Identification of potential inhibitors of Zika virus targeting NS3 helicase using molecular dynamics simulations and DFT studies.

Despite the various research efforts towards the drug discovery program for Zika virus treatment, no antiviral drugs or vaccines have yet been discovered. The spread of the mosquito vector and ZIKV infection exposure is expected to accelerate globally due to continuing global travel. The NS3-Hel is a non-structural protein part and involved in different functions such as polyprotein processing, genome replication, etc. It makes an NS3-Hel protein an attractive target for designing novel drugs for ZIKV treatment. This investigation identifies the novel, potent ZIKV inhibitors by virtual screening and elucidates the binding pattern using molecular docking and molecular dynamics simulation studies. The molecular dynamics simulation results indicate dynamic stability between protein and ligand complexes, and the structures keep significantly unchanged at the binding site during the simulation period. All inhibitors found within the acceptable range having drug-likeness properties. The synthetic feasibility score suggests that all screened inhibitors can be easily synthesizable. Therefore, possible inhibitors obtained from this study can be considered a potential inhibitor for NS3 Hel, and further, it could be provided as a lead for drug development.

The Chemistry of Triazine Isomers: Structures, Reactions, Synthesis and Applications.

Triazine is the six-membered heterocyclic ring containing three nitrogens, which replace the carbon-hydrogen unit in the benzene ring. Based on nitrogen position present in the ring system, it is categorized in three isomeric forms, i.e., 1, 2, 3-triazine (vicinal triazine), 1, 2, 4-triazine (asymmetrical triazine or isotriazine) and 1, 3, 5-triazine (symmetrical or s-triazine or cyanidine). Triazines have a weakly basic property. Their isomers have much weaker resonance energy than benzene structure, so nucleophilic substitution reactions are more preferred than electrophilic substitution reactions. Triazine isomers and their derivatives are known to play important roles possessing various activities in medicinal and agricultural fields such as anti-cancer, antiviral, fungicidal, insecticidal, bactericidal, herbicidal, antimalarial and antimicrobial agents.

Evaluation of USDA approved antimicrobials on the reduction of Salmonella and Campylobacter in ground chicken frames and their effect on meat quality.

The main objective of this study was to examine the efficacy of USDA approved antimicrobials in reducing Salmonella Heidelberg (S. H.) and Campylobacter jejuni (C. j.) in ground chicken frames and to determine the treatment effects on total aerobic counts and meat color. Six antimicrobials (0.1% peracetic acid [PAA], 0.6% cetylpyridinium chloride [CPC], 0.005% sodium hypochlorite, 1.5% acidified lactic acid [ALA], 0.3% propionic acid, and 0.1% lauric arginate [LAE]) applied as dip treatments were evaluated in their efficacy in reducing S. Heidelberg and C. jejuni. Fresh chicken frames were spot inoculated with nalidixic acid resistant S. H. and C. j. (ATCC 33291) to achieve a recovery level of ca. 3 log CFU/g in the ground product. Frames were dipped for 10 s in each antimicrobial solution and each treatment was replicated on 3 frames. Three separate replications were conducted for this experiment. Frames were blended, and ground samples similar to mechanically separated chicken (MSC) were obtained and stored at 4°C for 24 hours. Samples were analyzed after grinding on d zero (2 h) and d one (24 h) to determine reduction in S. H. and C. j. counts in MSC. PAA and LAE treatments had the highest reductions on Salmonella counts (P ≤ 0.05), both treatments resulting in 0.9 log CFU/g reduction as compared to control on d zero. PAA and CPC reduced Salmonella counts by 1.4 and 0.9 log CFU/g, respectively, on d one; PAA, propionic acid, ALA, and LAE resulted in one log CFU/g reductions of C. j. as compared to control on d one. There was no significant difference among the treatments in their ability to reduce C. j. on d one. The treatments had no effect on total aerobic counts. The findings from the study indicate that PAA, CPC, and LAE can reduce S. H. in ground chicken frames, whereas all the antimicrobials tested in the study, except chlorine, have the ability to reduce C. j. in ground chicken frames, a product similar to commercial MSC.

