Advances In Pharmacotherapy Research Articles

Brain Cancer Chemotherapy through a Delivery System across the Blood-Brain Barrier into the Brain Based on Receptor-Mediated Transcytosis Using Monoclonal Antibody Conjugates.

Advances in pharmacotherapy have brought extraordinary benefits to humanity. However, unmet medical needs in patients remain, particularly in the treatment of central nervous system (CNS) diseases and cancers. CNS drug delivery into the brain across the endothelium is difficult due to the blood-brain barrier (BBB), which is composed mainly of tight junctions and efflux transporters, such as multiple drug resistance 1 (MDR1) (P-glycoprotein). On the other hand, the development of anti-cancer drugs is a challenging task due to their frequent off-target side effects and the complicated mechanisms of cancer pathogenesis and progression. Brain cancer treatment options are surgery, radiation therapy, and chemotherapy. It is difficult to remove all tumor cells, even by surgical removal after a craniotomy. Accordingly, innovative brain cancer drugs are needed. Currently, antibody (Ab) drugs that show high therapeutic effects are often used clinically. Furthermore, antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan, an anti-HER2 (human epidermal receptor 2) ADC with low-molecular cancer drugs through the suitable linker, have been developed. In the case of trastuzumab deruxtecan, it is internalized into cancer cells across the membrane via receptor-mediated endocytosis. Moreover, it is reported that drug delivery into the brain across the BBB was carried out via receptor-mediated transcytosis (RMT), using anti-receptor Abs as a vector against the transferrin receptor (TfR) or insulin receptor (InsR). Thus, anti-TfR ADCs with cancer drugs are promising brain cancer agents due to their precise distribution and low side effects. In this review, I introduce the implementations and potential of brain cancer drug delivery into the brain across the BBB, based on RMT using ADCs.

Increasing trend of radiographic features of knee osteoarthritis in rheumatoid arthritis patients before total knee arthroplasty

To investigate the trend and factors related to the occurrence of osteoarthritis (OA)-like features on knee radiographs of rheumatoid arthritis (RA) patients undergoing total knee arthroplasty (TKA) in the recent decades. To classify antero-posterior knee radiographs into ‘RA’ and ‘OA-like RA’ groups, a deep learning model was developed by training the network using knee radiographs of end-stage arthropathy in RA patients obtained during 2002–2005 and in primary OA patients obtained during 2007–2009. We used this model to categorize 796 knee radiographs, which were recorded in RA patients before TKA during 2006–2020, into ‘OA-like RA’ and ‘RA’ groups. The annual ratio of ‘OA-like RA’ was investigated. Moreover, univariate and multivariate analyses were performed to identify the factors associated with the classification as OA-like RA using clinical data from 240 patients. The percentage of ‘OA-like RA’ had significant increasing trend from 20.9% in 2006 to 67.7% in 2020. Higher body mass index, use of biologics, and lower level of C-reactive protein were identified as independent factors for ‘OA-like RA’. An increasing trend of knee radiographs with OA-like features was observed in RA patients in the recent decades, which might be attributed to recent advances in pharmacotherapy.

Curcumin - The Nutraceutical With Pleiotropic Effects? Which Cardiometabolic Subjects Might Benefit the Most?

Despite continuous advances in pharmacotherapy, atherosclerotic cardiovascular disease remains the world's leading killer. Atherosclerosis relates not only to an increased level of cholesterol, but involves the development of atherosclerotic plaques, which are formed as a result of processes including inflammation and oxidative stress. Therefore, in addition to the classical risk factors for ASCVD (such as type 2 diabetes, overweight, obesity, hypertension and metabolic syndrome), residual risk factors such as inflammation and oxidative stress should also be reduced. The most important intervention in ASCVD is prevention, which includes promoting a healthy diet based on products of natural origin. Curcumin, which is often present in the diet, has been demonstrate to confer several benefits to health. It has been shown in numerous clinical trials that curcumin exhibited anti-diabetic, lipid-lowering, antihypertensive, antioxidant and anti-inflammatory effects, as well as promoting weight loss. All this means that curcumin has a comprehensive impact on the most important risk factors of ASCVD and may be a beneficial support in the treatment of these diseases. Recently, it has also been shown that curcumin may have a beneficial effect on the course of SARS-CoV-2 infection and might be helpful in the prevention of long-COVID complications. The aim of this review is to summarize the current knowledge regarding the safety and efficacy of curcumin in the prevention and treatment of cardiometabolic diseases.

