Discovery and development of COVID-19 vaccine from laboratory to clinic.

The world has recently experienced one of the biggest and most severe public health disasters with severe acute respiratory syndrome coronavirus (SARS-CoV-2). SARS-CoV-2 is responsible for the coronavirus disease of 2019 (COVID-19) which is one of the most widespread and powerful infections affecting human lungs. Current figures show that the epidemic had reached 216 nations, where it had killed about 6,438,926 individuals and infected 590,405,710. WHO proclaimed the outbreak of the Ebola virus disease (EVD), in 2014 that killed hundreds of people in West Africa. The development of vaccines for SARS-CoV-2 becomes more difficult due to the viral mutation in its non-structural proteins (NSPs) especially NSP2 and NSP3, S protein, and RNA-dependent RNA polymerase (RdRp). Continuous monitoring of SARS-CoV-2, dynamics of the genomic sequence, and spike protein mutations are very important for the successful development of vaccines with good efficacy. Hence, the vaccine development for SARS-CoV-2 faces specific challenges starting from viral mutation. The requirement of long-term immunity development, safety, efficacy, stability, vaccine allocation, distribution, and finally, its cost is discussed in detail. Currently, 169 vaccines are in the clinical development stage, while 198 vaccines are in the preclinical development stage. The majority of these vaccines belong to the Ps-Protein subunit type which has 54, and the minor BacAg-SPV (Bacterial antigen-spore expression vector) type, at least 1 vaccination. The use of computational methods and models for vaccine development has revolutionized the traditional methods of vaccine development. Further, this updated review highlights the upcoming vaccine development strategies in response to the current pandemic and post-pandemic era, in the field of vaccine development.

Peer Crowd Identification and Adolescent Health Behaviors: Results From a Statewide Representative Study.

PURPOSE: Peer crowds are macro-level subcultures that share similarities across geographic areas. Over the past decade, dozens of studies have explored the association between adolescent peer crowds and risk behaviors, and how they can inform public health efforts. However, despite the interest, researchers have not yet reported on crowd size and risk levels from a representative sample, making it difficult for practitioners to apply peer crowd science to interventions. The current study reports findings from the first statewide representative sample of adolescent peer crowd identification and health behaviors. METHODS: Weighted data were analyzed from the 2015 Virginia Youth Survey of Health Behaviors ( n = 4,367). Peer crowds were measured via the I-Base Survey™, a photo-based peer crowd survey instrument. Frequencies and confidence intervals of select behaviors including tobacco use, substance use, nutrition, physical activity, and violence were examined to identify high- and low-risk crowds. Logistic regression was used to calculate adjusted odds ratios for each crowd and behavior. RESULTS: Risky behaviors clustered in two peer crowds. Hip Hop crowd identification was associated with substance use, violence, and some depression and suicidal behaviors. Alternative crowd identification was associated with increased risk for some substance use behaviors, depression and suicide, bullying, physical inactivity, and obesity. Mainstream and, to a lesser extent, Popular, identities were associated with decreased risk for most behaviors. CONCLUSIONS: Findings from the first representative study of peer crowds and adolescent behavior identify two high-risk groups, providing critical insights for practitioners seeking to maximize public health interventions by targeting high-risk crowds.

Tumor targeting using polyamidoamine dendrimer-cisplatin nanoparticles functionalized with diglycolamic acid and herceptin.

Polymer mediated drug delivery system represents a novel promising platform for tumor-targeting with reduced systemic side effects and improved chemotherapeutical efficacy. In this study, we report the preparation and characterization of herceptin targeted, diglycolamic acid (DGA) functionalized polyamidoamine (PAMAM) dendrimer as a potent drug carrier for cisplatin. DGA dendrimers carrying cisplatin demonstrated enhanced anticancer activity when targeted with herceptin. In vitro cell line studies with herceptin-DGA-G4-cisplatin in HER-2 +ve and HER-2 -ve human ovarian cancer cell lines showed that these nanoparticles possessed remarkable features such as lower IC50 value, improved S-phase arrest, and enhanced apoptosis due to increased cellular uptake and accumulation than the untargeted DGA-G4-cisplatin and free cisplatin. Furthermore, in vivo results in SCID mice bearing SKOV-3 tumor xenografts, herceptin-DGA-G4-cisplatin, appeared to be more effective in inducing tumor regression as compared to free cisplatin. Collectively, these results indicate that herceptin targeted DGA functionalized PAMAM-cisplatin conjugates serve as better anti-tumor agents than individual therapeutic agents.

