Peroxisome deficiency underlies failures in hepatic immune cell development and antigen presentation in a severe Zellweger disease model.

Peroxisome biogenesis disorders (PBDs) represent a group of metabolic conditions that cause severe developmental defects. Peroxisomes are essential metabolic organelles, present in virtually every eukaryotic cell and mediating key processes in immunometabolism. To date, the full spectrum of PBDs remains to be identified, and the impact PBDs have on immune function is unexplored.

Modulation of the cell membrane lipid milieu by peroxisomal β-oxidation induces Rho1 signaling to trigger inflammatory responses.

Phagocytosis, signal transduction, and inflammatory responses require changes in lipid metabolism. Peroxisomes have key roles in fatty acid homeostasis and in regulating immune function. We find that Drosophila macrophages lacking peroxisomes have perturbed lipid profiles, which reduce host survival after infection.

An unusual example of hereditary multiple exostoses: a case report and review of the literature.

Background: Hereditary multiple exostoses (HME) is a rare skeletal disorder characterised by a widespread. distribution of osteochondromas originating from the metaphyses of long bones.

Case Presentation: This case study examines a 55-year-old male cadaver bequeathed to the University of Liverpool who suffered from HME, thus providing an exceptionally rare opportunity to examine the anatomical changes associated with this condition.

Workforce predictive risk modelling: development of a model to identify general practices at risk of a supply-demand imbalance.

Objective: This study aimed to develop a risk prediction model identifying general practices at risk of workforce supply-demand imbalance.

Design: This is a secondary analysis of routine data on general practice workforce, patient experience and registered populations (2012 to 2016), combined with a census of general practitioners' (GPs') career intentions (2016).

Setting/participants: A hybrid approach was used to develop a model to predict workforce supply-demand imbalance based on practice factors using historical data (2012-2016) on all general practices in England (with over 1000 registered patients n=6398).

Free-Wilson Analysis of Comprehensive Data on Phosphoinositide-3-kinase (PI3K) Inhibitors Reveals Importance of -Methylation for PI3Kδ Activity.

Phosphoinositide-3-kinase δ (PI3Kδ) is a critical regulator of cell growth and transformation and has been explored as a therapeutic target for a range of diseases. Through the exploration of the thienopyrimidine scaffold, we have identified a ligand-efficient methylation that leads to remarkable selectivity for PI3Kδ over the closely related isoforms. Interrogation through the Free-Wilson analysis highlights the innate selectivity the thienopyrimidine scaffold has for PI3Kδ and provides a predictive model for the activity against the PI3K isoforms.

Identifying policies and strategies for general practitioner retention in direct patient care in the United Kingdom: a RAND/UCLA appropriateness method panel study.

Background: The United Kingdom (UK) is experiencing a general practitioner (GP) workforce retention crisis. Research has focused on investigating why GPs intend to quit, but less is known about the acceptability and effectiveness of policies and strategies to improve GP retention. Using evidence from research and key stakeholder organisations, we generated a set of potential policies and strategies aimed at maximising GP retention and tested their appropriateness for implementation by systematically consulting with GPs.

Labour outcomes in siblings with channelopathy associated insensitivity to pain due to bi-alleleic SCN9A mutations.

The gene SCN9A encodes for the voltage-gated sodium channel Nav1.7, which is highly expressed in pain sensing neurons. Bi-allelic 'loss of function' mutations result in a channelopathy associated with insensitivity to pain and anosmia.

A specific cognitive deficit within semantic cognition across a multi-generational family.

We report a study of eight members of a single family (aged 8-72 years), who all show a specific deficit in linking semantic knowledge to language. All affected members of the family had high levels of overall intelligence; however, they had profound difficulties in prose and sentence recall, listening comprehension and naming. The behavioural deficit was remarkably consistent across affected family members.

Development of a novel protocol for isolation and purification of human granulosa cells.

Purpose: To develop an optimal method of isolation and purification of human granulosa cells from ovarian follicular fluid.

