Association analysis of polymorphism in KIAA1717, HUMMLC2B, DECR1 and FTO genes with meat quality traits of the Berkshire breed

Single nucleotide polymorphisms (SNPs) in KIAA1717, HUMMLC2B, DECR1, and FTO genes have been found to be associated with some pork meat quality traits. In this study, we discovered that, in addition to meat quality traits reported previously, SNPs in these genes also are significantly associated with other meat quality traits in the Berkshire breed. A total of 323 Berkshire pigs bred under the same conditions were used for meat quality evaluation and polymerase chain reaction-amplified genes with restriction endonucleases (PCR-RFLP) genotyping analyses. The association analysis of RFLP genotyping with meat quality traits revealed that the SNPs in these 4 genes have novel associations with multiple meat quality traits (p < 0.01 or p < 0.05); a SNP in KIAA1717 was associated with meat color (CIE L), backfat thickness, drip loss, water-holding capacity, and pH24hr; a SNP in HUMMLC2B was associated with chemical composition (collagen), drip loss, shear force, and pH24hr; a SNP in DECR1 was associated with meat color (CIE a and b) and backfat thickness; and a SNP in FTO was associated with meat color (CIE L, a and b), protein content, drip loss, and water-holding capacity. Taken collectively, our results suggest that these 4 SNPs may be used for marker-assisted selection as a genetic marker for meat quality traits in Berkshire pigs.Key words: Berkshire, genetic markers, meat quality, SN

An unexpected evolution of symptomatic mild middle cerebral artery (MCA) stenosis: asymptomatic occlusion

<p>Abstract</p> <p>Background</p> <p>The intracranial localization of large artery disease is recognized as the main cause of ischemic stroke in the world, considering all countries, although its global burden is widely underestimated. Indeed it has been reported more frequently in Asians and African-American people, but the finding of intracranial stenosis as a cause of ischemic stroke is relatively common also in Caucasians. The prognosis of patients with stroke due to intracranial steno-occlusion is strictly dependent on the time of recanalization. Moreover, the course of the vessel involvement is highly dynamic in both directions, improvement or worsening, although several data are derived from the atherosclerotic subtype, compared to other causes.</p> <p>Case description</p> <p>We report the clinical, neurosonological and neuroradiological findings of a young woman, who came to our Stroke Unit because of the abrupt onset of aphasia during her work. An urgent neurosonological examination showed a left M1 MCA stenosis, congruent with the presenting symptoms; magnetic resonance imaging confirmed this finding and identified an acute ischemic lesion on the left MCA territory. The past history of the patient was significant only for a hyperinsulinemic condition, treated with metformine, and a mild overweight. At this time a selective cerebral angiography was not performed because of the patient refusal and she was discharged on antiplatelet and lipid-lowering therapy, having failed to identify autoimmune or inflammatory diseases. Within 1 month, she went back to our attention because of the recurrence of aphasia, lasting about ten minutes. Neuroimaging findings were unchanged, but the patient accepted to undergo a selective cerebral angiography, which showed a mild left distal M1 MCA stenosis.</p> <p>During the follow-up the patient did not experienced any recurrence, but a routine neurosonological examination found an unexpected evolution of the known MCA stenosis, i.e. left M1 MCA occlusion. Neuroradiological imaging did not identify new lesions of the brain parenchyma and a repeated selective cerebral angiography confirmed the left M1 MCA occlusion.</p> <p>Conclusions</p> <p>Regardless of the role of metabolic and/or inflammatory factors on the aetiology of the intracranial stenosis in this case, the course of the vessel disease was unexpected and previously unreported in the literature at our knowledge.</p

Mineral maturity and crystallinity index are distinct characteristics of bone mineral

The purpose of this study was to test the hypothesis that mineral maturity and crystallinity index are two different characteristics of bone mineral. To this end, Fourier transform infrared microspectroscopy (FTIRM) was used. To test our hypothesis, synthetic apatites and human bone samples were used for the validation of the two parameters using FTIRM. Iliac crest samples from seven human controls and two with skeletal fluorosis were analyzed at the bone structural unit (BSU) level by FTIRM on sections 2–4 lm thick. Mineral maturity and crystallinity index were highly correlated in synthetic apatites but poorly correlated in normal human bone. In skeletal fluorosis, crystallinity index was increased and maturity decreased, supporting the fact of separate measurement of these two parameters. Moreover, results obtained in fluorosis suggested that mineral characteristics can be modified independently of bone remodeling. In conclusion, mineral maturity and crystallinity index are two different parameters measured separately by FTIRM and offering new perspectives to assess bone mineral traits in osteoporosis

