Citrullinated inter-alpha-trypsin inhibitor heavy chain 4 in arthritic joints and its potential effect in the neutrophil migration.

The citrullinated inter-alpha-trypsin inhibitor heavy chain 4 (cit-ITIH4) was identified as its blood level was associated with the arthritis score in peptide glucose-6-phosphate-isomerase-induced arthritis (pGIA) mice and the disease activity in patients with rheumatoid arthritis (RA). This study aimed to clarify its citrullination pathway and function as related to neutrophils. In pGIA-afflicted joints, ITIH4 and cit-ITIH4 levels were examined by immunohistochemistry (IHC), immunoprecipitation (IP) and Western blotting (WB), while peptidylarginine deiminase (PAD) expression was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), IHC and immunofluorescent methods. The pGIA mice received anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibodies to deplete neutrophils and the expression of cit-ITIH4 was investigated by WB. The amounts of ITIH4 and cit-ITIH4 in synovial fluid (SF) from RA and osteoarthritis (OA) patients were examined by I.P. and W.B. Recombinant ITIH4 and cit-ITIH4 were incubated with sera from healthy volunteers before its chemotactic ability and C5a level were evaluated using Boyden's chamber assay and enzyme-linked immunosorbent assay (ELISA). During peak arthritic phase, ITIH4 and cit-ITIH4 were increased in joints while PAD4 was over-expressed, especially in the infiltrating neutrophils of pGIA mice. Levels of cit-ITIH4 in plasma and joints significantly decreased upon neutrophil depletion. ITIH4 was specifically citrullinated in SF from RA patients compared with OA patients. Native ITIH4 inhibited neutrophilic migration and decreased C5a levels, while cit-ITIH4 increased its migration and C5a levels significantly. Cit-ITIH4 is generated mainly in inflamed joints by neutrophils via PAD4. Citrullination of ITIH4 may change its function to up-regulate neutrophilic migration by activating the complement cascade, exacerbating arthritis.

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer.

BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Pathogenicity of memory Th2 cells is linked to stage of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) consists of three developmental stages that are based on the presence/absence of antigen-specific IgE and symptoms. The pathogenic Th2 (Tpath2) cells constitute a population of Th2 cells with additional potentially pathogenic characteristics. We examined the relationship between Tpath2 cells and the stages of allergic rhinitis by focusing on ST2, which is an IL-33 receptor. METHODS: Patients with Japanese cedar pollen-induced AR (JCP-AR) and healthy volunteers were divided into "nonsensitized," "asymptomatic sensitized (AS)," and "JCP-AR" groups. We analyzed the ST2 expression and the Th2 function of cultured CD4+ T cells. Next, we observed the progress of patients in the AS stage around the time of seasonal pollen dispersal, with the characteristics of Th2 cells. RESULTS: The ST2 expression of T cells was only upregulated in the AR group. The production of IL-4 and IL-13 was found in CD4+ T cells obtained from AS by stimulation with JCP, but reactivity to IL-33 was not observed. Although IL-33 did not induce the elevation of IL-4 production in the JCP-AR group, IL-33 substantially increased the production of IL-5 and IL-13 in comparison with antigen stimulation alone. In newly afflicted patients, the increased expression of ST2 and elevated reactivity to IL-33 was observed, even before the pollen dispersal season. CONCLUSIONS: Our study demonstrated that the pathogenicity of memory Th2 cells is linked to sensitization and the stage of allergic rhinitis. Therefore, Tpath2 cells may provide useful insights into the mechanism of the onset and progression of allergic rhinitis.

Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy.

BACKGROUND: Although Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, which Th2 cell subsets are important in house dust mite-induced AR (HDM-AR), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified. METHODS: The cytokine production and frequency of HDM-reactive T-cell subsets in peripheral blood mononuclear cells (PBMCs) were evaluated using flow cytometry in 89 HDM-AR patients (placebo [n = 43] and HDM 300 IR [n = 46]) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. The PBMCs were stained with CellTrace™ Violet (CTV) before culture with HDM extract, and HDM-reactive T cells were detected as the proliferated cells with diminished CTV. RESULTS: HDM-reactive IL-5+ IL-13+ CD27- CD161+ CD4+ cells and ST2+ CD45RO+ CD4+ cells were observed in the peripheral blood from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2+ CD45RO+ CD4+ cells were significantly lower in active-responders. CONCLUSION: Allergen-reactive ST2+ CD45RO+ CD4+ cells or those combined with IL-5+ IL-13+ CD27- CD161+ CD4+ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.

