Association between anemia severity and migraine in iron deficiency anemia.

OBJECTIVE: Migraine is an episodic public health problem that usually occurs with a severe headache. Various mechanisms and outcomes have been reported between iron deficiency anemia (IDA) and migraine. We aimed to investigate the effect of the presence and severity of anemia and iron parameters on the frequency and severity of migraine attacks. PATIENTS AND METHODS: The study included 104 patients with IDA and newly diagnosed migraine in the neurology outpatient clinic and 38 age and gender-matched controls with normal hemoglobin levels. Patients were divided into 3 subgroups (mild, moderate, and severe anemia) to determine a significant relationship between the severity of IDA and migraine attacks. All patients were asked validated questions with the Visual Analogue Scale (VAS), Headache Impact Test-6 (HIT-6), and the Hamilton Anxiety Rating Scale (HAM-A) face-to-face. RESULTS: In this study, 85.6% of the participants were female, and 22 (14.6%) of them were male. Thirty-two mild anemia patients' mean age was 36.6 ± 12.5, 41 with moderate anemia was 46 ± 14.2, and 31 with severe anemia patients' mean age was 48 ± 14.1. There was no significant difference between the subgroups in VAS, HIT-6 score, headache type, and headache frequency. Menstrual migraine is associated with low hemoglobin levels. A significant increase was found in VAS and HIT-6 scores with low ferritin levels. CONCLUSIONS: The presence and severity of anemia and iron deficiency do not affect the frequency and severity of migraine attacks in groups other than menstruation-related migraine. An inverse relationship was found between VAS, HIT-6, and ferritin levels. VAS was found to be more effective than HIT-6.

The effect of BMSCs on implantation mechanisms and pregnancy process in the experimental Asherman model.

OBJECTIVE: In this study, we aimed to investigate the role of bone marrow-derived mesenchymal stem cells (BMSC) on the molecular mechanisms involved in the removal of endometrial adhesions and the implantation process in the experimentally-created Asherman syndrome model in rats. MATERIALS AND METHODS: An experimental model chemical agent was used. Culture medium (CM), only BMSC, 48-hour culture medium (Niche), and BMSC+ niche were used as therapy. Each group was divided into two subgroups, and changes in the endometrial tissue were investigated by histochemical and immunohistochemical staining. RESULTS: The results of the study show that BMSCs exhibit therapeutic properties in endometrial damage, increase endometrial thickness and vascularization, and contribute to the implantation of embryos by reducing fibrous areas. These results are promising for the prevention of Asherman-induced infertility. CONCLUSIONS: It has been shown that BMSC and Niche applications can be helpful in preventing adhesion molecules in the mechanisms that cause infertility.

DSP p.(Thr2104Glnfs*12) variant presents variably with early onset severe arrhythmias and left ventricular cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is a condition characterized by dilatation and systolic dysfunction of the left ventricle in the absence of severe coronary artery disease or abnormal loading conditions. Mutations in the titin (TTN) and lamin A/C (LMNA) genes are the two most significant contributors in familial DCM. Previously mutations in the desmoplakin (DSP) gene have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) and more recently with DCM. METHODS: We describe the cardiac phenotype related to a DSP mutation which was identified in ten unrelated Finnish index patients using next-generation sequencing. Sanger sequencing was used to verify the presence of this DSP variant in the probands' relatives. Medical records were obtained, and clinical evaluation was performed. RESULTS: We identified DSP c.6310delA, p.(Thr2104Glnfs*12) variant in 17 individuals of which 11 (65%) fulfilled the DCM diagnostic criteria. This pathogenic variant presented with left ventricular dilatation, dysfunction and major ventricular arrhythmias. Two patients showed late gadolinium enhancement (LGE) and myocardial edema on cardiac magnetic resonance imaging (MRI) that may suggest inflammatory process at myocardium. CONCLUSIONS: The patients diagnosed with DCM showed an arrhythmogenic phenotype as well as SCD at young age supporting the recently proposed concept of arrhythmogenic cardiomyopathy. This study also demonstrates relatively low penetrance of truncating DSP variant in the probands' family members by the age of 40. Further studies are needed to elucidate the possible relations between myocardial inflammation and pathogenic DSP variants.

