Designing one-compartment H2O2 fuel cell using electroactive phenalenyl-based [Fe2(hnmh-PLY)3] complex as the cathode material.

The sustainable chemical energy of H2O2 as a fuel and an oxidant in an advantageous single-compartment fuel cell design can be converted into electric energy, which requires molecular engineering to design suitable cathodes for lowering the high overpotential associated with H2O2 reduction. The present work covers the synthesis and structural characterization of a novel cathode material, [FeIII2(hnmh-PLY)3] complex, 1, designed from a PLY-derived Schiff base ligand (E)-9-(2-((2-hydroxynaphthalen-1-yl)methylene)hydrazineyl)-1H-phenalen-1-one, hnmh-PLYH2. Complex 1, when coated on the surface of a glassy carbon electrode (GC-1) significantly catalyzed the reduction of H2O2 in an acidic medium. Therefore, a complex 1 modified glassy carbon electrode was employed in a one-compartment H2O2 fuel cell operated in 0.1 M HCl with Ni foam as the corresponding anode to produce a high open circuit potential (OCP) of 0.65 V and a peak power density (PPD) of 2.84 mW cm-2. CV studies of complex 1 revealed the crucial participation of two Fe(III) centers for initiating H2O2 reduction, and the role of coordinated redox-active PLY units is also highlighted. In the solid state, the π-conjugated network of coordinating (hnmh-PLY) ligands in complex 1 has manifested interesting face-to-face π-π stacking interactions, which have helped the reduction of the complex and facilitated the overall catalytic performance.

A closed-shell phenalenyl-based dinuclear iron(III) complex as a robust cathode for a one-compartment H2O2 fuel cell.

Closed-shell phenalenyl (PLY) systems are increasingly becoming more attractive as building blocks for developing promising catalysts and electroactive cathode materials, as they have tremendous potential to accept electrons and participate in redox reactions. Herein, we report a PLY-based dinuclear [FeIII2(hmbh-PLY)3] complex, 1, and its utility as a cathode material in a H2O2 fuel cell. Complex 1 was synthesized from a new Schiff base ligand, (E)-9-(2-(2-hydroxy-3-methoxybenzylidene)hydrazineyl)-1H-phenalen-1-one, hmbh-PLYH2, designed using a PLY precursor, Hz-PLY. The newly derived ligand and complex 1 were characterized by various analytical techniques, including single-crystal X-ray diffraction (SCXRD). The cyclic voltammetry (CV) study revealed that complex 1 undergoes five electron reductions under an applied electric potential. When the electroactive complex 1 was employed as a cathode in a membrane-less one-compartment H2O2 fuel cell, with Ni foam as the corresponding anode, the designed fuel cell exhibited an exceptionally high peak power density (PPD) of 2.41 mW cm-2, in comparison with those of all the previously reported Fe-based molecular complexes. DFT studies were performed to gain reasonable insights into the two-electron catalytic reduction (pathway I) of H2O2 by the Fe-center of complex 1 and to explore the geometries, energetics of the electrocatalyst, reactive intermediates and transition states.

Needle-free injection system delivery of ZyCoV-D DNA vaccine demonstrated improved immunogenicity and protective efficacy in rhesus macaques against SARS-CoV-2.

The apprehension of needles related to injection site pain, risk of transmitting bloodborne pathogens, and effective mass immunization have led to the development of a needle-free injection system (NFIS). Here, we evaluated the efficacy of the NFIS and needle injection system (NIS) for the delivery and immunogenicity of DNA vaccine candidate ZyCoV-D in rhesus macaques against SARS-CoV-2 infection. Briefly, 20 rhesus macaques were divided into 5 groups (4 animals each), that is, I (1 mg dose by NIS), II (2 mg dose by NIS), III (1 mg dose by NFIS), IV (2 mg dose by NFIS) and V (phosphate-buffer saline [PBS]). The macaques were immunized with the vaccine candidates/PBS intradermally on Days 0, 28, and 56. Subsequently, the animals were challenged with live SARS-CoV-2 after 15 weeks of the first immunization. Blood, nasal swab, throat swab, and bronchoalveolar lavage fluid specimens were collected on 0, 1, 3, 5, and 7 days post infection from each animal to determine immune response and viral clearance. Among all the five groups, 2 mg dose by NFIS elicited significant titers of IgG and neutralizing antibody after immunization with enhancement in their titers postvirus challenge. Besides this, it also induced increased lymphocyte proliferation and cytokine response. The minimal viral load post-SARS-CoV-2 challenge and significant immune response in the immunized animals demonstrated the efficiency of NFIS in delivering 2 mg ZyCoV-D vaccine candidate.

Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): the interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India.

BACKGROUND: ZyCoV-D, a DNA-based vaccine, showed promising safety and immunogenicity in a phase 1/2 trial. We now report the interim efficacy results of phase 3 clinical trial with ZyCoV-D vaccine in India. METHODS: We conducted an interim analysis of a multicentre, double-blind, randomised, placebo-controlled phase 3 trial at 49 centres in India. Healthy participants aged at least 12 years were enrolled and randomly assigned (1:1) to receive either ZyCov-D vaccine (Cadila Healthcare; 2 mg per dose) or placebo. An interactive web response system was used for randomisation (blocks of four) of participants as well as to enrol those aged 60 years and older with or without comorbid conditions, and those aged 12-17 years. It was also used to identify 600 participants for immunogenicity (blocks of six). Participants, investigators, and outcome assessors were masked to treatment assignment. Three doses of vaccine or placebo were administered intradermally via a needle-free injection system 28 days apart. The primary outcome was the number of participants with first occurrence of symptomatic RT-PCR-positive COVID-19 28 days after the third dose, until the targeted number of cases (interim analysis n=79, full analysis n=158) have been achieved. The analysis was done in the per-protocol population, which consisted of all participants with negative baseline SARS-CoV-2 status who received three doses of vaccine or placebo. Assessment of safety and tolerability was based on the safety population, which consisted of all enrolled participants who were known to have received at least one dose of study vaccine or placebo. This trial is registered with Clinical Trial Registry India, CTRI/2021/01/030416, and is ongoing. FINDINGS: Between Jan 16, and June 23, 2021 (data cutoff), 33 194 individuals were screened, of whom 5241 did not meet screening criteria and 27 703 were enrolled and randomly assigned to receive ZyCoV-D (n=13 851) or placebo (n=13 852). Per-protocol, 81 cases were eligible and included in efficacy analysis (20 of 12 350 in the ZyCoV-D group and 61 of 12 320 in placebo group). The ZyCoV-D vaccine efficacy was found to be 66·6% (95% CI 47·6-80·7). The occurrence of solicited adverse events was similar between the treatment groups (623 [4·49%] in the ZyCoV-D group vs 620 [4·47%] in the placebo group). There were two deaths (one in each group) reported at the data cutoff, neither of which was considered related to the study treatments. INTERPRETATION: In this interim analysis, ZyCoV-D vaccine was found to be efficacious, safe, and immunogenic in a phase 3 trial. FUNDING: National Biopharma Mission, Department of Biotechnology, Government of India and Cadila Healthcare, Ahmedabad, Gujarat India.

Neuropsychiatric Treatment for Mild Traumatic Brain Injury: Nonpharmacological Approaches.

Postconcussive symptoms following mild traumatic brain injury (mTBI)/concussion are common, disabling, and challenging to manage. Patients can experience a range of symptoms (e.g., mood disturbance, headaches, insomnia, vestibular symptoms, and cognitive dysfunction), and neuropsychiatric management relies heavily on nonpharmacological and multidisciplinary approaches. This article presents an overview of current nonpharmacological strategies for postconcussive symptoms including psychoeducation; psychotherapy; vestibular, visual, and physical therapies; cognitive rehabilitation; as well as more novel approaches, such as neuromodulation. Ultimately, treatment and management of mTBI should begin early with appropriate psychoeducation/counseling, and be tailored based on core symptoms and individual goals.

Nocturnal Hemodialysis: Why Aren't More People Doing It?

