Statistical approaches for the analysis of dependency among neurons under noise

Neuronal noise is a major factor affecting the communication between coupled neurons. In this work, we propose a statistical toolset to infer the coupling between two neurons under noise. We estimate these statistical dependencies from data which are generated by a coupled Hodgkin–Huxley (HH) model with additive noise. To infer the coupling using observation data, we employ copulas and information-theoretic quantities, such as the mutual information (MI) and the transfer entropy (TE). Copulas and MI between two variables are symmetric quantities, whereas TE is asymmetric. We demonstrate the performances of copulas and MI as functions of different noise levels and show that they are effective in the identification of the interactions due to coupling and noise. Moreover, we analyze the inference of TE values between neurons as a function of noise and conclude that TE is an effective tool for finding out the direction of coupling between neurons under the effects of noise.No sponso

Kinetic and in silico analysis of thiazolidin-based inhibitors of α-carbonic anhydrase isoenzymes.

Durdagi, Serdar/0000-0002-0426-0905 WOS: 000314531000019 PubMed: 23173744 Carbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, inorganic anions, phenols, salicylic acid derivatives (acting as drug or prodrugs). A novel class of CA inhibitors (CAIs), interacting with the CA isozymes I and II (cytosolic) in a different manner, is reported here. Kinetic measurements allowed us to identify thiazolidin-based compounds as submicromolar-low micromolar inhibitors of these two CA isozymes. Molecular docking studies of a set of such inhibitors within CA I and II active site allowed us to understand the inhibition mechanism. This new class of inhibitors bind differently compared to other classes of inhibitors known to date: they were found between the phenol-binding site, filling thus the middle of the enzyme cavity

Attitudes and behaviors of individuals aged 90 and over towards rational use of drugs: cross-sectional research

Introduction: The current study was aimed to evaluate the attitudes and behaviors of individuals 90 years and older living in Malatya regarding rational drug use. Methods: This cross-sectional, descriptive study was carried out with people aged 90 and over (n=1022) living in Malatya province and its districts. Face-to-face interview method was used to collect study data. In the first part of the form used for data collection, the descriptive characteristics of the participants were questioned, and in the second part, the attitudes and behaviors towards rational drug use were examined. Rational drug use features are evaluated by World Health Organization (WHO) prescribing indicators. Results: The frequency of rational drug use was 84.1%, and the rate of over-the-counter drug use was 19.2% among individuals 90 years and older. 52.3% of the participants had over-the-counter medication at home for use, when necessary, without doctor's recommendation. The most commonly available over-the-counter group of drugs at home were painkillers. Conclusion: The frequency of rational drug use in individuals aged 90 and older has been determined higher than in the literature on individuals aged 65 and older. Education, guidance and counseling programs can be created to increase rational drug use within elderly people communities. Keywords: rational drug use; oldest-old; elderly; attitude; behavio

İntertrokanterik kırıklarda hangi sınıflandırma sistemi daha kullanışlıdır? AO/ASIF ya da Jensen?

Amaç: Bu çalışmanın amacı AO/ASIF and Jensen sınıflama sistemlerinin gözlemcilerin kendi içindeki (intraobserver) ve gözlemciler arası (interobserver) uyumunu saptamak ve deneyimli ve deneyimsiz ortopedik cerrahlar tarafından uygulandığındaki uyumu kıyaslamaktı. Hastalar ve Yöntemler: Altmış intertrokanterik femur kırığına ait ön-arka ve yan radyografiler, iki gruba (G1, G2) ayrılmış 10 ortopedik cerrah tarafından üçer ay ara ile AO ve Jensen sınıflamaları kullanılarak incelendi ve sınıflandırıldı. Her grupta beş cerrah vardı. Grup 1'dekiler beş yıldan daha az, Grup 2'dekiler 10 yıldan daha fazla deneyimli idiler. İntraobserver ve interobserver varyasyonların belirlenmesinde Kappa istatistiksel analizi kullanıldı. Bulgular: Alt grupları kullanılmadan yapılan AO sınıflaması için intraobserver uyum kappa değeri 0.67 (0.47-0.90), interobserver uyum kappa değeri 0.42 (0.10-0.73) olarak bulundu. Jensen sınıflaması için intraobserver uyum kappa değeri 0.57 (0.35-0.80), interobserver uyum kappa değeri 0.30 (0.10-0.60) olarak bulundu. Altgruplar kullanılarak yapılan AO sınıflama sistemi için intraobserver uyum kappa değeri 0.49 (0.21-0.81) ve interobserver uyum kappa değeri 0.23 (0.09-0.51) olarak bulundu. Sonuç: Bu çalışmada, kullanılan sınıflama sistemlerinin dezavantajlarının olmasına karşın, intertrokanterik kırıklarda alt gruplar kullanılmadan yapılan AO sınıflamasının, Jensen ve alt gruplar kullanılarak yapılan AO sınıflamasına göre daha kullanılabilir olduğu gösterilmiştir.Objectives: The aim of this study was to determine intra- and interobserver reliability of AO/ASIF and Jensen classification systems, and to compare reliability when applied by unexperienced and experienced orthopaedic surgeons. Patients and Methods: The anteroposterior and lateral radiographs of 60 intertrochanteric hip fractures were reviewed and classified by two groups (G1, G2) of orthopaedic surgeons using the AO and Jensen classification systems on two separate occasions three months apart. Each group consisted of five orthopaedic surgeons. Group 1 had less than five years, and group 2 had more than 10 years of experience. Kappa statistical analysis was used for determination of intra- and interobserver variation. Results: For the AO classification system without subgroups, the mean kappa value was 0.67 (range 0.47-0.90) for intraobserver variation and 0.42 (range 0.10-0.73) for interobserver variation. For the Jensen classification, the mean kappa value was 0.57 (range 0.35-0.80) for intraobserver variation and 0.30 (range 0.10-0.60) for interobserver variation. For the AO classification system with subgroups, the mean kappa value was 0.49 (range 0.21-0.81) for intraobserver variation and 0.23 (range 0.09-0.51) for interobserver variation. Conclusion: Although these classification systems have disadvantages, this study suggests that AO system without subgroups is more useful than Jensen and AO system with subgroups to classify intertrochanteric fractures of the proximal femur

