The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Background/Aims: While distal radial artery (DRA) access is increasingly being used for diagnostic coronary angiography, limited information is available regarding DRA size. We aimed to determine the DRA reference diameters of Korean patients and identify the predictors of DRA diameter < 2.3 mm. Methods: The outer bilateral DRA diameters were assessed using a linear ultrasound probe in 1,162 consecutive patients who underwent transthoracic echocardiography. The DRA diameter was measured by the perpendicular angle in the dorsum of the hand, and the average values were compared by sex. DRA diameter < 2.3 mm was defined as unsuitable for routine diagnostic coronary angiography using a 5 Fr introducer sheath. Results: The mean DRA diameters were 2.31 ± 0.43 mm (right) and 2.35 ± 0.45 mm (left). The DRA was smaller in women than men (right: 2.15 ± 0.38 mm vs. 2.43 ± 0.44 mm, p < 0.001; left: 2.18 ± 0.39 mm vs. 2.47 ± 0.45 mm, p < 0.001). The DRA diameter was approximately 20% smaller than the radial artery diameter. A total of 630 (54.2%) and 574 (49.4%) patients had DRA diameter < 2.3 mm in the right and left hands, respectively. Female sex, low body mass index (BMI), and low body surface area (BSA) were significant predictors of DRA diameter < 2.3 mm. Conclusions We provided reference DRA diameters for Korean patients. Approximately 50% of the studied patients had DRA diameter < 2.3 mm. Female sex, low BMI, and low BSA remained significant predictors of DRA diameter < 2.3 mm.

This study elucidates the anti-cancer potential of gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay, tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and cisplatin (CDDP) also inhibited colony formation and tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of p53 (tumor suppressor protein), which in turn regulated cell cycle related proteins such as p21, p27, Cyclin D1 and E1, and intrinsic apoptotic proteins such as Bax, Bcl-2 and cleaved caspase-3. The anti-cancer effect of GA was further confirmed in an in vivo mouse model. Intraperitoneal injection with GA for 4 weeks in an A549-derived tumor xenograft model reduced the size of tumor mass. Injection of them downregulated the expression of proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved caspase-3 in tumor tissues. Taken together, these results indicated that GA hindered lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against non-small cell lung cancer.

Background: Copeptin is secreted in equimolar amounts as arginine vasopressin, main hormone regulating body fluid homeostasis. A recent study reported a copeptin-based classification of osmoregulatory defects in syndromes of inappropriate antidiuresis that may aid in prediction of therapeutic success. We investigated usefulness of copeptin for differentiating etiologies of hyponatremia and predicting efficacy and safety of hypertonic saline treatment in hyponatremic patients. Methods: We performed a multicenter, prospective cohort study of 100 inpatients with symptomatic hyponatremia (corrected serum sodium [sNa] ≤ 125 mmol/L) treated with hypertonic saline. Copeptin levels were measured at baseline and 24 hours after treatment initiation, and patients were classified as being below or above median of copeptin at baseline or at 24 hours, respectively. Correlations between target, under correction, and overcorrection rates of sNa within 24 hours/24–48 hours and copeptin levels at baseline/24 hours were analyzed. Results: Mean sNa and median copeptin levels were 117.9 and 16.9 pmol/L, respectively. Ratio of copeptin-to-urine sodium allowed for an improved differentiation among some (insufficient effective circulatory volume), but not all hyponatremia etiologic subgroups. Patients with below-median copeptin levels at baseline achieved a higher target correction rate in 6/24 hours (odds ratio [OR], 2.97; p = 0.02/OR, 6.21; p = 0.006). Patients with below-median copeptin levels 24 hours after treatment showed a higher overcorrection rate in next 24 hours (OR, 18.00, p = 0.02). Conclusion There is a limited diagnostic utility of copeptin for differential diagnosis of hyponatremia. However, copeptin might be useful for predicting responses to hypertonic saline treatment in hyponatremic patients.

Background: The coronavirus disease 2019 (COVID-19) pandemic is a major public health problem of international concern. It is important to estimate its impact of COVID-19 for health policy decision-making. We estimated the years of life lost (YLLs) due to COVID-19 in high-incidence countries. Methods: We collected the YLLs due to COVID-19 in 30 high-incidence countries as of April 13, 2020 and followed up as of July 14, 2020. Incidence and mortality were collected using each country's formal reports, articles, and other electronic sources. The life expectancy of Japanese females by age and the UN population data were used to calculate YLLs in total and per 100,000. Results: As of April 22, 2020, there were 1,699,574 YLLs due to COVID-19 in 30 high-incidence countries. On July 14, 2020, this increased to 4,072,325. Both on April 22 and July 14, the total YLLs due to COVID-19 was highest in the USA (April 22, 534,481 YLLs; July 14, 1,199,510 YLLs), and the YLLs per 100,000 population was highest in Belgium (April 22, 868.12 YLLs/100,000;July 14, 1,593.72 YLLs/100,000). YLLs due to COVID-19 were higher among males than among females and higher in those aged ≥ 60 years than in younger individuals. Belgium had the highest proportion of YLLs attributable to COVID-19 as a proportion of the total YLLs and the highest disability-adjusted life years per 100,000 population. Conclusion This study estimated YLLs due to COVID-19 in 30 countries. COVID-19 is a high burden in the USA and Belgium, among males and the elderly. The YLLs are very closely related with the incidence as well as the mortality. This highlights the importance of the early detection of incident case that minimizes severe acute respiratory syndrome coronavirus-2 fatality.

