

Two thousand three hundred sixty-eight​​ THA patients (m = 978; f = 1390) and 1629 TKA patients (m = 715; f = 914) were considered. The regression analysis of the individual EQ-5D-5L dimensions showed that female gender was significantly associated with better self-care (THA and TKA) and better post-operative mobility (THA). In contrast, male gender was significantly associated with less pain/discomfort (TKA) and less anxiety/depression (THA) pre-surgery and 3-months post-surgery.

Conclusion

Our results confirmed that the self-perceived health status improved after surgery. However, due to the different associations of gender to the individual dimensions of the EQ-5D-5L, the weighted index score clouds the comparability between patients with different gender undergoing THA or TKA. Therefore, we argue to use the individual five dimensions for health status analysis, to reveal relevant additional information.
Inconsistent radiographic diagnostic criteria for lisfranc injuries: a systematic review
Authors: Seow Dexter , Yasui Youichi , Chan Li Yi Tammy , Murray Gareth , Kubo Maya , Nei Masashi , Matsui Kentaro , Kawano Hirotaka , Miyamoto Wataru
Published: November 2023

Purpose

To evaluate the radiographic diagnostic criteria and propose standardised radiographic criteria for Lisfranc injuries.

Methods

A systematic review of the PubMed and Embase databases was performed according to the PRISMA guidelines. The various radiographic criteria for the diagnosis of Lisfranc injuries were extracted. Descriptive statistics were presented for all continuous (as mean ± standard deviation) and categorical variables (as frequencies by percentages).

Results

The literature search included 29 studies that totalled 1115 Lisfranc injuries. The risk of bias ranged from “Low” to “Moderate” risk according to the ROBINS-I tool. The overall recommendations according to the GRADE assessment ranged from “Very Low” to “High”. 1st metatarsal to 2nd metatarsal diastasis was the most common of the 12 various radiographic diagnostic criteria observed, as was employed in 18 studies. This was followed by 2nd cuneiform to 2nd metatarsal subluxation, as was employed in 11 studies.

Conclusion

The radiographic diagnostic criteria of Lisfranc injuries were heterogeneous. The proposition for homogenous radiographic diagnostic criteria is that the following features must be observed for the diagnosis of Lisfranc injuries: 1st metatarsal to 2nd metatarsal diastasis of ≥ 2 mm on anteroposterior view or 2nd cuneiform to 2nd metatarsal subluxation on anteroposterior or oblique views. Further advanced imaging by CT or MRI may be required in patients with normal radiographs but with continued suspicion for Lisfranc injuries.

Level of evidence

4, systematic review.
Potential of whole-body dual-energy X-ray absorptiometry to predict muscle size of psoas major, gluteus maximus and back muscles
Authors: Tanaka Masaru , Kanayama Masahiro , Oha Fumihiro , Shimamura Yukitoshi , Tsujimoto Takeru , Hasegawa Yuichi , Hashimoto Tomoyuki , Nojiri Hidetoshi , Ishijima Muneaki
Published: November 2023

Background

Measurement of trunk muscle cross-sectional area (CSA) using axial magnetic resonance imaging (MRI) is considered clinically meaningful for understanding several spinal pathologies, such as low back pain and spinal sagittal imbalance. However, it remains unclear whether trunk muscle mass (TMM) measured using dual-energy X-ray absorptiometry (DXA) can predict the trunk muscle CSA. The aim of this study is to determine if DXA-derived TMM is associated and predicts with CSA of paraspinal muscles and gluteus maximus measured using MRI in healthy volunteers.

Methods

A total of 48 healthy volunteers underwent whole-body DXA and MRI of the spinopelvic region. The CSA of the psoas major, back muscles, and gluteus maximus were measured on axial MRI. Correlations and linear regressions between the TMM measured using DXA and the CSA of each musculature were investigated.

