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Abstract The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12–30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit.

Abstract As bacteriophages continue to gain regulatory approval for personalized human therapy against antibiotic-resistant infections, there is a need for transformative technologies for rapid target identification through multiple, large, decentralized therapeutic phages biobanks. Here, we design a high throughput phage screening platform comprised of a portable library of individual shelf-stable, ready-to-use phages, in all-inclusive solid tablets. Each tablet encapsulates one phage along with luciferin and luciferase enzyme stabilized in a sugar matrix comprised of pullulan and trehalose capable of directly detecting phage-mediated adenosine triphosphate (ATP) release through ATP bioluminescence reaction upon bacterial cell burst. The tablet composition also enhances desiccation tolerance of all components, which should allow easier and cheaper international transportation of phages and as a result, increased accessibility to therapeutic phages. We demonstrate high throughput screening by identifying target phages for select multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Salmonella enterica, Escherichia coli, and Staphylococcus aureus with targets identified within 30-120 min.

Abstract Background Laboratory test overuse in hospitals is a form of healthcare waste that also harms patients. Developing and evaluating interventions to reduce this form of healthcare waste is critical. We detail the protocol for our study which aims to implement and evaluate the impact of an evidence-based, multicomponent intervention bundle on repetitive use of routine laboratory testing in hospitalized medical patients across adult hospitals in the province of British Columbia, Canada. Methods We have designed a stepped-wedge cluster randomized trial to assess the impact of a multicomponent intervention bundle across 16 hospitals in the province of British Columbia in Canada. We will use the Knowledge to Action cycle to guide implementation and the RE-AIM framework to guide evaluation of the intervention bundle. The primary outcome will be the number of routine laboratory tests ordered per patient-day in the intervention versus control periods. Secondary outcome measures will assess implementation fidelity, number of all common laboratory tests used, impact on healthcare costs, and safety outcomes. The study will include patients admitted to adult medical wards (internal medicine or family medicine) and healthcare providers working in these wards within the participating hospitals. After a baseline period of 24 weeks, we will conduct a 16-week pilot at one hospital site. A new cluster (containing approximately 2–3 hospitals) will receive the intervention every 12 weeks. We will evaluate the sustainability of implementation at 24 weeks post implementation of the final cluster. Using intention to treat, we will use generalized linear mixed models for analysis to evaluate the impact of the intervention on outcomes. Discussion The study builds upon a multicomponent intervention bundle that has previously demonstrated effectiveness. The elements of the intervention bundle are easily adaptable to other settings, facilitating future adoption in wider contexts. The study outputs are expected to have a positive impact as they will reduce usage of repetitive laboratory tests and provide empirically supported measures and tools for accomplishing this work. Trial Registration This study was prospectively registered on April 8, 2024, via ClinicalTrials.gov Protocols Registration and Results System (NCT06359587). https://classic.clinicaltrials.gov/ct2/show/NCT06359587?term=NCT06359587&recrs=ab&draw=2&rank=1

Abstract Introduction In EVOLVE-MS-1 (NCT02634307), mean absolute lymphocyte count (ALC) on diroximel fumarate (DRF) declined from baseline by approximately 28% in year 1, then stabilized, similar to ALC decline observed with dimethyl fumarate (DMF). Prior studies reported that clinical efficacy of DMF was not substantially different in patients with and without lymphopenia. Methods EVOLVE-MS-1—an open-label, 96-week, phase 3 study—assessed DRF safety and exploratory efficacy in patients with relapsing–remitting multiple sclerosis. This study analyzes efficacy-related outcomes comparing (1) patients with lymphopenia (≥ 1 ALC below lower limit of normal [LLN]) and without (all ALCs ≥ LLN); (2) across quartiles stratified by week 96 ALC decline from baseline: Q1 (≥ 47% decline); Q2 (30% to

