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In this paper, we introduce a new class of statistical models to deal with the data sets in the sports and health sectors. The new class is called, a novel exponent power-Y (NovEP-Y) family of distributions. By implementing the NovEP-Y approach, a new model, namely, a novel exponent power-Weibull (NovEP-Weibull) distribution is introduced. Some distributional properties of the NovEP-Y family such as identifiability, order statistics, quantile function, and moments are obtained. The maximum likelihood estimators of the parameters are also derived. Furthermore, a brief Monto Carlo simulation study is conducted to evaluate the performances of the estimators. To show the applicability of the NovEP-Weibull model, two data sets from the sports and health sciences are considered. The first data set represents the time-to-even data collected from different football matches during the period 1964–2018. Whereas, the second data set is taken from the health sector, representing the survival times of the COVID-19 infected patients. Based on some well-known statistical tests, it is observed that the NovEP-Weibull model is a very competitive distribution for modeling the data sets in the sports and health sectors.

KRAS is one of the most frequently mutated proto-oncogenes in pancreatic ductal adenocarcinoma (PDAC) and aberrantly activated in triple-negative breast cancer (TNBC). A profound role of microRNAs (miRNAs) in the pathogenesis of human cancer is being uncovered, including in cancer therapy. Using in silico prediction algorithms, we identified miR-873 as a potential regulator of KRAS, and we investigated its role in PDAC and TNBC. We found that reduced miR-873 expression is associated with shorter patient survival in both cancers. miR-873 expression is significantly repressed in PDAC and TNBC cell lines and inversely correlated with KRAS levels. We demonstrate that miR-873 directly bound to the 3′ UTR of KRAS mRNA and suppressed its expression. Notably, restoring miR-873 expression induced apoptosis; recapitulated the effects of KRAS inhibition on cell proliferation, colony formation, and invasion; and suppressed the activity of ERK and PI3K/AKT, while overexpression of KRAS rescued the effects mediated by miR-873. Moreover, in vivo delivery of miR-873 nanoparticles inhibited KRAS expression and tumor growth in PDAC and TNBC tumor models. In conclusion, we provide the first evidence that miR-873 acts as a tumor suppressor by targeting KRAS and that miR-873-based gene therapy may be a therapeutic strategy in PDAC and TNBC. Keywords: KRAS, oncogene, non-coding RNA, microRNA, ncRNA, miR-873, proliferation, invasion, gene regulation, tumorigenesis, gene silencing, therapy, nanoparticles, pancreatic cancer, liposomes, breast cancer, triple-negative breast cancer

Apricot pectin polysaccharides' fine structure was performed using HPSEC, HPAEC-PAD, GC-MS, NMR and FTIR spectroscopies. Purified pectin fraction (F1AP) was composed of D-galacturonic acid, L-rhamnose, D-arabinose and D-galactose, Mw ∼ 1588 kDa. F1AP was eluted by water and with 0.2 M NaCl from DEAE Sepharose fraction resulting in two distinct fractions, F1AP1 and F1AP6, with different structures, molecular weights, and conformations, providing insights into their structural diversity. F1AP1 neutral properties were related to its association with protein. F1AP1 had a backbone of (1 → 4)-linked-D-galacturonic acid and (1 → 2)-linked-L-rhamnopyranosyl residues branched with arabinogalactan including multiple glycosidic linkages of T-α-Araf, 3-α-Araf, 5-α-Araf, T-α-Arap, 2-α-Arap, t-Galp, 2-Galp, 3-Galp, 4-Galp, 6-Galp, 2,4-Galp, 3,4-Galp, 3,6-Galp and 4,6-Galp side chains, having methyl and acetylated groups, and a high molecular weight (1945 kDa). The Mark-Houwink exponent was 0.276, indicating a compact spherical conformation. While the other F1AP6 fraction consists predominately of less methylated HG regions of pectin polysaccharides. The molar mass of this fraction was 117.5 kDa, which adopted a stiffer and random coil conformation. This knowledge allows us to evaluate how the balance of chemical structure and physical properties of the two pectin domains may manifest itself in the isolated structure of apricot pectin and its applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

A green, sensitive and rapid spectrofluorimetric method for quantitative assay of an anti-allergic medication composed of montelukast and fexofenadine mixture in raw materials and dosage form was developed. The method was based on measuring the synchronous fluorimetric peak without interference, pre-separation or pre-extraction procedures. Montelukast was analyzed at 360 nm while fexofenadine was measured at 263 nm using Δλ = 20 nm for both drugs using ethanol as diluting solvent and acetate buffer of pH 4. The assay was rectilinear over the concentration range of 1.0-10.0 μg/mL for fexofenadine and 0.1-0.6 μg/mL for montelukast. The method was full validated according to ICH guidelines. The applicability of the method enables the assay of both drugs in raw materials, synthetic mixture as well as combined tablets. Moreover, the greenness of the method was assessed using different methods including; analytical eco-scale, GAPI and AGREE. All of these methods confirm that the proposed method is an eco-friendly method., 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 B.V. All rights reserved.)