Abstract #1183815: Diagnosis of Cushing’s Disease Post Bariatric Surgery

Obesity is a major risk factor for the development of metabolic comorbidities and is the leading cause of preventable death. Despite recent advances in pharmacotherapy, bariatric surgery (BS) remains the most effective treatment for obesity, leading to weight loss and improvement of metabolic comorbidities. The preoperative evaluation for BS does not recommend for the routine screening of secondary causes for weight gain such as hypercortisolism, unless clinically indicated. The diagnosis of Cushing syndrome can be challenging and many BS patients do not see an endocrinologist preoperatively.

More than 20 years’ follow-up of metatarsal neck shortening oblique osteotomy for rheumatoid forefoot deformity

BackgroundIn recent years, advances in pharmacotherapy for rheumatoid arthritis (RA) have dramatically improved the control of disease activity. However, a significant number of patients still develop forefoot deformity. The purpose of this study was to investigate the results of more than 20 years’ follow-up of metatarsal neck shortening oblique osteotomy (SOO) for forefoot deformity in patients with RA. MethodsThe metatarsal neck SOO was performed on 163 feet in 108 patients between January 1985 and December 1996 in the authors’ hospital. For the patients, who met the survey criteria, an observational study was performed clinically and radiologically at the baseline and at more than 20 years after surgery. ResultsA retrospective cohort study was conducted on 36 feet in 22 patients, all of whom were female, and the mean age at surgery was 45.6 (35.0–63.0) years old. The follow-up period was 25.1 (21.0–31.0) years. The presence of painful callosities in the surgically treated feet without revised surgeries decreased from 32 feet (100%) to 4 feet (12.5%) at the last follow-up with mild pain that did not cause any footwear problems. Re-osteotomy at the metatarsal of the lessor toe was performed on four feet in two patients. Radiologically, among 128 toes without revised surgeries, 85% were able to have the joint space preserved, and 89% maintained a pain-free condition without any recurrence of deformity. The mean total Japanese Society for Surgery for the Foot (JSSF) RA foot and ankle score was 64.0/100, and the visual analogue scale (VAS) of overall satisfaction was 62 (0: dissatisfied, 100: highly satisfied). The overall satisfaction had a positive correlation with calcaneal pitch and negative correlation with joint space narrowing at the talocrural joint. ConclusionsMetatarsal neck SOO appeared to be effective for patients with RA. The deformity was corrected and retained for a long time.

Antimicrobial Treatment Options for Difficult-to-Treat Resistant Gram-Negative Bacteria Causing Cystitis, Pyelonephritis, and Prostatitis: A Narrative Review.

Urinary tract infections, including cystitis, acute pyelonephritis, and prostatitis, are among the most common diagnoses prompting antibiotic prescribing. The rise in antimicrobial resistance over the past decades has led to the increasing challenge of urinary tract infections because of multidrug-resistant and "difficult-to-treat resistance" among Gram-negative bacteria. Recent advances in pharmacotherapy and medical microbiology are modernizing how these urinary tract infections are treated. Advances in pharmacotherapy have included not only the development and approval of novel antibiotics, such as ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, ceftolozane/tazobactam, cefiderocol, plazomicin, and glycylcyclines, but also the re-examination of the potential role of legacy antibiotics, including older aminoglycosides and tetracyclines. Recent advances in medical microbiology allow phenotypic and molecular mechanism of resistance testing, and thus antibiotic prescribing can be tailored to the mechanism of resistance in the infecting pathogen. Here, we provide a narrative review on the clinical and pre-clinical studies of drugs that can be used for difficult-to-treat resistant Gram-negative bacteria, with a particular focus on data relevant to the urinary tract. We also offer a pragmatic framework for antibiotic selection when encountering urinary tract infections due to difficult-to-treat resistant Gram-negative bacteria based on the organism and its mechanism of resistance.

Advances in pharmacotherapy for advanced thyroid cancer of follicular origin (PTC, FTC). New approved drugs and future therapies

