Benefits of Chinese family caregivers of patients with urostomy: a qualitative study.

BACKGROUND: Family caregivers, also known as informal caregivers, are critical for the home care of patients with urostomy. The present study aimed to investigate the benefits of family caregivers in China while taking care of patients with urostomy from a positive perspective. METHODS: A qualitative research design was adopted, with a thematic analysis. The qualitative research software NVivo was used for data analysis. Twenty-two family caregivers of urostomy patients participated in an in-depth interview for 60-90 min. A qualitative analysis was performed using a thematic approach in accordance with the six-stage thematic analysis process reported by Braun and Clarke (2006). RESULTS: The following four benefits were identified: mastering knowledge and skills, promoting self-growth, establishing close family ties, and changing the way of life. Among these four themes, 11 sub-themes were constructed by coders. CONCLUSIONS: This study provides new insights into intervention measures for family caregivers of patients with urostomy, which could play an important role in developing the overall model of family-centered nursing.

Pediatric Oral Health Service Access in Racial/Ethnic Minority Neighborhoods: A Geospatial Analysis in Washington, D.C., USA.

Oral health plays a crucial role in overall well-being. One of the goals set by the US Department of Health and Human Service, Healthy People 2030 is to reducing dental caries in children and adolescents. The study aims to investigate the accessibility of pediatric dental care in neighborhoods with mixed-race and predominantly African American populations in the Washington District of Columbia (DC) area. Our objective is to uncover and highlight the disparities that exist in pediatric dental care within these communities. We have specifically examined the geographic and socio-demographic aspects of pediatric dental care facilities, utilizing geospatial tools such as modeling and mapping, as well as data from the clinical database at Howard University College of Dentistry. The detailed analysis of dental care access revealed significant disparities among various Wards in the region. Specifically, Wards 5, 7, and 8 stood out as having both the highest concentrations of African American residents and the lowest availability of pediatric dentistry providers when compared to the more affluent Wards 1, 2, and 3. Howard University College of Dentistry's pediatric dentistry department played a crucial role in providing dental care services to the community. Over the course of the year 2022, they recorded a total of 3,855 visits from residents of the DC area. Notably, a substantial portion of these visits, specifically 1,566 visits, were from individuals residing in Wards 5, 7 and 8. This data underscores the significant demand for pediatric dental services in these underserved communities and highlights the importance of addressing the disparities in access to care.

Predictive value of immediate early response 5 like (IER5L) in the prognosis and immune checkpoint blockade therapy of non-small cell lung cancer patients.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a malignancy with high mortality. Immediate early response 5 like (IER5L) has been found to associate with worse prognosis in colorectal cancer patients. However, its role in the prognosis prediction of NSCLC has remained largely unknown. METHODS: The IER5L expression in NSCLC and normal tissues was analyzed in two public cohorts: TCGA-LUAD-LUSC and GSE159857. Additionally, functional enrichment, survival analysis, CIBERSORT and tumor mutation burden (TMB) were investigated between low- and high-IER5L level groups. The in vitro IER5L mRNA and protein levels were determined using RT-qPCR and western blot, respectively. RESULTS: The data from TCGA-LUAD-LUSC and GSE159857 cohorts showed a high IER5L mRNA expression in NSCLC tissue samples compared to normal controls. The increased expression of IER5L in NSCLC cells were also validated by RT-qPCR and western blot analysis. Additionally, NSCLC patients with high-IER5L level had significantly worse prognosis and IER5L could be used as an independent prognostic factor for NSCLC patients. Meanwhile, patients in the high-IER5L group had higher TMB level. IER5L expression was negatively correlated with the proportion of Monocytes and T cells CD4 memory resting, and was positively related to the proportion of Tregs and M0 macrophages in tumor tissues. Besides, transcription factors TFAP4 and ZNF692 may bind to the promoter region of IER5L, and then modulate IER5L gene transcription, thereby affecting IER5L gene expression. Furthermore, GSEA results showed that IER5L gene was closely related to MAPK, PI3K-Akt, NF-kappaB signaling pathways in NSCLC. CONCLUSION: Collectively, high IER5L expression may be a promising unfavorable prognostic biomarker and therapeutic target for NSCLC patients.

