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Background: Although pancreaticoduodenectomy (PD) is feasible in patients greater than or equal to 80 years, little is known about the potential strain on resource utilization., Methods: Outcomes and inpatient charges were compared across age cohorts (I: ≤70, II: 71 to 79, III: ≥80 years) in 99 patients who underwent PD (2005 to 2013) at our institution. The generalized linear modeling approach was used to estimate the impact of age., Results: Perioperative complications were equivalent among cohorts. Increasing age was associated with intensive care unit use, increased length of stay (LOS), and the likelihood of discharge to a skilled facility. After controlling for covariates, hospital charges were significantly higher in Cohort III (P = .006) and Cohort II (P = .035) when compared with Cohort I. However, hospital charges between Cohorts II and III were equivalent (P = .374). Complications (P = .005) and LOS (P < .001) were associated with higher hospital charges., Conclusions: Increasing age was associated with increased intensive care unit, LOS, and discharge to skilled facilities. However, octogenarians had equivalent PD charges and outcome measures when compared with septuagenarians and future studies should validate these findings in larger national studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

An efficient, fast and green method for synthesis of Carbon dots (C-dots) using natural precursor Citrus limone under ultrasonic condition is demonstrated. Such as-synthesized C-dots were further purified using Sucrose density gradient centrifugation method (SDGC) which resulted in the separation of water-soluble, photo luminescent, monodispersed, highly photostable and chemically stable C-dot fractions (F1 and F2). They possess very small size (5-20 nm) as evidenced by High angle annular dark field-Scanning Transmission electron microscopy (HAADF-STEM) and very strong luminescence as shown by fluorescence spectroscopic studies. Cytocompatibility and bio imaging properties of both the fractions (F1 and F2) were then studied on Hep-2 cells. Quantum yield of F1 and F2 fraction was found to be 12.1 and 15 %, respectively.

Background: We compared outcomes and postpancreatectomy quality of life (QOL) in paired cohorts of patients undergoing conventional open pancreaticoduodenectomy (OPD) or laparoscopic-assisted pancreaticoduodenectomy (LAPD)., Methods: Comparative analysis of QOL was performed in a matched cohort of 53 patients after OPD or LAPD between 2010 and 2013. The Medical Outcomes Study Short Form-36 Health Survey and the Karnofsky score were used., Results: Physical component score, mental component score, and Karnofsky scores were calculated at multiple time points for OPD (n = 25) and LAPD (n = 28). Operative times, complications, and readmission rates were equivalent. Time to starting adjuvant therapy trended toward clinical importance in LAPD (61 vs 110 days, P = .0878). Duration of stay was less in LAPD (7.10 vs 9.44 days, P = .02). LAPD had a superior QOL centered on functional status compared with OPD (physical component score 49.09 vs 38.4, P = .04; Karnofsky 92.22 vs 66.92%, P = .003). These statistical differences were not observed beyond 6 months., Conclusion: LAPD provided a more favorable QOL within the first 6 months and shorter length of stay compared with conventional OPD. LAPD may serve as an alternative operative therapy to potentially minimize delays in receipt of and enhance tolerability of adjuvant therapies., (Copyright © 2014 Mosby, Inc. All rights reserved.)

