Left Ventricular Dysfunction Correlates With Mortality in Pulmonary Embolism.

BACKGROUND: Risk stratification of patients with pulmonary embolism (PE) is essential to guide advanced interventional management and proper disposition. OBJECTIVES: In this study, we sought to assess individual echocardiographic markers of right ventricular (RV) strain and left ventricular (LV) function in patients with high-risk PE and identify their association with the need for advanced intervention (such as thrombolysis) and 30-day mortality. METHODS: This was a retrospective study of ED patients with PE who were subject to a pulmonary embolism response team activation over a 5-year period. Cardiac point-of-care ultrasound studies were performed as part of patient care and later assessed for septal bowing, RV hypokinesis, McConnell sign, RV enlargement, tricuspid annular place systolic excursion, and LV systolic dysfunction. Outcome variables included need for advanced intervention and 30-day mortality. RESULTS: The pulmonary embolism response team was activated in 893 patients, of which 718 had a confirmed PE. Of these, 90 had adequate cardiac point-of-care ultrasound images available for review. Patients who needed an advanced intervention were more likely to have septal bowing (odds ratio [OR] 8.69, 95% confidence interval [CI] 2.37-31.86), RV enlargement (OR 4.02, 95% CI 1.43-11.34), and a McConnell sign (OR 2.79, 95% CI 1.09-7.13). LV dysfunction was the only statistically significant predictor of 30-day mortality (OR 9.63, 95% CI 1.74-53.32). CONCLUSION: In patients with PE in the ED, sonographic findings of RV strain that are more commonly associated with advanced intervention included septal bowing, McConnell sign, and RV enlargement. LV dysfunction was associated with a higher 30-day mortality. These findings can help inform decisions about ED management and disposition of patients with PE.

Denosumab: a potential treatment option for aneurysmal bone cyst of the atlas.

PURPOSE: Aneurysmal bone cysts (ABCs) of spine are conventionally treated with en-bloc resection or intralesional excision/curettage and reconstruction or filling of defects with bone cement. For the treatment of upper cervical ABCs, en-bloc resections are often not desirable considering the risk/benefit ratio while the risk of recurrence after intralesional excision is high. Hence, alternative management options are often necessary. We describe our clinical experience with one such treatment alternative-denosumab for the treatment of ABC of Atlas. METHODS AND RESULTS: We present a case of 16-year-old boy who presented with neck pain and restriction of neck movements. A large lytic lesion with multiple fluid-fluid interfaces involving vertebral arch of atlas was identified on further imaging. There was destruction of right lateral mass and the lesion was found encasing the right vertebral artery. Core needle biopsy confirmed the diagnosis of ABC. With no visible CT response after first session of intra-lesional injection of Calcitonin and Methylprednisolone, the patient was treated with denosumab (120 mg SC once-a-month) for a period of 12 months. His symptoms resolved within 7 months of onset of treatment and serial CT scans over 12-month treatment period showed complete ossification of the lesion. Further there was no evidence of recurrence at 12 months after completion of treatment. CONCLUSION: Our case report contributes to the accruing evidence on the effectiveness of denosumab for the treatment of spinal ABCs. However, long-term safety, risk of recurrence, optimal duration of treatment and consistency of denosumab are yet to be determined.

Basic concepts in metal work failure after metastatic spine tumour surgery.