Introduction: Residency programs and their directors frequently receive funding from industry payers. Both general surgery residency program directors (PDs) and assistant program directors (APDs) receive industry funding for various reasons, including educational advancement. This study investigates recent trends in industry payments to both PDs and APDs to better understand the financial relationships among leaders in residency education., Methods: We compared industry payments to general surgery residency PDs and APDs from 2019 to 2021 utilizing the U.S. Centers for Medicare & Medicaid Services (CMS) open payments database. In addition, secondary analyses were performed among PDs to assess differences based on gender, practicing surgical specialty, and geographical region., Results: During the study period (2019-2021), PDs received payments amounting to 2,882,821 USD. PDs were found to receive more funding than APDs, with each receiving average funding of 10,045 vs. 323 USD (p < 0.01), respectively, over the study period. There was a significant decrease in total payments from 2019 to 2020 (1,512,190 vs. 868,811 USD; p < 0.01). Total payments made in 2021 were similar compared to 2020 (905,836 vs. 868,811 USD; p = 0.1). We found that male PDs received significantly more in-industry payments when compared to female PDs (11,702 USD per PD vs. 3971 USD per PD, p < 0.01)., Conclusion: This study presents initial data that residency program leadership has robust biomedical industry relationships, and further research is warranted to investigate the impacts of these payments on program resources, educational opportunities for residents, and program outcomes. Male PDs received significantly more industry payments when compared to female PDs. Leaders in the surgical training community must cautiously ensure that these industry relationships are appropriately navigated., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Fixed-dose combinations for treatment of hypertension are observed in many dosages in the global market because of their high efficacy compared to single component dosage forms. One of these effective combinations is atenolol/amlodipine which is usually administered to patients with hypertension. Hence, development of facile, accurate, and sensitive methods for simultaneous estimation of atenolol and amlodipine is of great importance for quality control testing and pharmacokinetic studies. In our study, we developed two spectrofluorimetric methods to estimate both compounds in different pharmaceuticals. The first method is based on the estimation of atenolol and amlodipine by double-scan conventional spectrofluorimetry where the fluorescence intensities of atenolol and amlodipine were measured at 299 and 434 nm after excitation at 274 and 358 nm, respectively. The second method depends on synchronous spectrofluorimetric measurements at Δλ = 70 nm, where atenolol is assayed at 266 nm and amlodipine is assayed at 363 nm. Methods' optimizations were carried out to select the optimum conditions that render high selectivity and sensitivity. Such optimizations included assessment of solvents, surfactants, buffer volumes and pHs. The conventional spectrofluorimetric method was rectilinear over concentration range of 30.0-300.0 ng mL -1 for atenolol and 0.25-7.00 µg mL -1 for amlodipine while the synchronous spectrofluorimetric method showed linearity over the ranges of 0.60-6.00 µg mL -1 for atenolol and 0.25-7.00 µg mL -1 for amlodipine with low detection limits (≤0.12 µg mL -1 ) for both compounds in the two methods. It is the first work that demonstrates estimation of atenolol and amlodipine in their combinations by conventional and synchronous spectrofluorimetry. Both methods were applied to estimate atenolol and amlodipine in different pharmaceuticals with high %recovery and low %RSD., 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: General surgery education has continued to evolve regarding test preparation, simulation, and skill acquisition. The "Resident as Educator" (RAE) model has been proposed and enacted by programs as a viable education model for general surgery education. This study examines the current education structures in general surgery residency programs in the United States and how many programs have adopted the RAE model or aspects of the model., Methods: A 20-question survey regarding education structure was distributed to all program directors in October 2021. Questions focused on the involvement of residents in leading education sessions, creating the weekly education schedule, program feedback to residents on teaching, and recognition for distinguished resident educators., Results: A total of 156 programs responded to the survey. The response rate was 60%. 76.4% of the respondents have a combination of resident and faculty-led didactic sessions, 8.5% have an RAE model, and 15% have faculty-led education sessions. In terms of concerns regarding resident-led didactics-24.4% of respondents stated that their main concern would be the quality of education provided, and 20.4% referenced low resident satisfaction levels with resident-led education. There were no differences among the groups regarding the American Board of Surgery board passage rates., Conclusions: Most residency programs have adopted a model in which residents have significant involvement in creating and maintaining the education calendar and leading formal education sessions. However, only 8.5% have a purely resident-led educational curriculum among the responding programs. More studies are needed to assess how to implement a resident as educator model successfully., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

The fluidized bed is an essential and standard equipment in the field of process development. It has a wide application in various areas and has been extensively studied. This review paper aims to discuss computational modeling of a fluidized bed with a focus on pharmaceutical applications. Eulerian, Lagrangian, and combined Eulerian-Lagrangian models have been studied for fluid bed applications with the rise of modeling capabilities. Such models assist in optimizing the process parameters and expedite the process development cycle. This paper discusses the background of modeling and then summarizes research papers relevant to pharmaceutical unit operations., (Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Accumulation of heavy metals in the environment can pose a potential risk to living organisms. Ingestion of leafy vegetables, containing heavy metals, is one of the main routes through which these elements enter the human body. The present study was conducted to assess the accumulation of lead (Pb) and zinc (Zn) in spinach grown on metal contaminated soil, and to examine the bioassimilation of these metals in spinach-fed rabbits. Spinach grown in the fields spiked with Pb (1000 mg kg -1 soil) and