Predisposing, Enabling, and Need Factors Associated with Psychotropic Medication and Mental Health Service Use among Children in Out-of-Home Care in the United States: A Scoping Review.

This scoping review aimed to identify predisposing, enabling, and need factors associated with the use of mental health services, including psychotropic medications, among children in out-of-home care in the United States. We searched the PsycInfo, SocINDEX, Medline, and Scopus databases, and 22 studies met inclusion criteria and were systematically analyzed. Among the included studies, 7 studies examined predictors associated with taking psychotropic medications, and 16 examined factors associated with using other mental health services. Significant predisposing, enabling, and need factors associated with greater use of mental health services, including psychotropic medications, were identified. The most frequently identified predisposing factors were child race/ethnicity, age, gender, and maltreatment. Important enabling factors were out-of-home placement type and length of care, and need factors included children's mental/behavioral problems. The results provide insight into maximizing factors facilitating children's use of mental health services to address mental health problems of children in out-of-home care. Further, the results imply the importance of the appropriate use of psychotropic medication (e.g., the type and dosage of medications) among children in out-of-home care. The identified factors can inform child welfare agencies and stakeholders on ways to improve access to mental health services and the appropriate use of psychotropic medications among children in out-of-home care in the United States.

[Establishment of risk prediction nomograph model for sepsis related acute respiratory distress syndrome].

OBJECTIVE: To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model. METHODS: The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO2/FiO2), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model. RESULTS: There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO2/FiO2, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914). CONCLUSIONS: Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.

Sickle cell disease: Contributing factors and radiological assessments.

Sickle Cell Disease (SCD) is genetically described as an autosomal blood disorder resulting from the presence of a mutated form of hemoglobin. Morbidity, frequency of crisis, degree of anemia, and organ systems involved vary considerably per patient. Dental health professionals and other specialists commonly request comprehensive medical consultations prior to performing complex periodontal, endodontic, and surgical procedures. In order to have successful dental outcomes and minimize posttreatment dental complications, relevant disease indicators are noted. This review is to raise awareness of the impact of oral diseases in patients with sickle cell disease and to emphasize the importance of full medical disclosure, radiographic interpretation, and a well-documented medical history, and a well-written consultation which can guide treatment planning and greatly improve the course of dental treatment.

Remote ischemic postconditioning ameliorates stroke injury via the SDF-1α/CXCR4 signaling axis in rats.

Remote Ischemic Postconditioning (RIPostC) has become a research hotspot due to its protective effect on the brain in clinical studies related to ischemic stroke. The purpose of this study is to investigate the protective effect of RIPostC after ischemic stroke in rats. The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by the wire embolization method. RIPostC was obtained by inducing temporary ischemia in the hind limbs of rats. First, based on the results of short-term behavioral measures and long-term neurological function experiments, RIPostC was found to have a protective effect on the MCAO/R model and to improve neurological recovery in rats. Compared to the sham group, RIPostC upregulated the expression levels of C-X-C motif chemokine receptor 4(CXCR4) in the brain and stromal cell-derived factor-1(SDF-1α) in peripheral blood. In addition, RIPostC upregulated CXCR4 expression on CD34 + stem cells in peripheral blood in flow cytometric assays. Meanwhile, according to the results of EdU/DCX co-staining and CD31 staining, it was found that the effect of RIPostC on ameliorating brain injury via SDF-1α/CXCR4 signaling axis may be associated with vascular neogenesis. Finally, after inhibiting the SDF-1α/CXCR4 signaling axis using AMD3100(Plerixafor), we found that the neuroprotective effect of RIPostC was diminished. Taken together, RIPostC can improve neurobehavioral damage induced by MCAO/R in rats, and its mechanism may be related to SDF-1α/CXCR4 signaling axis. Therefore, RIPostC can be used as an intervention strategy for stroke. SDF-1α/CXCR4 signaling axis can also be a potential target for intervention.

Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II.

