Assessing the Impact of the Prostate Cancer Patient Empowerment Program (PC-PEP) on Relationship Satisfaction, Quality of Life, and Support Group Participation: A Randomized Clinical Trial.

The Prostate Cancer Patient Empowerment Program (PC-PEP) is a 6-month, home-based intervention aimed at enhancing mental health in men undergoing curative prostate cancer treatment. This exploratory secondary analysis evaluates PC-PEP's impact on relationship satisfaction, quality of life, and support group attendance among partnered participants. In a crossover randomized clinical trial ClinicalTrials.

The Cancer Patient Empowerment Program: A Comprehensive Approach to Reducing Psychological Distress in Cancer Survivors, with Insights from a Mixed-Model Analysis, Including Implications for Breast Cancer Patients.

Background/objectives: Psychological distress is a significant concern among cancer patients, negatively affecting their quality of life and adherence to treatment. The Cancer Patient Empowerment Program (CancerPEP) was developed as a comprehensive, home-based intervention aimed at reducing psychological distress by incorporating physical activity, dietary guidance, and social support. This study aimed to evaluate the feasibility, accrual and attrition rates, safety, and effectiveness of the CancerPEP intervention, with and without the biofeedback device, on psychological distress from baseline to 6 months, specifically focusing on the effects of group randomization and the difference between pre- and post-intervention results.

Activation of p38MAPK contributes to expanded polyglutamine-induced cytotoxicity.

Background: The signaling pathways that may modulate the pathogenesis of diseases induced by expanded polyglutamine proteins are not well understood.

Methodologies/principal Findings: Herein we demonstrate that expanded polyglutamine protein cytotoxicity is mediated primarily through activation of p38MAPK and that the atypical PKC iota (PKCiota) enzyme antagonizes polyglutamine-induced cell death through induction of the ERK signaling pathway. We show that pharmacological blockade of p38MAPK rescues cells from polyglutamine-induced cell death whereas inhibition of ERK recapitulates the sensitivity observed in cells depleted of PKCiota by RNA interference.

An in silico model of the ubiquitin-proteasome system that incorporates normal homeostasis and age-related decline.

Background: The ubiquitin-proteasome system is responsible for homeostatic degradation of intact protein substrates as well as the elimination of damaged or misfolded proteins that might otherwise aggregate. During ageing there is a decline in proteasome activity and an increase in aggregated proteins. Many neurodegenerative diseases are characterised by the presence of distinctive ubiquitin-positive inclusion bodies in affected regions of the brain.

Delayed spinocerebellar ataxia in transgenic mice expressing mutant ubiquitin.

Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease resulting from loss of Purkinje neurones within the cerebellum. The ubiquitin proteasome pathway (UPP) has been implicated in SCA1 but the role of proteolysis in the disease is still poorly understood. To further investigate this issue in vivo, genetic crosses were performed between an established mouse model of SCA1 and novel strains expressing elevated levels of wild type or mutant isoforms of ubiquitin.

Protective effects of mutant ubiquitin in transgenic mice.

The K48R mutant ubiquitin can exert profound in vivo protective effects against a variety of insults, including agents of direct clinical relevance. The manipulation of the ubiquitin/proteasome pathway has enormous potential for clinical benefit, and it is not unreasonable to expect that such benefits will include diseases of aging.

Stimulation of the murine Uchl1 gene promoter by the B-Myb transcription factor.

It has been reported that human lung cancers frequently overexpress both the ubiquitous cell cycle transcription factor B-myb and the ubiquitin carboxyterminal hydrolase UCHL1, an enzyme whose expression is normally limited to neurons and neuroendocrine cells in the lung. A possible explanation for the co-expression of these markers is that Uchl1 is subject to transcriptional regulation by B-Myb, and in tumors the ectopic expression of UCHL1 is a direct consequence of B-Myb overexpression. We have tested this hypothesis in the mouse model system by cloning the murine Uchl1 promoter and analyzing its regulation by murine B-Myb.

Ubiquitin, proteasomes, and the aging brain.

Ubiquitinated proteinaceous inclusions are the hallmark of many neurodegenerative diseases. Inefficient proteolysis might lead to the accumulation and ultimate deposition of potentially toxic entities as inclusions within neurons or glial cells. This hypothesis is supported by genetic evidence both from patient populations and from engineered mutations in genes that encode ubiquitin/proteasome components in mice.

