Unconventional Crystal Structure of the High-Pressure Superconductor La_{3}Ni_{2}O_{7}.

The discovery of high-temperature superconductivity in La_{3}Ni_{2}O_{7} at pressures above 14 GPa has spurred extensive research efforts. Yet, fundamental aspects of the superconducting phase, including the possibility of a filamentary character, are currently subjects of controversial debates. Conversely, a crystal structure with NiO_{6} octahedral bilayers stacked along the c-axis direction was consistently posited in initial studies on La_{3}Ni_{2}O_{7}. Here, we reassess this structure in optical floating zone-grown La_{3}Ni_{2}O_{7} single crystals that show signs of filamentary superconductivity. Employing scanning transmission electron microscopy and single-crystal x-ray diffraction under high pressures, we observe multiple crystallographic phases in these crystals, with the majority phase exhibiting alternating monolayers and trilayers of NiO_{6} octahedra, signifying a profound deviation from the previously suggested bilayer structure. Using density functional theory, we disentangle the individual contributions of the monolayer and trilayer structural units to the electronic band structure of La_{3}Ni_{2}O_{7}, providing a firm basis for advanced theoretical modeling and future evaluations of the potential of the monolayer-trilayer structure for hosting superconductivity.

Hemato-biochemical and ultrasonographic evaluation of hepatic lipidosis in dairy buffaloes.

Around 60% dairy animals developed moderate to severe hepatic lipidosis at the time of parturition or during early lactation stage. Most of clinician suspect the hepatic lipidosis during above time window only. However, negative energy balance or feeding of high concentrate diet can lead to hepatic lipidosis at any phase of life. The aim of the present study was to evaluate the potential for diagnosis of hepatic lipidosis by means of hemato-biochemical parameters and ultrasonography of the liver at any stage of life. Here, ultrasonographic back fat thickness measurement was correlated with ultrasonographic features of hepatic lipidosis. A total 60 buffaloes were included under the study and sampled for hematological and biochemical parameters. Hematological parameters did not exhibit any significant difference between healthy and hepatic lipidosis-affected buffaloes. Biochemical parameters like beta hydroxy butyric acid, non esterified fatty acid, aspartate amino transferase, gamma glutamyl transferase and alkaline phosphatase revealed a significant increase, while triglyceride, cholesterol, and glucose declined significantly in hepatic lipidosis-affected buffaloes. Total protein, albumin, and total bilirubin levels did not exhibit any significant difference. Based on ultrasonographic findings, the hepatic lipidosis-affected buffaloes were further sub divided into mild, moderate, and severe groups. Portal vein diameter and depth of portal vein were also estimated in current study. Ultrasonographic examination could diagnose 53.33% hepatic lipidosis cases in buffaloes. Among it, 37.50% buffalo had mild hepatic lipidosis, 33.33% had moderate hepatic lipidosis, and 29.16% had severe hepatic lipidosis. Depth of portal vein significantly increased in hepatic lipidosis cases. However, portal vein diameter exhibited a non-significant difference in mild, moderate, and severe groups of hepatic lipidosis. Back fat thickness also revealed a non-significant difference in mild, moderate, and severe hepatic lipidosis. Above study indicate that B mode ultrasonography of the liver can be employed to differentiate various grades of hepatic lipidosis in buffaloes. Biochemical parameters like NEFA, BHBA, AST, GGT, ALP, TG, cholesterol, and glucose can be helpful to screen the hepatic lipidosis at farm level.

Anti-piroplasmic activity of novobiocin as heat shock protein 90 inhibitor against in vitro cultured Theileria equi and Babesia caballi parasites.

