bluuebunny/crossref_metadata_2025 huggingface dataset:
Er:YAG laser removal of zirconia crowns on titanium abutment of dental implants: an in vitro study
Authors: Cai Pingping , Zhuo Yingying , Lin Jie , Zheng Zhiqiang
Published: September 2022

Background

This research aimed to explore feasibility and the time required when erbium-doped yttrium aluminum garnet (Er:YAG) laser as a non-invasive treatment modality to retrieve different thicknesses of zirconia material bonded by two dental cements from titanium implant abutments.

Methods

Prepared 80 titanium blocks (length: 20 mm, width: 10 mm, height: 10 mm) and square zirconia sheets (length: 10 mm) with different thicknesses (1 mm, 2 mm, 3 mm, and 4 mm) were 20 pieces each. Resin modified glass ionomer cement (RelyX Luting 2; RXL) and resin cement (Clearfil SA luting; CSL) were used to bond zirconia sheet and titanium block. Specimens were kept in 100% humidity for 48 h. Er:YAG laser was used to retrieve the zirconia sheet and recorded the time. Universal testing machine was used to measure the residual adhesion of the samples that did not retrieve after 5 min of laser irradiation. Shear bond strength (MPa) and the time data (s) were analyzed using Kruskal–Wallis Test. The bonding surface and the irradiation surface of the zirconia sheet was examined with the scanning electron microscopy (SEM).

Results

Within 5 min of laser irradiation, RXL group: 1 mm group all fell off, 2 mm group had 3 specimens did not fall off, there was no statistical difference in the average time between the two groups; CSL group: half of the 1 mm group fell off. Shear bond strength test results: there was no statistical difference between 1 and 2 mm in RXL group and 1 mm in CSL group, there was no statistical difference between 3 mm in RXL group and 2 mm in CSL group, and there were significant differences statistically in comparison between any two groups in the rest. SEM inspection showed that the bonding surface and the irradiation surface of the zirconia sheet had changes.

Conclusion

In this vitro study, the following could be concluded: it is faster to remove zirconia crowns with thickness less than 2 mm from titanium abutment when luted with RelyX Luting 2 compared to Clearfil SA luting.
Nephrophobia: a retrospective study of medical students’ attitudes towards nephrology education
Authors: Hull William , Jewell Emilia , Shabir Shazia , Borrows Richard
Published: September 2022

Background

Nephrology is a subject which is challenged by a lack of applicants for trainee places. This study addresses the attitudes of medical students towards the subject and explores the causes of this lack of interest amongst potential specialty trainees.

Methods

Students were asked to complete a survey ranking their attitudes towards nephrology and other specialties. This data was collated and analysed to show trends and allow comparison of the attitudes towards each specialty.

Results

Students felt that along with geriatrics, their least favourite subject was nephrology. Students felt unconfident in diagnosing, managing and understanding chronic conditions more so than acute conditions. Nephrology was consistently amongst the least popular subject for all areas of diagnosis, management and pathophysiology. Renal anatomy was the only area of nephrology that students felt confident in. The less popular specialties of nephrology and geriatrics had the greatest room for improvement when directly instructed in specialty medical training.

Conclusions

Nephrology remains a problematic and unpopular specialty for medical students, driving their unwillingness to consider it as a future career route. This study identifies areas of misconception amongst medical students toward the specialty and highlights areas for improvement in renal training for students.
Differential attainment and recruitment to Intensive Care Medicine Training in the UK, 2018–2020
Authors: Tridente Ascanio , Parry-Jones Jack , Chandrashekaraiah Shashi , Bryden Daniele
Published: September 2022

Background

Differences exist among doctors in examination performance, clinical and academic career progression, and prevalence of performance assessment by professional regulatory bodies. Some of these differences have been reported in relation to individual characteristics. The purpose of this study is to establish whether any specific individual characteristics are associated with performance in selection for entry into specialty training in Intensive Care in the United Kingdom.

Methods

We evaluated data of 509 candidates from the national recruitment rounds of 2018/19 and 2019/20. The outcome evaluated was “success at interview". Variables reaching statistical significance at univariate logistic regression analysis were fed in the multivariable analysis to identify independent predictors of success, with additional exploratory analyses performed, where indicated.

Results

The candidates’ median age was 31.5 (interquartile range, IQR 30–33.7) years, 324 (63.7%) were male, 256 (50.3%) not married/in civil partnership, 6 (1.2%) pregnant. The majority (316, 62.1%) were White British, 99 (19.5%) of Asian background, other ethnicities represented less than 20% of the sample. Of the 509 candidates, 155 (30.5%) were Atheist, 140 (27.5%) Christian; most were heterosexual (440, 86.4%); 432 (84.9%) reported no disability, while 4 (0.8%) had a minor and 1 (0.2%) had a major disability; 432 (84.9%) candidates held a UK medical degree; 77 (15.1%) a non-UK degree. At univariate logistic regression analysis (LRA) multiple factors were found to be associated with a lower likelihood of success, the strongest being an international medical graduate (IMG, holding a non-UK medical degree); others were increasing age, male gender, being married, Asian or mixed ethnicity, specific religious beliefs (Buddhism, Islam and Hinduism).

