bluuebunny/crossref_metadata_2025 huggingface dataset:
A global investigation into antimicrobial knowledge in medicine, pharmacy, nursing, dentistry and veterinary undergraduate students: A scoping review to inform future planetary health multidisciplinary education
Authors: Alzard Shahd , Exintaris Betty , Sarkar Mahbub , Grieve Averil , Chuang Sara , Coetzee Renier , Lim Angelina
Published: October 2024

Background

Inappropriate use of antimicrobials can push the environment out of balance, and cause unnecessary waste that can contaminate our soil, animals and waterways. Health professional education is committed to preparing students for antimicrobial stewardship (AMS) and supporting planetary health, but a more multidisciplinary action is needed to curb the expansion of antimicrobial resistance (AMR). The aim of this scoping review is to showcase the current antimicrobial knowledge of undergraduate students across the disciplines of medicine, pharmacy, nursing, dentistry and veterinary. This will consequently showcase the gaps and trends across the different disciplines and countries to help inform planetary health multidisciplinary undergraduate curriculums.

Methods

A search of the existing literature published prior to December 2023 was conducted using CINAHL, EMBASE, MEDLINE, SCOPUS, and ERIC databases. Studies were excluded if they included postgraduate students or discussed the knowledge, attitude and practice (KAP) of students towards antimicrobial prescribing, AMR and AMS related to a specific learning activity.

Results

A total of 144 articles were included. The most represented countries were India and Pakistan accounting for 17% and 8% of the studies, respectively. Single-disciplinary research accounted for approximately 80% of the studies. Medicine was the most represented discipline in both single-disciplinary and multidisciplinary research, appearing in approximately 62% of the studies, followed by pharmacy appearing in approximately 30% of the studies and dentistry appearing in approximately 18% of the studies. Three major priority themes were identified: students are more familiar with the term AMR compared to AMS; inappropriate use of antimicrobials is seen as the main driver of AMR; and the need for more training and education in the field of appropriate antimicrobial prescribing, AMR and AMS.

Conclusion

This review has highlighted that there is a need for more AMS interprofessional education (IPE) activities in all five disciplines, and especially within the disciplines of nursing, veterinary and dentistry, as shown by a lack of multidisciplinary research in this area. Most of the knowledge assessments have just touched the surface of AMS and focused on inappropriate antimicrobial use alone. Interdisciplinary planetary health education needs to go beyond these skills and broaden the understanding of other factors that can contribute to AMR such as inappropriate disposal, environmental contamination, monitoring and surveillance, one health, false allergies, and more importantly, how each health professional can contribute to a team.
Lessons learned from implementing a digital rehabilitation care planning platform to improve care access for patients with work disability: qualitative process evaluation of the RehaPro-SERVE study
Authors: Buch Kristina , Hamme Viktoria , Becker Annette , Seifart Ulf , Maulbecker-Armstrong Catharina , Moser Karin , Seferi Pellumbesha , Keller Antonia , van der Wardt Veronika
Published: October 2024

Background

Inpatient rehabilitation therapies can be applied for in Germany by patients of working age to support their return to work. However, there are some problems that impede an easy and uncomplicated application process. An interdisciplinary case management approach for rehabilitation care planning was developed to facilitate the access to rehabilitation. Case conferences (CCs) were held with relevant stakeholders and took place on a digital communication platform. We conducted a qualitative process evaluation to understand the implementation of the intervention and to identify contextual factors as well as mechanisms for a successful implementation in the context of primary care.

Methods

The process evaluation included interviews with primary care physicians (PCPs), patients and stakeholders involved in the intervention process. Reflexive thematic analysis was used to analyse the data. Emerging themes were structured according to the Donabedian framework of structure, process and outcomes.

Results

A total of 18 interviews were conducted. Important results included the desire for more patient involvement and case management. Patients especially valued the opportunity to receive support from a social worker. Limitations of the platform related to usability and limited opportunities for stakeholder communication. Despite training for PCPs, several problems arose regarding the clarity of the intervention process. Patients were satisfied with their application process and the treatments offered, while PCPs reported an increase in workload.

Conclusions

A digitalisation of the application procedure for rehabilitation and further treatment options is acceptable to patients and personal support of a social worker is particularly valued. However, patients should be included in the CC in terms of a shared decision-making process. The digital platform requires sufficient training and adjustments have to be made to enhance usability and to improve the efficiency of the process for PCPs. Overall, the exchange between the various stakeholders in the CC is considered particularly useful in more complex cases.

Trial registration

DRKS German Clinical Trials Register, DRKS0 00242 07. Registered on 22 March 2021.
Developing a gender measure and examining its association with cardiovascular diseases incidence: a 28-year prospective cohort study
Authors: Gilbert-Ouimet Mahée , Zahiriharsini Azita , Blanchette Caty , Talbot Denis , Trudel Xavier , Milot Alain , Brisson Chantal , Smith Peter
Published: October 2024

Background

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Examining gender (socio-cultural) in addition to sex (biological) is required to untangle socio-cultural characteristics contributing to inequities within or between sexes. This study aimed to develop a gender measure including four gender dimensions and examine the association between this gender measure and CVD incidence, across sexes.

