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Objectives: Electronic consultations, or e-consults, between primary care providers and specialists have been shown to improve access to specialty care, shorten wait times, and reduce outpatient visits. The objective of this study was to evaluate differences in health care costs between patients who received an electronic specialty consultation and patients who received a face-to-face specialty consultation., Study Design: Retrospective cohort evaluation of patients who received a specialty consultation in the Veterans Health Administration during 2016., Methods: Patients who received an e-consult were matched 1:1 to patients who received a face-to-face consultation using propensity scores. Total, outpatient, and inpatient health care costs over 3 and 6 months following the specialty consultation were compared using a generalized linear model with a gamma distribution and log link., Results: e-Consults accounted for 1.8% (urology) to 9.6% (hematology) of specialty consultations, on average. Across 11 specialties, patients receiving an e-consult had significantly lower health care costs compared with patients receiving a face-to-face consultation, ranging from 3.6% (cardiology) to 30.7% (hematology) lower. This was largely driven by differences in outpatient costs. Patients receiving an e-consult had significantly lower outpatient costs for all specialties except cardiology, ranging from 6.9% (endocrinology) to 31.2% (hematology) lower. Three-month inpatient costs among those who received an e-consult were significantly lower only in cardiology (5.2%), nephrology (9.3%), pulmonary (13.0%), and gastroenterology (14.3%)., Conclusions: Electronic specialty consultations are a potential mechanism to reduce health care costs and promote the efficient use of health care resources.

Objectives: To assess the early impact of implementation of the electronic consults (e-consults) initiative by the Veterans Health Administration (VHA), designed to improve specialty care access., Study Design: Observational cohort study exploiting a natural experiment begun in May 2011 at 12 VHA medical centers and expanded to 122 medical centers by December 2013., Methods: The following were assessed: 1) growth of e-consults by VHA regional networks, medical centers, and specialty; 2) location of patient's primary care provider (medical center vs community-based outpatient clinic [CBOC]); 3) potential patient miles needed to travel for a specialty care face-to-face consult in place of the observed e-consults using estimated geodesic distance; 4) use of specialty care subsequent to the e-consult., Results: Of 11,270,638 consults completed in 13 clinics of interest, 217,014 were e-consults (adjusted rate, 1.93 e-consults per 100 consults). The e-consult rate was highest in endocrinology (5.0 per 100), hematology (3.0 per 100), and gastroenterology (3.0 per 100). The percentage of e-consult patients with CBOC-based primary care grew from 28.5% to 44.4% in the first year of implementation and to 45.6% at year 3. Of those e-consult patients from community clinics, the average potential miles needed to travel was 72.1 miles per patient (SD = 72.6; median = 54.6; interquartile range = 17.1-108), translating to a potential savings of 6,875,631 total miles and travel reimbursement costs of $2,853,387., Conclusions: E-consult volume increased significantly since inception within many medical and surgical specialties. For patients receiving primary care at one of more than 800 CBOCs, e-consults may decrease travel burden and direct travel costs for patients.

Endotracheal intubation is a medical procedure to secure a patient’s airways, which can be challenging in emergency situations due to an individual’s anatomy. Intubation blades can benefit from an adjustable design with shape memory alloys. We present a novel blade design with two degrees of freedom, continuously transforming a straight into a curved blade. Our demonstrators reached mean angular deflections up to 16∘ without exceeding outer blade temperatures of 40∘C. Mean forces of almost 24N were applicable. This approach has the potential to reduce the complexity of intubation procedures and increase the success rate, especially in time-critical emergency situations.

Medicine is a gendered discipline, in which women, both as patients and practitioners, have often held subordinate positions. The reproduction of dominant gender biases in the medical setting can negatively impact the professional development of medical students and the wellbeing of patients. In this analysis of medical students' narratives of professionalism dilemmas, we explore students' experiences of gender bias in hospital settings. Seventy-one students participated in 12 group interviews, where they discussed witnessing or participating in various activities that they thought were professionalism lapses. Within the dataset, 21 narratives had a distinctly gendered component broadly pertaining to patient dignity and safety dilemmas, informed consent issues, and female student abuse. Interestingly, perpetrators of such acts were commonly female healthcare professionals and educators. Although students recognized such acts as professionalism lapses and often expressed concern for patient wellbeing, students did not intervene or report such acts due to hierarchical cultural contexts, and at times even reproduced the discriminatory behavior they were criticizing. This raises concerns about medical students' professionalism development and the extent to which gender bias is ingrained within particular medical systems. The normalization of disrespectful and abusive treatment of female patients poses immediate and future consequences to the wellbeing and safety of women. Furthermore, the same socio-cultural values that sustain these acts may account for perpetrators often being women themselves as they strive to overcome their subordinate position within medicine.

The aim of this study is to evaluate a 3D (Three Dimensional) Traditional Chinese Medicine (TCM) e-learning platform and determine the factors affecting students' intention to continue to use the platform in TCM courses. Students from two classes were invited to participate in the experiment. To compare the effectiveness of both learning methods, one class serves as the control group and used the traditional classroom lecture method while the other serves as the experimental group using the 3D e-learning platform. To determine the factors affecting TCM students' intention to continue to use the platform, we propose an evaluation model modified from the post-acceptance model of information systems. Data collected from the experimental group students are used to test the proposed research model via the PLS-SEM method. We find that TCM students using the 3D e-learning platform outperformed those who used the traditional classroom lecture method. Meanwhile, the integrated evaluation model is found to provide reasonable explanatory power regarding TCM students' intention to continue to use the e-learning platform.

