Lipids Fortified Nano Phytopharmaceuticals: A Breakthrough Approach in Delivering Bio-actives for Improved Therapeutic Efficacy.

Phytopharmaceuticals, derived from natural sources, manifest tremendous potential for therapeutic applications. Nevertheless, effective delivery of these bio-actives presents significant challenges. A breakthrough in fortifying phytopharmaceuticals within phosphatidylcholine is a promising remedy to overcome solubility, permeability, and other related drawbacks. This intrinsic lipid, which is obtained from both natural and synthetic sources, confers numerous benefits, encompassing heightened solubility, augmented bioavailability, and enhanced stability. The conjugation of phytopharmaceuticals with phosphatidylcholine enables improved dermal permeation, absorption, targeted distribution, and the possibility of synergistic results, eventually improving therapeutic efficacy. Additionally, the use of phytopharmaceuticals enriched with phosphatidylcholine presents a promising route for overcoming the limitations imposed by conventional delivery techniques, encouraging more effective treatments. The review provides a thorough analysis of phosphatidylcholine- incorporated phytopharmaceuticals as nanomedicine with variables that significantly affect their therapeutic efficacy. Moreover, the review elaborates on how phosphatidylcholine improves solubility, permeability, and tissue distribution and boosts the potential of phytopharmaceuticals. Further, the review underscores the significance of nano-formulation strategies, analytical methodologies, and forthcoming prospects to propel this field forward. Furthermore, the review emphasizes the potential inherent in this innovative approach while highlighting the importance of additional research endeavors and collaborative initiatives to unlock the therapeutic benefits of phosphatidylcholinefortified phytopharmaceuticals, enhancing patient well-being.

Item Level Psychometrics of the Dizziness Handicap Inventory in Vestibular Migraine and Meniere's Disease.

OBJECTIVES: Evaluate the measurement properties of the Dizziness Handicap Inventory (DHI) using item response theory in patients diagnosed with vestibular migraine (VM) and Meniere's disease (MD). DESIGN: One hundred twenty-five patients diagnosed with VM and 169 patients diagnosed with MD by a vestibular neurotologist according to the Bárány Society criteria in two tertiary multidisciplinary vestibular clinics and who completed the DHI at their initial visit, were included in the study. The DHI (total score and individual items) was analyzed using the Rasch Rating Scale model for patients in each subgroup, VM and MD, and as a whole group. The following categories were assessed: rating-scale structure, unidimensionality, item and person fit, item difficulty hierarchy, person-item match, and separation index, standard error of measurement, and minimal detectable change (MDC). RESULTS: Patients were predominantly female (80% of the VM subgroup and 68% of the MD subgroup) with a mean age of 49.9 ± 16.5 years and 54.1 ± 14.2 years, respectively. The mean total DHI score for the VM group was 51.9 ± 22.3 and for the MD group was 48.5 ± 26.6 ( p > 0.05). While neither all items nor the separate constructs met all criteria for unidimensionality (i.e., items measuring a single construct), post hoc analysis showed that the all-item analysis supported a single construct. All analyses met the criterion for showing a sound rating scale and acceptable Cronbach's alpha (≥0.69). The all-item analysis showed the most precision, separating the samples into three to four significant strata. The separate-construct analyses (physical, emotional, and functional) showed the least precision, separated the samples into less than three significant strata. Regarding MDC, the MDC remained consistent across the analyses of the different samples; approximately 18 points for the full analyses and approximately 10 points for the separate construct (physical, emotional, and functional). CONCLUSIONS: Our evaluation of the DHI using item response theory shows that the instrument is psychometrically sound and reliable. The all-item instrument fulfills criteria for essential unidimensionality but does seem to measure multiple latent constructs in patients with VM and MD, which has been reported in other balance and mobility instruments. The current subscales did not show acceptable psychometrics, which is in line with multiple recent studies favoring the use of the total score. The study also shows that the DHI is adaptable to episodic recurrent vestibulopathies. The total score shows better precision and separation of subjects in up to four strata compared to the separate construct that separate subjects into less than three strata. The measurement error smallest detectable change was found in our analysis to be 18 points, which means any change in the DHI of less than 18 points is not likely to be clinically significant. The minimal clinically important difference remains indeterminate.