Methods

A cohort of 9188 white-collar workers (49.9% females) in the Quebec region was recruited in 1991–1993 and follow-up was carried out 28 years later for CVD incidence. Data collection involved a self-administered questionnaire and extraction of medical-administrative CVD incident cases. Cox proportional models allowed calculations of hazard ratios (HR) and 95% confidence intervals (CI), stratified by sex.

Results

Sex and gender were partly independent, as discordances were observed in the distribution of the gender score across sexes. Among males, being in the third tertile of the gender score (indicating a higher level of characteristics traditionally ascribed to women) was associated with a 50% CVD risk increase compared to those in the first tertile (HR = 1.50; 95% CI: 1.24 to 1.82). This association persisted after adjustment for several CVD risk factors (HR = 1.42; 95% CI: 1.16 to 1.73). Conversely, no statistically significant association between the third tertile of the gender score and CVD incidence was observed in females (HR = 0.79, 95% CI: 0.60–1.05).

Conclusions

The findings suggested that males within the third tertile of the gender score were more likely to develop CVD, while females with those characteristics did not exhibit an increased risk. These findings underline the necessity for clinical and population health research to integrate both sex and gender measures, to further evaluate disparities in cardiovascular health and enhance the inclusivity of prevention strategies.
Efficacy and safety of diclazuril nanoemulsion in control of Eimeria tenella in broilers
Authors: El-Sawah Azza A. , Aboelhadid Shawky M. , El-Nahass El-Shymaa N. , Helal Hassan E.
Published: October 2024

Background

Nanotechnology has the potential to reduce drug dosage while increasing efficacy; thus, the current work intends to synthesize diclazuril nanoemulsion and assess its performance against experimental coccidiosis in broilers.

Methods

Diclazuril nanoemulsion (DZN) was formulated and characterized by zeta seizer and zeta potential. The formulated DZN was evaluated in vivo against Eimeria tenella infected chicks. DZN and DZ were used in 2 programs; therapeutic and prophylactic. A total of 210 one-day-old broiler chicks were distributed equally into six groups. The controls were negative uninfected untreated and positive infected untreated (G1 & G2). Therapeutic groups (G3 & G4) treated by DZ and DZN after appearance of the clinical signs of coccidiosis and continued for 5 days. Prophylaxis groups (G5 & G6) received DZ and DZN at 3 days before challenge and continued for 5 days after infection. The treatments dosages were 10 mg/mL for DZ of commercial origin and 2.5 mg/mL for the prepared DZN. All groups (except negative control) orally infected then followed up for clinical signs of coccidiosis, mortality rate, oocysts count, performance, hematological and biochemical parameters in addition to histopathological lesions.

Results

The therapeutic groups showed that both treated groups (DZ and DZN) revealed similar results including good body weight gain, a low lesion caecal score, a low daily and total oocyst shedding count, and a low mortality rate. Regarding the biochemical parameters, all parameters were affected during infection then restored after the 12th day post infection. However, in the prophylactic groups, showed mild clinical signs and the blood pictures and biochemical parameters were nearly like the control negative without infection.

Conclusion

DZN at a quarter dose of standard DZ produced the same outcomes as DZ at 10 mg/mL. Furthermore, DZN does not impair the typical safety of diclazuril in treated chicks.
Effect of single parenteral administration of marbofloxacin on bacterial load and selection of resistant Enterobacteriaceae in the fecal microbiota of healthy pigs
Authors: Miyauchi Micaela , EL Garch Farid , Thériault William , Leclerc Bruno G. , Lépine Edith , Giboin Henry , Rhouma Mohamed
Published: October 2024

Background

Antimicrobial resistance (AMR) is a global concern impacting both humans, animals and their environment. The use of oral antimicrobials in livestock, particularly in pigs, has been identified as a driver in the selection of AMR bacteria. The aim of the present study was to evaluate the effects of a single intramuscular (IM) dose of marbofloxacin (8 mg/kg) on Enterobacteriaceae and E. coli populations, as well as on fluoroquinolone resistance within the fecal microbiota of pigs. Twenty healthy pigs, 60-days old, were divided into two groups: a treated group (n = 13) and a control group (n = 7) and were monitored over a 28-day experimental period. Fecal samples were collected from all animals for the isolation of E. coli and Salmonella strains. The minimum inhibitory concentration (MIC) of marbofloxacin for the isolates recovered on MacConkey agar supplemented with 1 or 4 µg/mL of marbofloxacin and for some generic E. coli isolates (recovered from MacConkey agar not supplemented with marbofloxacin) was determined using the broth microdilution method. Genomic DNA was extracted from the confirmed bacterial strains and sequenced using the Sanger method to identify mutations in the quinolone resistance determining regions (QRDRs) of the gyrA and parC genes.

Results

The single IM administration of marbofloxacin resulted in a significant decrease in Enterobacteriaceae and E. coli fecal populations from days 1 to 3 post- treatment. No Salmonella isolates were detected in either group, and no marbofloxacin-resistant E. coli isolates were identified. The MIC of the selected generic E. coli strains (n = 100) showed an increase to up to 0.5 µg/mL between days 1 and 3 post-treatment but remained below the clinical breakpoint of marbofloxacin resistance (4 µg/mL). Sequencing of these isolates revealed no mutations in gyrA and parC genes.