Glutaric aciduria type II (GA II) is an autosomal recessive metabolic disorder of fatty acid, amino acid, and choline metabolism. The late-onset form of this disorder is caused by a defect in the mitochondrial electron transfer flavoprotein dehydrogenase or the electron transfer flavoprotein dehydrogenase (ETFDH) gene. Thus far, the high clinical heterogeneity of late-onset GA II has brought a great challenge for its diagnosis. In this study, we reported a 21-year-old Chinese man with muscle weakness, vomiting, and severe pain. Muscle biopsy revealed myopathological patterns of lipid storage myopathy, and urine organic acid analyses showed a slight increase in glycolic acid. All the aforementioned results were consistent with GA II. Whole-exome sequencing (WES), followed by bioinformatics and structural analyses, revealed two compound heterozygous missense mutations: c.1034A > G (p.H345R) on exon 9 and c.1448C>A (p.P483Q) on exon 11, which were classified as "likely pathogenic" according to American College of Medical Genetics and Genomics (ACMG). In conclusion, this study described the phenotype and genotype of a patient with late-onset GA II. The two novel mutations in ETFDH were found in this case, which further expands the list of mutations found in patients with GA II. Because of the treatability of this disease, GA II should be considered in all patients with muscular symptoms and acute metabolism decompensation such as hypoglycemia and acidosis.

Hypothalamic hypernatremic myopathy: A single-center case series.

INTRODUCTION/AIMS: Hypernatremia myopathy is a rare disease often unrecognized by clinicians. This study aimed to present a case series of hypernatremic myopathy with an emphasis on profiling its clinical characteristics and exploring its pathogenesis. METHODS: We reviewed seven patients with hypernatremic myopathy and reported their demographic data, etiology, clinical manifestations, and laboratory and electrophysiological characteristics. A muscle biopsy was performed on one patient. RESULTS: All patients had hypothalamic lesions as the cause of the hypernatremia including craniopharyngioma, germinoma, pituitary adenoma, Langerhans cell histiocytosis, and glioma. The clinical manifestations varied from mild weakness to complete paralysis. Myalgia and muscle cramps were also observed. Four of the patients had rhabdomyolysis on admission and developed acute kidney injury. All patients had markedly elevated serum creatine kinase (CK) and sodium levels. There was a significant positive correlation between serum sodium and CK levels. A high prevalence of hypopituitarism in different axes was observed in our study. Central hypogonadism (5 of 7), central hypothyroidism (3 of 7), and central diabetes insipidus (3 of 7) were the most common manifestations of hypothalamic dysfunction. Myopathic changes were observed on needle electromyography. The muscle biopsy of one patient showed diffuse necrotic fibers and scattered hypercontracted fibers with increased ragged red fibers. DISCUSSION: Hypernatremia myopathy should be considered in hypernatremic patients with muscle weakness and myalgia. Rhabdomyolysis frequently occurs and may lead to acute kidney injury in hypernatremia myopathy. Testing of hormone levels and performance of brain magnetic resonance imaging for possible hypothalamic lesions is strongly recommended.

Features of MRI honeycomb edema signals in cancer-associated dermatomyositis patients: a brief report.

Dermatomyositis (DM) is an autoimmune inflammatory disease that is a possible paraneoplastic phenomenon. The aim of this study was to explore the difference in thigh MRI findings between DM patients with and without cancer to further assist clinicians in the early discovery of underlying malignancy. Thigh muscle MRI with T2 fs/STIR images obtained from 47 patients diagnosed with DM at a single center were retrospectively assessed for the involvement of muscle compartments, as well as the pattern and distribution of the edema signal. Among 47 patients, 14 had cancer within three years of DM diagnosis. Honeycomb edema signals were more frequently observed in cancer patients (10 in the cancer group, 11 in the noncancer group, p = 0.020), while foggy signals were not found in cancer patients. Among patients with honeycomb signals, we found that cancer patients had a relatively longer disease duration (p = 0.012), lower creatine kinase levels (p = 0.011), and barely showed adductor involvement (p = 0.016). Logistic regression analysis identified honeycomb edema signals in the quadriceps without adductor involvement as an independent risk factor for having cancer in DM patients. Honeycomb pattern edema signals showed in quadriceps but not adductors on thigh muscle MRI STIR/T2 fs sequence were more frequently found in cancer-associated DM patients. Key points • MRI honeycomb edema signals in the quadriceps without adductor involvement may be a predictor for underlying cancer in DM patients.