Efficacy of Lytic Bacteriophage Preparation in Reducing Salmonella In Vitro, on Turkey Breast Cutlets, and on Ground Turkey.

The efficacy of the recently approved Salmonella lytic bacteriophage preparation (SalmoFresh) in reducing Salmonella enterica serotype Heidelberg on turkey breast cutlets and ground turkey was evaluated. In a broth model assay, the phage preparation completely inhibited the growth of four S. enterica serotypes (Salmonella Enteritidis, Salmonella Heidelberg, Salmonella Kentucky, and Salmonella Typhimurium) at 37°C at a multiplicity of infection of 10,000 PFU/CFU. At 4°C in 0.1% peptone water (PW), phage treatment at a multiplicity of infection of 10,000 resulted in ca. 4.0-log CFU/ml reductions of Salmonella Enteritidis, Salmonella Heidelberg, and Salmonella Typhimurium. When raw turkey breast cutlets inoculated with Salmonella Heidelberg (∼10(3) CFU/g) were treated with phage preparation (10(7) PFU/g) and stored at 4°C, the phage treatment caused reductions of 0.8, 0.6, and 1.3 log CFU/g (P ≤ 0.05) of Salmonella Heidelberg on day 0, 1, and 7, respectively, compared with the counts in the control. However, no significant reduction of Salmonella Heidelberg (P > 0.05) was observed in ground turkey when turkey meat pieces inoculated with Salmonella Heidelberg were surface treated with phage preparation (10(7) PFU/g) before grinding. These findings indicate that the bacteriophage preparation was effective in reducing Salmonella on turkey breast cutlets as a surface treatment but did not cause any reduction of Salmonella Heidelberg in ground turkey.

Preliminary analysis of polycyclic aromatic hydrocarbons in air particles (PM10) in Amritsar, India: sources, apportionment, and possible risk implications to humans.

Preliminary analysis was performed to assess human health risks of exposure to 16 polycyclic aromatic hydrocarbons (PAHs) by way of inhalation by children and adults living in urban area of Amritsar, Punjab, India. In particular, the United States Environmental Protection Agency's (USEPA's) 16 priority PAH compounds were analyzed in air particulate matter (PM10) from different geographical locations by high-volume air sampler. Sum concentrations of PAHs (37-274 ng m(-3)) were comparable with those of other cities in India as well many cities on a global scale. Pyrene, naphthalene, acenaphthene, acenaphthylene, fluoranthene, fluorene, and dibenzo(a,h)anthracene accounted for >80% of ∑16PAH concentrations. Furthermore, the contribution of seven carcinogenic PAHs accounted for 12% of ∑16PAHs. The estimated carcinogenicity of PAHs in terms of benzo(a)pyrene toxic equivalency (BaPTEQ) was assessed and confirmed that dibenzo(a,h)anthracene was the dominant PAH contributor (88.7%) followed by benzo(a)pyrene (6.67%). Homolog pattern and diagnostic ratios of PAHs suggested that mixed pyrogenic sources--including biomass burning, coal combustion, and petrogenic sources, such as vehicular emissions--are dominant PAH sources in Amritsar. Health risk of adults and children by way of PAHs was assessed by estimating the lifetime average daily dose (LADD) and corresponding incremental lifetime cancer risk (ILCR) using USEPA guidelines. The assessed cancer risk (ILCR) was found to be within the acceptable range (10(-6)-10(-4)).

Reduction of Salmonella in skinless chicken breast fillets by lauric arginate surface application.