ABSTRACT Introduction The most common altered signaling found in aggressive iodine-refractory thyroid cancers derived from follicular cells (RAI-TC) are RTK, MAPK, PI3K, WNT, BRAF, RAS, RET, and TP53. Tyrosine Kinase Inhibitors (TKI) are multi-kinase inhibitors able to act against different pathways, that elicit an anti-neoplastic activity. Areas covered The aim of this paper is to review recent novel molecular therapies of RAI-TC. Recently, sorafenib and lenvatinib, have been approved for the treatment of aggressive RAI-TC. Other studies are evaluating vandetanib and selumetinib in RAI-TC. Furthermore, preliminary studies have evaluated dabrafenib, and vemurafenib in BRAF mutated RAI-TC patients to re-induce 131-iodine uptake. The interplay between cells of the immune system and cancer cells can be altered by immune checkpoints inhibitors. The expression of PDL1 in RAI-TC was related to tumor recurrence and poor survival. Several clinical trials are investigating a combination of different therapies, such as lenvatinib and pembrolizumab. Expert opinion Mechanisms of resistance to TKIs inhibitors can be of intrinsic or acquired origin. An acquired resistance to lenvatinib, or sorafenib can be due to upregulation of FGFR; therefore, anti-FGFR agents are evaluated. A new strategy is to combine TKIs with immunotherapy. Several studies are evaluating lenvatinib and pembrolizumab in RAI-TC patients.

Advances in pharmacotherapy for postpartum depression: a structured review of standard-of-care antidepressants and novel neuroactive steroid antidepressants.

Postpartum depression is one of the most common morbidities of childbearing, yet it is underdiagnosed and undertreated with negative consequences for mother and offspring. Despite the widespread use of standard-of-care antidepressants as the mainstay of treatment for postpartum depression, there is limited evidence on their safety and efficacy due to their slow onset of action and suboptimal outcomes. The emergence of gamma-aminobutyric acidergic neuroactive steroids may offer faster response and remission times and improved patient outcomes. This article reviews the evidence base for the efficacy of standard-of-care antidepressants, hormonal therapeutics including progestins and estradiol, and gamma-aminobutyric acidergic neuroactive steroids in the treatment of postpartum depression, as well as the safety of infant exposure to these agents during lactation.

Advances in pharmacotherapy for cholangiocarcinoma: from conventional therapies to targeted drugs

ABSTRACT Introduction Cholangiocarcinomas (CCA) are rare, highly invasive tumors often diagnosed at an advanced disease stage with an associated poor prognosis. Surgery represents the only chance for curative-intent treatment, but recurrence rates remain high. Neoadjuvant or adjuvant chemotherapy are options for patients with resectable CCA to increase recurrence-free survival and overall survival, while palliative chemotherapy represents the treatment for unresectable disease. Global efforts are currently focused on the development of novel more effective therapies. Areas covered A review was conducted in August 2021 using the PubMed database with the following keywords: ‘cholangiocarcinoma,’ ‘chemotherapy,’ and ‘therapy.’ Manuscripts reporting on first- and second-line chemotherapy, neoadjuvant and adjuvant treatment regimens, and targeted therapies currently being tested or employed in the management of CCA were examined. Expert opinion The prognosis of CCA is negatively affected by several factors including a lack of reliable biomarkers leading to delayed diagnoses, high inter- and intra-tumoral heterogeneity, and few effective chemotherapy regimens. In pursuit of more effective therapies, ongoing trials are testing both conventional and targeted drugs.

Advances with pharmacotherapy for the treatment of interstitial lung disease

ABSTRACT Introduction In recent decades, the primary focus of pharmaceutical research in interstitial lung diseases (ILD) has been on idiopathic pulmonary fibrosis (IPF). Recently, pharmaceutical development has also focused on other forms of ILDs, including connective tissue diseases associated ILD, fibrotic hypersensitivity pneumonitis, and sarcoidosis. Areas Covered The authors summarize the advances in pharmacotherapy for the treatment of ILD. Specifically, the authors review the most recent studies and discuss the most recent research findings and future prospects. Expert opinion Data collected over the past years have confirmed the efficacy of antifibrotic drugs on slowing disease progression in IPF. The usual strategy for CTD-ILD management is represented by the combined use of corticosteroids and immunosuppressive agents. There is an urgent need for new target therapies. The concept of progressive fibrosing ILD has emerged in the ILD community in recent years, which has led to grouping several diseases with a common disease behavior to find an effective treatment . At present, selecting the best therapy in ILDs should be reasonably performed on a case-by-case basis through a multidisciplinary team discussion in tertiary ILD centers, taking into consideration patients’ symptoms, lung functional trends, and radiological changes.

The Gut Microbiota Metabolite Urolithin B Improves Cognitive Deficits by Inhibiting Cyt C-Mediated Apoptosis and Promoting the Survival of Neurons Through the PI3K Pathway in Aging Mice.

