Stray Dogs (Mongrels) Are Potent Reservoir of Drug-Resistant Pathogens: A Study in Peri-Urban Areas of Kolkata, India.

This study depicts the drug-resistance and phylogenomic characteristics of 365 Escherichia coli (EC) and 76 Klebsiella pneumoniae (KP) isolated from stray dogs (293) in and around Kolkata, India. Initial screening found 59 isolates, including 48 E. coli and 11 KP multidrug resistant, which included 33 extended-spectrum ß-lactamase, 41 AmpC ß-lactamase and 18 metallo-ß-lactamase producers carrying blaNDM-1 (11) and blaNDM-5 (7) genes. Majority of them had the resistant genes such as blaCTX-M (33), blaTEM (18), blaSHV (4), blaOXA (17), blaFOX (2), blaDHA (2), blaCITM (15), blaCMY-2 (13), blaGES (2) and blaVEB (2), qnrS (15), qnrB (3), aac-6'-Ib-cr (14), tetA (26), tetB (14), sul-1 (25), armA (2) and rmtB (6), in addition to adherence genes such as csgA (33), fimA (27), fliC (13), sdiA (33), rcsA (38), and rpoS (39). They also carried plasmid of diverse replicon types of which IncFIA and FIB were the most frequent. Phylogrouping categorized most of the MDR E. coli in phylogroup A (20), B1 (14), and B2 (6). Enterobacteriaceae repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) showed genetic diversity of multidrug resistant isolates irrespective of their origin, resistance, and virulence types, differentiating the EC in five clades (A-E) and KP in four clades (A-D). As these stray dogs, which had no history or scope of previous antimicrobial therapy, were found to have contracted potential antimicrobial resistance pathogens, the role of environment in spread of such pathogens and further possibility of human infections cannot be ruled out.

Excited-State Dynamics of a Photoacid: A Potential Probe for Recognizing Transition from Lamellar to Nonlamellar Inverted Structures of Liposome based Nanocarriers.

Liposomes of a cationic lipid dioctadecyldimethylammonium bromide (DODAB) are efficient nanocarriers of nucleic acids. Incorporation of a neutral lipid monoolein (MO) in excess (xMO >0.5) changes the lamellar organization of DODAB liposomes into non-lamellar inverted structures of DODAB/MO liposomes facilitating nucleic acid delivery to cells. Photoexcitation of 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS), a photoacid, initiates an excited state proton transfer (ESPT) reaction in its protonated form (ROH*) generating the deprotonated anionic form (RO- *). The fluorescence intensity ratio (IROH* /IRO-* ) of these two forms is governed by the ESPT dynamics, and increases with increasing MO content (xMO ) in the cationic liposomes of DODAB. Transition from lamellar organization of DODAB liposomes into non-lamellar inverted structures of DODAB/MO liposomes, due to incorporation of MO (xMO ~0.7), is manifested by a significant increase of ESPT time (τPT ) and the time constant of wobbling motion (τW ) of HPTS. Thus, the lamellar organizations of DODAB or DODAB-rich (xMO 0.2) liposomes and the non-lamellar organizations of MO-rich (xMO ~0.7) liposomes are recognized by significantly different excited state dynamics of the photoacid.

Expanding Indications of Nonvitamin K Oral Anticoagulants Beyond Nonvalvular Atrial Fibrillation and Venous Thromboembolism: A Review of Emerging Clinical Evidence.

Direct oral anticoagulants (DOAC) have emerged as a new therapy for patients who need and can tolerate oral anticoagulation. DOACs were initially approved for nonvalvular atrial fibrillation (NVAF) and treatment for deep vein thrombosis (DVT) and pulmonary embolism (PE). Ease of administration, no requirement of bridging with other anticoagulants, and less frequent dosing have made DOACs preferable choice for anticoagulation. Studies are showing promising results regarding use of DOACs beyond the common indications. Studies have been done to show the potential benefit of DOACs in valvular atrial fibrillation, heart failure, acute coronary syndrome, stroke, and peripheral arterial disease. Data have shown safety as well as comparable bleeding incidences with DOACs compared to vitamin K antagonist anticoagulants. Naturally interest is growing to see the use of DOACs apart from the NVAF, DVT, or PE. Authors have highlighted various study results to show the potential beneficial role of DOACs in the above-mentioned situations.

