Physiological features of parvalbumin-expressing GABAergic interneurons contributing to high-frequency oscillations in the cerebral cortex.

Parvalbumin-expressing (PV+) inhibitory interneurons drive gamma oscillations (30-80 Hz), which underlie higher cognitive functions. In this review, we discuss two groups/aspects of fundamental properties of PV+ interneurons. In the first group (dubbed Before Axon), we list properties representing optimal synaptic integration in PV+ interneurons designed to support fast oscillations. For example: [i] Information can neither enter nor leave the neocortex without the engagement of fast PV+ -mediated inhibition; [ii] Voltage responses in PV+ interneuron dendrites integrate linearly to reduce impact of the fluctuations in the afferent drive; and [iii] Reversed somatodendritic Rm gradient accelerates the time courses of synaptic potentials arriving at the soma. In the second group (dubbed After Axon), we list morphological and biophysical properties responsible for (a) short synaptic delays, and (b) efficient postsynaptic outcomes. For example: [i] Fast-spiking ability that allows PV+ interneurons to outpace other cortical neurons (pyramidal neurons). [ii] Myelinated axon (which is only found in the PV+ subclass of interneurons) to secure fast-spiking at the initial axon segment; and [iii] Inhibitory autapses - autoinhibition, which assures brief biphasic voltage transients and supports postinhibitory rebounds. Recent advent of scientific tools, such as viral strategies to target PV cells and the ability to monitor PV cells via in vivo imaging during behavior, will aid in defining the role of PV cells in the CNS. Given the link between PV+ interneurons and cognition, in the future, it would be useful to carry out physiological recordings in the PV+ cell type selectively and characterize if and how psychiatric and neurological diseases affect initiation and propagation of electrical signals in this cortical sub-circuit. Voltage imaging may allow fast recordings of electrical signals from many PV+ interneurons simultaneously.

Methods of crop improvement and applications towards fortifying food security.

Agriculture has supported human life from the beginning of civilization, despite a plethora of biotic (pests, pathogens) and abiotic (drought, cold) stressors being exerted on the global food demand. In the past 50 years, the enhanced understanding of cellular and molecular mechanisms in plants has led to novel innovations in biotechnology, resulting in the introduction of desired genes/traits through plant genetic engineering. Targeted genome editing technologies such as Zinc-Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) have emerged as powerful tools for crop improvement. This new CRISPR technology is proving to be an efficient and straightforward process with low cost. It possesses applicability across most plant species, targets multiple genes, and is being used to engineer plant metabolic pathways to create resistance to pathogens and abiotic stressors. These novel genome editing (GE) technologies are poised to meet the UN's sustainable development goals of "zero hunger" and "good human health and wellbeing." These technologies could be more efficient in developing transgenic crops and aid in speeding up the regulatory approvals and risk assessments conducted by the US Departments of Agriculture (USDA), Food and Drug Administration (FDA), and Environmental Protection Agency (EPA).

Nitric Oxide and its Derivatives Containing Nasal Spray and Inhalation Therapy for the Treatment of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major health concern worldwide and has evolved into different variants. SARS-CoV-2 possesses a spike glycoprotein on its envelope that binds to the angiotensin-converting enzyme 2 (ACE-2) receptor of the host cell via the receptor-binding domain (RBD) in the upper respiratory tract. Since the SARS-CoV-2 virus variants change the severity of the diesease and treatment scenarios, repurposing current medicines may provide a quick and appealing method with established safety features. The efficacy and safety of antiviral medicines against the coronavirus disease 2019 (COVID-19) have been investigated, and several of them are now undergoing clinical studies. Recently, it has been found that nitric oxide (NO) shows antiviral properties against SARS-CoV-2 and prevents the virus from binding to a host cell. In addition, NO is a well-known vasodilator and acts as an important coagulation mediator. With the fast-track development of COVID-19 treatments and vaccines, one avenue of research aimed at improving therapeutics is exploring different forms of drug delivery, including intranasal sprays and inhalation therapy. The nasal mucosa is more prone to be the site of infection as it is in more direct contact with the physical environment via air during inhalation and exhalation. Thus, the use of exogenous nasal NO therapy via the intranasal route displays a distinct advantage. Therefore, the objective of this review is to summarize the relevant actions of NO via the intranasal spray and inhalation delivery, its mechanism of action, and its use in the treatment of COVID-19.