CADASIL with Atypical Clinical Symptoms, Magnetic Resonance Imaging, and Novel Mutations: Two Case Reports and a Review of the Literature.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy with adult onset caused by a missense mutation in the NOTCH3 gene in chromosome 19p13. It presents with autosomal dominant arteriopathy, subcortical infarctions, and leukoencephalopathy. Its common clinical presentations are seen as recurrent strokes, migraine or migraine-like headaches, progressive dementia, pseudobulbar paralysis, and psychiatric conditions. Two patients with CADASIL syndrome, whose diagnosis was made based on clinical course, age of onset, imaging findings, and genetic assays in the patients and family members, are presented here because of new familial polymorphisms. The first patient, with cerebellar and psychotic findings, had widespread non-confluent hyperintense lesions as well as moderate cerebellar atrophy in cranial magnetic resonance scanning. The other patient, with headache, dizziness, and forgetfulness, had gliotic lesions in both cerebral hemispheres. CADASIL gene studies revealed a new polymorphism in exon 33 in the first patient. In the other patient, the NOTCH3 gene was identified as a new variant of p.H243P (c.728A > C heterozygous). By reporting a family presenting with various clinical symptoms in the presence of new polymorphisms, we emphasize that CADASIL syndrome may present with various clinical courses and should be considered in differential diagnoses.

Impact of mild and moderate/severe vertebral fractures on physical activity: a prospective study of older women in the UK.

Little is known about the long-term impact of vertebral fractures on physical activity. There is also uncertainty over the clinical significance of mild vertebral fracture. We showed that women with moderate/severe but not mild vertebral fracture do less walking duration and housework than those without fracture after 5.4 years of follow-up. INTRODUCTION: Little is known about the long-term impact of vertebral fractures on physical activities. There is also uncertainty over the clinical significance of mild fracture. Therefore, the aim of this study was to evaluate the prospective association between vertebral fracture and future physical activity. METHODS: This is a 5-year prospective study of a mixed community and secondary care cohort of women aged > 50 from the UK. Vertebral fractures were identified at baseline on radiographs or DXA-based Vertebral Fracture Assessment by a Quantitative Morphometric approach and defined as moderate/severe (≥ 25% height decrease) or mild (20-24.9% height decrease). Physical activity data were collected 5.4 years later by self-completion questionnaires. Multivariable logistic regression was used to determine the association between presence of fracture and various physical activities while adjusting for potential confounders. RESULTS: Two hundred eighty-six women without, 58 with mild, and 69 with moderate/severe fracture were recruited. Those with mild and moderate/severe fracture were older than women without fracture and had more concomitant diseases at baseline. At 5.4 years follow-up, women with moderate/severe fracture self-reported shorter walking duration compared to those without fracture, even after adjusting for potential confounders (OR 2.96, 95%CI 1.11-7.88, P = 0.030). No independent association was seen between the presence of mild fractures and reduced physical activity at follow-up. CONCLUSION: This is the first study of older women from the UK that explored the prospective association between vertebral fracture and physical activity duration. Moderate/severe fractures were associated with reduced walking duration. Mild fractures had no impact on future physical ability.

Heterozygous junctophilin-2 (JPH2) p.(Thr161Lys) is a monogenic cause for HCM with heart failure.

During the last two decades, mutations in sarcomere genes have found to comprise the most common cause for hypertrophic cardiomyopathy (HCM), but still significant number of patients with dominant HCM in the family are left without molecular genetic diagnosis. Next generation sequencing (NGS) does not only enable evaluation of established HCM genes but also candidate genes for cardiomyopathy are frequently tested which may lead to a situation where conclusive interpretation of the variant requires extensive family studies. We aimed to characterize the phenotype related to a variant in the junctophilin-2 (JPH2) gene, which is less known non-sarcomeric candidate gene. In addition, we did extensive review of the literature and databases about JPH2 variation in association with cardiac disease. We characterize nine Finnish index patients with HCM and heterozygous for JPH2 c.482C>A, p.(Thr161Lys) variant were included and segregation studies were performed. We identified 20 individuals affected with HCM with or without systolic heart failure and conduction abnormalities in the nine Finnish families with JPH2 p.(Thr161Lys) variant. We found 26 heterozygotes with the variant and penetrance was 71% by age 60 and 100% by age 80. Co-segregation of the variant with HCM phenotype was observed in six families. Main clinical features were left ventricular hypertrophy, arrhythmia vulnerability and conduction abnormalities including third degree AV-block. In some patients end-stage severe left ventricular heart failure with normal or mildly enlarged diastolic dimensions was detected. In conclusion, we propose that the heterozygous JPH2 p.(Thr161Lys) variant is a new Finnish mutation causing atypical HCM.

