Biological significance of C-reactive protein, the ancient acute phase functionary.

C-reactive protein (CRP) is one of the major members of the family of acute phase proteins (APP). Interest in this CRP was the result of a seminal discovery of its pattern of response to pneumococcal infection in humans. CRP has the unique property of reacting with phosphocholine-containing substances, such as pneumococcal C-polysaccharide, in the presence of Ca2+. The attention regarding the origin of CRP and its multifunctionality has gripped researchers for several decades. The reason can be traced to the integrated evolution of CRP in the animal kingdom. CRP has been unequivocally listed as a key indicator of infectious and inflammatory diseases including autoimmune diseases. The first occurrence of CRP in the evolutionary ladder appeared in arthropods followed by molluscs and much later in the chordates. The biological significance of CRP has been established in the animal kingdom starting from invertebrates. Interestingly, the site of synthesis of CRP is mainly the liver in vertebrates, while in invertebrates it is located in diverse tissues. CRP is a multifunctional player in the scenario of innate immunity. CRP acts as an opsonin in the area of complement activation and phagocytosis. Interestingly, CRP upregulates and downregulates both cytokine production and chemotaxis. Considering various studies of CRP in humans and non-human animals, it has been logically proposed that CRP plays a common role in animals. CRP also interacts with Fcγ receptors and triggers the inflammatory response of macrophages. CRP in other animals such as primates, fish, echinoderms, arthropods, and molluscs has also been studied in some detail which establishes the evolutionary significance of CRP. In mammals, the increase in CRP levels is an induced response to inflammation or trauma; interestingly, in arthropods and molluscs, CRP is constitutively expressed and represents a major component of their hemolymph. Investigations into the primary structure of CRP from various species revealed the overall relatedness between vertebrate and invertebrate CRP. Invertebrates lack an acquired immune response; they are therefore dependent on the multifunctional role of CRP leading to the evolutionary success of the invertebrate phyla.

Minimizing fall-related injuries in at-risk older adults: The falling safely training (FAST) study protocol.

Background: Falls are the leading cause of accidental injury among the elderly. Fall prevention is currently the main strategy to minimize fall-related injuries in at-risk older adults. However, the success of fall prevention programs in preventing accidental injury in elderly populations is inconsistent. An alternative novel approach to directly target fall-related injuries is teaching older adults movement patterns which reduce injury risk. The purpose of the current study will be to explore the feasibility and preliminary efficacy of teaching at-risk older adults safe-falling strategies to minimize the risk of injury. Methods/design: The Falling Safely Training (FAST) study will be a prospective, single-blinded randomized controlled trial. A total of 28 participants will be randomly assigned to four weeks of FAST or to an active control group with a 1:1 allocation. People aged ≥65 years, at-risk of injurious falls, and with normal hip bone density will be eligible. The FAST program will consist of a standardized progressive training of safe-falling movement strategies. The control group will consist of evidence-based balance training (modified Otago exercise program). Participants will undergo a series of experimentally induced falls in a laboratory setting at baseline, after the 4-week intervention, and three months after the intervention. Data on head and hip movement during the falls will be collected through motion capture. Discussion: The current study will provide data on the feasibility and preliminary efficacy of safe-falling training as a strategy to reduce fall impact and head motion, and potentially to reduce hip and head injuries in at-risk populations. Registration: The FAST study is registered at http://Clinicaltrials.gov (NCT05260034).

Correlation between visuo-cognitive tests and simulator performance of commercial drivers in the United States.

