Prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan

<p>Abstract</p> <p>Background</p> <p>In Taiwan, a distinct ethnic group variation in incidence and mortality rates has been suggested for most carcinomas. Our aim is to identify the role of prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan.</p> <p>Methods</p> <p>Taiwan Cancer Registry records of 9039 subjects diagnosed with oral and pharyngeal carcinoma were analyzed. The population was divided into three ethnic groups by residence, which were Taiwanese aborigines, Hakka and Hokkien communities. Five-year survival rates were estimated by Kaplan-Meier methods. Ethnic curves differed significantly by log-rank test; therefore separate models for Taiwanese aborigines, Hakka and Hokkien were carried out. The Cox multivariate proportional hazards model was used to examine the role of prognostic factors on ethnic survival.</p> <p>Results</p> <p>The five-year survival rates of oral and pharyngeal carcinoma were significantly poorer for Hokkien community (53.9%) and Taiwanese aborigines community (58.1%) compared with Hakka community (60.5%). The adjusted hazard ratio of Taiwanese aborigines versus Hakka was 1.07 (95%CI, 0.86–1.33) for oral and pharyngeal carcinoma mortality, and 1.16 (95%CI, 1.01–1.33) for Hokkien versus Hakka. Males had significantly poor prognosis than females. Subjects with tongue and/or mouth carcinoma presented the worst prognosis, whereas lip carcinoma had the best prognosis. Subjects with verrucous carcinoma had better survival than squamous cell carcinoma. Prognosis was the worst in elderly subjects, and subjects who underwent surgery had the highest survival rate.</p> <p>Conclusion</p> <p>Our study presented that predictive variables in oral and pharyngeal carcinoma survival have been: ethnic groups, period of diagnosis, gender, diagnostic age, anatomic site, morphologic type, and therapy.</p

Physicochemical properties of rainbow trout (Oncorhynchus mykiss) filet treated with high-voltage electrostatic field under different storage temperatures

The post-mortem rigid of farmed rainbow trout (Oncorhynchus mykiss) affects the texture of the meat and might even be risky for microorganisms, undermining the popularity of frozen filets among consumers. This study investigated the importance of different conditions (0°C, 4°C, and 25°C for 0–4 days) and physicochemical characteristics of rainbow trout filet storage on fish’s characteristics, freshness, quality, and shelf-life. Results showed that the fish easily underwent rigor mortis and resolution of rigor mortis when stored at 25°C. However, rigor mortis was more likely to occur under storage at 0°C than at 4°C [with 100 kV/m high voltage electrostatic fields (HVEF)] due to low-temperature stimulation, but resolution of rigor mortis began to appear after 24 h of storage at either temperature. The protein solubility and gel strength of fish stored at 25°C continued to decrease due to thermal denaturation, and those of fish stored at 4°C and 0°C also showed a decrease owing to rigor mortis and then an increase when rigor mortis disappeared. The K values increased rapidly at 25°C and reached 61% at 14 h. Under storage at 4°C and 0°C, the K values only slightly increased before resolution of rigor mortis. However, the K-values did not exceed 40% for 4 days post-resolution of rigor mortis. Differential Scanning Calorimetry analysis and tissue sectioning showed that protein denaturation and separation between muscle fibers persisted during storage at various temperatures, most notably at 25°C. It is important to note that storing at 0°C for 96 h did not result in any significant changes in the molecular protein composition. Moreover, the muscle tissue remained in excellent condition compared to storage at 25°C and 4°C. Additionally, there was no significant difference in the total viable count (TVC) and psychrophilic bacteria between storage at 0°C and 4°C, considered safe for food consumption. These promising findings are conveyed in a circular economy based on the food industry, particularly adequate raw materials, stable prices, measures to reduce food loss and waste, and contributing to developing efficient, diverse, and sustainable food processing systems

