In this study, the performances of type of demountable connectors used as connecting elements in the frame construction furniture are compared with the forces against shear force. The test samples ...were prepared from melamine-coated particle board (YL-Lam) and medium density fiberboard (MDF-Lam). Four types of demountable type of connection elements are used: metal L connection, plastic T connection, metal T connection and moon connection. The experimental samples were subjected to static stress tests under the critical loads that could be affected during the use. As a result of the experiments, the highest shear force was obtained from the test specimens prepared by using MDF-Lam and metal T connectors. The lowest was determined by using YL-Lam and plastic T connector. According to the results of the experiment, in the H type construction prepared with YL-Lam, when the shear force bearing capacity of the connection element is ordered from highest to lowest, respectively; Metal T, Moon, Metal L and Plastic T connectors were determined while in the construction prepared with MDF-Lam it is ordered as Metal T, Metal L, Plastic T and Moon connectors. In this study, the load-bearing capacity of the test samples and the load-deflection graph formed under this loading are given.
Neonatal diabetes is caused by single gene mutations reducing pancreatic β cell number or impairing β cell function. Understanding the genetic basis of rare diabetes subtypes highlights fundamental ...biological processes in β cells. We identified 6 patients from 5 families with homozygous mutations in the YIPF5 gene, which is involved in trafficking between the endoplasmic reticulum (ER) and the Golgi. All patients had neonatal/early-onset diabetes, severe microcephaly, and epilepsy. YIPF5 is expressed during human brain development, in adult brain and pancreatic islets. We used 3 human β cell models (YIPF5 silencing in EndoC-βH1 cells, YIPF5 knockout and mutation knockin in embryonic stem cells, and patient-derived induced pluripotent stem cells) to investigate the mechanism through which YIPF5 loss of function affects β cells. Loss of YIPF5 function in stem cell-derived islet cells resulted in proinsulin retention in the ER, marked ER stress, and β cell failure. Partial YIPF5 silencing in EndoC-βH1 cells and a patient mutation in stem cells increased the β cell sensitivity to ER stress-induced apoptosis. We report recessive YIPF5 mutations as the genetic cause of a congenital syndrome of microcephaly, epilepsy, and neonatal/early-onset diabetes, highlighting a critical role of YIPF5 in β cells and neurons. We believe this is the first report of mutations disrupting the ER-to-Golgi trafficking, resulting in diabetes.
Context:
Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near-total lack of body fat.
Objective:
We aimed to study natural history and disease ...burden of various subtypes of CGL.
Design:
We attempted to ascertain nearly all patients with CGL in Turkey.
Setting:
This was a nationwide study.
Patients or Other Participants:
Participants included 33 patients (22 families) with CGL and 30 healthy controls.
Main Outcome Measure(s):
We wanted to ascertain genotypes by sequencing of the known genes. Whole-body magnetic resonance imaging was used to investigate the extent of fat loss. Metabolic abnormalities and end-organ complications were measured on prospective follow-up.
Results:
Analysis of the AGPAT2 gene revealed four previously reported and four novel mutations (CGL1; c.144C>A, c.667_705delinsCTGCG, c.268delC, and c.316+1G>T). Analysis of the BSCL2 gene revealed four different homozygous and one compound heterozygous possible disease-causing mutations (CGL2), including four novel mutations (c.280C>T, c.631delG, c.62A>T, and c.465-468delGACT). Two homozygous PTRF mutations (c.481-482insGTGA and c.259C>T) were identified (CGL4). Patients with CGL1 had preservation of adipose tissue in the palms, soles, scalp, and orbital region, and had relatively lower serum adiponectin levels as compared to CGL2 patients. CGL4 patients had myopathy and other distinct clinical features. All patients developed various metabolic abnormalities associated with insulin resistance. Hepatic involvement was more severe in CGL2. End-organ complications were observed at young ages. Two patients died at age 62 years from cardiovascular events.
Conclusions:
CGL patients from Turkey had both previously reported and novel mutations of the AGPAT2, BSCL2, and PTRF genes. Our study highlights the early onset of severe metabolic abnormalities and increased risk of end-organ complications in patients with CGL.
