Family adaptation in families of individuals with Down syndrome from 12 countries.

Our current understanding of adaptation in families of individuals with Down syndrome (DS) is based primarily on findings from studies focused on participants from a single country. Guided by the Resiliency Model of Family Stress, Adjustment, and Adaptation, the purpose of this cross-country investigation, which is part of a larger, mixed methods study, was twofold: (1) to compare family adaptation in 12 countries, and (2) to examine the relationships between family variables and family adaptation. The focus of this study is data collected in the 12 countries where at least 30 parents completed the survey. Descriptive statistics were generated, and mean family adaptation was modeled in terms of each predictor independently, controlling for an effect on covariates. A parsimonious composite model for mean family adaptation was adaptively generated. While there were cross-country differences, standardized family adaptation mean scores fell within the average range for all 12 countries. Key components of the guiding framework (i.e., family demands, family appraisal, family resources, and family problem-solving communication) were important predictors of family adaptation. More cross-country studies, as well as longitudinal studies, are needed to fully understand how culture and social determinants of health influence family adaptation in families of individuals with DS.

Effects of Parental Involvement on Glycemic Control in Adolescents With Type 1 Diabetes Mellitus: A Scoping Review.

Type 1 diabetes mellitus (T1DM) is typically diagnosed in pediatric patients. Transitioning from supported management in childhood to self-management in adolescence is an important step. Parental psychosocial influence is a possible factor in adolescents' disease control. This review summarized the effects of parental involvement on glycemic control in adolescents with T1DM by focusing on hemoglobin A1c (HgbAIc). A scoping review per the Guidance for Systematic Scoping Reviews was conducted with the following inclusion criteria: (a) studies in English, (b) focused on adolescents with T1DM, (c) outcomes included HgbAIc, and (d) focused on parental influence of children with T1DM. Of 476 articles, 14 were included. The study outcomes were classified based on direct or indirect influence. "Parental support for adherence" and "parental conflict" significantly affected HgbAIc control. This study provides current evidence on parental influence on glycemic control in adolescents.

Development and Validity of the Japanese Version of the Questionnaire on Factors That Influence Family Engagement in Acute Care Settings.

There exists an international consensus on the importance of family-centered care (FCC) in intensive care settings and the evaluation of collaboration between nurses and families; however, FCC is currently practiced blindly in Japan. In this study, we developed a Japanese version of the questionnaire, Factors that Influence Family Engagement (QFIFE-J) and examined its reliability and validity. A web-based survey was conducted with 250 nurses working in the intensive care unit (ICU). Exploratory and validatory factor analyses were used to ascertain factor validity. Criterion-related validity was tested using correlation analysis with the ICU Nurses' Family Assistance Practice Scale. Internal consistency and reproducibility were verified for reliability. Following exploratory and confirmatory factor analyses, a 15-item measure emerged comprising four factors: "ICU environment", "nurses' attitudes", "nurses' workflow", and "patient acuity". Confirmatory factor analyses showed a generally good fit. Cronbach's α for the overall scale was 0.78, indicating acceptable internal consistency. The intraclass coefficient for test-retest reliability was 0.80. It was found that the QFIFE-J was reliable and valid and may help determine the factors that promote or inhibit FCC. Additionally, this study has also clarified the current status and family support related issues in ICUs in Japan.

Aspects of emotional labor of public health nurses engaged in interpersonal support.

AIM: Clarifying the emotional labor of public health nurses while providing interpersonal support. DESIGN: Qualitative descriptive study conducted using content analysis to clarify the aspect of emotional labor of PHNs regarding interpersonal support. METHODS: Individual semi-structured interviews were conducted with 28 public health nurses employed by seven city governments in Japan. The data items obtained were categorized using deductive content analysis. RESULTS: When attempting interpersonal support, PHNs showed the following aspects of emotional labor: (1) negative emotions towards residents and resident-focused emotions; (2) emotional rules based on duty performance, emotional rules based on fairness, emotional rules based on intimacy; (3) adaptive emotional regulation, maladaptive emotional regulations and (4) emotional expressions based on friendliness, emotional expressions based on calmness. CONCLUSION: PHNs used adaptive emotional regulation in some cases and sometimes resorted to maladaptive forms. A system of support should be established to ensure the smooth and effective provision of interpersonal support.

