bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of medical students’ clinical performance using high-fidelity simulation: comparison of peer and instructor assessment
Authors: Yu Ji Hye , Lee Mi Jin , Kim Soon Sun , Yang Min Jae , Cho Hyo Jung , Noh Choong Kyun , Lee Gil Ho , Lee Su Kyung , Song Mi Ryoung , Lee Jang Hoon , Kim Miran , Jung Yun Jung
Published: September 2021

Background

High-fidelity simulators are highly useful in assessing clinical competency; they enable reliable and valid evaluation. Recently, the importance of peer assessment has been highlighted in healthcare education, and studies using peer assessment in healthcare, such as medicine, nursing, dentistry, and pharmacy, have examined the value of peer assessment. This study aimed to analyze inter-rater reliability between peers and instructors and examine differences in scores between peers and instructors in the assessment of high-fidelity-simulation-based clinical performance by medical students.

Methods

This study analyzed the results of two clinical performance assessments of 34 groups of fifth-year students at Ajou University School of Medicine in 2020. This study utilized a modified Queen’s Simulation Assessment Tool to measure four categories: primary assessment, diagnostic actions, therapeutic actions, and communication. In order to estimate inter-rater reliability, this study calculated the intraclass correlation coefficient and used the Bland and Altman method to analyze agreement between raters. A t-test was conducted to analyze the differences in evaluation scores between colleagues and faculty members. Group differences in assessment scores between peers and instructors were analyzed using the independent t-test.

Results

Overall inter-rater reliability of clinical performance assessments was high. In addition, there were no significant differences in overall assessment scores between peers and instructors in the areas of primary assessment, diagnostic actions, therapeutic actions, and communication.

Conclusions

The results indicated that peer assessment can be used as a reliable assessment method compared to instructor assessment when evaluating clinical competency using high-fidelity simulators. Efforts should be made to enable medical students to actively participate in the evaluation process as fellow assessors in high-fidelity-simulation-based assessment of clinical performance in situations similar to real clinical settings.
Biomedical engineering and ethics: reflections on medical devices and PPE during the first wave of COVID-19
Authors: Maccaro Alessia , Piaggio Davide , Dodaro Concetta Anna , Pecchia Leandro
Published: September 2021

In March 2019, the World Health Organization (WHO) declared that humanity was entering a global pandemic phase. This unforeseen situation caught everyone unprepared and had a major impact on several professional categories that found themselves facing important ethical dilemmas. The article revolves around the category of biomedical and clinical engineers, which were among those most involved in dealing with and finding solutions to the pandemic. In hindsight, the major issues brought to the attention of biomedical engineers have raised important ethical implications, such as the allocation of resources, the responsibilities of science and the inadequacy and non-universality of the norms and regulations on biomedical devices and personal protective equipment. These issues, analyzed one year after the first wave of the pandemic, come together in the appeal for responsibility for thought, action and, sometimes, even silence. This highlights the importance of interdisciplinarity and the definitive collapse of the Cartesian fragmentation of knowledge, calling for the creation of more fora, where this kind of discussions can be promoted.
Neonatologists’ decision-making for resuscitation and non-resuscitation of extremely preterm infants: ethical principles, challenges, and strategies—a qualitative study
Authors: Cavolo Alice , de Casterlé Bernadette Dierckx , Naulaers Gunnar , Gastmans Chris
Published: September 2021

Background

Deciding whether to resuscitate extremely preterm infants (EPIs) is clinically and ethically problematic. The aim of the study was to understand neonatologists’ clinical–ethical decision-making for resuscitation of EPIs.

Methods

We conducted a qualitative study in Belgium, following a constructivist account of the Grounded Theory. We conducted 20 in-depth, face-to-face, semi-structured interviews with neonatologists. Data analysis followed the qualitative analysis guide of Leuven.

Results

The main principles guiding participants’ decision-making were EPIs’ best interest and respect for parents’ autonomy. Participants agreed that justice as resource allocation should not be considered in resuscitation decision-making. The main ethical challenge for participants was dealing with the conflict between EPIs’ best interest and respect for parents’ autonomy. This conflict was most prominent when parents and clinicians disagreed about births within the gray zone (24–25 weeks). Participants’ coping strategies included setting limits on extent of EPI care provided and rigidly following established guidelines. However, these strategies were not always feasible or successful. Although rare, these situations often led to long-lasting moral distress.

Conclusions

Participants’ clinical–ethical reasoning for resuscitation of EPIs can be mainly characterized as an attempt to balance EPIs’ best interest and respect for parents’ autonomy. This approach could explain why neonatologists considered conflicts between these principles as their main ethical challenge and why lack of resolution increases the risk of moral distress. Therefore, more research is needed to better understand moral distress in EPI resuscitation decisions.

