bluuebunny/crossref_metadata_2025 huggingface dataset:
Printing in Time for Cranio-Maxillo-Facial Trauma Surgery: Key Parameters to Factor in
Authors: Bergeron Léonard , Bonapace-Potvin Michelle , Bergeron François
Published: April 2022

Study Design

retrospective cohort study.

Objective

3D printing is used extensively in cranio-maxillo-facial (CMF) surgery, but difficulties remain for surgeons to implement it in an acute trauma setting because critical information is often omitted from reports. Therefore, we developed an in-house printing pipeline for a variety of cranio-maxillo-facial fractures and characterized each step required to print a model in time for surgery.

Methods

All consecutive patients requiring in-house 3D printed models in a level 1 trauma center for acute trauma surgery between March and November 2019 were identified and analyzed.

Results

Sixteen patients requiring the printing of 25 in-house models were identified. Virtual Surgical Planning time ranged from 0h 08min to 4h 41min (mean = 1h 46min). The overall printing phase per model (pre-processing, printing, and post-processing) ranged from 2h 54min to 27h 24min (mean = 9h 19min). The overall success rate of prints was 84%. Filament cost was between $0.20 and $5.00 per model (mean = $1.56).

Conclusions

This study demonstrates that in-house 3D printing can be done reliably in a relatively short period of time, therefore allowing 3D printing usage for acute facial fracture treatment. When compared to outsourcing, in-house printing shortens the process by avoiding shipping delays and by having a better control over the printing process. For time-critical prints, other time-consuming steps need to be considered, such as virtual planning, pre-processing of 3D files, post-processing of prints, and print failure rate.
Magnification assessment of radiographs for knee replacement (MARKeR) – A pilot study in a low-resource setting
Authors: Mencia Marlon. M , Goalan Raakesh , White Kimani
Published: April 2022

Background

Selecting the correct size of implants to be used in total knee arthroplasty is critical for a successful outcome. Marker-less templating systems use an institutionally derived magnification factor for all radiographs.

Purpose

To determine the institutional magnification of knee radiographs for patients awaiting total knee arthroplasty.

Material and Methods

Eighty patients awaiting total knee arthroplasty underwent preoperative knee radiographs using a standardized protocol. A marker attached to the patients’ knees at the level of the knee joint was used to calculate the magnification factor on both anteroposterior (AP) and lateral (LAT) views. Two independent observers estimated the magnification to determine the intra and inter-observer reliability.

Results

The mean magnification of the AP (15.3%) radiograph was significantly greater than the LAT (12.1%) radiograph ( p< 0.0001). Patients with absent markers on their radiographs were heavier than patients in whom the marker was visible (84.7 kgs vs. 76.6 kgs, p=0.01). No marker was visible on the radiographs in 56.3% (45/80) of patients. There was excellent inter and intra-observer reliability of both the AP and LAT measurements.

Conclusion

After standardizing the protocol for preoperative knee radiographs, our results show significantly greater institutional magnification of the anteroposterior compared with the lateral images. Accurate templating in knee arthroplasty requires both radiographic images. To reduce errors in implant sizing, we recommend surgeons use different institutional magnification factors for the anteroposterior and lateral radiographs.
Management of scleroderma gastrointestinal disease: Lights and shadows
Authors: Cheah Jenice X , Khanna Dinesh , McMahan Zsuzsanna H
Published: April 2022

Gastrointestinal symptoms affect the great majority of patients with systemic sclerosis. Management of these complications is often challenging as any region of the gastrointestinal tract may be involved, and significant heterogeneity exists in clinical presentation, kinetics, and outcomes. Here, we highlight new findings relevant to the management of systemic sclerosis-related gastrointestinal disease (lights) and consider areas that we have yet to elucidate (shadows).
Quintessential Case of POEMS Syndrome Associated With Multicentric Castleman Disease
Authors: Kannan Krishnarathnam , Vaikundaraja Indhuja Muthiah , Murhekar Kanchan , Umasankar Swathy Pitti
Published: April 2022

Castleman disease (CD) is a rare lymphoproliferative disorder, closely related to Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, and Skin changes (POEMS) syndrome. We report a typical patient of multicentric CD with POEMS syndrome with all the classical features.
Long-Term Quality of Life in Achalasia Patients After Esophagectomy: A Single Center Experience
Authors: Jones Amy E. , Crafts Trevor D. , Torres-Landa Samuel , Wood Stephanie G.
Published: April 2022

Introduction:

Achalasia is a chronic motility disorder of the esophagus with difficult to manage symptoms. Despite multi-modal therapies, some patients progress to end-stage disease requiring esophagectomy. Quality of life (QOL) has not been fully described in this population.

Methods:

A cross-sectional QOL study was performed on a cohort of end-stage achalasia patients who underwent an esophagectomy (2010-2020). Patients who met inclusion criteria were contacted by phone in 2021 to complete GIQLI and OES-18 questionnaires. Descriptive statistics were performed.

Results:

Of 14 patients who met inclusion criteria, 9 (64.3%) completed the QOL questionnaires. Mean age was 53-years, and the majority were white (88.9%) women (63.7%). Prior to esophagectomy, management of achalasia included Botox (33.3%), dilation (66.7%), and Heller myotomy (100%). All patients reported dysphagia and 88.9% reported regurgitation prior to esophagectomy. All patients underwent a minimally invasive surgical approach. At the time of QOL surveillance, the mean time from operation was 66 months. The mean GIQLI score in this population was 97 (Max 144), compared to previously reported scores of 126 in a healthy population and 119 after Heller myotomy. Only ICU and hospital LOS had a statistically significant association with poorer GIQLI scores. The results of the OES-18 showed higher median severity scores for reflux, dry mouth and trouble with coughing.

