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Background High adherence to remote monitoring (RM) in pacemaker (PM) patients improves outcomes; however, adherence remains suboptimal. Bluetooth low-energy (BLE) technology in newer-generation PMs enables communication directly with patient-owned smart devices using an app without a bedside console. Objective To evaluate the success rate of scheduled RM transmissions using the app compared to other RM methods. Methods The BlueSync Field Evaluation was a prospective, international cohort evaluation, measuring the success rate of scheduled RM transmissions using a BLE PM or cardiac resynchronization therapy PM coupled with the MyCareLink Heart app. App transmission success was compared to 3 historical “control” groups from the Medtronic de-identified CareLink database: (1) PM patients with manual communication using a wand with a bedside console (PM manual transmission), (2) PM patients with wireless automatic communication with the bedside console (PM wireless); (3) defibrillator patients with similar automatic communication (defibrillator wireless). Results Among 245 patients enrolled (age 64.8±15.6 years, 58.4% men), 953 transmissions were scheduled through 12 months, of which 902 (94.6%) were successfully completed. In comparison, transmission success rates were 56.3% for PM manual transmission patients, 77.0% for PM wireless patients, and 87.1% for defibrillator wireless patients. Transmission success with the app was superior across matched cohorts based on age, sex, and device type (single vs dual vs triple chamber). Conclusion The success rate of scheduled RM transmissions was higher among patients using the smart device app compared to patients using traditional RM using bedside consoles. This novel technology may improve patient engagement and adherence to RM., Graphical abstract

Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system for anti-epileptic drug Oxcarbazepine. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of solid lipid material and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus on HMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization (by CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

Background Nonhuman primates are essentially used for research purposes such as studying diseases, different biological processes and in drug discovery and development programs. Various clinical pathology parameters are used as biomarkers of disease conditions in biomedical research. Detailed reports of these parameters are not available for Indian-origin rhesus macaques. In order to meet the increasing need of information, we conducted this study on 121 adult Indian rhesus macaques (57 wild-sourced and 64 inhouse animals, aged 3-7 years). A total of 18 hematology and 18 biochemistry parameters were evaluated and reported in this study. Data from these parameters were statistically evaluated for significance amongst inhouse and wild-born animals and for difference amongst sexes. Reference range was calculated according to C28-A3 guidelines for reporting reference intervals of clinical laboratory parameters. Results: Source of the animals and sex appeared to have statistically significant effects on reference values and range. Wild-born animals reported higher WBC, platelets, neutrophils, RBC, hemoglobin, HCT, MCV and total protein values in comparison to inhouse monkeys. Sex-based differences were observed for parameters such as RBCs, hemoglobin, HCT, creatinine, calcium, phosphorus, albumin and total protein amongst others. Conclusions: Through this study, we have established a comprehensive data set of reference values and intervals for certain hematological and biochemical parameters which will help researchers in planning, conducting and interpreting various aspects of biomedical research employing Indian-origin rhesus monkeys.

Conventional coating processes are based on aqueous or organic solvent system, resulting in the lengthy and tedious processes where use and removal of solvents consumes lots of energy and resources. Also, solvent disposal is a critical issue considering environmental hazard.Hot melt coating process avoids use of solvent and is short and energy-efficient process. Here, Hot-melt coating process (HMCP) is being developed to formulate lipid based oral controlled release formulation system to deliver highly water soluble Biopharmaceutical Classification System (BCS) class-I drug Levetiracetam. Pellets containing Active ingredient in the core portion were prepared by extrusion spheronization process with use of appropriate filler and binder. These core pellets were then coated using hot-melt coating technology with different levels of lipid and a hydrophilic component. Formulation and Process parameters were optimized to achieve targeted drug release profile and other target product profile with particular focus onHMCP. Quality by design (QbD) with DOE approach was used for designing and development of the formulation, by putting risk assessment Failure Mode and Effect analysis (FMEA, Fish-bone diagram), screening (by Plackett Burman), and optimization by Central Composite Design (CCC) studies. Appropriate ‘design space’ was proposed based on the optimization studies. The results demonstrated that the level of Low melting coating component and a hydrophilic component influenced the drug release rate from the formulation, and the rate of release could be optimized by varying the amount of these components in the formulation. Processing parameters like Temperature of the coating solution and atomization air, Atomization air pressure and Spray rate also affects the drug release rate and other parameters like coating efficiency and mean particle size. For optimized formulation, dissolution data model fitting was also carried out which adequately fits to Higuchi model suggesting that the drug release occurred predominantly by diffusion.

