Calpain 3 and CaMKIIβ signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy.

Mutations in CAPN3 cause autosomal recessive limb girdle muscular dystrophy 2A. Calpain 3 (CAPN3) is a calcium dependent protease residing in the myofibrillar, cytosolic and triad fractions of skeletal muscle. At the triad, it colocalizes with calcium calmodulin kinase IIβ (CaMKIIβ). CAPN3 knock out mice (C3KO) show reduced triad integrity and blunted CaMKIIβ signaling, which correlates with impaired transcriptional activation of myofibrillar and oxidative metabolism genes in response to running exercise. These data suggest a role for CAPN3 and CaMKIIβ in gene regulation that takes place during adaptation to endurance exercise. To assess whether CAPN3- CaMKIIβ signaling influences skeletal muscle remodeling in other contexts, we subjected C3KO and wild type mice to hindlimb unloading and reloading and assessed CaMKIIβ signaling and gene expression by RNA-sequencing. After induced atrophy followed by 4 days of reloading, both CaMKIIβ activation and expression of inflammatory and cellular stress genes were increased. C3KO muscles failed to activate CaMKIIβ signaling, did not activate the same pattern of gene expression and demonstrated impaired growth at 4 days of reloading. Moreover, C3KO muscles failed to activate inducible HSP70, which was previously shown to be indispensible for the inflammatory response needed to promote muscle recovery. Likewise, C3KO showed diminished immune cell infiltration and decreased expression of pro-myogenic genes. These data support a role for CaMKIIβ signaling in induction of HSP70 and promotion of the inflammatory response during muscle growth and remodeling that occurs after atrophy, suggesting that CaMKIIβ regulates remodeling in multiple contexts: endurance exercise and growth after atrophy

Personal Health Records: Beneficial or Burdensome for Patients and Healthcare Providers?

Personal health records (PHRs) have been mandated to be made available to patients to provide increased access to medical care information, encourage participation in healthcare decision making, and enable correction of errors within medical records. The purpose of this study was to analyze the usefulness of PHRs from the perspectives of patients and providers. The methodology of this qualitative study was a literature review using 34 articles. PHRs are powerful tools for patients and healthcare providers. Better healthcare results and correction of medical records have been shown to be positive outcomes of the use of PHRs. PHRs have also been shown to be difficult for patients to use and understand, and providers had concerns about correct information transferring to the portals and patients eliminating information from the record. Concerns regarding patient understanding of medical records, legal liability, and the response time required of providers were also identified. For the PHR to succeed in the US healthcare system, assurance that the information will be protected, useful, and easily accessed is necessary

Systems of Care and the Prevention of Mental Health Problems for Children and their Families: Integrating Counseling Psychology and Public Health Perspectives

The purpose of this paper is to present systems of care as an example of how counseling psychology and public health overlap with regards to prevention and intervention approaches for children\u27s mental health. A framework for prevention is presented as is the state of children\u27s mental health promotion, with a particular focus on ecological and systemic approaches to children\u27s mental health and how these approaches cut across multiple perspectives. Systems of care are highlighted as an example of the congruence of prevention and ecological or systemic approaches to address the mental health promotion of children and their families, with the potential to impact at the universal, selective, and indicated levels of risk. Results from a longitudinal outcome study of a school-based system of care are presented to exemplify the positive outcomes experienced by children. An increase in the awareness and implementation of systems of care across mental health perspectives is recommended, along with continued research from the public health and counseling psychology communities focused on which prevention and intervention services within systems of care work, why they work, and how they can be improved upon

Germline and Somatic DNA Damage Repair Gene Mutations and Overall Survival in Metastatic Pancreatic Adenocarcinoma Patients Treated with FOLFIRINOX