Zn (150 mg kg -1 soil), was fed to the rabbits for 14 days. Concentrations of Pb and Zn in the leaves of spinach were 39.1 and 113 mg kg -1 , respectively. For the assessment of Pb and Zn concentration, blood samples were collected after 24 h, 7 days and 14 days of feeding, while the essential organs, i.e. liver and kidneys of rabbits were collected at the end of feeding trials. Concentrations (mg L -1 ) of Pb (3.28) and Zn (7.10) increased in blood after 24 h compared to control treatment and then decreased (Pb 1.12; Zn 3.32) to a steady state with the passage of time after 7 days. A significant increase in the concentrations of Pb (1.20%, 3.95% and 5.58%) and Zn (10.7%, 6.89% and 18.4%) as compared to control treatment was also found in liver, kidney and bones of the rabbits, respectively, which was further confirmed by multivariate analysis. The highest significant values of correlation coefficient (r) were observed for blood and bones, i.e. 0.992 followed by blood and liver, i.e. 0.989. The bioassimilation of Pb in the body of rabbits was in the order of bone > kidney > liver > blood, while for Zn the order was bone > liver > kidney > blood. The bioassimilation of Pb and Zn in the blood, essential organs and bones depicted the serious health risks associated by consuming the metal contaminated vegetable., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: COVID-19 emerged as a global pandemic in 2020 and has affected millions of lives. Surgical training has also been significantly affected by this pandemic, but the exact effect remains unknown. We sought to perform a national survey of general surgery residents in the United States to assess the effect of COVID-19 on surgical resident training, education, and burnout., Methods: An anonymous online survey was created and distributed to general surgery residents across the United States. The survey aimed to assess changes to surgical residents' clinical schedules, operative volume, and educational curricula as a result of the COVID-19 pandemic. Additionally, we sought to assess the impact of COVID-19 on resident burnout., Results: One thousand one hundred and two general surgery residents completed the survey. Residents reported a significant decline in the number of cases performed during the pandemic. Educational curricula were largely shifted toward online didactics. The majority of residents reported spending more time on educational didactics than before the pandemic. The majority of residents feared contracting COVID-19 or transmitting it to their family during the pandemic., Conclusions: COVID-19 has had significant impact on surgical training and education. One positive consequence of the pandemic is increased educational didactics. Online didactics should continue to be a part of surgical education in the post-COVID-19 era. Steps need to be taken to ensure that graduating surgical residents are adequately prepared for fellowship and independent practice despite the significantly decreased case volumes during this pandemic. Surgery training programs should focus on providing nontechnical clinical training and professional development during this time., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Aims: STW 5 is an herbal drug combination used for the treatment of functional gastrointestinal disorders (FGIDs) with visceral hypersensitivity as the therapy-resistant hallmark. STW 5 has been clinically proven to alleviate visceral hypersensitivity-related symptoms, including abdominal pain, bloating, nausea, and early satiety. However, the molecular and cellular mechanisms underlying the antinociceptive action of STW 5 remain unknown. Here, we investigate the role of STW 5 in the calcium mobilisation of dorsal root ganglion (DRG) sensory neurons., Main Methods: Calcium imaging experiments were performed with freshly dissociated cultured murine DRG neurons isolated from mice by microfluorometry. TRPA1-deficient DRGs, TRPV1-deficient DRGs, TRPA1/V1 double-deficient DRGs, and wild-type DRGs have been used to investigate the role of TRPs ion channels in mediating STW 5 action., Key Findings: STW 5 (1.74 and 5.8 mg/ml) induced calcium ion influx into DRG neurons in a concentration-dependent manner. Calcium transients were desensitised during repeated exposure to STW 5, an effect that was facilitated in TRPA1-deficient DRGs and less pronounced in TRPV1-deficient DRGs compared to wild-type (WT) DRGs., Significance: Repeated exposure to STW 5 induced desensitisation of sensory neurons and may ultimately contribute to its proven clinical efficacy against sensory-related symptoms in patients with FGID, including abdominal pain, bloating, nausea, and early satiety. This effect is modulated by the two prominent irritant sensors in nociceptors, TRPA1 and TRPV1., Competing Interests: Declaration of competing interest This study was funded by Bayer Consumer Health (Steigerwald Arzneimittelwerk GmbH), Havelstrase 5, 64295, Darmstadt, Germany. HAA, RMA, and SR are fully employed by Bayer Consumer Health. ME and MK received support from the Deutsche Forschungsgemeinschaft (DFG SFB TRR 241/1 TP B05). All other authors report no declarations of interest. The present work was performed in fulfilment of the requirements for obtaining the degree “Dr. med.” for ZZ at the Friedrich-Alexander-University Erlangen-Nürnberg (FAU)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Alkaline phosphatases (APs) are a class of homodimeric enzymes which physiologically possess the dephosphorylation ability. APs catalyzes the hydrolysis of monoesters into phosphoric acid which in turn catalyze a transphosphorylation reaction. Thiazoles are nitrogen and sulfur containing aromatic heterocycles considered as effective APs inhibitors. In this context, the current research paper presents the successful synthesis, spectroscopic characterization and in vitro alkaline phosphatase inhibitory potential of new thiazole derivatives. The structure activity relationship and molecular docking studies were performed to find out the binding modes of the screened compounds with the target site of tissue non-specific alkaline phosphatase (h-TNAP) as well as intestinal alkaline phosphatase (h-IAP). Compound 5e was found to be potent inhibitor of h-TNAP with IC 50 value of 0.17 ± 0.01 µM. Additionally, compounds 5a and 5i were found to be highly selective toward h-TNAP with IC 50 values of 0.25 ± 0.01 µM and 0.21 ± 0.02 µM, respectively. In case of h-IAP compound 5f was the most potent inhibitor with IC 50 value of 1.33 ± 0.10 µM. The most active compounds were resort to molecular docking studies on h-TNAP and h-IAP to explore the possible binding interactions of enzyme-ligand complexes. Molecular dynamic simulations were carried out to investigate the overall stability of protein in apo and holo state., 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 © 2020 Elsevier Inc. All rights reserved.)

