Targeting monocarboxylate transporters (MCTs) in cancer: How close are we to the clinics?

As a result of metabolic reprogramming, cancer cells display high rates of glycolysis, causing an excess production of lactate along with an increase in extracellular acidity. Proton-linked monocarboxylate transporters (MCTs) are crucial in the maintenance of this metabolic phenotype, by mediating the proton-coupled lactate flux across cell membranes, also contributing to cancer cell pH regulation. Among the proteins codified by the SLC16 gene family, MCT1 and MCT4 isoforms are the most explored in cancers, being overexpressed in many cancer types, from solid tumours to haematological malignancies. Similarly to what occurs in particular physiological settings, MCT1 and MCT4 are able to mediate lactate shuttles among cancer cells, and also between cancer and stromal cells in the tumour microenvironment. This form of metabolic cooperation is responsible for important cancer aggressiveness features, such as cell proliferation, survival, angiogenesis, migration, invasion, metastasis, immune tolerance and therapy resistance. The growing understanding of MCT functions and regulation is offering a new path to the design of novel inhibitors that can be foreseen in clinical practices. This review provides an overview of the role of MCT isoforms in cancer and summarizes the recent advances in their pharmacological targeting, highlighting the potential of new potent and selective MCT1 and/or MCT4 inhibitors in cancer therapeutics, and anticipating its inclusion in clinical practice.

Strengthening facility-based integrated emergency care services for time sensitive emergencies at all levels of healthcare in India: An implementation research study protocol.

BACKGROUND: The healthcare system in India is tiered and has primary, secondary and tertiary levels of facilities depending on the complexity and severity of health challenges at these facilities. Evidence suggests that emergency services in the country is fragmented. This study aims to identify the barriers and facilitators of emergency care delivery for patients with time-sensitive conditions, and develop and implement a contextually relevant model, and measure its impact using implementation research outcomes. METHODS: We will study 85 healthcare facilities across five zones of the country and focus on emergency care delivery for 11 time-sensitive conditions. This implementation research will include seven phases: the preparatory phase, formative assessment, co-design of Model "Zero", co-implementation, model optimization, end-line evaluation and consolidation phase. The "preparatory phase" will involve stakeholder meetings, approval from health authorities and the establishment of a research ecosystem. The "formative assessment" will include quantitative and qualitative evaluations of the existing healthcare facilities and personnel to identify gaps, barriers and facilitators of emergency care services for time-sensitive conditions. On the basis of the results of the formative assessment, context-specific implementation strategies will be developed through meetings with stakeholders, providers and experts. The "co-design of Model 'Zero'" phase will help develop the initial Model "Zero", which will be pilot tested on a small scale (co-implementation). In the "model optimization" phase, iterative feedback loops of meetings and testing various strategies will help develop and implement the final context-specific model. End-line evaluation will assess implementation research outcomes such as acceptability, adoption, fidelity and penetration. The consolidation phase will include planning for the sustenance of the interventions. DISCUSSION: In a country such as India, where resources are scarce, this study will identify the barriers and facilitators to delivering emergency care services for time-sensitive conditions across five varied zones of the country. Stakeholder and provider participation in developing consensus-based implementation strategies, along with iterative cycles of meetings and testing, will help adapt these strategies to local needs. This approach will ensure that the developed models are practical, feasible and tailored to the specific challenges and requirements of each region.

Role of LDH in tumor glycolysis: Regulation of LDHA by small molecules for cancer therapeutics.

Lactate dehydrogenase (LDH) is one of the crucial enzymes in aerobic glycolysis, catalyzing the last step of glycolysis, i.e. the conversion of pyruvate to lactate. Most cancer cells are characterized by an enhanced rate of tumor glycolysis to ensure the energy demand of fast-growing cancer cells leading to increased lactate production. Excess lactate creates extracellular acidosis which facilitates invasion, angiogenesis, and metastasis and affects the immune response. Lactate shuttle and lactate symbiosis is established in cancer cells, which may further increase the poor prognosis. Several genetic and phenotypic studies established the potential role of lactate dehydrogenase A (LDHA) or LDH5, the one homo-tetramer of subunit A, in cancer development and metastasis. The LDHA is considered a viable target for drug design and discovery. Several small molecules have been discovered to date exhibiting significant LDHA inhibitory activities and anticancer activities, therefore the starvation of cancer cells by targeting tumor glycolysis through LDHA inhibition with improved selectivity can generate alternative anticancer therapeutics. This review provides an overview of the role of LDHA in metabolic reprogramming and its association with proto-oncogenes and oncogenes. This review also aims to deliver an update on significant LDHA inhibitors with anticancer properties and future direction in this area.

