Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated β-cell maturation

The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E.

Control or gestational low-protein diet perinatal rat pancreas was harvested at embryonic day 20 (E20), day of birth (P0) and postnatal day 2 (P2). TFF3 mRNA was upregulated 4.5-fold at P0 vs. E20 and downregulated again at P2. In protein-undernourished pups induction of TFF3 at P0 was further increased to 9.7-fold and was increased at P2. TFF3 caused tyrosine phosphorylation of EGFR in INS-1E β-cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E β-cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal β-cell maturation, TFF3 increased cellular spreading as well as insulin mRNA levels. TFF3 also increased the expression of Pref1/Dlk1 that shares similarities in expression and regulation with TFF3.

These results suggest that TFF3 may promote adhesion and spreading of cells to accelerate β-cell maturation. This study indicates a functional role for TFF3 in pancreatic β-cell maturation in the perinatal period, which is altered by low protein diet during gestation.     

Ginsenoside Rg3 prevents INS-1 cell death from intermittent high glucose stress

Background: Ginsenoside Rg3 has been proposed to mediate anti-diabetic effects, but their direct effect on pancreatic β cell viability and mechanisms are not clearly understood. Recent studies suggest that intermittent high glucose (IHG) could be more harmful to pancreatic β cells than sustained high glucose. There are few reports about the effect of the ginsenosideRg3 to β cell apoptosis and proliferation against IHG.

Methods: INS-1 cells were treated with alternative glucose concentration with or without ginsenoside Rg3. Cell apoptosis and viability were detected by Annexin V staining and MTT assay. The activation of mitogen-activated protein kinases (MAPKs) was analyzed by Western blotting using specific antibodies. Quantification of secreted insulin protein was measured using rat/mouse Insulin ELISA kits. Bromodeoxyuridine (BrdU) staining and florescence in situ hybridization (FISH) analysis was performed to compare cell proliferation.

Result: INS-1 cell viability was decreased under IHG and increased with Rg3 treatment.Rg3 significantly reduced the apoptotic INS-1 cells against IHG. The quantification of secreted insulin concentration was increased with Rg3. Rg3 increased INS-1 cell proliferation. ERK and p38 MAPK pathways reduced by IHG were activated by the ginsenoside Rg3.

Conclusion: Ginsenoside Rg3 protected INS-1 cell death from IHG with reducing apoptosis and increasing proliferation.     

The impact of pneumatic tube transport on whole blood coagulation and platelet function assays

Pneumatic tube is an attractive way to transport blood samples from the emergency department to the central laboratory facility. We aimed to investigate the impact of pneumatic tube transportation on blood samples for analysis of whole blood coagulation and platelet function.

We included 21 healthy adult individuals and measured global coagulation assays by rotational thromboelastometry (ROTEM) and platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) using impedance aggregometry (ROTEM Platelet), on samples transported manually or by pneumatic tube transport. Statistical testing was performed with paired tests with post-hoc Bonferroni correction for multiple testing.

Our data revealed no difference in the far majority of ROTEM parameters (P > 0.003), while significantly decreased values were observed for INTEM clotting time (CT) (P = 0.002) and maximum clot firmness (MCF) including the amplitude after 10 min (A10) (P < 0.0001).

No statistically significant difference was observed on impedance aggregometry results when manual transport was compared to pneumatic tube transport (P > 0.003).

This study indicates that only minor and unsystematic differences between manual transport and pneumatic tube transport may be observed in ROTEM analyses, and that there is no influence from pneumatic tube transport on impedance aggregometry analyses using AA and ADP.     

Pazopanib for renal cell carcinoma leads to elevated mean arterial pressures in a murine model

Background: In the setting of metastatic RCC (mRCC), pazopanib is approved as first line therapy. Unfortunately treatment may lead to cardiotoxicity such as hypertension, heart failure, and myocardial ischemia.

Objective: Define the in vivo role of pazopanib in the development of cardiotoxicity.