Synthesis of CeO2/ZrO2/ZnO nano alloy oxide and investigation of photocatalysis of naphthol orange under sunlight.

Novel metal-like cerium- and zirconium-doped ZnO photocatalysts were prepared herein with various proportions of molar ratios via a cost-effective co-precipitation method. The effects of novel metal doping on the photocatalytic activity of ZnO were studied. Various techniques were used to investigate the structural, morphological, and elemental composition, particle size, optical properties, and catalytic activity of the synthesized photocatalysts. It was found that the crystallite size and particle size of the nano alloy oxides were 15.12 ± 1 and 5 ± 1 nm, respectively, and the surface morphology of the nanoparticles indicated a satisfactory surface area. Among all synthesized nanocomposites, CexZrxZnxO5 (x = 1) [CZ1Z2-A] exhibited satisfactory photo-oxidation activity against naphthol orange (NO) under sunlight with a rate constant of 57.5 × 10-3 min-1. The effects of pH, inorganic salts, dye concentrations, and catalytic dosage on NO degradation were studied. A probable mechanistic pathway for the degradation of NO in the presence of CZ1Z2-A was proposed, and studies of sacrificial agents indicated that superoxide radical anion (O2˙-) was the main accountable active species in NO degradation. In addition, CZ1Z2-A exhibited excellent recyclability potential, and XRD studies revealed that there was no change in the crystal structure before or after degradation, which indicated its high stability. The intriguing finding was that Ce- and Zr-doped ZnO did not exhibit satisfactory catalytic performance in the photo-oxidation of NO. However, the composite formula of CexZrxZnxO5 (x = 1) with a 1 : 1 : 1 ratio of metal ions offered excellent catalytic activity.

Meta-analysis Comparing the Efficacy of Dobutamine Versus Milrinone in Acute Decompensated Heart Failure and Cardiogenic Shock.

This study aims to evaluate the difference between dobutamine and milrinone in patients presenting with acute decompensated heart failure (AHF). Inotropes are indicated for treating AHF, especially in patients with concomitant hypoperfusion indicative of cardiogenic shock. However, previous studies have not identified the optimal inotrope. We sought to compare outcomes associated with milrinone versus dobutamine in patients with AHF. A systematic literature search was performed to identify relevant trials from inception to August 2021. Our primary outcome of interest was mortality. Analysis was sub-categorized according to subpopulation, including AHF, AHF with cardiogenic shock (AHF-shock), AHF with a bridge to transplantation, and AHF with destination therapy. Summary effects were calculated using a fixed-effects model as risk ratio or mean difference with 95% confidence intervals for all the clinical endpoints. Ten studies, including one randomized controlled trial with 21,106 patients, were included in the analysis (4918 patients were in the Milrinone group, while 15188 were in the Dobutamine group). Milrinone was associated with a lower risk of mortality in patients with AHF (relative risk 0.87; confidence interval :0.79-0.97; P < 0.05, heterogeneity I²â€¯= 0%) with event rates of 9.4% vs 9.8% (number needed to treat of 250). Milrinone was also associated with improved mortality with relative risk 0.76 (0.79-0.95; P < 0.05) in patients with AHF with destination therapy. There was a non-significant trend towards improved mortality in AHF-shock patients. However, AHF with a bridge to transplantation patients had a non-significant trend towards improved mortality with dobutamine. There was no difference between the 2 strategies for the outcomes of acute kidney injury, initiation of renal replacement therapy, mechanical ventilation, arrhythmias, symptomatic hypotension, and length of hospital stay in the overall population. Intensive care unit length of hospital stay was lower in AHF-shock patients in the milrinone group, whereas dobutamine was associated with a lower length of intensive care unit stay in AHF patients. The cumulative data comparing milrinone with dobutamine indicate an overall marginal benefit of milrinone compared to dobutamine in the totality of patients with AFH with or without cardiogenic shock, and whether or not they are bridged to transplantation or destination assist device. More appropriately powered prospective studies are needed to identify a conclusive benefit of one inotrope over another.

Present Knowledge on Direct Oral Anticoagulant and Novel Oral Anti Coagulants and Their Specific Antidotes: A Comprehensive Review Article.