We report 33 patients with CGL from a nationwide study from Turkey. Our study highlights the early onset of severe metabolic abnormalities and end-organ complications in CGL.
Aim
Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by adrenal insufficiency, achalasia, and alacrimia. This disorder is caused by mutations in the
AAAS
gene. The aim of ...this study is to discuss the clinical, laboratory and molecular genetic analysis results of 12 patients with TAS.
Method
We evaluated 12 patients from 8 families. Clinical and laboratory data were retrospectively collected from the medical records of the patients in the database for the period 2015–2020. All exons and exon-intron junctions of the
AAAS
gene were evaluated by next-generation sequencing method. Detected variants were classified according to American Collage of Medical Genetics criteria.
Results
Alacrimia was found in all patients (100%); achalasia was found in 10 patients (83.3%) and adrenal insufficiency was found in 10 patients (83.3%). In addition, hyperreflexia(6/12), learning disability(5/12), hypernasal speech(5/12), muscle weakness(8/12), delayed walking(7/12), delayed speech(6/12), excessive sweating(7/12), optic atrophy(1/12), epilepsy(1/12), palmoplantar hyperkeratosis(5/12), multiple dental caries(9/12), atrophy of the thenar/hypothenar muscles(4/12) and short stature(4/12) were detected. The DHEA-S levels were measured in 10 patients and were found to be low in 8 of them. In all patients, the sodium and potassium levels were found to be normal. AAAS gene sequencing revealed four previously reported c.1066_1067del (p.Leu356fs*8), c.1432 C > T (p.Arg478*), c.688 C > T (p.Arg230*), and c.1368_1372del (p.Gln456fs*38) variants and two novel homozygous c.1250-1 G > A and c.398_399 + 2del variants in the
AAAS
gene.
Conclusion
We detected two novel variants in the
AAAS
gene. While the classic triad is present in 66.7% of the cases, neurological dysfunction, skin and dental pathologies also occur quite frequently. The earliest and most common finding of TAS is alacrimia. Therefore, adrenal insufficiency should be investigated in all patients with alacrimia and if necessary, genetic analysis should be performed for TAS. In addition, TAS should be followed up with a multidisciplinary approach since it involves many systems.
P450 oxidoreductase (POR) deficiency is a rare form of congenital adrenal hyperplasia. In both genders, it can lead to ambiguous genitalia, impaired steroidogenesis, and skeletal findings similar to ...those of Antley-Bixler syndrome.
We describe two cases of POR deficiency. The first case was an 8.5-year-old girl who was admitted to our clinic due to ambiguous genitalia. Karyotype was 46, XX. There were mild dysmorphic facial findings and mild metacarpophalangeal joint deformity. The patient's basal cortisol and ACTH levels were normal, while 17-hydroxyprogesterone (17OHP) levels were high. Peak cortisol response to the ACTH stimulation test was found to be insufficient. Our second case, a sibling of the first case, was admitted for routine checkup at the age of 15 months. As in our first case, there were dysmorphic facial findings and metacarpophalangeal joint deformity. The genital structure was normal. Karyotype was 46, XY. Basal cortisol and ACTH levels were normal, while 17OHP level was slightly high. Peak cortisol response to the ACTH stimulation test was found to be insufficient. Based on our findings, POR deficiency was considered in both of these cases and NM_000941.3:c.929_937delTCTCGGACT(p.Ile310_Ser313delinsThr) (homozygous) mutation was detected in the POR gene that had not previously been described.
We detected a novel variant in the POR gene in two sibling cases with adrenal insufficiency, dysmorphic face, and mild skeletal findings. While the detected mutation caused ambiguous genitalia in the female case, it did not cause ambiguous genitalia in the male case.
Abstract
Context
Biallelic mutations in the PTF1A enhancer are the commonest cause of isolated pancreatic agenesis. These patients do not have severe neurological features associated with ...loss-of-function PTF1A mutations. Their clinical phenotype and disease progression have not been well characterized.
Objective
To evaluate phenotype and genotype characteristics and long-term follow-up of patients with PTF1A enhancer mutations.
Setting
Twelve tertiary pediatric endocrine referral centers.
Patients
Thirty patients with diabetes caused by PTF1A enhancer mutations. Median follow-up duration was 4 years.