BACKGROUND: Driving commercial vehicles requires intact visuo-cognitive skills. Approximately 13% of all fatal motor vehicle crashes in the United States involve commercial drivers. The ability to accurately predict risk factors for unsafe commercial driving is essential for public safety. Accurate prediction tools will advance the field of commercial driver science, provide policy guidance for driver testing and assist healthcare providers during testing. Prior studies have correlated clinical tools to roadway safety; translating these results to commercial drivers has not yet been done. OBJECTIVE: This study aimed to identify specific demographic, driving history and visuo-cognitive test results that correlate with driving simulator performance. Using the Cumulative Simulator Score (CSS) as a surrogate for driving ability, the objective was to correlate both sets of data (self-reported and visuo-cognitive testing) with the CSS to identify screening tools for unsafe driving in commercial drivers. PRINCIPAL RESULTS: Baseline assessments of 120 variables were collected from October 2020 to January 2022. Of the 31 participants, 3 were female and 28 were male with a mean age of 53 years. Average BMI was 32, blood pressure 136/84, 32 years of CDL driving experience, 36,500 annual CDL mileage, 11,000 annual personal mileage, 14 years of education, average number of medications: 2, average number of medical conditions: 2, six participants with personal and/or commercial crashes or tickets in past five years, MOCA 27/30, Trails B time 66 s, UFOV Speed of Processing 15 ms, Stroke Disease Severity Assessment pass rate 94 %. The Cumulative Simulator Score (CSS), correlated significantly with education (r = 0.42; p = 0.02), commercial driving experience (r = 0.42; 0 = 0.02), and number of tickets as a commercial driver (Spearman rho = 0.40; p = 0.02). In a stepwise multivariable linear regression analysis, the number of tickets as a CDL driver in the past five years and years of education were retained as significant variables in the multivariable linear regression model, explaining 38 % of the variance of total scores on the CSS. MAJOR CONCLUSIONS: Descriptive and self-reported driving characteristics correlate better with the Cumulative Simulator Score in CDL drivers than visuo-cognitive tests. Since simulator performance has been shown to be a reliable surrogate for driving performance, the number of tickets as a CDL driver in the past five years and years of education can be considered as additions to annual physicals for policy makers and health care providers to help assess their on-the-road safety.

The SPEER: An interprofessional team behavior rubric to optimize geriatric clinical care.

Geriatric patients with complex health care needs can benefit from interprofessional (IP) care; however, a major gap in health professional education is determining how to prepare future providers for IP collaboration. Effective IP team behavior assessment tools are needed to teach, implement, and evaluate IP practice skills. After review of IP evaluation tools, the Standardized Patient Encounter Evaluation Rubric (SPEER) was created to evaluate team dynamics in IP practice sites.Independent sample t-tests between faculty and learner SPEER scores showed learners scored themselves 15 points higher than their faculty scores (p < .001). Cronbach's α showed high internal consistency (α = 0.91). Paired t-tests found that learners identified improvements in the team's ability to address the patient's education needs and to allow the patients to voice their expectations. Faculty identified improvements in the teams' ability to make recommendations. Faculty evaluations of learner teams showed improvements in raw ratings on all but two items. Qualitative data analysis for emergent themes showed learners desired team functioning feedback and how teamwork could improve to provide optimal IP care.In conclusion, the SPEER can help faculty and learners identify growth in their teams' ability to perform key IP skills in clinical sites.

Eco-bioengineering tools in ecohydrological assessment of eutrophic water bodies.

Eutrophication of water bodies and deterioration of water quality are emerging environmental crises. The root causes and consequences of eutrophication are multidirectional. Thus, they provide a huge scope of risk-analysis and risk-assessment in the domain of remediation studies. However, recent restoration studies reveal a global trend of utilizing traditional restoration methods combined with advanced pioneer innovative techniques developed in the field of science and technology. This review introduces a novel approach to consider ecohydrological assessment of eutrophication by classical biomanipulation practices emphasising on their evolution into innovative 'eco-bioengineering' methods. The main objective of this study is to critically analyse and recognize the research gaps in classical biomanipulation and appreciate the reproducibility and efficacy of eco-bioengineering methods at micro- and macrolevel aquatic ecosystems. Comprehensive literature review was conducted on offline and online platforms. Our survey revealed (a) continuation of a historical trend in classical biomanipulation practices (61.64%) and (b) an ascending drift in eco-bioengineering research (38.36%) in the last decade (2010-2021). At a global scale, recent biomanipulation research has a skewed distribution in Europe (41.10%), East Asia (32.88%), North America (10.96%), South Africa (4.11%), South America (2.74%), Middle East (1.37%), Oceania (1.37%), and non-specific regions (5.48%). Finally, this review analysis revealed the comprehensiveness of eco-bioengineering methods and their strong ecological resilience to recurrence of eutrophication and fluctuating environmental flows in the future. Therefore, our review reinforces the supremacy of eco-bioengineering methods as cost-effective green technologies providing sustainable solutions to restore the eutrophic waters at a global scale.

