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Alzheimer’s disease (AD) is one of the major reasons for 60-80% cases of senile dementia occurring as a result of the accumulation of plaques and tangles in the hippocampal and cortical neurons of the brain leading to neurodegeneration and cell death. The other pathological features of AD comprise abnormal microvasculature, network abnormalities, interneuronal dysfunction, increased β-amyloid production and reduced clearance, increased inflammatory response, elevated production of reactive oxygen species, impaired brain metabolism, hyperphosphorylation of tau, and disruption of acetylcholine signaling. Among all these pathologies, Mitochondrial Dysfunction (MD), regardless of it being an inciting insult or a consequence of the alterations, is related to all the associated AD pathologies. Observed altered mitochondrial morphology, distribution and movement, increased oxidative stress, dysregulation of enzymes involved in mitochondrial functioning, impaired brain metabolism, and impaired mitochondrial biogenesis in AD subjects suggest the involvement of mitochondrial malfunction in the progression of AD. Here, various pre-clinical and clinical evidence establishing MD as a key mediator in the progression of neurodegeneration in AD are reviewed and discussed with an aim to foster future MD based drug development research for the management of AD.

Monoamine oxidase (MAO) is an enzyme that catalyzes the deamination of monoamines and other proteins. MAO’s hyperactivation results in the massive generation of reactive oxygen species, which leads to a variety of neurological diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and depression-like disorders. Although synthetic MAO inhibitors are clinically available, they are associated with side effects such as hepatotoxicity, cheese reaction, hypertensive crisis, and so on, necessitating the investigation of alternative MAO inhibitors from a natural source with a safe profile. Herbal medications have a significant impact on the prevention of many diseases; additionally, they have fewer side effects and serve as a precursor for drug development. This review discusses the potential of herbal MAO inhibitors as well as their associated mechanism of action, with an aim to foster future research on herbal MAO inhibitors as a potential treatment for neurological diseases.

Cancer treatment has become a major challenge amidst the resistance and relapse caused by the various treatments available. The PROteolysis TAargeting Chimera (PROTAC) technology involves the degradation of target protein against the inhibition by small drug molecules. The PROTACs with high potency and activity have been frequently reported; however, no PROTAC acting against cancer has reached the clinical trials. The concept of PROTACs involves the reduction in the disease-causing protein by its degradation through the ubiquitin-proteasomal enzyme system. This concept has attracted a lot of attention from both industry and academia due to its potential in drug discovery (in the form of PROTACs), which can conquer the resistance associated with current treatments of cancer. Thus, it is the need of the hour to identify and synthesize more PROTACs for a viable treatment of cancer. This article reviews the design, activity and effects produced in cancer by some recently developed PROTACs.

In 2020, a considerable overlap occurred between the COVID-19 pandemic and seasonal dengue transmission in India. This study aimed to evaluate the effects of acute or recent infection with SARS-CoV-2 on the course and outcomes of dengue fever in children. We prospectively enrolled 44 children with a clinical and laboratory diagnosis of dengue fever. Assessment of acute and recent SARS-CoV-2 infection was done using reverse transcription–polymerase chain reaction and IgG antibody through ELISA. Children were grouped based on evidence of SARS-CoV-2 exposure and clinical severity, and outcomes were compared. The median age of the study cohort was 96 months (interquartile range [IQR]: 69–129 months). Fever (98%), vomiting (78%), abdominal pain (68%), hepatomegaly (68%), and edema (32%) were the common features. About two-thirds (N = 30) had severe dengue; 20 (45%) had dengue shock. Liver dysfunction (58%) and acute kidney injury (25%) were other major organ dysfunctions. Nineteen (43%) children stayed in the pediatric intensive care unit for a median duration of 5 days (IQR: 2–11 days). None had acute SARS-CoV2 infection; however, IgG against SARS-CoV-2 was detected in 15 (34%) cases. Children with recent exposure to SARS-CoV-2 showed a trend toward a lower incidence of acute kidney injury, fewer organ dysfunctions, and a lower frequency of invasive ventilation. Four children (9%) died; none of the deaths were in the SARS-CoV-2–exposed group. The present study exposes preliminary evidence that dengue fever might follow a less severe course in children with recent exposure to SARS-CoV-2 infection. However, it is pertinent to understand the antigenic similarity and cross-protective antibody response between the two viruses and their clinical relevance.

Pediatric Advanced Life Support (PALS) guidelines are updated every five years and the new 2020 guidelines were issued recently. We briefly review the important changes in terms of rates of rescue breaths, timing of epinephrine, resuscitation in septic shock, use of extracorporeal therapies, and the new component in the chain of survival - recovery.

Background: Controlled oral dosage forms have always been preferred for drugs with variable absorption, and short biological half life and frequent dosing. The prime goal with sustained release systems is to maintain uniform therapeutic blood levels for more extended periods of time. Interpenetrating networks (IPNs) have been evidenced as uniform sustained release systems. In the current study, polyvinyl alcohol (PVA) and locust bean gum (LBG) based IPNs were developed for the oral sustained release drug delivery of gliclazide (shows variable absorption). Methods: The IPNs were synthesized by emulsion cross-linking method using glutaraldehyde (GA) as a cross linking agent. Gliclazide is a potential second generation, and short-acting sulfonylurea oral hypoglycemic agent having a short biological half-life (2-4 h), variable absorption and poor oral bioavailability. Various batches of IPNs were formulated by varying LBG: PVA ratio and evaluated for percentage yield, drug entrapment efficiency (DEE), swelling properties and in vitro drug release studies. Further characterizations were done by Fourier Transform Infrared Spectroscopy (FTIR), C13 Solid state NMR, X-Ray diffraction study (XRD), Scanning electron microscopy (SEM), and Differential scanning microscopy (DSC) studies. Results: The percentage yield, drug entrapment and equilibrium swelling were observed to be dependent on PVA-LBG ratio and GA amount. Sustained release of drug was observed in all IPN formulations (approx 59 - 86% in 8 h in various batches) with variable release kinetics. SEM studies revealed the regular structures of IPNs. FTIR, XRD, C13 Solid state NMR and DSC studies proposed that drug was successfully incorporated into the formed IPNs. Conclusion: IPNs of LBG and PVA can be used as a promising carrier with uniform sustained release characteristics.

