Renal Tubular Basement Membrane Changes in Tubulointerstitial Damage in Patients with Glomerular Diseases

Injury to renal tubules and interstitium occur in various glomerular diseases, leading to functional impairment. Tubular basement membrane (TBM) is an important component in maintaining tubular epithelial cell integrity. Because ultrastructural changes in these structures had not been studied in detail, the authors analyzed 30 patients with various types of glomerular diseases, including minimal change disease (MCD), focal segmental glomerular sclerosis, IgA nephropathy, diffuse proliferative glomerulonephritis, membranous nephropathy, and lupus nephritis, by light, electron, and immunofluorescence microscopy. Ultrastructural changes in the TBM were studied and morphometric measurements were performed. The tubular basement membranes showed membranous structures, lucent or lytic areas, and tubular epithelial detachment. There was significant linear correlation between these tubular basement membrane changes and terminal complement complex neoantigens. The interstitial widening was due to banded collagen fibers, with anchoring fibers in the TBM. The various glomerular diseases lead to tubulointerstitial damage via changes in the TBM, leading to renal dysfunction.     

Mutation Analysis of the IL36RN Gene in 14 Japanese Patients with Generalized Pustular Psoriasis

Generalized pustular psoriasis (GPP) is a rare, potentially life threatening, and aggressive form of psoriasis, which is characterized by sudden onset with repeated episodic skin inflammation leading to pustule formation. Familial GPP is known to be caused by recessively inherited mutations in the IL36RN gene, which encodes interleukin 36 receptor antagonist (IL‐36Ra). In this article, we performed mutation analysis of the IL36RN gene in 14 Japanese patients with GPP, and identified mutations in two of these patients analyzed. One patient was compound heterozygous for mutations c.115+6T>C and c.368C>G (p.Thr123Arg), whereas the other carried compound heterozygous mutations c.28C>T (p.Arg10*) and c.115+6T>C in the IL36RN gene. Expression studies using total RNA from the patients’ skin revealed that the mutation c.115+6T>C resulted in skipping of exon 3, leading to a frameshift and a premature termination codon (p.Arg10Argfs*1). The protein structure analysis suggested that the missense mutation p.Thr123Arg caused misfolding and instability of IL‐36Ra protein. In vitro studies in cultured cells showed impaired expression of the p.Thr123Arg mutant IL‐36Ra protein, which failed to antagonize the IL‐36 signaling pathway. Our data further underscore the critical role of IL36RN in pathogenesis of GPP.     

A Homozygous Frameshift Mutation in the HOXC13 Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family

Pure hair and nail ectodermal dysplasia (PHNED) is a rare genetic disorder characterized by hypotrichosis or complete alopecia, as well as nail dystrophy. Mutations in the type II hair keratin gene KRT85 and the HOXC13 gene on chromosome 12q have recently been identified in families with autosomal‐recessive PHNED. In the present study, we have analyzed a consanguineous Syrian family with an affected girl having complete alopecia and nail dystrophy since birth. The family clearly showed linkage to chromosome 12q13.13–12q14.3, which excluded the KRT85 gene. Sequencing of another candidate gene HOXC13 within the linkage interval identified a homozygous frameshift mutation (c.355delC; p.Leu119Trpfs*20). Expression studies in cultured cells revealed that the mutant HOXC13 protein mislocalized within the cytoplasm, and failed to upregulate the promoter activities of its target genes. Our results strongly suggest crucial roles of the HOXC13 gene in the development of hair and nails in humans.     

The Evaluation of Left Ventricular Functions with Tissue Doppler Echocardiography in Adults with Celiac Disease

Background/Aim:

The aim of this study was to investigate the effects of celiac disease on cardiac functions using tissue Doppler echocardiography (TDE).

Patients and Methods:

The study included 30 patients with celiac disease (CD) and 30 healthy volunteers. Echocardiographic examinations were assessed by conventional echocardiography and tissue Doppler imaging. The peak systolic velocity (S^''m), early diastolic myocardial peak velocity (E^''m), late diastolic myocardial peak velocity (A^''m), E^''m/A^''m ratio, myocardial precontraction time (PCT^''m), myocardial contraction time (CT^''m), and myocardial isovolumetric relaxation time (IVRT^''m), E to E^''m ratio were measured.

Results:

In pulsed wave Doppler echocardiography, mitral late diastolic flow (A) velocity and E to E^''m ratio were significantly higher (P = 0.02 and P = 0,017), E/A ratio was significantly lower (P = 0.008) and IVRT was significantly prolonged (P = 0.014) in patients with CD. In TDE, S^''m, E^''m, and E^''m/A^''m ratio were significantly lower, IVRT^''m was longer (P = 0.009) from septal mitral annulus and S^''m, E^''m, E^''m/A^''m ratio were significantly lower, PCT^''m, PCT/ET ratio, IVRT^''m were longer, and MPI was higher from lateral mitral annulus in celiac group than controls.