The mammalian pyruvate dehydrogenase complex (PDC) is a multi-component mitochondrial enzyme that plays a key role in the conversion of pyruvate to acetyl-CoA connecting glycolysis to the citric acid cycle. Recent studies indicate that targeting the regulation of PDC enzymatic activity might offer therapeutic opportunities by inhibiting cancer cell metabolism. To facilitate drug discovery in this area, a well defined PDC sample is needed. Here, we report a new method of producing functional, recombinant, high quality human PDC complex. All five components were co-expressed in the cytoplasm of baculovirus-infected SF9 cells by deletion of the mitochondrial localization signal sequences of all the components and E1a was FLAG-tagged to facilitate purification. The protein FLAG tagged E1a complex was purified using FLAG-M2 affinity resin, followed by Superdex 200 sizing chromatography. The E2 and E3BP components were then Lipoylated using an enzyme based in vitro process. The resulting PDC is over 90% pure and homogenous. This non-phosphorylated, lipoylated human PDC was demonstrated to produce a robust detection window when used to develop an enzyme coupled assay of PDHK., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Pen needles (PNs) are essential for insulin injections using pen devices. PN characteristics affect patients' injection experience., Objective: The goal of this study was to evaluate the impact of a new extra-thin wall (XTW) PN versus usual PNs on overall patient preference, ease of injection, perceived time to complete the full dose, thumb button force to deliver the injection, and dose delivery confidence in individuals with diabetes mellitus (DM). Subjects injected insulin with the KwikPen(TM) (Eli Lilly and Company, Indianapolis, Indiana), SoloSTAR(®) (sanofi-aventis U.S. LLC, Bridgewater, New Jersey), and FlexPen(®) (Novo Nordisk A/S, Bagsvaerd, Denmark) insulin pens, and included some with impaired hand dexterity., Methods: We first performed quantitative testing of XTW and comparable PNs with the 3 insulin pens for thumb force, flow rate, and time to deliver medication. A prospective, randomized, 2-period, open-label, crossover trial was then conducted in patients aged 35 to 80 years with type 1 or type 2 DM who injected insulin by pen for ≥2 months, with at least 1 daily dose ≥10 U. Patients who used 4- to 8-mm length PNs with 31- to 32-G diameter were randomly assigned to use their current PN or the same/similar size XTW PN at home for ~1 week and the other PN the second week. They completed several comparative 150-mm visual analog scales and direct questions at the end of period 2., Results: XTW PNs had statistically significant better performance for each studied PN characteristic (thumb force, flow, and time to deliver medication) for all pens combined and each individual pen brand (all, P ≤ 0.05). Of 216 patients randomized to study groups (80, SoloSTAR; 77, FlexPen; 59, KwikPen), 209 completed both periods; 198 were evaluable. Baseline characteristics revealed a mean (SD) age of 60.8 (9.3) years, insulin pen use duration of 4.3 (4.1) years, and mean total daily dose of 75.1 (52.3) U (range, 10-420 U). Approximately 50% of patients were female; 81.5% were white and 14.8% were black; and 89.8% had type 2 DM. Nearly 99% used a single PN: 8 mm, 49.5%; 5 mm, 24.1%; 6 mm, 14.4%; and 4 mm, 12.0%. Patients rated the XTW PNs (mean [95% CI]) as preferable by a mean of 31.9 mm (27.2-36.6), P < 0.001; XTW PNs required less thumb force, less time to inject the dose, and were rated as providing greater confidence in full dose delivery by 28.4 mm (23.7-33.2), 21.7 mm (17.0-26.4), and 24.4 mm (19.7-29.1), respectively; all, P < 0.001. Results were similar for each of the 3 pens, those with impaired hand dexterity, and for all users of 4-mm PNs. Skin leakage and insulin dripping from the needle tip were rated as less frequent with the XTW PNs (P < 0.05). The most common adverse events were hypoglycemia in 8.3% and 6.0% of patients using XTW PNs and current PNs (P = NS), respectively; hyperglycemia occurred in 2.9% and 4.1% (P = NS). None of the adverse events was serious or considered device related., Conclusions: XTW PNs were preferred overall, rated as requiring less time and less thumb force to inject, and providing greater confidence in completing a full dose compared with usual PNs in this group of patients with type 1 or type 2 DM. ClinicalTrials.gov identifier: NCT01852136., (Copyright © 2013 The Authors. Published by EM Inc USA.. All rights reserved.)

Signal Transducer and Activator of Transcription 4 (STAT4) is a transcription factor that is activated by IL-12 signaling and promotes Th1-cell differentiation and IFN-γ production. Defective IFN-γ production because of STAT4 mRNA and protein deficiency occurs after autologous stem cell transplantation for lymphoma. In the present study, we investigated the mechanisms of STAT4 deficiency in lymphoma patients. The tumor-bearing state is not responsible, because STAT4 levels were not significantly different in PBMCs obtained from healthy control subjects compared with those from lymphoma patients before treatment. STAT4 protein levels were significantly decreased in PBMCs and T cells obtained from lymphoma patients after standard-dose chemotherapy. Furthermore, treatment of control PBMC cultures or a natural killer cell line with chemotherapy drugs in vitro also resulted in reduced STAT4 protein and diminished, IL-12-induced IFN-γ production. Translation of STAT4 protein was not impaired in chemotherapy-treated cells, whereas the STAT4 protein half-life was significantly reduced. Chemotherapy drugs promoted the ubiquitination and proteasomal degradation of STAT4. Treatment with the proteasome inhibitor bortezomib reversed chemotherapy-induced STAT4 deficiency and defective IFN-γ production. We conclude that acquired STAT4 deficiency in lymphoma patients is a consequence of treatment with chemotherapy, results that have important implications for the design of optimal immunotherapy for lymphoma.

