A rare case of isolated duodenal metastases from hepatocellular carcinoma associated with p53 and ki-67 expression: a case report

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver worldwide. The incidence of HCC is increasing in North America secondary to rises in chronic liver disease from alcohol abuse and viral hepatitis. HCC most commonly metastasizes hematogenously or through lymphatics to the lungs and regional lymph nodes. Involvement of small bowel is rare and typically results from direct invasion and extension. We examined the molecular features related to this extremely rare case of isolated duodenal metastasis of HCC and noted p53 and Ki-67 positive staining. Here, we review the possible molecular and immunohistochemical studies that may aid definitive diagnosis and the evidence for the management of metastatic hepatocellular carcinoma

Uniformization, Calogero-Moser/Heun duality and Sutherland/bubbling pants

Inspired by the work of Alday, Gaiotto and Tachikawa (AGT), we saw the revival of Poincar{\'{e}}'s uniformization problem and Fuchsian equations obtained thereof. Three distinguished aspects are possessed by Fuchsian equations. First, they are available via imposing a classical Liouville limit on level-two null-vector conditions. Second, they fall into some A_1-type integrable systems. Third, the stress-tensor present there (in terms of the Q-form) manifests itself as a kind of one-dimensional "curve". Thereby, a contact with the recently proposed Nekrasov-Shatashvili limit was soon made on the one hand, whilst the seemingly mysterious derivation of Seiberg-Witten prepotentials from integrable models become resolved on the other hand. Moreover, AGT conjecture can just be regarded as a quantum version of the previous Poincar{\'{e}}'s approach. Equipped with these observations, we examined relations between spheric and toric (classical) conformal blocks via Calogero-Moser/Heun duality. Besides, as Sutherland model is also obtainable from Calogero-Moser by pinching tori at one point, we tried to understand its eigenstates from the viewpoint of toric diagrams with possibly many surface operators (toric branes) inserted. A picture called "bubbling pants" then emerged and reproduced well-known results of the non-critical self-dual c=1 string theory under a "blown-down" limit.Comment: 17 pages, 4 figures; v2: corrections and references added; v3: Section 2.4.1 newly added thanks to JHEP referee advice. That classical four-point spheric conformal blocks reproducing known SW prepotentials is demonstrated via more examples, to appear in JHEP; v4: TexStyle changed onl

Heavy fermions and two loop electroweak corrections to b→s+γb\rightarrow s+\gamma

Applying effective Lagrangian method and on-shell scheme, we analyze the electroweak corrections to the rare decay $b\rightarrow s+\gamma$ from some special two loop diagrams in which a closed heavy fermion loop is attached to the virtual charged gauge bosons or Higgs. At the decoupling limit where the virtual fermions in inner loop are much heavier than the electroweak scale, we verify the final results satisfying the decoupling theorem explicitly when the interactions among Higgs and heavy fermions do not contain the nondecoupling couplings. Adopting the universal assumptions on the relevant couplings and mass spectrum of new physics, we find that the relative corrections from those two loop diagrams to the SM theoretical prediction on the branching ratio of $B\rightarrow X_{_s}\gamma$ can reach 5% as the energy scale of new physics $\Lambda_{_{\rm NP}}=200$ GeV.Comment: 30 pages,4 figure

EM-mosaic detects mosaic point mutations that contribute to congenital heart disease.