Development and Validation of the COVID-19-Related Stigma Scale for Healthcare Workers (CSS-HCWs).

Stigma among healthcare workers during the coronavirus disease 2019 (COVID-19) pandemic is an issue that requires immediate attention, as it may otherwise lead to the collapse of healthcare systems. In this study, we developed the COVID-19-related stigma scale for healthcare workers (CSS-HCWs) and assessed its reliability and validity. Data were collected online from 500 participants, including physicians and nurses involved in COVID-19 care. The first item of the draft scale was developed based on a literature review and qualitative study. The draft scale consisted of 24 items, which were rated on a six-point Likert scale. Descriptive statistics were calculated and the data distribution was analyzed. To assess the scale's validity and reliability, structural validity was evaluated through an exploratory factor analysis. Criterion-related validity was examined through a correlation analysis using the E16-COVID19-S, a COVID-19 scale developed for physicians in Egypt. Reliability was evaluated by examining the scale's stability and internal consistency. The findings revealed that the stigma scale was a valid and reliable instrument. The final scale consisted of 18 items across three domains: personal stigma, concerns of disclosure and others, and family stigma. In conclusion, the scale is a valid and reliable instrument that can measure COVID-19-related stigma among healthcare workers.

Intensive care nurse-family engagement from a global perspective: A qualitative multi-site exploration.

BACKGROUND: Critical illness is distressing for families, and often results in negative effects on family health that influence a family's ability to support their critically ill family member. Although recent attention has been directed at improving care and outcomes for families of critically ill patients, the manner in which nurses engage with families is not fully understood. OBJECTIVES: To describe nurses' perceptions and practices of family engagement in adult intensive care units from a global perspective. DESIGN: A qualitative-descriptive multi-site design using content analysis. SETTINGS: The study was conducted in 26 intensive care units of 12 urban, metropolitan, academic medical centers in ten countries, spanning five continents. PARTICIPANTS: A total of 65 registered nurses (77% women, age of M = 39.5, SD = 11.4 years) participated. Most held intensive care certification (72%) and had worked on average 10 (SD = 9.6) years in the ICU. METHODS: Semi-structured, individual interviews (M = 38.4 min, SD = 12.0) were held with ICU nurses at the hospital (94%) or their home using an interview guide. Qualitative interview data were analysed using inductive content analysis. RESULTS: We found that nurse-family engagement was an ebb and flow of relational power that needed to be carefully negotiated and balanced, with nurses holding and often exerting more power than families. Constant fluctuations in nurses' practices of engagement occurred in day-to-day practice from shift-to-shift and from nurse-to-nurse. Family engagement was dependent on individual nurses' attitudes and perceptions of family, the patient's condition, and workload. Lastly, family engagement was shaped by the ICU context, with team culture, collaborative relationships, unit structures and organizational resources either enabling or limiting nurses' ability to engage with families. CONCLUSIONS: This global study provides an in-depth understanding of the way nurses engage with families in ICU and reflects many different cultures and health systems. We found that nurse-family engagement was marked by a shifting, yet often unequal power distribution in the nurse-family relationship, inconsistent nurse engagement practices, both of which resulted in variable family engagement in intensive care. Our research contributes a detailed description of engagement as practiced in the everyday delivery of health care. A more concentrated team effort, based on a shared culture and defined framework of family care is needed to ensure that families of critically ill persons are fully engaged in all aspects of intensive care.

Development and psychometric testing of a family concordance competency scale for families with children having chronic illnesses.