Thromboembolic diseases are one of the leading causes of morbidity and mortality worldwide. For a long time, heparin and Vitamin K antagonist (VKA) drugs were used for treatment and prophylaxis of the thromboembolic diseases. The development of newer direct and novel oral anticoagulant medications (DOACs/NOACs) has changed clinical practice significantly. Lesser monitoring, ease with dosing, less drug interactions have made these drugs useful to the providers and the patients. But these drugs have bleeding as a side effect. There is ongoing research on the specific antidotes of these anticoagulants in case of life-threatening bleeding. Though the use of the DOACs and NOACs have increased, there is still not enough clinical evidence about the specific antidotes of these medications. Unlike heparin or VKA, reversal of life-threatening bleeding in the setting of DOAC use is still a clinical challenge. We need more data on the dose, pharmacokinetics, and clinical efficacy of those antidotes. Authors have reviewed articles on DOACs and their antidotes in Pubmed and also in the clinical trial website. Specific antidotes including Idarucizumab for Dabigatran, Andexanet alfa for factor Xa inhibitors are being used to reverse the actions of the anticoagulants. Ciraparantag is a universal antidote for the DOACs, which is still under investigation. FXaI16L is currently being investigated as a potential universal antidote for multiple anticoagulants, including dabigatran and rivaroxaban. Though mostly safe, the use of DOACs can still carry a risk of severe bleeding in patients. More data on the use of the antidotes is required to reverse the side effect of DOACs if clinically indicated.

Antimicrobial Resistance Pattern, Clustering Mechanisms and Correlation Matrix of Drug-Resistant Escherichia coli in Black Bengal Goats in West Bengal, India.

A cross-sectional study covering four agro-climatic zones of West Bengal, India, was carried out to understand the risk-factors, antimicrobial resistance mechanism and clustering of the resistance characteristics of Escherichia coli isolated from healthy (170) and diarrhoeic (74) goats reared under intensive (52) and semi-intensive (192) farming practices. Of the 488 E. coli isolates, the majority, including the extended spectrum (n: 64, 13.11%) and AmpC ß-lactamase (ACBL) (n: 86, 17.62%) producers, were resistant to tetracycline (25.2%), followed by enrofloxacin (24.5%), cefotaxime (21.5%) and amikacin (20.5%). Statistical modelling revealed that the isolates from diarrhoeic animals (p < 0.001) are likely to be more ACBL-positive than those from the healthy counterparts. Similarly, cefotaxime (p < 0.05) and enrofloxacin-resistance (p < 0.01) were significantly higher in diarrhoeic goats and in goats reared intensively. The isolates (n = 35) resistant to multiple drugs revealed the presence of ß-lactamase [blaCTXM-1-(21), blaSHV-(7), blaTEM-(3), blaCMY-6-(1), blaCITM-(3)]; quinolone [qnrB-(10), qnrS-(7), aac(6')-Ib-cr-(3)]; tetracycline [tetA-(19), tetB-(4)] and sulphonamide resistance determinants [sul1-(4)]; multiple plasmids, especially those belonging to the IncF and IncI1 replicon types; and active acrAB efflux pumps. Further, two isolates harbored the carbapenem resistance (blaNDM-5) gene and eight were strong biofilm producers. This first ever study conducted to unravel the status of AMR in goat farming reveals that not only the intensive farming practices but also certain clinical ailments such as diarrhoea can increase the shedding of the drug-resistant isolate. The emergence of multi-drug resistant (MDR) E. coli in goats, particularly those that are carbapenem resistant, is a cause for concern that indicates the spread of such pathogens even in the livestock sub-sector generally considered as naive.

Predictors and mortality risk of venous thromboembolism in patients with COVID-19: systematic review and meta-analysis of observational studies.