Nocturnal hemodialysis is a form of intensive hemodialysis, which may be done in center or at home. Despite the documented clinical and economic benefits of ncturnal hemodialysis, uptake of this modality has been relatively low. In this review, we aim to address the potential barriers and possible mitigation strategies. Among the patient-related barriers, lack of knowledge and awareness remains the most common barrier, while administrative inertia to change from conventional in-center hemodialysis continues to be a challenge. Current global effort to grow home dialysis will re-focus the need for better patient education, innovate home dialysis technology, and evolve new models of care. New patient-focused policy will allow changes in reimbursement and develop appropriate momentum toward an integrated "home first model" to kidney replacement therapy.

Challenges and possible solutions to mitigate the problems of single-use plastics used for packaging food items: a review.

Single-use plastic (SUP) being a versatile material, is adopted as an alternate to traditional materials specifically for the use in food packaging due to its inherent characteristics like high durability, inertness, and protecting ability but has become a curse for living being today due to its random usage and unplanned rejection to nature. Mostly plastics used in packaging of beverages, fresh meats, fruits and vegetables are under concern today. Single-use packages result in generation of several billion tons of garbage till date, which pollutes the environment. At the immediate past, it has come to light that micro plastics obtained due to slow degradation of SUP present in oceans, are also being consumed by marine organisms such as fishes and shellfish species which disturbs the marine life extensively. Hence, finding right strategy to mitigate the plastic waste related issues has becoming inevitable today. This review paper briefs various strategies undertaken worldwide to mitigate the pollution due to generation of plastic waste. Various notable impact of adopted strategies and recent innovations to replace the SUP products are also discussed and in view of this a roadmap is also suggested which can be used to achieve the milestone of Zero Plastic Waste.

Sleep disturbance and length of stay in the setting of acquired brain injury rehabilitation.

OBJECTIVE: The objective of this study was to investigate the impact and prevalence of sleep-wake disturbances among adult patients admitted for inpatient acquired brain injury rehabilitation. METHOD: This was a retrospective cohort study involving all adults admitted for inpatient ABI neurocognitive rehabilitation at UHN-Toronto Rehabilitation Institute over a 12-month period (n = 165). The primary endpoint of the study was the comparison of functional independent measure efficiency and hospital length of stay between patients reporting sleep disturbance (e.g. increased sleep latency, obstructive sleep apnea [OSA], sleep maintenance insomnia) versus those with normal sleep. RESULTS: We found that more than half (58.2%) of patients experienced sleep disturbance based on a combination of self-report and clinical documentation. The most common sleep disturbance was increased sleep onset latency (28.5%), followed by mixed sleep onset/maintenance insomnia (14.5%) and obstructive sleep apnea (8.5%). Notably, OSA was associated with longer length of hospital stay and reduced functional independence measure (FIM) efficiency in the cognitive domain after accounting for age and number of medical comorbidities. IMPLICATIONS: The results of this investigation underscore the importance of screening patients with brain injury for sleep disturbances due to its high prevalence and impact on rehabilitation efficiency.

Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India.

BACKGROUND: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell. METHODS: We conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity. FINDINGS: Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34·9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36·36%), 4/12 (33·33%), 10/10 (100·00%) and 8/10 (80·00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively. INTERPRETATION: ZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.

Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500 µg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also elicited Th-1 response as evidenced by elevated IFN-γ levels.

The Severe Typhoid Fever in Africa Program: Study Design and Methodology to Assess Disease Severity, Host Immunity, and Carriage Associated With Invasive Salmonellosis.

BACKGROUND: Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. METHODS: A prospective healthcare facility-based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. RESULTS: Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. CONCLUSIONS: SETA supports public health policy on typhoid immunization strategy in Africa.

Increasing the use of home medication lists in an outpatient neurorehabilitation clinic.