In Southeast Asia, the Malayan Pit Viper (Calloselasma rhodostoma) is a venomous snake species of medical importance and bioprospecting potential. To unveil the diversity of its toxin genes, this study de novo assembled and analyzed the venom gland transcriptome of C. rhodostoma from Malaysia. The expression of toxin genes dominates the gland transcriptome by 53.78% of total transcript abundance (based on overall FPKM, Fragments Per Kilobase Million), in which 92 non-redundant transcripts belonging to 16 toxin families were identified. Snake venom metalloproteinase (SVMP, PI > PII > PIII) is the most dominant family (37.84% of all toxin FPKM), followed by phospholipase A2 (29.02%), bradykinin/angiotensin-converting enzyme inhibitor-C-type natriuretic peptide (16.30%), C-type lectin (CTL, 10.01%), snake venom serine protease (SVSP, 2.81%), L-amino acid oxidase (2.25%), and others (1.78%). The expressions of SVMP, CTL, and SVSP correlate with hemorrhagic, anti-platelet, and coagulopathic effects in envenoming. The SVMP metalloproteinase domains encode hemorrhagins (kistomin and rhodostoxin), while disintegrin (rhodostomin from P-II) acts by inhibiting platelet aggregation. CTL gene homologues uncovered include rhodocytin (platelet aggregators) and rhodocetin (platelet inhibitors), which contribute to thrombocytopenia and platelet dysfunction. The major SVSP is a thrombin-like enzyme (an ancrod homolog) responsible for defibrination in consumptive coagulopathy. The findings provide insight into the venom complexity of C. rhodostoma and the pathophysiology of envenoming.

The Equatorial Spitting Cobra (Naja sumatrana) is a medically important venomous snake species in Southeast Asia. Its wide geographical distribution implies potential intra-specific venom variation, while there is no species-specific antivenom available to treat its envenoming. Applying a protein-decomplexing proteomic approach, the study showed that three-finger toxins (3FTX), followed by phospholipases A2 (PLA2), were the major proteins well-conserved across N. sumatrana venoms of different locales. Variations were noted in the subtypes and relative abundances of venom proteins. Of note, alpha-neurotoxins (belonging to 3FTX) are the least in the Penang specimen (Ns-PG, 5.41% of total venom proteins), compared with geographical specimens from Negeri Sembilan (Ns-NS, 14.84%), southern Thailand (Ns-TH, 16.05%) and Sumatra (Ns-SU, 10.81%). The alpha-neurotoxin abundance, in general, correlates with the venom’s lethal potency. The Thai Naja kaouthia Monovalent Antivenom (NkMAV) was found to be immunoreactive toward the N. sumatrana venoms and is capable of cross-neutralizing N. sumatrana venom lethality to varying degrees (potency = 0.49–0.92 mg/mL, interpreted as the amount of venom completely neutralized per milliliter of antivenom). The potency was lowest against NS-SU venom, implying variable antigenicity of its lethal alpha-neurotoxins. Together, the findings suggest the para-specific and geographical utility of NkMAV as treatment for N. sumatrana envenoming in Southeast Asia.

Envenoming by cobras (Naja spp.) often results in extensive local tissue necrosis when optimal treatment with antivenom is not available. This study investigated the cytotoxicity of venoms and purified cytotoxins from the Monocled Cobra (Naja kaouthia), Taiwan Cobra (Naja atra), and Equatorial Spitting Cobra (Naja sumatrana) in a mouse fibroblast cell line, followed by neutralization of the cytotoxicity by three regional antivenoms: the Thai Naja kaouthia monovalent antivenom (NkMAV), Vietnamese snake antivenom (SAV) and Taiwanese Neuro bivalent antivenom (NBAV). The cytotoxins of N. atra (NA-CTX) and N. sumatrana (NS-CTX) were identified as P-type cytotoxins, whereas that of N. kaouthia (NK-CTX) is S-type. All venoms and purified cytotoxins demonstrated varying concentration-dependent cytotoxicity in the following trend: highest for N. atra, followed by N. sumatrana and N. kaouthia. The antivenoms moderately neutralized the cytotoxicity of N. kaouthia venom but were weak against N. atra and N. sumatrana venom cytotoxicity. The neutralization potencies of the antivenoms against the cytotoxins were varied and generally low across NA-CTX, NS-CTX, and NK-CTX, possibly attributed to limited antigenicity of CTXs and/or different formulation of antivenom products. The study underscores the need for antivenom improvement and/or new therapies in treating local tissue toxicity caused by cobra envenomings.

Traditional medical education methodologies have been dramatically impacted by the introduction of new teaching approaches over the past few decades. In particular, the "flipped classroom" format has drawn a great deal of attention. However, evidence regarding the effectiveness of the flipped model remains limited due to a lack of outcome-based studies. In the present study, a pilot histology curriculum of the organ systems was implemented among 24 Traditional Chinese Medicine (TCM) students in a flipped classroom format at Jinan University. As a control, another 87 TCM students followed a conventional histology curriculum. The academic performance of the two groups was compared. In addition, a questionnaire was administered to the flipped classroom group. The test scores for the flipped classroom participants were found to be significantly higher compared to non-participants in the control group. These results suggest that students may benefit from using the flipped classroom format. Follow-up questionnaires also revealed that most of the flipped classroom participants undertook relatively more earnest preparations before class and were actively involved in classroom learning activities. The teachers were also found to have more class time for leading discussions and delivering quizzes rather than repeating rote didactics. Consequently, the increased teaching and learning activities contributed to a better performance among the flipped classroom group. This pilot study suggests that a flipped classroom approach can be used to improve histology education among medical students. However, future studies employing randomization, larger numbers of students, and more precise tracking methods are needed before definitive conclusions can be drawn.