Steady-state kinetic analysis of focal adhesion kinase-1 (FAK1) was performed using radiometric measurement of phosphorylation of a synthetic peptide substrate (Ac-RRRRRRSETDDYAEIID-NH(2), FAK-tide) which corresponds to the sequence of an autophosphorylation site in FAK1. Initial velocity studies were consistent with a sequential kinetic mechanism, for which apparent kinetic values k(cat) (0.052 +/- 0.001 s(-1)), K(MgATP) (1.2 +/- 0.1 microM), K(iMgATP) (1.3 +/- 0.2 microM), K(FAK-tide) (5.6 +/- 0.4 microM), and K(iFAK-tide) (6.1 +/- 1.1 microM) were obtained. Product and dead-end inhibition data indicated that enzymatic phosphorylation of FAK-tide by FAK1 was best described by a random bi bi kinetic mechanism, for which both E-MgADP-FAK-tide and E-MgATP-P-FAK-tide dead-end complexes form. FAK1 catalyzed the betagamma-bridge:beta-nonbridge positional oxygen exchange of [gamma-(18)O(4)]ATP in the presence of 1 mM [gamma-(18)O(4)]ATP and 1.5 mM FAK-tide with a progressive time course which was commensurate with catalysis, resulting in a rate of exchange to catalysis of k(x)/k(cat) = 0.14 +/- 0.01. These results indicate that phosphoryl transfer is reversible and that a slow kinetic step follows formation of the E-MgADP-P-FAK-tide complex. Further kinetic studies performed in the presence of the microscopic viscosogen sucrose revealed that solvent viscosity had no effect on k(cat)/K(FAK-tide), while k(cat) and k(cat)/K(MgATP) were both decreased linearly at increasing solvent viscosity. Crystallographic characterization of inactive versus AMP-PNP-liganded structures of FAK1 showed that a large conformational motion of the activation loop upon ATP binding may be an essential step during catalysis and would explain the viscosity effect observed on k(cat)/K(m) for MgATP but not on k(cat)/K(m) for FAK-tide. From the positional isotope exchange, viscosity, and structural data it may be concluded that enzyme turnover (k(cat)) is rate-limited by both reversible phosphoryl group transfer (k(forward) approximately 0.2 s(-1) and k(reverse) approximately 0.04 s(-1)) and a slow step (k(conf) approximately 0.1 s(-1)) which is probably the opening of the activation loop after phosphoryl group transfer but preceding product release.

Right-sided diverticulitis is difficult to distinguish from other sources of right-sided abdominal pain. Diverticula localized to the right colon occur at a rate of 6.6 to 14 per cent. Two types of diverticula have been described in the right colon on the basis of etiologic and pathologic features: multiple diverticula and solitary diverticulum of the cecum. The most common clinical presentation of right-sided colonic diverticula is an acute inflammatory complication, which is difficult to distinguish from other causes of right iliac fossa pain. We present two case reports on right-sided diverticulitis with one treated surgically and the other treated nonsurgically. The clinical manifestations, differential diagnosis and management options are discussed including a review of the literature.

Background: Pure mucinous carcinoma (PMC) of the breast has a better prognosis than does invasive ductal carcinoma not otherwise specified and is more prevalent in older patients. We investigated the correlation between prognostic indices and clinical outcome in this histologic subset., Methods: A retrospective review was done of patients with PMC treated between 1989 and 1996. Demographic data, pathologic indices of prognosis, axillary nodal status, and outcome were assessed., Results: Out of 6083 cases of breast carcinoma, 30 were PMC. Only 3 of 25 (12%) axillary dissections were positive. The average age of the group with positive nodes was 57 years, as compared to 69.5 years (95% CI; 63.24-75.76) in the group with negative nodes. All the tumors with positive nodes were aneuploid and had a high nuclear grade, compared to a 31.25% aneuploidy rate in the group without nodal disease (P = .058). Negative ER receptors were found in only 2 of 20 (10%) of the patients tested. Both had axillary disease (P = .016). Tumor size did not correlate with axillary metastasis. Two of the 29 patients died from unrelated diseases. The other 27 patients are alive with no evidence of disease., Conclusions: Axillary nodal disease is rare in PMC and correlates with a younger age, aneuploidy, high nuclear grade, or a negative ER receptor status. Sentinel lymph node biopsy may help identify the need for axillary dissection.

Change, challenge, and commitment motivate staff at the University of Miami/Jackson Memorial Medical Center in Miami, Florida, to prepare its health care system for the 21st century. Doctors, nurses, environmental workers, pharmacists, cashiers, nursing assistants, laboratory technologists, and many others are participating on a variety of teams to bring about the changes needed for our delivery system to be competitive.