Two new species of Diaporthe (Diaporthaceae, Diaporthales) associated with Camelliaoleifera leaf spot disease in Hainan Province, China.

Tea-oil tree (Camelliaoleifera Abel.) is an important edible oil woody plant with a planting area over 3,800,000 hectares in southern China. Species of Diaporthe inhabit a wide range of plant hosts as plant pathogens, endophytes and saprobes. Here, we conducted an extensive field survey in Hainan Province to identify and characterise Diaporthe species associated with tea-oil leaf spots. As a result, eight isolates of Diaporthe were obtained from symptomatic C.oleifera leaves. These isolates were studied, based on morphological and phylogenetic analyses of partial ITS, cal, his3, tef1 and tub2 gene regions. Two new Diaporthe species (D.hainanensis and D.pseudofoliicola) were proposed and described herein.

Chronic Viral Infection Compromises the Quality of Circulating Mucosal-Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors.

BACKGROUND: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. METHODS: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. RESULTS: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. CONCLUSION: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.

Genomic surveillance of omicron B.1.1.529 SARS-CoV-2 and its variants between December 2021 and March 2023 in Tamil Nadu, India-A state-wide prospective longitudinal study.

A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.

Mobile health and behavior tracking (mHBT) among cancer survivors: results from a large and diverse sample.

This study investigates the prevalence of mobile health and behavior tracking (mHBT) among a large and diverse sample of cancer survivors in the United States focusing on different mHBT adoption based on socio-demographic factors. Data was drawn from the 2020 to 2021 Health Information National Trends Survey (HINTS), which over-sampled cancer survivors from three cancer registries. Data analyses revealed that out of 1,234 cancer survivors studied, 39% had adopted mHBT, with 52% of these users engaging in daily tracking. A significant majority (86%) mHBT users were willing to share their data with healthcare providers. Notably, mHBT adoption was independently associated with younger age, female gender, college education, and better perceived health; but it was not significantly associated with race, income level, or state of residence after controlling for confounders. Cancer survivors' high rates of mHBT use and willingness to share data suggest the potential of using patient-generated data for personalized care and monitoring. However, caution is needed to address the digital divide and its impact on health disparities.

Effect of an NHE3 inhibitor in combination with an NPT2b inhibitor on gastrointestinal phosphate absorption in Rodent models.

Many of the pathological consequences of chronic kidney disease can be attributed to an elevation in serum phosphate levels. Current therapies focused on decreasing intestinal phosphate absorption to treat hyperphosphatemia are inadequate. The most effective therapeutic strategy may be to target multiple absorptive pathways. In this study, the ability of a novel inhibitor of the intestinal sodium hydrogen exchanger 3 (NHE3), LY3304000, which inhibits paracellular, diffusional uptake of phosphate, to work in combination with an inhibitor of the active transporter, sodium dependent phosphate cotransporter 2b (NPT2b), LY3358966, was explored. LY3304000 modestly inhibited the acute uptake of phosphate into plasma of rats, while surprisingly, it doubled the rate of phosphate uptake in mice, an animal model dominated by NPT2b mediated acute phosphate uptake. In rats, LY3004000 and LY3358966 work in concert to inhibit acute phosphate uptake. On top of LY3358966, LY3304000 further decreased the acute uptake of phosphate into plasma. Studies measuring the recovery of radiolabeled phosphate in the intestine demonstrated LY3304000 and LY3358966 synergistically inhibited the absorption of phosphate in rats. We hypothesize the synergism is because the NHE3 inhibitor, LY3304000, has two opposing effects on intestinal phosphate absorption in rats, first it decreases diffusion mediated paracellular phosphate absorption, while second, it simultaneously increases phosphate absorption through the NPT2b pathway. NHE3 inhibition decreases proton export from enterocytes and raises the cell surface pH. In vitro, NPT2b mediated phosphate transport is increased at higher pHs. The increased NPT2b mediated transport induced by NHE3 inhibition is masked in rats which have relatively low levels of NPT2b mediated phosphate transport, by the more robust inhibition of diffusion mediated phosphate absorption. Thus, the inhibition of NPT2b mediated phosphate transport in rats in the presence of NHE3 inhibition has an effect that exceeds its effect in the absence of NHE3 inhibition, leading to the observed synergism on phosphate absorption between NPT2b and NHE3 inhibition.