Aims: Liver fibrosis (LF) is a life-threatening complication of most chronic liver diseases resulting from a variety of injurious agents and hepatotoxic insults. To date, there are no specific therapies for LF, and all the currently available drugs have been developed for other indications. Thus, there is a pressing need to develop new drugs for treatment of LF. Therefore, the current study aimed to elucidate the potential antifibrotic effect of Pirfenidone (PFD) against concanavalin A (ConA)-induced immunological model of liver fibrosis in mice., Main Methods: Hepatic fibrosis was induced in mice by injecting ConA (10 mg/kg/wk./i.v) for 4 weeks. Then, the mice were treated with or without PFD (125 mg/kg/ip/day) for 2 weeks. Hepatic fibrosis was determined by Masson Trichrome staining; Haematoxylin & eosin (H&E) staining, immunohistochemistry staining of type II and IV collagens, and colorimetric assessment of hydroxyprolline (HP) content in the liver tissues. In addition, the expression of α-SMA mRNA was determined by real time RT-PCR. The serum levels of TGF-β, TNF-α, TIMP-1 and MMP-2 were measured by ELISA., Key Findings: Treatment with PFD significantly reduced ConA-induced expression of type II and IV collagens, α-SMA mRNA expression, and HP content and decreased inflammatory cells infiltration in hepatic tissues. Furthermore, serum levels of TGF-β, TNF-α, and TIMP-1 were significantly reduced with concomitant increase in MMP-2 expression., Significance: Treatment with PFD ameliorates concanavalin A-induced hepatic inflammation and fibrosis in mice. Thus, PFD may represent a promising therapeutic option for hepatic fibrosis and its related complications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Globally, cervical cancer is the fourth most common cancer in women and the seventh most common cancer overall, accounting for an estimated 300 000 annual deaths. Human papillomavirus (HPV) is the second most common cause of cervical cancer worldwide. HPV screening is not a common practice in Pakistan. The aim of this study was to determine the prevalence of HPV and HPV types in women with a normal cytology of the cervix living in the upper and lower regions of Punjab, Pakistan, and to analyze the risk factors for HPV in this region., Methods: PCR analysis was performed for 1011 female patients with a normal cytology of the cervix from various districts of Punjab Province, Pakistan. Risk factors for the acquisition of HPV were studied. High-risk HPV types (HPV16 and HPV18) were detected using the Abbott Real Time HR HPV test. To determine the genotype, partial L1 region sequences of HPV-positive samples were subjected to sequencing using MY/09/MY11 primers, and a phylogenetic tree was constructed using CLC software., Results: The study found a 4.74% prevalence of HPV, with the most frequent HPV type found being the low-risk HPV6 (in 25% of infected individuals), followed by HPV55 (22.9%), HPV11 (20.8%), and high-risk types HPV45 (12.5%), HPV33 (8.33%), HPV18 (6.25%), and HPV16 (4.16%). Phylogenetic analysis of all HPV types in this study showed 80-99% nucleotide identity with types related to the same species. The sequences were clustered with China, India, Mexico, Iran, Slovenia, and Germany, showing the diversity in origin of the various genotypes prevalent in Pakistan., Conclusions: In this population with a normal cervical cytology, the prevalence of high-risk HPV types was very low. The major prevalent HPV genotype in Punjab Province of Pakistan was the low-risk HPV type 6, followed by HPV type 55. Sequencing of the partial L1 region suggested that the region was highly conserved in all reported sequences. This study highlights the need to conduct robust epidemiological studies in the region and to develop regular HPV screening so that the situation does not reach an alarming stage resulting in cervical cancer., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Burn scars remain a serious physical and psychological problem for the affected people. Clinical studies as well as basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling has no influence on repigmentation of large hypopigmented scars. The goal of this study is to evaluate whether two established methods - needling (for improvement of scar quality) and non-cultured autologous skin cell suspension (for repigmentation) - can be successfully combined. Twenty subjects with mean age of 33 years (6-60 years) with scars from deep second and third degree burns have been treated. The average treated surface area was 94cm 2 (15-250cm 2 ) and was focused on prominent areas such as the face, neck, chest and arm. Percutaneous collagen induction or "medical needling" was performed using a roller covered with 3mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, non-cultured autologous skin cell suspension (NCASCS) was produced and applied using the ReNovaCell Autologous Cell Harvesting Device (Avita Medical), according to the manufacturer's instructions. The patients were followed 12 months postoperatively. Pigmentation changes were measured objectively, as well as with patient and observer ratings. Patient satisfaction/preference was also obtained. Taken together, the pigmentation ratings and objective measures indicate individual improvement in 17 of the study participants. The melanin increases seen 12 months after NCASCS treatment are statistically significant. Medical needling in combination with NCASCS shows promise for repigmentation of burn cars., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The replicative DNA polymerases are generally blocked by template DNA damage. The resulting replication arrest can be released by one of two post-replication repair (PRR) pathways, translesion DNA synthesis (TLS) and template switching by homologous recombination (HR). The HERC2 ubiquitin ligase plays a role in homologous recombination by facilitating the assembly of the Ubc13 ubiquitin-conjugating enzyme with the RNF8 ubiquitin ligase. To explore the role of HERC2 and RNF8 in PRR, we examined immunoglobulin diversification in chicken DT40 cells deficient in HERC2 and RNF8. Unexpectedly, the HERC2(-/-) and RNF8(-/-) cells and HERC2(-/-)/RNF8(-/-) double mutant cells exhibit a significant reduction in the rate of immunoglobulin (Ig) hypermutation, compared to wild-type cells. Further, the HERC2(-/-) and RNF8(-/-) mutants exhibit defective maintenance of replication fork progression immediately after exposure to UV while retaining proficient post-replicative gap filling. These mutants are both proficient in mono-ubiquitination of PCNA. Taken together, these results suggest that HERC2 and RNF8 promote TLS past abasic sites and UV-lesions at or very close to stalled replication forks., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Optimization of surgical outcomes after colectomy continues to be actively studied, but most studies group right-sided and left-sided colectomies together. The aim of our study was to determine whether the complication rate differs between right-sided and left-sided colectomies for cancer., Methods: We identified patients who underwent laparoscopic colectomy for colon cancer between 2005 and 2010 in the American College of Surgeons National Surgical Quality Improvement Program database and stratified cases by right and left side. The two groups were matched using propensity score matching for demographics, previous abdominal surgery, pre-operative chemotherapy and radiotherapy, and preoperative laboratory data. Outcome measures were: 30-day mortality and morbidity., Results: We identified 2512 patients who underwent elective laparoscopic colectomy for right-sided or left-sided colon cancer. The two groups were similar in demographics, and pre-operative characteristics. There was no difference in overall morbidity (15% vs. 17.7%; p value < 0.08) or 30-day mortality (1.5% vs. 1.5%; p value < 0.9) between the two groups. Sub-analysis revealed higher surgical site infection rates (9% vs. 6%; p value < 0.04), higher incidence of ureteral injury (0.6% vs. 0.4%; p value < 0.04), higher conversion rate to open colectomy (51% vs. 30%; p value < 0.01) and a longer hospital length of stay (10.5 ± 4 vs. 7.1 ± 1.3 days; p value < 0.02) in patients undergoing laparoscopic left colectomy., Conclusion: Our study highlights the difference in complications between right-sided and left-sided colectomies for cancer. Further research on outcomes after colectomy should incorporate right vs. left side colon resection as a potential pre-operative risk factor., Competing Interests: The authors have no financial or proprietary interest in the subject matter or materials discussed in the manuscript.