Clinical Trial Registration: The study received ethical approval from the ethics committee of UZ/KU Leuven (S62867). Confidentiality of personal information and anonymity was guaranteed in accordance with the General Data Protection Regulation of 25 May 2018.
Patient involvement at the managerial level: the effectiveness of a patient and family advisory council at a regional cancer centre in Sweden
Authors: Fredriksson Mio , Modigh Anton
Published: September 2021

Background

In cancer care as well as other types of treatment and care, little is known about the contribution of Patient and Family Advisory Councils (PFACs) operating at the managerial level in healthcare organizations. The aim of the study was to investigate the effectiveness of a Swedish PFAC operating at the managerial level at one of Sweden’s six regional cancer centres.

Methods

This was a qualitative, single-case study based on interviews with PFAC participants and meeting minutes from PFAC meetings. These were analysed using a modified version of a framework developed by Abelson et al. to design and evaluate collective involvement processes in the healthcare sector: (i) representation; (ii) information; (iii) process or procedures and (iv) outcomes and decisions.

Results

The descriptive representation was good regarding geographical location and cancer diagnosis. Information from the regional cancer centre was an important part of the meeting agenda. The procedures encouraged everyone to speak up, and the participants saw the representatives from the regional cancer centre as allies against the hospitals and regions, raising some questions about the PFAC's independence. Regarding outcomes, most participants did not know to what extent their work had led to any improvements in cancer care. However, they still regarded the council as effective, as issues the participants raised were listened to by the representatives from the regional cancer centre and ‘taken further’ in the healthcare organization.

Conclusions

The participants were satisfied with being listened to, but they found it difficult to know whether their work had led to improvements, in part because they did not know enough about how the healthcare organization worked above the care-provision level. This was a hurdle to achieving change. The study suggests it is more difficult for patients and next of kin to participate at the managerial level, compared to the care-provision level in healthcare systems, where they could potentially influence important aspects of cancer care and policy, since it is at these levels strategic decisions about priorities in cancer care and service configurations are made. This indicates that there is a particular need for guidance and support for patient and public involvement to work successfully at this level, which may include relevant education and training in system knowledge.
An in vivo pharmacokinetic study of metformin microparticles as an oral sustained release formulation in rabbits
Authors: Bouriche Sihem , Alonso-García Angela , Cárceles-Rodríguez Carlos M. , Rezgui Farouk , Fernández-Varón Emilio
Published: September 2021

Background

Metformin hydrochloride is a biguanide derivative that has been widely used to treat type 2 diabetes in humans. In veterinary medicine, metformin has shown increasing potential for diabetes treatment in different species, such as equids, dogs, cats and rabbits. It is highly hydrophilic, with incomplete gastrointestinal absorption and very large variability in absolute bioavailability between species, ranging from 4% in equids to 60% in humans. Metformin also shows a short half-life of approximately 2 h in dogs, cats, horses and humans. The objectives of this study were to evaluate a poly (lactic acid) (PLA) metformin microparticle formulation to test in rabbits and conduct a pharmacokinetics study of intravenous (SIV) and oral solution (SPO) metformin administration and oral PLA microparticle (SPLA) administration to rabbits to evaluate the improvement in the metformin pharmacokinetics profile.

Results

Metformin-loaded PLA microparticles were characterized by a spherical shape and high encapsulation efficiency. The results from Fourier transform infrared (FTIR) spectroscopy suggested the presence of interactions between metformin and PLA. X-Ray diffraction (XRD) analysis corroborated the results from the differential scanning calorimetry (DSC) studies, showing that metformin is present in an amorphous state within the microparticles. Physicochemical characterization suggested that PLA and metformin hydrochloride interacted within the microparticles via hydrogen bonding interactions. The pharmacokinetic study in rabbits showed sustained-release characteristics from the prepared microparticles with a delay in the time needed to reach the maximum concentration (Tmax), decreased Cmaxand bioavailability, and increased mean residence time (MRT) and half-life compared to the pure drug solution.

Conclusions

Metformin-loaded PLA microparticles showed optimal and beneficial properties in terms of their physicochemical characteristics, making them suitable for use in an in vivo pharmacokinetic study. The pharmacokinetic parameters of the metformin microparticles from the in vivo study showed a shorter Tmax, longer MRT and half-life, decreased Cmaxand the prolonged/sustained release expected for metformin. However, the unexpected decrease in bioavailability of metformin from the microparticles with respect to the oral solution should be evaluated for microparticle and dose design in future works, especially before being tested in other animal species in veterinary medicine.
Occurrence of potentially zoonotic and cephalosporin resistant enteric bacteria among shelter dogs in the Central and South-Central Appalachia
Authors: Verma Ashutosh , Carney Kimberly , Taylor Marina , Amsler Kaitlyn , Morgan Joey , Gruszynski Karen , Erol Erdal , Carter Craig , Locke Stephan , Callipare Ashton , Shah Devendra H.
Published: September 2021

Background

Antimicrobial resistance and presence of zoonotic enteropathogens in shelter dogs pose a public health risk to shelter workers and potential adopters alike. In this study we investigated the prevalence of zoonotic bacterial pathogens and cephalosporin resistant (CefR) enteric bacteria in the feces of apparently healthy shelter dogs in the Cumberland Gap Region (CGR) in the US states of Kentucky, Tennessee and Virginia.

