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The use of dietary ginger (Zingiber officinale) and curcumin as immunostimulants is a promising method in fish culture. This study evaluated the impacts of dietary ginger extract and curcumin on growth, hematology, immune and antioxidant status, and expression of some growth and immune related genes in rainbow trout (Oncorhynchus mykiss) fingerlings. Fish (7.5 ± 0.1 g) were randomly distributed into 12 fiberglass tanks (30 fish per tank), divided into four treatments in triplicate and received no supplementation (control) and diets supplemented with 0.5% ginger extract (ginger treatment), 0.5% curcumin (curcumin treatment), and 0.5% ginger extract plus 0.5% curcumin (mix treatment). The growth of fish and muscle crude protein content were highest in the mix treatment. Higher protein efficiency ratio, hemoglobin, and plasma ALP activity were observed in fish fed supplemented diets than the control. Red blood cells (RBC) counts and hematocrit value were higher in the ginger treatment, then curcumin and mix treatments and lower in the control. White blood cells (WBC) counts and plasma lysozyme, ACH50, catalase, and SOD activities were highest in fish fed the mix diet. Moreover, plasma C4 value and GPx activity were significantly higher and triglyceride value was lower in the curcumin and mix treatments compared to the control and ginger treatments. The highest plasma C3 and total immunoglobulin (Ig) values were found in fish fed curcumin and mix diets, but those were not significantly different from the ginger treatment. Growth hormone (GH) and lysozyme relative expression levels were highest in fish fed the mix diet and lowest in the control. Thus, the combination of 0.5% ginger extract and 0.5% curcumin (mix diet) to improve growth, body composition, hematology, immune responses, and antioxidant status in rainbow trout can be recommended.

In this study, gold nanoparticles were synthesized by laser ablation of Au bulk in distilled water. The laser used is Nd: YAG laser, which has a fundamental harmonic wavelength (λ=1064nm) and second harmonic wavelength (λ=532nm). In order to control the size of Au nanoparticles (NPs), we used sodium citrate as a stabilizer. Morphology, structure and linear optical properties of Au NPs samples were characterized by transmission electron microscopy (TEM observation), XRD diffraction (XRD) and UV–Visible spectroscopy. Furthermore, the chemical structure in solution of Au NPs was studied by Fourier transform-infrared spectroscopy (FTIR). The nonlinear optical parameters of these Au NPs were studied using the Z-scan method. We found the optimal values of fluencies and laser pulse repetition rates to achieve the smallest size values and the most distribution of the produced gold nanoparticles. It is resulted that due to the very small size of NPs, the nonlinear optical parameters show larger values. It is 107 order of magnitude larger than what has been reported for the nonlinear refractive index in previous researches. In addition, gold nanoparticles that are produced with a laser wavelength of 1064 nm and have a high nonlinear refractive index can be used in chip-based sensors. Finally, the use of these Au NPs in optical switching devices was investigated by the two figures of merit method, which indicated that these Au NPs are practical tools for optical switching devices.

Land cover maps play an integral role in environmental management. However, countries and institutes encounter many challenges with producing timely, efficient, and temporally harmonized updates to their land cover maps. To address these issues we present a modular Regional Land Cover Monitoring System (RLCMS) architecture that is easily customized to create land cover products using primitive map layers. Primitive map layers are a suite of biophysical and end member maps, with land cover primitives representing the raw information needed to make decisions in a dichotomous key for land cover classification. We present best practices to create and assemble primitives from optical satellite using computing technologies, decision tree logic and Monte Carlo simulations to integrate their uncertainties. The concept is presented in the context of a regional land cover map based on a shared regional typology with 18 land cover classes agreed on by stakeholders from Cambodia, Laos PDR, Myanmar, Thailand, and Vietnam. We created annual map and uncertainty layers for the period 2000–2017. We found an overall accuracy of 94% when taking uncertainties into account. RLCMS produces consistent time series products using free long term historical Landsat and MODIS data. The customizable architecture can include a variety of sensors and machine learning algorithms to create primitives and the best suited smoothing can be applied on a primitive level. The system is transferable to all regions around the globe because of its use of publicly available global data (Landsat and MODIS) and easily adaptable architecture that allows for the incorporation of a customizable assembly logic to map different land cover typologies based on the user's landscape monitoring objectives