Professional Quality of Life Among Medical Imaging Technologists and Radiologists During COVID-19 Pandemic in India.

Background: Professional quality of life is one of the growing concerns among healthcare workers especially during COVID-19 pandemic. Presence and work of radiologist and medical imaging technologist for prolonged hours with patients could be stressful and painful. Objectives: This study aimed to assess the professional quality of life among the radiologist and medical imaging technologist by analyzing professional satisfaction, compassion, and burnout during the COVID-19 pandemic. Methods: An online, cross-sectional, self-reported, and internet-based survey was carried out among 153 radiologists and medical imaging technologists. Descriptive statistics were used to summarize the sociodemographic variables and domains of professional quality of life scale. Cronbach's alpha was used to check internal consistency. Independent sample t-test (two-tailed) was used to compare the demographic variables and compassion satisfaction, burnout, and secondary traumatic stress. Results: Most participants reported moderate and higher level of compassion satisfaction, whereas moderate burnout and secondary traumatic stress was reported by most participants during COVID-19 pandemic. There was negative correlation between compassion satisfaction and burnout and secondary traumatic stress. Conclusion: The findings of this study are vital to understand the work-related quality of life among healthcare professionals not only during COVID-19 pandemic but also after the pandemic situation. There is a need to conduct qualitative evaluation to ascertain the risk factors associated with professional quality of life. The study also reflects the need to focus more on the mental health of healthcare professionals not only during and after pandemic situation.

Knowledge of Handling the Personal Protective Equipment by Frontline Allied Health Professionals in COVID-19 Outbreak-A Web-Based Survey Study.

Ever since the coronavirus disease 2019 (COVID-19) has emerged, the number of affected individuals has been increasing exponentially. The frontline health workers are in constant risk because of the etiology and mode of transmission of the disease. Thus, the proper use of personal protective equipment (PPE) is very crucial during this pandemic. This study is to assess the knowledge regarding the handling of PPE among frontline allied health professionals who are directly in contact with patients with COVID-19. A standard questionnaire was prepared in Google Forms and circulated within the network of health-care workers via online platforms. A total of 143 frontline health workers participated in the questionnaire survey. It was found that only 44.1% of the total participants had previously undergone training regarding the handling of PPE. About 86.0% of participants gave correct response to the safety etiquette questions. For another knowledge-based question about using the N95 respirator in conjunction with a face shield, 86.7% of participants responded correctly. Only 67.8% of participants gave the right response to the question regarding the sequence of donning and doffing of PPE. The last question was regarding knowledge about the disposal of PPE, where 95.8% of participants responded correctly. Despite the safety precautions and procedures set forth by the Centers for Disease Control and Prevention for handling patients with COVID-19, the health-care workers are still prone to occupational hazards. The only barrier standing between the health-care workers and COVID-19 is the PPE. Thus, in-depth training and education should be imparted on the health-care workers in the present pandemic situation.

Efficacy of non-opioid analgesics to control postoperative pain: a network meta-analysis.

BACKGROUND: The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30 mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. METHODS: We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000-2019, adult human subjects) of IV non-opioid analgesics (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in R to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 h postoperatively (sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish treatments on the basis of their outcomes such that higher SUCRA values indicate better outcomes. The study protocol was prospectively registered with by PROSPERO (CRD42019117360). RESULTS: Out of 2313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). MIV was associated with significantly less MME utilization versus all comparators for abdominal procedures, hysterectomy, and versus acetaminophen in orthopedic procedures. Elsewhere MME utilization outcomes for MIV were largely equivalent or nominally better than other comparators. Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). CONCLUSIONS: MIV 30 mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results as all comparisons involving MIV were indirect.

