Miracle-dz/UniFAR-FTUs huggingface dataset:
Interprofessional education for shared decision making in drug therapy: a scoping review

ABSTRACT The current complex scenario of medication use calls for the implementation of interprofessional education (IPE) initiatives focused on shared decision making (SDM) in drug therapy. A scoping review was conducted to collate, summarize, and report the evidence available on IPE teaching and learning approaches in this context, involving pre-licensure healthcare students. Searches were conducted in seven electronic databases, with 21 articles meeting the inclusion criteria. This review examines educational strategies employed for interprofessional SDM as well as characteristics of students, teachers, and tutors involved in IPE interventions. The reviewed studies lack detailed description of the students’ decision-making process, and none addresses aspects related to patient preferences as a part of learning outcomes. We identified shortcomings in how IPE interventions are assessed and reported. Only a few of the studies explicitly describe the use of competency-based frameworks proposed by national and international organizations, and less than 60% describe learning outcomes. The absence of experiences focused on interprofessional SDM in drug therapy suggests a gap that needs to be addressed with future studies evaluated in a robust way. We argue that such experiences enable students, as a team, to learn to share decisions with the patient as an effective team member.
Evolving patterns of antiretroviral drug interactions in people with HIV in British Columbia, Canada

Objectives: To characterize the annual prevalence of antiretroviral/nonantiretroviral drug interactions in relation to antiretroviral therapy (ART)-prescribing patterns, and to describe drug interaction-related ART changes. Design/methods: This cohort study included ART-treated adults in British Columbia, Canada between 01 January 2010 and 31 December 2016. Medication dispensing records were abstracted from a population-based, linked administrative-health dataset and used to identify antiretroviral-comedication drug interactions (’caution’/’avoid’ drug interactions in HIV-focused drug interaction checkers). We identified temporal trends in annual drug interaction prevalence and quantified the association between taking higher drug interaction-risk ART and receiving nonrecommended antiretroviral-comedication combinations using Poisson regression models, modified for binary outcomes and correlated data. Clinician-reported, drug interaction-related ART changes and associated adverse events were abstracted from an HIV drug treatment registry and summarized descriptively. Results: Among 8571 ART-treated adults who received nonantiretroviral comedications, prevalence of having any drug interaction or receiving nonrecommended drug combination(s) significantly declined from 85 to 71% and 5.6 to 3.2%, respectively, between 2010 and 2016 (P < 0.001). This paralleled a shift from higher drug interaction-risk ART (e.g. ritonavir/cobicistat-boosted protease inhibitors) to lower drug interaction-risk ART (e.g. unboosted integrase inhibitors). Risk of receiving a nonrecommended antiretroviral-comedication combination was greater for persons taking higher vs. lower drug interaction-risk ART [adjusted risk ratio (aRR) 3.12, 95% confidence interval (CI) 2.24–4.35]. Boosted antiretroviral-inhaled corticosteroid drug interactions accounted for the most commonly dispensed, nonrecommended drug combinations, and the most commonly reported drug interaction-related adverse events (adrenal insufficiency). Conclusion: The prevalence of antiretroviral-comedication drug interactions is declining as ART shifts towards antiretrovirals with lower drug interaction potential but nonrecommended drug combinations remain a concern. Healthcare providers should screen for drug interactions whenever drugs are prescribed or dispensed.
Amoxicillin-associated Stevens-Johnson syndrome or toxic epidermal necrolysis: systematic review

Abstract Our aim was to explore and summarize available cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) suspected to be associated with amoxicillin reported in the literature. Electronic searches were conducted in several databases. Fifty-one publications describing a total of 64 patients who satisfied inclusion criteria were included in the review. The age of the patients ranged from 1.5-80 years (median: 24.5 years). TEN, SJS and SJS/TEN overlap were diagnosed in 30 (46.9%), 28 (43.8%) and 1 (1.6%) patients, respectively. SJS/TEN may occur promptly after administration of amoxicillin, but it could also be a delayed adverse effect. The total length of hospital stay ranged from 3-70 days (median: 16 days). Amoxicillin-induced SJS/TEN is accompanied by frequent occurrence of serious complications, long-term ocular and skin sequelae and high mortality rate. Clinicians should be aware that amoxicillin alone or combined with clavulanic acid can cause SJS/TEN in patients of all ages.
Ginkgo biloba extract 761 reduces vascular permeability of the ovary and improves the symptom of ovarian hyperstimulation syndrome in a rat model