[A family with developmental glaucoma and microcornea due to novel ADAMTS18 gene mutations].

This case report presents a family with developmental glaucoma accompanied by microcornea resulting from novel mutations in the ADAMTS18 gene. The index case involves a 5-year-old twin brother, who, during a routine examination, exhibited elevated intraocular pressure persisting for over a month. The peak intraocular pressure reached approximately 25 mmHg (1 mmHg=0.133 kPa) in both eyes, with a corneal diameter of less than 10 mm. Ocular examination revealed an enlarged cup-to-disc ratio, and optical coherence tomography (OCT) demonstrated thinning of the retinal nerve fiber layer and ganglion cell layer. Ultrasound biomicroscopy combined with gonioscopy indicated partial angle closure and abnormal anterior chamber angle development. The ocular manifestations in the twin brother were consistent with those observed in the twin sister. The clinical diagnosis was bilateral developmental glaucoma with microcornea. Genetic sequencing identified two novel compound heterozygous mutations in the ADAMTS18 gene in the twins: Mutation 1 (M1) involving the variant site 1 (c.3436C>T:p.R1146W) and Mutation 2 (M2) involving the variant site 2 (c.1454T>G:p.F485C). Ocular examinations of four additional family members were normal. Genetic testing revealed that the twins' father and sister carried M1, while the index case's mother and brother carried M2. This report underscores a unique association between ADAMTS18 gene mutations and developmental glaucoma with microcornea within a familial context, emphasizing the importance of genetic screening for early diagnosis and targeted management strategies.

'It's a lonely journey': caregiving experiences and psychosocial distress among Chinese American dementia family caregivers.

OBJECTIVES: Chinese American family caregivers of persons with Alzheimer's disease and related dementia (ADRD) are a vulnerable but understudied population. The goal of this qualitative study was to examine their caregiving experiences and psychosocial distress process and explore intervention strategies. METHODS: In-depth individual interviews were conducted with 18 Chinese American dementia caregivers. All interviews were transcribed verbatim; thematic content analysis was conducted to construct a conceptual framework. RESULTS: All participants reported high levels of caregiving stress associated with care-recipients' advanced symptoms and required assistance in activities in daily living. The relationship of caregiver and care-recipient was strained in their roles transition. The complex healthcare system, insurance policies, and a lack of linguistically appropriate services aggravated their psychosocial distress. Chinese cultural norms on 'family harmony' hindered their seeking of social support. Prolonged caregiving stress led to physical and mental impairment, including poor sleep, depression, and chronic conditions. Participants described their caregiving experience as 'a lonely journey' with a pervasive sense of hopelessness and withdrawal; their distress process was positively or negatively influenced by their coping strategies. All participants were eager for any kind of support; especially culturally appropriate programs that could improve their caregiving skills, self-care, and access to services. CONCLUSION: Our data suggest that Chinese American dementia caregivers, especially those with limited English proficiency, experience elevated psychosocial distress, which was aggravated by the barriers to social support and health services due to their immigrant and minority status. Culturally appropriate targeted intervention is urgently needed for this underserved and vulnerable population.

High-Performance Dual-Responsive Sensing Skin Enabled by Bioinspired Transduction of Coplanar Square-Loop Electrodes.