Context: Today, India faces increasing morbidity and mortality due to malaria, which is a global health burden. Plasmodium vivax which was once considered to have a benign course, is now being increasingly associated with complicated malaria. Studies which have been done on the increasing virulence of P. Vivax in children, are exceptionally rare. Aims: This study has addressed some of the hitherto unanswered questions, such as: • This study has tried to explore the wide spectrum of severe illnesses which are associated with P.vivax malaria in children. • Other co-morbid conditions, which include a co-infection with P.falciparum, have been excluded with great care, to assess the increased virulence of P. Vivax. • The present study was focused on the paediatric population with a large sample size of 168 subjects. Settings and Design: This was an observational retrospective analysis on the clinicopathologic manifestations of the paediatric cases which were admitted with severe malaria due to a mono-infection with Plasmodium vivax, in a tertiary-care centre in the national capital region, India. Methods and Material: The diagnosis of the mono-infection with P. Vivax malaria was established by making peripheral blood films (PBFs) and by doing rapid diagnostic tests. The severe forms of malaria were categorized as per the World Health Organization guidelines and the clinical and laboratory findings in these cases of complicated malaria were studied. Statistics: A descriptive statistical analysis was done by using the SPSS software and an Excel worksheet. Results: This comprehensive study revealed a multisystem involvement. Abdominal manifestations were observed in 75(45.8%) cases (which included hepatosplenomegaly, hepatomegaly, splenomegaly and ascites) and hepatic dysfunction and jaundice were observed in 28(16.7%) cases. The haematological tests showed moderate to severe anaemia in 151(89.9%) cases and thrombocytopaenia in 138(82.1%) cases. Petechiae were noted in 45(26.8%) cases and a gross bleeding was noted in 9(5.3%) cases. The respiratory findings which included tachypnoea, pleural effusions and ARDS were observed in 22(13.1%) cases. Renal dysfunction was noted clinically in 20(11.9%) cases and biochemically in 16(9.5%) cases. Shock was observed in 7(4.1%) cases, cerebral malaria was observed in 10(5.9%) cases and hypoglycaemia was observed in 5(3%) cases. Multi-organ dysfunction was detected in 11(6.54%) cases. The complications were more severe in the younger children (0-5 years). Conclusions: A mono-infection with P. Vivax may lead to severe malaria and this increased virulence has resulted in the changing picture of P. Vivax malaria, leading to a spectrum of complications which are similar to those which are traditionally associated with P. Falciparum.

Aim: Diroximel fumarate (DRF), ozanimod (OZA) and interferon beta-1a (IFN) are disease-modifying therapies approved for the treatment of relapsing multiple sclerosis. No randomized trials have compared DRF versus OZA and IFN. We compared DRF versus OZA and DRF versus IFN using matching-adjusted indirect comparisons for efficacy outcomes, including annualized relapse rate (ARR), 12- and 24-week confirmed disability progression (CDP) and absence of gadolinium-enhancing (Gd+) T1 lesions and new/newly enlarging T2 lesions. Patients & methods:We used individual patient data from EVOLVE-MS-1 (NCT02634307), a 2-year, open-label, single-arm, phase III study of DRF (n = 1057) and aggregate data from RADIANCE (NCT02047734), a 2-year, double-blind, phase III study that compared OZA 1 mg once daily (n = 433) and intramuscular IFN 30 μg once weekly (n = 441). To account for cross-trial differences, the EVOLVE-MS-1 population was restricted to those who met the inclusion/exclusion criteria for RADIANCE, then weighted to match the average baseline characteristics of RADIANCE. Results: After weighting, DRF and OZA had similar ARRs (0.18 and 0.17, respectively), with a rate difference (DRF vs OZA) of 0.01 (95% confidence interval [CI]: -0.04 to 0.06). DRF had a lower ARR than IFN (0.18 and 0.28, respectively), with a rate difference (DRF vs IFN) of -0.10 (95% CI: -0.16 to -0.04) after weighting. Outcomes for 12- and 24-week CDP favored DRF versus OZA; 12-week CDP favored DRF versus IFN, but there was not strong evidence favoring DRF over IFN for 24-week CDP. Compared with OZA and IFN, DRF had higher proportions of patients without Gd+ T1 lesions and patients without new/newly enlarging T2 lesions. Conclusion: Disability progression and radiological outcomes were favorable for DRF versusOZA, although no differences were observed in ARR. Clinical and radiological outcomes generally favored DRF versus IFN. These findings may be informative for patients and clinicians considering different treatment options for MS.

West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid (Cp) by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade.

Background A retrospective chart audit was performed to review biliary stent utilisation from January 2020 to January 2021. Non-guideline-based stent insertion was identified in 16% of patients with common bile duct (CBD) stones presenting for endoscopic retrograde cholangiopancreatography (ERCP). To improve this knowledge-practice gap, a quality improvement (QI) intervention was devised and trialled.Aim To synchronise clinical indications for biliary stent insertion in patients with CBD stones in accordance with published guidelines.Methods Using a QI pre–post study design, chart audits were completed and shared with the ERCP team (n=6). Indication for biliary stent insertion was compared to published guidelines assessed by two reviewers independently (kappa statistic calculated). The QI intervention included an education session and quarterly practice audits. An interrupted time series with segmented regression was completed.Results A total of 661 patients (337 F), mean age 59±19 years (range 12–98 years), underwent 885 ERCPs during this postintervention period. Of 661 patients, 384 (58%) were referred for CBD stones. A total of 192 biliary stents (105 plastic, 85 metal) were placed during the first ERCP (192/661, 29%), as compared with the preintervention year (223/598, 37%, p=0.2). Furthermore, 13/192 stents (7%) were placed not in accordance with published guidelines (kappa=0.53), compared with 63/223 (28%) in the preintervention year (p

