Lateral sinus thrombosis in a young patient with sudden neurosensorial hearing loss and genetic thrombophilia: A case report.

Sensorineural hearing loss (SSHL) with a sudden onset is frequently encountered as a medical emergency in the ear, nose and throat (ENT) practice. The exact pathophysiology of the disease remains unknown, with the most likely etiologies being viral infection, inflammation, drug toxicity, trauma, or autoimmune response. Even though thrombophilia and cerebrovascular complications may lead, among others, to sudden neurosensorial hearing loss, its diagnosis is most often made following the onset of thrombotic complications. A case of a young female patient with unknown congenital hypercoagulation status complicated with lateral sinus thrombosis and unilateral drug-induced reversible hearing loss is presented. Molecular testing confirmed the diagnosis of genetic thrombophilia, due to the homozygous V Leiden, homozygous MTHFR A1298C, and heterozygous MTHFR C677T mutations. Although hereditary thrombophilia is a well-known topic in medical practice, current guidelines require continuous improvement, especially among patients treated in departments where this pathology is more difficult to recognize and manage.

Influence of vitamin D receptor polymorphism rs2228570 on pathological scarring.

The physiological process of scarring is a common denominator of interest in a plethora of medical specialties. The molecular basis whereby this process results in pathological scarring for some individuals is poorly understood at present, with clues pointing towards individual predisposition for pathological scarring. Vitamin D and its subsequent pathway plays a key role in skin metabolism and homeostasis, with alterations in the level of vitamin D receptor (VDR) seen within pathological scars. The present study investigated the role of the rs2228570 polymorphism of VDR with regards to scar formation and evolution in a group of 71 female patients recovering from Caesarian section. Blood samples were taken at the time of surgery, and the follow-up was collected remotely at 3 and 6 months after surgery. The rs2228570 polymorphism was investigated using an RFLP-PCR protocol. The results demonstrated that the CC genotype, in combination with the Patient Observer Scar Assessment Scale (POSAS) and SCAR scores are associated with pathological scarring, with more studies being necessary to draw a firm conclusion.

Role of hTERT rs2736100 in pathological scarring.

Hypertrophic and atrophic scars are the effect of a dysregulated wound-healing process in genetically predisposed individuals. The genetic predisposition has acquired significant attention due to the diverse phenotype of pathological scarring in individuals with a positive personal and family history. Recent studies have identified telomere shortening and decreased hTERT activity in pathological scarring, proposing the rs2736100 variant of human telomerase reverse transcriptase (hTERT) gene as a valuable variant gene candidate. We examined the scarring process in 71 female patients who had undergone Caesarean section and developed hypertrophic and atrophic scars with the objective to investigate the role of single nucleotide polymorphism (SNP) rs2736100 in pathological scarring. Genotyping was performed using RT-PCR and follow-up included the Patient Observer Scar Assessment Scale (POSAS) and SCAR scales. Comparative analysis for mean POSAS value between the check-ups at 3 and 6 months revealed a statistical decreased difference of 1.71 points [95% confidence interval (CI), 0.4-2.89; P=0.01], while SCAR highlighted a decreased difference of 0.670 (95% CI, -0.04-1.38; P=0.055). The C variant allele revealed a borderline statistical value for the risk of developing pathological scarring (OR=1.44; 95% CI, 0.876-1.332: P=0.066). In our study a pre-conceptional body mass index (BMI) >25 kg/m2 was statistically associated with pathological scarring. The Fitzpatrick type 4 phototype displayed an increased frequency for the heterozygous genotype in the current study, and it was demonstrated that dark skin tone was associated with abnormal scar formation. Our study investigated the role of hTERT gene variant rs2736100 in hypertrophic and atrophic scarring in a Caucasian population group. We report a borderline statistically significant value for the variant C allele of hTERT SNP for the risk of developing pathological scarring in female patients that had undergone Caesarean section.

Prenatal screening for Down syndrome: popularity, perceptions and factors associated with acceptance or refusal of testing.

