MEETING-BASED RESOURCE CONSUMPTION INTELLIGENCE

In an online meeting involving multiple users, the performance of the devices (e.g., personal computers, laptops, tablets, etc.) utilized by meeting attendees can vary drastically such that, when audio/video material is shared among the attendees, those attendees that are utilizing lower performance devices can experience resource shortages or choppiness in shared material, which can impact the expectations of the meeting attendees. In order to address such issues, meeting-based resource consumption intelligence techniques are described herein in which the resource consumption of devices utilized by participants involved in an online meeting can be monitored and balanced by porting workloads from a media sender\u27s device to any combination of a data center service and/or one or more media receiver\u27s devices

Unique genotype-phenotype correlations within LAMA2-related limb girdle muscular dystrophy in Chinese patients

BackgroundLAMA2-related limb girdle muscular dystrophy (LGMD R23) is rare. The detailed clinical phenotypes and genetic information associated with LGMD R23 are unknown.MethodsWe conducted a retrospective cross-sectional and longitudinal study on 19 LGMD R23 patients.ResultsNormal early motor development was observed in 84.2% patients. Mild orthopedic complications were observed in 42.1% patients. 36.8% patients had seizures, which is unusually frequent in LGMD. Epilepsy was eventually diagnosed in 26.3% patients. 46.7% patients presented with motor neuropathy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. The mutant sites were mainly distributed in the N-terminal and G-like domains of laminin. The missense variants are distributed near the N-terminus (exons 3–11), whereas frameshift variants are distributed in exons 12–65. Five patients were diagnosed with epilepsy and all of them harbor at least one missense variants in exon 4. 71.4% variants of patients with motor neuropathy located in the LN domain.ConclusionsMissense variants in exon 4 maybe correlated with epilepsy and variants in the LN domain maybe correlated with motor neuropathy in Chinese patients. Our study expands the clinical and genetic spectrum caused by LAMA2 variations and provides novel genotype-phenotype correlations of LGMD R23

General Public’s knowledge, awareness, and perception of Cardiometabolic diseases: data from a Singapore study population

BackgroundHealth literacy and illness perception play crucial roles in tackling the cardiometabolic disease epidemic. We aim to compare the attitudes, knowledge, self-perceived risks and actions taken, between individuals with and without metabolic risk factors (MFs).MethodsFrom 5 June to 5 October 2022, participants of the general public were invited to complete a self-administered questionnaire. MF status was defined as the presence of hypertension, hyperlipidemia, diabetes mellitus and/or current/previous smoking. Participants were assessed based on four categories (knowledge-based, attitude-based, perceived risk, and action-based) of questions pertaining to four cardiometabolic diseases – diabetes mellitus, hypertension, hyperlipidemia, and non-alcoholic fatty liver disease.ResultsA total of 345 participants were enrolled, of whom 34.5% had at least one MF. Compared to those without MFs, participants with MFs had lower knowledge scores, but higher perceived risk scores across all cardiometabolic diseases. The largest knowledge gap pertained to hypertension-related questions. After adjustment, linear regression demonstrated that the presence of MFs (β:2.752, 95%CI: 0.772–4.733, p = 0.007) and higher knowledge scores (β:0.418, 95%CI: 0.236–0.600, p < 0.001) were associated with higher perceived risk. Despite increased perceived risk in those with MFs, this translated to only few increased self-reported preventive actions, when compared to those without MFs, namely the reduction in red meat/processed food consumption (p = 0.045) and increase in fruits/vegetables consumption (p = 0.009).ConclusionThis study identified a vulnerable subpopulation living with MFs, with high perceived risks, and discordant levels of knowledge and preventive actions taken. Nationwide efforts should be channeled into addressing the knowledge-to-action gap

Icariin attenuates the calcification of vascular smooth muscle cells through ERα – p38MAPK pathway

Abstract Objective To investigate the relationship between icariin and the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) and the signal pathway involved. Methods We applied a universally accepted calcification model of VSMCs induced by β glycerophosphate. Then the VSMCs calcification was observed by treatment with icariin and/or inhibitors of estrogen receptors (ERs) and p38‐mitogen‐activated protein kinase (MAPK) signaling. Results Icariin inhibited osteoblastic differentiation and mineralization of VSMCs due to decreased ALP activity and Runx2 expression. Further study demonstrated that icariin exerted this suppression effect through activating p38‐MAPK but not extracellular‐regulated kinase, JNK or Akt. An inhibitor of p38‐MAPK partially reversed the inhibitory effects of icariin on osteoblastic differentiation. Interestingly, treatment of VSMCs with an ER antagonist ICI182780 and a selective ERα receptor antagonist PPT attenuated icariin‐mediated inhibition effect of VSMCs calcification, associated with suppression of p38‐MAPK phosphorylation. Conclusions Icariin inhibited the osteoblastic differentiation of VSMCs, and that the inhibitory effects were mediated by p38‐MAPK pathways through ERα