Few studies have explored the learning difficulties and misconceptions that students encounter when using information and communication technology for e-learning. To address this issue, this research developed a system for evaluating the learning efficiency of medical students by applying two-tier diagnosis assessment. The effectiveness of the proposed system was evaluated in 11 resident doctors of dermatology enrolled according to a one-group pre- and post-test experimental design. After using the proposed e-learning system, the resident doctors had significantly improved learning efficiency and high satisfaction with the system functions. Although the number of subjects in this study was low, the significant improvements in clinical skills observed at the end of the educational training program indicate that the proposed integrated e-learning system is user-friendly and effective for self-education in the diagnosis skills required by medical students and dermatology residents.

The equatorial spitting cobra, Naja sumatrana, is a distinct species of medically important venomous snakes, listed as WHO Category 1 in Southeast Asia. The diversity of its venom genes has not been comprehensively examined, although a few toxin sequences annotated to Naja sputatrix were reported previously through cloning studies. To investigate this species venom genes’ diversity, de novo venom-gland transcriptomics of N. sumatrana from West Malaysia was conducted using next-generation sequencing technology. Genes encoding toxins represented only 60 of the 55,396 transcripts, but were highly expressed, contributing to 79.22% of total gene expression (by total FPKM) in the venom-glands. The toxin transcripts belong to 21 families, and 29 transcripts were further identified as full-length. Three-finger toxins (3FTx) composed of long, short, and non-conventional groups, constituted the majority of toxin transcripts (91.11% of total toxin FPKM), followed by phospholipase A2 (PLA2, 7.42%)—which are putatively pro-inflammatory and cytotoxic. The remaining transcripts in the 19 families were expressed at extremely low levels. Presumably, these toxins were associated with ancillary functions. Our findings unveil the diverse toxin genes unique to N. sumatrana, and provide insights into the pathophysiology of N. sumatrana envenoming.

BackgroundStatins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors) consumption provides beneficial effects on cardiovascular systems. However, effects of statins on vascular KATP channel gatings are unknown.MethodsPig left anterior descending coronary artery and human left internal mammary artery were isolated and endothelium-denuded for tension measurements and Western immunoblots. Enzymatically-dissociated/cultured arterial myocytes were used for patch-clamp electrophysiological studies and for [Ca(2+)]i, [ATP]i and [glucose]o uptake measurements.ResultsThe cromakalim (10 nM to 10 µM)- and pinacidil (10 nM to 10 µM)-induced concentration-dependent relaxation of porcine coronary artery was inhibited by simvastatin (3 and 10 µM). Simvastatin (1, 3 and 10 µM) suppressed (in okadaic acid (10 nM)-sensitive manner) cromakalim (10 µM)- and pinacidil (10 µM)-mediated opening of whole-cell KATP channels of arterial myocytes. Simvastatin (10 µM) and AICAR (1 mM) elicited a time-dependent, compound C (1 µM)-sensitive [(3)H]-2-deoxy-glucose uptake and an increase in [ATP]i levels. A time (2-30 min)- and concentration (0.1-10 µM)-dependent increase by simvastatin of p-AMPKα-Thr(172) and p-PP2A-Tyr(307) expression was observed. The enhanced p-AMPKα-Thr(172) expression was inhibited by compound C, ryanodine (100 µM) and KN93 (10 µM). Simvastatin-induced p-PP2A-Tyr(307) expression was suppressed by okadaic acid, compound C, ryanodine, KN93, phloridzin (1 mM), ouabain (10 µM), and in [glucose]o-free or [Na(+)]o-free conditions.ConclusionsSimvastatin causes ryanodine-sensitive Ca(2+) release which is important for AMPKα-Thr(172) phosphorylation via Ca(2+)/CaMK II. AMPKα-Thr(172) phosphorylation causes [glucose]o uptake (and an [ATP]i increase), closure of KATP channels, and phosphorylation of AMPKα-Thr(172) and PP2A-Tyr(307) resulted. Phosphorylation of PP2A-Tyr(307) occurs at a site downstream of AMPKα-Thr(172) phosphorylation.

Objectives: This study describes the development and feasibility of Integrative Nutritional Counseling (INC), a Chinese medicine (CM)+biomedicine-based nutrition curriculum for Chinese Americans with type 2 diabetes. Although Chinese Americans often incorporate CM principles into their diet, scant research has explored how to integrate CM with biomedical nutrition standards in a culturally appropriate manner or if such a program could improve diabetes self-management. Design: This is a 1-month pre-post study design including three points of contact: baseline, in-person class, and 1-month follow-up. Subjects: Participants (n = 15) were Cantonese-speaking/reading Chinese Americans diagnosed with type 2 diabetes who had used some form of CM/medicinal foods in the last 12 months. Interventions and Outcome Measures: The INC program included baseline surveys and a CM intake interview conducted by a licensed acupuncturist. The acupuncturist generated a CM diagnosis, which was shared with the participant, and used this diagnosis to tailor brief nutrition education. To bolster this brief education, a bilingual registered dietitian provided a 2-h group education class in Cantonese to all participants, during which time participants also received a Chinese/English INC booklet. Participants completed surveys immediately after the class and at 1-month follow-up, with qualitative exit interviews. Results: Participants reported improved attitudes and dietary habits aligning directly with INC, and improvement in biomedically valued measures of type 2 diabetes, such as weight loss, and CM-valued measures of digestion/elimination and hot/cold feeling. Satisfaction with INC was high, but challenges included confusion with some INC information, structural barriers, and comorbidities. Conclusions: Chinese Americans with type 2 diabetes and interventionists found integrative nutrition approaches acceptable and feasible. Future research should examine INC with a larger population and explore optimal delivery of INC given reported challenges.

