The ciliopathy-associated protein homologs RPGRIP1 and RPGRIP1L are linked to cilium integrity through interaction with Nek4 serine/threonine kinase

Recent studies have established ciliary dysfunction as the underlying cause of a broad range of multi-organ phenotypes, known as 'ciliopathies'. Ciliopathy-associated proteins have a common site of action in the cilium, however, their overall importance for ciliary function differs, as implied by the extreme variability in ciliopathy phenotypes. The aim of this study was to gain more insight in the function of two ciliopathy-associated protein homologs, RPGR interacting protein 1 (RPGRIP1) and RPGRIP1-like protein (RPGRIP1L). Mutations in RPGRIP1 lead to the eye-restricted disease Leber congenital amaurosis, while mutations in RPGRIP1L are causative for Joubert and Meckel syndrome, which affect multiple organs and are at the severe end of the ciliopathy spectrum. Using tandem affinity purification in combination with mass spectrometry, we identified Nek4 serine/threonine kinase as a prominent component of both the RPGRIP1- as well as the RPGRIP1L-associated protein complex. In ciliated cells, this kinase localized to basal bodies, while in ciliated organs, the kinase was predominantly detected at the ciliary rootlet. Down-regulation of NEK4 in ciliated cells led to a significant decrease in cilium assembly, pointing to a role for Nek4 in cilium dynamics. We now hypothesize that RPGRIP1 and RPGRIP1L function as cilium-specific scaffolds that recruit a Nek4 signaling network which regulates cilium stability. Our data are in line with previously established roles in the cilium of other members of the Nek protein family and define NEK4 as a ciliopathy candidate gene.     

The frequency of Achilles and plantar calcaneal spurs in gout patients

Background/aim Gout may cause various radiographic abnormalities such as cartilage loss, spurs, sclerosis, and periostal new bone formation. The purpose of this study was to investigate the frequency of Achilles and plantar spurs and related factors in gout patients.Matherial and methodsWe performed a retrospective review of gout patients, treated at Hacettepe University hospitals between 2014 and 2019. We identified patients from the hospital records using the ICD-10 code (M10). Demographic and clinical features, comorbidities, and foot radiographies were collected. The radiographies were evaluated by a rheumatologist (U.K.) who was experienced in musculoskeletal radiography. Factors predicting the spurs were analyzed by logistic regression analysis.Results181 patients who had lateral foot radiograph were included in this study. Eighty-one (44.7%) patients had score ≥ 2 Achilles spur, 81 (44.7%) patients had score ≥ 2 plantar spur, and 22 (12.1%) patients had no spur. Age, disease duration, duration between the gout diagnosis and appearing spur, the presence of metabolic comorbidities and hypertension were higher in both Achilles and plantar spurs than no spur group. Forty (22.1%) patients had score ≥ 2 both Achilles and plantar spur. In this group, the mean age was older and the proportion of metabolic comorbidities was higher than the groups of Achilles and plantar spur with a score 0 or 1. Predictor of the development of large or moderate-severe calcaneal spur was the existence of metabolic comorbidity [OR (95% CI): 3.49 (1.11–11.0) and p = 0.033].ConclusionThe presence of metabolic comorbidities increases the frequency of calcaneal spurs in gout patients. This condition can be explained by the impaired microvascular structure and increased hypoxia resulting in calcification on the tendon and ligament insertion sites.     

Targeted vessel reconstruction in non‐contrast‐enhanced steady‐state free precession angiography

Image quality in non‐contrast‐enhanced (NCE) angiograms is often limited by scan time constraints. An effective solution is to undersample angiographic acquisitions and to recover vessel images with penalized reconstructions. However, conventional methods leverage penalty terms with uniform spatial weighting, which typically yield insufficient suppression of aliasing interference and suboptimal blood/background contrast. Here we propose a two‐stage strategy where a tractographic segmentation is employed to auto‐extract vasculature maps from undersampled data. These maps are then used to incur spatially adaptive sparsity penalties on vascular and background regions. In vivo steady‐state free precession angiograms were acquired in the hand, lower leg and foot. Compared with regular non‐adaptive compressed sensing (CS) reconstructions (CS_low), the proposed strategy improves blood/background contrast by 71.3 ± 28.9% in the hand (mean ± s.d. across acceleration factors 1–8), 30.6 ± 11.3% in the lower leg and 28.1 ± 7.0% in the foot (signed‐rank test, P < 0.05 at each acceleration). The proposed targeted reconstruction can relax trade‐offs between image contrast, resolution and scan efficiency without compromising vessel depiction. Copyright © 2016 John Wiley & Sons, Ltd.     

