Fibronectin-β1 Integrin Interaction in Teeth

The dental epithelium and extracellular matrix interact to ensure that cell growth and differentiation lead to the formation of teeth of appropriate size and quality. To determine the role of fibronectin in differentiation of the dental epithelium and tooth formation, we analyzed its expression in developing incisors. Fibronectin mRNA was expressed during the presecretory stage in developing dental epithelium, decreased in the secretory and early maturation stages, and then reappeared during the late maturation stage. The binding of dental epithelial cells derived from postnatal day-1 molars to a fibronectin-coated dish was inhibited by the RGD but not RAD peptide, and by a β1 integrin-neutralizing antibody, suggesting that fibronectin-β1 integrin interactions contribute to dental epithelial-cell binding. Because fibronectin and β1 integrin are highly expressed in the dental mesenchyme, it is difficult to determine precisely how their interactions influence dental epithelial differentiation in vivo. Therefore, we analyzed β1 integrin conditional knockout mice (Intβ1lox-/lox-/K14-Cre) and found that they exhibited partial enamel hypoplasia, and delayed eruption of molars and differentiation of ameloblasts, but not of odontoblasts. Furthermore, a cyst-like structure was observed during late ameloblast maturation. Dental epithelial cells from knockout mice did not bind to fibronectin, and induction of ameloblastin expression in these cells by neurotrophic factor-4 was inhibited by treatment with RGD peptide or a fibronectin siRNA, suggesting that the epithelial interaction between fibronectin and β1 integrin is important for ameloblast differentiation and enamel formation

Effect of the Tokyo 2020 Summer Olympic Games on COVID-19 incidence in Japan: A synthetic control approach

BACKGROUND: The Tokyo 2020 Summer Olympic Games (23 July-8 August 2021) were held in the middle of Japan\u27s fifth wave of COVID-19, when the number of cases was on the rise, and coincided with the fourth state of emergency implemented by the host city, Tokyo. AIM: This study aimed to assess whether the hosting of the Games was associated with a change in the number of COVID-19 cases in Japan using a synthetic control method. METHODS: A weighted average of control countries with a variety of predictors was used to estimate the counterfactual trajectory of daily COVID-19 cases per 1 000 000 population in the absence of the Games in Japan. Outcome and predictor data were extracted using official and open sources spanning several countries. The predictors comprise the most recent country-level annual or daily data accessible during the Games, including the stringency of the government\u27s COVID-19 response, testing capacity and vaccination capacity; human mobility index; electoral democracy index and demographic, socioeconomic, health and weather information. After excluding countries with missing data, 42 countries were ultimately used as control countries. RESULTS: The number of observed cases per 1 000 000 population on the last day of the Games was 109.2 (7-day average), which was 115.7% higher than the counterfactual trajectory comprising 51.0 confirmed cases per 1 000 000 population. During the Olympic period (since 23 July), the observed cumulative number of cases was 61.0% higher than the counterfactual trajectory, comprising 143 072 and 89 210 confirmed cases (p=0.023), respectively. The counterfactual trajectory lagged 10 days behind the observed trends. CONCLUSIONS: Given the increasing likelihood that new emerging infectious diseases will be reported in the future, we believe that the results of this study should serve as a sentinel warning for upcoming mega-events during COVID-19 and future pandemics

Clinical Findings on Fibroblast Activation Protein in Patients with Gastric Cancer

Human fibroblast activation protein (FAP) is a 97-kDa surface glycoprotein expressed in tumor-associated fibroblasts. In this study, we immunohistochemically examined FAP levels in surgically resected gastric carcinomas and explored their association with clini-copathological findings and prognosis. Sections of paraffin-embedded specimens were obtained from 100 patients with advanced gastric cancer between 1989 and 2001 at our institution, and they were stained with an anti-FAP antibody. Expression of FAP was detected in 64 patients (64%). Lymphatic vessel invasion was observed in 90% of FAP-positive patients (P = 0.015). Blood vessel invasion was observed in 98% of FAP-positive patients (P < 0.001). The disease-specific 5-year survival rate of in the 64 patients with FAP-positive tumors (22%) was significantly lower than in the 36 patients with FAP-negative tumors (34%, P = 0.036). This indicates that vessel invasion is connected with the expression of FAP and that a positive finding of FAP confer a worse prognosis in the patients with gastric cancer

Predicting Blood Flow from the Superior Mesenteric Artery to the Celiac Arterial Region on CT Angiography in Patients with Median Arcuate Ligament Syndrome