BackgroundCancer-related fatigue (CRF) is a debilitating condition which commonly affects cancer survivors. The management of CRF remains a challenge due to the lack of effective pharmacological interventions. Traditional Chinese medicine (TCM) could be a potential therapeutic option for CRF. The modified Xiang Bei Yang Rong Tang (XBYRT) is a TCM herbal decoction, formulated to improve fatigue symptoms in cancer survivors. This clinical trial aims to evaluate the efficacy and safety of XBYRT in improving CRF and quality of life (QOL) of cancer survivors.MethodsThis is a single centre, randomized, double-blind, placebo-controlled, parallel trial. Eighty cancer survivors will be recruited and randomized to receive the XBYRT or placebo decoction, in a ratio of 1:1. Participants will consume the XBYRT/placebo decoction daily for 8 weeks and undergo assessments at baseline and 4, 8 and 10 weeks after baseline. The participants will be assessed for patient-reported outcomes (PRO), blood biomarkers and adverse events at each time point. The primary outcome is the overall health and QOL status, at 8 weeks follow-up. The secondary outcomes are the effects of XBYRT on fatigue levels, cancer-related cognitive impairment and QOL, as assessed by PRO. The incidence of adverse events and the effects of the XBYRT decoction on blood biomarkers associated with CRF will also be evaluated.DiscussionEfficacy and safety outcomes from this trial will provide important clinical data to guide future large-scale randomized controlled trials, and the evaluation of the objective blood biomarkers can help to delineate the biological mechanisms of CRF.Trial registration numberClinicalTrials.gov NCT04104113 . Registered on 26 September 2019.

ObjectivesCurrent cardiovascular disease (CVD) nutrition guidelines do not take into account Chinese medicine (CM) principles. We created a heart healthy integrative nutritional counseling (H2INC) curriculum consistent with CM principles and current nutrition guidelines.MethodsWe conducted three phases of semi-structured interviews with key stakeholders (CM and biomedical providers and Chinese American (CAs) patients with CVD) followed by iterative development of H2INC. First, we interviewed licensed CM providers (n = 9) and laypeople with CM foods expertise (n = 1). Second, we interviewed biomedical providers (n = 11) and licensed CM providers (n = 3). Third, we conducted four focus groups with CAs (n = 20) with CVD.ResultsStakeholders emphasized different principles for creating H2INC. Phase one emphasized alignment of CM diagnoses to biomedical CVD conditions. Phase two overlaid CM concepts like the nature of foods and constitution (hot/neutral/cool) with heart healthy nutrition recommendations such as MyPlate, and avoiding excess salt, fat, and sugars. Phase three demonstrated patient acceptability.ConclusionBy integrating CM foods principles with biomedical nutrition, this integrative approach yields culturally relevant health education for an underserved population.Practice implicationsIntegrative nutritional counseling shows promise for CAs and could support biomedical providers with little knowledge about patients' use of CM for CVD.

Stroke is ranked third among the top 10 causes of death in Taiwan. Besides a high mortality rate, stroke survivors are often left with physical or functional sequela. This study aimed to explore ischemic stroke patients' decision-making process using Western medicine (WM) and complementary and alternative medicine (CAM). This study is a qualitative study based on grounded theory. A total of 12 participants were recruited. Findings revealed that the participants accepted WM and CAM treatments following the onset of ischemic stroke. Three categories and several subcategories emerged from stroke patients' decision-making process. These are "uncertainty of stroke," "delicate balance between WM and CAM," and "reestablishing confidence and faith." Eventually, they exhibited the core category of "breakthrough and the pursuit of a sense of rebirth." This study also found that the participants were unwilling to inform their health care professionals on their use of CAM. Therefore, health care professionals should empathize with the views and needs of their patients and respect their decision to combine WM with CAM. The views of other medical teams concerning CAM into their analysis of patients' decision-making process are recommended. Therefore, comprehensive insight into ischemic stroke patients' decision-making process for using CAM can be further explored. [ABSTRACT FROM AUTHOR]