Background: Coronavirus has become a life-threatening disease and it is caused by severe acute respiratory syndrome (SARS). This new strain of coronavirus is not completely understood and to date, there is no treatment for coronavirus. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. In the meantime, guidelines of the ministry of AYUSH (Ayurveda, yoga, unani, siddha and homoepathy) include a traditional medicinal treatment for flu and fever and also recommended to boost immunity to prevent the spread of coronavirus. It is not possible to find which essential oil will offer the best level of protection. However, it is likely to assume that some essential oils are likely to offer a measurable level of defense in the same way they do with many other known viruses. Methods: Literature relevant to various essential oils having antiviral activity has been collected and compiled. Various nanocarriers of essential oils have also been stated. The database was collected using various search engines such as J-Gate, Google Scholar, Sci-Hub, PubMed, ScienceDirect, etc. Results: Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activities and many more. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. Conclusion: Several essential oils possess potent antiviral activity and are characterized by fewer side effects and are safe for human use. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections. Lay Summary: Current COVID-19 era demands traditional treatment for immunity boost up as support therapy. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. Therefore, authors have summarized various essential oils having antiviral activity in current manuscript. Various nanocarriers of essential oils have been reported. Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activity. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections.

Novel coronavirus (COVID-19) is a highly contagious virus that originated from China and has become a major threat in the current time Presently, finding an effective treatment strategy for COVID-19 is in infancy Worldwide, numerous clinical trials employing different treatment strategies (antiviral drugs and vaccines) are in progress to develop an effective therapeutic regimen against COVID-19 Literature related to the epidemiology, mortality, pathogenicity, treatment strategies and clinical data was studied and database was collected using various search engines such as j-gate, google scholar, scihub, pubmed, sciencedirect etc The present review systematically summarises the published information about epidemiology, various stages of pandemic, mortality, pathogenicity, modes of transmission, clinical characteristics, methods of prevention, ongoing treatment strategies and drugs under clinical trials associated with COVID-19 with a hope to avoid possible threatening of the lives of millions of human beings and provide directions for future studies © 2020 The Authors

Natural products form a significant portion of medicinal agents that are currently used for the management of cancer. All these natural products have unique structures along with diverse action mechanisms with the capacity to interact with different therapeutic targets of several complex disorders. Although plants contribute as a major source of natural products with anti-cancer potential, the marine environment and microbes have also bestowed some substantial chemotherapeutic agents. A few examples of anti-cancer agents of natural origin include vincristine, vinblastine, paclitaxel, camptothecin and topotecan obtained from plants, bryostatins, sarcodictyin and cytarabine from marine organisms and bleomycin and doxorubicin from micro-organisms (dactinomycin, bleomycin and doxorubicin). The incredible diversity in the chemical structures and biological properties of compounds obtained from million species of plants, marine organisms and microorganisms present in nature has commenced a new era of potential therapeutic anti-cancer agents.

Background: Psoriasis is an autoimmune disease that ingeminates itself with the repeated proliferation of keratinocytes. It globally strikes a 2-5 % population on an average. Management of psoriasis remains a daunting task with various challenges influencing treatment, such as patient conformity and adherence to therapy, delicate patient profiles, psychological aspects, and skin as a barrier to topical delivery. The first part reviewed pathophysiology, triggering factors, and clinical classification. The second part reviewed all the therapies, such as topical, oral, biological, parenteral therapy, phototherapy, and the phyto-pharmaceuticals. Methods: The research data related to the existing and upcoming therapies for psoriasis treatment, several nanocarriers, existing marketed formulations, and detailed description of phytopharmaceuticals with their mechanism. Results: Topical therapy is the mainstay treatment option with limited adverse effects. Biological therapy has reformed conventional psoriasis treatment by being more efficacious and has increased patient acceptance due to decreased adverse events. Nanoformulations present an edge over conventional therapy due to improved anti-psoriatic effect and decreased side effects. Phyto-pharmaceuticals act as a complementary and alternative therapy for diminishing psoriasis symptoms. Conclusion: A rationalized cost-effective patient compliant therapy is required for effective management and complete cure of psoriasis.

Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg, i.p.) as a standard drug and chondroitin sulfate (100 &amp, 200 mg/kg, p.o.) significantly (p &lt, 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1β, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1β, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.

Objectives To describe the intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C). Methodology This retrospective study was conducted in the pediatric emergency, pediatric intensive care unit (PICUs) and the coronavirus disease 2019 (COVID 19) hospital of a tertiary teaching and referral hospital in North India over a period of 5 months (September 2020 to January 2021). Clinical details, laboratory investigations, intensive care needs, treatment and short-term outcome were recorded. Results Forty children with median interquartile range age of 7 (5–10) years were enrolled. The common clinical features were fever (97.5%), mucocutaneous involvement (80%), abdominal (72.5%) and respiratory (50%) symptoms. Shock was noted in 80% children. Most cases (85%) required PICU admission where they received nasal prong oxygen (40%), non-invasive (22.5%) and invasive (22.5%) ventilation and vasoactive drug support (72.5%). The confirmation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposure was in the form of positive serology (66.7%), reverse transcriptase polymerase chain reaction (10%), and contact with SARS-CoV-2 positive case (12.5%). The common echocardiographic findings included myocardial dysfunction (ejection fraction Conclusion Cardiovascular involvement and shock are predominant features in severe disease. Early diagnosis can be challenging given the overlapping features with other diagnoses. A high index of suspicion is warranted in children with constellation of fever, mucocutaneous, gastrointestinal and cardiovascular involvement alongwith evidence of systemic inflammation and recent or concurrent SARS-CoV-2 infection. The short-term outcome is good with appropriate organ support therapies and immunomodulation.