Conclusions:

Even after esophagectomy for end stage achalasia, symptoms can be persistent and impact QOL. While some patients may benefit from esophagectomy, future research should aim to identify which patients will benefit the most from this operation.
Computationally repurposing drugs for breast cancer subtypes using a network-based approach
Authors: Firoozbakht Forough , Rezaeian Iman , Rueda Luis , Ngom Alioune
Published: April 2022

‘De novo’drug discovery is costly, slow, and with high risk. Repurposing known drugs for treatment of other diseases offers a fast, low-cost/risk and highly-efficient method toward development of efficacious treatments. The emergence of large-scale heterogeneous biomolecular networks, molecular, chemical and bioactivity data, and genomic and phenotypic data of pharmacological compounds is enabling the development of new area of drug repurposing called ‘in silico’ drug repurposing, i.e., computational drug repurposing (CDR). The aim of CDR is to discover new indications for an existing drug (drug-centric) or to identify effective drugs for a disease (disease-centric). Both drug-centric and disease-centric approaches have the common challenge of either assessing the similarity or connections between drugs and diseases. However, traditional CDR is fraught with many challenges due to the underlying complex pharmacology and biology of diseases, genes, and drugs, as well as the complexity of their associations. As such, capturing highly non-linear associations among drugs, genes, diseases by most existing CDR methods has been challenging. We propose a network-based integration approach that can best capture knowledge (and complex relationships) contained within and between drugs, genes and disease data. A network-based machine learning approach is applied thereafter by using the extracted knowledge and relationships in order to identify single and pair of approved or experimental drugs with potential therapeutic effects on different breast cancer subtypes. Indeed, further clinical analysis is needed to confirm the therapeutic effects of identified drugs on each breast cancer subtype.
Exhausted phenotype of circulating CD8+ T cell subsets in hepatitis B virus carriers
Authors: Jiang Daixi , Chen Can , Yan Danying , Zhang Xiaobao , Liu Xiaoxiao , Yan Dong , Cui Dawei , Yang Shigui
Published: April 2022

Background

Chronic hepatitis B virus (HBV) infection is characterized by the presence of dysfunctional exhausted CD8+ T cells that hamper viral control. We investigated the phenotypic heterogeneity of exhausted CD8+ T cells in HBV carriers.

Methods

We enrolled 31 HBV carriers and 23 healthy controls (HCs) in our study. Peripheral blood mononuclear cells (PBMCs) were isolated, and flow cytometry was used to determine the phenotypic distribution of CD8+ T cell subsets. Expression of cytokines such as TNF-α and IFN-γ was detected by quantitative reverse transcription–PCR, a fluorescence flow cytometry-based immunomicrobead assay and flow cytometry.

Results

There were no significant differences in the baseline characteristics between the 31 HBV carriers and the 23 sex- and age-matched HCs. CD8+ T cells exhibited higher levels of inhibitory receptors (TIM3 and PD1) in the HBV carriers than in the HCs (P < 0.05); in particular, Tfc cells (CXCR5+CD25−) expressed higher levels of TIM3 and PD1 than non-Tfc cells in the HBV carriers. In addition, among the subsets of Tc cells, the Tc17 (CXCR5−CD25−CCR6+) subset displayed increased expression of TIM3 and LAG3 in the HBV carriers. Our findings further showed that CD8+ T cells produced lower levels of IFN-γ, TNF-α, and Granzyme B. Paired analysis of the Tfc subset and the Tc subset indicated that higher levels of cytokines (IFN-γ and TNF-α) were produced by the Tfc subset in the HBV carriers. Among the Tc subsets, the Tc17 subset produced lower levels of cytokines.

Conclusion

The Tfc subset exhibited an enhanced exhausted phenotype but possessed some functional properties during chronic HBV infection, while the Tc subset showed a lower functional level. The identification of these unique subsets may provide a potential immunotherapeutic target in chronic HBV infection.
Quality of end-of-life care in general practice – a pre–post comparison of a two-tiered intervention
Authors: van Baal Katharina , Wiese Birgitt , Müller-Mundt Gabriele , Stiel Stephanie , Schneider Nils , Afshar Kambiz
Published: April 2022

Background

General practitioners (GPs) play a crucial role in the provision of end-of-life care (EoLC). The present study aimed at comparing the quality of GPs’ EoLC before and after an intervention involving a clinical decision aid and a public campaign.

Methods

The study was part of the larger interventional study ‘Optimal care at the end of life’ (OPAL) (Innovation Fund, Grant No. 01VSF17028). The intervention lasted 12 months and comprised two components: (1) implementation of the Supportive and Palliative Care Indicators Tool (SPICT-DE™) in general practice and (2) a public campaign in two German counties to inform and connect regional health care providers and stakeholders in EoLC. Participating GPs completed the General Practice End of Life Care Index (GP-EoLC-I) pre- (t0) and post- (t1) intervention. The GP-EoLC-I (25 items, score range: 14–40) is a self-assessment questionnaire that measures the quality of GPs’ EoLC. It includes two subscales: practice organisation and clinical practice. Data were analysed descriptively, and a paired t-test was applied for the pre–post comparison.