Main Outcome Measures
Presenting and follow-up clinical (birthweight, gestational age, symptoms, auxology) and biochemical (pancreatic endocrine and exocrine functions, liver function, glycated hemoglobin) characteristics, pancreas imaging, and genetic analysis.
Results
Five different homozygous mutations affecting conserved nucleotides in the PTF1A distal enhancer were identified. The commonest was the Chr10:g.23508437A>G mutation (n = 18). Two patients were homozygous for the novel Chr10:g.23508336A>G mutation. Birthweight was often low (median SDS = –3.4). The majority of patients presented with diabetes soon after birth (median age of diagnosis: 5 days). Only 2/30 presented after 6 months of age. All patients had exocrine pancreatic insufficiency. Five had developmental delay (4 mild) on long-term follow-up. Previously undescribed common features in our cohort were transiently elevated ferritin level (n = 12/12 tested), anemia (19/25), and cholestasis (14/24). Postnatal growth was impaired (median height SDS: –2.35, median BMI SDS: –0.52 SDS) with 20/29 (69%) cases having growth retardation.
Conclusion
We report the largest series of patients with diabetes caused by PTF1A enhancer mutations. Our results expand the disease phenotype, identifying recurrent extrapancreatic features which likely reflect long-term intestinal malabsorption.
Aim
To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow‐up.
Methods
This study reports on 72 ...patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow‐up was 86 ± 78 months.
Results
The Kaplan–Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan–Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan–Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan–Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow‐up period. Causes of death were end‐stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma.
Conclusions
Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.
The incidence of type 1 diabetes mellitus (T1D) in children has an increasing trend globally, with a variable rate depending on region and ethnicity. Our group first reported T1D incidence in ...Diyarbakır in 2011. The aim of this study was to evaluate the current incidence rate of pediatric T1D in Diyarbakır, and compare the incidence, and clinical and presenting characteristics of more recent cases with those reported in our first report.
Hospital records of patients diagnosed with T1D in Diyarbakır city between 1
January 2020 and 31
December 2020 and aged under 18 years old were retrieved, and their medical data was extracted. Demographic population data were obtained from address-based census records of the Turkish Statistical Institution (TSI).
Fifty-seven children and adolescents were diagnosed with T1D. Of those, 34 were female (59.6%), indicating a male/female ratio of 1.47. The mean age at diagnosis was 9.5±3.9 years (0.8-17.9). TSI data indicated a population count of 709,803 for the 0-18 years age group. Thus the T1D incidence was 8.03/10
in the 0-18 age group and was higher in the 0-14 age group at 9.14/10
. The cumulative increase in the incidence of T1D in the 0-14 age group was 26.9% suggesting an increasing rate of 2.7% per year. The frequency of presentation with diabetic ketoacidosis was 64.9%.
The annual incidence of pediatric T1D in Diyarbakır city increased from 7.2/10
to 9.14/10
within the last decade. The rate of annual increase was 2.7% in the 0-14 age group comparing this study with our earlier report, with a predominance in male subjects and a shift of peak incidence from the 5-9 year age group in the first study to the 10-14 year age group in this one.