INTRODUCTION: Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in COVID-19 disease is associated with widespread inflammation and a prothrombotic state, resulting in frequent venous thromboembolic (VTE) events. It is currently unknown whether anticoagulation is protective for VTE events. Therefore, we conducted a systematic review to identify predictors of VTE in COVID-19. METHODS: We searched PubMed, EMBASE, Google Scholar, and Ovid databases for relevant observational studies of VTE in COVID-19 disease. The effect size for predictors of VTE was calculated using a random-effects model and presented as forest plots. Heterogeneity among studies was expressed as Q statistics and I2. Bias was assessed using the Newcastle Ottawa Scale for all identified observational studies. Publication bias was assessed with funnel plot analysis. RESULTS: We identified 28 studies involving 6053 patients with suspected or confirmed COVID-19. The overall pooled prevalence of VTE events was 20.7%. Male sex was associated with a higher risk of VTE events, whereas prior history of VTE, smoking, and cancer were not. VTE events were significantly higher in severely ill patients, mechanically ventilated patients, those requiring intensive care admission, and those with a low PaO2/FiO2 ratio (P/F ratio). Chronic comorbidities, including cardiovascular disease, heart failure, renal disease, and pulmonary disease, did not increase the risk of VTE events. Patients with VTE had higher leukocyte counts and higher levels of D-dimer, C-reactive protein, and procalcitonin. The occurrence of VTE was associated with increased length of stay but did not impact mortality. Therapeutic and prophylactic doses of anticoagulation were not protective against VTE. CONCLUSION: VTE in COVID-19 is associated with male gender and severe disease but not with traditional risk factors for VTE. The occurrence of VTE does not appear to be mitigated by either prophylactic or therapeutic anticoagulation. The occurrence of VTE in this population is associated with an increased length of stay but does not appear to impact mortality.

Catalytic Use toward the Redox Reaction of Toxic Industrial Wastes in Innocuous Aqueous Medium and Antibacterial Activity of Novel Cu x Ag x Zn1-2x O Nanocomposites.

In this work, we report the redox properties in organic catalytic transformation and antibacterial activity of novel Cu x Ag x Zn1-2x O nanocomposites. Cu- and Ag-doped ZnO [Cu x Ag x Zn1-2x O (x = 0.1)] (CAZ), Cu-doped ZnO [Cu x Zn1-x O (x = 0.1)] (CZ), and Ag-doped ZnO [Ag x Zn1-x O (x = 0.1)] (AZ) were prepared via a chemical co-precipitation method. The synthesized nanocomposites were characterized using different spectroscopic techniques. The catalytic activity of CAZ, CZ, and AZ was examined for the reduction of 4-nitrophenol (4-NP) and 4-nitroaniline (4-NA) in the presence of NaBH4 in an aqueous medium. The photocatalytic oxidation efficiency of these catalysts was also observed against naphthol orange (NO) under ultraviolet light. It was found that the catalytic reduction and oxidation efficiency of CAZ is higher than that of CZ and AZ in 4-NP/4-NA and NO in a water solvent, respectively. The antibacterial property of CAZ was also studied against Gram-positive and Gram-negative bacteria by agar well diffusion and the minimum inhibitory concentration methods. It was found that CAZ shows better antimicrobial activity compared to its parental Cu(NO3)2·3H2O, AgNO3, and ZnO. Therefore, the incorporation of Cu and Ag into ZnO increases its catalytic and antimicrobial activity remarkably. Fourier-transform infrared and X-ray diffraction (XRD) studies of CAZ indicate the incorporation of Cu and Ag into the lattice of ZnO. The phase structure of CAZ was wurtzite hexagonal, and the average crystallite size was 93 ± 1 nm measured from XRD. The average grain size and particle size of CAZ were found to be 200 and 100 ± 5 nm originating from SEM and transmission electron microscopy studies, respectively. The optical energy band gap of CAZ is 3.15 eV, which supports the excellent photocatalyst under UV light. CAZ also exhibits good agreement for photoluminescence properties with a high intensity peak at 571 nm, indicating surface oxygen vacancies and defects which might be responsible for higher photocatalytic activity compared to others. The nanocomposite shows excellent reusability without any significant loss of activity.

Initial treatment of patients with thyroid cancer: Outcomes and factors associated with care at academic versus nonacademic cancer centers.