Background: English Second Language (ESL) learners have difficulty constructing sentences due to internalising information in their home language and thereafter translating it into English. Learners who have difficulty speaking English generally encounter problems writing it, which hampers their creative writing ability. Objectives: The purpose of the research was to identify a teaching strategy to facilitate ESL learners with creative writing. This study explored the influence of flashcards on the creative writing skills of Grade 1 ESL learners and improved the researchers' teaching practice. Method: This qualitative study depicted an action research design and utilised an inductive approach to data analysis. Convenience sampling was used when selecting the participants who were 31 Grade 1 learners in a school in Pietermaritzburg. The flashcards were used during the implementation stage of the action research process as an intervention to enhance learners' creative writing skills. Findings: The findings indicate that learners who participated in the study had improved in their written assessments. There were three themes identified, which included misspelt words, incorrect use of tenses and ungrammatical sentence construction. Flashcards revealed the correct sentence writing techniques by depicting sentences. Learners' written pieces were more logical and they participated actively during lessons. This enhanced the researcher's teaching practice, which catered to both visual and auditory learners. Conclusion: The findings suggest that the use of flashcards had a positive effect on ESL learners' creative writing skills. This encouraged participatory teaching and learning, which can be of benefit to many teachers seeking to engage learners using alternate learning styles.

Abstract Background Auxins are known to have roles in the tuberization process in sweet potato (Ipomoea batatas [L.] Lam.) and these effects are mediated by various auxin signalling gene families. In this study, an analysis of the sweet potato genome was performed to identify the ARF, Aux/IAA, GH3, and SAUR auxin signalling gene family members in this crop. Results A total of 29 ARF, 39 Aux/IAA, 13 GH3, and 200 SAUR sequences were obtained, and their biochemical properties and gene expression profiles were analysed. The sequences were relatively conserved based on exon–intron structure, motif analysis, and phylogenetic tree construction. In silico expression analyses of the genes in fibrous and storage roots indicated that many sequences were not differentially expressed in tuberizing and non-tuberizing roots. However, some ARF, Aux/IAA, and SAUR genes were up-regulated in tuberizing storage roots compared to non-tuberizing fibrous roots while many GH3 genes were down-regulated. Additionally, these genes were expressed in a variety of plant parts, with some genes being highly expressed in shoots, leaves, and stems while others had higher expression in the roots. Some of these genes are up-regulated during the plant’s response to various hormone treatments and abiotic stresses. Quantitative RT-PCR confirmation of gene expression was also conducted, and the results were concordant with the in silico analyses. A protein–protein interaction network was predicted for the differentially expressed genes, suggesting that these genes likely form part of a complex regulatory network that controls tuberization. These results confirm those of existing studies that show that auxin signalling genes have numerous roles in sweet potato growth and development. Conclusion This study provides useful information on the auxin signalling gene families in Ipomoea batatas and suggests putative candidates for further studies on the role of auxin signalling in tuberization and plant development.

The success of deep brain stimulation (DBS) for treating Parkinsons disease has led to its application to several other disorders, including treatment-resistant depression. Results with DBS for treatment-resistant depression have been heterogeneous, with inconsistencies largely driven by incomplete understanding of the brain networks regulating mood, especially on an individual basis. We report results from the first subject treated with DBS for treatment-resistant depression using an approach that incorporates intracranial recordings to personalize understanding of network behavior and its response to stimulation. These recordings enabled calculation of individually optimized DBS stimulation parameters using a novel inverse solution approach. In the ensuing double-blind, randomized phase incorporating these bespoke parameter sets, DBS led to remission of symptoms and dramatic improvement in quality of life. Results from this initial case demonstrate the feasibility of this personalized platform, which may be used to improve surgical neuromodulation for a vast array of neurologic and psychiatric disorders.

