Breaking Barriers in Alzheimer's Disease: the Role of Advanced Drug Delivery Systems.

Alzheimer's disease (AD), characterized by cognitive impairment, brain plaques, and tangles, is a global health concern affecting millions. It involves the build-up of amyloid-ß (Aß) and tau proteins, the formation of neuritic plaques and neurofibrillary tangles, cholinergic system dysfunction, genetic variations, and mitochondrial dysfunction. Various signaling pathways and metabolic processes are implicated in AD, along with numerous biomarkers used for diagnosis, risk assessment, and research. Despite these, there is no cure or effective treatment for AD. It is critically important to address this immediately to develop novel drug delivery systems (NDDS) capable of targeting the brain and delivering therapeutic agents to modulate the pathological processes of AD. This review summarizes AD, its pathogenesis, related signaling pathways, biomarkers, conventional treatments, the need for NDDS, and their application in AD treatment. It also covers preclinical, clinical, and ongoing trials, patents, and marketed AD formulations.

Mechanistic insights of neuronal calcium and IP3 signaling system regulating ATP release during ischemia in progression of Alzheimer's disease.

The mechanisms of calcium ([Ca2+]) signaling in various human cells have been widely analyzed by scientists due to its crucial role in human organs like the heartbeat, muscle contractions, bone activity, brain functionality, etc. No study is reported for interdependent [Ca2+] and IP3 mechanics regulating the release of ATP in neuron cells during Ischemia in Alzheimer's disease advancement. In the present investigation, a finite element method (FEM) is framed to explore the interdependence of spatiotemporal [Ca2+] and IP3 signaling mechanics and its role in ATP release during Ischemia as well as in the advancement of Alzheimer's disorder in neuron cells. The results provide us insights of the mutual spatiotemporal impacts of [Ca2+] and IP3 mechanics as well as their contributions to ATP release during Ischemia in neuron cells. The results obtained for the mechanics of interdependent systems differ significantly from the results of simple independent system mechanics and provide new information about the processes of the two systems. From this study, it is concluded that neuronal disorders cannot only be simply attributed to the disturbance caused directly in the processes of calcium signaling mechanics, but also to the disturbances caused in IP3 regulation mechanisms impacting the calcium regulation in the neuron cell and ATP release.

A comparison of the quality of images of chest X-ray between handheld portable digital X-ray & routinely used digital X-ray machine.

Background & objectives: Chest X-ray (CXR) is an important screening tool for pulmonary tuberculosis (TB). Accessibility to CXR facilities in difficult-to-reach and underserved populations is a challenge. This can potentially be overcome by deploying digital X-ray machines that are portable. However, these portable X-ray machines need to be validated before their deployment in the field. Here, we compare the image quality of CXR taken by a newly developed handheld X-ray machine with routinely used reference digital X-ray machine through the conduct of a feasibility study. Methods: A total of 100 participants with suspected pulmonary TB were recruited from the outpatient departments of a medical college and a community health centre in Agra. Each participant underwent CXR twice, once with each machine. Both sets of de-identified images were independently read by two radiologists, who were blinded to the type of X-ray machine used. The primary outcome was agreement between image qualities produced by these two machines. Results: The intra-observer (radiologist) agreements regarding the status of the 15 CXR parameters ranged between 74 per cent and 100 per cent, with an unweighted mean of 87.2 per cent (95% confidence interval: 71.5-100). The median Cohen's kappa values for intra-observer agreement were 0.62 and 0.67 for radiologists 1 and 2, respectively. In addition, on comparison of the overall median score of quality of the image, the handheld machine images had a higher score for image quality. Interpretation & conclusions: The current study shows that a handheld X-ray machine, which is easy to use and can potentially be carried to any area, produces X-ray images with quality that is comparable to digital X-ray machines routinely used in health facilities.

Inequalities reinforced through online and distance education in the age of COVID-19: The case of higher education in Nepal.