Results

Forty-five GPs (female: 29%, median age: 57 years) from 33 general practices participated in the intervention and took part in the survey at both times of measurement (t0 and t1). The mean GP-EoLC-I score (t0 = 27.9; t1 = 29.8) increased significantly by 1.9 points between t0 and t1 (t(44) = − 3.0; p = 0.005). Scores on the practice organisation subscale (t0 = 6.9; t1 = 7.6) remained almost similar (t(44) = -2.0; p = 0.057), whereas those of the clinical practice subscale (t0 = 21.0; t1 = 22.2) changed significantly between t0 and t1 (t(44) = -2.6; p = 0.011). In particular, items regarding the record of care plans, patients’ preferred place of care at the end of life and patients’ preferred place of death, as well as the routine documentation of impending death, changed positively.

Conclusions

GPs’ self-assessed quality of EoLC seemed to improve after a regional intervention that involved both the implementation of the SPICT-DE™ in daily practice and a public campaign. In particular, improvement related to the domains of care planning and documentation.

Trial registration

The study was registered in the German Clinical Trials Register (DRKS00015108; 22/01/2019).
External validation of the BEST-J score and a new risk prediction model for ESD delayed bleeding in patients with early gastric cancer
Authors: Wang Jiaxu , Wu Shanshan , Xing Jie , Li Peng , Zhang Shutian , Sun Xiujing
Published: April 2022

Background

Delayed bleeding is an important adverse event after gastric endoscopic submucosal dissection (ESD). We aimed to externally validate the Bleeding after ESD Trend from Japan (BEST-J) score and subsequently develop a risk prediction model for bleeding in Chinese patients with early gastric cancer (EGC) after ESD.

Methods

The clinical data of patients who underwent ESD for EGC in Beijing Friendship Hospital from June 2013 to December 2019 were collected retrospectively. The BEST-J score was evaluated according to the clinical data. Through univariate and multivariate logistic regression analyses of the clinical data, the factors affecting delayed bleeding were identified, and a new risk prediction model for bleeding was established. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the two prediction models.

Results

A total of 444 patients with EGC undergoing ESD were included, of whom 27 patients had delayed bleeding (6.1%). Multivariate logistic regression analysis showed that a history of smoking (P = 0.029), tumor size > 20 mm (P = 0.022), intraoperative use of hemoclips (P = 0.025), resection of multiple tumors (P = 0.027), and prolongation of activated partial thromboplastin time (APTT) (P = 0.020) were independent influencing factors for delayed bleeding. ROC curve analysis showed that the areas under the curves (AUCs) were different between the BEST-J score and the newly built prediction model (0.624 vs. 0.749, P = 0.012).

Conclusions

The BEST-J score has moderately good discrimination for Chinese patients with EGC. However, for patients with EGC without severe comorbidities, the new risk prediction model may predict delayed bleeding better than the BEST-J score.
Fetal biometric and Doppler measurements following abdominal radical trachelectomy in the second trimester of the pregnancy
Authors: Shima Eiri , Itsukaichi Mina , Yoshihara Kosuke , Ishiguro Tatsuya , Haino Kazufumi , Nishino Koji , Nishikawa Nobumichi , Nishijima Koji , Enomoto Takayuki
Published: April 2022

Background

Our previous study demonstrated the safety and effectiveness of abdominal radical trachelectomy during pregnancy but did not focus on the fetus. This study aimed to clarify the influence of abdominal radical trachelectomy performed during pregnancy on the fetus.

Methods

Eight cervical cancer patients who underwent abdominal radical trachelectomy at our hospital between February 2013 and August 2020 were enrolled in this study. To assess the peri- and postoperative influence on the fetus, we performed fetal heart monitoring at 30-min intervals during abdominal radical trachelectomy and calculated the estimated fetal body weight and resistance indexes of the middle cerebral artery and umbilical artery from postsurgery until delivery.

Results

Four out of eight patients had preterm birth due to chorioamnionitis in one case and consideration of the recurrent risk of cervical cancer in three cases. Fetal heart monitoring during abdominal radical trachelectomy revealed deceleration just once in one case but no abnormal findings in the other cases. In all cases, the fetal growth after abdominal radical trachelectomy was normal until delivery. No abnormal Doppler findings were detected in the middle cerebral artery or umbilical artery.

Conclusion

Our findings clarified that abdominal radical trachelectomy performed for the treatment of early-stage cervical cancer during pregnancy has no obvious influence on fetal growth. Next, it is necessary to evaluate the growth and development of children delivered from mothers who have undergone abdominal radical trachelectomy during pregnancy.
Prognostic impact of angiotensin-converting enzyme inhibitors and angiotensin receptors blockers in esophageal or gastric cancer patients with hypertension - a real-world study
Authors: Li Po-Chih , Huang Ru-Yu , Yang Yu-Chien , Hsieh Kun-Pin , Yang Yi-Hsin
Published: April 2022

Background

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used in treating cardiovascular diseases. Previous studies indicated that ACEIs/ARBs may benefit cancer patients by inhibiting tumor angiogenesis and proliferation. The effect of ACEIs/ARBs on cancer survival in esophageal and gastric cancer is still unclear. This study is to investigate the association between ACEIs/ARBs usage and esophageal and gastric cancer prognosis.

