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Background The Ad5-nCoV vaccine is a single-dose adenovirus type 5 (Ad5) vectored vaccine expressing the SARS-CoV-2 spike protein that was well-tolerated and immunogenic in phase 1 and 2 studies. In this study, we report results on the final efficacy and interim safety analyses of the phase 3 trial. Methods This double-blind, randomised, international, placebo-controlled, endpoint-case driven, phase 3, clinical trial enrolled adults aged 18 years older at study centres in Argentina, Chile, Mexico, Pakistan, and Russia. Participants were eligible for the study if they had no unstable or severe underlying medical or psychiatric conditions; had no history of a laboratory-confirmed SARS-CoV-2 infection; were not pregnant or breastfeeding; and had no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine. After informed consent was obtained, 25 mL of whole blood was withdrawn from all eligible participants who were randomised in a 1:1 ratio to receive a single intramuscular dose of 0·5 mL placebo or a 0·5 mL dose of 5 × 1010 viral particle (vp)/mL Ad5-nCoV vaccine; study staff and participants were blinded to treatment allocation. All participants were contacted weekly by email, telephone, or text message to self-report any symptoms of COVID-19 illness, and laboratory testing for SARS-CoV-2 was done for all participants with any symptoms. The primary efficacy objective evaluated Ad5-nCoV in preventing symptomatic, PCR-confirmed COVID-19 infection occurring at least 28 days after vaccination in all participants who were at least 28 days postvaccination on Jan 15, 2021. The primary safety objective evaluated the incidence of any serious adverse events or medically attended adverse events postvaccination in all participants who received a study injection. This trial is closed for enrolment and is registered with ClinicalTrials.gov (NCT04526990). Findings Study enrolment began on Sept 22, 2020, in Pakistan, Nov 6, 2020, in Mexico, Dec 2, 2020, in Russia and Chile, and Dec 17, 2020, in Argentina; 150 endpoint cases were reached on Jan 15, 2021, triggering the final primary efficacy analysis. One dose of Ad5-nCoV showed a 57·5% (95% CI 39·7–70·0, p=0·0026) efficacy against symptomatic, PCR-confirmed, COVID-19 infection at 28 days or more postvaccination (21 250 participants; 45 days median duration of follow-up [IQR 36–58]). In the primary safety analysis undertaken at the time of the efficacy analysis (36 717 participants), there was no significant difference in the incidence of serious adverse events (14 [0·1%] of 18 363 Ad5-nCoV recipients and 10 [0·1%] of 18 354 placebo recipients, p=0·54) or medically attended adverse events (442 [2·4%] of 18 363 Ad5-nCoV recipients and 411 [2·2%] of 18 354 placebo recipients, p=0·30) between the Ad5-nCoV or placebo groups, or any serious adverse events considered related to the study product (none in both Ad5-nCoV and placebo recipients). In the extended safety cohort, 1004 (63·5%) of 1582 of Ad5-nCoV recipients and 729 (46·4%) of 1572 placebo recipients reported a solicited systemic adverse event (p

Access to safe drinking water is an emerging issue in Pakistan, both in urban and rural settlements. The water quality in the region is mainly declined by population explosion, vehicular and industrial emissions and agricultural activities. The aim of the study was to assess the water quality of the study area through integrated approach of water quality index and multivariate analysis. Water samples from the study area were analyzed for physicochemical and microbiological parameters using standard methods. The study site was divided into eight (8) different locations and the water samples were collected from commonly used water sources. The results of study indicated that the concentration of all studied chemical parameters were within the permissible limits when compared with WHO recommended standards except lead (Pb). Major cations were found in the order of Ca2+> Mg2+>Na+ whereas the trend of anions was HCO-3>Cl->SO4>NO3.Overall water was estimated to be of CaHCO-3 type. Water quality index illustrated that all water samples were unsuitable for drinking purposes. Microbiological assessment showed that water is contaminated with coliform bacteria and fungal spores. Multivariate techniques were found to be ideal tools in identifying spatial variability through cluster analysis (CA) and reducing the dimensionality of huge data set through PCA/FA. It is briefly, concluded from the results of current study, that water of the study area was unsuitable for drinking purposes due to presence of some biological and chemical contaminants. Results recommend that developing efficient water quality monitoring programs, promoting ceramic filters technology, and raising awareness about the issue in communities are the most important steps that might help the people of the study area to resolve the problem.