OBJECTIVE In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02−1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85–1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment–baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03−1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.

Background Neurenteric cysts rarely present in infancy. Compressive myelopathy or meningitis are the usual presenting features of these cysts in infants. Case Description We discuss a case of intradural extramedullary neurenteric cyst at the cervicomedullary junction in a 2-month-old infant who presented with features of acute onset flaccid upper limb weakness. The cyst was excised completely and the child improved. Conclusions Although rare, compressive lesions such as neurenteric cysts may present with acute flaccid paralysis in very young children. Differentiating from other causes and timely intervention bears an excellent outcome.

Aim: The purpose of the present study was to examine whether clinical differences exist between the biodegradable polymer (BDP)–coated Tetrilimus everolimus-eluting stent (EES) and the durable polymer (DP)–coated Xience EES by comparing the major adverse cardiac event (MACE) rate at 12 months in all-comer patients. Methods: This study was designed as a multicentre, observational, retrospective, investigator-initiated study between January 2016 and October 2016. Two hundred thirteen patients who underwent percutaneous coronary intervention (PCI) with the BDP-EES were compared with 204 patients who underwent PCI with the DP-EES, irrespective of lesion complexity, comorbidities and acute presentation. The primary end point was MACE defined as a composite of cardiac death, myocardial infarction and target lesion revascularization. Results: Baseline clinical and lesion characteristics of both the groups were similar, although the BDP-EES group had a significantly higher number of patients with diabetes mellitus (39.9% vs. 30.4%; p = 0.042) and type C lesion (67.4% vs. 48.1%; p

Epileptogenesis is most commonly associated with neurodegeneration and a bioenergetic defect attributing to the fact that mitochondrial dysfunction plays a key precursor for neuronal death. Mitochondria are the essential organelle of neuronal cells necessary for certain neurophysiological processes like neuronal action potential activity and synaptic transmission. The mitochondrial dysfunction disrupts calcium homeostasis leading to inhibitory interneuron dysfunction and increasing the excitatory postsynaptic potential. In epilepsy, the prolonged repetitive neuronal activity increases the excessive demand for energy and acidosis in the brain further increasing the intracellular calcium causing neuronal death. Similarly, the mitochondrial damage also leads to the decline of energy by dysfunction of the electron transport chain and abnormal production of the ROS triggering the apoptotic neuronal death. Thus, the elevated level of cytosolic calcium causes the mitochondria DNA damage coinciding with mtROS and releasing the cytochrome c binding to Apaf protein further initiating the apoptosis resulting in epileptic encephalopathies. The various genetic and mRNA studies of epilepsy have explored the various pathogenic mutations of genes affecting the mitochondria functioning further initiating the neuronal excitotoxicity. Based on the results of previous studies, the recent therapeutic approaches are targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria and hold great promise to attenuate epileptogenesis. Therefore, the current review emphasizes the emerging insights to uncover the relation between mitochondrial dysfunction and ROS generation contributing to mechanisms underlying epileptic seizures.

Hypertension is due to increased oxidative stress.As urate is natural anti-oxidant,increase in level of hypertension is a case or effect of raised uric acid level.Aim:Aim of the present study was to evaluate serum uric acid levels in cases of Essential Hypertension and comparison with normal controls in different grades of hypertension. Material and Methods: 100 subjects were taken out of which 50 were normal healthy control groups and 50 were of Essential Hypertension. Hypertensive subjects were further subdivided into 2 groups based on the level of Blood Pressure(JNC7). Results: Mean serum Uric Acid levels is found to be 4.8 mg/dl in 50 controls and 5.7 mg/dl in 50 cases of Essential Hypertension, 5.5 mg/dl in stage 1 hypertension(BP=140-159mmHg) and 5.8759 in stage 2 hypertension (BP>160mmHg).Conclusion:It is seen that hypertension is related to rise in mean serum uric acid levels and this rise is directly related to severity of hypertension.Randomized control trials need to be done to see whether lowering serum uric acid level will ameliorate the level of blood pressure.

Changes in human lifestyles and environmental deterioration globally causes emergence of new viruses posing research challenges. Recent outburst of disease COVID-19 (nCoV19) is a recent example wherein effective management of virus using conventional medication or adopting preventive and effective diagnostic measures is a challenge. While many ongoing strategies from vaccine development to drug repurposing, are currently being investigated, a targeted approach with nanotechnology can be helpful to meet the demand for preventive and diagnostic measures. The significant results of nanotechnology in resolving better efficacy in pharmaceutical drugs is expected to be helpful in combating nCoV19 by using nanotechnology-based solutions preventive, treatment, and diagnosis. As vaccine development involves long clinical trial procedures, preventive measures such as masks, disinfectants, sanitizers, and personal protective equipment's are gaining popularity for effective management. The present write-up addresses the dire need of the nanotechnology-based solutions in present pandemic and studies of the ongoing innovation and existing patents for developing better solutions. Multiple applications of nanotechnology is expected to be helpful in preventive and diagnostic measures, immune response modulation and immunity boosters along with projecting a pathway for industry and academic researchers for addressing such pandemic.

