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Drusen are retinal deposits comprising cell debris, immune material and complement that are characteristic of macular degeneration but also found in glomerulonephritis. This was a pilot cross-sectional study to determine how often drusen occurred in IgA glomerulonephritis and their clinical significance. Study participants underwent non-mydriatic retinal photography, and their deidentified retinal images were examined for drusen by two trained graders, who compared central drusen counts, counts ≥ 10 and drusen size with those of matched controls. The cohort comprised 122 individuals with IgA glomerulonephritis including 89 males (73%), 49 individuals (40%) of East Asian or Southern European ancestry, with an overall median age of 54 years (34–64), and median disease duration of 9 years (4–17). Thirty-nine (33%) had an eGFR < 60 ml/min/1.73 m 2 and 72 had previously reached kidney failure (61%). Overall mean drusen counts were higher in IgA glomerulonephritis (9 ± 27) than controls (2 ± 7, p  < 0.001). Central counts ≥ 10 were also more common (OR = 3.31 (1.42–7.73, p  = 0.006), and were associated with longer disease duration ( p  = 0.03) but not kidney failure ( p  = 0.31). Larger drusen were associated with more mesangial IgA staining ( p  = 0.004). Increased drusen counts were also present in IgA glomerulonephritis secondary to Crohn’s disease but not with Henoch-Schonlein purpura. The finding of retinal drusen in IgA glomerulonephritis is consistent with complement activation and represents a model for better understanding glomerular immune deposition and a supporting argument for treatment with anti-complement therapies.

Mesangial metrics reflect glomerular filtration surface area in diabetes. The point-sampled intercept (PSI) method is the conventional method to calculate these parameters. However, this is time consuming and subject to underestimation. We introduce a novel three-dimensional (3D) reconstruction method applicable to light microscopy to measure mesangial metrics. Transmission electron microscopy (TEM), PSI and our new 3D imaging methods were used to quantify mesangial metrics from 22 patients with type 2 diabetes, normo-, micro- and macroalbuminuria and an estimated glomerular filtration rate of <60 mL/min/1.73 m 2 . Repeated-measures ANOVA test was used to test the equality of the measurement means from the three methods and the degree of inter method variability. Repeated-measures and post-estimation ANOVA tests together with correlation coefficient measurements were used to compare the methods with TEM as reference. There was a statistically significant difference in mesangial volume measurements ( F (2, 16) = 15.53, p  = 0.0002). The PSI method underestimated measurements compared to TEM and 3D methods by 30% ( p  = 0.001) and 15%, respectively ( p  < 0.001). 3D and TEM measurements did not differ significantly. 3D reconstruction is a reliable and time efficient method for calculating mesangial metrics. It may prove to be a useful tool in clinical and experimental diabetic kidney disease.

Testicular plasmacytoma, whether occurring as a primary lesion or as a reflection of underlying multiple myeloma (MM), is a rare disease. We report the case of a 38-year-old male with multiply relapsed MM, who was found to have a testicular plasmacytoma. He presented with a gradually enlarging scrotal mass. Following orchidectomy, pathologic examination of the specimen demonstrated a plasmacytoma. In the context of active MM, the specimen was also sent for cytogenetic analysis but this was unhelpful in guiding a chemotherapy regime, which still continues at time of reporting. Although a rare lesion, there remains no definitive treatment protocol for the management of testicular plasmacytoma representing an extramedullary manifestation of MM.

We describe a novel approach that harnesses the ubiquity of copy number deletion polymorphisms in human genomes to definitively detect and quantify chimeric DNA in clinical samples. Unlike other molecular approaches to chimerism analysis, the copy number deletion (CND) method targets genomic loci (>50 base pairs in length) that are wholly absent from wild-type (i.e., self) background DNA sequences in a sex-independent manner. Bespoke quantitative PCR (qPCR) CND assays were developed and validated using a series of DNA standards and chimeric plasma DNA samples collected from 2 allogeneic kidney transplant recipients and 12 pregnant women. Assay performance and informativeness were assessed using appropriate statistical methods. The CND qPCR assays showed high sensitivity, precision, and reliability for linear quantification of DNA chimerism down to 16 genomic equivalents (i.e., 106 pg). Fetal fraction (%) in 12 singleton male pregnancies was calculated using the CND qPCR approach, which showed closer agreement with single-nucleotide polymorphism-based massively parallel sequencing than the SRY (sex determining region Y) (Y chromosome) qPCR assay. The latter consistently underestimated the fetal fraction relative to the other methods. We also were able to measure biological changes in plasma nonself DNA concentrations in 2 renal transplant recipients. The CND qPCR technique is suitable for measurement of chimerism for monitoring of rejection in allogeneic organ transplantation and quantification of the cell-free fetal DNA fraction in maternal plasma samples used for noninvasive prenatal genetic testing.