After feeding all factors significant at univariate analysis, the only two retained as independent predictors at multivariable regression were Asian ethnicity and holding a non-UK degree. Asian UK graduates success rate was 92.7%, comparable to the national average of 92.3%, the Asian IMGs success rate was significantly lower, at 45.5%.

Conclusions

As the imbalances seen within the candidates of Asian background are explained by considering the country of primary medical training, the variations in performance is likely to reflect differences in training systems and understanding of the UK NHS.
Is primary health care ready for artificial intelligence? What do primary health care stakeholders say?
Authors: Terry Amanda L. , Kueper Jacqueline K. , Beleno Ron , Brown Judith Belle , Cejic Sonny , Dang Janet , Leger Daniel , McKay Scott , Meredith Leslie , Pinto Andrew D. , Ryan Bridget L. , Stewart Moira , Zwarenstein Merrick , Lizotte Daniel J.
Published: September 2022

Background

Effective deployment of AI tools in primary health care requires the engagement of practitioners in the development and testing of these tools, and a match between the resulting AI tools and clinical/system needs in primary health care. To set the stage for these developments, we must gain a more in-depth understanding of the views of practitioners and decision-makers about the use of AI in primary health care. The objective of this study was to identify key issues regarding the use of AI tools in primary health care by exploring the views of primary health care and digital health stakeholders.

Methods

This study utilized a descriptive qualitative approach, including thematic data analysis. Fourteen in-depth interviews were conducted with primary health care and digital health stakeholders in Ontario. NVivo software was utilized in the coding of the interviews.

Results

Five main interconnected themes emerged: (1) Mismatch Between Envisioned Uses and Current Reality—denoting the importance of potential applications of AI in primary health care practice, with a recognition of the current reality characterized by a lack of available tools; (2) Mechanics of AI Don’t Matter: Just Another Tool in the Toolbox– reflecting an interest in what value AI tools could bring to practice, rather than concern with the mechanics of the AI tools themselves; (3) AI in Practice: A Double-Edged Sword—the possible benefits of AI use in primary health care contrasted with fundamental concern about the possible threats posed by AI in terms of clinical skills and capacity, mistakes, and loss of control; (4) The Non-Starters: A Guarded Stance Regarding AI Adoption in Primary Health Care—broader concerns centred on the ethical, legal, and social implications of AI use in primary health care; and (5) Necessary Elements: Facilitators of AI in Primary Health Care—elements required to support the uptake of AI tools, including co-creation, availability and use of high quality data, and the need for evaluation.

Conclusion

The use of AI in primary health care may have a positive impact, but many factors need to be considered regarding its implementation. This study may help to inform the development and deployment of AI tools in primary health care.
Effect of educational intervention on improving nurse’s general health in military hospitals of Iran: a quasi-experimental study
Authors: Ranaei Vahid , Kalroozi Fatemeh , Sadeghi Mojtaba , Yarmohammadi Soudabeh , Haglund Kristin , Mehrabi Nahid
Published: September 2022

Background

Nursing in military hospitals affects their general health. Educational interventions can help to maintain the general health of nurses. This study aimed to evaluate the effect of an educational intervention to improve the general health of nurses in military hospitals.

Methods

In this quasi-experimental study, 146 nurses working in military hospitals in Tehran, Iran in 2021 were included in the study. The one-month educational intervention included videos, pamphlets, and motivational messages about promoting general health. General health questionnaire with 28 items (GHQ28) was study tool. The allocation of nurses to groups was not random, it was based on personal interest. Frequency (percentage), and mean (standard deviation) were used to describe, and the chi-square test, Fisher’s exact test, independent and paired t-test were used for data analysis. All analyzes were performed in SPSS 24 software with a significance level of 5%.

Results

A total of 146 nurses participated in the study, most of them were in the age group of 30 to 40 years (64 people, 43.8%), and 76.7% (112 people) of them were women. The results of the independent sample t-test showed after the intervention, general health scores in the intervention group had a significant decrease compared to the control (p < 0.001) (change in intervention group = -31.1, V.S change in control = 0.55). The results of paired t-test showed that only in the intervention group, the value of the general health score and its dimensions were significantly different (p < 0.001).

Conclusions

The educational intervention performed well and decreased the score of the general health of military nurses. Given that these positive effects may be temporary, it is necessary to design and perform educational interventions over a longer period.
Exploring the impact of health worker strikes on maternal and child health in a Kenyan county
Authors: Mohiddin Abdu , Langat Eva , Orwa James , Naanyu Violet , Temmerman Marleen
Published: September 2022

Background

Studies of the impact of health care workers’ strikes tend to look at facility-level activity rather than populations, with evidence from low and middle-income countries relatively sparse. This study explored the effect of national strikes on maternal and child health. It looked at the impact on health system activity in both public and non-public sectors (e.g. private, faith-based), on health promotion investments like immunisation, and on disease detection like post-partum haemorrhage (PPH). A 100 day doctors’ strike started in December 2016, a 150 day nurses strike from June 2017 and then the clinical officers for 21 days that September.

Methods

Time series descriptive analysis of attendance data from the Kenyan Health Management Information System (public, non-public sector facilities). The setting was Kilifi, a coastal county in Kenya with a population of about 1.5 million.