Background: Do-not-resuscitate (DNR) orders allow patients to communicate their wishes regarding cardiopulmonary resuscitation. Although DNR status may influence physician decision making regarding resuscitation, the effect of DNR status on outcomes of patients undergoing emergency vascular operation remains unknown. The aim of this study was to analyze the effect of DNR status on the outcomes of emergency vascular surgery., Methods: The National Surgical Quality Improvement Program database was queried to identify all patients requiring emergency vascular surgical interventions between 2005 and 2010. Demographics, clinical data, and outcomes were extracted. Patients were compared according to DNR status. The primary outcome measure was 30-day mortality., Results: During the study period, 16,678 patients underwent emergency vascular operations (10.8% of the total vascular surgery population). Of those, 548 patients (3.3%) had a DNR status. The differences in rates of open or endovascular repair or of intraoperative blood requirement between the two groups were not significant. After adjusting for differences in demographics and clinical data, DNR patients were more likely to have higher rates of graft failure (8.7% vs 2.4%; adjusted P < .01) and failure to wean from mechanical ventilation (14.9 % vs 9.9%; adjusted P < .001). DNR status was associated with a 2.5-fold rise in 30-day mortality (35.0% vs 14.0%; 95% confidence interval, 1.7-2.9; adjusted P < .001)., Conclusions: The presence of a DNR order was independently associated with mortality. Patient and family counseling on surgical expectations before emergency vascular operations is warranted because the risks of perioperative events are significantly elevated when a DNR order exists., (Published by Elsevier Inc.)

Background: The gold standard treatment for chronic hepatitis C virus (HCV) infection is pegylated interferon (PEG-IFN) in combination with ribavirin. Most patients treated with PEG-IFN achieve a sustained virological response (SVR). However host genetic factors play a vital role in the spontaneous and treatment-induced clearance of HCV infection from these infected patients. In the current study, polymorphisms of IL28B (rs8099917 and rs12979860) were analyzed and their association with the virological response to PEG-IFN alpha treatment was determined., Methods: One hundred and fifty HCV genotype 3 patients were assessed to study the correlation of IL28B with a therapeutic regimen of PEG-IFN alpha plus ribavirin. Twenty patients were excluded due to a refusal to participate in the study and 25 patients failed to meet the inclusion criteria. Of the 105 patients recruited, 49 (46.7%) were male and 56 (53.3%) were female. In order to determine single nucleotide polymorphisms of rs8099917 and rs12979860, the sample was amplified by PCR and then IL28B typing was carried out by restriction fragment length polymorphism (RFLP) followed by standard sequencing., Results: We found three types of genotype in rs8099917 of IL28B: wild-type TT in 60.0% of patients, heterozygous GT minor genotype in 36.2%, and GG in 3.8%. The frequency of the CC genotype of rs12979860 was 54.3%, CT was 37.1%, and TT was 8.6%. Overall, SVR was achieved in 68.6% of patients. A higher SVR was achieved for patients with the favorable genotype CC of rs12979860, with 84.2% as compared to 56.4% and 22.2% for minor genotype CT and TT, respectively (p=0.0001). We did not find a significant association for SVR to antiviral treatment in patients with genotype TT (rs8099917) (71.9%, p=0.36). The rapid virological response (RVR) rate was significantly higher in patients with major genotype TT (88.9%, p=0.04). These results show that IL28B polymorphism is highly associated with SVR to therapy in the Pakistani population infected with HCV genotype 3., Conclusions: HCV-infected patients carrying homozygous C/C have a higher chance of SVR. In addition, patients who carry T/T (rs8099917) have a higher chance of RVR., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The surface charge and average size of manufactured ZnO nanoparticles (NPs) were studied as a function of pH to understand the aggregation behavior and importance of the electrostatic interactions in solution. The interactions between ZnO and Suwannee River humic acid (SRHA) were then investigated under a range of environmentally relevant conditions with the ZnO nanoparticles pHPZC as the point of reference. The anionic charges carried by aquatic humic substances were found to play a major role in the aggregation and disaggregation of ZnO nanoparticles. At low concentrations of SRHA (<0.05 mg/L) and below the pHPZC, anionic SRHA was rapidly adsorbed onto the positively charged ZnO NPs hence promoting aggregation. With similar SHRA concentrations, at pHPZC, SRHA was able to control the suspension behavior of the ZnO and promote partial disaggregation in small volumes. This was more distinguishable when the pH was greater than pHPZC as SRHA formed a surface coating on the ZnO nanoparticles and enhanced stability via electrostatic and steric interactions. In most cases, the NP coating by SRHA induced disaggregation behavior in the ZnO nanoparticles and decreased the aggregate size in parallel to increasing SRHA concentrations. Results also suggest that environmental aquatic concentration ranges of humic acids largely modify the stability of aggregated or dispersed ZnO nanoparticles., (© 2013.)

