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Abstract Biological systems are robust and redundant. The redundancy can manifest as alternative metabolic pathways. Synthetic double lethals are pairs of reactions that, when deleted simultaneously, abrogate cell growth. However, removing one reaction allows the rerouting of metabolites through alternative pathways. Little is known about these hidden linkages between pathways. Understanding them in the context of pathogens is useful for therapeutic innovations. We propose a constraint-based optimisation approach to identify inter-dependencies between metabolic pathways. It minimises rerouting between two reaction deletions, corresponding to a synthetic lethal pair, and outputs the set of reactions vital for metabolic rewiring, known as the synthetic lethal cluster. We depict the results for different pathogens and show that the reactions span across metabolic modules, illustrating the complexity of metabolism. Finally, we demonstrate how the two classes of synthetic lethals play a role in metabolic networks and influence the different properties of a synthetic lethal cluster.

Abstract Electronic inhalers provide information about patterns of routine inhaler use. During a 12-week study, 360 asthma patients using albuterol Digihaler generated 53,083 inhaler events that were retrospectively analyzed. A total of 41,528 (78%) of the recorded inhalation events were suitable for flow analysis (having a PIF ≥ 18 L/min and

Abstract Commensal relationships between wild plants and their dispersers play a key ecological and evolutionary role in community structure and function. While non-human dispersers are often considered critical to plant recruitment, human dispersers have received much less attention, especially when it comes to non-domesticated plants. Australia, as a continent historically characterized by economies reliant on non-domesticated plants, is thus a key system for exploring the ecological role of people as seed dispersers in the absence of agriculture. Here, we utilize a controlled observation research design, employing ecological surveys and ethnographic observations to examine how seed dispersal and landscape burning by Martu Aboriginal people affects the distribution of three preferred plants and one (edible, but non-preferred) control species. Using an information theoretic approach, we find that the three preferred plants show evidence of human dispersal, with the strongest evidence supporting anthropogenic dispersal for the wild bush tomato, Solanum diversiflorum.

ABSTRACT Background We evaluated the validity of surrogacy of progression‐free survival (PFS) or time‐to‐progression (TTP) and overall response rate (ORR) in phase II trials of pancreatic ductal adenocarcinoma (PDAC). In addition, we explored the impact of predictive variables on overall survival (OS) and developed an optimal OS model. Methods We analyzed 1867 clinical endpoint from 619 phase II PDAC trials with a systematic search from PubMed. Endpoint correlations were determined by Spearman's rank correlation. The assessed predictive factors included PFS/TTP, treatment size, therapy type, stage, and previous treatment. The relationship between predictors and OS was explored by a gamma generalized linear model (GLM) with a log‐link function and compared with linear models. Results The Spearman rank correlation coefficient between PFS/TTP and OS was 0.88 (95% confidence interval [CI] 0.85–0.89; p

Abstract Background Melanomas are highly aggressive in nature known for metastasis and death. Melanocytes that gave rise to melanomas are neural crest progenitor cells. Our research was primarily concerned with uveal melanoma (UM) and cutaneous melanoma (CM), respectively. Although they both have the same melanocytic origin, the biology of their respective is different. Aim The aim of our study was to recognize the common differentially expressed genes (DEGs) between UM and CM. Methodology The gene expression profile was downloaded from the GEO and analyzed by GEO2R to recognize DEGs. By applying DAVID, GO, and KEGG, pathway enrichment analysis was performed. PPI of these DEGs was analyzed using STRING and visualized by Cytoscape and MCODE. Further, we utilized HPA and GEPIA to obtain Kaplan–Meier graph for survival analysis in order to assess the prognostic value of hub genes. Results We examined the UM and CM datasets and discovered three common upregulated and eight downregulated DEGs based on computational analysis. HMGCS1 and ELOVL5 were shown to be enriched in a variety of altered molecular pathways and pathways in cancer. Overexpression of HMGCS1 and ELOVL5 was linked to a poor prognosis in CM. Conclusion Computational evaluation found that HMGCS1 and ELOVL5 were upregulated in both melanomas. Enrichment analysis showed that these genes are involved in cancer metabolism pathway and associated with poor prognosis in CM. However, the molecular study of these genes in UM is limited. Therefore, a better understanding of the cancer metabolism pathways should be carried to pave the way for clinical benefits.

Societal Impact Statement It is important to recognize how our current understanding of plants has been shaped by diverse cultural contexts, as this underscores the importance of valuing and incorporating contributions from all knowledge systems in scientific pursuits. This approach emphasizes the ongoing bias, including within scientific practices, and the necessity of discussing problematic histories within spaces of learning. It is crucial to acknowledge and address biases, even within scientific endeavors. Doing so fosters a more inclusive and equitable scientific community. This article, while not comprehensive, serves as a starting point for conversation and an introduction to current work on these topics. Summary In response to a global dialog about systemic racism, ongoing inequalities, appeals to decolonize science, and the many recent calls for diversity, equity, accessibility, and inclusion, we draw on the narratives of plants to revisit the history of botany. Our goal is to uncover how exclusionary practices have functioned in the past and persist today. We also explore the numerous opportunities and challenges that arise in the era of information as we strive to establish a more inclusive field of botany. This approach recognizes and honors the contributions of historically marginalized groups, such as Black and Indigenous communities. We hope that this article can serve as a catalyst for raising awareness, fostering contemplation, and driving action toward a more equitable and just scientific community.

Aim: The aim of this study was to evaluate specific single nucleotide polymorphisms (SNP) of transforming growth factor-beta (TGF-β) (rs1800469) and insulin-like growth factor-1 (IGF-1) (rs17032362) genes in Class II individuals with a normal maxilla and retrognathic (short) mandible. Materials and methods: The study had 25 participants: 5 were assigned to the control group, which had a normal maxilla and mandible, and 20 to the experimental group, which had a structurally retrognathic mandible and a normal maxilla. The polymerase chain reaction was used with preselected primers after which Sanger sequencing was used to identify individual mutations. Results: SNP at rs1800469 (TGF-β) in the study and control groups showed significant difference (p=0.009). The Odds Ratio of 5.28 signified that the individuals with SNP at rs1800469 were at 5.28 times higher risk of developing mandibular retrognathism. The IGF SNP showed its presence in experimental group but was not statistically significant. Conclusion: Our study reports for the first time on the association between TGF-β SNP and mandibular retrognathism. Other SNP also showed its presence in the study group and its complete absence from control group directs us for further research.

