An Interactive Module to Teach Common Biostatistical Tests to Learners in the Health Professions.

Biostatistics are ubiquitous in medicine, providing quantitative insights into trials and experiments that shape the healthcare field. Despite training in evidence-based medicine, medical students and residents struggle to master biostatistical concepts and apply biostatistics to appraise research. There are limited resources available for students to quickly and cost-effectively learn biostatistical tests. From this problem, a two-part biostatistical educational module was created using Rise Articulate 360® software, an interactive module platform. The study aimed to assess the effectiveness of an educational biostatistics module's ability to improve learners' knowledge and application of commonly used biostatistical tests, as well as their confidence in biostatistics. Each part of the module contained five biostatistical test tutorials. Each biostatistical test was explained, as well as how the test was typically applied in healthcare. Knowledge acquisition, test application, and confidence regarding biostatistical tests were assessed using a pretest and a posttest. The module was completed by 33 first- and second-year medical students.  Knowledge acquisition improved from a mean of 2.41 to 3.53 (P <= 0.001). Participants expressed that the biostatistical educational module was easy to use and improved both their confidence and knowledge of specific biostatistical tests. Most students found that the biostatistical educational module applied to their future work. In summary, our module was successful in exposing learners in the health professions to commonly used biostatistical tests and tests' applications to the medical literature and their future research. Biostatistics is a pillar of medical research and education, and students' mastery of the concept will prove to be of longitudinal valuable, whether they pursue careers as clinicians and/or researchers.

Mini-Residencies to Improve Care for Women Veterans: A Decade of Re-Educating Veterans Health Administration Primary Care Providers.

Background: Many primary care providers (PCPs) in the Veterans Health Administration need updated clinical training in women's health. The objective was to design, implement, and evaluate a training program to increase participants' comfort with and provision of care to women Veterans, and foster practice changes in women's health care at their local institutions. Methods: The Women's Health Mini-Residency was developed as a multi-day training program, based on principles of adult learning, wherein knowledge gleaned through didactic presentations was solidified during small-group case study discussions and further enhanced by hands-on training and creation of a facility-specific action plan to improve women Veterans' care. Pre, post, and 6-month surveys assessed attendees' comfort with and provision of care to women. The 6-month survey also queried changes in practice, promulgation of program content, and action plan progress. Results: From 2008 to 2019, 2912 PCPs attended 26 programs. A total of 2423 (83.2%) completed pretraining and 2324 (79.3%) completed post-training surveys. The 6-month survey was sent to the 645 attendees from the first 14 programs; 297 (46.1%) responded. Comparison of pre-post responses indicated significant gains in comfort managing all 19 content areas. Six-month data showed some degradation, but comfort remained significantly improved from baseline. At 6 months, participants also reported increases in providing care to women, including performing more breast and pelvic examinations, dissemination of program content to colleagues, and progress on action plans. Conclusions: This interactive program appears to have been successful in improving PCPs' comfort in providing care for women Veterans and empowering them to implement institutional change.

Investigation of Ferrocene Linkers in ß-Substituted Porphyrins.

A series of ß-ferrocene-modified zinc porphyrins, with various electron-withdrawing units appended to the ferrocene, were synthesized, and their electronic properties were investigated. The ferrocene was able to be modified with the substituents, with its oxidation potential increased by up to 0.3 V, without significantly perturbing the porphyrin core. A small red-shift of the strongest absorption band (B band) occurred upon the addition of the electron-withdrawing substituents (270 cm-1), occurring alongside a broadening of the band. The singlet state is unaffected by the ferrocene substitution; however, the triplet state lifetimes are decreased by 10.4-10.6 µs from that of the unsubstituted ferrocene porphyrin (18.1 µs). Computational studies showed that the changes in the optical properties are due to a loss of degeneracy of the porphyrin lowest unoccupied molecular orbitals; this is supported by resonance Raman spectroscopy studies, which show different enhancement patterns when probing the high- and low-energy edges of the B band.