The silkworm is the larva or caterpillar of the domesticated silkmoth, Bombyx mori and being a primary producer of silk is an economically important insect. These days the silk is emerging as a resource for solving a broad range of biological problems. The silk (Abresham) is popularly known as Abresham muqriz (muqriz means cut) in Unani medicine. Its cocoons are extensively used as an ingredient of various Unani formulations like Khameer-E- Abresham Sada, Khameere Abresham Hakeem Arshad Wala, Khameere Abresham Ood Mastagi Wala etc. and are used to treat many cardiac and nervous disorders. The hypolipidemic activity of this drug, along with Nepata Hindostana (Badranjboya) and Terminalia Arjuna (Arjan) has been documented. But action of extract of Bombyx mori cocoons as a single drug is not documented. That′s why; it was decided to study its effect on hyperlipidemia and atherosclerosis. The Male New Zealand White rabbits all of 1.5kgs were selected for the study. After stabilization period (2 weeks) the rabbits were divided into 3 groups (Group I - Control, Group II Lesion Control and Group III treated with extract of Bombyx mori silk cocoon). Hyperlipidemia and atherosclerosis were induced with 1% cholesterol diet. After induction of hyperlipidemia and atherosclerosis for twelve weeks, Group III rabbits were treated with Bombyx mori for 6 weeks (45 days). A significant decrease in hyperlipidemia was seen within 4 weeks of treatment. Histopathologically, the atherosclerotic plaques showed reduction in size. The third group showed a significant increase in the body weight and also an increase in the HDL cholesterol levels. The study concludes that extract of Bombyx mori cocoons has a significant effect on hypercholesterolemia and atherosclerosis probably because of its antioxidant and hypolipidemic effect.

Breast carcinoma is the leading factor in women's cancer-related fatalities. Due to its numerous inherent molecular subtypes, breast cancer is an extremely diverse illness. The human epidermal growth factor receptor 2 (HER2) positive subtypes stands out among these subtypes as being especially prone to cancer development and illness recurrence. The regulation of embryonic stem cells' pluripotency and self-renewal is carried out by the SALL4 (Spalt-like transcription factor 4) family member. Numerous molecular pathways operating at the transcriptional, post-transcriptional, and epigenomic levels regulate the expression of SALL4. Many transcription factors control the expression of SALL4, with STAT3 being the primary regulator in hepatocellular carcinoma (HCC) and breast carcinoma. Moreover, this oncogene has been connected to a number of cellular functions, including invasion, apoptosis, proliferation, and resistance to therapy. Reduced patient survival rates and a worse prognosis have been linked to higher levels of SALL4. In order to target the undruggable SALL4 that is overexpressed in breast carcinoma, we investigated the prognostic levels of SALL4 in breast carcinoma and its interaction with various related proteins. Using TIMER 2.0 analysis, the expression pattern of SALL4 was investigated across all TCGA datasets. The research revealed that SALL4 expression was elevated in various cancers. The UALCAN findings demonstrated that SALL4 was overexpressed in all tumor samples including breast cancer especially TNBC (Triple negative breast cancer). The web-based ENRICHR program was used for gene ontology analysis that revealed SALL4 was actively involved in the development of the nervous system, positive regulation of stem cell proliferation, regulation of stem cell proliferation, regulation of the activin receptor signaling pathway, regulation of transcription using DNA templates, miRNA metabolic processes, and regulation of transcription by RNA Polymerase I. Using the STRING database, we analyzed the interaction and involvement of SALL4 with other abruptly activated proteins and used Cytoscape 3.8.0 for visualization. Additionally, using bc-GenExMiner, we studied the impact of SALL4 on pathways abruptly activated in different breast cancer subtypes that revealed SALL4 was highly correlated with WNT2B, NOTCH4, AKT3, and PIK3CA. Furthermore, to target SALL4, we evaluated and analyzed the impact of CLP and its analogues, revealing promising outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