Conclusions

The present study showed that this dosing regimen of marbofloxacin significantly decreases the fecal shedding of Enterobacteriaceae and E. coli populations in pigs, while limiting the selection of marbofloxacin-resistant E. coli isolates. These findings warrant validation in sick pigs to support the selective use of this antibiotic solely in cases of clinical disease, thereby minimizing the reliance on conventional (metaphylactic) group treatments in pigs.
Parental participation in newborn care in the view of health care providers in Uganda: a qualitative study
Authors: Wanduru Phillip , Hanson Claudia , Kwesiga Doris , Kakooza-Mwesige Angelina , Mölsted Alvesson Helle , Waiswa Peter
Published: October 2024

Background

Evidence suggests that family-centered care for sick newborns, where parents are co-caregivers in newborn care units, can result in increased breastfeeding frequency, higher weight gain, earlier discharge, and reduced parental anxiety. This study explored healthcare providers' perceptions and experiences of parental participation in care for sick newborns in the newborn care units in two high-volume maternity units in Uganda, with the aim of informing interventions that promote family-centered care for newborns.

Methods

An exploratory qualitative study was conducted between August and December 2023. Sixteen in-depth interviews were held at a regional and general hospital in the rural eastern region of Uganda. The interviews were audio-recorded and then transcribed, followed by a reflexive thematic analysis approach to generate themes.

Findings

We identified four key themes: (1) creating order to ensure the safety of newborns in the newborn care unit; (2) parental participation as a tool for overcoming workload in the Newborn care unit; (3) redirecting parental involvement to focus on medically endorsed newborn care practices; and (4) stress management targeting mothers to ensure newborn survival.

Conclusion

Healthcare providers encourage parents to participate in caring for their newborns in the newborn care units, mainly to reduce their workload. However, our study highlights the imbalanced nature of parental involvement, where HCPs control the tasks parents can or cannot perform, essentially deploying them as "assistants" rather than equal partners, contrary to the ideals of family-centered care. Transforming the current "healthcare provider-centered" model of caring for sick newborns to one that is family-centered will require training providers on the benefits of family-centered care and developing guidelines for its structured implementation within a resource-limited setting.
Histopathological spectrum of primordial odontogenic tumor with co-existing dentigerous cyst: 1st reported case of the world with a proposed ‘updated diagnostic criteria’
Authors: Dwivedi Dhara , Prabhakar Nitin , Yuwanati Monal , Aswal Gunjan S. , Rawat Renu
Published: October 2024

Background

POT is a relatively newly described benign odontogenic tumor with very few cases registered to date. We present the 1st case of Primordial odontogenic tumor (POT) from Sub-Saharan Africa with unique clinicopathological features; also, this is the first case to report POT’s existence as a Hybrid Odontogenic lesion (HOL), with a pertinent review of the literature.

Case presentation

This was a 17-year-old patient who presented with slow-growing, painless posterior mandibular swelling. The imaging revealed a well-defined, unilocular, expansile, lytic lesion with internal calcific foci surrounding an impacted #36, indicating a calcifying odontogenic cyst. The incisional biopsy revealed the presence of POT. The tumor was excised along with the involved tooth.

Conclusion

POT is predominantly a non-aggressive and mostly affects the pediatric population. Hence, clinicians must be updated on all the aspects of this tumor to diagnose it appropriately and avoid any undue over—or under-treatment.
Digital rehabilitation care planning for people with chronic diseases (RehaPro-SERVE): study protocol for a German multicentre randomised controlled trial
Authors: Buch Kristina , van der Wardt Veronika , Seifart Ulf , Haasenritter Jörg , Maulbecker-Armstrong Catharina , Seferi Pellumbesha , Becker Annette
Published: October 2024

Background

Chronic diseases are a significant and growing problem of our time. They impair the ability to work and increase the risk of early retirement. To support the return to work, rehabilitation services can be applied for in Germany. Currently, the application system for rehabilitation allows only a limited degree of individualisation of the treatment and is associated with a lack of multidisciplinary communication. To facilitate rehabilitation care planning, we developed a complex intervention. A digital, platform-based case management approach (intervention) will ensure multidisciplinary communication and the tailored selection of medical treatments and/or non-medical support measures. The overall objective is to assess the effectiveness of the intervention compared to treatment as usual (control condition). The German Federal Ministry of Labour and Social Affairs (BMAS) funds the RehaPro-SERVE study (grant number: 661R0053K1).

Methods

This is the protocol for an investigator-initiated, pragmatic, multicentre, randomised and controlled two-arm parallel-group superiority trial with embedded qualitative process evaluation. The study will be conducted in Hesse state, Germany. N = 59 primary care physicians will be recruited and tasked with the recruitment of six eligible patients each. Eligibility criteria: age 40–60; minimum of 4-week work disability due to musculoskeletal, oncologic or psychological conditions or the post-COVID-19 syndrome within the last 6 months; at high risk for early retirement. In total, n = 352 patients will be randomised with a 1:1 allocation to intervention or control group and stratified by primary care practice using permuted blocks. The primary outcome is the number of days of sick leave during a 12-month period after the assumed completion of treatments (t1 to t2). Secondary outcomes include the number of days of sick leave (self-report), work ability, and health-related quality of life, as well as data from the qualitative process evaluation.