Advancements in intelligent robots and human-machine interaction necessitate a shift in artificial skins toward multimodal perception. Dual-responsive skins that can detect proximity and pressure information are significant to establishing continuous sensing of interaction processes and extending interactive application scenarios. To address the current limitations of inadequate dual-mode performance, such as limited proximal response change and low tactile sensitivity, this paper presents a bioinspired complementary gradient architecture-enabled (CGA) transduction design and a high-performance dual-responsive skin based on coplanar square-loop electrodes. Through systematic investigation into the transduction of various electrode configurations, comparative results reveal the remarkable potential of coplanar electrodes to deliver superior dual-mode performance without compromise. Simulations and experiments prove that the proposed CGA response mechanism can capture local interface deformation and overall compression signals, further enhancing response sensitivity. The final developed artificial skin is sensitive to external pressure and the approach of objects simultaneously, exhibiting a long detection distance (∼40 mm), a high proximity response (>0.4), and outstanding touch sensitivity (0.131 kPa-1). Furthermore, we demonstrate proof-of-concept applications for the proposed sensing skin in a dual-mode teleoperation interface and adaptive grasping interactions.

[Coiled tube of femoral anterolateral flap for repair of circumferential defect after operation of advanced hypopharyngeal carcinoma].

Objective: To investigate the clinical application value of coiled tube of femoral anterolateral flap in the repair of circumferential defect after resection of advanced hypopharyngeal carcinoma. Methods: Clinical data of 42 patients with advanced hypopharyngeal cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to April 2022 were retrospectively analyzed, including 41 males and 1 female, aged from 33 to 82 years old. All patients received surgical treatment, including total laryngectomy plus total laryngopharyngectomy in 20 cases, total laryngectomy, total laryngopharyngectomy and resection of partial tongue base in 8 cases, total laryngectomy, total laryngopharyngectomy and resection of cervical esophagus in 9 cases, total laryngectomy, total laryngopharyngectomy, and resection of partial tongue base and cervical esophagus in 5 cases. The postoperative circumferential defects were repaired with the coil tube of anterolateral femoral skin flap in phase Ⅰ, and the healing status of the flap, wound healing and swallowing function were observed. All cases were followed up. Results: The lengths of the hypopharyngeal defects were 7-18 cm and the sizes of the harvested flaps were 6 cm×9.5 cm-10 cm×20 cm. Flaps survived in 41 cases, flap necrosis occurred in one case, and the survival rate of flaps was 97.6%. One artery and one vein were anastomosed in 40 cases, and one artery and two veins were anastomosed in 2 cases. Postoperative cervical wound infection occurred in 5 cases, and pharyngeal fistula occurred in 2 cases. Three months of follow-up after surgery, 31 cases had normal diet, 9 cases presented with semi-liquid diet and 2 cases with liquid diet. Following up for 6-65 months, recurrence and metastasis occurred in 14 patients (33.3%), including primary site recurrence in 4 cases (9.5%), cervical lymph node recurrence in 6 cases (14.3%), and distant metastasis in 4 cases (9.5%). The 1-year and 3-year overall survival rates were respectively 79.4% and 60.5%. Conclusion: Coiled tube of femoral anterolateral flap is an ideal skin flap for repair of circumferential defects after resection of advanced hypopharyngeal carcinoma.

Chimeric kinase ALK induces expression of NAMPT and selectively depends on this metabolic enzyme to sustain its own oncogenic function.

As we show in this study, NAMPT, the key rate-limiting enzyme in the salvage pathway, one of the three known pathways involved in NAD synthesis, is selectively over-expressed in anaplastic T-cell lymphoma carrying oncogenic kinase NPM1::ALK (ALK + ALCL). NPM1::ALK induces expression of the NAMPT-encoding gene with STAT3 acting as transcriptional activator of the gene. Inhibition of NAMPT affects ALK + ALCL cells expression of numerous genes, many from the cell-signaling, metabolic, and apoptotic pathways. NAMPT inhibition also functionally impairs the key metabolic and signaling pathways, strikingly including enzymatic activity and, hence, oncogenic function of NPM1::ALK itself. Consequently, NAMPT inhibition induces cell death in vitro and suppresses ALK + ALCL tumor growth in vivo. These results indicate that NAMPT is a novel therapeutic target in ALK + ALCL and, possibly, other similar malignancies. Targeting metabolic pathways selectively activated by oncogenic kinases to which malignant cells become "addicted" may become a novel therapeutic approach to cancer, alternative or, more likely, complementary to direct inhibition of the kinase enzymatic domain. This potential therapy to simultaneously inhibit and metabolically "starve" oncogenic kinases may not only lead to higher response rates but also delay, or even prevent, development of drug resistance, frequently seen when kinase inhibitors are used as single agents.