Abstract Aims Ginkgo biloba extract (EGb) has been widely applied in the treatment of cerebrovascular and neurological diseases. However, the effect of EGb761 on ovarian hyperstimulation syndrome (OHSS), a vascular disorder and life-threatening complication of in vitro fertilization and intracytoplasmic sperm injection therapy (IVF/ICSI), has not been evaluated. Materials and methods Forty female Wistar rats aged 22-days old (D22) were divided into eight groups: Control rats received intraperitoneal injection of saline for five consecutive days (D22–D26); OHSS model group received 10 IU equine chorionic gonadotropin (eCG) for four consecutive days (D22–D25) and 30 IU of human chorionic gonadotropin (hCG) on the 5th day (D26); Prophylactic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/day) 1 h before injection of eCG (hCG) for seven consecutive days; Therapeutic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/day) 48 h after injection of eCG (hCG) for seven consecutive days. Results All three doses of EGb761 therapeutic medication significantly reduced ovarian mass index of OHSS model rats (p ≤ .01). Furthermore, therapeutic treatment group exhibited improved vascular permeability, decreased estradiol and progesterone levels, lower corpus luteum, and higher follicle numbers compared with the OHSS model. Elevated protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) in both ovary and kidney of the OHSS model was restrained by EGb761 therapeutic treatment. Conclusions EGb761 therapeutic medication decreases vascular permeability in OHSS rat model by inhibiting VEGF and VEGFR expression, which may contribute to the treatment of OHSS.
MicroRNA‐455‐3p functions as a tumor suppressor by targeting HDAC2 to regulate cell cycle in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers. MicroRNA has been studied more and more deeply and may become a new target for the treatment of HCC. Here, we investigated the role of miR‐455‐3p in HCC progression. Compared with non‐tumor tissues and normal human hepatic cells, miR‐455‐3p expression was significantly downregulated in HCC tissues and cell lines. And overexpression of miR‐455‐3p inhibited cell proliferation and migration but promoted cell apoptosis in HCC cell lines HepG2 and Huh7. Mechanism studies displayed that miR‐455‐3p targeted HDAC2 and negatively regulated HDAC2 expression. Moreover, HDAC2 was highly expressed in HCC tissues and cell lines. Overexpression of HDAC2 reversed the inhibitory effects of miR‐455‐3p on cell proliferation, migration and cell cycle protein (CDK6 and cyclin D1) expression, and neutralized the promotion effects of miR‐455‐3p on cell apoptosis and the activation of p53 pathway. Furthermore, a p53 inhibitor Pifithrin‐α (PFT‐α) effectively abolished the effects of miR‐455‐3p on HCC cell behaviors. Additionally, the role of miR‐455‐3p in tumorigenesis was evaluated by using a mouse xenograft model, and the data showed that miR‐455‐3p suppressed tumor growth in vivo. In summary, our results suggested that miR‐455‐3p targeted HDAC2 to inhibit cell proliferation, migration and promote cell apoptosis via the activation of p53 pathway.
Genetically encoded fluorescent sensors for imaging neuronal dynamics in vivo

The brain relies on many forms of dynamic activities in individual neurons, from synaptic transmission to electrical activity and intracellular signaling events. Monitoring these neuronal activities with high spatiotemporal resolution in the context of animal behavior is a necessary step to achieve a mechanistic understanding of brain function. With the rapid development and dissemination of highly optimized genetically encoded fluorescent sensors, a growing number of brain activities can now be visualized in vivo. To date, cellular calcium imaging, which has been largely used as a proxy for electrical activity, has become a mainstay in systems neuroscience. While challenges remain, voltage imaging of neural populations is now possible. In addition, it is becoming increasingly practical to image over half a dozen neurotransmitters, as well as certain intracellular signaling and metabolic activities. These new capabilities enable neuroscientists to test previously unattainable hypotheses and questions. This review summarizes recent progress in the development and delivery of genetically encoded fluorescent sensors, and highlights example applications in the context of in vivo imaging.
Bacterial Homologs of Progestin and AdipoQ Receptors (PAQRs) Affect Membrane Energetics Homeostasis but Not Fluidity