PURPOSE: The development of spinal implants marks a watershed in the evolution of metastatic spine tumour surgery (MSTS), which has evolved from standalone decompressive laminectomy to instrumented stabilization and decompression with reconstruction when necessary. Fusion may not be feasible after MSTS due to poor quality of graft host bed along with adjunct chemotherapy and/or radiotherapy postoperatively. With an increase in the survival of patients with spinal tumours, there is a probability of an increase in the rate of implant failure. This review aims to help establish a clear understanding of implants/constructs used in MSTS and to highlight the fundamental biomechanics of implant/construct failures. METHODS: Published literature on implant failure after spine surgery and MSTS has been reviewed. The evolution of spinal implants and their role in MSTS has been briefly described. The review defines implant/construct failures using radiological parameters that are practical, feasible, and derived from historical descriptions. We have discussed common modes of implant/construct failure after MSTS to allow further understanding, interception, and prevention of catastrophic failure. RESULTS: Implant failure rates in MSTS are in the range of 2-8%. Variability in patterns of failure has been observed based on anatomical region and the type of constructs used. Patients with construct/implant failures may or may not be symptomatic and present either as early (< 3months) or late failures (> 3months). It has been noted that not all the implant failures after MSTS result in revisions. CONCLUSION: Based on the observed radiological criteria and clinical presentations, we have proposed a clinico-radiological classification for implant/construct failure after MSTS.

Advanced Targeted Drug Delivery of Bioactive Agents Fortified with Graft Chitosan in Management of Cancer: A Review.

Cancer is characterized by the uncontrolled proliferation and spread of abnormal cells in the body, resulting in the development of tumors or clusters of irregular cells. The factors contributing to cancer are intricate, involving a combination of genetic, environmental, and lifestyle elements. Risk factors for cancer include the use of nicotine, excessive alcohol consumption, exposure to radiation or specific chemicals, and a family history of the disease. Common treatment methods for cancer encompass surgery, radiation therapy, chemotherapy, immunotherapy, and targeted therapy. These treatments aim to eliminate cancer cells while minimizing harm to healthy cells. Recent research has extensively explored the potential of bioactive compounds as agents for combating cancer. However, effectively delivering such compounds to specific target sites is a complex undertaking. Consequently, there has been widespread exploration of polymer applications in the development of nanomedicine for delivering bioactive substances. Additionally, the technique of grafting native excipients onto polymers has been investigated to enhance their versatility in the delivery of these compounds to specific tumor cells. This review offers a brief yet informative summary of how grafted chitosan is employed as a delivery system for bioactive phytopharmaceuticals possessing anticancer properties. In essence, it delves into the use of grafted chitosan in facilitating the transport and targeted release of these natural compounds that have demonstrated potential in combating cancer. This innovative approach has the potential to enhance the effectiveness of anticancer treatments and minimize their adverse effects on healthy cells.

The Astonishing Accomplishment of Biological Drug Delivery using Lipid Nanoparticles: An Ubiquitous Review.

Biotech drugs, including proteins, hormones, enzymes, DNA/RNA therapies, and cell-based treatments, are gaining popularity due to their effectiveness. However, effective delivery systems are needed to overcome administration challenges. Lipid nanoparticles (LNPs) have emerged as promising carriers for various therapies. LNPs are biocompatible, less likely to cause adverse reactions, and can stabilize delicate biological drugs, enhancing their stability and solubility. Scalable and cost-effective manufacturing processes make LNPs suitable for largescale production. Despite recent research efforts, challenges in stability, toxicity, and regulatory concerns have limited the commercial availability of LNP-based products. This review explores the applications, administration routes, challenges, and future directions of LNPs in delivering biopharmaceuticals.

Nanotechnology-Powered Meningitis Therapies: Lipid Nanoparticles Lead the Way.

The meninges serve as a protective layer, and the fluid around the brain and spinal cord can become inflamed, known as meningitis. Lipid-based pharmaceutical formulations, by their high lipophilicity, can negotiate the Blood-Brain Barrier (BBB). The current mode of treatment of meningitis is mainly through antibiotics, which, at best, is partially effective. The success of antibiotic therapy depends on several factors, for example, the difficulty of reaching the infection site, maintaining proper concentrations of the drug after crossing the BBB, and finally, its efficacy in preventing recurrent infection. In this context, interest has focused on organic and inorganic nanostructures for meningitis and transporting antibiotics to the selected region through the BBB. A focus has also been placed on several polymeric nanotechnology techniques for detecting various types of meningitis. This review focuses on nano interventions and their most recent meningitis treatments using nanotechnology.