Stability Indicating RP-HPLC-DAD method for simultaneous estimation of tadalafil and macitentan in synthetic mixture for treatment of pulmonary arterial hypertension.

OBJECTIVE: High Performance liquid chromatography is an integral analytical tool in assessing drug product stability. A simple, selective, precise, accurate and stability indicating RP-HPLC method was developed and validated for analysis of Tadalafil and Macitentan in synthetic mixture. MATERIAL AND METHOD: Chromatographic separation was performed using Phenomex Gemini C18 (25cm×4.6nm, 5µm) Column. The mobile phase consists of (10mM Ammonium Acetate in water and [Methanol: ACN 20: 80% v/v]) (40: 60% v/v). The flow rate was set to be 1.0mL/min. The injection volume was 10.00µL. The detection was carried out at 260nm at column temperature 35°C. RESULTS: The method was validating according to ICH Q2R1 guideline for accuracy, precision, reproducibility, specificity, robustness and detection and quantification limits. Stability testing was performed on Tadalafil and Macitentan and it was found that these degraded sufficiently in all applied chemical and physical conditions. Linearity for Tadalafil and Macitentan was observed 0.4-100µg/mL and 0.1-25µg/mL with correlation coefficient at 0.9999. LOD and LOQ 0.008µg/mL and 0.024µg/mL and 0.001µg/mL and 0.0029µg/mL for Tadalafil and Macitentan respectively. CONCLUSION: The developed RP-HPLC method was found to be suitable for the determination of both the drugs.

Secondary autoimmune immune ear disease (AIED): a systematic review and meta-analysis on vestibular manifestations of systemic autoimmune and inflammatory disorders.

Secondary autoimmune inner ear disease (AIED) is often bilateral and asymmetric in patients presenting with audiovestibular symptoms due to a systemic autoimmune disease. This systematic review and meta-analysis are aimed at identifying and highlighting patterns in prevalence of vestibular dysfunction, symptom presentation, and diagnostic methods in extant literature by combining clinical context from case reports with quantitative analyses from cohort studies. Screening of articles by title, abstract, and full text was completed by four reviewers (K.Z., A.L., S.C., and S.J.). In this study, we grouped secondary AIED and systemic autoimmune diseases by pathophysiologic mechanism: (1) connective tissue disease (CTD), (2) vasculitides (VAS), (3) systemic inflammatory disorders (SID), and (4) other immune-mediated disorders (OIMD). The search for AIED disease identified 120 articles (cohorts and case reports) that met the final inclusion criteria. All 120 were included in the qualitative review, and 54 articles were included for meta-analysis. Of these 54 articles, 22 included a control group (CwC). Ninety individual cases or patient presentations from 66 articles were included for analysis in addition to the 54 cohort articles. Secondary AIED does not have a diagnostic algorithm for managing vestibular symptoms. The management of audiovestibular symptoms requires close collaboration between otolaryngologists and rheumatologists to preserve end-organ function of the ear. To improve our ability to understand the impact on the vestibular system, vestibular clinicians need to develop a standardized reporting method. Clinical presentation should frequently be paired with vestibular testing to contextually investigate symptom severity and provide higher quality care.

Chitosan and chito-oligosaccharide: a versatile biopolymer with endless grafting possibilities for multifarious applications.

Chito-oligosaccharides (COS), derived from chitosan (CH), are attracting increasing attention as drug delivery carriers due to their biocompatibility, biodegradability, and mucoadhesive properties. Grafting, the process of chemically modifying CH/COS by adding side chains, has been used to improve their drug delivery performance by enhancing their stability, targeted delivery, and controlled release. In this review, we aim to provide an in-depth study on the recent advances in the grafting of CH/COS for multifarious applications. Moreover, the various strategies and techniques used for grafting, including chemical modification, enzymatic modification, and physical modification, are elaborated. The properties of grafted CH/COS, such as stability, solubility, and biocompatibility, were reported. Additionally, the review detailed the various applications of grafted CH/COS in drug delivery, including the delivery of small drug molecule, proteins, and RNA interference therapeutics. Furthermore, the effectiveness of grafted CH/COS in improving the pharmacokinetics and pharmacodynamics of drugs was included. Finally, the challenges and limitations associated with the use of grafted CH/COS for drug delivery and outline directions for future research are addressed. The insights provided in this review will be valuable for researchers and drug development professionals interested in the application of grafted CH/COS for multifarious applications.