Amyloidoses are abnormal deposits of insoluble proteins in tissues that can lead to tissue dysfunction. Although elderly patients often have amyloid deposition in the gastrointestinal tract, they are usually asymptomatic. When symptoms are present, they are most often functional in nature; rarely are they caused by a localized amyloid deposition (amyloidoma). We report the case of an elderly man who presented with severe dysphagia secondary to an upper esophageal amyloidoma. Unfortunately, the patient died of his disease before management could be instituted.

Testicular plasmacytoma, whether occurring as a primary lesion or as a reflection of underlying multiple myeloma (MM), is a rare disease. We report the case of a 38-year-old male with multiply relapsed MM, who was found to have a testicular plasmacytoma. He presented with a gradually enlarging scrotal mass. Following orchidectomy, pathologic examination of the specimen demonstrated a plasmacytoma. In the context of active MM, the specimen was also sent for cytogenetic analysis but this was unhelpful in guiding a chemotherapy regime, which still continues at time of reporting. Although a rare lesion, there remains no definitive treatment protocol for the management of testicular plasmacytoma representing an extramedullary manifestation of MM.

IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysisThis is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and disseminationThis trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbersNCT04232969, ISRCTN14552789.

Digital health technology (DHT) holds the potential to improve health services, and its adoption has proliferated in recent decades owing to technological advancement. Optimal evaluation methodologies appropriate for generating quality evidence on DHT have yet to be established; traditional comparative designs present several limitations. This study aimed to scope the literature to highlight common methodological approaches used and their limitations to inform considerations for designing robust DHT evaluation studies. A scoping review was conducted following the Joanna Briggs Institute (JBI) scoping review guidelines. A systematic search was conducted using the CINAHL (EBSCO), MEDLINE (EBSCOhost), PsycINFO (EBSCO), EMBASE (Elsevier) and Web of Science (Clarivate Analytics) databases using iteratively developed search terms. We selected studies published in English between January 2016 and March 2022 and focussed on primary research evaluating the effectiveness of DHT with technology-user interactive or asynchronous features for adults (≥18 years) with cancer, diabetes or cardiovascular conditions. The final number of articles, after the screening and selection process, comprised 140 records. Data were analysed descriptively (frequency and percentages) and summarised thematically. Results showed most studies ( n = 104, 74.3%) employed the standard two-arm parallel RCT design, with usual/standard care as the preferred comparator in nearly half ( n = 65, 47.1%) of all included studies. Of the 104 comparative studies reviewed, limitations in recruitment were most frequently reported ( n = 70, 37%), followed by limitations in evaluation/measurement techniques ( n = 57, 27%), presence of confounding factors ( n = 50, 24%) and short duration of studies ( n = 24, 11%). The review highlights the need to consider inclusive approaches to recruitment and adoption of the emerging methodological approaches that account for the fast-paced, multi-component and group contamination problem resulting from the unconcealable nature of DHT interventions.

Helicobacter pylori, the major cause of gastric cancer, have mechanisms that allow colonization of the inhospitable gastric mucosa, including enzymes such as superoxide dismutase (SOD) which protect against reactive oxygen species. As SOD is essential for in vivo colonization, we theorized it might constitute a viable vaccine target. H. pylori SOD was expressed in E. coli and a purified recombinant protein used to vaccinate mice, prior to live H. pylori challenge. Partial protective immunity was induced, similar to that commonly observed with other antigens tested previously. This suggests SOD may have utility in a combination vaccine comprising several protective antigens.