Recent review of COVID-19 management: diagnosis, treatment and vaccination.

The idiopathic Coronavirus disease 2019 (COVID-19) pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached global proportions; the World Health Organization (WHO) declared it as a public health emergency during the month of January 30, 2020. The major causes of the rise of new variants of SARS-CoV-2 are genetic mutations and recombination. Some of the variants with high infection and transmission rates are termed as variants of concern (VOCs) like currently Omicron variants. Pregnant women, aged people, and immunosuppressed and compromised patients constitute the most susceptible human population to the SARS-CoV-2 infection, especially to the new evolving VOCs. To effectively manage the pathological condition of infection, the focus should be directed towards prevention and prophylactic approach. In this narrative review, we aimed to analyze the current scenario of COVID-19 management and discuss the treatment and prevention strategies. We also focused on the complications prevalent during the COVID-19 and post-COVID period and to discuss the novel approaches developed for mitigation of the global pandemic. We have also emphasized on the COVID-19 management approaches for the special population including children, pregnant women, aged groups, and immunocompromised patients. We conclude that the advancements in therapeutic and pharmacological domains have provided opportunities to develop and design novel diagnosis, treatment, and prevention strategies. New advanced techniques such as RT-LAMP, RT-qPCR, High-Resolution Computed Tomography, etc., efficiently diagnose patients with SARS-CoV-2 infection. In the case of treatment options, new drugs like paxlovid, combinations of ß-lactum drugs and molnupiravir are found to be effective against even the new emerging variants. In addition, vaccination is an essential approach to prevent the infection or to reduce its severity. Vaccines for against COVID-19 from Comirnaty by Pfizer-BioNTech, SpikeVax by Moderna, and Vaxzevria by Oxford-AstraZeneca are approved and used widely. Similarly, numerous vaccines have been developed with different percentages of effectiveness against VOCs. New developments like nanotechnology and AI can be beneficial in providing an efficient and reliable solution for the suppression of SARS-CoV-2. Public health concerns can be efficiently treated by a unified scientific approach, public engagement, and better diagnosis.

Fast-track development of vaccines for SARS-CoV-2: The shots that saved the world.

In December 2019, an outbreak emerged of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which leads to coronavirus disease 2019 (COVID-19). The World Health Organisation announced the outbreak a global health emergency on 30 January 2020 and by 11 March 2020 it was declared a pandemic. The spread and severity of the outbreak took a heavy toll and overburdening of the global health system, particularly since there were no available drugs against SARS-CoV-2. With an immediate worldwide effort, communication, and sharing of data, large amounts of funding, researchers and pharmaceutical companies immediately fast-tracked vaccine development in order to prevent severe disease, hospitalizations and death. A number of vaccines were quickly approved for emergency use, and worldwide vaccination rollouts were immediately put in place. However, due to several individuals being hesitant to vaccinations and many poorer countries not having access to vaccines, multiple SARS-CoV-2 variants quickly emerged that were distinct from the original variant. Uncertainties related to the effectiveness of the various vaccines against the new variants as well as vaccine specific-side effects have remained a concern. Despite these uncertainties, fast-track vaccine approval, manufacturing at large scale, and the effective distribution of COVID-19 vaccines remain the topmost priorities around the world. Unprecedented efforts made by vaccine developers/researchers as well as healthcare staff, played a major role in distributing vaccine shots that provided protection and/or reduced disease severity, and deaths, even with the delta and omicron variants. Fortunately, even for those who become infected, vaccination appears to protect against major disease, hospitalisation, and fatality from COVID-19. Herein, we analyse ongoing vaccination studies and vaccine platforms that have saved many deaths from the pandemic.

A Proposed Approach for the Management of Clot-in-Transit.

