Predicting Progression From Mild Cognitive Impairment to Alzheimer's Dementia With Adversarial Attacks.

Early diagnosis of Alzheimer's disease plays a crucial role in treatment planning that might slow down the disease's progression. This problem is commonly posed as a classification task performed by machine learning and deep learning techniques. Although data-driven techniques set the state-of-the-art in many domains, the scale of the available datasets in Alzheimer's research is not sufficient to learn complex models from patient data. This study proposes a simple yet promising framework to predict the conversion from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). The proposed framework comprises a shallow neural network for binary classification and a single-step gradient-based adversarial attack to find an adversarial progression direction in the input space. The step size required for the adversarial attack to change a patient's diagnosis from MCI to AD indicates the distance to the decision boundary. The patient's diagnosis at the next visit is predicted by employing this notion of distance to the decision boundary. We also present a potential application of the proposed framework to patient subtyping. Experiments with two publicly available datasets for Alzheimer's disease research imply that the proposed framework can predict MCI-to-AD conversions and assist in subtyping by only training a shallow neural network.

Multi-cue temporal modeling for skeleton-based sign language recognition.

Sign languages are visual languages used as the primary communication medium for the Deaf community. The signs comprise manual and non-manual articulators such as hand shapes, upper body movement, and facial expressions. Sign Language Recognition (SLR) aims to learn spatial and temporal representations from the videos of the signs. Most SLR studies focus on manual features often extracted from the shape of the dominant hand or the entire frame. However, facial expressions combined with hand and body gestures may also play a significant role in discriminating the context represented in the sign videos. In this study, we propose an isolated SLR framework based on Spatial-Temporal Graph Convolutional Networks (ST-GCNs) and Multi-Cue Long Short-Term Memorys (MC-LSTMs) to exploit multi-articulatory (e.g., body, hands, and face) information for recognizing sign glosses. We train an ST-GCN model for learning representations from the upper body and hands. Meanwhile, spatial embeddings of hand shape and facial expression cues are extracted from Convolutional Neural Networks (CNNs) pre-trained on large-scale hand and facial expression datasets. Thus, the proposed framework coupling ST-GCNs with MC-LSTMs for multi-articulatory temporal modeling can provide insights into the contribution of each visual Sign Language (SL) cue to recognition performance. To evaluate the proposed framework, we conducted extensive analyzes on two Turkish SL benchmark datasets with different linguistic properties, BosphorusSign22k and AUTSL. While we obtained comparable recognition performance with the skeleton-based state-of-the-art, we observe that incorporating multiple visual SL cues improves the recognition performance, especially in certain sign classes where multi-cue information is vital. The code is available at: https://github.com/ogulcanozdemir/multicue-slr.

An MCEM Framework for Drug Safety Signal Detection and Combination from Heterogeneous Real World Evidence.

Delayed drug safety insights can impact patients, pharmaceutical companies, and the whole society. Post-market drug safety surveillance plays a critical role in providing drug safety insights, where real world evidence such as spontaneous reporting systems (SRS) and a series of disproportional analysis serve as a cornerstone of proactive and predictive drug safety surveillance. However, they still face several challenges including concomitant drugs confounders, rare adverse drug reaction (ADR) detection, data bias, and the under-reporting issue. In this paper, we are developing a new framework that detects improved drug safety signals from multiple data sources via Monte Carlo Expectation-Maximization (MCEM) and signal combination. In MCEM procedure, we propose a new sampling approach to generate more accurate SRS signals for each ADR through iteratively down-weighting their associations with irrelevant drugs in case reports. While in signal combination step, we adopt Bayesian hierarchical model and propose a new summary statistic such that SRS signals can be combined with signals derived from other observational health data allowing for related signals to borrow statistical support with adjustment of data reliability. They combined effectively alleviate the concomitant confounders, data bias, rare ADR and under-reporting issues. Experimental results demonstrated the effectiveness and usefulness of the proposed framework.

Stochastic convex sparse principal component analysis.

Principal component analysis (PCA) is a dimensionality reduction and data analysis tool commonly used in many areas. The main idea of PCA is to represent high-dimensional data with a few representative components that capture most of the variance present in the data. However, there is an obvious disadvantage of traditional PCA when it is applied to analyze data where interpretability is important. In applications, where the features have some physical meanings, we lose the ability to interpret the principal components extracted by conventional PCA because each principal component is a linear combination of all the original features. For this reason, sparse PCA has been proposed to improve the interpretability of traditional PCA by introducing sparsity to the loading vectors of principal components. The sparse PCA can be formulated as an ℓ1 regularized optimization problem, which can be solved by proximal gradient methods. However, these methods do not scale well because computation of the exact gradient is generally required at each iteration. Stochastic gradient framework addresses this challenge by computing an expected gradient at each iteration. Nevertheless, stochastic approaches typically have low convergence rates due to the high variance. In this paper, we propose a convex sparse principal component analysis (Cvx-SPCA), which leverages a proximal variance reduced stochastic scheme to achieve a geometric convergence rate. We further show that the convergence analysis can be significantly simplified by using a weak condition which allows a broader class of objectives to be applied. The efficiency and effectiveness of the proposed method are demonstrated on a large-scale electronic medical record cohort.