Conclusion:

Our study confirms that patients with CD have impaired diastolic function. More importantly, we also demonstrated an impairment of myocardial systolic function in patients with CD by TDE. We recommend using TDE in addition to conventional echocardiography parameters for the cardiovascular risk assessment of patients with CD.     

The Premonitory Phase of Migraine – What Can We Learn From It?

This review aims to understand the prevalence of premonitory symptoms in migraine, postulate their mechanisms, and compare these with functional imaging studies. A thorough literature review was conducted using PubMed for prevalence studies of premonitory symptoms in migraine and functional imaging studies in the premonitory phase. The majority of studies have been retrospective reporting a prevalence of 7‐88% for premonitory symptoms in migraine. Only one study has investigated premonitory symptoms prospectively and used preselected patients with recognized premonitory symptoms. The majority of patients were able to predict correctly the onset of migraine headache. Only one functional imaging study has been conducted in the premonitory phase that showed activation of posterolateral hypothalamus, midbrain tegmental area and substantia nigra, periaqueductal gray, dorsal pons, and various cortical areas including occipital, temporal, and prefrontal cortex. Subgroup analysis of patients with photophobia more than without photophobia in the premonitory phase showed activation of the occipital cortex. Comparison of patients with nausea more than without nausea in the premonitory phase showed activation in upper dorsal medulla and periaqueductal gray. Premonitory symptoms are common in migraine, although the true prevalence cannot be stated with certainty in the absence of prospective studies in unselected patients. Hypothalamic involvement can explain many of the premonitory symptoms. Activation of the the brainstem structures and hypothalamus before pain suggests a pivotal role of these structures in the pathogenesis of migraine. Hypersensitivity to light and occurrence of nausea in migraine is associated with activation of central brain structures involved in these pathways, and this can occur in the absence of pain.     

Prevalence of dental caries in primary and permanent teeth and its relation with tooth brushing habits among schoolchildren in Eastern Saudi Arabia

Objectives:

To determine the prevalence of dental caries in the primary and permanent teeth, and evaluate the brushing habits of school children in Dammam, Kingdom of Saudi Arabia (KSA).

Methods:

This study was conducted at Dammam, KSA. Oral examination of the participants was conducted from February to May 2014. The total sample size for this cross-sectional study was 711. There were 397 children between the age of 6-9 years, who were examined for primary teeth caries, and 314 between the age 10-12 years were examined for permanent teeth caries. Primary and permanent dentitions were studied for decayed, missing, and filled teeth (dmft [primary teeth], DMFT [permanent teeth]).

Results:

The overall prevalence of dental caries in primary and permanent teeth was almost 73% (n=711). Among the 6-9-year-old, the prevalence of caries was approximately 78% (n=397) whereas, among the 10-12-year-old children, it was approximately 68% (n=314). Mean dmft value among the 6-9-year-olds was 3.66±3.13 with decayed (d) component of 3.28±2.92, missing (m) component of 0.11±0.69, and filled (f) component of 0.26±0.9. Mean DMFT value among the 10-12-year-old children was 1.94±2.0 with decayed (D) component of 1.76±1.85, missing (M) component of 0.03±0.22, and filled (F) of component 0.15±0.73. Daily tooth brushing had a positive effect on caries prevention, and this effect was statistically significant for caries in primary teeth.

Conclusion:

Although the prevalence of dental caries in primary and permanent teeth was not found to be as high as other researchers reported from different cities of KSA, still the prevalence was high considering the World Health Organization future oral health goals. Awareness should be provided to students, as well as, teachers and parents regarding the importance of good brushing habits and regular dental visits.Dental caries is one of the most common cause of extraction of primary teeth in Saudi Arabia.1 In the past few decades, an increase in the prevalence of dental caries has been observed, which can be attributed to a change in lifestyle of Saudis, involving increased consumption of sugary food, carbonated drinks, and lack of awareness towards proper oral health maintenance.2,3 Generally, the prevalence of dental caries in developed countries is decreasing, while in underdeveloped and developing countries, the prevalence is on the rise.4 According to the statistics available from the World Health Organization (WHO), caries prevalence among the 12-year-old children from many European Union states (EU) has decreased considerably from 1970’s to 2006.5 This decline in the caries’ prevalence among EU countries over a period of 35 years could be attributed to an increased awareness of oral hygiene maintenance, and use of fluoridated toothpaste.6 However, among underdeveloped countries where fluoridated toothpaste is not easily available, or not affordable in some cases, caries prevalence is still high.7 The area of dental caries prevalence is of great interest to local and international researchers, which can be indicated by a number of studies that have been performed in developed and developing countries regarding caries’ prevalence.8-10 A study conducted in the urban and rural areas of Lahore, Pakistan to determine whether urbanization and family earnings are related to dental caries reported caries prevalence of 40.5%, and decayed (d), missing (m), and filled (f) teeth (dmft [primary teeth]) score of 1.85 ± 3.26 in preschool children aged 3-5 years,11 while another cross-sectional study performed in Chikar, Pakistan with convenience sampling of 311 schoolchildren revealed an overall DMFT (permanent teeth) score of 3.3 in 5-20-year-olds.12 Several studies have been conducted in different parts of the Kingdom of Saudi Arabia (KSA) to report the prevalence of dental caries in schoolchildren. A study performed in Riyadh reported a dmft score of 6.1, decayed factor of 4.6, and no significant difference in the prevalence of caries in relation to gender among 789 pre-school children.13 Farsi14 conducted a study to develop an association between enamel defects and caries occurrence in Jeddah, KSA, and reported a dmft score of 3.9, and a strong association between enamel defects and caries prevalence among 4-5-year-olds.14 In 2012, caries prevalence in the maxillary and mandibular first molar in the age group of 7-10 years schoolchildren was determined in Abha city, and a mean DMFT of 2.74 was reported.15 It was also concluded in the same study that caries prevalence in the first permanent molars from this region is higher than the recommended standards of the WHO.15 Extensive literature search was carried out to find studies regarding caries’ prevalence from Dammam, KSA. The search resulted in only one study, which was conducted in 2008 on children with cleft lip and palate aged 1-6 years, and it reported a high dmft of 10.54 from Dammam region.16 Since Dammam is one of the largest cities of the Eastern province of KSA, it would be interesting to observe caries’ prevalence among schoolchildren from this city. Therefore, the aim of the present study was to determine the prevalence of dental caries in schoolchildren aged 6-12 years in Dammam, KSA using the dmft/DMFT index of dental caries.     