Clot-in-transit (CIT) is defined as a mobile echogenic material in the right atrium or ventricle as observed on ultrasound. A right heart free-floating thrombus is unusual when there is no structural disease of the heart or atrial fibrillation. Cardiopulmonary collapse and quick death can come from CIT, which occurs when a blood clot moves from the heart to the lungs. There are some clinical case reports of a large volume thrombus that was freely floating in the right heart in an asymptomatic patient, and the best therapeutic options are uncertain. Although several trials have been conducted on the treatment of CIT, clinical judgment is still used to determine the best treatment for right heart thrombus (RHT), especially when associated with pulmonary embolism (PE). In this review article, we discuss various diagnostic modalities and treatment options for this rare malady. We studied in detail their clinical impact on patients according to past research studies.

Dendritic cell-based vaccine: the state-of-the-art vaccine platform for COVID-19 management.

INTRODUCTION: A correlation between new coronaviruses and host immunity, as well as the role of defective immune function in host response, would be extremely helpful in understanding coronavirus disease (COVID-19) pathogenicity, and a coherent structure of treatments and vaccines. As existing vaccines may be inadequate for new viral variants emerging in various regions of the world, it is a vital requirement for fresh and effective therapeutic alternatives. AREA COVERED: Immunotherapy may give a viable protective option for COVID-19, a disease that is currently a big burden on global health and economic systems. Herein, we have outlined three dendritic cell (DC)-based vaccines for COVID-19 which are in human clinical trials and have shown encouraging outcomes. EXPERT OPINION: With existing knowledge of the virus, and the nature of DC, DC-based vaccines may be proven to be effective in inducing long-lasting protective immunity, especially T cell responses.

An Ayurgenomics Approach: Prakriti-Based Drug Discovery and Development for Personalized Care.

Originating in ancient India, Ayurveda is an alternative medicinal approach that provides substantial evidence for a theoretical-level analysis of all aspects of life. Unlike modern medicine, Ayurveda is based upon tridoshas (Vata, pitta, and Kapha) and Prakriti. On the other hand, the research of all the genes involved at the proteomics, metabolomics, and transcriptome levels are referred to as genomics. Geoclimatic regions (deshanupatini), familial characteristics (kulanupatini), and ethnicity (jatiprasakta) have all been shown to affect phenotypic variability. The combination of genomics with Ayurveda known as ayurgenomics provided new insights into tridosha that may pave the way for precision medicine (personalized medicine). Through successful coordination of "omics," Prakriti-based treatments can help change the existing situation in health care. Prakriti refers to an individual's behavioral trait, which is established at the moment of birth and cannot be fully altered during one's existence. Ayurvedic methodologies are based on three Prakriti aspects: aushadhi (medication), vihara (lifestyle), and ahara (diet). A foundation of Prakriti-based medicine, preventative medicine, and improvement of life quality with longevity can be accomplished through these ayurvedic characteristics. In this perspective, we try to understand prakriti's use in personalized medicine, and how to integrate it with programs for drug development and discovery.

Nano-Drug Delivery Systems Entrapping Natural Bioactive Compounds for Cancer: Recent Progress and Future Challenges.

Cancer is a prominent cause of mortality globally, and it becomes fatal and incurable if it is delayed in diagnosis. Chemotherapy is a type of treatment that is used to eliminate, diminish, or restrict tumor progression. Chemotherapeutic medicines are available in various formulations. Some tumors require just one type of chemotherapy medication, while others may require a combination of surgery and/or radiotherapy. Treatments might last from a few minutes to many hours to several days. Each medication has potential adverse effects associated with it. Researchers have recently become interested in the use of natural bioactive compounds in anticancer therapy. Some phytochemicals have effects on cellular processes and signaling pathways with potential antitumor properties. Beneficial anticancer effects of phytochemicals were observed in both in vivo and in vitro investigations. Encapsulating natural bioactive compounds in different drug delivery methods may improve their anticancer efficacy. Greater in vivo stability and bioavailability, as well as a reduction in undesirable effects and an enhancement in target-specific activity, will increase the effectiveness of bioactive compounds. This review work focuses on a novel drug delivery system that entraps natural bioactive substances. It also provides an idea of the bioavailability of phytochemicals, challenges and limitations of standard cancer therapy. It also encompasses recent patents on nanoparticle formulations containing a natural anti-cancer molecule.