Medication reconciliation in ambulatory care settings helps prevent adverse drug events. Patient involvement in the process is crucial, as clinicians must verify the reported medication history with other sources such as home medication lists or brown-bagged home medications provided by patients. However, only 47.8% of brain injury and stroke adult outpatients at Toronto Rehabilitation Institute, an academic rehabilitation hospital, bring their medications/medication lists to clinic visits. In turn, missing medication information impacts the clinic by causing delays in treatment and interrupted clinic flow. This project aimed to increase the percentage of patients who bring their medications/medication lists to 80% and decrease the impact on clinic visits caused by missing medication information to 10%. This was a controlled before-after study, with the outpatient rehabilitation assessment (OPRA) clinic as the intervention and the spasticity clinic as the control. The model for improvement was used as the project framework. Process mapping, Ishikawa diagrams, driver diagrams and patient surveys generated the change ideas. Verbal reminders during confirmation phone calls, written reminders and medication list templates were implemented. Data were collected on a biweekly basis and analysed using statistical control charts. After six Plan-Do-Study-Act cycles conducted over 49 weeks, both project aims were achieved. The percentage of OPRA clinic patients who brought medications/medication lists was 81.8% and the impact on clinic visits caused by missing medication information was 9.1% of clinic visits. Special cause variation was detected on the statistical control charts. Conversely, there was no special cause variation for the spasticity clinic (the control) for either aim. Lessons learnt include the importance of prolonged data collection when implementing interventions with long lag time, and that verbal reminders may not be effective for patients with cognitive impairments. Future efforts may focus on implementing the bundle of project interventions for the spasticity clinic.

Cognitive heterogeneity among community-dwelling older adults with cerebral small vessel disease.

Some degree of ischemic injury to white matter tracts occurs naturally with age and is visible on magnetic resonance imaging as focal or confluent white matter hyperintensities. Its relationship to cognition, however, remains unclear. To explore this, community-dwelling adults between the ages 55 and 80 years completed structural imaging, neuropsychological testing, and questionnaires to provide objective measures and subjective experience of executive functioning. Volumetric lesion burden derived from structural MRI identified those with significant white matter hyperintensity burden (∼10 cm3). Half of those recruited met this criterion and were designated as the cerebral small vessel disease (CSVD) group. Subjective cognitive complaints but not objective test scores differentiated adults with and without CSVD. Hierarchical clustering revealed 2 CSVD subgroups that differentiated those with impaired versus preserved executive function relative to controls. Overall these results provide some explanation for behavioral heterogeneity often observed in studies of age-related white matter changes. They also support the use of questionnaires to assess subjective cognitive complaints that may point to subtle effects of vascular pathology not evident on standardized cognitive scores.

Rates of Screening for Breast, Colorectal, and Cervical Cancers in Older People With Cognitive Impairment or Dementia: A Meta-Analysis.

Purpose: Cancer screening may not be appropriate for some older people. We compare the likelihood of screening for colorectal, breast, and cervical cancers in older people with versus without cognitive impairment or dementia. Method: Systematic search of MEDLINE, Embase, and PsycINFO (to March 9, 2018) for articles reporting screening for colon, breast, and cervical cancers in patients with and without cognitive impairment or dementia. Studies were summarized quantitatively (random effects meta-analysis), according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Studies reported data 1989-2008. The rate of screening for breast cancer by mammography was lower in women with cognitive impairment or dementia compared with those without (pooled odds ratio [OR] = 0.81, 95% confidence interval [CI] = [0.71, 0.91], p = .0007, six studies, N = 18,562). The rates of screening for cervical cancer by Pap smear (pooled OR = 0.88, 95% CI = [0.71, 1.08], p = 0.22, five studies, N = 409,131) and colorectal cancer by fecal occult blood test (pooled OR = 0.87, 95% CI = [0.55, 1.38], p = .55, two studies, N = 2,718) were not significantly lower in people with cognitive impairment or dementia. Conclusion: These historical rates provide a baseline for discussions around the need for more specific guidance to assist with decisions to discontinue screening. The study also identifies a gap in reported knowledge with respect to screening under current guidelines.

A randomized, observer-blinded, equivalence trial comparing two variations of Euvichol®, a bivalent killed whole-cell oral cholera vaccine, in healthy adults and children in the Philippines.