The introduction of traditional, complementary and integrative medicine (TCIM) services into health systems has been advocated by the World Health Organization, but there is a paucity of reviews synthesising the experiences of (i) implementing TCIM services in conventional healthcare settings and (ii) introducing evidence-based practice in TCIM. Knowledge of the first issue will assist policymakers to innovate implementation interventions in their own health system contexts. Addressing the second issue will facilitate the closure of the evidence–practice gap in TCIM and improve the translation of research evidence into health outcome benefits. The aim of this study was to identify, describe and analyse publications on these two key TCIM policy issues via an overview from an implementation science perspective. Publications describing international experiences of implementing TCIM services or evidence for TCIM practices were identified by searching MEDLINE, EMBASE and Global Health databases in November 2021. The findings were summarised using a narrative synthesis approach. Sixty-three relevant publications were included in the analysis. Current experiences in China and the United Sates (US) reflect varying policy priorities at different stages of implementing TCIM services. In the US, where TCIM have yet to be introduced into mainstream healthcare settings, implementation interventions were designed to facilitate the provision of specific, evidence-based TCIM modalities via referrals from conventional clinicians. The application of these strategies at the health system, regulatory, financial, community, provider and patient levels provided a comprehensive picture of how TCIM implementation may be facilitated via multi-level interventions. In China, the major form of TCIM is traditional Chinese medicine (TCM), for which service provision has already been adopted at all levels of healthcare. With the high volume of clinical research that has been generated in the past several decades, a key policy question at this stage is how to translate TCM-related clinical evidence into practice. The development of clinical practice guidelines (CPGs) is the main implementation intervention, but adherence by TCM clinicians has been poor, due to the conflict between classical individualised practice and CPG standardisation. While tailoring interventions to facilitate CPG uptake is indicated, concurrent innovations in TCM clinical research methods would improve the compatibility between classical and CPG-based practice. Policymakers managing different stages of TCIM implementation will benefit from the experiences of practitioners in the US and China. Multi-level implementation interventions launched in the US provide ideas for the initial introduction of TCIM into a conventional medicine-dominated health system. As TCIM service provision and related clinical research become more common, China's experience will inform how clinical evidence related to TCIM may be disseminated and implemented to improve service quality. [ABSTRACT FROM AUTHOR]

Introduction In traditional Chinese medicine (TCM), decision on prescription is based on a process called Bian Zheng Lun Zhi (syndrome differentiation guided treatment decision). Syndrome differentiation process may not be recognized in conventional standards of randomized controlled trial (RCT), limiting model validity and generalizability of results. Method Three major international databases were searched up to July 2016 for articles which discussed how syndrome differentiation, a classical TCM approach in diagnosis, can be incorporated into RCT design. Results Four methodological solutions were proposed: (i) Lessons learnt from the design of patient reported outcome questionnaire can inform how a TCM diagnosis instrument can be developed. A proper TCM diagnostic tool with sound psychometric properties can reduce variation in the syndrome differentiation process. (ii) Treatment strategies for a specific TCM diagnosis could be highly diversified. Delphi technique can inform the design of an optimal treatment program by facilitating consensus among experts. (iii) Subgroup analysis is often needed in RCTs recruiting patients with several TCM diagnoses. It is highlighted that investigators should consider whether the design, analysis and context of the trial are robust enough to support a reliable claim of the subgroup effect associated with a particular TCM diagnosis. (iv) Finally, we discuss alternative research and analysis approaches for handling misalignment of Western and TCM diagnoses, including the possibility of unifying TCM syndrome with Western phenotypes using latent class analysis. Conclusion Further methodological advances are needed for better alignment of classical TCM theories and diagnostic instrument development, as well as in reducing bias during expert consensus processes. [ABSTRACT FROM AUTHOR]

Schizophrenia is a major mental disorder in which patients’ cognitive functions gradually deteriorate. Pharmacological intervention with antipsychotics has proven effective, yet it is still debatable whether to initiate treatment in patients’ premorbid stage. Based on the developmental origins of schizophrenia, we hypothesize that for those who are at high risk for schizophrenia, particularly with gating problems, an early pharmacological intervention would be beneficial. We performed a pilot rodent study to evaluate this hypothesis. Our results demonstrated that isolation rearing-induced sensorimotor gating dysfunction could be reversed by a chronic risperidone regimen initiated at different age time points. As expected, interventions that we initiated earlier (in adolescent stage) appeared to have better efficacy than interventions initiated four weeks later (in young adult stage). Our hypothesis may contribute new insight for both prevention and treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

Background This study investigated whether the time from emergency room registration to appendectomy (ETA) would affect the incidence of perforation and postoperative complications in patients with acute appendicitis. Methods Patients who underwent an appendectomy at the Ren-Ai branch of Taipei City Hospital between January 2010 and October 2012 were retrospectively reviewed. Their demographics, white blood cell count, C-reactive protein, body temperature, computed tomography scan usage, operation method, pathology report, postoperative complication, length of hospital stay, and ETA were abstracted. Multivariate analysis was performed to search the predictors, including ETA, of outcomes for the perforation and postoperative complication rates. Results A total of 236 patients were included in the study. Perforation occurred in 12.7% (30/236) and postoperative complications developed in 24.1% (57/236) of these patients. There were 121 patients with ETA <8 hours, 88 patients with ETA of 8–24 hours, and 27 patients with ETA >24 hours; patients with ETA >24 hours had significantly longer hospital stay. Univariate analysis showed that perforated patients were significantly older, and had higher C-reactive protein level, longer hospital stay, and higher complication rate. Patients who developed postoperative complications were significantly older, and had higher neutrophil count, less use of computed tomography, and higher open appendectomy rate. After multivariate analysis, age ≥55 years was the only predictor for perforation [odds ratio (OR) = 3.65; 95% confidence interval (CI), 1.54–8.68]; for postoperative complications, age ≥55 years (OR = 1.65; 95% CI, 1.84–3.25), perforated appendicitis (OR = 3.17; 95% CI, 1.28–7.85), and open appendectomy (OR = 3.21; 95% CI, 1.36–7.58) were associated. ETA was not a significant predictor in both analyses. Conclusion In our study, it was observed that although longer ETA was associated with longer hospitalization, ETA was not correlated with postoperative complications. Our results inclined toward the position that appendectomy can be performed as a semielective surgery. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation (RFA) has been widely applied for the treatment of hepatocellular carcinoma and liver metastases. The reported mortality and morbidity rates are low. The aim of this study is to evaluate the safety and efficacy of RFA, and compare the results performed percutaneously versus surgically. Patients and Methods: From 2003 to 2006, 79 patients with hepatic malignancies (59 hepatocellular carcinoma, 20 liver metastases) with a total of 110 lesions underwent RFA in our centre. Post-ablation assessment by CT scan was performed in all patients at 1-, 3- and 6-month intervals. Post-procedural complications, recurrence and survival were analysed. Results: The patients'' mean age was 60.0 years. In 46.8% of cases, we used a percutaneous approach; in 53.2% of cases, a surgical approach (8.9% laparoscopic; 44.3% open) was used if percutaneous approach was not feasible. The mean tumour size was 2.4 cm. Within the surgical group, 69% of patients received concomitant operative procedures such as cholecystectomy and hepatectomy. No treatment-related mortality was observed. Immediate complications occurred in five patients (6.3%), including gastric serosal burn (n = 1), ground pad superficial skin burn (n = 1), intra-abdominal bleeding (n = 2) and pleural effusion (n = 1). All patients except one attended subsequent follow-up, with a mean period of 16 months. Ablation was considered complete in 82.3% of patients (percutaneous approach 81.1%, surgical approach 83.3%, p = 0.72). Intrahepatic recurrence was observed in 52.3%, the majority of them located away from the RFA site. Extrahepatic recurrences were observed in 16.9% (percutaneous approach 16.7%, surgical approach 17.1%, p = 0.76). The overall one- and two-year survival rate was 93.7% and 74.4% respectively, and no statistically significant difference was observed between the two approaches. Conclusion: RFA is a safe and effective procedure for treating patients with malignant liver tumours. No difference in short term outcomes was observed between percutaneous and surgical approaches. A more prolonged follow-up study is required to assess longer-term outcomes. [Copyright &y& Elsevier]