Discussion

The results of the study will inform the design of future care services and provide valuable information on multidisciplinary case management in the context of rehabilitation care planning. The results of the qualitative process evaluation will further contribute to the understanding of facilitating and hindering factors.

Trial registration

DRKS-German Clinical Trials Register, DRKS0 00242 07. Registered on 22 March 2021.
Assessing the metabolism of the olfactory circuit by use of 18F-FDG PET-CT imaging in patients suspected of suffering from Alzheimer’s disease or frontotemporal dementia
Authors: Loewenstein Daniël S. L. , van Grinsven Max , de Pont Cécile , Dautzenberg Paul L. J. , van Strien Astrid M. , Henssen Dylan
Published: October 2024

Purpose

The loss of olfactory function is known to occur in patients suffering from (behavioral variant) frontotemporal dementia ((bv)FTD) and Alzheimer’s disease (AD), although different pathophysiological mechanisms underpin this clinical symptom in both disorders. This study assessed whether brain metabolism of the olfactory circuit as assessed by positron emission tomography (PET) imaging with 2-[fluorine-18]fluoro-2-deoxy-d-glucose ([18F]-FDG) can distinguish these entities in different subsets of patients.

Methods

Patients presenting with cognitive decline were included from a prospectively kept database: (1) bvFTD patients, (2) AD patients and (3) patients with logopenic primary progressive aphasia (PPA). Metabolic rates were calculated for different regions of the olfactory circuit for each subgroup and compared with a cohort of subjects with normal brain metabolism. Additionally, in patients with a logopenic PPA pattern on PET-imaging, statistical parametric mapping (SPM) analysis was performed.

Results

The metabolism of subdivisions of the olfactory circuit as assessed by [18F]-FDG PET brain imaging to bvFTD and AD from control subjects resulted in sensitivity/specificity rates of 95/87.5% and 80/83.3%, respectively. A sensitivity/specificity rate of 100/87.5% was achieved when used to differentiate AD from bvFTD. In patients with the PPA pattern on imaging, the underlying cause (either FTD or AD) could be determined with a sensitivity/specificity rate of 88/82%. SPM analysis concurred that different regions of the olfactory circuit were affected in patients suffering from AD PPA or bvFTD PPA.

Conclusion

Metabolic dysfunction in the olfactory circuit is different in various neurodegenerative disorders. Further investigation of the correlations between the cerebral metabolism and the mechanisms which drive olfactory dysfunction is needed.
The Hungarian fossil record of the Pliocene pig Sus arvernensis (Suidae, Mammalia)
Authors: Iannucci Alessio , Pazonyi Piroska , Sebe Krisztina
Published: October 2024

Sus arvernensis is a Pliocene species that occupies a key position in the evolution of suids (Suidae, Artiodactyla, Mammalia) in Eurasia, and besides, it is considered important for biochronological correlations and paleoecological inferences. However, our knowledge on S. arvernensis is largely based on fossil remains from southwestern Europe. Here, we present a revision of the Hungarian fossil record of S. arvernensis. Up to now, the species was known from only two localities of Hungary, Gödöllő (central Hungary) and Süttő (northwest Hungary), and the latter occurrence has even been questioned. After the comparison with other relevant samples of S. arvernensis, of the Early Pleistocene S. strozzii, and of the extant wild boar S. scrofa (motivated by previous attributions and the chronology of the localities), the presence of S. arvernensis from Gödöllő and Süttő is confirmed, and more material of the species is described from Beremend (southern Hungary) and Kisláng (western Hungary). Collectively, the results of the revision carried out herein reveal a relatively widespread distribution of S. arvernensis in Hungary, hence providing an important link from the eastern to western European fossil record of the species. The specimens from Gödöllő and Süttő are slightly larger than the other material of S. arvernensis from France and Italy included in the biometric comparison, although the paucity of the material precludes to evaluate whether these differences are significant and to relate them to a chronological and/or geographical context. The occurrence of S. arvernensis in the Hungarian localities considered in this work is a biochronological indication of an age older than at least 2.6 Ma, since the species is not recorded after the Pliocene–Pleistocene transition. This in agreement with the age estimates available so far for some of the localities or provides new insights. At Süttő, in particular, the identification of S. arvernensis reinforces the view that travertine deposition started already in the Pliocene.
A prediction model of PTSD in the Israeli population in the aftermath of october 7th, 2023, terrorist attack and the Israel–Hamas war
Authors: Katsoty Dana , Greidinger Michal , Neria Yuval , Segev Aviv , Lurie Ido
Published: October 2024

Background

On October 7th, 2023, a mass terror attack was launched by Hamas militants, which was followed by the Israel-Hamas war. These events constitute a nationwide trauma with major ramifications for public mental health. This article presents an evidence-based model for the prediction of the prevalence of posttraumatic stress disorder (PTSD) related to the terrorist attack and the war.