Molecular characterization of a new begomovirus infecting Mirabilis jalapa in northern India.

Begomoviruses are whitefly-transmitted single-stranded DNA viruses that are responsible for considerable economic losses. A begomovirus, alphasatellite and betasatellite were characterized in a Mirabilis jalapa plant exhibiting severe leaf curling and mottling symptoms. The complete viral genome shared highest sequence identity of 87% with pedilanthus leaf curl virus (AM712436), reported from Pakistan. Additionally, the viral genome was 84% identical to that of chilli leaf curl India virus (KX951415) and 83% identical to that of tobacco curly shoot virus (GU1999584), which were previously reported to infect M. jalapa in India and China, respectively. Based on the ICTV criterion for begomovirus species demarcation (≥91% sequence identity for the complete genome), the virus represents a new species, for which we propose the name Mirabilis leaf curl virus. The alphasatellite and betasatellite sequences were similar to the corresponding sequences of ageratum yellow vein India alphasatellite (KU852743; 99% identity) and tomato leaf curl Patna betasatellite (HQ180394; 86% identity) sequences, respectively. This report describes a new begomovirus-satellite disease complex in M. jalapa.

Treatment Pathways in Patients With Crohn's Disease and Ulcerative Colitis: Understanding the Road to Advanced Therapy.

Background: Patients with Crohn's disease (CD) or ulcerative colitis (UC) often cycle through conventional therapies (CT) with different mechanisms of action (MOA) before initiating advanced therapy (AT). We describe treatment patterns among patients with CD/UC. Methods: Using Merative MarketScan Research databases, adult patients with CD/UC were identified from medical/pharmacy claims (2017-2021). Patients had ≥1 hospitalization or ≥2 outpatient visits (≥30 days apart within 1 year) for CD/UC. Two cohorts were established; cohort 1: Newly diagnosed patients (index date is the date of first diagnosis) and cohort 2: Patients initiating AT (index date is the date of first AT). First-line treatment patterns (cohort 1) and CT pathways before AT initiation (cohort 2) by the number of episodes (ie, adding a new therapy, switching to another therapy, or restarting the same therapy after ≥60 days) and MOA are reported. Results: Among newly diagnosed patients in cohort 1 (CD: n = 1739; UC: n = 2740), 14.4% (CD) and 5.9% (UC) of patients had any AT use during the follow-up period (mean: 2.3 years; ≥ 77% initiated corticosteroids). Among patients in cohort 2 (CD: n = 2594; UC: n = 2431), the mean number of CT episodes before AT initiation was 4.0 ±â€…4.3 (CD) and 5.9 ±â€…5.0 (UC). Among those with ≥1 corticosteroid episode (CD: 82.2%; UC: 91.5%), the mean number of episodes was 4.6 ±â€…4.3 (CD) and 6.3 ±â€…5.0 (UC). Overall, 13.3% (CD) and 23.7% (UC) of patients cycled through 3 MOAs before AT initiation. Conclusions: Despite treatment recommendations, few newly diagnosed CD/UC patients initiated AT as their first treatment. Moreover, patients cycled through multiple CTs before initiating AT.

A Single Centric Quantitative Assessment of Male Breast Cancer Knowledge, Perception, and Awareness: Breaking the Stigma in Indian Population.

Most people throughout the world are still uninformed of the problem of breast cancer in men. Despite increasing awareness programs targeting women, most people are unaware that breast cancer can also affect men. Our purpose is to assess the knowledge, perception, and awareness of male breast cancer among the adult male population. A descriptive cross-sectional survey included 128 male employees who agreed to participate in our study. We distributed pre-validated questionnaires to participants and gathered data following the one-on-one interview. The mean age of the participants was 37.71 years with a standard deviation of 7.65. About 55.5% of the participants were unaware that changes in the nipple position could be a sign of breast cancer. Majority of the participants, i.e., 60.9% believe positive family history will not increase the risk of breast cancer and 93% of participants have no idea about self-breast examination to detect lumps. On the other hand, 33.6% of participants stated that diagnosis and treatment of male breast cancer is embarrassing. Majority of the participants have no idea about the screening methods, 59.4% of participants have not heard about mammography, which is considered a modality of choice for early detection of breast cancer. The male university staff were lacking in knowledge and awareness about male breast cancer. In Indian community, because of shyness, they feel very embarrassed when it comes to openly discussing breast cancer. Because of this, it needs to receive more attention and to educate the male population about male breast cancer.