BACKGROUND: Prenatal screening tests for aneuploidies have become increasingly used in maternal and fetal medicine. Given that all pregnancies associate a potential risk of Down syndrome, adequate knowledge of the tests, and their characteristics as well as facilitating decision-making autonomy are fundamental rights that must be respected. OBJECTIVES: Identification of the popularity of the tests, their perception and the factors associated with the acceptance or refusal to perform them. METHODS: A cross-sectional study was carried out in the South-East region of Romania, between April and September 2016. The data were collected from 275 postpartum women. The instrument used was a self-administered questionnaire and the data obtained were processed using the IBM SPSS 20.0 statistical software (IBM Corp., Armonk, NY, USA). The normality of the distribution was analyzed with Chi-square, Kolmogorov-Smirnov and Shapiro-Wilk tests. Factorial Analysis was carried out for the Principal Components of the scales for the reasons for performing and not performing. RESULTS: The 2nd Trimester Morphology had the popularity as well as the highest rate of accomplishment (98.2% respectively 67.6%) among the investigated women. It is also the preferred recommendation of the specialists (81.1%). The least popular test was the TPNI, only 13.1% of the participants heard about it, as it was recommended in only 2% of the situations. Most of the participants perceived the screening tests as essential and useful, but 43.3% considered that they become mandatory if the doctor recommends them. The acceptance of the child with DS and the misperception of the risk were the main factors associated with the refusal of the test and the compliance with the recommendation of the specialist (system confidence), and social influence (non-acceptance of the Down syndrome by the society) were the main factors associated with the acceptance. CONCLUSIONS: The number of women who made the decision to accept the test was greater than the ones who refused. The amendment is that acceptance was based on the custom of socio-economic-medical compliance and responsibility. For many women, the motivation of acceptance meant alignment with the normality directed by the society and the system. Even the popularity of the tests carries the imprint of the beliefs and values of the system and the specialists involved. For an adequate perception and an autonomous and informed choice of women, the screening program must include adequate information and communication services by involving specialists responsible for multidisciplinary competencies. The percentage of completion and the type of test performed almost perfectly align with the recommendations received.

Involvement of COL5A2 and TGF-ß1 in pathological scarring.

Dysregulation in the cutaneous wound-healing process is a consequence of alterations in the efficiency and activity of the various components involved in the healing process. This dysregulation may result in various clinical appearances of a lesion, such as skin ulcers, keloids, hypertrophic and atrophic scars. The collagen type V alpha 2 (COL5A2) gene provides a template for a component of type V collagen, found primarily within the skin basement membrane. Transforming growth factor (TGF)-ß is involved in inflammation, angiogenesis, proliferation of fibroblasts, collagen synthesis and extracellular matrix remodeling. Hypertrophic scar fibroblasts possess a disrupted expression pattern of the TGF-ß signaling compared to normal healing, while an increased TGF-ß signaling reduces the epidermal proliferation rate, triggering atrophic scarring. In the present study, 71 female patients who had undergone planned Caesarean section, without postoperative complications, were examined. These patients were clinically and molecularly evaluated after developing scars in order to determine the role of TGF-ß1 (rs201700967 and rs200230083) and COL5A2 (rs369072636) in pathological scarring. Clinical scar evaluation was carried out using SCAR and POSAS scales and genotyping was performed by RT-PCR. No statistical differences were found between the subgroups regarding the genotype and the pathological scarring, since all the patients included were wild-type allele carriers. Further investigations and a more representative study group may highlight the involvement of COL5A2 and TGF-ß1 single nucleotide variants in pathological scarring.

Role of Adiponectin and Tumor Necrosis Factor-Alpha in the Pathogenesis and Evolution of Type 1 Diabetes Mellitus in Children and Adolescents.

Type 1 diabetes mellitus (T1DM) is a complex condition caused by the destruction of pancreatic beta cells by autoimmune mechanisms. As a result, insulin deficiency and subsequent hyperglycemia occur. The aim of the present study is to investigate the role of adiponectin and tumor necrosis factor alpha (TNF-α) in the development of T1DM. The study is designed as an observational case-control study, involving 52 diabetic patients and 66 controls. Z scores for Body Mass Index (BMI), weight, height, and adiponectin and TNF-α serum levels were assessed in both groups. The T1DM group had significantly higher TNF-α levels and a significantly higher proportion of high-risk patients for inflammation based on TNF-α values as compared to the control group, while both groups had statistically similar adiponectin levels and a similar proportion of high/medium-risk patients based on adiponectin values. TNF-α plays a significant role in the pathogenesis and evolution of T1DM and it may represent an additional marker of disease progression, as well as a potential target of immunotherapeutic strategies. In the present study, no statistically significant differences were recorded in adiponectin levels neither in diabetic patients and controls, nor in high/medium severity risk diabetic patients.

The Role Of Adiponectin, TNF-α And Glutathione In The Pathogenesis And Evolution Of Type 1 Diabetes.