Changes in antimicrobial resistance and demographics of UTIs in pediatric patients in a single institution over a 6-year period.

PURPOSE: To determine changes in antimicrobial resistance and demographics of UTIs in pediatric patients in a single institution over a 6-year period. MATERIALS AND METHODS: The current study examined outpatient urinary isolates from patients aged <18 years. A retrospective cross-sectional analysis of bacteria isolated from children with UTI was performed between 2009 and 2014. The most common bacterial pathogens were determined in the following four age groups: <2 years; 2-5 years; 6-12 years; and 13-17 years. The study analyzed the prevalence and antibiotic resistance patterns for the six most common uropathogens: Escherichia coli, Proteus, Klebsiella, Enterobacter, Pseudomonas and Enterococcus (Summary table). The antibiotic resistance pattern for UTI during 2009-2014 was also examined. RESULTS: A total of 6515 urinary cultures was examined. The majority of these isolates were from female patients (66.8%). E. coli was the most common uropathogen overall, but the prevalence of E. coli was higher among females (79.5%) than males (54.9%). The biggest percentage of isolates in males was from children aged <2 years (46.1%). Conversely, the majority of isolates in females were from children aged >6 years (46.8%). Results of antimicrobial resistance for E. coli were the highest for ampicillin (70%) and lowest for meropenem (0.19%). Comparing the hospital network data from 2009 to 2014, E. coli resistance increased for ampicillin (from 47.1% to 89%), trimethoprim-sulfamethoxazole (TMP-SMX) (from 44.8% to 56%) and nitrofurantoin (from 5.3% to 15.1%). In contrast, cephalosporins have maintained low antibiotic resistance. CONCLUSION: UTI in females was nearly twice as common than in males. E. coli remained the most common pediatric uropathogen. Although widely used in other tract infections, ampicillin was a poor empiric choice for pediatric UTIs. Cephalosporins were appropriate alternatives given their low resistance rates. A successful empirical treatment protocol should be based on local epidemiology and susceptibility rates.

Self-reported everyday physical activities in older people with osteoporotic vertebral fractures: a systematic review and meta-analysis.

Previous work has shown that patients with vertebral fractures do less physical activity. However, the association between vertebral fracture and different components of physical activity is unclear. Our results suggest that vertebral fracture (VF) is associated with a reduction in activities involving bending, ambulation, and daily living, regardless of age. INTRODUCTION: The aim of this study was to determine whether osteoporotic VF is associated with reduced self-reported everyday routine physical activity and/or ability (PAA). METHODS: A comprehensive search was undertaken using the databases of PubMed, Embase, Medline, Web of Science, and the "grey" literature from 1950 to the end of July 2016. Standardised search terms for VF and PAAs were used. Four categories of PAA were included: (1) bending ability, (2) ambulatory activities, (3) reaching arms above shoulder level, and (4) activities of daily living (ADLs). Strict inclusion and exclusion criteria were used, and only studies that adjusted for age were included. For the meta-analysis, pooled OR and 95% confidence interval (CI) were calculated using a random-effects model. RESULTS: Eleven studies in total were identified which had investigated the associations between the prevalent VF and the selected PAAs and expressed these as ORs or RR. Women (six studies) with VF had a 64% increase in difficulty forward bending compared to those without VF. Women (nine studies) with VF had a 27% increase in difficulty doing ambulatory activities, while no association was observed for men (four studies). Women also have 73% (five studies), 127% (three studies), and 100% (four studies) increase in difficulty reaching arms above shoulder, shopping, and preparing meals, respectively. CONCLUSION: Studies consistently show women with VF have reduced everyday activities, while much less research has been carried out in men. This information may be useful when designing interventions to improve physical function in people with osteoporotic VFs.

Electrocardiogram changes and atrial arrhythmias in individuals carrying sodium channel SCN5A D1275N mutation.