Results

Along the care pathway from antenatal, postnatal and out-patient child health clinics, activity levels dropped markedly in the public sector with only partial compensatory increases in non-public sector activity. The number of fully immunised children fell during the nurses strike as did women seen with PPH during all strikes. These health care strikes caused significant adverse health impacts at the time and potentially inter-generationally as exemplified by the fall in antenatal haematinics supplementation and syphilis testing. Some post-strike ‘’catch-up” activity occurred, however this may have been too late in some instances.

Conclusions

Policy-makers at national and county level need to ensure population health is protected at times of strikes and ideally resolve disputes without such action. Not to do so risks major negative effects on maternal and child health. Increased use of the non-public health sector could be done by the authorities in mitigation should strikes occur again.
Using the Delphi method to establish pediatric emergency triage criteria in a grade A tertiary women’s and children’s hospital in China
Authors: Zhao Yingying , He Liqing , Hu Juan , Zhao Jing , Li Mingxuan , Huang Lisha , Jin Qiu , Wang Lan , Wang Jianxiong
Published: September 2022

Background

We aimed to establish simplified and quantifiable triage criteria in pediatric emergency care, improving the efficiency of pediatric emergency triage and ensuring patient safety.

Methods

We preliminarily determined the pediatric emergency triage criteria with references to pediatric emergency department characteristics and internationally recognized triage tools after literature review and discussion. The final determination of the triage criteria was reached after two rounds of Delphi surveys completed by18 experts from 3 hospitals in China.

Results

Both round 1 and round 2 surveys had a 100% response rate. The overall expert authority coefficient in the two rounds of surveys was 0.872. The experts had 100% enthusiasm for participating in the surveys. Kendall’s coefficients of concordance for conditions/symptoms in patients triaged to level 1, 2, 3, and 4 were 0.149, 0.193, 0.102, and 0.266, respectively. All p-values were less than 0.05. The coefficients of variation in conditions/symptoms, vital signs, and the Pediatric Early Warning Score (PEWS) ranged between 0.00 and 0.205, meeting the inclusion criteria. The pediatric emergency triage criteria containing conditions/symptoms, vital signs, PEWS scores, and other 4 level 1 indicators, 51 level 2 indicators and 23 level 3 indicators were built. The maximum waiting time to treatment for the patients triaged to level 1, 2, 3, and 4 was immediate, within 10 min, within 30 min, and within 240 min, respectively.

Conclusion

The pediatric emergency triage criteria established in this study was scientific and reliable. It can be used to quickly identify the patients requiring urgent and immediate care, thereby ensuring the priorities for the care of critically ill patients.
Physical and psychological workloads and their association with occupational fatigue among hospital service personnel
Authors: Ahmadi Morteza , Choobineh Alireza , Mousavizadeh Ali , Daneshmandi Hadi
Published: September 2022

Background

Physical and psychological workloads are a vital issue in the workplace. This study aimed to investigate the association between physical and psychological workloads and occupational fatigue among Iranian hospital service personnel. In Iran, hospital service personnel refers to a group of healthcare workers who undertake a range of duties, such as moving and carrying the hospital waste, transporting patients by wheelchair or gurney to the operating room, x-ray department, other wards, or other locations around the facility, performing cleaning tasks such as changing linens, mopping floors, and sterilizing equipment, and following infection control procedures to reduce the risk of spreading germs within the hospital setting.

Methods

This cross-sectional study was conducted on 198 Iranian hospital service personnel. The response rate was 86%. The data were gathered using 1) The Persian version of the Job Content Questionnaire (P-JCQ) for assessing physical and psychosocial workloads and 2) The Persian version of the Swedish Occupational Fatigue Inventory (P-SOFI-20) for assessing fatigue dimensions.

Results

According to the P-JCQ, the physical and psychological workload intensities were high in 72.7% and 47% of the participants, respectively. Based on the P-SOFI, the participants’ mean scores of “physical fatigue” (21.73 ± 6.2), “psychological fatigue” (13.61 ± 5.76), and “fatigue due to shift work” (18.17 ± 5.6) were moderate, while the mean score of “general fatigue” was high (27.3 ± 6.98). The findings revealed that various types of fatigue are associated with age, gender, marital status, daily working hours, and psychological workload.

Conclusions

Psychological workload was a determinant of occupational fatigue among Iranian hospital service personnel. Hence, an interventional program, including job enrichment, job rotation, and work-rest cycle, is recommended.
Single nucleotide polymorphism genes and mitochondrial DNA haplogroups as biomarkers for early prediction of knee osteoarthritis structural progressors: use of supervised machine learning classifiers
Authors: Bonakdari Hossein , Pelletier Jean-Pierre , Blanco Francisco J. , Rego-Pérez Ignacio , Durán-Sotuela Alejandro , Aitken Dawn , Jones Graeme , Cicuttini Flavia , Jamshidi Afshin , Abram François , Martel-Pelletier Johanne
Published: September 2022

Background

Knee osteoarthritis is the most prevalent chronic musculoskeletal debilitating disease. Current treatments are only symptomatic, and to improve this, we need a robust prediction model to stratify patients at an early stage according to the risk of joint structure disease progression. Some genetic factors, including single nucleotide polymorphism (SNP) genes and mitochondrial (mt)DNA haplogroups/clusters, have been linked to this disease. For the first time, we aim to determine, by using machine learning, whether some SNP genes and mtDNA haplogroups/clusters alone or combined could predict early knee osteoarthritis structural progressors.