Is endometrial sampler SAP-1 a good way to diagnose the common intrauterine occupying lesions?-A diagnostic study.

Background: Intrauterine occupying lesion is clinically common in the female reproductive organs. Endometrial cancer is the most critical one among intrauterine occupying lesions, which accordingly is considered as the main indication for endometrial cancer screening, for which endometrial sampler SAP-1 was recommended as an effective sampling tool. Objective: This study aimed to evaluate the diagnostic efficacy of SAP-1 for endometrial polyp and uterine submucous myoma. Materials and Methods: From August 2018 to June 2022, patients who were hospitalized for undergoing hysteroscopy examination were enrolled in this study. Before the procedure, endometrial samples were collected by the method of SAP-1. The histological results were compared with those by hysteroscopy sampling to analyze the diagnostic efficacy of SAP-1. Results: The qualified rate for the SAP-1 sampling was 92.1%, which is a bit lower than that by method of hysteroscopy (95.3%). And the difference was not statistically significant (P > 0.05). Endometrial polyp (47.5%) and uterine submucous myoma (7.1%) accounted for the majority of endometrial lesions, while only 11.3% endometrial polyps (17/151) and 0% submucous myomas (0/23) were detected by SAP-1 sampling. Conclusion: Endometrial sampler SAP-1 is not effective in detection of solid intrauterine lesions indicated by the imaging examination. Hysteroscopy is recommended for definite diagnosis.

[Diagnostic and prognostic values of flow cytometry in diffuse large B-cell lymphoma with bone marrow involvement].

Objective: To analyze the diagnostic and prognostic values of flow cytometry (FC) in diffuse large B cell lymphoma (DLBCL) with bone marrow involvement (BMI). Methods: The clinical data of 412 patients with newly diagnosed DLBCL, including 243 males and 169 females, aged 64 (28-92) years old, in the Department of Hematology at Peking University Third Hospital from December 2012 to June 2022 were retrospectively analyzed. All patients underwent bone marrow biopsy (BMB) and bone marrow FC. The patients with BMI by FC were further detected by fluorescence in situ hybridization (FISH) for gene analysis. The positive rates and consistency of BMI detected by BMB and FC were evaluated. According to the results of BMB and FC examinations, all patients were divided into four groups: the BMB+FC+group (115 cases), the BMB-FC+group (50 cases), the BMB+FC-group (8 cases, the results did not include in statistical analysis because of small sample size), and the BMB-FC-group (239 cases). The clinical features, treatment response rates, 5-year survival rates, and immunophenotype characteristics by FC in different groups were analyzed. Results: Among the 412 patients with DLBCL, the positivity rates of BMB and FC for BMI detection were 29.9% (123/412) and 40.0% (165/412), respectively. Good consistency between BMB and FC was found (Kappa=0.841, P=0.001). The numbers of extranodal involvement≥2, splenomegaly, huge mass, higher Ki-67 score, higher international prognostic index (IPI) score, thrombocytopenia, and elevated lactate dehydrogenase level were more prevalent in the BMB+FC+group than those in the BMB-FC+group and the BMB-FC-group (all P<0.05). The treatment response rate in BMB+FC+group was 63.5% (73/115), which was lower than those in BMB-FC+group (88.0%, 44/50, P=0.048) and BMB-FC-group (90.0%, 215/239, P=0.032), respectively. The 5-year overall survival rates in three groups were (53.6±9.7) %, (72.5±8.6) %, and (75.2±7.6) %, respectively, with a statistically significant difference (P=0.037). According to the FISH results of bone marrow, 102 cases were diagnosed as not otherwise specified (NOS), 48 cases were diagnosed as double hit lymphoma (DHL), and 15 cases were diagnosed as triple hit lymphoma (THL). Compared with NOS subtypes, the tumor cells in DHL or THL subtypes had higher proportion of increased side scatter (SSC), higher positive rates of CD10 expression, CD38 strong expression and CD56 expression, and lower proportion of surface immunoglobulin light chain restriction (all P<0.05). Conclusions: FC is well consistent with BMB in diagnosing DLBCL with BMI. Combined with FISH detection, FC can contribute to the auxiliary diagnosis and risk stratification for DHL and THL, and provide reference for the prognostic evaluation in DLBCL with BMI.