Trichoderma spp. are the most versatile biocontrol agents which have long been used for biocontrol, biofertilization, and alleviators of various abiotic stresses. They are known to produce several bioactive compounds and elicitors which directly interact with the host roots, thereby increasing the growth of plants and resistance to several biotic and abiotic stresses. They may protect the plants from phytopathogens by the formation of antibiotic, hydrolytic enzymes, mycoparasitism, competition for nutrients, induction of defense-related genes, induced systemic resistance, and production of various secondary metabolites. These mechanisms may directly or indirectly inhibit the growth of phytopathogens, rendering them ineffective to cause any disease. They are also known to induce tolerance in response to various abiotic stresses like drought, cold, salinity, heavy metal, etc. The current knowledge related to the mechanisms employed by Trichoderma spp. in alleviating the biotic and abiotic stresses in plants could be further investigated to improve its potential to combat various stresses in plants. This chapter presents the updates on published research findings about the potential of Trichoderma species in alleviating biotic and abiotic stresses in plants and the underlying mechanisms thereof.

This investigation was carried out to examine the effect of some biocontrol agents (Trichoderma viride, T. harzianum, Azotobacter chroococcum, Pseudomonas putida) and botanicals (Melia azedarach, Eucalyptus globulus, Calotropis procera) both alone and in combination on growth, yield and stem gall disease of coriander (Coriandrum sativum L.) caused by Protomyces macrosporus Unger in a pot experiment. Plants inoculated with P. macrosporus caused significant reduction in growth and yield attributes as compared to untreated control. Stem gall intensity was recorded 59% in plants treated with pathogen alone. The results revealed that, application of biocontrol agents / botanicals both alone and in combination caused significant reduction in stem gall intensity (20.33–84.82%) as compared to control. Among the tested biocontrol agents, T. viride was found superior in enhancing the growth and yield as well as reduction in stem gall intensity (44.37%). Application of biocontrol agents in soil supplemented with botanicals was found more beneficial in enhancing plant growth and yield attributes as well as reducing stem gall intensity (52.54–84.82%). Among various combinations tested T. viride + Melia azedarach and T. viride + E. globulus caused greater increase in plant growth and yield characters both in pathogen inoculated as well as uninoculated plants. Keywords: Biocontrol agents, Botanicals, Protomyces macrosporus, Stem gall, Coriander

Famotidine 40 mg film coated tablet by invitro comparative study , together with the official and non official compendial test. Famotidine is an aggressive inhibitor of histamine H2-receptors. The pivotal clinically critical pharmacologic activity of Famotidine is to hold of gastric discharge. Both the acid concentration and volume of gastric secreation are concealed by famotidine, while changes in pepsin discharge are relative to volume generation. Famotidine is more potent than other class of drugs like.the drug is intended to release after oral administration for immediate release so we execute testing analysis to illustrate the procedure, the major test for analyzing the effectiveness of drug comprises, dissolution , assay, disintegration time, thickness and weight variation in three brands available in market of Karachi Pakistan. The weight variation test shows outcomes within the limits and all brands dissolves within 30 minutes, every brand showed the drug dissolution more than 75 % within the 30 minutes ,all outcome showed good effectiveness and producing outcomes within the limits and complying the USP recomendation. Key Words: Compendial test, immediate release, competitive inhibitor, famotidine, tablets

Pakistan is the highly fertile region for the envenoming and deadly snakes. The envenoming fatality and snake bite cases are increasing day by day not only in Pakistan but also in World. In Pakistan, almost 40,000 snake bite cases and 8000 fatal cases has been identified. This high-risk issue needs to be addressed with an easy accessible and affordable treatment by producing anti snake venom serum. LD50 (50% Lethal Dose) of venom is the prime parameter to determine the toxicity and lethality of venom extracted from the four poisonous snakes present in the Pakistan. The main objective of this study waste produces highly potent and costeffective anti-snake venom serum by the determination of LD50. The venom was extracted from four different species of snakes i.e., Echis carinatus, Vipera russelli, Bungares caeruleus and Naja naja (Cobra) present in Biological Production Division of NIH, Pakistan. The four to five serial dilutions were injected intravenously into the mice tail and observations were recorded to calculate the LD50 of each species by Reed and Munch method in Bacteriology section of Quality Control Laboratory, National Institute of Health, Islamabad. Then 3 to 5 fold LD50 is the neutralization dose of Anti-snake venom serum used for the calculation of ED50 of each batch/lot of anti-snake venom serum(as per WHO). The results of the study shows that LD50 of Naja Naja (Cobra) lies approximate between 6 to 7 μg/dose, Echis carinatus (Saw Scaled Viper) 11 to 12 μg/dose, Vipera russelli (Russel viper) 5 to 6 μg/dose and Bungares caeruleus (Krait) 4 to 5 μg/dose in intravenous injection of dilution.

