Anti-tumor necrosis factor-alpha therapy during murine Klebsiella pneumoniae bacteremia: increased mortality in the absence of liver injury.

Klebsiella pneumoniae is a leading cause of gram-negative bacterial pneumonia, often resulting in bacteremia concurrent with the localized pulmonary infection. The beneficial role of tumor necrosis factor (TNF)-alpha during pulmonary infection has been well documented; however, consequences of TNF-alpha production during systemic bacterial infection are controversial. A murine model of K. pneumoniae was developed to address this important issue. Liver-associated TNF-alpha mRNA was induced within 30 min after intravenous bacterial inoculation and remained elevated through 6 h before returning to near-baseline at 24 h postinfection. Intravenous K. pneumoniae infection induced liver cellular injury that was completely ablated when mice were pretreated with a neutralizing anti-TNF-alpha antibody. Interestingly, this reduction in liver injury failed to translate into improved survival. Mice receiving anti-TNF-alpha continued to succumb to the infection even out to day 10 postinfection. Bacterial clearance after TNF-alpha neutralization was significantly impaired at later time points during infection. Correlating with impaired bacterial clearance was diminished production of liver-associated MIP-2, MIP-1alpha, MCP-1, and interferon-gamma. Further evidence of diminished antibacterial immune responses was noted when the activational status of splenic natural killer cells in anti-TNF-alpha-treated mice was examined 24 h postinfection. Natural killer cells displayed decreased CD69 expression. Combined, these data indicate that the beneficial effects of TNF-alpha during systemic K. pneumoniae infection outweigh the detrimental effects of TNF-alpha-mediated hepatocyte cellular injury. Anti-TNF-alpha therapy, although preventing liver injury during blood-borne bacterial infection, results in a dampened anti-bacterial host response, resulting in decreased bacterial clearance and overall survival

Analisis Resiko Perbankan pada Bankaltim

Bankaltim bergerak dibidang jasa keuangan sebagaimana bank lainnya melakukan kegiatan funding, lending dan services tentunya melayani berbagai lapisan masyarakat, berharap tetap survival. Survivalnya bankaltim terpelihara jika bankaltim mampu mempertahankan dan menambah nasabah baru, dimana kunci suksesnya adalah memelihara kepercayaan dalam setiap pelaksanaan funding, lending dan services. Kepercayaan ini sangat ditentukan oleh kemampuan bank dalam mengelola resiko perbankan baik dari aspek likuiditas maupun dari aspek solvabilitas. Berpijak pada dasar pemikiran tersebut, maka rumusan masalah penelitian ini adalah Apakah penelitian adalah sebagai berikut: Apakah resiko-resiko perbankan Bank Pembangunan Daerah Kalimantan Timur dari aspek likuiditas dan aspek solvabilitas pada tahun 2012 sampai dengan tahun 2014 semakin meningkat ?”Apakah Bank Pembangunan Daerah Kalimantan Timur telah memenuhi ketentuan Modal Inti Bank ?”Teori utama yang digunakan dalam penelitian ini adalah akuntansi perbankan yang berfokus pada resiko-resiko dari aspek likuiditas dalan solvabilitas serta modal inti. Berdasarkan rumsan masalah dan dasar teori yang digunakan dirumuskan hipotesis penelitian berikut: Resiko-resiko perbankan Bank Pembangunan Daerah Kalimantan Timur dari aspek likuiditas maupun dari aspek solvabilitas pada tahun 2013 meningkat dibandingkan dengan kondisi pada tahun 2013, Resiko-resiko perbankan Bank Pembangunan Daerah Kalimantan Timur dari aspek likuiditas maupun dari aspek solvabilitas pada tahun 2014 mengalami penurunan dibandingkan dengan kondisi pada tahun 2013.Bank Pembangunan Daerah Kalimantan Timur telah memenuhi modal bank sesuai Kriteria modal inti Bank.Alat analisis yang digunakan analisis resiko perbankan dari aspek likuiditas dan solvabilitas yakni Investment Risk Ratio, Liquidity Risk Ratio, Credit Risk Ratio, Deposit Risk Ratio, Risk Assets Ratio, Secondary Risk Ratio, Capital Adequacy Ratio dan aspek keuangan yang mendukung yaitu Modal Inti bank. Hasil analisis menunjukkan bahwa Investment Risk Ratio, Liquidity Risk Ratio, Credit Risk Ratio, Deposit Risk Ratio, Risk Assets Ratio, Secondary Risk Ratio, Capital Adequacy Ratio Bankaltim dapat dikategorikan meningkat pada tahun 2013 dan cenderung menurun pada tahun dengan 2014, namun masih dalam batas yang wajar menunjukkan bahwa Bankaltim likuid dan solvabel dalam memenuhi kewajiban terhadap deposannya. Hasil analisis juga menunjukkan bahwa Bankaltim memiliki ketersediaan Modal Inti yang memenuhi bahkan melampaui ketentuan dalam PeraturanPerbankan.Temuan penelitian ini mendukung beberapa hipotesis, tetapi juga ada hipotesis penelitian yang ditola