Eukaryotic homologs of the progestin and AdipoQ receptor family (PAQR) have been shown to regulate membrane fluidity by affecting, through unknown mechanisms, unsaturated fatty acid (FA) metabolism. The bacterial homologs studied here mediate small and consistent changes in unsaturated FA metabolism that do not seem to impact membrane fluidity but, rather, alter membrane energetics homeostasis. ABSTRACT Membrane potential homeostasis is essential for cell survival. Defects in membrane potential lead to pleiotropic phenotypes, consistent with the central role of membrane energetics in cell physiology. Homologs of the progestin and AdipoQ receptors (PAQRs) are conserved in multiple phyla of Bacteria and Eukarya. In eukaryotes, PAQRs are proposed to modulate membrane fluidity and fatty acid (FA) metabolism. The role of bacterial homologs has not been elucidated. Here, we use Escherichia coli and Bacillus subtilis to show that bacterial PAQR homologs, which we name “TrhA,” have a role in membrane energetics homeostasis. Using transcriptional fusions, we show that E. coli TrhA (encoded by yqfA) is part of the unsaturated fatty acid biosynthesis regulon. Fatty acid analyses and physiological assays show that a lack of TrhA in both E. coli and B. subtilis (encoded by yplQ) provokes subtle but consistent changes in membrane fatty acid profiles that do not translate to control of membrane fluidity. Instead, membrane proteomics in E. coli suggested a disrupted energy metabolism and dysregulated membrane energetics in the mutant, though it grew similarly to its parent. These changes translated into a disturbed membrane potential in the mutant relative to its parent under various growth conditions. Similar dysregulation of membrane energetics was observed in a different E. coli strain and in the distantly related B. subtilis. Together, our findings are consistent with a role for TrhA in membrane energetics homeostasis, through a mechanism that remains to be elucidated. IMPORTANCE Eukaryotic homologs of the progestin and AdipoQ receptor family (PAQR) have been shown to regulate membrane fluidity by affecting, through unknown mechanisms, unsaturated fatty acid (FA) metabolism. The bacterial homologs studied here mediate small and consistent changes in unsaturated FA metabolism that do not seem to impact membrane fluidity but, rather, alter membrane energetics homeostasis. Together, the findings here suggest that bacterial and eukaryotic PAQRs share functions in maintaining membrane homeostasis (fluidity in eukaryotes and energetics for bacteria with TrhA homologs).
Exploring Bacillus thuringiensis as a model for endospore adhesion and its potential to investigate adhesins in Pasteuria penetrans

Phytonematodes are a constraint on crop production and have been controlled using nematicides; these are highly toxic and legislation in Europe and elsewhere is prohibiting their use and alternatives are being sought. Pasteuria penetrans is a hyperparasitic bacterium that form endospores and have potential to control root‐knot nematodes (Meloidogyne spp.), but their attachment to the nematode cuticle is host‐specific. Understanding host specificity has relied upon endospore inhibition bioassays using immunological and biochemical approaches. Phylogenetic analysis of survey sequences has shown P. penetrans to be closely related to Bacillus and to have a diverse range of collagen‐like fibres which we hypothesise to be involved in the endospore adhesion. However, due to the obligately hyperparasitic nature of Pasteuria species, identifying and characterizing these collagenous‐like proteins through gain of function has proved difficult and new approaches are required.
Clinicopathologic Evaluation of CTNNB1 Mutations in High-Intermediate Risk Endometrial Endometrioid Carcinoma