SARS-CoV-2 variants and vulnerability at the global level.

Numerous variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have evolved. Viral variants may evolve with harmful susceptibility to the immunity established with the existing COVID-19 vaccination. These variants are more transmissible, induce relatively extreme illness, have evasive immunological features, decrease neutralization using antibodies from vaccinated persons, and are more susceptible to re-infection. The Centers for Disease Control and Prevention (CDC) has categorized SARS-CoV-2 mutations as variants of interest (VOI), variants of concern (VOC), and variants of high consequence (VOHC). At the moment, four VOC and many variants of interest have been defined and require constant observation. This review article summarizes various variants of SARS-CoV-2 surfaced with special emphasis on VOCs that are spreading across the world, as well as several viral mutational impacts and how these modifications alter the properties of the virus.

Comparison of Four Classroom-Based Strategies for Middle School Students With ADHD: A Pilot Randomized Controlled Trial.

Middle school students with ADHD often experience negative academic outcomes. To intervene, schools frequently provide services through special education or section 504. These services include strategies, such as breaks, prompting, and sensory proprioception to remove the impact of construct-irrelevant variance. Student plans rarely include strategies, such as selfmanagement, designed to teach students skills to increase independent functioning. The purpose of this study was to compare the effectiveness of four strategies on engagement, disruptive behavior, and time to initiate tasks. Fifteen sixth and seventh grade students were randomized daily to one of four conditions. Results indicated large statistically significant differences. Social validity data indicated that students found prompting and self-management helpful, but preferred breaks and sensory proprioception. This study builds on a growing empirical base that supports the prioritization of strategies to teach skills over strategies to remove the impact of ADHD on performance.

Phytochemical Delivery Through Transferosome (Phytosome): An Advanced Transdermal Drug Delivery for Complementary Medicines.

Transdermal drug delivery aims to create a safe and effective method of administering drugs through the skin that attracts a lot of attention and investment due to the constant progress in the field. Transferosomes are flexible or malleable vesicles (having almost the same structure as liposomes but with better skin penetration properties) discovered initially in the early 90s. The name transferosomes, which means "carrying bodies," is coined from the Latin phrase "Transferee," which means "to carry through," and the Greek term "soma," meaning "body." In comparison to typical herbal extracts, phytosomes (Transferosomes) are created by attaching specific herbal extracts to phosphatidylcholine, resulting in a formulation with increased solubility and, hence, better absorption, resulting in improved pharmacokinetic and pharmacodynamic features of the entrapped drugs. We are using the word phytosomes and transferosomes interchangeably as we have consolidated vesicular delivery of herbal drugs through skin. In this mini-review, we have demonstrated the enormous potential of developing nanotechnology to deliver bioactive phytochemicals, with a special emphasis on phytosomes (Transferosomes) as a unique lipid-based nanocarrier for transdermal drug delivery.

Herbal Remedies, Nutraceuticals, and Dietary Supplements for COVID-19 Management: An Update.

Currently, the world is facing a Coronavirus pandemic with a grave deficiency of specific therapy for Coronavirus Disease (COVID-19). Moreover, scientists attempt to discover the most refined approach to prevent this condition. Regarding COVID-19 infection, herbal medicines with immunomodulatory effects may offer patients a promising preventive treatment option. Several ayurvedic and Traditional Chinese Medicine (TCM) are effective during this worrisome Coronavirus pandemic i.e. Tinospora cordifolia (Willd.) Miers, Withania somnifera (L.) Dunal, Scutellaria baicalensis Georgi, Curcuma longa L. etc. TCM was shown to be utilized with over 90% efficacy when the COVID-19 pandemic broke out in early 2020. In addition to herbal treatments and nutraceutical drugs, dietary supplements such as vitamins and amino acid derivatives also play a significant part in COVID-19 management. Diet can assist in regulating inflammation, while nutraceuticals can aid in the prevention of viral invasion. Functional amino acids (e.g., arginine, cysteine, glutamate, glutamine, glycine, taurine, and tryptophan) and glutathione, which are all abundant in animal-sourced foodstuffs, are crucial for optimum immunity and health in humans and animals. The goal of this article is to thoroughly evaluate recent statistics on the effectiveness of herbal medicines in COVID-19, the antiviral activity of nutraceuticals, and the significance of these results in creating dietary supplements that would enhance innate immunity and contribute as preventive measures against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2).