Changes in retinal vessels related to varicocele: a pilot investigation.

The aim of this study was to investigate whether retinal vasculature changes had occurred (retinal artery diameter, retinal vein diameter and artery/vein ratio) in patients with varicocele. This pilot study included 50 healthy subjects with any eye disease apart from slight refractive errors and 55 patients with varicocele. Retinal arteriolar and venular diameters were measured and summarised as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Retinal microvascular diameters and the arteriolar-to-venular ratio (AVR) were assessed with a digital retinal camera. All measurements and calculations were performed using a computer-based program. The mean CRAE value was 151.8 ± 3.6 µm in the study group and 150.4 ± 4.5 µm in the control group. Mean CRVE value was 209.4 ± 5.9 µm in the study group and 200.1 ± 8.7 µm in the control group. AVR was found 0.72 ± 0.02 in the study group and 0.75 ± 0.03 in the control group. There were significant differences between groups in terms of CRVE and AVR. There were no significant differences between groups in terms of CRAE. The results of this study showed that the patients with varicocele showed significant changes on retinal vascular diameter.

Beta-lactamase Enzymes of Clinical Pseudomonas aeruginosa Strains.

OBJECTIVES: In this study, the production of extended spectrum beta-lactamase (ESBL), metallo-betalacatamase (MBL) and AmpC beta-lactamase enzymes of Pseudomonas aeruginosa (P aeruginosa) strains which were isolated from clinical samples were investigated. AmpC gene was also detected by the polymerase chain reaction (PCR) analysis. METHODS: A hundred strains of P aeruginosa were included in the study. The presence of ESBL was investigated with combined disk confirmation test, MBL was investigated with E-test method and AmpC beta-lactamase was investigated with disk induction test. In order to detect the production of AmpC betalactamase genotypically, the PCR method was used. RESULTS: Only one strain was found to be MBL positive. Four per cent of strains were found to be ESBL positive. AmpC beta-lactamase production was positive in 73% of the strains with disk induction test. AmpC gene was detected in 96% of the studied strains with the PCR method. CONCLUSION: While ESBL and MBL rates in this study were significantly lower than those found in other studies, the rate of AmpC beta-lactamase was higher. Although AmpC gene was detected in some strains (23%), they were not found to produce AmpC beta-lactamase with disk induction test.

Significant correlation between uric acid levels and flow-mediated dilatation in patients with masked hypertension.

BACKGROUND: Serum uric acid (UA) level is associated with prognosis in cardiovascular disorders such as sustained hypertension, diabetes mellitus and chronic kidney diseases. Increased UA levels in sustained hypertension may reflect early renal vascular alterations. However, it remains unclear if serum UA is associated with endothelial dysfunction in masked hypertensive patients. METHODS: A total of 100 individuals (57% men and 43% women; mean 45 ± 8 years) with masked hypertension were included in the present study. The clinical and laboratory data were collected. Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter. RESULTS: Univariate regression analysis showed that the FMD was significantly negative correlated with uric acid (r = -0.300, p = 0.002), ambulatory 24-h systolic blood pressure (SBP) (r = -0.275, p = 0.008), hs-CRP (r = -0.222, p = 0.033) and diastolic aortic diameter (r = -0.243, p = 0.019). In multivariate linear regression analysis, only uric acid levels and ambulatory 24-h SBP were significantly associated with FMD. CONCLUSION: There was an independent correlation between UA and FMD, and a higher UA level was related to worse endothelial function which may contribute to hypertension and cardiovascular morbidity.

A Radiographic Correlation between Renal and Pulp Stones.