Recent Review on Biological Barriers and Host-Material Interfaces in Precision Drug Delivery: Advancement in Biomaterial Engineering for Better Treatment Therapies.

Preclinical and clinical studies have demonstrated that precision therapy has a broad variety of treatment applications, making it an interesting research topic with exciting potential in numerous sectors. However, major obstacles, such as inefficient and unsafe delivery systems and severe side effects, have impeded the widespread use of precision medicine. The purpose of drug delivery systems (DDSs) is to regulate the time and place of drug release and action. They aid in enhancing the equilibrium between medicinal efficacy on target and hazardous side effects off target. One promising approach is biomaterial-assisted biotherapy, which takes advantage of biomaterials' special capabilities, such as high biocompatibility and bioactive characteristics. When administered via different routes, drug molecules deal with biological barriers; DDSs help them overcome these hurdles. With their adaptable features and ample packing capacity, biomaterial-based delivery systems allow for the targeted, localised, and prolonged release of medications. Additionally, they are being investigated more and more for the purpose of controlling the interface between the host tissue and implanted biomedical materials. This review discusses innovative nanoparticle designs for precision and non-personalised applications to improve precision therapies. We prioritised nanoparticle design trends that address heterogeneous delivery barriers, because we believe intelligent nanoparticle design can improve patient outcomes by enabling precision designs and improving general delivery efficacy. We additionally reviewed the most recent literature on biomaterials used in biotherapy and vaccine development, covering drug delivery, stem cell therapy, gene therapy, and other similar fields; we have also addressed the difficulties and future potential of biomaterial-assisted biotherapies.

Advancing against drug-resistant tuberculosis: an extensive review, novel strategies and patent landscape.

Drug-resistant tuberculosis (DR-TB) represents a pressing global health issue, leading to heightened morbidity and mortality. Despite extensive research efforts, the escalation of DR-TB cases underscores the urgent need for enhanced prevention, diagnosis, and treatment strategies. This review delves deep into the molecular and genetic origins of different types of DR-TB, highlighting recent breakthroughs in detection and diagnosis, including Rapid Diagnostic Tests like Xpert Ultra, Whole Genome Sequencing, and AI-based tools along with latest viewpoints on diagnosis and treatment of DR-TB utilizing newer and repurposed drug molecules. Special emphasis is given to the pivotal role of novel drugs and discusses updated treatment regimens endorsed by governing bodies, alongside innovative personalized drug-delivery systems such as nano-carriers, along with an analysis of relevant patents in this area. All the compiled information highlights the inherent challenges of current DR-TB treatments, discussing their complexity, potential side effects, and the socioeconomic strain they impose, particularly in under-resourced regions, emphasizing the cost-effective and accessible solutions. By offering insights, this review aims to serve as a compass for researchers, healthcare practitioners, and policymakers, emphasizing the critical need for ongoing R&D to improve treatments and broaden access to crucial TB interventions.

Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration.

The number of patients with ocular disorders has increased due to contributing factors such as aging populations, environmental changes, smoking, genetic abnormalities, etc. Age-related macular degeneration (AMD) is one of the common ocular disorders which may advance to loss of vision in severe cases. The advanced form of AMD is classified into two types, dry (non-exudative) and wet (exudative) AMD. Although several therapeutic approaches are explored for the management of AMD, no approved therapy can substantially slow down the progression of dry AMD into the later stages. The focus of researchers in recent times has been engaged in developing targeted therapeutic products to halt the progression and maintain or improve vision in individuals diagnosed with AMD. The delivery of anti-VEGF agents using intravitreal therapy has found some success in managing AMD, and novel formulation approaches have been introduced in various studies to potentiate the efficacy. Some of the novel approaches, such as hydrogel, microspheres, polymeric nanoparticles, liposomes, implants, etc. have been discussed. Apart from this, subretinal, suprachoroidal, and port delivery systems have also been investigated for biologics and gene therapies. The unmet potential of approved therapeutic products has contributed to several patent applications in recent years. This review outlines the current treatment options, outcomes of recent research studies, and patent details around the novel drug delivery approach for the treatment of AMD.

