bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of bleeding associated with transbronchial biopsy using flexible bronchoscopy in patients with echocardiographic or chest CT evidence of pulmonary hypertension
Authors: Takashima Yuta , Shinagawa Naofumi , Morinaga Daisuke , Nakamura Junichi , Furuta Megumi , Shoji Tetsuaki , Asahina Hajime , Kikuchi Eiki , Kikuchi Junko , Sakakibara-Konishi Jun , Tsujino Ichizo , Konno Satoshi
Published: November 2022

Background

Endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) facilitates the diagnosis of various respiratory diseases. The safety of performing EBUS-guided TBB in patients with a finding of pulmonary hypertension (PH) is controversial. Little is known about the relationship between the risk of bleeding associated with EBUS-guided TBB in the presence of PH suspected on echocardiography or chest CT.

Methods

To assess the risk of bleeding associated with EBUS-guided TBB in patients with presumed PH per echocardiography or chest CT, we retrospectively reviewed the medical records of 314 consecutive patients who underwent EBUS-guided TBB using a guide sheath (GS), as well as echocardiography and chest CT. Bleeding complication was defined as over one minute of suctioning; repeated wedging of the bronchoscope; instillation of cold saline, diluted vasoactive substances, or thrombin due to persistent bleeding. Findings of suspected PH were defined as peak tricuspid regurgitation velocity (TRV) > 2.8 m/s on echocardiography or pulmonary artery to aorta ratio (PA:A ratio) > 0.9 on chest CT.

Results

In total, 35 (11.1%) patients developed bleeding, and all cases were managed safely. Furthermore, 17 (5.4%) and 59 (18.8%) patients were suspected to have PH based on echocardiography and chest CT, respectively. Among the patients suspected to have PH on echocardiography, five (5/17 = 29.4%) patients developed bleeding. Among the patients suspected to have PH on chest CT, 11 (11/59 = 18.6%) patients developed bleeding. Univariate analysis revealed that long diameter (≥ 30 mm) of the lesion, lesion location (the biopsy site was inner than the segmental bronchus), bronchoscopic diagnosis of malignancy, and additional biopsy were potential predictive factors for bleeding. The finding of suspected PH on echocardiography correlated significantly with bleeding (p = 0.03). On multivariate analysis, long diameter (≥ 30 mm) of the lesion (p = .021) and findings of suspected PH on echocardiography (p = .049) were significantly associated with bleeding.

Conclusion

All cases of bleeding in the present study were managed safely. The risk of bleeding is moderately elevated when PH is suspected by echocardiography in patients undergoing EBUS-guided TBB using a GS.
Duration of infertility and assisted reproductive outcomes in non-male factor infertility: can use of ICSI turn the tide?
Authors: Zhang Liting , Cai He , Li Wei , Tian Li , Shi Juanzi
Published: November 2022

Background

Intracytoplasmic sperm injection (ICSI) is increasingly used among in vitro fertilization (IVF) cycles without male factor infertility. For couples with prolonged infertility duration, the preferred insemination method may vary across laboratories and clinics. We analyzed whether ICSI is effective for non-male factor infertility with long infertility duration.

Methods

Seventeen thousand four hundred seventy-seven IVF/ICSI cycles from women with non-male factor infertility were included, of these 4177 women with infertility duration ≥ 5 years were in the final analysis. Primary outcome was the live birth rate after first embryo transfer. Secondary outcomes were rates of clinical pregnancy and fertilization.

Results

A nonlinear relationship was observed between infertility duration and IVF fertilization rate, which decreased with infertility years up to the turning point (4.8 years). 4177 women with infertility ≥ 5 years were categorized by IVF (n = 3806) or ICSI (n = 371). Live birth rate after first embryo transfer was 43.02% in ICSI and 47.85% in IVF group (adjusted odds ratio (aOR), 0.91; 95% confidence interval (CI), 0.72–1.15). Fertilization rate per metaphaseII (aOR, 1.10; 95% CI, 0.86–1.40) and clinical pregnancy rate (aOR, 0.89; 95% CI, 0.71–1.13) were similar between the two groups. Sensitive analyses (women ≥ 35 years) did not show a benefit of ICSI over IVF.

Conclusions

Women with infertility exceeding 4.8 years had decreased incidence of IVF fertilization. The use of ICSI showed no significant improvement in fertilization and live birth rates for non-male factor couples with ≥ 5 years of infertility.
Exploration of exposure to artificial intelligence in undergraduate medical education: a Canadian cross-sectional mixed-methods study
Authors: Pucchio Aidan , Rathagirishnan Raahulan , Caton Natasha , Gariscsak Peter J. , Del Papa Joshua , Nabhen Jacqueline Justino , Vo Vicky , Lee Wonjae , Moraes Fabio Y.
Published: November 2022

Background

Emerging artificial intelligence (AI) technologies have diverse applications in medicine. As AI tools advance towards clinical implementation, skills in how to use and interpret AI in a healthcare setting could become integral for physicians. This study examines undergraduate medical students’ perceptions of AI, educational opportunities about of AI in medicine, and the desired medium for AI curriculum delivery.

Methods

A 32 question survey for undergraduate medical students was distributed from May–October 2021 to students to all 17 Canadian medical schools. The survey assessed the currently available learning opportunities about AI, the perceived need for learning opportunities about AI, and barriers to educating about AI in medicine. Interviews were conducted with participants to provide narrative context to survey responses. Likert scale survey questions were scored from 1 (disagree) to 5 (agree). Interview transcripts were analyzed using qualitative thematic analysis.

Results

We received 486 responses from 17 of 17 medical schools (roughly 5% of Canadian undergraduate medical students). The mean age of respondents was 25.34, with 45% being in their first year of medical school, 27% in their 2nd year, 15% in their 3rd year, and 10% in their 4th year. Respondents agreed that AI applications in medicine would become common in the future (94% agree) and would improve medicine (84% agree Further, respondents agreed that they would need to use and understand AI during their medical careers (73% agree; 68% agree), and that AI should be formally taught in medical education (67% agree). In contrast, a significant number of participants indicated that they did not have any formal educational opportunities about AI (85% disagree) and that AI-related learning opportunities were inadequate (74% disagree). Interviews with 18 students were conducted. Emerging themes from the interviews were a lack of formal education opportunities and non-AI content taking priority in the curriculum.