Targeting Virus-Induced Reprogrammed Cell Metabolism via Glycolytic Inhibitors: An Effective Therapeutic Approach Against SARS-CoV-2.

Reprogrammed cell metabolism has been observed in a wide range of virally infected cells. Viruses do not have their metabolism; they rely on the cellular metabolism of the host to ensure the energy and macromolecules requirement for replication. Like other viruses, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) does not own its metabolism, but virus infected cells adopt aberrant cell metabolism. Infected viral use the energy and macromolecules to make their own copies; to do so, they need to increase the rate of metabolism to ensure the requirement of macromolecules. In contrast, the cellular metabolism of noninfected cells is more plastic than infected cells. Therefore, it is essential to examine the virus infection in the context of metabolic alterations of host cells. A novel therapeutic approach is urgently required to treat highly infectious COVID-19 disease and its pathogenesis. Interference of glucose metabolism might be a promising strategy to determine COVID-19 treatment options. Based on the recent research, this mini-review aims to understand the impact of reprogrammed cell metabolism in COVID-19 pathogenesis and explores the potential of targeting metabolic pathways with small molecules as a new strategy for the development of a novel drug to treat COVID-19 disease. This type of research line provides new hope in the development of antiviral drugs by targeting hijacked cell metabolism in case of viral diseases and also in COVID-19.

Design and Synthesis of Thiazole Scaffold-Based Small Molecules as Anticancer Agents Targeting the Human Lactate Dehydrogenase A Enzyme.

A new series of thiazole central scaffold-based small molecules of hLDHA inhibitors were designed using an in silico approach. Molecular docking analysis of designed molecules with hLDHA (PDB ID: 1I10) demonstrates that Ala 29, Val 30, Arg 98, Gln 99, Gly 96, and Thr 94 possessed strong interaction with the compounds. Compounds 8a, 8b, and 8d showed good binding affinity (-8.1 to -8.8 kcal/mol), whereas an additional interaction of NO2 at the ortho position in compounds 8c with Gln 99 through hydrogen bonding enhanced the affinity to -9.8 kcal/mol. Selected high-scored compounds were synthesized and screened for hLDHA inhibitory activities and in vitro anticancer activity in six cancer cell lines. Biochemical enzyme inhibition assays showed the highest hLDHA inhibitory activity observed with compounds 8b, 8c, and 8l. Compounds 8b, 8c, 8j, 8l, and 8m depicted significant anticancer activities, exhibiting IC50 values in the range of 1.65-8.60 µM in HeLa and SiHa cervical cancer cell lines. Compounds 8j and 8m exhibited notable anticancer activity with IC50 values of 7.90 and 5.15 µM, respectively, in liver cancer cells (HepG2). Interestingly, compounds 8j and 8m did not induce noticeable toxicity in the human embryonic kidney cells (HEK293). Insilico absorption, distribution, metabolism, and excretion profiling demonstrates that the compounds possess drug-likeness, and results may pave the way for the development of novel thiazole-based biologically active small molecules for therapeutics.

Efficacy and Safety of Advanced Therapies for Moderately to Severely Active Ulcerative Colitis at Induction and Maintenance: An Indirect Treatment Comparison Using Bayesian Network Meta-analysis.