Novel model to teach health care delivery in geriatrics.

Introducing health policy to interprofessional graduate students, anchoring health policy to older adult health needs, while conveying how current policy issues will affect their individual careers is challenging, yet essential, for health profession education. This novel program integrated graduate level health profession learners from medicine, nurse practitioner, pharmacy, psychology, social work, physical therapy and occupational therapy disciplines. The aim was to embed health policy into an existing interprofessional (IP) geriatrics course at an academic medical center. Selection of disciplines was based on prior collaborative work and faculty interest. The objectives were to 1. Introduce current health policies that affect older adults; 2. Understand the effects of health policy and social determinants of health on the older adults in their future practice; 3. Challenge learners to apply their knowledge and develop health advocacy strategies for older adults; and 4) Teach the importance of teamwork in interprofessional practice within a geriatric population.The health policy curriculum impacted 487 learners for 12 sessions over three years. Four themes emerged with the sessions: health policy awareness, interprofessional appreciation, patient care "pearls," and pharmacological considerations in geriatrics. Each of the eight modules generated thoughtful recommendations by the learners, providing a glimpse into future workforce priorities.

Advances in targeting the WNT/ß-catenin signaling pathway in cancer.

WNT/ß-catenin signaling orchestrates various physiological processes, including embryonic development, growth, tissue homeostasis, and regeneration. Abnormal WNT/ß-catenin signaling is associated with various cancers and its inhibition has shown effective antitumor responses. In this review, we discuss the pathway, potential targets for the development of WNT/ß-catenin inhibitors, available inhibitors, and their specific molecular interactions with the target proteins. We also discuss inhibitors that are in clinical trials and describe potential new avenues for therapeutically targeting the WNT/ß-catenin pathway. Furthermore, we introduce emerging strategies, including artificial intelligence (AI)-assisted tools and technology-based actionable approaches, to translate WNT/ß-catenin inhibitors to the clinic for cancer therapy.

Preparing a healthcare workforce for geriatrics care: an Interprofessional team based learning program.

BACKGROUND: Improving the care of older adults in our healthcare system involves teams working together. As the geriatrics population rises globally, health science learners need to be prepared to work collaboratively to recognize and treat common conditions in geriatrics. To enable workforce preparation, the Institute of Medicine and the National League for Nursing emphasize the need to implement interprofessional active learning activities for undergraduate healthcare learners at academic medical centers. METHODS: The Geriatrics Champions Program was a team-based learning activity created to meet this task. It was a 24-month program, repeated twice, that impacted 768 learners and 151 faculty from medicine, occupational therapy, physical therapy, nursing, social welfare, psychology, pharmacy and dietetics. Each class was intentionally divided into 20 interprofessional teams that met four times annually. Each session focused on one geriatrics domain. The objectives were centered around the specific geriatrics competencies for each health profession, divided into the eight domains written in the "American Geriatrics Society IM-FM Residency Competencies". Evaluation consisted of individual and team Readiness Assessment Tests (iRAT and tRAT). Surveys were also used to collect feedback using a Likert scale. Wilcoxon signed rank tests were used to compare iRAT and tRAT scores. Other analyses identified characteristics associated with tRAT performance group (Unpaired t-tests) and tRAT performance on the raw scale (Pearson correlation). Paired t-tests using a 7-level Likert Scale measured pre-post change in learner knowledge. RESULTS: Student tRAT scores were 30% higher than iRAT scores (p < 0.001). Teams were more likely to score 100% on the initial tRAT attempt if more team members attended the current session (p < 0.001), more health professions were represented by team members in attendance (p = 0.053), and the team had a better track record of past attendance (p < 0.01). In the post-program evaluation, learners felt this program was helpful for their career preparation in interprofessional geriatrics care. CONCLUSIONS: Learners understood that teams performed better than individuals in the care of older adults. Feedback from the learners and faculty was consistently positive and learners felt better prepared for geriatrics care. The program's benefits may extend beyond individual sessions.