Phosphatidylcholine (PCL) fortified nano-phytopharmaceuticals for improvement of therapeutic efficacy.

Phytopharmaceuticals, derived from plants, are increasingly recognized for their potential therapeutic benefits. However, their effectiveness is often hindered by challenges such as poor bioavailability, stability, and targeted delivery. In this study, we aimed to address these limitations by developing PCL (phosphatidylcholine) fortified nano-phytopharmaceuticals to enhance therapeutic efficacy. PCL, a biocompatible and biodegradable polymer, was employed to encapsulate the phytopharmaceuticals, thereby improving their stability and bioavailability. The encapsulation process utilized nanoprecipitation, resulting in the formation of nanoparticles with controlled size and morphology. Various analytical techniques were employed to characterize the physicochemical properties of PCL fortified nano-phytopharmaceuticals, including dynamic light scattering, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Furthermore, the release kinetics of encapsulated phytopharmaceuticals from PCL nanoparticles were evaluated, demonstrating sustained and controlled release profiles, essential for prolonged therapeutic effects. Cytotoxicity studies conducted on in vitro cell culture models confirmed the biocompatibility and non-toxic nature of the developed nano-phytopharmaceuticals. Additionally, in vivo studies were conducted to assess the therapeutic efficacy of PCL fortified nano-phytopharmaceuticals in animal models. The results showIased improved bioavailability, targeted tissue distribution, and enhanced therapeutic effects compared to free phytopharmaceuticals. Moreover, the developed nano-phytopharmaceuticals exhibited prolonged circulation time in the bloodstream, enabling improved drug delivery and reduced dosing frequency. This review highlights the promising potential of PCL fortified nano-phytopharmaceuticals as an effective approach for enhancing the therapeutic efficacy of phytopharmaceuticals. The improved stability, bioavailability, sustained release, and targeted delivery achieved through this formulation strategy offer promising opportunities for advancing plant-based therapies. See also the Graphical abstract(Fig. 1).

Chitosan-Based Hydrogel in the Management of Dermal Infections: A Review.

The main objective of this review is to provide a comprehensive overview of the current evidence regarding the use of chitosan-based hydrogels to manage skin infections. Chitosan, a naturally occurring polysaccharide derived from chitin, possesses inherent antimicrobial properties, making it a promising candidate for treating various dermal infections. This review follows a systematic approach to analyze relevant studies that have investigated the effectiveness of chitosan-based hydrogels in the context of dermal infections. By examining the available evidence, this review aims to evaluate these hydrogels' overall efficacy, safety, and potential applications for managing dermal infections. This review's primary focus is to gather and analyze data from different recent studies about chitosan-based hydrogels combating dermal infections; this includes assessing their ability to inhibit the growth of microorganisms and reduce infection-related symptoms. Furthermore, this review also considers the safety profile of chitosan-based hydrogels, examining any potential adverse effects associated with their use. This evaluation is crucial to ensure that these hydrogels can be safely utilized in the management of dermal infections without causing harm to patients. The review aims to provide healthcare professionals and researchers with a comprehensive understanding of the current evidence regarding the use of chitosan-based hydrogels for dermal infection management. The findings from this review can contribute to informed decision-making and the development of potential treatment strategies in this field.

Design and optimization of curcumin loaded nano lipid carrier system using Box-Behnken design.

