Sex-specific proximal tubular cell differentiation pathways identified by single-nucleus RNA sequencing.

Postnatal kidney growth is substantial and involves expansion in kidney tubules without growth of new nephrons, which are the functional units of the kidney. Proliferation and differentiation pathways underpinning nephron elongation are not well defined. To address this, we performed sequential characterization of mouse kidney transcriptomics at the single cell level.

Strabismic Adults' Experiences of Psychosocial Influence of Strabismus-A Qualitative Study.

Introduction: Strabismus influences health-related quality of life. Individuals may have functional and psychosocial consequences of strabismus that impact their well-being. As strabismus is prevalent in all age groups, patients are seen in varied specialties in healthcare organizations.

Dextrin conjugation to colistin inhibits its toxicity, cellular uptake and acute kidney injury .

The acute kidney injury (AKI) and dose-limiting nephrotoxicity, which occurs in 20-60% of patients following systemic administration of colistin, represents a challenge in the effective treatment of multi-drug resistant Gram-negative infections. To reduce clinical toxicity of colistin and improve targeting to infected/inflamed tissues, we previously developed dextrin-colistin conjugates, whereby colistin is designed to be released by amylase-triggered degradation of dextrin in infected and inflamed tissues, after passive targeting by the enhanced permeability and retention effect. Whilst it was evident that polymer conjugation can reduce toxicity and prolong plasma half-life, without significant reduction in antimicrobial activity of colistin, it was unclear how dextrin conjugation would alter cellular uptake and localisation of colistin in renal tubular cells .

Strabismus is more than a misalignment; a cross-sectional pilot study of HRQOL in Finnish strabismic adults referred to a university hospital.

Purpose: To evaluate associations between the health-related quality of life (HRQOL) and demographic, self-reported strabismus-related and orthoptic status variables in Finnish strabismic adults.

Methods: Participants (n = 137) of this study were adult patients who previously participated in the pilot study to translate and validate Adult Strabismus Questionnaire (AS-20) into Finnish. For this study, the participants' orthoptic status were collected among the previously obtained self-reported demographic and strabismus-related data.

"INTEGRO INTEGRated Psychotherapeutic InterventiOn" on the Management of Chronic Pain in Patients with Fibromyalgia: The Role of the Therapeutic Relationship.

Fibromyalgia (FM) is a chronic disease characterized by a heterogeneous set of physical and psychological conditions. The chronic experience of disability felt by patients and the impact on quality of life (QoL) of the disease may worsen the cognitive reappraisal ability and contribute to maintaining an altered pain modulation mechanism. This paper presents the study protocol of an INTEGRated psychotherapeutic interventiOn on the management of chronic pain in patients with fibromyalgia (INTEGRO).

Health-Related Quality of Life in Adult Patients with Strabismus-Translation and Psychometric Testing of the Adult Strabismus Questionnaire (AS-20) into Finnish.

(1) Strabismus has an impact on individuals' health-related quality of life. The impact should be assessed with valid patient-reported outcome measures such as the Adult Strabismus Questionnaire (AS-20). The AS-20 was further refined using a Rasch analysis for the American population.

Histopathology reporting for personalised medicine: focus on clinical utility.

Histopathology guidelines generally focus on standardised collection of data items to facilitate completeness and reproducibility of histopathology reporting. A data item is categorised as either core (mandatory) or non-core (recommended but not mandatory), irrespective of the clinical scenario. However, a data item that is critical for patient management in one clinical setting may have little clinical significance in another setting.

Mutations That Affect the Surface Expression of TRPV6 Are Associated with the Upregulation of Serine Proteases in the Placenta of an Infant.

Recently, we reported a case of an infant with neonatal severe under-mineralizing skeletal dysplasia caused by mutations within both alleles of the gene. One mutation results in an in frame stop codon (Rstop) that leads to a truncated, nonfunctional TRPV6 channel, and the second in a point mutation (GR) that, surprisingly, does not affect the Ca permeability of TRPV6. We mimicked the subunit composition of the unaffected heterozygous parent and child by coexpressing the TRPV6 GR and Rstop mutants and combinations with wild type TRPV6.

A critical re-analysis of cases of post-transplantation recurrence in genetic nephrotic syndrome.