BACKGROUND: To contribute to the global demand for oral cholera vaccine (OCV), the production of Euvichol® was scaled up with elimination of thimerosal. To demonstrate the equivalence of the variations, a study was carried out in the Philippines. METHODS: Healthy male and female adults and children in Manila were randomized to receive two doses of Euvichol® two weeks apart from either the 100L (Comparator) or the 600L (Test) variation. Primary and secondary immunogenicity endpoints were respectively geometric mean titer (GMT) of vibriocidal antibodies (two weeks post second dose) and seroconversion rate (two weeks after each dose) against O1 Inaba, Ogawa, and O139 serogroups. The GMT of vibriocidal antibodies against O1 Inaba, Ogawa, and O139 two weeks post first dose was also measured. To show the equivalence of two variations of Euvichol®, the ratio of GMT and the difference of seroconversion rate between Test and Comparator vaccines were tested with equivalence margin of [0.5, 2.0] for GMT ratio and of 15% for seroconversion rate, respectively. Safety assessment included solicited reactogenicity within 6 days after each dose and unsolicited and serious adverse events. RESULTS: A total of 442 participants were enrolled. For the overall population, equivalence between Test and Comparator was demonstrated for vibriocidal antibody response against O1 Inaba and Ogawa serotypes and O139 serogroup in both modified intention-to-treat (mITT) and per protocol analysis, since the 95% confidence intervals (CI) of GMT to any serotypes were within the lower and upper boundary [0.5, 2.0]. Seroconversion rates after two doses also showed equivalence for O1 Inaba, Ogawa, and O139. The vaccine was safe and well tolerated, similarly between the two groups. CONCLUSION: The study results support the equivalence of the 600L Euvichol® to the 100L formulation in healthy children and adults. The 600L Euvichol® is safe and immunogenic in adults and children. ClinicalTrials.gov registration number: NCT02502331.

External modulation of the sustained attention network in traumatic brain injury.

OBJECTIVE: Traumatic brain injury (TBI) is associated with impairments in processing speed as well as higher-level cognitive functions that depend on distributed neural networks, such as regulating and sustaining attention. Although exogenous alerting cues have been shown to support patients in sustaining attentive, goal-directed behavior, the neural correlates of this rehabilitative effect are unclear. The purpose of this study was to explore the effects of moderate to severe TBI on activity and functional connectivity in the well-documented right-lateralized frontal-subcortical-parietal sustained attention network, and to assess the effects of alerting cues. METHOD: Using multivariate analysis of fMRI data, TBI patients and matched neurologically healthy (NH) comparison participants were scanned as they performed the Sustained Attention to Response Task (SART) in 60-s blocks, with or without exogenous cueing through brief auditory alerting tones. RESULTS: Results documented inefficient voluntary control of attention in the TBI patients, with reduced functional connectivity in the sustained attention network relative to NH participants. When alerting cues were present during the SART, however, functional connectivity increased and became comparable to activity patterns seen in the NH group. CONCLUSIONS: These findings provide novel evidence of a neural mechanism for the facilitatory effects of alerting cues on goal-directed behavior in patients with damaged attentional brain systems, and support their use in cognitive rehabilitation. (PsycINFO Database Record

Reactive perforating collagenosis: An important differential diagnosis in hemodialysis patients.

This is a case report of a 68-year-old hypertensive, diabetic woman who was on regular thrice weekly hemodialysis (HD). She presented with gradually worsening left lower limb pain and swelling. Clinical examination revealed significant edema over the left calf and ankle joint with significant calf tenderness. Extensive workup including magnetic resonance imaging of the lower limb and venous Doppler failed to show any significant abnormality. In view of developing papular lesions over the area, skin biopsy was performed, which finally confirmed reactive perforating collagenosis. This diagnosis ensured reassurance to the patient with halting of further extensive and probably expensive testing. Simple conservative management and symptomatic relief improved the pain over the next few days. This case report highlights the importance of keeping a wide differential for calf tenderness in diabetic HD patients and projects reactive perforating collagenosis as one of the important but frequently missed entities in such a scenario.

Antibody secreting B cells and plasma antibody response to rotavirus vaccination in infants from Kolkata India.