Conclusion

A lack of educational opportunities about AI in medicine were identified across Canada in the participating students. As AI tools are currently progressing towards clinical implementation and there is currently a lack of educational opportunities about AI in medicine, AI should be considered for inclusion in formal medical curriculum.
Choice of intraoperative ultrasound adjuncts for brain tumor surgery
Authors: Kumar Manoj , Noronha Santosh , Rangaraj Narayan , Moiyadi Aliasgar , Shetty Prakash , Singh Vikas Kumar
Published: November 2022

Background

Gliomas are among the most typical brain tumors tackled by neurosurgeons. During navigation for surgery of glioma brain tumors, preoperatively acquired static images may not be accurate due to shifts. Surgeons use intraoperative imaging technologies (2-Dimensional and navigated 3-Dimensional ultrasound) to assess and guide resections. This paper aims to precisely capture the importance of preoperative parameters to decide which type of ultrasound to be used for a particular surgery.

Methods

This paper proposes two bagging algorithms considering base classifier logistic regression and random forest. These algorithms are trained on different subsets of the original data set. The goodness of fit of Logistic regression-based bagging algorithms is established using hypothesis testing. Furthermore, the performance measures for random-forest-based bagging algorithms used are AUC under ROC and AUC under the precision-recall curve. We also present a composite model without compromising the explainability of the models.

Results

These models were trained on the data of 350 patients who have undergone brain surgery from 2015 to 2020. The hypothesis test shows that a single parameter is sufficient instead of all three dimensions related to the tumor ($$p < 0.05$$

p
<
0.05

). We observed that the choice of intraoperative ultrasound depends on the surgeon making a choice, and years of experience of the surgeon could be a surrogate for this dependence.

Conclusion

This study suggests that neurosurgeons may not need to focus on a large set of preoperative parameters in order to decide on ultrasound. Moreover, it personalizes the use of a particular ultrasound option in surgery. This approach could potentially lead to better resource management and help healthcare institutions improve their decisions to make the surgery more effective.
Implementing the language comprehension test C-BiLLT: a qualitative description study using the COM-B model of behaviour change
Authors: Bootsma J. N. , Phoenix M. , Geytenbeek J. J. M. , Stadskleiv K. , Gorter J. W. , Fiske S. , Cunningham B. J.
Published: November 2022

Background

It is challenging to reliably assess the language comprehension of children with severe motor and speech impairments using traditional assessment tools. The Computer Based instrument for Low motor Language Testing (C-BiLLT) aims to reduce barriers to evidence-based assessment for this population by allowing children to access the test using non-traditional methods such as eye gaze so they can independently respond to test items. The purpose of this study is to develop a contextualized understanding of the factors that influenced clinicians’ implementation of the C-BILLT in practice in the Netherlands and Norway.

Materials and methods

A qualitative approach including semi-structured individual interviews with 15 clinicians (speech-language pathologists, neuropsychologists, and one teacher, counsellor, and vision specialist) was used. Data analysis was conducted in two rounds. First, a deductive approach including a codebook was used to code data within the COM-B components describing clinicians’ capability, opportunity, and motivation for behaviour change. Then, an abductive approach applying thematic analysis was used to identify meaningful patterns within the COM-B components.

Results

Several meaningful barriers and facilitators were identified across the data. Clinicians used the C-BiLLT with two distinct groups of clients: (1) the population it was originally developed for, and (2) clients that could have also been assessed using a traditional language test. Clinicians working with the first group experienced more, and more complex barriers across all COM-B components, to successful C-BiLLT use than the latter.

Conclusion

This study provides timely insights into the capability, opportunity, and motivation factors important for creating and sustaining assessment behaviour change in clinicians who used or attempted to use the C-BiLLT. Potential tailored intervention strategies aimed at improving implementation of novel assessment tools are discussed and may be helpful for others working to improve service delivery for children with complex needs.
Barriers and facilitators to the implementation and scale up of differentiated service delivery models for HIV treatment in Africa: a scoping review
Authors: Belay Yihalem Abebe , Yitayal Mezgebu , Atnafu Asmamaw , Taye Fitalew Agimass
Published: November 2022

Background

In the face of health-system constraints, local policymakers and decision-makers face difficult choices about how to implement, expand and institutionalize antiretroviral therapy (ART) services. This scoping review aimed to describe the barriers and facilitators to the implementation and scale up of differentiated service delivery (DSD) models for HIV treatment in Africa.

Methods

PubMed, Web of Science, Embase, Scopus, CINAHL, Global Health, Google, and Google Scholar databases were searched. There was no start date thereby all references up until May 12, 2021, were included in this review. We included studies reported in the English language focusing on stable adult people living with human immune deficiency virus (HIV) on ART and the healthcare providers in Africa. Studies related to children, adolescents, pregnant and lactating women, and key populations (people who inject drugs, men having sex with men, transgender persons, sex workers, and prisoners), and studies about effectiveness, cost, cost-effectiveness, and pre or post-exposure prophylaxis were excluded. A descriptive analysis was done.

Results

Fifty-seven articles fulfilled our eligibility criteria. Several factors influencing DSD implementation and scale-up emerged. There is variability in the reported factors across DSD models and studies, with the same element serving as a facilitator in one context but a barrier in another. Perceived reduction in costs of visit for patients, reduction in staff workload and overburdening of health facilities, and improved or maintained patients’ adherence and retention were reported facilitators for implementing DSD models. Patients’ fear of stigma and discrimination, patients’ and providers’ low literacy levels on the DSD model, ARV drug stock-outs, and supply chain inconsistencies were major barriers affecting DSD model implementation. Stigma, lack of model adoption from providers, and a lack of resources were reported as a bottleneck for the DSD model scale up. Leadership and governance were reported as both a facilitator and a barrier to scaling up the DSD model.