Herbal antioxidant like curcumin holds great potential to treat neurodegenerative disease like Alzheimer's disease. However, its therapeutic potency is obstructed due to rapid metabolism, poor solubility, GI susceptibility, enzymatic degradation and lower bioavailability. Thus, the present work aimed to design and optimize curcumin-loaded NLC (CNL) with higher drug entrapment, prolonged release and better stability. CNL was prepared by modified melt emulsification method followed by ultrasonication. The formulation was optimized by 3 factor 3 level Box-Behnken design using solid: liquid lipid, surfactant concentration and ultrasonication time as independent variable while particle size, entrapment efficiency and % drug release as dependant variable. The design suggested 3.092 solid:liquid lipid, 2.131% surfactant and 4.757 min ultrasonication fit best to get the optimized formulation. The size of the optimized CNL was noted 124.37 ± 55.81 nm, which is in the acceptable range for brain delivery. SEM results also comply with this size range (near 150 nm) and demonstrated almost spherical and uniform particles with porous and uneven surface structures. PDI, zeta potential, entrapment efficiency and % drug release were observed as 0.201 ± 0.00, - 17.2 ± 2.35 mV, 93.62 ± 0.68% and 92.73 ± 0.06%, respectively. The NLC demonstrated initial burst release with subsequent prolonged release of drug for 48 h. Weibull kinetic equation with 0.9958 R2, minimum AIC and maximum MSC value was found best fit to explain the release behavior. The ß exponent and diffusional coefficient (n) indicated combined release mechanism with Fickian diffusion as drug release mechanism. Formulation was also found stable at different storage condition.

Asymptomatic Construct Failure after Metastatic Spine Tumor Surgery: A New Entity or a Continuum with Symptomatic Failure?

STUDY DESIGN: Retrospective cohort study. PURPOSE: To study the incidence, onset, underlying mechanism, clinical course, and factors leading to asymptomatic construct failure (AsCF) after metastatic spinal tumor surgery (MSTS). OVERVIEW OF LITERATURE: The reported incidence rates for implant and/or construct failure after MSTS are low (1.9%-16%) and based on clinical presentations and revisions required for symptomatic failures (SFs). AsCF after MSTS has not been reported. METHODS: We conducted a retrospective analysis of 288 patients (246 for final analysis) who underwent MSTS between 2005-2015. Data collected were demographics and peri/postoperative clinical and radiological features. Early and late radiological AsCF were defined as presentation before and after 3 months, respectively. We analyzed patients with AsCF for risk factors and survival duration by performing competing risk regression analyses where AsCF was the event of interest, with SF and death as competing events. RESULTS: We observed AsCF in 41/246 patients (16.7%). The mean time to onset of AsCF after MSTS was 2 months (range, 1-9 months). Median survival of patients with AsCF was 20 and 41 months for early and late failures, respectively. Early AsCF accounted for 80.5% of cases, while late AsCF accounted for 19.5%. The commonest radiologically detectable AsCF mechanism was angular deformity (increase in kyphus) in 29 patients. Increasing age (p<0.02) and primary breast (13/41, 31.7%) (p<0.01) tumors were associated with higher AsCF rates. There was a non-significant trend towards AsCF in patients with a spinal instability neoplastic score ≥7, instrumentation across junctional regions, and construct lengths of 6-9 levels. None of the patients with AsCF underwent revision surgery. CONCLUSIONS: AsCF after MSTS is a distinct entity. Most patients with early AsCF did not require intervention. Patients who survived and maintained ambulation for longer periods had late failure. Increasing age and tumors with a better prognosis have a higher likelihood of developing AsCF. AsCF is not necessarily an indication for aggressive/urgent intervention.

Symptomatic Construct Failure after Metastatic Spine Tumor Surgery.