Obesity-induced renal dysfunction is a potential risk factor for causing cardiometabolic diseases, but the underlying mechanism remains unclear. Present study was designed to evaluate the protective role of estradiol benzoate in high fat diet (HFD)-induced renal dysfunction in male rats. Six groups of rats (7 animals/group) were randomly assigned to different treatment groups. Adult male and female rats were fed high fat diet (HFD) containing 30% fat for 12 consecutive weeks. One group of male rats simultaneously received daily injections of estradiol benzoate (50 and 100 µg/kg/day, i.p.) over 12 weeks. HFD-induced obesity was assessed by calculating obesity index, adiposity index, and serum lipid profile. Renal function was determined by measuring creatinine clearance, serum urea, uric acid, electrolytes, and microproteinuria. Serum estradiol level and systolic blood pressure (SBP) were measured using standardized techniques. Hydroxyproline content was quantified in the kidneys to estimate collagen deposition. Renal oxidative stress was measured through quantification of thiobarbituric acid reactive substances, superoxide anion generation and reduced glutathione levels. Hematoxylin and Eosin and special Picrosirius red staining of the isolated kidney tissues was done to observe changes in gross morphology, glomerular volume and collagen content, respectively. As opposed to the control group, HFD-fed rats demonstrated significant increase in obesity and adiposity indices, lipid profile, SBP and renal dysfunction along with increased hydroxyproline content and oxidative stress in the renal tissues. HFD also caused marked increase in SBP in both sexes. Biochemical and histological studies revealed that the males exposed to HFD were more susceptible to renal dysfunction than females. However, estradiol benzoate administration to male rats showed protection against HFD-induced renal dysfunction accompanied by significant reductions of SBP, renal oxidative stress and fibrosis. It is concluded that estradiol protects against HFD-induced hypertension and renal dysfunction in male rats. To the best of our knowledge, we are the first ones to report the renal protective action of estradiol in male rats exposed to chronically fed HFD. While the findings of this study cannot be directly extrapolated to humans, nevertheless, the renoprotective effects of estradiol warrant verification in obese men suffering from acute renal malfunction.

Background: Cancer is the world’s second-largest cause of death, with an estimated 9.6 million fatalities in 2018. Malignant tumour (cancer) is caused by a mixture of genetic modifications due to the environmental variables that tend to activate or inactivate different genes, ultimately resulting in neoplastic transformations. Cancer is a multi-stage process that results from the conversion of the ordinary cells to tumour cells and progresses from a pre-cancer lesion to abnormal growth. Methods: Chemotherapy inhibits the ability of the cells to divide rapidly in an abnormal manner, but this treatment simultaneously affects the entire cellular network in the human body leading to cytotoxic effects. In this review article, the same issue has been addressed by discussing various aspects of the newer class of drugs in cancer therapeutics, i.e., Gold Nanoparticles (AuNPs) from metal nanoparticle (NP) class. Results: Metal NPs are advantageous over conventional chemotherapy as the adverse drug reactions are lesser. Additionally, ease of drug delivery, targeting and gene silencing are salient features of this treatment. Functionalized ligand-targeting metal NPs provide better energy deposition control in tumour. AuNPs are promising agents in the field of cancer treatment and are comprehensively studied as contrast agents, carriers of medicinal products, radiosensitizers and photothermal agents. For the targeted delivery of chemotherapeutic agents, AuNPs are used and also tend to enhance tumour imaging in vivo for a variety of cancer types and diseased organs. Conclusion: The first part of the review focuses on various nano-carriers that are used for cancer therapy and deals with the progression of metal NPs in cancer therapy. The second part emphasizes the use of nanotechnology by considering the latest studies for diagnostic and therapeutic properties of AuNPs. AuNPs present the latest studies in the field of nanotechnology, which leads to the development of early-stage clinical trials. The next part of the review discusses the major features of five principal types of AuNPs: gold nanorods, gold nanoshells, gold nanospheres, gold nanocages, and gold nanostars that have their application in photothermal therapy (PTT).

Objective: Omega-3 fatty acids, especially alpha-linolenic acid (ALA), which are present in nuts may reduce cardiovascular disease (CVD) risk, by changing vascular inflammation and improving endothelial dysfunction. The objective of the study was to evaluate the acute effects of two different diets, one containing walnuts and the other almonds on endothelial function. Methods: Twenty-seven overweight volunteers underwent a randomized 2-period, crossover, controlled intervention study. The subjects were given either walnut or almond diets which varied in monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) content. The walnut diet provided 23.1% energy from PUFA and the almond diet provided 7.6% energy from PUFA. Endothelial function was assessed physiologically by flow-mediated dilation (FMD) and biochemically by sVCAM (soluble vascular cell adhesion molecules). Results: The walnut diet significantly improved FMD (p = 0.004) and decreased sVCAM (p = 0.009) whereas the almond diet tended to improve FMD (p = 0.06) and significantly decreased sVCAM (p = 0.004). Conclusion: Both walnut and almond diets improved FMD and sVCAM and there was no significant difference in physiological and biochemical markers between the two diets. Keywords: Almonds, Walnuts, Endothelial Function, sVCAM, Flow mediated dilation (FMD), MUFA, PUFA

Polyfunctional compounds comprise a novel class of therapeutic agents for the treatment of multi-factorial diseases. A series of 2-Phenyl-4H-chromen-4-one and its derivatives (5a–n) were designed, synthesized, and evaluated for their poly-functionality against acetylcholinestrase (AChE) and advanced glycation end products (AGEs) formation inhibitors against Alzheimer’s disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit AChE AGEs formation with additional radical scavenging activity. Especially, 5m, 5b, and 5j displayed the greatest ability to inhibit AChE (IC50 = 8.0, 8.2, and 11.8 nM, respectively) and AGEs formation (IC50 = 55, 79, and 54 µM, respectively) with good antioxidant activity. Molecular docking studies explored the detailed interaction pattern with active, peripheral, and mid-gorge sites of AChE. These compounds, exhibiting such multiple pharmacological activities, can be further taken a lead for the development of potent drugs for the treatment of Alzheimer’s disease.