Using thematic analysis, this qualitative research interrogates the influence and relevance of Bollywood cinema, Indian Hindi movies considered both a brand, a cultural artefact, and a complex indu...

This study examined the relationship between a diagnosis of cancer and the likelihood of having any out-of-pocket costs (OOPC) and medical debt, and the amounts of OOPC and medical debt, at the household level. We used the 2013 Panel Study of Income Dynamics, a continuous, representative panel survey that collects demographic, economic, and social data in the United States. The analytic sample included head of households and their spouse (if married), 18–64 years old. Two-part models were used. The first part consisted of logistic regression models and the second part consisted of generalized linear models with logarithmic link and a gamma distribution. Logistic regression results showed odds of 2.13 (CI: 1.27, 3.57, p &lt, 0.01) for any OOPC and odds of 1.55 (CI: 0.93, 2.58, p &lt, 0.1) for any medical debt for households in which either the head or spouse (if married) reported a diagnosis of cancer compared to those that did not report a diagnosis of cancer. Likewise, results from the second part of the model for households with a positive amount of OOPC showed an exponentiated coefficient of 1.73 (CI: 1.33, 2.25, p &lt, 0.01) for households in which either the head or spouse (if married) reported a diagnosis of cancer compared to households without a diagnosis of cancer. This study shows that a diagnosis of cancer places a financial burden on families, particularly with all types of debt, in the United States even after controlling for differences between households with a diagnosis of cancer and those without a diagnosis of cancer.

This paper examines the relationship between self-reported health status and medical debt outcomes using data from the 2013 Panel Study of Income Dynamics. There were two outcomes of interest: (a) the likelihood of having any medical debt, which included 4,227 households and (b) the amount of medical debt (medical debt > 0), which included 631 households. The results from the multivariate models showed that fair/poor health status increased the likelihood of having any medical debt by 73% and was associated with an increase in the amount of medical debt among those with medical debt by about 77% (p < .001) compared to those who reported better health. Poor health status appears to impose a financial burden on some households.

Background Data suggest that topical antibiotic and antiseptic use in the operating room is common but not commonly monitored by antimicrobial stewardship programs. Although some data suggest a benefit in certain surgical procedures, the CDC and WHO advise against the routine use of topical antibiotics in surgery due to uncertainty and heterogeneity in the overall data. Methods We conducted a retrospective 28-day period prevalence study of topical antibiotic and antiseptic use during surgical procedures performed in the operating room by 6 surgical specialties at a tertiary care medical center. For the subset of patients undergoing orthopedic surgeries, we evaluated the types of topical antibiotics received and the rates of surgical site infections (SSI) and adverse drug events within 28 days of the procedure. Results Of 744 surgical procedures reviewed, topical antibiotics were used in 127 (17.1%), topical antiseptics in 71 (9.5%), and both in 18 (2.4%) (Table 1). Antiseptic use was higher in orthopedics relative to all other surgical specialties while topical antibiotic use was higher in neurosurgery. Hand, vascular and plastics had distinguishably lower use. In the orthopedic subgroup, after exclusions, 218 procedures were evaluated. Topical antibiotics were used in 42 (19.2%). Topical antibiotic therapy was more likely to be administered if prosthetic material was implanted, the procedure was emergent, or if a Staphylococcus aureus infection was present. Vancomycin was the most commonly used topical antibiotic and powder was the most commonly used type of application. As shown in table 2, SSI occurred more often when both topical antibiotics and antiseptics were applied; however, SSI events were relatively uncommon, and these were more likely to have infection present at the time of surgery. Adverse events were rare. Conclusion In our institution we noted significant variability in use of topical antibiotic and antiseptic therapy among surgical specialties as well as within the orthopedic surgical specialty. Although opportunities to standardize use/nonuse of these therapies exist, this may be challenging due to the uncertainty and heterogeneity of currently available data. Disclosures All Authors: No reported disclosures