Pain Assessment in the Emergency Department: A Prospective Videotaped Study

Introduction: Research suggests that pain assessment involves a complex interaction between patients and clinicians. We sought to assess the agreement between pain scores reported by the patients themselves and the clinician’s perception of a patient’s pain in the emergency department (ED). In addition, we attempted to identify patient and physician factors that lead to greater discrepancies in pain assessment. Methods: We conducted a prospective observational study in the ED of a tertiary academic medical center. Using a standard protocol, trained research personnel prospectively enrolled adult patients who presented to the ED. The entire triage process was recorded, and triage data were collected. Pain scores were obtained from patients on a numeric rating scale of 0 to 10. Five physician raters provided their perception of pain ratings after reviewing videos.&nbsp; Results: A total of 279 patients were enrolled. The mean age was 53 years. There were 141 (50.5%) female patients. The median self-reported pain score was 4 (interquartile range 0-6). There was a moderately positive correlation between self-reported pain scores and physician ratings of pain (correlation coefficient, 0.46; P &lt;0.001), with a weighted kappa coefficient of 0.39. Some discrepancies were noted: 102 (37%) patients were rated at a much lower pain score, whereas 52 (19%) patients were given a much higher pain score from physician review. The distributions of chief complaints were different between the two groups. Physician raters tended to provide lower pain scores to younger (P = 0.02) and less ill patients (P = 0.008). Additionally, attending-level physician raters were more likely to provide a higher pain score than resident-level raters (P &lt;0.001). Conclusion: Patients’ self-reported pain scores correlate positively with the pain score provided by physicians, with only a moderate agreement between the two. Under- and over-estimations of pain in ED patients occur in different clinical scenarios. Pain assessment in the ED should consider both patient and physician factors

Supercritical Fluid Extract of Spent Coffee Grounds Attenuates Melanogenesis through Downregulation of the PKA, PI3K/Akt, and MAPK Signaling Pathways

The mode of action of spent coffee grounds supercritical fluid CO2extract (SFE) in melanogenesis has never been reported. In the study, the spent coffee grounds were extracted by the supercritical fluid CO2extraction method; the chemical constituents of the SFE were investigated by gas chromatography-mass spectrometry (GC-MS). The effects of the SFE and its major fatty acid components on melanogenesis were evaluated by mushroom tyrosinase activity assay and determination of intracellular tyrosinase activity and melanin content. The expression level of melanogenesis-related proteins was analyzed by western blotting assay. The results revealed that the SFE of spent coffee grounds (1–10 mg/mL) and its major fatty acids such as linoleic acid and oleic acid (6.25–50 μM) effectively suppressed melanogenesis in the B16F10 murine melanoma cells. Furthermore, the SFE decreased the expression of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). The SFE also decreased the protein expression levels of p-JNK, p-p38, p-ERK, and p-CREB. Our results revealed that the SFE of spent coffee grounds attenuated melanogenesis in B16F10 cells by downregulation of protein kinase A (PKA), phosphatidylinositol-3-kinase (PI3K/Akt), and mitogen-activated protein kinases (MAPK) signaling pathways, which may be due to linoleic acid and oleic acid.</jats:p

Emerged HA and NA Mutants of the Pandemic Influenza H1N1 Viruses with Increasing Epidemiological Significance in Taipei and Kaohsiung, Taiwan, 2009–10

The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas -Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post–peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001). E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure). In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post–peak (p = 0.000004) in seven districts with higher spatial clusters (p<0.001). This is the first study examining viral changes during the naïve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001) and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001). Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at exponential and peak phases in areas with high cluster cases

Crystal structure of IcaR, a repressor of the TetR family implicated in biofilm formation in Staphylococcus epidermidis