RELATIONSHIP OF HLA-DR EXPRESSION WITH REJECTION AND MONONUCLEAR CELL INFILTRATION IN RENAL ALLOGRAFT BIOPSIES

DNA methods have resulted in improved renal allograft survival rates in cadaveric renal transplantation. This paper describes the impact of DNA typing by PCR-SSP on a living-related renal transplant (LRRT) programme. It evaluates error rates in serology, acute rejections, graft function and survival rates between the two typing methods. Serological typing was carried out on CTS 120 antisera Class 1, 60 antisera Class 2, 72 antisera Terasaki Class 1 and 72 antisera Class 2 antigens. Low-resolution PCR-SSP typing was carried out by 24 primers for HLA-A, 48 for HLA-B and 24 for HLA-DR. Of the 585 transplants: 159 (Group I) were serology based; 172 were serology and PCR-SSP based for HLA-DR (Group II); and 254 were serology and PCR-SSP based for HLA-A and -B, and only PCR-SSP based for HLA-DR (Group III). Error rates in serology compared with PCR-SSP were 24% for HLA-A, 16% for HLA-B and 35% for HLA-DR. Acute rejections were 39%, 30% 26% in Groups I, II and III, respectively ( P= 0.02). Graft function of serum creatinine <1.5 mg/dl at 1 year was found in 26% of the Group I patients compared with 48% of those in Group III ( P <0.0001). One- and 3-year graft survival was 93% and 87% for Group II compared with 81% and 69% for Group I, respectively ( P= 0.0001). Matching by this combination of serology and PCR-SSP is not only economical for a developing country but also improves graft survival by 12% and 18% at 1 and 3 years, respectively.     

Morphometry of the gallbladder during the fetal period

Purpose  

In this study, our objective was to investigate the development of the gallbladder, its morphological structure and relationship with the adjacent organs during the fetal period.     

Prenatal diagnosis of 20p13 microdeletion syndrome

ObjectiveThe objective of this study was to report the first case of prenatal diagnosis of the fetal 20p13 microdeletion syndrome in the literature.Case reportThe mother was 31 years old and had a first trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound at 23 weeks of gestation showed mild ventriculomegaly (10.2 mm) and absent septum pellucidum. She underwent amniocentesis because of the abnormal imaging results. Karyotype analysis revealed normal results. Chromosome microarray analysis (CMA) was then performed to provide genetic analysis of the fetus and parents. CMA detected 317.902 kb deletion of 20p13 in fetus. Finally, pregnancy was terminated at 32 weeks of gestation.ConclusionThis study is the first to report the prenatal diagnosis of a 20p13 microdeletion syndrome. Our results further confirmed that genes in this region, including SOX12, NRSN2 are essential for normal fetal growth and TBC1D20 for normal brain development.     

The “vaccine” hubbub: Viral load comparisons of SARS-CoV-2 Delta and Omicron variants against different vaccine–booster vaccine combinations

There is a significant body of evidence showing that efficient vaccination schemes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is helping control the coronavirus disease 2019 (COVID-19) pandemic. However, this goal cannot be achieved without real world data highlighting the impact of vaccines against viral spread. In this study, we have aimed at differentially investigating the impact of COVID-19 vaccines (CoronaVac, Pfizer/BioNTech, Astra/Zeneca Oxford, Janssen) used in North Cyprus in limiting the viral load of Delta and Omicron variants of SARS-COV-2. We have utilized real-time quantitative polymerase chain reaction cycle threshold values (Ct values) as a proxy of viral load of the two SARS-CoV-2 variants. Our results indicate that the administration of at least two doses of the messenger RNA-based Pfizer/BioNTech vaccine leads to the lowest viral load (highest Ct values) obtained for both Omicron and Delta variants. Interestingly, regardless of the vaccine type used, our study revealed that Delta variant produced significantly higher viral loads (lower Ct values) compared with the Omicron variant, where the latter was more commonly associated with younger patients. Viral spread is a crucial factor that can help determine the future of the pandemic. Thus, prioritizing vaccines that will play a role in not only preventing severe disease but also in limiting viral load and spread may contribute to infection control strategies.     