Conclusions

This review has important implications for policy, practice, and research as it increases understanding of the factors that influence DSD model implementation and scale up. Large-scale studies based on implementation and scale up theories, models, and frameworks focusing on each DSD model in each healthcare setting are needed.
Specialized healthcare practitioners’ challenges in performing video consultations to patients in Nordic Countries – a systematic review and narrative synthesis
Authors: Baluszek Joanna Barbara , Wiig Siri , Myrnes-Hansen Kai Victor , Brønnick Kolbjørn Kallesten
Published: November 2022

Background

Video consultations are becoming an important telemedicine service in Nordic countries. Its use in specialized healthcare increased significantly during COVID-19 pandemic. Despite advantages video consultations have, it may also produce challenges for practitioners. Identifying and understanding these challenges may contribute to how managers can support these practitioners and thereby improve work related wellbeing and quality of care.

Methods

We designed this study as systematic review of the literature with narrative synthesis and conducted a thematic analysis. We conducted review about the use of video consultations in specialized healthcare in Nordic countries to identify and categorize challenges experienced and/or perceived by practitioners. We searched Ovid MEDLINE(R), EMBASE, APA PsycINFO, and CINAH, from 2011 to 2021. Eligibility criteria were population - practitioners in specialized healthcare with experience in video consultations to patients, interest - challenges experienced and/or perceived by practitioners and, context - outpatient clinics in Nordic countries.

Results

We included four qualitative and one mixed method studies, published between 2018 and 2021 in Norway, Denmark, and Sweden. By thematic analysis we identified three main themes: challenges related to video consultation, challenges related to practitioner and, challenges related to patient. These themes are composed of 8 categories: technology uncertainties, environment and surroundings, preparation for requirements, clinical judgment, time management, practitioners’ idiosyncrasies, patients’ idiosyncrasies and patients’ suitability and appropriateness. Challenges from technology uncertainties category were most frequent (dominant) across all clinical specializations.

Conclusion

Findings indicate the scarcity of the research and provide rationale for further research addressing challenges in providing video consultations in the Nordic context. We suggest updating this review when the amount of available research increases.
Association between service readiness and PMTCT cascade effectiveness: a 2018 cross-sectional analysis from Manica province, Mozambique
Authors: Dinis Aneth , Augusto Orvalho , Ásbjörnsdóttir Kristjana H. , Crocker Jonny , Gimbel Sarah , Inguane Celso , Ramiro Isaías , Coutinho Joana , Agostinho Mery , Cruz Emilia , Amaral Fernando , Tavede Esperança , Isidoro Xavier , Sidat Yaesh , Nassiaca Regina , Murgorgo Filipe , Cuembelo Fátima , Hazim Carmen E. , Sherr Kenneth
Published: November 2022

Background

Despite high coverage of maternal and child  health services in Mozambique, prevention of mother-to-child transmission of HIV (PMTCT) cascade outcomes remain sub-optimal. Delivery effectiveness is modified by health system preparedness. Identifying modifiable factors that impact quality of care and service uptake can inform strategies to improve the effectiveness of PMTCT programs. We estimated associations between facility-level modifiable health system readiness measures and three PMTCT outcomes: Early infant diagnosis (polymerase chain reaction (PCR) before 8 weeks of life), PCR ever (before or after 8 weeks), and positive PCR test result.

Methods

A 2018 cross-sectional, facility-level survey was conducted in a sample of 36 health facilities covering all 12 districts in Manica province, central Mozambique, as part of a baseline assessment for the SAIA-SCALE trial (NCT03425136). Data on HIV testing outcomes among 3,427 exposed infants were abstracted from at-risk child service registries. Nine health system readiness measures were included in the analysis. Logistic regressions were used to estimate associations between readiness measures and pediatric HIV testing outcomes. Odds ratios (OR) and 95% confidence intervals (95%CI) are reported.

Results

Forty-eight percent of HIV-exposed infants had a PCR test within 8 weeks of life, 69% had a PCR test ever, and 6% tested positive. Staffing levels, glove stockouts, and distance to the reference laboratory were positively associated with early PCR (OR = 1.02 [95%CI: 1.01–1.02], OR = 1.73 [95%CI: 1.24–2.40] and OR = 1.01 [95%CI: 1.00–1.01], respectively) and ever PCR (OR = 1.02 [95%CI: 1.01–1.02], OR = 1.80 [95%CI: 1.26–2.58] and OR = 1.01 [95%CI: 1.00–1.01], respectively). Catchment area size and multiple NGOs supporting PMTCT services were associated with early PCR testing OR = 1.02 [95%CI: 1.01–1.03] and OR = 0.54 [95%CI: 0.30–0.97], respectively). Facility type, stockout of prophylactic antiretrovirals, the presence of quality improvement programs and mothers’ support groups in the health facility were not associated with PCR testing. No significant associations with positive HIV diagnosis were found.

Conclusion

Salient modifiable factors associated with HIV testing for exposed infants include staffing levels, NGO support, stockout of essential commodities and accessibility of reference laboratories. Our study provides insights into modifiable factors that could be targeted to improve PMTCT performance, particularly at small and rural facilities.
CYP4 subfamily V member 2 (CYP4V2) polymorphisms were associated with ischemic stroke in Chinese Han population
Authors: Long Faqing , Wang Desheng , Su Qingjie , Zhang Yuhui , Li Jianhong , Xia Shiliang , Wang Hailun , Wu Yongping , Qu Qiumin
Published: November 2022

Background

CYP4 subfamily V member 2 (CYP4V2) polymorphisms are related to venous thromboembolism. However, the influence of CYP4V2 polymorphisms on the susceptibility to ischemic stroke (IS) remains undetermined.

Methods

We selected and genotyped five polymorphisms of CYP4V2 in 575 cases and 575 controls to test whether CYP4V2 variants were associated with the risk for IS in a Chinese Han population. Genotyping of CYP4V2 polymorphisms was performed using the Agena MassARRAY platform. Logistic regression analysis was used to assess the association between CYP4V2 polymorphisms and IS risk by calculating odds ratios (ORs) and 95% confidence interval (CI). False-positive report probability analysis was applied to assess the noteworthy relationship of the significant findings.