Main body: The creation of the model consisted of several steps. Firstly, the Israeli population was divided into six groups based on the intensity, context, and type of traumatic exposure (direct exposure to terror, close proximity to terror, soldiers in combat and support units, intense exposure to rocket attacks, moderate exposure to rocket attacks, and indirectly affected communities), and the population size of each group was assessed using official national databases. Secondly, an estimation of the expected prevalence of PTSD in each of the exposure groups was based on a review of the relevant literature. A random-effects meta-analysis of the prevalence rates was conducted separately per each exposure group. Finally, the predicted number of PTSD causalities in the population was calculated by multiplying the group size and the PTSD prevalence estimation. Based on population size and estimated PTSD prevalence within each exposure category, the model predicts that approximately 5.3% (N = 519,923) of the Israeli population (95% confidence interval, 1.64–9%), may develop PTSD as a result of the terrorist attack and the war.

Conclusions

The predicted number of individuals with PTSD following mass trauma is expected to be considerable. The presented model can assist policymakers, clinicians, and researchers in preparing and devising adequate interventions for the mental health needs of large populations. Moreover, this model can be applied in other instances of mass-trauma exposure.
Application and new findings of scRNA-seq and ST-seq in prostate cancer
Authors: Li Zhuang , Li Zhengnan , Luo Yuanyuan , Chen Weiming , Fang Yinyi , Xiong Yuliang , Zhang Qinyi , Yuan Dongbo , Yan Bo , Zhu Jianguo
Published: October 2024

Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world, which seriously threatens the life and health of middle-aged and elderly men. The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment. Understanding the mechanisms of prostate cancer pathogenesis and disease progression is important to guide diagnosis and therapy. The emergence of single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) technologies has brought breakthroughs in the study of prostate cancer. It makes up for the defects of traditional techniques such as fluorescence-activated cell sorting that are difficult to elucidate cell-specific gene expression. This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq, aims to provide a reference for the optimal diagnosis and treatment of prostate cancer.
Development of craquelure patterns in paintings on canvas
Authors: Bury Marcin , Bratasz Łukasz
Published: October 2024

Canvas paintings are layered structures composed of canvas support sized with animal glue, a preparatory layer of the ground, and paint and varnish layers on the top. Preventing or limiting humidity-induced stresses in these structures requires an understanding of the relevant processes and risks. A three-dimensional model of a canvas painting was used to analyse stresses and crack development in the two-layer structure comprised of a glue-sized canvas on a wooden stretcher with a layer of stiff chalk-glue ground representing a pictorial layer in historic canvas paintings. The model was subjected to a large relative humidity fall which induced shrinkage of the glue-sized canvas. The modelling revealed that when a stretcher with flexible wooden bars is considered, high tensile stresses arise in the ground layer at the corners of the painting, and cracks are formed in these areas in the direction perpendicular to the painting’s diagonal. Ratios of critical distances between cracks to the ground layer thickness for which stresses in the midpoints between the cracks dropped to below the level inducing fracture in the material were estimated for various magnitudes of the relative humidity drop and thicknesses of the ground layer. Increasing ground layer thickness limits the hygric response of the sized canvas and makes the paintings less vulnerable to humidity variations. The ratio of stress along the diagonal calculated for painting with one crack to the solution without cracks was described by the double Lorentz function. A simple procedure of calculating stress variations along the diagonal—using the function—on a sequential addition of cracks was developed. Cracks in central parts of canvas painting were found to be induced by permanent cumulative drying shrinkage of the oil-based paints and grounds due to the evolution of the molecular composition of the oil binder. The outcome of the modelling indicated that the risk of cracking of the pictorial layers in canvas paintings due to drops in ambient relative humidity was small.
Quadricuspid aortic valve with complete heart block: a double whammy
Authors: Dhillon Mukesh , Sharma Aditi
Published: October 2024

Background

Developmental abnormalities of aortic valve cusps are relatively common with the bicuspid valve being the most frequently encountered congenital heart disease. However, the quadricuspid aortic valve (QAV) is an exceedingly rare abnormality.

Case presentation

We report a case involving a young, otherwise healthy male who presented with non-exertional syncope and was subsequently diagnosed with complete heart block (CHB). Further evaluation revealed the coexistence of a rare quadricuspid aortic valve and CHB. This combination, in the absence of surgery or infective endocarditis, has only been reported once before in the literature.The patient underwent successful permanent pacemaker implantation and continues to be monitored for aortic regurgitation.

Conclusions

The coexistence of a QAV with CHB, in the absence of infective endocarditis or aortic valve surgery, is extremely rare and necessitates careful evaluation and follow-up.
Second Primary Cancer Risks After Breast Cancer in
BRCA1
and
BRCA2
Pathogenic Variant Carriers
Authors: Allen Isaac , Hassan Hend , Walburga Yvonne , Huntley Catherine , Loong Lucy , Rahman Tameera , Allen Sophie , Garrett Alice , Torr Bethany , Bacon Andrew , Knott Craig , Jose Sophie , Vernon Sally , Lüchtenborg Margreet , Pethick Joanna , Santaniello Francesco , Goel Shilpi , Wang Ying-Wen , Lavelle Katrina , McRonald Fiona , Eccles Diana , Morris Eva , Hardy Steven , Turnbull Clare , Tischkowitz Marc , Pharoah Paul , Antoniou Antonis C.
Published: October 2024

PURPOSE

Second primary cancer (SPC) risks after breast cancer (BC) in
BRCA1/BRCA2
pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.