Background: Given rapid innovation in advanced therapies for moderately to severely active ulcerative colitis (UC), we investigated their comparative efficacy and safety during induction and maintenance through network meta-analysis. Methods: Using Bayesian methods, endpoints of clinical remission and clinical response per Full Mayo score, and endoscopic improvement were assessed in bio-naive and -exposed populations. Safety was assessed in overall populations by all adverse events (AEs), serious AEs, discontinuation due to AEs, and serious infections. Phase 3 randomized controlled trials were identified via systematic literature review, including the following advanced therapies: infliximab, adalimumab, vedolizumab, golimumab, tofacitinib, ustekinumab, filgotinib, ozanimod, and upadacitinib. Random effects models were used to address between-study heterogeneity. Intent-to-treat (ITT) efficacy rates were calculated by adjusting maintenance outcomes by likelihood of induction response. Results: Out of 48 trials identified, 23 were included. Across all outcomes and regardless of prior biologic exposure, ITT efficacy rates were highest for upadacitinib, owing to its highest ranking for all efficacy outcomes in induction and for all but clinical remission during maintenance among bio-naive induction responders. For all advanced therapies versus placebo, there were no significant differences in serious AEs or serious infections across therapies. For all AEs, golimumab had higher odds versus placebo during maintenance; for discontinuation due to AEs, upadacitinib had lower odds versus placebo during induction, while ustekinumab and vedolizumab had lower odds versus placebo during maintenance. Conclusions: Upadacitinib may be the most efficacious therapy for moderately to severely active UC based on ITT analyses, with similar safety across advanced therapies.

An Eye on the Future of COVID-19: Prediction of Likely Positive Cases and Fatality in India over a 30-Day Horizon Using the Prophet Model.

OBJECTIVE: The coronavirus disease (COVID-19) pandemic was initiated in Wuhan Province of mainland China in December 2019 and has spread over the world. This study analyzes the effects of COVID-19 based on likely positive cases and fatality in India during and after the lockdown period from March 24, 2020, to May 24, 2020. METHODS: Python has been used as the main programming language for data analysis and forecasting using the Prophet model, a time series analysis model. The data set has been preprocessed by grouping together the days for total numbers of cases and deaths on few selected dates and removing missing values present in some states. RESULTS: The Prophet model performs better in terms of precision on the real data. Prediction depicts that, during the lockdown, the total cases were rising but in a controlled manner with an accuracy of 87%. After the relaxation of lockdown rules, the predictions have shown an obstreperous situation with an accuracy of 60%. CONCLUSION: The resilience could have been better if the lockdown with strict norms was continued without much relaxation. The situation after lockdown has been found to be uncertain as observed by the experimental study conducted in this work.

Current understanding of biological interactions and processing of DNA origami nanostructures: Role of machine learning and implications in drug delivery.

DNA origami has emerged as an exciting avenue that provides a versatile two and three-dimensional DNA-based platform for nanomedicine and drug delivery applications. Their incredible programmability, custom synthesis, efficiency, biocompatibility, and physio-chemical nature make DNA origami ideal for biomedical applications. Several recent studies demonstrated the potential of DNA origami for different technological applications, especially in drug delivery. However, several challenges related to their intracellular stability, elicitation of the immune response, and cellular fate limit the in-vivo application of these nanostructures. In this review, we critically assess the molecular-level interactions of DNA nanostructures with biological systems that will be helpful to engineer and optimize DNA nanostructures for bio applications. We highlight the hurdles that impair the potential applicability of DNA origami nanostructures in the biology and medicine field. We have also expanded the details of key strategies to overcome the limitations and extend the boundaries of DNA origami closer to nanomedicine. Finally, we explore the role Artificial Intelligence and Machine Learning techniques can play to accelerate the process of their clinical applications.

Severe heat stress modulated nuclear factor erythroid 2-related factor 2 and macrophage migration inhibitory factor pathway in rat liver.