INTRODUCTION: Type 1 diabetes (T1DM) is a chronic autoimmune or idiopathic condition, featuring complex and unique interactions between proteins and enzyme systems. The purpose of the present study is to investigate the role of AdipoQ +276G>T, TNF-α-308G>A, GSTT1/GSTM1 polymorphic variants in the development of T1DM. MATERIALS AND METHODS: The study is designed as a cross-sectional study, involving 72 diabetic cases and 90 controls. Genotyping was carried out according to specific protocols for the above-mentioned polymorphic variants. RESULTS: The G allele of AdipoQ was associated with the development of type 1 diabetes (OR 0.577, CI95% 0.336-0.802, p=0.001), similar to the GG and GA genotypes (OR 0.405, CI95% 0.156-0.654, p=0.001 and OR 0.623, CI95% 0.401-0.855, p=0.004). The G allele of TNF-α was marginally associated with the development of type 1 diabetes (OR 0.789, CI95% 0.579-0.956, p=0.005). The presence of the T1 genotype was a strong predictor for type 1 diabetes (OR 3.4, CI95% 1.433-6.243, p<0.001). CONCLUSION: The results of our study suggest that G alleles of AdipoQ and TNFα act as a protective factor in T1DM, while the T1 allele for GST could be considered a risk factor for the development of Type 1 diabetes in our study group.

The influence of GSTT/GSTM null genotypes in scarring.

BACKGROUND AND AIMS: The process of scarring is a common denominator of interest for the medical field. From general medicine to dentistry, pathological scar tissue represents a challenge in providing optimal care to a patient. The present study aims to investigate whether a systemically reduced antioxidant potential, revealed by null isoforms of glutathione S transferase, affects the process of scarring in a group of female patients. METHODS: The study is based on a group of 54 patients with physiological scars after a 6-month observation period, as well as 18 patients with hypertrophic or atrophic scars. Peripheral venous blood was collected, from which DNA was extracted using a commercial kit. Genotyping followed a Multiplex PCR protocol for GSTT1/GSTM1. RESULTS: In a dominant model, the combination of wild type (heterozygous or homozygous) GSTT1 and GSTM1 was negatively associated with pathological scarring, with the wild type (heterozygous or homozygous) GSTM1 genotype being potentially responsible for this effect. Other factors affecting pathological scarring were investigated: family history, phototype, as well as scores on the POSAS and SCAR scales. CONCLUSIONS: The presence of GSTT1 and GSTM1 alleles brings forward an increased antioxidant capacity, serving as a protective factor for patients during scar formation.

Attitude, knowledge and informed choice towards prenatal screening for Down Syndrome: a cross-sectional study.

BACKGROUND: Down Syndrome screening test is a bridge between knowledge and uncertainty, safety and risk, unpredictability and desire to know in order to gain control. It may be accepted either not to have a baby with Down syndrome, or to prepare to have a baby with this condition. Every woman should understand that it is an option and should be encouraged to make their own decisions based on information and personal values. The implications and possible subsequent scenarios differentiate this type of test from the common biochemical tests performed during pregnancy, of paramount importance being the right to make informed choices. The aim of this study was to investigate the knowledge and attitude towards prenatal Down syndrome screening in order to asses to what extent the Romanian women make informed choices in this area. METHODS: A cross-sectional study was carried out that included 530 postpartum women, clients of Romania' south-east region maternities, during April-September 2016. The level of knowledge and the attitude concerning the Down syndrome screening were evaluated using a questionnaire. Data were analyzed using SPSS version 20.0. RESULTS: 48.1% of the women have never heard about any tests for Down Syndrome and from those 51.9% who have heard, only 14.2% made an informed choice, 78.9% had a positive attitude for screening, 88% were classified as having insufficient knowledge and 68.3% made a value-consistent decision to accept or decline prenatal screening. A higher knowledge level was associated with a higher education level and the urban residence. The information satisfaction and confidence in the overall value of screening were predictive factors of positive attitude. More informed choices were made by women monitored by an obstetrician in a private practice. CONCLUSIONS: The prenatal screening tests for Down Syndrome were mostly unknown and the women who accepted or not to perform a test were insufficiently knowledgeable that means that the ethical concept of the informed choice wasn't followed. In our opinion the Romanian Health System needs to improve the antenatal policy by developing an adequate information strategy at the reproductive population level based on a network of trained specialists.

Health Related Quality of life in bladder cancer. Current approach and future perspectives.