Introduction: Older adults racialized as Black experience higher rates of dementia than those racialized as White. Structural racism produces socioeconomic challenges, described by artist Marvin Gaye as ?hang ups, let downs, bad breaks, setbacks? that likely contribute to dementia disparities. Robust dementia literature suggests socioeconomic factors may also be key resiliencies. Methods: We linked state-level data reflecting the racialized landscape of economic opportunity across the 20th Century from the U.S. Census (1930?2010) with individual-level data on cognitive outcomes from the U.S. Health and Retirement Study participants racialized as Black. A purposive sample of participants born after the Brown v. Board ruling (born 1954?59) were selected who completed the modified Telephone Interview for Cognitive Status between 2010 and 2020 (N=1381). We tested associations of exposure to structural racism and resilience before birth, and during childhood, young-adulthood, and midlife with cognitive trajectories in mid-late life using mixed-effects regression models. Results: Older adults born in places with higher state-level structural socioeconomic racism experienced a more rapid cognitive decline in later life compared to those with lower levels of exposure. In addition, participants born in places with higher levels of state-level structural socioeconomic resilience experienced slower cognitive change over time than their counterparts. Discussion: These findings reveal the impact of racist U.S. policies enacted in the past that influence cognitive health over time and dementia risk later in life.

Abstract Introduction Prosocial behavior has been shown to be protective against burnout. Yet, we know little about prosocial behavior in medical students. We wanted to know what are chinese medical students' understanding of prosocial behavior and which factors influence their participation in it? Methods We undertook a grounded theory study, following Corbin & Strauss. We used convenience sampling and conducted semi-structured individual interviews. We analyzed data using open, axial, and selective coding techniques. Next, we grouped data into concepts. We noticed these concepts aligned with three existing social theories, so we developed our theory in concert with these: the Theory of Planned Behavior, Self-Determination Theory, and Social Support Theory. Results Twenty-eight medical students participated in this study. Medical students hold especial views on the roles of medical physicians, and most of these views align with students' core values, including the value of prosocial behavior. Students are intrinsically motivated to engage in prosocial behaviors that align with their core values. Personal values, personality traits, perceived self-competence, career motivation, environmental factors, and family influences are the core factors influencing medically positive prosocial behavior. Conclusions This study supports a focus on prosocial behavior instead of altruistic behavior in medical education. We anticipate that promoting prosocial behavior through medical curricula will reduce moral distress and burnout among medical students.

The 2020 COVID-19 pandemic proved challenging for people working and teaching in the health professions. What was it like to learn or teach in the health professions during the pandemic? What challenges were experienced, and how were these navigated? We undertook duoethnography to provide answers to these questions. The authors are an endodontist from Chile who undertook her Master of Clinical Education in New Zealand during the COVID-19 pandemic and one of her postgraduate supervisors. A dataset of 40 photo-reflection dyads and duoethnographic text are presented. We experienced this pandemic as isolating, sombre and tough, albeit for different reasons. Managing relationships and family needs from a distance or in the same space in which work was to occur proved difficult. Postgraduate research was slowed. The educator workload was significantly increased, especially for the first six months of the pandemic, whereby she was tasked with rapidly creating a lot of online virtual learning material. We draw on Emotional Labour theory to make sense of these experiences. Support for clinical educators during pandemics should cater to situational contexts. We recommend Communities of Practice, psychological supports, acts of care (including self-care), wellbeing initiatives, and arts-based practice as potential mechanisms to support educators and learners.

# Background Chlorhexidine gluconate (CHG) bathing has proven to reduce central line--associated bloodstream infections (CLABSI) in hospitalized patients. The aim of this study is to evaluate whether the implementation of a compliance monitoring process for CHG bathing and strict hand hygiene as part of the traditional CLABSI prevention bundle will reduce the overall hospital CLABSI standardized infection ratio (SIR). # Methods A quasi-experimental study was conducted in intensive care and non-intensive care inpatient hospital units in an urban 361-bed teaching hospital in Western Pennsylvania. The pre-intervention period consisted of January--August 2021, the intervention period consisted of September--November 2021, and the post-intervention and sustainability period consisted of December 2021--June 2022. A compliance monitoring process for the initiation of a daily bath using a 4% CHG solution and strict hand hygiene surveillance was implemented as part of the standard CLABSI prevention bundle (which includes standardized insertion checklists and processes, daily necessity assessment, dressing change and integrity standards, five moments hand hygiene standards, CHG disk \[Biopatch\], end caps \[Curos\], and care of tubing). # Outcomes A statistically significant increase in hand hygiene (p=\

Introduction To make motherhood safe and joyful for the mother and baby, Birth preparedness and complication readiness (BPACR) is a globally accepted strategy. BPACR encourages pregnant women, their families, and communities to effectively plan for births and deal with emergencies, if they occur. BPACR improves preventive behaviours, improves knowledge of mothers about danger signs, and leads to improvement in care-seeking during obstetric emergencies. Objectives The study was undertaken to assess the status and determinants of BPACR among the women who had experienced motherhood recently. Methodology This cross-sectional study was carried out among recently delivered 141 postpartum mothers and admitted in our hospital during March 2023 to June 2023. A semi-structured interview schedule was used for data collection. Results Mean age of study participants were 25.64±3.85 years. BPACR index among 51.5% of study subjects ranged between 1-4 while for 48.9% of candidates it varied from 5-8. There was a significant association between educational status and occupation of study participants, education and occupation of spouse, socio-economic status of family, number of ANC visits, Td vaccination, IFA intake with BPACR status of study participants (p value

In a retrospective view, this review examines the impact of mucormycosis on health workers and researchers during the COVID era. The diagnostic and treatment challenges arising from unestablished underlying pathology and limited case studies add strain to healthcare systems. Mucormycosis, caused by environmental molds, poses a significant threat to COVID-19 patients, particularly those with comorbidities and compromised immune systems. Due to a variety of infectious Mucorales causes and regionally related risk factors, the disease's incidence is rising globally. Data on mucormycosis remains scarce in many countries, highlighting the urgent need for more extensive research on its epidemiology and prevalence. This review explores the associations between COVID-19 disease and mucormycosis pathology, shedding light on potential future diagnostic techniques based on the fungal agent's biochemical components. Medications used in ICUs and for life support in ventilated patients have been reported, revealing the challenge of managing this dual onslaught. To develop more effective treatment strategies, it is crucial to identify novel pharmacological targets through “pragmatic” multicenter trials and registries. In the absence of positive mycology culture data, early clinical detection, prompt treatment, and tissue biopsy are essential to confirm the specific morphologic features of the fungal agent. This review delves into the history, pathogens, and pathogenesis of mucormycosis, its opportunistic nature in COVID or immunocompromised individuals, and the latest advancements in therapeutics. Additionally, it offers a forward-looking perspective on potential pharmacological targets for future drug development.