AIM: The purpose of this study was to determine the correlation between pulp stones and renal stones. This study also aims to report associations between the presence of pulp stone and gender, age, tooth type, dental arches and sides. PATIENTS AND METHODS: Data were collected through radiographic examination of bitewing radiographs of 116 kidney stone patients and a similar number of age-matched controls, referred to the Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Erciyes University. Two oral radiologists examined the radiographs to identify pulp stones. The Chi-squared and Mann Whitney U tests were used to investigate the correlations between the presence of pulp chamber calcification and age, gender, dental status and kidney stone. RESULTS: Pulp chamber opacities were detected in 199 (19.3%) out of the 1031 examined teeth, and in 84 (72.4%) out of the 116 kidney stone patients. There was no statistically significant difference between the study and control group (p = 0.882). The occurrence of pulp stones was significantly higher in molars than premolars and similar prevalences were found between dental arches and sides. CONCLUSION: In this study, no correlation was found between the presence of pulp stones and kidney stones in the investigated group. Therefore, the presence of pulp stones does not seem to be correlated with that of kidney stones.

Anti-inflammatory and antioxidant activity of thymoquinone in a rat model of acute bacterial prostatitis.

Prostatitis plays a major role in morbidity and mortality related to prostate diseases. The aim of this study was to detect whether thymoquinone (TQ) could ameliorate oxidative damage and the proliferative response induced by Escherichia coli (E. coli) in rats. A total of 42 adult male Wistar rats were used. The rats were randomly divided into seven groups (three treatment groups, three infected groups and one control group). Control group received saline and was killed 24 h after saline administration. Infected rats were killed after 24, 48 and 72 h following direct injection of E. coli into the prostate. Treatment groups were administered with 10 mg/kg dose of TQ intraperitoneally following E. coli injection and after 24 and 48 h following E. coli injection. The rats were killed at 24, 48 and 72 h after the first drug administration. Each group was compared with each other and with the control group. In addition, infected groups were compared with treatment groups. Our findings show that the treatment with TQ has a protective effect against bacterial prostatitis-induced tissue injury. Increase in malondialdehyde levels and histological damage caused by E. coli were improved markedly with TQ treatment. TQ treatment particularly increased the activity of glutathione peroxidase and decreased the activities of catalase and superoxide dismutase. These observations might be attributed, at least in part, to the antioxidant effect of TQ and suggest that it could be a clinically valuable agent in the prevention of acute prostatitis caused by E. coli.

Radiological aspect of fungus ball within a mucocele of the sphenoid sinus.

Paranasal sinus fungus ball is within the non-invasive forms and is characterized by the presence of aggregated hyphae that do not invade the sinus mucosa. Mucoceles are benign, expansile, cyst-like lesions of the paranasal sinuses. The mucoid secretions of mucoceles are usually sterile. However, secondary infections, mostly bacterial, may lead to the development of pyocoeles. Although an association between a fungus ball and a mucocele is rare in the paranasal sinuses, this disease entity should be considered in the differential diagnosis of expansile, cystic sinus lesions. In this article, clinical and radiological findings of a 61-year-old male patient with isolated sphenoid sinus fungus ball within a mucocele presented with headache and periorbital pain were discussed with recent literature.

Prevalence of toxoplasmosis, cytomegalovirus and rubella IgG antibodies in Hatay women and children.

OBJECTIVE: Toxoplasmosis, cytomegalovirus and rubella may cause congenital infections. The aim of this study is to investigate toxoplasmosis, cytomegalovirus and rubella IgG antibodies in women and children who were admitted to the Hatay Women and Children Hospital between January 1 and December 31, 2009. METHODS: Levels of IgG antibodies for toxoplasmosis, cytomegalovirus and rubella established with chemiluminescence immunoassay (Architect i2000, Abbott, USA) method were evaluated, retrospectively. RESULTS: The results were obtained from 1103 cases. Seropositivity of IgG antibodies for toxoplasmosis (n = 743), cytomegalovirus (n = 929) and rubella (n = 746) were 59.9%, 98.9% and 93.6%, respectively CONCLUSION: Routine serological screening should be recommended in women of childbearing age. Seronegative subjects should be vaccinated for rubella and educated for protection from toxoplasmosis.

Prevalence of toxoplasmosis, cytomegalovirus and rubella IgG antibodies in hatay women and children / Prevalencia de los anticuerpos IgG contra la toxoplasmosis, el citomegalovirus y la rubéola en mujeres y niños de hatay

OBJECTIVE: Toxoplasmosis, cytomegalovirus and rubella may cause congenital infections. The aim of this study is to investigate toxoplasmosis, cytomegalovirus and rubella IgG antibodies in women and children who were admitted to the Hatay Women and Children Hospital between January 1 and December 31, 2009. METHODS: Levels of IgG antibodies for toxoplasmosis, cytomegalovirus and rubella established with chemiluminescence immunoassay (Architect i2000, Abbott, USA) method were evaluated, retrospectively. RESULTS: The results were obtained from 1103 cases. Seropositivity of IgG antibodies for toxoplasmosis (n = 743), cytomegalovirus (n = 929) and rubella (n = 746) were 59.9%, 98.9% and 93.6%, respectively. CONCLUSION: Routine serological screening should be recommended in women of childbearing age. Seronegative subjects should be vaccinated for rubella and educated for protection from toxoplasmosis.