Photocatalytic hydrogen production using polymeric carbon nitride with a hydrogenase and a bioinspired synthetic Ni catalyst.

Solar-light-driven H2 production in water with a [NiFeSe]-hydrogenase (H2ase) and a bioinspired synthetic nickel catalyst (NiP) in combination with a heptazine carbon nitride polymer, melon (CN(x)), is reported. The semibiological and purely synthetic systems show catalytic activity during solar light irradiation with turnover numbers (TONs) of more than 50,000 mol H2(mol H2ase)(-1) and approximately 155 mol H2 (mol NiP)(-1) in redox-mediator-free aqueous solution at pH 6 and 4.5, respectively. Both systems maintained a reduced photoactivity under UV-free solar light irradiation (λ>420 nm).This is the final version. It was first published in Angewandte Chemie International Edition at http://onlinelibrary.wiley.com/doi/10.1002/anie.201406811/abstract

A new nanocrystalline diamond-based biosensor for the detection of cardiovascular risk markers

In this paper, a new method to probe associative interactions of C-reactive protein (CRP) antigen with CRP antibody immobilized on a gold-interdigitated diamond electrodes was investigated. The CRP antigen detection was performed by capacitive/dielectric-constant measurements. Our results showed that the dynamic detection range using optimized conditions for a given antibody concentration (100 μg/ml) was found to be in the range 25-800 ng/ml of CRP-antigen. Biosensor developed in this study can be potentially used for detection of elevated CRP levels in suspected subjects for early diagnosis

Transhiatal esophagectomy in the profoundly obese: implications and experience.

BACKGROUND: Historically, obesity contraindicated an abdominal approach to the esophagogastric junction. The technique of transhiatal esophagectomy (THE) evolved without specific regard to body habitus. The dramatic increase in obese patients requiring an esophagectomy for complications of reflux disease prompted this evaluation of the impact of obesity on the outcomes of esophagectomy to determine whether profound obesity should contraindicate the transhiatal approach. METHODS: We used our Esophagectomy Database to identify 133 profoundly obese patients (body mass index [BMI] > or = 35 kg/m2) from among 2176 undergoing a THE from 1977 to 2006. This group was matched to a randomly selected, non-obese (BMI, 18.5 to 30 kg/m2) control population of 133 patients. Intraoperative, postoperative, and long-term follow-up results were compared retrospectively. RESULTS: Profoundly obese patients had significantly greater intraoperative blood loss (mean, 492.2 mL versus 361.8 mL, p = 0.001), need for partial sternotomy (18 versus 3, p = 0.001), and frequency of recurrent laryngeal nerve injury (6 versus 0, p = 0.04). The two groups did not differ significantly in the occurrence of chylothorax, wound infection, or dehiscence rate; length of hospital stay or need for intensive care unit stay; or hospital or operative mortality. Follow-up results for dysphagia, dumping, regurgitation, and overall functional score were also comparable between the two groups. CONCLUSIONS: With appropriate instrumentation, transhiatal esophagectomy in obese patients has similar morbidity and outcomes as in non-obese patients. Obesity, even when profound, does not contraindicate a transhiatal esophagectomy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/6/Scipione 2007.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/5/Benign BMI Control.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/4/Benign BMI CS07.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/3/CA BMI Control no pt id.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/2/CA BMI 35 CS.tx