Novel integrated 3D multidetector computed tomography and fluoroscopy fusion for left atrial appendage occlusion procedures.

OBJECTIVES: This report demonstrates the application and feasibility of novel 3D-MDCT real-time fusion technology with fluoroscopy, for left atrial appendage (LAA) occlusion procedures. BACKGROUND: A successful LAA occlusion procedure relies on multiple imaging modalities, including TEE or 3D-MDCT, and fluoroscopy. Effectively integrating these imaging modalities may improve implantation safety and success. To our knowledge this technique has not been previously described for LAA occlusions. METHODS: This observational study compared clinical and procedural parameters for procedures performed with or without fusion integration. All patients had a pre-procedural 3D-MDCT for LAA measurements, along with 3D analyses of LAA morphology and surrounding structures. Using the image fusion software (Valve ASSIST 2, GE Healthcare, UK), landmarks were identified on fluoroscopy, and MDCT LAA anatomy outlines were then projected onto the real-time fluoroscopy image during the procedure, to guide all steps of the intervention. RESULTS: A total of 57 patients underwent LAA occlusion, with 16 performed using fusion software. In comparison to the pre-fusion group, reductions in contrast volume (21.0 ± 11.7 vs. 95.9 ± 80.5 ml, P < 0.001), procedure time (63.0 ± 22.0 vs. 87.3 ± 43.0 min, P = 0.01), and fluoroscopy time (6.2 vs. 8.3 min, P = 0.03) were observed. Incomplete sealing (0 vs. 14.6%, P = 0.16) and device deployment success (100 vs. 92.7%, P = 0.17) were not significantly different. CONCLUSIONS: The addition of this novel fusion technology is safe and feasible. To optimize LAA procedural success, fusion integration may offer a promising addition, or alternative, to current imaging modalities. © 2017 Wiley Periodicals, Inc.

Cytological diagnostic clues in poorly differentiated squamous cell carcinomas of the breast: Streaming arrangement, necrotic background, nucleolar enlargement and cannibalism of cancer cells.

OBJECTIVE: Squamous cell carcinoma (SCC) is a rare histological type of breast cancer. The cytological diagnosis of non-keratinising, poorly differentiated SCC is often difficult, and distinguishing it from invasive ductal carcinoma or apocrine carcinoma (AC) is especially challenging. We aimed to define the diagnostic cytological features of poorly differentiated SCC of the breast. METHODS: We studied the cytological findings of poorly differentiated SCC (n=10) and compared them to those of IDC (n=15) and AC (n=14). The following six cytological features were evaluated: streaming arrangement, nucleolar enlargement, dense nuclei, cannibalism, atypical keratinocytes and necrotic background. RESULTS: SCC exhibited significantly higher frequencies of streaming arrangement (70% vs 6.7%, P=.002), nucleolar enlargement (80% vs 27%, P=.02), and necrotic background (80% vs 36%, P=.002) than invasive ductal carcinoma. The detection of two or three of these features yielded a higher sensitivity (80%) and specificity (93%) for the diagnosis of SCC. Streaming arrangement (70% vs 0%, P<.001), cannibalism (60% vs 0%, P=.002), and a necrotic background (80% vs 36%, P=.047) were all significantly more frequent in SCC than in AC. When distinguishing SCC from AC, the presence of two or three of these features yielded a high sensitivity (80%) and specificity (100%). CONCLUSIONS: Cytological features such as a streaming arrangement, a necrotic background, nucleolar enlargement and cannibalism are useful indicators for the diagnosis of SCC of the breast. As such, greater attention should be paid to these morphological features in daily clinical practice.

Telomere length determined by the fluorescence in situ hybridisation distinguishes malignant and benign cells in cytological specimens.