Methods

Participants (901) were first classified for the probability of being structural progressors. Genotyping included SNP genes TP63, FTO, GNL3, DUS4L, GDF5, SUPT3H, MCF2L, and TGFA; mtDNA haplogroups H, J, T, Uk, and others; and clusters HV, TJ, KU, and C-others. They were considered for prediction with major risk factors of osteoarthritis, namely, age and body mass index (BMI). Seven supervised machine learning methodologies were evaluated. The support vector machine was used to generate gender-based models. The best input combination was assessed using sensitivity and synergy analyses. Validation was performed using tenfold cross-validation and an external cohort (TASOAC).

Results

From 277 models, two were defined. Both used age and BMI in addition for the first one of the SNP genes TP63, DUS4L, GDF5, and FTO with an accuracy of 85.0%; the second profits from the association of mtDNA haplogroups and SNP genes FTO and SUPT3H with 82.5% accuracy. The highest impact was associated with the haplogroup H, the presence of CT alleles for rs8044769 at FTO, and the absence of AA for rs10948172 at SUPT3H. Validation accuracy with the cross-validation (about 95%) and the external cohort (90.5%, 85.7%, respectively) was excellent for both models.

Conclusions

This study introduces a novel source of decision support in precision medicine in which, for the first time, two models were developed consisting of (i) age, BMI, TP63, DUS4L, GDF5, and FTO and (ii) the optimum one as it has one less variable: age, BMI, mtDNA haplogroup, FTO, and SUPT3H. Such a framework is translational and would benefit patients at risk of structural progressive knee osteoarthritis.
Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses
Authors: Yang Qian , Magnus Maria C. , Kilpi Fanny , Santorelli Gillian , Soares Ana Gonçalves , West Jane , Magnus Per , Wright John , Håberg Siri Eldevik , Sanderson Eleanor , Lawlor Deborah A. , Tilling Kate , Borges Maria Carolina
Published: September 2022

Background

Observational studies have reported maternal short/long sleep duration to be associated with adverse pregnancy and perinatal outcomes. However, it remains unclear whether there are nonlinear causal effects. Our aim was to use Mendelian randomization (MR) and multivariable regression to examine nonlinear effects of sleep duration on stillbirth (MR only), miscarriage (MR only), gestational diabetes, hypertensive disorders of pregnancy, perinatal depression, preterm birth and low/high offspring birthweight.

Methods

We used data from European women in UK Biobank (N=176,897), FinnGen (N=~123,579), Avon Longitudinal Study of Parents and Children (N=6826), Born in Bradford (N=2940) and Norwegian Mother, Father and Child Cohort Study (MoBa, N=14,584). We used 78 previously identified genetic variants as instruments for sleep duration and investigated its effects using two-sample, and one-sample nonlinear (UK Biobank only), MR. We compared MR findings with multivariable regression in MoBa (N=76,669), where maternal sleep duration was measured at 30 weeks.

Results

In UK Biobank, MR provided evidence of nonlinear effects of sleep duration on stillbirth, perinatal depression and low offspring birthweight. Shorter and longer duration increased stillbirth and low offspring birthweight; shorter duration increased perinatal depression. For example, longer sleep duration was related to lower risk of low offspring birthweight (odds ratio 0.79 per 1 h/day (95% confidence interval: 0.67, 0.93)) in the shortest duration group and higher risk (odds ratio 1.40 (95% confidence interval: 1.06, 1.84)) in the longest duration group, suggesting shorter and longer duration increased the risk. These were supported by the lack of evidence of a linear effect of sleep duration on any outcome using two-sample MR. In multivariable regression, risks of all outcomes were higher in the women reporting <5 and ≥10 h/day sleep compared with the reference category of 8–9 h/day, despite some wide confidence intervals. Nonlinear models fitted the data better than linear models for most outcomes (likelihood ratio P-value=0.02 to 3.2×10−52), except for gestational diabetes.

Conclusions

Our results show shorter and longer sleep duration potentially causing higher risks of stillbirth, perinatal depression and low offspring birthweight. Larger studies with more cases are needed to detect potential nonlinear effects on hypertensive disorders of pregnancy, preterm birth and high offspring birthweight.
Stakeholder perspectives on veterinary student preparedness for workplace clinical training – a qualitative study
Authors: Routh Jennifer , Paramasivam Sharmini Julita , Cockcroft Peter , Nadarajah Vishna Devi , Jeevaratnam Kamalan
Published: September 2022

Background

The success of workplace clinical training (WCT) is important given that veterinary students are licensed to work independently upon graduation. Considering this, it is perhaps surprising that there is limited published work describing what it means to be prepared for this educational experience, particularly given that the transition to WCT can be stressful for students. This paper reports the results of a qualitative study aiming to generate a rich understanding of veterinary student preparedness for WCT using emic, or insider, perspectives of key stakeholders.