Bu çalışmada, farklı ağaç malzemelerden elde edilen kavelalar kullanılarak hazırlanmış L-tipi mobilya
birleştirmelerinin moment taşıma kapasiteleri araştırılmıştır. Çalışmada, birleştirme elemanı ...olarak Kestane
(Castanea sativa), Meşe (Quercus petraea Lieble), DoğuKayını (Fagus orientalis Lipsky) ve Dişbudak
(Fraxinus excelsior L.)odunlarından elde edilen kavelelar kullanılmıştır. Ahşap esaslı malzemelerden melamin
plaka ile kaplanmış yonga levha (Lam-YL) ve orta yoğunlukta lif levha (MDF-Lam) konstrüksiyon
malzemesiolarakseçilmiştir.Yapıştırma işleminde fiziksel olarak kuruyan ve mobilya endüstrisinde en çok
kullanılan polivinilasetat (PVAc-D3) tutkalı kullanılmıştır. Deneyler ASTM-D1037 standartlarına göre statik
yük altında gerçekleştirilmiştir. Çalışma sonucunda, diyagonal çekme yükü altında en yüksek moment taşıma
kapasite değeri dişbudak kavelada (82.19 N.m), en düşük moment taşıma kapasitesi değeri ise kestane
kavelasında (51.15 N.m) olduğu belirlenmiştir. Diyagonal basınç yüküaltında en yüksek moment taşıma kapasite
değeri dişbudak kavelada (36.84 N.m), en düşük moment taşıma kapasitesi değeri ise kestane kavelasında (22.98
N.m) olduğu tespit edilmiştir. Varyans analizi sonuçlarına göre, basınç ve çekme yükü altında moment taşıma
kapasitesi ortalama değeri üzerinde levha tipi ve kavela malzeme çeşidinin etkileri p<0.05 önem düzeyinde
anlamlı iken, ikili etkileşim grupları incelendiğinde aralarında farkın istatistiksel olarak anlamlı olmadığı
tespitedilmiştir. Levha türü sonuçlarına gore ise en yüksek değer melamin plaka ile kaplanmış orta yoğunlukta lif
levha (MDF Lam), en düşük ise melamin plaka ile kaplanmış yonga levhada (Lam-YL) elde edilmiştir. Mobilya
mukavemetinde önem arz eden “L” köşe birleştirmelerinde MDF-Lam malzemesi ve dişbudak kavelası ile
birleştirilmiş konseptin kullanılması önerilebilir.
In this study, moment carrying capacities of L-type furniture joints prepared using dowels obtained from
different wood materials were investigated. Dowel pins which are obtained from Turkish Beech (Fagus Orientalis Lipsky), Oak (Quercus Petraea Lieble), Chestnut (Castanea SativaMill) and Ashen(Fraxinus Excelsior
L.) were used as the wooden particleboard coated (Sunta-Lam) and medium density fiberboard coated (MDFLam) with melamine sheet. These dowel pins wood-based materials were selected as construction materials. In
the joining process, polyvinyl acetate (PVAc-D4) glue which is the most used in the furniture industry and
physically dries quickly was used. The tests were carried out under static load according to the principles
specified in the ASTM-D1037 standard. It is aimed to determine the moment transfer in the effect of diagonal
pulling and diagonal pushing forces of corner join. As a result of the study, the highest moment carrying capacity
value under diagonal tensile load was found in the ashen dowel (82.19 N.m) and the lowest moment carrying
capacity value was found in the chestnut dowel (51.15 N.m). Under the diagonal pressure load, the highest
moment carrying capacity value was found in the ash dome (36.84 N.m) and the lowest moment carrying
capacity value was found in the chestnut dowel (22.98 N.m). According to the sheet type results, the highest
value was obtained at medium density fiberboard surfaced with melamine sheet (MDF Lam) and the lowest at
particleboard surfaced with melamine sheet (Lam YL). It can be suggested to use the medium density fiberboard
material and concept joined with the ashen dowel at the corner joints that are important in furniture strength.
Hypophosphatemic rickets (HR) is a rare renal phosphate-wasting disorder, which is usually X-linked and is commonly caused by PHEX mutations. The treatment and follow-up of HR is challenging due to ...imperfect treatment options.
Here we present nationwide initial and follow-up data on HR.
From 24 centers, 166 patients were included in the study. Genetic analysis (n=75) showed
mutation in 80% of patients. The mean follow-up period was 6.7±2.4 years. During the first 3-years of treatment (n=91), mild increase in phosphate, decrease in alkaline phosphatase and elevation in parathyroid hormone (PTH) levels were detected. The height standard deviation scores were -2.38, -2.77, -2.72, -2.47 at initial, 1
, 2
and 3
year of treatment, respectively (p>0.05). On follow-up 36% of the patients showed complete or significant improvement in leg deformities and these patients had similar phosphate levels at presentation with better levels in 1
and 2
years of treatment; even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis (NC), the patients showed no difference in biochemical differences at presentation and follow-up, but 3
year PTH was higher. However, higher treatment doses of phosphate and calcitriol were found in the NC group.
HR treatment and follow-up is challenging and our results showed higher treatment doses were associated with NC without any change in serum phosphate levels, suggesting that giving higher doses led to increased phosphaturia, probably through stimulation of fibroblast growth factor 23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed.
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