Ulcerated primary fibrosarcoma of breast: case report and review of literature.

Breast carcinoma is a common condition worldwide but stromal sarcomas of breast are rarity in day to day surgical practice. Out of primary breast sarcomas, fibrosarcoma constitutes only 16% of cases. We report a primary fibrosarcoma of breast in a young female patient which presented as ulcerated growth and fixity to chest wall and multiple ipsilateral axillary lympadenopathy (Stage IIIb). After biopsy confirmation palliation mastectomy was done and patient was sent for chemoradiotherapy.

Comparison of Proximal Caries Detection in Primary Teeth between Laser Fluorescence and Bitewing Radiography: An in vivo Study.

BACKGROUND AND OBJECTIVE: Proximal caries detection is of great importance because of the rapid rate of caries progression and the difficulty in determining the absence or presence of a lesion in primary dentition. Although, various methods for caries diagnosis offer good diagnostic performances, they provide varying sensitivities for detecting proximal carious lesions. The objective of this study was to compare, in vivo, the accuracy of DIAGNOdent and bitewing radiography at detecting proximal caries in primary teeth. MATERIALS AND METHODS: One Hundred and one primary maxillary and mandibular molars without obvious cavities of children between the age group of 3 and 10 years were included. The teeth were first subjected to DIAGNOdent examination followed by bitewing radiography. The specificity and sensitivity of the systems were calculated. RESULTS: At the dentin caries (D3) level, the sensitivity of DIAGNOdent and bitewing radiography was 78.5%; at the enamel caries (D1 and D2) level it was 39.12% and for the sound teeth (D0) it was found to be 76.52%. A strong association was observed between the DIAGNOdent and the bitewing radiograph (p < 0.001). CONCLUSION: The DIAGNOdent can be used as an alternative diagnostic method in detection of proximal caries in primary teeth. But when seen at the each caries level, the DIAGNOdent is more accurate at the D0 and D3 threshold. How to cite this article: Mepparambath R, Bhat SS, Hegde SK, Anjana G, Sunil M, Mathew S. Comparison of Proximal Caries Detection in Primary Teeth between Laser Fluorescence and Bitewing Radiography: An in vivo Study. Int J Clin Pediatr Dent 2014;7(3):163-167.

Specific PCR-based detection of Alternaria helianthi: the cause of blight and leaf spot in sunflower.

Alternaria helianthi is an important seed-borne pathogenic fungus responsible for blight disease in sunflower. The current detection methods, which are based on culture and morphological identification, are time-consuming, laborious and are not always reliable. A PCR-based diagnostic method was developed with species-specific primers designed based on the sequence data of a region consisting of the 5.8S RNA gene and internal transcribed spacers-ITS 1 and ITS 2 of nuclear ribosomal RNA gene (rDNA) repeats of A. helianthi. The specificity of the primer pairs AhN1F and AhN1R designed was verified by PCR analysis of DNA from 18 Alternaria helianthi strains isolated from India, 14 non-target Alternaria spp. and 11 fungal isolates of other genera. A single amplification product of 357-bp was detected from DNA of A. helianthi isolates. No cross-reaction was observed with any of the other isolates tested. The detection limit of the PCR method was of 10 pg from template DNA. The primers could also detect the pathogen in infected sunflower seed. This species-specific PCR method provides a quick, simple, powerful and reliable alternative to conventional methods in the detection and identification of A. helianthi. This is the first report of an A. helianthi-specific primer set.

Effect of intermittent hypobaric hypoxia on efficacy & clearance of drugs.

BACKGROUND & OBJECTIVES: People travelling to high altitude for occupational, recreational or religious purposes are mostly healthy and fit but sometimes they use drugs for common ailments like influenza, acute mountain sickness or chronic disease like diabetes. Limitation of oxygen at high altitude may compromise metabolism of drugs. Hence, we undertook this study to assess the effect of hypobaric hypoxia on some commonly used drugs in rats and rabbits. METHODS: Effect of intermittent hypobaric hypoxia on phenotypic expression of anesthetic drugs pentabarbitone, thiopentone and zoxazolamine (sleeping time) was assessed in rats exposed to 282.4 mm Hg equivalent to 25000 feet in a decompression chamber. Plasma clearance of some commonly used drugs was investigated in rabbits exposed to 429 mm Hg equivalent to 15000 feet. Pharmacokinetic parameters were computed by plotting drug concentration versus time curve on semi log scale. RESULTS: A significant delay in regaining rightening reflex was observed in rats exposed to intermittent hypobaric hypoxia in response to zoxazolamine, pentobarbitone and thiopentone sodium. Pharmacokinetics of acetyl salicylic acid, gentamicin, phenobarbitone and acetazolamide showed increase in plasma half life (t 1/2), decrease in elimination rate constant (k el) and hence prolonged residence of these drugs in hypoxic animals. INTERPRETATION & CONCLUSIONS: This experimental study showed that hypoxia altered therapeutic effectiveness and clearance of several drugs, in rats and rabbits exposed to intermittent hypobaric hypoxia. s0 uch studies need to be done in human volunteers to see the effect of hypoxia on pharmacokinetics of some common drugs.