Methods

This retrospective cohort study identified esophageal and gastric cancer patients during 2008–2016 from the Taiwan Cancer Registry, and obtained medication usage and follow-up information from the National Health Insurance Research Database and Death Registry. Analysis groups were defined as ACEIs/ARBs user or non-user based on the usage of ACEIs/ARBs within the 6 months after cancer diagnosis. The stabilized inverse probability of treatment weighting using propensity scores was applied to balance covariates between study groups. We also used Kaplan-Meier estimates and Cox regression to compare survival outcome and estimate hazard ratios (HRs).

Results

We identified 14,463 and 21,483 newly-diagnosed esophageal and gastric cancer patients during 2008–2016. ACEIs/ARBs users were associated with lower risk of cancer-specific mortality, although only significantly in gastric cancer (gastric: adjusted HR = 0.87, 95% CI = 0.78–0.97; esophageal: adjusted HR =0.88, 95% CI = 0.76–1.02). A better survival outcome was observed among patients who received higher cumulative defined daily dose of ACEIs/ARBs.

Conclusions

We found that using ACEIs/ARBs after cancer diagnosis were associated with lower risk of mortality. Our results add to the knowledge of the benefit of ACEIs/ARBs against mortality in individuals with esophageal/gastric cancer patients with hypertension.
The impact of NRG1 expressions and methylation on multifactorial Hirschsprung disease
Authors: Gunadi  , Kalim Alvin Santoso , Marcellus  , Budi Nova Yuli Prasetyo , Iskandar Kristy
Published: April 2022

Background

Hirschsprung disease (HSCR) is a complex genetic disorder characterized by the lack of ganglion cells in the intestines. A current study showed that the NRG1 rare variant frequency in Indonesian patients with HSCR is only 0.9%. Here, we investigated the impact of NRG1 expressions and methylation patterns on the pathogenesis of HSCR.

Methods

This cross-sectional study determined NRG1 type I (HRGα, HRGβ1, HRGβ2, HRGβ3, HRGγ, and NDF43 isoforms), type II and type III expressions in both ganglionic and aganglionic colons of 20 patients with HSCR and 10 control colons by real-time polymerase chain reaction (qPCR). For methylation studies, we treated the extracted gDNA from 16 HSCR patients’ and 17 control colons with sodium bisulfate and analyzed the methylation pattern of NRG1 exon 1 with methylation-specific PCR. The samples were collected and analyzed at our institution from December 2018 to December 2020.

Results

NRG1 types I, II and III expressions were upregulated (17.2-, 3.2-, and 7.2-fold, respectively) in the ganglionic colons compared with control colons (type I: 13.32 ± 1.65 vs. 17.42 ± 1.51, p < 0.01; type II: 13.73 ± 2.02 vs. 16.29 ± 2.19, p < 0.01; type III: 13.47 ± 3.01 vs. 16.32 ± 2.58, p = 0.03; respectively); while only type I (7.7-fold) and HRGβ1/HRGβ2 (3.3-fold) isoforms were significantly upregulated in the aganglionic colons compared to the controls (type I: 14.47 ± 1.66 vs. 17.42 ± 1.51, p < 0.01; HRGβ1/HRGβ2: 13.62 ± 3.42 vs 14.75 ± 1.26, p = 0.01). Moreover, the frequency of partially methylated NRG1 was higher in the ganglionic (81%) and aganglionic (75%) colons than in the controls (59%).

Conclusions

Our study provides further insights into the aberrant NRG1 expression in the colons of patients with HSCR, both ganglionic and aganglionic bowel, which might contribute to the development of HSCR, particularly in Indonesia. Furthermore, these aberrant NRG1 expressions might be associated with its methylation pattern.
A retrospective case notes review of the effectiveness and tolerability of metoclopramide in the treatment of clozapine-induced hypersalivation (CIH)
Authors: Livermore Cecilia , White Hannah , Bailey Loren , Osborne Ian , Oloyede Ebenezer , Dzahini Olubanke , Whiskey Eromona
Published: April 2022

Objective

The objective of the study is to explore the long-term effectiveness and tolerability of metoclopramide in the treatment of CIH.

Method

This study is a retrospective, observational cohort study of patients prescribed metoclopramide for CIH at the South London & Maudsley (SLaM) NHS Foundation Trust.

Results

Of the 96 patients identified, 14 patients were eligible for inclusion in our study. Five patients continued treatment with a mean duration of 27 months (SD = 17.8), and one patient continued until transfer with a duration of 3 months. Eight patients discontinued treatment after a mean duration of 8 months.

Conclusion

Metoclopramide may be an effective and tolerated drug in CIH, but more data is required to establish its place in the pharmacotherapy of this condition.
A systematic review on the economic burden of interstitial lung disease and the cost-effectiveness of current therapies
Authors: Wong Alyson W. , Koo John , Ryerson Christopher J. , Sadatsafavi Mohsen , Chen Wenjia
Published: April 2022

Background

The economic burden of interstitial lung disease (ILD) is unknown, limiting informed resource allocation and planning. We sought to conduct the first systematic review on the direct, indirect, and overall costs associated with ILD and to evaluate the cost-effectiveness of current therapies globally.