Lauric arginate (LAE) has been found to be effective against various foodborne pathogens. In this study, the antimicrobial efficacy of LAE against Salmonella and mesophilic organisms was evaluated in fresh, skinless, boneless, uncooked chicken breast fillets. The effect of LAE treatments on pH and color of breast fillets was also assessed. Chicken breast fillets were inoculated with a 4-strain Salmonella cocktail (Salmonella Enteritidis ATCC 4931, Salmonella Heidelberg ATCC 8326, Salmonella Kentucky ATCC 9263, and Salmonella Typhimurium ATCC 14028) and then treated with sterile dionized water (positive control) and 200 ppm and 400 ppm of LAE. The chicken breast fillets were stored at 4 ± 1°C and analyzed on d 0, 1, 3, 5, and 7 for Salmonella, total aerobes, color, and pH. The fillets destined for color analysis were not inoculated with Salmonella cocktail and stored under conditions simulating the retail display. The fillets treated with 400 ppm LAE had lower (P < 0.05) Salmonella counts compared with the positive control from d 0 through d 7 of storage except on d 3, when no effect of LAE was observed. Treating fillets with 200 ppm of LAE caused a significant reduction in Salmonella counts (P < 0.1) on d 0, 1, and 7. Reductions in Salmonella spp. were 0.7 log cfu/g and 0.7 to 1.0 log cfu/g for 200 and 400 ppm treatments, respectively. Lauric arginate did not exhibit any treatment effect on the growth of mesophilic microorganisms, pH, and color of chicken breast fillets (P > 0.05) when applied at 200 and 400 ppm concentrations. These results indicate that surface application of LAE in chicken breast fillets significantly reduces Salmonella during refrigerated aerobic storage without negatively affecting the color of chicken breast fillets.

Sodium metasilicate affects growth of Campylobacter jejuni in fresh, boneless, uncooked chicken breast fillets stored at 4 degrees Celsius for 7 days.

The objectives of this study were to determine the antimicrobial effects of sodium metasilicate (SMS) treatments against Campylobacter jejuni in fresh, boneless, uncooked chicken breast fillets and to ascertain the effects of SMS treatments on pH. The fillets were inoculated with C. jejuni, treated with 0% SMS and no inoculum (negative control), 0% SMS and inoculum (positive control), 1 and 2% SMS solutions, and stored at 4 ± 1°C. All samples were analyzed after 0, 1, 3, 5, and 7 d storage for C. jejuni, psychrotrophic organisms, and pH. Campylobacter jejuni and psychrotrophic counts for samples treated with 1 and 2% SMS solutions were similar (P > 0.05) to the positive control on all storage days. The pH values for 2% SMS marinade treatments were higher (P < 0.05) when compared with the negative and positive controls through 7 d of storage. Based on the findings in this study, a second study was conducted to determine the level of SMS necessary to reduce C. jejuni by at least 1 log cfu/g. The treatments were the same as previously discussed, except SMS was used at levels of 1 and 2% of the weight of the meat instead of percentage of the solution. Chicken fillets treated with 1 and 2% SMS (by weight of meat) resulted in 1.12 to 1.26 and 3.27 to 3.79 log cfu/g reductions in C. jejuni, respectively, when compared with the positive control. Except for d 0, psychrotrophic counts for samples treated with 2% SMS were lower (P < 0.05) than negative and positive controls on all storage days. The pH values were higher (P < 0.05) for all SMS treatments when compared with the negative and positive controls. This study revealed that SMS, when used at elevated levels in excess of the USDA Food Safety and Inspection Service 2% approved level, could function to control Campylobacter jejuni and extend the shelf life of raw poultry by retarding the growth of psychrotrophic bacteria.

Epidural volume extension: a review.

Epidural volume extension is a technical modification of the combined spinal epidural block. It involves the epidural injection of normal saline or a small volume of local anaesthetic after an intrathecal injection, aiming to augment the post-spinal sensory level. Although the consequent sensory block augmentation has been adequately documented, the probable factors influencing epidural volume extension and its implications for clinical practice are not well defined. This article reviews published literature relating to the probable factors affecting epidural volume extension, its clinical implications, case reports of its successful clinical application and summarises its unexplored effects.

Sodium metasilicate affects growth of Salmonella Typhimurium in fresh, boneless, uncooked chicken breast fillets stored at 4°C for 7 days.

