Bidirectional intraflagellar transport (IFT) consists of two major protein complexes, IFT-A and IFT-B. In contrast to the IFT-B complex, all components of IFT-A have recently been linked to human ...ciliopathies when defective. We therefore hypothesised that mutations in additional IFT-B encoding genes can be found in patients with multisystemic ciliopathies.
We screened 1628 individuals with reno-ocular ciliopathies by targeted next-generation sequencing of ciliary candidate genes, including all IFT-B encoding genes.
Consequently, we identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. Further, we detected a loss-of-stop mutation with extension of the deduced protein by 10 amino acids in an individual with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy and brain lesions including cerebellar atrophy, a phenotype to which the IFT81 variant might contribute. Cultured fibroblasts of this latter affected individual showed a significant decrease in ciliated cell abundance compared with controls and increased expression of the transcription factor GLI2 suggesting deranged sonic hedgehog signalling.
This work describes identification of mutations of IFT81 in individuals with symptoms consistent with the clinical spectrum of ciliopathies. It might represent the rare case of a core IFT-B complex protein found associated with human disease. Our data further suggest that defects in the IFT-B core are an exceedingly rare finding, probably due to its indispensable role for ciliary assembly in development.
Background
Diabetic peripheral neuropathy (DPN) is the major microvascular complication of type 2 diabetes mellitus (T2DM). Adropin is a peptide hormone that has essential roles in metabolic ...homeostasis and the pathogenesis of T2DM and its complications. This study was designed to estimate serum adropin levels in patients with T2DM in correlation with risk factors of DPN. The authors also aimed to investigate the association between serum adropin level and clinical and electrophysiological tests of DPN.
Patients and methods
This case–control study enrolled 100 patients with T2DM (40 diabetic cases without DPN and 60 diabetic cases with DPN) and 50 controls. All participants were subjected to a complete neurological examination. The motor and sensory conduction velocities of the median nerve, ulnar nerve, and common peroneal nerve were measured. The severity of DPN was assessed by Toronto clinical scoring system (TCSS). Serum adropin levels were assessed using an enzyme-linked immunosorbent assay.
Results
Our results revealed decreased circulating serum adropin levels in patients with T2DM (3.5±1.2), especially diabetic patients with DPN (3.1±1.07), compared with controls (6.1±0.89). There is a negative correlation between serum adropin level and TCSS as well as electrophysiological tests: motor nerve conduction velocity of median and ulnar nerve, sensory nerve conduction velocity of median and ulnar nerve, compound muscle action potential amplitude (median and ulnar nerve), and sensory nerve action potential amplitude (median, ulnar, and perception threshold nerve) (
P
<0.001*).
Conclusion
Diabetic patients with DPN had lower values of serum adropin than diabetic patients without DPN, and serum adropin levels were negatively correlated with metabolic risk factors, TCSS, as well as electrophysiological tests of DPN.
Background
Surgery is the first line of treatment for early, localized, or operable breast cancer and it is associated with severe post-operative pain. Although opioids have been the mainstay for ...managing post-operative pain, they have undesirable side effects. A variety of methods, including thoracic epidural, paravertebral, and intercostal blocks have been used to manage breast surgery pain; however, each of these blocks has some drawbacks. Serratus anterior plane block is a relatively novel technique that can block the lateral cutaneous branches of the intercostal nerves as well as the long thoracic nerve. This study compares between the effect of serratus anterior plane block and conventional IV analgesia on post-operative pain after modified radical mastectomy.
Results
Post-operative pain scores were significantly lower in the SAPB group in the first 8 h compared to the control group (
P
< 0.05), the time to the first rescue analgesic was significantly longer in the SAPB group with a mean 354 min compared to the control group; the mean is 17.8 min, the total dose of rescue analgesic was significantly lower in the SAPB group with a mean 50 mg in the first 24 h compared to a mean of 212.5 mg in the control group. The patient’s satisfaction scores were higher, the incidence of post-operative nausea and vomiting was significantly lower among the SAPB group compared to the control group. No other complications were recorded in either group.
Conclusions
The serratus anterior plane block can be used as one of the modalities in managing the pain of patients undergoing MRM surgery. This procedure was effective in reducing the need for post-operative opioids usage, better patient satisfaction with fewer side effects as post-operative nausea and vomiting. It is simple and easy-to-learn technique.
Background
Peripheral nervous system and the central nervous system involvement in systemic lupus erythematosus (SLE) patients are one of the major causes of morbidity and mortality. The aim of this ...work was to study the nervous system clinically and electrophysiologically in children with systemic lupus erythematosus.