There is a scarcity of research establishing a relationship between mental illness and the U.S. military service members who participate in the field of military humanitarian assistance/disaster relief (HA/DR). One of the few studies in this area showed that participation in military HA/DR was not associated with depressive symptoms, however, the study was limited by sample size. This study examined (1) the relationship between participation in military HA/DR and mental health symptoms and military stress and (2) the relationship between HA/DR and mental health treatment and therapy.Data from the 2011 Health Related Behaviors Survey was used. The analytic sample consisted of U.S. military service members who participated in HA/DR (the Haiti earthquake and Deepwater Horizon oil spill in the Gulf) (n = 573) compared to those who participated in non-HA/DR deployments from 2007 to 2011 (n = 986). Multivariate models were used to examine the relationship between the independent variables and dependent variables while controlling for a set of variables that may confound the relationship between the two.The logistic regression model found that participating in HA/DR deployments decreased the likelihood of service members reporting post-traumatic stress disorder (PTSD) symptoms by 3% (p0.1) and depressive symptoms by 1% (p0.05). Furthermore, participation decreased the likelihood of having a prescription for antidepressants during and/or 3 months after deployment by 1% (p0.05). Additional results showed that junior enlisted and senior enlisted members were more likely to report symptoms of PTSD than senior officers (p0.05). Marines were more likely to seek treatment and therapy for depression than U.S. Coastguard members (p0.1).Results showed that participation in HA/DR was associated with significant reductions in PTSD symptoms, depressive symptoms, and the use of antidepressants by service members. Further research needs to understand the mechanism of these associations for better planning and implementation of HA/DR and delivery of care to service members who participate in these missions.

The controlled introduction of impurities into the crystal lattice of solid-state compounds is a cornerstone of materials science. Intercalation, the insertion of guest atoms, ions or molecules between the atomic layers of a host structure, can produce novel electronic, magnetic and optical properties in many materials. Here we describe an intercalation compound in which the host [Co6Te8(PnPr3)6][C60]3, formed from the binary assembly of atomically precise molecular clusters, is a superatomic analogue of traditional layered atomic compounds. We find that tetracyanoethylene (TCNE) can be inserted into the superstructure through a single-crystal-to-single-crystal transformation. Using electronic absorption spectroscopy, electrical transport measurements and electronic structure calculations, we demonstrate that the intercalation is driven by the exchange of charge between the host [Co6Te8(PnPr3)6][C60]3 and the intercalant TCNE. These results show that intercalation is a powerful approach to manipulate the material properties of superatomic crystals. Intercalation — a cornerstone of materials science with wide-ranging applications — has now been demonstrated in a superatomic crystal. A redox-active tetracyanoethylene guest was inserted into the lattice of a material consisting of alternate layers of {Co6Te8} clusters and C60 fullerenes, leading to a single-crystal-to-single-crystal transformation that significantly modulates the material's optical and electrical transport properties.

Background: Poststroke patients with residual deficits that do not require inpatient rehabilitation are at an increased risk of adverse events during transition of care especially readmission within 30 days of discharge. However, using readmission as a marker for successful discharge is misleading as lack of readmission does not always translate into a measure of patient wellbeing. Identifying specific needs instead allows for targeted interventions in improving the discharge process and patient satisfaction. Methods: This QI project analyzed transition of care issues identified in poststroke patients discharged home from a large academic center via a post discharge phone call by an advanced practice provider (APP) between July 2017 and April 2018. All patients admitted to the neurology stroke or neurosurgery service with a diagnosis of stroke and discharged home received a phone call within 7days of discharge by an APP. The telephone encounter was documented in the medical record. Results: Of 324 patients, 67% answered, 32% did not answer and 1% had contact deferred. Fifty-eight percent had no issues identified. Common issues identified were related to medications, rehabilitation therapy, follow-up appointments and new health issues. More SAH patients had issues with medication insurance coverage (17%) and more ICH patients had knowledge deficits related to their medications (6%). More SAH patients lacked scheduled appointments at discharge (33%) and lacked insurance coverage for appointments (6%). More ICH patients reported no contact from therapy (6%) but ischemic stroke patients reported more falls (2%). SAH patients had more unexpected new health issues (6%). Patient satisfaction with discharge ranged from 92 to 96%. Conclusion: ICH and SAH patients discharged home have more transition of care needs. A post discharge follow-up phone call by an APP within 7 days of discharge allows for early intervention of identified post discharge complications. These early interventions result in timely connection with rehabilitation services, medication regimen adherence and appointments with follow-up providers in the community. Additionally, the APP can intervene on unexpected health problems that develop prior to contact with a community provider.

