Ready for antiretroviral therapy? Therapy decision making experiences of persons living with HIV

Readiness for therapy of people living with HIV is of major importance in the process of antiretroviral decision making. This qualitative study is part of a prospective multicentre investigation describing readiness for antiretroviral therapy (ART) and decision making in HIV-infected patients. The qualitative results present the daily experiences of people living with HIV in the treatment decision making process related to starting or changing ART. Based on a critical hermeneutic research design, interviews with twelve persons have been conducted. Two main categories were generated: "dealing with oneself and others" and "understanding and being understood". They describe the dialectical process of decision making with a focus on interactions with others. This process includes four themes: illness beliefs, health perspectives, therapy beliefs, life perspectives. The findings of this study reveal that partnerships of health care providers with HIV-infected patients are necessary for treatment decisions. Moreover; it is of major importance for health care providers to include patients' experiences and expertise and to allow time for the different dialogues.     

Cell-autonomous and systemic context-dependent functions of iron regulatory protein 2 in mammalian iron metabolism

Mice with total and constitutive iron regulatory protein 2 (IRP2) deficiency exhibit microcytosis and altered body iron distribution with duodenal and hepatic iron loading and decreased iron levels in splenic macrophages. To explore cell-autonomous and systemic context-dependent functions of IRP2 and to assess the systemic consequences of local IRP2 deficiency, we applied Cre/Lox technology to specifically ablate IRP2 in enterocytes, hepatocytes, or macrophages, respectively. This study reveals that the hepatic and duodenal manifestations of systemic IRP2 deficiency are largely explained by cell-autonomous functions of IRP2. By contrast, IRP2-deficient macrophages from otherwise IRP2-sufficient mice do not display the abnormalities of macrophages from systemically IRP2-deficient animals, suggesting that these result from IRP2 disruption in other cell type(s). Mice with enterocyte-, hepatocyte-, or macrophage-specific IRP2 deficiency display normal red blood cell and plasma iron parameters, supporting the notion that the microcytosis in IRP2-deficient mice likely reflects an intrinsic defect in hematopoiesis. This work defines the respective roles of IRP2 in the determination of critical body iron parameters such as organ iron loading and erythropoiesis.     

Effect of dihydroergosine (DHESN) on the serotoninergic system and behaviour: Is DHESN a new antidepressive agent?

Acute (50.0 mg/kg) and repeated (0.1–10.0 mg/kg) administration of dihydroergosine (DHESN) to rats over 5 days lowered the concentration of 5-HIAA in the brain. DHESN given acutely increased the brain 5-HT in p-CPA-treated animals and diminished the probenecid-induced increase in brain 5-HIAA. In pargyline-treated rats DHESN enhanced the 5-HT/5-HIAA ratio. DHESN administered to rats repeatedly over 5 days decreased the level of 5-HT in blood platelets, and in vitro at concentrations of 10^-4 M and 10^-3 M inhibited the uptake of [¹⁴C]-5-HT in platelets. DHESN (10.0–100.0 mg/kg) potentiated the 5-HT syndrome produced in rats by pargyline and 5-HTP. This potentiation was blocked with cyproheptadine but not with haloperidol. DHESN (1.0 and 10.0 mg/kg) lowered the locomotor activity of rats and 10.0 mg/kg DHESN also reduced the duration of immobility in rats forced to swim in a restricted space. The results indicate that DHESN, like antidepressants, decreases the turnover of serotonin in the brain and potentiates the 5-HT-mediated behaviour. This might suggest that the drug should be further investigated for its potential antidepressive properties.     

Antioxidant properties of extracts of wild medicinal mushroom species from Croatia

Antioxidant activity and total phenol (TP) content of methanol and water extracts of three wild Croatian mushroom species Auricularia auricula-judae (Bull.) Quél., Sarcoscypha austriaca (Sacc.) Boud., and Strobilurus esculentus (Wulfen) Singer were determined and compared with the values obtained for extracts of four cultivated mushrooms Agaricus bisporus (J.E. Lange) Imbach (brown and white strains), Pleurotus ostreatus (Jacq.) P. Kumm., and Lentinus edodes (Berk.) Singer. Spectrophotometric determination of the TP content was performed using the Folin-Ciocalteu method, while antioxidant activity was measured in a reaction with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH assay) and ferric-tripyridyltriazine (Fe3+-TPTZ) complex (FRAP assay). On the average, 5.8-fold higher TP content was observed for water in comparison to methanol extracts of all analyzed mushrooms. Consequently, antioxidant activity was also higher for water extracts, which is evident from the obtained higher values in the FRAP assay and lower EC50 values in the DPPH assay. Among the three tested wild species, the water extract of S. esculentus exhibited the highest concentration of TP, 8.12 mg/g gallic acid equivalents (GAE), the highest reducing power, 19.42 mmol Fe2+/kg, and the best radical scavenging properties, EC50= 13.5 mg/mL.     