Diagnosis and management of candiduria in hospitalized patients is often a gray zone for clinicians and microbiologists alike. The presence of Candida in urine could mean anything ranging from contamination and colonization to frank urinary tract infection. This study aims to enhance the understanding of candiduria among critically ill patients admitted in the intensive care unit (ICU). Out of 226 urine samples received in the laboratory from patients admitted in the ICU with an indwelling urinary catheter, 15 were found to have candiduria, prevalence being 6.6%. Various species isolated were Candida tropicalis (40%), Candida albicans (33.33%), Candida lusitaniae (13.33%), Candida parapsilosis (6.66%), and Candida dubliniensis (6.66%). In all patients, candiduria resolved spontaneously upon removal of the catheter. No antifungal was administered, and no concurrent positive blood culture was found in any of these patients. This study emphasizes that simply culturing the organism does not imply clinical significance. Removal or change of catheter must be undertaken once such a report is received from the laboratory.

Abstract Background Owing to the limited research on Takotsubo Cardiomyopathy (TCM) in Asia, we aim to evaluate in detail the clinical profiles, lab parameters, investigations, and major adverse cardiovascular events (MACE) seen in patients with TCM in the Indian subcontinent. Additionally, we have compared the electrocardiographic findings of patients with TCM to those of patients with myocardial infarction (MI). Results The average age of the patients affected was found to be 60 ± 11 years. Women (87.5%) and patients with hypertension (40%) were found to be at an increased risk of developing the syndrome. The most common presenting symptom was dyspnea (48%) following a trigger most commonly emotional (45%). ST elevation and significant T wave inversions were observed in 40% of patients with TCM. Echocardiography revealed a low left ventricular ejection fraction of 43 ± 9%. Coronary angiography was normal in 60%, the rest had mild/subcritical stenoses. The 6-month MACE was 20% and the mortality rate was 7.5%. Follow-up echocardiography of patients with TCM showed improvement in EF in 75% patients. Conclusions TCM was majorly seen in postmenopausal women following an emotional trigger, but a variety of other triggers were noted. T-wave inversions in TCM follow a diffuse pattern in contrast to specific leads seen in MI. Normal or subcritical stenosis in coronaries at presentation, along with a low EF which improves on follow up provide greater evidence for the diagnosis of TCM.

Abstract Background Drug delivery systems (DDSs) encompass a wide range of methods, including oral, injectable, and topical routes of administration, all tailored to meet specific patient needs. Micro and nanorobots, equipped with pioneering propulsion mechanisms that convert external energy sources into precise movements, have revolutionized drug delivery. This cutting-edge technology ensures highly efficient drug delivery, particularly when targeting specific targets within intricate physiological environments. In contrast to traditional drug delivery approaches that rely on bloodstream circulation, engineered micro/nanorobots have autonomous mobility, enabling drug delivery to previously unreachable areas. Main body of the abstract Integrating micro/nanorobots into drug delivery raises vital safety and biocompatibility issues. These encompass material selection, degradation in-vivo, overcoming biological barriers, controlled movement, external interference, immune response, chemical reactions, systemic effects, long-term impact, and real-time monitoring. While micro/nanorobots hold immense transformative potential, they confront significant hurdles in their journey toward practical applications. Chief among these challenges are concerns regarding biocompatibility, ensuring that these tiny devices do not trigger adverse reactions. Long-term safety remains a critical issue, as understanding the effects of prolonged exposure and potential accumulations within the body and navigating complex biological environments with precision is another obstacle. Short conclusion The paper summarizes how to explore the various ways in which micro/nanorobots can be employed to enhance drug delivery, including their precision, targeting capabilities, and adaptability to different physiological conditions. Additionally, the review seeks to highlight the transformative potential of these technologies and their impact on the pharmaceutical industry.

Background and aim: The seeds of Nelumbo nucifera, Chenopodium quinoa and Salvia hispanica are known as super foods due to their various therapeutic properties. The present study aimed to develop an optimized polyherbal formulation from edible seeds aqueous extract and to evaluate its anti-diabetic and lipase inhibitory effect on diet-induced obese diabetic mice. Experimental procedure: Response surface methodology based various formulations were evaluated for their potent anti-diabetic, lipase-inhibitory and antioxidant activities. Acute toxicity of the best optimized formulation was conducted. The mice were fed a high fat diet for 10 weeks resulting in hyperglycemia and obesity. Oral tolerance tests (sucrose, starch and lipid) of the formulation were performed. The mice were supplemented with different doses (125, 250 and 500 mg/kg) of the formulation for 6 weeks. The body weight and blood glucose level were monitored on a weekly basis. Finally, histological alterations and lipid profiles were analysed. Results and conclusion: The formulation containing equal concentration (1.5 mg/ml) of each seed extract showed maximum bioactivities. The formulation was found to be safe during toxicity assay. The tolerance tests supported the anti-diabetic and anti-obesity effect. Higher dose (500 mg/kg) of the formulation significantly (p < 0.01) lowered elevated fasting blood glucose, lipid indices and ameliorated the histological alterations in liver, kidney and pancreas caused by high fat diet. We demonstrated for the first time that the developed aqueous extract optimized formulation possess anti-diabetic and anti-obesity potential and thus could be used as adjuvant therapy for holistic management of type 2 diabetes mellitus.