Electrofluidic control of bioactive molecule delivery into soft tissue models based on gelatin methacryloyl hydrogels using threads and surgical sutures.

The delivery of bioactive molecules (drugs) with control over spatial distribution remains a challenge. Herein, we demonstrate for the first time an electrofluidic approach to controlled delivery into soft tissue models based on gelatin methacryloyl (GelMA) hydrogels. This was achieved using a surgical suture, whereby transport of bioactive molecules, including drugs and proteins, was controlled by imposition of an electric field. Commonly employed surgical sutures or acrylic threads were integrated through the hydrogels to facilitate the directed introduction of bioactive species. The platform consisted of two reservoirs into which the ends of the thread were immersed. The anode and cathode were placed separately into each reservoir. The thread was taken from one reservoir to the other through the gel. When current was applied, biomolecules loaded onto the thread were directed into the gel. Under the same conditions, the rate of movement of the biomolecules along GelMA was dependent on the magnitude of the current. Using 5% GelMA and a current of 100 µA, 2 uL of fluorescein travelled through the hydrogel at a constant velocity of 7.17 ± 0.50 um/s and took less than 8 minutes to exit on the thread. Small molecules such as riboflavin migrated faster (5.99 ± 0.40 µm/s) than larger molecules such as dextran (2.26 ± 0.55 µm/s with 4 kDa) or BSA (0.33 ± 0.07 µm/s with 66.5 kDa). A number of commercial surgical sutures were tested and found to accommodate the controlled movement of biomolecules. Polyester, polyglactin 910, glycolide/lactide copolymer and polyglycolic acid braided sutures created adequate fluid connection between the electrodes and the hydrogel. With a view to application in skin inflammatory diseases and wound treatment, wound healing, slow and controlled delivery of dexamethasone 21-phosphate disodium salt (DSP), an anti-inflammatory prodrug, was achieved using medical surgicryl PGA absorbable suture. After 2 hours of electrical stimulation, still 81.1% of the drug loaded was encapsulated within the hydrogel.

When "Donor-Acceptor" Dyes Delocalize: A Spectroscopic and Computational Study of D-A Dyes Using "Michler's Base".

In this study, we show that the "Michler's base" motif can be combined in a donor-acceptor arrangement with a range of acceptor units (indandione, indandione with cyano substituents, barbituric acid, or rhodanine) to give photophysical properties that are dominated by delocalized excited states. By changing the acceptor unit and by altering the planarity of this system, it is possible to tune the low-energy absorption feature in terms of intensity from 23 000 to 67 000 M-1 cm-1 and energy between 500 and 700 nm. Resonance Raman spectroscopy and time-dependent density functional theory indicate that this absorption feature has two underlying transitions: a weaker charge-transfer transition around 500 nm and a strong mixed or delocalized transition between 550 and 700 nm. Generally, these compounds are not strongly emissive; however, dual emission is observed, and the relative intensity of the two states can be modulated by solvent polarity. The energy of these emissive states does not correlate with the Lippert-Mataga analysis in which the Stokes shift is related to the solvent polarity (Δf).

Development of rhamnose-rich hydrogels based on sulfated xylorhamno-uronic acid toward wound healing applications.

An array of biological properties is demonstrated in the category of extracts broadly known as ulvans, including antibacterial, anti-inflammatory and anti-coagulant activities. However, the development of this category in biomedical applications is limited due to high structural variability across species and a lack of consistent and scalable sources. In addition, the modification and formulation of these molecules is still in its infancy with regard to progressing to product development. Here, a sulfated and rhamnose-rich, xylorhamno-uronic acid (XRU) extract from the cell wall of a controlled source of cultivated Australian ulvacean macroalgae resembles mammalian connective glycosaminoglycans. It is therefore a strong candidate for applications in wound healing and tissue regeneration. This study targets the development of polysaccharide modification for fabrication of 3D scaffolds for skin cell (fibroblast) culture. The XRU extract is methacrylated and UV-crosslinked to produce hydrogels with tuneable mechanical properties. The hydrogels demonstrate high cell viability and support cell proliferation over 14 days, which are far more functional than comparable alginate gels. Importantly, an XRU-based bioink is developed for extrusion printing 3D constructs both with and without cell encapsulation. These results highlight the close to product potential of this rhamnose-rich XRU extract as a promising biomaterial toward wound healing. Future studies should be focused on in-depth in vitro characterizations to examine the role of the material in dermal extracellular matrix (ECM) secretion of 3D printed structures, and in vivo characterizations to assess its capacity in supporting wound healing.