Despite decades of research and education, sexual and gender-based violence remain distressingly prevalent on university and college campuses globally. The taboos associated with sex, gender inequity, and living in a patriarchal world where misogyny is glorified and criminalised are key socio-cultural determinants driving these forms of violence. Less is known about the ways in which sexual slang or terminology impact how students experience and talk about these events. This paper reports on findings from a participatory action study that explored sexual slang use among female and male undergraduate students (n = 23) with the aim of creating more responsive sexual and gender-based violence policies and practices. The terms identified (n = 59) provide a window into the daily lives of these young people, who display remarkable socio-linguistic adaptation and creativity. They also demonstrate how cultural appropriation, the exclusion of queer students, toxic masculinity contribute to ongoing incidents of sexual and gender-based violence on campus. These findings contribute new insights into sexual terminology among post-secondary students, particularly in the Canadian context where few studies of this nature exist. They also acknowledge the critical role universities can play in making meaningful structural change to prevent traumatic events from occurring.

Background: Enhanced Recovery After Surgery (ERAS) protocols for bariatric surgery improve clinical outcomes. However, the impact of ERAS protocols on patient satisfaction is unknown. Virtual reality has been implemented as an effective adjunct to standard analgesic regimens. This study seeks to find out if immersive virtual reality in the immediate postoperative period could improve the subjective quality of recovery and further reduce opioid requirements for bariatric surgery patients compared with ERAS care alone. Methods: This is a single-centre, randomised clinical trial of patients recovering from laparoscopic bariatric surgery. Once in the post-anaesthesia care unit (PACU), participants will receive either an immersive virtual reality plus ERAS protocol or ERAS protocol alone. The primary outcome will be the Quality of Recovery-15 (QoR-15) score at PACU discharge. Secondary outcomes include PACU opioid requirements, length of PACU stay, PACU pain scores, QoR-15 score on postoperative day 1, hospital length of stay, opioid requirements, and opioid-related adverse effects until hospital discharge. Conclusions: Positive findings from this study could introduce virtual reality as a non-pharmacological adjunct during PACU care that improves subjective recovery for patients undergoing bariatric surgery. Clinical trial registration: NCT04754165.

Background Ensuring language concordant care through medical interpretation services (MIS) allows for accurate information sharing and positive healthcare experiences. The COVID-19 pandemic led to a regional halt of in-person interpreters, leaving only digital MIS options, such as phone and video. Due to longstanding institutional practices, and lack of accessibility and awareness of these options, digital MIS remained underused. A Multimodal Medical Interpretation Intervention (MMII) was developed and piloted to increase digital MIS usage by 25% over an 18-month intervention period for patients with limited English proficiency.Methods Applying quality improvement methodology, an intervention comprised digital MIS technology and education was trialled for 18 months. To assess intervention impact, the number of digital MIS minutes was measured monthly and compared before and after implementation. A questionnaire was developed and administered to determine healthcare providers’ awareness, technology accessibility and perception of MIS integration in the clinical workflow.Results Digital MIS was used consistently from the beginning of the COVID-19 pandemic (March 2020) and over the subsequent 18 months. The total number of minutes of MIS use per month increased by 44% following implementation of our intervention. Healthcare providers indicated that digital MIS was vital in facilitating transparent communication with patients, and the MMII ensured awareness of and accessibility to the various MIS modalities.Conclusion Implementation of the MMII allowed for an increase in digital MIS use in a hospital setting. Providing digital MIS access, education and training is a means to advance patient-centred and equitable care by improving accuracy of clinical assessments and communication.

BackgroundThe efficacy of psychiatric DBS is thought to be driven by the connectivity of stimulation targets with mood-relevant fronto-temporal networks, which is typically evaluated using diffusion-weighted tractography.ObjectiveLeverage intracranial electrophysiology recordings to better predict the circuit-wide effects of neuromodulation to white matter targets. We hypothesize strong convergence between tractography-predicted structural connectivity and stimulation-induced electrophysiological responses.MethodsEvoked potentials were elicited by single-pulse stimulation to two common DBS targets for treatment-resistant depression - the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VCVS) - in two patients undergoing DBS with stereo-electroencephalographic (sEEG) monitoring. Evoked potentials were compared with predicted structural connectivity between DBS leads and sEEG contacts using probabilistic, patient-specific diffusion-weighted tractography.ResultsEvoked potentials and tractography showed strong convergence in both patients in orbitofrontal, ventromedial prefrontal, and lateral prefrontal cortices for both SCC and VCVS stimulation targets. Low convergence was found in anterior cingulate (ACC), where tractography predicted structural connectivity from SCC targets but produced no evoked potentials during SCC stimulation. Further, tractography predicted no connectivity to ACC from VCVS targets, but VCVS stimulation produced robust evoked potentials.ConclusionThe two connectivity methods showed significant convergence, but important differences emerged with respect to the ability of tractography to predict electrophysiological connectivity between SCC and VCVS to regions of the mood-related network. This multimodal approach raises intriguing implications for the use of tractography in surgical targeting and provides new data to enhance our understanding of the network-wide effects of neuromodulation.