Genome wide single cell analysis of chemotherapy resistant metastatic cells in a case of gastroesophageal adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Metastatic progression due to development or enrichment of therapy-resistant tumor cells is eventually lethal. Molecular characterization of such chemotherapy resistant tumor cell clones may identify markers responsible for malignant progression and potential targets for new treatment. Here, in a case of stage IV adenocarcinoma of the gastroesophageal junction, we report the successful genome wide analysis using array comparative genomic hybridization (CGH) of DNA from only fourteen tumor cells using a bead-based single cell selection method from a bone metastasis progressing during chemotherapy.</p> <p>Case presentation</p> <p>In a case of metastatic adenocarcinoma of the gastroesophageal junction, the progression of bone metastasis was observed during a chemotherapy regimen of epirubicin, oxaliplatin and capecitabine, whereas lung-, liver and lymph node metastases as well as the primary tumor were regressing. A bone marrow aspirate sampled at the site of progressing metastasis in the right iliac bone was performed, and single cell molecular analysis using array-CGH of Epithelial Specific Antigen (ESA)-positive metastatic cells, and revealed two distinct regions of amplification, 12p12.1 and 17q12-q21.2 amplicons, containing the KRAS (12p) and ERBB2 (HER2/NEU) (17q) oncogenes. Further intrapatient tumor heterogeneity of these highlighted gene copy number changes was analyzed by fluorescence in situ hybridization (FISH) in all available primary and metastatic tumor biopsies, and ErbB2 protein expression was investigated by immunohistochemistry.</p> <p>ERBB2 was heterogeneously amplified by FISH analysis in the primary tumor, as well as liver and bone metastasis, but homogenously amplified in biopsy specimens from a progressing bone metastasis after three initial cycles of chemotherapy, indicating a possible enrichment of erbB2 positive tumor cells in the progressing bone marrow metastasis during chemotherapy. A similar amplification profile was detected for wild-type KRAS, although more heterogeneously expressed in the bone metastasis progressing on chemotherapy. Correspondingly, the erbB2 protein was found heterogeneously expressed by immunohistochemical staining of the primary tumor of the gastroesophageal junction, while negative in liver and bone metastases, but after three initial cycles of palliative chemotherapy with epirubicin, oxaliplatin and capecetabine, the representative bone metastasis stained strongly positive for erbB2.</p> <p>Conclusion</p> <p>Global analysis of genetic aberrations, as illustrated by performing array-CGH analysis on genomic DNA from only a few selected tumor cells of interest sampled from a progressing bone metastasis, can identify relevant therapeutic targets and genetic aberrations involved in malignant progression, thus emphasizing the importance and feasibility of this powerful tool on the road to more personalized cancer therapies in the future.</p

A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia

\ua9 The Author(s) 2024.Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2- to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8+ T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease

Numerical comparison of the closing dynamics of a new trileaflet and a bileaflet mechanical aortic heart valve

[[abstract]]The closing velocity of the leaflets of mechanical heart valves is excessively rapid and can cause the cavitation phenomenon. Cavitation bubbles collapse and produce high pressure which then damages red blood cells and platelets. The closure mechanism of the trileaflet valve uses the vortices in the aortic sinus to help close the leaflets, which differs from that of the monoleaflet or bileaflet mechanical heart valves which mainly depends on the reverse flow. We used the commercial software program Fluent to run numerical simulations of the St. Jude Medical bileaflet valve and a new trileaflet mechanical heart valve. The results of these numerical simulations were validated with flow field experiments. The closing velocity of the trileaflet valve was clearly slower than that of the St. Jude Medical bileaflet valve, which would effectively reduce the occurrence of cavitation. The findings of this study are expected to advance the development of the trileaflet valve.[[incitationindex]]SCI[[booktype]]電子版[[booktype]]紙

The role of PET/CT in detection of gastric cancer recurrence

<p>Abstract</p> <p>Background</p> <p>In the course of surveillance of gastric cancer recurrence after curative resection, contrast CT scan is used in general. However, new findings from CT scan are not always confirmatory for the recurrence. In this case, we usually use short-term follow up strategy or therapeutic intervention with clinical decision. Recently, the use of fusion Positron Emission Tomography/Computed Tomography (PET/CT) is increasing. The purpose of this study is to evaluate the efficacy and usefulness of PET/CT for detecting recurrence of gastric cancer after curative resection.</p> <p>Methods</p> <p>Fifty two patients who received curative resection of gastric cancer and had undergone PET/CT and contrast CT for surveillance of recurrence until Dec 2006 in Seoul National University Hospital were analyzed retrospectively. Recurrence of gastric cancer was validated by histologic confirmation (n = 17) or serial contrast CT follow up with at least 5 month interval (n = 35). McNemar's test and Fisher's exact test were used to evaluate sensitivity and specificity of PET/CT and contrast CT.</p> <p>Results</p> <p>Of 52 patients, 38 patients were confirmed as recurrence. The sensitivity was 68.4% (26/38) for PET/CT and 89.4% (34/38) for contrast CT (p = 0.057). The specificity was 71.4% (10/14) and 64.2% (9/14), respectively (p = 1.0). In terms of the recurred sites, the sensitivity and specificity of PET/CT were similar to those of contrast CT in all sites except peritoneum. Contrast CT was more sensitive than PET/CT (p = 0.039) for detecting peritoneal seeding. Additional PET/CT on contrast CT showed no further increase of positive predictive value regardless of sites. Among 13 patients whose image findings between two methods were discordant and tissue confirmation was difficult, the treatment decision was made in 7 patients based on PET/CT, showing the final diagnostic accuracy of 42.8% (3/7).</p> <p>Conclusion</p> <p>PET/CT was as sensitive and specific as contrast CT in detection of recurred gastric cancer except peritoneal seeding. However, additional PET/CT on contrast CT did not increase diagnostic accuracy in detection of recurred gastric cancer. Further studies are warranted to validate the role of PET/CT in detection of gastric cancer recurrence.</p