This study used data from the Military Health System Data Repository to examine the association between mild traumatic brain injuries (mTBI) and work functioning such as work duty limitations, hospital emergency room visits and inpatient admissions for active-duty service members (ADSMs). Further, this study assessed the role that common symptoms of mTBI play in work functioning. Multivariate results showed that having a mTBI diagnosis is not a major factor that results in being “released with work duty limitations”. However, findings from these regression models also showed that the interaction of mTBI with cognitive and linguistic symptoms resulted in odds of 3.63 (CI: 1.40–9.36, p &lt, 0.01) for being “released with work duty limitations” and odds of 4.98 (CI: 1.16–21.39, p &lt, 0.05) for having any emergency department visits compared to those with no diagnosis of mTBI and none of these symptoms. Additionally, the interaction of mTBI with sleep disturbance and chronic pain showed odds of 2.72 (CI: 1.31–5.65, p &lt, 0.01) and odds of 11.56 (CI: 2.65–50.44, p &lt, 0.01) for being “released with work duty limitations” compared to those with no diagnosis of TBI and none of these symptoms, respectively. Further research is needed to investigate the association between mTBI and duration of time off work to provide a comprehensive understanding of the effect of mTBI on work functioning in the Military Health System.

Introduction: Opioid dependence is a major problem in the Western world. There have been significant efforts seeking to optimize pain control pathways and minimize risk of dependence on opioid pain relievers. However, little is known in low- to middle-income countries regarding current practices in postoperative pain control and its efficacy. This study evaluates subjective pain scores of patients following head and neck surgeries in a Ugandan hospital. These patients are unique in that most are opioid naive. We hope to contribute to the understanding of adequate postoperative pain control in opioid naive patients. Methods: Twenty-five patients without chronic opioid use underwent head and neck surgery during a semiannual surgical outreach trip. Ages ranged from 4-77 years (mean 38). The most common procedures performed were hemithyroidectomy (5), total thyroidectomy (3), parotidectomy (3), tonsillectomy (2), and cystic hygroma removal (2). Charts were reviewed retrospectively for daily subjective pain scores assessed on a numerical scale of 0-5, length of hospital stay, postoperative medications given for pain, surgery type, and postoperative analgesic medications administered, including dosage and frequency. Wilcoxon analysis was used to compare medians between groups receiving paracetamol alone or in combination with opioids or other analgesics. Results: All patients received IV paracetamol postoperatively; 16% of patients also requested opioids, and 8% requested another nonopioid analgesic. Average age for the 6 patients receiving paracetamol and either opioids or another nonopioid analgesic was 49.17 years compared to 34.47 years in the group that received paracetamol only (p=0.26; 95% CI -12.5, 42.9). For the whole study population, there was a reduction in the median pain score of -1.9 points (p Conclusion: Despite language and cultural barriers, we were able to assess postoperative pain scores in a Ugandan population. Intravenous paracetamol alone was effective and adequate for postoperative pain management for the majority of patients in this study. Although this study was limited in sample size, there was no significant improvement observed in pain score for patients using opioids or nonopioid analgesics other than paracetamol compared to paracetamol only. Opioids or additional analgesics were requested by a minority of patients, who tended to be older and/or have undergone more extensive procedures. Citation Format: Sara Maskal, Nilam Patel, Claudia Cabrera, Akina Tamaki, Fiona Kabagenyi, Ian Bwete, Isaac Mukiibi, Edrisa Kabazzi, Katrina Harrill, Jeffrey Otiti, Jason Thuener, Chad Zender. Postoperative analgesia in a Ugandan population [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A32.