Bacopasaponins with cytotoxic activity against human breast cancer cells in vitro.

Globally, breast cancer is a serious concern that exhibits a persistent rise in its incidence and related mortality even after significant advancement in the field of cancer research. To find an alternative cure for the disease from natural resources we selected Bacopa monniera, a perennial ethnomedicinal plant popularly used for boosting memory and mental health. We isolated four different types of dammarane saponins, namely bacopasaponins C-F (1-4) from the plant and evaluated their toxic effects on two different types of human breast cancer cell lines-a hormone-responsive MCF7 and a triple-negative MDA-MB-231. Interestingly, MTT assay revealed a dose-dependent toxic effect of all four types of bacopasaponins on both of these cell lines, 4 being the most effective with 48 h-inhibitory concentration (IC50) of 32.44 and 30 µM in MCF7 and MDA-MB-231 respectively. Further, 4 caused significant alterations in normal cytomorphology and induction of apoptosis in both of these cell lines after 48 h of treatment. No caspase-8 activity was detected in these cell lines when exposed to 4 for 2, 24, and 48 h; instead, Western blotting analysis confirmed involvement of either caspase-9 (MCF7) or both caspase-9 and caspase-3 (MDA-MB-231) in the process of apoptosis indicating the occurrence of intrinsic mode. Additionally, at comparable effective doses to cancer, bacopasaponins showed much less toxicity in normal human peripheral blood lymphocytes (≥ 85% cell survival). Overall, the findings project bacopasaponin F, a natural constituent of Bacopa monniera, as an efficient and safer alternative for breast cancer therapeutics.

Vector-free in vivo trans-determination of adult hepatic stem cells to insulin-producing cells.

A reduction in the number of functional ß-cells is the central pathological event in diabetes. Liver and ventral pancreas differentiates simultaneously in the same general domain of cells within embryonic endoderm. In addition, the precursor cell population being bi-potential may be targeted for either pancreas or liver development. Hepatic stem cells were redirected in vivo to functional insulin producing cells in a acetylaminofluorene-partial hepatectomy (AAF/PH) adult male rat model with/without GLP-1 treatment. In routine H&E histology and immunohistochemistry, stem cells resembled ß cells in GLP-1 injected rats. Immunoblots revealed involvement of adenylate cyclase, TLR4 and PDX1 in insulin synthesis. Expression of genes (GLP-1R, MAFA, PDX1, INS1 and INS2) augmented in the GLP-1 treated regenerated liver. Results strongly indicated the key role of GLP-1 in the induction of insulin secretion in trans-determined reprogrammed cell in vivo. The present method being vector free poses no risk of vector spillover in the host and holds promise.

Bhagavad Gita for the Physician.

This communication presents verses from the Bhagavad Gita which help define a good clinician's skills and behavior. Using the teachings of Lord Krishna, these curated verses suggest three essential skills that a physician must possess: Excellent knowledge, equanimity, and emotional attributes. Three good behaviors are listed (Pro-work ethics, Patient-centered care, and Preceptive leadership) and supported by thoughts written in the Gita.

Mentha arvensis (Linn.)-mediated green silver nanoparticles trigger caspase 9-dependent cell death in MCF7 and MDA-MB-231 cells.