Methods

From a constructivist standpoint, homogenous online group interviews were held with final year veterinary students, recent student alumni, clinical supervisors, faculty, and academic educationalists to discuss what it means to be prepared for WCT. The data was analysed using a template analysis approach.

Results

A three-tier taxonomy to describe preparedness for WCT was constructed from the data. At the topmost level, there were seven themes to illuminate different aspects of preparedness: students should be prepared 1) for the transition to learning and working in a clinical and professional environment, 2) for self-directed and experiential learning whilst working, 3) with a growth mindset, 4) with intrinsic motivation and enthusiasm for learning and working, 5) for communication, consultation and clinical reasoning, 6) with the knowledge for work, and 7) with the practical competence and confidence for work.

Conclusions

This study provides a deeper understanding of the tools we can provide, and the attributes we can nurture in, senior veterinary students to facilitate their learning and working during WCT. This improved understanding is a necessary precursor to refining pedagogical support and curriculum design within veterinary schools.
Precision medicine from a citizen perspective: a survey of public attitudes towards pharmacogenomics in Flanders
Authors: Edris Ahmed , Callier Evi , Lahousse Lies
Published: September 2022

Background

Personalized medicine is an emerging field, aiming to improve the safety and efficacy of pharmacotherapy. The field’s implementation in clinical care is steadily increasing. Pharmacogenomics are one example of personalized approaches in the clinic and direct-to-consumer (DTC) pharmacogenomic tests have become publicly available. We aimed to assess public opinion on pharmacogenomic research and testing to foster integration within Belgian health care.

Methods

A cross-sectional survey was created and disseminated online, focusing on the citizen perspective. Participants’ willingness to engage in pharmacogenomic research was the primary outcome. In addition, their awareness, understanding, expectations and overall acceptance towards pharmacogenomic testing was investigated.

Results

A total of 156 participants (54.5% aged between 18 and 30 years, 45.5% > 30 years; 73.1% females) completed the survey. Half ever experienced side effects (46.2%) and treatment failure (52.6%). Up to 45.5% (n = 71) were willing to participate in pharmacogenomics research, and the majority (78.8%) were convinced that pharmacogenomic tests could help doctors to prescribe them the right medications. Additionally, 76.3% (n = 118) supported a partial reimbursement of pharmacogenomics tests. A minority (5.1%, n = 8) of participants showed interest in DTC tests, and 15.4% (n = 24) expressed privacy concerns regarding pharmacogenomics testing. Participants preferred their healthcare professionals’ to perform the test and access their data, but refused commercial providers.

Conclusion

Overall, participants showed a positive attitude towards precision medicine and pharmacogenomics research. Our findings may help guiding future pharmacogenomic implementation initiatives to optimize drug use by using pharmacogenomic information integrated within health care.
Cardiovascular and metabolic morbidity in women with previous gestational diabetes mellitus: a nationwide register-based cohort study
Authors: Christensen Maria Hornstrup , Rubin Katrine Hass , Petersen Tanja Gram , Nohr Ellen Aagaard , Vinter Christina Anne , Andersen Marianne Skovsager , Jensen Dorte Moeller
Published: September 2022

Background

Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes and has maternal health implications reaching beyond the perinatal period. We aimed to investigate the incidence and severity of cardiovascular and metabolic morbidity in women with previous GDM in a Danish population and to study whether proxies of impaired beta cell function—insulin treatment during GDM pregnancy and development of subsequent manifest diabetes mellitus—influence incident risk of cardiovascular and metabolic morbidity.

Methods

A nationwide register-based cohort study was conducted on the complete cohort of 700,648 women delivering in Denmark during 1997–2018. The exposure variable was GDM and primary outcome was overall cardiovascular and metabolic morbidity. Secondary outcomes were major cardiovascular disease (ischemic heart disease, heart failure, and/or stroke/transient cerebral ischemia), hypertension, dyslipidemia, and venous thrombosis. Severity of morbidity was assessed using number of hospital contacts with diagnosis codes related to cardiovascular and metabolic morbidity and number of redemptions of prescribed medication related to cardiovascular and metabolic morbidity in women who developed cardiovascular and metabolic morbidity after pregnancy.

Results

The median follow-up period was 10.2–11.9 years with a total range of 0–21.9 years. GDM was associated with increased risk of any cardiovascular and metabolic morbidity (adjusted HR 2.13 [95% CI 2.07–2.20]), major cardiovascular disease (adjusted HR 1.69 [95% CI 1.55–1.84]), hypertension (adjusted HR 1.89 [95% CI 1.82–1.96], dyslipidemia (adjusted HR 4.48 [95% CI 4.28–4.69]), and venous thrombosis (adjusted HR 1.32 [95% CI 1.16–1.50]). Insulin treatment during pregnancy and subsequent development of manifest diabetes exacerbated the risk estimates. Previous GDM was associated with more hospital contacts and more redeemed prescriptions in women developing cardiovascular and metabolic morbidity (p < 0.001).