STUDY DESIGN: Retrospective cohort study. PURPOSE: To evaluate the incidence and presentation of symptomatic failures (SFs) after metastatic spine tumor surgery (MSTS). To identify the associated risk factors. To categorize SFs based on the management in these patients. OVERVIEW OF LITERATURE: Few studies have reported on the incidence (1.9%-16%) and risk factors of SF after MSTS. It is unclear whether all SFs, occurring in MSTS-patients, result in revision surgery. METHODS: We conducted a retrospective analysis on 288 patients (246 for final analysis) who underwent MSTS between 2005-2015. Data collected were demographics and peri/postoperative clinical and radiological features. Early and late radiological SF were defined as presentation before and after 3 months from index surgery, respectively. Univariate and multivariate models of competing risk regression analysis were designed to determine the risk factors for SF with death as a competing event. RESULTS: We observed 14 SFs (5.7%) in 246 patients; 10 (4.1%) underwent revision surgery. Median survival was 13.4 months. The mean age was 58.8 years (range, 21-87 years); 48.4% were women. The median time to failure was 5 months (range, 1-60 months). Patients with SF were categorized into three groups: (1) SF when the primary implant was revised (n=5, 35.7%); (2) peri-construct progression of disease requiring extension (n=5, 35.7%); and (3) SFs that did not warrant revision (n=4, 28.5%). Four patients (28.5%) presented with early failure. SF commonly occurred at the implant-bone interface (9/14) and all patients had a spinal instability neoplastic score (SINS) >7. Thirteen patients (92.8%) who developed failure had fixation spanning junctional regions. Multivariate competing risk regression showed that preoperative Eastern Cooperative Oncology Group score was a significant risk factor for implant failure (adjusted sub-hazard ratio, 7.0; 95% confidence interval, 1.63-30.07; p<0.0009). CONCLUSIONS: The incidence of SF (5.7%) was low in patients undergoing MSTS although these patients did not undergo spinal fusion. Preoperative ambulators involved a 7 times higher risk of failure than non-ambulators. Preoperative SINS >7 and fixations spanning junctional regions were associated with SF. Majority of construct failures occurred at the implant-bone interface.

The "Spinal Metastasis Invasiveness Index": A Novel Scoring System to Assess Surgical Invasiveness.

STUDY DESIGN: Retrospective review. OBJECTIVE: The aim of this study was to develop a surgical invasiveness index for metastatic spine tumor surgery (MSTS) that can serve as a standardized tool in predicting intraoperative blood loss and surgical duration; for the purpose of ascertaining resource requirements and aiding in patient education. SUMMARY OF BACKGROUND DATA: Magnitude of surgery is important in the metastatic spine disease (MSD) population since these patients have a continuing postoperative oncological process; a consideration that must be taken into account to maintain or improve quality of life. Surgical invasiveness indices have been established for general spine surgery, adult deformity, and cervical deformity, but not yet for spinal metastasis. METHODS: Demographic, oncological, and procedural data were collected from consecutive patients that underwent MSTS. Binary logistic regression, using median values for surgical duration and intraoperative estimated blood loss (EBL), was used to determine statistical significance of variables to be included in the "spinal metastasis invasiveness index" (SMII). The corresponding weightage of each of these variables was agreed upon by experienced spine surgeons. Multivariable regression analysis was used to predict operative time and EBL while controlling for demographical, procedural, and oncological characteristics. RESULTS: Two hundred and sixty-one MSD patients were included with a mean age of 59.7-years and near equal sex distribution. The SMII strongly predicted extended surgical duration (R2 = 0.28, P < 0.001) and high intraoperative blood loss (R2 = 0.18, P < 0.001). When compared to a previously established surgical invasiveness index, the SMII accounted for more variability in the outcomes. For every unit increase in score, there was a 42-mL increase in mean blood loss (P < 0.001) and 5-minute increase in mean operative time (P < 0.001). CONCLUSION: Long surgical duration and high blood loss were strongly predicted by the newly developed SMII. The use of the SMII may aid in preoperative risk assessment with the goal of improving patient outcomes and quality of life.Level of Evidence: 4.

Intranasal delivery of topiramate nanoemulsion: Pharmacodynamic, pharmacokinetic and brain uptake studies.