STAT3 is a crucial member within a family of seven essential transcription factors. Elevated STAT3 levels have been identified in various cancer types, notably in breast cancer (BC). Consequently, inhibiting STAT3 is recognized as a promising and effective strategy for therapeutic intervention against breast cancer. We herein synthesize a library of isoxazole (PAIs) from piperic acid [2E, 4E)-5-(2H-1,3-Benzodioxol-5-yl) penta-2,4-dienoic acid] on treatment with propargyl bromide followed by oxime under prescribed reaction conditions. Piperic acid was obtained by hydrolysis of piperine extracted from Piper nigrum. First, we checked the binding potential of isoxazole derivatives with breast cancer target proteins by network pharmacology, molecular docking, molecular dynamic (MD) simulation and cytotoxicity analysis as potential anti-breast cancer (BC) agents. The multi-source databases were used to identify possible targets for isoxazole derivatives. A network of protein-protein interactions (PPIs) was generated by obtaining 877 target genes that overlapped gene symbols associated with isoxazole derivatives and BC. Molecular docking and MD modelling demonstrated a strong affinity between isoxazole derivatives and essential target genes. Further, the cell viability studies of isoxazole derivatives on the human breast carcinoma cell lines showed toxicity in all breast cancer cell lines. In summary, our study indicated that the isoxazole derivative showed the significant anticancer activity. The results highlight the prospective utility of isoxazole derivatives as new drug candidates for anticancer chemotherapy, suggesting route for the continued exploration and development of drugs suitable for clinical applications., Competing Interests: Declaration of competing interest No conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Multi Drugs Resistance (MDR) is among the most worrisome healthcare issues resulting from inappropriate and indiscriminate utilization of antimicrobial agents which has compromised the efficacy and reliability of antimicrobial agents (AMAs). This has not only put a huge burden on the health care system but also is a major cause of morbidity and mortality. This project was designed to evaluate the prevalence of various microbial strains among patients admitted to various teaching hospitals and to assess their susceptibility and resistance towards clinically approved antibiotics., Methods: The study was conducted during August 2021-February 2022 to determine the prevalence of common resistant strains of bacteria and to analyze their susceptibility pattern to the commonly prescribed antibiotics using standard procedures. One hundred and thirty biological samples including urine, blood, cerebrospinal fluid (CSF), wound swabs, pus and sputum were collected from the site of infection from the patients admitted at different wards of North West General Hospital (NWGH), Peshawar, Pakistan, Khyber Teaching Hospital (KTH), Peshawar Pakistan, and Hayat Abad Medical Complex (HMC) Peshawar Pakistan. Samples were collected and cultured following standard hospital procedures. The cultured samples were subjected to identification procedures including Gram staining, morphological characterization of bacterial colonies and biochemical assessments. The identified bacteria were tested for their susceptibility using Kirby-Bauer disc diffusion method. The diameter of Inhibitory Zones (DIZ) was analyzed following Clinical and Laboratory Standards Institute (CLSI) criteria. Minimum Inhibitory Concentrations (MICs) were evaluated using agar dilution method. Antimicrobials sensitivity were presented as antibiogram following CLSI M39 standard., Results: A total of one hundred and thirty biological samples were collected, out of which one hundred and nine samples were positive for bacterial growth and were further processed for detailed analysis. The frequency and type of bacteria isolated from various cultures indicated that Gram negative bacteria (n = 92/109) were more dominant than Gram-positive (n = 17/109) pathogens. The most prevalent bacteria isolated was Escherichia coli (29.35 %), followed by Staphylococcus aureus (15.59 %), and Klebsiella spp, (12.84 %). In addition, other pathogens including, Enterobacter spp, Citrobacter spp, and Acinetobacter spp. showed a prevalence of 9.175 %, 8.25 %, and 5.50 % respectively. As indicated in the antbiogram, several organisms exhibited considerble decline in the sensitivies towards various antibiotics. A high percentage of resistance was observed against some antibiotics including trimethoprim, co-trimoxazole, amoxicillin/clavulanate, ciprofloxacin, piperacillin/tazobactam, cefotaxime and ceftazidime., Conclusion: The prevalence of resistant strains of pathogens is increasing day by day, while the antibiotics commonly prescribed against them are losing their efficacy, which is pushing the world to the era of pre-antibiotics. Unfortunately, the discovery of novel antibiotics is limited and researchers speculate that the is pushing towards pre-antibiotics era. Subsequently, efforts must be directed towards ensuring rational antibiotics use to prevent emergence of MDR pathogens. Our findings indicated that Gram negative bacteria including Escherichia coli was most prevalent. Other bacterial strains including S. aureus, Klebsiella spp, Enterobacter spp, Citrobacter spp, and Acinetobacter spp. were found among the causative agents. Unfortunately, considerable decline in the sensitivities of various bacterial isolated were observed towards the tested antibiotics. Previous studies reported the high prevalence of E. coli and S. aureus in clinical samples of Pakistani hospitals including hospitals in Peshawar and thus our findings are in agreement with the previous reports. Pharmacists being experts can play their role by promoting the optimal use of antimicrobial agents and educating healthcare professionals, patients and the public., Competing Interests: Declaration of Competing Interest Authors of the manuscript declare to have no conflict of interest in relation to this manuscript., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Polycystic ovary syndrome (PCOS), an intricate and multifaceted metabolic-endocrine disorder that typically affects 6-20% of women of reproductive age and accounts for 70-80% of all occurrences of infertility globally. In this study we focussed on the effect of diacerein (DIC) on steroidogenesis and follicle development in addition to the basic metabolic and endocrine problems which are associated with PCOS. Eighteen mature female parkes strain mice were separated into three groups at random with 6 animals in a group as follows: Group I, received water and normal diet for 66 days; group II received letrozole (LETZ) (6 mg/kg bw) for the induction of PCOS; Group III received LETZ (6 mg/kg) for 3 weeks followed by the administration of DIC (35 mg/kg) for 45 days. In our study we observed that mice with PCOS had irregular estrous cycle with increased LH/FSH, estrogen level and decline in expression of Kitl, Bmp, Cyp11a1, CYP19a1, Ar, lhr, Fshr and Esr1 as well as decreased SOD and CAT activity in ovary. Moreover, we observed increase in the expression of CYP17a1, as well as increase in serum cholesterol, triglycerides, testosterone, LH, VEGF and insulin levels. All these changes were reversed after the administration of DIC in PCOS mice. Diacerin administration reversed abnormalities in mice with PCOS by modulating the regulation of genes which are related to steroidogenesis and folliculogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Breast cancer (BC), one of the most prevalent malignancies, is the second major cause of mortality from cancer among women worldwide. Even though substantial progress has been made in breast cancer treatment, metastasis still accounts for the majority of the deaths. The tumor microenvironment (TME) comprising stromal and non-stromal components is central to tumor growth and development and is partly regulated by chemokines. Chemokines regulate immune cell trafficking, the development of stroma and play a key role in inflammation, a cancer hallmark., Methods: In the present study, we used a bioinformatics approach to identify highly deregulated chemokines in BC patients. We performed expression analysis, survival analysis, gene ontology analysis, KEGG analysis, and protein-protein interaction network analysis of the deregulated chemokines using Gepia2, UALCAN, Kaplan-Meier Plotter, DAVID, and STRING tools., Results: We identified >2-fold change (FC) increase in CXCL9/10/11/13 and >-2 FC decrease in CCL14/21/28, CXCL2/12 CX3CL1. Also, increased expression of CCL14, CCL21, CXCL13, CXCL9, CXCL12 correlated with better overall survival (OS) of BC patients., Conclusions: Our results strongly indicate that chemokines may have potential biomarker characteristics, and the constructed PPI network contributed to an in-depth understanding of the chemokine networks. The deregulated chemokines may prove to be therapeutic targets for the effective management of BC., (Copyright © 2022. Published by Elsevier Inc.)

Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive B-cell lymphoma arising from thymic B-cells having clinicopathologic features distinct from systemic diffuse large B-cell lymphoma (DLBCL). PMBCL comprises 2% to 4% of all non-Hodgkin lymphomas (NHL), 7% of DLBCL and seen predominantly in young females with a median age of 35 years at diagnosis. The annual incidence of PMBCL is 0.4 per million with a 5-year survival rate exceeding 70% with improving supportive care and genetic characterization of the disease. Pathogenesis involves dysregulation of Janus kinase-signal transducer and activator of transcription (JAK-STAT), nuclear factor-kB (NF-kB) pathways and amplification of the 9p24.1 region of chromosome 9. PMBCL patients have a prolonged life expectancy necessitating the need for treatment approaches that are based on maximizing cure with minimal long-term toxicity. Due to rarity and its recognition as a distinct entity, therapeutic decisions are guided by clinical presentation, clinician and center experience, and analysis of patients with PMBCL within DLBCL registries. Historically R-CHOP has been the usual first line treatment for PMBCL followed by involved site radiotherapy (ISRT), however clinical practice varies across centers with emerging consensus to avoid upfront RT by utilizing dose intense regimens (DA-EPOCH-R) in younger and fit patients. Prognosis of relapsed refractory PMBCL not responding to salvage chemotherapy is dismal, however there are many emerging options including Brentuximab Vedotin, immune check point inhibitors and chimeric antigen receptor T-cell therapy. In this article, we focus on the pathogenesis, current and evolving treatments, and provide recommendations for optimal management of patients with PMBCL., (Copyright © 2021. Published by Elsevier Inc.)

The present study reports the multi-technique results of the interaction of a series of bile salts, sodium cholate (NaC), sodium taurocholate (NaTC), sodium deoxycholate (NaDC), and sodium taurodeoxycholate (NaTDC) with trypsin under the experimental conditions of 25 °C and pH 7.0. The interactions between trypsin and the bile salts were characterized by the surface tension measurements and various spectroscopic techniques like UV-Visible absorption, steady-state fluorescence, and circular dichroism. The results of surface tension measurements reveal a strong interaction of trypsin (50 μM) with the increasing concentration of bile salts, being higher with the bile salt of greater hydrophobicity. The critical aggregation concentration of bile salts in the presence of trypsin (C 1 ) showed that the bile salts interact strongly with the trypsin in the order of NaTDC > NaDC > NaTC > NaC. UV-visible, steady-state fluorescence, and circular dichroism spectroscopic results confirmed significant unfolding of trypsin due to its interaction with the bile salts, the extent of which followed the same sequence as observed in the surface tension results. It could be concluded that the hydrophobic bile salts that show lower C 1 values and have less delocalized charge, are more effective in unfolding the trypsin. The study would help understand the hydrophobicity-driven unfolding of proteins aided by biological surfactants like bile salts and help devise efficient proteolytic enzyme-based detergent formulations and understand the role of such amphiphiles as antimicrobial agents., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier B.V.)