Bladder cancer is a real health problem due to its increased incidence, high recurrence rate and the fact that usually it is detected in advanced stages with limited number of diagnostic tools and different therapy response rates to current therapeutic strategies. Because of these issues we must develop screening programs and sensitive diagnostic strategies capable of detecting the disease during its early stages but also for characterizing evolution, prognosis and therapeutic response. Issues of great importance are those related to health quality of life of patients from the moment of diagnosis till the use of existing therapeutic approaches. This paper reviews some facets of life quality in patients diagnosed with bladder cancer stressing upon some proposed questionnaires and some new cell and molecular biology and genomic acquisitions (molecular biomarkers) that may become indicators of prognosis, therapeutic response and life quality but also essential tools in guiding therapeutic strategies.

Clinical and genetic characteristics in a group of 45 patients with Turner syndrome (monocentric study).

INTRODUCTION: Recent years have seen a shift in perspective on Turner syndrome, as it is no longer considered a significant disability due to therapeutic advances. The delay of diagnosis and the underdiagnosis are common in Turner syndrome, especially because of the great phenotypic variability and lack of firm diagnostic criteria. AIM: Our first aim was to assess the clinical and the cytogenetic characteristics and growth rate in growth hormone (GH)-treated patients as compared to those with spontaneous growth. The second aim was to analyze the Y chromosomal sequences. MATERIALS AND METHODS: We analyzed 45 patients diagnosed with Turner syndrome in Genetic Pathology Centre of Cluj Emergency Children's Hospital. We carried out a study of the clinical features, the correlations between the karyotype and the phenotype, and we also made a research of Y chromosome sequences. RESULTS: The average age at diagnosis was 8.9±5.4 years. A significant association was observed between the number of external phenotypical abnormalities and internal malformations (r=0.45), particularly the cardiovascular ones (r=0.44). Patients treated with GH showed improvement in growth rate, with final stature significantly better than in untreated patients; benefits following treatment were greater if diagnosis was made before the age of 5 years. Thirteen percent of patients experienced spontaneous and complete puberty, whereas 30% experienced incomplete puberty. Patients with the 45,X genotype had a greater stature deficit and a higher incidence of cardiac malformations, compared with patients with 45,X/46,XX mosaic karyotype. Y chromosome sequences were found in only one patient, who subsequently underwent gonadectomy. CONCLUSION: The importance of this study resides, to the best of our knowledge, in the fact that the largest group of patients in Romania was analyzed and assessed. To draw firm conclusions on the most valuable clinical indicators for Turner syndrome diagnosis in clinical practice, studies on large groups of patients should be conducted.

Novel non invasive diagnostic strategies in bladder cancer.

Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, -145, -222, -210, -10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population.

XRCC3 Thr241Met Polymorphism is not Associated with Lung Cancer Risk in a Romanian Population.

BACKGROUND AND AIMS: Deoxyribonucleic Acid (DNA) repair mechanisms play a critical role in protecting the cellular genome against carcinogens. X-ray cross-complementing gene 3 (XRCC3) is involved in DNA repair and therefore certain genetic polymorphisms that occur in DNA repair genes may affect the ability to repair DNA defects and may represent a risk factor in carcinogenesis. The purpose of our study was to investigate the association between XRCC3 gene substitution of Threonine with Methionine in codon 241 of XRCC3 gene (Thr241Met) polymorphism and the risk of lung cancer, in a Romanian population. METHODS: We recruited 93 healthy controls and 85 patients with lung cancer, all smokers. Thr241Met, XRCC3 gene genotyping was determined by multiplex Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Statistical analysis (OR, recessive model), did not revealed an increased risk for lung cancer, for the variant 241Met allele and Thr241Met genotypes (p=0.138, OR=0.634, CI=0.348-1.157; p=0.023, OR=0.257, CI=0.085-6.824). Also, there were no positive statistical associations between Thr241Met polymorphism of XRCC3 gene, gender, tobacco and various histopathological tumor type of lung cancer. CONCLUSION: In conclusion, the results of the study suggest that the XRCC3 gene Thr241Met polymorphism is not associated with an increased risk for the development of lung cancer in this Romanian group.

Genetic testing in patients with global developmental delay / intellectual disabilities. A review.

