Antitumor activity of the tea polyphenol epigallocatechin-3-gallate encapsulated in targeted vesicles after intravenous administration

The therapeutic potential of epigallocatechin gallate, a green tea polyphenol with anti-cancer properties, is limited by its inability to specifically reach tumors following intravenous administration. The purpose of this study is to determine whether a tumor-targeted vesicular formulation of epigallocatechin gallate would suppress the growth of A431 epidermoid carcinoma and B16-F10 melanoma in vitro and in vivo. Transferrin-bearing vesicles encapsulating epigallocatechin gallate were intravenously administered to mice bearing subcutaneous A431 and B16-F10 tumors. The intravenous administration of epigallocatechin gallate encapsulated in transferrin-bearing vesicles resulted in tumor suppression for 40% of A431 and B16-F10 tumors. Animal survival was improved by more than 20 days compared to controls. Encapsulation of epigallocatechin gallate in transferrin-bearing vesicles is a promising therapeutic strategy

Elevation of hilar mossy cell activity suppresses hippocampal excitability and avoidance behavior

Modulation of hippocampal dentate gyrus (DG) excitability regulates anxiety. In the DG, glutamatergic mossy cells (MCs) receive the excitatory drive from principal granule cells (GCs) and mediate the feedback excitation and inhibition of GCs. However, the circuit mechanism by which MCs regulate anxiety-related information routing through hippocampal circuits remains unclear. Moreover, the correlation between MC activity and anxiety states is unclear. In this study, we first demonstrate, by means of calcium fiber photometry, that MC activity in the ventral hippocampus (vHPC) of mice increases while they explore anxiogenic environments. Next, juxtacellular recordings reveal that optogenetic activation of MCs preferentially recruits GABAergic neurons, thereby suppressing GCs and ventral CA1 neurons. Finally, chemogenetic excitation of MCs in the vHPC reduces avoidance behaviors in both healthy and anxious mice. These results not only indicate an anxiolytic role of MCs but also suggest that MCs may be a potential therapeutic target for anxiety disorders

Common Bile Duct Dilatations in Asymptomatic Neonates: Incidence and Prognosis

Background. This retrospective study reviewed 213 asymptomatic neonates with common bile duct (CBD) dilatations diagnosed via ultrasound to evaluate their incidence and outcomes. Materials and Methods. From August 2001 to July 2010, 18,230 abdominal ultrasound scans were performed as newborn screening. There were 213 (1.17%) cases of CBD dilatation. Dilatation of neonatal CBD was defined when its diameter was ≥2 mm. The neonates’ birth history, CBD size, and follow-up results were analyzed. Results. In the 213 infants, four cystic dilatations (1.88%, 4/213) that were eventually diagnosed as choledochal cysts (CC). Among 209 neonates with fusiform dilatations (size 2.0–6.7 mm), 77 had ultrasound follow-up and 87% of them resolved spontaneously which were diagnosed as transient CBD dilatation (TCBDD). Eighty percent of TCBDDs resolved within 6 months. Patients with initial CBD size ≥3 mm had significantly lower resolution rate and neonates whose mothers are older than 35 years took longer time to resolve. Conclusion. The incidence of CBD dilatation in asymptomatic neonates was 1.17%. Eighty percent of TCBDDs resolved within 6 months. Regular ultrasound follow-up every 6 months may be appropriate for asymptomatic neonates with fusiform CBD dilatations to ensure resolution or progression

Large CP violation in radiative B decays in supersymmetry without R-parity

We demonstrate that the R-parity breaking interactions within their current experimental upper bounds can give rise to large mixing-induced CP asymmetry in exclusive radiative B decays that may be detectable in the upcoming B factories.Comment: 9 pages, Latex, requires axodraw.sty; in v2 two more PS figs included and more discussion on how our prediction of large CP asymmetry is consistent with the constraints from b \to s \gamma rat

Association between the risk of seizure and COVID-19 vaccinations: A self-controlled case-series study

OBJECTIVE: The risk of seizure following BNT162b2 and CoronaVac vaccinations has been sparsely investigated. This study aimed to evaluate this association. METHOD: Patients who had their first seizure-related hospitalization between February 23, 2021 and January 31, 2022 were identified in Hong Kong. All seizure episodes happening on the day of vaccination (day 0) were excluded since clinicians validated that most of the cases on day 0 were syncopal episodes. Within-individual comparison using a modified self-controlled case series analysis was applied to estimate the incidence rate ratio (IRR) with 95% confidence intervals (CI) of seizure using conditional Poisson regression. RESULTS: We identified 1656 individuals who had their first seizure-related hospitalization (BNT162b2: 426; CoronaVac: 263; unvaccinated: 967) within the observation period. The incidence of seizure was 1.04 (95% CI: 0.80-1.33) and 1.11 (95% CI: 0.80-1.50) per 100,000 doses of BNT162b2 and CoronaVac administered respectively. 16 and 17 individuals received second dose after having first seizure within 28 days after first dose of BNT162b2 and CoronaVac vaccinations, respectively. None had recurrent seizures after the second dose. There was no increased risk during day 1-6 after the first (BNT162b2: IRR=1.39, 95% CI=0.75-2.58; CoronaVac: IRR=1.19, 95% CI=0.50-2.83) and second doses (BNT162b2: IRR=1.36, 95% CI 0.72-2.57; CoronaVac: IRR=0.71, 95% CI=0.22-2.30) of vaccinations. During 7-13, 14-20- and 21-27-days post-vaccination, no association was observed for both vaccines. SIGNIFICANCE: The findings demonstrated no increased risk of seizure following BNT162b2 and CoronaVac vaccinations. Future studies will be warranted to evaluate the risk of seizure following COVID-19 vaccinations in different populations with subsequent doses to ensure the generalizability

Moment-To-moment affective dynamics in schizophrenia and bipolar disorder

Background: Affective disturbances in schizophrenia and bipolar disorder may represent a transdiagnostic etiological process as well as a target of intervention. Hypotheses on similarities and differences in various parameters of affective dynamics (intensity, successive/acute changes, variability, and reactivity to stress) between the two disorders were tested.Methods: Experience sampling method was used to assess dynamics of positive and negative affect, 10 times a day over 6 consecutive days. Patients with schizophrenia (n = 46) and patients with bipolar disorder (n = 46) were compared against age-matched healthy controls (n = 46).Results: Compared to controls, the schizophrenia group had significantly more intense momentary negative affect, a lower likelihood of acute changes in positive affect, and reduced within-person variability of positive affect. The bipolar disorder group was not significantly different from either the schizophrenia group or the healthy control group on any affect indexes. Within the schizophrenia group, level of depression was associated with weaker reactivity to stress for negative affect. Within the bipolar disorder group, level of depression was associated with lower positive affect.Conclusions: Patients with schizophrenia endured a more stable and negative affective state than healthy individuals, and were less likely to be uplifted in response to happenings in daily life. There is little evidence that these affective constructs characterize the psychopathology of bipolar disorder; such investigation may have been limited by the heterogeneity within group. Our findings supported the clinical importance of assessing multiple facets of affective dynamics beyond the mean levels of intensity.</p