Clostridium difficile Toxoid Vaccine Candidate Confers Broad Protection against a Range of Prevalent Circulating Strains in a Nonclinical Setting.

Clostridium difficile infection (CDI) is a leading cause of nosocomial and antibiotic-associated diarrhea. A vaccine, based on formalin-inactivated toxins A and B purified from anaerobic cultures of C. difficile strain VPI 10463 (toxinotype 0), has been in development for the prevention of symptomatic CDI. We evaluated the breadth of protection conferred by this C. difficile toxoid vaccine in cross-neutralization assessments using sera from vaccinated hamsters against a collection of 165 clinical isolates. Hamster antisera raised against the C. difficile toxoid vaccine neutralized the cytotoxic activity of culture supernatants from several toxinotype 0 strains and heterologous strains from 10 different toxinotypes. Further assessments performed with purified toxins confirmed that vaccine-elicited antibodies can neutralize both A and B toxins from a variety of toxinotypes. In the hamster challenge model, the vaccine conferred significant cross-protection against disease symptoms and death caused by heterologous C. difficile strains from the most common phylogenetic clades, including the most prevalent toxinotypes.

Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs.

HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine.

Readying the workforce: evaluation of VHA's comprehensive women's health primary care provider initiative.

BACKGROUND: Veterans Health Administration (VHA) primary care providers (PCPs) often see few women, making it challenging to maintain proficiency in women's health (WH). Therefore, VHA in 2010 established Designated WH Providers, who would maintain proficiency in comprehensive WH care and be preferentially assigned women patients. OBJECTIVE: To evaluate early implementation of this national policy. METHODS: At each VHA health care system (N=140), the Women Veterans Program Manager completed a Fiscal Year 2012 workforce capacity assessment (response rate, 100%), representing the first time the national Designated WH Provider workforce had been identified. Assessment data were linked to administrative data. RESULTS: Of all VHA PCPs, 23% were Designated WH Providers; 100% of health care systems and 83% of community clinics had at least 1 Designated WH Provider. On average, women veterans comprised 19% (SD=27%) of the patients Designated WH Providers saw in primary care, versus 5% (SD=7%) for Other PCPs (P<0.001). For women veterans using primary care (N=313,033), new patients were less likely to see a Designated WH Provider than established women veteran patients (52% vs. 64%; P<0.001). CONCLUSIONS: VHA has achieved its goal of a Designated WH Provider in every health care system, and is approaching its goal of a Designated WH Provider at every hospital/community clinic. Designated WH Providers see more women than do Other PCPs. However, as the volume of women patients remains low for many providers, attention to alternative approaches to maintaining proficiency may prove necessary, and barriers to assigning new women patients to Designated WH Providers merit attention.

Reproductive health diagnoses of women veterans using department of Veterans Affairs health care.

