Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

The role of T-cell protein tyrosine phosphatase in epithelial carcinogenesis

T-cell protein tyrosine phosphatase (TC-PTP, encoded by PTPN2) is a non-receptor PTP that is mostly highly expressed in hematopoietic tissues. TC-PTP modulates a variety of physiological functions including cell cycle progression, cell survival and proliferation, and hematopoiesis through tyrosine dephosphorylation of its target substrates, such as EGFR, JAK1, JAK3, STAT1, and STAT3. Studies with whole or tissue-specific loss of TC-PTP function transgenic mice have shown that TC-PTP has crucial roles in the regulation of the immune response, insulin signaling, and oncogenic signaling. More recently, generation of epidermal-specific TC-PTP-deficient mice for use in multistage skin carcinogenesis bioassays demonstrated that TC-PTP suppresses skin tumor formation by negatively regulating STAT3 and AKT signaling. Further investigation showed that TC-PTP also minimizes UVB-induced epidermal cell damage by promoting apoptosis through the negative regulation of Flk-1/JNK signaling. These findings provide major evidence for a tumor suppressive function for TC-PTP against environment-induced skin cancer. Here, we will discuss TC-PTP, its substrates, and its functions with an emphasis on its role in skin carcinogenesis

Electrosurgical bipolar vessel sealing for a standing flank ovariectomy in beef heifers

Traditional ovariectomy techniques for heifers (e.g. colpotomy) have adverse effects ranging from hemorrhage to mortality. Electrosurgical bipolar vessel sealing devices offer a superior ligation of ovarian pedicle and associated structures. In ruminants, standing flank laparotomy has been used for abdominal visibility. We performed ovariectomy in 2 companion beef heifers via a unilateral flank approach, combined with electrosurgical ligation. Surgeries were performed in standing animals, under local anesthesia, with no observed short- or long-term adverse effects. This technique is worth considering for cases where the security of electrosurgical ligation combined with the accessibility of a flank laparotomy are desired. Additional research is needed to determine the viability of the technique for cattle of various ages and breeds

Overexpression of TC-PTP in murine epidermis attenuates skin tumor formation

T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, has been shown to function as a tumor suppressor during skin carcinogenesis. In the current study, we generated a novel epidermal-specific TC-PTP-overexpressing (K5HA.Ptpn2) mouse model to show that TC-PTP contributes to the attenuation of chemically induced skin carcinogenesis through the synergistic regulation of STAT1, STAT3, STAT5, and PI3K/AKT signaling. We found overexpression of TC-PTP increased epidermal sensitivity to DMBA-induced apoptosis and it decreased TPA-mediated hyperproliferation, coinciding with reduced epidermal thickness. Inhibition of STAT1, STAT3, STAT5, or AKT reversed the effects of TC-PTP overexpression on epidermal survival and proliferation. Mice overexpressing TC-PTP in the epidermis developed significantly reduced numbers of tumors during skin carcinogenesis and presented a prolonged latency of tumor initiation. Examination of human papillomas and squamous cell carcinomas (SCCs) revealed that TC-PTP expression was significantly reduced and TC-PTP expression was inversely correlated with the increased grade of SCCs. Our findings demonstrate that TC-PTP is a potential therapeutic target for the prevention of human skin cancer given that it is a major negative regulator of oncogenic signaling

Innovative treatments for multiple myeloma in adults who are not candidates for stem transplantation

In the reviewed article, we evaluated the different innovative therapeutic options for the treatment of multiple myeloma in patients who are not candidates for stem cell transplantation. Multiple myeloma (MM) is a malignant neoplasm whose incidence is increasing in developed countries. It represents around 1% of neoplastic diseases and 13% of hematologic cancers. It arises from an asymptomatic proliferation of premalignant monoclonal plasma cells derived from B cells after they pass through the germinal center stage in various genetic steps and microenvironmental changes. Although in this study we discuss various therapeutic options that seem promising, we must keep in mind that these still require further research for their application in order to reduce the adverse effects that some of them may present.