Abstract: Lhermitte-Duclos disease or dysplastic gangliocytoma of the cerebellum, is a rare cerebellar lesion, which can cause mass effects in the posterior fossa. It may occur sporadically, or in association with Cowden syndrome. Cowden syndrome or multiple hamartoma-neoplasia syndrome, is an uncommon autosomal dominant condition characterized by mucocutaneous lesions and systemic malignancies. We report two patients with Lhermitte-Duclos disease and associated Cowden syndrome. The clinical, radiological and histopathological features and management strategies of this rare disease complex are discussed. [Copyright &y& Elsevier]

Abstract: Two endoparasitoids, Cotesia plutellae and C. glomerata, parasitize the diamondback moth, Plutella xylostella, and induce significant host immunosuppression. This study analyzed the susceptibility changes of the parasitized P. xylostella against other pathogens using an entomopathogenic bacterium, Xenorhabdus nematophila (Xn), and a viral pathogen, Autographa californica nucleopolyhedrosis virus (AcNPV). The P. xylostella parasitized by either C. plutellae or C. glomerata exhibited higher susceptibilities to both microbial pathogens than the nonpara-sitized. To determine the parasitism factors inducing the enhanced susceptibility, three polydnaviral genes so far successfully cloned were selected from C. plutellae bracovirus (CpBV). CpBV-lectin and CpBV15 α/β were inserted into AcNPV under a CpBV promote and analyzed in their pathogenicities against P. xylostella larvae. Two AcNPVs recombined with CpBV15α/β were more potent than the control AcNPV recombined with an enhanced green fluorescent protein gene or the AcNPV recombined with CpBV-lectin. These results suggest that the wasp parasitization enhances other pathogen susceptibilities by inducing host immunosuppression, in which the symbiotic polydnavirus can play significant role in the enhanced susceptibility. [Copyright &y& Elsevier]

Abstract: Fabrication of next-generation biologically active materials will involve the integration of proteins with synthetic membrane materials toward a wide spectrum of applications in nanoscale medicine, including high-throughput drug testing, energy conversion for powering medical devices, and bio-cloaking films for mimicry of cellular membrane surfaces toward the enhancement of implant biocompatibility. We have used ABA triblock copolymer membranes (PMOXA-PDMS-PMOXA) of varied thicknesses as platform materials for Langmuir film–based functionalization with the OmpF pore protein from Escherichia coli by fabricating monolayers of copolymer amphiphile-protein complexes on the air/water interface. Here we demonstrate that the ability for protein insertion at the air/water interface during device fabrication is dependent upon the initial surface coverage with the copolymer as well as copolymer thickness. Methacrylate-terminated block copolymer structures that were 4 nm (4METH) and 8 nm (8METH) in length were used as the protein reconstitution matrix, whereas a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid (~4 nm thickness) was used as a comparison to demonstrate the effects of copolymer length on protein integration capabilities. Wilhemy surface pressure measurements (mN/m) revealed a greater protein insertion in the 4METH and POPC structures compared with the 8METH structure, indicating that shorter copolymer chains possess enhanced biomimicry of natural lipid-based membranes. In addition, comparisons between the isothermal characteristics of the 4METH, 8METH, and POPC membranes reveal that phase transitions of the 4METH resemble a blend of the 8METH and POPC materials, indicating that the 4METH chain may possess hybrid properties of both copolymers and lipids. Furthermore, we have shown that following the deposition of the amphiphilic materials on the air/water interface, the OmpF can be deposited directly on top of the amphiphiles (surface addition), thus effectively further enhancing protein insertion because of the buoying effects of the membranes. These characteristics of Langmuir-Blodgett–based fabrication of copolymer-biomolecule hybrids represent a synthesis strategy for next-generation biomedical materials. [Copyright &y& Elsevier]