Results

CYP4V2 rs1398007 might be a risk factor for IS (OR = 1.34, 95% CI 1.05–1.71, p = 0.009). Specially, confounding factors (age, gender, smoking and drinking status) might affect the relationship between rs1398007 and IS susceptibility. Moreover, rs1053094 and rs56413992 were associated with IS risk in males. Multifactor dimensionality reduction analysis showed the combination of rs13146272 and rs3736455 had the strongest interaction effect (information gain value of 0.40%). Furthermore, genotypes of rs1398007 (p = 0.006) and rs1053094 (p = 0.044) were associated with the levels of high-density lipoprotein cholesterol (HDL-C) among healthy controls.

Conclusion

Our results first provided evidence that CYP4V2 rs1398007 might be a risk factor for IS, which provides instructive clues for studying the mechanisms of CYP4V2 to the pathogenesis of IS.
Endotrophin is a risk marker of complications in CANagliflozin cardioVascular Assessment Study (CANVAS): a randomized controlled trial
Authors: Rasmussen Daniel Guldager Kring , Hansen Michael K. , Blair Joseph , Jatkoe Timothy A. , Neal Bruce , Karsdal Morten A. , Genovese Federica
Published: November 2022

Background

Enhanced de-novo collagen type VI (COL VI) formation has been associated with kidney and cardiovascular fibrosis. We hypothesized that endotrophin (ETP), a product specifically generated during collagen type VI formation, may be prognostic for heart failure (HF), cardiovascular death (CVD), kidney endpoints, and all-cause mortality in patients with type 2 diabetes.

Methods

We measured ETP in plasma (P-ETP) and urine (U-ETP) samples collected at baseline and follow-up (year 3) from the randomized controlled trial, CANagliflozin cardioVascular Assessment Study (CANVAS), by use of the PRO-C6 ELISA measuring COL VI formation and ETP. At baseline, plasma and urine samples were available for 3531 and 3423 patients, respectively. At year 3, plasma and urine samples were available for 2178 (61.7%) and 2070 (60.5%) patients, respectively Patients were followed for a median of 6.1 years, and endpoints included: incident HF, CVD, three kidney composite endpoints, and all-cause mortality. Backward selection was used to identify variables to be included in the analyses. Robustness of the association with outcome was assessed by bootstrap analyses.

Results

In univariable analysis, P-ETP predicted all investigated outcomes (all p < 0.0001), remained independently associated with all outcomes after adjustment for conventional risk factors (all p < 0.004), and increased C-statistics of the models for the outcomes HF, CVD, HFCVD, all-cause mortality, and kidney composite 2 (ΔC ≥ 0.002). In bootstrap analysis, P-ETP was retained with a frequency ranging from 41.0 to 98.4% for all outcomes. Levels of U-ETP were associated with outcomes in univariable analysis, but associations with most outcomes were lost after adjustment for conventional risk factors. The increase in P-ETP over time was greater with increasing albuminuria stage (p < 0.0001) and was independently associated with the kidney endpoints (p < 0.03). In the placebo arm, the increase in P-ETP was prognostic for all-cause mortality (HR [95% CI]; 1.14 [1.05–1.23], p = 0.003). Whereas levels of P-ETP were not impacted by treatment, levels of U-ETP significantly increased with canagliflozin treatment.

Conclusions

P-ETP generated during COL VI formation predicts cardiovascular, kidney and mortality outcomes in patients with type 2 diabetes. As ETP identifies patients at increased risk of experiencing relevant outcomes, it may be used for patient enrichment in future clinical trials.

Trial Registry Number(ClinicalTrials.gov Identifier): NCT01032629
Drug resistance of Plasmodium falciparum and Plasmodium vivax isolates in Indonesia
Authors: Rahmasari Farindira Vesti , Asih Puji B. S. , Dewayanti Farahana K. , Rotejanaprasert Chawarat , Charunwatthana Prakaykaew , Imwong Mallika , Syafruddin Din
Published: November 2022

This review article aims to investigate the genotypic profiles of Plasmodium falciparum and Plasmodium vivax isolates collected across a wide geographic region and their association with resistance to anti-malarial drugs used in Indonesia. A systematic review was conducted between 1991 and date. Search engines, such as PubMed, Science Direct, and Google Scholar, were used for articles published in English and Indonesian to search the literature. Of the 471 initially identified studies, 61 were selected for 4316 P. falciparum and 1950 P. vivax individual infections. The studies included 23 molecular studies and 38 therapeutic efficacy studies. K76T was the most common pfcrt mutation. K76N (2.1%) was associated with the haplotype CVMNN. By following dihydroartemisinin–piperaquine (DHA–PPQ) therapy, the mutant pfmdr1 alleles 86Y and 1034C were selected. Low prevalence of haplotype N86Y/Y184/D1246Ypfmdr1 reduces susceptibility to AS–AQ. SNP mutation pvmdr1 Y976F reached 96.1% in Papua and East Nusa Tenggara. Polymorphism analysis in the pfdhfr gene revealed 94/111 (84.7%) double mutants S108N/C59R or S108T/A16V in Central Java. The predominant pfdhfr haplotypes (based on alleles 16, 51, 59,108, 164) found in Indonesia were ANCNI, ANCSI, ANRNI, and ANRNL. Some isolates carried A437G (35.3%) or A437G/K540E SNPs (26.5%) in pfdhps. Two novel pfdhps mutant alleles, I588F/G and K540T, were associated with six pfdhps haplotypes. The highest prevalence of pvdhfr quadruple mutation (F57L/S58R/T61M/S117T) (61.8%) was detected in Papua. In pvdhps, the only polymorphism before and after 2008 was 383G mutation with 19% prevalence. There were no mutations in the pfk13 gene reported with validated and candidate or associated k13 mutation. An increased copy number of pfpm2, associated with piperaquine resistance, was found only in cases of reinfection. Meanwhile, mutation of pvk12 and pvpm4 I165V is unlikely associated with ART and PPQ drug resistance. DHA–PPQ is still effective in treating uncomplicated falciparum and vivax malaria. Serious consideration should be given to interrupt local malaria transmission and dynamic patterns of resistance to anti-malarial drugs to modify chemotherapeutic policy treatment strategies. The presence of several changes in pfk13 in the parasite population is of concern and highlights the importance of further evaluation of parasitic ART susceptibility in Indonesia.