BACKGROUND: Factors associated with receiving initial care for thyroid cancer (TC) at academic centers (ACs) versus nonacademic centers (NACs) and their impact on patient outcomes have not been reported. METHODS: The National Cancer Database with TC cases from 2004 to 2013 was evaluated for association of type of center for initial care with socioeconomic factors and disease and treatment characteristics, as well as overall survival (OS; all-cause mortality). RESULTS: The patients with TC (n = 200,824) included were predominantly women (74%), non-Hispanic Whites (85%), and from metro areas (84%). Sixty percent received initial care at a NAC. There were no significant differences between treatment groups by age or gender. Among those treated at an AC, a higher proportion belonged to racial/ethnic minorities (16.5%) versus at a NAC (11.6%). Hormone therapy was used more in an AC versus a NAC (60% vs 47%). Patients with all TC pathologies combined had a lower likelihood of death when they received initial care at an AC (hazard ratio [HR], 0.948; P = .0006). Among individual pathologic subtypes, a lower likelihood of death was noted when initial care was received at an AC for follicular (HR, 0.828, P = .0010) and Hurthle cell cancers (HR, 792; P = .0008), as well as stage II papillary thyroid cancer (HR, 0.828; P = .0026), but not for other histopathologic subtypes. CONCLUSIONS: Initial care at an AC was associated with lower likelihood of death for patients with TC, especially for those with follicular or Hurthle cell subtypes. Optimal resource use with consideration of patients' socioeconomic and demographic factors is imperative to ensure the most appropriate management of patients with TC in various treatment settings.

Meta-Analysis Comparing the Safety and Efficacy of Single vs Dual Antiplatelet Therapy in Post Transcatheter Aortic Valve Implantation Patients.

The relative safety and efficacy of aspirin versus dual antiplatelet therapy (DAPT; aspirin+clopidogrel) in patients who underwent transcatheter aortic valve implantation (TAVI) and did not have a long-term indication for oral anticoagulation remains controversial. Digital databases were searched to identify relevant articles. The major safety end point was bleeding, while the efficacy end points included after-TAVI ischemic and thrombotic events. Data were analyzed using a random effect model to calculate the pooled unadjusted odds ratio (OR) for dichotomous outcomes. Eleven studies comprising 4805 patients (aspirin 2258, DAPT 2547) were included in the quantitative analysis. Patients receiving aspirin-alone had significantly lower odds of all cause bleeding (OR 0.41, 95% CI 0.29 to .057, p <0.00001), major vascular bleeding (OR 0.51, 95% CI 0.34 to 0.77, p = 0.001), Valve Academic Research Consortium 2 (VARC-2) major bleeding (OR 0.50, 95% CI 0.30 to 0.83 p = 0.008), VARC-2 minor bleeding (OR 0.55, 95% CI 0.31 to 0.97, p = 0.04), transfusion requirement (OR 0.39, 95%CI 0.15 to 0.0.98, p = 0.05) and major vascular complications (OR0.41, 95% CI 0.26 to 0.66, p = 0.0002) compared with after-TAVI patients receiving both aspirin and clopidogrel. These was no significant difference in the odds of VARC-2 life threatening bleeding (OR 0.52, 95% CI 0.25 to 1.07, p = 0.08), prosthetic valve thrombosis (OR 1.17, 95% CI 0.22 to 6.30, p = 0.85), cardiac tamponade (OR 0.77, 95% CI 0.20 to 2.98, p = 0.70), conversion to open procedure (OR 1.99, 95 % CI 0.42 to 9.44, p = 0.39), MI (OR 0.79 95% CI 0.38 to 1.64, p = 0.52), transient ischemic attack (TIA) (OR 0.89, 95% CI 0.12 to 6.44, p = 0.91), major stroke (OR 0.68 95 % CI 0.43 to 1.08, p = 0.10), disabling stroke (0R 1.01, 95% CI 0.41 to 2.48, p = 0.99), cardiovascular mortality (OR 0.81 95% CI 0.38 to 1.74, p = 0.59) and all-cause mortality (OR 0.86, 95% CI 0.63 to 1.16, p = 0.31) between the 2 groups. In conclusion, after-TAVI patients who received aspirin alone had lower bleeding events with no significant differences in mortality and stroke rate compared with those who received DAPT.

Safety and efficacy of coronary intravascular lithotripsy for calcified coronary arteries- a systematic review and meta-analysis.