Epilepsy is the noncommunicable and chronic central nervous system disorder characterized by frequent, unprovoked seizures, or electrical disturbances in the brain. Topiramate is used as an antiepileptic drug for the treatment of partial onset seizures, generalized seizures and Lennox-Gastaut Syndrome. Topiramate, a BCS class II drug, has a relatively low bioavailability. It is also a substrate of P-glycoprotein and Blood Brain Barrier restricts its entry into the brain. This investigation was aimed to prepare O/W nanoemulsion delivery system of topiramate to improve its brain bioavailability. Topiramate loaded nanoemulsion was prepared by phase titration method. It was consisting of 2% w/w Capmul MCM C8, 32% w/w Tween 20:Carbitol (2:1) and 66% w/w water. It was characterized for globule size, viscosity, polydispersibility index, zeta potential, pH, conductivity values, transmittance and TEM. Pharmacodynamic, pharmacokinetic and brain drug uptake study was carried out using wistar albino rats post intranasal and oral administration. Topiramate loaded nanoemulsion was having a globule size of 4.73 ± 0.52 nm. It was stable for six months. Brain uptake of topiramate post intranasal administration of topiramate loaded nanoemulsion was significantly (P < 1.86 × 10-8) higher when it was compared with oral administration of topiramate loaded nanoemulsion. This study indicates that intranasal administration of topiramate containing nanoemulsion could be an encouraging approach for the treatment of epilepsy to minimize the dose of topiramate in direction to avoid dose related adverse events.

Point-of-care Ultrasound in Morbidity and Mortality Cases in Emergency Medicine: Who Benefits the Most?

INTRODUCTION: Point-of-care ultrasound (POCUS) is an essential tool in the timely evaluation of an undifferentiated patient in the emergency department (ED). Our primary objective in this study was to determine the perceived impact of POCUS in high-risk cases presented at emergency medicine (EM) morbidity and mortality (M&M) conferences. Additionally, we sought to identify in which types of patients POCUS might be most useful, and which POCUS applications were considered to be highest yield. METHODS: This was a retrospective survey of cases submitted to M&M at an EM residency program that spans two academic EDs, over one academic year. Postgraduate year 4 (PGY) residents who presented M&M cases at departmental sessions were surveyed on perceived impacts of POCUS on individual patient outcomes. We evaluated POCUS use and indications while the POCUS was used. RESULTS: Over the 12-month period, we reviewed 667 cases from 18 M&M sessions by 15 PGY-4 residents and a supervising EM attending physician who chairs the M&M committee. Of these cases, 75 were selected by the M&M committee for review and presentation. POCUS was used in 27% (20/75) of the cases and not used in 73% (55/75). In cases where POCUS was not used, retrospective review determined that if POCUS had been used it would have "likely prevented the M&M" in 45% (25/55). Of these 25 cases, the majority of POCUS applications that could have helped were cardiac (32%, 8/25) and lung (32%, 8/25) ultrasound. POCUS was felt to have greatest potential in identifying missed diagnoses (92%, 23/25), and decreasing the time to diagnosis (92%, 23/25). Patients with cardiopulmonary chief complaints and abnormal vital signs were most likely to benefit. There were seven cases (35%, 7/20, 95% CI 15-59%) in which POCUS was performed and thought to have possibly adversely affected the outcome of the M&M. CONCLUSION: POCUS was felt to have the potential to reduce or prevent M&M in 45% of cases in which it was not used. Cardiac and lung POCUS were among the most useful applications, especially in patients with cardiopulmonary complaints and in those with abnormal vital signs.

Nutraceutical regulations: An opportunity in ASEAN countries.