Graphical Abstract
Life-threatening paradoxical thromboembolism in a patient with patent foramen ovale
Authors: Rizza Antonio , Negro Francesco , Gasbarri Tommaso , Arpesani Roberto , Ferro Baldassare , Roncucci Paolo , Palmieri Cataldo , Sorbo Simone , Pasanisi Emilio Maria , Solinas Marco , Berti Sergio
Published: November 2022

Background

Venous thromboembolism represents the third most frequent acute cardiovascular syndrome worldwide. Its clinical manifestations are deep vein thrombosis and/or pulmonary embolism. Despite a considerable mortality, diagnosis is often missed. 

Case presentation

We report the management of a female patient with high-risk pulmonary thromboembolism treated initially with thromboaspiration, complicated by embolus jailing in a patent foramen ovale. In this situation, left cardiac chambers and systemic circulation were jeopardized by this floating embolus.

Conclusions

High-risk pulmonary embolism requires reperfusion strategy but sometimes mechanical thromboaspiration may be not fully successful; transesophageal echocardiography led to a prompt diagnosis of this unexpected finding; in this very particular case, open surgery represented a bail-out procedure to avoid cerebral and systemic embolism.
Healthcare costs associated with comorbid cardiovascular and renal conditions among persons with diabetes, 2008–2019
Authors: Shah Chintal H. , Dave Chintan V.
Published: November 2022

Background

There is paucity of data examining healthcare costs among persons with comorbid diabetes and cardiorenal conditions.

Objective

To elucidate the longitudinal trends and quantify the incremental healthcare costs associated with the following cardiorenal conditions: atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and kidney disease, among persons with diabetes.

Methods

Medical Expenditure Panel Survey data (2008–2019) were used to identify adults with diabetes and comorbid cardiorenal conditions. Overall, medical and pharmaceutical costs were ascertained (in 2019 US dollars). Analyses were adjusted for 14 variables using a two-part regression model.

Results

Among 32,519 adults with diabetes, the mean (standard error [SE]) annual healthcare costs were $13,829 ($213), with medical and prescription components contributing $9301 ($172) and $4528 ($98), respectively. Overall healthcare costs rose by 26.8% from $12,791 (2008–2009) to $16,215 (2018–2019) over the study period, driven by 42.5% and 20.3% increase in pharmaceutical and medical spending, respectively. Similar trends were observed for subgroup of persons with cardiorenal conditions. Compared to their counterparts without cardiorenal conditions and prior to adjustment, persons with ASCVD, HF and kidney disease incurred healthcare costs that were approximately 2.2, 3.3, and 2.7 times greater. After adjustment, comorbid ASCVD, HF and kidney disease were associated with annual excess spending of $8651 (95% CI $7729–$9573), $9373 (95% CI $9010–$9736), and $9995 (95% CI $8781–$11,209), respectively.

Conclusions

Study results are generalizable to non-institutionalized US persons. Healthcare costs associated with the management of diabetes are high—especially among those with comorbid cardiorenal conditions, and have risen in recent years.
Epigenetically regulated PCDHB15 impairs aggressiveness of metastatic melanoma cells
Authors: Carrier Arnaud , Desjobert Cécile , Lobjois Valérie , Rigal Lise , Busato Florence , Tost Jörg , Ensenyat-Mendez Miquel , Marzese Diego M. , Pradines Anne , Favre Gilles , Lamant Laurence , Lanfrancone Luisa , Etievant Chantal , Arimondo Paola B. , Riond Joëlle
Published: November 2022

The protocadherin proteins are cell adhesion molecules at the crossroad of signaling pathways playing a major role in neuronal development. It is now understood that their role as signaling hubs is not only important for the normal physiology of cells but also for the regulation of hallmarks of cancerogenesis. Importantly, protocadherins form a cluster of genes that are regulated by DNA methylation. We have identified for the first time that PCDHB15 gene is DNA-hypermethylated on its unique exon in the metastatic melanoma-derived cell lines and patients’ metastases compared to primary tumors. This DNA hypermethylation silences the gene, and treatment with the DNA demethylating agent 5-aza-2′-deoxycytidine reinduces its expression. We explored the role of PCDHB15 in melanoma aggressiveness and showed that overexpression impairs invasiveness and aggregation of metastatic melanoma cells in vitro and formation of lung metastasis in vivo. These findings highlight important modifications of the methylation of the PCDHβ genes in melanoma and support a functional role of PCDHB15 silencing in melanoma aggressiveness.
Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure
Authors: Euclydes Verônica , Gomes Catarina , Gouveia Gisele , Gastaldi Vinicius Daguano , Feltrin Arthur Sant’Anna , Camilo Caroline , Vieira Rossana Pulcineli , Felipe-Silva Aloísio , Grisi Sandra , Fink Günther , Brentani Alexandra , Brentani Helena
Published: November 2022

Background

Physiological maternal stress response, such as imbalance in the glucocorticoid pathway and immune system seems to be mediated by DNA methylation (DNAm) and might translate intrauterine stress exposures into phenotypic changes in a sex-specific manner. DNAm in specific sites can also predict newborn gestational age and gestational age acceleration (GAA). GAA occurs when the predicted biological age is higher than the chronological age. In adults, poor health outcomes related to this deviance are well documented and raise questions for the interpretation and prediction in early stages of life. Boys seem to be more vulnerable to intrauterine stress exposure than girls; however, the mechanisms of adaptive sex-specific responses are still unclear. We hypothesize that intrauterine stress exposure is associated with GAA and could be different in boys and girls if inflammatory or glucocorticoid pathways exposure is considered.