Results

Fecal samples of 59 dogs from 10 shelters in the CGR of Central and South-Central Appalachia were screened for the presence of Campylobacter jejuni, Clostridium perfringens, Salmonella and CefR enteric bacteria. C. jejuni, C. perfringens were detected by PCR based assays. Culture and PCR were used for Salmonella detection. Of 59 dogs, fecal samples from 14 (23.7%) and 8 (13.6%) dogs tested positive for cpa and hipO genes of C. perfringens and C. jejuni, respectively. Salmonella was not detected in any of the tested samples by PCR or culture. CefR enteric bacteria were isolated on MacConkey agar supplemented with ceftiofur followed by identification using MALDI-TOF. Fecal samples from 16 dogs (27.1%) yielded a total of 18 CefR enteric bacteria. Majority of CefR isolates (14/18, 77.8%) were E. coli followed by, one isolate each of Enterococcus hirae, Acinetobacter baumannii, Acinetobacter pittii, and Pseudomonas aeruginosa. CefR enteric bacteria were tested for resistance against 19- or 24-antibiotic panels using broth microdilution method. Seventeen (94.4%) CefR bacteria were resistant to more than one antimicrobial agent, and 14 (77.8%) displayed multidrug resistance (MDR).

Conclusions

This study shows that shelter dogs within the CGR not only carry zoonotic bacterial pathogens, but also shed multidrug resistant enteric bacteria in their feces that may pose public health risks.
Oxygenation strategies during flexible bronchoscopy: a review of the literature
Authors: Pelaia Corrado , Bruni Andrea , Garofalo Eugenio , Rovida Serena , Arrighi Eugenio , Cammarota Gianmaria , Navalesi Paolo , Pelaia Girolamo , Longhini Federico
Published: September 2021

During flexible fiberoptic bronchoscopy (FOB) the arterial partial pressure of oxygen can drop, increasing the risk for respiratory failure. To avoid desaturation episodes during the procedure several oxygenation strategies have been proposed, including conventional oxygen therapy (COT), high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV). By a review of the current literature, we merely describe the clinical practice of oxygen therapies during FOB. We also conducted a pooled data analysis with respect to oxygenation outcomes, comparing HFNC with COT and NIV, separately. COT showed its benefits in patients undergoing FOB for broncho-alveolar lavage (BAL) or brushing for cytology, in those with peripheral arterial oxyhemoglobin saturation < 93% prior to the procedure or affected by obstructive disorder. HFNC is preferable over COT in patients with mild to moderate acute respiratory failure (ARF) undergoing FOB, by improving oxygen saturation and decreasing the episodes of desaturation. On the opposite, CPAP and NIV guarantee improved oxygenation outcomes as compared to HFNC, and they should be preferred in patients with more severe hypoxemic ARF during FOB.
Contralateral risk-reducing local therapy in breast cancer patients with BRCA1/2 mutations: systemic review and meta-analysis
Authors: Jia Ziqi , Li Jiaxin , Zhang Yuelun , Wang Xin , Xing Jiahua , Xing Zeyu , Huang Xin , Liu Gang , Zhang Menglu , Feng Kexin , Wu Jiang , Wang Wenyan , Wang Jie , Liu Jiaqi , Wang Xiang
Published: September 2021

Background

Unilateral breast cancer (UBC) patients with germline pathogenicBRCA1/2variants have a higher risk of developing contralateral breast cancer (CBC) and need contralateral risk-reducing local treatments, including contralateral risk-reducing mastectomy (CRRM) and prophylactic irradiation (CPI). The aim of our study was to systematically explore the efficacy of CRRM and CPI in reducing CBC risk and increasing survival.

Methods

A search was done, and eligible randomized trials and cohort studies should include and compare UBC patients with germline pathogenicBRCA1/2variants who have and have not received contralateral risk-reducing local treatment. Random-effects meta-analysis was used in this study. Primary outcomes of the studies included overall survival (OS) and the incidence of contralateral breast cancer (CBC), and secondary outcomes included breast cancer-specific survival (BCSS).

Results

A total of five studies with 1769 UBC patients with germline pathogenicBRCA1/2variants were enrolled in our meta-analysis. CRRM was correlated with a lower risk of CBC in UBC patients with germline pathogenicBRCA1/2variants (summary RR = 0.07; 95%CI 0.03–0.13, I2 = 3%), a significantly increased OS (summary RR, 1.15; 95%CI 1.04–1.26, I2 = 26%) and a significantly increased BCSS (summary RR, 1.18; 95%CI 1.07–1.31, I2 = 64%) compared with surveillance. CPI also decreased the risk of CBC (RR 0.02; 95%CI 0.05–0.88) but did not significantly improve OS (RR 0.97; 95%CI 0.90–1.05) and BCSS (RR 0.97; 95%CI 0.90–1.05) compared with surveillance.