CTNNB1 mutations convey increased risk of recurrence in low-risk endometrial endometrioid carcinoma (EEC). Results from previous high-intermediate risk (HIR) cohorts are mixed. The aims of this study were to correlate CTNNB1 mutational status with clinical outcomes and to evaluate the relationship between CTNNB1 mutations and the 4 prognostic subgroups defined by The Cancer Genome Atlas in HIR EEC. CTNNB1 mutational status was determined by Sanger sequencing of exon 3 of the CTNNB1 gene. Mismatch repair, POLE, p53, and L1 cell-adhesion molecule (L1CAM) status were also evaluated. Descriptive statistics and survival analyses were performed. Eighty-eight cases of HIR EEC were identified, of which 22 (25%) were CTNNB1 mutant (CTNNB1-mut) and 66 (75%) were wild-type (CTNNB1-WT). Median follow-up was 60 mo. Recurrence occurred in 13/88 (15%) patients. Recurrence rates were not significantly different between patients with CTNNB1-mut and CTNNB1-WT tumors (14% vs. 15%, P=0.86). Recurrence-free survival and overall survival were not significantly different (recurrence-free survival hazard ratio: 0.97, 95% confidence interval: 0.27–3.52, P=0.96; overall survival hazard ratio: 0.23, 95% confidence interval: 0.03–1.71, P=0.15). Mismatch repair deficiency was more prevalent in CTNNB1-WT compared with CTNNB1-mut tumors (46% vs. 14%, P=0.01); prevalence of POLE mutations and aberrant p53 were not significantly different. In contrast to patients with low-risk EEC, no differences in recurrence or survival were found in patients with HIR EEC with CTNNB1-mut compared with CTNNB1-WT tumors.
Persistence of female genital mutilation/cutting in two Kenyan communities: What can we learn from change that falls short of abandonment?

ABSTRACT Literature on dynamics of change in female genital mutilation/cutting (FGM/C) portray two common but conflicting views. On one side, FGM/C is seen as static and deeply entrenched, with parents lacking agency to interpret culture, evaluate options and adopt changes. An alternative perspective focuses on the fluidity of social norms, influencing whether and how FGM/C is practised. This study asks: in counties where FGM/C persists at high rates, Kisii and Narok, are there changes in the way that FGM/C is performed? and what drives these changes? In-depth interviews and focus group discussions were conducted to illuminate these questions. Data showed five ways that FGM/C practices have changed: (1) reduction in severity of cutting, (2) medicalised cutting, (3) performing FGM/C at younger ages, (4) cutting in secret, and (5) occasionally, abandonment of FGM/C. Messaging on health risks of FGM/C and fear of criminal punishment have motivated less severe cutting and medicalisation. Legislation has also driven the practice underground. Programmes aimed at ending FGM/C should create a critical dialogue on changes in norms with the intent of reducing stigmatisation of uncut girls and their families, and the ways cutting practices are shifting, thereby building on change that is already underway.
FAT1 and MSH2 Are Predictive Prognostic Markers for Chinese Osteosarcoma Patients Following Chemotherapeutic Treatment

Osteosarcoma is characterized by diverse genetic mutations, including single‐nucleotide variants (SNVs), which can complicate clinical outcomes of the treatment. This study identified key mutations or polymorphisms in genes that correlate with osteosarcoma prognoses. A total of 110 patients with osteosarcoma were assigned to “good” or “poor” cohorts depending on their 5‐year disease‐free survival (DFS) after surgery and chemotherapeutic treatment. We performed next‐generation sequencing analysis of tumor tissues for prognosis‐associated SNVs in 315 tumorigenesis‐related genes, followed by modeling of clinical outcomes for these patients using random forest classification via a support vector machine (SVM). Data from the Chinese Millionome Database were used to compare SNV frequency in osteosarcoma patients and healthy people. SVM screening identified 17 nonsynonymous SNVs located in 15 genes, of which rs17224367 and rs3733406 (located in MSH2 and FAT1, respectively) were strongly correlated with osteosarcoma prognosis. These results were verified in a 26‐patient validation cohort, confirming that these SNVs could be used to predict prognosis. These results demonstrated that two SNVs located in MSH2 and FAT1 are associated with prognosis of osteosarcoma patients. © 2022 American Society for Bone and Mineral Research (ASBMR).
Effects of exercise intensity on white adipose tissue browning and its regulatory signals in mice