Background: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders. Objective: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field. Methods: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators. Results: Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°). Conclusion: This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.

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Abstract Background Indiscriminate use of laboratory blood testing in hospitals contributes to patient discomfort and healthcare waste. Patient engagement in low‐value healthcare can help reduce overuse. Understanding patient experience is necessary to identify opportunities to improve patient engagement with in‐hospital laboratory testing. Objectives To understand patient experience with the process of in‐hospital laboratory blood testing. Methods We used a qualitative study design via semistructured interviews conducted online or over the phone. Participants were adult patients or family members/caregivers (≥18 years of age) with a recent (within 12 months of interview) experience of hospitalization in Alberta or British Columbia, Canada. We identified participants through convenience sampling and conducted interviews between May 2021 and June 2022. We analysed transcripts using thematic content analysis. Recruitment was continued until code saturation was reached. Results We interviewed 16 participants (13 patients, 1 family member and 2 caregivers). We identified four themes from patients' experiences of in‐hospital laboratory blood testing: (i) patients need information from healthcare teams about expected blood testing processes, (ii) blood draw processes should consider patient comfort and preferences, (iii) patients want information from their healthcare teams about the rationale and frequency of blood testing and (iv) patients need information on how their testing results affect their medical care. Conclusion Current laboratory testing processes in hospitals do not facilitate shared decision‐making and patient engagement. Patient engagement with laboratory testing in hospitals requires an empathetic healthcare team that provides clear communication regarding testing procedures, rationale and results, while considering patient preferences and offering opportunities for involvement. Patient or Public Contribution We interviewed 16 patients and/or family members/caregivers regarding their in‐hospital laboratory blood testing experiences. Our findings show correlations between patient needs and patient recommendations to make testing processes more patient‐centred. To bring a lived‐experience lens to this study, we formed a Patient Advisory Council with 9–11 patient research partners. Our patient research partners informed the research design, co‐developed participant recruitment strategies, co‐conducted data collection and informed the data analysis. Some of our patient research partners are co‐authors of this manuscript.

Prefrontal circuits in the human brain play an important role in cognitive and affective processing. Neuromodulation therapies delivered to certain key hubs within these circuits are being used with increasing frequency to treat a host of neuropsychiatric disorders. However, the detailed neurophysiological effects of stimulation to these hubs are largely unknown. Here, we performed intracranial recordings across prefrontal networks while delivering electrical stimulation to two well-established white matter hubs involved in cognitive regulation and depression: the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VC/VS). We demonstrate a shared frontotemporal circuit consisting of the ventromedial prefrontal cortex, amygdala, and lateral orbitofrontal cortex where gamma oscillations are differentially modulated by stimulation target. Additionally, we found participant-specific responses to stimulation in the dorsal anterior cingulate cortex and demonstrate the capacity for further tuning of neural activity using current-steered stimulation. Our findings indicate a potential neurophysiological mechanism for the dissociable therapeutic effects seen across the SCC and VC/VS targets for psychiatric neuromodulation and our results lay the groundwork for personalized, network-guided neurostimulation therapy.

In our modern society, digital devices, social media platforms, and artificial intelligence (AI) tools have become integral components of our daily lives, profoundly intertwined with our daily activities. These technologies have undoubtedly brought convenience, connectivity, and speed, making our lives easier and more efficient. However, their influence on our brain function and cognitive abilities cannot be ignored. This review aims to explore both the positive and negative impacts of these technologies on crucial cognitive functions, including attention, memory, addiction, novelty-seeking and perception, decision-making, and critical thinking, as well as learning abilities. The review also discusses the differential influence of digital technology across different age groups and the unique challenges and benefits experienced by children, adolescents, adults, and the elderly. Strategies to maximize the benefits of the digital world while mitigating its potential drawbacks are also discussed. This review aims to provide a comprehensive overview of the intricate relationship between humans and technology. It underscores the need for further research in this rapidly evolving field and the importance of informed decision-making regarding our digital engagement to support optimal cognitive function and wellbeing in the digital era.