Heat stress impairs physiology and overall functionality of the body at tissue and organ level in animals. Liver being a vital organ performs more than hundreds regulatory functions of the body. Present study investigates the modulation of molecular pathways that are responsible for liver damage triggered by heat stress. Male Sprague dawley rats were exposed to heat stress (45 °C) in heat simulation chamber till core temperature reaches 40 °C and 42 °C in 25 and 42 min respectively. For in-depth evaluation of liver functions during severe heat stress, hepatic transcriptome and proteome were analysed by microarray and two dimensional gel electrophoresis respectively. Results revealed major alterations in redox status, inflammation, mitochondrial dysfunction and proteostasis related pathways. Data of molecular pathway analysis demonstrate that nuclear factor erythroid 2-related factor 2 (NRF-2) mediated oxidative stress response and macrophage migration inhibitory factor (MIF) regulated inflammatory pathways were upregulated in severe heat stressed liver. Expression levels of downstream molecules of above pathways such as heat shock protein 90AB 1, peroxiredoxin 5, Jun N-terminal kinases 1/2, heme-oxygenase 1, apolipoprotein 1 and interleukin 10 were examined and result suggested the upregulation of these genes modulates the NRF-2 and MIF regulated pathways in heat stressed liver. Irregularity in molecular signalling networks lead to mitochondrial dysfunction indicated by upregulation of ATP synthase ß and peroxiredoxin 1 along with decreased levels of glucose-6-phosphate dehydrogenase and enhanced activity of cytochrome c in liver mitochondria. Thus, current study demonstrated heat induced alterations in key liver functions were regulated by NRF-2 and MIF pathways.

Perceptions of Medical and Allied Health Students Towards Online Education during the COVID-19 Pandemic Phases and Its Future Impact in India.

The outbreak of COVID-19 has caused sensation and fear among the world population. Globally, the teaching and learning process has been greatly impacted by the pandemic. University and teaching institutes adopted the online mode for the continuation of the teaching-learning process. This research aims to evaluate the current online education practice, its effectiveness, and future prospects in various medical and allied health education in India. A standard self-administered questionnaire was prepared and circulated among the medical and allied health care students from different parts of India via the online platform. A total of 1042 participants submitted their responses. About 77% of students stated that they have attended online classes conducted by their respective educational institutes. The majority of the students were enthusiastic about online learning (via Google platform, Zoom, etc.), yet they all agreed that their practical knowledge was insufficient. Online education can be a good approach to learning, but it may not be as effective as traditional education in Medical and Allied Health students. Beyond pandemic lockdown, online learning may be implemented in conjunction with traditional methods.

Cost of home vs clinic administration of paclitaxel in metastatic breast cancer.

OBJECTIVES: To estimate the costs associated with home administration of oral paclitaxel and encequidar (novel P-glycoprotein pump inhibitor allowing oral paclitaxel bioavailability) compared with clinic/office administration of intravenous (IV) paclitaxel (175 mg/m2) and protein-bound paclitaxel in US patients with metastatic breast cancer. STUDY DESIGN: Economic analysis. METHODS: A cost calculator was constructed from a payer's perspective including all costs related to administration of the chemotherapies, including drug administration, premedications and concomitant medications, oncologist office visits, laboratory testing, and administration-related adverse events. Total administration cost per patient per month (PPPM) and 6-month costs per patient were estimated for oral paclitaxel and encequidar, 175 mg/m2 IV paclitaxel, and protein-bound paclitaxel. Three scenarios for oral paclitaxel and encequidar, a weekly IV paclitaxel scenario (80-100 mg/m2), and univariate sensitivity analyses were conducted. RESULTS: Home administration of oral paclitaxel and encequidar was associated with a total administration cost of $523 PPPM, 64.4% lower than once-every-3-weeks IV paclitaxel (175 mg/m2; $1469 PPPM) and 63.8% lower than protein-bound paclitaxel (260 mg/m2; $1445 PPPM). Difference in costs was driven largely by higher administration and premedication costs associated with IV therapies. Scenario analyses showed that increased clinical experience with home administration of oral paclitaxel and encequidar was associated with reduction in cost of care associated with its administration over time. For the weekly IV (80-100 mg/m2) paclitaxel scenario, the total administration cost was $2510 PPPM (4.8 times higher than for oral paclitaxel and encequidar). Univariate sensitivity analysis demonstrated that the model findings were robust. CONCLUSIONS: Home administration of oral paclitaxel and encequidar was associated with lower administration costs compared with once-every-3-weeks IV paclitaxel (175 mg/m2) and protein-bound paclitaxel, resulting in potential cost savings for payers.