Safely Shaping the Breast After Implant Removal and Total Intact Capsulectomy Using the Mammary Imbrication Lift and Fixation Technique.

Background: Implant-based breast augmentation is one of the most popular plastic surgery procedures performed worldwide. As the number of patients who have breast implants continues to rise, so does the number of those who request breast implant removal without replacement. There is little in the current scientific literature describing total intact capsulectomy and simultaneous mastopexy procedures. Objectives: Here, the authors present their current method using the mammary imbrication lift and fixation technique after explant and total capsulectomy. Methods: Between 2016 and 2021, a total of 64 patients (mean age: 42.95 years; range, 27-78 years) underwent the described mammary imbrication lift and fixation technique with bilateral breast implant removal and total capsulectomy. Results: Mean follow-up was 6.5 months (range, 1-36 months). Postoperative complications included minor cellulitis in 1 patient (1.6%), late onset hematoma with infection in 1 patient (1.6%), fat necrosis and pulmonary embolism in 1 patient with prior history of thromboembolic events (1.6%), and breast scar irregularity in 4 patients (6.2%) who required subsequent minor scar revision or steroid injections. Two patients (1.6%) underwent revision surgery with bilateral breast fat grafting to improve shape and add volume. Conclusions: The mammary imbrication lift and fixation technique described here can safely and simultaneously be performed with a total intact capsulectomy and explant procedure. This technique avoids wide undermining, intentionally opening the capsule, performing subtotal capsulectomy, and preserving blood supply to the breast tissue and nipple with low complication rates.

Otolaryngologic Presentations to Emergency Departments During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

OBJECTIVES: To perform a systematic review of otolaryngologic presentation rates to emergency department settings before and after lockdown due to the COVID-19 pandemic. SOURCES: PubMed, Scopus, and CINAHL. METHODS: A systematic search was conducted following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses) for studies describing otolaryngologic presentations to emergency department and rapid access clinic settings both in the before-lockdown and after-lockdown periods. The start of after-lockdown period varied based on initiation of lockdown, ranging from March 1st to June 1st of 2020 across general emergency department studies. RESULTS: A total of 14 studies were included in this review. About 10 were general emergency departments, 3 were specifically pediatric emergency departments, and 1 study focused on the geriatric population (>65 years). A total of 13 790 patients were included, with 9446 in the before-lockdown period (68.5%) and 4344 in the after-lockdown period (31.5%). Meta-analysis of proportions for otolaryngologic presentations across general emergency departments was performed. Comparison of weighted proportions found significant differences between before-lockdown and after-lockdown presentation rates for infectious etiologies, tonsillitis specifically, foreign bodies, non-infectious airway issues, and epistaxis among these studies. CONCLUSIONS: The increased proportions of various non-infectious presentations (eg, epistaxis, foreign bodies, and airway issues) following lockdown might be associated with proportional decreases in infectious pathologies, given decreased social contact to prevent SARS-CoV-2 transmission. Overall, it is important for otolaryngologists to recognize what presentations might more commonly be seen and require evaluation and potential intervention in light of a global pandemic.

Diagnostic accuracy and management concordance of otorhinolaryngological diseases through telehealth or remote visits: A systematic review & meta-analysis.

INTRODUCTION: COVID-19 has led to delays in providing healthcare in both emergency and non-emergency settings, especially in surgical subspecialties which rely heavily on referrals and in-person visits. Without an established telehealth infrastructure, many otorhinolaryngological departments experienced decreases in consultations. Telemedicine has attempted to bridge the gap between pre- and post-pandemic periods by creating a safe avenue of communication between otorhinolaryngologists and patients. This review hopes to address the accuracy of telemedicine in patient diagnosis and management. METHODS: Searches were conducted since study conception until June 30, 2022, on multiple databases including PubMed, SCOPUS, and CINAHL for this systematic review and meta-analysis. Diagnostic accuracy, management accuracy, kappa, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were meta-analyzed by comparing virtual visits to in-person visits (gold standard). RESULTS: Nineteen studies were included in this review. A total of 1518 patients were included across all studies. When comparing virtual visits against in-person visits, accurate diagnosis was made in 86.2% [82.1,89.9, I2 = 73.5%, P < 0.0001] of patients and management accuracy was 91.5% [86.1,95.7, I2 = 81.8%, P < 0.0001] when treating patients. Kappa value determining interrater reliability was 0.8 [0.7,0.9, I2 = 81.8%, P < 0.0001]. CONCLUSION: Our data suggest that diagnostic and management concordance is above 80% when comparing diagnosis and management strategies in patients who underwent both telehealth and in-person visits with an otorhinolaryngologist. In uncomplicated patients, telehealth might be a reliable source for diagnosis and management however, in-person consultation is likely still required for pathologies in which physical exam, imaging or procedural elements represent a vital component of the work-up.