Identification of immune-related features involved in Duchenne muscular dystrophy: A bidirectional transcriptome and proteome-driven analysis.

Background: We aimed to investigate the biological mechanism and feature genes of Duchenne muscular dystrophy (DMD) by multi-omics and experimental verification strategy. Methods: We integrated the transcriptomic and proteomic methods to find the differentially expressed mRNAs (DEMs) and proteins (DEPs) between DMD and Control groups. Weighted gene co-expression network analysis (WGCNA) was then used to identify modules of highly correlated genes and hub genes. In the following steps, the immune and stromal cells infiltrations were accomplished by xCELL algorithm. Furthermore, TF and miRNA prediction were performed with Networkanalyst. ELISA, western blot and external datasets were performed to verify the key proteins/mRNAs in DMD patient and mouse. Finally, a nomogram model was established based on the potential biomarkers. Results: 4515 DEMs and 56 DEPs were obtained from the transcriptomic and proteomic study respectively. 14 common genes were identified, which is enriched in muscle contraction and inflammation-related pathways. Meanwhile, we observed 33 significant differences in the infiltration of cells in DMD. Afterwards, a total of 22 miRNAs and 23 TF genes interacted with the common genes, including TFAP2C, MAX, MYC, NFKB1, RELA, hsa-miR-1255a, hsa-miR-130a, hsa-miR-130b, hsa-miR-152, and hsa-miR-17. In addition, three genes (ATP6AP2, CTSS, and VIM) showed excellent diagnostic performance on discriminating DMD in GSE1004, GSE3307, GSE6011 and GSE38417 datasets (all AUC > 0.8), which is validated in patients (10 DMD vs. 10 controls), DMD with exon 55 mutations, mdx mouse, and nomogram model. Conclusion: Taken together, ATP6AP2, CTSS, and VIM play important roles in the inflammatory response in DMD, which may serve as diagnostic biomarkers and therapeutic targets.

A home visit program for low-income African American children with asthma: Caregivers' perception of asthma triggers and a gap in action.

PURPOSE: The goals are to gauge caregivers' knowledge of at-home asthma triggers and identify the areas on which educational campaigns can focus to alleviate a child's asthma symptoms. DESIGN AND METHODS: Families with children with moderate to severe asthmatic symptoms who had been recently hospitalized or in the emergency room were invited to participate in a home visit program. As part of the home visit, caregivers of the asthmatic children were asked a series of questions on asthma triggers and the measures for eliminating the triggers (N = 218). RESULTS: Findings show a gap between caregivers' perception of asthma triggers and the actions to mitigate or avoid such triggers. CONCLUSIONS: Overall findings show that home environments were suboptimal for the management and control of child asthma conditions. Knowledge about home triggers as well as the actions and efforts by caregivers and landlords to mitigate these was found to be inadequate. Even when caregivers are aware of the presence of at-home triggers, actions to minimize exposure to the trigger do not always follow due to a lack of power, resource, and knowledge. PRACTICE IMPLICATIONS: The findings raise the need for additional research to investigate the reasons for the lack of actions, advocacy for low-income families to live in a healthy environment, continued education and empowerment, and patient/caregiver-doctor partnership. Additionally, the provision of community support through community advocacy and training of culturally competent healthcare providers are needed for the successful management of pediatric asthma among African American children.

The Prediction of Surgery Outcomes in Abdominal Tumor Patients with Sepsis by Pcv-aCO2/Ca-cvO2.