Background: Rapid virological response (RVR) is now thought to be the strongest predictor of sustained virological response (SVR) in hepatitis C virus (HCV) patients undergoing antiviral therapy. It can be used as a guide to individualize treatment duration. The aim of this study was to assess the role of RVR in tailoring the duration of treatment., Methods: Patients with HCV genotype 3 infections were enrolled and treated with pegylated interferon alfa-2a (PEG IFN alfa-2a) 180 μg/week and ribavirin. HCV RNA was analyzed at weeks 4, 12, 16, and 24. Treatment duration was individualized on the basis of RVR. Patients who achieved RVR and who were aged ≤ 40 years with a body mass index (BMI) ≤ 27 kg/m(2) received 16 weeks of treatment (group A). Patients who achieved RVR and were aged >40 years with a BMI >27 kg/m(2), aged >40 years with a BMI ≤ 27 kg/m(2), and aged ≤ 40 years with a BMI >27 kg/m(2) received 24 weeks of treatment (group B). Patients who did not achieve RVR but who achieved an early virological response (EVR; HCV PCR-negative or ≥ 2 log drop in HCV RNA at week 12) were treated with 24 weeks of therapy (group C)., Results: SVR was observed in 86% in group A, 82.2% in group B, and 46.8% in group C. A difference was observed in SVR for patients with and without RVR and receiving the standard duration of treatment (82.2% vs. 46.8%, p<0 .001). The results show that the rate of SVR is not inferior in those with RVR treated with 16 weeks of therapy compared to 24 weeks (86% vs. 82.2%, p=0.004)., Conclusions: RVR is useful to individualize the duration of treatment and to predict the treatment outcome. A short treatment of 16 weeks is as effective as 24 weeks in HCV genotype 3 patients who achieve RVR, who have a low BMI, and are younger in age., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The optimal use of lumbar cerebrospinal fluid drainage for the prevention of spinal cord ischemia (SCI) with thoracic endovascular aortic repair (TEVAR) remains unclear. Here, we report our experience with selective preoperative lumbar drain placement with TEVAR., Methods: Between May 2002 and January 12, 381 TEVAR procedures were performed at a single referral institution. Preoperative lumbar drains were placed selectively in patients considered high-risk for SCI due to planned long-segment aortic coverage with a history of prior aortic intervention or planned hybrid Crawford extent I to III thoracoabdominal aortic aneurysm repair., Results: Preoperative lumbar drains were placed in 81 patients (21%); of these, drain placement in 38 (47%) was for procedures involving long-segment descending thoracic aortic coverage in the setting of prior descending thoracic or infrarenal aortic repair, and in 43 (53%) was for hybrid thoracoabdominal aortic aneurysm repair. SCI occurred in 12 patients (14.8%) who received a preoperative lumbar drain, transient in 6 (7.4%) and permanent in 6 (7.4%), whereas SCI occurred in 13 patients (4.3%) who did not receive a preoperative lumbar drain, 12 transient (4.0%) and 1 permanent (0.3%). A lumbar drain complication occurred in 9 drain patients (11.1%), although none resulted in permanent disability. Age, postoperative hypotension, and the number of endografts implanted were independently associated with SCI. Preoperative lumbar drain placement was not associated with reduced SCI., Conclusions: Restricted use of preoperative lumbar drains for patients at high-risk of SCI undergoing TEVAR appears safe and leads to low rates of SCI in nondrained patients. However, the utility of preoperative lumbar drains in preventing SCI with TEVAR remains questionable and should be weighed against the risk of drain complications., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Hepatitis C virus (HCV) is a causative agent of chronic liver disease, cirrhosis, and hepatocellular carcinoma. In Pakistan, more than 10 million people are living with HCV. Very little is known about the genotype distribution in Punjab Province, the largest province of Pakistan. Pretreatment genotype identification is very important, as different HCV genotypes respond differently to interferon therapy., Methods: In this study we performed HCV genotyping for 1537 HCV-infected patients from different districts of Punjab Province, Pakistan. Sequencing of partial HCV NS5B sequences from 14 samples belonging to genotypes 3 and 1 was also done. A sequence comparison was made of our reported sequences with those reported in the National Center for Biotechnology Information (NCBI), and a phylogenetic tree was constructed., Results: Our study showed that the most frequent HCV genotype was 3a (in 88.1% of infected individuals), followed by 1a (3.5%), 3b (3.0%), 1b (0.8%), and 2a (1.0%). A mixed genotype infection was found in 3.6% of infected individuals, with 0.3% living with 1a + 1b co-infection, 3.1% with 3a+3b, and 0.2% suffering from 3a+1b co-infection. The sequence comparison showed that HCV NS5B motif B residues G283, T287, and N291 were highly conserved in both genotype 1 and genotype 3 sequences, while the motif B residue T286 was mutated to proline in all the genotype 3 sequences. The GDD motif, which forms the catalytic pocket and binding site for the divalent cations, was highly conserved in all the reported sequences. The phylogenetic tree suggests clustering of genotype 1 sequences with sequences from the USA, UK, Germany, and France, while genotype 3 sequences are clustered with sequences from Japan and the UK., Conclusions: The major prevalent genotype in Punjab Province of Pakistan was genotype 3a, followed by genotype 1a, and only 3.6% of infected individuals had a mixed genotype infection. Sequencing of the HCV NS5B gene suggested that the active site residues were highly conserved in all the reported sequences. Our sequences, which are clustered with sequences from the USA, UK, France, and Japan, show the diversity in origin of the different genotypes prevalent in