Atypical Presentation of Hashimoto’s Disease in an Adolescent: Thyroid-Associated Ophthalmopathy

Hashitoxicosis is generally differentiated from Graves’ hyperthyroidism by its shorter course and absence of ophthalmopathy. In this case report, we describe an adolescent girl who presented with significant clinical findings of hyperthyroidism, a diffuse goiter with homogenously increased uptake in scintigraphy, and with ocular findings of ophthalmopathy. The thyroid stimulating hormone receptor antibody test was positive, and the family history revealed thyroid-associated ophthalmopathy. Clinical findings supported the diagnosis of Hashimoto’s disease (HD) in the follow-up period. Radioactive iodine uptake investigation was found to be a reliable method for differential diagnosis. Attention was drawn to the rarity of pediatric cases of HD who present with ophthalmopathy.     

Indirect effects of cigarette butt waste on the dengue vector Aedes aegypti (Diptera: Culicidae)

Despite major insecticide-based vector control programs, dengue continues to be a major threat to public health in urban areas. The reasons for this failure include the emergence of insecticide resistance and the narrowing of the spectrum of efficient products. Cigarette butts (CBs), the most commonly discarded piece of waste, also represent a major health hazard to human and animal life. CBs are impregnated with thousands of chemical compounds, many of which are highly toxic and none of which has history of resistance in mosquitoes. This study was performed to examine whether exposure to CB alters various biological parameters of parents and their progeny. We examined whether the mosquito changes its ovipositional behaviors, egg hatching, reproductive capacity, longevity and fecundity in response to CB exposure at three different concentrations. Females tended to prefer microcosms containing CBs for egg deposition than those with water only. There were equivalent rates of eclosion success among larvae from eggs that matured in CB and water environments. We also observed decreased life span among adults that survived CB exposure. Extracts of CB waste have detrimental effects on the fecundity and longevity of its offspring, while being attractive to its gravid females. These results altogether indicate that CB waste indirectly affect key adult life traits of Aedes aegypti and could conceivably be developed as a novel dengue vector control strategy, referring to previously documented direct toxicity on the larval stage. But this will require further research on CB waste effects on non-target organisms including humans.     

Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease

Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.Essential tremor is one of the most frequent movement disorders in humans (1). It is characterized primarily by postural or kinetic tremor of the arms and hands, but head, legs, voice, and other regions of the body may also be affected (2). The worldwide prevalence is 0.9%, increasing to more than 4% in elderly populations (1). Familial essential tremor is genetically heterogeneous. Genetic linkage studies of multiply affected families revealed three genomic regions segregating with the condition, on chromosomes 3q13 [ETM1; Online Mendelian Inheritance in Man (OMIM) 190300], 2p22-24 (ETM2; OMIM 602134), and 6p23 (ETM3; OMIM 611456) (3–5). No clearly causal mutations have been identified in these regions, although the common variant DRD3 p.S9G in the ETM1 region has been proposed as a risk factor and HS1BP3 p.A265G in the ETM2 region appeared in two multiply affected families (6, 7). Genomewide association studies of essential tremor reported associations with common variants in an intron of LINGO1 and in an intron of SLC1A2 (8–10). Recently, DNAJC13 p.N855S, which had been identified in Parkinson disease patients, was also found in two unrelated patients with essential tremor (11). Nonsense mutation p.Q290X in the RNA-binding protein FUS was identified by whole exome sequencing in a large family with essential tremor (ETM4; OMIM 614782) (12). Screening other subjects with essential tremor for FUS revealed two rare missense variants, suggesting that mutations in FUS explain a subset of cases with the condition (13, 14).In this study, we examined a six-generation family segregating essential tremor, and in multiple relatives, essential tremor as a feature of Parkinson disease. We carried out whole exome sequencing of genomic DNA from three severely affected family members and subsequent pedigree analysis to identify the genetic basis of essential tremor and Parkinson disease in the family.     

DPP4 inhibitor induces beta cell regeneration and DDR-1 protein expression as an endocrine progenitor cell marker in neonatal STZ-diabetic rats

BackgroundWe aim to investigate the effects of dipeptidyl-peptidase-4 inhibitor (Vildagliptin-VG) on DDR-1 as a marker for endocrine progenitor cells, β-cell regeneration, and apoptosis in neonatal streptozotocin (n2-STZ) diabetics.MethodsNeonatal rats were divided into two main groups as short- and long-term treatment, each consisted of four groups; (1) Control, (2) n2-STZ diabetic (single dose of 100 mg/kg STZ at 2nd day of birth), (3) n2-STZ + VG (60 mg/kg/day VG orally; for 8 and 28 days), (4) VG (60 mg/kg/day orally; for 8 and 28 days). Blood glucose levels and body weights were measured, and the tissue sections were immunostained using insulin, glucagon, somatostatin, PCNA, Pdx-1 and DDR-1 antibodies. The TUNEL method was used for apoptosis.ResultsThe number of β cells in islets of the n2-STZ + VG group increased compared to the n2-STZ group; insulin (+) cells were observed individually or as small clusters in exocrine tissue, between pancreatic duct epithelial cells, and around the ducts. The number of Pdx-1 and DDR-1 positive cells in islet and extra-islet pancreas tissue was elevated as a result of VG application compared to the STZ diabetic group; the number of double positive cells for DDR-1 and insulin increased in n2-STZ + VG rats.ConclusionWe showed that vildagliptin promotes β cell neogenesis and regeneration, stimulates DDR-1 expression as an endocrine cell progenitor marker, suppresses apoptosis, induces islet cell proliferation and rearranges islet morphology in the n2-STZ diabetes model.     