BACKGROUND: Little is known regarding the reproductive health needs of women Veterans using Department of Veterans Affairs (VA) health care. OBJECTIVE: To describe the reproductive health diagnoses of women Veterans using VA health care, how these diagnoses differ across age groups, and variations in sociodemographic and clinical characteristics by presence of reproductive health diagnoses. RESEARCH DESIGN: This study is a cross-sectional analysis of VA administrative and clinical data. SUBJECTS: The study included women Veterans using VA health care in FY10. MEASURES: Reproductive health diagnoses were identified through presence of International Classification of Disease, 9th Revision (ICD-9) codes in VA clinical and administrative records. The prevalence of specific diagnosis categories were examined by age group (18-44, 45-64, ≥65 y) and the most frequent diagnoses for each age group were identified. Sociodemographic and clinical characteristics were compared by presence of at least 1 reproductive health diagnosis. RESULTS: The most frequent reproductive health diagnoses were menstrual disorders and endometriosis among those aged 18-44 years (n=16,658, 13%), menopausal disorders among those aged 45-64 years (n=20,707, 15%), and osteoporosis among those aged ≥65 years (n=8365, 22%). Compared with women without reproductive health diagnoses, those with such diagnoses were more likely to have concomitant mental health (46% vs. 37%, P<0.001) and medical conditions (75% vs. 63%, P<0.001). CONCLUSIONS: Women Veterans using VA health care have diverse reproductive health diagnoses. The high prevalence of comorbid medical and mental health conditions among women Veterans with reproductive health diagnoses highlights the importance of integrating reproductive health expertise into all areas of VA health care, including primary, mental health, and specialty care.

A simple and versatile method for microencapsulation of anti-epileptic drugs for focal therapy of epilepsy.

Nearly 30% of epilepsy cases cannot be adequately controlled with current medical treatments. The reasons for this are still not well understood, but there is a significant body of evidence pointing to the blood-brain barrier. Resective surgery can provide an alternative method of epilepsy control; however this treatment option is not suitable for most epilepsy sufferers. Local drug delivery through micro-injection to or implantation into the brain provides an innovative approach to bypass the blood-brain barrier for epilepsy treatment. In order to develop effective local delivery systems for anti-epilepsy drug (AED), we have prepared a variety of core-shell microcapsules via electrojetting, where a more hydrophobic polymer shell acts as a physical barrier to control the rate of drug release from the drug-loaded polymeric core. The resulting microcapsules demonstrate highly drug encapsulation efficiency, narrow size distribution and uniform morphology. Moreover, the release rate of AED can be modulated by controlling the morphologies of the core-shell microcapsules.

Improving trends in gender disparities in the Department of Veterans Affairs: 2008-2013.

Increasing numbers of women veterans using Department of Veterans Affairs (VA) services has contributed to the need for equitable, high-quality care for women. The VA has evaluated performance measure data by gender since 2006. In 2008, the VA launched a 5-year women's health redesign, and, in 2011, gender disparity improvement was included on leadership performance plans. We examined data from VA Office of Analytics and Business Intelligence quarterly gender reports for trends in gender disparities in gender-neutral performance measures from 2008 to 2013. Through reporting of data by gender, leadership involvement, electronic reminders, and population management dashboards, VA has seen a decreasing trend in gender inequities on most Health Effectiveness Data and Information Set performance measures.

Delivery of gender-sensitive comprehensive primary care to women veterans: implications for VA Patient Aligned Care Teams.

The Veterans Health Administration (VA) has undertaken a major initiative to transform primary care delivery through implementation of Patient Aligned Care Teams (PACTs). Based on the patient-centered medical home concept, PACTs aim to improve access, continuity, coordination, and comprehensiveness using team-based care that is patient driven and patient centered. However, how PACT principles should be applied to meet the needs of special populations, including women veterans, is not entirely clear. While historical differences in military participation meant women veterans were rarely seen in VA healthcare settings, they now represent the fastest growing segment of new VA users. They also have complex healthcare needs, adding gender-specific services and other needs to the spectrum of services that the VA must deliver. These trends are changing the VA landscape, introducing challenges to how VA care is organized, how VA providers need to be trained, and how VA considers implementation of new initiatives, such as PACT. We briefly describe the evolution of VA primary care delivery for women veterans, review VA policy for delivering gender-sensitive comprehensive primary care for women, and discuss the challenges that women veterans' needs pose in the context of PACT implementation. We conclude with recommendations for addressing some of these challenges moving forward.

Students delivering health care to a vulnerable Appalachian population through interprofessional service-learning.