KBG syndrome is an autosomal dominant syndrome presenting with macrodontia, distinctive facial features, skeletal anomalies, and neurological problems caused by mutations in the ankyrin repeat domain 11 (ANKRD11) gene. The diagnosis of KBG is difficult in very young infants as the characteristic macrodontia and typical facial features are not obvious. The youngest patient diagnosed to date was almost one year of age. We here describe a 2-month-old Korean boy with distinctive craniofacial features but without any evidence of macrodontia due to his very early age. He also had a congenital megacolon without ganglion cells in the rectum. A de novo deletion of exons 5–9 of the ANKRD11 gene was identified in this patient by exome sequencing and real-time genomic polymerase chain reaction. As ANKRD11 is involved in the development of myenteric plexus, a bowel movement disorder including a congenital megacolon is not surprising in a patient with KBG syndrome and has possibly been overlooked in past cases.
Ankyrin Repeat ; Diagnosis ; Exome ; Exons ; Ganglion Cysts ; Hirschsprung Disease ; Humans ; Infant ; Male ; Movement Disorders ; Myenteric Plexus ; Polymerase Chain Reaction ; Rectum

BACKGROUND: Head and neck anatomy affects the laryngeal mask airway (LMA) cuff volume. The purpose of this study was to identify physical parameters that can be standardized to predict LMA cuff volume and measure the optimal and minimal LMA cuff volume in adults. METHODS: The predictors of volume or pressure of the LMA cuff were investigated in 167 patients. Manufacturers recommend a maximal cuff pressure (MCP) (i.e., 40 ml for size 5, 30 ml for size 4), an optimal cuff volume (OCV) at a cuff pressure of 60 cmH2O, and a minimal cuff volume (MCV) just before audible air leakage. The physical parameters measured included height, weight, body mass index, modified Mallampati classification (MMP), neck circumference, neck length, and thyro-mental distance. Data were analyzed by stepwise multilinear analysis. RESULTS: The regression equations (REs) were as follows: OCV (1.2 + [0.1 × height] + [0.5 × neck length]); MCV for men (−35.7 + [0.25 × height] + [0.7 × neck length] − [4.1 × MMP]); and MCV for women (−42.5 + [0.27 × height] + [0.75 × neck length] − [2.5 × MMP]). The mean values were as follows: MCP > 200 cmH2O, minimal cuff pressure < 20 cmH2O, OCV of 24.7 ml for men and 15.9 ml for women, and MCV of 12.1 ml for men and 7.1 ml for women. CONCLUSIONS: LMA cuff volume is estimated from the patient's height, neck length, and MMP. The RE for calculating the MCV shows a high correlation with height, neck length, and MMP.
Adult ; Airway Management ; Body Weight ; Classification ; Female ; Head ; Humans ; Laryngeal Masks* ; Male ; Neck ; Physical Examination*

BACKGROUND: Head and neck anatomy affects the laryngeal mask airway (LMA) cuff volume. The purpose of this study was to identify physical parameters that can be standardized to predict LMA cuff volume and measure the optimal and minimal LMA cuff volume in adults. METHODS: The predictors of volume or pressure of the LMA cuff were investigated in 167 patients. Manufacturers recommend a maximal cuff pressure (MCP) (i.e., 40 ml for size 5, 30 ml for size 4), an optimal cuff volume (OCV) at a cuff pressure of 60 cmH2O, and a minimal cuff volume (MCV) just before audible air leakage. The physical parameters measured included height, weight, body mass index, modified Mallampati classification (MMP), neck circumference, neck length, and thyro-mental distance. Data were analyzed by stepwise multilinear analysis. RESULTS: The regression equations (REs) were as follows: OCV (1.2 + [0.1 × height] + [0.5 × neck length]); MCV for men (−35.7 + [0.25 × height] + [0.7 × neck length] − [4.1 × MMP]); and MCV for women (−42.5 + [0.27 × height] + [0.75 × neck length] − [2.5 × MMP]). The mean values were as follows: MCP > 200 cmH2O, minimal cuff pressure < 20 cmH2O, OCV of 24.7 ml for men and 15.9 ml for women, and MCV of 12.1 ml for men and 7.1 ml for women. CONCLUSIONS: LMA cuff volume is estimated from the patient's height, neck length, and MMP. The RE for calculating the MCV shows a high correlation with height, neck length, and MMP.
Adult ; Airway Management ; Body Weight ; Classification ; Female ; Head ; Humans ; Laryngeal Masks* ; Male ; Neck ; Physical Examination*

To investigate the influence of leukoaraiosis (LA) on the functional outcomes of subcortical stroke in the subacute phase after onset. We retrospectively analyzed 41 patients with subacute subcortical infarct at a single center from 2011 to 2015. We explored the relationship between LA severity at admission/transfer (initial evaluation) and functional outcome at the time of discharge (follow-up evaluation), as assessed using the modified Rankin Scale (mRS), Functional Ambulation Category (FAC), and modified Barthel Index (mBI). LA severity was graded as mild, moderate, or severe according to the Fazekas scale. Scores of the mRS, FAC, and mBI were compared in patients grouped based on LA severity: no LA (n = 12), mild LA (n = 19), and moderate-to-severe LA (n = 10). Significant inter-group differences were observed in all 3 scores at both the initial and follow-up evaluations. After adjustment for age, scores at follow-up evaluation were significantly different between the 2 groups. LA is related to functional outcomes of subcortical stroke in the subacute phase after onset. After adjustment for age, severe LA was correlated with poor functional outcomes in the subacute phase.
Cerebral Infarction ; Follow-Up Studies ; Humans ; Leukoaraiosis* ; Retrospective Studies ; Stroke ; Walking