Results
The study was carried out on thirty-eight children with SLE. Their age ranged from 5 to 16 years. The most encountered neurologic manifestations were tremors. It was observed in 47.4% of children, followed by headache in 39.5%, sensory manifestation as numbness in 23.7%, cerebrovascular stroke in 5.3%, and chorea in 2.6%, which was unilateral mostly in the upper limb, tics, and convulsion had the same percentage. Around 16% of children had positive findings in MRI, such as cerebrovascular disease, minimal hematoma, pseudotumorcerebri, vasculitis, and ectatic ventricles. Subclinical peripheral neuropathy was reported in nearly 52.6% of children, and clinical peripheral neuropathy was reported in 23.6%. Pure sensory subclinical peripheral neuropathy was detected in 13.1% of children, but mixed subclinical peripheral neuropathy was detected in 39.4%. Nearly 53% of studied children had an abnormal somatosensory-evoked potential study of posterior tibial and median nerves.
Conclusion
The current study reported that the clinical neurological manifestations in juvenile SLE is common. Peripheral neuropathy is commonly detected, which could be either clinical or sub-clinical. Somatosensory evoked potential study is of value for early detection of central affection.
So, we recommend more studies to determine the guidelines when to order these informative investigations for children with JSLE.
Background
An epidemic of obesity has spread across the globe. Obesity has numerous comorbidities, including airway disease, insulin resistance, type 2 diabetes, cardiovascular disease, ...atherosclerosis, degenerative neurological disease, cognitive dysfunction, and cancer. Inflammatory cytokine is suggested to play a role in obesity and its complications. The current study aimed to estimate the expression and serum visfatin concentrations in obese Egyptian women. Moreover, we aimed to evaluate the possible association of visfatin gene expression and its serum levels with idiopathic intracranial hypertension (IIH) and cognitive dysfunction
Participants and methods
This cross-sectional study enrolled 60 obese women and 40 lean healthy women as controls. Obese women were classified according to grades of obesity into three groups. All participants underwent full clinical, neurological, and psychiatric examination. IIH group included patients with intracranial pressure greater than 25 cm H
2
O (opening pressure measured during lumber puncture in lateral decubitus position). Cognitive function was evaluated by using Montreal Cognitive Assessment scale (MoCA), Arabic version. Estimation of visfatin expression levels was determined by real-time PCR, and serum visfatin concentrations were measured using enzyme-linked immunosorbent assay.
Results
Our results revealed that obese women had higher values of visfatin expression (1.44±0.29) and serum levels (124.1±) compared with lean women (1.01±0.3 and 46.1±33.8, respectively). The visfatin expression and serum levels were significantly positively correlated with obesity indices, metabolic risks, MoCA, cerebrospinal fluid opening pressure, and cognitive dysfunction. Linear regression test showed that BMI, cerebrospinal fluid opening pressure, and MoCA were the main predictors of both serum and expression levels of visfatin in obese women. The receiver operating characteristic curve analysis revealed that the power of serum visfatin levels was higher than visfatin expression in differentiating obese women from lean ones.
Conclusion
There was a strong independent association between both higher visfatin expression and serum levels and obesity indices, metabolic risks, IIH, and cognitive dysfunction in obese Egyptian women.
Objective
Ischemic stroke (IS) is one of the major causes of disability and death worldwide. Effective prevention remains the best approach to reduce the burden of stroke. Adipokines can serve as a ...key messenger to central energy homeostasis and metabolic homeostasis. Retinol-binding protein 4 (RBP4), a retinol transporter, is elevated in insulin resistance. Controversy exists regarding the role of RBP4 in thyroid diseases. The objective of this study was to evaluate serum RBP4 in patients with hypothyroidism and to assess the association of serum RBP4 with susceptibility of IS.
Patients and methods
This case–control study included 50 healthy individuals as a control group and 90 patients with hypothyroidism, who were stratified into two subgroups: patients with IS and patients without IS. All participants were subjected to history taking and clinical, laboratory, and radiological evaluation.
Results
Serum RBP4 levels were significantly higher in hypothyroid patient, especially patients with IS, compared with the nonstroke group. Interestingly, serum RBP4 level was positively correlated with vascular and metabolic risk factors. Moreover, diastolic and systolic blood pressures, triglyceride, free T3, as well as thyroid-stimulating hormone, were independently correlated with serum RBP4 by linear regression analysis test. The diagnostic power of serum RBP4 level in differentiating hypothyroidism from controls was revealed at the cutoff value of 12.25, with area under the curve of 0.909 (95% confidence interval: 0.861–0.957). However, the diagnostic power of serum RBP4 level in differentiating hypothyroid patient with IS from those without stroke was revealed at the cutoff values of 11.4, with area under the curve of 0.822 (95% confidence interval: 0.737–0.906). In conclusion, the higher levels of serum RBP4 in hypothyroidism, especially in patients with IS, were associated with metabolic and glucose abnormalities, and thus, it could be used as a promising predictive biomarker of IS in hypothyroidism.