INTRODUCTION: The cardiac sodium channel SCN5A regulates atrioventricular and ventricular depolarization as well as cardiac conduction. Patients with cardiac electrical abnormalities have an increased risk of sudden cardiac death (SCD) and cardio-embolic stroke. Optimal management of cardiac disease includes the understanding of association between the causative mutations and the clinical phenotype. A 12-lead electrocardiogram (ECG) is an easy and inexpensive tool for finding risk patients. MATERIALS AND METHODS: A blood sample for DNA extraction was obtained in a Finnish family with 43 members; systematic 12-lead ECG analysis was performed in 13 of the family members carrying an SCN5A D1275N mutation. Conduction defects and supraventricular arrhythmias, including atrial fibrillation/flutter, atrioventricular nodal re-entry tachycardia (AVNRT) and junctional rhythm were searched for. RESULTS: Five (38%) mutation carriers had fascicular or bundle branch block, 10 had atrial arrhythmias; no ventricular arrhythmias were found. Notching of the R- and S waves - including initial QRS fragmentation - and prolonged S-wave upstroke were present in all the affected family members. Notably, four (31%) affected family members had a stroke before the age of 31 and two experienced premature death. CONCLUSIONS: A 12-lead ECG can be used to predict arrhythmias in SCN5A D1275N mutation carriers. Key messages The 12-lead ECG may reveal cardiac abnormalities even before clinical symptoms occur. Specific ECG findings - initial QRS fragmentation, prolonged S-wave upstroke as well as supraventricular arrhythmias - were frequently encountered in all SCN5A D1257N mutation carriers. ECG follow-up is recommended for all SCN5A D1275N mutation carriers.

Comparison of combined antioxidants and thymoquinone in the prevention of testis ischemia - reperfusion injury.

We aimed to compare the preventive effects of combined antioxidants (CA1, 2) with a single antioxidant drug (thymoquinone; TQ) on experimental testis Ischemia/Reperfusion (I/R) injury. Thirty-five adult male Wistar rats were divided into five groups of seven rats each: control, testis I/R, testis I/R + CA1, testis I/R + CA2, and testis I/R + TQ. After 1 h of testicular ischemia, reperfusion was achieved by detorsion for 4 h. Antioxidants were intraperitoneally administered for 30 min prior to reperfusion. All rats were sacrificed 4 h after reperfusion to evaluate the tissue levels of malondialdehyde (MDA) and total antioxidant status (TAS) and the immunohistochemical evaluation of tissue inducible and endothelial nitric acid synthase (iNOS, eNOS) and apoptosis protease-activating factor 1 (APAF-1). MDA levels were lower and TAS values were higher in the I/R + antioxidant groups than in the I/R group (p < 0.05). iNOS and eNOS levels in the I/R + antioxidant groups were also lower than those in the I/R group (p < 0.05). There were no significant differences between the CA groups and the TQ group according to aforementioned parameters. In addition, tissue APAF-1 values were significantly higher in the I/R group than in the other groups. However, there was a significant difference between the TQ and CA groups in APAF-1 levels, which were highest in the TQ group (p < 0.05). Although TQ alone increased TAS values and reduced tissue iNOS and eNOS levels, combined antioxidant treatment may more effectively reduce apoptosis and increase preventive effects in testis I/R injury.

Habitual levels of higher, but not medium or low, impact physical activity are positively related to lower limb bone strength in older women: findings from a population-based study using accelerometers to classify impact magnitude.

This study assessed the effect of accelerometry-measured higher impacts resulting from habitual weight-bearing activity on lower limb bone strength in older women. Despite higher impacts being experienced rarely in this population-based cohort, positive associations were observed between higher vertical impacts and lower limb bone size and strength. INTRODUCTION: We investigated whether the benefit of habitual weight-bearing physical activity (PA) for lower limb bone strength in older women is explained by exposure to higher impacts, as previously suggested by observations in younger individuals. METHODS: Four hundred and eight women from the Cohort for Skeletal Health in Bristol and Avon (COSHIBA), mean 76.8 years, wore tri-axial accelerometers at the waist for a mean of 5.4 days. Y-axis peaks were categorised, using previously identified cutoffs, as low (0.5-1.0 g), medium (1.0-1.5 g), and higher (≥1.5 g) impacts. Mid and distal peripheral quantitative computed tomography scans of the tibia and radius were performed, as were hip and lumbar spine Dual X-ray Absorptiometry (DXA) scans. Regressions between (log transformed) number of low, medium and high impacts, and bone outcomes were adjusted for artefact error grade, age, height, fat and lean mass and impacts in other bands. RESULTS: Eight thousand eight hundred and nine (4047, 16,882) low impacts were observed during the measurement week, 345 (99, 764) medium impacts and 42 (17, 106) higher impacts (median with 25th and 75th quartiles). Higher vertical impacts were positively associated with lower limb bone strength as reflected by cross-sectional moment of inertia (CSMI) of the tibia [0.042 (0.012, 0.072) p = 0.01] and hip [0.067 (0.001, 0.133) p = 0.045] (beta coefficients show standard deviations change per doubling in impacts, with 95 % confidence interval). Higher impacts were positively associated with tibial periosteal circumference (PC) [0.015 (0.003, 0.027) p = 0.02], but unrelated to hip BMD. Equivalent positive associations were not seen for low or medium impacts. CONCLUSIONS: Despite their rarity, habitual levels of higher impacts were positively associated with lower limb bone size and strength, whereas equivalent relationships were not seen for low or medium impacts.

