Technical Assistance and Training Needs of Comprehensive Cancer Control Programs: a Qualitative Analysis.

The National Comprehensive Cancer Control Program (NCCCP) was established in 1998 by the Centers for Disease Control and Prevention (CDC) to advance national cancer control implementation across US states and affiliated tribes and territories. To build capacity of NCCCP recipients, technical assistance and training (TAT) is offered in the form of online trainings, webinars, toolkits, workshops, tip sheets, and other products. To determine TAT needs of NCCCP recipients, the George Washington University (GW) Cancer Center conducted a qualitative evaluation to inform TAT planning and implementation. Data on the utilization, applicability, impact, and dissemination of TAT received were collected from comprehensive cancer control practitioners through semi-structured interviews. Detailed memos of interviewee responses were documented and deductively coded based on three themes: promotion of TAT, use of existing TAT, and recommendations for future TAT. Interviewees reported a need for diverse topics, modalities, and TAT reminders. The most widely used TAT resources were social media toolkits, webinars, newsletters, patient navigation resources, and online trainings. Recommendations for future TAT included a focus on coalition support, adaptation and evaluation of evidence-based cancer control strategies, and health equity. Offering a blend of TAT, including educational webinars and trainings, was preferred by CCC professionals and could increase use. Future TAT will provide new opportunities for coalition capacity building, adaptation of evidence-based strategies for cancer control, and center health equity.

Results of the George Washington University cancer center's comprehensive cancer control cancer communication mentorship program and implications for future practice.

PURPOSE: The Comprehensive Cancer Control Cancer Communication Mentorship Program ("Mentorship Program") was created by the George Washington University Cancer Center (GWCC) to provide technical assistance (TA) in implementing evidence-based cancer screening communication interventions and support networking for comprehensive cancer control (CCC) professionals. The Mentorship Program matched entry-to mid-level CCC professionals with health communication and/or CCC experts and offered monthly web-based discussions with academic researchers and practitioners who shared their knowledge and provided applied learning opportunities throughout mentees' project planning, implementation and evaluation. The program objective was for mentees to improve health communication skills and apply evidence-based knowledge to reduce the burden of cancer. METHODS: A mixed methods evaluation was conducted, including a qualitative description of each project and its outcomes as well as quantitative measures of satisfaction with the program and self-rated changes in competence. RESULTS: Mentees represented the following locations: New Jersey, Arkansas, Michigan, West Virginia, and Republic of Palau. Project topics ranged from increasing Human papillomavirus (HPV) vaccinations to increasing screening uptake for colorectal cancer, lung cancer, cervical cancer, and breast cancer. Evaluation results from pre- and post-program communication competency self-assessments and mid- and post-program surveys revealed that the Mentorship Program advanced personal and professional goals and improved public health communication skills. CONCLUSION: The Mentorship Program achieved its objectives for peer networking and offering expert TA in cancer prevention and control communication, offering a promising model for others involved in supporting implementation of evidence in practice.

Immune Checkpoints Receptors Expression of Macrophage/Monocytes in Response to Acute Viral Respiratory Infection.

Background: We aimed to monitor the phenotypic changes in macrophages and their polarization in patients with acute viral respiratory diseases, including coronavirus disease diagnosis, focusing on the variations in the percentages of macrophages and monocytes and their sub-populations in those patients compared to healthy control. Moreover, we defined the correlation between macrophage subtypes and some inflammatory indices. Methods: Twenty-seven patients with clinical and radiologic diagnosis of acute viral respiratory infection admitted in Al-Azhar and Assiut University hospitals were recruited. Fresh peripheral blood samples were collected from all patients and healthy controls for flow cytometric analysis using BD FACSCanto II analyzer equipped with three lasers. Results: Compared to healthy controls, accumulation of cluster of differentiation (CD)11B+CD68+ macrophages (M) (P = 0.018), CD274+ M1 (P = 0.01), CD274+ M2 (P < 0.001), and CD80-CD206+ M2 (P = 0.001) was more evident in patients. Moreover, CD273+ M2 (P = 0.03), CD80+CD206- M1 (P = 0.002), and CD80+CD86+ M1 (P = 0.002) were highly expressed in controls compared with patients. Conclusion: The examination of clinical specimens obtained from patients with signs of acute respiratory viral infection showed the role of the macrophage in the immune response. Dysfunction in macrophages results in heightened immune activity and inflammation, which plays a role in the progression of viral diseases and the emergence of accompanying health issues. This malfunction in macrophages is a common characteristic seen in various viruses, making it a promising focus for antiviral therapies with broad applicability. The immune checkpoint could be a target for immune modulation in patients with severe symptoms.