Background: To determine whether Pcv-aCO2/Ca-cvO2 combined with Pcv-aCO2 could predict the outcomes in patients complicated with abdominal infection and sepsis after abdominal tumor operation. Methods: Total 92 patients admitted to our hospital from January 2017 to December 2020 who underwent abdominal tumor operation were enrolled. Blood gas analysis of artery and central vein, various laboratory indexes, SOFA score, hemodynamic parameters at different time points and treatment outcome were recorded. Results: ROC curve analysis showed that hemodynamic parameter alone could not predict ICU treatment outcome and mortality of patients, but 72-hour SOFA score could predict treatment outcome of patients (AUC = 0.930, 95% CI: 0.803-1.000, p = 0.019). The significant hemodynamic parameter for evaluating treatment outcome and prognosis of patients was Pcv-aCO2 + Ratio of T3. Kaplan-Meier univariate survival curve and Log-rank suggested that patients who had higher combined predictive parameter of T3 Ratio + T3 Pcv-aCO2 still had ischemia and hypoxia of tissues and organs after standard fluid resuscitation, and treatment outcome was not good. In subgroup analysis, patients with higher Ratio had higher lactate, higher T72 SOFA score, and poor treatment outcome. Conclusion: The combination of Ratio and Pcv-aCO2 could evaluate clinical treatment outcome of patients complicated with abdominal infection and sepsis after abdominal tumor operation.

Safety and efficacy of tyrosine kinase inhibitors for the treatment of multiple sclerosis: A systematic review and meta-analysis from randomized controlled trials.

Background: Multiple sclerosis (MS), an autoimmune disease, is characterized by inflammatory demyelinating lesions in the white matter of the central nervous system. Drugs targeting tyrosine kinase, a critical component of immune cell receptor signaling, have been developed to treat MS. However, the exact efficacy and safety of tyrosine kinase inhibitors (TKIs) are still controversial, and comprehensive analysis with a high level of evidence is needed. Methods: Medline, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials (RCTs) evaluating TKIs versus placebo for MS were searched up to April 1st, 2022. The risk ratio (RR) and mean difference (MD) or standard mean difference (SMD) were analyzed using dichotomous outcomes and continuous outcomes, respectively, with a random effect model. Results: A total of 1,043 patients derived from four clinical trials were included to investigate the efficacy and safety of TKI therapy for MS. According to our analysis, TKIs decreased the cumulative number of gadolinium-enhancing lesions on T1-weighted MRI with the application of high dose (SMD = -0.61, 95% CI: -0.93 to -0.30, P = 0.0001). Meanwhile, TKIs prevented the expanded disability status scale (EDSS) from rising (MD = -0.10, 95% CI: -0.19 to -0.00, P = 0.046). In terms of MS relapse, TKIs have not revealed an obvious statistical difference compared with placebo (RR = 0.96, 95% CI: 0.55-1.65, P = 0.8755). However, more adverse events seem to occur in the TKIs group, both for adverse events (RR = 1.12, 95% CI: 1.05-1.19, P = 0.0009) and serious adverse events (RR = 1.91, 95% CI: 1.30-2.81, P = 0.001). Conclusion: Tyrosine kinase inhibitors have shown promise in treating MS. Generally, TKIs that attain the effective dose demonstrate definite efficacy and have tolerable side effects. More clinical trials and validation are needed, and we anticipate that TKIs will be a viable alternative for MS patients.

Discrepancies between children's and caregivers' child maltreatment reporting and their associations with child wellbeing.

BACKGROUND: Child maltreatment reporting is critical for case investigation and service disposition. However, reporting discrepancies across informants is a challenge for child welfare services. METHODS: Using data from the Fragile Families and Child Wellbeing Study (n = 3150), the current study examined child-caregiver discrepancies in reporting the frequencies of psychological and physical maltreatment. Multivariate models were used to examine how caregivers' reports, children's reports, and discrepancies between the two were associated with child anxiety, depression, aggression, and delinquency. RESULTS: A quarter of the children reported psychological maltreatment at a higher (25.7 %) or lower (23.8 %) frequency than their caregivers' report, respectively; 8.4 % and 8.7 % of the children did so in physical maltreatment reports, respectively. Multivariate models showed that children's maltreatment reports were more closely associated with children's anxiety, depression, and delinquency than caregivers' reports, while caregivers' reports were more closely associated with children's aggression. After accounting for caregivers' reporting and other covariates, children who reported more frequent psychological maltreatment than their caregivers' report had a higher level of anxiety, depression, and delinquency (b = 0.17 to 0.25, p < 0.001), and the opposite was true (b = -0.36 to -0.13, p < 0.001). Similarly, children who reported more frequent physical maltreatment than their caregivers' report had a higher level of all negative outcomes (b = 0.04 to 0.44; p = 0.04 to <0.00), and the opposite was true for aggression (b = -0.08, p = 0.004). CONCLUSIONS: The findings suggest that in addition to other reporting barriers, children and caregivers may perceive maltreatment differently, and such discrepancies are related to children's wellbeing.