Results

There was a weak correlation between TMM and CSA of the psoas major in men (r = 0.39,P = 0.0678), and the linear regression was y = 301.74x – 401.24 (R2 = 0.2976,P = 0.0070). A moderate correlation was found in women (r = 0.58,P = 0.0021), and the linear regression was y = 230.21x − 695.29 (R2 = 0.4445,P = 0.0003). Moderate correlations were observed between TMM and CSA of the back muscles in both men (r = 0.63,P = 0.0012) and women (r = 0.63,P = 0.0007), the linear regression was y = 468.52x + 3688.5 (R2 = 0.5505,P < 0.0001) in men and y = 477.39x + 2364.1 (R2 = 0.564,P < 0.0001) in women. There was a strong correlation between TMM and CSA of the gluteus maximus in men (r = 0.72,P < 0.0001), and the linear regression was y = 252.69x − 880.5 (R2 = 0.6906,P < 0.0001). A moderate correlation was found in women (r = 0.69,P < 0.0001), and the linear regression was y = 230.74x – 231.32 (R2 = 0.6542,P < 0.0001).

Conclusions

The DXA-derived TMM was able to predict the CSA of the psoas major, back muscles, and gluteus maximus, and significantly correlated with the CSA of the back muscles and gluteus maximus. It might be a safer and cheaper alternative for evaluating the size of the back muscles and gluteus maximus.
Knowledge, attitude and practice of physical exercises among pregnant women attending prenatal care clinics of public health institutions in Hawassa city, Sidama, Ethiopia, in 2021: descriptive cross-sectional study
Authors: Negash Berhan Tsegaye , Alelgn Yitateku
Published: November 2023

Background

Participating in physical exercise enhances the physical and mental health of pregnant women. Preventing excessive weight gain, decreasing gestational hypertension, reducing back pain and labor complications are some of the main benefits of physical exercise during pregnancy and childbirth. Scrutinizing factors associated with sedentary life style among women during pregnancy could aid to design effective strategies to tackle the problem. Despite its benefit, little is explored about knowledge, attitude and practice of physical exercise among pregnant women in the study setting.

Objective

To assess prevalence of knowledge, attitude and practice of physical exercise among pregnant women who visit antenatal care at public health facilities of Hawassa town, Ethiopia, in 2023.

Methods

Facility based survey was conducted from November-December, in 2021. Data were collected using interview administered and structured questionnaire. Data were cleaned, coded and entered using Epi-data 4.6 and exported into SPSS 25 for analysis. Descriptive statistics was done using frequency count, percentage and mean values of variables. Finally, findings are presented using text, tables and charts.

Results

All of the study subjects completed interview making a response rate of 100% in this study. The mean adequate knowledge score was 42.2%. Positive attitude towards physical exercise during pregnancy was accounted as 63.7% and proportion of good practice of physical exercise was as 35.8%. Regarding practice of exercise, most (95.9%) of the subjects walk, however; only 11(8.9%) women perform pelvic floor exercise were the highest and least practiced physical exercise. Concerning knowledge of exercise, prevent excess weight 72.1% and increasing energy 53.2% were the commonly known benefits of physical exercise. Breathing difficulty (41.3%), chest pain (39.8%) and premature labor (34.0%) were the predominant perceptions of contra-indication of physical exercise during pregnancy.

Conclusions

In conclusion, the proportion of knowledge, attitude and practice of antenatal exercise is found to be sub-optimum in the study area. Therefore, health education should be enhanced about the benefit of physical exercise during pregnancy.
Medical students’ perceptions, experiences, and barriers towards research implementation at the faculty of medicine, Tanta university
Authors: Orebi Hisham Ahmed , Shahin Mohamed Reda , Awad Allah Meret Tawfik , Hegazy Arwa Hassan , Alshakhs Muslim Aqeel , Alaithan Ahmed Mohamed , Alhindi Abdallah Ahmoud , Kabbash Ibrahim Ali
Published: November 2023

Background

Research is essential for advancing medical knowledge and improving patient care. However, research capacity and output are low in low- and middle-income countries due to various challenges, including a lack of research training among medical students. Integrating research training into undergraduate medical curricula can help address this issue.

Methods

A cross-sectional study was conducted between December 2022 and March 2023 among 462 undergraduate medical students at Tanta University, Egypt to assess their knowledge, attitudes, and perceived barriers toward conducting research. Data were collected using a self-administered questionnaire and analyzed using SPSS.