[LRG1 inhibits hepatic macrophage activation by enhancing TGF-ß1 signaling to alleviate MAFLD in mice].

OBJECTIVE: To explore the effect of leucine-rich α-2-glycoprotein (LRG1) derived from hepatocytes on activation of hepatic M1 Kupffer cells. METHODS: A metabolic dysfunction-associated fatty liver disease (MAFLD) model was established in BALB/c mice by high-fat diet (HFD) feeding for 16 weeks. Oleic acid was used to induce steatosis in primary cultures of mouse hepatocytes. The mRNA and protein expressions of LRG1 in mouse liver tissues and hepatocytes were detected by real-time PCR and Western blotting. Primary hepatic macrophages were stimulated with the conditioned medium (CM) from steatotic hepatocyte along with LRG1 or transforming growth factor-ß1 (TGF-ß1), or both for 24 h, and the expression levels of inducible nitric oxide synthase (iNOS) was detected with Western botting, and the mRNA expressions of iNOS, chemokine ligand 1 (CXCL-1) and interleukin-1ß (IL-1ß) were measured by RT-PCR. The MAFLD mice were injected with LRG1 (n=6), TGF-ß1 (n=6), or both (n=6) through the caudal vein, and the live tissues were collected for HE staining and immumohistochemical detection of F4/80 expression; the mRNA expressions of iNOS, CXCL-1 and IL-1ß in liver tissues were detected using RT-PCR. RESULTS: The mRNA and protein expression levels of LRG1 were significantly downregulated in the liver tissues of MAFLD mice and steatotic hepatocytes (P < 0.05). Treatment of the hepatic macrophages with CM from steatosis hepatocytes significantly enhanced the mRNA expression levels of iNOS, CXCL-1 and IL-1ß, and these changes were significantly inhibited by the combined treatment with TGF-ß1 and LRG1 (P < 0.05). In MAFLD mice, injections with either LRG1 or TGF-ß1 alone reduced hepatic lipid deposition and intrahepatic macrophage infiltration, and these effects were significantly enhanced by their combined treatment, which also more strongly inhibited the mRNA expression levels of iNOS, CXCL-1 and IL-1ß (P < 0.05). CONCLUSION: LRG1 inhibits hepatic macrophage infiltration by enhancing TGF-ß1 signaling to alleviate fatty liver inflammation in MAFLD mice.

Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. METHODS: Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. RESULTS: Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. CONCLUSIONS: Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.

Canadian SARS-CoV-2 serological survey using antenatal serum samples: a retrospective seroprevalence study.