Conclusions

Previous GDM was associated with significantly higher risk of cardiovascular and metabolic morbidity, especially incident dyslipidemia. Risks were exacerbated by proxies of beta cell impairment. Severity of morbidity was significantly worse if GDM preceded cardiovascular and metabolic morbidity.
Effect of empagliflozin on left ventricular contractility and peak oxygen uptake in subjects with type 2 diabetes without heart disease: results of the EMPA-HEART trial
Authors: Nesti Lorenzo , Pugliese Nicola Riccardo , Sciuto Paolo , Trico Domenico , Dardano Angela , Baldi Simona , Pinnola Silvia , Fabiani Iacopo , Di Bello Vitantonio , Natali Andrea
Published: September 2022

Background

The mechanism through which sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent the incidence of heart failure and/or affect cardiac structure and function remains unclear.

Methods

The EMPA-HEART trial is aimed at verifying whether empagliflozin improves myocardial contractility (left ventricle global longitudinal strain, LV-GLS) and/or cardiopulmonary fitness (peak oxygen uptake, VO2peak) in subjects with type 2 diabetes (T2D) without heart disease. Patients with T2D, normal LV systolic function (2D-Echo EF > 50%), and no heart disease were randomized to either empagliflozin 10 mg or sitagliptin 100 mg for 6 months and underwent repeated cardiopulmonary exercise tests with echocardiography and determination of plasma biomarkers.

Results

Forty-four patients completed the study, 22 per arm. Despite comparable glycaemic control, modest reductions in body weight (− 1.6; [− 2.7/− 0.5] kg, p = 0.03) and plasma uric acid (− 1.5; [− 2.3/− 0.6], p = 0.002), as well as an increase in haemoglobin (+ 0.7; [+ 0.2/+ 1.1] g/dL, p = 0.0003) were evident with empagliflozin. No difference was detectable in either LV-GLS at 1 month (empagliflozin vs sitagliptin: + 0.44; [− 0.10/+ 0.98]%, p = 0.11) and 6 months of therapy (+ 0.53; [− 0.56/+ 1.62]%), or in VO2peak (+ 0.43; [− 1.4/+ 2.3] mL/min/kg, p = 0.65). With empagliflozin, the subgroup with baseline LV-GLS below the median experienced a greater increase (time*drug p < 0.05) in LV-GLS at 1 month (+ 1.22; [+ 0.31/+ 2.13]%) and 6 months (+ 2.05; [+ 1.14/+ 2.96]%), while sitagliptin induced a modest improvement in LV-GLS only at 6 months (+ 0.92; [+ 0.21/+ 0.62]%).

Conclusions

Empagliflozin has neutral impact on both LV-GLS and exercise tolerance in subjects with T2D and normal left ventricular function. However, in patients with subclinical dysfunction (LV-GLS < 16.5%) it produces a rapid and sustained amelioration of LV contractility.

Trial registration EUDRACT Code 2016-002225-10
Evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria and prevalence of pfhrp2/3 deletions in Aweil, South Sudan
Authors: Lynch Emily , Jensen Tomas O. , Assao Bachir , Chihana Menard , Turuho Thadeous , Nyehangane Dan , Manyok John B. , Pasquale Harriet , Khim Nimol , Witkowski Benoit , Coldiron Matthew E.
Published: September 2022

Background

Rapid diagnostic tests (RDT) for malaria are the primary tool for malaria diagnosis in sub-Saharan Africa but the utility of the most commonly used histidine-rich protein 2 (HRP2) antigen-based tests is limited in high transmission settings due to the long duration of positivity after successful malaria treatment. HRP2 tests are also threatened by the emergence of Plasmodium that do not carry pfhrp2 or pfhrp 3 genes. Plasmodium lactate dehydrogenase (pLDH)-based tests are promising alternatives, but less available. This study assessed the performances of HRP2 and pLDH(pan) tests under field conditions.

Methods

The study performed a prospective facility-based diagnostic evaluation of two malaria RDTs in Aweil, South Sudan, during the high transmission season. Capillary blood by fingerprick was collected from 800 children under 15 years of age with fever and no signs of severity. SD Bioline HRP2 and CareStart pLDH(pan) RDTs were performed in parallel, thick and thin smears for microscopy were examined, and dried blood was used for PCR testing.

Results

Using microscopy as the gold standard, the sensitivity of both tests was estimated at  > 99%, but the specificity of each was lower: 55.0% for the pLDH test and 61.7% for the HRP2 test. When using PCR as the gold standard, the sensitivity of both tests was lower than the values assessed using microscopy (97.0% for pLDH and 96.5% for HRP2), but the specificity increased (65.1% for pLDH and 72.9% for HRP2). Performance was similar across different production lots, sex, and age. Specificity of both the pLDH and HRP2 tests was significantly lower in children who reported taking a therapeutic course of anti-malarials in the 2 months prior to enrollment. The prevalence of pfhrp2/3 deletions in the study population was 0.6%.

Conclusions

The low specificity of the pLDH RDT in this setting confirms previous results and suggests a problem with this specific test. The prevalence of pfhrp2/3 deletions in the study area warrants continued monitoring and underscores the relevance of assessing deletion prevalence nationally. Improved malaria RDTs for high-transmission environments are needed.
Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss
Authors: Xia Anping , Thai Anthony , Cao Zhixin , Chen Xiaohua , Chen Jing , Bacacao Brian , Bekale Laurent A. , Schiel Viktoria , Bollyky Paul L. , Maria Peter L. Santa
Published: September 2022

Background

Chronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model.