Conclusions

CRRM reduces CBC risk and increases OS and BCSS in UBC patients with germline pathogenicBRCA1/2variants, and could be offered as a risk-reducing local treatment. For those who oppose CRRM, CPI could be offered for CBC-risk reduction, while its survival benefit is still uncertain.
Improving interagency service integration of the Australian Nurse Family Partnership Program for First Nations women and babies: a qualitative study
Authors: Massi Luciana , Hickey Sophie , Maidment Sarah-Jade , Roe Yvette , Kildea Sue , Nelson Carmel , Kruske Sue
Published: September 2021

Background

The Australian Nurse Family Partnership Program (ANFPP) is an evidence-based, home visiting program that offers health education, guidance, social and emotional support to first-time mothers having Aboriginal and/or Torres Strait Islander (First Nations) babies. The community-controlled sector identified the need for specialised support for first time mothers due to the inequalities in birthing and early childhood outcomes between First Nations’ and other babies in Australia. The program is based on the United States’ Nurse Family Partnership program which has improved long-term health outcomes and life trajectories for mothers and children. International implementation of the Nurse Family Partnership program has identified interagency service integration as key to program recruitment, retention, and efficacy. How the ANFPP integrates with other services in an Australian urban setting and how to improve this is not yet known. Our research explores the barriers and enablers to interagency service integration for the Australian Nurse Family Partnership Program ANFPP in an urban setting.

Methods

A qualitative study using individual and group interviews. Purposive and snowball sampling was used to recruit clients, staff (internal and external to the program), Elders and family members. Interviews were conducted using a culturally appropriate ‘yarning’ method with clients, families and Elders and semi-structured interview guide for staff. Interviews were audio-recorded and transcribed prior to reflexive thematic analysis.

Results

Seventy-six participants were interviewed: 26 clients, 47 staff and 3 Elders/family members. Three themes were identified as barriers and three as enablers. Barriers: 1) confusion around program scope, 2) duplication of care, and 3) tensions over ‘ownership’ of clients. Enablers (existing and potential): 1) knowledge and promotion of the program; 2) cultural safety; and 3) case coordination, co-location and partnership forums.

Conclusion

Effective service integration is essential to maximise access and acceptability of the ANFPP; we provide practical recommendations to improve service integration in this context.
Prevalence of dyslipidemia and gene polymorphisms of ABCB1 and SLCO1B1 in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe populations with coronary heart disease in Xinjiang, China
Authors: Wang Tingting , Sun Li , Xu Li , Zhao Ting , Feng Jie , Yu Luhai , Wu Jianhua , Li Hongjian
Published: September 2021

Background

Dyslipidemia is a predisposing factor for coronary heart disease (CHD). High-intensity statin therapy is recommended as secondary prevention. ABCB1 and SLCO1B1 genes influence the efficacy and safety of statins. Xinjiang is a multi-ethnic area; however, little is known about the prevalence of dyslipidemia and gene polymorphisms of ABCB1 and SLCO1B1 in minority groups with CHD.

Objective

To measure levels of lipid and apolipoprotein and the prevalence of dyslipidemia and gene polymorphisms of ABCB1, SLCO1B1 in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe populations with CHD in Xinjiang.

Methods

This descriptive retrospective study compares lipid levels in ethnic groups using Kruskal-Wallis test or analysis of variance. The study compared gene polymorphisms and the prevalence of dyslipidemia among different ethnic groups using the chi-square test. The lipid profiles in plasma were measured before lipid-lowering therapy using commercially available kits. Genotyping of SLCO1B1 and ABCB1 variants was performed using sequencing by hybridization.

Results

A total of 2218 patients were successfully screened, including 1044 Han, 828 Uygur, 113 Kazak, 138 Hui, 39 Tatar, 36 Kirgiz, and 20 Sibe patients. The overall mean age was 61.8 ± 10.8 years, and 72.5% of participants were male. Dyslipidemia prevalence in these ethnic groups was 42.1, 49.8, 52.2, 40.6, 48.7, 41.7, and 45.0%, respectively. The prevalence of dyslipidemia, high total cholesterol (TC), high triglycerides (TG), and high low density lipoprotein cholesterol (LDL-C) differed significantly among the groups (P = 0.024; P < 0.001; P < 0.001; P < 0.001, respectively). For the Han group, high LDL-C, high TC, and high TG prevalence differed significantly by gender (P = 0.001, P = 0.022, P = 0.037, respectively). The prevalence of high TC, high TG, and low high density lipoprotein cholesterol (HDL-C) differed significantly by gender in the Uygur group (P = 0.006, P = 0.004, P < 0.001, respectively). The prevalence of high TC in Hui patients significantly differed by gender (P = 0.043). These findings suggest that polymorphisms in ABCB1 and C3435T differ significantly across ethnicities (P < 0.001).