Rassf2 overexpression mediated by AAV promotes the supporting cell-to-hair cell transformation in the cochlea

Sensory hair cells are responsible for detecting and transmitting sound in the inner ear, and damage to HCs leads to hearing loss. HCs do not regenerate spontaneously in adult mammals, which makes the hearing loss permanent. However, hair cells and supporting cells have the same precursors in the inner ear, and in newborn mice, the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells. Here, we demonstrate the role of the Ras association domain family member 2 (Rassf2) in supporting cell to hair cell trans-differentiation in the inner ear. Using the AAV vector (AAV-ie) to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids. Also, AAV-Rassf2 enhanced the regenerative ability of Lgr5+ SCs in the postnatal cochlea without impairing hearing, and this might due to the modulation of the Wnt, Hedgehog and Notch signaling pathways. Furthermore, AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model. In summary, our results suggest that Rassf2 is a key component in HC regenerative repair, and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair

Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo

Influenza A virus is a highly variable and contagious respiratory pathogen that can cause annual epidemics and it poses an enormous threat to public health. Therefore, there is an urgent need for a new generation of antiviral drugs to combat the emergence of drug-resistant strains of the influenza virus. A novel series of butene lactone derivatives were screened and the compound 3D was selected, as it exhibited in vitro potential antiviral activity against A/Weiss/43 H1N1 virus with low toxicity. In addition, 3D dose-dependently inhibited the viral replication, expression of viral mRNA and viral proteins. 3D exerted a suppressive effect on A/Virginia/ATCC2/2009 H1N1 and A/California/2/2014 H3N2 in vitro. The time-of-addition analysis indicated that 3D suppressed H1N1 in the early stage of its life cycle. A/Weiss/43 H1N1-induced apoptosis in A549 cells was reduced by 3D via the mitochondrial apoptosis pathway. 3D could decrease the production of H1N1-induced pro-inflammatory cytokines that are induced by H1N1 in vitro and in vivo. The administration of 3D reduced lung lesions and virus load in vivo. These results suggest that 3D, which is a butene lactone derivative, is a promising agent for the treatment of influenza A virus infection

Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo

Influenza A virus is a highly variable and contagious respiratory pathogen that can cause annual epidemics and it poses an enormous threat to public health. Therefore, there is an urgent need for a new generation of antiviral drugs to combat the emergence of drug-resistant strains of the influenza virus. A novel series of butene lactone derivatives were screened and the compound 3D was selected, as it exhibited in vitro potential antiviral activity against A/Weiss/43 H1N1 virus with low toxicity. In addition, 3D dose-dependently inhibited the viral replication, expression of viral mRNA and viral proteins. 3D exerted a suppressive effect on A/Virginia/ATCC2/2009 H1N1 and A/California/2/2014 H3N2 in vitro. The time-of-addition analysis indicated that 3D suppressed H1N1 in the early stage of its life cycle. A/Weiss/43 H1N1-induced apoptosis in A549 cells was reduced by 3D via the mitochondrial apoptosis pathway. 3D could decrease the production of H1N1-induced pro-inflammatory cytokines that are induced by H1N1 in vitro and in vivo. The administration of 3D reduced lung lesions and virus load in vivo. These results suggest that 3D, which is a butene lactone derivative, is a promising agent for the treatment of influenza A virus infection

Preclinical Efficacy And Safety Evaluation of AAV‐OTOF in DFNB9 Mouse Model And Nonhuman Primate

Abstract OTOF mutations are the principal causes of auditory neuropathy. There are reports on Otof‐related gene therapy in mice, but there is no preclinical research on the drug evaluations. Here, Anc80L65 and the mouse hair cell‐specific Myo15 promoter (mMyo15) are used to selectively and effectively deliver human OTOF to hair cells in mice and nonhuman primates to evaluate the efficacy and safety of OTOF gene therapy drugs. A new dual‐AAV‐OTOF‐hybrid strategy to transfer full‐length OTOF is generated, which can stably restore hearing in adult OTOFp.Q939*/Q939* mice with profound deafness, with the longest duration being at least 150 days, and the best therapeutic effect without difference in hearing from wild‐type mice. An AAV microinjection method into the cochlea of cynomolgus monkeys without hearing impairment is further established and found the OTOF can be safely and effectively driven by the mMyo15 promoter in hair cells. In addition, the therapeutic dose of AAV drugs has no impact on normal hearing and does not cause significant systemic toxicity both in mouse and nonhuman primates. In summary, this study develops a potential gene therapy strategy for DFNB9 patients in the clinic and provides complete, standardized, and systematic research data for clinical research and application

General Public's knowledge, awareness, and perception of Cardiometabolic diseases: data from a Singapore study population

10.3389/fmed.2023.1193829FRONTIERS IN MEDICINE1