Aim: Children with otitis media (OM) experience long waiting times to access Australia's public hospitals due to limited capacity. The aim of this article is to utilize an Ear, Nose, and Throat (ENT) telehealth service (the Ear Portal) to examine whether delayed access to specialist care is associated with poorer behavioral outcomes for children with OM. Methods: Participants in the study included 45 children who were referred to ENT specialists due to recurrent and persistent OM. Children were triaged as semiurgent with a target time-to-assessment of 90 days or nonurgent with a target time-to-assessment of 365 days. The behavioral outcomes of children were assessed using the parent report Strengths and Difficulties Questionnaire (SDQ). Descriptive statistics and adjusted multiple linear regression models were used to compare children who received access to the service within the time-to-assessment target of their triage category (?on-boundary?; n?=?17) and outside the time-to-assessment target (?off-boundary?; n?=?28). Spearman correlation analysis was used to explore the relationship between the internalizing, externalizing, and total SDQ scores as a function of waiting times in days. Results: Borderline or abnormal SDQ scores ranged from 24.4% to 42.2% across the study participants. The regression analysis showed a statistically significant association between the off-boundary group and higher scores (i.e., poorer) on the peer, emotional, conduct, internalizing, and total problems subscales. Further, lengthy waiting times were significantly correlated with higher internalizing problems. These findings indicate that longer waiting times may lead to poorer behavioral outcomes for children with OM. Clinical Trial Registration: (ACTRN1269000039189p). Conclusion: Children with recurrent and persistent OM referred to ENT outpatient care were found to have significantly more behavioral difficulties if their waiting times exceeded the recommended timeframes for their triaged referrals. Additionally, they experienced more internalizing problems that correlated with longer waiting times. This highlights the calls for alterations in current clinical practice given the lengthy waiting times in Australia's public hospitals.

Background: Diabetic people on metformin are more likely to develop vitamin B12 deficiency. There has been little research into the duration of therapy and dose of metformin that causes B12 deficiency and peripheral neuropathy. This study is being done to determine the same. Objective: To determine the association between vitamin B12 deficiency and its neuropathy to long-term metformin therapy in diabetic patients. Study design: This observational cross-sectional study was conducted at SRIHER Chennai. Patients on long-term metformin were taken and separated into two groups: B12 Vitamin deficiency and normal Vitamin B12 levels. Results: B12 Vitamin deficiency was found in 15.72% of 159 patients on metformin. Only 2 of the 59 people on vitamin supplements in our study showed Vitamin B-12 deficiency, whereas 23 out of 100 people in the non-supplemented group had Vitamin B-12 deficiency. The difference (OR - 0.11; P 0.005) was statistically important. There was a statistically important difference observed between the prevalence of deficiency of vitamin B-12, Duration (>5 years), and dosage (>1 g/day) of Metformin use (p-value - 5 years) and dose > 1g/day are linked to B12 Vitamin deficiency and neuropathy in diabetic patients.

Tardive Dyskinesia (TD) is a medication induced movement disorder characterised by involuntary athetoid or choreiform movements generally of the tongue, lower face and jaw, and extremities developing in association with the use of a neuroleptic medication for at least a few months that persists despite discontinuation or change of the medications. This study was done to help in the early recognition and management of tardive dyskinesia and to obtain useful data to help prevent the same. The study aimed to estimate the prevalence of tardive dyskinesia in patients with psychiatric illness having more than 3 months cumulative exposure to neuroleptics, and to determine the clinical correlates of tardive dyskinesia in them. Methodology: This cross sectional observational study was carried out after obtaining clearance from the Institution’s Ethics Committee (YEC2/658) between January 1st, 2021 and April 2022. A total of 207 participants were enrolled who were patients with psychiatric illness having more than 3 months of cumulative exposure to neuroleptics. Participants were then evaluated using the Schooler Kane criteria, Abnormal Involuntary Movement Scale and various sociodemographic and clinical variables were assessed. Results: Patients with schizophrenia are most at risk of developing tardive dyskinesia (67.1%). It was also discovered that chlorpromazine comparable dosages were significantly higher among participants with tardive dyskinesia. Orofacial tardive dyskinesia had the highest overall prevalence (23.2%). Conclusion: Many patients with psychotic diseases experienced movement difficulties brought on by conventional antipsychotics, which are viewed as burdensome and stigmatizing events. Designing treatment guidelines, expanding the availability of medications with minimum adverse effects, and providing psychoeducation on related aspects are crucial.

Key Clinical Message Sebaceous cysts are a prevalent form of benign cutaneous cysts that often manifest as epidermal cysts when their size exceeds 5 cm in diameter. Despite their infrequent occurrence, cases of massive epidermal cysts measuring 5 cm or larger have been documented. Malignant transformations within epidermal cysts are exceedingly rare but not impossible. Although their development into malignancies is a rare event, it is essential to acknowledge the potential for benign epidermal cysts to undergo such transformation. In clinical terminology, these cysts predominantly affect the facial, cervical, and dorsal regions. They usually remain asymptomatic, with their formation attributed to the sequestration of epithelial remnants during embryonic fusion or trauma. In this report, we present a remarkable case of a colossal epidermal cyst found on the upper back of a 75‐year‐old male individual, highlighting the uncommon nature of such occurrences within the medical domain. This case adds to the literature by presenting a rare case report highlighting the clinical presentation, probable consequences, and surgical therapy of larger epidermal cysts.

Objective To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes.Design Systematic review and meta-analysis.Data sources Major databases between December 2019 and January 2023.Study selection Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included.Quality assessment, data extraction and analysis Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs.Results Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women).Conclusion COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women.PROSPERO registration number CRD42020178076.

ABSTRACT Objective: This study aimed to assess the frequency with which orthodontic patients decided to shift to another type of orthodontic appliance, among conventional metal brackets, ceramic brackets, lingual brackets and clear aligner, based on their personal experiences of pain, ulcers, bad breath, hygiene issues and social difficulties. Material and Methods: This study comprises of patients seeking orthodontic treatment. The sample (n = 500; age group = 19-25 years) was divided equally into four groups based on the treatment modality: conventional metal brackets, ceramic brackets, lingual brackets and clear aligner. Patients rated the questionnaire using a visual analogue scale, to assess variables (such as pain, ulcer etc) that impact various treatment modalities. Subsequently, patients from all groups provided feedback regarding their treatment experiences, and expressed their preference for an alternative modality. Intergroup comparison among the four groups was done using one-way analysis of variance with Tukey’s HSD post-hoc test (p ≤ 0.05). Results: Patients who received lingual brackets reported higher levels of pain and ulceration, as compared to those who received clear aligners. All four groups showed statistically significant differences for ulcers during treatment (p ≤ 0.05). Of the 125 patients who received conventional metal brackets, 28% expressed a preference for clear aligner therapy, while 20% preferred ceramic brackets. In the lingual group, 56% of 125 patients preferred clear aligner therapy, and 8% preferred ceramic brackets to complete their treatment. In the ceramic group, 83% did not want to switch, whereas 17% desired to switch to clear aligner, while in aligner group no patient desired to switch. Conclusions: A higher percentage of patients from lingual brackets group chose to shift to clear aligners, followed by conventional metal brackets group and by ceramic brackets group, in this descending order. The clear aligner group demonstrated fewer issues than the other treatment modalities.