Effect of prolonged stay at high altitude on platelet aggregation and fibrinogen levels.

Increased liability for thrombosis has been suspected at high altitude. Platelet function and fibrinogen levels are known to play a major role in thrombogenic disorders. In order to investigate effect of chronic hypobaric hypoxia on platelet function and fibrinogen concentration, a study was conducted on 40 healthy men at sea level and following 3 and 13 months sojourn at high altitude (4100 m-4500 m). A consistent decline in platelet number was observed in high altitude sojourners during 13 months stay at high altitude. Platelet counts decreased by 12% after 3 months of stay at high altitude and by 31% after 13 months stay in comparison to sea level counts (266.01 +/- 65.10 x 10(3)/microl). Mean platelet volume increased from 9.18 +/- 0.83 fl at sea level to 10.8 +/- 0.98 fl after 3 months stay at high altitude and showed a further increase to 12.15 +/- 1.18 fl following 13 months residency in the hypoxic environment. There was significant reduction in maximal platelet aggregation in response to ADP, epinephrine and collagen, the effect being most pronounced with collagen (75%) and least with ADP (24%). Plasma fibrinogen concentration was 53% higher in sojourners after 3 months stay at high altitude and 61% higher after 13 months stay at high altitude. This implies that increased platelet activity may not be responsible for precipitation of thrombotic phenomenon during prolonged stay at high altitude but increased availability of substrate for coagulation could still favor pro-coagulant tendencies.

Design and synthesis of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones as a novel class of analgesic and anti-inflammatory agents.

A new series of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-ethylphenyl)-3H-quinazolin-4-one from 4-ethyl aniline with a variety of aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 2-(N'-3-pentylidene-hydrazino)-3-(4-ethylphenyl)-3H-quinazolin-4-one (AS2) emerged as the most active compound of the series and was moderately more potent than the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.

Synthesis and pharmacological investigation of 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-ones as analgesic and anti-inflammatory agents.

In the present work, design, synthesis, and pharmacological evaluation of the analgesic, anti-inflammatory, and ulcerogenic-index activities of new 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-ones, structurally planed by exploiting a clear concept of bio-isosterism, are reported. All compounds exhibited significant analgesic and anti-inflammatory activity. Compounds A1, A3 showed higher analgesic activity and more potent anti-inflammatory activity than that of the reference compound diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to that of acetylsalicylic acid.

Acclimatization to oxidative stress at high altitude.

Hypoxia-mediated oxidative stress has been implicated in the pathophysiology of high altitude maladaptations. To explore whether prolonged exposure to high altitude can trigger an adaptive response to oxidative stress and restore redox homeostasis in the body, the study was conducted to evaluate biochemical variables related to oxidative stress and antioxidant status in humans at sea level (190 m) and following 3- and 13- month sojourns at altitude (4,500 m). After 3 months at altitude, whole-blood thiobarbituric acid reactive substances (TBARS) were significantly higher (65.6%), nonenzymatic antioxidants like ascorbic acid and caeruloplasmin were significantly lower (41% and 22%, respectively) and plasma total antioxidant status (TAS), glutathione levels, and superoxide dismutase activity were marginally altered as compared to their basal values. After 13 months at altitude, TBARS levels regressed back to preexposure levels. Plasma total antioxidant status (TAS) improved by 21%, glutathione levels by 32.8%, and plasma bilirubin by 35.8% as compared to sea level. Average concentrations of ascorbic acid and caeruloplasmin were 18% and 37% higher as compared to the subjects studied after a 3-month stay at high altitude. In addition, there was a progressive rise in erythrocytic superoxide dismutase activity and persistent hyperurecemia. The study observed that on prolonged exposure to high altitude humans could mount an effective adaptive response to oxidative stress by activating the antioxidant defense. Hence, strengthening the antioxidant defense could be an effective strategy to prevent free-radical-mediated pathophysiological alterations and quicken acclimatization to oxidative stress.