Coronavirus disease (COVID-19) has triggered serious disruption in economic, social and cultural dynamics around the globe. Higher education has also suffered undeniable challenges as a result of the pandemic, with thousands of university students all over the world experiencing displacement, disconnect and disengagement from formal learning. In the Global South, online and distance education programmes tend to be concentrated in urban centres. In Nepal, students from rural areas, low socio-economic and gendered spaces, and those with low proficiencies in English and technological skills are experiencing inequalities in access to and participation in online and distance education. This article outlines how universities' shift to online teaching and learning modes due to the COVID-19 pandemic has reinforced social inequalities in Nepal. For the study presented here, the author collected data through netnographic research methods. These included online interviews with university executives, online focus group discussions (FGDs) with university teachers and students, observation of and participation in online classes and policy conferences and reviews of online documents. The article analyses three overriding mechanisms which are reinforcing social inequalities in higher education: (1) universities' policy trajectories in shifting teaching/learning from face-to-face to online mode; (2) infrastructural limitations challenging effective implementation of online teaching/learning; and (3) a lack of strong pedagogic support for students from disadvantaged and marginalised spaces, including those with low proficiencies in English and technological skills. The author presents a number of tangible strategies for universities to implement in order to mitigate social inequalities. He recommends the adoption of policies and practices that optimise the inclusive use of online and distance education programmes for best effect, both now and in the post-pandemic era.

L'aggravation des inégalités en raison de l'éducation en ligne et à distance à l'ère de la COVID-19: le cas de l'enseignement supérieur au Népal ­ La COVID-19, maladie due au coronavirus, perturbe gravement la dynamique économique, sociale et culturelle aux quatre coins du globe. Avec des milliers d'étudiants universitaires du monde entier déplacés, déconnectés et désengagés de l'apprentissage formel, l'enseignement supérieur s'est vu confronté à d'indéniables difficultés provoquées par la pandémie. Dans les pays du Sud, les programmes d'éducation en ligne et à distance tendent à se concentrer dans des centres urbains. Au Népal, les étudiants des zones rurales, de communautés socio-économiques défavorisées et genrées, et qui maîtrisent mal l'anglais et l'informatique se trouvent confrontés à des inégalités quant à l'accès et la participation à l'éducation en ligne et à distance. Cet article expose brièvement comment le passage des universités à des modes d'enseignement et d'apprentissage en ligne, dû à la pandémie de COVID-19, a creusé les inégalités au Népal. Pour l'étude présentée ici, l'auteur a collecté des données selon des méthodes de recherche netnographiques, en s'appuyant, notamment, sur des interviews en ligne avec des dirigeants d'universités, sur des discussions de groupe en ligne avec des enseignants et étudiants universitaires, sur l'observation de cours et de conférences politiques en ligne ­ et la participation à ces cours et conférences ­ et sur l'analyse de documents en ligne. L'article analyse trois mécanismes prépondérants qui creusent les inégalités sociales dans le domaine de l'enseignement supérieur : (1) la démarche politique des universités concernant la transition de l'enseignement/de l'apprentissage en face-à-face au mode en ligne ; (2) les limites infrastructurelles qui compliquent la mise en œuvre efficace de l'enseignement/de l'apprentissage en ligne ; (3) enfin, l'absence de soutien pédagogique puissant pour les étudiants de communautés défavorisées et marginalisées, y compris ceux qui maîtrisent mal l'anglais et l'informatique. L'auteur présente tout un ensemble de stratégies concrètes que les universités pourraient mettre en œuvre pour réduire les inégalités sociales. Il recommande l'adoption de politiques et de pratiques optimisant l'utilisation inclusive de programmes d'enseignement en ligne et à distance pour garantir des résultats optimaux, tant maintenant que quand la pandémie appartiendra au passé.

Design, Synthesis, and Screening of Triazolopyrimidine-Pyrazole Hybrids as Potent Apoptotic Inducers.