BACKGROUND: Telomeres are tandem repeats of TTAGGG at the end of eukaryotic chromosomes that play a key role in preventing chromosomal instability. The aim of the present study is to determine telomere length using fluorescence in situ hybridisation (FISH) on cytological specimens. METHODS: Aspiration samples (n = 41) were smeared on glass slides and used for FISH. RESULTS: Telomere signal intensity was significantly lower in positive cases (cases with malignancy, n = 25) as compared to negative cases (cases without malignancy, n = 16), and the same was observed for centromere intensity. The difference in DAPI intensity was not statistically significant. The ratio of telomere to centromere intensity did not show a significant difference between positive and negative cases. There was no statistical difference in the signal intensities of aspiration samples from ascites or pleural effusion (n = 23) and endoscopic ultrasound-guided FNA samples from the pancreas (n = 18). CONCLUSIONS: The present study revealed that telomere length can be used as an indicator to distinguish malignant and benign cells in cytological specimens. This novel approach may help improve diagnosis for cancer patients.

Can radiological technologists serve as primary screeners of low-dose computed tomography for the diagnosis of lung cancer?

BACKGROUND: The Accreditation Council for Lung Cancer CT Screening of Japan established guidelines for the certification of Radiological Technologists in 2009. OBJECTIVE: To analyze the trends in examination pass rates of the Radiological Technologists and discuss the reasons. METHODS: The cohort comprised 1593 Radiological Technologists (as examinees) based on 10-year of data (with a total of 17 examination runs). First, the examinees' written test results were analyzed. Second, an abnormal finding detection test was conducted using >100 client PCs connected to a dedicated server containing low-dose lung cancer CT screening images of 60 cases. The passing scores were correct answer rate >60% and sensitivity (TP) of >90%, respectively. RESULTS: Overall, 1243 examinees passed with an overall rate of 78%. The average pass rate for the written test was 91%, whereas that for the abnormal findings detection test was 85%. There was a moderate correlation between the test pass rate and average years of clinical experience of the examinees for the abnormal findings detection test (R = 0.558), whereas no such correlation existed for the written test (R = 0.105). CONCLUSIONS: In order for accredited Radiological Technologists to serve as primary screeners of low-dose computed tomography, it is important to revise the educational system according to current standard practices.

Triggering immunological memory against the tapeworm Hymenolepis diminuta to protect against colitis.

Infection with parasitic helminths can ameliorate the severity of concomitant inflammatory disease. To use the tapeworm, Hymenolepis diminuta, and to extend this concept by assessing whether triggering a memory response against the worm inhibits dinitrobenzene sulphonic acid (DNBS)-induced colitis in Balb/c mice. Initial studies revealed that oral infection with 1, 3 or 5 H. diminuta cysticercoids 8 days before intrarectal administration of DNBS (3 mg) resulted in less severe inflammation and that infected mice displayed an increased propensity for T helper-2 immunity. A 1 mg dose of a PBS-soluble extract of the worm (HdAg) delivered intraperitoneally concomitant with DNBS was anticolitic as determined by macroscopic and histological disease scores 72 hour post-DNBS. Mice infected 28 days previously had a memory response as determined by HdAg-evoked increases in interleukin (IL)-4 and IL-10 from in vitro stimulated splenocytes and serum anti-H. diminuta IgG. Moreover, mice infected with 5 H. diminuta 28 days previously were protected from DNBS-induced colitis by secondary infection or 100 µg HdAg (ip.) at the time of DNBS treatment. An additional approach to managing inflammatory disease could be infection with H. diminuta followed by eliciting antiworm recall responses.

In vitro investigation of molecules involved in Lactobacillus gasseri SBT2055 adhesion to host intestinal tract components.

AIMS: The adhesion ability of Lactobacillus gasseri SBT2055 was investigated in vitro by searching for its adhesion molecules. METHODS AND RESULTS: Lactobacillus gasseri SBT2055 showed adherence to host components, including two commercially available mucins, Caco-2 epithelial-like cells and the extracellular matrix molecule fibronectin (Fn). Its adhesion rates to host components were generally higher than those of other Lactobacillus strains. We examined sortase-dependent proteins (SDPs) anchored by a sortase enzyme encoded by srtA1. The adhesion rates of an srtA1 disruptant were lower than those of Lact. gasseri SBT2055, and the relative adherences were as follows: two mucins, 43 and 40%; Caco-2, 66% and Fn, 28%. Seven additional gene disruptants were generated to determine the precise SDPs that contribute to adhesion to each component. CONCLUSIONS: The adhesion ability of Lact. gasseri SBT2055 was superior to those of other Lactobacillus strains. Additionally, four adhesion molecules were newly identified from candidate SDPs. SIGNIFICANCE AND IMPACT OF THE STUDY: Although the contribution of SDPs to adhesion has been reported using sortase gene disruptants, this is the first report to identify the precise SDPs that act as adhesion molecules. Our results will contribute to achieving better understanding of probiotic bacterial adherence.