In healthcare settings, workplace learning is often supported by clinicians who strive to combine service provision and educator roles. We evaluated an international 12-month programme that supports widely distributed critical care health professional educators (HPEs) through a virtual community of practice (vCoP). Specifically, we evaluate if and how the vCoP approach affects learning experiences using an innovative evaluation framework in medical education—the value-creation framework (VCF). We used a mixed-methods approach to evaluation, including an anonymous survey and semistructured interviews. Themes from data sources were identified using the VCF as the common thread. Themes discussed by at least two-thirds of interview participants were analysed using narrative inquiry. 27 of 66 participants responded to the survey, and 15 participated in interviews. Positive and negative indicators of value creation were extracted and organised according to the framework’s eight value cycles. Framework analysis made value-creation and potential flow-on effects in one value-creation cycle to another visible, offering insight into relationships. Themes from narrative inquiry elaborated on the results of the framework analysis. Using the VCF to evaluate the Incubator programme brings to bear the complexity of boundary-crossing HPE faculty development for critical care educators. The framework can be a valuable tool for evaluating a vCoP associated with faculty development programmes.

Abstract Background In stroke rehabilitation, wearable technology can be used as an intervention modality by providing timely, meaningful feedback on motor performance. Stroke survivors’ preferences may offer a unique perspective on what metrics are intuitive, actionable, and meaningful to change behavior. However, few studies have identified feedback preferences from stroke survivors. This project aims to determine the ease of understanding and movement encouragement of feedback based on wearable sensor data (both arm/hand use and mobility) for stroke survivors and to identify preferences for feedback metrics (mode, content, frequency, and timing). Methods A sample of 30 chronic stroke survivors wore a multi-sensor system in the natural environment over a 1-week monitoring period. The sensor system captured time in active movement of each arm, arm use ratio, step counts and stance time symmetry. Using the data from the monitoring period, participants were presented with a movement report with visual displays of feedback about arm/hand use, step counts and gait symmetry. A survey and qualitative interview were used to assess ease of understanding, actionability and components of feedback that users found most meaningful to drive lasting behavior change. Results Arm/hand use and mobility sensor-derived feedback metrics were easy to understand and actionable. The preferred metric to encourage arm/hand use was the hourly arm use bar plot, and similarly the preferred metric to encourage mobility was the hourly steps bar plot, which were each ranked as top choice by 40% of participants. Participants perceived that quantitative (i.e., step counts) and qualitative (i.e., stance time symmetry) mobility metrics provided complementary information. Three main themes emerged from the qualitative analysis: (1) Motivation for behavior change, (2) Real-time feedback based on individual goals, and (3) Value of experienced clinicians for prescription and accountability. Participants stressed the importance of having feedback tailored to their own personalized goals and receiving guidance from clinicians on strategies to progress and increase functional movement behavior in the unsupervised home and community setting. Conclusion The resulting technology has the potential to integrate engineering and personalized rehabilitation to maximize participation in meaningful life activities outside clinical settings in a less structured environment.

The probiotic potential of Shouchella clausii is widely recognized, but little is known about its adhesive properties. Hence, this study aims to investigate the adhesion potential and cell surface properties of four human-origin S. clausii strains (B619/R, B603/Nb, B106, and B637/Nm). We evaluated epithelial adhesion, Extracellular Matrix (ECM) binding, aggregation ability, and cell surface hydrophobicity and used genome analysis for validation. Our results demonstrate that adhesion capability is a strain-specific attribute, with significant variations observed among the four strains. B619/R, B603/Nb, and B106 displayed stronger adhesion properties than B637/Nm. Supplementary adhesion assays showed that B637/Nm displayed high hydrophobicity, significant auto-aggregation, and significant mucin-binding abilities. Conversely, B619/R, B603/Nb, and B106 had mildly hydrophobic surfaces and low aggregation abilities. Genome annotation revealed the presence of various adhesion proteins in four strains. Notably, the reduced adhesion potential of B637/Nm was supported by the absence of the cell wall surface anchor family protein (LPxTG motif), which is crucial for interactions with intestinal epithelial cells or mucus components. Further, docking studies provided insights into the interaction of adhesion proteins with gut mucins. These findings contribute to a better understanding of how S. clausii strains interact with the gut environment, facilitating the development of probiotic formulations tailored for improved gut health and well-being.

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain–Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases.

Abstract Background Homelessness is a complex societal and public health challenge. Limited information exists about the population-level health and social care-related predictors and consequences of persons with lived experience of homelessness (PEH). Studies that focus on population subgroups or ad hoc questionnaires to gather data are of relatively limited generalisability to whole-population health surveillance and planning. The aim of this study was to find and synthesise information about the risk factors for, and consequences of, experiencing homelessness in whole-population studies that used routine administrative data. Method We performed a systematic search using EMBASE, MEDLINE, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO research databases for English-language studies published from inception until February 2023 that reported analyses of administrative data about homelessness and health and social care-related predictors and consequences. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Of the 1224 articles reviewed, 30 publications met the inclusion criteria. The included studies examined a wide range of topic areas, and the homelessness definitions used in each varied considerably. Studies were categorised into several topic areas: Mortality, morbidity and COVID-19; health care usage and hospital re-admission; care home admission and shelter stay; and other (e.g. employment, crime victimisation). The studies reported that that the physical and mental health of people who experience homelessness was worse than that of the general population. Homeless individuals were more likely to have higher risk of hospitalisation, more likely to use emergency departments, have higher mortality rates and were at greater risk of needing intensive care or of dying from COVID-19 compared with general population. Additionally, homeless individuals were more likely to be incarcerated or unemployed. The effects were strongest for those who experienced being homeless as a child compared to those who experienced being homeless later on in life. Conclusions This is the first systematic review of whole-population observational studies that used administrative data to identify causes and consequences associated with individuals who are experiencing homelessness. While the scientific literature provides evidence on some of the possible risk factors associated with being homeless, research into this research topic has been limited and gaps still remain. There is a need for more standardised best practice approaches to understand better the causes and consequences associated with being homeless.

The aim of this study was to present a framework for clinicians to use when discussing electronic cigarette (e-cigarette) use and its association with pre-diabetes. A communication tool was designed using evidence-based strategies from the academic literature. A four-step framework is presented, which includes: step (1) helping patients to understand the association between e-cigarette use and pre-diabetes; step (2) the synergistic health impacts of e-cigarette use and pre-diabetes; step (3) management of diabetes-related lifestyle factors; and step (4) stages of change assessment related to e-cigarette reduction. This communication tool provides support for clinicians to discuss the risk of pre-diabetes associated with e-cigarette use. Moving forward, implementation and evaluation of this model are needed.