Femoral shaft fractures account for 1.6% of all paediatric injuries. The best treatment for children between five to sixteen years of age is still questioned. patients in this transitional age group have high risk of shortening and mal union when conservative measures are used Fixation with flexible intramedullary nails have become a trendy technique, for stabilizing femoral fractures in school aged children. The present study consisted of 25 cases with diaphyseal lower limb fractures of either gender within age group 5-16 years, admitted in Orthopaedics Department of a tertiary care hospital of Punjab and were treated with elastic stable intramedullary nail. RTA accounted for 92% cases. Isolated femur fracture was seen in 40% cases. 8% cases also had ipsilateral tibial fracture with it & 52% had only tibial shaft fractures. Transverse fracture was observed in 56% cases. All cases were fixed with elastic titanium nail. Minor complications, as per Flynn’s criteria were seen in 12% cases. No case developed any major complication. Excellent results were obtained in 76% cases and satisfactory results were obtained in the remaining 24% cases.

Introduction Pharmacologic treatment options for allergic rhinitis include intranasal corticosteroids, oral and topical antihistamines, decongestants, intranasal cromolyn, intranasal anticholinergics and leukotriene receptor antagonists. The present study was undertaken to compare the efficacy of leukotriene receptor antagonist and antihistamines in relieving nasal congestion/ obstruction symptom and itching /irritation in eyes. Material and Methods The study was conducted among 125 patients clinically diagnosed suffering from allergic rhinitis Patients were divided into 5 groups and were given oral treatment with oral antihistamines (chlorpheniramine maleate, levocetrizine, fexofenadine, desloratadine) and leukotriene receptor antagonist (montelukast) for a period of 6 weeks. The results were tabulated and analyzed by Chi-square and Kruskal-Wallis test with p value

A novel and simple approach to the synthesis of glimepiride is reported. It involves the preparation of a carbamate of 3-ethyl-4-methyl-1H-pyrrol-2(5H)-one, followed by its reaction with 4-(2-aminoethyl)benzenesulfonamide to produce the intermediate sulfonamide. This sulfonamide, upon reaction with phenyl (trans-4-methylcyclohexyl)carbamate, gave glimepiride. This process avoids the use of phosgene, isocyanates, or chloroformates. Furthermore, sulfonation of the aryl group was eliminated, rendering the product free of the impurities reported in earlier processes.

A novel and simple approach for the preparation of 3-substituted, 5-substituted, or 3,5-disubstituted hydantoins is reported. It involves the reaction of α-amino methyl ester hydrochlorides with carbamates to yield the corresponding ureido derivatives, which subsequently cyclize under basic conditions to produce substituted ­hydantoins in good yields. By applying this method, the bioactive anticonvulsant drug ethotoin was synthesized in good yield. The process avoids conventional multistep protocols and does not use the hazardous, irritant, toxic, or moisture-sensitive reagents, such as isocyanates or chloroformates, that are commonly used for the synthesis of these important compounds.

Aim: Autoimmune disorders have complex pathophysiology and focus is laid on the development of multitargeted agents. Two well-established kinases: SYK and JAK3, were considered to design dual inhibitors as potential therapeutics using various molecular-modeling approaches. Mehodology: Pharmacophore models for SYK and JAK3 were generated using oxindole-based inhibitors. Furthermore, an in-house database was designed that was screened against the best selected models. The obtained hits were employed for docking analysis and subjected to MM-GBSA analysis and molecular dynamic simulation. Results: Top five oxindole derivatives were synthesized and evaluated for in vitro SYK and JAK3 activity. The most active compound 4a was evaluated for in vivo antiarthritic activity. It showed significant anti-arthritic activity. Conclusion: Thus, the designed inhibitors resulted in potential therapeutic agents for rheumatoid arthritis.

Any kind of injury may lead to wound formation. As per World Health Organization Report, “more than 5 million people die each year due to injuries. This accounts for 9% of the world’s population death, nearly 1.7 times the number of fatalities that result from HIV/AIDS, tuberculosis and malaria combined. In addition, ten million people suffer from non-fatal injuries which require treatment”. This scenario leads to increased health and economic burden worldwide. Rapid wound healing is exigent subject-field in the health care system. It is imperative to be updated on wound care strategies as impaired wound healing may lead to chronic, non-healing wounds and thus further contributes to the national burden. This article is a comprehensive review of wound care strategies. The first and second part of this review article focuses on the understanding of wound, its types and human body’s healing mechanism. Wound healing is natural, highly coordinated process that starts on its own, immediately after the injury. However, individual health condition influences the healing process. Discussion of factors affecting wound healing has also been included. Next part includes the detailed review of diverse wound healing strategies that have already been developed for different types of wound. A detailed description of various polymers that may be used has been discussed. Amongst drug delivery systems, oligomers, dendrimers, films, gels, different nano-formulations, like nanocomposites, nanofibers, nanoemulsions and nanoparticles are discussed. Emphasis on bandages has been made in this article.