Results

Nearly half (49.8%) of the students had an acceptable level of knowledge about research concepts while over two-thirds (66.2%) had a positive attitude. The most common barriers were lack of funding, time, and training in research methods. Previous research training was reported by 66.7% of students, but less than half had participated in or presented research. Students in the competency-based program had significantly higher knowledge and more positive attitudes than those in the mainstream program. Knowledge level was positively correlated with attitude.

Conclusion

While attitudes were generally positive, improvements are needed in research training and opportunities among undergraduate medical students at Tanta University to help address low research capacity challenges in low- and middle-income countries. Integration of formal research training into the curriculum may help increase knowledge and participation in research.
Attitude and concerns of healthy individuals regarding post-mortem brain donation. A qualitative study on a nation-wide sample in Italy
Authors: Cattaneo Chiara , Urakcheeva Iuliia , Giacomini Gianmarco , Stazi Maria Antonietta , Lana Susanna , Arnofi Antonio , Salemi Miriam , Toccaceli Virgilia
Published: November 2023

Background

Collecting post-mortem brain tissue is essential, especially from healthy “control” individuals, to advance knowledge on increasingly common neurological and mental disorders. Yet, healthy individuals, on which this study is focused, are still understudied. The aim of the study was to explore, among healthy potential brain donors and/or donors’ relatives, attitude, concerns and opinion about post-mortem brain donation (PMBD).

Methods

A convenience sampling of the general population (twins and their non-twin contacts) was adopted. From June 2018 to February 2019, 12 focus groups were conducted in four Italian cities: Milan, Turin, Rome and Naples, stratified according to twin and non-twin status. A qualitative content analysis was performed with both deductive and inductive approaches. Emotional interactions analysis corroborated results.

Results

One hundred and three individuals (49–91 yrs of age) participated. Female were 60%. Participants had scarse knowledge regarding PMBD. Factors affecting attitude towards donation were: concerns, emotions, and misconceptions about donation and research. Religion, spirituality and secular attitude were implied, as well as trust towards research and medical institutions and a high degree of uncertainty about brain death ascertainment. Family had a very multifaceted central role in decision making. A previous experience with neurodegenerative diseases seems among factors able to favour brain donation.

Conclusions

The study sheds light on healthy individuals’ attitudes about PMBD. Brain had a special significance for participants, and the ascertainment of brain death was a source of debate and doubt. Our findings emphasise the importance of targeted communication and thorough information to promote this kind of donation, within an ethical framework of conduct. Trust in research and health professionals emerged as an essential factor for a collaborative attitude towards donation and informed decision making in PMBD.
Barriers experienced by community midwives to provide basic emergency obstetric and newborn care in rural Pakistan
Authors: Kumar Ramesh , Mehraj Vikram , Ahmed Jamil , Khan Shahzad Ali , Ali Tariq Mehmood , Batool Saima , Rashid Fozia , Pongpanich Sathirakorn
Published: November 2023

Background

Considering the high maternal mortality rate, the government of Pakistan has deployed Community Midwives (CMWs) in rural areas of Pakistan. This relatively new cadre of community-based skilled birth attendants has previously reported to experience several challenges in providing maternal and child healthcare. However, what barriers they experience in providing basic emergency obstetric and newborn care needs to be further studied.

Methods

This was a cross-sectional study conducted in twelve districts in Sindh province, Pakistan, with poor maternal and child health indicators. A total of 258 CMWs participated in this study and completed the questionnaire on a pretested, validated tool in their community-based stations. The trained data collectors completed the questionnaires from the respondents. The problems identified were categorized into three major issues: financial, and transport and security related; and were analyzed accordingly. Ethical approval was obtained from the institutional review board (IRB) of Health Services Academy (HSA) Islamabad, Pakistan.