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrinopathy affecting women of reproductive age group at a global level. According to many community-based studies, the prevalence of PCOS in India ranges from 3.7 to 22.5% due to the country's enormous population. Upon ultrasound, it shows multiple cysts arranged in a bead of necklace-like appearance causing irregular menstrual cycles and infertility in most cases. It is manifested with abnormally raised testosterone and insulin levels and increased luteinizing hormone (LH)-to-follicle-stimulating hormone (FSH) ratio. Phenotypically, it is presented as obesity, hirsutism, acne and male pattern baldness, which impacts the self-esteem of young girls leading to depression and compromised quality of life. Aim Numerous potential genes have been shown to contribute to PCOS, and the genetic linkage of PCOS has been investigated in many studies. In this study we are looking into the candidate genes, the variants, and other responsible factors behind the genesis of PCOS. This will help in better understanding of its pathogenesis and, as a result, deciphering the mechanism by proper medication. Method of the study We comprehensively searched for publications including PCOS-relevant keywords in different areas in five different electronic databases: PubMed, Google Scholars, Elsevier, Springer Link and Science Direct up to March 2023 focusing on the new ones. We excluded non-English articles, conference papers and studies that were overlapping. Chosen articles were carefully read and further articles that were retrieved from their references were also reviewed so as to make the search complete with the inclusion criterion. Result This review summarizes PCOS as an polygenic and a multifactorial complex disease in which a vast array of genetic and environmental factors are involved. Genes that affect steroidogenesis (ovarian and adrenal), gonadotropin action and regulation, insulin action and secretion, body mass index and chronic inflammation are directly or indirectly associated with PCOS. Conclusion In this study, research of the genetic propensity to PCOS was made, though not in-depth. With the acquired knowledge of array of genes involved, targeted efforts can be made for the potential therapeutic management of the PCOS patients via the novel discovered routes. Moreover, understanding more about PCOS would be beneficial in prevention of the associated metabolic disorders, life-threatening morbidities, restoring fertility and raising the self-esteem of the young women.

Abstract Background Public involvement (often referred to as patient and public involvement or PPI) integrates the voices of the public in health and care research. However, groups such as care home residents are often excluded from involvement opportunities due to the complexities of involving people with additional care and communication needs. Despite a range of approaches being used, there is little understanding about how best to incorporate their experiences, and those of other care home stakeholders, into the design and conduct of research. Objective A systematic review was conducted to identify PPI methods that better meet the specific needs of care home stakeholders. This was undertaken by (1) outlining effective PPI approaches used in care home research and the key stakeholders involved; (2) describing the role of PPI in different care home contexts and (3) identifying stakeholders’ experiences and attitudes towards PPI in care homes. Methods Databases CINAHL, Embase, MEDLINE, PsycINFO and Scopus were searched for English language papers from inception to November 2021. A narrative synthesis approach was utilised to organise the extracted data into five themes. Results The search initially yielded 2314 articles (following de-duplication), with 27 meeting the inclusion criteria. Articles reported a range of input from stakeholders (including residents, staff, relatives and community stakeholders), with the impact of PPI varying according to the type of care establishment and research context. The experiences and reflections of stakeholders’ about their involvement in care home research varied, with some studies offering first-hand accounts compared with summaries from researchers. Some articles explicitly evaluated the effectiveness of the PPI approach using specific outcome measures whilst others indirectly described the impact of their approach. Five themes were identified as characterising an effective PPI approach: (1) valuing stakeholders’ perspectives, (2) awareness of the multi-faceted research context, (3) ensuring inclusivity and transparency, (4) maintaining flexibility and adaptability and (5) utilising resources and wider support. Conclusion Effective PPI in care home research requires researchers to create person-centred opportunities to adequately involve groups with physical and cognitive impairments. The findings led to the creation of evidence-based practical recommendations to support future involvement opportunities and help researchers develop strategies for inclusive opportunities for involvement. Systematic Review Registration: The review was prospectively registered on PROPSERO (CRD42021293353).

Objective: This paper outlines the design and implementation of iManage SCD, a self-management mobile health application for adolescents and young adults (AYA) with sickle cell disease (SCD) during transition from pediatric to adult health care. Methods: The Integrate, Design, Assess, Share (IDEAS) framework, emphasizing user insights, iterative design, rigorous assessment, and knowledge sharing, guided the development process. The design team consisted of researchers, psychologists, physicians, social workers, AYA with SCD, and parents of AYA with SCD (n = 16) across three states. Qualitative focus groups and interviews were conducted and analyzed using thematic analysis across the integrate and design phases. Point of use feedback from AYA with SCD was used to assess feasibility and acceptability. Results: The development process was centered around tenants of the Social-ecological Model of Adolescent and Young Adult Readiness to Transition. Development integrated multidisciplinary perspectives, fostering a person-centered approach. The iterative design process involved collaboration with a digital health firm, Agency39A. Health equity and implementation considerations were addressed at individual, community, and healthcare system levels. Themes that emerged from focus groups with AYA, clinicians, and researchers in the integrate and design phases of development included recommendations for content and user experience features. Conclusions: iManage SCD emerges as a comprehensive, user-friendly mobile health application, incorporating theoretical principles and direct user input. The development process demonstrated feasibility and acceptability, and the paper discusses dissemination strategies for the Community Health Workers and Mobile Health Programs to Help Young Adults with SCD Transition to Using Adult Healthcare Services (COMETS) study.

Eukaryotic proteins often feature long stretches of amino acids that lack a well-defined three-dimensional structure and are referred to as intrinsically disordered proteins (IDPs) or regions (IDRs). Although these proteins challenge conventional structure-function paradigms, they play vital roles in cellular processes. Recent progress in experimental techniques, such as NMR spectroscopy, single molecule FRET, high speed AFM and SAXS, have provided valuable insights into the biophysical basis of IDP function. This review discusses the advancements made in these techniques particularly for the study of disordered regions in proteins. In NMR spectroscopy new strategies such as 13C detection, non-uniform sampling, segmental isotope labeling, and rapid data acquisition methods address the challenges posed by spectral overcrowding and low stability of IDPs. The importance of various NMR parameters, including chemical shifts, hydrogen exchange rates, and relaxation measurements, to reveal transient secondary structures within IDRs and IDPs are presented. Given the high flexibility of IDPs, the review outlines NMR methods for assessing their dynamics at both fast (ps-ns) and slow (μs-ms) timescales. IDPs exert their functions through interactions with other molecules such as proteins, DNA, or RNA. NMR-based titration experiments yield insights into the thermodynamics and kinetics of these interactions. Detailed study of IDPs requires multiple experimental techniques, and thus, several methods are described for studying disordered proteins, highlighting their respective advantages and limitations. The potential for integrating these complementary techniques, each offering unique perspectives, is explored to achieve a comprehensive understanding of IDPs.