OBJETIVO: La toxoplasmosis, el citomegalovirus y la rubéola pueden causar infecciones congénitas. El objetivo de este estudio es investigar los anticuerpos IgG contra la toxoplasmosis, el citomegalovirus y la rubéola en las mujeres y ninos ingresados en el Hospital de Hatay para Mujeres y Niños, entre el 1ero de enero y el 31 de diciembre de 2009. MÉTODOS: Los niveles de anticuerpos IgG de la toxoplasmosis, el citomegalovirus, y la rubéola establecidos mediante el método de inmunoensayos por quimioluminiscencia (Architect i2000, Abbott, USA), fueron evaluados retrospectivamente. RESULTADOS: Los resultados se obtuvieron de 1103 casos. La seropositividad de anticuerpos de IgG para la toxoplasmosis (n = 743), el citomegalovirus (n = 929) y la rubéola (n = 746) fue de 59.9%, 98.9% y 93.6%, respectivamente. CONCLUSIÓN: Deben recomendarse tamizajes serológicos de rutina para las mujeres en ead de maternidad. Los sujetos seronegativos deben ser vacunados contra la rubéola y educados para protegerse contra la toxoplasmosis.

Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats.

AIM: Oxidative stress has been implicated as a potential responsible mechanism in the pathogenesis of vancomycin (VCM)-induced renal toxicity. Therefore, we aimed to investigate the protective effect of thymoquinone (TQ) against VCM-induced nephrotoxicity by tissue oxidant/antioxidant parameters and histological changes in rats. MATERIALS AND METHODS: Wistar albino rats were randomly separated into four groups consisting of seven rats per group. The groups had normal saline (control group), VCM, VCM and TQ and TQ, respectively. VCM was injected intraperitoneally at a dose of 200 mg/kg and continued at 12-h intervals for 7 days. TQ was injected intraperitoneally at a dose of 10 mg/kg and continued at 24 h intervals for 8 days. Animals were killed and blood samples were analyzed for the levels of serum blood urea nitrogen (BUN) and creatinine (Cr). Kidney specimens were analyzed for levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as for histopathological changes. RESULTS: We found that the levels of serum BUN, Cr and kidney tissue MDA were increased in the VCM group. Activities of SOD and GSH-Px in kidney tissue were decreased. TQ administration ameliorated significantly these changes. CONCLUSION: These results indicate that the TQ produces a protective mechanism against VCM-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.

The prevalence of interdigital erythrasma in southern region of Turkey.

BACKGROUND: Erythrasma is a skin infection which is caused by Corynebacterium minutissimum. Interdigital erythrasma is the most common form. OBJECTIVE: The aim of this study was to detect the frequency and risk factors of interdigital erythrasma in patients with clinically suspected tinea pedis. METHODS: This study was conducted between June and December 2010 and included 122 patients who had interdigital foot lesions. All patients were examined using a Wood's lamp. The smears were stained using Gram's method. Direct examination was performed using 20% potassium hydroxide. Sabouraud dextrose agar and brain heart infusion agar were used for cultures. Moreover, the demographical characteristics of patients, concomitant diseases and clinical findings were also recorded. Cases that were found to be positive on Wood's lamp examination and/or Gram staining/culture were considered as erythrasma. RESULTS: The rate of erythrasma was found to be 46.7%. The mean age was 43.6 years, and the disease was more prevalent in men. The most common clinical finding was desquamation. Mycological examination was found as positive in 40.35% of the patients. No growth was observed in bacteriological cultures. It was found that using only Wood's lamp examination or Gram staining resulted in 11 (9%) and 19 positive patients (15.6%), respectively, whereas using both Wood's lamp examination and Gram staining concurrently resulted in 27 positive patients (22.1%). CONCLUSION: Interdigital erythrasma is a commonly seen condition and can clinically mimic tinea pedis. A Wood's lamp is a good diagnostic tool, but Gram staining, particularly in those with a negative Wood's lamp result, may be a useful method.

Brucellosis with very high ferritin levels: report of five cases.

Brucellosis is a zoonotic disease caused by a kind of Brucella bacteria, which commonly appears in humans and rarely causes mortality. In our study, five cases, who were diagnosed by evaluation of clinical findings and serological tests, they also had very high ferritin levels, were reported. Ages of the patients were 16, 12, 10, 16 and 8 years, respectively. Serum ferritin levels were 1200, 985, 886, 748 and 435 ng/ml, respectively. We observed that complaints of the patients reduced after the treatment and ferritin levels returned to its normal range. In the situations of extremely evaluated serum ferritin which is an acute-phase reactant, its levels are able to raise in brucellosis, without existing hemochromatosis and Still's disease.