Incorporation of dUTP does not mediate mutation of A:T base pairs in Ig genes in vivo

Activation-induced cytidine deaminase (AID) protein initiates Ig gene mutation by deaminating cytosines, converting them into uracils. Excision of AID-induced uracils by uracil-N-glycosylase is responsible for most transversion mutations at G:C base pairs. On the other hand, processing of AID-induced G:U mismatches by mismatch repair factors is responsible for most mutation at Ig A:T base pairs. Why mismatch processing should be error prone is unknown. One theory proposes that long patch excision in G1-phase leads to dUTP-incorporation opposite adenines as a result of the higher G1-phase ratio of nuclear dUTP to dTTP. Subsequent base excision at the A:U base pairs produced could then create non-instructional templates leading to permanent mutations at A:T base pairs (1). This compelling theory has remained untested. We have developed a method to rapidly modify DNA repair pathways in mutating mouse B cells in vivo by transducing Ig knock-in splenic mouse B cells with GFP-tagged retroviruses, then adoptively transferring GFP+ cells, along with appropriate antigen, into primed congenic hosts. We have used this method to show that dUTP-incorporation is unlikely to be the cause of AID-induced mutation of A:T base pairs, and instead propose that A:T mutations might arise as an indirect consequence of nucleotide paucity during AID-induced DNA repair

Skill Mix and Patient Outcomes: A Multi-country Analysis of Heart Disease and Breast Cancer Patients

Policymakers are becoming aware that increasing the size of the healthcare workforce is no longer the most viable way to address the increasing demand for healthcare. Consequently, a focus of recent healthcare workforce reform has been extending existing roles and creating new roles for health professionals. However, little is known of the influence on outcomes from this variation in labour inputs within hospital production functions. Using a unique combination of primary and administrative data, this paper provides evidence of associations between the composition of care delivery teams and patient outcomes. The primary data enabled the construction of a task component-based measure of skill mix. This novel measure of skill mix has the advantage of capturing how workforce planning can restructure the relative input of nurses or physicians into task components while keeping the overall level of staff fixed. The analysis focuses on specific care pathways and individual hospitals, thus controlling for an under-investigated source of heterogeneity. Additionally, stratifying by country (England, Scotland, and Norway) enabled analysis of skill mix within different health systems. We provide evidence that variations in labour inputs within the breast cancer and heart disease care pathways are associated with both positive and adverse outcomes. The results illustrate the scope for substitution of task components within care pathways as a potential method of healthcare reform

Monitoring regulatory T cells as a prognostic marker in lung transplantation

Lung transplantation is the major surgical procedure, which restores normal lung functioning and provides years of life for patients suffering from major lung diseases. Lung transplant recipients are at high risk of primary graft dysfunction, and chronic lung allograft dysfunction (CLAD) in the form of bronchiolitis obliterative syndrome (BOS). Regulatory T cell (Treg) suppresses effector cells and clinical studies have demonstrated that Treg levels are altered in transplanted lung during BOS progression as compared to normal lung. Here, we discuss levels of Tregs/FOXP3 gene expression as a crucial prognostic biomarker of lung functions during CLAD progression in clinical lung transplant recipients. The review will also discuss Treg mediated immune tolerance, tissue repair, and therapeutic strategies for achieving in-vivo Treg expansion, which will be a potential therapeutic option to reduce inflammation-mediated graft injuries, taper the toxic side effects of ongoing immunosuppressants, and improve lung transplant survival rates