An efficient synthesis of novel 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-5,7-dimethyl-[1,2,4]triazolo[4,3-a]-pyrimidines was accomplished by the oxidation of pyrimidinylhydrazones by using organoiodine(III) reagent. All new triazolopyrimidine derivatives bearing the pyrazole scaffold were screened to evaluate them as a reproductive toxicant in the testicular germ cells of goat (Capra hircus). This study aimed at assessing the cytological and biochemical changes in testicular germ cells after the exposure to triazolopyrimidines in a dose- and time-dependent manner. Histomorphological analysis, fluorescence assays, apoptosis quantification, and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) assays were performed to determine cytological changes, whereas thiobarbituric acid-reactive substance (TBARS) and ferric reducing antioxidant power (FRAP) assays were carried out to measure the oxidative stress in triazolopyrimidines treated germ cells. The parallel use of these methods enabled us to determine the role of triazolopyrimidines in inducing apoptosis as a consequence of cytogenetic damage and oxidative stress generated in testicular germ cells of goat.

TlyA protein of Mycobacterium leprae: a probable bio-marker of active infection.

The extent of pathogenicity of the mycobacterial infections depends on virulence factors that mediate survival inside macrophages. Virulence factors are generally believed to be specific for pathogenic species and mutated/non-functional in nonpathogenic strains. Mycobacterial TlyA can modulate the phagolysosome maturation pathway, immediately after entry into macrophages. Over-expression of open reading frame (ORF) ML1358 (tlyA) in tissues of leprosy patients by partial DNA chip and real time PCR analysis during active infection attracted our interest to explore the properties of this gene at molecular and serological levels, to understand its role in the host. Molecular properties were studied by cloning and expression of the corresponding gene in pASK-iba 43(þ) expression vector in E. coli and bioinformatics tools while sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and ELISA were applied to investigate the serological significance of rTlyA protein in different clinical states of leprosy. We observed that TlyA has a close relation among mycobacteria with specific protein domains in slow growing intracellular adapted pathogenic species. The presence of trans-membrane domains indicates its association to the cell membrane. The study revealed its highly significant sero-reactivity (P value , 0·001) in borderline lepromatous (BL) patients, and those with reversal reaction (RR) and erythema nodosum leprosum (ENL). Its role in active infection, association with the cell membrane, presence in pathogenic species and high sero-reactivity, suggested the tlyA gene as a strong disease progression marker.

Risk Factors For Necrotizing Fasciitis And Its Outcome At A Tertiary Care Centre.

BACKGROUND: Necrotizing fasciitis (NF) is a serious and potentially fatal condition where there is rapid progression of inflammation of skin, subcutaneous tissue, and superficial fascia and can be mono-microbial or poly-microbial. The disease is rapidly progressive in nature and if not promptly treated leads to significant morbidity or even mortality. This study was designed to explore the various risk factors commonly present and study the outcome of the disease. METHODS: This was a cross sectional study done in tertiary centre over period of one year from April 2014 to March 2015. Patient admitted with soft tissue infection were presumptively made diagnosis of NF based on clinical features and final diagnosis was made after pre-operative surgical findings. RESULTS: Forty two (40.38%) patients had final diagnosis of NF out of 102 soft tissue infections. Twentynine (69%) of 42 patients with NF fully recovered with surgical and medical management. Eleven (26.2%) of these patients succumbed to their illness and two (4.8%) needed amputation of limb to control the infection. The most common co-morbid condition was alcoholism, followed by diabetes mellitus. CONCLUSIONS: The incidence of necrotizing fasciitis in patients admitted with soft tissue infection was 40.38%. Mortality and morbidity due to this condition was found to be high.

Healing the diabetic wound: Unlocking the secrets of genes and pathways.

Diabetic wounds (DWs) are open sores that can occur anywhere on a diabetic patient's body. They are often complicated by infections, hypoxia, oxidative stress, hyperglycemia, and reduced growth factors and nucleic acids. The healing process involves four phases: homeostasis, inflammation, proliferation, and remodeling, regulated by various cellular and molecular events. Numerous genes and signaling pathways such as VEGF, TGF-ß, NF-κB, PPAR-γ, MMPs, IGF, FGF, PDGF, EGF, NOX, TLR, JAK-STAT, PI3K-Akt, MAPK, ERK, JNK, p38, Wnt/ß-catenin, Hedgehog, Notch, Hippo, FAK, Integrin, and Src pathways are involved in these events. These pathways and genes are often dysregulated in DWs leading to impaired healing. The present review sheds light on the pathogenesis, healing process, signaling pathways, and genes involved in DW. Further, various therapeutic strategies that target these pathways and genes via nanotechnology are also discussed. Additionally, clinical trials on DW related to gene therapy are also covered in the present review.