Assessment of the relationship between coronary artery ectasia and erectile function score.

The relation between coronary artery ectasia (CAE) and erectile dysfunction (ED) has not been studied so far. Hence, we decided to investigate the erectile function score in patients with CAE. We investigated the international index of erectile function (IIEF)-5 score in 34 men with CAE, 38 men with coronary artery disease (CAD), and 30 male controls with normal coronary arteries whose mean ages were 53.2 ± 5.6, 51.4 ± 7.8, and 49.6 ± 8.6 years, respectively. Erectile function was evaluated by the five-item version of the IIEF-5. Each question is scored from 0 to 5. CAE was defined as being without any stenotic lesions with a visual assessment of the coronary arteries showing a luminal dilatation 1.5-fold or more of the adjacent normal coronary segments. IIEF-5 scores in CAE group were found statistically significantly lower than the control group (P<0.001). There were no statistically significant differences in IIEF-5 scores between CAE and CAD groups (P=0.13). We have shown for the first time that patients with CAE have lower IIEF-5 scores compared with controls with normal coronary angiograms. Many studies reported that endothelial dysfunction in patients with CAE was more dominant than those with CAD. This study suggests that ED and CAE may be different manifestations of a common underlying vascular pathology and vasculogenic ED is frequently seen in CAE at least as much as in CAD.

FRET between BODIPY azide dye clusters within PEG-based hydrogel: a handle to measure stimuli responsiveness.

The purpose of this paper is to investigate the dynamics of the fluorescence mechanism of boradiazaindacene (BODIPY) dye molecules, which are covalently bound to a polyethylene glycol based hydrogel structure with different concentrations, using a picosecond time-resolved spectroscopic technique. Since the hydrogel structure is capable of absorbing a large amount of water, without dissolving and without losing its shape, upon swelling, the distance between the BODIPY azide dyes is controllably changed; it is observed that the intensity weighted fluorescence lifetime for the highly concentrated donor dye molecules embedded in the hydrogel cluster network changes from 2.03 to 7.14 ns. Calculations based on our experimental results suggest that the fluorescence dynamics of the BODIPY azide dye molecules confined within the hydrogel network obeys the Forster resonance energy transfer (FRET) rather than self (or contact) quenching. If the hydrogel is dry, in which the distance between donors and acceptors is minimum, the energy transfer efficiency is found to be about 72%, and the distance between the two dye molecules is calculated to be 4.59 nm. Such a close placement causes a significant reduction in the fluorescence intensity due to a strong dipole-dipole interaction of the dye molecules. As the separation increases upon hydrogel swelling, the FRET efficiency reduces to 2%, which corresponds to a separation of 10 nm between two BODIPY dyes and hence a considerable increase in the level of fluorescence intensity. For the dilute hydrogel samples, the distance between the dye molecules is larger than the critical Forster distance. Therefore, the energy transfer efficiency for this type of dilute samples is found to be much lower.

Introducing a mouse model of brain death.

Experimental animal models of brain death increasing intracranial pressure (ICP) by inflating an intracranial placed balloon-catheter are well established and used in transplant-associated studies. Our aim was to develop an experimental mouse model of brain death (BD) and to compare explosive and gradual brain death induction under ICP monitoring. We therefore induced BD in female OF-1 mice by injecting 40 microl saline every 5 min into an intracranial placed balloon increasing ICP rapidly [BD ex, n=7], or gradually [BD grad, n=7] with 20 microl volume every 5 min under electroencephalogram (EEG) and ICP monitoring until BD occurred. The major criterion for BD was a flat-line-EEG, confirmed by cessation of spontaneous respiration and maximally dilated and fixed pupils. ICP, central activity and heart rate were continuously monitored during the entire 6h follow-up. In sham-operated controls [control, n=7] a burr hole was drilled but no balloon inserted. The BD groups showed equal ICP levels at the time of BD. Both groups had increased heart rates (HR) 15 min after BD, HR decreased to 402+/-29.39 bpm (beats per minute) [BD ex] and 409.33+/-26.46 bpm [BD grad] (n.s. vs. control) by 30 min after the inflation of the balloon, but only BD ex showed a significant decrease in HR compared to control, progressively decreasing thereafter. On the basis of these results, we conclude that the mouse model of brain death can be performed in a standardized, reproducible and successful way.