Brain health refers to the state of a person’s brain function across various domains, including cognitive, behavioral and motor functions. Healthy brains are associated with better individual health, increased creativity, and enhanced productivity. A person’s brain health is intricately connected to personal, social and environmental factors. Racial, ethnic, and social disparities affect brain health and on the global scale these disparities within and between regions present a hurdle to brain health. To overcome global disparities, greater collaboration between practitioners and healthcare providers and the people they serve is essential. This requires cultural humility driven by empathy. Empathy is a core prosocial value, a cognitive-emotional skill that helps us understand ourselves and others. This position paper aims to provide an overview of the vital roles of empathy, cooperation, and interdisciplinary partnerships. By consciously integrating this understanding in practice, leaders can better position themselves to address the diverse challenges faced by communities, promote inclusivity in policies and practices, and further more equitable solutions to the problem of global brain health.

ABSTRACT EseN is an Edwardsiella ictaluri type III secretion system effector with phosphothreonine lyase activity. In this work, we demonstrate that EseN inactivates p38 and c-Jun-N-terminal kinase (JNK) in infected head-kidney-derived macrophages (HKDMs). We have previously reported inactivation of extracellular-regulated kinase 1/2 (ERK1/2). Also, for the first time, we demonstrated that EseN is involved in the inactivation of 3-phosphoinositide-dependent kinase 1 (PDK1), which has not been previously demonstrated for any of the EseN homologs in other species. We also found that EseN significantly affected mRNA expression of IL-10, pro-apoptotic baxa, and p53, but had no significant effect on anti-apoptotic bcl2 or pro-apoptotic apoptotic peptidase activating factor 1. EseN is also involved in the inhibition of caspase-8 and caspase-3/7 but does not affect caspase-9 activity. Repression of apoptosis was further confirmed with flow cytometry using Alexa Fluor 647-labeled annexin V and propidium iodide. In addition, we found that the E. ictaluri T3SS is essential for the inhibition of IL-1β maturation, but EseN is not involved in this process. EseN did not affect cell pyroptosis, as indicated by the lack of EseN impact on the release of lactate dehydrogenase from infected HKDM. The transmission electron microscopy data also indicate that HKDM infected with WT or an eseN mutant died by apoptosis, while HKDM infected with the T3SS mutant more likely died by pyroptosis. Collectively, our results indicate that E. ictaluri EseN is involved in inactivation of ERK1/2, p38, JNK, and PDK1 signaling pathways that lead to modulation of cell death among infected HKDMs. IMPORTANCE This work has global significance in the catfish industry, which provides food for increasing global populations. E. ictaluri is a leading cause of disease loss, and EseN is an important player in E. ictaluri virulence. The E. ictaluri T3SS effector EseN plays an essential role in establishing infection, but the specific role EseN plays is not well characterized. EseN belongs to a family of phosphothreonine lyase effectors that specifically target host mitogen activated protein kinase (MAPK) pathways important in regulating host responses to infection. No phosphothreonine lyase equivalents are known in eukaryotes, making this family of effectors an attractive target for indirect narrow-spectrum antibiotics. Targeting of major vault protein and PDK1 kinase by EseN has not been reported in EseN homologs in other pathogens and may indicate unique functions of E. ictaluri EseN. EseN targeting of PDK1 is particularly interesting in that it is linked to an extraordinarily diverse group of cellular functions.

ABSTRACTThe identification of immune correlates of protection against infectious pathogens will accelerate the design and optimization of recombinant and subunit vaccines. Systematic analyses such as immunoprofiling including serological, cellular, and molecular assessments supported by computational tools are key to not only identify correlates of protection but also biomarkers of disease susceptibility. The current study expands our previous cellular and serological profiling of vaccine-induced responses to a whole parasite malaria vaccine. The irradiated sporozoite model was chosen as it is considered the most effective vaccine against malaria. In contrast to whole blood transcriptomics analysis, we stimulated peripheral blood mononuclear cells (PBMC) with sporozoites and enriched for antigen-specific cells prior to conducting transcriptomics analysis. By focusing on transcriptional events triggered by antigen-specific stimulation, we were able to uncover quantitative and qualitative differences between protected and non-protected individuals to controlled human malaria infections and identified differentially expressed genes associated with sporozoite-specific responses. Further analyses including pathway and gene set enrichment analysis revealed that vaccination with irradiated sporozoites induced a transcriptomic profile associated with Th1-responses, Interferon-signaling, antigen-presentation, and inflammation. Analyzing longitudinal time points not only post-vaccination but also post-controlled human malaria infection further revealed that the transcriptomic profile of protected vs non-protected individuals was not static but continued to diverge over time. The results lay the foundation for comparing protective immune signatures induced by various vaccine platforms to uncover immune correlates of protection that are common across platforms.

This commentary is a critical reflection by early career researchers (ECRs) working in qualitative health research (QHR) during the COVID-19 pandemic. The consequences of the pandemic have been acutely felt by ECRs working in QHR. Many studies stopped, almost overnight, as healthcare institutions restricted access and redeployed staff, forcing researchers to redesign or even abandon projects. We reflect on the burden of these challenges for insecurely employed QHR ECRs and discuss the approaches adopted to retain scientific integrity and redesign studies. We also highlight the impact of COVID-19 on career development and relationship building – both during the emergency pandemic period and in the reshaped context of academia that continues to operate under the long shadow of COVID-19. We conclude by outlining a programme of change for how the practice and organisation of QHR could be reshaped, identifying opportunities for learning from the pandemic. Embracing these learnings will benefit not only the careers and wellbeing of QHR ECRs, but also universities, funders and the overall health and future of QHR.