Estimating the Burden of Disability From Road Traffic Injuries in 5 Low- and Middle-Income Countries: Protocol for a Prospective Observational Study.

BACKGROUND: Road traffic injuries (RTIs) are a leading cause of death and unintentional injuries globally. They claim 1.35 million lives and produce up to 50 million injuries each year, causing a major drain on health systems. Despite this high burden, there is a lack of robust data on the long-term consequences of RTIs, specifically the level of disability experienced by many survivors and its impact on their everyday lives. OBJECTIVE: This study aims to characterize RTIs, disability level, and related consequences affecting adult road traffic crash survivors in 5 low- and middle-income countries (LMICs). In addition, this study estimates the role of demographic and crash- and treatment-related factors in predicting adverse outcomes and disability as well as examining the disability level among patients with RTIs, likelihood of return to normal life, and the environmental factors that may influence these outcomes after discharge from the hospital. METHODS: This prospective observational study was conducted at selected hospitals in Bangladesh, Cambodia, Ethiopia, Mexico, and Zambia. The study sample included all adult patients with RTIs admitted to the hospital for at least 24 hours. Consecutive sampling was performed until the minimum required sample size of 400 was reached for each participating country. Data were collected from patients or their caregivers using a hospital-based surveillance tool administered at the participating sites as well as a telephone-based follow-up instrument administered 1, 3, and 6 months after discharge. Descriptive analysis and multivariate models will be used to estimate the contribution of a range of factors in predicting adverse outcomes, disability, and return to normal life. RESULTS: Enrollment began in June 2021 and was completed in April 2022. Follow-up data collection ended in September 2022. Data analysis is currently underway, with results expected for publication in mid-2023. Expected results include estimates of disability among patients with RTIs as well as identifying the predictors of adverse outcomes, disability, and the likelihood of return to normal life. CONCLUSIONS: Research findings will help better understand the long-term burden of disability from RTIs in the 5 LMICs and the challenges facing survivors of road traffic crashes. They will be used to inform interventions aimed at improving the health care, social, physical, and policy conditions in LMICs that can facilitate recovery and rehabilitation for patients with RTIs, reduce the burden of disability, and enhance their participation in society. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40985.

Comparative analysis of Neph gene expression in mouse and chicken development.

Neph proteins are evolutionarily conserved members of the immunoglobulin superfamily of adhesion proteins and regulate morphogenesis and patterning of different tissues. They share a common protein structure consisting of extracellular immunoglobulin-like domains, a transmembrane region, and a carboxyl terminal cytoplasmic tail required for signaling. Neph orthologs have been widely characterized in invertebrates where they mediate such diverse processes as neural development, synaptogenesis, or myoblast fusion. Vertebrate Neph proteins have been described first at the glomerular filtration barrier of the kidney. Recently, there has been accumulating evidence suggesting a function of Neph proteins also outside the kidney. Here we demonstrate that Neph1, Neph2, and Neph3 are expressed differentially in various tissues during ontogenesis in mouse and chicken. Neph1 and Neph2 were found to be amply expressed in the central nervous system while Neph3 expression remained localized to the cerebellum anlage and the spinal cord. Outside the nervous system, Neph mRNAs were also differentially expressed in branchial arches, somites, heart, lung bud, and apical ectodermal ridge. Our findings support the concept that vertebrate Neph proteins, similarly to their Drosophila and C. elegans orthologs, provide guidance cues for cell recognition and tissue patterning in various organs which may open interesting perspectives for future research on Neph1-3 controlled morphogenesis.

Features of Inflammatory Heart Reactions Following mRNA COVID-19 Vaccination at a Global Level.