AIM: This study aimed to develop a Family Concordance Competency Scale for Family System Units (FCCS-Fa) for families with children having chronic disease, and to evaluate its reliability and validity. METHODS: FCCS-Fa was developed by taking the following steps: (a) drafting based on the elements comprising concordance between healthcare professionals and families with patients suffering from chronic illness; (b) evaluation of face and content validity by an expert panel; and (c) re-examination of face and content validity by semi-structured interviews with 16 families. Criterion-related validity was evaluated using the existing scale and construct validity was evaluated using exploratory factor analysis. Analysis of each FCCS-Fa evaluation item, internal consistency, and the 2-week test-retest reliability was also conducted. An anonymous self-reported questionnaire survey was conducted, targeting families with chronically ill children who were outpatients at three hospitals. RESULTS: A total of 196 subjects were analyzed. As results of FCCS-Fa item analysis and exploratory factor analysis, a scale structure comprised of 17 evaluation items and three factors were adopted. In addition, a significant correlation with several existing scales was identified and the criterion-related validity was also confirmed. The Cronbach's α coefficient for the overall scale was .927, the intraclass correlation coefficient applying the retest method was .905, and internal consistency and test-retest reliability were both confirmed. CONCLUSIONS: We developed FCCS-Fa with reliability and validity. Assessing family concordance competency using this scale and supporting families to achieve family concordance can lead to self-management by families.

Measurement of Family Management in Families of Individuals With Down Syndrome: A Cross-Cultural Investigation.

Down syndrome (DS) is the most common genetic cause of intellectual disability worldwide. The purpose of this analysis was to determine the internal consistency reliability of eight language versions of the Family Management Measure (FaMM) and compare family management of DS across cultures. A total of 2,740 parents of individuals with DS from 11 countries completed the FaMM. The analysis provided evidence of internal consistency reliability exceeding .70 for four of six FaMM scales for the entire sample. Across countries, there was a pattern of positive family management. Cross-cultural comparisons revealed parents from Brazil, Spain, and the United States had the most positive family management and respondents from Ireland, Italy, Japan, and Korea had the least positive. The rankings were mixed for the four remaining countries. These findings provide evidence of overall strong internal consistency reliability of the FaMM. More cross-cultural research is needed to understand how social determinants of health influence family management in families of individuals with DS.

Interprofessional Collaborative Practice for Child Maltreatment Prevention in Japan: A Literature Review.

This literature review explored the factors promoting interprofessional collaborative practice for the child maltreatment prevention in Japan. We searched the Japanese database of ICHUSHI-web, focusing on studies published between 1990 and 2015. The studies were examined for methodological quality using the critical appraisal checklists. We initially identified 161 articles and finally selected eight studies that met the selection criteria and were analyzed. The Collaborative Practice Circle based on the Interprofessional Education for Collaborative Patient-Centered Practice framework, was used as a conceptual framework to analyze the data and to discuss the review findings. Data analysis continued until categories were saturated using content analysis. Five categories as interactional factors, two categories as organizational factors and three categories as systemic factors were identified. The findings revealed that interactional factors were composed of practical competencies and experiences of professionals. Our findings also indicate that educational programs for improving practical competencies of professionals at the individual level and establishing a system of training and human resource development at the organizational level are required. Further research is warranted to examine the impact the challenges outlined in the interactional factors, the organizational interventions and support for clients.

Withholding and withdrawal of life-sustaining treatments for neonate in Japan: Are hospital practices associated with physicians' beliefs, practices, or perceived barriers?