BackgroundThe contribution of somatic mosaicism, or genetic mutations arising after oocyte fertilization, to congenital heart disease (CHD) is not well understood. Further, the relationship between mosaicism in blood and cardiovascular tissue has not been determined.MethodsWe developed a new computational method, EM-mosaic (Expectation-Maximization-based detection of mosaicism), to analyze mosaicism in exome sequences derived primarily from blood DNA of 2530 CHD proband-parent trios. To optimize this method, we measured mosaic detection power as a function of sequencing depth. In parallel, we analyzed our cohort using MosaicHunter, a Bayesian genotyping algorithm-based mosaic detection tool, and compared the two methods. The accuracy of these mosaic variant detection algorithms was assessed using an independent resequencing method. We then applied both methods to detect mosaicism in cardiac tissue-derived exome sequences of 66 participants for which matched blood and heart tissue was available.ResultsEM-mosaic detected 326 mosaic mutations in blood and/or cardiac tissue DNA. Of the 309 detected in blood DNA, 85/97 (88%) tested were independently confirmed, while 7/17 (41%) candidates of 17 detected in cardiac tissue were confirmed. MosaicHunter detected an additional 64 mosaics, of which 23/46 (50%) among 58 candidates from blood and 4/6 (67%) of 6 candidates from cardiac tissue confirmed. Twenty-five mosaic variants altered CHD-risk genes, affecting 1% of our cohort. Of these 25, 22/22 candidates tested were confirmed. Variants predicted as damaging had higher variant allele fraction than benign variants, suggesting a role in CHD. The estimated true frequency of mosaic variants above 10% mosaicism was 0.14/person in blood and 0.21/person in cardiac tissue. Analysis of 66 individuals with matched cardiac tissue available revealed both tissue-specific and shared mosaicism, with shared mosaics generally having higher allele fraction.ConclusionsWe estimate that ~ 1% of CHD probands have a mosaic variant detectable in blood that could contribute to cardiac malformations, particularly those damaging variants with relatively higher allele fraction. Although blood is a readily available DNA source, cardiac tissues analyzed contributed ~ 5% of somatic mosaic variants identified, indicating the value of tissue mosaicism analyses

Early Ahmed Glaucoma Valve Implantation after Penetrating Keratoplasty Leads to Better Outcomes in an Asian Population with Preexisting Glaucoma

To evaluate the efficacy of Ahmed Glaucoma Valve (AGV) surgery and the optimal interval between penetrating keratoplasty (PKP) and AGV implantation in a population of Asian patients with preexisting glaucoma who underwent PKP.In total, 45 eyes of 45 patients were included in this retrospective chart review. The final intraocular pressures (IOPs), graft survival rate, and changes in visual acuity were assessed to evaluate the outcomes of AGV implantations in eyes in which AGV implantation occurred within 1 month of post-PKP IOP elevation (Group 1) and in eyes in which AGV implantation took place more than 1 month after the post-PKP IOP evaluation (Group 2). Factors that were associated with graft failure were analyzed, and the overall patterns of complications were reviewed. By their final follow-up visits, 58% of the patients had been successfully treated for glaucoma. After the operation, there were no statistically significant differences between the groups with respect to graft survival (p = 0.98), but significant differences for IOP control (p = 0.049) and the maintenance of visual acuity (VA) (p<0.05) were observed. One year after surgery, the success rates of IOP control in Group 1 and Group 2 were 80% and 46.7%, respectively, and these rates fell to 70% and 37.3%, respectively, by 2 years. Factors that were associated with a high risk of AGV failure were a diagnosis of preexisting angle-closure glaucoma, a history of previous PKP, and a preoperative IOP that was >21 mm Hg. The most common surgical complication, aside from graft failure, was hyphema.Early AGV implantation results in a higher probability of AGV survival and a better VA outcome without increasing the risk of corneal graft failure as a result of post-PKP glaucoma drainage tube implantation

Calcium-dependent dynamics of cadherin interactions at cell–cell junctions

Cadherins play a key role in the dynamics of cell–cell contact formation and remodeling of junctions and tissues. Cadherin–cadherin interactions are gated by extracellular Ca^(2+), which serves to rigidify the cadherin extracellular domains and promote trans junctional interactions. Here we describe the direct visualization and quantification of spatiotemporal dynamics of N-cadherin interactions across intercellular junctions in living cells using a genetically encodable FRET reporter system. Direct measurements of transjunctional cadherin interactions revealed a sudden, but partial, loss of homophilic interactions (τ = 1.17 ± 0.06 s^(−1)) upon chelation of extracellular Ca^(2+). A cadherin mutant with reduced adhesive activity (W2A) exhibited a faster, more substantial loss of homophilic interactions (τ = 0.86 ± 0.02 s^(−1)), suggesting two types of native cadherin interactions—one that is rapidly modulated by changes in extracellular Ca^(2+) and another with relatively stable adhesive activity that is Ca^(2+) independent. The Ca^(2+)-sensitive dynamics of cadherin interactions were transmitted to the cell interior where β-catenin translocated to N-cadherin at the junction in both cells. These data indicate that cadherins can rapidly convey dynamic information about the extracellular environment to both cells that comprise a junction