Background: Reports of injuries caused by bear attacks are scarce in the Himalayan region of India, such as Uttarakhand, which is surrounded by hills and thick forests. We retrospectively studied 18 patients attacked by Himalayan black and sloth bears to understand the pattern of the attacks and their management., Materials and Methods: Patients attacked by bears between January 2018 to December 2019 were retrospectively studied., Results: Most of the patients were of low socioeconomic status. The incidence was highest between June and December. The attacks mostly caused soft tissue injuries. There were also fractures of facial bones noted in some cases, but there was no mortality. The best outcomes were found in those cases that were managed with generous tissue preservation, rather than aggressive debridement. We could also follow the bear attack pattern. Himalayan black bears and sloth bears were found to be involved in the attacks., Conclusion: Injuries due to bear attacks mainly affect the face and neck. Although there were no cases of mortality in this study, facial disfigurement had a long-lasting impact on survivors. Tissue preservation and early reconstruction had the best outcomes., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest. We hereby declare that we have no conflicts of interest in the study. No financial support was obtained . The study was not influenced by an interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: CSE-1034 is a novel antibiotic adjuvant entity (AAE) with proven activity against broad range of multi-drug resistant (MDR) pathogens causing various bacterial infections. This phase 3 clinical trial was designed to evaluate the efficacy and safety of CSE-1034 therapy for the treatment of community-acquired pneumonia (CAP) patients of Pneumonia Outcomes Research Team (PORT) risk III-IV., Methods: In this multi-centric, controlled, open-labeled phase 3 trial, adult patients with PORT risk III-IV CAP were randomized to receive either intravenous CSE-1034 (3g every 12h) or Ceftriaxone (2g every 12h) for 3-10 days. The primary endpoint was clinical response in clinically-evaluable (CE) population and microbiological eradication in microbiologically-evaluable (ME) population at test of cure (TOC) visits. Secondary endpoints included verification of the primary endpoints across all other visits, treatment duration and safety of patients., Results: 156 patients were screened at 5 study centers of which 93 subjects were enrolled in the study and randomized in CSE-1034 and Ceftriaxone treatment arms. In CE population (n=90), the clinical cure rates at TOC visit were 96% and 64% in CSE-1034 (n=46) and Ceftriaxone (n=44) treatment arms respectively (treatment difference: 32.0%; 95% CI, 15.8%-47.1%). The bacterial eradication in ME population of two treatment arms were 94% (n=36) and 56% (n=27) at TOC visit (treatment difference: 38.9%; 95% CI, 17.8%-57.6%). Overall, the total number of adverse events (AEs) reported in both groups were 21 (22.5%). The AEs rates reported in two treatment arms were 15.2% in CSE-1034 and 29.8% in Ceftriaxone group., Conclusion: Overall assessment of clinical cure rate, microbiological eradication rate and safety assessment in this study has shown that CSE-1034 is an effective and safe option for the treatment of CAP patients of PORT risk III-IV. Moreover, the superiority of CSE-1034 over Ceftriaxone is also proven., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Allogeneic transplant in myeloma remains controversial., Patients and Methods: We performed a retrospective review of 76 patients in the Mayo Clinic database from 1993 to 2013 who underwent allogeneic hematopoietic stem cell transplant (HSCT) for myeloma., Results: After excluding ineligible patients, among the remaining 66 patients, median age at transplant was 42 years and 87% had residual disease at the time of transplant. Myeloablative (71%) versus reduced intensity conditioning (29%), matched sibling donors (70%) versus unrelated donors showed no outcome difference. Median overall survival from the time of diagnosis and transplant were 75 and 24 months, respectively. Median time to disease progression (TTP) was 15 months and treatment-related mortality was 20% at day 100. Acute and chronic graft versus host disease (cGVHD) developed in 61% and 48% patients, respectively. In univariate analysis of overall survival (OS), factors predicting adverse outcome were pretransplant 24-hour total urinary protein (P = .035), peripheral blood versus bone marrow (OS 18 vs. 41 months; P = .02), number of previous therapies (P = .014), time from autologous to allogeneic HSCT (P = .019), and cGVHD (P = .01). TTP was adversely affected by number of previous regimens (P = .036) and PB as graft source (P = .016). In multivariate analysis for progression-free survival, number of previous regimens (P = .04), and for OS, time between autologous and allogeneic HSCT was significant (P = .009)., Conclusion: In 162 matched control subjects who were human leukocytoe antigen-typed, there were no survivors at 12 years compared with 20% in the group who received a transplant. In a second control group with 197 second autologous transplants, 10-year OS was 8%., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n = 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy. Correlations with outcome in chemotherapy treated patients were further examined in a separate cohort of 183 South West Oncology Group (SWOG) patients and all patients were then included in a meta-analysis. Six cytokines were associated with outcome in the Molecular Epidemiology Resource (MER) after adjusting for the FL international prognostic index. In patients who were observed or treated with rituximab alone, increased serum IL-12 and interleukin 1 receptor antagonist (IL-1RA) (P = .005 and .02) were associated with a shorter event-free survival. In patients receiving chemotherapy, hepatocyte growth factor, IL-8, IL-1RA, and CXCL9 (P = .015, .048, .004, and .0005) predicted a shorter EFS. When the MER chemotherapy treated patients and SWOG patients were combined in a meta-analysis, IL-2R, IL-1RA, and CXCL9 (P = .013, .042, and .0012) were associated with a poor EFS., (© 2015 by The American Society of Hematology.)