High prevalence of physical inactivity among patients from the Swiss HIV Cohort Study

Physical activity (PA) can improve cardiorespiratory status, strength, body composition and quality of life for patients infected with HIV. Evidence from HIV-uninfected populations also shows that PA is associated with a lower risk of mortality, primarily death due to cardiovascular causes. There is, however, a lack of data on how physically active HIV-infected patients are. In this study, we assessed levels of self-reported PA over time in patients enrolled in the Swiss HIV Cohort Study, a large multicentre prospective observational cohort study. We included a total of 10,540 patients who completed at least one report of PA between December 2009 and November 2014 during routine clinical follow-up (scheduled every 6 months). In the first year after December 2009 there was a higher rate of non-response so these data are of a lesser reliability. Over the next four years, the percentage of patients reporting no free-time PA at all declined from 49% to 44%. In contrast, in two “Sport Switzerland” surveys of the general population in 2008 and 2014, the percentage of individuals reporting no sports activities at all was considerably lower and relatively stable over time (27% in 2008; 26% in 2014). In our analysis, the percentage of patients reporting sedentary activity at work increased from 23% to 26% over the four years. Subgroup findings suggest differences between women and men and between patients classified by their age, stage of infection and CD4 cell count. Integrating PA counselling into the routine care of HIV-infected patients and promoting PA among this population has the potential to improve the general state of health and quality of life for HIV-infected patients and reduce their risk of cardiovascular disease.     

Gene expression profile of the regeneration epithelium during axolotl limb regeneration

Urodele amphibians are unique among adult vertebrates in their ability to regenerate missing limbs. The process of limb regeneration requires several key tissues including a regeneration‐competent wound epidermis called the regeneration epithelium (RE). We used microarray analysis to profile gene expression of the RE in the axolotl, a Mexican salamander. A list of 125 genes and expressed sequence tags (ESTs) showed a ≥1.5‐fold expression in the RE than in a wound epidermis covering a lateral cuff wound. A subset of the RE ESTs and genes were further characterized for expression level changes over the time‐course of regeneration. This study provides the first large scale identification of specific gene expression in the RE. Developmental Dynamics 240:1826–1840, 2011. © 2011 Wiley‐Liss, Inc.     

S2k-Leitlinie: Fertilitätserhaltende Maßnahmen bei onkologischen Erkrankungen

Oncological and nononcological diseases can affect current or future fertility, either through the disease itself or through necessary surgery, hormonal and/or gonadotoxic treatments. They therefore require an adequate fertility-protective approach—i.?e. counselling is essential and, if the prerequisites are met, an appropriate fertility-protective therapy. Cryopreservation of oocytes is usually the first-choice method for postpubertal women. Metaphase II oocyte cryopreservation by vitrification is the preferred and recommended option. However, cumulative evidence of restoration of ovarian endocrine function and resulting spontaneous pregnancies and births, or after the use of assisted reproductive techniques, after orthotopic transplantation of cryopreserved ovarian tissue also advocates this method as an open clinical application, especially in prepubertal girls who are no less affected by germ cell-damaging treatments than adolescent or adult patients of reproductive age and for whom no other possible option for fertility preservation is currently available.     

Concise review: human pluripotent stem cells in the treatment of spinal cord injury

Spinal cord injury (SCI) results in neural loss and consequently motor and sensory impairment below the injury. There are currently no effective therapies for the treatment of traumatic SCI in humans. Different kinds of cells including embryonic, fetal, and adult stem cells have been transplanted into animal models of SCI resulting in sensorimotor benefits. Transplantation of human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neural cells is nowadays a promising therapy for SCI. This review updates the recent progress in preclinical studies and discusses the advantages and flaws of various neural cell types derived from hESCs and hiPSCs. Before introducing the stem cell replacement strategies in clinical practice, this complex field needs to advance significantly in understanding the lesion itself, the animal model adequacy, and improve cell replacement source. This knowledge will contribute to the successful translation from animals to humans and lead to established guidelines for rigorous safety screening in order to be implemented in clinical practice. Stem Cells2012;30:1787-1792.     

The role of core antigen detection in management of hepatitis C: a critical review.

Several assays in research format and two commercial assays for the detection of hepatitis C virus (HCV) core protein or HCV core antigen have been developed in recent years. In order to elucidate the role and significance of HCV core antigen detection in the diagnosis and management of hepatitis C, we reviewed 56 studies published in peer-reviewed journals until September 2004. Evaluations in transfusion settings showed that the HCV core antigen assay detects HCV infection, similarly as nucleic acid techniques (NAT), between 40 and 50 days earlier than the current third generation HCV antibody screening assays. HCV core antigen levels closely track HCV RNA dynamics, and allow clinical monitoring of a patient's therapy, independently of HCV genotype, however, mainly in the samples with HCV RNA levels above 20,000 IU/ml. Considering the lower sensitivity of HCV core antigen detection in comparison to NAT, the HCV core antigen assay is not practical for the determination of the end of treatment response and sustained viral response, but could be useful for the determination of early viral response in the pegylated interferon-alpha and ribavirin treated patients infected with HCV genotype 1. The HCV core antigen detection is a viable tool for study of hepatitis C pathogenesis. The HCV core antigen can be used as a marker of HCV replication in anti-HCV positive individuals in the areas of the world that cannot afford NAT and/or in the settings that are not equipped or competent to perform HCV RNA testing. Because the manufacturer of HCV core antigen assays recently stopped an active marketing of these assays in several countries, it will, unfortunately and probably, never be possible to determine the actual potential and usefulness of HCV core antigen testing in the management of hepatitis C.