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

Help-Seeking Behavior during Elevated Temperature in Chinese Population

The negative impact of extreme temperatures on health is well-established. Individual help-seeking behavior, however, may mitigate the extent of morbidity and mortality during elevated temperatures. This study examines individual help-seeking behavior during periods of elevated temperatures among a Chinese population. Help-seeking patterns and factors that influence behavior will be identified so that vulnerable subgroups may be targeted for health protection during heat crises. A retrospective time-series Poisson generalized additive model analysis, using meteorological data of Hong Kong Observatory and routine emergency help call data from The Hong Kong Senior Citizen Home Safety Association during warm seasons (June–September) 1998–2007, was conducted. A “U”-shaped association was found between daily emergency calls and daily temperature. About 49% of calls were for explicit health-related reasons including dizziness, shortness of breath, and general pain. The associate with maximum temperature was statistically significant (p = 0.034) with the threshold temperature at which the frequency of health-related calls started to increase being around 30–32°C. Mean daily relative humidity (RH) also had a significant U-shaped association with daily emergency health-related calls with call frequency beginning to increase with RH greater than 70–74% (10–25% of the RH distribution). Call frequency among females appeared to be more sensitive to high temperatures, with a threshold between 28.5°C and 30.5°C while calls among males were more sensitive to cold temperatures (threshold 31.5–33.5°C). Results indicate differences in community help-seeking behavior at elevated temperatures. Potential programs or community outreach services might be developed to protect vulnerable subgroups from the adverse impact of elevated temperatures

Healthcare costs associated with progressive diabetic retinopathy among National Health Insurance enrollees in Taiwan, 2000-2004

<p>Abstract</p> <p>Background</p> <p>Diabetic retinopathy is one of the most common microvascular complications of diabetes and one of the major causes of adult visual impairment in national surveys in Taiwan. This study aimed to identify the healthcare costs of Taiwan's National Health Insurance program on behalf of diabetic patients with stable or progressive retinopathy.</p> <p>Methods</p> <p>A retrospective cohort study was conducted with 4,988 medication-using diabetic retinopathy subjects ≥ 40 years of age under National Health Insurance Program coverage between 2000 and 2004. Study cohort subjects were recorded as having diabetic retinopathy according to ICD-9-CM codes. States of diabetic retinopathy were strategically divided into stable and progressive categories according to subjects' conditions at follow-up in 2004. Expenditures were calculated and compared for the years 2000 and 2004.</p> <p>Results</p> <p>During the 4-year follow-up (2000 through 2004), 4,116 subjects (82.5%) of 4,988 diabetic subjects were in the stable category, and 872 (17.5%) were in the progressive category. Average costs of those in the normal category increased by US $48 from US$1921 in 2000 to US $1969 in 2004 (p = 0.594), whereas costs for those progressing from normal to non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) increased by US$1760, from US $1566 in 2000 to US$3326 in 2004 (p < 0.001). The PDR category had the highest average costs at US $3632 in 2000. The NPDR-to-PDR category experienced the greatest increase in costs at US$3482, from US $2723 in 2000 to US$6204 in 2004 (p = 0.042), and the greatest percentage of increase at 2.3% (2.2% when adjusted by comparing to normal category).</p> <p>Conclusions</p> <p>This large-scale longitudinal study provides evidence that increased healthcare costs are associated with progressive diabetic retinopathy among diabetic NHI enrollees in Taiwan.</p