Modelling Cross Talk in the Spatiotemporal System Dynamics of Calcium, IP3 and Nitric Oxide in Neuron Cells.

The bioenergetic system of calcium ([Ca2+]), inositol 1, 4, 5-trisphophate (IP3) and nitric oxide (NO) regulate the diverse mechanisms in neurons. The dysregulation in any or all of the calcium, IP3 and nitric oxide dynamics may cause neurotoxicity and cell death. Few studies are noted in the literature on the interactions of two systems like [Ca2+] with IP3 and [Ca2+] with nitric oxide in neuron cells, which gives limited insights into regulatory and dysregulatory processes in neuron cells. But, no study is available on the cross talk in dynamics of three systems [Ca2+], IP3 and NO in neurons. Thus, the cross talk in the system dynamics of [Ca2+], IP3 and NO regulation processes in neurons have been studied using mathematical model. The two-way feedback process between [Ca2+] and IP3 and two-way feedback process between [Ca2+] and NO through cyclic guanosine monophosphate (cGMP) with plasmalemmal [Ca2+]-ATPase (PMCA) have been incorporated in the proposed model. This coupling handles the indirect two-way feedback process between IP3 and nitric oxide in neuronal cells automatically. The numerical outcomes were acquired by employing the finite element method (FEM) with the Crank-Nicholson scheme (CNS). The present model incorporating the sodium-calcium exchanger (NCX) and voltage-gated calcium channel (VGCC) provides novel insights into the various regulatory and dysregulatory processes due to buffer, IP3-receptor, ryanodine receptor, cGMP kinetics through PMCA channel, etc. and their impacts on the interactive spatiotemporal system dynamics of [Ca2+], IP3 and NO in neurons. It is concluded that the behavior of different crucial mechanisms is quite different for interactions of two systems of [Ca2+] and NO and the interactions of three systems of [Ca2+], IP3 and nitric oxide in neuronal cell due to mutual regulatory adjustments. The association of several neurological disorders with the alterations in calcium, IP3 and NO has been explored in neurons.

Emerging Nanotechnology Involved in Skin Cancer: Pathogenesis, Biomarkers, Ethosomal Formulation and Future Perspective.

Skin cancer, which comprises both melanoma and non-melanoma forms, is frequently diagnosed as the predominant malignancy among today's population. Existing treatments are often prolonged and complex, have a low rate of success, and have side effects. This complexity leads to poor patient adherence and increases the risk of disease recurrence. Ethosomes, extensively studied for their applications in topical and transdermal therapies, are distinguished by their high ethanol content, which facilitates enhanced skin penetration and efficient drug delivery. Compared to traditional liposomes, ethosomes offer notable advantages due to their unique composition, demonstrating potential efficacy in treating various skin conditions, including basal cell carcinoma, squamous cell carcinoma, and melanoma. The present review provides a brief introduction to skin melanoma and its pathogenesis, signalling pathways, biomarkers, the need for ethogel-based drug delivery, applications of ethosomes against skin cancer, and clinical trials.

The Risk of Crimean Congo Haemorrhagic Fever in India as a Growing Health Concern.

Every year witnesses an outbreak of some or the other zoonotic disease that causes the unparalled loss of human life. The year 2022 presented the outbreak of Crimean Congo haemorrhagic fever (CCHF), which brought unprecedented challenges to individuals as well as to the healthcare system all around the world, making it a serious health concern. Rising health concerns have highlighted the importance of managing and decreasing the further transmission of the CCHF virus. CCHF is one of tick-borne viral diseases, which spreads due to various reasons like changes in global warming, environmental influences, and other ecological factors. All these factors somehow impact the disease prevalence. This disease has a negative impact on both humans and livestock. The diverse climate and significant livestock population of India make it susceptible to the prevalence of CCHF. Therefore, it is the need of the hour to develop some strategies in order to tackle the challenges posed by CCHF. This article includes all the cases of CCHF that have occurred in India from the year 2011, along with the fatality rates associated with this disease. Also this study discusses the need to explore some specific drugs for the management and prevention of such diseases. In addition, the pathogenesis of the disease progression, along with some protective measures suggested by the government has been described for prevention of CCHF. Subsequently, this article attempted to draw attention towards the risk that may be posed by CCHF in the coming scenario, emphasizing the importance of taking proactive measures in anticipation of such risks.