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with lack of predictive biomarkers. We conducted a study to assess DNA damage repair (DDR) gene mutations as a predictive biomarker in PDAC patients treated with FOLFIRINOX. Experimental Design: Indiana University Simon Cancer Center pancreatic cancer database was used to identify patients with metastatic PDAC, treated with FOLFIRINOX and had tissue available for DNA sequencing. Baseline demographic, clinical, and pathologic information was gathered. DNA isolation and targeted sequencing was performed using the Ion AmpliSeq protocol. Overall survival (OS) analysis was conducted using Kaplan–Meier, logistic regression and Cox proportional hazard methods. Multivariate models were adjusted for age, gender, margin status, CA 19-9, adjuvant chemotherapy, tumor and nodal stage. Results: Overall, 36 patients were sequenced. DDR gene mutations were found in 12 patients. Mutations were seen in BRCA1 (N = 7), BRCA2 (N = 5), PALB2 (N = 3), MSH2 (N = 1), and FANCF (N = 1) of all the DDR genes sequenced. Median age was 65.5 years, 58% were male, 97.2% were Caucasian and 51.4% had any family history of cancer. The median OS was near significantly superior in those with DDR gene mutations present vs. absent [14 vs. 5 months; HR, 0.58; 95% confidence interval (CI), 0.29–1.14; log-rank P = 0.08]. Multivariate logistic (OR, 1.47; 95% CI, 1.04–2.06; P = 0.04) and Cox regression (HR, 0.37; 95% CI, 0.15–0.94; P = 0.04) showed presence of DDR gene mutations was associated with improved OS. Conclusions: In a single institution, retrospective study, we found that the presence of DDR gene mutations are associated with improved OS in PDAC patients treated with FOLFIRINOX

Analisis Laporan Keuangan dalam Mengukur Kinerja Keuangan pada PT. Bank Artha Graha Internasional, Tbk

Bank sebagai badan usaha di bidang keuangan yang memiliki berbagai jasa yang dapat digunakan oleh pengguna jasa. Bank secara periodik wajib membuat laporan keuangan untuk dapat mengetahui tingkat keuangan yang dimiliki dan kondisi keuangan Bank tersebut. Tujuan penelitian ini untuk menganalisis laporan keuangan dalam mengukur kinerja keuangan pada PT. Bank Artha Graha Internasional, Tbk Jakarta. Metode analisis data adalah analisis deskriptif komparatif. Dari laporan keuangan Bank kemudian dianalisis likuiditas, solvabilitas, dan profitabilitas untuk mendapatkan perbandingan hasil pada tiap tahun dan akan disesuaikan dengan standar Bank Indonesia (BI) yang dapat dianalisis untuk mengukur seperti apa tingkat keuangan dan kinerja bank tersebut. Hasil penelitian menunjukan, likuiditas Bank Artha Graha mampu memenuhi kewajiban jangka pendek yang dimiliki. Hasil solvabilitas memperlihatkan kemampuan bank dalam permodalan yang dimiliki mampu untuk menutupi penurunan maupun kerugian. Hasil profitabilitas memperlihatkan bank memiliki hasil rasio yang terus meningkat. Ketiga rasio keuangan sesuai dengan standar yang ditentukan BI. Kondisi keuangan Bank Artha Graha masih dalam keadaan baik dan dapat memenuhi kewajiban terhadap pihak ketiga. Manajemen Bank Artha Graha sebaiknya terus melakukan pengelolaan keuangan dengan baik, agar tidak terjadi penurunan yang dapat menyebabkan bank menjadi tidak sanggup untuk menyelesaikan masalah keuangan yang ada nantinya. Kata kunci: analisis, laporan keuangan, kinerja keuanga

Impact of Nab–Paclitaxel-based Second-line Chemotherapy in Metastatic Pancreatic Cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with median survival of 20% at 1 year. We conducted a retrospective study to assess the efficacy and tolerability of nab-paclitaxel (NP)-based second-line chemotherapy in metastatic PDAC. Patients and Methods: The Indiana University Simon Cancer Center pancreatic cancer program was used to identify patients with metastatic PDAC who received any second-line chemotherapy. Demographic, clinical and outcomes data were collected by manual chart abstraction. Patients were divided into two groups: a NP-based treatment group and a non- NP-based treatment group. Overall (OS) and progression-free (PFS) survival were estimated using Kaplan–Meier method. Cox proportional hazards regression was used for multivariate analyses. Results: A total of 120 patients received second-line chemotherapy. There were 47 (39%) patients in the NP group and 73 (61%) in the non-NP group. As compared to the non-NP group, the NP group showed improved median PFS [2.8 vs. 2.1 months; hazard ratio (HR)=0.62, 95% confidence interval (CI)=0.38-1.02; p=0.06] and median OS (7.5 vs. 4.7 months; HR=0.67, 95% CI=0.45-1.00; p=0.05). Multivariate analyses adjusted for age showed a significantly improved PFS (adjusted HR=0.60, 95% CI=0.36-0.98; p=0.04) and a suggestion of improved OS (adjusted HR=0.67, 95% CI=0.44-1.01, p=0.05) in the NP group as compared to non-NP group. Serious adverse events were seen in 13.3% of patients in the non-NP group and 17.1% patients in the NP group. Conclusion: In a single-institution retrospective cohort study, we report a significant improvement in the PFS and suggestion of improvement in the OS with NP-based second-line chemotherapy with an acceptable toxicity rate