In today's era of increased standards of lifestyle and life expectancy, there has been a constant demand for supplements by consumers. Nutraceuticals are among the supplements in demand. Although there is a big opportunity for the nutraceutical business, there are no uniform regulatory requirements in different regions. Nations are looking to the nutraceutical sector to help keep their populations healthy and safe by introducing certain rules and regulations. Generally, developed countries have regulations in place, but there are some countries, such as those in the Asia Pacific regions or in Association of Southeast Asian Nations (ASEAN) countries, that have not yet fine-tuned their regulations for nutraceutical products. The ASEAN countries involve highly commercialized markets such as Singapore, Thailand, Malaysia, and the Philippines. The overall nutraceutical market of ASEAN countries is growing at a compound annual growth rate of ∼8.4%. About 40% of the ASEAN population consumes nutraceuticals on a daily basis. ASEAN countries are forming harmonized regulations for dietary supplements. This could be a big opportunity for manufacturers to introduce their products into the ASEAN market. A special unit of the Traditional Medicine and Health Supplements Product Working Group (TMHA PWG) helps manufacturers understand the regulatory procedures of these countries. Despite countries' own special requirements, manufacturers can follow the standards and harmonized guidelines put forth by TMHA PWG. The aim of this review is to introduce the regulatory procedure and requirements for international business developers to launch any new nutraceutical products into the ASEAN market.

Recent strategies and advances in the fabrication of nano lipid carriers and their application towards brain targeting.

In last two decades, the lipid nanocarriers have been extensively investigated for their drug targeting efficiency towards the critical areas of the human body like CNS, cardiac region, tumor cells, etc. Owing to the flexibility and biocompatibility, the lipid-based nanocarriers, including nanoemulsion, liposomes, SLN, NLC etc. have gained much attention among various other nanocarrier systems for brain targeting of bioactives. Across different lipid nanocarriers, NLC remains to be the safest, stable, biocompatible and cost-effective drug carrier system with high encapsulation efficiency. Drug delivery to the brain always remains a challenging issue for scientists due to the complex structure and various barrier mechanisms surrounding the brain. The application of a suitable nanocarrier system and the use of any alternative route of drug administration like nose-to-brain drug delivery could overcome the hurdle and improves the therapeutic efficiency of CNS acting drugs thereof. NLC, a second-generation lipid nanocarrier, upsurges the drug permeation across the BBB due to its unique structural properties. The biocompatible lipid matrix and nano-size make it an ideal drug carrier for brain targeting. It offers many advantages over other drug carrier systems, including ease of manufacturing and scale-up to industrial level, higher drug targeting, high drug loading, control drug release, compatibility with a wide range of drug substances, non-toxic and non-irritant behavior. This review highlights recent progresses towards the development of NLC for brain targeting of bioactives with particular reference to its surface modifications, formulations aspects, pharmacokinetic behavior and efficacy towards the treatment of various neurological disorders like AD, PD, schizophrenia, epilepsy, brain cancer, CNS infection (viral and fungal), multiple sclerosis, cerebral ischemia, and cerebral malaria. This work describes in detail the role and application of NLC, along with its different fabrication techniques and associated limitations. Specific emphasis is given to compile a summary and graphical data on the area explored by scientists and researchers worldwide towards the treatment of neurological disorders with or without NLC. The article also highlights a brief insight into two prime approaches for brain targeting, including drug delivery across BBB and direct nose-to-brain drug delivery along with the current global status of specific neurological disorders.

Compulsive methamphetamine taking and abstinence in the presence of adverse consequences: Epigenetic and transcriptional consequences in the rat brain.

Methamphetamine addiction is characterized by compulsive binges of drug intake despite adverse life consequences. A model of methamphetamine self-administration that includes contingent footshocks to constitute adverse consequences has helped to segregate rats that reduce or stop lever pressing for methamphetamine (sensitive) from those that continue to lever press for the drug (resistant) in the presence of negative outcomes. We have observed differential DNA hydroxymethylation and increased expression of potassium channel mRNAs in the nucleus accumbens of sensitive compared to resistant rats, suggesting a role of these channels in suppressing methamphetamine intake. There were also significant increases in nerve growth factor (NGF) expression and activation of its downstream signaling pathway (NGF-TrkA and p75NTR/MAPK signaling) in only the dorsal striatum of sensitive rats after a month of abstinence. In contrast, oxytocin mRNA expression was increased in only the nucleus accumbens of resistant rats compared to sensitive rats euthanized after that time. These results indicate that footshocks can differentiate two behavioral phenotypes with differential biochemical and epigenetic consequences in the ventral and dorsal striatum.