WT1 is a key regulator of podocyte function: reduced expression levels cause crescentic glomerulonephritis and mesangial sclerosis

Glomerular disease is one of the most common causes of end-stage renal failure. Increasing evidence suggests that these glomerulopathies are frequently caused by primary lesions in the renal podocytes. One of the major consequences of podocyte lesions is the accumulation of mesangial matrix in the glomerular basement membrane, a process called glomerulosclerosis. Mesangial sclerosis is one of the most consistent findings in Denys-Drash patients and can be caused by dominant mutations in the Wilms' tumor 1 gene (WT1). The underlying mechanism, however, is poorly understood. WT1 is expressed in the podocytes throughout life, but its function in this cell type is unknown. Combining Wt1-knockout and inducible yeast artificial chromosome transgenic mouse models, we demonstrate that reduced expression levels of WT1 result in either crescentic glomerulonephritis or mesangial sclerosis depending on the gene dosage. Strikingly, the two podocyte-specific genes nphs1 and podocalyxin are dramatically downregulated in mice with decreased levels of Wt1, suggesting that these two genes act downstream of Wt1. Taken together, our data provide genetic evidence that reduced levels of Wt1 are responsible for the pathogenesis of two distinct renal diseases and offer a molecular explanation for the increased occurrence of glomerulosclerosis in patients with WAGR syndrome.     

Mycophenolate in idiopathic inflammatory myositis: outcome data of a large South Asian cohort

Clinical Rheumatology - Consensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the...     

Anterior cervical discectomy plus intervertebral polyetheretherketone cage fusion over three and four levels without plating is safe and effective long-term

Anterior cervical discectomy and fusion (ACDF) is an established treatment for single-level cervical spondylotic myelopathy and radiculopathy, yet its stand-alone use for multi-level disease of the subaxial cervical spine remains controversial. We report a prospectively studied case series of 30 patients receiving polyetheretherketone (PEEK) cage fusion over three and four cervical levels without anterior plating. Seven (23.3%) four-level procedures (all C3 to C7) were performed, the other 23 (76.7%) being three-level, with 19 (64.4%) at C4 to C7 and four (12.3%) at C3 to C6. Long-term follow-up of more than 2 years was available in 67% of patients. This cohort showed statistically significant improvements in visual analogue score for neck pain (p = 0.0006), arm pain (p = 0.0003) and Japanese Orthopaedic Association myelopathy score (p = 0.002). Fused segment heights increased by 0.6–1.1%. Adjacent segment disease requiring ACDF at C3–4 was seen in 6.7% of patients (one after trauma) at a mean follow-up of 62 months. Same segment recurrence requiring posterior decompression with instrumented fusion was found in 10% of patients at a mean follow-up of 49 months, only one of whom had radiological evidence of cage subsidence. The results suggest the procedure is safe and effective with potentially less morbidity than anterior plating, shorter inpatient stays than posterior approaches, acceptable same segment recurrence and lower than predicted adjacent segment disease rates.     

Correction: Consequences of gamma-ray irradiation on structural and electronic properties of PEDOT:PSS polymer in air and vacuum environments

Correction for ‘Consequences of gamma-ray irradiation on structural and electronic properties of PEDOT:PSS polymer in air and vacuum environments’ by Aswin kumar Anbalagan et al., RSC Adv., 2021, 11, 20752–20759, DOI: 10.1039/D1RA03463D.

The authors regret that incorrect details were given for ref. 18. The correct version of ref. 18 is given here as ref. 1.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Quantification of prostate shrinkage after microwave thermotherapy: a comparison of calculated cell-kill versus 3D transrectal ultrasound planimetry