Background Eye lesions, occur in nearly half of patients with Behçet's Disease (BD), can lead to irreversible damage and vision loss; however, limited studies are available on identifying risk ...factors for the development of vision-threatening BD (VTBD). Using an Egyptian college of rheumatology (ECR)-BD, a national cohort of BD patients, we examined the performance of machine-learning (ML) models in predicting VTBD compared to logistic regression (LR) analysis. We identified the risk factors for the development of VTBD. Methods Patients with complete ocular data were included. VTBD was determined by the presence of any retinal disease, optic nerve involvement, or occurrence of blindness. Various ML-models were developed and examined for VTBD prediction. The Shapley additive explanation value was used for the interpretability of the predictors. Results A total of 1094 BD patients 71.5% were men, mean + or - SD age 36.1 + or - 10 years were included. 549 (50.2%) individuals had VTBD. Extreme Gradient Boosting was the best-performing ML model (AUROC 0.85, 95% CI 0.81, 0.90) compared with logistic regression (AUROC 0.64, 95%CI 0.58, 0.71). Higher disease activity, thrombocytosis, ever smoking, and daily steroid dose were the top factors associated with VTBD. Conclusions Using information obtained in the clinical settings, the Extreme Gradient Boosting identified patients at higher risk of VTBD better than the conventional statistical method. Further longitudinal studies to evaluate the clinical utility of the proposed prediction model are needed. Keywords: Behçet's disease, Vision-threatening BD, Machine learning, SHAP analysis
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most of the approximately 60 genes that if mutated cause steroid-resistant nephrotic syndrome (SRNS) are highly expressed in the glomerular podocyte, rendering SRNS a “podocytopathy.”
We performed ...whole-exome sequencing (WES) in 1200 nephrotic syndrome (NS) patients.
We discovered homozygous truncating and homozygous missense mutation in SYNPO2 (synaptopodin-2) (p.Lys1124∗ and p.Ala1134Thr) in 2 patients with childhood-onset NS. We found SYNPO2 expression in both podocytes and mesangial cells; however, notably, immunofluorescence staining of adult human and rat kidney cryosections indicated that SYNPO2 is localized mainly in mesangial cells. Subcellular localization studies reveal that in these cells SYNPO2 partially co-localizes with α-actinin and filamin A−containing F-actin filaments. Upon transfection in mesangial cells or podocytes, EGFP-SYNPO2 co-localized with α-actinin-4, which gene is mutated in autosomal dominant SRNS in humans. SYNPO2 overexpression increases mesangial cell migration rate (MMR), whereas shRNA knockdown reduces MMR. Decreased MMR was rescued by transfection of wild-type mouse Synpo2 cDNA but only partially by cDNA representing mutations from the NS patients. The increased mesangial cell migration rate (MMR) by SYNPO2 overexpression was inhibited by ARP complex inhibitor CK666. SYNPO2 shRNA knockdown in podocytes decreased active Rac1, which was rescued by transfection of wild-type SYNPO2 cDNA but not by cDNA representing any of the 2 mutant variants.
We show that SYNPO2 variants may lead to Rac1-ARP3 dysregulation, and may play a role in the pathogenesis of nephrotic syndrome.
The number of obese individuals is surging in developed and developing countries. Obesity predisposes to many serious illnesses. Peripheral neuropathy (PN) is one of its major complications. ...Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by the adipose tissue and is believed to play a principal role in obesity complications. Meanwhile, hs-CRP is a known inflammatory biomarker. This study was designed to detect the role of serum IL-6 and hs-CRP as inflammatory biomarkers in early diagnosis of peripheral neuropathy (PN) in non-diabetic obese patients. Additionally, we aimed to explore the association between IL-6 with the clinical and electrophysiological tests of PN. This cross-sectional controlled study enrolled 150 obese patients and 50 subjects as a control group. The obese groups were subclassified according to BMI into three groups; all participants were subjected to a complete neurological examination and motor, and sensory peripheral nerve conduction studies. Serum IL-6 and hs-CRP levels were assessed using a commercially available ELISA. Our results revealed that obese patients with PN had statistically significant higher values of IL-6 and hs-CRP compared to obese patients without PN and controls (P < 0.001). Meanwhile, levels of both marker were inversely related to nerve conduction velocities (P < 0.001). Obese patients with PN had higher values of serum IL-6 and hs-CRP than diabetic patients without DPN. Because the diagnostic power of both markers in serum was significant, we conclude that they could be a useful diagnostic biomarker of PN.
The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find ...any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4 ± 6.3 ng/ml) compared to control (3.5 ± 2.6 ng/ml) (
p
< 0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (
r
= 0.32,
p
= 0.03) and CHAQ (
r
= 0.37,
p
= 0.01) and negatively with the presence of GG alleles (
r
= −0.48,
p
= 0.001). The GG alleles were significantly negatively associated with C-reactive protein (
r
= −0.32,
p
= 0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (
r
= −0.28,
p
= 0.06;
r
= −0.25,
p
= 0.09 and
r
= −0.25,
p
= 0.09, respectively). There is evidence of a possible influence of the
−
308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.
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