Quercetin in Oncology: A Phytochemical with Immense Therapeutic Potential.

Quercetin is a natural flavonoid with various pharmacological actions such as anti-inflammatory, antioxidant, antimicrobial, anticancer, antiviral, antidiabetic, cardioprotective, neuroprotective, and antiviral activities. Looking at these enormous potentials, researchers have explored how they can be used to manage numerous cancers. It's been studied for cancer management due to its anti-angiogenesis, anti-metastatic, and antiproliferative mechanisms. Despite having these proven pharmacological activities, the clinical use of quercetin is limited due to its first-- pass metabolism, poor solubility, and bioavailability. To address these shortcomings, researchers have fabricated various nanocarriers-based formulations to fight cancer. The present review overshadows the pharmacological potential, mechanisms, and application of nanoformulations against different cancers.

A Comprehensive Guide to the Development, Evaluation, and Future Prospects of Self-nanoemulsifying Drug Delivery Systems for Poorly Water-soluble Drugs.

Self-nano Emulsifying Drug Delivery Systems (SNEDDS) are novel formulations that can enhance the solubility and bioavailability of poorly water-soluble drugs. SNEDDS are composed of lipids, surfactants, co-solvents, and drugs and can spontaneously form nanoemulsions when mixed with water under mild agitation. SNEDDS can be formulated as liquid or solid dosage forms and can improve drug absorption by increasing the interfacial area, protecting the drug from degradation, and facilitating lymphatic transport. SNEDDS is characterized by various parameters such as particle size, zeta potential, droplet morphology, emulsification efficiency, drug solubility, and stability. SNEDDS offers several advantages over conventional dosage forms, such as dose reduction, faster onset of action, reduced variability, versatility, and ease of formulation. However, SNEDDS also face some limitations and challenges, such as drug precipitation, cost-effectiveness, compatibility with capsule shells, and lack of predictive in vitro models. SNEDDS has a promising future in the field of pharmaceuticals, especially for personalized medicine and targeted drug delivery.

Polypharmacy in Psychiatry: An In-depth Examination of Drug-drug Interactions and Treatment Challenges.

Polypharmacy in psychiatry is an in-depth examination of drug-drug interactions and treatment challenges that explores the intricate landscape of psychiatric polypharmacy, a practice involving the prescription of multiple medications to individuals with mental health disorders. This review is based on the critical aspects of drug-drug interactions and the associated treatment challenges. Psychiatric polypharmacy is motivated by the complexity of mental health conditions, where monotherapy may be insufficient. While it offers potential benefits, the practice raises concerns related to drug interactions that can compromise safety and efficacy. The review delves into the prevalence and clinical indications for psychiatric polypharmacy, thoroughly analyzing drug interactions, treatment challenges, and strategies for mitigation. Real-world case studies illustrate the complexities and outcomes of managing complex medication regimens, while emerging trends in personalized medicine, advancements in psychopharmacology, multidisciplinary approaches, and digital health solutions offer a glimpse into the future of psychiatric polypharmacy. This examination underscores the importance of a patient-centered, evidence-based approach in optimizing psychiatric polypharmacy to achieve therapeutic benefits while minimizing risks.

Novel drug delivery systems in colorectal cancer: Advances and future prospects.