PURPOSE: To compare prostate shrinkage after transurethral microwave thermotherapy (TUMT) with calculated cell-kill. MATERIALS AND METHODS: The calculated cell-kill from 33 males with benign prostatic hyperplasia (BPH) treated with TUMT according to the ProstaLund Feedback Treatment (PLFT) method was compared to the post-treatment prostate volume change. The prostate volume was estimated with three-dimensional transrectal ultrasound (3D-TRUS) planimetry at baseline, 3, 6, and 12 months follow-up. A paired t-test was used to test the statistical significance of differences between the cell-kill volume and the prostate volume change. Linear regression was used to infer a relationship between the cell-kill and the 3D-TRUS data. The reproducibility of the 3D-TRUS method was assessed in repeated measurements. RESULTS: The mean prostate volume at baseline (N=33) was 56.1cm(3). After 3 (N=25), 6 (N=29) and 12 months (N=23), it was 45.5 cm(3), 39.7 cm(3), and 45.1cm(3), respectively. The corresponding average cell-kill volume was 16.4 cm(3), 17.1cm(3), and 17.2 cm(3), respectively. Predicted cell-kill volume was significantly larger than prostate shrinkage at 3 (p<0.0001), 6 (p=0.0002), and 12 months (p<0.0001), and showed a strong correlation at 3 and 6 months (r=0.74, p<0.0001). Correlation at 12 months was moderate (r=0.57, p=0.0041). Examination and investigation variability both averaged 2.5%. CONCLUSIONS: Cell-kill calculations of the PLFT method are proportional to the 3D-TRUS prostate shrinkage by a factor of 0.5 and have a precision of approximately +/-10 cm(3) for 90% of the patients during the first year after treatment.     

Comparison Between Hot-Melt Extrusion and Spray-Drying for Manufacturing Solid Dispersions of the Graft Copolymer of Ethylene Glycol and Vinylalcohol

Purpose  

To investigate the effect of the manufacturing method (spray-drying or hot-melt extrusion) on the kinetic miscibility of miconazole and the graft copolymer poly(ethyleneglycol-g-vinylalcohol). The effect of heat pre-treatment of solutions used for spray-drying and the use of spray-dried copolymer as excipient for hot-melt extrusion was investigated.     

Purulent Pericarditis Caused by Haemophilus parainfluenzae

Bacterial pericarditis is a rare disease in the era of antibiotics. Purulent pericarditis is most often caused by Staphylococcus aureus, Streptococcus pneumoniae, or Haemophilus influenzae. The number of H. parainfluenzae infections has been increasing; in rare cases, it has caused endocarditis. We report a case of purulent pericarditis caused by H. parainfluenzae in a 62-year-old woman who reported a recent upper respiratory tract infection. The patient presented with signs and symptoms of pericardial tamponade. Urgent pericardiocentesis restored her hemodynamic stability. However, within 24 hours, fluid reaccumulation led to recurrent pericardial tamponade and necessitated the creation of a pericardial window. Cultures of the first pericardial fluid grew H. parainfluenzae. Levofloxacin therapy was started, and the patient recovered. Haemophilus parainfluenzae should be considered in a patient who has signs and symptoms of purulent pericarditis. Prompt diagnosis, treatment, and antibiotic therapy are necessary for the patient''s survival. To our knowledge, this is the first report of purulent pericarditis caused by H. parainfluenzae.Key words: Endocarditis, bacterial/diagnosis/microbiology/pathology; haemophilus/isolation & purification; haemophilus infections/diagnosis/drug therapy; haemophilus parainfluenzae; pericarditis/complications/diagnosis/etiology/microbiology/therapy; suppuration/diagnosis; treatment outcomePurulent pericarditis is a disease process that is usually described as a secondary infection from a primary site in the respiratory tract. The condition has been associated with respiratory disease processes such as pneumonia or empyema, but it can be a sequela of endocarditis, chest trauma, chest surgery, or the hematogenous spread of infection from elsewhere in the body.¹ Haemophilus influenzae has been suspected as a cause of purulent pericarditis; however, H. parainfluenzae has not previously been reported as a cause. Haemophilus parainfluenzae organisms are considered to be normal respiratory flora with low pathogenicity. However, H. parainfluenzae is being more frequently implicated in a variety of infections.^2,3 We present what we think is the first report of purulent pericarditis caused by H. parainfluenzae.