Maternal and Neonatal Tetanus is a severe, often fatal ailment characterized by sweeping augmented strictness and convulsive spasms of skeletal muscles. Vaccination is the most steadfast method of forbearance against this disease and has inculcated to lessen mortalities. The present study was carried out with a view to assess the serum levels of tetanus antitoxins in randomly selected rural and urban women to find out the effect of age, number of pregnancy, parity and number of injections at the time of delivery. The study was cross-sectional in design and hospital-based. The gold standard mouse neutralization assay was employed despite being costly and cumbersome. Antibody titre of each sample was determined by seroneutralization method. 1504 women, randomly selected from various hospitals of age 15 to 40 years, 1064 (0.000) were vaccinated, which are significant while 440 were unvaccinated women and taken as control. The 65% (p = 0.000) women had antibody titre higher than protective level which is significant, 28% equal to protective level and 6.7% below protective level. Average antibody titre of 3rd trimester was higher than 2nd trimester (p = 0.000) which is significant. Immunization awareness and practice was higher in 30 years in women (63%) of both rural and urban areas but practice was comparatively higher in urban (74%) than rural area (67%). These finding shows that tetanus vaccination in our population is generally effective and cannot be protected by herd immunity, as tetanus is not communicable disease. Key words: Antitetanus antibodies, seroneutralization, childbearing age, Pakistan. INTRODUCTION Tetanus caused by Clostridium tetani , is a vaccine-preventable, global infectious disease with significant morbidity and mortality. The global status of serological immunity against tetanus varies between countries as a result of different national vaccination policies and methods, and the criteria used for determination of serum levels of tetanus antitoxin. Protective immunity was noted

In the present study, 12 varieties of tomato, viz., Arka Vikas, Damayanti, F-hybrid, Hybrid Padmarag, Hybrid Tripti, Marudam, Punjab chhoara, Pusa early dwarf, Punjab kesari, P.K.M.I, Roma and Pusa Ruby were screened for the presence of the root-knot nematode, M. javanica to obtain information on the varying degrees of resistances to tomato cultivars. All the cultivars of tomato tested were found to be infected with the root-knot nematode, M. javanica, however, to a varying extent. Consequently, there was a reduction in the growth parameters of cultivars leading to have an impact on the yield and quality of fruits. The cultivar, Marudam was found resistant while the cultivar the Pusa early dwarf was moderately resistant and rest of the 10 cultivars was highly susceptible.

Worldwide drug expenditures have been one of the main concerns of health care managers, and its containment is one of the primary goals of health care authorities. The present study was conducted through a cross sectional survey in Pakistan during January to June, 2010 not only to find out the importance and influence of promotional tools used by pharmaceutical industry on prescribing behaviors of doctors/consultants, but to also establish comparison between doctors/consultants versus medical representatives and consultant versus doctors with an auxiliary of difference between local and multinational company’s representative. The study revealed that promotional tools are considered vital from doctors and medical representatives’ point of view. There exists significant difference in doctors and consultant’s perception for sponsorships and low value gifts, but no difference in scientific promotional tools. No significant difference exits in perception of medical representatives of multinational and local company representatives. The companies tried to come up as per expectations of doctors to build its reputation and good image by employing different promotional tools. The study also revealed that marketing managers, product managers, chief executive officers or any decision makers involved in budget allocations and making promotional strategy should not rely heavily on medical representative’s feedback as their perception is different from doctors/consultants about relevant importance of each promotional tool. The study will also help product managers and CEOs while allocating promotional budgets and developing promotional mix strategy, to gain maximum return out of investment. Detailed doctors’ demographics can further be researched as predictor for preferring any promotional tools. Key words: Prescribing patterns, promotional tools, physicians, pharmaceutical industry.