Methods

We conducted systematic reviews of ILD disease cost studies and cost-effectiveness analyses (CEAs) using MEDLINE, Embase, and Web of Science databases between 2000 and 2020. We compared ILD costs between countries according to the share of costs towards each country’s respective gross domestic product (GDP) per capita. Costs are reported in 2020 USD.

Results

We identified 25 disease cost studies and 7 CEAs. The direct medical costs ranged between $1824 and $116,927 annually per patient (median $32,834; 14–180% of GDP per capita in Western countries). The leading drivers of direct costs were inpatient (55%), outpatient (22%), and medication costs (18%), based on pooled estimates. Annual indirect costs ranged from $7149 to $10,902 per employed patient (median $9607; 12–23% of GDP per capita). Among the 7 CEAs, only 1 study (14%) showed an ILD therapy (ambulatory oxygen) was cost-effective compared to best supportive care.

Conclusion

The direct and indirect costs associated with ILD are consistently high in all countries with available data, with cost-effectiveness profiles of new therapies generally undesirable. Globally, the median total direct cost for ILD equates to 51% of a country’s GDP per capita and has been increasing over time.
Suppression of MIR31HG affects the functional properties of thyroid cancer cells depending on the miR-761/MAPK1 axis
Authors: Peng Shuwang , Chen Luyang , Yuan Zhengtai , Duan Shanshan
Published: April 2022

Background

Thyroid cancer is the most prevalent endocrine malignancy. Long non-coding RNA (lncRNA) MIR31HG is abnormally expressed in thyroid cancer tissues. However, the precise, critical role of MIR31HG in thyroid cancer development remains unclear.

Methods

MIR31HG, microRNA (miR)-761 and mitogen-activated protein kinase 1 (MAPK1) were quantified by quantitative real-time PCR (qRT-PCR) and immunoblotting. Cell viability, proliferation, apoptosis, invasion and migration abilities were evaluated by MTS, 5-Ethynyl-2′-Deoxyuridine (EdU), flow cytometry, transwell and wound-healing assays, respectively. Dual-luciferase reporter assays were used to validate the direct relationship between miR-761 and MIR31HG or MAPK1.

Results

MIR31HG was overexpressed in human thyroid cancer, and its overexpression predicted poor prognosis. Suppression of MIR31HG impeded cell proliferation, invasion and migration, as well as promoted cell apoptosis in vitro, and diminished the growth of xenograft tumors in vivo. Mechanistically, MIR31HG targeted and regulated miR-761. Moreover, miR-761 was identified as a molecular mediator of MIR30HG function in regulating thyroid cancer cell behaviors. MAPK1 was established as a direct and functional target of miR-761 and MAPK1 knockdown phenocopied miR-761 overexpression in impacting thyroid cancer cell behaviors. Furthermore, MIR31HG modulated MAPK1 expression by competitively binding to miR-761 via the shared binding sequence.

Conclusion

Our findings demonstrate that MIR31HG targets miR-761 to regulate the functional behaviors of thyroid cancer cells by upregulating MAPK1, highlighting a strong rationale for developing MIR31HG as a novel therapeutic target against thyroid cancer.
Palliative Care education in Armenia: perspectives of first-year Armenian physician residents
Authors: Hagedorn Carolin , Tadevosyan Artashes , Mason Stephen , Elsner Frank
Published: April 2022

Background

Due to developing demographic changes, including an aging society and the increasing prevalence of non-communicable diseases, Palliative Care is increasingly highlighted as a universal healthcare need. The need for Palliative Care in Armenia is set against the context of an underdeveloped healthcare system. Further, the absence of palliative medicine within medical education, particularly undergraduate education in Armenia presents a major barrier to improving care. This research aimed to assess the perception of young Armenian physicians’ understanding of Palliative Care, its perceived status in Armenia and the experience and influence of any engaged Palliative Care education.

Methods

Twenty Armenian first-year residents with different specializations were interviewed July and September 2016 regarding: understanding/knowledge, experiences, perceived competence, and expectations of Palliative Care and Palliative Care education. The transcripts from these semi-structured interviews were analyzed using Qualitative Content Analysis.

Results

Participants perceived that Armenia’s health care system lacked sufficient Palliative Care and Palliative Care education. Although elements of Palliative Care were included in different specialty teaching, this provided just a partial understanding of typical Palliative Care patients/symptoms, approaches to holistic care, and crucially key communication skills. Challenges noted by participants in caring for Palliative Care patients included emotional difficulties, communication of diagnosis/prognosis, uninformed patients and concerns for patients, families, and physicians. Self-confidence in caring for patients with incurable illness varied. Participants hoped for increasing availability and accessibility of Palliative Care, and extension of clinical education in Palliative Care at all levels (undergraduate, postgraduate, specialization).

Conclusions

Absence of training has resulted in misconceptions and ignorance of common concepts and practices in Palliative Care. Palliative Care education needs to be systematically developed and integrated into clinical training within Armenia. This research may provide a rallying call for changes within the core curricula in Armenia and may also encourage collaborative development in associated countries of the Caucasus region.
Effect of phone call distraction on the performance of medical students in an OSCE
Authors: Toader Justus F. , Kleinert Robert , Dratsch Thomas , Fettweis Louisa , Jakovljevic Nadja , Graupner Martina , Zeeh Moritz , Kroll Anna C. , Fuchs Hans F. , Wahba Roger , Plum Patrick , Bruns Christiane J. , Datta Rabi R.
Published: April 2022

Background

The usage of smartphones in the daily clinical routine is an essential aspect however it seems that they also present an important distractor that needs to be evaluated. The aim of this prospective study was the evaluation of the influence of phone calls as distractors on the performance levels of medical students during an objective structured clinical examination (OSCE), simulating the normal clinical practice.