Colorectal cancer (CRC) is an abnormal proliferation of cells within the colon and rectum, leading to the formation of polyps and disruption of mucosal functions. The disease development is influenced by a combination of factors, including inflammation, exposure to environmental mutagens, genetic alterations, and impairment in signaling pathways. Traditional treatments such as surgery, radiation, and chemotherapy are often used but have limitations, including poor solubility and permeability, treatment resistance, side effects, and post-surgery issues. Novel Drug Delivery Systems (NDDS) have emerged as a superior alternative, offering enhanced drug solubility, precision in targeting cancer cells, and regulated drug release. Thereby addressing the shortcomings of conventional therapies and showing promise for more effective CRC management. The present review sheds light on the pathogenesis, signaling pathways, biomarkers, conventional treatments, need for NDDS, and application of NDDS against CRC. Additionally, clinical trials, ongoing clinical trials, marketed formulations, and patents on CRC are also covered in the present review.

Comparative Evaluation of Multiplex PCR, RLEP PCR and LAMP PCR in Urine, Stool and Blood Samples for the Diagnosis of Pediatric Leprosy - A Cross-Sectional Study.

OBJECTIVE: To compare the diagnostic efficacy of multiplex polymerase chain reaction (PCR), Mycobacterium leprae-specific repetitive element (RLEP) PCR and loop-mediated isothermal amplification (LAMP) PCR in the diagnosis of pediatric leprosy as an alternative to slit-skin smear (SSS) examination. METHODS: A cross-sectional study was performed on 26 children aged 0-18 years with characteristic skin lesions of leprosy. SSS examination for acid fast bacilli (AFB) was performed for all children. Additionally, urine, stool and blood samples were tested by three PCR techniques - multiplex, RLEP and LAMP. The results of these tests were compared with each other and with results of SSS examination for acid fast bacilli (AFB) using appropriate statistical tests. RESULTS: Out of 26 patients studied, SSS examination was positive for AFB in 7 cases (26.9%). In blood samples, the positivity of multiplex PCR, RLEP PCR and LAMP PCR was 84.6%, 80.8%, and 80.8%, respectively. Multiplex PCR in blood samples was positive in 100% (n = 7) of SSS positive cases and 84.2% (16 out of 19) of the SSS negative cases (P < 0.001). The positivity of all PCR methods in urine and stool samples was significantly lesser than in blood. CONCLUSION: Multiplex PCR in blood sample is a superior diagnostic tool for pediatric leprosy compared to RLEP PCR and LAMP PCR as well as SSS examination.

Investigating flock-associated mimicry: examining the evidence for, and drivers of, plumage mimicry in the greater and lesser necklaced laughingthrush.

Visual mimicry is less understood in birds than in other taxa. The interspecific social dominance mimicry (ISDM) hypothesis asserts that subordinate species resemble dominant ones to reduce aggression. Plumage mimicry has also been consistently noted in mixed-species flocks (MSFs), suggesting a connection to grouping behaviour, although it is unclear whether this is linked to ISDM. We studied greater necklaced laughingthrush (GNLT, Pterorhinus pectoralis) and lesser necklaced laughingthrush (LNLT, Garrulax monileger), which were recently placed in different genera. Measurements of 162 museum specimens showed LNLT converging in sympatry with GNLT in necklace colour, but diverging in necklace to body ratio, with proportionally smaller necklaces. The species were closely associated in six of seven MSF systems from Nepal to China. In a study of foraging behaviour in Nepal, aggression was rare between the species, LNLT followed GNLT and had lower foraging rates when further from GNLT. Our data suggest a link between this MSF-associated mimicry and ISDM, and that the subordinate LNLT may be the mimic and gain more from the resemblance. The species spend much time together in dense and poorly lit vegetation, where the LNLTs resemblance to GNLTs potentially allows them to forage closer to GNLTs than would be otherwise possible.

Spectroscopic and computational study of a naphthalene derivative as colorimetric and fluorescent sensor for bioactive anions.

The anion recognition property of a naphthalene based receptor (L) was investigated by naked-eye, UV-Vis, fluorescence, (1)H NMR and computational methods. The receptor L showed fluoride selective naked-eye detectable colorimetric and UV-Vis spectral changes over other tested anions due to the formation of hydrogen bonding complex in 1:1 stoichiometry and/or deprotonation between fluoride and the receptor. Interestingly, the fluorescence of L was quenched by fluoride but enhanced by acetate.