BACKGROUND: Insufficient data on the rate and distribution of SARS-CoV-2 infection in Canada has presented a substantial challenge to the public health response to the COVID-19 pandemic. Our objective was to assess SARS-CoV-2 seroprevalence in a representative sample of pregnant people throughout Canada, across multiple time points over 2 years of the pandemic, to describe the seroprevalence and show the ability of this process to provide prevalence estimates. METHODS: This Canadian retrospective serological surveillance study used existing serological prenatal samples across 10 provinces over multiple time periods: Feb. 3-21, 2020; Aug. 24-Sept. 11, 2020; Nov. 16-Dec. 4, 2020; Nov. 15-Dec. 3, 2021; and results from the province of British Columbia during a period in which the SARS-CoV-2 B.1.1.529 (Omicron) variant was predominant, from Nov. 15, 2021, to June 11, 2022. Age and postal code administrative data allowed for comparison with concurrent polymerase chain reactivity (PCR)-positive results collected by Statistics Canada and the Canadian Surveillance of COVID-19 in Pregnancy (CANCOVID-Preg) project. RESULTS: Seropositivity in antenatal serum as early as February 2020 indicates SARS-CoV-2 transmission before the World Health Organization's declaration of the pandemic. Seroprevalence in our sample of pregnant people was 1.84 to 8.90 times higher than the recorded concurrent PCR-positive prevalence recorded among females aged 20-49 years in November-December 2020. Overall seropositivity in our sample of pregnant people was low at the end of 2020, increasing to 15% in 1 province by the end of 2021. Seroprevalence among pregnant people in BC during the Omicron period increased from 5.8% to 43% from November 2021 to June 2022. INTERPRETATION: These results indicate widespread vulnerability to SARS-CoV-2 infection before vaccine availability in Canada. During the time periods sampled, public health tracking systems were under-reporting infections, and seroprevalence results during the Omicron period indicate extensive community spread of SARS-CoV-2 infection.

A WeChat-based Intervention, Wellness Enhancement for Caregivers (WECARE), for Chinese American Dementia Caregivers: Pilot Assessment of Feasibility, Acceptability, and Preliminary Efficacy.

BACKGROUND: Chinese American family caregivers of persons with dementia experience high rates of psychosocial distress and adverse health outcomes. Due to their immigrant and minority status, they face substantial obstacles to care and support, including stigma and misperception of dementia, limited knowledge and use of welfare and services, and poor social support. Few interventions have been developed or tested for this vulnerable population. OBJECTIVE: This study aims to pilot-test the Wellness Enhancement for Caregivers (WECARE) intervention, a culturally tailored program delivered via WeChat, a social media app highly popular in the Chinese population. The 7-week WECARE was designed specifically for Chinese American dementia caregivers to improve their caregiving skills, reduce stress, and enhance psychosocial well-being. Feasibility, acceptability, and preliminary efficacy of the WECARE were assessed in this pilot. METHODS: A total of 24 Chinese American family caregivers of persons with dementia were recruited for a pre-post 1-arm trial of the WECARE. By subscribing to the WECARE official account, participants received interactive multimedia programs on their WeChat account multiple times a week for 7 weeks. A backend database automatically delivered program components and tracked user activities. Three online group meetings were organized to facilitate social networking. Participants completed a baseline and a follow-up survey. Feasibility was assessed by the follow-up rate and curriculum completion rate; acceptability was assessed by user satisfaction and perceived usefulness of the program; and efficacy was assessed with pre-post differences in 2 primary outcomes of depressive symptoms and caregiving burden. RESULTS: The intervention was completed by 23 participants with a retention rate of 96%. Most of them (n=20, 83%) were older than 50 years and the majority (n=17, 71%) were female. The backend database revealed that the mean curriculum completion rate was 67%. Participants also reported high rates of user satisfaction and perceived usefulness of the intervention and high ratings of weekly programs. The intervention led to significant improvement in participants' psychosocial health outcomes; their depressive symptoms reduced from 5.74 to 3.35 with an effect size of -0.89 and caregiving burden decreased from 25.78 to 21.96 with an effect size of -0.48. CONCLUSIONS: This pilot study suggests that WeChat-based WECARE intervention was feasible and acceptable; it also demonstrated initial efficacy in improving psychosocial well-being in Chinese American dementia caregivers. Further research with a control group is needed to assess its efficacy and effectiveness. The study highlights the need for more culturally appropriate mobile health interventions for Chinese American family caregivers of persons with dementia.

Synthesis and Characterization of Spirocyclic Mid-Block Containing Triblock Copolymer.