Pakistan., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The recommended standard therapeutic regimen for chronic hepatitis patients with hepatitis C virus (HCV) genotype 3 is pegylated interferon plus ribavirin for 24 weeks. The aim of the present study was to evaluate treatment efficacy and variables predictive of treatment success, interactions among variables contributing to a response to therapy, and the utility of the rapid virological response (RVR; week 4 virological response) to predict treatment outcomes in HCV genotype 3-infected patients in routine clinical practice., Methods: We prospectively studied baseline and during-treatment factors associated with a sustained virological response (SVR) in HCV genotype 3-infected patients who received pegylated interferon alfa-2a (PEG-IFN α2a) 180 μg/week plus ribavirin 800 mg daily for 24 weeks and who were followed for 24 weeks after the completion of treatment., Results: Four hundred and twenty-six treated patients were included in the analysis; 320 (75.1%) showed an SVR. The following factors were assessed for their ability to predict SVR by means of univariable and multivariable logistic regression analysis: patient age, sex, pre-treatment viral load, pre-treatment alanine aminotransferase (ALT), body mass index (BMI), and RVR. Four factors - age, pre-treatment viral load, pre-treatment ALT, and RVR - were statistically significant predictors of SVR (p<0.05) in the univariable analysis. Factors showing a significant association with SVR were assessed by multivariable logistic regression analysis. In the multivariable analysis, independent factors associated with SVR were the attainment of RVR (odds ratio (OR) 11, 95% confidence interval (CI) 6.15-20.69; p<0.0001), patient age ≤40 years (OR 4.2, 95% CI 2.30-7.96, p<0.0001), and a low pre-treatment viral load (≤8 × 10(5) IU/ml; OR 3.4, 95% CI 1.87-6.25; p<0.0001). The effect of RVR in patients aged >40 years was more pronounced than in those aged ≤40 years: 81.1% of patients aged >40 years who achieved an RVR had an SVR, whereas only 7.5% of patients aged >40 years who did not achieve an RVR had an SVR (p<0.05)., Conclusions: RVR is an independent variable that is predictive of SVR. Moreover older patients (>40 years) who achieve an RVR are likely to have an SVR, while patients who do not achieve an RVR and who have a high pre-treatment viral load (>8 × 10(5) IU/ml) are unlikely to have an SVR., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to evaluate the prognostic significance of neurological manifestations in falciparum malaria., Methods: We analyzed adult patients with malaria admitted from 2001 to 2003, diagnosed by asexual forms of Plasmodium falciparum in peripheral blood films and identified cases of malaria with neurological involvement. A patient was classified as having neurological involvement if they reported or had one or more of the following symptoms; headache, altered mental status, seizures, neck rigidity, brisk reflexes, cranial neuropathy and hyper or hypotonia., Results: A total of 454 patients were included in the study. Out of these, 123 (27%) were diagnosed as complicated (severe) malaria and 331 (73%) as uncomplicated malaria at admission. Overall 70 (15.4%) patients had evidence of neurological involvement at initial evaluation. Twenty-seven patients out of 123 (22%) with complicated malaria and 43 patients out of 331 (13%) with uncomplicated malaria had neurological involvement. Over all, 16 (4%) patients died, 13 (11%) had complicated malaria (n=123) and 3 (1%) had uncomplicated malaria (n=381). Mortality in patients having neurological involvement (n=70) was 9 (13%) as compared to 7 (2%) in patients with malaria having no neurological involvement (n=384). This difference was statistically significant (p=0.012). Seizure was identified as predictor of mortality on Univariate analysis [OR 5.091 (1.835-14.121)]., Conclusion: Fifteen percent of patients with falciparum malaria admitted to our hospital had neurological symptoms and neurological involvement was associated with increased mortality., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Purpose: Bloodstream infection remains a major cause of morbidity and mortality in patients undergoing treatment for cancer. Severe infections due to Gram-negative bacilli & staphylococci are common in cancer patients. Altered gut flora because of frequent antibiotic administration and damage of epithelial surfaces contribute to the development of infection. To access the use of new potent antibiotics against bloodstream infection in cancer patients and to determine the cross resistance of Gram-negative bacterial strains., Materials and Methods: We studied the bacterial spectrum & antimicrobial susceptibility pattern of cephalosporins, fluoroquinolones, carbapenems and aminoglycosides against Gram-negative bacterial strains in cancer patients. The susceptibility was determined by broth dilution method according to National Committee for Clinical Laboratory Standards (NCCLS) now called Clinical Laboratory Standards Institute (CLSI) during study period (July 2006 to Jan 2007)., Results: A total of 60 Gram-negative bacterial blood cultures were examined. Among these, Pseudomonas aeruginosa was the most common (38%). The Minimum Inhibitory Concentration at which 50% (MIC 50 ) and 90% (MIC 90 ) of Enterobacteriaceae and P. aeruginosa inhibited were found. Resistance in P.aeruginosa against cefepime, meropenem, ciprofloxacin, ceftriaxone, tobramycin, cefoperazone and imipenem was 60%, 13%, 80%, 67%, 40%, 90% and 10% respectively while for Enterobacteriaceae 80%, 20%, 88%, 72%, 20%, 90% and four per cent resistance was observed. Meropenem was found to be the most effective antimicrobial against Gram-negative bacteria., Conclusion: High resistance observed in this study warrants the needs of surveillance of resistant pattern of antimicrobial agents. Due to increased level of drug resistance, carbapenem would be a prudent choice in high- risk cases.