INTRODUCTION: Leaf extract of Mentha arvensis or mint plant was used as reducing agent for the synthesis of green silver nanoparticles (GSNPs) as a cost-effective, eco-friendly process compared to that of chemical synthesis. The existence of nanoparticles was characterized by ultraviolet-visible spectrophotometry, dynamic light scattering, Fourier transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray analysis, atomic-force microscopy and transmission electron microscopy analyses, which ascertained the formation of spherical GSNPs with a size range of 3-9 nm. Anticancer activities against breast cancer cell lines (MCF7 and MDA-MB-231) were studied and compared with those of chemically synthesized (sodium borohydride [NaBH4]-mediated) silver nanoparticles (CSNPs). MATERIALS AND METHODS: Cell survival of nanoparticle-treated and untreated cells was studied by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Cell-cycle analyses were carried out using fluorescence-activated cell sorting. Cell morphology was observed by fluorescence microscopy. Expression patterns of PARP1, P53, P21, Bcl2, Bax and cleaved caspase 9 as well as caspase 3 proteins in treated and untreated MCF7 and MDA-MB-231 cells were studied by Western blot method. RESULTS: MTT assay results showed that Mentha arvensis-mediated GSNPs exhibited significant cytotoxicity toward breast cancer cells (MCF7 and MDA-MB-231), which were at par with that of CSNPs. Cell cycle analyses of MCF7 cells revealed a significant increase in sub-G1 cell population, indicating cytotoxicity of GSNPs. On the other hand, human peripheral blood lymphocytes showed significantly less cytotoxicity compared with MCF7 and MDA-MB-231 cells when treated with the same dose. Expression patterns of proteins suggested that GSNPs triggered caspase 9-dependent cell death in both cell lines. The Ames test showed that GSNPs were nonmutagenic in nature. CONCLUSION: GSNPs synthesized using Mentha arvensis may be considered as a promising anticancer agent in breast cancer therapy. They are less toxic and nonmutagenic and mediate caspase 9-dependent apoptosis in MCF7 and MDA-MB-231 cells.

Differential modulation of cellular antioxidant status in zebrafish liver and kidney exposed to low dose arsenic trioxide.

Zebrafish were exposed to a nonlethal dose (1/350LC50; 50µg/L) of As2O3 and sampled at 7, 15, 30, 60 and 90 days of treatment. The oxidative stress response was assessed in terms of time-dependent histopathological changes, lipid peroxidation, GSH status, activities of detoxification enzymes and expression of antioxidant genes in liver and kidney. As2O3 treatment enhanced lipid peroxidation except at day 90 in liver and day 30 in kidney. Glutathione depleted significantly in the liver except on day 30; whereas in kidney, it increased initially but thereafter depleted significantly. The liver GST activity was high until day 30, low on day 60 and high on day 90. On the other hand, activity of GST in kidney remained high throughout the exposure. GR activity in liver decreased initially but augmented from 30 days onwards whereas in kidney it remained high until 30 days of exposure. Significant increase in GPx and CAT activities in liver and kidney confirmed oxidative stress in zebrafish which correlated with mRNA expression of antioxidant genes. Upregulation in mRNA level of Cu-Zn Sod in liver and kidney was prominent. Gpx1 upregulation was more conspicuous in kidney as compared to liver while the pattern of Cat expression was almost similar in both the organs. Among the mitochondrial genes, expression of Cox1 was significantly high only after 90 days in liver, while in kidney it enhanced at 7, 30 and 60 days of arsenic exposure. Ucp2 was upregulated in liver after 15 days of exposure but significantly downregulated at day 90; in kidney it remained unchanged at other time points except at day 90. An overall increased expression of Bcl2 further confirmed As2O3 induced oxidative stress in zebrafish liver and kidney. The pattern of mRNA expression of Nrf2 was not uniform and was in accordance to its downstream antioxidant genes. Present findings elucidate that low dose of As2O3 exposure induces a time dependent differential modulation of antioxidant status in liver and kidney of zebrafish in a tissue-specific manner.

Late-Onset Hypogonadism and Testosterone Replacement in Older Men.

Late-onset hypogonadism is an underdiagnosed and easily treated condition defined by low serum testosterone levels in men older than 65 years. When treated, a significant improvement in quality of life may be reached in this rapidly rising sector of the population. During the evaluation, laboratory tests and a full medication review should be performed to exclude other illnesses or adverse effects from medications. The major goal of treatment in this population is treating the symptoms related to hypogonadism. There has not been clear evidence supporting universally giving older men with low serum testosterone levels and hypogonadal symptoms testosterone replacement therapy.

Differential in vivo genotoxicity of arsenic trioxide in glutathione depleted mouse bone marrow cells: expressions of Nrf2/Keap1/P62.