Expression of the gene cluster icaADBC is necessary for biofilm production in Staphylococcus epidermidis. The ica operon is negatively controlled by the repressor IcaR. Here, the crystal structure of IcaR was determined and the refined structure revealed a homodimer comprising entirely α-helices, typical of the tetracycline repressor protein family for gene regulations. The N-terminal domain contains a conserved helix-turn-helix DNA-binding motif with some conformational variations, indicating flexibility in this region. The C-terminal domain shows a complementary surface charge distribution about the dyad axis, ideal for efficient and specific dimer formation. The results of the electrophoretic mobility shift assay and isothermal titration calorimetry suggested that a 28 bp core segment of the ica operator is implicated in the cooperative binding of two IcaR dimers on opposite sides of the duplex DNA. Computer modeling based on the known DNA-complex structure of QacR and site-specific mutagenesis experiments showed that direct protein–DNA interactions are mostly conserved, but with slight variations for recognizing the different sequences. By interfering with the binding of IcaR to DNA, aminoglycoside gentamicin and other antibiotics may activate the icaADBC genes and elicit biofilm production in S. epidermidis, and likely S. aureus, as a defense mechanism

Replication and Meta-Analysis of GWAS Identified Susceptibility Loci in Kawasaki Disease Confirm the Importance of B Lymphoid Tyrosine Kinase (BLK) in Disease Susceptibility

The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD ) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10(-31)). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD

Risk factors for overtaking, rear-end, and door crashes involving bicycles in the United Kingdom: Revisited and reanalysed

Background and objective: Relevant research has provided valuable insights into risk factors for bicycle crashes at intersections. However, few studies have focused explicitly on three common types of bicycle crashes on road segments: overtaking, rear-end, and door crashes. This study aims to identify risk factors for overtaking, rear-end, and door crashes that occur on road segments. Material and methods: We analysed British STATS19 accident records from 1991 to 2020. Using multivariate logistic regression models, we estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for multiple risk factors. The analysis included 127,637 bicycle crashes, categorised into 18,350 overtaking, 44,962 rear-end, 6,363 door, and 57,962 other crashes. Results: Significant risk factors for overtaking crashes included heavy goods vehicles (HGVs) as crash partners (AOR = 1.30, 95% CI 1.27–1.33), and elderly crash partners (AOR = 2.01, 95% CI = 1.94–2.09), and decreased risk in rural area with speed limits of 20–30 miles per hour (AOR = 0.45, 95% CI = 0.43–0.47). For rear-end crashes, noteworthy risk factors included unlit darkness (AOR = 1.49, 95% CI = 1.40–1.57) and midnight hours (AOR = 1.28, 95% CI = 1.21–1.40). Factors associated with door crashes included urban areas (AOR = 16.2, 95% CI = 13.5–19.4) and taxi or private hire cars (AOR = 1.61, 95% CI = 1.57–1.69). Our joint-effect analysis revealed additional interesting results; for example, there were elevated risks for overtaking crashes in rural areas with elderly drivers as crash partners (AOR = 2.93, 95% CI = 2.79–3.08) and with HGVs as crash partners (AOR = 2.62, 95% CI = 2.46–2.78). Conclusions: The aforementioned risk factors remained largely unchanged since 2011, when we conducted our previous study. However, the present study concluded that the detrimental effects of certain variables became more pronounced in certain situations. For example, cyclists in rural settings exhibited an elevated risk of overtaking crashes involving HGVs as crash partners

Three New Structures of Left-Handed RadA Helical Filaments: Structural Flexibility of N-Terminal Domain Is Critical for Recombinase Activity

RecA family proteins, including bacterial RecA, archaeal RadA, and eukaryotic Dmc1 and Rad51, mediate homologous recombination, a reaction essential for maintaining genome integrity. In the presence of ATP, these proteins bind a single-strand DNA to form a right-handed nucleoprotein filament, which catalyzes pairing and strand exchange with a homologous double-stranded DNA (dsDNA), by as-yet unknown mechanisms. We recently reported a structure of RadA left-handed helical filament, and here present three new structures of RadA left-handed helical filaments. Comparative structural analysis between different RadA/Rad51 helical filaments reveals that the N-terminal domain (NTD) of RadA/Rad51, implicated in dsDNA binding, is highly flexible. We identify a hinge region between NTD and polymerization motif as responsible for rigid body movement of NTD. Mutant analysis further confirms that structural flexibility of NTD is essential for RadA's recombinase activity. These results support our previous hypothesis that ATP-dependent axial rotation of RadA nucleoprotein helical filament promotes homologous recombination