As a complex condition that often arises due to numerous social, environmental and political factors, “obesity” can be understood by healthcare providers as a health outcome that is directly linked to issues that are outside of individual control. UK GPs who participated in a series of focus groups examining attitudes about the role of individual responsibility in weight loss often demonstrated contradictory beliefs when asked about the relationship between obesity, personal responsibility and their patients’ (in)ability to take individual action. Whilst GPs who practised in affluent areas were more likely to draw connections between poverty and high rates of obesity, GPs who practised in disadvantaged areas were more likely to discuss the need for all patients to assume personal responsibility for their health behaviours regardless of their individual circumstances. This article examines how GPs from both groups conceptualised personal responsibility in relation to their patients’ weight and socioeconomic circumstances. We conclude by outlining the need for GPs to demonstrate empathy when engaging in weight-loss discussions with patients and offer practical support for patients who seek it that is mindful of their material circumstances.

Sanitization is essential in limiting the spread of infectious diseases. Alcohol based sanitizer formulations consists of toxic compounds which are harmful to human health and not environmental friendly. The purpose of the present research is to formulate a bio-derived alcohol free hand sanitizer. Saponins are secondary metabolites that are stored in the roots of many plant species, where they may act as antimicrobial phytoprotectants. Saponins were extracted by Soxhlet extractor using methanol as solvent. Saponins were tested for their individual and synergetic antimicrobial (Agar plate diffusion method) and anti-oxidant (Ferric Reducing Antioxidant Power (FRAP) assay) activity. Polyherbal sanitizer was formulated using saponin as the main ingredient. It was evaluated for its physical parameters and antimicrobial properties. The synergistic effect of saponins was higher when compared to the individual saponins’ antimicrobial activity. The formulated polyherbal sanitizer evinced acceptable organoleptic properties with slightly acidic pH and demonstrated antimicrobial properties against selected microorganisms with maximum activity against Staphylococcus aureus (concentration =100µl, zone of inhibition diameter =24±1 mm). The antimicrobial efficacy of the formulated sanitizer was comparable to that of a commercially available hand sanitizer.

The use of electronic cigarettes among young people has been increasing in recent years. Electronic cigarettes are marketed in ways that attract young people and downplay the risks of these products. For example, electronic cigarettes are available in a variety of flavours, such as mint or chocolate, and it can be quite challenging for young people to understand the potential harms of these products when they are marketed through enticing advertisements under the veil of harmless flavours. Moreover, recent research has shown that electronic cigarette usage may be disproportionately higher for youth with lower socioeconomic status. It is well documented in the literature that electronic cigarettes can have a multitude of negative health impacts on young people. Electronic cigarette use affects all biopsychosocial domains, including but not limited to cardiovascular disease, pulmonary disease, renal disease, mental health, substance use, and interpersonal relationships. Given the increase in electronic cigarette use and lower levels of understanding of the harms these products can have on health, it is essential to develop additional strategies to ensure that young people are made aware of the risks associated with the use of electronic cigarettes. We propose a five factor model that aims to provide support to policymakers, educators, health care professionals, families, and youth. For policymakers, it is necessary to develop policies that limit the access the youth have to electronic cigarettes. In educational settings, educators can incorporate education on electronic cigarettes in the classroom. Health care professionals should have access to tools to ensure they feel comfortable discussing the risks of electronic cigarettes with their young patients. Additionally, families should have access to evidence-based information on the risks associated with electronic cigarettes and on how to communicate with their children about electronic cigarettes. Finally, we should aim to directly reach youth and communicate the potential risks of electronic cigarette use through the social media platforms that they frequent. Ultimately, this paper provides a model that can be used by various stakeholders involved in the public health system. Moving forward, implementing and conducting short, intermediate and long-term evaluation of this model can provide insight into its effectiveness in communicating the risks associated with electronic cigarette use for young people.

Humans continue to be at risk from the Zika virus. Although there have been significant research advancements regarding Zika, the absence of a vaccine or approved treatment poses further challenges for healthcare providers. In this study, we developed a microparticulate Zika vaccine using an inactivated whole Zika virus as the antigen that can be administered pain-free via intranasal (IN) immunization. These microparticles (MP) were formulated using a double emulsion method developed by our lab. We explored a prime dose and two-booster-dose vaccination strategy using MPL-A® and Alhydrogel® as adjuvants to further stimulate the immune response. MPL-A® induces a Th1-mediated immune response and Alhydrogel® (alum) induces a Th2-mediated immune response. There was a high recovery yield of MPs, less than 5 µm in size, and particle charge of −19.42 ± 0.66 mV. IN immunization of Zika MP vaccine and the adjuvanted Zika MP vaccine showed a robust humoral response as indicated by several antibodies (IgA, IgM, and IgG) and several IgG subtypes (IgG1, IgG2a, and IgG3). Vaccine MP elicited a balance Th1- and Th2-mediated immune response. Immune organs, such as the spleen and lymph nodes, exhibited a significant increase in CD4+ helper and CD8+ cytotoxic T-cell cellular response in both vaccine groups. Zika MP vaccine and adjuvanted Zika MP vaccine displayed a robust memory response (CD27 and CD45R) in the spleen and lymph nodes. Adjuvanted vaccine-induced higher Zika-specific intracellular cytokines than the unadjuvanted vaccine. Our results suggest that more than one dose or multiple doses may be necessary to achieve necessary immunological responses. Compared to unvaccinated mice, the Zika vaccine MP and adjuvanted MP vaccine when administered via intranasal route demonstrated robust humoral, cellular, and memory responses. In this pre-clinical study, we established a pain-free microparticulate Zika vaccine that produced a significant immune response when administered intranasally.

Background Globally, tertiary teachers are increasingly being pushed and pulled into online teaching. While most developments in online education have focused on the student perspective, few studies have reported faculty development (FD) initiatives for increasing online teaching capability and confidence from a staff perspective. Methods We designed and evaluated FD workshops, using five datasets, and the use of H5P software for interactive online teaching. We used educational theory to design our FD (Mayer multimedia principles, active learning) and evaluated our FD initiatives using the Best Evidence Medical Education (BEME) 2006 modified Kirkpatrick levels. Results Teaching staff reported that Communities of Practice were important for their learning and emotional support. Uptake and deployment of FD skills depended on the interactivity of FD sessions, their timeliness, and sufficient time allocated to attend and implement. Staff who applied FD learning to their online teaching created interactive learning resources. This content was associated with an increase in student grades, and the roll-out of an institutional site-wide H5P license. Conclusion This paper demonstrates an effective strategy for upskilling and upscaling faculty development. The use of H5P as a teaching tool enhances student learning. For successful FD, we make four recommendations. These are: provide just-in-time learning and allocate time for FD and staff to create online teaching material; foster supportive communities; offer personalized support; and design hands on active learning.