Generation of reactive oxygen species is one of the major contributors in arsenic-induced genotoxicity where reduced glutathione (GSH) could be an important determining factor. To understand the role of endogenous GSH, arsenic trioxide (As2O3) was administered in buthionine sulfoximine (BSO)- and N-acetyl-L-cysteine (NAC)-treated mice. As2O3-induced significant chromosome aberrations (CAs) in all treatment groups compared with the control. BSO-treated mouse bone marrow cells showed significant CAs at a dose of 2 mg As2O3 kg(-1) b.w. Similar induction was not evident at 4 mg As2O3 kg(-1) b.w. and exhibited antagonistic effect at 8 mg As2O3 kg(-1) b.w. To understand this differential effect, expression pattern of Nrf2 was observed. Nrf2 expression increased following As2O3 treatment in a dose-dependent manner up to 4 mg As2O3 kg(-1) b.w after which no further increase was noticed. NAC pre-treatment significantly reduced the extent of As2O3-induced CAs suggesting the protective role of endogenous GSH against arsenic-induced genotoxicity.

Toxic metals and autophagy.

The earth's resources are finite, and it can no longer be considered a source of inexhaustible bounty for the human population. However, this realization has not been able to contain the human desire for rapid industrialization. The collateral to overusing environmental resources is the high-level contamination of undesirable toxic metals, leading to bioaccumulation and cellular damage. Cytopathological features of biological systems represent a key variable in several diseases. A review of the literature revealed that autophagy (PCDII), a high-capacity process, may consist of selective elimination of vital organelles and/or proteins that intiate mechanisms of cytoprotection and homeostasis in different biological systems under normal physiological and stress conditions. However, the biological system does survive under various environmental stressors. Currently, there is no consensus that specifies a particular response as being a dependable biomarker of toxicology. Autophagy has been recorded as the initial response of a cell to a toxic metal in a concentration- and time-dependent manner. Various signaling pathways are triggered through cellular proteins and/or protein kinases that can lead to autophagy, apoptosis (or necroptosis), and necrosis. Although the role of autophagy in tumorigenesis is associated with promoting tumor cell survival and/or acting as a tumor suppressive mechanism, PCDII in metal-induced toxicity has not been extensively studied. The aim of this review is to analyze the comparative cytotoxicity of metals/metalloids and nanoparticles (As, Cd, Cr, Hg, Fe, and metal-NP) in cells enduring autophagy. It is noted that metals/metalloids and nanoparticles prefer ATG8/LC3 as a potent inducer of autophagy in several cell lines or animal cells. MAP kinases, death protein kinases, PI3K, AKT, mTOR, and AMP kinase have been found to be the major components of autophagy induction or inhibition in the context of cellular responses to metals/metalloids and nanoparticles.

Anti-bacterial activity of Achatina CRP and its mechanism of action.

The physiological role of C-reactive protein (CRP), the classical acute-phase protein, is not well documented, despite many reports on biological effects of CRP in vitro and in model systems in vivo. It has been suggested that CRP protects mice against lethal toxicity of bacterial infections by implementing immunological responses. In Achatina fulica CRP is a constitutive multifunctional protein in haemolymph and considered responsible for their survival in the environment for millions of years. The efficacy of Achatina CRP (ACRP) was tested against both Salmonella typhimurium and Bacillus subtilis infections in mice where endogenous CRP level is negligible even after inflammatory stimulus. Further, growth curves of the bacteria revealed that ACRP (50 microg/mL) is bacteriostatic against gram negative salmonellae and bactericidal against gram positive bacilli. ACRP induced energy crises in bacterial cells, inhibited key carbohydrate metabolic enzymes such as phosphofructokinase in glycolysis, isocitrate dehydrogenase in TCA cycle, isocitrate lyase in glyoxylate cycle and fructose-1,6-bisphosphatase in gluconeogenesis. ACRP disturbed the homeostasis of cellular redox potential as well as reduced glutathione status, which is accompanied by an enhanced rate of lipid peroxidation. Annexin V-Cy3/CFDA dual staining clearly showed ACRP induced apoptosis-like death in bacterial cell population. Moreover, immunoblot analyses also indicated apoptosis-like death in ACRP treated bacterial cells, where activation of poly (ADP-ribose) polymerase-1 (PARP) and caspase-3 was noteworthy. It is concluded that metabolic impairment by ACRP in bacterial cells is primarily due to generation of reactive oxygen species and ACRP induced anti-bacterial effect is mediated by metabolic impairment leading to apoptosis-like death in bacterial cells.