Methods

As the goal of an OSCE presents the examination of clinical skills of medical students in a realistic setting, more than 100 students recruited from the university hospital of Cologne participated in either OSCE I or II. During the OSCE I intravenous cannulation was simulated while OSCE II simulated an acute abdominal pain station. Participants had to perform each of these stations under two circumstances: a normal simulated OSCE and an OSCE station with phone call distraction. Their performance during both simulations was then evaluated.

Results

In OSCE I students achieved significantly more points in the intravenous cannulation station if they were not distracted by phone calls (M=6.44 vs M=5.95). In OSCE II students achieved significantly more points in the acute abdominal pain station if they were not distracted by phone calls (M=7.59 vs M=6.84). While comparing only those students that completed both stations in OSCE I/II participating students achieved significantly more points in both OSCE I and II if they were not distracted by phone calls.

Conclusion

The presented data shows that phone call distraction decreases the performance level of medical students during an OSCE station. Therefore, it is an indicator that distraction especially for younger doctors should be held to a minimum. On a second note distraction should be integrated in the medical education system as it plays an important role in clinical routine.
Simulation-based medical education in Thailand: a cross-sectional online national survey
Authors: Boonmak Polpun , Suraseranivongse Suwannee , Pattaravit Ngamjit , Boonmak Suhattaya , Jirativanont Tachawan , Lertbunnaphong Tripop , Arora Rajin , Watcharotayangul Jittiya , Imsuwan Intanon , Kwangwaropas Panithan , Wittayachamnankul Borwon
Published: April 2022

Background

Simulation-Based Medical Education (SBME) is a teaching method commonly used in undergraduate medical education. Although Thai medical schools have developed a system that incorporates SBME, various aspects of that system require improvement. We surveyed medical school administrators, instructors, and students about SBME in their institutions and the obstacles involved in its implementation, as well as their experiences, expectations, and attitudes regarding the current system.

Methods

We conducted a cross-sectional online survey between August 2019 and July 2020 among administrators, instructors, and 6th-year medical students. A structured questionnaire was developed and distributed to volunteers as an online survey. We recorded details about the SBME system as well as participant characteristics, obstacles, experiences, expectations, and attitudes. We used descriptive statistics as appropriate.

Results

We received responses from 15 (68.2%) administrators, 186 instructors, and 371 (13.7%) sixth-year medical students. SBME was commonly used in teaching and evaluation but less so in research. It was mainly used to improve psychomotor tasks, knowledge, patient care, and communication skills. The expected outcomes were improvements in students’ performance, knowledge, and practice. The clinical courses were longer and had fewer participants than the pre-clinical courses. Obstacles encountered included shortages of faculty and simulators, time and space limitations, inadequate faculty training, and insufficient financial support. The administrators surveyed had positive attitudes toward SBME. Medical students reported having experience with SBME and strongly agreed that it was beneficial; however, they expected fewer students per class and more learning time to be devoted to these methods.

Conclusions

SBME in Thailand is focused on teaching and assessment. The system could be improved through better-trained faculty, greater available space, more simulators, and sufficient funding. There were also some aspects that failed to meet students’ expectations and need to be addressed. However, participants expressed positive attitudes toward SBME.

Trial Registration

TCTR20210524003 (Thai Clinical Trials Registry).
Study protocol: a randomised, controlled trial of a nurse navigator program for the management of hepatitis C virus in patients with severe mental disorder
Authors: Quemada-González Casta , Morales-Asencio José Miguel , Hurtado María M. , Martí-García Celia
Published: April 2022

Background

To evaluate the impact of a nurse navigation program on treatment adherence and resolution of hepatitis C infection in patients with severe mental disorder.

Methods

An open, randomized, controlled trial with blinded outcome assessment. The intervention group will engage in a nurse navigation program designed by mental health nurses. The program involves active screening for patients with severe mental disorder. The patients and caregivers included in the program will receive information, training, support and guidance throughout the treatment and recovery process, which involves different healthcare professionals and units. The control group will receive the standard of care, which includes follow-up by a family physician, referral to the hepatologist, serological testing, new referral to the hepatologist, onset of treatment, and follow-up. Multidisciplinary care will be provided along a coordinated and seamless clinical pathway led by a nurse navigator.

The primary endpoints are total recovery (hepatitis C cure) and treatment adherence. Occurrence of symptoms of schizophrenia and health-related quality of life will be also recorded. Follow-up of patients will be performed three and six months after the administration of antiviral treatment.

The study was authorised by the Ethics Committee of Malaga in December 2021. Funding was approved in March 2021.

Discussion

If this intervention is proven to be effective in improving treatment access and adherence, it will represent a step forward in addressing a chronic health issue that is 16 times more prevalent in the population with severe mental disease. Finally, this intervention may lead to the detection of undertreated HCV infection in this population of patients.