Myocarditis and pericarditis may constitute adverse reactions of mRNA coronavirus disease 2019 (COVID-19) vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case-non-case design (also called disproportionality study) on inflammatory heart reactions reported with mRNA COVID-19 vaccines within the World Health Organization (WHO) global safety database (VigiBase), up to June 30, 2021. Results are expressed using reporting odds ratios (RORs) and their 95% confidence interval (95% CI). Of 716,576 reports related to mRNA COVID-19 vaccines, 2,277 were cases of inflammatory heart reactions, including 1241 (55%) myocarditis and 851 (37%) pericarditis. The main age group was 18-29 years (704, 31%), and mostly male patients (1,555, 68%). Pericarditis onset was delayed compared with myocarditis with a median time to onset of 8 (3-21) vs. 3 (2-6) days, respectively (P = 0.001). Regarding myocarditis, an important disproportionate reporting was observed in adolescents (ROR, 22.3, 95% CI 19.2-25.9) and in 18-29 years old (ROR, 6.6, 95% CI 5.9-7.5) compared with older patients, as well as in male patients (ROR, 9.4, 95% CI 8.3-10.6). Reporting rate of myocarditis was increased in young adults and adolescents. Inflammatory heart reactions may rarely occur shortly following mRNA COVID-19 vaccination. Although an important disproportionate reporting of myocarditis was observed among adolescents and young adults, particularly in male patients, reporting rates support a very rare risk, that does not seem to compromise the largely positive benefit-risk balance of these vaccines. Furthermore, this study confirmed the value of disproportionality analyses for estimation of relative risks among subgroups of patients.

Chromatin Reorganization during Myoblast Differentiation Involves the Caspase-Dependent Removal of SATB2.

The induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report that the removal of the special AT-rich binding protein 2 (SATB2), a nuclear protein known to bind matrix attachment regions, is a key event in initiating myogenic differentiation. The deletion of myoblast SATB2 in vitro initiates chromatin remodeling and accelerates differentiation, which is dependent on the caspase 7-mediated cleavage of SATB2. A genome-wide analysis indicates that SATB2 binding within chromatin loops and near anchor points influences both loop and sub-TAD domain formation. Consequently, the chromatin changes that occur with the removal of SATB2 lead to the derepression of differentiation-inducing factors while also limiting the expression of genes that inhibit this cell fate change. Taken together, this study demonstrates that the temporal control of the SATB2 protein is critical in shaping the chromatin environment and coordinating the myogenic differentiation program.

Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure.

Heart failure (HF) is a rising global cardiovascular epidemic driven by aging and chronic inflammation. As elderly populations continue to increase, precision treatments for age-related cardiac decline are urgently needed. Here we report that cardiac and blood expression of IGFBP7 is robustly increased in patients with chronic HF and in an HF mouse model. In a pressure overload mouse HF model, Igfbp7 deficiency attenuated cardiac dysfunction by reducing cardiac inflammatory injury, tissue fibrosis and cellular senescence. IGFBP7 promoted cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, preventing DNA repair and reactive oxygen species (ROS) detoxification, thereby accelerating the progression of HF. In vivo, AAV9-shRNA-mediated cardiac myocyte Igfbp7 knockdown indicated that myocardial IGFBP7 directly regulates pathological cardiac remodeling. Moreover, antibody-mediated IGFBP7 neutralization in vivo reversed IGFBP7-induced suppression of FOXO3a, restored DNA repair and ROS detoxification signals and attenuated pressure-overload-induced HF in mice. Consequently, selectively targeting IGFBP7-regulated senescence pathways may have broad therapeutic potential for HF.

A new modification in the porous polyethylene-coated lester jones tube.

PURPOSE: Conjunctivodacryocystorhinostomy (CDCR) is the gold standard for the treatment of many cases of canalicular obstruction since 1965 (Kominek & Cervenka, 2004). With a proper CDCR and a well-placed Jones tube, the success rate in our experience is almost 100%. The most frequent complication is extrusion and dislocation. Rates as high as 49% have been reported in some studies (Rose & Welham, 1991). Various modifications have been introduced in the tube design in order to minimize extrusion, including tubes with suture holes, the frosted Jones tubes, and regular porous polyethylene-coated tubes. The regular porous polyethylene-coated tubes are covered by a long sleeve of porous polyethylene, which irritates the conjunctiva causing discharge and sometimes granuloma formation. We describe here a modification of this tube with a much shorter porous polyethylene sleeve to minimize the ocular irritation and discharge. METHODS: Ten patients, age 29-50 years, with complete canalicular obstruction and excessive tearing after failed DCR with canaliculoplasty were included in this study. All patients underwent CDCR with anastomoses of the sac mucosa with that of the nasal mucosa via posterior and anterior flaps. Subsequent placement of porous polyethylene-coated Lester Jones tubes were done at the site of carunculectomy. The regular porous polyethylene coat was shortened using a surgical blade to correspond to the fistula opening, only without extension to the caruncle. The average length of the coat in the 10 cases was about 5 mm. RESULTS: Postoperatively, all patients had surgically successful outcomes, with no complaints of epiphora or discomfort. All tubes are still in proper position and functioning well. Our follow-up has been limited to an 18-month period. CONCLUSION: CDCR with the modified porous polyethylene-coated Lester Jones tube has the same advantages of the traditional porous polyethylene-coated tube. Moreover, it reduces the discharge and ocular irritation, which are the main complications of the CDCR with the current porous polyethylene-coated Jones tube.