Methods

We generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR.

Results

We observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14 days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea.

Conclusions

Taken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).
Chronic delta-9-tetrahydrocannabinol (THC) treatment counteracts SIV-induced modulation of proinflammatory microRNA cargo in basal ganglia-derived extracellular vesicles
Authors: Kaddour Hussein , McDew-White Marina , Madeira Miguel M. , Tranquille Malik A. , Tsirka Stella E. , Mohan Mahesh , Okeoma Chioma M.
Published: September 2022

Background

Early invasion of the central nervous system (CNS) by human immunodeficiency virus (HIV) (Gray et al. in Brain Pathol 6:1–15, 1996; An et al. in Ann Neurol 40:611–6172, 1996), results in neuroinflammation, potentially through extracellular vesicles (EVs) and their micro RNAs (miRNA) cargoes (Sharma et al. in FASEB J 32:5174–5185, 2018; Hu et al. in Cell Death Dis 3:e381, 2012). Although the basal ganglia (BG) is a major target and reservoir of HIV in the CNS (Chaganti et al. in Aids 33:1843–1852, 2019; Mintzopoulos et al. in Magn Reson Med 81:2896–2904, 2019), whether BG produces EVs and the effect of HIV and/or the phytocannabinoid–delta-9-tetrahydrocannabinol (THC) on BG-EVs and HIV neuropathogenesis remain unknown.

Methods

We used the simian immunodeficiency virus (SIV) model of HIV and THC treatment in rhesus macaques (Molina et al. in AIDS Res Hum Retroviruses 27:585–592, 2011) to demonstrate for the first time that BG contains EVs (BG-EVs), and that BG-EVs cargo and function are modulated by SIV and THC. We also used primary astrocytes from the brains of wild type (WT) and CX3CR1+/GFPmice to investigate the significance of BG-EVs in CNS cells.

Results

Significant changes in BG-EV-associated miRNA specific to SIV infection and THC treatment were observed. BG-EVs from SIV-infected rhesus macaques (SIV EVs) contained 11 significantly downregulated miRNAs. Remarkably, intervention with THC led to significant upregulation of 37 miRNAs in BG-EVs (SIV–THC EVs). Most of these miRNAs are predicted to regulate pathways related to inflammation/immune regulation, TLR signaling, Neurotrophin TRK receptor signaling, and cell death/response. BG-EVs activated WT and CX3CR1+/GFPastrocytes and altered the expression of CD40, TNFα, MMP-2, and MMP-2 gene products in primary mouse astrocytes in an EV and CX3CR1 dependent manners.

Conclusions

Our findings reveal a role for BG-EVs as a vehicle with potential to disseminate HIV- and THC-induced changes within the CNS.
COVID-19 vaccination in the Gaza Strip: a cross-sectional study of vaccine coverage, hesitancy, and associated risk factors among community members and healthcare workers
Authors: Majer Jennifer , Elhissi Jehad H. , Mousa Nabil , Kostandova Natalya
Published: September 2022

Background

The Gaza Strip, like other settings of complex humanitarian emergencies, faces immense challenges in vaccinating its population against COVID-19. This study was conducted in October 2021 among Gaza’s adult population and healthcare workers (HCWs). The primary aim was to estimate two indicators, coverage of COVID-19 vaccination and the prevalence of vaccine hesitancy. The secondary aim was to evaluate the two indicators’ associations with globally identified risk factors.

Methods

A cross-sectional study was conducted using a population-based survey of adults and a purposive survey of HCWs in Gaza. A multi-stage sampling design was used for the population survey component. For the HCW component, five health facilities were purposively selected as entry points; HCWs in the facilities holding clinical or other specialized positions were approached to participate in the survey. Data were summarized as univariable descriptive statistics with unweighted and weighted point estimates. Logistic regression was used to evaluate associations of risk factors with vaccination status and vaccine hesitancy.

Results

A total of 1075 individuals were surveyed, of whom 906 were community members and 169 were HCWs. Population-weighted vaccine coverage was estimated to be 49.08% (95% CI 43.10–55.08). 89.35% of HCWs were vaccinated. Population-weighted vaccine hesitancy was estimated to be 34.08% (95% CI 28.14–40.56) in the overall population and 67.24% (95% CI 49.04–81.41) among the unvaccinated sub-group. In logistic regression vaccination was independently associated with male sex (aOR 1.88, p = 0.006, 95% CI 1.20–2.95), older age (40+ vs. 18–39 age group) (aOR 1.92, p < 0.001, 95% CI 1.73–2.13), higher education (aOR 2.19, p < 0.001, 95% CI 1.51–3.17), and confidence in the safety of the vaccine (aOR 13.8, p < 0.001, 95% CI 10.1–18.8). Risk factors for hesitancy were similar to those identified for vaccination status, however hesitant individuals were somewhat more likely to obtain vaccine information from family members (aOR 1.29, p = 0.051, 95% CI 1.00–1.67) and less likely to trust healthcare providers (aOR 0.58, p < 0.001, 95% CI 0.49–0.68).