Background Heart failure (HF) is a chronic condition affecting nearly 5.7 million Americans and is a leading cause of morbidity and mortality. With an aging population, the cost associated with managing HF is expected to more than double from US $31 billion in 2012 to US $70 billion by 2030. Readmission rates for HF patients are high—25% are readmitted at 30 days and nearly 50% at 6 months. Low medication adherence contributes to poor HF management and higher readmission rates. Remote telehealth monitoring programs aimed at improved medication management and adherence may improve HF management and reduce readmissions. Objective The primary goal of this randomized controlled pilot study is to compare the MedSentry remote medication monitoring system versus usual care in older HF adult patients who recently completed a HF telemonitoring program. We hypothesized that remote medication monitoring would be associated with fewer unplanned hospitalizations and emergency department (ED) visits, increased medication adherence, and improved health-related quality of life (HRQoL) compared to usual care. Methods Participants were randomized to usual care or use of the remote medication monitoring system for 90 days. Twenty-nine participants were enrolled and the final analytic sample consisted of 25 participants. Participants completed questionnaires at enrollment and closeout to gather data on medication adherence, health status, and HRQoL. Electronic medical records were reviewed for data on baseline classification of heart function and the number of unplanned hospitalizations and ED visits during the study period. Results Use of the medication monitoring system was associated with an 80% reduction in the risk of all-cause hospitalization and a significant decrease in the number of all-cause hospitalization length of stay in the intervention arm compared to usual care. Objective device data indicated high adherence rates (95%-99%) among intervention group participants despite finding no significant difference in self-reported adherence between study arms. The intervention group had poorer heart function and HRQoL at baseline, and HRQoL declined significantly in the intervention group compared to controls. Conclusions The MedSentry medication monitoring system is a promising technology that merits continued development and evaluation. The MedSentry medication monitoring system may be useful both as a standalone system for patients with complex medication regimens or used to complement existing HF telemonitoring interventions. We found significant reductions in risk of all-cause hospitalization and the number of all-cause length of stay in the intervention group compared to controls. Although HRQoL deteriorated significantly in the intervention group, this may have been due to the poorer HF-functioning at baseline in the intervention group compared to controls. Telehealth medication adherence technologies, such as the MedSentry medication monitoring system, are a promising method to improve patient self-management,the quality of patient care, and reduce health care utilization and expenditure for patients with HF and other chronic diseases that require complex medication regimens. Trial Registration ClinicalTrials.gov NCT01814696; https://clinicaltrials.gov/ct2/show/study/NCT01814696 (Archived by WebCite® at http://www.webcitation.org/6giqAVhno)

Colorectal cancer (CRC) is one of the major causes of carcinogenic mortality in numbers only after lung and breast cancers. The mutations in adenomatous polyposis coli (APC) gene leads to formation of colorectal polyps in the colonic region and which develop as a malignant tumour upon coalition with patient related risk factors. The protein-protein interaction (PPI) of APC with Asef (A Rac specific guanine nucleotide exchange factor) overwhelms the patient's conditions by rapidly spreading in the entire colorectal region. Most mutations in APC gene occur in mutated cluster region (MCR), where it specifically binds with the cytosolic β-catenin to regulate the Wnt signalling pathway required for CRC cell adhesion, invasion, progression, differentiation and stemness in initial cell cycle phages. The current broad spectrum perspective is attempted to elaborate the sources of identification, development of selective APC inhibitors by targeting emopamil-binding protein (EBP) & dehydrocholesterol reductase-7 & 24 (DHCR-7 & 24); APC-Asef, β-catenin/APC, Wnt/β-catenin, β-catenin/TCF4 PPI inhibitors with other vital Wnt signal cellular proteins and APC/Pol-β interface of colorectal cancer. In this context, this perspective would serve as a platform for design of new medicinal agents by targeting cellular essential components which could accelerate anti-colorectal potential candidates.

Background: Drug-eluting stents (DES) have been shown to reduce the rate of acute complications and the need for subsequent revascularization in cases where single-vessels are treated. The performance of DES in patients with multivessel disease and complex lesions, however, remains controversial. This study assessed and compared clinical outcomes following single vs. multivessel percutaneous coronary intervention (PCI), using the Supraflex sirolimus-eluting stent (SES), in an all-comers patient population. Methods: We conducted retrospective, multicenter, all-comers, observational study of 995 patients, who underwent either single-vessel PCI (n=769 patients; group-I) or multivessel PCI (n=226 patients; group-II), treated with the biodegradable polymer coated Supraflex SES, between July-2013 and May-2014 at nine different centers in India. Pre-specified primary endpoint, rate of major adverse cardiac events (MACE) [defined as composite of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and non-target lesion target vessel revascularization (non-TL TVR)], was analyzed during 12 months after the post-index procedure. We also analyzed the incidence of stent thrombosis (ST) as a safety endpoint during the follow-up period, as defined by the Academic Research Consortium (ARC). Results: Of the whole study group, 1,242 lesions were treated in 995 patients (mean age 61.6±10.8 years; 80.0% male) with average stent length of 26.8±9.3 mm. Multivessel PCI patients were older, had a higher prevalence of arterial hypertension, were smoker, had a family history of coronary artery disease, previous stroke and previous PCI compared to single-vessel PCI patients. Follow-up was available in 99.0% (761/769) of patients with single-vessel intervention and 96.9% (219/226) of patients with multivessel intervention at the end of 12 months. In-hospital MACE was similar for both the groups [group-I, 3 (0.4%) vs. group-II, 1 (0.4%); p=1.000]. The observed MACE for group-I and group-II, at 30 days, 6 and 12 months follow-up were 9 (1.2%) vs. 2 (0.9%); p=1.000, 15 (2.0%) vs. 7 (3.2%); p=0.302 and 24 (3.2%) vs. 12 (5.5%); p=0.109, respectively. The cumulative incidence curves for MACE showed no significant differences between the two groups, at the end of 12 months (p=0.109). Conclusion: Our study shows that use of the Supraflex SES in single and multivessel coronary artery disease produces good clinical outcomes during 12 months of follow-up with a low rate of revascularization, despite complex lesion morphology.