Trial registration

This protocol has been registered in ClinicalTrials.gov with identifier code NCT04891445 on May 18, 2021.
Determination and pharmacokinetics study of UK-5099 in mouse plasma by LC–MS/MS
Authors: Zeng Qingyuan , Si Hongfei , Lv Kun , Mo Jiao , Wang Xinnian , Yan Biqing , Zhang Jili
Published: April 2022

Background

UK-5099 is a potent mitochondrial acetone carrier inhibitor, that exhibits anticancer activity. Recently, the anti-Toxoplasma gondii activity of UK-5099 was proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effect of UK-5099.

Methods and results

A simple and fast high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) analysis method was established and verified in terms of its linearity, matrix effect, accuracy, precision, recovery and stability. The analytes were separated by an Agilent ZORBAX XDB-C18 column (2.1 × 50 mm, 3.5 μm) at 30 °C. A gradient mobile phase consisting of water with 0.1% formic acid (FA) (phase A) and acetonitrile (ACN) (phase B) was delivered at a flow rate of 0.40 mL·min−1 with an injection volume of 5 μL. A good linear response was obtained in a concentration range of 5–5000 ng·mL−1 (r2 = 0.9947). The lower limit of quantification (LLOQ) was 5 ng·mL−1. The extraction recovery of UK-5099 was greater than 95%. The inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) of less than 15%. This method has been successfully applied to the pharmacokinetic evaluation of UK-5099 in mouse plasma. In health mice, the main pharmacokinetic parameters of UK-5099 after intraperitoneal administration were measured using a noncompartmental model, in which the AUC0-t was 42,103 ± 12,072 ng·h·mL−1 and the MRT0-t was 0.857 ± 0.143 h. The peak concentration (Cmax) was 82,500 ± 20,745 ng·h·mL−1, which occurred at a peak time (Tmax) = 0.250 ± 0.000 h.

Conclusions

A fast and sensitive HPLC–MS/MS method was developed, validated and successfully used for the determination of UK-5099 levels in mice after intraperitoneal administration. This study was the first report of the pharmacokinetic parameters of UK-5099 in mice, which will help to further study the administration of UK-5099 in animals and humans.
Determination of the regulatory network and function of the lysR-type transcriptional regulator of Lactiplantibacillus plantarum, LpLttR
Authors: Liu Xin-Xin , Liu Lei , Song Xin , Wang Guang-Qiang , Xiong Zhi-Qiang , Xia Yong-Jun , Ai Lian-Zhong
Published: April 2022

Background

Lactiplantibacillus plantarum has various healthcare functions including the regulation of immunity and inflammation, reduction of serum cholesterol levels, anti-tumor activity, and maintenance of the balance of intestinal flora. However, the underlying metabolic and regulatory mechanisms of these processes remain unclear. Our previous studies have shown that the LysR type transcriptional regulator of L. plantarum (LpLttR) regulates the biotransformation of conjugated linoleic acids (CLAs) through the transcriptional activation of cla-dh (coding gene for CLA short-chain dehydrogenase) and cla-dc (coding gene for CLA acetoacetate decarboxylase). However, the regulatory network and function of LpLttR have not yet been characterized in L. plantarum.

Results

In this study, the regulatory role of LpLttR in various cellular processes was assessed using transcriptome analysis. The deletion of LpLttR had no evident influence on the bacterial growth. The transcriptome data showed that the expression of nine genes were positively regulated by LpLttR, and the expression of only two genes were negatively regulated. Through binding motif analysis and molecular interaction, we demonstrated that the regulatory region of the directly regulated genes contained a highly conserved sequence, consisting of a 15-base long box and rich in AT.

Conclusion

This study revealed that LpLttR of L. plantarum did not play a global regulatory role similar to that of the other transcriptional regulators in this family. This study broadens our knowledge of LpLttR and provides a theoretical basis for the utilization of L. plantarum.
Win or loss? Combination therapy does improve the oncolytic virus therapy to pancreatic cancer
Authors: Luo Wenhao , Wang Yawen , Zhang Taiping
Published: April 2022

Pancreatic cancer (PC) is a growing global burden, remaining one of the most lethal cancers of the gastrointestinal tract. Moreover, PC is resistant to various treatments such as chemotherapy, radiotherapy, and immunotherapy. New therapies are urgently needed to improve the prognosis of PC. Oncolytic virus (OV) therapy is a promising new treatment option. OV is a genetically modified virus that selectively replicates in tumor cells. It can kill tumor cells without harming normal cells. The activation of tumor-specific T-cells is a unique feature of OV-mediated therapy. However, OV-mediated mono-therapeutic efficacy remains controversial, especially for metastatic or advanced patients who require systemically deliverable therapies. Hence, combination therapies will be critical to improve the therapeutic efficacy of OV-mediated therapy and prevent tumor recurrence. This review aims to investigate novel combinatorial treatments with OV therapy and explore the inner mechanism of those combined therapies, hopefully providing a new direction for a better prognosis of PC.
Delta-5® oil, containing the anti-inflammatory fatty acid sciadonic acid, improves skin barrier function in a skin irritation model in healthy female subjects
Authors: Berger Alvin
Published: April 2022

Background

Sciadonic acid (SA) is an anti-inflammatory fatty acid displacing arachidonic acid (ARA) from specific phospholipid pools, thus modulating downstream pro-inflammatory lipid mediators. Its novel anti-inflammatory actions have been studied in vitro, in pre-clinical models, and stemming from testimonials, after topical- and oral application. It has not been tested in a formal clinical study for topical benefits previously. Skin barrier layer was our focus as it has a critically important role in maintaining skin moisture balance.