Case report: A novel APTX p.Ser168GlufsTer19 mutation in a Chinese family with ataxia with oculomotor apraxia type 1.

Ataxia with oculomotor apraxia type 1 (AOA1) is a rare genetic disorder and is inherited in an autosomal recessive manner. It is mainly characterized by childhood-onset progressive cerebellar ataxia, with dysarthria and gait disturbance being the two most common and typical manifestations. Axonal sensorimotor peripheral neuropathy, dystonia, chorea, and cognitive impairment are common associated symptoms, as are hypoalbuminemia and hypercholesterolemia. Oculomotor apraxia (OMA)has been reported to be a feature often, although not exclusively, associated with AOA1. The Aprataxin gene, APTX, is ubiquitously expressed, and numerous APTX mutations are associated with different clinical phenotypes have been found. In the present study, we enrolled a 14-year-old boy who developed ataxia with staggering gait from the age of 4 years. Early-onset cerebellar ataxia, peripheral axonal neuropathy, cognitive impairment and hypoalbuminemia, hypercholesterolemia were presented in this patient, except for OMA. We applied ataxia-related genes filtering strategies and whole-exome sequencing (WES) to discover the genetic factors in a Chinese family. Sanger sequencing was used in the co segregation analysis in the family members. A compound heterozygous mutation in APTX gene (c.739C>T and c.501dupG) was identified. This is the first description of a genetically confirmed patient of AOA1 in a Chinese family in addition to a novel mutation of c.501dupG in APTX.

Activation of cGAS-STING pathway - A possible cause of myofiber atrophy/necrosis in dermatomyositis and immune-mediated necrotizing myopathy.

OBJECTIVE: The objective was to investigate the expression of the cGAS-STING pathway-associated protein in idiopathic inflammatory myopathy (IIM) and to investigate whether it is related to myofiber atrophy/necrosis in patients with dermatomyositis and immune-mediated necrotizing myopathy. MATERIAL AND METHODS: Muscle specimens obtained by open biopsy from 26 IIM patients (14 with dermatomyositis (DM), 8 with immune-mediated necrotizing myopathy (IMNM), and 4 with other types of IIM), 4 dystrophinopathy, and 9 control patients were assessed for expression of cGAS-STING pathway members via Western blot, quantitative real-time PCR analysis (qRT-PCR), and immunochemistry. Meanwhile, analysis its location distribution througn immunochemistry. RESULTS: Compared to the control group, the expression of cGAS, STING, and related molecules was obviously increased in muscle samples of IIM patients. Upregulated cGAS and STING were mainly located in the vascular structure, inflammatory infiltrates, and atrophic and necrotic fibers. While comparing to the Dys patients, the mRNA level of cGAS, STING, and TNF-a was upregulated, meanwhile, the protein of the TBK1, P-TBK1, and P-IRF3 associated with interferon upregulation was overexpressed through Western blot in IMNM and DM. Considering that cGAS and STING are located in necrotic and Mx1-positive atrophic fibers, it is really possible that the cGAS-STING pathway may lead to fibers atrophy/necrosis by producing IFNs. CONCLUSION: The cGAS-STING pathway was activated in the muscle samples of IIM patients and its activation may be the reason of myofiber atrophy and necrosis in DM and IMNM patients.