Conclusions

The prevalences of dyslipidemia, high TC, high TG, and high LDL-C in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe CHD patients in Xinjiang differed concerning ethnicity. Ethnic, gender, and lifestyle were the key factors that affected the lipid levels of the population. The prevalence of polymorphisms of ABCB1 and C3435T significantly differed across ethnicities. These findings will aid the selection of precision lipid-lowering medications and prevention and treatment of CHD according to ethnicity in Xinjiang.
Health-related quality of life in men with localized prostate cancer treated with radiotherapy: validation of an abbreviated version of the Expanded Prostate Cancer Index Composite for Clinical Practice in Spain
Authors: Zapatero Almudena , Maldonado Pijoan Xavier , Gómez-Caamaño Antonio , Pardo Masferrer José , Macías Hernández Víctor , Hervás Morón Asunción , Muñoz García Julia Luisa , Palacios Eito Amalia , Anguita-Alonso Paloma , González-Junco Cristina , López Torrecilla José
Published: September 2021

Background

Health-related quality of life (HRQoL) is greatly affected by prostate cancer (PCa) and associated treatments. This study aimed to measure the impact of radiotherapy on HRQoL and to further validate the Spanish version of the 16-item Expanded Prostate Cancer Index Composite (EPIC-16) in routine clinical practice.

Methods

An observational, non-interventional, multicenter study was conducted in Spain with localized PCa patients initiating treatment with external beam radiotherapy (EBRT) or brachytherapy (BQT). Changes from baseline in EPIC-16, University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), and patient-perceived health status were longitudinally assessed at end of radiotherapy (V2) and 90 days thereafter (V3). Psychometric evaluations of the Spanish EPIC-16 were conducted.

Results

Of 516 patients enrolled, 495 were included in the analysis (EBRT, n = 361; BQT, n = 134). At baseline, mean (standard deviation [SD]) EPIC-16 global scores were 11.9 (7.5) and 10.3 (7.7) for EBRT and BQT patients, respectively; scores increased, i.e., HRQoL worsened, from baseline, by mean (SD) of 6.8 (7.6) at V2 and 2.4 (7.4) at V3 for EBRT and 4.2 (7.6) and 3.9 (8.2) for BQT patients. Changes in Spanish EPIC-16 domains correlated well with urinary, bowel, and sexual UCLA-PCI domains. EPIC-16 showed good internal consistency (Cronbach’s alpha = .84), reliability, and construct validity.

Conclusion

The Spanish EPIC-16 questionnaire demonstrated sensitivity, strong discriminative properties and reliability, and validity for use in clinical practice. EPIC-16 scores worsened after radiotherapy in different HRQoL domains; however, a strong tendency towards recovery was seen at the 3-month follow-up visit.
Viability of a MSQOL-54 general health-related quality of life score using bifactor model
Authors: Giordano Andrea , Testa Silvia , Bassi Marta , Cilia Sabina , Bertolotto Antonio , Quartuccio Maria Esmeralda , Pietrolongo Erika , Falautano Monica , Grobberio Monica , Niccolai Claudia , Allegri Beatrice , Viterbo Rosa Gemma , Confalonieri Paolo , Giovannetti Ambra Mara , Cocco Eleonora , Grasso Maria Grazia , Lugaresi Alessandra , Ferriani Elisa , Nocentini Ugo , Zaffaroni Mauro , De Livera Alysha , Jelinek George , Solari Alessandra , Rosato Rosalba
Published: September 2021

Background

MSQOL-54 is a multidimensional, widely-used, health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). Findings from the validation study suggested that the two MSQOL-54 composite scores are correlated. Given this correlation, it could be assumed that a unique total score of HRQOL may be calculated, with the advantage to provide key stakeholders with a single overall HRQOL score. We aimed to assess how well the bifactor model could account for the MSQOL-54 structure, in order to verify whether a total HRQOL score can be calculated.

Methods

A large international database (3669 MS patients) was used. By means of confirmatory factor analysis, we estimated a bifactor model in which every item loads onto both a general factor and a group factor. Fit of the bifactor model was compared to that of single and two second-order factor models by means of Akaike information and Bayesian information criteria reduction. Reliability of the total and subscale scores was evaluated with Mc Donald’s coefficients (omega, and omega hierarchical).

Results

The bifactor model outperformed the two second-order factor models in all the statistics. All items loaded satisfactorily (≥ 0.40) on the general HRQOL factor, except the sexual function items. Omega coefficients for total score were very satisfactory (0.98 and 0.87). Omega hierarchical for subscales ranged between 0.22 to 0.57, except for the sexual function (0.70).

Conclusions

The bifactor model is particularly useful when it is intended to acknowledge multidimensionality and at the same time take account of a single general construct, as the HRQOL related to MS. The total raw score can be used as an estimate of the general HRQOL latent score.
Bone morphogenetic protein receptor 2 inhibition destabilizes microtubules promoting the activation of lysosomes and cell death of lung cancer cells
Authors: Mondal Arindam , NeMoyer Rachel , Vora Mehul , Napoli Logan , Syed Zoya , Langenfeld Elaine , Jia Dongxuan , Peng Youyi , Gilleran John , Roberge Jacques , Rongo Christopher , Jabbour Salma K. , Langenfeld John
Published: September 2021

Background

Recent studies have shown that bone morphogenetic protein receptor 2 (BMPR2) regulates cell survival signaling events in cancer cells independent of the BMP type 1 receptor (BMPR1) or the Smad-1/5 transcription factor. Mutations in BMPR2 trafficking proteins leads to overactive BMP signaling, which leads to neurological diseases caused by BMPR2 stabilization of the microtubules. It is not known whether BMPR2 regulates the microtubules in cancer cells and what effect this has on cell survival. It is also not known whether alterations in BMPR2 trafficking effects activity and response to BMPR2 inhibitors.