Half of all medicines are prescribed or sold inappropriately and half of all patients fail to take their medicines correctly worldwide. The present study was conducted to evaluate the pattern and practice of drugs within the modern medical system by investigating the prescription pattern, drug use in private and public health care facilities, assessment of the magnitude of the problem, identifying factors responsible for the problem, suggesting measures in Pakistan. There were marked differences between the qualities of consultation indicators between general practitioners (GPs) and public health care providers. The average number of drugs per prescription was 2.92 for all types of health care providers, mean number of drugs dispensed was 2.41 and 50% of the dispensed drugs were adequately labeled. Five categories of drugs comprised around 70% of all drugs prescribed. Injections prescribed per prescription were 0.32, infusions 0.07, capsules/tablets 1.85, syrups/suspensions 0.8. Number of drugs prescribed by GP’s was 4.3 and was 2.9 (P = 0.001) for public health care providers and antibiotics prescribed per prescription were 0.9 and 0.8 (P = 0.176) for the GP’s and public health care providers. The availability of drugs at public health care facilities influenced prescription in 88% of cases as compared to 57% (P = 0.001) at GPs clinics. Prescribing and dispensing practices are irrational both in public and private sector in Pakistan like many developing countries. Workable and appropriate interventions need to be developed and implemented in countries to improve trends of prescribing. The essential drug list and standard treatment guidelines should be disbursed to all medical, dental and pharmacy students. Key words: Pakistan, prescribing practices, irrational prescribing, general practitioners.

Twenty-seven varieties of coriander were evaluated for their resistance against stem gall disease caused by Protomyces macrosporus. Out of 27 varieties screened only four varieties viz., UD-125, UD-317, UD-749 and Rlr- 480 having less than 10% stem gall intensity were graded as resistant. The mean yield of healthy seeds was found between 1.33 to 1.97 g/plant and of diseased seeds was between 0.13 to 0.68 g/plant. Average seed yield loss (%) ranged between 6.04 to 27.87%. Minimum yield loss was recorded in UD-125 and maximum in American green.

The results of experiment clearly reveal that cadmium inhibited root penetration by the second stage juveniles (J2) of Meloidogyne incognita which subsequently affected the development of root galls in tomato. The heavy metal was highly injurious to tomato plants at all the concentrations tested for (7.5, 15.0, 30.0 and 60.0 ppm). The inhibitory effect on plant growth and other parameters (fresh and dry weight of plant, chlorophyll content of leaves, water absorption capability of roots) significantly increased with an increase in the concentration of the metal. It was further increased in the presence of the nematode.

Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune - 411 008, IndiaFax +91(20)5893153; E-mail: arasd@dalton.ncl.res.inReceived 30 May 2002Synlett 2002, No. 9, Print: 02 09 2002. Art Id.1437-2096,E;2002,0,09,1455,1458,ftx,en;G15202ST.pdf. © Georg Thieme Verlag Stuttgart · New YorkISSN 0936-5214Abstract: An efficient use of triphosgene for the preparation of var-ious azidoformates from alcohols and sodium azide is described.The method is applied to various chiral alcohols including glucosediacetonide to get the corresponding azidoformates. One of theseazidoformates has been successfully utilized for the synthesis of N-carbobenzyloxy- -lactams.Key words: azidoformate, alcohol, sodium azide, triphosgene,azetidin-2-one

All the cultivars of tomato tested were found to be infected with the root‐knot nematode, Meloidogyne incognita, however, to varying extent. There was also reducton in plant growth parameters accordingly. Further reduction in plant growth of tomato cultivars was recorded when plants also received the treatment with the heavy metal, lead, notwithstanding the fact that the presence of lead also reduced the root‐knot development. Tomato cv. Arka Vikas showed minimum reduction in plant growth with single or combined treatment with the nematode and the heavy metal.

Pollution Pathology has emerged as a distinct discipline which deals with the impact of pollutants on plants and its disease causing agencies. Pollutants have been found to adversely affect not only the plants but also the phytopathogens and above all their pathogenesis. The hitherto scattered information on this aspect has been reviewed in the present write‐up.

Tetanus is an acute illness represented by comprehensive increased inflexibility and spastic spasms of skeletal muscles. The poor quality tetanus toxoid vaccine can raise the prevalence of neonatal tetanus. WHO has taken numerous steps to assist national regulatory authorities and vaccine manufacturers to ensure its quality and efficacy. It has formulated international principles for stability evaluation of each vaccine, which are available in the form of recommendations and guidelines. The aim of present study was to ensure the stability of tetanus vaccines produced by National Institute of Health, Islamabad, Pakistan by employing standardized methods to ensure constancy of tetanus toxoid at elevated temperature, if during storage/transportation cold chain may not be maintained in hot weather. A total of three batches filled during full-scale production were tested. All Stability studies determination were performed on final products stored at 2-8°C and elevated temperatures in conformance with the ICH Guideline of Stability Testing of Biological Products. These studies gave comparison between real time shelf-life stability and accelerated stability studies. The findings indicate long-term thermo stability and prove that this tetanus vaccine can remain efficient under setting of routine use when suggested measures for storage and handling are followed in true spirit.