Genetic factors are responsible for up to 40% developmental disability cases, such as global developmental delay/intellectual disability (GDD/DI). The American and more recently the European guidelines on this group of diseases state that genetic testing is essential and should become a standardized diagnostic practice. The main arguments for the necessity of implementing such a practice are: (1) the high prevalence of developmental disabilities (3% of the population); (2) the high genetic contribution to this type of pathology; (3) insufficient referral for genetic consultation. In an attempt to address these issues, the purpose of this paper is to present the genetic etiology of global developmental delay / intellectual disability with emphasis on the need to implement a genetic testing protocol for the patients with GDD/DI, as indicated by the current guidelines. Chromosomal abnormalities and fragile X syndrome are the most frequent causes of developmental disabilities and the techniques employed to detect such genetic disorders should be used as first line investigations of GDD/DI.

Relationship between VKORC1 single nucleotide polymorphism 1173C>T, bone mineral density & carotid intima-media thickness.

BACKGROUND & OBJECTIVES: The effects of vitamin K-dependent proteins in bone mineralization and vascular calcification and the implication of vitamin K epoxide reductase gene (VKORC1) 1173C>T polymorphism in warfarin sensitivity are well known. The main objective of the study was to investigate the relationship between VKORC1 1173C>T polymorphism, bone mineral density (BMD), and atherosclerosis (evaluated by intima-media thickness of the carotid artery and the presence of calcified plaques) in patients suspected to have osteoporosis or osteopenia and referred for BMD determination. METHODS: VKORC1 1173C>T polymorphism was evaluated in 239 consecutive patients referred by their physicians for BMD measurement (dual energy X-ray absorptiometry at L2-L4 lumbar spine, femoral neck and total hip). Ultrasonography of the carotid arteries was performed, intima-media thickness (IMT) was measured and the presence of atherosclerotic calcified plaques was recorded. RESULTS: In the patients with osteoporosis and osteopenia there was a higher frequency of TT genotype of VKORC1 1173C>T (P=0.04). The TT genotype was significantly more frequent in the osteoporotic group compared to the osteopenic group (P=0.01). The mean age and body mass index were lower in the patients with normal BMD and TT genotype (P=0.02, P=0.03). There was no correlation between the IMT and VKORC1 1173C>T genotype but the TT genotype had a significant association with the presence of calcified atherosclerotic plaques (P=0.05). This finding was not correlated with normal or pathologic BMD. INTERPRETATION & CONCLUSIONS: VKORC1 1173C>T polymorphism (TT genotype) was associated with osteoporosis and calcified plaques in the carotid artery in patients referred for BMD measurement. Different mechanisms are probably involved in these associations. TT genotype may serve as a potential genetic marker for the risk of OP and ATS.

276G>T Polymorphism of the ADIPOQ Gene Influences Plasma Adiponectin in Type 2 Diabetes Patients but Is Not Predictive for Presence of Type 2 Diabetes in a Caucasian Cohort from Romania.

BACKGROUND: Previous reports associated ADIPOQ 276G>T polymorphism with plasma adiponectin levels and diabetes. Our objective was to study this polymorphism in type 2 diabetes (T2D) Romanian patients and to assess its influence on plasma adiponectin levels; possible link to prevalence of T2D was also addressed. DESIGN: Case control studyMaterial and Methods: Consecutive T2D patients, age and sex matched controls were genotyped for the 276 ADIPOQ locus. Medical history, laboratory evaluation, plasma adiponectin were assessed. OUTCOMES: 105 T2D patients and 48 controls were included. Adiponectin was higher in controls (17.04±3.02 µg/ml) than in T2D patients (10.32±1.16 µg/ml), difference failed to reach significance (p=0.06). Genotype distribution wasn't different between T2D patients and controls. 44 (41.90%) of T2D patients had GG genotype, 51 (48.57%) GT and 10 (9.52%) TT genotype. Adiponectin was higher (19.03±3.46 µg/ml) in diabetic TT allele carriers than in GT (9.96±1.76 µg/ml) or GG patients (8.71±1.60 µg/ml) p=0.003. In controls, 28 (58.33 %) subjects were carriers of the GG genotype, 16 (33.33%) had GT genotype and 4 (8.33%) had TT genotype. There weren't significant differences in the studied parameters between different genotypes in the control group. Logistic regression disclosed age p=0.0001 (OR 1.086; CI 1.041/1.133), waist circumference p=0.00049 (OR 1.084; CI 1.036/1.135), adiponectinemia p=0.036 (OR 0.963; CI 0.929/0.998) but not genotype as predictors for the presence of diabetes. CONCLUSION: Presence of the TT allele at the 276 locus of the ADIPOQ gene is associated with higher plasma adiponectin levels in type 2 diabetes patients. Plasma adiponectin, and not genotype at the 276 locus is predictive for the presence of T2D.