Theileria equi and Babesia caballi are the causative agents of equine piroplasmosis (EP). Currently, imidocarb dipropionate (ID) is the only available drug for treating the clinical form of EP. Serious side effects and incomplete clearance of infection is a major drawback of ID. Heat-shock proteins (Hsp) play a vital role in the life cycle of these haemoprotozoans by preventing alteration in protein conformation. These Hsp are activated during transmission of EP sporozoites from the tick vector (poikilotherm) to the natural host (homeotherm) and facilitate parasite survival. In the present study, we targeted the heat shock protein 90 (Hsp-90) pathway of T. equi and B. caballi by using its inhibitor drug - novobiocin. Dose-dependent efficacy of novobiocin on the growth of T. equi and B. caballi was observed in in vitro culture. Additionally, we examined dose-dependent cell cytotoxicity on host peripheral mononuclear cells (PBMCs) and haemolytic activity on equine red blood cells (RBC). In vivo organ toxicity of novobiocin was also assessed in a mouse model. The IC50 (50 % inhibitory concentration) value of novobiocin against T. equi and B. caballi was 165 µM and 84.85 µM, respectively. Novobiocin significantly arrested the in vitro growth of T. equi and B. caballi parasites at 100 µM and 200 µM drug concentration, respectively. In vitro treated parasites had distorted nuclear material and showed no further viability. Based on the equine PBMCs and RBC, the drug was found to be safe even at 1000 µM concentration and the CC50 (50 % cytotoxicity concentration) values were 11.63 mM and 261.97 mM. Very high specific selective index (SSI) values (70.47 and 1587) were observed for equine PBMCs and RBC, respectively. Organ-specific biochemical markers and histopathological examination indicated no adverse effect of the drug at a dose rate of 50 mg kg body weight in the mouse model. The results demonstrate the growth inhibitory effect of novobiocin against T. equi and B. caballi parasites and its safety for host cell lines with very high SSI. Hence, it can be inferred that the Theileria/Babesia Hsp-90 family are potential drug targets worthy of further investigation.

Lumefantrine and o-choline - Parasite metabolism specific drug molecules inhibited in vitro growth of Theileria equi and Babesia caballi in MASP culture system.

Theileria equi and Babesia caballi are tick-borne apicomplexan haemoprotozoan parasites of equines and are responsible for considerable economic losses to stakeholders. Chemotherapeutic drugs that are available not only require multiple dosages but also prompt multiple organ toxicity in treated host though incapable of clearing parasitaemia completely. In this study, we have screened the in vitro inhibitory efficacy of four different drug molecules (o-choline, DABCO®, lumefantrine and eugenol) against T. equi and B. caballi, targeting different parasite metabolism pathways. Imidocarb dipropionate and diminazene aceturate were used as reference control drugs. The 50% in vitro growth inhibitory concentration (IC50) of lumefantrine, o-choline, DABCO® and eugenol for T. equi were: 30.90 µM; 84.38 µM; 443 µM; 120 µM and for B. caballi growth inhibition were: 5.58 µM; 135.29 µM; 150 µM; 197.05 µM, respectively. Imidocarb dipropionate inhibited the in vitro growth of T. equi at IC50 of 257.5 nM, while diminazene aceturate inhibited the in vitro growth of B. caballi at IC50 of 22 nM. DABCO® and eugenol were not so effective in inhibiting the in vitro growth of T. equi and B. caballi, while lumefantrine and o-choline significantly (p ≤ 0.05) inhibited the in vitro growth of these piroplasms targeting haem digestion and parasite membrane phospholipid synthesis.

Ending tuberculosis by 2030: can we do it?

The Sustainable Development Goals aim to end tuberculosis (TB) related deaths, transmission and catastrophic costs by 2030. Multisectorial action to accelerate socio-economic development, a new vaccine and novel diagnostics and medicines for treatment are key advances needed to end TB transmission. Achieving 90-90-90 targets for TB (i.e., 90% of vulnerable populations screened, 90% diagnosed and started on treatment, and at least 90% cured) will help accelerate progress towards reductions in mortality; however, passive case detection strategies, multidrug-resistant TB, human immunodeficiency virus coinfection and outdated pathways to care need to be overcome. Ending the catastrophic costs associated with TB will require expansion of health insurance coverage, comprehensive coverage of TB services, and limited indirect costs by vulnerable and poor populations.

In vitro growth inhibitory efficacy of some target specific novel drug molecules against Theileria equi.