Background: Despite considerable advances in pharmacotherapy, more effective therapeutic interventions for aging-related neurodegenerative disorders (NDs), such as Alzheimer’s disease (AD), remain limited. Urolithin B (UB), one of the major subcategories of urolithins (microbiota metabolites) found in various tissues after ellagitannin consumption, has been shown to possess antioxidant, anti-inflammatory, and antiapoptotic effects. However, the neuroprotective effect of UB on brain aging in mice and its potential mechanisms were still unknown. Methods: In the current research, we first assessed the ameliorative effects of UB on oxidative injury and apoptosis induced by H2O2 in neuro-2a cells. Then a subcutaneous injection of D-galactose in mice for 8 weeks was used to establish the aging model to evaluate the protective effects of UB. The capacity of memory and learning, alterations of hippocampus histology and corresponding molecular mechanisms were all evaluated. Results: The D-gal-induced accelerated aging model in vivo demonstrated that UB could significantly ameliorate deficits in learning and memory by inhibiting the accumulation of advanced glycation end products (AGEs) and elevating the expression and activity of Cu, Zn-SOD and CAT. Furthermore, UB downregulated the c-Jun N-terminal kinase (JNK) signaling pathway and prevented cytochrome c release from isolated mitochondria, thereby inhibiting neuronal apoptosis during the aging process. More importantly, UB stimulation of aging mice activated ERK and phosphoinositide 3-kinase (PI3K), leading to neuronal survival along with Akt and p44/42 mitogen-activated protein kinase (MAPK) phosphorylation and activation. Conclusion: In summary, UB effectively alleviated cognitive deficits and ameliorated brain aging-related conditions and could be considered a healthcare product to prevent aging-associated NDs such as AD.

Early-Life Origins of Metabolic Syndrome: Mechanisms and Preventive Aspects.

One of the leading global public-health burdens is metabolic syndrome (MetS), despite the many advances in pharmacotherapies. MetS, now known as “developmental origins of health and disease” (DOHaD), can have its origins in early life. Offspring MetS can be programmed by various adverse early-life conditions, such as nutrition imbalance, maternal conditions or diseases, maternal chemical exposure, and medication use. Conversely, early interventions have shown potential to revoke programming processes to prevent MetS of developmental origins, namely reprogramming. In this review, we summarize what is currently known about adverse environmental insults implicated in MetS of developmental origins, including the fundamental underlying mechanisms. We also describe animal models that have been developed to study the developmental programming of MetS. This review extends previous research reviews by addressing implementation of reprogramming strategies to prevent the programming of MetS. These mechanism-targeted strategies include antioxidants, melatonin, resveratrol, probiotics/prebiotics, and amino acids. Much work remains to be accomplished to determine the insults that could induce MetS, to identify the mechanisms behind MetS programming, and to develop potential reprogramming strategies for clinical translation.

Modern achievements in pharmacotherapy of osteoarthritis based on endo- and phenotyping

The review of medical literature is devoted to modern data in the field of diagnosis and treatment of osteoarthritis using endo- and phenotyping. It includes the latest data on the epidemiology of osteoarthritis of different localizations, modern definitions and classifications of osteoarthritis endotypes and phenotypes, pathobiochemical patterns and pathomorphological parallels of disease phenotypes, new methodological approaches to the phenotyping of osteoarthritis (prognostic, prescriptive phenotyping, alternative methods), as well as modern advances in pharmacotherapy of the disease based on data from selected randomized controlled trials and meta-analyzes.

What Is the Status of Regenerative Therapy in Heart Failure?

Heart failure remains a major public health concern with high burden of morbidity and mortality despite advances in pharmacotherapy, device therapy, and surgical and percutaneous techniques. Cardiac regeneration may have a role to play in these patients with a huge unmet need for these therapies in patients with chronic ischemic heart disease, post-infarct heart failure, dilated cardiomyopathy, and heart failure with preserved ejection fraction. In this review, we focus on the pre-clinical and translational basis for different modes of cardiac regenerative medicine and then critically appraise the clinical evidence amassed from pivotal clinical trials focused on cardiac regeneration for ischemic and non-ischemic cardiomyopathies. Cardiac regenerative medicine is rapidly evolving with novel approaches involving cell-based, cell-free, tissue engineering, and hybrid therapies to achieve myocardial regeneration and repair. Further studies are warranted with a robust comparison arm with optimal contemporary medical therapy to translate regenerative therapies to a clinical reality.

Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis.

Despite advances in pharmacotherapy, intervention devices and techniques, residual cardiovascular risks still cause a large burden on public health. Whilst most guidelines encourage achieving target levels of specific lipids and lipoproteins to reduce these risks, increasing evidence has shown that molecular modification of these lipoproteins also has a critical impact on their atherogenicity. Modification of low-density lipoprotein (LDL) by oxidation, glycation, peroxidation, apolipoprotein C-III adhesion, and the small dense subtype largely augment its atherogenicity. Post-translational modification by oxidation, carbamylation, glycation, and imbalance of molecular components can reduce the capacity of high-density lipoprotein (HDL) for reverse cholesterol transport. Elevated levels of triglycerides (TGs), apolipoprotein C-III and lipoprotein(a), and a decreased level of apolipoprotein A-I are closely associated with atherosclerotic cardiovascular disease. Pharmacotherapies aimed at reducing TGs, lipoprotein(a), and apolipoprotein C-III, and enhancing apolipoprotein A-1 are undergoing trials, and promising preliminary results have been reported. In this review, we aim to update the evidence on modifications of major lipid and lipoprotein components, including LDL, HDL, TG, apolipoprotein, and lipoprotein(a). We also discuss examples of translating findings from basic research to potential therapeutic targets for drug development.

Implementing Nonphysician Provider Guideline-Directed Medical Therapy Heart Failure Clinics: A Multi-National Imperative

Heart failure (HF) is a global epidemic, with more than 60 million patients living with HF worldwide. 1 Lippi G Sanchis-Gomar F. Global epidemiology and future trends of heart failure. AME Med J. 2020; 5 Crossref Google Scholar With an ageing population, this number is projected to continue to increase and will result in significant economic and resource strain on health care systems. Despite recent advances in pharmacotherapy, morbidity and mortality related to HF remains high. This, in part, may be related to a significant portion of patients receiving sub-optimal, guideline-directed medical pharmacotherapy (GDMT). Greene et al 2 Greene SJ Butler J Albert NM et al. Medical therapy for heart failure with reduced ejection fraction: the champ-hf registry. J Am Coll Cardiol. 2018; 72: 351-366 Crossref PubMed Scopus (270) Google Scholar highlighted this trend in the United States through the Change the Management of Patients with Heart Failure (CHAMP-HF) registry. Among patients with HF with reduced ejection fraction (HFrEF) eligible for angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors (ARNi), beta blockers (BB), and mineralocorticoid receptor antagonists, these therapies were, concerningly, only prescribed in 27%, 33%, and 67% of eligible patients. Only a small portion of patients started on these foundational therapies were receiving target doses. Most notably, only 1% of the 3518 patients (approximately 35 patients) were simultaneously receiving target doses of all 3 therapies. The picture is similar internationally, with British registry data showing that failure to prescribe all 3 disease-modifying therapies is negatively associated with mortality in patients discharged after a recent HF hospitalization. It should also be mentioned that current registry data was collected before the release of recent sodium-glucose transport protein 2 inhibitor data, which has now led to an additional class of medications being recommended as part of the therapeutic backbone for HFrEF. 3 Maddox TM Januzzi JL et al. 2021 update to the 2017 acc expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology solution set oversight committee. J Am Coll Cardiol. 2021; 77: 772-810 Crossref PubMed Scopus (83) Google Scholar Furthermore, recent data from CONNECT-HF continues to reveal suboptimal dosing for patients with HFrEF, between 25% and 40% for ACEI, angiotensin receptor blocker, ARNI, BB, and mineralocorticoid receptor antagonist therapy. 4 CONNECT-HF: Can Additional HospitalPost-Discharge QI Interventions Improve HF Outcomes, Care?. American College of Cardiology, 2021https://www.acc.org/Latest-in-Cardiology/Articles/2021/05/12/19/40/Mon-8am-CONNECT-HF-acc-2021 Google Scholar

Cannabidiol prevents lipopolysaccharide-induced sickness behavior and alters cytokine and neurotrophic factor levels in the brain.