Disease-Modifying Antirheumatic Drugs in the Treatment of Autoimmune Inner Ear Disease: A Systematic Review and Meta-Analysis of Auditory and Vestibular Outcomes.

OBJECTIVE: To answer the following question: In patients with primary autoimmune inner ear disease (AIED), (population) what impact do disease-modifying antirheumatic agents (DMARDs) (intervention) when compared with no treatment or corticosteroids (comparison) have on auditory and vestibular outcomes (outcome)? STUDY DESIGN: Systematic review and meta-analysis. DATA SOURCES: According to PRISMA guidelines, PubMed, Scopus, CINAHL, and Cochrane Library databases were searched from inception to March 10, 2022. STUDY SELECTION: Studies of patients receiving DMARDs for the treatment of AIED were selected for review. Case reports, phase I/II trials, studies of patients with secondary AIED, and studies of AIED patients receiving solely corticosteroids were excluded. DATA EXTRACTION: Primary outcomes were pure-tone audiometry and speech discrimination scores at baseline and after DMARD treatment. Secondary outcomes were rates of subjective audiovestibular complaints and rates of adverse reactions. No objective vestibular outcomes underwent meta-analysis. DATA SYNTHESIS: Mean differences were calculated using RevMan 5.4. Heterogeneity was assessed with the Q test and I2 statistic. Pooled prevalence rates of audiovestibular symptoms were expressed as a percentage with 95% confidence intervals. RESULTS: Ten studies with a total of 187 patients were included. Treatments included methotrexate, etanercept, azathioprine, anakinra, cyclophosphamide, rituximab, and infliximab. Mean treatment duration was 10.8 ± 22.2 months and mean follow-up was 13.7 ± 8.1 months. The pure-tone audiometry and speech discrimination scores mean differences between baseline and post-DMARD were -2.1 [-4.1, -0.1] dB and 13.9 [8.5, 19.4] %, respectively. Seven studies reported 38 adverse events, four of which were classified as serious. CONCLUSION: DMARDs showed statistically significant improvement in auditory outcomes, as well as subjective symptoms, with relatively low rates of adverse events. They warrant further exploration to better compare with corticosteroids.

Systematic review of cochlear implantation in patients with inner ear malformations.

OBJECTIVES: To evaluate the outcomes of cochlear implantation in patients with severe to profound sensorineural hearing loss due to inner ear malformations (IEMs) when compared to patients without IEMs. We discussed audiological outcomes such as open-set testing, closed-set testing, CAP score, and SIR score as well as postoperative outcomes such as cerebrospinal fluid gusher and incomplete insertion rate associated with cochlear implantation in individuals with IEMs. DATA SOURCES: PubMed, Science Direct, Web of Science, Scopus, and EMBASE databases. REVIEW METHODS: After screening a total of 222 studies, twelve eligible original articles were included in the review to analyze the speech and hearing outcomes of implanted patients with IEMs. Five reviewers independently screened, selected, and extracted data. The "Tool to Assess Risk of Bias in Cohort Studies" published by the CLARITY group was used to perform quality assessment on eligible studies. Systematic review registration number: CRD42021237489. RESULTS: IEMs are more likely to be associated with abnormal position of the facial nerve, raising the risk of intraoperative complications. These patients may benefit from cochlear implantation, but audiological outcomes may also be less favorable than in individuals without IEMs. Furthermore, due to the risk of cerebrospinal fluid gusher, incomplete insertion of electrodes, and postoperative facial nerve stimulation, surgeons can employ precautionary measures such as preoperative imaging and proper counseling. Postoperative imaging is suggested to be beneficial in ensuring proper electrode placement. CONCLUSIONS: Cochlear implants (CIs) have the potential to provide auditory rehabilitation to individuals with IEMs. Precise classification of the malformation, preoperative imaging and anatomical mapping, appropriate electrode selection, intra-operative techniques, and postoperative imaging are recommended in this population.

