Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. Methods For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. Results We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Conclusions Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease

Protecting the sexual and reproductive health of immigrant women in italy: building relationships of care and trust through a patient-centered approach

The advancement of sexual and reproductive healthcare for all women and the implementation of their respective rights can be achieved through adopting measures tailored to the specific needs of immigrant women; such measures should be aimed at overcoming linguistic, cultural, administrative, bureaucratic, and socio-economic barriers that hinder access to services and constrain their effective accessibility, with obvious implications for sexual and reproductive health. It is essential to develop prevention, diagnosis, and treatment pathways that consider cultural specificities while simultaneously promoting the autonomy of women: only a patient-centered approach, aimed at accommodating and providing appropriate responses to the patient’s cultural specificities, within the framework of fundamental rights and freedoms whilst taking into account the irreducibility of the person to their culture of origin, can sanction the creation of the conditions required for the pursuit of the best interests of the individual, whilst respecting their autonomy and dignity

La vaccinazione anti-HPV: i soggetti coinvolti e il processo decisionale

Il tema della vaccinazione anti-HPV è particolarmente delicato, trattandosi di una vaccinazione relativa ad un virus sessualmente trasmissibile e per la giovane età in cui tale vaccinazione è offerta. L’articolo riguarda in particolare il processo decisionale relativo alla vaccinazione anti-HPV: il consenso a tale vaccinazione dovrebbe essere frutto di un procedimento condiviso nel quale il minore, i genitori, i professionisti sanitari sono coinvolti. I professionisti sanitari devono fornire ai genitori una chiara informazione relativa al Papillomavirus, alla vaccinazione (sicurezza, efficacia ed eventi avversi), all’età appropriata per la vaccinazione, al fine di ridurre eventuali preoccupazioni circa la vaccinazione stessa e consentire ai genitori di effettuare scelte libere e consapevoli; anche i minori coinvolti devono ottenere una adeguata informazione in materia, al fine di esprimere la propria opinione: un dialogo efficace su tali temi può contribuire a rendere gli adolescenti soggetti attivi nelle scelte in materia di salute, anche in relazione a scelte future

Parto cesareo su richiesta materna: i confini tra autodeterminazione e rischio

Italian Law No. 219/ 2017 regarding informed consent and advance directives, contributed to identifying the boundaries between competence, professional autonomy and responsibility of the physician and the decisional autonomy of the patient. When a woman requests to have a cesarean delivery without medical indication, the decision-making process requires: the clinical assessment of the physician – who is responsible for identifying and proposing health treatments, and for adequately informing the patient – and the identification of the reasons that are contributing to the patient’s request, in order to reconcile both perspectives in favor of protecting the best interest – not merely clinical – of the patient

Cancer in Pregnancy: safety of chemotherapy on fetal outcome

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Structural and molecular adaptations to dexamethasone and unacylated ghrelin administration in skeletal muscle of the mice.

The central goal of this study was to identify the primary mechanisms triggering steroid atrophy. Adaptations of soleus (Sol) and vastus lateralis (VL) muscles of C57BL/6 female mice were studied following 3, 7 and 15 days of daily intraperitoneal injection (5 mg kg-1 day-1) of dexamethasone (dEx) (chronic treatment) and 1, 3 and 10 hours after a single dEx injection (acute treatment). In the chronic treatment, analyses were performed 24 hours after the last injection. Gene expression of major components of the intracellular signalling pathways controlling mass and metabolism were assessed. Analyses were repeated following dEx and unacylated ghrelin (uAG) (100 μg kg-1day-1), co-administration. We found a significant VL fibres atrophy after 7 (13%) and 15 (28%) days and a Sol fibres atrophy (23%) after 15 days of dEx treatment. The acute treatment showed, in both muscles, several responses in most signalling pathways, among which the enhanced gene expression of Murf-1 (6-fold change in VL and 3-fold in Sol) and myostatin (6-fold change in VL and 20-fold in Sol). In Sol, uAG administration was able to fully counteract muscle atrophy and Murf-1 upregulation, but not the upregulation of myostatin, suggesting a causal relationship between muscle atrophy and Murf-1. Results indicate that: a) the primary mechanism triggering steroid atrophy is an early transient activation of Murf-1; b) uAG inhibits Murf-1 induction counteracting steroid atrophy. The present work contributes to the understanding of the complexity of the muscle response to glucocorticoids