Verbascoside: comprehensive review of a phenylethanoid macromolecule and its journey from nature to bench.

Polyphenolic compounds are among the most widely researched compounds for various therapeutic applications. However, naturally occurring phenylethanoid glycosides are least explored under this class of compounds. One such phenylethanoid glycoside, verbascoside (Vb), abundantly found among 200 species of 23 families, has gained recent attention due to its wide-spectrum therapeutic properties such as antioxidant, antimicrobial, anti-inflammatory, neuroprotective, cardioprotective, skin-protective, and anti-cancer. Despite having multiple therapeutic benefits, due to its large size, the compound has poor bioavailability for oral and topical applications. To meet these limitations, current research on Vb focuses on delivering it through nanoformulations. Presently, most developed formulations are liposome based for various applications, such as corneal epithelial wound healing, anti-neuropathic, anti-wrinkle, anti-hyperalgesia, atopic dermatitis, alopecia, and cutaneous wound healing. Multiple studies have confirmed the least acute and sub-acute toxicity for Vb. Few clinical studies have been performed for the therapeutic application of Vb to manage COVID-19, nephropathy, platelet aggregation, chronic primary glomerulonephritis, and acute hepatitis. Recent studies have shown the immense therapeutic potential of Vb in wound healing, dermatitis, neuroprotection, and anti-cancer activities, which creates a need for developing novel formulations for their respective uses. Long-term toxicity studies and techniques for scaling up Vb production by biotechnological approaches should be emphasized.

Non-structural protein 1 (NS1) variants from dengue virus clinical samples revealed mutations that influence NS1 production and secretion.

Dengue diagnosis primarily relies on NS1 ELISA and serological (IgG/IgM) tests. There are reports of low and variable sensitivity of the widely used NS1 ELISA tests. Poor sensitivity has been attributed to patient's infection status, prevalent serotypes, and the geographical origin of the samples. We investigated whether NS1 mutations directly have any impact on NS1 ELISA-based dengue virus (DENV) detection in clinical samples. Fifty-eight serum samples were collected from dengue-endemic area during 2015-2017 and tested with three commonly used NS1 ELISA kits. The samples were subjected to diagnostic RT-PCR and sequencing of structural gene(s). Sequencing of NS1 gene revealed amino acid changes which were transferred to respective wild type NS1 backbone to determine their effects on NS1 production and secretion in Huh-7, Vero, and A549 cells. Eighty-seven percent samples were virus RNA-positive but 65% of these were NS1 ELISA-positive. NS1-gene mutations like Val236➔Ala (DENV2) or Trp68➔stop codon in DENV3 were associated with decreased NS1 production and secretion. These mutations were originally identified in NS1 ELISA-negative clinical isolates. All DENV1 and > 80% DENV2 were NS1 ELISA-positive. The three NS1 ELISA could not detect recently circulating DENV3 single infections despite being RNA-positive. Among serotypes 1-3, wild-type NS1 production was highest for DENV1 and lowest for DENV3 in all cell lines tested. Mutations in circulating DENV directly correlated with NS1 production and secretion and, hence, ELISA-based NS1 detection. Further studies to define more NS1 mutations in clinical samples are needed to optimize ELISA kits for more sensitive dengue diagnosis.

A novel chitosan-PEG hydrogel embedded with in situ silver nanoparticles of Clerodendrum glandulosum Lindl. extract: evaluation of its in vivo diabetic wound healing properties using an image-guided machine learning model.

The pathophysiology of chronic wounds related to diabetes mellitus is a result of a series of complications induced by hyperglycemia. The symptoms include impaired growth factor production, decreased keratinocyte proliferation and migration, reduced angiogenesis and cytokine synthesis, lowered matrix metalloproteinase (MMP) production, neuropathy, reduced nitric oxide synthase production, decreased fibroblast synthesis and migration, and impaired inflammatory cell functions. This multifaceted mechanism of diabetic wounds needs a suitable novel topical formulation that can deliver the active constituent by a controlled means, target the various stages of wound healing, absorb the wound exudates, and prevent secondary infections. To meet the above requirements, the Clerodendrum glandulosum (CG) extract reduced silver nanoparticle (AgNP) impregnated chitosan-polyethylene glycol (PEG) hydrogel was synthesized. The findings of the physicochemical characterization studies suggested that the hydrogel exhibited excellent formulation characteristics and showed controlled release for seven days, making it suitable for chronic wound healing studies. In subsequent studies, these formulations showed good antioxidant and antimicrobial properties, and hemocompatibility, with the least cytotoxic properties. The results of the diabetic wound healing studies showed a faster wound closure rate and improved extracellular matrix formation. These antioxidant, antimicrobial, anti-inflammatory and wound-healing properties suggest that the CG-AgNP loaded chitosan-PEG hydrogel is a promising material for novel topical formulation of diabetic wounds.

The outbreak of the monkeypox virus in the shadow of the pandemic.

The human monkeypox virus (MPXV) was first identified in 1959. Since then, the incidence of the disease has been sporadic. The endemic regions were identified in Africa's central and western areas. However, the infection started to spread in 2017 to non-endemic regions such as North and South America, Europe, and Asia. Since May 2022, the non-endemic areas reported 62,635 till 20th September 2022. Although the monkeypox virus has a mortality of ≥ 10%, it showed only 82 mortalities worldwide in 2022. The common symptoms include chills, fever, fatigue, and skin lesions, and the complications include secondary respiratory tract infections, encephalitis, blindness, and severe diarrhea. The factors responsible for spreading the virus include improper handling and consumption of infected bushmeat, unprotected sexual intercourse, contact with an infected person, no smallpox vaccination, improper hygiene, lower diagnostic capacity, and strong travel history from the endemic regions. The therapeutic strategy is symptom-based treatment and supportive care. Antivirals and vaccines such as Tecovirimat, Brincidofovir, Cidofovir, Imvamune, and ACAM2000 have shown promising results. The primary purpose of the review is to perform an epidemiological study and investigate the pathobiology, diagnosis, prevention, treatment, and some associated complications of the monkeypox virus in 2022.

Molecular Determinants, Clinical Manifestations and Effects of Immunization on Cardiovascular Health During COVID-19 Pandemic Era - A Review.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has enveloped the world into an unprecedented pandemic since 2019. Significant damage to multiple organs, such as the lungs and heart, has been extensively reported. Cardiovascular injury by ACE2 downregulation, hypoxia-induced myocardial injury, and systemic inflammatory responses complicate the disease. This virus causes multisystem inflammatory syndrome in children with similar symptoms to adult SARS-CoV-2-induced myocarditis. While several treatment strategies and immunization programs have been implemented to control the menace of this disease, the risk of long-term cardiovascular damage associated with the disease has not been adequately assessed. In this review, we surveyed and summarized all the available information on the effects of COVID-19 on cardiovascular health as well as comorbidities. We also examined several case reports on post-immunization cardiovascular complications.

Neuroprotective effect of Vitamin K2 against gut dysbiosis associated cognitive decline.

Vitamin K2/ Menaquinones produced predominantly by the gut microbiome improve bone health and prevent coronary calcification. The central nervous system has been linked with gut microbiota via the gut-brain axis and is strongly associated with psychiatric conditions. In the present study, we show the role of Vitamin K2 (MK-7) in gut dysbiosis-associated cognitive decline. Gut dysbiosis was induced in mice by administering Ampicillin (250 mg/kg twice a day orally) for 14 days and Vitamin K2 (0.05 mg/kg) for 21 days with or without antibiotic treatment and altered gene expression profile of intestinal microbes determined. This was followed by behavioural studies to determine cognitive changes. The behavioural observations are then correlated with proinflammatory, oxidative, and brain and intestinal histopathological changes in antibiotic-treated animals with or without vitamin K2 administration. With the use of antibiotics, Lactobacillus, Bifidobacterium, Firmicutes, and Clostridium's relative abundance reduced. When vitamin K2 was added to the medication, their levels were restored. Cognitive impairment was observed in behavioural trials in the antibiotic group, but this drop was restored in mice given both an antibiotic and vitamin K. Myeloperoxidase levels in the colon and brain increased due to gut dysbiosis, which vitamin K2 prevented. The acetylcholine esterase and oxidative stress markers brought on by antibiotics were also decreased by vitamin K2. Additionally, vitamin K2 guarded against alterations in intestine ultrastructure brought on by antibiotic use and preserved hippocampus neurons. So, it can be concluded that vitamin K2 improved cognitive skills, avoided hippocampus neuronal damage from antibiotics, and lowered intestine and brain inflammation and oxidative stress.

The Current Indian Epidemic of Dermatophytosis: A Study on Causative Agents and Sensitivity Patterns.

BACKGROUND: In the recent years, the frequency, severity, clinical characteristics, treatment response, and relapse rate of dermatophytosis have dramatically changed in India. Given the surge in dermatophytosis, we had undertaken a study to isolate and identify the common species causing dermatophyte infection and to know the in vitro efficacy of the common antifungals against them. MATERIALS AND METHODS: A total of 103 new cases that were not on any treatment for the past 3 months were included. Skin scrapings were collected for direct microscopic examination and for fungal culture in Sabouraud 4% dextrose agar (SDA) with chloramphenicol and cycloheximide slant tubes, and dermatophyte test media. Fungi were identified on the basis of their macroscopic and microscopic features with the help of lactophenol cotton blue staining and urease test. Also, the drug sensitivity of the dermatophytes was tested with the common antifungals. RESULTS: Of the 55 cases (53.4%) that were positive for dermatophytes in the culture, 29 showed possible contamination. Trichophyton was the predominant organism (49 cases) with T. verrucosum being the commonest species (26 cases), followed by T. rubrum (15 patients), and T. mentagrophytes (8 cases). All species of Trichophyton were found to be most sensitive to itraconazole amongst systemic antifungals and luliconazole amongst topical antifungals. CONCLUSION: This study concluded that the causative agent for the dermatophytosis was changing in India and in our subset, T. verrucosum caused the maximum number of infections. Itraconazole and luliconazole had the highest sensitivity amongst systemic and topical antifungals, respectively. It also showed that terbinafine had comparatively less sensitivity to most organisms.

In-depth molecular analysis of a small cohort of human and Aedes mosquito (adults and larvae) samples from Kolkata revealed absence of Zika but high prevalence of dengue virus.

PURPOSE: Zika virus infections have recently been reported in many dengue-endemic areas globally. Both dengue (DENV) and Zika (ZIKV) virus are transmitted by Aedes mosquitoes, raising the possibility of mixed infections in both vector and host. We evaluated DENV and ZIKV prevalence in human and vector samples in Kolkata, a DENV-endemic city. METHODOLOGY: Blood samples were collected from 70 patients presenting dengue-like fever symptoms at a hospital in Kolkata during 2015-16. Serum was obtained and tested for DENV infection by DENV NS1-based ELISA. Adult (n=8) and larval stages (n=12) of Aedes were also collected. A RT-PCR-based screening of both viruses supplemented by amplicon sequencing was performed. RESULTS: Of the 70 samples, 20 DENV NS1-positive serum samples were used for detailed molecular study for DENV infection. Eighteen of these (90 %) were positive by hemi-nested serotype-specific RT-PCR for DENV1/2/3, with four samples showing evidence of DENV2-3 or DENV1-3 mixed infection. None were ZIKV-positive using NS5 or ENV-based PCR, though weak amplification of a DENV1 NS5 sequence was detected in three serum samples indicating cross-reactivity of the primers. All mosquito samples were ZIKV-negative, whereas 5/8 (63 %) of adult mosquitoes and 11/12 (92 %) of larvae were DENV3-positive. CONCLUSION: Both host and vector samples showed absence of ZIKV but high prevalence of DENV. The high rate of infection of larvae with DENV is suggestive of trans-ovarial transmission that could contribute to the surge of human infections during each post-monsoon season. It would be important to guard against false positives using the available Zika-reporting primer sets.

Non-Gaussian random-matrix ensembles with banded spectra.

Non-Gaussian random-matrix ensembles are important in many applications. We propose Monte Carlo and Langevin methods for generating non-Gaussian ensembles and their eigenvalue spectra. We also provide a general framework for analytic studies of the level density in these ensembles. We show that, in general, the level densities exhibit banded spectra, with important implications for mesoscopic systems and complex nuclei. The universality of energy-level fluctuations is confirmed.

Expression of phosphatase and tensin homolog, epidermal growth factor receptor, and Ki-67 in astrocytoma: A prospective study in a tertiary care hospital.

BACKGROUND: Though the tumor grade is a key factor influencing the choice of therapies, particularly determining the use of adjuvant radiation and specific chemotherapy protocols, role of abnormality in phosphatase and tensin homolog (PTEN) expression and variation in epidermal growth factor receptor (EGFR) labeling index (LI) and Ki-67 LI in survival and clinical outcome have been studied by many researchers in the recent past. AIMS: The aim was to evaluate the expression of PTEN, EGFR and Ki-67 in different grades of astrocytic tumors by means of immunohistochemistry and to judge their role in overall survival (OS). MATERIALS AND METHODS: This study was conducted on 57 cases of different grades of astrocytomas. Expression of PTEN, EGFR and Ki-67 was assessed by immunohistochemistry on formalin fixed and paraffin-embedded sections and the OS was evaluated by Kaplan-Meier survival curves and log-rank test for 2.5 years from the date of primary resection. RESULTS: Most of the tumors (59.6%; 34 cases out of 57) displayed WHO Grade IV features. Distribution of age, EGFR LI and Ki-67 LI expressed strong positive (≥0.5) correlation with the grade of tumors. However, the PTEN positivity was inversely related with the grade of the tumors. Lower WHO grades, lower values of Ki-67 LI, EGFR LI and PTEN positivity were associated with better survival. CONCLUSION: Expression of PTEN, EGFR LI and Ki-67 LI should be combined with the basic histopathological features including WHO grade to predict the prognosis and therapeutic outcome.

Multidrug-resistant acinetobacter infection and their susceptibility patterns in a tertiary care hospital.

BACKGROUND: Antibiotic-resistant Acinetobacter nosocomial infection is a leading problem. It acts as an opportunistic pathogen to cause a wide spectrum of infection including nosocomial pneumonia, meningitis, endocarditis, skin and soft tissue infections, urinary tract infection, conjunctivitis, burn wound infection and bacteremia. Multidrug-resistant Acinetobacter infection creates a great problem in hospital setting. MATERIALS AND METHODS: The clinical specimens obtained from ICU and different surgical and medical wards were investigated using standard microbiological techniques to know the distribution of and their resistant profile. Antimicrobial resistance was studied using the modified Kirby Bauer disk diffusion technique following the CLSI protocol. RESULTS: Major infections found in different medical wards, surgical wards and ICU were due to Acinetobacter baumannii (74.02%), A. lowfii (14.2%), A. haemolyticus (7.79%), A. junii (3.8%) among Acinetobacter spices. Acinetobacter showed increased resistant against majority of commercially available drugs imipenem (5.2%), meropenem (9.75%), piperacillin-tazobactum (18.2%), netilmicin (16.24%), amikacin (14.29%), ceftazidime (74.1%), gentamicin (70.13%), ofloxacin (42.21%). CONCLUSION: A. baumannii was found to be associated with UTI, RTI, septicemia, bacteremia, and meningitis and wound infection. A. baumannii displayed higher resistance to more number of antibiotics than other nosocomial pathogens from ICU.

Right-sided scrotal ascariasis.

We report a case of 35-year-old male patient who presented with painful right side of scrotum and worm pouting out of the scrotum. The patient had undergone surgery for strangulated right inguinal hernia 2 years back. On exploration we found multiple adult Ascaris worms in the scrotum with right-sided hydrocele. All the worms were removed and eversion of sac was done.

Tunneling under coherent control by sequences of unitary pulses.

A general coherent control scenario to suppress or accelerate tunneling of quantum states decaying into a continuum is investigated. The method is based on deterministic, or stochastic, sequences of unitary pulses that affect the underlying interference phenomena responsible for quantum dynamics, without inducing decoherence, or collapsing the coherent evolution of the system. The influence of control sequences on the ensuing quantum dynamics is analyzed by using perturbation theory to first order in the control pulse fields and compared to dynamical decoupling protocols and to sequences of pulses that collapse the coherent evolution and induce quantum Zeno (QZE) or quantum anti-Zeno effects (AZE). The analysis reveals a subtle interplay between coherent and incoherent phenomena and demonstrates that dynamics analogous to the evolution due to QZE or AZE can be generated from stochastic sequences of unitary pulses when averaged over all possible realizations.

Herman-Kluk semiclassical dynamics of molecular rotations in laser fields.

The action-angle mapping algorithm [R. Saha and M. Ovchinnikov, J. Chem. Phys. 124, 204112 (2006)] is utilized to provide a Herman-Kluk semiclassical initial value representation (SC-IVR) treatment of quantum dynamics of systems with non-Cartesian degrees of freedom. The non-Cartesian system under investigation is a linear rotor molecule in static electric and pulsed laser field. The results demonstrate that the SC-IVR procedure described in this work provides an accurate representation of quantum rotational dynamics of the system.

Herman-Kluk semiclassical dynamics in action-angle representation: new approaches to mapping quantum degrees of freedom.

A general approach to mapping a discrete quantum mechanical problem by a continuous Hamiltonian is presented. The method is based on the representation of the quantum number by a continuous action variable that extends from -infinity to infinity. The projection of this Hilbert space onto the set of integer quantum numbers reduces the Hamiltonian to a discrete matrix of interest. The theory allows the application of the semiclassical methods to discrete quantum mechanical problems and, in particular, to problems where quantum Hamiltonians are coupled to continuous degrees of freedom. The Herman Kluk semiclassical propagation is used to calculate the nonadiabatic dynamics for a model avoided crossing system. The results demonstrate several advantages of the new theory compared to the existing mapping approaches.