Predicting the Role of Preoperative Intramedullary Lesion Length and Early Decompressive Surgery in ASIA Impairment Scale Grade Improvement Following Subaxial Traumatic Cervical Spinal Cord Injury.

BACKGROUND: Traumatic cervical spinal cord injury (TCSCI) is a disabling condition with uncertain neurologic recovery. Clinical and preclinical studies have suggested early surgical decompression and other measures of neuroprotection improve neurologic outcome. We investigated the role of intramedullary lesion length (IMLL) on preoperative magnetic resonance imaging (MRI) and the effect of early cervical decompressive surgery on ASIA impairment scale (AIS) grade improvement following TCSCI. METHODS: In this retrospective study, we investigated 34 TCSCI patients who were admitted over a 12-year period, from January 1, 2008 to January 31, 2020. We studied the patient demographics, mode of injury, IMLL and timing of surgical decompression. The IMLL is defined as the total length of edema and contusion/hemorrhage within the cord. Short tau inversion recovery (STIR) sequences or T2-weighted MR imaging with fat saturation increases the clarity of edema and depicts abnormalities in the spinal cord. All patients included had confirmed adequate spinal cord decompression with cervical fixation and a follow-up of at least 6 months. RESULTS: Of the 34 patients, 16 patients were operated on within 24 hours (early surgery group) and 18 patients were operated on more than 24 hours after trauma (delayed surgery group). In the early surgery group, 13 (81.3%) patients had improvement of at least one AIS grade, whereas in the delayed surgery group, AIS grade improvement was seen in only in 8 (44.5%) patients (early vs. late surgery; odds ratio [OR] = 1.828; 95% confidence interval [CI]: 1.036-3.225). In multivariate regression analysis coefficients, the timing of surgery and intramedullary edema length on MRI were the most significant factors in improving the AIS grade following cervical SCI. Timing of surgery as a unique variance predicted AIS grade improvement significantly (p < 0.001). The mean IMLL was 41.47 mm (standard deviation [SD]: 18.35; range: 20-87 mm). IMLL was a predictor of AIS grade improvement on long-term outcome in bivariate analysis (p < 0.001). This study suggests that patients who had IMLL of less than 30 mm had a better chance of grade conversion irrespective of the timing of surgery. Patients with an IMLL of 31 to 60 mm had chances of better grade conversion after early surgery. A longer IMLL predicts lack of improvement (p < 0.05). If the IMLL is greater than 61 mm, the probability of nonconversion of AIS grade is higher, even if the patient is operated on within 24 hours of trauma. CONCLUSION: Surgical decompression within 24 hours of trauma and shorter preoperative IMLL are significantly associated with improved neurologic outcome, reflected by better AIS grade improvement at 6 months' follow-up. The IMLL on preoperative MRI can reliably predict outcome after 6 months. The present study suggests that patients have lesser chances of AIS grade improvement when the IMLL is ≥61 mm.

Study of disorders in regulatory spatiotemporal neurodynamics of calcium and nitric oxide.

Experimental studies have reported the dependence of nitric oxide (NO) on the regulation of neuronal calcium ([Ca2+]) dynamics in neurons. But, there is no model available to estimate the disorders caused by various parameters in their regulatory dynamics leading to various neuronal disorders. A mathematical model to analyze the impacts due to alterations in various parameters like buffer, ryanodine receptor, serca pump, source influx, etc. leading to regulation and dysregulation of the spatiotemporal calcium and NO dynamics in neuron cells is constructed using a system of reaction-diffusion equations. The numerical simulation is performed with the finite element approach. The disturbances in the different constitutive processes of [Ca2+] and nitric oxide including source influx, buffer mechanism, ryanodine receptor, serca pump, IP3 receptor, etc. can be responsible for the dysregulation in the [Ca2+] and NO dynamics in neurons. Also, the results reveal novel information about the magnitude and intensity of disorders in response to a range of alterations in various parameters of this neuronal dynamics, which can cause dysregulation leading to neuronal diseases like Parkinson's, cerebral ischemia, trauma, etc.