METHODS

We followed 25,811 females and 480 males diagnosed with BC and tested for germline
BRCA1/BRCA2
PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks.

RESULTS

There were 1,840
BRCA1
and 1,750
BRCA2
female PV carriers. Compared with population incidences,
BRCA1
carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks.
BRCA2
carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without
BRCA1/BRCA2
PVs on testing,
BRCA1
carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks.
BRCA2
carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% (
BRCA1
carriers), 12%/3.0%/6.2% (
BRCA2
carriers), and 3.6%/0.4%/4.9% (noncarriers). Male
BRCA2
carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers.

CONCLUSION

Survivors of BC carrying
BRCA1
and
BRCA2
PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.
Associations Between Balance Measures and Risk of Fractures in 70-Year-Old Individuals
Authors: Nordström Peter , Ballin Marcel , Nordström Anna
Published: October 2024

Context

There are uncertainties regarding to what extent poor vision and distracting tasks reduce balance and are associated with fracture risk.

Objective

This work aimed to investigate the associations between body sway assessed under different visual and multitasking conditions and later risk of fractures in older adults.

Methods

This cohort study was conducted in Umeå municipality, Sweden. A total of 5437 community-dwelling 70-year-old individuals participated in a population-based health examination. Body sway at baseline was measured using a Wii balance board in the lateral and anterior-posterior direction during 3 different tests, including with eyes open, dual-tasking, and eyes closed. Fractures during follow-up were ascertained using nationwide registers.

Results

During a mean (range) follow-up of 4.8 (0.0-10.6) years, 348 women (12.3%) and 149 men (5.7%) sustained a fracture. In women, both anterior-posterior sway velocity (hazard ratio [HR], 1.05; 95% CI, 1.01-1.08, per mm/s increase) and variation in sway velocity (HR, 1.05; 95% CI, 1.01-1.09, per SD increase) during dual-tasking testing were associated with higher risk of fracture after adjustment for covariates. During testing with eyes closed, all measures of lateral sway were associated with the risk of fracture (P < .01 for all). In men, variation in lateral (HR, 1.03; 95% CI, 1.00-1.07 per SD increase) and anterior-posterior sway velocity (HR 1.05; 95% CI, 1.01-1.10 per SD increase) during dual-tasking testing were associated with higher risk of fracture.

Conclusion

Higher body sway velocity and larger variation in sway velocity were associated with a higher risk of fractures both in 70-year-old men and women, especially under more challenging testing conditions.
Disrupting the interaction between AMBRA1 and DLC1 prevents apoptosis while enhancing autophagy and mitophagy
Authors: Hawkins Kate , Watt Meg , Gillotin Sébastien , Hanspal Maya , Helley Martin , Richardson Jill , Corbett Nicola , Brownlees Janet
Published: October 2024

AMBRA1 has critical roles in autophagy, mitophagy, cell cycle regulation, neurogenesis and apoptosis. Dysregulation of these processes are hallmarks of various neurodegenerative diseases and therefore AMBRA1 represents a potential therapeutic target. The flexibility of its intrinsically disordered regions allows AMBRA1 to undergo conformational changes and thus to perform its function as an adaptor protein for various different complexes. Understanding the relevance of these multiple protein–protein interactions will allow us to gain information about which to target pharmacologically. To compare potential AMBRA1 activation strategies, we have designed and validated several previously described mutant constructs in addition to characterising their effects on proliferation, apoptosis, autophagy and mitophagy in SHSY5Y cells. AMBRA1TAT, which is a mutant form of AMBRA1 that cannot interact with DLC1 at the microtubules, produced the most promising results. Overexpression of this mutant protected cells against apoptosis and induced autophagy/mitophagy in SHSY5Y cells in addition to enhancing the switch from quiescence to proliferation in mouse neural stem cells. Future studies should focus on designing compounds that inhibit the protein–protein interaction between AMBRA1/DLC1 and thus have potential to be used as a drug strategy for neurodegeneration.
A Revealed Preference Test for Choquet and Max-Min Expected Utility with Ambiguity Aversion
Authors: Demuynck Thomas , Staner Clément
Published: October 2024

We develop a revealed preference test for the Choquet expected utility model with ambiguity aversion, which does not rely on specific functional form assumptions on the utility index. It is computationally efficient if the number of states is not too large, even for a large number of observations. This is a nice feature compared to other existing revealed preference tests for decision models with ambiguity. We illustrate the usefulness of our results by implementing our test on two experimental datasets from the literature, and we compare the empirical fit of this model to the subjective expected utility model. (JEL C91, D81, D91, G41)
Investigating the role of RNA-binding protein Ssd1 in aneuploidy tolerance through network analysis
Authors: Dutcher H. Auguste , Gasch Audrey P.
Published: October 2024