Results

The majority (90%) of 258 CMWs had formal training in maternal and neonatal care from the recognized institutions. Financial difficulties faced by CMWs were identified as the most frequent barriers and others were transport, security, and other issues. In univariate analysis, 38.1% and 61.9% of the community midwives who faced financial difficulties had completed a graduation or intermediate level of education, respectively (p = 0.006). Round-the-clock availability for emergencies was inversely associated with having financial difficulties, i.e., 71.4%, in contrast to 28.4% who had financial difficulties were available round-the-clock for emergency calls in their community clinics (p = 0.008). Formal training (p = 0.001), work experience (p = 0.015), longer duration of work (p = 0.003), and liaison with health workers and posting district (p = 0.001) had statistically significantly higher transport related issues. Security difficulties faced by CMWs and a set of correlates such as formal training (p = 0.019), working experience (p = 0.001), longer duration of work (p = 0.023), 24 h of availability on call (p = 0.004), liaison with traditional birth attendants (TBAs) in the community (p = 0.002), and district of posting (p = 0.001) were statistically significantly different. Other issues like working experience (p = < 0.001) and Liaison with TBAs in the community (p = < 0.001) were found statistically significant.

Conclusion

Financial, transportation and security related barriers were commonly reported by community midwives in the delivery of basic emergency obstetric and newborn care in rural Pakistan.
Relevance of next generation sequencing (NGS) data re-analysis in the diagnosis of monogenic diseases leading to organ failure
Authors: Saglia Claudia , Bracciamà Valeria , Trotta Luca , Mioli Fiorenza , Faini Angelo Corso , Brach Del Prever Giulia Margherita , Kalantari Silvia , Luca Maria , Romeo Carmelo Maria , Scolari Caterina , Peruzzi Licia , Calvo Pier Luigi , Mussa Alessandro , Fenoglio Roberta , Roccatello Dario , Alberti Claudio , Carli Diana , Amoroso Antonio , Deaglio Silvia , Vaisitti Tiziana
Published: November 2023

Background

In 2018, our center started a program to offer genetic diagnosis to patients with kidney and liver monogenic rare conditions, potentially eligible for organ transplantation. We exploited a clinical exome sequencing approach, followed by analyses of in silico gene panels tailored to clinical suspicions, obtaining detection rates in line with what reported in literature. However, a percentage of patients remains without a definitive genetic diagnosis. This work aims to evaluate the utility of NGS data re-analysis for those patients with an inconclusive or negative genetic test at the time of first analysis considering that (i) the advance of alignment and variant calling processes progressively improve the detection rate, limiting false positives and false negatives; (ii) gene panels are periodically updated and (iii) variant annotation may change over time.

Methods

114 patients, recruited between 2018 and 2020, with an inconclusive or negative NGS report at the time of first analysis, were included in the study. Re-alignment and variant calling of previously generated sequencing raw data were performed using the GenomSys Variant Analyzer software.

Results

21 previously not reported potentially causative variants were identified in 20 patients. In most cases (n = 19), causal variants were retrieved out of the re-classification from likely benign to variants of unknown significance (VUS). In one case, the variant was included because of inclusion in the analysis of a newly disease-associated gene, not present in the original gene panel, and in another one due to the improved data alignment process. Whenever possible, variants were validated with Sanger sequencing and family segregation studies. As of now, 16 out of 20 patients have been analyzed and variants confirmed in 8 patients. Specifically, in two pediatric patients, causative variants were de novo mutations while in the others, the variant was present also in other affected relatives. In the remaining patients, variants were present also in non-affected parents, raising questions on their re-classification.

Conclusions

Overall, these data indicate that periodic and systematic re-analysis of negative or inconclusive NGS data reports can lead to new variant identification or reclassification in a small but significant proportion of cases, with benefits for patients’ management.
Experiences of healthcare personnel on the efficacy of artemisinin-based combination therapy and malaria diagnosis in hospitals in Uganda
Authors: Ocan Moses , Bakubi Racheal , Tayebwa Mordecai , Basemera Joan , Nsobya Sam
Published: November 2023

Background

The risk of widespread resistance to artemisinin-based combination therapy (ACT) remains high in Uganda following detection of Plasmodium falciparum parasites with delayed artemisinin clearance genotype and phenotype. Establishment of context specific interventions to mitigate emergence and spread of artemisinin resistance is thus key in the fight against malaria in the country. The aim of this study was to explore the experiences of healthcare personnel on malaria diagnosis and self-reported efficacy of ACT in the management of malaria symptomatic patients in hospitals in low and high malaria transmission settings in Uganda.