The interactions of bovine serum albumin (BSA) with cationic gemini surfactants alkanediyl-alpha,omega-bis(dimethylcetylammonium bromide) (designated as C(16)C(s)C(16)Br(2), s=4, 5, and 6) and single chain surfactant cetyltrimethylammonium bromide (CTAB) have been investigated with tensiometry, Rayleigh's scattering, fluorescence spectroscopy, and circular dichroism at physiological pH and 25 degrees C. The results of the multi-technique approach showed that the gemini surfactants interact more efficiently with the proteins than their conventional single chain counterparts and their efficiency increases with decrease in the length of the spacer. The saturation in interfacial tension occurred at a lower concentration in presence of BSA compared to CMC of the surfactants in absence of BSA and the concentration of gemini surfactants corresponding to interfacial saturation decreases with decrease in the spacer length. Fluorescence and circular dichroism spectroscopy results revealed increase in unfolding of BSA with decrease in spacer length of gemini surfactants., (2010 Elsevier B.V. All rights reserved.)

The cytokinetic protein FtsZ plays a pivotal role in regulation of cell division in bacteria. Multiple promoters regulate transcription of the ftsZ gene in Escherichia coli, Streptomyces and Bacillus species. In order to identify promoter activity-containing regions of the ftsZ gene of Mycobacterium tuberculosis H37Rv (MtftsZ) in vivo, different regions upstream of MtftsZ, namely, the ftsQ-ftsZ intergenic region, the ftsQ open reading frame (ORF), and different regions of ftsQ ORF, were analyzed in a gfp reporter plasmid in Mycobacterium smegmatis mc(2)155 cells. Flow cytometric analysis of mid-logarithmic M. smegmatis mc(2)155 cells containing these transcription fusion constructs revealed GFP expression in the cells harboring the ftsQ-ftsZ intergenic region (172 bp), the entire ftsQ ORF (945 bp), and 5' 467-bp and 3' 217-bp regions of ftsQ ORF. RT-PCR analyses on RNA from M. smegmatis mc(2)155 cells, transformed with the entire ftsQ ORF-ftsQ-ftsZ intergenic region-containing construct, as well as on RNA from M. tuberculosis, confirmed that the regions identified indeed elicit promoter activity. Semi-quantitative RT-PCR analyses of gfp transcripts driven by cloned MtftsZ promoter regions in M. smegmatis cells showed threefold higher promoter activity from ftsQ ORF than from the ftsQ-ftsZ intergenic region. Expression from the individual 5' and 3' regions of ftsQ ORF was almost equivalent to that from the ftsQ-ftsZ intergenic region. RT-PCR analyses on RNA from M. tuberculosis quantitatively confirmed these promoter activities. Thus, at least three independent regions in the immediate upstream sequence of MtftsZ contain promoter activity, with the major contribution coming from ftsQ ORF.

Introduction: Working in coal mines is a risk factor for pneumoconiosis and COPD. There still exist, however, doubts and debates about the risk involved in such work for tuberculosis and lung cancer. The aim of this study was to clarify some of these uncertainties through the study of a cohort group., Methods: The cohort comprises 2,579 miners. An initial medical examination was carried out when they began to work in the mine, and three further examinations were performed over the 20 years of the study. The follow-up failure rate was 23.7%., Results: Ninety-nine workers (3.8%) developed round opacities (category 1) that were significantly related to the kind of work in a crude analysis (p = 0.045), with a greater frequency (7.3%) among rock workers, who have greater exposure to silica, and were almost significantly related to tobacco use (p = 0.092). These round opacities also show a significant relation to smoking, being more frequent (4.9%) among smokers, both in the crude analysis (p = 0.028) and in the multivariable analysis (p = 0.001) controlling for rock work. In 240 workers (12.7%), accelerated FEV(1) decreases were observed with significant relations to tobacco use (p = 0.001) and rock work (p = 0.044). Pulmonary tuberculosis was diagnosed in four cases, with an incidence of eight in 10(5) person-years. This rate falls within the limits expected for the region. No case of lung cancer was observed., Conclusion: In summary, our results showed the following: round opacities (category 1) were related to smoking and, probably, to rock work; accelerated FEV(1) decreases were related to rock work and tobacco consumption. There was no identified increase in tuberculosis or lung cancer in this cohort.