Summary: Although naturally mummified corpses have frequently been found in medieval tombs of Korea, there have been no scientific reports on the physical status of the mummies. In this study, we first tried to investigate the mummy using radiological methods. On physical examination, there were no findings suggestive of the cause of the death. From the radiological studies, we found that some internal organs were well preserved, while the bones showed similar appearances to those of living cases. From the stage of development of the teeth and carpal bones, the age of the mummy was estimated to be 4.5 to 6.6 years old. Although the exact cause of the mummification could not be clearly elucidated, it may be due to the lime-soil mixture outside the outer coffin, completely sealing the inner coffin from the outer spaces. In this study, as the mummy in the medieval tomb has proved to be well preserved over the last 400 years, similar cases could give invaluable clues to the physical status of medieval Koreans. [Copyright &y& Elsevier]

Purpose: The authors report their experience with three types of retrievable covered nitinol stents in patients with malignant esophageal strictures.Materials and Methods: Three types of retrievable covered nitinol stents were designed. Type A stents were placed in 45 patients, type B stents were placed in 29 patients, and type C stents were placed in 34 patients. The stents were removed with use of a stent retrieval set under fluoroscopic guidance when the stents caused complications. Stent patency, symptom relief, survival rate, and complications were analyzed relative to stent type and radiation therapy.Results: The timing of radiation and the stent type have significant effects on occurrence of complications such as stent migration and fistula formation (P =.002 and P = 0.029, respectively). Complications were significantly more frequent in patients with the type B stent than those with type A or type C stents (P =.008). Patients who underwent radiation therapy before stent placement or who underwent no radiation therapy experienced substantially less complications than those who underwent radiation therapy after stent placement (P =.005 and P <.001, respectively). The survival period was significantly longer in patients who underwent radiation therapy after stent placement than in the other groups (P =.034). Stents were removed from 15 patients (14%) 2 days to 16 weeks (mean, 4 weeks) after stent placement as a result of severe pain (n = 7), stent migration (n = 6), or stent deformity (n = 2). Stent removal was well tolerated in all patients.Conclusion: Use of retrievable covered nitinol stents seems to be a safe and effective method of treatment in patients with malignant esophageal strictures. However, removal of the stents was needed in 14% of the patients because of complications. Patients who underwent radiation therapy after stent placement and those with the type B stent experienced more complications than other patients. [ABSTRACT FROM AUTHOR]

Objectives. Balloon dilation of the Eustachian tube (BDET) is widely recognized as a minimally invasive treatment for obstructive Eustachian tube dysfunction (ETD). We employed a Delphi consensus methodology to develop recommendations for the clinical management of BDET in cases of obstructive ETD. Methods. A Delphi panel consisting of 26 expert physicians specializing in otology participated in two rounds of anonymous, iterative questionnaires. Consensus was defined as agreement from ≥70% of the panelists on a recommendation, while disagreement was defined as

Abstract Processing-in-memory (PIM) is gaining tremendous research and commercial interest because of its potential to replace the von Neumann bottleneck in current computing architectures. In this study, we implemented a PIM hardware architecture (circuit) based on the charge-trap flash (CTF) as a synaptic device. The PIM circuit with a CT memory performed exceedingly well by reducing the inference energy in the synapse array. To evaluate the image recognition accuracy, a Visual Geometry Group (VGG)-8 neural network was used for training, using the Canadian Institute for Advanced Research (CIFAR)-10 dataset for off-chip learning applications. In addition to the system accuracy for neuromorphic applications, the energy efficiency, computing efficiency, and latency were closely investigated in the presumably integrated PIM architecture. Simulations that were performed incorporated cycle-to-cycle device variations, synaptic array size, and technology node scaling, along with other hardware-sense considerations.

Abstract This study investigates the effects of the sport education model on physical literacy and its subsequent impact on daily physical activity levels among university students. Through mediation analysis, this study seeks to uncover the role of situational motivation in these effects. The participants in this study consist of 188 university students (male n = 132, female n = 70; mean age: 18.53 years) who were exposed to an 8-class, 10-lesson season as part of their physical education curriculum. Self-report measures were collected at baseline (1st lesson), post-intervention (10th lesson), and follow-up phases (5 weeks after). The results reveal significant mediation effects at the post-intervention (β = 0.201, t = 3.576, p

Abstract Alkali-free aluminoborosilicate glasses without (GDMC-Si) and with La2O3 addition (GDMC-La) were fabricated with an aim to develop low dielectric glass fibers for use in printed circuit boards (PCBs) as a reinforcing material in high-speed 5G/6G telecommunications application. This study presents the structural, thermo-physical, and dielectric properties of the glasses. The decrease in glass transition temperature (Tg) and the increase in coefficient of thermal expansion (CTE) were found by the addition of SiO2 and La2O3 in the present glass system, which are due to the depolymerization of the glass networks confirmed by the FTIR analysis. The dielectric constants (Dk) and the dissipation factors (Df) of the glasses were investigated at a high frequency of 10 GHz. The Dk values of the GDMC-Si and GDMC-La glass systems reached a minimum of 4.50 and 4.75, while their Df values reached a minimum of 2.86 × 10−3 and 3.01 × 10−3, respectively. Notably, the Dk and Df values of the present glasses were lower than the commercial E-glass (Dk: 6.9, Df: 7.0 × 10−3 at 10 GHz) and L-glass (Dk: 4.8, Df: 3.0 × 10−3 at 10 GHz). Glass fibers with a diameter of 10 μm were successfully drawn by the continuous melt-spinning process and their mechanical properties were investigated.