The objectives of this study were to determine the antimicrobial effects of sodium metasilicate (SMS) against Salmonella and psychrotrophic organisms in fresh, boneless, uncooked chicken breast fillets and to ascertain the effects of SMS treatments on pH. Chicken breast fillets were inoculated with Salmonella enterica serovar Typhimurium treated with 0% SMS and no inoculum (negative control), 0% SMS and inoculum (positive control), 1% SMS, or 2% SMS solutions and stored at 4 ± 1°C. All samples were analyzed after 0, 1, 3, 5, and 7 d for Salmonella, psychrotrophic organisms, and pH. The fillets that were treated with 1 or 2% SMS had lower (P < 0.05) Salmonella counts as compared with those of the positive control at 3 through 7 d. Reductions in Salmonella Typhimurium were 0.83 to 0.91 log cfu/g and 1.04 to 1.16 log cfu/g for 1 and 2% SMS treatments, respectively. The psychrotrophic counts were similar (P > 0.05) for all treatments. The pH values for samples treated with 1 or 2% SMS were higher (P < 0.05) when compared with those of the negative and positive controls. This study revealed that SMS could restrict the growth of pathogenic Salmonella Typhimurium in fresh poultry.

Organochlorine pesticide residue levels and oxidative stress in preterm delivery cases.

A number of studies have focused attention on various biochemical abnormalities evoked due to exposure to organochlorine pesticides (OCPs). The aim of the present study was to analyze the OCP residues in maternal and cord blood of women and assess the levels of different non-enzymatic oxidative stress markers as well as to establish correlation with OCP levels, if any. Thirty women in each group of full-term delivery (FTD; > or =37 weeks of gestation) and preterm delivery (PTD; <37 weeks of gestation) were enrolled in this study. Levels of OCPs like Hexachlorocyclohexane (HCH), endosulfan, p,p(') Dichlorodiphenyldichloroethylene (DDE) and p,p' Dichlorodiphenyltrichloroethane (DDT) were analyzed by gas chromatography. Non-enzymatic oxidative stress was measured by the quantification of malondialhyde (MDA), protein carbonyl, reduced glutathione (GSH) and ferric-reducing ability of plasma (FRAP). MDA and protein carbonyl levels were increased significantly, while the levels of GSH and FRAP were decreased in PTD in comparison to FTD cases. We have observed higher levels of beta-HCH and alpha-endosulfan and increased oxidative stress in PTD than FTD cases. In PTD cases, a significant positive correlation was observed between maternal blood levels of beta-HCH and MDA (r = .78), beta-HCH and GSH (r = -.65), gamma-HCH and MDA (r = .89), gamma-HCH and GSH (r = -.74) and alpha-endosulfan and MDA (r = .54) in PTD cases. We also found significant correlations between cord blood levels of beta-HCH and MDA (r = .59), beta-HCH and GSH (r = -.69), gamma-HCH and MDA (r = .62) and alpha-endosulfan and MDA (r = .54) in PTD cases. In conclusion, our results suggest that higher levels of some of the OCP residues may be associated with PTD and increased oxidative stress.

Aberrant infestation of goat mandibles with Oestrus ovis larvae.

Nasal oestrosis is primarily an infestation of sheep. However, a non descript goat, aged three years was presented in lateral recumbency with clinical history of sneezing fits, laboured breathing, eroded mandibular lesions and bilaterally housing nasal bots therein. The first ever occurrence of nasal bots in an aberrant location (mandibles) in a goat, its therapeutic management and public health significance have been documented and discussed.

Maternal and cord blood levels of organochlorine pesticides: association with preterm labor.

OBJECTIVES: Organochlorine pesticides (OCPs) have been reported to cause adverse reproductive outcomes. Hence, the present study was conducted to estimate and compare the levels of OCPs in maternal and cord blood of preterm labor and full term labor cases as well as assess their role in preterm delivery. DESIGN AND METHODS: 23 cases each of preterm labor and full term labor were included in the study. Maternal and cord blood OCP levels were determined by using a GC-MS equipped with an electron capture detector. RESULTS: Maternal and cord blood levels of alpha-HCH, beta-HCH, gamma-HCH, total-HCH, p,p'DDE and p,p'DDT were found higher in preterm labor than full term labor cases. However, a statistically significant relation was observed between preterm birth and beta-HCH levels only. CONCLUSIONS: Higher blood levels of beta-HCH may be associated with risk of preterm labor.