Background: Although nerve block facilitatory effects of dexmedetomidine when used as a perineural adjunct to local anesthetics in supraclavicular brachial plexus blocks are well recognized in multiple studies, but whether this action is at directly on peripheral nerve fibers or is at central level after systemic absorption is unclear. Aim of this study was to evaluate the effect of adding dexmedetomidine 1 microgram/kg to ropivacaine 0.5% in supraclavicular brachial plexus block in terms of duration of analgesia and 24hour cumulative analgesic requirement and to test the hypothesis whether the effect of dexmedetomidine, is due to direct local action on nerve plexus or is centrally mediated after systemic absorption. Methods: 105 patients of ASA grade I and II of either sex undergoing upper limb orthopedic surgeries were divided in 3 groups of 35 patients in each group. Group Rc (control group) received supraclavicular block with 30ml of 0.5% ropivacaine and intravenous infusion of 30ml of normal saline; group RDexP received supraclavicular block with 30ml solution of 0.5% ropivacaine+ dexmedetomidine 1mcg/kg and intravenous infusion of 30ml of normal saline; and group RDexIV received supraclavicular block with 30ml of 0.5% ropivacaine and intravenous infusion of 30ml of normal saline solution containing dexmedetomidine 1mcg/kg. Primary outcome was duration of analgesia and 24hour cumulative analgesic requirement. Results: The demographic data were comparable in all three groups. Duration of analgesia was longest in group RDexP followed by group RDexIV and least in control group. 24hour cumulative analgesic requirement was least in group RDexP and maximum in group R. 2 patients, one from each group RDexP and group RDexIV reported bradycardia and 6 patients from group RDexIV reported hypotension. Conclusion: We conclude that action of dexmedetomidine is most probably peripheral on brachial plexus nerve fibers directly rather than centrally mediated after systemic absorption.

Abstract Background Canadian medical schools offer limited clinical dermatology training. In addition, there is a lack of educational resources that are designed specifically for clerkship students that focus on the multidisciplinary nature of dermatology. Objectives After developing case-based educational resources to address the lack of clinical exposure and learning of multidisciplinary care in dermatology, this study aimed to evaluate the educational intervention and gather feedback for future module development. Methods Ten online interactive dermatology case-based modules involving 14 other disciplines were created. Medical students (n = 89) from two Canadian schools were surveyed regarding perceptions of the existing dermatology curriculum. Among 89 students, 46 voluntarily completed the modules, and a survey (a five-point Likert scale ratings) including narrative feedback was provided to determine an improvement in dermatology knowledge and understanding of multidisciplinary care. Results Among 89 surveyed students, only 17.1% agreed that their pre-clerkship dermatology education was sufficient and 10.2% felt comfortable managing patients with skin conditions in a clinical setting. Among 46 students, 95.7% of students agreed that the modules fit their learning style (4.17 ± 0.73 on Likert scale) with positive narrative feedback. 91.3% agreed or strongly agreed that the modules enhanced their dermatology knowledge (4.26 ± 0.61). 79.6% of students agreed that the modules helped with understanding the multidisciplinary nature of dermatological cases (3.98 ± 0.81). Student comfort to manage skin conditions increased 7.7 times from 10.2% to 78.3% post-module. Conclusions Clerkship students had limited knowledge of dermatologic conditions; the case-based modules were able to successfully address these deficits and assist students in understanding the multidisciplinary nature of dermatology.

Background: The COVID-19 has a varied mode of presentation in different regions of the world. This multicentric study was planned to evaluate the survival outcomes in intensive care unit-admitted patients admitted during the third wave of the COVID-19 pandemic on the basis of clinicodemographic profile and vaccination status. Methodology: Data from 299 patients admitted to three tertiary care centers in Western India were collected and analyzed. Based on survival outcomes, all patients were divided into two groups: survivors and nonsurvivors. Univariate analysis of the demographic profile, comorbidities, vaccination status, and disease severity was performed, whereas multivariate analysis was performed to predict independent factors associated with mortality. Results: Among total 299 studied patients, 208 (69.5%) patients survived and 91 (30.4%) did not. The number of elderly patients and patients with comorbidities such as diabetes, tuberculosis, chronic obstructive pulmonary disease, cardiovascular and respiratory diseases, and malignancy were more prevalent among nonsurvivors. Patients who did not receive a single dose of vaccine were higher in the nonsurvivor group (P = 0.037); however, no significant difference in survival outcome was found if patients had received the first or both doses of vaccine. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score at 24 h after admission and Sequential Organ Failure Assessment (SOFA) score at admission were significantly higher in nonsurvivors compared to survivors (P < 0.0001). On multivariate analysis, APACHE II and SOFA scores were found to be independent predictors of outcome. Conclusions: Older age, presence of comorbidities, nonvaccination and higher disease severity scores affected mortality during the third wave of COVID-19.