BACKGROUND: Assessing immune response after rotavirus vaccination consists in measuring serum or plasma IgA and IgG antibodies, but these assays provide very little information about the mucosal immune response. Thus the development of assays for detection of mucosal immune response following rotavirus vaccination is essential. We evaluate to assess circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immune responses to rotavirus vaccine. METHODS: 372 subjects, aged 6 weeks, were enrolled in the study. All the subjects were assigned to receive two doses of Rotarix® vaccine. Using a micro-modified whole blood-based ELISPOT assay, circulating rotavirus type-specific IgA- and IgG-ASCs, including gut homing ß7+ ASCs, were enumerated on week 6 before the first dose of Rotarix vaccination at 7 weeks of age and week 18 after the second vaccination at 17 weeks of age. Plasma samples collected before vaccination, and after two doses of Rotarix® vaccination were tested for plasma rotavirus IgA titers. RESULTS: Two doses of Rotarix® provided to induce sero-protective titer of ≥ 20 Units in 35% of subjects. Total blood IgA- ASC responses were detected in 26.4% of subjects who were non-responder before vaccination. Among responders, 47% of the subjects also have sero-protective plasma IgA titers. DISCUSSION: Our results suggest that virus-specific blood gut homing ASCs were detected and provide insight into mucosal immune response after rotavirus vaccination. Further studies are needed to evaluate the duration of such immune responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the rotavirus immunization program.

Characteristics and outcomes of Canadian MD/PhD program graduates: a cross-sectional survey.

BACKGROUND: Combined MD/PhD programs provide a structured path for physician-scientist training, but assessment of their success within Canada is limited by a lack of quantitative data. We collected outcomes data for graduates of Canadian MD/PhD programs. METHODS: We developed and implemented a Web-based survey consisting of 41 questions designed to collect outcomes data for Canadian MD/PhD program alumni from 8 Canadian universities who had graduated before September 2015. Respondents were categorized into 2 groups according to whether they had or had not completed all training. RESULTS: Of the 186 eligible alumni of MD/PhD programs, 139 (74.7%) completed the survey. A total of 136/138 respondents (98.6%) had completed or were currently completing residency training, and 66/80 (82%) had completed at least 1 postgraduate fellowship. Most (58 [83%]) of the 70 respondents who had completed all training were appointed as faculty at academic institutions, and 37 (53%) had been principal investigators on at least 1 recent funded project. Among the 58 respondents appointed at academic institutions, 44/57 (77%) dedicated at least 20% of their time to research, and 25/57 (44%) dedicated at least 50% to research. During their combined degree, 102/136 respondents (75.0%) published 3 or more first-author papers, and 133/136 (97.8%) matched with their first choice of specialty. The median length of physician-scientist training was 13.5 years. Most respondents graduated with debt despite having been supported by Canadian Institutes of Health Research MD/PhD studentships. INTERPRETATION: Most Canadian MD/PhD program alumni pursued careers consistent with their physician-scientist training, which indicates that these programs are meeting their primary objective. Nevertheless, our findings highlight that a minority of these positions are research intensive; this finding warrants further study. Our data provide a baseline for future monitoring of the output of Canadian MD/PhD programs.

Role of non-government organizations in engaging medical students in research.

The continued decline in medical trainees entering the workforce as clinician-scientists has elevated the need to engage medical students in research. While past studies have shown early exposure to generate interest among medical students for research and academic careers, financial constraints have limited the number of such formal research training programs. In light of recent government budget cuts to support research training for medical students, non-government organizations (NGOs) may play a progressively larger role in supporting the development of clinician-scientists. Since 2005, the Mach-Gaensslen Foundation has sponsored 621 Canadian medical student research projects, which represents the largest longitudinal data set of Canadian medical students engaged in research. We present the results of the pre- and post-research studentship questionnaires, program evaluation survey and the 5-year and 10-year follow-up questionnaires of past recipients. This paper provides insight into the role of NGOs as stakeholders in the training of clinician-scientists and evaluates the impact of such programs on the attitudes and career trajectory of medical students. While the problem of too few physicians entering academic and research-oriented careers continues to grow, alternative-funding strategies from NGOs may prove to be an effective approach in developing and maintaining medical student interest in research.