Results

Using the Western Region Birth Cohort (ROC—São Paulo, Brazil) (n = 83), we calculated DNAm age and GAA from cord blood samples. Two epigenetic risk scores were calculated as an indirect proxy for low-grade inflammation (i-ePGS) and for glucocorticoid exposure (GES). Multivariate linear regression models were applied to investigate associations of GAA with prenatal exposures. The i-ePGS and GES were included in different models with the same co-variates considering sex interactions. The first multivariate model investigating inflammatory exposure (adj. R2 = 0.31, p =  < 0.001) showed that GAA was positively associated with i-ePGS (CI, 0.26–113.87, p = 0.049) and negative pregnancy-related feelings (CI, 0.04–0.48 p = 0.019). No sex interaction was observed. The second model investigating glucocorticoid exposure (adj. R2 = 0.32, p =  < 0.001) showed that the higher was the GAA was associated with a lower the lower was the GES in girls (CI, 0.04–2.55, p = 0.044). In both models, maternal self-reported mental disorder was negatively associated with GAA.

Conclusion

Prenatal epigenetic score of exposure to low-grade inflammatory was a predictor of GAA for both sexes. Glucocorticoid epigenetic score seems to be more important to GAA in girls. This study supports the evidence of sex-specificity in stress response, suggesting the glucocorticoid as a possible pathway adopted by girls to accelerate the maturation in an adverse condition.
The economic valuation of Gedo Natural Forest conservation benefits, Ethiopia
Authors: Tolera Tadesse
Published: November 2022

Forest ecosystem economic valuation is responsible for ecologically aware and reasonable gains to the country and particularly to the surrounding groups through different means. Thus, the central objective of this study was to analyze the economic valuation Gedo Natural Forest conservation benefits of using the contingent valuation method. Both primary and secondary data were employed in this study. The interview responses of 342 households nominated from three kebeles around Gedo natural forest were collected in purpose and random sampling procedures through a semi-structure questionnaire. The mean willingness to pay calculated by means of Krinsky–Robb technique after running of Seemingly Unrelated Bivariate Probit Regression from the dichotomous choice format and open-ended questions was 24.97 and 23.91 birr per year, respectively. The outcomes of Tobit model show that the total livestock unit, total annual income of the household, and the amount of credit utilization are meaningful variables positively and significantly related to the likelihood of willingness to pay for the conservation benefits of Gedo natural forest. On the other hand, the households’ family size, the households’ age, and initial bid value were other important variables negatively and significantly influence households’ willingness to pay for the conservation benefits of Gedo natural forest. The liable body could, therefore, apply the scenario of willingness to pay in the study area, so that the Gedo natural forest could be conserved, measurable benefit to the households could be practical, and future awareness of respective household could be raised.
A pilot assessment of the career and job satisfaction of the pharmaceutical workforce in Lebanon
Authors: Nassar Elsa , Kassouf Sibelle , Hajj Aline , Sacre Hala , Akel Marwan , Zeenny Rony M. , Haddad Chadia , Salameh Pascale
Published: November 2022

Background

Lebanon has been recognized as a center for high-quality healthcare services in the Middle East because of its prestigious facilities certified by international bodies, competent health workers, and credible pharmaceutical sector. This study assessed the professional situation of the Lebanese pharmaceutical workforce upon graduation and entry to the job market. It also evaluated the satisfaction of pharmacists with the financial, physical, and psychological aspects of their job and the effect of the current socioeconomic crisis on their profession.

Methods

A cross-sectional study was performed between January and May 2021 among 114 Lebanese pharmacists from all pharmaceutical sectors across Lebanon. A self-administered questionnaire was elaborated to assess the pharmaceutical workforce in Lebanon. The online questionnaire was built using Google Forms and disseminated via emails and social platforms.

Results

Fresh graduates seemed more oriented toward community pharmacies, and 78.1% of the participants worked at least once in their lifetime in a community pharmacy. Pharmacists from the public university worked predominantly in the community pharmacy sector, while those who graduated from private universities worked mainly as medical representatives. Hospital pharmacy comprised significantly more PharmD graduates than other sectors; medical representatives had mainly a BS pharmacy, while those working as industrial pharmacists had a Master’s degree. A low percentage (31.6%) of participants found it easy to get hold of a job across different pharmaceutical sectors while 64.0% considered the internships experience insufficient to get employed. Nearly half (48.2%) of the respondents were poorly satisfied with their job, and 54.0% of community pharmacists reported not working in their preferred field compared to 39.1% of pharmacists from other sectors. Also, 65.79% felt that the economic crisis and the consequent medication shortages affected their credibility and how society perceived them. About half (45.61%) of the participants reported that their employment status was not affected by the crisis; the rest got a second job to cover their expenses (15.79%) or changed jobs (14.91%).

Conclusion

Our study findings revealed that most Lebanese fresh graduates worked as community pharmacists, which does not correspond to their preference, the available job market, and the modern pharmacy wingspan. Most pharmacists were also financially, physically, and emotionally dissatisfied due to the Lebanese economic crisis that added heavy workloads and responsibilities without any financial raise.
Why are we still living in the past? Sri Lanka needs urgent and timely reforms of its archaic mental health laws
Authors: Hapangama Aruni , Mendis Jayan , Kuruppuarachchi K.A.L.A.
Published: November 2022

Mental health legislation protects the rights of people with mental illnesses. However, despite major social, political and cultural changes, Sri Lankan mental health services still operate on laws enacted mostly during the British rule more than a century ago, in the pre-psychotropics era, and focusing more on the detention of people with mental illnesses than on their treatment. It is high time all stakeholders made efforts for the much-awaited new Mental Health Act to pass through parliament urgently to meet the needs and protect the rights of patients, their caregivers and service providers.
Γενετικές και επιγενετικές μεταβολές στην επιπλεγμένη ή μη επιπλεγμένη με προεκλαμψία διαβητική κύηση
Authors: Τσοκάκη Θεοδώρα
Published: November 2022