The present study investigated the infiltration of mast cells into the kidney tissue and the preventive role of mast cell stabilizers against high fat diet (HFD)-induced renal injury in rats. The animals were fed on HFD (30% fat) for 12 consecutive weeks to induce renal injury. The HFD-induced obesity was assessed by calculating obesity index, adiposity index, and estimation of total cholesterol, triglycerides, and high density lipoproteins in plasma. The renal dysfunction was evaluated by measuring creatinine clearance, blood urea nitrogen, uric acid, electrolytes and microproteinuria. The oxidative stress in renal tissues was determined by myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation and reduced glutathione level. The systolic blood pressure (SBP) was monitored using non-invasive blood pressure measuring apparatus. Histamine and hydroxyproline contents were quantified in renal tissues. Gross histopathological changes, mast cell density and collagen deposition in the renal tissue was determined by means of histopathology. The mast cell stabilizers, sodium cromoglycate and ketotifen were administered daily for 12 weeks. The HFD fed rats demonstrated significant increase in lipid profile, kidney injury with marked increase in renal oxidative stress, SBP, mast cell density, histamine content and hydroxyproline content that was attenuated by sodium cromoglycate and ketotifen treatment. Hence, the novel findings of this investigation suggest that HFD induced mast cells infiltration into kidney tissue seems to play an important role in renal pathology, and treatment with mast cell stabilizers serves as potential therapy in management of HFD induced renal dysfunction in rats.

Background Sildenafil is a phosphodiesterase inhibitor used clinically for treating erectile dysfunction. Few studies suggest sildenafil to be a renoprotective agent. The present study investigated the involvement of peroxisome proliferator–activated receptor γ (PPAR-γ) in sildenafil-mediated protection against ischemia-reperfusion–induced acute kidney injury (AKI) in rats. Materials and methods The rats were subjected to ischemia–reperfusion injury (IRI) with 40 min of bilateral renal ischemia followed by reperfusion for 24 h. The renal damage was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, electrolytes, and microproteinuria in rats. The thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. The hematoxylin-eosin staining was carried out to demonstrate histopathologic changes in renal tissues. Sildenafil (0.5 and 1.0 mg/kg, intraperitoneal) was administered 1 h before subjecting the rats to renal IRI. In a separate group, bisphenol A diglycidyl ether (30 mg/kg, intraperitoneal), a PPAR-γ receptor antagonist, was given before sildenafil administration followed by IRI. Results The ischemia–reperfusion demonstrated marked AKI with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. The administration of sildenafil demonstrated significant protection against ischemia-reperfusion–induced AKI. The prior treatment with bisphenol A diglycidyl ether abolished sildenafil-mediated renal protection, thereby confirming involvement of PPAR-γ agonism in the sildenafil-mediated renoprotective effect. Conclusions It is concluded that sildenafil protects against ischemia-reperfusion–induced AKI through PPAR-γ agonism in rats.

The purpose of this study was to develop folic acid functionalized long-circulating co-encapsulated docetaxel (DTX) and curcumin (CRM) solid lipid nanoparticles (F-DC-SLN) to improve the pharmacokinetic and efficacy of DTX therapy. F-DC-SLN was prepared by hot melt-emulsification method and optimized by face centered-central composite design (FC-CCD). The SLN was characterized in terms of size and size distribution, drug entrapment efficiency and release profile. The cytotoxicity and cell uptake of the SLN formulations were evaluated in MCF-7 and MDA-MB-231 cell lines. The in vivo pharmacokinetic and biodistribution were studied in Wistar rats. F-DC-SLN exhibited 247.5 ± 3.40 nm particle size with 73.88 ± 1.08% entrapment efficiency and zeta potential of 14.53 ± 3.6 mV. Transmission electron microscopy (TEM) revealed spherical morphology of the SLN. Fluorescence microscopy confirmed the targeting efficacy of F-DC-SLN in MCF-7 cells. F-DC-SLN exhibited a significant increase in area under the curve (594.21 ± 64.34 versus 39.05 ± 7.41 μg/mL h) and mean residence time (31.14 ± 19.94 versus 7.24 ± 4.51 h) in comparison to Taxotere®. In addition, decreased DTX accumulation from F-DC-SLN in the heart and kidney in comparison to Taxotere may avoid to toxicity these vital organs. In conclusion, the F-DC-SLN improved the efficacy and pharmacokinetic profile of DTX exhibiting enhanced potential in optimizing breast cancer therapy.