Background: Genetic defects in podocyte proteins account for up to 30% of steroid-resistant nephrotic syndrome (SRNS) in the paediatric population. Most children with genetic SRNS are resistant to immunosuppression and at high risk of progression to stage 5 chronic kidney disease. Kidney transplantation is often the treatment of choice.

Response to First Course of Intensified Immunosuppression in Genetically Stratified Steroid Resistant Nephrotic Syndrome.

Background And Objectives: Intensified immunosuppression in steroid-resistant nephrotic syndrome is broadly applied, with disparate outcomes. This review of patients from the United Kingdom National Study of Nephrotic Syndrome cohort aimed to improve disease stratification by determining, in comprehensively genetically screened patients with steroid-resistant nephrotic syndrome, if there is an association between response to initial intensified immunosuppression and disease progression and/or post-transplant recurrence.

Design, Setting, Participants, & Measurements: Pediatric patients with steroid-resistant nephrotic syndrome were recruited the UK National Registry of Rare Kidney Diseases.

Family factors and health behaviour of thin adolescent boys and girls.

Aim: The aim of this study was to examine prevalence of extreme thinness and thinness in adolescent boys and girls and to study associations between family factors, health behaviour and thinness in boys and girls.

Background: Extreme thinness carries high health risks. The family and health behavioural factors related to adolescent thinness have not been studied previously using a nationally representative data.

Qualitative Exploration of Illness Perceptions of Rheumatoid Arthritis in the General Public.

Treating patients with rheumatoid arthritis (RA) within three months of symptom onset leads to significantly improved outcomes. However, many people delay seeking medical attention. In order to understand the reasons for this delay, it is important to have a thorough understanding of public perceptions about RA.

Interaction between the biological effects of high- and low-LET radiation dose components in a mixed field exposure.

Purpose: The relative biological effectiveness of two epithermal neutron sources, a reactor based source at Studsvik, Sweden, and a proton accelerator-based source in Birmingham, UK, was studied in relation to the proportional absorbed dose distribution as a function of neutron energy. Evidence for any interactions between the effects of biological damage induced by high- and low-linear energy transfer (LET) dose components, in this 'mixed field' irradiation, was also examined

Materials And Methods: Clonogenic survival in Chinese Hamster-derived V79 cells was used to assess biological effectiveness in this study. Cells were irradiated in suspension at 4 °C at depths of 20, 35, 50 and 65 mm in a water phantom.

In vivo regulation of experimental autoimmune encephalomyelitis by NK cells: alteration of primary adaptive responses.

Innate immune responses provide the host with its first line of defense against infections. Signals generated by subsets of lymphocytes, including NK cells, NKT cells, and APC during this early host response determine the nature of downstream adaptive immune responses. In the present study, we have examined the role of innate NK cells in an autoimmune model through the use of primary immunization with the myelin oligodendrocyte glycoprotein peptide to induce experimental autoimmune encephalomyelitis (EAE).

Modulation of lymphocyte function with inhibitory CD2: loss of NK and NKT cells.

Analysis of the NK cell developmental pathway suggests that CD2 expression may be important in regulating NK maturation. To test this hypothesis, we developed mice containing only an inhibitory CD2 molecule by linking the extracellular domain of CD2 to an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM) motif. Mice containing the CD2 Tg(ITIM) transgene, introduced into a CD2 KO background, have no morphologically detectable lymph nodes, although development of the thymus appears normal.

Regulation of ITAM-positive receptors: role of IL-12 and IL-18.

Our previous studies have identified mechanisms by which cytokine production, blocked by Ly49G2 receptor cross-linking, can be overridden. In this study we analyzed the regulation of other ITAM-positive receptor signaling on NK, NKT, and T cells and characterized the biochemical pathways involved in this signaling. Our studies demonstrate that cross-linking of NKG2D and NK1.

In-phantom characterisation studies at the Birmingham Accelerator-Generated epIthermal Neutron Source (BAGINS) BNCT facility.

A broad experimental campaign to validate the final epithermal neutron beam design for the BNCT facility constructed at the University of Birmingham concluded in November 2003. The final moderator and facility designs are overviewed briefly, followed by a summary of the dosimetric methods and presentation of a small subset of the results from this campaign. The dual ionisation chamber technique was used together with foil activation to quantify the fast neutron, photon, and thermal neutron beam dose components in a large rectangular phantom exposed to the beam with a 12 cm diameter beam delimiter in place.