A Case Study of Community-Academic Partnership in Improving the Quality of Life for Asthmatic Urban Minority Children in Low-Income Households.

Community-academic partnerships (CAPs) are being increasingly used to study and address health disparity issues. CAPs help to create new bodies of knowledge and innovative solutions to community problems, which benefits the community and academia. Supported by a grant, a partnership was formed between an academic research team and a community health organization to analyze and interpret data collected from the caregivers of asthmatic African American children living in urban low-income households. Using a case study approach, we discuss how we built a healthy CAP and the lessons learned from the process. Our analysis was guided by the six main factors that facilitate success in developing collaborative relationships, including (1) environment; (2) membership; (3) process and structure; (4) communication; (5) purpose; and (6) resources. Based on these six factors, we describe our collaboration process, challenges, and areas for improvement. We aimed to provide a "points-to-consider" roadmap for academic and community partners to establish and maintain a mutually beneficial and satisfactory relationship. Collaborating with community members and organizations provides unique opportunities for researchers and students to apply their skills and knowledge from textbooks and the classroom, engage with community members, and improve real-life community needs. Building a constructive CAP involves efforts, energy, and resources from both parties. The six major themes derived from our project offer suggestions for building a healthy, collaborative, and productive relationship that best serves communities in the future.

Oral Health Service Access in Racial/Ethnic Minority Neighborhoods: A Geospatial Analysis in Washington, DC, USA.

Previous studies on individual-level variables have improved our knowledge base of oral health service use. However, environmental or contextual variables are also important in understanding oral health disparities in racial and ethnic neighborhoods. Based on Bronfenbrenner's ecological framework, this study examines the geographic availability of oral health providers in Washing-ton DC, U.S.A. Census tract-level data were drawn from the American Community Survey, joined with tract-level shapefiles, and overlaid with the geographic location of dental services throughout the city. Visual maps, descriptive statistics, and spatial lag regression models showed that census tracts with higher concentrations of African Americans were significantly farther from their nearest oral health providers (r = 0.19, p < 0.001), after controlling for neighborhood poverty rate, median age, and gender. Such findings confirm that in urban areas with highly di-verse populations such as Washington DC, racial disparities in oral health care access are signifi-cant. The study highlights that identifying neighborhoods with limited oral health care providers should be a priority in diminishing racial disparities in oral health service access. Improving access to racial/ethnic minority communities, especially African American neighborhoods, will require changes in health policies and programs, workforce development, resource allocation, community outreach, and educational programs.

Artesunate restores mitochondrial fusion-fission dynamics and alleviates neuronal injury in Alzheimer's disease models.

Alzheimer's disease (AD) remains a leading cause of dementia and no therapy that reverses underlying neurodegeneration is available. Recent studies suggest the protective role of artemisinin, an antimalarial drug, in neurological disorders. In this study, we investigated the therapeutic potential of artesunate, a water-soluble derivative of artemisinin, on amyloid-beta (Aß)-treated challenged microglial BV-2, neuronal N2a cells, and the amyloid precursor protein/presenilin (APP/PS1) mice model. We found that Aß significantly induced multiple AD-related phenotypes, including increased expression/production of pro-inflammatory cytokines from microglial cells, enhanced cellular and mitochondrial production of reactive oxygen species, promoted mitochondrial fission, inhibited mitochondrial fusion, suppressed mitophagy or biogenesis in both cell types, stimulated apoptosis of neuronal cells, and microglia-induced killing of neurons. All these in vitro phenotypes were attenuated by artesunate. In addition, the over-expression of the mitochondrial fission protein Drp-1, or down-regulation of the mitochondrial fusion protein OPA-1 both reduced the therapeutic benefits of artesunate. Artesunate also alleviated AD phenotypes in APP/PS1 mice, reducing Aß deposition, and reversing deficits in memory and learning. Artesunate protects neuronal and microglial cells from AD pathology, both in vitro and in vivo. Maintaining mitochondrial dynamics and simultaneously targeting multiple AD pathogenic mechanisms are associated with the protective effects of artesunate. Consequently, artesunate may become a promising therapeutic for AD.