Heat precondition is a potential strategy to combat hepatic injury triggered by severe heat stress.

AIM: Environmental heat stress alters physiological and biochemical functions which leads to multiorgan dysfunction including severe hepatic injury in animals. We hypothesize that heat preconditioning can be potential intervention in combating heat illnesses. MAIN METHODS: Sprague Dawley rats were exposed to moderate heat stress, severe heat stress and heat preconditioning in heat simulation chamber. Mean arterial pressure, heart rate, skin and core temperature were monitored in pre and post heat exposed animals. After stress exposure, blood for hemodynamic and liver tissue for liver function tests, oxidative stress, inflammatory variables and structural studies were collected from rats. Hepatic mitochondria were isolated to study the key structural alterations and functional changes by transmission electron microscopy. KEY FINDINGS: The effect of heat precondition shows improvement in time to attain the core temperature, weight loss, blood pressure and heart rate in rats. Results exhibited decreased levels of liver function tests, elevated levels of free radicals and inflammatory cytokines in heat exposed liver as compared with heat preconditioned animals. Expression levels of mitochondrial heat shock protein 60, superoxide dismutase 1 and uncoupling protein 1 along with activity of electron transport chain complexes I-V were examined and found to be increased in heat preconditioned as compared to heat stressed animals. Morphological studies of liver parenchyma demonstrated reduction in structural deterioration of hepatic lobules and restoration of mitochondrial structural integrity in heat preconditioned rats. SIGNIFICANCE: Present study suggests that heat preconditioning intervention plays a crucial role in protection against heat induced hepatic injury in animals.

Psychiatrist and Psychiatric Pharmacists Beliefs and Preferences for Atypical Antipsychotic Treatments in Patients With Schizophrenia and Bipolar Disorders.

BACKGROUND: Selection of schizophrenia or bipolar disorder treatments is complicated by treatment-effect heterogeneity. OBJECTIVES: This study assessed how clinicians' beliefs and health system/ insurace policies impact choice of atypical antipsychotic agent in schizophrenia and bipolar disorder. METHODS: A cross-sectional survey was conducted of members of the American College of Clinical Pharmacy and College of Psychiatric & Neurologic Pharmacists. Beliefs regarding atypical antipsychotic effectiveness and safety, impact of comorbidity on drug selection, and factors influencing atypical antipsychotic therapy selection were assessed. RESULTS: Twenty-four psychiatric pharmacists and 18 psychiatrists participated. Mean age was 39.6 years, 57.1% were female. Most clinicians (64.3%) believed medication effectiveness and safety equally important, while 26.2% believed safety and 9.4% believed effectiveness more important. The most important medication properties for schizophrenia were reducing positive symptoms (92.7%) and hospitalizations (87.8%) and for bipolar disorder were reducing manic episodes (87.8%), episode relapse (53.7%), and hospitalizations (53.7%). Agranulocytosis (78.1%), arrhythmias (70.7%), and extrapyramidal side effects (68.3%) were most concerning. Restrictions affected antipsychotic choice at 80.5% of sites and were believed to affect medication adherence (55.0%) and outcomes (53.4%). CONCLUSION: Efficacy and safety were considered equally important when choosing atypical antipsychotics. Formulary restrictions were perceived as impacting treatment choice and outcomes.

A potential energy and mutual information based link prediction approach for bipartite networks.

Link prediction in networks has applications in computer science, graph theory, biology, economics, etc. Link prediction is a very well studied problem. Out of all the different versions, link prediction for unipartite graphs has attracted most attention. In this work we focus on link prediction for bipartite graphs that is based on two very important concepts-potential energy and mutual information. In the three step approach; first the bipartite graph is converted into a unipartite graph with the help of a weighted projection, next the potential energy and mutual information between each node pair in the projected graph is computed. Finally, we present Potential Energy-Mutual Information based similarity metric which helps in prediction of potential links. To evaluate the performance of the proposed algorithm four similarity metrics, namely AUC, Precision, Prediction-power and Precision@K were calculated and compared with eleven baseline algorithms. The Experimental results show that the proposed method outperforms the baseline algorithms.