Methods

This was a qualitative study in which data was collected from healthcare personnel in hospitals using key informant interviews. The key informant interview guide was developed, pre-tested prior to use and covered the following areas, (i) sociodemographic characteristics, (ii) malaria diagnosis (clinical and parasite based), (iii) quality-assured artemisinin-based combination therapy, (iv) malaria patient follow-up, (v) artemisinin resistance, (vi) anti-malarial self-medication. Data was entered in Atlas.ti ver 9.0 and analysis done following a framework criterion.

Results

A total of 22 respondents were interviewed of which 16 (72.7%) were clinicians. Majority, 81.8% (18/22) of the respondents were male. The following themes were developed from the analysis, malaria diagnosis (procedures and challenges), use of malaria laboratory test results, malaria treatment in hospitals, use of quality assured ACT (QAACT) in malaria treatment, and efficacy of ACT in malaria treatment.

Conclusion

Most healthcare personnel-initiated malaria treatment after a positive laboratory test. Cases of malaria patients who report remaining symptomatic after prior use of ACT exist especially in high malaria transmission settings in Uganda. There is need for regular monitoring of artemisinin resistance emergence and spread in the country.
Pericyte-derived exosomal miR-210 improves mitochondrial function and inhibits lipid peroxidation in vascular endothelial cells after traumatic spinal cord injury by activating JAK1/STAT3 signaling pathway
Authors: Gao Peng , Yi Jiang , Chen Wenjun , Gu Jun , Miao Sheng , Wang Xiaowei , Huang Yifan , Jiang Tao , Li Qingqing , Zhou Wei , Zhao Shujie , Wu Mengyuan , Yin Guoyong , Chen Jian
Published: November 2023

Background

Spinal cord injury (SCI) remains a significant health concern, with limited available treatment options. This condition poses significant medical, economic, and social challenges. SCI is typically categorized into primary and secondary injuries. Inflammation, oxidative stress, scar formation, and the immune microenvironment impede axon regeneration and subsequent functional restoration. Numerous studies have shown that the destruction of the blood–brain barrier (BBB) and microvessels is a crucial factor in severe secondary injury. Additionally, reactive oxygen species (ROS)-induced lipid peroxidation significantly contributes to endothelial cell death. Pericytes are essential constituents of the BBB that share the basement membrane with endothelial cells and astrocytes. They play a significant role in the establishment and maintenance of BBB.

Results

Immunofluorescence staining at different time points revealed a consistent correlation between pericyte coverage and angiogenesis, suggesting that pericytes promote vascular repair via paracrine signaling. Pericytes undergo alterations in cellular morphology and the transcriptome when exposed to hypoxic conditions, potentially promoting angiogenesis. We simulated an early ischemia-hypoxic environment following SCI using glucose and oxygen deprivation and BBB models. Co-culturing pericytes with endothelial cells improved barrier function compared to the control group. However, this enhancement was reduced by the exosome inhibitor, GW4869. In vivo injection of exosomes improved BBB integrity and promoted motor function recovery in mice following SCI. Subsequently, we found that pericyte-derived exosomes exhibited significant miR-210-5p expression based on sequencing analysis. Therefore, we performed a series of gain- and loss-of-function experiments in vitro.

Conclusion

Our findings suggest that miR-210-5p regulates endothelial barrier function by inhibiting JAK1/STAT3 signaling. This process is achieved by regulating lipid peroxidation levels and improving mitochondrial function, suggesting a potential mechanism for restoration of the blood-spinal cord barrier (BSCB) after SCI.
Adopting standardized cancer patient pathways as a policy at different organizational levels in the Swedish Health System
Authors: Fjällström Petter , Coe Anna-Britt , Lilja Mikael , Hajdarevic Senada
Published: November 2023

Background

Standardized cancer patient pathways as a new policy has been adopted in healthcare to improve the quality of cancer care. Within the health systems, actors at different levels manage the adoption of new policies to develop healthcare. The various actors on different levels play an important role and influence the policy adoption process. Thus, knowledge about how these actors use strategies when adopting cancer patient pathways as a policy in the health system becomes central.