Improvement of androgenetic alopecia with topical Sophora flavescens Aiton extract, and identification of the two active compounds in the extract that stimulate proliferation of human hair keratinocytes.

BACKGROUND: Androgenetic alopecia (AGA) is a hair loss disorder that commonly affects middle-aged men. To date, the properties of a number of natural or synthetic substances have been investigated for their ability to improve the condition. AIM: To evaluate the hair growth-promoting activities of an extract from the root of Sophora flavescens Aiton. METHODS: We used a human hair keratinocyte proliferation assay and ex vivo organ cultures of human hair follicle to examine the potential of the extract to stimulate hair growth via anagen elongation. We isolated the compounds promoting the growth of epithelial cells, and determined their chemical structures. A randomized, double-blinded, placebo-controlled clinical study for S. flavescens extract was carried out for 6 months with patients with AGA. RESULTS: The extract stimulated the proliferation of hair keratinocytes at a concentration of 0.1 ng/mL, while 100 ng/mL of the extract had a marked effect on hair shaft elongation in an organ culture of human hair follicle. Cell proliferation assay-directed fractionation led to the identification of two pterocarpan derivatives, L-maackiain and medicarpin, as active compounds that promote the proliferation of human hair keratinocytes. Studies in human subjects showed that improvement in the inspected alopecia scores in the lotion plus extract group were significant over a period of 6 months (P < 0.01). CONCLUSIONS: S. flavescens root extract is effective for the treatment of AGA. The isolated two pterocarpans might have important role in this effect.

Sublingual immunotherapy for allergic rhinitis: subjective versus objective tools to evaluate its success.

BACKGROUND: Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified. METHODS: This study included 40 patients who were enrolled in a large randomized, double-blind, placebo-controlled, multicenter study examining the efficacy of sublingual immunotherapy (SLIT) using Japanese cedar (JC) pollen extract during two consecutive pollen seasons from 2010 to 2012. Based on changes in total nasal symptom medication score, patients in the SLIT and placebo groups were subdivided into two subgroups: good responders and poor responders. The levels of JC pollen-specific IL-10+Foxp3+ cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed. RESULTS: The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group. The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group; however, the increases were inhibited in the good responders in the SLIT group. The number of JC pollen-specific IL-10+Foxp3+ cells increased only in these good responders. CONCLUSIONS: Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10+Foxp3+ cells could be objective biomarkers for SLIT.

Prognostic impact of lymph node metastasis in distal cholangiocarcinoma.

BACKGROUND: The aim of the study was to investigate the prognostic impact of lymph node metastasis in cholangiocarcinoma using three different classifications. METHODS: Patients who underwent pancreaticoduodenectomy for distal cholangiocarcinoma in 24 hospitals in Japan between 2001 and 2010 were included. Survival was calculated by means of the Kaplan-Meier method and differences between subgroups were assessed with the log rank test. The Cox proportional hazards model was used to identify independent predictors of survival. χ(2) scores were calculated to determine the cut-off value of the number of involved nodes, lymph node ratio (LNR) and total lymph node count (TLNC) for discriminating survival. RESULTS: Some 370 patients were included. The median (range) TLNC was 19 (3-59). Nodal metastasis occurred in 157 patients (42·4 per cent); the median (range) number of involved nodes and LNR were 2 (1-19) and 0·11 (0·02-0·80) respectively. Four or more involved nodes was associated with a significantly shorter median survival (1·3 versus 2·2 years; P = 0·001), as was a LNR of at least 0·17 (1·4 versus 2·3 years; P = 0·002). Involvement of nodes along the common hepatic artery, present in 21 patients (13·4 per cent), was also associated with a shorter survival (median 1·3 versus 2·1 years; P = 0·046). Multivariable analysis among 157 node-positive patients identified the number of involved nodes as an independent prognostic factor (risk ratio 1·87; P = 0·002). CONCLUSION: The number of involved nodes was a strong predictor of survival in patients with distal cholangiocarcinoma.

Origin of the tetragonal-to-orthorhombic phase transition in FeSe: a combined thermodynamic and NMR study of nematicity.