Interprofessional student service-learning experiences are integrated into the preventive care of older adult residents of public housing in Appalachia. Receiving a Health Resources and Services Administration grant provided the College of Nursing at East Tennessee State University the opportunity to expand interprofessional clinical experiences for students by partnering with the College of Pharmacy, the College of Clinical & Rehabilitative Health Sciences, and the local public housing authority. Select faculty from each college met and developed a plan to form student teams from all three colleges to conduct in-home comprehensive medical and nutrition assessments and medication chart reviews of high-risk older adults. Following the in-home visit, students and faculty discuss the assessment findings at planned interprofessional meetings. Students present their findings from each discipline's perspective and collaboratively set health priorities and develop intervention strategies and an inclusive follow-up plan. Excerpts from students' reflective narratives discussing the impact of the interprofessional service-learning experiences are shared.

Psammaplysin derivatives from the Balinese marine sponge Aplysinella strongylata.

Twenty-one new psammaplysin derivatives (4-24) exhibiting a variety of side chains, as well as six previously known psammaplysins, were identified from the Indonesian marine sponge Aplysinella strongylata. The double bond on the side chain of the fatty acid-containing psammaplysins was located by GC-MS analysis of the fatty acid methyl esters and their pyrrolidide derivatives. HPLC and Mosher ester studies confirmed that the isolated metabolites possessing a 19-OH substituent were mixtures of diastereomers. Selected compounds (4, 5, 7, 8, 12, 18, and 22) were screened for in vitro activity against chloroquine-sensitive (3D7) P. falciparum malaria parasites. Of the new psammaplysins, 19-hydroxypsammaplysin E (4) showed the best antimalarial activity, with an IC(50) value of 6.4 µM.

Enzyme-substrate complementarity governs access to a cationic reaction manifold in the P450(BM3)-catalysed oxidation of cyclopropyl fatty acids.

The products of cytochrome P450(BM3)-catalysed oxidation of cyclopropyl-containing dodecanoic acids are consistent with the presence of a cationic reaction intermediate, which results in efficient dehydrogenation of the rearranged probes by the enzyme. These results highlight the importance of enzyme-substrate complementarity, with a cationic intermediate occurring only when the probes used begin to diverge from ideal substrates for this enzyme. This also aids in reconciling literature reports supporting the presence of cationic intermediates with certain cytochrome P450 enzyme/substrate pairs.

Immunogenicity and efficacy of intramuscular replication-defective and subunit vaccines against herpes simplex virus type 2 in the mouse genital model.

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted virus that is highly prevalent worldwide, causing a range of symptoms that result in significant healthcare costs and human suffering. ACAM529 is a replication-defective vaccine candidate prepared by growing the previously described dl5-29 on a cell line appropriate for GMP manufacturing. This vaccine, when administered subcutaneously, was previously shown to protect mice from a lethal vaginal HSV-2 challenge and to afford better protection than adjuvanted glycoprotein D (gD) in guinea pigs. Here we show that ACAM529 given via the intramuscular route affords significantly greater immunogenicity and protection in comparison with subcutaneous administration in the mouse vaginal HSV-2 challenge model. Further, we describe a side-by-side comparison of intramuscular ACAM529 with a gD vaccine across a range of challenge virus doses. While differences in protection against death are not significant, ACAM529 protects significantly better against mucosal infection, reducing peak challenge virus shedding at the highest challenge dose by over 500-fold versus 5-fold for gD. Over 27% (11/40) of ACAM529-immunized animals were protected from viral shedding while 2.5% (1/40) were protected by the gD vaccine. Similarly, 35% (7/20) of mice vaccinated with ACAM529 were protected from infection of their dorsal root ganglia while none of the gD-vaccinated mice were protected. These results indicate that measuring infection of the vaginal mucosa and of dorsal root ganglia over a range of challenge doses is more sensitive than evaluating survival at a single challenge dose as a means of directly comparing vaccine efficacy in the mouse vaginal challenge model. The data also support further investigation of ACAM529 for prophylaxis in human subjects.