The in vitro growth inhibitory efficacies of five drug molecules against Theileria equi were evaluated in in vitro cultured parasites. A continuous microaerophilic stationary-phase culture (MASP) system was established for propagation of T. equi parasites. This in vitro culture system was used to assess the growth inhibitory effect of harmaline hydrochloride dihydrate (HHD), hexadecyltrimethylammonium bromide (HDTAB), hesparidin methyl chalcone (HMC), andrographolide and imidocarb dipropionate against T. equi. The 50% inhibitory concentration value of HHD, HDTAB, HMC, and imidocarb dipropionate for T. equi growth were 17.42 µM, 14.00 µM, 246.34 µM and 0.279 µM (equivalent to 0.139 µg/ml), respectively (P<0.05). The andrographolide was not effective in inhibiting in vitro growth of T. equi in the present study. Furthermore, the in vitro cytotoxicity of these five drugs was evaluated on horse PBMC. At 2000 µM concentration of HHD, HDTAB, HMC, andrographolide and imidocarb dipropionate were 8.34, 46.44, 58.53, 31.06, 15.14% cytotoxic on PBMC, respectively. Out of our four tested drug molecules, HHD was having low IC50 value along with least cytotoxicity, as compared to reference drug imidocarb dipropionate. The difference in IC50 value of HDTAB and HHD was significant, but HDTAB was moderately more cytotoxic on PBMC cell lines. HHD and HDTAB are selective inhibitor for heat shock protein 90 (Hsp90) and choline kinase pathway. It can be concluded that HHD and HDTAB are potential drug molecules against T. equi parasite by acting on Hsp90 and choline kinase pathway.

Cost-effectiveness of the Three I's for HIV/TB and ART to prevent TB among people living with HIV.

OBJECTIVE: To evaluate the cost-effectiveness of the Three I's for HIV/TB (human immunodeficiency virus/tuberculosis): antiretroviral therapy (ART), intensified TB case finding (ICF), isoniazid preventive treatment (IPT), and TB infection control (IC). METHODS: Using a 3-year decision-analytic model, we estimated the cost-effectiveness of a base scenario (55% ART coverage at CD4 count â©¿350 cells/mm(3)) and 19 strategies that included one or more of the following: 1) 90% ART coverage, 2) IC and 3) ICF using four-symptom screening and 6- or 36-month IPT. The TB diagnostic algorithm included 1) sputum smear microscopy with chest X-ray, and 2) Xpert® MTB/RIF. RESULTS: In resource-constrained settings with a high burden of HIV and TB, the most cost-effective strategies under both diagnostic algorithms included 1) 55% ART coverage and IC, 2) 55% ART coverage, IC and 36-month IPT, and 3) expanded ART at 90% coverage with IC and 36-month IPT. The latter averted more TB cases than other scenarios with increased ART coverage, IC, 6-month IPT and/or IPT for tuberculin skin test positive individuals. The cost-effectiveness results did not change significantly under the sensitivity analyses. CONCLUSION: Expanded ART to 90% coverage, IC and a 36-month IPT strategy averted most TB cases and is among the cost-effective strategies.

Community-based multi-disease prevention campaigns for controlling human immunodeficiency virus-associated tuberculosis.

Human immunodeficiency virus (HIV) infection increases the risk of tuberculosis (TB) 21-34 fold, and has fuelled the resurgence of TB in sub-Saharan Africa. The World Health Organization (WHO) recommends the Three I's for HIV/TB (infection control, intensified case finding [ICF] and isoniazid preventive therapy) and earlier initiation of antiretroviral therapy for preventing TB in persons with HIV. Current service delivery frameworks do not identify people early enough to maximally harness the preventive benefits of these interventions. Community-based campaigns were essential components of global efforts to control major public health threats such as polio, measles, guinea worm disease and smallpox. They were also successful in helping to control TB in resource-rich settings. There have been recent community-based efforts to identify persons who have TB and/or HIV. Multi-disease community-based frameworks have been rare. Based on findings from a WHO meta-analysis and a Cochrane review, integrating ICF into the recent multi-disease prevention campaign in Kenya may have had implications in controlling TB. Community-based multi-disease prevention campaigns represent a potentially powerful strategy to deliver prevention interventions, identify people with HIV and/or TB, and link those eligible to care and treatment.

Protease inhibitor-containing antiretroviral treatment and tuberculosis: can rifabutin fill the breach?