Introduction: The objective of this quality improvement, interventional study regarding patients with diabetes undergoing diabetic ophthalmology outpatient surgery aimed to develop, implement, and evaluate a new diabetic algorithm to improve safety, operating room efficiency, and decrease supply cost. Methods: A multidisciplinary study team was assembled, including ophthalmologists, endocrinologists, anesthesiologists, management, and nurses to review the current diabetic protocol. From August 2016 to July 2017, 13 patient safety concerns or incident reports were reviewed that identified two serious cases of hypoglycemia. Using the concerns data, frontline perspectives, and reviewing best practice guidelines, a new diabetic algorithm was developed and trialed for 24 months. The new algorithm limited the use of an existing preoperative insulin protocol and reduced the number of nurses required. The number of adverse events, nursing setup process steps, setup time, and preoperative insulin infusion protocols used were collected. An evaluation of the supply costs was performed. Results: After implementing the new diabetic algorithm, zero safety incidents were reported, and a 97.5% reduction in the use of preoperative insulin protocol resulted. Nursing staff perceived that the new diabetic algorithm was easier to configure, 23 minutes faster to set up, and required one nursing staff member. Supply cost was reduced by $30.63 (Canadian Dollars, CAD) per patient. Conclusion: Perioperative glucose irregularities may threaten patient safety and surgical outcomes. Healthcare professionals must improve patient safety, decrease healthcare expenditure, and prevent unnecessary delays. Multidisciplinary frontline staff experiential knowledge aided in the recognition of potential problems and comprehensive solutions to optimize patient care.

Background A coalition (Strategic Clinical Improvement Committee), with a mandate to promote physician quality improvement (QI) involvement, identified hospital laboratory test overuse as a priority. The coalition developed and supported the spread of a multicomponent initiative about reducing repetitive laboratory testing and blood urea nitrogen (BUN) ordering across one Canadian province. This study’s purpose was to identify coalition factors enabling medicine and emergency department (ED) physicians to lead, participate and influence appropriate BUN test ordering.Methods Using sequential explanatory mixed methods, intervention components were grouped as person focused or system focused. Quantitative phase/analyses included: monthly total and average of the BUN test for six hospitals (medicine programme and two EDs) were compared pre initiative and post initiative; a cost avoidance calculation and an interrupted time series analysis were performed (participants were divided into two groups: high (>50%) and low (

Abstract Objective This study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new‐onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30‐day mortality and cause of death are also reported. Methods Children living with HIV (CLWHIV) with new‐onset seizures were prospectively evaluated at one large urban teaching hospital and two non‐urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed. Results From April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2‐10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non‐accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty‐two (30%) children died within 30 days of the index seizure. Significance Despite widespread ART roll out in Zambia, new‐onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

Abscisic acid (ABA) signaling in plants is essential to several aspects of plant development, such as tolerance to environmental stresses and growth. ABA signaling is also important for storage organ formation in crops, such as sweet potato. However, the repertoire of I. batatas ABA signaling gene families has not yet been fully characterized, so that it is unclear which members of these families are necessary for tuberization. Therefore, genome-wide identification of the sweet potato ABF/ AREB/ ABI5, SnRK2, and PYL gene families was performed, along with phylogenetic, motif, cis-regulatory element (CRE), and expression analyses. Nine ABF, eight SnRK2, and eleven PYL gene family members were identified, and there was high sequence conservation among these proteins that were revealed by phylogenetic and motif analyses. The promoter sequences of these genes had multiple CREs that were involved in hormone responses and stress responses. In silico and qRT-PCR expression analyses revealed that these genes were expressed in various tissues and that IbABF3, IbABF4, IbDPBF3, IbDPBF4, IbPYL4, IbSnRK2.1, and IbSnRK2.2 were significantly expressed during storage root development. These results are an important reference that can be used for functional validation studies to better understand how ABA signaling elicits storage root formation at the molecular level.

Urine testing on asymptomatic patients is not aligned with guidelines; however, stroke survivors have trouble communicating symptoms, and urinary tract infections (UTIs) are a recognised poststroke complication. All stroke inpatients at a tertiary rehabilitation hospital underwent urine testing on admission. We led a quality improvement (QI) project on one stroke rehabilitation unit aimed to reduce admission urine testing from 100% to 0%. Baseline audit representing 2 weeks of admissions identified 27 of 28 patients had urine tests; however, none required UTI treatment despite 3 positive culture results. Estimated cost of testing was $C675. QI tools identified that a standardised paper-based admission form facilitated automatic urine testing. Project intervention strategies included education, clinicians crossing off urine orders and unit clerks flagging unaddressed orders for reassessment. A chart audit after 4 weeks and prescriber survey after 6 months assessed impact. Postintervention audit (n=23) revealed 1 patient had admission urine tests, 22 orders were crossed out, 1 chart was flagged and estimated testing cost declined from $C675 to $C25. Six urine tests were completed after admission and two patients required UTI treatment. Post 6 months, unit clerks assumed the role to cross out the order on the standardised form, and no patient had routine admission urine testing. There was no clinical benefit in screening for UTIs prior to stroke rehabilitation. This project is a practical example of deadopting a practice promoted by standardised order forms.