Purpose: This study aimed to assess whether computed tomography (CT) findings can be used to predict blood flow from the superior mesenteric artery (SMA) to the celiac artery (CA) region in patients with median arcuate ligament syndrome (MALS). Materials and methods: Two radiologists who reviewed 1,290 conventional SMA angiograms and CT scans identified 36 patients with MALS. MALS was classified by their blood flow angiography findings as type A (CA region not or barely visualized) and type B (CA region clearly visualized). The association between patient age, sex, post-stenotic dilatation ratio of the celiac axis, maximum diameter of the pancreaticoduodenal arcade (PDA), and MALS classification based on SMA angiography was assessed. Results: Of 36 MALS patients, 17 had MALS type A and 19 had MALS type B. The mean of the maximum diameter of the PDA in MALS type A was 1.6 ± 0.9 mm (SD) and 4.3 ± 1.3 mm in MALS type B. The poststenotic dilatation ratio of the celiac axis was 2.4 ± 1.2 in MALS type A and 2.2 ± 1.4 in MALS type B. Only maximum diameter of the PDA was a predictor of MALS type B (odds ratio, 15.7; 95% confidence interval, 2.3–108.1). Conclusion: The maximum diameter of the PDA on CT angiography can be used to predict the blood flow from the SMA to the CA region in patients with MALS

Laparoscopy-Assisted Pylorus-Preserving Gastrectomy for Treating Early Gastric Cancer

Laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG) with lymphadenectomy has been used for treating early gastric cancer located in the middle-third of the stomach. However, firm evidence supporting its safety and usefulness is scant. This study examined 24 and 10 gastric adenocarcinoma patients who had undergone conventional pylorus-preserving gastrectomy (CPPG) and LAPPG, respectively, at our institution. Operation time for LAPPG (362.8 ± 49.6 min) was significantly longer than that for CPPG (221.9 ± 50.0 min; P = 0.04). Estimated blood loss with LAPPG (127.5 ± 91.2 mL) was not significantly different from that with CPPG (167.9 ± 149.9 mL; P = 0.44). Total number of resected lymph nodes was 26.3 ± 9.5 and 21.3 ± 10.8 with LAPPG and CPPG, respectively, with no statistically significant difference. C-reactive protein in serum on postoperative day 1 was significantly lower in the LAPPG than in the CPPG group (5.3 ± 1.7 mg/dL versus 7.8 ± 3.6 mg/dL; P = 0.049). The requirement for analgesia after surgery was more frequent in the CPPG than in the LAPPG group (3.7 ± 2.0 versus 2.2 ± 1.7; P = 0.04). Time to first flatus was shorter in the LAPPG than in the CPPG group (1.9 ± 0.9 days versus 3.1 ± 0.9 days; P = 0.0006). Postoperative hospital stay was significantly shorter in the LAPPG than in the CPPG group (12.0 ± 4.0 days versus 23.0 ± 10.7days; P = 0.0036). With regard to postoperative complications, stasis was observed more frequently in the CPPG (33.3%) than in the LAPPG (10%) group. In conclusion, patients treated by LAPPG showed a comparable quality of surgical operation compared with those treated by CPPG

Scirrhous Gastric Cancer: Therapeutic Strategy

The prognosis of patients with scirrhous gastric cancer is extremely poor. The management protocol for this type of cancer has not well been documented. In this paper, recent therapeutic outcomes of this type of gastric cancer are reviewed, and we introduce a new treatment protocol for scirrhous gastric cancer

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis

Kumazaki S., Hikita H., Tahata Y., et al. Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis. Alimentary Pharmacology and Therapeutics , (2024); https://doi.org/10.1111/apt.18063.Background and Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. Methods: Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. Results: In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index 1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. Conclusions: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance

Far-East Asian Toxoplasma isolates share ancestry with North and South/Central American recombinant lineages

Ihara F., Kyan H., Takashima Y., et al. Far-East Asian Toxoplasma isolates share ancestry with North and South/Central American recombinant lineages. Nature Communications 15, 4278 (2024); https://doi.org/10.1038/s41467-024-47625-6.Toxoplasma gondii is a global protozoan pathogen. Clonal lineages predominate in Europe, North America, Africa, and China, whereas highly recombinant parasites are endemic in South/Central America. Far East Asian T. gondii isolates are not included in current global population genetic structure analyses at WGS resolution. Here we report a genome-wide population study that compared eight Japanese and two Chinese isolates against representative worldwide T. gondii genomes using POPSICLE, a novel population structure analyzing software. Also included were 7 genomes resurrected from non-viable isolates by target enrichment sequencing. Visualization of the genome structure by POPSICLE shows a mixture of Chinese haplogroup (HG) 13 haploblocks introgressed within the genomes of Japanese HG2 and North American HG12. Furthermore, two ancestral lineages were identified in the Japanese strains; one lineage shares a common ancestor with HG11 found in both Japanese strains and North American HG12. The other ancestral lineage, found in T. gondii isolates from a small island in Japan, is admixed with genetically diversified South/Central American strains. Taken together, this study suggests multiple ancestral links between Far East Asian and American T. gondii strains and provides insight into the transmission history of this cosmopolitan organism