The nature of the tetragonal-to-orthorhombic structural transition at T_{s}≈90 K in single crystalline FeSe is studied using shear-modulus, heat-capacity, magnetization, and nuclear magnetic resonance measurements. The transition is shown to be accompanied by a large shear-modulus softening, which is practically identical to that of underdoped Ba(Fe,Co)_{2}As_{2}, suggesting a very similar strength of the electron-lattice coupling. On the other hand, a spin-fluctuation contribution to the spin-lattice relaxation rate is only observed below T_{s}. This indicates that the structural, or "nematic," phase transition in FeSe is not driven by magnetic fluctuations.

Terminal RFLP analysis to determine the oral microbiota with hyposalivation.

Previous studies of oral microbiota by culture-dependent or targeted DNA approaches demonstrated that hyposalivation, a reduction in salivary secretions, might increase the amount of certain oral pathogens. However, the relationship between hyposalivation and the balance of oral microbiota, especially uncultivable bacteria, remains still unclear. The aim of this study was to elucidate the relationship between hyposalivation and oral microbiota by analyzing terminal restriction fragment length polymorphism (T-RFLP) of 16S rDNA. The 61 subjects were divided into two groups, hyposalivation group and normo-salivation group. The microbiota of tongue-coating samples was analyzed by T-RFLP. The amount of saliva, the number of Candida albicans, and also the dental status including plaque index, gingival index, bleeding on probing, probing pocket depth and decayed, missing, and filled teeth (DMFT) were assessed. Regarding the dental status, none of the evaluated factors were significantly different between the groups except the number of DMFT. According to the T-RFLP profiles, the patterns of microbiota in the tongue coating were classified into two groups, Clusters I and II. Cluster I is made up 76% of subjects with hyposalivation, while Cluster II is made up 61% of subjects with normo-salivation (p<0.001). Compared with the microbiota found in Cluster II, that in Cluster I had higher proportions of T-RFs corresponding to genera Veillonella, Dialister, Prevotella, Fusobacterium, and Streptococcus. T-RFLP analysis showed a significant role of salivary volume in determining the composition of the microbial community, regardless of the cultivability of the bacteria.

Effect of cricoid pressure on placement of the I-gel™ : a randomised study.

We studied 40 adult patients to see if cricoid pressure affected placement of the I-gel(™). In a randomised crossover design, the i-gel was placed with and without cricoid pressure, and we compared the success rate of adequate ventilation through the i-gel, time to placement and the rate of optimal position of the device between the two circumstances. Cricoid pressure significantly decreased the success rate of adequate ventilation through the i-gel (40 vs 34 patients) (p = 0.041, 95% CI for difference 4-26%), and significantly decreased the rate of the optimal position (39 vs 17 patients) (p < 0.001). The time to achieve adequate ventilation was significantly longer (p < 0.001) with cricoid pressure than without (median difference 8 s; 95% CI for median difference 3-12 s). Cricoid pressure significantly decreases the success rate of ventilation through the i-gel, but the success rate of ventilation through the i-gel is reasonably high.

Coesite and stishovite in a shocked lunar meteorite, Asuka-881757, and impact events in lunar surface.

Microcrystals of coesite and stishovite were discovered as inclusions in amorphous silica grains in shocked melt pockets of a lunar meteorite Asuka-881757 by micro-Raman spectrometry, scanning electron microscopy, electron back-scatter diffraction, and transmission electron microscopy. These high-pressure polymorphs of SiO(2) in amorphous silica indicate that the meteorite experienced an equilibrium shock-pressure of at least 8-30 GPa. Secondary quartz grains are also observed in separate amorphous silica grains in the meteorite. The estimated age reported by the (39)Ar/(40)Ar chronology indicates that the source basalt of this meteorite was impacted at 3,800 Ma ago, time of lunar cataclysm; i.e., the heavy bombardment in the lunar surface. Observation of coesite and stishovite formed in the lunar breccias suggests that high-pressure impact metamorphism and formation of high-pressure minerals are common phenomena in brecciated lunar surface altered by the heavy meteoritic bombardment.

Myocardial necrosis depth prediction during extracellular photosensitization reaction of talaporfin sodium by defined index using fluorescence measurement.