Effects of mutant ubiquitin on ts1 retrovirus-mediated neuropathology.

ts1 is a temperature-sensitive mutant of Moloney murine leukemia virus that induces a rapid spongiform encephalopathy in mice infected as newborns. The pathological features include the formation of ubiquitinated inclusions resembling Lewy bodies. To determine how perturbation of the ubiquitin-proteasome pathway might affect ts1-mediated neurodegeneration, the virus was introduced into transgenic mice in which the assembly of ubiquitin chains was compromised by the expression of dominant-negative mutant ubiquitin.

Sensitivity of mammalian cells expressing mutant ubiquitin to protein-damaging agents.

There is convincing evidence from studies in yeast that a functional ubiquitin/proteasome pathway is required to degrade misfolded or oxidatively damaged proteins but for technical reasons, it has been difficult to perform comparable studies in mammalian cells. To investigate the possibility that the ubiquitin/proteasome pathway is cytoprotective for mammalian cells, we have introduced epitope-tagged wild-type ubiquitin or dominant-negative mutant versions of ubiquitin into mouse HT4 neuroblastoma cells. Cells expressing mutant versions of ubiquitin were found to be sensitive to cadmium, an agent that causes oxidative damage to cellular components, and to canavanine, an amino acid analog that generates misfolded proteins.

Analysis of ubiquitination in vivo using a transgenic mouse model.

The primary pathway for the proteolytic destruction of cellular proteins is through ubiquitin-mediated targeting to the proteasome. This pathway is pivotal not only in the elimination of damaged or misfolded proteins but also in the temporal, developmental, or signal-mediated destruction of normal cellular substrates. The list of known substrates of the ubiquitin/proteasome pathway is long, but most substrates have been identified in yeast or, more recently, in cultured mammalian cells.

Testicular needle aspiration as an alternative to biopsy for the assessment of spermatogenesis.

The technique of fine needle aspiration (FNA) may have a role as a reliable, quick and easy method of obtaining testicular tissue. Recent advances in the management of male subfertility and, in particular, the finding that spermatozoa recovered from the epididymis and testis can result in embryo generation after intracytoplasmic sperm injection (ICSI), question the traditional role of open testicular biopsy for the assessment of spermatogenesis. FNA of the testis was performed on 19 cases of male subfertility and histological and cytological preparations obtained were assessed by light microscopy.

Cumulative experience of percutaneous epididymal sperm aspiration (PESA) with intracytoplasmic sperm injection.

Objective: Our objective was to evaluate the recovery rate of spermatozoa from the epididymis using a percutaneous aspiration technique and to assess the fertilisation rate after intracytoplasmic sperm injection.

Materials And Methods: Fifty-four patients with azoospermia had a total of 59 cycles at IVF with intracytoplasmic sperm injection (ICSI). The cause of the azoospermia was failed vasectomy reversal in 23 cases, congenital absence of the vas in 22 cases, partial testicular failure in 5 cases, and retrograde ejaculation in 2 cases, while the remaining 2 patients had erectile disorders.

Simplified sperm retrieval and intracytoplasmic sperm injection in patients with azoospermia.

Objective: To evaluate the rate of recovery of spermatozoa from the epididymis using a percutaneous aspiration technique and to assess the fertilization rate following intracytoplasmic sperm injection (ICSI).

Patients And Methods: Forty-two patients with azoospermia underwent a total of 46 treatment cycles of in vitro fertilization (IVF) and ICSI. The sperm used for ICSI was retrieved percutaneously by fine-needle aspiration and syringe suction (percutaneous epididymal sperm aspiration, PESA) from the epididymis in 28 patients (mean age 34.

Factors influencing the outcome of in-vitro fertilization with percutaneous aspirated epididymal spermatozoa and intracytoplasmic sperm injection in azoospermic men.

In-vitro fertilization (IVF) by intracytoplasmic sperm injection (ICSI) with spermatozoa retrieved by percutaneous epididymal sperm aspiration (PESA) is a novel, simple and effective treatment for azoospermic men. In all, 38 azoospermic men had an IVF/PESA/ICSI cycle. A total of 42 cycles were performed.

Percutaneous epididymal sperm aspiration and intracytoplasmic sperm injection in the management of infertility due to obstructive azoospermia.

Objective: To evaluate the recovery rate of spermatozoa from the epididymis using a percutaneous aspiration technique and to examine the fertilization rate after intracytoplasmic sperm injection.

Design: Prospective observational study.

Setting: Private infertility clinic, London.

Late intracytoplasmic sperm injection in unexpected failed fertilization in vitro: diagnostic or therapeutic?

Objective: To evaluate fertilization potential of 24-hour-old unfertilized oocytes using intracytoplasmic sperm injection and the pregnancy potential of resultant embryos.

Design: Prospective observational study.

Setting: Private infertility clinic, London, United Kingdom.