O αυξανόμενος επιπολασμός της παχυσαρκίας στη σημερινή εποχή φαίνεται ότι δημιουργεί αρνητικό αντίκτυπο στην περίοδο της κύησης, οδηγώντας ολοένα και περισσότερες έγκυες ασθενείς να εμφανίζουν επιπλοκές, όπως Σακχαρώδη Διαβήτη Κύησης ή Προεκλαμψία, που αποτελεί σοβαρή υπερτασική νόσο της κύησης. Επιγενετικές τροποποιήσεις που διαμορφώνουν τη γονιδιακή ρύθμιση θεωρούνται ότι εμπλέκονται στην παθογένεια του Σακχαρώδη Διαβήτη Κύησης, ενώ επιπλέον θεωρείται ότι επιγενετικές αλλοιώσεις μπορούν να διαδραματίσουν ρόλο στη διαμεσολάβηση επιπλοκών που σχετίζονται με την εγκυμοσύνη, όπως η προεκλαμψία. Έχοντας διερευνήσει επιγενετικούς μηχανισμούς, όπως αλλαγές στη μεθυλίωση του DNA του προαγωγέα των γονιδίων που εμπλέκονται στη φλεγμονή και τροποποιήσεις της γονιδιακής έκφρασης κατά τη διάρκεια της κύησης, καταλήξαμε σε συγκεκριμένα συμπεράσματα. Τα σημαντικότερα από αυτά ήταν τα εξής: Σε ό,τι αφορά την προεκλαμψία, τα γονίδια IL15 και IL17RA είναι σημαντικά υπερμεθυλιωμένα σε ασθενείς με προεκλαμψία σε σύγκριση με υγιή άτομα. Επιπλέον, τα γονίδια ATF2, CCL25, IL12B και IL6ST υπερμεθυλιώνονται στο Σακχαρώδη Διαβήτη Κύησης σε σύγκριση με την Προεκλαμψία. Δεδομένου ότι αναδείχθηκαν διαφορετικά μοτίβα μεθυλίωσης σε γονίδια των προφλεγμονωδών παραγόντων μεταξύ Σακχαρώδη Διαβήτη Κύησης και Προεκλαμψίας, μελετήσαμε γενετικές μεταβολές στην προφλεγμονώδη κυτοκίνη ιντερλευκίνη 6 (IL-6) και στον αγγειακό ενδοθηλιακό αυξητικό παράγοντα VEGF και τον υποδοχέα του VEGF-R, μορίων που είναι γνωστό ότι εμπλέκονται στην εκδήλωση των ανωτέρω επιπλοκών, με στόχο την πιθανή αναγνώριση προδιαθεσικών παραγόντων για την έγκαιρη διάγνωση των προβλημάτων στην κύηση. H γονιδιακή ανάλυση ανέδειξε μειωμένη έκφραση του VEGF με ταυτόχρονα αυξημένη έκφραση του VEGF-R στις επιπλέγμενες κυήσεις, όπως στην Προεκλαμψία και στις κυήσεις με προϋπάρχοντα Σακαχαρώδη Διαβήτη Τύπου 2. Ανάλογα ήταν τα ευρήματα στις έγκυες γυναίκες με αυξημένο δείκτη μάζας-σώματος, οδηγώντας στο συμπέρασμα πως το γονιδιακό προφίλ της παχύσαρκης εγκύου έχει κοινό υπόβαθρο με αυτό της διαβητικής και επομένως προδιαθέτει σε επιπλεγμένη κύηση. Σε ό,τι αφορά την ανάλυση των πολυμορφισμών της ιντερλευκίνης 6, το αλλήλιο G φάνηκε να σχετίζεται με την εμφάνιση επιπλοκών στην κύηση, είτε με τη μορφή Σακχαρώδη Διαβήτη είτε με τη μορφή Προεκλαμψίας. Και σε αυτήν την περίπτωση, οι παχύσαρκες έγκυες έφεραν τον ίδιο πολυμορφισμό με τις γυναίκες με επιπλεγμένη κύηση, υποδηλώνοντας πως η παχυσαρκία αποτελεί ένα σημαντικό παράγοντα πρόκλησης επιπλεγμένης κύησης. Συνολικά, η κατανόηση της γενετικής και επιγενετικής ρύθμισης στην προεκλαμψία τόσο στο γονιδίωμα στη συστηματική κυκλοφορία της μητέρας όσο και τοπικά στον πλακούντα και σε άλλα εμπλεκόμενα όργανα, θα μπορούσε να οδηγήσει στην ανάδειξη νέων βιοδεικτών και πιθανών θεραπευτικών στόχων για τη βέλτιστη διαχείριση της κατάστασης, η οπoία δυστυχώς ακόμη και σήμερα αποτελεί σημαντική αιτία αυξημένης μητρικής θνητότητας και/ή περιγεννητικής θνησιμότητας.
Ιδέα και Ον, Κάλλος και Αλήθεια στον Πλάτωνα και στον Αριστοτέλη
Authors: Νίκας Βασίλειος
Published: November 2022

Η παρούσα διατριβή στοχεύει να (επαν)εξετάσει σύνολη την πλατωνική και αριστοτελική μεταφυσική, μέσα από ένα νέο πρίσμα που θέλει τους δύο φιλοσόφους μετόχους μιας κοινής πάλης με το αιώνιο πρόβλημα της ανεξάλειπτης διχοστασίας του Έξω και του Μέσα, του Πράγματος και του Εαυτού του, ήτοι -καλύτερα- του Όντος και της Ουσίας (του). Συγκεκριμένα, εκκινώντας από τον σκεπτικισμό απέναντι στις διαδεδομένες εξισώσεις (σε κάθε πιθανό συνδυασμό) των όρων Ον/Ιδέα/Ουσία/Είδος, στοχεύει να εξερευνήσει την αινιγματική δομή αυτού του προβλήματος μέσα από την εκ του σύνεγγυς εξέταση των λεπτών και επικαλυπτόμενων συσχετίσεων αυτών των εννοιών, που ενίοτε εκβάλλουν στο όριο της παραδοξότητας, ενέχοντας σχέσεις ταυτόχρονης διάζευξης και σύζευξης ή μιαν αλληλοπεριχώρηση που καθιστά τα όρια της κάθε έννοιας δυσδιάκριτα. Μέσα από αυτήν την μελέτη, που λαμβάνει την μορφή μιας νοητ(ικ)ής χωρο-λογίας, θα ισχυροποιηθεί η υπόθεση μιας σχετικής συνέχειας και μιας αντίστροφης συμμετρικότητας των φιλοσοφικών εγχειρημάτων του Πλάτωνα και του Αριστοτέλη, καθώς ακριβώς αυτή η παραδοξότητα ίσως επιζεί "κάτω από τα μάτια" τους και -ίσως ακόμη- παρά την πεποίθηση τους ότι την εκρίζωσαν. Όμως, ακόμη πιο σημαντικό είναι το γεγονός ότι, τελικά, όλα τα μεταφυσικά προβλήματα που αποδυναμώνουν τις φιλοσοφίες τους μπορούν να αρθρωθούν γύρω και, συνάμα, να φωτιστούν από το πρόβλημα της Διχοστασίας του Όντος και της Ουσίας: γιατί γίνεται σταδιακά φανερό ότι θα πρέπει να κινηθούμε -μέσω της εξερεύνησης της πολυεπίπεδης διαλεκτικής της μέθεξης και του χωρισμού- πέρα από το δυναστικό δίλημμα της εμμένειας και της υπερβατικότητας. Τέλος, στοχεύει να εξετάσει την πιθανότητα το ζεύγος του Κάλλους και της Αληθείας (λόγω των πρόδηλων δεσμών με τις άλλες έννοιες) να συνεισφέρει, ως "διαμεσολαβητής" στην θέση του ζεύγους Ιδέα-Ον, στην ολιστική κατανόηση της καταστατικής διχοστασίας του Όντος και της Ουσίας.
Βελτιστοποίηση διαχείρισης ενεργών δικτύων διανομής ηλεκτρικής ενέργειας με ετερογενείς πηγές ευελιξίας
Authors: Ευαγγελόπουλος Βασίλειος
Published: November 2022