Objectives: Intravascular lithotripsy (IVL) clinical efficacy and safety in the treatment of calcified coronary artery disease (CAC) is not well known. We sought to assess IVL safety and efficacy in CAC. Methods: A comprehensive online databases search were performed to identify intravascular lithotripsy studies in patients with coronary artery disease. The primary outcome was IVL related change in the mean pre and post-procedural diameter of the coronary artery. Results: A total of 4 studies with 282 patients were included. The mean pre-IVL coronary diameter for all patients was 1.01 mm, while the mean post-IVL coronary diameter was 2.70 mm. The mean pre-post IVL diameter difference of coronary arteries on the pooled analysis was significantly lower by 4.08 mm (95% CI -4.94 to -3.30, p ≤ 0.00001). The Overall increase in the post-IVL lumen diameter was significantly higher than the pre-IVL diameter with a mean difference of -4.16 (95% CI -5.08 to -3.24, p = 0.000001). However, compared to pre-IVL, there was a significant reduction in the overall mean difference of luminal calcium angle after IVL of the stented coronary arteries (0.09, 95% CI 0.002-0.16, p = 0.01). Conclusion: Intravascular lithotripsy can offer a significant improvement in the vessel lumen to facilitate coronary stent delivery and deployments in severely calcified coronary arteries.

Evaluation of ameliorative effect of two selected plant drugs on experimentally induced arsenic toxicity in sheep.

Chronic arsenic poisoning is one of the serious health hazards in West Bengal, India, and Bangladesh. It occurs due to contaminated subsoil water. The aim of this study is conducted to find out the ameliorative effect of turmeric and P. foetida powder on experimentally induced arsenic toxicity in sheep. Twelve sheep were divided into four groups; groups I, II and III were orally administered with sodium arsenite at 6.6 mg/kg body weight for 133 days; groups I and II animals were treated by turmeric and P. foetida powders respectively at 500 mg/kg dose for the last 49 days; the fourth group was control. Arsenic content was estimated in faeces, urine and wool in every 15 days. Biochemical, haematological, antioxidant parameters and DNA fragmentation were also assessed. Turmeric and P. foetida powder treatment significantly (P < 0.05) increased arsenic elimination through faeces, urine and wool. Haemoglobin content and TEC were decreased in groups I, II and III; however, these were improved significantly (P < 0.05) by turmeric and P. foetida powder treatment. Increased activity of AST, ALT, blood urea nitrogen and plasma creatinine were significantly (P < 0.05) decreased in groups I and II. The reduced SOD and catalase activity were significantly (P < 0.05) restored at the end of the experiment in turmeric and P. foetida-treated groups. The test drugs are found significantly effective not only to eliminate arsenic from the body but also give protection from possible damage caused by arsenic exposure in sheep.

Trends in the risk of second primary malignancies among survivors of chronic lymphocytic leukemia.

With improving survivorship in chronic lymphocytic leukemia (CLL), the risk of second primary malignancies (SPMs) has not been systematically addressed. Differences in risk for SPMs among CLL survivors from the Surveillance, Epidemiology, and End Results (SEER) database (1973-2015) were compared to risk of individual malignancies expected in the general population. In ~270,000 person-year follow-up, 6487 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI:1.17-1.23). The higher risk was for both solid (SIR 1.15; 95% CI:1.12-1.18) and hematological malignancies (SIR 1.61; 95% CI:1.5-1.73). The highest risk for SPMs was noted between 2 and 5 months after CLL diagnosis (SIR 1.57; 95% CI:1.41-1.74) and for CLL patients between 50- and 79-years-old. There was a significant increase in SPMs in years 2003-2015 (SIR 1.36; 95% CI:1.3-1.42) as compared to 1973-1982 (SIR 1.19; 95% CI:1.12-1.26). The risk of SPMs was higher in CLL patients who had received prior chemotherapy (SIR 1.38 95% CI:1.31-1.44) as compared to those untreated/treatment status unknown (SIR 1.16, 95% CI:1.13-1.19, p < 0.001). In a multivariate analysis, the hazard of developing SPMs was higher among men, post-chemotherapy, recent years of diagnosis, advanced age, and non-Whites. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL.

Picosecond Solvation Dynamics in Nanoconfinement: Role of Water and Host-Guest Complexation.