Methods

We utilized BMPR2 siRNA and the BMP receptor inhibitors JL5 and Ym155, which decrease BMPR2 signaling and cause its mislocalization to the cytoplasm. Using the JL5 resistant MDA-MD-468 cell line and sensitive lung cancer cell lines, we examined the effects of BMPR2 inhibition on BMPR2 mislocalization to the cytoplasm, microtubule destabilization, lysosome activation and cell survival.

Results

We show that the inhibition of BMPR2 destabilizes the microtubules. Destabilization of the microtubules leads to the activation of the lysosomes. Activated lysosomes further decreases BMPR2 signaling by causing it to mislocalizated to the cytoplasm and/or lysosome for degradation. Inhibition of the lysosomes with chloroquine attenuates BMPR2 trafficking to the lysosome and cell death induced by BMPR2 inhibitors. Furthermore, in MDA-MD-468 cells that are resistant to JL5 induced cell death, BMPR2 was predominately located in the cytoplasm. BMPR2 failed to localize to the cytoplasm and/or lysosome following treatment with JL5 and did not destabilize the microtubules or activate the lysosomes.

Conclusions

These studies reveal that the inhibition of BMPR2 destabilizes the microtubules promoting cell death of cancer cells that involves the activation of the lysosomes. Resistance to small molecules targeting BMPR2 may occur if the BMPR2 is localized predominantly to the cytoplasm and/or fails to localize to the lysosome for degradation.
Systemic inflammation alters the neuroinflammatory response: a prospective clinical trial in traumatic brain injury
Authors: Lassarén Philipp , Lindblad Caroline , Frostell Arvid , Carpenter Keri L. H. , Guilfoyle Mathew R. , Hutchinson Peter J. A. , Helmy Adel , Thelin Eric Peter
Published: September 2021

Background

Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition.

Methods

TBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used.

Results

Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood.

Conclusions

Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations.

Graphical abstract
The HIV-1 capsid and reverse transcription
Authors: Aiken Christopher , Rousso Itay
Published: September 2021

The viral capsid plays a key role in HIV-1 reverse transcription. Recent studies have demonstrated that the small molecule IP6 dramatically enhances reverse transcription in vitro by stabilizing the viral capsid. Reverse transcription results in marked changes in the biophysical properties of the capsid, ultimately resulting in its breakage and disassembly. Here we review the research leading to these advances and describe hypotheses for capsid-dependent HIV-1 reverse transcription and a model for reverse transcription-primed HIV-1 uncoating.
Frequency-dependent force direction elucidates neural control of balance
Authors: Shiozawa Kaymie , Lee Jongwoo , Russo Marta , Sternad Dagmar , Hogan Neville
Published: September 2021

Background

Maintaining upright posture is an unstable task that requires sophisticated neuro-muscular control. Humans use foot–ground interaction forces, characterized by point of application, magnitude, and direction to manage body accelerations. When analyzing the directions of the ground reaction forces of standing humans in the frequency domain, previous work found a consistent pattern in different frequency bands. To test whether this frequency-dependent behavior provided a distinctive signature of neural control or was a necessary consequence of biomechanics, this study simulated quiet standing and compared the results with human subject data.

Methods

Aiming to develop the simplest competent and neuromechanically justifiable dynamic model that could account for the pattern observed across multiple subjects, we first explored the minimum number of degrees of freedom required for the model. Then, we applied a well-established optimal control method that was parameterized to maximize physiologically-relevant insight to stabilize the balancing model.

Results

If a standing human was modeled as a single inverted pendulum, no controller could reproduce the experimentally observed pattern. The simplest competent model that approximated a standing human was a double inverted pendulum with torque-actuated ankle and hip joints. A range of controller parameters could stabilize this model and reproduce the general trend observed in experimental data; this result seems to indicate a biomechanical constraint and not a consequence of control. However, details of the frequency-dependent pattern varied substantially across tested control parameter values. The set of parameters that best reproduced the human experimental results suggests that the control strategy employed by human subjects to maintain quiet standing was best described by minimal control effort with an emphasis on ankle torque.