RNA-binding proteins (RBPs) play critical cellular roles by mediating various stages of RNA life cycles. Ssd1, an RBP with pleiotropic effects, has been implicated in aneuploidy tolerance inSaccharomyces cerevisiaebut its mechanistic role remains unclear. Here, we used a network-based approach to inform on Ssd1's role in aneuploidy tolerance, by identifying and experimentally perturbing a network of RBPs that share mRNA targets with Ssd1. We identified RBPs whose bound mRNA targets significantly overlap with Ssd1 targets. For 14 identified RBPs, we then used a genetic approach to generate all combinations of genotypes for euploid and aneuploid yeast with an extra copy of chromosome XII, with and withoutSSD1and/or the RBP of interest. Deletion of 10 RBPs either exacerbated or alleviated the sensitivity of wild-type and/orssd1Δ cells to chromosome XII duplication, in several cases indicating genetic interactions withSSD1in the context of aneuploidy. We integrated these findings with results from a global overexpression screen that identified genes whose duplication complementsssd1Δ aneuploid sensitivity. The resulting network points to a subgroup of proteins with shared roles in translational repression and P-body formation, implicating these functions in aneuploidy tolerance. Our results reveal a role for new RBPs in aneuploidy tolerance and support a model in which Ssd1 mitigates translation-related stresses in aneuploid cells.
Αναπτυξιακή κατάσταση και δυναμική στην Ήπειρο
Authors: Γαβριηλίδης Γκάμπυ
Published: October 2024

Στόχος της παρούσας διδακτορικής διατριβής ήταν να εξετάσει την αναπτυξιακή δυναμική της Ηπείρου σε συνδυασμό με τη διερεύνηση των παραγόντων που επηρεάζουν την εφαρμογή πρακτικών βιώσιμου ορεινού τουρισμού στην περιοχή. Επιπρόσθετα, διερευνήθηκαν στρατηγικές πολιτικές που μπορούν να εφαρμοστούν σε ορεινές περιφέρειες, όπως αυτή της Ηπείρου, για να ενισχύουν την τοπική οικονομική και κοινωνική τους ανάπτυξη μέσα στο πλαίσιο των ήπιων μορφών τουρισμού. Για τους παραπάνω σκοπούς, ερωτηματολόγια διανεμήθηκαν σε ένα δείγμα 1.524 τουριστών που είχαν επισκεφθεί την περιφέρεια της Ηπείρου τα τελευταία 7 χρόνια. Τα ερωτηματολόγια συγκεντρώθηκαν μέσω διαδικτύου με τη μέθοδο της απλής τυχαίας δειγματοληψίας. Για την ανάλυση των δεδομένων χρησιμοποιήθηκαν τεχνικές όπως Διερευνητική και Επιβεβαιωτική Παραγοντική Ανάλυση, Δομικά Μοντέλα Εξισώσεων και Παραμετρικά Τεστ. Τα αποτελέσματα της έρευνας έδειξαν ότι το κοινωνικό και οικονομικό τοπίο στην Ήπειρο, καθώς και η φυσική ομορφιά και μοναδικότητα της περιοχής υποδηλώνουν ότι η ανάπτυξη βιώσιμων τουριστικών δραστηριοτήτων, σε συνδυασμό με την προβολή της πολιτιστικής ταυτότητας της περιοχής, την καλλιέργεια προϊόντων διατροφής υψηλής ποιότητας και την ανάδειξη των στοιχείων του φυσικού περιβάλλοντός της μπορούν να αποτελέσουν βασικούς μοχλούς οικονομικής ανάπτυξης. Αυτό το οικονομικό μοντέλο δίνει ιδιαίτερη έμφαση στη διατήρηση των περιβαλλοντικών πόρων για τις μελλοντικές γενιές, ενισχύοντας μια πιο ανθρωποκεντρική φιλοσοφία για το πώς θα πρέπει να αναπτυχθούν οι κοινωνίες και οι κοινότητες. Η απρογραμμάτιστη τουριστική ανάπτυξη, που οδηγεί στην άδικη κατανομή των οικονομικών της ωφελειών και στην επιβάρυνση του φυσικού περιβάλλοντος, πρέπει να αντικατασταθεί από στρατηγικά σχεδιασμένες πολιτικές εναλλακτικού τουρισμού που οδηγούν στην τοπική οικονομική ανάπτυξη, αξιοποιώντας τις ενδογενείς δυνάμεις κάθε περιοχής. Συνολικά, το παράδειγμα μελέτης της περίπτωσης της Ηπείρου ανέδειξε τις αδυναμίες του παραγωγικού μοντέλου της Ελλάδας, οι οποίες, σε συνδυασμό με τη δημογραφική κρίση, την αναπτυξιακή υστέρηση και τις περιφερειακές ανισότητες, καθιστούν επιτακτική ανάγκη την αναζήτηση και εφαρμογή εναλλακτικών πολιτικών και στρατηγικών που θα οδηγήσουν στη βιώσιμη ανάπτυξη των τοπικών κοινωνιών.
The effect of soaking heat-polymerized acrylic resin denture base in avocado seed extract (Persea americana Mill.) on the inhibition of denture-plaque microorganisms biofilm growth
Authors: Angela Thalia , Wahyuni Siti , Halim Susanna
Published: October 2024