Amelioration of intracerebroventricular streptozotocin-induced cognitive dysfunction by Ocimum sanctum L. through the modulation of inflammation and GLP-1 levels.

DPP-4 inhibitors have been shown to reverse amyloid deposition in Alzheimer's disease (AD) patients with cognitive impairment. Ocimum sanctum L. leaves reported the presence of important phytoconstituents which are reported to have DPP-4 inhibitory activity. To investigate the effects of petroleum ether extract of Ocimum sanctum L. (PEOS) in Intracerebroventricular streptozotocin (ICV-STZ) induced AD rats. ICV-STZ (3 mg/kg) was injected bilaterally into male Wistar rats, while sham animals received the artificial CSF. The ICV-STZ-induced rats were administered with three doses of PEOS (100, 200, and 400 mg/kg, p.o.) for thirty days. All experimental rats were subjected to behaviour parameters (radial arm maze task and novel object recognition test), neurochemical parameters such as GLP-1, Aß42, and TNF-α levels, and histopathological examination (Congo red staining) of the left brain hemisphere. PEOS significantly reversed the spatial learning and memory deficit exhibited by ICV-STZ-induced rats. Furthermore, PEOS also shows promising results in retreating Aß deposition, TNF α, and increasing GLP-1 levels. The histopathological study also showed a significant dose-dependent reduction in amyloid plaque formation and dense granule in PEOS -treated rats as compared to the ICV-STZ induced rats (Negative control). The results show that extract of Ocimum sanctum L. attenuated ICV-STZ-induced learning and memory deficits in rats and has the potential to be employed in the therapy of AD.

Lipid-based emulsion drug delivery systems - a comprehensive review.

Lipid-based emulsion system - a subcategory of emulsion technology, has emerged as an enticing option to improve the solubility of the steadily rising water-insoluble candidates. Along with enhancing solubility, additional advantages such as improvement in permeability, protection against pre-systemic metabolism, ease of manufacturing, and easy to scale-up have made lipid-based emulsion technology very popular among academicians and manufacturers. The present article provides a comprehensive review regarding various critical properties of lipid-based emulsion systems, such as microemulsion, nanoemulsion, SMEDDS (self microemulsifying drug delivery system), and SNEDDS (self nanoemulsifying drug delivery system). The present article also explains in detail the similarities and differences between them, the stabilization mechanism, methods of preparation, excipients used to prepare them, and evaluation techniques. Subtle differences between nearly related terminologies such as microemulsion and nanoemulsion, SMEDDS, and SNEDDS are also explained in detail to clarify the basic differences. The present article also gives in-depth information regarding the chemical structure of various lipidic excipients, various possible chemical modifications to modify their inherent properties, and their regulatory status for rational selection.

Effect of Postoperative Radiation Therapy Timing on Survival in Pediatric and Young Adult Ependymoma.