Abstract The early microbiota of neonates is crucial for developing the postnatal immune system and establishing normal physiological, metabolic, and neurological functions. This study aimed to investigate the factors influencing the diversity of the neonatal oral microbiome, including mother-to-newborn microbial transmission. The study includes a prospective cohort comprising 73 mothers and 87 neonates and a retrospective cohort comprising 991 mothers and 1,121 neonates. Samples from the maternal cervix and neonatal gastric, bronchial, and oral cavities were analyzed using culture-based methods. Neonatal oral swab samples were also analyzed using 16S rRNA gene sequencing to characterize microbial diversity and composition. Similar genera were detected in the neonatal gastric, bronchial, and oral samples, and the neonatal gastric culture was the most similar to the maternal cervical culture. In addition to mother-to-newborn microbial transmission, various natal factors including birth type, birth weight, delivery mode, maternal chorioamnionitis, maternal diabetes and the presence of microbes in other sites influenced neonatal oral microbiome diversity. Among these factors, the birth type was the most significant, and preterm neonates exhibited decreased oral microbiome diversity, with fewer beneficial bacteria and more pathogens. These findings could serve as a baseline for research on the establishment of the oral microbiota in preterm neonates and its health implications.

Abstract Fluorescence-guided surgery has emerged as an innovative technique with promising applications in the treatment of various tumors, including colon cancer. Tumor-initiating probe yellow (TiY) has been discovered for identifying tumorigenic cells by unbiased phenotypic screening with thousands of diversity-oriented fluorescence library (DOFL) compounds in a patient-derived lung cancer cell model. This study demonstrated the clinical feasibility of TiY for tumor-specific fluorescence imaging in the tissues of patients with colorectal cancer (CRC). To evaluate the efficacy of TiY in tumor imaging, surgical specimens were obtained, consisting of 36 tissues from 18 patients with CRC, for ex vivo molecular fluorescence imaging, histology, and immunohistochemistry. Orthotopic and chemically induced CRC mice models were administered TiY topically, and distinct tumor lesions were observed in 10 min by real-time fluorescence colonoscopy and ex vivo imaging. In a hepatic metastasis mouse model using splenic injection, TiY accumulation was detected in metastatic liver lesions through fluorescence imaging. Correlation analysis between TiY intensity and protein expression, assessed via immunohistochemistry and Western blotting, revealed a positive correlation between TiY and vimentin and Zeb1, which are known as epithelial–mesenchymal transition (EMT) markers of cancers. A comparative analysis of TiY with other FDA-approved fluorescence probes such as ICG revealed greater quantitative differences in TiY fluorescence intensity between tumor and normal tissues than those observed with ICG. Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC.

Abstract Background Stress-induced activation of ERK/Drp1 serves as a checkpoint in the segregation of damaged mitochondria for autophagic clearance (mitophagy). Elevated cytosolic calcium (Ca2+) activates ERK, which is pivotal to mitophagy initiation. This process is altered in Parkinson’s disease (PD) with mutations in leucine-rich repeat kinase 2 (LRRK2), potentially contributing to mitochondrial dysfunction. Pathogenic LRRK2 mutation is linked to dysregulated cellular Ca2+ signaling but the mechanism involved remains unclear. Methods Mitochondrial damages lead to membrane depolarization. To investigate how LRRK2 mutation impairs cellular response to mitochondrial damages, mitochondrial depolarization was induced by artificial uncoupler (FCCP) in wild-type (WT) and LRRK2R1441G mutant knockin (KI) mouse embryonic fibroblasts (MEFs). The resultant cytosolic Ca2+ flux was assessed using live-cell Ca2+ imaging. The role of mitochondria in FCCP-induced cytosolic Ca2+ surge was confirmed by co-treatment with the mitochondrial sodium-calcium exchanger (NCLX) inhibitor. Cellular mitochondrial quality and function were evaluated by Seahorse™ real-time cell metabolic analysis, flow cytometry, and confocal imaging. Mitochondrial morphology was visualized using transmission electron microscopy (TEM). Activation (phosphorylation) of stress response pathways were assessed by immunoblotting. Results Acute mitochondrial depolarization induced by FCCP resulted in an immediate cytosolic Ca2+ surge in WT MEFs, mediated predominantly via mitochondrial NCLX. However, such cytosolic Ca2+ response was abolished in LRRK2 KI MEFs. This loss of response in KI was associated with impaired activation of Ca2+/calmodulin-dependent kinase II (CaMKII) and MEK, the two upstream kinases of ERK. Treatment of LRRK2 inhibitor did not rescue this phenotype indicating that it was not caused by mutant LRRK2 kinase hyperactivity. KI MEFs exhibited swollen mitochondria with distorted cristae, depolarized mitochondrial membrane potential, and reduced mitochondrial Ca2+ store and mitochondrial calcium uniporter (MCU) expression. These mutant cells also exhibited lower cellular ATP: ADP ratio albeit higher basal respiration than WT, indicating compensation for mitochondrial dysfunction. These defects may hinder cellular stress response and signals to Drp1-mediated mitophagy, as evident by impaired mitochondrial clearance in the mutant. Conclusions Pathogenic LRRK2R1441G mutation abolished mitochondrial depolarization-induced Ca2+ response and impaired the basal mitochondrial clearance. Inherent defects from LRRK2 mutation have weakened the cellular ability to scavenge damaged mitochondria, which may further aggravate mitochondrial dysfunction and neurodegeneration in PD.

Abstract This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods:Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 coun-tries were analyzed descriptively, with a Delphi process used for expert recommendations. Results:Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoosper-mia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differ-entiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions:Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.