Evaluating the Bias of Two Point-of-Care Glucometers for Calves and Ewes: Awareness for Ruminant Practitioners

(1) Background: Multiple point-of-care (POC) glucometers are in use in veterinary medicine, but few are compared to each other. This leaves the potential for clinicians to be unaware of the effect of bias when comparing results from different POC glucometers. (2) Methods: Samples from healthy calves and ewes were simultaneously compared with two POC veterinary glucometers, the Precision Xtra and the AlphaTrak2, under both the “canine” and “feline” settings. The results of each sample were statistically analyzed with linear regression and Bland–Altman analysis. (3) Results: 170 samples from healthy calves and 108 samples from healthy ewes were available for comparison. Calves: The AT2 consistently overestimated blood glucose concentrations when compared to the PX device with the calves. Correlationt with the PX was r = 0.8496 (canine setting) and r = 0.8861 (feline setting). Both the canine and feline settings demonstrated a consistent bias (41.11 and 33.64 mg/dL, respectively). Ewes: The AT2 consistently overestimated blood glucose concentrations when compared to the PX device with the ewes. Correlation with the PX was R = 0.4710 (canine setting) and R = 0.7269 (feline setting). Both the canine and feline settings demonstrated a consistent bias (21.23 and 14.54 mg/dL, respectively). (4) Clinicians should be aware of the potential for consistent bias when evaluating calf and sheep blood glucose concentrations as the AT2 device, at both settings, overestimated blood glucose compared to the previously validated PX. This reliability appears to change when the values are farther from the normal ranges, which should be considered when making clinical decisions based on data from these devices

Piston core record of Late Paleogene (31 Ma) to recent seafloor hydrothermal activity in the Southwest Pacific Basin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94790/1/palo1386.pd

Evidence for Changes in Subsurface Circulation in the Late Eocene Equatorial Pacific from Radiolarian-Bound Nitrogen Isotope Values

Microfossil-bound organic matter represents an important archive of surface ocean environmental information. Sedimentary nitrogen (N) isotope reconstructions of surface nitrate consumption and nitrogen source changes are made using fossil diatom (autotrophs) and planktic foraminiferal (heterotrophs)-bound organic matter with success. However, because diatoms and planktic foraminifera are poorly preserved and sedimentary organic matter content is near zero during the late Eocene, our ability to examine nutrient dynamics across this important climate transition is limited. Here we present new data exploring the use of N isotope records from radiolarian tests. A comparison of surface ocean nitrate and core top bulk and radiolarian N isotope values (as δ15N) from the equatorial Pacific indicates that radiolarian-N records δ15N variability with fidelity but that a significant offset exists between bulk sedimentary and diatom δ15N values and those measured from radiolarians (~7.1 ± 1.1‰). A downcore profile of radiolarian δ15N values is compared to siliceous microfossil assemblage changes across the Eocene-Oligocene boundary. Average of radiolarian-bound δ15N values is 0.5 ± 2.0‰, which, when corrected using the offset derived from the modern surface samples, suggests that the mean nitrogen isotopic composition of the early Cenozoic eastern Pacific was not significantly different from today. The overall trend, of decreasing δ15N values with decreasing export productivity, is consistent with either a regional decline in pelagic denitrification or a large-scale change in nutrient sources to the eastern equatorial Pacific (EEP), both linked to the cooling climate and changing intermediate water circulation. Decreasing/low δ15N values cooccur with high radiolarian species turnover at ~35.5 and 34 Ma, suggestive of a significant ecological change in the EEP, consistent with cooling and water mass distribution changes. The preliminary results suggest that radiolarian-bound organic nitrogen represents another promising archive and underscores the fact that the different microfossil fractions must be separated to ensure robust results

Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis

<p>Abstract</p> <p>Background</p> <p>Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels.</p> <p>Methods</p> <p>Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns) were classified as SE or SS by immunohistochemistry (IHC) using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF) and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS) program was used for various statistical analyses.</p> <p>Results</p> <p>The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8%) and PLAP-/PAS- SSs were 15/23 (61.2%). All SE cases (8/8, 100%) were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%), 9 diffuse (9/15, 60%), and 4 intratubular/diffuse (4/15, 26.7%) types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion.</p> <p>Conclusion</p> <p>In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels were a correlated vascular parameter. Although metastasis of canine seminomas has rarely been reported, our results support that canine SE could have high metastatic potential similar to the human counterpart. Further studies are required to clarify the relationship between canine SE and clinical data with metastatic factors.</p