Threat induces a state of sustained anxiety that can disrupt cognitive processing, and, reciprocally, cognitive processing can modulate an anxiety response to threat. These effects depend on the level of cognitive engagement, which itself varies as a function of task difficulty. In adults, we recently showed that induced anxiety impaired working memory accuracy at low and medium but not high load. Conversely, increasing the task load reduced the physiological correlates of anxiety (anxiety-potentiated startle). The present work examines such threat-cognition interactions as a function of age. We expected threat to more strongly impact working memory in younger individuals by virtue of putatively restricted cognitive resources and weaker emotion regulation. This was tested by examining the influence of age on the interaction of anxiety and working memory in 25 adolescents (10 to 17 years) and 25 adults (22 to 46 years). Working memory load was manipulated using a verbal n-back task. Anxiety was induced using the threat of an aversive loud scream and measured via eyeblink startle. Findings revealed that, in both age groups, accuracy was lower during threat than safe conditions at low and medium but not high load, and reaction times were faster during threat than safe conditions at high load but did not differ at other loads. Additionally, anxiety-potentiated startle was greater during low and medium than high load. Thus, the interactions of anxiety with working memory appear similar in adolescents and adults. Whether these similarities reflect common neural mechanisms would need to be assessed using functional neuroimaging.

A loss of functioning motor units underlies many neuromuscular disorders. The facial nerve innervates the muscles of facial expression, including nasal muscles, which also play an important role in the regulation of airflow resistance. It is difficult to accurately assess motor unit number in the facial muscles, because the muscles are difficult to activate in isolation. Here, we apply the manual McComas method to estimate the number of motor units in a nasal dilator muscle. EMG of the dilator naris was recorded during graded stimulation of the zygomatic branch of the facial nerve in 26 subjects (12 males and 14 females), aged 20-41 years. Each subject was studied twice, on separate days, to estimate method reproducibility. As a check on our use of the McComas method, we also estimated motor unit number in the first dorsal interosseus muscle (FDI) of six subjects, as the muscle is also small and has been studied with the McComas method. Reproducibility was evaluated with a rigorous statistical approach, the Bland-Altman procedure. We estimate that dilator naris is composed of 75 ± 15.6 (SD) motor units, compared to 144 ± 35.5 in FDI. The coefficient of variation for test-retest reproducibility of dilator naris motor unit estimates was 29.6 %, similar to separate-day reproducibility reported for other muscles. Recording and stimulation were done with surface electrodes, and the recordings were of high quality and reproducible. This simple technique could be applied clinically to track motor neuron loss and to monitor facial nerve integrity.

The modulation of risk-taking is critical for adaptive and optimal behavior. This study examined how oxytocin (OT) and arginine vasopressin (AVP) influence risk-taking in function of three parameters: sex, risk-valence, and social context. Twenty-nine healthy adults (14 males) completed a risk-taking task, the Stunt task, both in a social-stress (evaluation by unfamiliar peers) and non-social context, in three separate drug treatment sessions. During each session, one of three drugs, OT, AVP, or placebo (PLC), was administered intra-nasally. OT and AVP relative to PLC reduced betting-rate (risk-averse effect). This risk-averse effect was further qualified: AVP reduced risk-taking in the positive risk-valence (high win-probability), and regardless of social context or sex. In contrast, OT reduced risk-taking in the negative risk-valence (low win-probability), and only in the social-stress context and men. The reduction in risk-taking might serve a role in defensive behavior. These findings extend the role of these neuromodulators to behaviors beyond the social realm. How the behavioral modulation of risk-taking maps onto the function of the neural targets of OT and AVP may be the next step in this line of research.