PURPOSE: Postoperative radiation therapy (RT) is commonly used for World Health Organization grade II-III intracranial ependymoma. Clinicians generally aim to begin RT ≤5 weeks after surgery, but postoperative recovery and need for second look surgery can delay the initiation of adjuvant therapy. On ACNS 0831, patients were required to enroll ≤8 weeks after initial surgery and begin adjuvant therapy within 3 weeks after enrollment. The purpose of this study was to determine the optimal timing of RT after surgery. METHODS AND MATERIALS: The National Cancer Database was queried for patients (aged 1-39 years) with localized World Health Organization grade II-III intracranial ependymoma treated with surgery and postoperative RT. Overall survival (OS) curves were plotted based on RT timing (≤5 weeks, 5-8 weeks, and >8 weeks after surgery) and were compared by log-rank test. Factors associated with OS were identified by multivariate analysis. After 2009, complete data were available on whether patients underwent gross total resection or subtotal resection. Planned subset analysis was performed to examine the effect of RT timing on OS in patients with known extent of resection. RESULTS: In the final analytical data set of 1043 patients, no difference in 3-year OS was observed in patients who initiated RT ≤5 weeks, 5 to 8 weeks, and >8 weeks after surgery (89.8% vs 89.1% vs 88.4%; P = .796). On multivariate analysis, grade III tumors (hazard ratio, 2.752; 95% confidence interval, 1.969-3.846, P < .001) and subtotal resection (hazard ratio, 2.253; 95% confidence interval, 1.405-3.611, P < .001) were significantly associated with reduced OS. Timing of RT, total RT dose, age, and other factors were not significant. These findings were affirmed in the subset of patients treated between 2010 and 2016, when extent of resection was routinely recorded. CONCLUSIONS: Delayed postoperative RT was not associated with inferior survival in patients with intracranial ependymoma. Delayed RT initiation may be acceptable in patients who require longer postoperative recovery or referral to an appropriate RT center, but should be minimized whenever practical.

Development and Optimization of Inhalable Levofloxacin Nanoparticles for The Treatment of Tuberculosis.

BACKGROUND: Levofloxacin has been recommended by the WHO for the treatment of pulmonary tuberculosis and inhalable delivery of levofloxacin can be advantageous over conventional delivery. OBJECTIVE: This study aimed to develop and optimize inhalable levofloxacin Loaded Chitosan Nanoparticles (LCN). The objective was to achieve the mean particle size of LCN less than 300nm, sustain the drug release up to 24 h, and achieve MMAD of LCN of less than 5µm. METHODS: LCN were prepared by ionic gelation of chitosan with sodium tripolyphosphate (STPP) and subsequent lyophilization. A Plackett Burman screening design, 32 full factorial design, and overlay plots were sequentially employed to optimize the formulation. The mean particle size, % entrapment efficiency, in vitro drug release, and minimum inhibitory concentration were all evaluated. RESULTS: The Pareto chart from the Placket Burman screening design revealed that the concentrations of chitosan and STPP was found to be significant (p < 0.05). Further analysis by 32 full factorial design revealed that F-ratio for each model generated was found to be greater than the theoretical value (p < 0.05), confirming the significance of each model. CONCLUSION: The optimized formulation showed a mean particle size of 171.5 nm, sustained the drug release up to 24 h in simulated lung fluid, and revealed MMAD of 3.18 µm, which can confirm delivery of the drug to the deep lung region. However, further in vivo studies are required to design a suitable dosage regimen and establish the fate of nanoparticles for safe and efficacious delivery of the drug.

Pharmacokinetics and in vivo distribution of optimized PLGA nanoparticles for pulmonary delivery of levofloxacin.

OBJECTIVES: The aim of this study was to develop and optimize levofloxacin loaded PLGA nanoparticles (LN) for pulmonary delivery employing screening and experimental design and evaluate their in-vitro and in-vivo performance. The objective was to achieve Mass Median Aerodynamic Diameter (MMAD) of LN of less than 5µm, sustain the drug release up to 120 h and a higher AUC/MIC at the site of action. METHODS: LN were prepared by modified emulsion solvent evaporation technique employing high speed homogenization, probe sonication and subsequent lyophilization. KEY FINDINGS: The Pareto chart from Placket Burman screening design revealed that homogenization speed and amount of PLGA were found to be significant (P < 0.05). Further analysis by 3 full-factorial design revealed that F-ratio was found to be far greater than the theoretical value (P < 0.05) for each regression model. CONCLUSION: The optimized formulation with desirability value 0.9612 showed mean particle size of 146 nm, MMAD of 4.40 µm and sustained the drug release up to 120 h in simulated lung fluid. Augmentation in Cmax (1.71-fold), AUC 0-∞ (5.46-fold), Mean Residence Time (6.64-fold) and AUC/MIC (6.21-fold) of LN through pulmonary route was found to significantly higher (P < 0.05) than levofloxacin (p. o.).

An approach to evaluate myocardial perfusion defect assessment for projection-based DECT: A phantom study.