Co-infection associated with SARS-CoV-2 and their management.

SARS-CoV-2 was discovered in Wuhan, China and quickly spread throughout the world. This deadly virus moved from person to person, resulting in severe pneumonia, fever, chills and hypoxia. Patients are still experiencing problems after recovering from COVID-19. This review covers COVID-19 and associated issues following recovery from COVID-19, as well as multiorgan damage risk factors and treatment techniques. Several unusual illnesses, including mucormycosis, white fungus infection, happy hypoxia and other systemic abnormalities, have been reported in recovered individuals. In children, multisystem inflammatory syndrome with COVID-19 (MIS-C) is identified. The reasons for this might include uncontrollable steroid usage, reduced immunity, uncontrollable diabetes mellitus and inadequate care following COVID-19 recovery.

COVID-19 infection has reported in the development several other infections and co-morbidity in patients. The present review discusses risk and management strategies in patients suffeting from co-infections caused by COVID-19 infection.

Selection and validation of reference genes for normalization of qRT-PCR data to study the cannabinoid pathway genes in industrial hemp.

There has been significant interest in researching the pharmaceutical applications of Industrial hemp since its legalization three years ago. The crop is mostly dioecious and known for its production of phytocannabinoids, flavonoids, and terpenes. Although many scientific reports have showed gene expression analysis of hemp through OMICs approaches, unreliable reference genes for normalization of qRT-PCR data make it difficult to validate the OMICs data. Four software packages: geNorm, NormFinder, BestKeeper, and RefFinder were used to evaluate the differential gene expression patterns of 13 candidate reference genes under osmotic, heavy metal, hormonal, and UV stresses. EF-1α ranked as the most stable reference gene across all stresses, TUB was the most stable under osmotic stress, and TATA was the most stable under both heavy metal stress and hormonal stimuli. The expression patterns of two cannabinoid pathway genes, AAE1 and CBDAS, were used to validate the reliability of the selected reference genes. This work provides useful information for gene expression characterization in hemp and future research in the synthesis, transport, and accumulation of secondary metabolites.

The study of clinical profile and outcome of patients with snakebite in a rural community.

CONTEXT: Snakebite remains an underrated cause of accidental death in modern India, primarily in rural India, where people fail to reach out to modern medicine and fall victim to the handful of quacks using traditional healing methods. If promptly diagnosed and treated based on various clinical determinants like mode of presentation, time of medical intervention, recognition of the species, and analysis of a series of reliably identified bites, the treatment outcome would be more promising. We aimed to study snakebite patients' clinical profile and treatment outcome in a rural tertiary care setup. MATERIALS AND METHOD: This is a retrospective study in which the data evaluated from an epidemiological viewpoint; gender and age of the snake bite victim, time when bitten, interval between the bite and medical consultation, pattern of toxicity, and response to anti-snake venom (ASV). RESULTS: Of a total of 200 patients bitten by a snake, 121 were males, with 77% adults. In nearly all cases, the type of snake was unknown; however, most of the bites were poisonous, showing one or the other type of toxicity. One hundred seventy-one patients survived the snake bite, and 29 succumbed. When Logistic regression was done with Death/discharge as the dependent variable and "Time to bite and reaching hospital, Age, Sex, number of ASV given, Ventilation needed or not, pack cell volume (PCV) numbers, Fresh Frozen Plasma (FFP) numbers, Dialysis and presence or absence of toxicity" as the independent variables, the model developed did not account for any respectable amount of variation in the outcome. The only variable found to be predicting the outcome significantly was FFP. CONCLUSION: It is often difficult to identify the type of snake, and thus polyvalent antisnake venom remains the only available treatment resource. Readily available treatment resources, timely intervention, appropriate referral, and close ICU will alleviate mortality.

Omega 3 Fatty Acids and COVID-19: A Comprehensive Review.

The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to "cytokine storm". This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed.