Increased Antibody Affinity Confers Broad In Vitro Protection against Escape Mutants of Severe Acute Respiratory Syndrome Coronavirus

Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (KD) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization in vitro and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants in vitro. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection

Evaluation of appropriateness of prescription and polypharmacy in the geriatric population: a cross sectional study at a comprehensive geriatric clinic in a tertiary care hospital

Objective: To assess the prescription quality in a comprehensive geriatric clinic and to determine the frequency of inappropriate prescription and polypharmacy.Methods: Both males and female patients above the age of 60 y attending a comprehensive geriatric clinic of a tertiary care hospital were included in the study. Medications taken by the patients, excluding vitamins, minerals and herbal medications were counted in each patient and analyzed by considering their medical history and using universally accepted tools like medication appropriateness index, START, STOPP & Beer's criteria. In this study, polypharmacy was considered as having 6 or more medications per prescription. Results: A total of 120 patients were included in the study. Around 82 (68.33%) patients had less than 6 prescribed medications and 38 patients (31.66%) were on 6 or more than 6 medications. The number of medications used by the patients is 4.37±2.33. Around 21 (17.5%) were on medications that are not indicated, 25 patients (20.83%) were receiving medications which are to be avoided in elderly as per the Beer's and STOPP criteria. Medication was underused in 24 patients (20%) as per START criteria. When both overused drugs and drugs to be avoided were considered for assessment of inappropriateness, 39 patients (32.5%) were found to be receiving inappropriate medication. Among the drugs to be avoided in elderly, amitriptyline was the most common drug and was used in 15 (12.5%) patients. Antihypertensives were the most common potential prescribing omissions in geriatric patients.Conclusion: Polypharmacy is seen in a significant proportion of geriatric patients. Inappropriate prescription and potential prescribing omissions were observed in a significant proportion of geriatric patients.Keywords: Polypharmacy, Geriatrics, Beer's criteria, STOPP criteri

A Review on Oxadiazole

ABSTRACT Oxadiazoles are important five membered heterocyclic classes of compounds with 2 azo groups and one oxygen in its ring system. It is widely researched as a lead compound for designing potent bioactive agents. In this article we have reviewed on physical and chemical properties of oxadiazole, spectra and some methods for its synthesis. We have explored various pharmacological activities of oxadiazole derivatives like anti-inflammatory, anti-cancer, anti-fungal, anti-osteoporotic and anti-microbial. A brief on drugs containing oxadiazole ring and naturally occurring oxadiazole moiety have also been mentioned

Assessment of oral hygiene habits, oral hygiene practices and tooth wear among fertilizer factory workers of Northern India: a Cross sectional study

Background: The association between oral hygiene habits & practices and severity of tooth wear lesion varies from community to community and also from occupation to occupation. The present study was conducted with to assess oral hygiene habits & practices and tooth wear among fertilizer factory workers of Punjab, India. Material and Methods: A descriptive cross sectional survey was conducted among 965 male workers who were aged between 19–58 years, who were the workers of fertilizers factory of Bathinda, India. An interview on the demographic profile, oral hygiene practices, and adverse habits followed a clinical examination for recording the Tooth Wear (Smith and Knight Index 1984) using Type III examination. The Chi–square test and a Stepwise multiple linear regression analysis were used for the statistical analysis. Confidence interval and p-value set at 95% and ≤ 0.05 respectively. Results: In the present study majority (47.2%) of the study population used chew sticks for cleaning their teeth. Overall prevalence of adverse habits was reported (92.4%). Study population showed higher prevalence of tooth wear (77.1%). Best predictors identified for Tooth Wear were oral hygiene practices, adverse habits, years of work experience and age respectively. Conclusions: Considerable percentages of fertilizer factory workers have demonstrated a higher prevalence of tooth surface loss. This may be useful in designing the investigations that aim to further explore the causes for these findings and more importantly to plan oral health promotion program implementing both preventive and curative strategies

Toxicity Evaluation and Biocompatibility of Nanostructured Biomaterials

Biomaterials have occupied a prominent place in regenerative procedures to restore human health. Moreover, there is a greater need in understanding, analyzing and establishing their toxicity profile. These, when made into nano-sized constructions called nanostructured biomaterials, their regenerative potential is enhanced, which could influence their toxicity nature. This chapter intends to give comprehensive information on their nanotoxicology pathways at the cellular level, their entry pathways into the human body, and their potential consequences on human health. It clearly explains the cytocompatibility and biocompatibility of various nanostructured biomaterials for potential human health applications like drug delivery and tissue engineering. A detailed overview of various in vitro and in vivo evaluation methods of biocompatibility of nanomaterials are outlined in this chapter that researchers should address as they move forward in developing new systems for the field of regeneration

Reconstructive complications and early toxicity in breast cancer patients treated with proton-based postmastectomy radiation therapy

BackgroundPostmastectomy radiation therapy (PMRT) decreases the risk of locoregional recurrence and increases overall survival rates in patients with high-risk node positive breast cancer. While the number of breast cancer patients treated with proton-based PMRT has increased in recent years, there is limited data on the use of proton therapy in the postmastectomy with reconstruction setting. In this study, we compared acute toxicities and reconstructive complications in patients treated with proton-based and photon-based PMRT.MethodsA retrospective review of our institutional database was performed to identify breast cancer patients treated with mastectomy with implant or autologous reconstruction followed by PMRT from 2015 to 2020. Baseline clinical, disease, and treatment related factors were compared between the photon-based and proton-based PMRT groups. Early toxicity outcomes and reconstructive complications following PMRT were graded by the treating physician.ResultsA total of 11 patients treated with proton-based PMRT and 26 patients treated with photon-based PMRT were included with a median follow-up of 7.4 months (range, 0.7-33 months). Six patients (55%) in the proton group had a history of breast cancer (3 ipsilateral and 3 contralateral) and received previous RT 38 months ago (median, range 7-85). There was no significant difference in mean PMRT (p = 0.064) and boost dose (p = 0.608) between the two groups. Grade 2 skin toxicity was the most common acute toxicity in both groups (55% and 73% in the proton and photon group, respectively) (p = 0.077). Three patients (27%) in the proton group developed grade 3 skin toxicity. No Grade 4 acute toxicity was reported in either group. Reconstructive complications occurred in 4 patients (36%) in the proton group and 8 patients (31%) in photon group (p = 0.946).ConclusionsAcute skin toxicity remains the most frequent adverse event in both proton- and photon-based PMRT. In our study, reconstructive complications were not significantly higher in patients treated with proton- versus photon-based PMRT. Longer follow-up is warranted to assess late toxicities

Microstrip antennas for mobile telephone handset with reduced radiation hazards

A novel antenna configuration comprised of two circular micro strip antennas (CMAs) resonating in the TMtt and TM2, modes, producing radiation characteristics suitable for a mobile telephone handset, is presented. The antennas operating at the same frequency are placed back to back with a separation comparable to the thickness of a typical handset. The radiation pattern consists of a region of reduced radiation intensity, which minimizes the radiation hazards to the use

Microstrip Antennas For Mobile Telephone Handset With Reduced Radiation Hazards

A novel antenna configuration comprised of two circular microstrip antennas (CMAs) resonating in the TMtt and TM2, modes, producing radiation characteristics suitable for a mobile telephone handset, is presented. The antennas operating at the same frequency are placed back to back with a separation comparable to the thickness of a typical handset. The radiation pattern consists of a region of reduced radiation intensity, which minimizes the radiation hazards to the userCochin University of Science and TechnologyMicrowave and Optical Technology Letters,VOL 23,issue 6.pp 370-37