Depletion of histone H1 after covalent modification from chromatin is a key step in eukaryotic transcription initiation. We have studied the effect of depletion of linker histone H1 upon the association of transcription inhibitor, (mithramycin)(2):Mg(2+) complex, with chromatin. We have compared the binding characteristics of the above complex with native, H1-depleted chromatin and naked DNA. Binding site size (number of bases per ligand molecule) of the above complex to the chromosomal DNA increases upon removal of histone H1. It implies an increase in the accessibility of the ligand for the linker DNA. Spectroscopic data, and associated enthalpy and entropy values of the interaction of the complex with H1-depleted chromatin are similar to naked DNA rather than native chromatin. These results suggest that under in vivo conditions, depletion of histone H1 from transcriptionally inert native chromatin during gene activation would lead to an enhanced accessibility of linker DNA to the small ligands with the potential to inhibit transcription.

Mithramycin (MTR) is an anticancer drug that blocks macromolecular biosynthesis via reversible interaction with DNA in the presence of bivalent cation such as Mg2+. Mithramycin forms two types of complexes with Mg2+: complex I (1:1 in terms of MTR:Mg2+) and complex II (2:1 in terms of MTR:Mg2+). In vivo antibiotic would interact with chromatin, a protein-DNA complex. For the first time we have demonstrated and characterized the association of both complexes of MTR with chromatin and nucleosome core. From an evaluation and comparison of the binding and thermodynamic parameters and CD spectra of bound complexes, we have shown the following. Histone(s) stand in the say of the access of the ligand(s) to chromosomal DNA. Chromatin and core particle interact differentially with the same ligand. Mode of interaction of the two complexes, I and II, with the same system is different. Significance of these results to understand the transcription inhibitory property of the drug in eukaryotic chromosome is discussed., (Copyright 2001 Academic Press.)

In an attempt to resolve the prevailing confusion about erythrocyte sodium pump activity in obesity, we measured sodium-potassium-ATPase, ouabain-inhibitable (active) sodium efflux rate constant and intracellular sodium concentration in erythrocytes from 107 non-obese and obese subjects, with a body-mass index ranging from 17 to 54 kg X m-2. All the three independently measured variables were not significantly different between the two groups and no correlations were found between these three indices and body-mass index. The expression of ATPase activity in units of membrane protein allowed our previous data to be compared with this study and other reports. Our studies and most of the published reports suggest that there is no difference in erythrocyte sodium-potassium-ATPase and sodium transport between the vast majority of obese and non-obese subjects, but there is a subgroup of obese subjects (about 5%) with abnormally high erythrocyte sodium pump activity. The variable treatment of data from this subgroup and the small numbers of obese subjects studied by various investigators are largely responsible for the conflicting results about erythrocyte sodium pump activity.

In this study we attempted to explore the relationship between salt and blood pressure in a salted-tea drinking population of Northern Kashmir which has not been exposed to a Western way of life. All the available family members of randomly selected houses in 14 villages were studied. Dietary intake was documented for the whole month of the study period to estimate the daily salt consumption in 281 subjects (193 males, 88 females), whose ages were reliably known. Their age ranged from 15 to 85 years (median 35) and their mean daily salt intake was 150 +/- 52 mmol (range 80-440). Both the systolic and diastolic blood pressures showed a significant increase with the salt intake and age; multiple regression analysis suggested an independent effect of salt intake on blood pressure after adjusting for age. Twenty-six subjects (9.3%) had hypertension (blood pressure greater than or equal to 160/95 mm Hg); their daily salt intake was significantly higher than that of normotensive subjects (mean 167 +/- SD 53 vs 142 +/- 46 mmol; P less than 0.001). These studies suggest a relationship between habitual high salt intake and blood pressure.

To determine whether muscle sodium-potassium-ATPase activity, an expression of energy turnover, is increased in obesity, we studied a group of nine non-obese and seven obese subjects undergoing elective cholecystectomy. The muscle ATPase activity was 87 per cent higher (p less than 0.001) in obese subjects compared with non-obese subjects. The increase in the ATPase activity positively correlated with both the body mass index (r = 0.81) and excess body weight (r = 0.75). No relationship was found between erythrocyte and muscle sodium-potassium-ATPase activities (r = 0.25). These findings demonstrate an increased ATPase activity in skeletal muscle obtained from obese subjects and that the erythrocyte is an inaccurate marker of this enzyme with respect to other body tissue.