An application of photodynamic therapy for myocardial ablation, which would induce myocardial electrical conduction block, is proposed. For the proposed application, an extracellular photosensitization reaction (PR) is performed while photosensitizer is distributed in myocardial interstitial space by employing a short drug-light interval. Because the myocardial necrosis depth must be accurately controlled to prevent surrounding tissue injury during the myocardial ablation procedure, the necrosis depth during PR needs to be predicted. The purpose of this study is to investigate the availability of predicting PR-induced myocardial necrosis depth (d(nec)) using a defined fluorescence-fall amount (FA), which is the calculated result of fluorescence intensity decrease from the start of the PR multiplied by irradiation duration and corresponds to photosensitizer consumption amount under an assumption that the photosensitizer consumption rate is faster than the photosensitizer supply rate. The correlation between FA and d nec was experimentally investigated in vivo using an open-chested canine heart model with 2.5 and 5.0 mg/kg of talaporfin sodium at an irradiance of 5-20 W/cm(2) for 5-20 s. The fluorescence measurement was performed at a wavelength of 710 nm during the PR to derive FA. One week after the PR, a uniform necrosis depth was measured histopathologically as d(mnec). A logarithmic correlation between d(mnec) and FA was confirmed with R(2) = 0.69-0.80 and a d(mnec) range of 0.2-7.1 mm. The defined FA might be useful for predicting d nec for the extracellular PR in myocardium when using talaporfin sodium.

New record of Philometra species from the marine edible fish Terapon jarbua collected from the Sindh, Arabian Sea, Pakistan.

Diseases in fish due to helminth parasites, especially Philometra species, are the primary worry in aquaculture. Philometra are responsible for health problem in fishes they directly affect fish growth and population parameters. A comprehensive survey was conducted involving the examination of the marine fish species Terapon jarbua, gathered from the coastal waters of Sindh, Pakistan In this research different Philometra species from marine fish Terapon jarbua during 2021 and 2022. Philometra nematodes, belonging to the family Philometridae, are common parasitic organisms inhabiting both marine and freshwater environments. Their prevalence, particularly when existing in high numbers within host organisms, can lead to severe and potentially lethal consequences. Employing light microscopy techniques, diverse species of Philometra were identified, including Philometra teraponi, P. jarbuai, P. arabiai, P. karachii, and P. awarii, localized primarily within the ovaries of the host fish. A total of 140 fish samples were examined and 76 were infected. The intensity of infected fish was 54.28%. The identification process encompassed meticulous analysis of crucial parameters, such as body size, esophagus length, positioning of the nerve ring, dimensions of the ventriculus, and ligament size. Intriguingly, the parasites were found in varying contexts; while some were free within the ovaries, others were embedded within tissues, inducing severe muscular dystrophy. This research presents novel findings of Philometra nematodes in the marine waters of Pakistan, extending their host and geographical distribution records. Future studies are needed to better evaluate and describe the dynamics and the epidemiology of Philometra infection in wild and cultured fish species.

KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study.

BACKGROUND: Inhibitors of the epidermal growth factor (EGFR) signaling pathway have a major role in the treatment of KRAS wild-type colorectal cancer patients. The EGFR pathway has been shown to be activated in gastric cancer (GC). However, published data on KRAS and BRAF mutation status is limited in GC and has not been compared between GC from different geographic regions. METHODS: The prevalence of KRAS and BRAF mutations was established in 712 GC: 278 GC from the United Kingdom, 230 GC from Japan and 204 GC from Singapore. The relationship between KRAS/BRAF mutation status, DNA mismatch repair (MMR) status, clinicopathological variables and overall survival was analysed. RESULTS: Overall, 30 (4.2%) GC carried a KRAS mutation. In total, 5.8% of the UK GC, 4% of Japan GC and 1.5% of Singapore GC were KRAS mutant. KRAS mutant GC had fewer lymph node metastases in the UK cohort (P=0.005) and were more frequent in elderly patients in the Japan cohort (P=0.034). KRAS mutations were more frequent in MMR-deficient GC in the UK and the Japanese cohort (P<0.05). A BRAF mutation was only detected in a single Japanese GC. CONCLUSIONS: This large multicentre study demonstrated that KRAS mutations and DNA MMR deficiency have a role in a small subgroup of GC irrespective of country of origin, suggesting that this subgroup of GC may have developed along a common pathway. Further studies need to establish whether concomitant mutations or amplifications of other EGFR signalling pathway genes may contribute to the activation of this pathway in GC.