Methods: Wild type mice were dosed for 42 days via oral gavage, and separated into control and treatment (pazopanib) groups. Baseline ECG’s, echocardiograms, and blood pressures were recorded. At the conclusion of the study functional parameters were again recorded, and animals were used for pathological, histological, and protein analysis.

Results: After 2 weeks of dosing with pazopanib, the treatment group exhibited a statistically significant increase in mean arterial pressure compared to control mice (119 ± 11.7 mmHg versus 108 ± 8.2 mmHg, p = 0.049). Treatment with pazopanib led to a significant reduction in the cardiac output of mice.

Conclusion: Our findings in mice clearly demonstrate that treatment with pazopanib leads to a significant elevation in blood pressure after 2 weeks of dosing and this persists for the duration of dosing. The continued development of the cardio-oncology field will be paramount in providing optimal oncologic care while simultaneously improving cardiac outcomes through further investigation into the mechanisms of CV toxicity.     

ABO blood type and risk of hepatocellular carcinoma: a meta-analysis

Background: ABO blood type is an invariant factor. There is a link between ABO blood type and some malignancies, such as gastric, pancreatic, and skin cancer. The role of ABO blood type in the pathogenesis of hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to explore the relationship between ABO blood type and risk of HCC.

Methods: Literature search was conducted among the PubMed, EMBASE, and Cochrane Library databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results: Seven papers were included. They included 92,847 healthy subjects, 5,463 patients with hepatitis, 294 cirrhotic patients, and 3,322 HCC patients. The proportion of blood type O was significantly lower in HCC patients than healthy subjects (OR = 0.76, 95%CI = 0.66–0.87, P < 0.0001) without any significant heterogeneity (P = 0.55, I² = 0%). The proportions of blood types A, B, and AB were not significantly different between HCC patients and healthy subjects. The proportion of ABO blood type was not significantly different between patients with HCC and those with hepatitis or cirrhosis.

Conclusion: HCC patients might have a lower proportion of blood type O than healthy subjects. Among the patients with chronic liver diseases, ABO blood type might not be associated with the risk of HCC.     

Bringing Creative Writing Instruction into Reminiscence Group Treatment

Objectives: This article describes the program evaluation of a group intervention combining reminiscence with literary creative writing instruction.

Method: This 10-week, 1-hour group was completed seven times in an outpatient geriatric mental health clinic. Each session introduced a different reminiscence theme and creative writing practice. Feasibility and acceptability were assessed through group monitoring and qualitative feedback. Effectiveness was assessed with pre- and post-test depression screening (PHQ-9) and qualitative feedback.

Results: A total of 34 veterans participated in the groups, with a mean group size of 4.86 (SD = .69). Participants were 85% male (n = 29) and 15% female (n = 5) with a mean age of 70.89 (SD = 8.30). To increase accessibility, several adaptations were made. There were statistically significant reductions in PHQ-9 depression scores (p = .005). Veterans reported qualitative improvements including increased motivation and self-expression.

Conclusions: This intervention was feasible and acceptable to the veterans being served. Randomized controlled research is needed to better understand efficacy.

Clinical Implications: Clinicians may consider ways to augment or adapt reminiscence interventions to meet the needs of their patient population. Clinicians may find it useful to integrate creative writing instruction into reminiscence interventions.     

An engineered cell sheet composed of human islets and human fibroblast,bone marrow–derived mesenchymal stem cells,or adipose–derived mesenchymal stem cells: An in vitro comparison study

Background: We previously reported the utility of engineered cell sheets composed of human islets and supporting cells in vitro and in vivo. It is unclear which type of supporting cell is most suitable for constructing cell sheets with human islets. The present study aimed to compare human fibroblasts, bone marrow–derived mesenchymal stem cells (BM–MSCs), and adipose–derived mesenchymal stem cells (ADSCs) as a supporting source for cell sheets.

Methods: Engineered cell sheets were fabricated with human islets using human fibroblasts, BM–MSCs, or ADSCs as supporting cells. The islet viability, recovery rate, glucose–stimulated insulin release (determined by the stimulation index), and cytokine secretion (TGF–β1, IL–6, and VEGF) of groups—including an islet–alone group as a control-were compared.