OBJECTIVE: To describe the current status of withholding or withdrawal of life-sustaining interventions (LSI) for neonates in Japan and to identify physician- and institutional-related factors that may affect advance care planning (ACP) practices with parents. STUDY DESIGN: A self-reported questionnaire was administered to assess frequency of withholding and withdrawing intensive care at the respondent's facility, the physician's degree of affirming various beliefs about end-of-life care that was compared to 7 European countries, their self-reported ACP practices and perceived barriers to ACP. Three neonatologists at all 298 facilities accredited by the Japan Society for Neonatal Health and Development were surveyed, with 572 neonatologists at 217 facilities responding. RESULTS: At 76% of facilities, withdrawing intensive care treatments was "never" done, while withholding intensive care had been done "sometimes" or more frequently at 82% of facilities. Japanese neonatologists differed from European neonatologists regarding their degree of affirmation of 3 out of 7 queried beliefs about end-of-life care. In hospitals that were more likely to "sometimes" (or more often) withdraw treatments, respondents were less likely to affirm beliefs about doing "everything possible" or providing the "maximum of intensive care". Self-reported ACP practices did not vary between neonatologists based on their hospital's overall pattern of withholding or withdrawing treatments. CONCLUSION: Among NICU facilities in Japan, 21% had been sometimes withdrawing LSI and 82% had been "sometimes" withholding LSI. Institutional treatment practices may have a strong association with physicians' beliefs that then affect end-of-life discussions, but not with self-reported ACP practices.

Development and Validity Testing of an Assessment Tool for Domestic Elder Abuse.

BACKGROUND: The older adult population is increasing in number, and elder abuse is expected to become a more pressing problem. Developing tools to assess the presence and severity of elder abuse is important to both effectively prevent this abuse and provide increased support for families. PURPOSE: This study was intended to test the validity of an Assessment Tool for Domestic Elder Abuse (ATDEA). The items that constitute this tool were derived from a literature review. METHODS: Two rounds of self-administered questionnaire surveys were conducted with nurses working at home-visit nursing stations. Round 1 was used to evaluate the face validity, and Round 2 was used to test the content using the content validity index (CVI). RESULTS: Two hundred forty nurses participated in the two studies. In Round 1, 56 nurses evaluated 38 items derived from a literature review, resulting in the development of a 36-item ATDEA. In Round 2, 184 nurses evaluated the content validity of the 36-item ATDEA. The Item-CVI (I-CVI) scores ranged from .61 to 1. Twenty-eight of the items met or exceeded the I-CVI threshold of .78, whereas the eight items assessing self-neglect did not. The overall Scale-CVI score for the assessment tool was .90, which met the threshold of .90. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of validity testing established the preliminary validity of this assessment tool. In addition, as self-neglect is known to damage the well-being of older adults, six of the eight items assessing self-neglect were retained in the ATDEA despite their failure to meet the threshold I-CVI of .78. The remaining two self-neglect items were not included in the ATDEA because of excessively low I-CVI scores (< .70). Thus, the final version of the ATDEA includes 34 items. The authors recommend that nursing professionals use the ATDEA as a checklist to assess the presence of elder abuse and to discern the subtypes and severity of this abuse. When evaluating elder abuse, the higher the degree of severity, the greater the urgency to provide support.

Frequent downregulation of LRRC26 by epigenetic alterations is involved in the malignant progression of triple-negative breast cancer.

Triple-negative breast cancer (TNBC), defined as breast cancer lacking estrogen- and progesterone­receptor expression and human epidermal growth factor receptor 2 (HER2) amplification, is a heterogeneous disease. RNA-sequencing analysis of 15 TNBC specimens and The Cancer Genome Atlas-TNBC dataset analysis identified the frequent downregulation of leucine-rich repeat-containing 26 (LRRC26), which negatively regulates nuclear factor-κB (NF-κB) signaling, in TNBC tissues. Quantitative polymerase chain reaction and bisulfite pyrosequencing analyses revealed that LRRC26 was frequently silenced in TNBC tissues and cell lines as a result of promoter methylation. LRRC26 expression was restored by 5-aza-2'-deoxycytidine (5'-aza-dC) treatment in HCC1937 TNBC cells, which lack LRRC26 expression. Notably, small interfering RNA-mediated knockdown of LRRC26 expression significantly enhanced the anchorage-independent growth, invasion and migration of HCC70 cells, whereas ectopic overexpression of LRRC26 in BT20 cells suppressed their invasion and migration. Conversely, neither knockdown nor overexpression of LRRC26 had an effect on cell viability in the absence of tumor necrosis factor-α (TNF-α) stimulation. Meanwhile, overexpression of LRRC26 caused the reduction of TNF-α-mediated NF-κB luciferase reporter activity, whereas depleting LRRC26 expression resulted in the upregulation of TNF-α-mediated NF-κB downstream genes [interleukin-6 (IL-6), IL-8 and C-X-C motif chemokine ligand-1]. Taken together, these findings demonstrate that LRRC26 is frequently downregulated in TNBC due to DNA methylation and that it suppresses the TNF-α-independent anchorage-independent growth, invasion and migration of TNBC cells. Loss of LRRC26 function may be a critical event in the aggressiveness of TNBC cells through a TNF-α/NF-κB-independent mechanism.

Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast cancer therapeutics.

Estradiol (E2) and the oestrogen receptor-alpha (ERα) signalling pathway play pivotal roles in the proliferative activity of breast cancer cells. Recent findings show that the brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex plays a crucial role in E2/ERα signalling modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2 interaction using the ERα activity-regulator synthetic peptide (ERAP: 165-177 amino acids), derived from α-helical BIG3 sequence, resulted in a significant anti-tumour effect. However, the duration of this effect was very short for viable clinical application. We developed the chemically modified ERAP using stapling methods (stapledERAP) to improve the duration of its antitumour effects. The stapledERAP specifically inhibited the BIG3-PHB2 interaction and exhibited long-lasting suppressive activity. Its intracellular localization without the membrane-permeable polyarginine sequence was possible via the formation of a stable α-helix structure by stapling. Tumour bearing-mice treated daily or weekly with stapledERAP effectively prevented the BIG3-PHB2 interaction, leading to complete regression of E2-dependent tumours in vivo. Most importantly, combination of stapledERAP with tamoxifen, fulvestrant, and everolimus caused synergistic inhibitory effects on growth of breast cancer cells. Our findings suggested that the stapled ERAP may be a promising anti-tumour drug to suppress luminal-type breast cancer growth.

A-kinase anchoring protein BIG3 coordinates oestrogen signalling in breast cancer cells.

Approximately 70% of breast cancer cells express oestrogen receptor alpha (ERα). Previous studies have shown that the Brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex has a crucial role in these cells. However, it remains unclear how BIG3 regulates the suppressive activity of PHB2. Here we demonstrate that BIG3 functions as an A-kinase anchoring protein that binds protein kinase A (PKA) and the α isoform of the catalytic subunit of protein phosphatase 1 (PP1Cα), thereby dephosphorylating and inactivating PHB2. E2-induced PKA-mediated phosphorylation of BIG3-S305 and -S1208 serves to enhance PP1Cα activity, resulting in E2/ERα signalling activation via PHB2 inactivation due to PHB2-S39 dephosphorylation. Furthermore, an analysis of independent cohorts of ERα-positive breast cancers patients reveal that both BIG3 overexpression and PHB2-S39 dephosphorylation are strongly associated with poor prognosis. This is the first demonstration of the mechanism of E2/ERα signalling activation via the BIG3-PKA-PP1Cα tri-complex in breast cancer cells.

Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis.

Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.

Assay of serum E2 concentration in postmenopausal breast cancer patients using a high-sensitivity RIA method is generally useful.

BACKGROUND: Serum E2 must be monitored for aromatase inhibitor (AI) therapy, but conventional assays lack sensitivity. SUBJECTS/METHODS: Forty amenorrheic breast cancer patients scheduled for AI treatment but requiring hormonological confirmation of their menopausal status were studied. Serum E2 data generated by high-sensitivity RIA and by LC-MS/MS were analyzed for correlation. RESULTS: RIA gave a higher E2 value than LC-MS/MS in 62% of cases, but there was a significant positive correlation. Patients whose E2 levels by RIA were ≥ 2.5 pg/mL higher than those by LC-MS/MS (RIA-H group) and all other patients (RIA-N group) were compared. Both groups showed strong correlations between the two assay methods. With both methods patients with a high BMI had significantly elevated E2. Multiple regression analysis used age, age at menarche, number of births and BMI as explanatory variables. Significant variables were the BMI with LC-MS/MS, and both BMI and age with RIA. The RIA-H and RIA-N groups showed no difference in regard to the BMI, whereas the age was significantly lower in the RIA-H group. SUMMARY: Serum E2 levels determined for postmenopausal women by RIA and LC-MS/MS generally correlated well. High-sensitivity RIA is a potentially useful clinical assay, but it overestimated serum E2 in some women. J. Med. Invest. 63: 236-240, August, 2016.

Immunocytochemical results for HER2 and Ki67 in breast cancer touch-smear cell specimens are reliable.

BACKGROUND: Re-evaluation of the subtype of recurrent breast cancer is necessary for deciding the treatment approach, but it is often not performed due to the difficulty of obtaining tissue specimens from a recurrent lesion, etc. However, when a recurrent lesion is close to the body surface, fine-needle aspiration cells (FNA cells) can be easily obtained, and immunocytochemical (ICC) analysis of hormone receptors expression in FNA cells is said to be highly reliable. However, there is no consensus regarding ICC analysis of human epidermal growth factor receptor type 2 (HER2) expression and the Ki67 index using FNA cells. METHODS: Touch-smear cells (TSC) were prepared from resected specimens from 36 patients with primary invasive ductal carcinoma of the breast. The TSC were fixed in 95 % ethanol and subjected to ICC analysis for HER2 using HercepTest™ (Dako) and Ki67 using MIB-1™ (Dako). HER2 expression and the Ki67 index for the TSC were compared with the results of immunohistochemical analysis of histological section (HS). Statistical analyses used the kappa test and Pearson's correlation coefficients. RESULTS: HER2 and Ki67 were analyzed in TSC from 36 and 28 patients, respectively. The HER2 expression scores in the TSC and HS groups showed good agreement (kappa value =0.640) and significant correlation (correlation coefficient =0.860, p < 0.001). The Ki67 indexes in the TSC and HS groups also showed significant correlation (correlation coefficient =0.861, p < 0.001). CONCLUSIONS: The reliability of ICC analysis of HER2 expression and the Ki67 index using TSC were recognized.

Therapeutic advances in BIG3-PHB2 inhibition targeting the crosstalk between estrogen and growth factors in breast cancer.

Our previous studies demonstrated that specific inhibition of the BIG3-PHB2 complex, which is a critical modulator in estrogen (E2) signaling, using ERAP, a dominant negative peptide inhibitor, leads to suppression of E2-dependent estrogen receptor (ER) alpha activation through the reactivation of the tumor suppressive activity of PHB2. Here, we report that ERAP has significant suppressive effects against synergistic activation caused by the crosstalk between E2 and growth factors associated with intrinsic or acquired resistance to anti-estrogen tamoxifen in breast cancer cells. Intrinsic PHB2 released from BIG3 by ERAP effectively disrupted each interaction of membrane-associated ERα and insulin-like growth factor 1 receptor beta (IGF-1Rß), EGFR, PI3K or human epidermal growth factor 2 (HER2) in the presence of E2 and the growth factors IGF or EGF, followed by inhibited the activation of IGF-1Rß, EGFR or HER2, and reduced Akt, MAPK and ERα phosphorylation levels, resulting in significant suppression of proliferation of ERα-positive breast cancer cells in vitro and in vivo. More importantly, combined treatment with ERAP and tamoxifen led to a synergistic suppression of signaling that was activated by crosstalk between E2 and growth factors or HER2 amplification. Taken together, our findings suggest that the specific inhibition of BIG3-PHB2 is a novel potential therapeutic approach for the treatment of tamoxifen-resistant breast cancers activated by the crosstalk between E2 and growth factor signaling, especially in premenopausal women.