Η διαρκώς αυξανόμενη παρουσία διανεμημένων ενεργειακών πόρων (ΔΕΠ) στο ηλεκτρικό δίκτυο, υπό τη μορφή διανεμημένης παραγωγής, αποθήκευσης ενέργειας και ευέλικτων φορτίων, θέτει σημαντικές προκλήσεις στον Διαχειριστή του δικτύου διανομής (ΔΔ). Την ίδια στιγμή, οι ΔΕΠ μπορούν να αποτελέσουν πηγές ευέλικτης διαχείρισης της λειτουργίας του ΔΔ. Η παρούσα διδακτορική διατριβή εστιάζει στη βελτιστοποίηση της διαχείρισης των ενεργών ΔΔ αξιοποιώντας ετερογενείς πηγές ευελιξίας, δηλαδή την ευελιξία που προέρχεται από ΔΕΠ διαφόρων τεχνολογιών με διαφορετικά τεχνικά χαρακτηριστικά. Αρχικά, παρουσιάζονται οι επιπτώσεις που προκύπτουν από τη διαρκώς αυξανόμενη διείσδυση των ΔΕΠ, αλλά και τα οφέλη τους ως πηγές ευελιξίας στα ενεργά ΔΔ. Ακολουθεί μια βιβλιογραφική ανασκόπηση σχετικά με τα μοντέλα βελτιστοποίησης και τις μεθόδους που χρησιμοποιούνται για τη διαχείριση των ενεργών ΔΔ, τόσο στο στάδιο προγραμματισμού λειτουργίας, όσο και στο στάδιο λειτουργίας και κατανομής σε πραγματικό χρόνο. Στη συνέχεια, η έρευνα εστιάζεται στην ανάπτυξη καινοτόμων μοντέλων βελτιστοποίησης που καλύπτουν, τεχνικά και οικονομικά, τα παραπάνω στάδια διαχείρισης των ενεργών ΔΔ. Το πρόβλημα του προγραμματισμού λειτουργίας των ενεργών ΔΔ προσεγγίζεται με ένα καινοτόμο μοντέλο στοχαστικού προγραμματισμού δύο σταδίων που λαμβάνει υπόψη σταθμισμένα σενάρια πρόβλεψης του ηλεκτρικού φορτίου και της μεταβλητής παραγωγής από ανανεώσιμες πηγές ενέργειας (ΑΠΕ). Με τον προγραμματισμό λειτουργίας καθορίζονται: α) το πρόγραμμα ροών ισχύος στη διασύνδεση του ΔΔ με το σύστημα μεταφοράς, και β) η ευελιξία των ΔΕΠ που δεσμεύεται για το στάδιο της κατανομής σε πραγματικό χρόνο. Στη συνέχεια, το πρόβλημα της κατανομής της ευελιξίας των ΔΕΠ σε πραγματικό χρόνο επιλύεται με ένα καινοτόμο μοντέλο προβλεπτικού ελέγχου προκειμένου να περιοριστούν οι αποκλίσεις από το πρόγραμμα λειτουργίας και να ελαχιστοποιηθεί το λειτουργικό κόστος του ΔΔ. Επιπλέον, λαμβάνεται υπόψη ο χρόνος απόκρισης των πηγών ευελιξίας στις εντολές κατανομής που αποστέλλει ο Διαχειριστής του ΔΔ. Τέλος, η οικονομική διαχείριση των ενεργών ΔΔ μοντελοποιείται με διεπίπεδο προγραμματισμό βασισμένο στο μοντέλο ηγεσίας του Stackelberg με έναν ηγέτη και πολλούς ακόλουθους, και επιλύεται ως πρόβλημα μαθηματικού προγραμματισμού με περιορισμούς ισορροπίας. Ο Διαχειριστής του ΔΔ (ηγέτης) οργανώνει μία τοπική αγορά ευελιξίας, στην οποία συμμετέχουν φορείς σωρευτικής εκπροσώπησης ευέλικτων φορτίων, ΑΠΕ και συστημάτων αποθήκευσης ενέργειας, ως πάροχοι υπηρεσιών ευελιξίας (ακόλουθοι).
Properties of theta-H-compact sets in hereditary m-spaces
Authors: Al-Omari Ahmad , Noiri Takashi
Published: November 2022

Let (X,m, H) be a hereditary m-space. A subset A of X is said to be θ-H-compact relative to X if for every cover U of A by m(θ)-open sets of X, there exists a finite subset U0 of U such that A \ ∪ U0 ∈ H. We obtain several properties of these sets. Also, we define and investigate two kinds of strong forms of “θ-H-compact relative to X”.