Methods: Follicular fluid was collected from patients undergoing oocyte retrieval. A series of isolation and purification techniques was performed, involving density gradient centrifugation and use of different antibody-bead complexes.

Sex differences in autism spectrum disorder: evidence from a large sample of children and adolescents.

Sex differences have been found amongst toddlers and young children with autism spectrum disorder (ASD). We investigated the presence and stability of these ASD sex differences throughout childhood and adolescence. Participants (N = 325, 52 females; aged 3-18 years) consecutively received an ASD diagnosis at a clinic for assessing high-functioning ASD (mean verbal IQ = 92.

Avoiding legal pitfalls in surrogacy arrangements.

The goal of this article is to discuss the legal pitfalls that reproductive endocrinologists face when participating in gestational surrogacy contracts. This paper was composed using Westlaw and LexisNexis commercial legal search engines to perform a review of statutes and cases pertaining to gestational surrogacy. The search results demonstrated that in the absence of suitable preparation, there is significant potential for litigation while participating in gestational agreements.

Investigation into the occupational lives of healthy older people through their use of time.

Background/aim: Older people are one of the largest groups using health-care services; therefore, it is important for occupational therapists to have an understanding of their occupational lives. Temporality is a key element of occupation, yet little research exists regarding older people and time use, despite the considerable temporal adjustments taking place at this lifestage. The aim of this study was to identify the occupational lives of healthy older people through the activities they undertake in a 24-hour period.

The ethical challenges of providing fertility care to patients with chronic illness or terminal disease.

The field of fertility is rapidly evolving, bringing opportunities for improvement in our patients' quality of life as well as bringing new ethical dilemmas. As medical science continues to advance, significant numbers of the reproductive-aged population are living with chronic and/or terminal conditions but have reasonable odds of lengthy survival and wish to have children. Likewise, there are adolescents diagnosed with cancer who are increasingly expected to achieve an improved, if not normal, life expectancy after treatment.

Implementing a clinical supervision programme for nurses in a hospice setting.

Access to clinical supervision for registered nurses is an important way of maintaining and improving standards of patient care. Ten years ago clinical supervision only existed for the community nurse specialists within a group of hospices in the south east of England managed under one clinical governance framework. With the appointments of a lead nurse for patient safety and quality and an education and training co-ordinator the whole system of clinical supervision was reviewed to include all nursing staff (registered nurses, health-care assistants and community associate practitioners) from the inpatient, day hospice and community services.

Infection control: a hospice perspective.

Infection prevention and control is paramount to securing patient safety within a healthcare establishment. Independent sector hospices in the south east of England provide specialist palliative care and must be able to demonstrate risk-reducing strategies in order to comply with their registering body and the UK Health Act (2006). Using the clinical governance framework ensures that policies, processes and procedures are in place.

Twenty-four hour care for schizophrenia.

Background: Despite modern treatment approaches and a focus on community care, there remains a group of people who cannot easily be discharged from psychiatric hospital directly into the community. Twenty-four hour residential rehabilitation (a 'ward-in-a-house') is one model of care that has evolved in association with psychiatric hospital closure programmes.

Objectives: To determine the effects of 24 hour residential rehabilitation compared with standard treatment within a hospital setting.

Toward gene therapy of primary ovarian failure: adenovirus expressing human FSH receptor corrects the Finnish C566T mutation.

Resistance ovarian syndrome is a heterogeneous disorder inherited as a Mendelian recessive trait and characterized by infertility, primary amenorrhea, normal karyotype and elevated serum FSH and LH levels. An inactivating mutation, C566T, in FSH receptor gene (FSHR) has been identified initially in Finland. We investigated if an adenovirus expressing a normal copy of human FSHR (Ad-hFSHR) has the ability to: (i) transfect granulosa cell lines, (ii) render the transfected cell lines responsive to FSH stimulation and (iii) transcomplement the malfunctioning form of human FSHR gene with C566T mutation.