Health-related quality of life in older people with osteoporotic vertebral fractures: a systematic review and meta-analysis.

Health-related quality of life in osteoporotic patients with vertebral fracture is of increasing interest, but relevant studies have yielded debatable results. This systematic review and meta-analysis of 16 observational studies demonstrate a clear association between physical health status and presence of vertebral fracture after accounting for age. This meta-analysis was conducted to identify if there are any differences between physical and/or mental health-related quality of life (HRQoL) in older people with osteoporosis based on conventional T-score definitions and the presence or absence of vertebral fracture. A comprehensive search was undertaken using the databases of PubMed, Embase, Medline, Web of Science, and the "grey" literature from 1950 to the end of April 2015. Search terms for vertebral fracture (VF) included VF, osteoporotic fracture, fragility fracture, and spinal fracture. Quality of life was searched using the following terms: quality of life, health-related quality of life, HRQoL, and QoL. Strict inclusion and exclusion criteria were used. The standardized mean difference (SMD) was calculated for each HRQoL domain by the difference in means between case and control groups divided by the pooled SD of participants. Sixteen eligible studies were identified involving 3131 men and women. There was evidence of publication bias and heterogeneity. The meta-analysis showed worse physical (SMD = 0.53, 95 % confidence interval (CI) 0.38 to 0.68; P < 0.001) and mental (SMD = 0.19, 95 % CI 0.05 to 0.33; P = 0.009) HRQoL in osteoporotic older people with vertebral fracture compared to those without fracture. Similar differences were observed for physical HRQoL in further analyses accounting for possible confounding effects of age. Sub-analysis to assess associations between number/severity of fractures and time since fracture was not possible due to small numbers of studies that accounted for age. Osteoporotic older people with vertebral fracture have worse physical HRQoL than osteoporotic older people without vertebral fracture, even after accounting for age differences.

Papillary Carcinoma Occurrence in a Thyroglossal Duct Cyst with Synchronous Papillary Thyroid Carcinoma without Cervical Lymph Node Metastasis: Two-Cases Report.

Background. We present two rare cases of papillary carcinomas which appeared in thyroglossal duct cysts. These cases highlight that thyroglossal duct cyst can serve as malignancy of thyroid gland. Methods. A retrospective case report was carried out on 2 patients at Cipto Mangunkusumo Hospital. Results. A 57-year-old man presented with enlarged right anterior and midline neck mass, which preoperatively were diagnosed as thyroglossal duct cyst (TDC) and nontoxic multinodular goiter. A total thyroidectomy and Sistrunk procedure were performed. In the second case, a 35-year-old woman presented with a lump which occurred at anterior neck region without palpable mass at the thyroid. Preoperatively, it was diagnosed as TDC. Sistrunk procedure was performed, followed by total thyroidectomy a month after the first operation. Histopathology showed papillary thyroid carcinoma in both patients. Conclusion. The occurrence of carcinoma in TDC is very rare but should always be considered as an option in making diagnosis for a neck mass.

Electrocardiogram acquisition errors or myocardial infarct.

Incorrect lead placement may result in unnecessary therapeutic interventions. We present a case report of 53-year-old man with new inferior T-wave inversions in the 12-lead electrocardiogram (ECG) noted during routine followup of hypertension without any cardiovascular symptoms.