Low dose of arsenic trioxide triggers oxidative stress in zebrafish brain: expression of antioxidant genes.

Occurrence of arsenic in the aquatic environment of West Bengal (India), Bangladesh and other countries are of immediate environmental concern. In the present study, zebrafish (Danio rerio) was used as a model to investigate oxidative stress related enzyme activities and expression of antioxidant genes in the brain to 50µg/L arsenic trioxide for 90 days. In treated fish, generation of reactive oxygen species (ROS), malondialdehyde (MDA) and conjugated diene (CD) showed a triphasic response attaining a peak at the end of the exposure. In addition, a gradual increase in GSH level was noted until 60 days and at 90 days, a sudden fall was recorded which heightened arsenic toxicity. However, GSH level does not correlate well with the glutathione reductase (GR) activity. Generation of ROS in zebrafish brain due to As2O3 exposure was further evidenced by significant alteration of glutathione peroxidase (GPx) and catalase (CAT) activity, which converts H2O2 to water and helps in detoxication. Moreover, enhanced mRNA level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in As2O3 exposed zebrafish indicates a protective role of Nrf2. kelch-like ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, inversely correlates with the mRNA expression of Nrf2. As2O3 induced toxicity was also validated by the alteration in NRF2 and NRF2 dependent expression of proteins such as heme oxygenase1 (HO1) and NAD(P)H dehydrogenase quinone1 (NQO1). The mRNA expression of glutathione peroxidase (Gpx1), catalase (Cat), manganese superoxide dismutase (Mn-Sod), copper/zinc superoxide dismutase (Cu/Zn Sod) and cytochrome c oxidase1 (Cox1) were also up regulated. The expression of uncoupling protein 2 (Ucp2), an important mitochondrial enzyme was also subdued in arsenic exposed zebrafish. The oxidative stress induced by arsenic also cause reduced mRNA expression of B-cell lymphoma 2 (Bcl2) present in the inner mitochondrial membrane and thereby indicating onset of apoptosis in treated fish. It is concluded that even a low dose of arsenic trioxide is toxic enough to induce significant oxidative stress in zebrafish brain.

Optimizing strategies to improve interprofessional practice for veterans, part 1.

INTRODUCTION: Interprofessional patient care is a well-recognized path that health care systems are striving toward. The Veteran's Affairs (VA) system initiated interprofessional practice (IPP) models with their Geriatric Evaluation and Management (GEM) programs. GEM programs incorporate a range of specialties, including but not limited to, medicine, nursing, social work, physical therapy and pharmacy, to collaboratively evaluate veterans. Despite being a valuable resource, they are now faced with significant cut-backs, including closures. The primary goal of this project was to assess how the GEM model could be optimized at the Pittsburgh, Pennsylvania VA to allow for the sustainability of this important IPP assessment. Part 1 of the study evaluated the IPP process using program, patient, and family surveys. Part 2 examined how well the geriatrician matched patients to specialists in the GEM model. This paper describes Part 1 of our study. METHODS: THREE STRATEGIES WERE USED: 1) a national GEM program survey; 2) a veteran/family satisfaction survey; and 3) an absentee assessment. RESULTS: Twenty-six of 92 programs responded to the GEM IPP survey. Six strategies were shared to optimize IPP models throughout the country. Of the 34 satisfaction surveys, 80% stated the GEM clinic was beneficial, 79% stated their concerns were addressed, and 100% would recommend GEM to their friends. Of the 24 absentee assessments, the top three reasons for missing the appointments were transportation, medical illnesses, and not knowing/remembering about the appointment. Absentee rate diminished from 41% to 19% after instituting a reminder phone call policy. DISCUSSION: Maintaining the sustainability of IPP programs is crucial for the health of our veterans. This project uncovered tools to improve the GEM IPP model for our veterans that can be incorporated nationally. Despite the lengthy nature of IPP models, patients and families appreciated the thoroughness, requested transportation and food, and responded well to reminder phone calls. A keen eye on these issues and concomitant medical complexity needs to be observed when planning IPP models to ensure sustainability.