INTRODUCTION: Dual-energy CT (DECT) can improve the accuracy of myocardial perfusion CT with projection-based monochromatic (DECT-MCE) and quantification of myocardial iodine in material decomposition (DECT-MD) reconstructions. However, evaluation of multiple reconstructions is laborious and the optimal reconstruction to detect myocardial perfusion defects is unknown. METHODS: Left ventricular (LV) phantoms with artificial perfusion defects were scanned using DECT and single energy cardiac computed tomography angiography (SECT). Reconstructions of DECT-MCE at 40, 70, 100 and 140 keV, DECT-MD pairs of water, iodine, iron and fat, and SECT were evaluated using a 17-segment myocardial model. The diagnostic performance of each reconstruction was calculated on a per-segment basis and compared across DECT reconstructions. RESULTS: Over 34 phantoms with artificial perfusion defects were found in 64/578 (11%) of segments, the sensitivity of DECT-MCE at 40, 70, 100, and 140 keV was 100% (95% confidence interval (CI): 93-100), 100% (95% CI: 93-100), 71% (95% CI: 56-83), and 25% (95% CI: 14-40), respectively, with a significant decline between 70 keV and 100 keV (p < 0.001). The specificity of DECT-MCE was 100% at all energies (95% CI: 99-100). As a group, the DECT-MD iodine background reconstructions had significantly lower sensitivity than the remaining modes (2.1% [95% CI, 0.05-11.1], vs. 100% [95% CI, 92.6-100], p < 0.001). Specificity of all material pair modes remained 100%. CONCLUSIONS: Using LV phantom models, the approach with the best sensitivity and specificity to assess myocardial perfusion defects with DECT are reconstructions of DECT-MCE at 40 or 70 KeV and DECT-MD without iodine background.

A rodent cage change insomnia model disrupts memory consolidation.

Insomnia involves disruption of sleep initiation, maintenance and/or overall quality, and may interfere with cognition. Here, we evaluated memory impairment produced by rodent mild (acute) insomnia models. Insomnia models consisted of either single or repeated exposure to cages previously occupied (dirtied) by an unfamiliar rat for 5-7 days. Rats were trained in the Morris water maze to remember the platform location (acquisition), and were then exposed to: (a) 6 hr of undisturbed baseline; (b) dirty cage change-induced insomnia (animal placed into a cage dirtied by another rat for 6 hr); or (c) double-dirty cage change-induced insomnia (animal placed into a cage dirtied by another rat for 3 hr, and then another dirty cage 3 hr later). The animal's memory for the platform location was then evaluated in a probe trial. Double-dirty cage change-induced insomnia significantly disrupted sleep, although the effects of dirty cage change-induced insomnia were overall not significant. In the fourth hour of double-dirty cage change-induced insomnia (following the second cage change), sleep episode number and duration alterations indicated sleep fragmentation. Furthermore, power spectral analysis revealed diminished wake and, to a lesser extent, rapid eye movement theta power (indicated by trend difference) in the last 3 hr of exposure. Significant deficits were noted for measures of water maze performance following double-dirty cage change-induced insomnia, indicating impaired memory. In summary, one variant of the rodent insomnia model, double-dirty cage change-induced insomnia, disrupted sleep and attenuated memory consolidation, indicating this paradigm may be useful to evaluate the effects of hypnotics on memory consolidation.

Current Technologies and Recent Developments for Screening of HPV-Associated Cervical and Oropharyngeal Cancers.

Mucosal infection by the human papillomavirus (HPV) is responsible for a growing number of malignancies, predominantly represented by cervical cancer and oropharyngeal squamous cell carcinoma. Because of the prevalence of the virus, persistence of infection, and long latency period, novel and low-cost methods are needed for effective population level screening and monitoring. We review established methods for screening of cervical and oral cancer as well as commercially-available techniques for detection of HPV DNA. We then describe the ongoing development of microfluidic nucleic acid-based biosensors to evaluate circulating host microRNAs that are produced in response to an oncogenic HPV infection. The goal is to develop an ideal screening platform that is low-cost, portable, and easy to use, with appropriate signal stability, sensitivity and specificity. Advances in technologies for sample lysis, pre-treatment and concentration, and multiplexed nucleic acid detection are provided. Continued development of these devices provides opportunities for cancer screening in low resource settings, for point-of-care diagnostics and self-screening, and for monitoring response to vaccination or surgical treatment.

Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.