Risk-taking behavior increases during adolescence, leading to potentially disastrous consequences. Social anxiety emerges in adolescence and may compound risk-taking propensity, particularly during stress and when reward potential is high. However, the manner in which social anxiety, stress, and reward parameters interact to impact adolescent risk-taking is unclear. To clarify this question, a community sample of 35 adolescents (15-18yo), characterized as having high or low social anxiety, participated in a study over two separate days, during each of which they were exposed to either a social stress or a control condition, while performing a risky decision-making task. The task manipulated, orthogonally, reward magnitude and probability across trials. Three findings emerged. First, reward magnitude had a greater impact on the rate of risky decisions in high social anxiety (HSA) than low social anxiety (LSA) adolescents. Second, reaction times (RTs) were similar during the social stress and the control conditions for the HSA group, whereas the LSA group's RTs differed between conditions. Third, HSA adolescents showed the longest RTs on the most negative trials. These findings suggest that risk-taking in adolescents is modulated by context and reward parameters differentially as a function of social anxiety.

Background There is limited knowledge on the impact of education on veterans' health in the United States. This study specifically examines the relationship between the education benefits from the G.I. Bill and veterans' health. Methods This study used data from the 2010 National Survey of Veterans. The subjects for this study were 5,052 veterans who were eligible to receive G.I. Bill benefits, representing a total of about 12.7 million non-institutionalized veterans in the United States in 2010. The dependent variables included self-reported health status and smoking behavior. The key independent variable was whether veterans used the education benefits from the G.I. Bill compared with those who were eligible but did not use them. Findings Results from multivariate regression analyses showed that those who used the education benefits from the G.I. Bill were 4% less likely to report fair/poor health (p < 0.01) and 3% less likely to report any smoking (p < 0.05) compared with those who did not use the education benefits. Additional analyses showed that using the education benefits to attend college decreased the probability of being in fair/poor health by 4% (p < 0.10) and being a smoker by 4% (p < 0.05) compared with those who did not attend college but used their benefits for non-college attainment such as business, technical, or vocational schools. More importantly, a larger association was found between the use of the education benefits from the G.I. Bill to obtain a college degree and fair/poor health (7%, p < 0.05) and smoking behavior (9%, p < 0.01) compared with those who attended college but did not obtain a college degree. Discussion This study shows that providing opportunities for service members to complete their education also has important health benefits.

This study examines the influence of trait anxiety on working memory (WM) in safety and threat. Interactions between experimentally induced anxiety and WM performance (on different cognitive loads) have been reported in healthy, nonanxious subjects. Differences in trait anxiety may moderate these interactions. Accordingly, these interactions may be potentiated by high trait anxiety (HTA), or show a resilient pattern that protects cognitive performance. HTA and low trait anxiety (LTA) were defined by a median split of scores on the trait component of the state-trait anxiety inventory. Sustained anxiety was evoked by a probabilistic exposure to an aversive scream, and was measured by eyeblink startle and self-report. WM was tested using an n-back task (1-, 2-, and 3-back). Results revealed that, as expected, the HTA group reported greater anxiety during the task. However, trait anxiety did not impact the modulation of WM performance by induced anxiety. Notably, HTA influenced anxiety-potentiated startle (startle during threat minus startle during safe; APS) differently as a function of memory load. Accordingly, APS decreased with increasing WM load, but HTA antagonized this reduction. The HTA group showed no impairment on the 3-back WM task despite a higher APS. The amplified APS could be associated with the increase in effort-related cognitive arousal. Furthermore, this third replication of the interaction of induced anxiety by load on WM performance testifies to the robustness of the unique interplay between anxiety and WM.

A simple, rapid, and highly selective RP-HPLC method was developed for the simultaneous determination of Ambrisentan (AMB) and Tadalafil (TADA) drug substances in the fixed dosage strength of 10 mg and 40 mg, respectively. Effective chromatographic separation was achieved using a Hypersil GOLD C18 column (150 mm × 4.6 mm internal diameter, 5 μm particle size) with a mobile phase composed of methanol, water, and acetonitrile in the ratio of 40:40:20 (by volume). The mobile phase was pumped using a gradient HPLC system at a flow rate of 0.5 mL/min, and quantification of the analytes was based on measuring their peak areas at 260 nm. The retention times for Ambrisentan and Tadalafil were about 2.80 and 7.10 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 1–20 μg/mL for Ambrisentan and 4–80 μg/mL for Tadalafil with correlation coefficients &gt, 0.990. The proposed method proved to be selective and stability-indicating by the resolution of the two analytes from the forced degradation (hydrolysis, oxidation, and photolysis) products. The validated HPLC method was successfully applied to the analysis of AMB and TADA in pharmaceutical dosage form.