Adipose tissue has been classified into white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue the latter of which is produced as WAT changes into BAT due to exposure to cold temperature or exercise. In response to these stimulations, WAT produces heat by increasing mitochondrial contents and the expression of uncoupling protein 1 (UCP1), thus facilitating browning. Exercise is known to be one of the triggers for WAT browning, but the effects of exercise intensity on the browning of WAT remain to be unclear. Therefore, in this study, we aimed to examine the effects of high‐ or low‐intensity exercises on the browning of WAT. Mice performed high‐ or low‐intensity running on a treadmill running 3 days a week for four weeks. As per our findings, it was determined that four weeks of running did not significantly reduce inguinal WAT (iWAT) wet weight but did significantly reduce adipocytes size, regardless of exercise intensity. The protein expression level of UCP1 was significantly increased in iWAT by high‐intensity running. In addition, the expression of oxidative phosphorylation proteins (OXPHOS) in iWAT was significantly increased by high‐intensity running. These results demonstrated that high‐intensity exercise might be effective for increasing mitochondrial contents and heat production capacity in iWAT. Furthermore, we found that high‐intensity running increased the protein expression level of fibroblast growth factor 21 (FGF21) in skeletal muscle compared with that in low intensity running. We have also examined the relationship between browning of WAT and the expression of FGF21 in skeletal muscle and found a positive correlation between the protein expression of UCP1 in iWAT and the protein expression of FGF21 in gastrocnemius muscle. In conclusion, we suggest that high‐intensity exercise is effective for the browning of WAT and the increase of FGF21 in skeletal muscle.
The patient's perspective of diabetic foot ulceration: A phenomenological exploration of causes, detection and care seeking.

AIMS Diabetic foot ulceration can contribute to lowered life expectancy and quality of life for people with diabetes, and yet, scant attention has been given to improving preventive and educational measures. This article uses a phenomenological approach to explore individuals' lived experiences of diabetic foot ulcerations to explore factors that can be harnessed to achieve improved outcomes. DESIGN This was a qualitative study using semi-structured interviews grounded in a phenomenological framework to explore how patients perceive and understand their foot problems. METHODS Study participants were recruited from February 2020 to February 2021 from a tertiary referral centre that treats foot problems in persons with diabetes. A total of 15 Hispanic, Native American and White patients participated in the study. We conducted in-depth semi-structured interviews which were audio recorded with the participant's consent. Interview data were transcribed and analysed with Dedoose data management software. RESULTS Analysis revealed findings in two primary domains: (1) how patients perceive foot ulceration, with themes around limited understandings of foot ulceration, close sensory observation of foot problems and barriers to ulcer perception and (2) how patients experience the timing of foot ulceration, with themes on how time perceptions shifted as foot problems became more serious, which correlated closely to how patients responded to their foot problems. CONCLUSION Despite the close sensory observation of their feet, people with diabetes face an array of barriers to recognizing and understanding the implications of diabetic foot ulceration, which can lead to delayed care seeking. Nurses can play a critical role in promoting patient education and improving patient self-management of foot ulcers. IMPACT This phenomenological study offers important lessons to guide nurses and other providers in enhancing patient self-management of DFUs and improving care outcomes by expanding an understanding of DFU early warning signs, the imperative to seek medical care quickly, and addressing possible barriers.
What Is the Brainstem Control of Locomotion?

Locomotion in humans is defined as bipedal progression through stages of a gait cycle to move from one place to another while maintaining balance and posture. Locomotion can be categorized in temporal phases (initiation, actual locomotive episode/execution, and termination) or in behavioral categories (slow exploratory and fast speed locomotion). The motivation behind a locomotive episode may be driven by internal needs (goal driven from the motor cortex or emotion driven from the limbic system) or external environmental cues. Locomotion is mediated by a spinal central pattern generator (CPG) under the influence of the brainstem reticular formation and is integrated with control of muscle tone and posture. Control of gait, muscle tone, and posture involves complex interactions among the sensorimotor cortex, basal ganglia, basal forebrain, cerebellum, brainstem, and spinal cord.1-3 Pioneering studies in cats4 and monkeys5,6 and more recently in rodents7-12 have contributed to elucidate the brainstem mechanisms controlling locomotion. This information, together with indirect evidence from human electrophysiologic and functional neuroimaging studies, provides testable pathophysiologic hypotheses and potential therapeutic targets for gait control disorders. The focus of this review is on brainstem mechanisms controlling locomotion. The role of other CNS areas in control of gait and posture and their abnormalities in disorders such as Parkinson disease (PD) have been extensively reviewed1 and are only briefly discussed here.