To evaluate the effects of chronic smoking on exercise performance we studied 5 smokers and 7 nonsmokers of comparable age and physical characteristics. The resting heart rate in smokers (75 +/- 3 beats/min; mean +/- SD) was significantly (P less than 0.01) higher than in nonsmokers (64 +/- 5). During exercise on a bicycle ergometer the heart rate remained significantly (P less than 0.01) higher in smokers than in nonsmokers. After exercise, the heart rate in nonsmokers settled to 78 +/- 9 beats/min at 10 minutes compared with 105 +/- 11 (P less than 0.01) in smokers. Oxygen consumption was similar in both groups throughout. Beta-adrenergic blockade reduced the exercise tachycardia in both groups but the heart rate for the same workload remained significantly (P less than 0.01) higher in smokers. Beta-blockade significantly reduced (P less than 0.05) oxygen consumption in nonsmokers but not in smokers who also incurred a significantly (P less than 0.05) greater oxygen debt and had higher serum lactate levels. These differences were attributed mainly to carboxyhaemoglobinaemia and partly to the effect of prolonged smoking on the heart and on intermediary metabolism.

To study the effects of a low carbohydrate, isoenergetic diet on pulmonary physiology and sleep behavior, we measured pulmonary functions and respiratory gas exchange and carried out ambulatory electroencephalographic studies after a week's intake of isoenergetic diet containing only 50 g carbohydrate per day in 6 healthy female adult humans in a free-living condition. Compared with their normal intake, during the week of low carbohydrate intake there was a rise in the level of fasting plasma 3-hydroxybutyrate from 0.12 +/- 0.07 (mean +/- SD) to 1.01 +/- 0.40 mmol/L(P less than 0.01, paired t-test); a fall in serum bicarbonate from 26.2 +/- 0.75 to 25.0 +/- 1.41 mmol/L (P less than 0.05) and in serum chloride from 107 +/- 1.3 to 105 +/- 1.8 mmol/L (P less than 0.05). Serum urea rose from 4.3 +/- 0.71 to 5.7 +/- 0.70 mmol/L (P less than 0.01), and serum uric acid from 0.34 +/- 0.08 to 0.39 +/- 0.10 mmol/L (P less than 0.05). Functional residual capacity was increased from 2.07 +/- 0.35 to 2.26 +/- 0.34 L (P less than 0.01). Respiratory gas exchange ratio fell from 0.81 +/- 0.05 to 0.75 +/- 0.04 (P less than 0.05) and partial pressure of expired carbon dioxide reduced from 22 +/- 3.3 to 21 +/- 3.1 mmHg (P less than 0.05). There was a reduction in endogenous carbon dioxide production and arterial carbon dioxide tension. An analysis of ambulatory electroencephalogram showed that REM latency increased from 66 +/- 8 to 111 +/- 38 min (P less than 0.05), with no significant changes in sleep time and stages. These studies show that a low carbohydrate isoenergetic diet is tolerable, influences sleep behavior, reduces carbon dioxide production and respiratory gas exchange ratio, and may be therapeutically useful in patients with hypercapnic respiratory failure.

Studies on erythrocyte sodium pump activity in obesity have yielded conflicting results probably because the erythrocyte is an atypical cell, and it may not reflect ATPase activity of other cells in the body. This study was undertaken to establish a reproducible procedure to measure sodium transport in human diploid fibroblasts, and apply this method to explore any differences in the cells from obese and nonobese humans. Cell cultures were established from 12 nonobese (body mass index (BMI) = wt in kg/height in m2 (Khosla and Lowe, Br J Prev Soc Med 1967; 21: 122-128); less than 27 kg/m2) and 10 obese (BMI) greater than 35 kg/m2) subjects. Triplicate measurements of sodium efflux rate constant were made with and without ouabain (1 mmol/l) to determine the total, active (ouabain-sensitive) and passive (ouabain-insensitive) components. Reproducible results were obtained as suggested by a coefficient of variation (CV) of less 10% on successive experiments on the same cell-line, and 11 and 15% of the active sodium efflux rate constant measured in fibroblasts from nonobese and obese subjects, respectively. The active sodium efflux rate constant in fibroblasts from nonobese (0.202 +/- 0.023 (SD)) was not significantly different from that obtained in the cells from obese subjects (0.21 +/- 0.030; p greater than 0.10). These results suggest that there is no intrinsic differences in basal sodium pump activity in fibroblasts related to obesity.