A simple, rapid, and highly selective RP-HPLC method was developed for the simultaneous determination of Azelnidipine (AZL) and Olmesartan (OLM) drug substances in the fixed dosage strength of 16 mg and 20 mg, respectively. Effective chromatographic separation was achieved using a Hypersil GOLD C18 column (150 mm × 4.6 mm internal diameter, 5 μm particle size) with a mobile phase composed of methanol, acetonitrile, and water in the ratio of 40:40:20 (by volume). The mobile phase was pumped using a gradient HPLC system at a flow rate of 0.5 mL/min, and quantification of the analytes was based on measuring their peak areas at 260 nm. The retention times for Azelnidipine and Olmesartan were about 8.56 and 3.04 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 2–48 μg/mL for Azelnidipine and 2.5–60 μg/mL for Olmesartan with correlation coefficients &gt, 0.990. The proposed method proved to be selective and stability-indicating by the resolution of the two analytes from the forced degradation (hydrolysis, oxidation, and photolysis) products. The validated HPLC method was successfully applied to the analysis of AZL and OLM in their combined dosage form.

Background: Micronuclei (MN) assessment so far was done directly, individually, and intra- and, here, inter-observer bias could not be eliminated. It was subjective. Methods: In this study, accurate and reproducible MN counting was facilitated by the use of liquid cytology and image capturing with MN identification analysis. Results: Comparing the two nuclear staining techniques - DNA specific Feulgen stain and commonly available Papanicolaou (PAP) stain we found that both techniques gave statistically comparable accurate and reproducible MN results. T-test and non-parametric followed by paired non-parametric and then Wilcoxon matched-pairs signed rank test tell us that both the staining procedures have no difference at P Conclusion: These protocols are comparable and reproducible, and may be adoptable for mass screening to assess the genotoxic effects of substances like tobacco.

Although risk-taking has been studied from a developmental perspective, no study has examined how anxiety, age, risk-valence and social context interact to modulate decision-making in youths. This study probes this question using a risk-taking task, the Stunt Task, in clinically anxious children (n = 17, 10 F, age = 8.3-12.1 years), healthy children (n = 13, 4 F, age = 9.3-12.2 years), clinically anxious adolescents (n = 18, 6 F, age = 12.3-17.7 years), and healthy adolescents (n =14, 10 F, age = 12.5-17.3 years). Social context was manipulated: in one condition, participants were led to believe that a group of peers were observing and judging their performance (peer-judge), while, in the other condition, they were led to believe that peers were not observing them (control). Only anxious children showed an influence of social context on their risk-taking behavior. Specifically, anxious children bet significantly less and had slower reaction times (RT) during the peer-judge than control condition. However, across social conditions, risk-valence modulated RT differently in function of age and diagnosis. Anxious children were slower on the positive-valence risky trial, whereas anxious adolescents were slower on the negative-valence risky trials relative to their respective healthy peers. In conclusion, clinically anxious children were the only group that was sensitive (risk-averse) to the effect of a negative peer-judge context. The negative peer-judge context did not affect risky decision-making in adolescents, whether they were anxious or healthy. Future work using a stronger aversive social context might be more effective at influencing risky behavior in this age group.

Threat induces a state of sustained anxiety that can disrupt cognitive processing, and reciprocally, cognitive processing can modulate an anxiety response to threat. These effects depend on the level of cognitive engagement, which itself varies as a function of task difficulty. In adults, we recently showed that induced anxiety impaired working memory accuracy at low- and medium- but not high-load. Conversely, increasing the task load reduced the physiological correlates of anxiety (anxiety-potentiated startle). The present work examines such threat-cognition interactions as a function of age. We expected threat to more strongly impact working memory in younger individuals by virtue of putatively restricted cognitive resources and weaker emotion regulation. This was tested by examining the influence of age on the interaction of anxiety and working memory in 25 adolescents (10 to 17 years) and 25 adults (22 to 46 years). Working memory load was manipulated using a verbal n-back task. Anxiety was induced using the threat of an aversive loud scream and measured via eye-blink startle. Findings revealed that, in both age groups, accuracy was lower during threat than safe conditions at low- and medium- but not high-load, and reaction times were faster during threat than safe conditions at high-load but did not differ at other loads. Additionally, anxiety-potentiated startle was greater during low- and medium- than high-load. Thus, the interactions of anxiety with working memory appear similar in adolescents and adults. Whether these similarities reflect common neural mechanisms would need to be assessed using functional neuroimaging.