Concordance between the diagnostic guidelines for alcohol and cannabis use disorders in the draft ICD-11 and other classification systems: analysis of data from the WHO's World Mental Health Surveys.

BACKGROUND AND AIMS: The World Health Organization's (WHO's) proposed International Classification of Diseases, 11th edition (ICD-11) includes several major revisions to substance use disorder (SUD) diagnoses. It is essential to ensure the consistency of within-subject diagnostic findings throughout countries, languages and cultures. To date, agreement analyses between different SUD diagnostic systems have largely been based in high-income countries and clinical samples rather than general population samples. We aimed to evaluate the prevalence of, and concordance between diagnoses using the ICD-11, The WHO's ICD 10th edition (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders, 4th and 5th editions (DSM-IV, DSM-5); the prevalence of disaggregated ICD-10 and ICD-11 symptoms; and variation in clinical features across diagnostic groups. DESIGN: Cross-sectional household surveys. SETTING: Representative surveys of the general population in 10 countries (Argentina, Australia, Brazil, Colombia, Iraq, Northern Ireland, Poland, Portugal, Romania and Spain) of the World Mental Health Survey Initiative. PARTICIPANTS: Questions about SUDs were asked of 12 182 regular alcohol users and 1788 cannabis users. MEASUREMENTS: Each survey used the World Mental Health Survey Initiative version of the WHO Composite International Diagnostic Interview version 3.0 (WMH-CIDI). FINDINGS: Among regular alcohol users, prevalence (95% confidence interval) of life-time ICD-11 alcohol harmful use and dependence were 21.6% (20.5-22.6%) and 7.0% (6.4-7.7%), respectively. Among cannabis users, 9.3% (7.4-11.1%) met criteria for ICD-11 harmful use and 3.2% (2.3-4.0%) for dependence. For both substances, all comparisons of ICD-11 with ICD-10 and DSM-IV showed excellent concordance (all κ ≥ 0.9). Concordance between ICD-11 and DSM-5 ranged from good (for SUD and comparisons of dependence and severe SUD) to poor (for comparisons of harmful use and mild SUD). Very low endorsement rates were observed for new ICD-11 feature for harmful use ('harm to others'). Minimal variation in clinical features was observed across diagnostic systems. CONCLUSIONS: The World Health Organization's proposed International Classification of Diseases, 11th edition (ICD-11) classifications for substance use disorder diagnoses are highly consistent with the ICD 10th edition and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). Concordance between ICD-11 and the DSM 5th edition (DSM-5) varies, due largely to low levels of agreement for the ICD harmful use and DSM-5 mild use disorder. Diagnostic validity of self-reported 'harm to others' is questionable.

Erratum to: The beneficial role of proteolysis in skeletal muscle growth and stress adaptation.

[This corrects the article DOI: 10.1186/s13395-016-0086-6.].

The beneficial role of proteolysis in skeletal muscle growth and stress adaptation.

Muscle atrophy derived from excessive proteolysis is a hallmark of numerous disease conditions. Accordingly, the negative consequences of skeletal muscle protein breakdown often overshadow the critical nature of proteolytic systems in maintaining normal cellular function. Here, we discuss the major cellular proteolysis machinery-the ubiquitin/proteosome system, the autophagy/lysosomal system, and caspase-mediated protein cleavage-and the critical role of these protein machines in establishing and preserving muscle health. We examine how ordered degradation modifies (1) the spatiotemporal expression of myogenic regulatory factors during myoblast differentiation, (2) membrane fusion during myotube formation, (3) sarcomere remodeling and muscle growth following physical stress, and (4) energy homeostasis during nutrient deprivation. Finally, we review the origin and etiology of a number of myopathies and how these devastating conditions arise from inborn errors in proteolysis.