The downstream processing of biotechnological products from fermentation broth is an important step of production and development of cost effective, efficient downstream processing of many biotechnological products. The present study was conducted by employing aqueous two phase systems (ATPSs) for the extraction of cephalosporin C (CPC) from whole fermentation broth of Acremonium chrysogenum . The biphasic system was prepared by mixing equal aliquots of 15% w/w polyethylene glycol (PEG) 3350 with 15% (NH 4 ) 2 SO 4 . The effects of pH, neutral salts, temperature and centrifugal force on partitioning in ATPS to develop efficient extraction system for recovery of CPC from fermentation broth were also examined. The extraction efficiency was improved by enhancing the centrifugal force. Similarly centrifugation for 12.5 min also gave the maximum extraction. Improvement in the recovery yield was also observed by the addition of 0.1% NaCl. The concentration of CPC was determined by high performance liquid chromatography (HPLC). Slight modifications in the mobile phase from 10 to 5% MeOH improved CPC resolution. Further development of more inexpensive systems for extraction can be the future target of research. Keywords: Cephalosporin C, Acremonium chrysogenum , fermentation, aqueous two phase system (ATPS)

Allergic diseases are fairly common in all parts of the world and involve all ethnic groups with bronchial asthma, allergic rhinitis, conjunctivitis and eczema being the commonest manifestations. Despite our efforts, their incidence is on an escalating path. The use of herbal remedies and standardized extracts for treatment of allergy and other diseases has been gaining momentum in recent years. The qualitative and quantitative determination of phyto-chemicals and assessment of the anti-allergic and anti-inflammatory activities using aqueous and organic extracts of different plant parts (root, stem and leaves) of Mentha arvensis in animals showed that all parts of M. arvensis (specifically, leaves) are rich source of secondary phytoconstituents, which impart their therapeutic effects against allergic andinflammatory diseases. These results support the claim about the use of this herb in folk medicines. Key words: Anti-allergic, anti-inflammatory activity, medicinal plants, Mentha arvensis,Pakistan.

Lactic acid bacteria (LAB) commonly used in food, as starter cultures are known to produce antimicrobial substances such as bacteriocins and have great potential as food bio-preservatives. Yogurt is a probiotic dairy product having Lactobacillus bulgaricus as natural source for fermentation. The aim of this study was to determine the antimicrobial activity of bacteriocin, produced by Lactobacillus bulgaricus isolated from yogurt and tested against pathogenic organisms. The identification of the culture was based on characteristics of the strains of Lactobacillus spp. on the basis of microscopy (morphology), Gram straining, growth at 37 and 45°C, fermentation of different carbohydrate sources and growth in MRS broth. On the basis of all of the identification tests, one strain isolated from the yogurt was identified as L. bulgaricus. Culture supernatants were obtained from the sixty out of hundred isolates of Lactobacillus spp. exhibited varying degrees of inhibitory activity against strains of Bacillus subtilis, ATCC #6633, Escherichia coli, ATCC, #10536, Salmonella typhi, ATCC# 19430,Staphylococcus aureus, ATCC #6538, Vibrio cholerae, ATCC #25870. Specifically, Vibrio cholerae was found most sensitive to bacteriocin, exhibiting maximum zone of inhibition 18.3 mm. Key words: Lactic acid bacteria (LAB), Lactobacillus bulgaricus, bacteriocin, yogurt, antimicrobial activity, Pakistan.

Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune - 411 008, IndiaFax +91(20)5893153; E-mail: arasd@dalton.ncl.res.inReceived 30 May 2002Synlett 2002, No. 9, Print: 02 09 2002. Art Id.1437-2096,E;2002,0,09,1455,1458,ftx,en;G15202ST.pdf. © Georg Thieme Verlag Stuttgart · New YorkISSN 0936-5214Abstract: An efficient use of triphosgene for the preparation of var-ious azidoformates from alcohols and sodium azide is described.The method is applied to various chiral alcohols including glucosediacetonide to get the corresponding azidoformates. One of theseazidoformates has been successfully utilized for the synthesis of N-carbobenzyloxy- -lactams.Key words: azidoformate, alcohol, sodium azide, triphosgene,azetidin-2-one