Conclusions

The findings suggest that the frequency-dependent pattern of ground reaction forces observed in quiet standing conveys quantitative information about human control strategies. This study’s method might be extended to investigate human neural control strategies in different contexts of balance, such as with an assistive device or in neurologically impaired subjects.
Enabling visually impaired people to learn three-dimensional tactile graphics with a 3DOF haptic mouse
Authors: Memeo Mariacarla , Jacono Marco , Sandini Giulio , Brayda Luca
Published: September 2021

Background

In this work, we present a novel sensory substitution system that enables to learn three dimensional digital information via touch when vision is unavailable. The system is based on a mouse-shaped device, designed to jointly perceive, with one finger only, local tactile height and inclination cues of arbitrary scalar fields. The device hosts a tactile actuator with three degrees of freedom: elevation, roll and pitch. The actuator approximates the tactile interaction with a plane tangential to the contact point between the finger and the field. Spatial information can therefore be mentally constructed by integrating local and global tactile cues: the actuator provides local cues, whereas proprioception associated with the mouse motion provides the global cues.

Methods

The efficacy of the system is measured by a virtual/real object-matching task. Twenty-four gender and age-matched participants (one blind and one blindfolded sighted group) matched a tactile dictionary of virtual objects with their 3D-printed solid version. The exploration of the virtual objects happened in three conditions, i.e., with isolated or combined height and inclination cues. We investigated the performance and the mental cost of approximating virtual objects in these tactile conditions.

Results

In both groups, elevation and inclination cues were sufficient to recognize the tactile dictionary, but their combination worked at best. The presence of elevation decreased a subjective estimate of mental effort. Interestingly, only visually impaired participants were aware of their performance and were able to predict it.

Conclusions

The proposed technology could facilitate the learning of science, engineering and mathematics in absence of vision, being also an industrial low-cost solution to make graphical user interfaces accessible for people with vision loss.
Visceral adiposity index outperforms conventional anthropometric assessments as predictor of diabetes mellitus in elderly Chinese: a population-based study
Authors: Tsou Meng-Ting , Chang Yu-Chen , Hsu Ching-Ping , Kuo Yang-Che , Yun Chun-Ho , Huang Wei-Hsin , Hu Kuang-Chun , Liu Chia-Yuan , Chen Ying-Ju , Sung Kuo-Tzu , Liu Chuan-Chuan , Hung Chung-Lieh , Kuo Jen-Yuan , Chen Tung-Ying , Hung Ta-Chuan , Yeh Hung-I.
Published: September 2021

Background

This study assessed the performance of visceral adiposity index and body shape index in predicting diabetes mellitus (DM) risk and compared their predictive ability to that of body mass index and waist circumference.

Methods

Among 8249 consecutive subjects who attended the Nationwide Health Check Up System for Senior Citizens (≥ 65 years) between 2008 and 2018, we examined the associations of several adiposity indices with DM risk and explored gender differences.

Results

Among all adiposity indicators, Chinese visceral adiposity index (CVAI) demonstrated the highest discriminatory ability for diabetes mellitus with area under receiver operating characteristic curves (AUC) of 0.65, 0.68, and 0.66 for men, women, and all participants, respectively, and optimal cut-offs set as 126.09 in men and 117.77 in women. Compared with body shape index (ABSI), both CVAI and VAI were strongly associated with baseline DM (adjusted OR: 4.85, 95% CI: 4.05–5.82 and 4.22, 95% CI: 3.53–5.05 for 4th vs 1st quartile groups by CVAI and VAI, P < 0.001), which was more pronounced in older adult women (Pinteraction < 0.05). Over a median of 5.25 years (IQR: 3.07–6.44 years) follow-up, Cox regression models showed higher predictive ability of CVAI and VAI compared to ABSI. Further, both CVAI and VAI independently predicted new-onset DM (adjusted HR: 1.29, 95% CI: 1.22–1.37 and 1.16, 95% CI: 1.11–1.21 by CVAI and VAI) and composite endpoint of new DM and death among those without baseline DM.

Conclusions

Our population-based data demonstrated that Chinese visceral adiposity index may serve as a superior clinical indicator of diabetes when compared with conventional anthropometric indices among older adult Chinese, especially in women.
Ghanaian views of short-term medical missions: The pros, the cons, and the possibilities for improvement
Authors: Mantey Efua Esaaba , Doh Daniel , Lasker Judith N. , Alang Sirry , Donkor Peter , Aldrink Myron
Published: September 2021

Background

Various governments in Ghana have tried to improve healthcare in the country. Despite these efforts, meeting health care needs is a growing concern to government and their citizens. Short term medical missions from other countries are one of the responses to meet the challenges of healthcare delivery in Ghana. This research aimed to understand Ghanaian perceptions of short-term missions from the narratives of host country staff involved. The study from which this paper is developed used a qualitative design, which combined a case study approach and political economy analysis involving in-depth interviews with 28 participants.

Result

Findings show short term medical mission programs in Ghana were largely undertaken in rural communities to address shortfalls in healthcare provision to these areas. The programs were often delivered free and were highly appreciated by communities and host institutions. While the contributions of STMM to health service provision have been noted, there were challenges associated with how they operated. The study found concerns over language and how volunteers effectively interacted with communities. Other identified challenges were the extent to which volunteers undermined local expertise, using fraudulent qualifications by some volunteers, and poor skills and lack of experience leading to wrong diagnoses sometimes. The study found a lack of awareness of rules requiring the registration of practitioners with national professional regulatory bodies, suggesting non enforcement of volunteers’ need for local certification.