Background and Objective: In the contemporary practice, the use of drug-eluting stents is still associated with low mortality benefits, restenosis and stent thrombosis. To address these issues, newer generation, thin-strut, biodegradable polymer coated stents has been designed. Thus, the aim of the study is to assess the safety and clinical performance of the Everoflex (Sahajanand Medical Technologies Pvt. Ltd., Surat, India), a newer generation biodegradable polymer coated everolimus-eluting stent, in unselected “real-world” patients with coronary artery disease. Methods: It is a multicentre, retrospective, non-randomized, single-arm study enrolling all the consecutive patients who underwent implantation with the Everoflex for coronary artery disease from April 2014 to March 2016. The primary end-point of the study is 30-day major adverse cardiovascular events (MACE) rate, which consists of cardiac death, myocardial infarction, target lesion revascularization and target vessel revascularization. Stent thrombosis was also analyzed and reported. Results: A total of 340 patients were intervened successfully with 395 everolimus eluting stents (1.3 ± 0.6 stents per patient). Out of total patients (58.7 ± 10.5 years), 77.9% were male and comorbidities like diabetes and hypertension were observed in 31.2% and 35.3% patients, respectively. According to ACC/AHA classification, there were 34.4% type B lesions and 53.2% type C lesions, indicating a higher proportion of complexity involved. Moreover, 57.9% patients had multivessel disease and there were 15.4% total occlusions. At 30 days, follow-up was completed in 100% patients. The MACE was found to be 1.5%, which is a composite of 1.2% cardiac death and 0.3% target lesion revascularization. Stent thrombosis at 30 days was found to be 0.3%. Conclusion: The low incidence of MACE and stent thrombosis clearly depicts excellent safety and clinical performance of the Everoflex in unselected real world patients with coronary artery disease.

BACKGROUND The prognosis for patients with atypical and malignant meningioma is guarded; whether the extent of resection is associated with survival-based outcomes in this population remains poorly defined. This study investigated the association between gross total resection (GTR) and all-cause mortality in patients with atypical and malignant meningioma. METHODS The Surveillance, Epidemiology, and End Results program was used to identify 575 and 64 patients betweens the ages of 18 and 70 years who were diagnosed with atypical and malignant meningioma, respectively, between 2004 and 2009. Multivariate Cox proportional hazards regression was used to assess the adjusted impact of GTR versus subtotal resection on all-cause mortality. RESULTS Baseline patient characteristics were similar for patients who did undergo GTR and patients who did not undergo GTR. The 5-year overall survival rates were 91.3% (95% confidence interval [CI], 86.2%-94.5%) and 78.2% (95% CI, 70.0%-84.3%) for patients with atypical meningioma who did and did not undergo GTR, respectively, and 64.5% (95% CI, 45.9%-78.1%) and 41.1% (95% CI, 17.9%-63.1%) for patients with malignant meningioma who did and did not undergo GTR, respectively. After adjustments for available, pertinent confounding variables, GTR was associated with lower all-cause mortality in patients with atypical (hazard ratio, 0.39; 95% CI, 0.23-0.67; P

Background: Nerve conduction studies (NCSs) are essential for diagnosing various kinds of focal and diffuse neuropathies. Due to the paucity of local NCS data, electrodiagnostic laboratories in Punjab rely on values from Western and other Indian studies. Aim: This study was conducted to provide normative data for median nerve conduction parameters (motor and sensory) in Punjabi populace. Materials and Methods: A cross-sectional study was done on 290 participants (150 males and 140 females), aged 17–21 years, as per standardized protocol. The data were analyzed separately for both genders using SPSS version 20. It consisted of distal latencies and conduction velocities of motor and sensory divisions of median nerve. Student's unpaired t-test was used for statistical analysis. Results: There was no effect of gender on any of the median nerve conduction parameters. Height and weight had nonsignificant negative and positive correlation, respectively (P > 0.05), with conduction velocity in both motor and sensory median nerves. For median motor nerve, the values of distal latency and conduction velocity in males were 2.9 ± 0.16 ms and 60.25 ± 2.99 m/s, respectively, whereas, in females, they were 2.6 ± 0.43 ms and 59.83 ± 2.82 m/s. Similarly, for median sensory nerve, the latency and velocity values in males were 2.8 ± 0.56 ms and 54.81 ± 3.70 m/s, whereas, in females, they were 2.4 ± 0.33 ms and 54.56 ± 3.65 m/s, respectively. Conclusion: The data in this study compared favorably with already existing data. It would help the local electrodiagnostic laboratories in assessing the median nerve abnormalities with greater accuracy in this population subset.

Homeless children are those who live alone on the street. UNICEF estimated that India has 18 million homeless children which is the largest population in the world. Use of psychoactive substance is particularly high in street children as seen in 40-70% of street children across various Indian cities are substance abusers. The study was conducted at District Ludhiana, Punjab. 60 Homeless children of age group 6-18 years were selected by snowball sampling. WHO Assist V 3.0 and a structured questionnaire were used to collect data. Findings reveals that 55 (91.7%) of the homeless children were psychoactive substance abusers with 14.95 ± 02.50 years as mean age of initiation of the substance abuse. Major factors to initiate substance abuse were enjoyment and peer pressure. Age (p=0.02), Male gender (p=0.43), Illiteracy (p=43) were associated with substance abuse among homeless children.

Flavones have antioxidant, anti-proliferative, anti-tumor, anti-microbial, estrogenic, acetyl cholinesterase, anti-inflammatory activities and are also used in cancer, cardiovascular disease, neurodegenerative disorders, etc. Also, flavonoids are found to have an effect on several mammalian enzymes like protein kinases that regulate multiple cell signaling pathways and alterations in multiple cellular signaling pathways are frequently found in many diseases. Flavones have been an indispensable anchor for the development of new therapeutic agents. The majority of metabolic diseases are speculated to originate from oxidative stress, and it is therefore significant that recent studies have shown the positive effect of flavones on diseases related to oxidative stress. Due to the wide range of biological activities of flavones, their structure-activity relationships have generated interest among medicinal chemists. The outstanding development of flavones derivatives in diverse diseases in very short span of time proves its magnitude for medicinal chemistry research. The present review gives detail about the structural requirement of flavone derivatives for various pharmacological activities. This information may provide an opportunity to scientists of medicinal chemistry discipline to design selective, optimize as well as poly-functional flavone derivatives for the treatment of multi-factorial diseases.