Conclusions

The continued emergence of SARS-CoV-2 variants reinforces the importance of achieving high levels of vaccination coverage globally—a difficult undertaking in Gaza. This study estimated half of Gaza’s adult population received at least one dose of any COVID-19 vaccine by October 2021, and the majority of unvaccinated individuals were hesitant. Disparities in vaccination across the territory’s demographic groups underscore the need for targeted outreach to these populations and messaging through community-based channels to permeate social networks of the unvaccinated.
Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies
Authors: Tian Hailong , Zhang Tingting , Qin Siyuan , Huang Zhao , Zhou Li , Shi Jiayan , Nice Edouard C. , Xie Na , Huang Canhua , Shen Zhisen
Published: September 2022

Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice.
Genome-wide analysis of the JAZ subfamily of transcription factors and functional verification of BnC08.JAZ1-1 in Brassica napus
Authors: Wang Ying , Li Na , Zhan Jiepeng , Wang Xinfa , Zhou Xue-Rong , Shi Jiaqin , Wang Hanzhong
Published: September 2022

Background

JAZ subfamily plays crucial roles in growth and development, stress, and hormone responses in various plant species. Despite its importance, the structural and functional analyses of the JAZ subfamily in Brassica napus are still limited.

Results

Comparing to the existence of 12 JAZ genes (AtJAZ1-AtJAZ12) in Arabidopsis, there are 28, 31, and 56 JAZ orthologues in the reference genome of B. rapa, B. oleracea, and B. napus, respectively, in accordance with the proven triplication events during the evolution of Brassicaceae. The phylogenetic analysis showed that 127 JAZ proteins from A. thaliana, B. rapa, B. oleracea, and B. napus could fall into five groups. The structure analysis of all 127 JAZs showed that these proteins have the common motifs of TIFY and Jas, indicating their conservation in Brassicaceae species. In addition, the cis-element analysis showed that the main motif types are related to phytohormones, biotic and abiotic stresses. The qRT-PCR of the representative 11 JAZ genes in B. napus demonstrated that different groups of BnJAZ individuals have distinct patterns of expression under normal conditions or treatments with distinctive abiotic stresses and phytohormones. Especially, the expression of BnJAZ52 (BnC08.JAZ1-1) was significantly repressed by abscisic acid (ABA), gibberellin (GA), indoleacetic acid (IAA), polyethylene glycol (PEG), and NaCl treatments, while induced by methyl jasmonate (MeJA), cold and waterlogging. Expression pattern analysis showed that BnC08.JAZ1-1 was mainly expressed in the vascular bundle and young flower including petal, pistil, stamen, and developing ovule, but not in the stem, leaf, and mature silique and seed. Subcellular localization showed that the protein was localized in the nucleus, in line with its orthologues in Arabidopsis. Overexpression of BnC08.JAZ1-1 in Arabidopsis resulted in enhanced seed weight, likely through regulating the expression of the downstream response genes involved in the ubiquitin–proteasome pathway and phospholipid metabolism pathway.

Conclusions

The systematic identification, phylogenetic, syntenic, and expression analyses of BnJAZs subfamily improve our understanding of their roles in responses to stress and phytohormone in B. napus. In addition, the preliminary functional validation of BnC08.JAZ1-1 in Arabidopsis demonstrated that this subfamily might also play a role in regulating seed weight.
The median age of a city’s residents and population density influence COVID 19 mortality growth rates: policy implications
Authors: Arbel Yuval , Arbel Yifat , Kerner Amichai , Kerner Miryam
Published: September 2022

Background

SARS-CoV-2 is an infectious virus, which has generated a global pandemic. Israel was one of the first countries to vaccinate its population, inaugurating the program on December 20, 2020. The objective of the current study is to investigate the projected daily COVID19 mortality growth rate with higher median age and population size of cities under two scenarios: with and without the BNT162b2 Pfizer vaccination against the SAR-COV2 virus.

Methods

This study employs a panel data-set. We follow the COVID19 mortality growth rate in each of the 173 Israeli cities and towns starting from March 21, 2020 (10 days after the first documentation of COVID19 cases in Israel) until September 21, 2021, where the BNT162b2 Pfizer vaccinations were available starting from December 20, 2020.

Results

Referring to the median age of municipal residents, findings suggest that the BNT162b2 Pfizer vaccinations attenuate the rise in anticipated daily mortality growth rate for cities and towns in which the median population age is 30 years old (the range in median age among the residents in the municipalities surveyed is 11–41 years). Moreover, referring to population size of cities, findings demonstrate that while under the scenario without vaccination, the daily mortality growth rate is anticipated to rise, under a comparable scenario with vaccination, daily mortality growth rate is anticipated to drop.

Conclusions

In crowded cities, where the median age is high, two perspectives of early and intensive public policy interventions are clearly required. The first perspective is extensive medical treatment, namely, extension of availability of medical physical and online services; dispensing designated medications; expansion of hospitalization facilities and information services particularly to susceptible populations. All measures will be taken with attention to age accessibility of these means. The second perspective is prevention via establishment of testing and vaccination complexes; elevation of dedicated health services, generating selective lockdowns; education for increasing awareness to social distancing, wearing masks and other preventive means.