Polymers containing cyclic derivatives are a new class of macromolecular topologies with unique properties. Herein, we report the synthesis of a triblock copolymer containing a spirocyclic mid-block. To achieve this, a spirocyclic polystyrene (cPS) mid-block was first synthesized by atom transfer radical polymerization (ATRP) using a tetra-functional initiator, followed by end-group azidation and a copper (I)-catalyzed azide-alkyne cycloaddition reaction. The resulting functional cPS was purified using liquid chromatography techniques. Following the esterification of cPS, a macro-ATRP initiator was obtained and used to synthesize a poly (methyl methacrylate)-block-cPS-block-poly (methyl methacrylate) (PMMA-b-cPS-b-PMMA) triblock copolymer. This work provides a synthetic strategy for the preparation of a spirocyclic macroinitiator for the ATRP technique and as well as liquid chromatographic techniques for the purification of (spiro) cyclic polymers.

Social Determinants of COVID-19 Vaccination Rates: A Time-Constrained Multiple Mediation Analysis.

Objective To estimate the multiple direct/indirect effects of social, environmental, and economic factors on COVID-19 vaccination rates (series complete) in the 3109 continental counties in the United States (U.S.). Study design  The dependent variable was the COVID-19 vaccination rates in the U.S. (April 15, 2022). Independent variables were collected from reliable secondary data sources, including the Census and CDC. Independent variables measured at two different time frames were utilized to predict vaccination rates. The number of vaccination sites in a given county was calculated using the geographic information system (GIS) packages as of April 9, 2022. The Internet Archive (Way Back Machine) was used to look up data for historical dates. Methods  A chain of temporally-constrained least absolute shrinkage and selection operator (LASSO) regressions was used to identify direct and indirect effects on vaccination rates. The first regression identified direct predictors of vaccination rates. Next, the direct predictors were set as response variables in subsequent regressions and regressed on variables that occurred before them. These regressions identified additional indirect predictors of vaccination. Finally, both direct and indirect variables were included in a network model. Results  Fifteen variables directly predicted vaccination rates and explained 43% of the variation in vaccination rates in April 2022. In addition, 11 variables indirectly affected vaccination rates, and their influence on vaccination was mediated by direct factors. For example, children in poverty rate mediated the effect of (a) median household income, (b) children in single-parent homes, and (c) income inequality. For another example, median household income mediated the effect of (a) the percentage of residents under the age of 18, (b) the percentage of residents who are Asian, (c) home ownership, and (d) traffic volume in the prior year. Our findings describe not only the direct but also the indirect effect of variables. Conclusions  A diverse set of demographics, social determinants, public health status, and provider characteristics predicted vaccination rates. Vaccination rates change systematically and are affected by the demographic composition and social determinants of illness within the county. One of the merits of our study is that it shows how the direct predictors of vaccination rates could be mediators of the effects of other variables.

Docetaxel as a Model Compound to Promote HDL (High-Density Lipoprotein) Biogenesis and Reduce Atherosclerosis.

The recent identification of the cell-surface protein DSC1 (desmocollin 1) as a negative regulator of HDL (high-density lipoprotein) biogenesis has attracted us to revisit the old HDL biogenesis hypothesis: HDL biogenesis reduces atherosclerosis. The location and function of DSC1 suggest that DSC1 is a druggable target for the promotion of HDL biogenesis, and the discovery of docetaxel as a potent inhibitor of the DSC1 sequestration of apolipoprotein A-I has provided us with new opportunities to test this hypothesis. The FDA-approved chemotherapy drug docetaxel promotes HDL biogenesis at low-nanomolar concentrations that are far lower than used in chemotherapy. Docetaxel has also been shown to inhibit atherogenic proliferation of vascular smooth muscle cells. In accordance with these atheroprotective effects of docetaxel, animal studies have shown that docetaxel reduces dyslipidemia-induced atherosclerosis. In the absence of HDL-directed therapies for atherosclerosis, DSC1 constitutes an important new target for the promotion of HDL biogenesis, and the DSC1-targeting compound docetaxel serves as a model compound to prove the hypothesis. In this brief review, we discuss opportunities, challenges, and future directions for using docetaxel in the prevention and treatment of atherosclerosis.