Attachment-based family therapy versus nondirective supportive therapy for lesbian, gay, bisexual and questioning adolescents with depression, and suicidal ideation: An exploratory study.

INTRODUCTION: Lesbian, gay, bisexual, and questioning (LGBQ) adolescents are particularly at risk for suicidal ideation; however, little clinical research is focused on treating this population. Attachment-based family therapy (ABFT) is among the few empirically supported youth suicide treatments adapted for LGBQ adolescents. The purpose of this exploratory study is to determine the differential treatment effects and rates of change for LGBQ and heterosexual adolescents with depression and suicidal ideation receiving either ABFT or family enhanced nondirective supportive therapy (FE-NST). METHOD: The sample included 129 adolescents (31% LGBQ), ages 12-18 randomized to the two treatment groups. Multilevel modeling was used to examine individual changes in depression and suicidal ideation over the 16-week treatment. RESULTS: Results revealed that LGBQ adolescents in the ABFT condition showed a greater rate of reduction in depressive symptoms over treatment, slope = -0.94, p < 0.001, than did LGBQ adolescents in the NST condition, slope = -0.41, p = 0.12. Heterosexual adolescents showed symptom reduction in both treatment conditions (ABFT slope = -0.47, p < 0.001; NST slope = -0.79, t (113) = -7.48, p < 0.001). Changes in suicidal ideation were found across time, but not across conditions. CONCLUSION: LGBQ adolescents in the ABFT condition had a sharper decrease in depressive symptoms and better outcomes at week 16.

Bayesian matrix completion for hypothesis testing.

We aim to infer bioactivity of each chemical by assay endpoint combination, addressing sparsity of toxicology data. We propose a Bayesian hierarchical framework which borrows information across different chemicals and assay endpoints, facilitates out-of-sample prediction of activity for chemicals not yet assayed, quantifies uncertainty of predicted activity, and adjusts for multiplicity in hypothesis testing. Furthermore, this paper makes a novel attempt in toxicology to simultaneously model heteroscedastic errors and a nonparametric mean function, leading to a broader definition of activity whose need has been suggested by toxicologists. Real application identifies chemicals most likely active for neurodevelopmental disorders and obesity.

Antifatigue and Anti-Inflammatory Effects of Cervus elaphus L., Angelica gigas Nakai, and Astragalus membranaceus Bunge Complex Extracts in Physically Fatigued Mice.

Fatigue is a common complaint among people under stress, causing an array of negative effects on physical function. In this study, we investigated the antifatigue and anti-inflammatory effects of Cervus elaphus L., Angelica gigas Nakai, and Astragalus membranaceus Bunge complex extracts (CAA) using a treadmill stress test in animal models. The mice were administered various doses of CAA (50-200 mg/kg bw per day) once daily for 21 days. After exhaustive treadmill exercise, the running time of CAA-treated mice increased 1.5 times; fatigue-related biochemical parameters, including lactate dehydrogenase (∼30%), creatine kinase (∼20%), and proinflammatory cytokines interleukin (IL)-1ß (∼10%), and IL-6 (∼10%) in the serum and muscle tissue were downregulated compared with those in exercised control mice. This study provides strong evidence for the prevention of CAA-induced inflammatory incidences mediated by the blockade of nuclear factor-κB activation. Collectively, our results indicate that CAA can alleviate symptoms of fatigue in mice as an effective anti-inflammatory agent.

The beneficial role of family enmeshment among South Korean immigrants in the United States.

Enmeshment is considered inimical to healthy family dynamics among European Americans. However, recent studies have failed to show negative associations between family enmeshment and individual outcomes among Asian Heritage families. Using structural equation modelling and multiple group analysis, this study examined whether enmeshed relationships are dysfunctional in Korean immigrant families in the United States and whether degree of acculturation moderated the associations between enmeshment and children's socioemotional functioning and academic performance. The sample consisted of 98 South Korean immigrant families with children between 9 and 14 years of age residing in the Greater New York City Area. Results showed that enmeshed family relationships tended to be beneficial to child socioemotional functioning and the association became more evident with lower than higher degree of acculturation. Findings are discussed in terms of the meaning of enmeshment when working with Korean immigrant families in the United States.

Implementing Attachment-Based Family Therapy for Depressed and Suicidal Adolescents and Young Adults in LGBTQ+ Services.

Background: Suicide is a serious public health problem for LGBTQ+ adolescents and young adults. Attachment-based family therapy (ABFT) is one of the few suicide treatment models that has been tested with this population. The challenge remains in how to implement ABFT into the ecology of LGBTQ+ service settings. Aims: In this study, we tested the feasibility, acceptability, and preliminary effectiveness of ABFT in LGBTQ+ community settings. Method: Ten participants were enrolled in 16 weeks of ABFT across three LGBTQ+ organizations. Feasibility (treatment completion) and acceptability (Working Alliance Inventory [WAI]; opinions about treatment [OAT]) were measured for youth and caregivers. Depression and suicide outcomes were assessed for nine participants. Results: ABFT was demonstrated to be both feasible and acceptable. All participants completed treatment, and there were no dropouts. Adolescents/young adults and their caregivers reported high WAI and adequate OAT scores throughout treatment. There was a significant decrease in suicidal ideation (ß = -12.16, t(10) = -3.14, p < .01). Decreases in depression, however, were not significant (ß = -1.83, t(9.11) = -0.88, p = .40). Limitations: The small sample limits our ability to estimate treatment effectiveness. A larger effectiveness trial is warranted. Conclusion: ABFT is a promising treatment for LGBTQ+ service settings.

Tacrolimus-induced neurotoxicity from bipolar disorder to status epilepticus under the therapeutic serum level: a case report.

BACKGROUND: Tacrolimus is a macrolide immunosuppressant widely used to prevent rejection after solid organ transplantation. In general, adverse events of tacrolimus occur more often as the concentration of tacrolimus in the blood increases. We report the case of a 39-year-old man who developed a variety of adverse events despite in the therapeutic level of tacrolimus in the blood. CASE PRESENTATION: A 39-year-old man underwent liver transplantation for liver cirrhosis due to alcoholic liver disease. The postoperative immunosuppressant consisted of tacrolimus (5 mg) and mycophenolate (500 mg) twice daily. Five months after taking tacrolimus, he presented with talkativeness, which gradually worsened. Brain magnetic resonance imaging performed 10 months after tacrolimus administration revealed a hyperintense lesion affecting the middle of the pontine tegmentum on T2WI. The blood concentration of tacrolimus was 7.2 ng/mL (therapeutic range 5-20 ng/mL). After 21 months, he exhibited postural tremor in both the hands. Twenty-four months after taking tacrolimus, he showed drowsy mentality, intention tremor, and dysdiadochokinesia. Electroencephalography presented generalized high-voltage rhythmic delta waves; therefore, tacrolimus was discontinued in suspicion of tacrolimus-induced neurotoxicity, and anticonvulsive treatment was started. The level of consciousness gradually improved, and the patient was able to walk independently with mild ataxia. CONCLUSION: This case shows that tacrolimus-induced neurotoxicity can occur even at normal concentrations. Therefore, if a patient taking tacrolimus exhibits psychiatric or neurologic symptoms, neurotoxicity should be considered even when the blood tacrolimus is within the therapeutic range.

"Getting Used to It, but Still Unwelcome": A Grounded Theory Study of Physical Identity Development in Later Life.

Given the global trends toward an aging society and the increased desire for healthy aging in late life, this study examines older adults' perceptions of aging and their physical identity through their engagement in physical activities. Adopting a grounded theory, we interviewed 15 individuals aged 65 years and older, who were involved in physical activities on a regular basis. This study provided a final model depicting (a) divergent and convergent modes of strategies and socioemotional aspects of physical identity development in later life and (b) different strategies employed between younger-old versus older-old age groups and between participants who have underlying health conditions and those who do not. These findings add a contextual explanation of identity development in later life and stress the recurring process of physical identity development.

Ageism in the Fitness and Health Industry: A Review of the Literature.

This review aims to understand how age-related stereotypes against older adults' physical capabilities influence their ability to engage in regular physical activity. The authors wanted to know how people construe ageism in the fitness and health arena, how ageism manifests in this field, and how ageism influences older adults' learning and practicing physical activity. Data was extracted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Twenty-two empirical studies met the selection criteria. The findings revealed that the attributes of ageism fell into either self-imposed or other-directed ageism categories and manifested as implicit or explicit ageism. The study also identified the following four themes: (a) perceptions of aging and exercise, (b) exercise motivation, (c) opportunities for older adults, and (d) ambiguous positionality as older exercisers. The research provides evidence for the existence of ageism against older exercisers. Further research considering the implication of ageism within the exercising industry is necessary.

HKR3 regulates cell cycle through the inhibition of hTERT in hepatocellular carcinoma cell lines.

Hepatocellular carcinoma is a malignant disease with improved hepatic regeneration and survival, and is activated by human telomere transferase (hTERT). hTERT is expressed during early fetal development and switched off in most adult tissues, but it becomes reactivated in HCC. The exact mechanism regulating these expression changes remains unknown during HCC progress. We evaluated the relationship between hTERT expression and human kruppel-related 3 (HKR3) and cell cycle-related factors in HCC cell lines. Following transfection for hTERT knockdown and HKR3 overexpression, proteomic and transcriptomic analyses related to hTERT were performed using liquid chromatography/mass spectrometry (LC/MS) and RNA sequencing (RNAseq) in HCC cell lines. The expression levels of hTERT, HKR3, and cell cycle-related factors were measured using western blotting, and tumor growth were evaluated via cell proliferation and cell cycle assays. Transcriptomic and proteomic analyses showed that HKR3, hTERT and cyclin-dependent kinase inhibitor 2A (CDKN2A) were correlated. Up-regulation of HKR3 expression decreased hTERT and cyclin activation and suppressed the G1/S phase of the cell cycle through CDKN2A activation. Our results suggest that HKR3 induced regulation of cell cycle through hTERT inhibition and CDKN2A activation. Our results will facilitate further exploration of the pathways regulating human telomerase activity in HCC cell lines.

Effect of S267F variant of NTCP on the patients with chronic hepatitis B.

Sodium taurocholate cotransporting polypeptide (NTCP) was identified as an entry receptor for hepatitis B virus (HBV) infection. The substitution of serine at position 267 of NTCP with phenylalanine (S267F) is an Asian-specific variation that hampers HBV entry in vitro. In this study, we aimed to evaluate the prevalence of S267F polymorphism in Korean patients with chronic hepatitis B (CHB) and its association with disease progression and potential viral evolution in the preS1 domain of HBV. We found that the frequency of the S267F variant of NTCP in CHB patients and controls was 2.7% and 5.7% (P = 0.031), respectively, and that those who had S267F variant were less susceptible to chronic HBV infection. The frequency of the S267F variant in CHB, cirrhosis and hepatocellular carcinoma (HCC) patients was 3.3%, 0.9%, and 3.5%, respectively. Thus, the S267F variant correlated significantly with a lower risk for cirrhosis (P = 0.036). Sequencing preS1 domain of HBV from the patients who had S267F variant revealed no significant sequence change compared to the wild type. In conclusion, the S267F variant of NTCP is clinically associated with a lower risk of chronic HBV infection and cirrhosis development, which implicates suppressing HBV entry could reduce the disease burden.

Standardized Mori ramulus extract improves insulin secretion and insulin sensitivity in C57BLKS/J db/db mice and INS-1 cells.

Abnormalities in the hyperbolic relationship between insulin sensitivity and insulin secretion may cause oxidative stress and non-enzymatic glycation, resulting in an increased risk of type 2 diabetes. Here, we performed a 14-week study to investigate the effects of ethanolic extract of Mori ramulus (MRE; 0, 800, and 1600mg/kg body weight) and its signature component oxyresveratrol (OXY; 800mg/kg body weight) on ß-cell dysfunction and insulin resistance in C57BLKS/J db/db mice fed with a high-fat diet. Compared with the diabetic control group, the high-dose MRE group showed a significant decrease in fasting blood glucose (p=0.0024); a significant increase in insulin secretion as measured by insulin (p=0.0012) and C-peptide (p=0.0103) levels in plasma and insulin content (p=0.0440) and homeobox factor-1 protein expression (p=0.0148) in the pancreas; and a significant increase in insulin sensitivity as measured by insulin receptor mRNA expression in the liver (p=0.0179) and adipose tissue (p=0.0491). In addition, improvements in the reactive oxygen species level and inflammatory pancreatic and hepatic tissue damage were also observed in the MRE group as assessed by histological findings. A similar but weaker effect was found in the OXY group. Furthermore, we observed a potentiating effect of MRE and OXY on insulin secretion in INS-1 cells in the presence of 27mM glucose, together with an anti-glycation effect as indicated by methylglyoxal-trapping capacity and inhibition of advanced glycation end-product formation. Taken together, these data suggest that MRE could ameliorate ß-cell dysfunction and insulin resistance by reducing oxidative damage and advanced glycation end-product (Wagenknecht et al., 2003) formation and that these effects are due, at least in part, to OXY.

Cell culture-adaptive mutations of NS5A affect replication of hepatitis C virus differentially depending on the viral genotypes.

Most of HCV RNAs require cell culture-adaptive mutations for efficient replication in cell culture and a number of such mutations have been described including a well-known S2204I substitution mutation in NS5A protein. In contrast, the replication of genotype 2a JFH1 RNA in cell culture does not require any cell culture-adaptive mutation. Rather, the presence of S2204I mutation impaired the JFH1 RNA replication. In this study, we examined the effect of reversions and substitutions of NS5A cell culture-adaptive mutations on virus replication in different genotypic backgrounds after either placing genotype 1a NS5A in the genotype 2a JFH1 or vice versa. The results from this investigation suggest that the S2204I mutation affects HCV RNA replication differentially depending on the viral genotypes but that the effect was not simply explained by the genotypic background. Perhaps, the effect of the S2204I mutation on HCV replication reflects both intra- and intergenic interactions of NS5A protein. J. Med. Virol. 89:146-152, 2017. © 2016 Wiley Periodicals, Inc.

A Herbal Formula HT051, a Combination of Pueraria lobata and Rehmannia glutinosa, Prevents Postmenopausal Obesity in Ovariectomized Rats.

Menopause is strongly associated with an increased risk of metabolic dysfunctions due to the decline in estrogen. Here, we hypothesized that dietary HT051, containing the roots of Pueraria lobata and Rehmannia glutinosa, has beneficial effects on ovariectomized (OVX) rats by regulating lipid metabolism. Forty-eight female Sprague-Dawley rats were randomly divided into 4 groups: sham-operated (Sham), OVX, OVX with low-dose HT051 supplementation, and OVX with high-dose HT051 supplementation. The rats were fed with a modified AIN-93G diet or an HT051-containing modified AIN-93G diet for 8 weeks. Body weight, fat mass, and serum levels of total cholesterol, triglyceride, glucose, alanine transaminase, and aspartate transaminase decreased in HT051-fed OVX rats. Dietary HT051 supplementation significantly decreased the mRNA expression of lipogenesis-related genes, including sterol regulatory element-binding protein 1c and fatty acid synthase, and increased the mRNA expression of ß-oxidation-related genes, including peroxisome proliferator-activated receptor and carnitine palmitoyl transferase 1 in the liver of OVX rats. Moreover, the expression of genes involved in adipogenesis and inflammation was significantly lower in the adipose tissue of OVX rats fed with HT051 than in the OVX group. These findings suggest that HT051 may be a potential natural alternative for the management of postmenopausal metabolic dysfunctions.

Herbal Formula HT048 Attenuates Diet-Induced Obesity by Improving Hepatic Lipid Metabolism and Insulin Resistance in Obese Rats.

It is well established that obesity causes a variety of chronic diseases such as cardiovascular diseases and diabetes. Despite the diligent scientific efforts to find effective ways to lower the level of obesity, the size of obese population grows continuously around the world. Here we present the results that show feeding diet containing HT048, a mixture of the extracts of Crataegus pinnatifida leaves and Citrus unshiu peel, two of the well-known traditional herbal medicines in Eastern Asia, decreases obesity in rats. We fed rats with five different diets for 10 weeks: chow diet (STD), high-fat diet (HFD), high-fat diet with 0.04% orlistat, a drug to treat obesity (HFD + Orlistat), high-fat diet with 0.2% HT048 (w/w; HFD + 0.2% HT048), and high-fat diet with 0.6% HT048 (w/w; HFD + 0.6% HT048). It was found that both body and total white adipose tissue weight of HT048 groups significantly decreased compared to those of the HFD group. Moreover, HT048 decreased serum insulin levels in HFD-fed obese rats. At the molecular level, HT048 supplementation downregulated genes involved in lipogenesis, gluconeogenesis, and adipogenesis, while the expression level of ß-oxidation genes was increased. Supplementation-drug interactions are not likely as HFD and HT048-containing diet did not significantly induce genes encoding CYPs. Collectively, this study suggests that HT048 taken as dietary supplement helps to decrease obesity and insulin resistance in HFD-fed obese rats.

Retinoic acid enhances lactoferrin-induced IgA responses by increasing betaglycan expression.

Lactoferrin (LF) and retinoic acid (RA) are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan (transforming growth factor-beta receptor III, TßRIII) and activation of canonical TGF-ß signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line α (GLα) transcription and GLα promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced TßRIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 (CCR9) and α4ß7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9+IgA+ plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses.

Clonal evolution of multidrug resistant hepatitis B virus during entecavir rescue therapy.

BACKGROUND & AIMS: Analysing the mutation pattern of multidrug resistance (MDR) is important in the treatment of chronic hepatitis B (CHB). In this study, the evolutionary pattern of MDR mutations was investigated in patients receiving entecavir (ETV) rescue therapy. METHODS: Eight CHB patients with lamivudine (LAM)- and adefovir (ADV)-resistant mutations showing suboptimal response to ETV and to subsequent ETV-plus-ADV therapy were enrolled. The clonal evolution of the mutation pattern was investigated through direct sequencing, multiplex restriction fragment mass polymorphism (RFMP), and clonal analysis and the utility of these methods was compared. RESULTS: Among 160 clones at baseline, wild-type hepatitis B virus (HBV) was present in 62 (38.8%), LAM-resistant mutations in 92 (57.6%) and ADV-resistant mutations in 55 (34.4%). LAM-resistant mutations increased to 70.6% at the end of ETV therapy and increased to 74.4% at the 12th month of ETV-plus-ADV therapy. During the same time periods, ETV-resistant mutations were present in 46.3% and 38.8%, and ADV-resistant mutations were present in 3.1% and 9.4% respectively. When 256 nucleotides from 32 samples were examined for mutations, clonal analysis detected 93 mutations (36.3%), direct sequencing detected 36 mutations (14.1%) and RFMP detected 73 mutations (28.5%). The sensitivity (73.1%, 95% CI; 64.1-82.1%) and specificity (96.9%, 95% CI; 94.4-99.4%) of RFMP were high, showing a concordance rate of 88.3% with the results from clonal analysis. All mutations exceeding 40% of the total clones detected by clonal analysis were also detected by RFMP. CONCLUSIONS: The clonal evolution of the mutation pattern in MDR HBV showed the selection of LAM-resistant (±ETV-resistant) HBV during ETV rescue therapy, which may be the primary reason for patients' suboptimal response. Multiplex RFMP is a useful method for detecting MDR mutations in clinical practice.

Lactoferrin Combined with Retinoic Acid Stimulates B1 Cells to Express IgA Isotype and Gut-homing Molecules.

It is well established that TGF-ß1 and retinoic acid (RA) cause IgA isotype switching in mice. We recently found that lactoferrin (LF) also has an activity of IgA isotype switching in spleen B cells. The present study explored the effect of LF on the Ig production by mouse peritoneal B cells. LF, like TGF-ß1, substantially increased IgA production in peritoneal B1 cells but little in peritoneal B2 cells. In contrast, LF increased IgG2b production in peritoneal B2 cells much more strongly than in peritoneal B1 cells. LF in combination with RA further enhanced the IgA production and, interestingly, this enhancement was restricted to IgA isotype and B1 cells. Similarly, the combination of the two molecules also led to expression of gut homing molecules α4ß7 and CCR9 on peritoneal B1 cells, but not on peritoneal B2 cells. Thus, these results indicate that LF and RA can contribute to gut IgA response through stimulating IgA isotype switching and expression of gut-homing molecules in peritoneal B1 cells.

Casein kinase II inhibitor enhances production of infectious genotype 1a hepatitis C virus (H77S).

Genotype 2a JFH1 virus has substantially contributed to the progress of HCV biology by allowing entire viral life cycle of HCV in cell culture. Using this genotype 2a virus, casein kinase II (CKII) was previously identified as a crucial host factor in virus assembly by phosphorylating NS5A. Since most of the prior studies employed genotype 2a JFH1 or JFH1-based intragenotypic chimera, we used genotype 1a H77S to study virus assembly. CKII inhibition by chemical inhibitors enhanced H77S virus production in contrast to that of JFH1 virus, but genetic inhibition of CKII by siRNA did not change H77S virus titer significantly. The different outcomes from these two approaches of CKII inhibition suggested that nonspecific target kinase of CKII inhibitors plays a role in increasing H77S virus production and both viral and host factors were investigated in this study. Our results emphasize substantial differences among the HCV genotypes that should be considered in both basic research and clinical practices.

Do Guyanese mothers' levels of warmth moderate the association between harshness and justness of physical punishment and preschoolers' prosocial behaviours and anger?

This study assessed the moderating role of Indo-Guyanese mothers' warmth and affection on the associations between harshness and justness of physical punishment and prosocial behaviours and anger in preschoolers. One hundred and thirty-nine rural Indo-Guyanese mothers filled out Rohner's Parental Acceptance-Rejection (PARQ) and Physical Punishment Questionnaires (PPQ). Teachers provided assessments of children's prosocial behaviours and anger in preschool settings. Maternal warmth did not moderate the relationship between harshness of physical punishment and children's prosocial behaviours and anger, but it did moderate the relationship between justness of physical punishment and prosocial behaviours for sons as well as the association between justness of physical punishment and anger for daughters. In Caribbean societies where harsh punishment is normative, maternal warmth may work more effectively with justness, and not with harshness of physical punishment, to lower negative childhood behavioural outcomes.