The dynamics of solvation of an excited chromophore, 5-(4″-dimethylaminophenyl)-2-(4'-sulfophenyl)oxazole, sodium salt (DMO), has been explored in confined nanoscopic environments of ß-cyclodextrin (ßCD) and heptakis(2,6-di- O-methyl)-ß-cyclodextrin (DIMEB). Solvation occurs on a distinctly slower time scale (τS3 ∼ 47 ps, τS4 ∼ 517 ps) in the host cavity of DIMEB than in that of ßCD (τS3 ∼ 20 ps, τS4 ∼ 174 ps). The calculated equilibrium solvation response of DMO was characterized by four relaxation components (τS1 ∼ 0.46-0.48 ps, τS2 ∼ 3.2-3.4 ps, τS3 ∼ 32.3-37.7 ps, and τS4 ∼ 232-485 ps), of which the longer ones (τS3, τS4) are well-consistent with experiments, whereas the ultrafast components (τS1, τS2) are unresolved. The observed time constant (τS3) within the ∼20-47 ps range arises from slow water molecules in the primary hydration layers of the host CDs and is slower for DIMEB than for ßCD presumably due to longer-lived and stronger hydrogen bonds that water forms with the former host relative to the latter. Decomposition of the calculated solvation response of DMO has revealed that conformational fluctuations of the macrocyclic hosts give rise to the observed long-time relaxation component (τS4), which is much slower for the inclusion complexes with DIMEB than for those with ßCD because of slower conformational dynamics of the former host than that of the latter.

Environment sensitive fluorescent analogue of biologically active oxazoles differentially recognizes human serum albumin and bovine serum albumin: Photophysical and molecular modeling studies.

An environment sensitive fluorophore, 4-(5-(4-(dimethylamino)phenyl)oxazol-2-yl)benzoic acid (DMOBA), that closely mimics biologically active 2,5-disubstituited oxazoles has been designed to probe two homologous serum proteins, human serum albumin (HSA) and bovine serum albumin (BSA) by means of photophysical and molecular modeling studies. This fluorescent analogue exhibits solvent polarity sensitive fluorescence due to an intramolecular charge transfer in the excited state. In comparison to water, the steady state emission spectra of DMOBA in BSA is characterized by a greater blue shift (~10nm) and smaller Stokes' shift (~5980cm-1) in BSA than HSA (Stokes'shift~6600cm-1), indicating less polar and more hydrophobic environment of the dye in the former than the latter. The dye-protein binding interactions are remarkably stronger for BSA than HSA which is evident from higher value of the association constant for the DMOBA-BSA complex (Ka~5.2×106M-1) than the DMOBA-HSA complex (Ka~1.0×106M-1). FÓ§rster resonance energy transfer studies revealed remarkably less efficient energy transfer (8%) between the donor tryptophans in BSA and the acceptor DMOBA dye than that (30%) between the single tryptophan moiety in HSA and the dye, which is consistent with a much larger distance between the donor (tryptophan)-acceptor (dye) pair in BSA (34.5Å) than HSA (25.4Å). Site specific competitive binding assays have confirmed on the location of the dye in Sudlow's site II of BSA and in Sudlow's site I of HSA, respectively. Molecular modeling studies have shown that the fluorescent analogue is tightly packed in the binding site of BSA due to strong steric complementarity, where, binding of DMOBA to BSA is primarily dictated by the van der Waals and hydrogen bonding interactions. In contrast, in HSA the steric complementarity is less significant and binding is primarily guided by polar interactions and van der Waals interactions appear to be less significant in the formation of the HSA-DMOBA complex. Electrostatic interactions contribute significantly in the binding of DMOBA to HSA (-2.09kcal/mol) compared to BSA (-0.47kcal/mol). Electrostatic surface potential calculation reveals that the DMOBA binding site within HSA is highly charged compared to BSA.