Studies have demonstrated a positive relationship between exposure and posttraumatic stress, but one's subjective appraisal of danger and threat at the time of exposure may be a better predictor of posttraumatic stress than more objective measures of exposure. We examined the role of peritraumatic response in posttraumatic stress reactions in over 2,000 middle school children 7 weeks after the 1995 Oklahoma City, Oklahoma, bombing. While many children reported hearing and feeling the blast and knowing direct victims, most were in school at the time of the explosion and therefore were not in direct physical proximity to the incident. Physical, interpersonal, and television exposure accounted for 12% of the total variance in our measure of posttraumatic stress when peritraumatic response was ignored. Peritraumatic response and television exposure accounted for 25% of the total variance, and physical and interpersonal exposure were not significant in this context. These findings suggest the importance of peritraumatic response in children's reactions to terrorism. These early responses can be used to help determine which children may experience difficulty over time.

Background: Dilated cardiomyopathy (DCM) is the most common form of heart disease, with a 50% survival rate 5yrs after diagnosis. Low thyroid hormone levels are an independent risk factor for heart failure progression. Recent studies in animal models with heart failure have shown re-expression of a fetal enzyme, type III deiodinase (D3) that functions to reduce thyroid hormone concentrations. Alternatively, an increase in β-adrenergic stimulation during heart failure may increase expression of type II deiodinase (D2) that would function to increase thyroid hormone concentration. We hypothesized that human hearts in end-stage dilated heart failure would have increased D3/D2 expression and lower myocardial and serum thyroid hormone concentrations. Methods and Results: Serum and left ventricular (LV) tissue from patients with dilated heart failure undergoing heart transplantation, and organ donors not meeting the criteria for heart donation were obtained with full consent and Institutional Review Board approval. Deiodinase expression was measures with real time rtPCR and thyroid hormone concentrations measured with radioimmunoassay. Interestingly, D3 expression and protein levels were not elevated in DCM patients vs. “non-failing” heart samples. On the other hand, D2 expression and protein levels were increased in DCM hearts and tended to have greater myocardial thyroid hormone concentrations (P =0.10). In spite of the increase in D2 expression in DCM patients, serum thyroid hormone concentrations were significantly lower than serum obtained from healthy volunteers, (P Conclusions: Contrary to our hypothesis, patients with end-stage DCM have a reduced D3/D2 expression ratio and tend to have elevated myocardial thyroid hormone concentrations. Compensatory increases in D2 expression may enhance myocardial T3 production in DCM patients; however changes in thyroid hormone receptors and downstream signaling may negate this effect. Importantly, serum T3 concentrations were significantly reduced which likely contributed to patients progression toward end stage heart failure.

A workflow is presented that integrates gene expression data, proteomic data, and literature-based manual curation to construct multicellular, tissue-specific models of human brain energy metabolism that recapitulate metabolic interactions between astrocytes and various neuron types. Three analyses are applied for gene identification, analysis of omics data, and analysis of physiological states. First, we identify glutamate decarboxylase as a target that may contribute to cell-type and regional specificity in Alzheimer’s disease. Second, the decreased metabolic rate seen in affected brain regions in Alzheimer’s disease is consistent with a suppression of central metabolic gene expression in histopathologically normal neurons. Third, we identify pathways in cholinergic neurons that couple mitochondrial metabolism and cytosolic acetylcholine production, and subsequently find that cholinergic neurotransmission accounts for ∼3% of brain neurotransmission. Constraint-based modeling can thus contribute to the study and analysis of multicellular metabolic processes in human tissues, and provide detailed mechanistic insight into high-throughput data analysis.