OBJECTIVE: To assess how to best manage co-administration of rifabutin (RFB) and human immunodeficiency virus 1 (HIV-1) protease inhibitor (PI) containing antiretroviral treatment (ART). Recommended for initial anti-tuberculosis treatment, rifampicin (RMP) lowers PI concentrations below therapeutic levels, posing significant challenges for ART. As RFB has little effect on PI concentrations, it could be an alternative to RMP. METHODS: A review of the scientific literature on the safety and efficacy of RFB for adult tuberculosis (TB) treatment was conducted, focusing on ART-TB co-therapy. A cost comparison was performed between treatment regimens, and estimates of the burden of TB disease in patients on ART were used to model RFB demand in low- and middle-income countries (LMICs). RESULTS: Eleven clinical studies were identified, comprising 1543 TB patients treated with RFB; 980 (64%) were living with HIV. RFB was as safe and effective as RMP, including in 313 patients receiving co-administered ART (unboosted PIs included indinavir, nelfinavir or saquinavir; a minority received ritonavir [RTV] boosted amprenavir or saquinavir). The total cost for 6 months of all HIV and TB treatment containing RTV-boosted lopinavir (LPV) and RFB is US$410, compared to US$455 if RMP is used with LPV super-boosted with RTV. Our model suggests that demand for RFB in LMICs could be between 10,000 and 18,000 courses by 2012. CONCLUSION: RFB is effective and safe in combination with the PIs studied, cost-saving for co-therapy with currently recommended boosted PIs, and may have a pivotal role in the roll-out of ART. Further research into a daily dose of RFB to simplify dosing regimens and developing fixed-dose combinations can enhance the public sector roll-out of ART.

The chemistry, pharmacologic, and therapeutic applications of Polyalthia longifolia.

Medicinal plants are nature's gift to human beings to lead a disease-free, healthy life. They play a vital role in preserving our health. India is one of the most medicoculturally diverse countries in the world, where the medicinal plant sector is part of a time-honored tradition that is respected even today. Medicinal plants are believed to be much safer and proved as elixir in the treatment of various ailments. In our country, more than 2000 medicinal plants are recognized. Polyalthia longifolia cv. pendula (Annonaceae) is native to the drier regions of India and is locally known as "Ashoka" and is commonly cultivated in Pakistan and Sri Lanka. This plant is used as an antipyretic agent in indigenous systems of medicine. Pharmacologic studies on the bark and leaves of this plant show effective antimicrobial activity, cytotoxic function, antiulcer activity, hypoglycemic activity, and hypotensive effect. The present article includes the detailed exploration of pharmacologic properties of P. longifolia in an attempt to provide a direction for further research.

Antihyperglycemic effects of three extracts from Momordica charantia.

Momordica charantia (L.) (Cucurbitaceae) commonly known as bitter gourd or karela is a medicinal plant, used in Ayurveda for treating various diseases, one of which is diabetes mellitus. In this study, various extract powders of the fresh and dried whole fruits were prepared and their blood glucose lowering effect compared by administrating them orally to diabetic rats. The aqueous extract powder of fresh unripe whole fruits at a dose of 20mg/kg body weight was found to reduce fasting blood glucose by 48%, an effect comparable to that of glibenclamide, a known synthetic drug. This extract was tested for nephrotoxicity, hepatotoxicity and biochemical parameters such as SGOT, SGPT and lipid profile. The extract did not show any signs of nephrotoxicity and hepatotoxicity as judged by histological and biochemical parameters. Thus the aqueous extract powder of Momordica charantia, an edible vegetable, appears to be a safe alternative to reducing blood glucose.

Immunomodulatory activity of boswellic acids of Boswellia serrata Roxb.

Extract of gum resin of B. serrata containing 60% acetyl 11-keto beta boswellic acid (AKBA) along with other constituents such as 11-keto beta-boswellic acid (KBA), acetyl beta-boswellic acid and beta-boswellic acid has been evaluated for antianaphylactic and mast cell stabilizing activity using passive paw anaphylaxis and compound 48/80 induced degranulation of mast cell methods. The extract inhibited the passive paw anaphylaxis reaction in rats in dose-dependant manner (20, 40 and 80 mg/kg, po). However, the standard dexamethasone (0.27 mg/kg, po) revealed maximum inhibition of edema as compared to the extract. A significant inhibition in the compound 48/80 induced degranulation of mast cells in dose-dependant manner (20, 40 and 80 mg/kg, po) was observed thus showing mast cell stabilizing activity. The standard disodium cromoglycate (50 mg/kg, ip) was found to demonstrate maximum per cent protection against degranulation as compared to the extract containing 60% AKBA. The results suggest promising antianaphylactic and mast cell stabilizing activity of the extract.

Pharmacological activities of Genistein, an isoflavone from soy (Glycine max): part I--anti-cancer activity.

Phytoestrogens represent a family of plant compounds such as isoflavones, flavones and lignans. A variety of these plant compounds have been identified in various human body fluids. A wide range of commonly consumed foods contains appreciable amounts of these different phytoestrogens, viz. soy products are particularly good sources of isoflavones and lignans. Accumulating evidences from molecular and cellular biology experiments, animal studies, and to a limited extent, human clinical trials suggests that phytoestrogens may potentially confer health benefits related to various cancers and diseases such as cardiovascular disorder. The evidences reviewed here represent the beneficial effects of most potential and promising isoflavone, Genistein in various types of cancers.