Low Prevalence of Hepatitis C Virus Infection Among HIV-Positive Patients: Data From a Large-Scale Cohort Study in Istanbul,Turkey

Background:

Rate of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) varies in different countries. This may be attributable to common transmission routes as well as social, economic, and cultural factors.

Objectives:

The purpose of this study was to investigate the prevalence and risk factors of HCV infection among HIV-positive patients in Istanbul, Turkey.

Patients and Methods:

Since January 2006 to November 2013, 949 HIV-positive patients that were enrolled in this study by ACTHIV-IST (Action Against HIV in Istanbul) Study Group, which consists of five centers to follow up HIV-positive patients in Istanbul. Epidemiologic and clinical data were collected retrospectively from medical records and were transferred to an HIV database system.

Results:

Among 949 patients, 84% were men and the mean age was 37.92 ± 11.54 years (range, 17-79). The most frequent route of transmission was heterosexual intercourse (48.8%), followed by men having sex with men (30.5%). Only nine patients (0.9%) had history of injection drug use (IDU). The prevalence of HIV/HCV coinfection was 0.9% (9:949). The IDU rate was 44.4% (4:9) in patients with HIV/HCV coinfection (three of them were not Turkish citizens), whereas this rate was only 0.6% (5:881) in patients with only HIV infection (P < 0.01). Genotypes 1b, 2a/2c, and 3 were determined in five, one, and two patients, respectively. Genotype could not be determined in one patient. History of residence in a foreign country (P < 0.01) and imprisonment (P < 0.01) were also considered as risk factors in terms of HIV/HCV coinfection.

Conclusions:

Prevalence of HIV/HCV coinfection is considerably low in Turkey. The extremely rare prevalence of IDU might have a role in this low prevalence.     

Bleeding and non-bleeding phenotypes in patients with GGCX gene mutations

Functional limitations for the vitamin K cycle, caused either by mutations in gamma-glutamyl carboxylase or vitamin K epoxide reductase genes, result in hereditary deficiency of vitamin K-dependent coagulation factors (VKCFD1 and VKCFD2, respectively). Patients suffering from VKCFD often share several other anatomical irregularities which are not related to haemostasis. Here we report on nine patients, eight of them previously unreported, who presented with VKCFD1. All were examined with special attention to vitamin K-dependent coagulation factors as well as to bone and heart development and to other anatomical signs of embryonal vitamin K deficiency. In total, we detected ten mutations in the gamma-glutamyl carboxylase gene of which seven have not been previously reported. Most interestingly, additional non-bleeding phenotypes were observed in all patients including midfacial hypoplasia, premature osteoporosis, cochlear hearing loss, heart valve defects, pulmonary stenosis, or pseudoxanthoma elasticum-like phenotype. Undercarboxylated matrix Gla protein, osteocalcin, and periostin appear to be responsible for these defects which are also observed in cases of fetal warfarin syndrome.     

Increased inflammatory markers are associated with obesity and not with target organ damage in newly diagnosed untreated essential hypertensive patients

The aim of this study was to investigate whether inflammatory markers are associated with hypertensive end organ damage or obesity in patients with hypertension. Seventy newly diagnosed essential hypertensive patients (29 men and 41 women aged 49.6 ± 9.5 y) and 25 age-sex-matched normotensive subjects (12 men and 13 women aged 45.8 ± 7.3 y) were asked about their family history of hypertension and smoking habits, and body mass index (BMI) was recorded and blood samples were taken to measure fibrinogen, C-reactive protein (CRP), and homocysteine levels. In hypertensive patients, creatinine clearance, urinary albumin extraction, and left ventricular mass index were determined. Hypertensive patients had significantly higher BMIs and inflammatory markers when compared with normotensive healthy controls. The CRP was positively associated with BMI (P < .05), diastolic blood pressure (P < .05), fibrinogen (P < .01), urinary albumin extraction (P < .01), and left ventricular mass index (P < .05). The BMI and serum fibrinogen level were independently associated with CRP. The effect of inflammation on the development of hypertensive end organ damage may be associated with obesity, so that control of obesity may eliminate the inflammatory state in hypertensive patients and also hypertensive end organ damage.     

The Association of Metabolic Syndrome, Insulin Resistance and Non-alcoholic Fatty Liver Disease in Overweight/Obese Children

Background/Aim:

To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT).

Patients and Methods:

Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy.

Results:

Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%).

Conclusion:

There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.