Sleep disturbance among women with chronic pelvic pain

Objective

To investigate the effect of chronic pelvic pain (CPP), a debilitating condition, on sleep quality.

Methods

The present case–control study enrolled women older than 18 years attending the Gynecology Clinic of Çanakkale Onsekiz Mart University Hospital, Çanakkale, Turkey, with CPP between August 2011 and August 2012. The control group was selected from women attending the clinic for another complaint. Sleep quality was evaluated via the Pittsburgh Sleep Quality Index, and differences between the groups were compared by t and χ² tests.

Results

During the study period, 157 women were enrolled. Seventy-two had CPP symptoms, and 85 attended the clinic for other complaints. Poor sleep quality was found in 80% (n = 58) of the women with CPP, and 55% (n = 47) of the control group (P < 0.05).

Conclusion

Women with CPP were found to have poor sleep quality. Sleep education should be recommended in psychiatry and neurology clinics to increase the awareness of sleeping problems among these women.     

The Effect of Removable Partial Dentures on Alveolar Bone Resorption: A Retrospective Study with Cone‐Beam Computed Tomography

Purpose: The aim of this study was to compare vertical and horizontal mandibular alveolar bone resorption by measuring bone morphological variation in Kennedy Class II removable partial denture (RPD) wearers and non‐wearers using cone‐beam computed tomography (CBCT). Materials and Methods: In total, 124 sites in the CBCT scans of 62 (29 RPD non‐wearers, 33 RPD wearers) Kennedy Class II patients were analyzed retrospectively. Three‐dimensional representations of the mandible with superimposed cross‐sectional slices were developed with the CBCT scans to evaluate the mandibular alveolar height and width by measuring distances between the mandibular canal, mylohyoid ridge, alveolar crest, and lower border of the mandible in four regions (eight sites) of Kennedy Class II non‐wearers and wearers of RPDs. Results: Mandibular alveolar bone height and width were significantly lower in edentulous sites when compared with dentate sites in both Kennedy Class II non‐wearers and wearers of RPDs (p < 0.05). Additionally, mean vertical and horizontal mandibular bone resorption was significantly higher in RPD wearers than in non‐wearers (p < 0.05). Conclusions: Vertical and horizontal alveolar bone resorption was found to be higher in the RPD wearing patients when comparing the dentate and edentulous sites.     

Differential relationship of vitamin A and E levels in methylnitrosourea-induced Sprague-Dawley rats following prolonged feeding of fatty diets enriched with the vitamins

Summary Prolonged supplementation of vitamins A and E (2500 IU and 11.3 IU/rat daily) in 10.3% and 21.6% fatty diets administered to methylnitrosourea-induced Sprague-Dawley rats caused alterations in plasma and liver levels of both vitamins as well as of the total lipids. Liver vitamin A levels increased steadily (more than four-fold) until termination of the experiment, whereas plasma vitamin A levels only showed a minor increase at the end of the study in comparison to rats fed a standard diet. Liver vitamin E levels initially showed no difference from those of rats treated with a standard diet, and were decreased at the end of the experiment, whereas the respective plasma levels were increased throughout the study, only showing a decrease relative to initial values at termination of the experiment. Plasma total lipids increased with age and following supplementation of the vitamins in the high-fat diet, whereas liver total lipids were influenced less by aging than by the fat and vitamin contents of the respective diets. The observed alterations were, however, not related to significant chemopreventive activity of the vitamins A and E contained in high-fat diets.Dedicated to Professor Dr. Dietrich Schmähl on the occasion of his 65th birthday