Pharmacological activities of Genistein, an isoflavone from soy (Glycine max): part II--anti-cholesterol activity, effects on osteoporosis & menopausal symptoms.

Phytoestrogens represent a family of plant compounds such as isoflavones, flavones and lignans. A wide range of commonly consumed foods contains appreciable amounts of different phytoestrogens such as isoflavones and lignans. Soy and its products are particularly good sources of isoflavones and lignans. The evidence reviewed here represents the beneficial effects of most potential and promising isoflavone, Genistein in various types of diseases such as osteoporosis, cardiovascular diseases, menopausal symptoms by accumulating evidence from molecular and cellular biology experiments, animal studies, and, to a limited extent, human clinical trials. This review suggests that phytoestrogens may potentially confer health benefits related to various diseases such as cardiovascular disorder, menopausal symptoms, and osteoporosis.

Direct selection for mutators in Escherichia coli.

We have constructed strains that allow a direct selection for mutators of Escherichia coli on a single plate medium. The plate selection is based on using two different markers whose reversion is enhanced by a given mutator. Plates containing limiting amounts of each respective nutrient allow the growth of ghost colonies or microcolonies that give rise to full-size colonies only if a reversion event occurs. Because two successive mutational events are required, mutator cells are favored to generate full-size colonies. Reversion of a third marker allows direct visualization of the mutator phenotype by the large number of blue papillae in the full-size colonies. We also describe plate selections involving three successive nutrient markers followed by a fourth papillation step. Different frameshift or base substitution mutations are used to select for mismatch-repair-defective strains (mutHLS and uvrD). We can detect and monitor mutator cells arising spontaneously, at frequencies lower than 10(-5) in the population. Also, we can measure a mutator cascade, in which one type of mutator (mutT) generates a second mutator (mutHLS) that then allows stepwise frameshift mutations. We discuss the relevance of mutators arising on a single medium as a result of cells overcoming successive growth barriers to the development and progression of cancerous tumors, some of which are mutator cell lines.

Humoral immunological profile of workers exposed to asbestos in asbestos mines.

Humoral immunological profile including immunoglobulins IgG, IgA, IgM, C-reactive protein, rheumatoid factor, antinuclear antibodies and circulating immune complexes were studied in a representative sample of 36 workers suffering from asbestosis (group A), 35 workers who are exposed to asbestos but not having evidence of asbestosis (group B) and 28 control workers (group C). Mean IgG and IgA levels were found to be significantly higher in the two exposed groups than in the controls. Circulating immune complexes of IgG, IgA and IgM class were detected in a significant percentage of cases in exposed groups than in controls. In groups A and B, the percentage of positive ANF cases was much higher than in the controls. The results suggest that immunological changes are associated with exposure to asbestos and these may play an important role in the pathogenesis of the disease process.

Role of circulating immune complexes in the immunopathogenesis of silicosis.

The sera of 19 silica-dust-exposed subjects and of an equal number of age-, sex- and socioeconomic-strata-matched controls were analysed for antinuclear factor, rheumatoid factor, C-reactive protein, immunoglobulins G, M, A, and complement C3 and C4. Circulating immune complexes were also precipitated in all subjects and their immunoglobulin and complement C3 and C4 were estimated. Silica-exposed subjects were divided into two groups depending upon the radiological findings and it is suggested that IgA plays an important role in the immunopathogenesis of the disease and that lung changes could be due to the immune-complex-mediated mechanisms utilizing an alternative complement pathway.

Two-dimensional and Dopple rechocardiographic identification of infrahepatic interruption of inferior vena cava with azygos continuation.

Congenital anomalies of systemic venous return have been associated with pacemaker complications. Awareness of the existence of these anomalies prior to catheterization can lead to the utilization of an alternate route for pacing, avoiding undue delay in the institution of pacing which may be urgently needed. Pulse Doppler echocardiographic demonstration of turbulent flow in the azygos vein and superior vena cava combined with subcostal two-dimensional echocardiographic finding of a small channel opening into the right atrium appear to be highly specific findings in the diagnosis of infrahepatic interruption of inferior vena cava with azygos continuation.