BackgroundMajor depressive disorder (MDD) affects millions of people worldwide. While the exact pathogenesis is yet to be elucidated, the role of neuro-immune signaling has recently emerged. Despite major advances in pharmacotherapy, antidepressant use is marred by limited efficacy and potential side effects. Cannabidiol (CBD), a phytocannabinoid, exerts antidepressant-like effects in experimental animals. This study investigated the impact of CBD on sickness behavior (SB), a measure of depressive-like response, and neuro-immune changes induced by lipopolysaccharides (LPS) in mice.MethodsSocially isolated rodents were administered with LPS to trigger SB. and treated with CBD or its vehicle. Animals were submitted to forced swimming test, to evaluate depressive-like behavior, and to open field test, to evaluate locomotory activity. Immediately after behavioral analyses, animals were euthanized and had their hypothalamus, prefrontal cortex and hippocampus dissected, to proceed neurotrophins and cytokines analyses. ELISA was used to detect IL-1β, BDNF and NGF; and cytometric beads array to measure IL-2, IL-4, IL-6, IFN-γ, TNF-α and IL-10 levels.ResultsCBD effectively prevented SB-induced changes in the forced swim test without altering spontaneous locomotion. This phytocannabinoid also partially reversed LPS-evoked IL-6 increase in both the hypothalamus and hippocampus. In addition, CBD prevented endotoxin-induced increase in BDNF and NGF levels in the hippocampus of SB animals.ConclusionsApparently, CBD prevents both behavioral and neuro-immunological changes associated with LPS-induced SB, which reinforces its potential use as an antidepressant which modulates neuroinflammation. This opens up potentially new therapeutic avenues in MDD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43440-021-00301-8.

Advances in pharmacotherapy for head and neck cancer

ABSTRACT Introduction: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and is a leading cause for cancer-related mortality. This review attempts to give a comprehensive summary of the recent developments in pharmacotherapeutic options for locally advanced/metastatic HNSCC. Areas covered: In this review, the authors conducted a systematic literature search for published articles on HNSCC in the PubMed database using the keywords ‘head and neck squamous cell carcinoma or HNSCC,’ ‘targeted therapy,’ ‘immunotherapy.’ The search was restricted to meta-analyses, clinical trials, practice guidelines, and abstract presentations at international meetings. The final search encompassed articles published from 2010 to 2021. Articles published in languages other than English were excluded. Expert opinion: Immune checkpoint inhibition has been the most significant advance in the treatment of R/M HNSCC. Oral metronomic therapy has emerged as an important therapeutic option for low to middle-income countries. H-RAS inhibition is one of the most promising areas of research.

English

BACKGROUND Schizophrenia is a chronic mental illness with severe disruptions in thought, perception, language, and sense of self. Although there are a lot of recent advances in pharmacotherapy, a large percentage of persons with Schizophrenia remain treatment resistant or at least partially non-resistant to drugs. The recent increase of interest in the neurobiology of Schizophrenia and other psychiatric disorders, the emergence of neuropsychiatry, and the recent advances in computerized analyses of EEG have resulted in a revival of interest in electrophysiology among mental health professionals. METHODS This is a prospective observational study. A total of 84 subjects who were drug naïve and diagnosed with Schizophrenia were included in the study by convenience sampling. General information sheet to collect the socio-demographic and clinical details, Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression scale, Electroencephalogram recordings were used. Data analysis was performed by using the SPSS Software version 23. Descriptive statistics and correlational statistics were used to analyse the collected data. RESULTS A total of 84 subjects who were diagnosed with Schizophrenia were included in the study. Out of 84 patients, 22 were lost to follow up bringing the valid sample of the study to 62. EEGs of the sample subjects were classified based on the modified sample, EEGs of 45 (72.58 %) subjects were normal, EEGs of 13 (20.97 %) subjects were essentially normal, and EEGs of 4 (6.45 %) subjects were classified as abnormal. CONCLUSIONS No statistically significant differences were found in Positive and negative syndrome scale scores at baseline when compared between normal, essentially normal and abnormal EEG groups of first episode schizophrenia subjects. KEYWORDS Electroencephalogram (EEG), Schizophrenia, PANSS, CGI Scale, SPSS Software Version 23.0

Mechanotransduction assays for neural regeneration strategies: A focus on glial cells.

Glial cells are mechanosensitive, and thus, engineered systems have taken a step forward to design mechanotransduction platforms in order to impart diverse mechanical stresses to cells. Mechanical strain encountered in the central nervous system can arise from diverse mechanisms, such as tissue reorganization, fluid flow, and axon growth, as well as pathological events including axon swelling or mechanical trauma. Biomechanical relevance of the in vitro mechanical testing requires to be placed in line with the physiological and mechanical changes in central nervous tissues that occur during the progression of neurodegenerative diseases. Mechanotransduction signaling utilized by glial cells and the recent approaches intended to model altered microenvironment adapted to pathological context are discussed in this review. New insights in systems merging substrate's stiffness and topography should be considered for further glial mechanotransduction studies, while testing platforms for drug discoveries promise great advancements in pharmacotherapy. Potential leads and strategies for clinical outcomes are expected to be developed following the exploration of these glial mechanosensitive signaling pathways.