Conclusion

Short Term Medical Missions appear to contribute to addressing some of the critical gaps in healthcare delivery. However, there is an urgent need to address the challenges of ineffective utilisation and lack of oversight of these programs to maximise their benefits.
Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques
Authors: Preman Pranav , TCW Julia , Calafate Sara , Snellinx An , Alfonso-Triguero Maria , Corthout Nikky , Munck Sebastian , Thal Dietmar Rudolf , Goate Alison M , De Strooper Bart , Arranz Amaia M
Published: September 2021

Background

Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular and functional studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression.

Results

To address these challenges, we established an approach to study human astrocytes within the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived astrocyte progenitors into neonatal brains. Xenografted hiPSC-derived astrocyte progenitors differentiated into astrocytes that integrated functionally within the mouse host brain and matured in a cell-autonomous way retaining human-specific morphologies, unique features, and physiological properties. In Alzheimer´s chimeric brains, transplanted hiPSC-derived astrocytes responded to the presence of amyloid plaques undergoing morphological changes that seemed independent of theAPOEallelic background.

Conclusions

In sum, we describe here a promising approach that consist of transplanting patient-derived and genetically modified astrocytes into the mouse brain to study human astrocyte pathophysiology in the context of Alzheimer´s disease.
A controlled trial of Cognitive Behavioural Therapy-based strategies for insomnia among in-school adolescents in southern Nigeria
Authors: Egbegi Diseyei R. , Bella-Awusah Tolulope , Omigbodun Olayinka , Ani Cornelius
Published: September 2021

Background

Sleep difficulties are highly prevalent among adolescents, and are associated with significant impairments. The effectiveness and acceptability of Cognitive Behavioural Therapy-based (CBT-based) treatment for insomnia in adolescents is established for High Income Countries, but unknown for African settings. Thus, the aim of this study was to assess the effect of CBT-based intervention among in-school adolescents with sleep difficulties in Southern Nigeria.

Methods

This was a pilot controlled trial involving 50 adolescents with highest ranked scores on the Insomnia Severity Index (ISI) recruited from four schools (two government and two privately owned). Balloting was used to assign two schools (public and private) with 25 participants to the intervention group, and the other two schools (public and private) with 25 participants as waiting-list controls. The two groups were dyad-matched for baseline ISI scores, gender, and type of school to reduce baseline differences. The treatment group received weekly group-based manualised CBT-based intervention over 5 weeks. Primary outcome was ISI score at 6th week. Secondary outcomes were sleep onset latency (SOL), Total sleep duration (TSD), depressive symptoms, sleep hygiene, and knowledge about sleep.

Results

Participants were aged 13–17 years (M = 14.9, SD = 1.16) and consisted of 18 males and 32 females. Controlling for baseline scores, the intervention group showed significantly lower post-intervention insomnia scores compared with the control group {F (1, 34) = 1.10, p = 0.0001, (ηp2 = 0.59}, shorter SOL {F (1, 33) = 1.41, p = 0.0001, ηp2 = 0.39}, longer TSD {F (1, 33) = 1.03, p = 0.0001, ηp2 = 0.47}, lower depressive symptoms {F (1, 31) = 1.32, p = 0.002 (ηp2 = 0.34}, higher knowledge of sleep {F (1, 34) = 1.02, p = 0.001, ηp2 = 0.36}, but no significant change in sleep hygiene {F (1, 32) = 1.08, p = 0.08, ηp2 = 0.15}. All participants in the intervention group rated the programme as good or excellent.

Conclusion

This pilot CBT-based intervention for adolescents with insomnia was feasible, well received and showed promising efficacy in this setting. Larger controlled trials are recommended to establish the generalisability of these findings in this region.

Trial registrationPan African Clinical Trial Registry (Registration Number PACTR202001710494962)
Efficacy of exposure in group settings for youth with posttraumatic stress symptoms
Authors: Pfeiffer Elisa
Published: September 2021

Background

Exposure to traumatic experiences is a fundamental part of evidence-based trauma-focused cognitive behavioral treatment (CBT) but in group settings it is discussed controversially among researchers and practitioners. This study aims to examine the individual participants’ stress level during group sessions with exposure and disclosure of traumatic events.

Method

N = 47 traumatized youth (Mage = 17.00, 94% male) participated in a group intervention comprising six 90-min group sessions (exposure in sessions 2–5). It is based on trauma-focused CBT principles. The individual stress level was assessed by the participants and group facilitators at the beginning, during, and at the end of every session.

Results

During the sessions including exposure, the stress level of the participants was higher than during sessions without exposure (Z = − 3.79;p ≤ .001). During the exposure sessions, the participants showed significant changes in stress level (d = 0.34–0.87) following an inverse U-shaped trend.

Conclusion

The results show that exposure is feasible within the scope of a trauma-focused group intervention for youth. The further dissemination of trauma-focused group treatments is an important component in the mental health care of children and youth who are traumatized.