Podocytes are a crucial cell type in the kidney and play an important role in the pathology of glomerular kidney diseases like membranous nephropathy (MN). The identification of new factors involved in the progression of glomerular kidney diseases is of great importance to the development of new strategies for the treatment of renal injury. Here we demonstrate that CXCL16 and ADAM10 are constitutively expressed in human podocytes in normal renal tissue. Proinflammatory cytokines like interferon-gamma and tumor necrosis factor-alpha induced the expression of cellular CXCL16 and the release of its soluble form from human podocytes. Using different metalloproteinase inhibitors, we provide evidence that ADAM10 is involved in the interferon-gamma- and tumor necrosis factor-alpha-induced shedding of CXCL16 from human podocytes. In addition, ADAM10 knockdown by siRNA significantly increased both CXCL16 levels and, surprisingly, its ADAM17-mediated release. Notably, targeting of CXCL16 in human podocytes both decreased the chemotaxis of CXCR6-expressing T cells and strongly reduced oxidized low-density lipoprotein uptake in human podocytes. Importantly, in kidney biopsies of patients with MN, increased glomerular CXCL16 expression was accompanied by high levels of oxidized low-density lipoprotein and decreased expression of ADAM10. In addition, we found increased glomerular ADAM17 expression in patients diagnosed with MN. In summary, we presume important roles for CXCL16, ADAM10, and ADAM17 in the development of MN, suggesting these proteins as new therapeutic targets in this glomerular kidney disease.

Gankyrin is an oncoprotein commonly overexpressed in hepatocellular carcinomas. It interacts with multiple proteins and accelerates degradation of tumor suppressors Rb and p53. Since gankyrin consists of 7 ankyrin repeats and is structurally similar to IkappaBs, we investigated its interaction with NF-kappaB. We found that gankyrin directly binds to RelA. In HeLa and 293 cells, overexpression of gankyrin suppressed the basal as well as TNFalpha-induced transcriptional activity of NF-kappaB, whereas down-regulation of gankyrin increased it. Gankyrin did not affect the NF-kappaB DNA-binding activity or nuclear translocation of RelA induced by TNFalpha in these cells. Leptomycin B that inhibits nuclear export of RelA suppressed the NF-kappaB activity, which was further suppressed by gankyrin. The inhibitory effect of gankyrin was abrogated by nicotinamide as well as down-regulation of SIRT1, a class III histone deacetylase. Thus, gankyrin binds to NF-kappaB and suppresses its activity at the transcription level by modulating acetylation via SIRT1.

The effects of Ginkgo biloba extract (EGb 761) and L-carnitine on bleomycin (BLM)-induced lung fibrosis were studied in rats. BLM (cumulative dose of 180 mgkg(-1)) was given intraperitoneally (i.p.) three times weekly for 4 consecutive weeks. Treatment with BLM enhanced the responsiveness of isolated pulmonary arterial rings to serotonin (5-HT), significantly increased the normal serum level of tumour necrosis factor (TNF-alpha) by approximately 105% and markedly elevated the level of lipid peroxide (LPO) and collagen content in the lung homogenates by 34 and 83%, respectively. EGb 761 (100 mgkg(-1) ), given in drinking water for the whole study period, totally abolished the BLM-induced alterations in the measured biochemical and pharmacological parameters. Meanwhile, L-carnitine (500 mg kg(-1) ), administered in drinking water, significantly decreased the BLM-induced elevations of serum TNF-alpha, LPO level in lung tissues and the enhanced responsiveness of pulmonary arterial rings to 5-HT. However,L-carnitine did not reduce the increase in the collagen content produced by BLM. The results of the present study indicate the beneficial effects of EGb 761 and L-carnitine against lung toxicity induced by BLM treatment. Furthermore, the present data shows the advantageous use of EGb 761 as a protective agent in BLM-induced lung fibrosis under the experimental circumstances.

The survival of 117 patients with carcinoma of the prostate treated with radiation at SUNY-Health Science Center at Brooklyn and Kings County Hospital Center was analyzed according to their pretreatment method of diagnosis. Sixty-four patients (54.7%) underwent a transurethral resection of the prostate (TURP) for obstructive symptoms prior to definitive therapy, while 53 patients (45.3%) were diagnosed with needle biopsy. The overall 5-year survival rate was 46% in the needle biopsy group and 38% in the TURP group. Black and white patients with high Gleason scores (7 to 10) and black patients with low-grade tumors who underwent TURP had an adverse 5-year survival rate compared with those patients diagnosed by needle biopsy. The 5-year survival rate of patients with high Gleason scores comparing needle and TURP was 37% versus 16%. The 5-year survival rate of black patients with low-grade tumors comparing needle biopsy versus TURP was 50% and 22%, respectively, although not statistically significant because of the small sample size. When evaluated by stage, there was no difference in survival rates of TURP versus needle biopsy. Black patients who underwent TURP had a 28% 5-year survival rate compared with a 44% 5-year survival rate in white TURP patients. This analysis reveals that black and white patients with high-grade tumors and black patients, even with low-grade tumors, may have a lower survival rate if they undergo TURP prior to radiation, but this may be due to higher stage and larger volume disease in these patients.

Effects of solvent composition and ligand variation on the retention of organometallic compounds have been studied using an amino, an octadecylsilica (ODS) and a beta-cyclodextrin (beta-CD) bonded phase column in either a normal-phase or a reversed-phase mode. The retention behavior for the organometallic compounds with the amino column can be rationalized using the displacement model. The "apparent" molecular areas are greater for compounds capable of strong hydrogen bonding. The retention in the ODS column roughly follows an argument based on the expected solubility behavior while mixed retention mechanisms are involved for the solubility behavior while mixed retention mechanisms are involved for the beta-CD column, i.e. both inclusion process and solubility or solvophobic interactions are possibly operative.