Endosulfan and other organochlorine pesticide residues in maternal and cord blood in North Indian population.

Humans are exposed to various environmental chemicals such as organochlorine pesticide residues, heavy metals, polychlorinatedbiphenyls (PCBs) etc. There is paucity of data regarding the present blood levels of organochlorine residues in North Indian population with reference to reproductive health. The present study was designed to analyze the levels of organochlorine pesticide residues in maternal and cord blood samples of normal healthy women with full term pregnancy to gain insight into the current status of pesticide burden in newborns. Hexachlorocyclohexane (HCH) contributed maximum towards the total organochlorine residues present in maternal and cord blood followed by endosulfan, pp' DDE and pp' DDT being the least. This is also the first report indicating endosulfan levels in this population. Our data indicates a transfer rate of 60-70% of these pesticides from mothers to newborns and this high rate of transfer of pesticides is of great concern as it may adversely affect the growth and development of newborn.

Plumbism--a mimicker of common childhood symptoms.

Lead poisoning is a preventable entity that can affect almost every system of the body. Its toxic effects range from subtle common childhood symptoms to even death. In a prospective study forty six children with at least one symptom compatible with plumbism were enrolled after screening patients attending medical services at AIIMS. The work-up included a detailed clinical history and examination including intelligence quotient (IQ) and behaviour. Blood lead levels were estimated in all with due precautions. Their ages ranged from 2.5 to 18 years and M:F ratio was 2:1. The common symptoms included unexplained recurrent colic (39), anorexia (21), sporadic vomiting and constipation (13), pigmented gum lines (11), growth failure (11), history of pica (9) etc. None of the children had acceptable blood lead levels (< 10 micrograms/dl). Ninety three per cent children had levels > 20 micrograms/dl and 47.8% had > 45 micrograms/dl. Statistically significant correlation with blood lead levels was seen with most symptoms. Plumbism can mimic common childhood illnesses and should be investigated in children with a clinically compatible profile. Community awareness with regard to pica reduction may be an important preventive measure. This silent epidemic needs to be aggressively tackled by a multipronged approach.

Unusual posterior hip dislocation with ipsilateral fractures of the femoral neck and head.

An unusual combination of posterior hip dislocation with ipsilateral femoral neck and head fractures is reported. The femoral head migrated too far inferiorly in the posterior part of the thigh, making it different from the previously reported solitary case report of obturator hip dislocation associated with femoral neck and head fractures.

Esophageal atresia: tragedies and triumphs over two decades in a developing country.

During a period of two decades, 1972-1991, 303 patients with esophageal atresia and/or tracheo-esophageal fistula were treated at the department of Pediatric Surgery, SMS Medical College, Jaipur, India. More than half of our patients fall into Waterston's risk category C. To evaluate the improvement in our results, the patients were divided into four phases of 5 years each. Over the period of observation, the incidence of new cases as well as the number of associated anomalies has considerably increased. With time, more patients are being diagnosed and referred early for treatment. This has resulted in more patients being treated by primary repair with or without a gastrostomy. Extrapleural approach and single layer end-to-end anastomosis has been practised in all cases. Results have shown a steady improvement primarily because of early recognition, improved perioperative care and newer antibiotics. Although postoperative pulmonary complications and anastomotic leak have shown a decreasing trend, but the presence of severe associated anomalies, pulmonary complications and sepsis still remain the major killers in our set-up. Although our results may not match those from the developed countries, we have still come a long way, improving our overall survival rate of 4.6% in 1972-76 to 45.7% in 1987-91. Through the present article, we wish to highlight the practical problems faced in the management of these patients in underprivileged developing countries.