Method

The study’s aim was to explore how actors at different organizational levels in the health system adopted cancer patient pathways. Our overarching case was the Swedish health system at the national, regional, and local levels. Constructivist Grounded Theory Method was used to collect and analyze qualitative interviews with persons working in organizations directly involved in adopting cancer patient pathways at each level. Twelve individual and nine group interviews were conducted including 53 participants.

Results

Organizational actors at three different levels used distinct strategies during the adoption of cancer patient pathways: acting as—missionaries, fixers, and doers. Acting as missionaries consisted of preaching the idea of cancer patient pathways and framing it with a common purpose to agree upon. Acting as fixers entailed creating a space to put cancer patient pathways into practice and overcome challenges to this. Acting as doers comprised balancing breadth and speed in healthcare provision with not being involved in the development of cancer patient pathways for the local context. These strategies were not developed in isolation from the other organizational levels but rather, each level interacted with one another.

Conclusions

When adopting new policies, it is important to be aware of the different strategies and actors at various organizational levels in health systems. Even when actors on different levels developed separate strategies, if these contribute to fulfilling the four domains of inter-organizational collaboration, they can work well together to adopt new policies. Our study highlighted that the application of two domains was lacking, which meant that local actors were not sufficiently involved in collaboration, thus constricting the local use and optimization of cancer patient pathways in practice.
Metabolomic profiles of intact tissues reflect clinically relevant prostate cancer subtypes
Authors: Dudka Ilona , Lundquist Kristina , Wikström Pernilla , Bergh Anders , Gröbner Gerhard
Published: November 2023

Background

Prostate cancer (PC) is a heterogenous multifocal disease ranging from indolent to lethal states. For improved treatment-stratification, reliable approaches are needed to faithfully differentiate between high- and low-risk tumors and to predict therapy response at diagnosis.

Methods

A metabolomic approach based on high resolution magic angle spinning nuclear magnetic resonance (HR MAS NMR) analysis was applied on intact biopsies samples (n = 111) obtained from patients (n = 31) treated by prostatectomy, and combined with advanced multi- and univariate statistical analysis methods to identify metabolomic profiles reflecting tumor differentiation (Gleason scores and the International Society of Urological Pathology (ISUP) grade) and subtypes based on tumor immunoreactivity for Ki67 (cell proliferation) and prostate specific antigen (PSA, marker for androgen receptor activity).

Results

Validated metabolic profiles were obtained that clearly distinguished cancer tissues from benign prostate tissues. Subsequently, metabolic signatures were identified that further divided cancer tissues into two clinically relevant groups, namely ISUP Grade 2 (n = 29) and ISUP Grade 3 (n = 17) tumors. Furthermore, metabolic profiles associated with different tumor subtypes were identified. Tumors with low Ki67 and high PSA (subtype A, n = 21) displayed metabolite patterns significantly different from tumors with high Ki67 and low PSA (subtype B, n = 28). In total, seven metabolites; choline, peak for combined phosphocholine/glycerophosphocholine metabolites (PC + GPC), glycine, creatine, combined signal of glutamate/glutamine (Glx), taurine and lactate, showed significant alterations between PC subtypes A and B.

Conclusions

The metabolic profiles of intact biopsies obtained by our non-invasive HR MAS NMR approach together with advanced chemometric tools reliably identified PC and specifically differentiated highly aggressive tumors from less aggressive ones. Thus, this approach has proven the potential of exploiting cancer-specific metabolites in clinical settings for obtaining personalized treatment strategies in PC.
Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer’s disease mouse model
Authors: Kim Namkwon , Ju In Gyoung , Jeon Seung Ho , Lee Yeongae , Jung Min-Ji , Gee Min Sung , Cho Jae Seok , Inn Kyung-Soo , Garrett-Sinha Lee Ann , Oh Myung Sook , Lee Jong Kil
Published: November 2023

Background

The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer’s disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown.

Methods

Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age.

Results

In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib−/− mice.

Conclusion

Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications.