''Pseudo-aldosteronism'' induced by intravenous glycyrrhizin treatment of chronic hepatitis C patients

BACKGROUND AND AIMS: Treatment with intravenous glycyrrhizin reduces the progression of liver disease caused by chronic hepatitis C (HCV) infection. Glycyrrhetinic acid, a metabolite of glycyrrhizin, inhibits the renal conversion of cortisol to cortisone by inhibiting the enzyme 11 beta-hydroxysteroiddehydrogenase in the kidney. The resulting excess of cortisol subsequently stimulates the mineralocorticoid receptor, leading to pseudo-aldosteronism with hypertension, hypokalemia and eventually renin and aldosterone suppression. The aim of this study was to evaluate the occurrence of pseudo-aldosteronism after treatment of chronic hepatitis C (HCV) patients with increasing doses of intravenous glycyrrhizin. METHODS: Forty-four HCV patients with chronic hepatitis or compensated cirrhosis were treated with intravenous glycyrrhizin 6 x 200 mg/week, 3 x 240 mg/week or 3 x 0 mg/week (placebo) for 4 weeks. In all patients, bodyweight, blood pressure and plasma concentrations of sodium, potassium, cortisol, DHEA-S (dehydroepiandrosterone sulfate), renin and aldosterone were measured before, and at 0 and 4 weeks after treatment. RESULTS: Within the placebo group, no significant changes were observed. Within the 1200 mg group systolic blood pressure was significantly higher at the end of treatment, while aldosterone was significantly lower; at the end of the follow-up period these values had returned to baseline. The changes from baseline in systolic and diastolic blood pressure at the end of treatment were significantly higher in the 1200 mg group compared to the placebo group. The changes in aldosterone and potassium concentrations at the end of treatment increased with increasing dosage, although not significantly. CONCLUSION: Hepatitis C virus patients with chronic hepatitis or compensated cirrhosis show minor reversible symptoms of pseudo-aldosteronism after treatment with 1200 mg glycyrrhizin weekly for 4 weeks.     

Age and attachment style impact stress and depressive symptoms among caregivers: a prospective investigation

Introduction Family members begin their role as caregivers to persons with cancer with little advance notice. In this situation, the caregivers’ existing psychosocial resources, including their stage in life and the nature of their relationship with the patient, can play important roles in the extent of stress caregivers experience during this unique time. Materials and methods Family caregivers (N = 98) of diagnosed colorectal cancer patients at community hospitals participated in the study around the time of diagnosis (T1) and at 6 months post-diagnosis (T2). Results Hierarchical regression analyses revealed that younger caregivers reported greater increases in caregiving stress at T2, controlling for the level of caregiving stress at T1. This was more prominent when they had an anxious attachment orientation to the care recipient (i.e., cancer survivor), which was characterized as a strong desire for closeness to the cancer survivor, hypervigilance for cues of abandonment, and emotional upset both at separation and reunion with the survivor. The same interaction effect between age and anxious attachment was found for depressive symptoms. Conclusions Results suggest that younger caregivers are more vulnerable to the challenges imposed by their relative’s cancer, and this vulnerability is exacerbated by the quality of their relationship. Implications for cancer survivors Our findings imply that younger caregivers whose relationship with the survivor can be characterized by the features above can be identified early and might benefit from intervention or additional support to reduce the caregiving stress and depressive symptoms as they carry out their new role as a cancer caregiver.     

New therapeutic approaches for type 1 diabetes: Disease-modifying therapies

It has been 100 years since the first successful clinical use of insulin, yet it remains the only treatment option for type 1 diabetes mellitus (T1DM) patients. Advances in diabetes care, such as insulin analogue therapies and new devices, including continuous glucose monitoring with continuous subcutaneous insulin infusion have improved the quality of life of patients but have no impact on the pathogenesis of the disease. They do not eliminate long-term complications and require several lifestyle sacrifices. A more ideal future therapy for T1DM, instead of supplementing the insufficient hormone production (a consequence of β-cell destruction), would also aim to stop or slow down the destructive autoimmune process. The discovery of the autoimmune nature of type 1 diabetes mellitus has presented several targets by which disease progression may be altered. The goal of disease-modifying therapies is to target autoimmune mechanisms and prevent β-cell destruction. T1DM patients with better β-cell function have better glycemic control, reduced incidence of long-term complications and hypoglycemic episodes. Unfortunately, at the time symptomatic T1DM is diagnosed, most of the insulin secreting β cells are usually lost. Therefore, to maximize the salvageable β-cell mass by disease-modifying therapies, detecting autoimmune markers in an early, optimally presymptomatic phase of T1DM is of great importance. Disease-modifying therapies, such as immuno- and regenerative therapies are expected to take a relevant place in diabetology. The aim of this article was to provide a brief insight into the pathogenesis and course of T1DM and present the current state of disease-modifying therapeutic interventions that may impact future diabetes treatment.     

A Systematic Review of the Efficacy of Interventions to Control Aflatoxins in the Dairy Production Chain—Feed Production and Animal Feeding Interventions

The study presents a systematic review of published scientific articles investigating the effects of interventions aiming at aflatoxin reduction at the feed production and animal feeding phases of the milk value chain in order to identify the recent scientific trends and summarize the main findings available in the literature. The review strategy was designed based on the guidance of the systematic review and knowledge synthesis methodology that is applicable in the field of food safety. The Web of Science and EBSCOhost online databases were searched with predefined algorithms. After title and abstract relevance screening and relevance confirmation with full-text screening, 67 studies remained for data extraction, which were included in the review. The most important identified groups of interventions based on their mode of action and place in the technological process are as follows: low-moisture production using preservatives, acidity regulators, adsorbents and various microbiological additives. The results of the listed publications are summarized and compared for all the identified intervention groups. The paper aimed to help feed producers, farmers and relevant stakeholders to get an overview of the most suitable aflatoxin mitigation options, which is extremely important in the near future as climate change will likely be accompanied by elevated mycotoxin levels.     

Postoperative AMH reduction is not associated with reduced fecundity two years following ovarian cyst surgery

In a prospective study, we investigated the impact of anti-Müllerian hormone (AMH) changes following ovarian cyst surgery on the probability to achieve pregnancy and live birth. Women of reproductive age (n?=?60) were included before surgery for benign ovarian cysts. Serum AMH concentrations were determined pre- and postoperative at 6 and 24 months. Information regarding pregnancy wish and attempts to conceive were obtained by a questionnaire. At the time of inclusion, 45/60 women reported desire of children. At six months, the levels of AMH decreased significantly in the whole group and further reduction was observed at two years (from 2.7?μg/L to 2.0?μg/L to 1.1?μg/L, respectively, p< 0.008), with a percentage reduction of 42.9%. At two-year follow-up, 36 women reported to have attempted to conceive and 18 achieved pregnancy (50%), with a live birth rate of 33%. The percentage change in AMH at two years did not differ significantly between the women who conceived versus those who did not (p?=?0.117). Data reported herein demonstrate that the AMH reduction following ovarian cyst surgery is maintained two years after surgery; however, the postoperative AMH decrease that follows ovarian cyst surgery might not reduce the chances to achieve pregnancy.     

Fatigue behavior of endodontically treated premolars restored with different fiber-reinforced designs

ObjectivesThe aim was to investigate the fatigue survival and marginal-gap inside the root-canal of endodontically treated (ET) premolars reinforced by various fiber-reinforced post-core composites (FRCs). Moreover, composite-curing at different depths in the canal was evaluated.Methods170 intact upper-premolars were collected and randomly divided into ten groups (n = 15). One group served as control (intact-teeth). After endodontic procedure standard MO cavities were prepared and restored with different post-core fiber-reinforced materials and designs. Three-group (A1-A3) were restored with either packable and flowable short fiber-reinforced composite (SFRC) core or conventional composite-core. Two-group (B1-B2) were restored with SFRCs as short post (3 mm) and core. Four-group (C1-C4) were restored with SFRCs as post (6 mm) and core with or without unidirectional FRC posts (individually-made or conventional). After completing the restorations, teeth from Group C1-C4 (n = 5/group) were sectioned and stained. Specimens were viewed under a stereo-microscope and the percentage of microgaps within the root-canal was calculated. Fatigue-survival was measured using a cyclic-loading machine in the rest of the specimens.ResultsApplication of flowable SFRC as luting-core material with individually-made FRC post (Group C3) did not differ from intact-teeth regarding fatigue-survival (p > 0.05). The rest of the groups produced significantly lower survival (p < 0.05) compared to intact-teeth. Post/core restorations made from packable SFRC (Group C1) had a lower microgap (19.1%) at the examined interphase in the root-canal than other groups.SignificanceThe restoration of ET premolars with the use of individually-made FRC post and SFRC as luting-core material showed promising achievement regarding fatigue-resistance and survival.     

PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia

We have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in ～ 6% of T-cell acute lymphoblastic leukemia (T-ALL) cases. T-ALL is an aggressive disease of the thymocytes characterized by the stepwise accumulation of chromosomal abnormalities and gene mutations. In the present study, we confirmed the strong association of the PTPN2 deletion with TLX1 and NUP214-ABL1 expression. In addition, we found cooperation between PTPN2 deletion and activating JAK1 gene mutations. Activating mutations in JAK1 kinase occur in ～ 10% of human T-ALL cases, and aberrant kinase activity has been shown to confer proliferation and survival advantages. Our results reveal that some JAK1 mutation-positive T-ALLs harbor deletions of the tyrosine phosphatase PTPN2, a known negative regulator of the JAK/STAT pathway. We provide evidence that down-regulation of Ptpn2 sensitizes lymphoid cells to JAK1-mediated transformation and reduces their sensitivity to JAK inhibition.     

Transgender Youth Executive Functioning: Relationships with Anxiety Symptoms,Autism Spectrum Disorder,and Gender-Affirming Medical Treatment Status

Child Psychiatry & Human Development - Executive function (EF) underlies broad health and adaptive outcomes. For transgender youth, navigating gender discernment and gender affirmation demand...     

Charged ultrafiltration membranes based on TEMPO-oxidized cellulose nanofibrils/poly(vinyl alcohol) antifouling coating

This study reports the potential of TEMPO-oxidized cellulose nanofibrils (T-CNF)/poly(vinyl alcohol) (PVA) coatings to develop functionalized membranes in the ultrafiltration regime with outstanding antifouling performance and dimensional/pH stability. PVA acts as an anchoring phase interacting with the polyethersulfone (PES) substrate and stabilizing for the hygroscopic T-CNF via crosslinking. The T-CNF/PVA coated PES membranes showed a nano-textured surface, a change in the surface charge, and improved mechanical properties compared to the original PES substrate. A low reduction (4%) in permeance was observed for the coated membranes, attributable to the nanometric coating thickness, surface charge, and hydrophilic nature of the coated layer. The coated membranes exhibited charge specific adsorption driven by electrostatic interaction combined with rejection due to size exclusion (MWCO 530 kDa that correspond to a size of ∼35–40 nm). Furthermore, a significant reduction in organic fouling and biofouling was found for T-CNF/PVA coated membranes when exposed to BSA and E. coli. The results demonstrate the potential of simple modifications using nanocellulose to manipulate the pore structure and surface chemistry of commercially available membranes without compromising on permeability and mechanical stability.

Crosslinked cellulose nanofiber-polyvinyl alcohol antifouling membrane.     

Needs assessment of family caregivers of cancer survivors: three cohorts comparison

Purpose/Background: Caregivers' quality of life (QOL) may be maximized when the caregivers' needs in the context of cancer care are met. Therefore, determining what needs are not being satisfied for family caregivers should be the first step in the development of programs designed to enhance caregivers' QOL. Method: The 28‐item Needs Assessment of Family Caregivers‐Cancer (NAFC‐C) scale was developed and validated with caregivers at three different survivorship phases: at 2 months (n=162), 2 years (n=896), and 5 years (n=608) post‐diagnosis. Results: The NAFC‐C helped to identify caregivers whose needs were less likely to be met, based on their age and ethnicity. Furthermore, the extent to which caregivers' psychosocial needs were not being met was a consistent and strong predictor of poor mental health across all phases of survivorship, beyond the effects of a host of demographic characteristics. Conclusion: Findings suggest that interventions designed to help caregivers manage their own emotional distress as well as the survivors' distress, find meaning in the cancer caregiving experience, and foster supportive familial relationship will benefit caregivers by improving their QOL, not only during the time of diagnosis and treatment but years after. Copyright © 2009 John Wiley & Sons, Ltd.