Dipeptidyl peptidase-4 expression in pancreatic tissue from patients with congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is caused by unregulated insulin release and leads to hyperinsulinaemic-hypoglycaemia (HH). Glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY) and the enzyme; dipeptidyl peptidase-4 (DPP-4) all regulate appetite and glucose homeostasis. These proteins have been identified as possible contributors to HH but the mechanism remains poorly understood. We aimed to look at the expression pattern of pancreatic DPP-4 in children with focal and diffuse CHI (FCHI and DCHI, respectively). Using immunohistochemistry; we determined DPP-4 expression patterns in the pancreas of CHI patients. DPP-4 was found to be expressed in the pancreatic β, α and δ-cells in and around the focal area. However, it was predominantly co-localised with β-cells in the paediatric tissue samples. Additionally, proliferating β-cells expressed DPP-4 in DCHI, which was absent in the FCHI pancreas. Insulin was found to be present in the exocrine acini and duct cells of the DCHI pancreas suggestive of exocrine to endocrine transdifferentiation. Furthermore, 6 medically-unresponsive DCHI pancreatic samples showed an up-regulation of total pancreatic DPP-4 expression. In conclusion; the expression studies have shown DPP-4 to be altered in HH, however, further work is required to understand the underlying role for this enzyme.     

Evaluation and comparison of the marginal adaptation of two different substructure materials

PURPOSE

In this study, we aimed to evaluate the amount of marginal gap with two different substructure materials using identical margin preparations.

MATERIALS AND METHODS

Twenty stainless steel models with a chamfer were prepared with a CNC device. Marginal gap measurements of the galvano copings on these stainless steel models and Co-Cr copings obtained by a laser-sintering method were made with a stereomicroscope device before and after the cementation process and surface properties were evaluated by scanning electron microscopy (SEM). A dependent t-test was used to compare the mean of the two groups for normally distributed data, and two-way variance analysis was used for more than two data sets. Pearson''s correlation analysis was also performed to assess relationships between variables.

RESULTS

According to the results obtained, the marginal gap in the galvano copings before cementation was measured as, on average, 24.47 ± 5.82 µm before and 35.11 ± 6.52 µm after cementation; in the laser-sintered Co-Cr structure, it was, on average, 60.45 ± 8.87 µm before and 69.33 ± 9.03 µm after cementation. A highly significant difference (P<.001) was found in marginal gap measurements of galvano copings and a significant difference (P<.05) was found in marginal gap measurements of the laser-sintered Co-Cr copings. According to the SEM examination, surface properties of laser sintered Co-Cr copings showed rougher structure than galvano copings. The galvano copings showed a very smooth surface.

CONCLUSION

Marginal gaps values of both groups before and after cementation were within the clinically acceptable level. The smallest marginal gaps occurred with the use of galvano copings.     

The Peculiar Epidemiology of Dracunculiasis in Chad

Dracunculiasis was rediscovered in Chad in 2010 after an apparent absence of 10 years. In April 2012 active village-based surveillance was initiated to determine where, when, and how transmission of the disease was occurring, and to implement interventions to interrupt it. The current epidemiologic pattern of the disease in Chad is unlike that seen previously in Chad or other endemic countries, i.e., no clustering of cases by village or association with a common water source, the average number of worms per person was small, and a large number of dogs were found to be infected. Molecular sequencing suggests these infections were all caused by Dracunculus medinensis. It appears that the infection in dogs is serving as the major driving force sustaining transmission in Chad, that an aberrant life cycle involving a paratenic host common to people and dogs is occurring, and that the cases in humans are sporadic and incidental.