Ameliorative effect of two Ayurvedic herbs on experimentally induced arsenic toxicity in calves.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic arsenic poisoning due to contaminated subsoil water is a threat to society in West Bengal, India and in Bangladesh. The human being may also be affected by the exposed cattle from the affected area by consuming milk, egg, meat and others. In Ayurveda, several herbs like Haridra (turmeric), Shunthi (dried ginger root) and others are used for the management of arsenic poisoning. AIM OF THE STUDY: The study was conducted to find out the ameliorative effect of turmeric and ginger powder against experimentally induced arsenic toxicity in calves. MATERIALS AND METHODS: Twenty four calves were divided into four groups (group I, II, III and IV) having six animals in each group. Animals of group I, II and III were orally administered with sodium arsenite at 1mg/kg body weight for 90 days and in addition group II and group III animals were treated orally with turmeric and ginger powder respectively at 10mg/kg body weight from 46th day onwards. Group IV animals were given food and water without drug and served as control. Arsenic content was estimated in faeces, hair, urine and plasma in every 15 days. Bio-chemical, haematological and anti-oxidant parameters were also assessed. RESULTS: Turmeric and ginger powder significantly (P<0.05) reduced the plasma and hair arsenic levels through increased excretion via faeces and urine. Haemoglobin level, TEC and TLC were decreased in groups I, II and III, however these were improved significantly (P<0.05) from 75th day onwards in turmeric and ginger treated groups. Increased activity of AST and ALT were significantly decreased (P<0.05) from 75th day onwards in group II and III. Blood urea nitrogen and plasma creatinine were also significantly decreased (P<0.05) in group II and III than group I from 60th day onwards. The SOD and catalase activity were significantly (P<0.05) reduced in groups I, II and III, but these were restored at the end of the experiment in turmeric and ginger treated groups. CONCLUSION: The test drugs are found significantly effective not only to eliminate arsenic from the body but also give protection from possible damage caused by arsenic exposure, it may be concluded from the present study that turmeric and ginger can be helpful in the therapy of chronic arsenic toxicity in calves.

Bovine herpesvirus-1 (BHV-1) - a re-emerging concern in livestock: a revisit to its biology, epidemiology, diagnosis, and prophylaxis.

Bovine herpesvirus-1 (BHV-1) is known to cause several diseases worldwide. It is a double-stranded DNA virus consisting of 33 structural proteins out of which 13 are associated with the envelope. Based on genomic analysis and viral peptide patterns, BHV-1 virus can be divided into several subtypes like BHV-1.1, BHV-1.2, and BHV-1.3. However, all subtypes are antigenically similar. The symptoms of the related diseases are mainly non-life-threatening but have a rather wide host range that limits animal trade. The different modes of transmission as unique feature of this virus and the tendency to cause infection in the early age with latency development in trigeminal and sacral ganglion cause huge economic losses around the world. The virus also affects endangered bovine species like mithun (Bos frontalis) and yak (Poephagus grunniens). The disease can be diagnosed by using conventional procedures (like cell culture, immune-histopathology, and enzyme-linked immunosorbent assay (ELISA)) as well as highly sensitive modern techniques (like nested PCR and southern hybridization) with the virus neutralization test regarded as gold standard. With the currently available diagnostic tests it is not possible to identify animals which have a latent BHV-1 infection. Different types of modern and conventional vaccines are available for immunoprophylaxis. Inactivated vaccines are not as efficacious as modified live virus (MLV) vaccines. Marker vaccines allow the distinction between vaccinated and naturally infected animals. In this review the present status of BHV-1 around the world will be addressed besides the current knowledge with regard to its biology, epidemiology, diagnosis, and prophylaxis.

Quantitative imaging of arsenic and its species in goat following long term oral exposure.

Severity of arsenic toxicity was reported to vary depending on its species. The present study reflects the status of different species of arsenic in goat following long-term exposure of arsenic leading to hepatic damage. The experiment was conducted with six black Bengal goats, which were administered with sodium arsenite orally at a dose rate of 2 mgkg(-1) daily for 84 days. Faeces, urine, hair and blood samples were collected from those animals at 14 days interval. Excretion of total arsenic was reduced from 56 days onwards through both faeces and urine indicating higher accumulation of arsenic in body. The speciation study revealed that urinary arsenic was mainly of organic type, whereas hair accumulated almost equal proportion of arsenite, arsenate and organo arsenicals. Goats excreted high proportion of organo arsenicals through faeces possibly due to hepatobiliary secretion of organo arsenic into the gut. Significantly elevated serum alanine aminotransferase and aspartate aminotransferase activities (p<0.05) along with histopathological changes in liver indicated hepatotoxicity. The arsenite fraction increased and organic proportion decreased in urine as the time progressed, which indicates that arsenite gets methylated in liver of goat. The study thus alluded that the toxicity of arsenic would aggravate if the animals were exposed for long time as the hepatotoxicity progressed resulting in decreased methylation and formation of organo arsenicals and decreased excretions through urine.