Bidirectional deep brain stimulation (DBS) platforms have enabled a surge in hours of recordings in naturalistic environments, allowing further insight into neurological and psychiatric disease states. However, high amplitude, high frequency stimulation generates artifacts that contaminate neural signals and hinder our ability to interpret the data. This is especially true in psychiatric disorders, for which high amplitude stimulation is commonly applied to deep brain structures where the native neural activity is miniscule in comparison. Here, we characterized artifact sources in recordings from a bidirectional DBS platform, the Medtronic Summit RC + S, with the goal of optimizing recording configurations to improve signal to noise ratio (SNR). Data were collected from three subjects in a clinical trial of DBS for obsessive-compulsive disorder. Stimulation was provided bilaterally to the ventral capsule/ventral striatum (VC/VS) using two independent implantable neurostimulators. We first manipulated DBS amplitude within safe limits (2–5.3 mA) to characterize the impact of stimulation artifacts on neural recordings. We found that high amplitude stimulation produces slew overflow, defined as exceeding the rate of change that the analog to digital converter can accurately measure. Overflow led to expanded spectral distortion of the stimulation artifact, with a six fold increase in the bandwidth of the 150.6 Hz stimulation artifact from 147–153 to 140–180 Hz. By increasing sense blank values during high amplitude stimulation, we reduced overflow by as much as 30% and improved artifact distortion, reducing the bandwidth from 140–180 Hz artifact to 147–153 Hz. We also identified artifacts that shifted in frequency through modulation of telemetry parameters. We found that telemetry ratio changes led to predictable shifts in the center-frequencies of the associated artifacts, allowing us to proactively shift the artifacts outside of our frequency range of interest. Overall, the artifact characterization methods and results described here enable increased data interpretability and unconstrained biomarker exploration using data collected from bidirectional DBS devices.

Through two stories of youth voice, learning, and identity development in an afterschool science program for girls only, we show the ways in which such programs can be understood as important identity-building practices. We describe key dimensions of a socio-cultural approach to youth voice, learning, and identity, situated also in the context of the literature on afterschool programs. We then explore the manner in which youth voice and identity were marked by time and space. We conclude with a discussion of youth voice and ethics in collaborative research projects with youth.

Rice crop endures several biotic stresses among which sheath blight is one of the devastating diseases. This disease is caused by necrotrophic fungus Rhizoctonia solani AG1 IA that reduces 20 to 40% yield. Forty two diverse rice germplasms were evaluated against sheath blight under artificial epiphytotic condition in the field of National Wheat Research Program Bhairahawa, Nepal during the year 2019. Four disease variables viz. PDLI (Percent diseased leaf incidence), PDTI (Percent diseased tiller incidence), PRCHI (Percent relative collar height infection), and AUDPC (Area under disease progress curve) were considered for evaluation of germplasms. Out of forty two genotypes Sabitri, GSR 310 and Hardinath-3 were found moderately resistant with mean AUDPC values 217.99, 252.78 and 214.67 per day respectively. Furthermore IR 15D 110, Pant-1, NR 2152-23-1-2-1-1-1-1 and IR 82635-B-B-114-3 were found moderately susceptible with mean AUDPC values 438.48, 445.55, 421.81 and 437.59 respectively. Moderately resistant genotypes viz. Sabitri, GSR 310 and Hardinath-3 had PDLI range 30.98-31.67, PDTI range 10.56-15 and PRCHI range 9.01-28.64 whereas moderately susceptible genotypes IR 15D 110, Pant-1, NR 2152-23-1-2-1-1-1-1 and IR 82635-B-B-114-3 had PDLI range 31.25-51.29, PDTI range 25.82-38.75 and PRCHI range 22.18-45.8. Disease variables PDLI, PDTI and PRCHI were positively and significantly correlated with AUDPC with correlation coefficient value 0.75, 0.65 and 0.62 respectively. Moderately resistant rice genotypes found in this study could be evaluated for yield potential and its stability across different geographical region of Nepal and could be a good alternative against sheath blight diseases for Nepalese farmers. [Fundam Appl Agric 2021; 6(1.000): 57-66]