Methods

Herein, forearm skin was left undamaged; or barrier layer was chemically-damaged with 2% sodium lauryl sulfate (SLS) for 24 h. SLS-damaged skin was left untreated or treated with Delta-5® oil containing 24% SA twice daily for 27 days. Barrier function was assessed by open chamber transepidermal water loss (TEWL) and skin surface impedance on days 0 (clear skin), -1 (1-day post-SLS), -2 (2-days post-SLS, 1-day post-Delta-5), -3, -7, and − 28.

Results

Relative to day 1, Delta-5 oil statistically significantly decreased TEWL vs. untreated damaged sites, on days 3 (125% more reduced), -7 (74% more reduced), and − 28 (69% more reduced). Decreases in TEWL following chemical damage indicates improved skin barrier repair and healing. Similar patterns were quantified for skin impedance. There was also reduced redness observed on days 3 and − 7 with Delta-5 oil vs. untreated SLS-damaged skin.

Conclusions

Delta-5 oil thus has anti-inflammatory potential in human skin, under controlled clinical conditions, to accelerate irritant-induced healing, and improve skin barrier function. Improvement in barrier function would benefit dermatitis, acne, eczema, and skin scarring. In normal skin, Delta-5 oil has potential to promote healthy, moisturized skin; and improve skin structure, elasticity, and firmness.
Photogenerated reactive oxygen species and hyperthermia by Cu3SnS4 nanoflakes for advanced photocatalytic and photothermal antibacterial therapy
Authors: Yang Yangzi , Wang Chengwei , Wang Ning , Li Jiaxin , Zhu Yingchun , Zai Jiantao , Fu Jingke , Hao Yongqiang
Published: April 2022

Background

The rapid spread of infectious bacteria has brought great challenges to public health. It is imperative to explore effective and environment-friendly antibacterial modality to defeat antibiotic-resistant bacteria with high biosafety and broad-spectrum antibacterial property.

Results

Herein, biocompatible Cu3SnS4nanoflakes (NFs) were prepared by a facile and low-cost fabrication procedure. These Cu3SnS4NFs could be activated by visible light, leading to visible light-mediated photocatalytic generation of a myriad of reactive oxygen species (ROS). Besides, the plasmonic Cu3SnS4NFs exhibit strong near infrared (NIR) absorption and a high photothermal conversion efficiency of 55.7%. The ROS mediated cellular oxidative damage and the NIR mediated photothermal disruption of bacterial membranes collaboratively contributed to the advanced antibacterial therapy, which has been validated by the efficient eradication of both Gram-negativeEscherichia coliand Gram-positive methicillin-resistantStaphylococcus aureusstrains in vitro and in vivo. Meanwhile, the exogenous copper ions metabolism from the Cu3SnS4NFs facilitated the endothelial cell angiogenesis and collagen deposition, thus expediting the wound healing. Importantly, the inherent localized surface plasmon resonance effect of Cu3SnS4NFs empowered them as an active substrate for surface-enhanced Raman scattering (SERS) imaging and SERS-labeled bacteria detection.

Conclusions

The low cost and biocompatibility together with the solar-driven broad-spectrum photocatalytic/photothermal antibacterial property of Cu3SnS4NFs make them a candidate for sensitive bacteria detection and effective antibacterial treatment.

Graphical Abstract
Building evidence into youth health policy: a case study of the Access 3 knowledge translation forum
Authors: Waller Daniel , Robards Fiona , Schneider Carmen Huckel , Sanci Lena , Steinbeck Katharine , Gibson Sally , Usherwood Tim , Hawke Catherine , Jan Stephen , Kong Marlene , Kang Melissa
Published: April 2022

Background

Effective integration of evidence and youth perspectives into policy is crucial for supporting the future health and well-being of young people. The aim of this project was to translate evidence from the Access 3 project to support development of a new state policy on youth health and well-being within New South Wales (NSW), Australia. Ensuring the active contribution of young people within policy development was a key objective of the knowledge translation (KT) process.

Methods

The KT activity consisted of a 1-day facilitated forum with 64 purposively sampled stakeholders. Participants included eight young people, 14 policy-makers, 15 academics, 22 clinicians or managers from NSW health services, four general practitioners and one mental health service worker. Research to be translated came from the synthesized findings of the NSW Access 3 project. The design of the forum included stakeholder presentations and group workshops, guided by the 2003 Lavis et al. KT framework that was improved by the Grimshaw et al. KT framework in 2012. Members of the Access 3 research team took on the role of knowledge brokers throughout the KT process. Participant satisfaction with the workshop was evaluated using a brief self-report survey. Policy uptake was determined through examination of the subsequent NSW Youth Health Framework 2017–2024.

Results

A total of 25 policy recommendations were established through the workshop, and these were grouped into six themes that broadly aligned with the synthesized findings from the Access 3 project. The six policy themes were (1) technology solutions, (2) integrated care and investment to build capacity, (3) adolescent health checks, (4) workforce, (5) youth participation and (6) youth health indicators. Forum members were asked to vote on the importance of individual recommendations. These policy recommendations were subsequently presented to the NSW Ministry of Health, with some evidence of policy uptake identified. The majority of participants rated the forum positively.

Conclusions

The utilization of KT theories and active youth engagement led to the successful translation of research evidence and youth perspectives into NSW youth health policy. Future research should examine the implementation of policy arising from these KT efforts.