Background Heat polymerized acrylic (HPA) resins are known to have high porosity that contributes to increased surface roughness and microcrack formation in stress areas. This facilitates the attachment and growth of polymicrobial biofilms contributing to increased antimicrobial resistance. Many research had been carried out on avocado seeds, but no research that studies avocado seeds effect on denture-plaque microorganism biofilm on HPA resin has been found. Methods This study used 144 samples (n=144), namely HPA resin discs covered with mono-species and polymicrobial biofilms. The discs were soaked for 8 hours in the 5%, 10%, 15%, 20% avocado seed extract, positive control (alkaline peroxide), and negative control (aquadest). Each disc was shaken with a vortex mixer for 1 minute, and 100 μL was added into 96-well microplates with three times repetition and incubated for 24 hours. A microtiter plate biofilm formation assay was then conducted The inhibition values were determined from the percentage inhibition value formula which required absorption values from a microplate reader (595 nm). The research data were analyzed using a univariant test, and a one-way ANOVA test, accompanied by Welch ANOVA on non-homogenous data. Results In this research, it was found that the MBIC50 of avocado seed extract against the mono-species of C. albicans (5%), C. glabrata (5%), A. odontolyticus (15%), S. gordonii (15%), S. aureus (10%), while against polymicrobial was 20%. There was a significant effect of soaking HPA resin in avocado seed extract on the inhibition of mono-species and polymicrobial biofilms with a value of p<0.001 (p<0.05). Conclusion The MBIC50 of avocado seed extract in polymicrobial biofilm group was higher than that in the mono-species biofilm groups. Although alkaline peroxide showed higher inhibition value than that of the MBIC50 in polymicrobial biofilm group, 20% avocado seed extract was concluded effective as it inhibited >50% polymicrobial biofilm.
Vaccination against COVID-19 in a geographically dispersed and underserved population, challenges and solutions in access and distribution of vaccines
Authors: Mafla-Viscarra Alejandra , Caballero Evelyn , Levy Mireya , Owen Leena , Yépez Paola , Tobar Mirely , Hansoti Bhakti , Grunauer Michelle
Published: October 2024

Background As of July 2021, only 57% of Ecuador’s population had received the first vaccine dose against COVID-19. The national immunization campaign faced difficulties in reaching and providing vaccines to underserved population in remote areas. Methods The RISE project, funded by USAID and implemented by Jhpiego, aimed to develop an immunization strategy, that through the collaboration of an international non-profit organization, an academic institution and the public sector, could effectively support the national vaccination campaign of the Ecuadorian Ministry of Public Health. Results The program identified gaps in vaccination access and uptake, established specific strategies for targeted communities, analyzed official geographical information on vaccination coverage, ran micro-planning exercises at the local level, and adapted to new needs identified to ensure an effective vaccination uptake. From November 2021 up to May 2023, more than 1.8 million COVID-19 vaccine doses were administered to underserved populations living in geographically dispersed areas, in 18 provinces. Conclusions Employing data-targeted approaches and microplanning to identify underserved populations, strategic planning and collaboration between local governments, private sector, academic institution, and community leaders can substantially improve COVID-19 vaccines coverage and, thus, equity to vaccine access. The lessons learned might be useful to improve overall immunization service delivery.
Chest Wall Hydatid Disease: Surgical management and risk Factors for Recurrence and Mortality
Authors: Saad Asma , Bouassida Imen , Rouis Houda , Bellali Hedia , Abdelkbir Amina , Abdennadher Mahdi , Houcine Yoldez , Kwas Hamida , Makhlouf Hassen , Mestiri Mondher , Kooli Mondher , Bouali Sofiene , Kallel Jalel , Zribi Hazem , Marghli Adel
Published: October 2024

Background Hydatidosis of the thoracic wall differs from other hydatid localizations in its pathophysiology, diagnostic, and therapeutic management. It is a little-studied entity. The objectives of our work were to describe its surgical management and to analyze the factors that may influence recurrence and mortality. Methods A retrospective, descriptive, longitudinal, and multicenter study on four university hospital surgical centers of Tunis, from January 1995 to December 2022 including operated hydatid cysts of the thoracic wall. Overall survival (OS) and cumulative recurrence rates were calculated. Univariate and multivariable Cox regression analyses were performed to identify recurrence and mortality risk factors. Results Forty-nine patients were included. The mean age was 41 ± 17 years [8-76]. The main presenting sign was thoracic parietal swelling (n=22). Chest ultrasound and CT scan showed multivesicular formation in 17 and 33 cases, respectively. Muscle involvement was in the intercostal (n=4), paravertebral (n=13), and pectoralis major (n=3) muscles. Bone involvement was vertebral (n=11), costal (n=12), costo-vertebral (n=21) and sternal (n=2). A posterolateral thoracotomy was performed (n=20). Surgical excision at various levels of the chest wall with spinal stabilization (n=15) was performed. Sixty-three percent of the patients received antiparasitic medical treatment. Recurrence occurred in 37% of cases. Four patients died from hydatidosis-related complications. Factors could be independently associated with recurrence such as male gender, and vertebral involvement. The presence of a visceral hydatid cyst located at a distance from the parietal lesion at the time of diagnosis and the occurrence of postoperative infectious complications could increase mortality. Conclusions Chest wall hydatidosis represents a rare medical condition where surgery remains the preferred treatment modality. However, it carries a substantial burden of morbidity and mortality, influenced by various factors. Further large-scale studies are necessary to gain a deeper understanding of these factors and to optimize management strategies accordingly.