Pool boiling of water-Al2O3 and water-Cu nanofluids on horizontal smooth tubes

Experimental investigation of heat transfer during pool boiling of two nanofluids, i.e., water-Al2O3 and water-Cu has been carried out. Nanoparticles were tested at the concentration of 0.01%, 0.1%, and 1% by weight. The horizontal smooth copper and stainless steel tubes having 10 mm OD and 0.6 mm wall thickness formed test heater. The experiments have been performed to establish the influence of nanofluids concentration as well as tube surface material on heat transfer characteristics at atmospheric pressure. The results indicate that independent of concentration nanoparticle material (Al2O3 and Cu) has almost no influence on heat transfer coefficient while boiling of water-Al2O3 or water-Cu nanofluids on smooth copper tube. It seems that heater material did not affect the boiling heat transfer in 0.1 wt.% water-Cu nanofluid, nevertheless independent of concentration, distinctly higher heat transfer coefficient was recorded for stainless steel tube than for copper tube for the same heat flux density

Expression of TopBP1 in hereditary breast cancer

TopBP1 protein displays structural as well as functional similarities to BRCA1 and is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Aberrant expression of TopBP1 may lead to genomic instability and can have pathological consequences. In this study we aimed to investigate expression of TopBP1 gene at mRNA and protein level in hereditary breast cancer. Real-time quantitative PCR was performed in 127 breast cancer samples. Expression of TopBP1 mRNA in lobular carcinoma was significantly lower compared with ductal carcinoma (p < 0.05). The level of TopBP1 mRNA appeared to be lower in poorly differentiated (III grade) hereditary breast cancer in comparison with moderately (II grade) and well-differentiated cancer (I grade) (p < 0.05 and p < 0.001 respectively). We analyzed TopBP1 protein expression using immunohistochemistry and Western blot techniques. Expression of TopBP1 protein was found to be significantly increased in poorly differentiated breast cancer (III grade) (p < 0.05). The percentage of samples with cytoplasmic apart from nuclear staining increased with increasing histological grade. There was no significant association between level and intracellular localization of TopBP1 protein in hereditary breast cancer and other clinicopathological parameters such as estrogen and progesterone receptors status, appearance of metastasis in the axillary lymph nodes and type of cancer. Our data suggest that decreased level of TopBP1 mRNA and increased level of TopBP1 protein might be associated with progression of hereditary breast cancer

Associations among hair loss, oral sulfur-containing gases, and gastrointestinal and metabolic linked diseases in Japanese elderly men: pilot study

<p>Abstract</p> <p>Background</p> <p>Male pattern baldness (MPB), an observable trait, has been reported to be associated with various diseases, such as prostate cancer and cardiovascular disease. Oral sulfur-containing gases have also been suggested to be useful as markers of systemic health condition. However, there are no known reports regarding the associations among MPB, and oral sulfur-containing gases, and systemic health conditions in males.</p> <p>Methods</p> <p>We studied 170 male subjects aged either 60 or 65 years old. The degree of MPB was assessed using the Norwood-Hamilton Baldness scale. Oral sulfur-containing gases were measured using a compact-designed device. All subjects completed physical and laboratory blood examinations, a face-to-face medical questionnaire, and an oral examination.</p> <p>Results</p> <p>There were significant differences between the levels of CH₃SCH₃and baldness patterns, independent of age. When we analyzed whether the association was linked to systemic health condition, a strong significant association was observed between the level of CH₃SCH₃and severe MPB in subjects with gastrointestinal diseases, hypertension, and hypercholesterolemia.</p> <p>Conclusion</p> <p>These results suggest that MPB is associated with the level of CH₃SCH₃, a sulfur-containing gas that causes oral malodor, in elderly Japanese males. Further, the association was intensified by the existence of gastrointestinal tract and metabolic disorders.</p