Temporal activation of XRCC1-mediated DNA repair is essential for muscle differentiation.

Transient DNA strand break formation has been identified as an effective means to enhance gene expression in living cells. In the muscle lineage, cell differentiation is contingent upon the induction of caspase-mediated DNA strand breaks, which act to establish the terminal gene expression program. This coordinated DNA nicking is rapidly resolved, suggesting that myoblasts may deploy DNA repair machinery to stabilize the genome and entrench the differentiated phenotype. Here, we identify the base excision repair pathway component XRCC1 as an indispensable mediator of muscle differentiation. Caspase-triggered XRCC1 repair foci form rapidly within differentiating myonuclei, and then dissipate as the maturation program proceeds. Skeletal myoblast deletion of Xrcc1 does not have an impact on cell growth, yet leads to perinatal lethality, with sustained DNA damage and impaired myofiber development. Together, these results demonstrate that XRCC1 manages a temporally responsive DNA repair process to advance the muscle differentiation program.

The associations between preexisting mental disorders and subsequent onset of chronic headaches: a worldwide epidemiologic perspective.

UNLABELLED: Although there is a significant association between preexisting depression and later onset of chronic headache, the extent to which other preexisting mental disorders are associated with subsequent onset of headache in the general population is not known. Also unknown is the extent to which these associations vary by gender or by life course. We report global data from the WHO's World Mental Health surveys (n = 52,095), in which, by means of the Composite International Diagnostic Interview-3.0, 16 mental disorders from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were retrospectively assessed in terms of lifetime prevalence and age of onset. Frequent or severe headaches were assessed using self-reports. After adjustment for covariates, survival models showed a moderate but consistent association between preexisting mood (odds ratios [ORs] = 1.3-1.4), anxiety (ORs = 1.2-1.7), and impulse-control disorders (ORs = 1.7-1.9) and the subsequent onset of headache. We also found a dose-response relationship between the number of preexisting mental disorders and subsequent headache onset (OR ranging from 1.9 for 1 preexisting mental disorder to 3.4 for ≥5 preexisting mental disorders). Our findings suggest a consistent and pervasive relationship between a wide range of preexisting mental disorders and the subsequent onset of headaches. This highlights the importance of assessing a broad range of mental disorders, not just depression, as specific risk factors for the subsequent onset of frequent or severe headaches. PERSPECTIVE: This study shows that there is a temporal association between a broad range of preexisting mental disorders and the subsequent onset of severe or frequent headaches in general population samples across the world.

Associations between DSM-IV mental disorders and onset of self-reported peptic ulcer in the World Mental Health Surveys.

OBJECTIVE: Recent research demonstrating concurrent associations between mental disorders and peptic ulcers has renewed interest in links between psychological factors and ulcers. However, little is known about associations between temporally prior mental disorders and subsequent ulcer onset. Nor has the potentially confounding role of childhood adversities been explored. The objective of this study was to examine associations between a wide range of temporally prior DSM-IV mental disorders and subsequent onset of ulcer, without and with adjustment for mental disorder comorbidity and childhood adversities. METHODS: Face-to-face household surveys conducted in 19 countries (n=52,095; person years=2,096,486). The Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Peptic ulcer onset was assessed in the same interview by self-report of physician's diagnosis and year of diagnosis. Survival analyses estimated associations between first onset of mental disorders and subsequent ulcer onset. RESULTS: After comorbidity and sociodemographic adjustment, depression, social phobia, specific phobia, post-traumatic stress disorder, intermittent explosive disorder, alcohol and drug abuse disorders were significantly associated with ulcer onset (ORs 1.3-1.6). Increasing number of lifetime mental disorders was associated with ulcer onset in a dose-response fashion. These associations were only slightly attenuated by adjustment for childhood adversities. CONCLUSIONS: A wide range of mental disorders were linked with the self-report of subsequent peptic ulcer onset. These associations require confirmation in prospective designs, but are suggestive of a role for mental disorders in contributing to ulcer vulnerability, possibly through abnormalities in the physiological stress response associated with mental disorders.