An Examination of Exposure to Traumatic Events and Symptoms and Strengths for Children Served in a Behavioral Health System of Care

The present study examined how exposure to traumatic events impacts children with severe emotional disturbance who are being served in a school-based system of care. Multilevel growth curve models were used to examine the relationships between a child’s history of traumatic events (physical abuse, sexual abuse, or domestic violence) and behavioral and emotional strengths, internalizing problem behaviors, or externalizing problem behaviors over 18 months. Results indicate that children receiving services (N = 134) exhibited increased emotional and behavioral strengths and decreased internalizing and externalizing problem behaviors from enrollment to 18 months follow-up. Children with a history of traumatic events improved more slowly than children without such a history on both strengths and internalizing problem behaviors, even after controlling for dosage of services received and other characteristics previously found to predict outcomes. Gender was also related to improvement in internalizing symptoms. Results highlight the continued need to assess the impact of exposure to traumatic events for children served in a system of care

A Randomized, Double‐Blind Study Comparing Pharmacokinetics and Pharmacodynamics of Proposed Biosimilar ABP 798 With Rituximab Reference Product in Subjects With Moderate to Severe Rheumatoid Arthritis

ABP 798 is a proposed biosimilar to rituximab reference product (RP), an anti-CD20 monoclonal antibody. Pharmacokinetics (PK), pharmacodynamics (PD), and safety results from the comparative clinical study that evaluated the PK, PD, safety, efficacy, and immunogenicity of ABP 798 versus rituximab RP are presented here. Subjects with moderate to severe rheumatoid arthritis (RA) received 2 doses of ABP 798, United States-sourced RP (rituximab US) or European Union-sourced RP (rituximab EU), each consisting of two 1000-mg infusions 2 weeks apart. For the second dose (week 24), ABP 798- and rituximab EU-treated subjects received the same treatment; rituximab US-treated subjects transitioned to ABP 798. End points included area under the serum concentration-time curve from time 0 extrapolated to infinity and maximum observed serum concentration following the second infusion of the first dose (PK) and percentage of subjects with complete CD19+ cell depletion days 1-33 (PD). Primary analysis established PK similarity between ABP 798 and rituximab RP based on 90% confidence intervals of the adjusted geometric mean ratios being within a prespecified equivalence margin of 0.8 and 1.25. Complete CD19+ B-cell depletion on day 3 among groups confirmed PD similarity. These findings demonstrated PK/PD similarity between ABP 798 and rituximab RP in subjects with moderate to severe RA

The Impact of Youth and Family Risk Factors on Service Recommendations and Delivery in a School-Based System of Care

The present study examines the impact of child and family risk factors on service access for youth and families in a school-based system of care. Regression analyses examined the relationships between risk factors and services recommended, services received, and dosage of services received. Logistic regression analyses examined the relationship between risk factors and whether or not youth received specific types of services within the system of care. Results revealed that youth with a personal or family history of substance use had more services recommended than youth without these risk factors, while youth with a family history of substance use received more services. Youth with a history of substance use received a significantly higher dosage of services overall. Finally, history of family mental illness was associated with receiving mental health and operational services (e.g., family advocacy, emergency funds). Implications and limitations are discussed. Systems of care were developed in response to the need for more appropriate and accessible preventive and treatment services for children with severe emotional and behavioral difficulties and their families. In 1992, the United States Congress established the Comprehensive Community Mental Health Services (CMHS) for Children and Their Families Program, which has provided funding to 126 communities over the past 14 years for the development of local systems of care.1 A system of care is a coordinated network of community-based services and supports that is created to meet the challenges of children