Results: All three sheet groups consistently exhibited higher viability, recovery rate, and stimulation index values than the islet-alone group. The ADSC group showed the highest viability and recovery rate among the three sheet groups. There were no discernible differences in the stimulation index values of the groups. The fibroblast group exhibited significantly higher TGF–β1 values in comparison to the other groups. The IL–6 level of the ADSC group was more than five times higher than that of the other groups. The ADSC group showed the VEGF level; however, it did not differ from that of the BM–MSC group to a statistically significant extent.

Conclusion: Engineered cell sheets composed of islets and supporting cells had a cytoprotective effect on islets. These results suggest that individual cell types could be a more attractive source for crafting engineered cell sheets in comparison to islets alone.     

The Aging Well through Interaction and Scientific Education (AgeWISE) Program

Objective: We conducted a randomized controlled trial of the Aging Well through Interaction and Scientific Education (AgeWISE) program, a 12-week manualized cognitive rehabilitation program designed to provide psychoeducation to older adults about the aging brain, lifestyle factors associated with successful brain aging, and strategies to compensate for age related cognitive decline.

Methods: Forty-nine cognitively intact participants ≥ 60 years old were randomly assigned to the AgeWISE program (n = 25) or a no-treatment control group (n = 24). Questionnaire data were collected prior to group assignment and post intervention. Two-factor repeated-measures analyses of covariance (ANCOVAs) were used to compare group outcomes.

Results: Upon completion, participants in the AgeWISE program reported increases in memory contentment and their sense of control in improving memory; no significant changes were observed in the control group. Surprisingly, participation in the group was not associated with significant changes in knowledge of memory aging, perception of memory ability, or greater use of strategies.

Conclusions: The AgeWISE program was successfully implemented and increased participants’ memory contentment and their sense of control in improving memory in advancing age.

Clinical Implications: This study supports the use of AgeWISE to improve perspectives on healthy cognitive aging.     

Positive correlation between blood pressure or heart rate and chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes measured by new ELISA

The aim of the present study was to establish a convenient clinically applicable assay method for chymase-dependent angiotensin II forming activity of circulating mononuclear leukocytes (CML), which was potentially a marker of tissue chymase activity. Using this method, association between CML chymase activity and clinical parameters was determined.

Cardiovascular outpatients (n = 170) without taking antihypertensive medication were recruited.

An ELISA for chymase-dependent angiotensin II-forming activity in CML was established using Nma /Dnp-modified angiotensin I.

Logistic regression analysis revealed that age and male gender were significant independent determinants of the increased CML chymase activity. After adjustment by age and gender, the CML chymase activity was positively correlated with systolic blood pressure, pulse rate, and the brain natriuretic peptide level.

The relation between blood pressure and CML chymase activity suggests that it might reflect that increased tissue chymase activity contributes to systemic high blood pressure and heart rate because plasma chymase is inactive due to inhibitory plasma inhibitors.     

High-Sensitivity Cardiac Troponin T levels in prehypertensive patients

Background: High-sensitivity cardiac troponin T (hs-cTNT) is an important non-invasive laboratory-based marker of subclinical myocardial injury. Prehypertension, which may be a precursor of hypertension, is a major public health issue. Our aim was to evaluate the importance of serum hs-cTnT as a marker predicting prehypertension.

Methods: A total of 100 subjects (45 women and 55 men) consisting of 50 consecutive prehypertensive patients with blood pressures between 120/80 and 139/89 mmHg and 50 normotensive patients with blood pressures < 120/80 mmHg were enrolled prospectively. The hs-cTNT level was calculated and compared between the two groups. Echocardiographic examinations were performed in all patients.

Results: The hs-cTnT level was significantly higher in the prehypertensive group (p < 0.001) and was positively correlated with prehypertension (r = 0.625, p < 0.001). Hs-cTnT was an independent predictor of prehypertension (odds ratio = 1.043, 95% confidence interval [CI] 1.019–1.067, p < 0.001). An Hs-cTnT level of 0.55 ng/L was predictive of prehypertension with a sensitivity of 86% and specificity of 60% (area under the curve = 0.861; 95% CI, 0.787–0.935; p < 0.001).

Conclusion: hs-cTnT may complement other diagnostic biomarkers in predicting prehypertension.

Abbrevations: high-sensitivity cardiac troponin T, prehypertension, subclinical myocardial injury     

Caregiving and Perceived Generativity: A Positive and Protective Aspect of Providing Care?

Objectives: Although a sizable body of research supports negative psychological consequences of caregiving, less is known about potential psychological benefits. This study aimed to examine whether caregiving was associated with enhanced generativity, or feeling like one makes important contributions to others. An additional aim was to examine the buffering potential of perceived generativity on adverse health outcomes associated with caregiving.

Methods: Analyses utilized a subsample of participants (n = 3,815, ages 30–84 years) from the second wave of the National Survey of Midlife Development in the United States (MIDUS).

Results: Regression analyses adjusting for sociodemographic factors indicated greater negative affect and depression (p < .001) and lower levels of positive affect (p < .01), but higher self-perceptions of generativity (p < .001), in caregivers compared with non-caregivers. This association remained after adjusting for varying caregiving intensities and negative psychological outcomes. Additionally, generativity interacted with depression and negative affect (p values < .05) to lessen the likelihood of health-related cutbacks in work/household productivity among caregivers.

Conclusions: Results suggest that greater feelings of generativity may be a positive aspect of caregiving that might help mitigate some of the adverse health and well-being consequences of care.

Clinical Implications: Self-perceptions of generativity may help alleviate caregiver burden and explain why some caregivers fare better than others.     

Selective apoptosis of multiple myeloma cells in primary samples induced by arsenic trioxide

Objectives

Currently, multiple myeloma (MM) is an incurable disease. Despite the fact that arsenic trioxide (ATO) shows promising results in vitro, data from treatment of patients with MM are disappointing. Due to these discrepancies, we compared the efficacy and selectivity of ATO at two different concentrations in samples from MM patients.

Methods

The extent of apoptosis induced by 2 and 5 µM ATO was evaluated by flow cytometry using annexin V. 34 diagnostic bone marrow samples obtained from MM patients were analysed.

Results

5 µM ATO efficiently induced apoptosis in primary samples. Besides efficacy, also selectivity of action on MM cells in comparison to remaining haematopoietic cells was demonstrated for 5 µM ATO but not for 2 µM ATO.

Discussion

Our study on primary samples confirmed that ATO has a potential role in therapeutic management of MM. Further controlled studies on MM patients are needed.     

Preliminary Evidence for the Validity and Reliability of the Caregiver Reaction Scale

Objective: Reliable and valid measures of caregiver experience are critical components of researching the caregiver experience and providing effective care to family caregivers. Assessments should be comprehensive, including positive aspects of caregiving as well as multiple dimensions of stress and burden (Family Caregiver Alliance, 2006). One such measure is the Caregiver Reaction Scale (CRS), a clinical tool adapted from research protocols in 1990.

Methods: This study is a preliminary examination of the psychometric properties of the CRS using a sample of family caregivers (N = 502) seeking services at a community based mental health and aging family service agency.

Results: The eight subscales of the CRS exhibited very good internal reliability α ≥ .81. Test-retest reliability was r ≥ .62, and convergent validity evidence is positive. Means and standard deviations are reported.

Conclusions: Initial psychometrics suggest the CRS offers a reliable and valid assessment of multiple dimensions of the caregiving experience and warrants further research.     

The Promotion of Well-Being in Aging Individuals Living in Nursing Homes: A Controlled Pilot Intervention with Narrative Strategies

Objectives: The study aimed: (1) to compare levels of well-being and distress in older adults living in nursing homes with those living in community; and (2) to test the feasibility of a positive narrative intervention for improving well-being versus a control art-and-craft intervention in a nursing home setting.

Methods: Sixty older adults participated in the study (M = 77.37; SD = 5.00), Male = 20 (33.3%). In Study 1, 30 adults living in nursing homes were compared with 30 community-dwellers using the following measures: Satisfaction with Life Scale, Psychological Well-being Scale, Social Well-being Scale, Geriatric Depression Scale, and sleep quality. In Study 2, the same 30 adults living in nursing homes were allocated to a positive narrative intervention group (N = 20) or to a control group (N = 10) and assessed at post-intervention.

Results: In Study 1, older adults in nursing homes presented more depression and impairments in well-being, compared to community-dwellers. In Study 2, at post-treatment, individuals assigned to the narrative intervention reported significantly increased well-being and sleep quality.

Conclusions: Although preliminary, results showed that older adults living in nursing homes are more vulnerable than community-dwellers. These patients experienced improvement when given a short group positive narrative intervention applicable in nursing homes.

Clinical Implications: A brief group intervention based on fairy tales yielded improvements in well-being and sleep quality in nursing home residents, who enjoyed and appreciated its content. These promising results need to be confirmed by future randomized controlled trials.     

Self-Management and Yoga for Older Adults with Chronic Stroke: A Mixed-Methods Study of Physical Fitness and Physical Activity

Objective: This study investigated changes in physical fitness and physical activity among older patients with chronic stroke (stroke ≥ 6 months previous) after participation in a yoga infused self-management intervention.

Methods: A mixed-methods secondary data analysis examined quantitative measures of endurance, strength, and gait speed and qualitative perspectives of intervention participants.

Results: Based on Wilcoxon analysis, physical fitness outcome measures including endurance and lower and upper body strength significantly (p < .02) improved. Based on qualitative results of 2 focus groups and 14 individual interviews, participants expressed positive changes in endurance, strength, gait speed, flexibility, and balance. They also reported improvements in walking ability and duration, and expressed a desire to continue yoga and increase levels of exercise.

Conclusions: With the objective of improving physical fitness and exercise for older adults with chronic stroke, it is important for self-management interventions to provide specific safe and feasible physical activity components, such as yoga.

Clinical Implications: Health professionals may improve offered chronic stroke self-management interventions by incorporating yoga.     

Alcohol Use and Frailty Risk among Older Adults over 12 Years: The Health and Retirement Study

Objectives: The primary goal was to examine the relationship between alcohol use and frailty, a variable characterizing late-life decline, in a national, longitudinal survey of older adults living in the United States.

Methods: The sample drawn from the Health and Retirement Study included 9,499 stroke-free participants over age 65 in 2000. The sample was 59.1% female, and had a mean age of 74.25 years (SD = 6.99). Follow-up data was from 2004, 2008, and 2012. Frailty was defined phenotypically using the Paulson-Lichtenberg Frailty Index (PLFI). Alcohol use was measured via self-report. Control variables included age, race, education, socio-economic status (SES), depressive symptomatology, medical burden score, body mass index (BMI), and partner status. With abstinent participants as the reference group, logistic regressions were conducted to determine prevalent frailty at 2000, and Cox’s proportional hazard models were utilized to determine time to incident frailty over a 12-year period.

Results: Results revealed that age, depressive symptomatology, and medical burden score were significant positive correlates of prevalent and incident frailty (p < .05) for both males and females. Logistic regressions revealed that consumption of 1–7 alcoholic drinks per week was associated with reduced prevalent frailty (OR = .49, p < .001) for females. Survival analysis results reveal that compared with nondrinkers, males and females who reportedly consumed 1–7 drinks per week had a decreased probability of incident frailty (HR = .78–081, p < .05).

Conclusions: Findings suggest that moderate alcohol use confers reduced frailty risk for both older men and women. Future research should examine the mechanism(s) relating alcohol consumption and frailty.

Clinical Implications: Findings support extant literature suggesting some healthcare benefits may be associated with moderate drinking.     

Child-Pugh,MELD, and ALBI scores for predicting the in-hospital mortality in cirrhotic patients with acute-on-chronic liver failure

Objectives: Our study aimed to evaluate the discriminative abilities of Child-Pugh, model for end-stage liver disease (MELD), and albumin-bilirubin (ALBI) scores in predicting the in-hospital mortality in cirrhotic patients with acute-on-chronic liver failure (ACLF).

Methods: Cirrhotic patients with ACLF admitted between 2010 January and 2014 June were retrospectively reviewed. Areas under the receiver operating characteristic curves (AUROCs) with 95% confidence intervals (CIs) were calculated.

Results: One hundred patients were eligible for the Asia-Pacific Association for the Study of the Liver (APASL) criteria. AUROCs of Child-Pugh, MELD, and ALBI scores in predicting the in-hospital mortality was 0.63 (95%CI: 0.52–0.72, P = 0.05), 0.75 (95%CI: 0.65–0.83, P < 0.0001), and 0.53 (95%CI: 0.42–0.63, P = 0.69), respectively. Eighty-eight patients were eligible for the EASL/AASLD criteria. AUROCs of Child-Pugh, MELD, and ALBI scores in predicting the in-hospital mortality were 0.59 (95%CI: 0.48–0.69, P = 0.14), 0.57 (95%CI: 0.46–0.68, P = 0.26), and 0.57 (95%CI: 0.46–0.67, P = 0.29), respectively. There was no significant difference among them.

Conclusion: Child-Pugh, MELD, and ALBI scores might be ineffective in predicting the in-hospital mortality of cirrhosis with ACLF.     

Compliance and satisfaction with deferasirox (Exjade®) compared with deferoxamine in patients with transfusion-dependent beta-thalassemia

Objective

The current standard option for iron chelation therapy (ICT) in transfusion-dependent patients with beta-thalassemia is deferoxamine (DFO). We aimed to compare the compliance with DFO vs. deferasirox (Exjade^®), a novel oral iron chelator, in patients with transfusion-dependent beta-thalassemia.

Methods

In this cross-sectional study, 220 patients from Southern Iran who were receiving DFO or Exjade^® for the last 2 years were investigated in 2012. Satisfaction, compliance, convenience, and life disturbances of the patients with ICT were evaluated. Assessments were performed at four different occasions during 1 year.

Results

According to the results, 114 patients received treatment with DFO and 106 patients were treated with Exjade^®. In comparison with the patients who were treated with DFO, those receiving Exjade^® reported a significantly higher rate of compliance and convenience (P < 0.05). However, no significant difference was observed between the two groups regarding their satisfaction (P > 0.05). In the DFO group, 44.9% of the patients reported irritation and pain at the injection site.

Conclusions

Considering higher rate of compliance and convenience with Exjade^® and the comparable efficacy of these two modalities of ICT documented in previous studies, Exjade^® can be used as a preferable choice of ICT in iron-overload patients with beta-thalassemia.     

Book reviews

The School Years. Current Issues in the Socialization of Young People John C. Coleman (Ed.) London, Routledge, 1992 (2nd edn) 208 pp.; £10.99 (paperback)

AIDS and the Hospice Community Madalon O'Rawe Amenta & Clair B. Tehan Binghampton, NY, Harrington Park Press, 1991 186 pp. + index

Social Care & HIV/AIDS The Hull York Research Team London, HMSO, 1993 214 pp., £13.70 (paperback)

Private Risks and Public Dangers Sue Scott, Gareth Williams, Stephen Platt & Hilary Thomas (Eds) Aldershot, Avebury, 1993 205 pp., £34.95 (hb)

AIDS: a problem for sociological research Michael Pollak, Geneviève Paicheler & Janine Pierret London, Sage Publications, 1992 124 pp., £10.95 (paperback)

AIDS: The Winter War Arthur D. Kahn Philadelphia, Temple University Press, 1993 236 pp., U£27.95 (hardback)

AIDS: Facing the Second Decade Peter Aggleton, Peter Davies & Graham Hart (Eds) Taylor & Francis, 1993 215 pp., £12.95 (Pb)

Women and AIDS: Psychological Perspectives Corrine Squire (Ed.) London, Sage Publications, 1993 196 pp., £12.95 (paperback)