Self-Supervised Learning with an Information Maximization Criterion

Self-supervised learning allows AI systems to learn effective representations from large amounts of data using tasks that do not require costly labeling. Mode collapse, i.e., the model producing identical representations for all inputs, is a central problem to many self-supervised learning approaches, making self-supervised tasks, such as matching distorted variants of the inputs, ineffective. In this article, we argue that a straightforward application of information maximization among alternative latent representations of the same input naturally solves the collapse problem and achieves competitive empirical results. We propose a self-supervised learning method, CorInfoMax, that uses a second-order statistics-based mutual information measure that reflects the level of correlation among its arguments. Maximizing this correlative information measure between alternative representations of the same input serves two purposes: (1) it avoids the collapse problem by generating feature vectors with non-degenerate covariances; (2) it establishes relevance among alternative representations by increasing the linear dependence among them. An approximation of the proposed information maximization objective simplifies to a Euclidean distance-based objective function regularized by the log-determinant of the feature covariance matrix. The regularization term acts as a natural barrier against feature space degeneracy. Consequently, beyond avoiding complete output collapse to a single point, the proposed approach also prevents dimensional collapse by encouraging the spread of information across the whole feature space. Numerical experiments demonstrate that CorInfoMax achieves better or competitive performance results relative to the state-of-the-art SSL approaches

Inhibition of human carbonic anhydrase isozymes I, II and VI with a series of bisphenol, methoxy and bromophenol compounds

Carbonic anhydrase inhibitors (CAI) are valuable molecules as they have several therapeutic applications, including anti-glaucoma activity. In this study, inhibition of three human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I, II and VI with a series of bisphenol and bromophenol derivatives was investigated. Molecular docking studies of a set of such inhibitors within CA I and II were also performed. K-I values of the molecules 2-9 were in the range of 10.025-892.109 mu M for hCA I, 1.437-59.107 mu M for hCA II and 11.143-919.182 mu M for hCA VI, respectively. Reported inhibitory activities of molecules 2-9 will assist in better understanding of structure-activity relationship studies of CAI.This study was financed by Turkish Republic Prime Ministry State Planning Organization (DPT), (project no: 2010K120440) and Agri Ibrahim Cecen University Scientific Research Council, (project no: Agri BAP-2010/K-10) for (MS) and by the Scientific and Technological Research Council of Turkey (TUBITAK, Grant No: TBAG-107T/348) for (SG, HTB and AM)

Demonstrating a powerful scale-up strategy for Biosimilar mAb in single use systems via physicochemical and functional characterization

Biosimilars have received a remarkable attention in the recent years. Due to the heterogeneity of biosimilar mAbs, they need to be well-characterized by various orthogonal techniques in order to identify their physicochemical and functional characteristics. Characterization of the post translational modifications, especially, glycosylation is vital to define the critical quality attributes (CQAs) which affect safety, efficacy and quality of drugs. In this study, we were able to manipulate the quality of the drug by using scale-up strategies for single use systems. By using ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry (MS), we were able to demonstrate physicochemical similarities between innovator and its biosimilar candidate. Even the PTM (N-terminal pyroglutamic acid formation, C-terminal lysine truncation, methionine and tryptophan oxidation, asparagine deamidation, N-glycosylation and glycation) levels of two products from 3 and 200-liter single-use bioreactors were highly similar compared to the innovator. The mass spectrometry studies showed that the scale-up strategy from 3 liter to 200 liter was successful. Deconvoluted mass spectrum for intact and reduced masses (heavy and light chain) of innovator and its biosimilar candidates from different production scales were significantly similar. Oxidation was observed to be lower in 200 liter bioreactor compared to the 3 liter. The N-glycan profiles for the major and minor glycan species were highly similar compared to the originator. Aggregation level in 200 liter was slightly lower than that of the small scale production. Mass spectrometry becomes an important tool to enhance the biosimilarity to the originator in order to decrease the clinical efforts to be able to provide affordable drugs to the patients

Antioxidant Activity, Sugar Content and Phenolic Profiling of Blueberries Cultivars: A Comprehensive Comparison

Commercial blueberry production has been a viable industry throughout the world for 95 years; because of blueberry is a good source of antioxidant. Blueberries are especially rich in anthocyanin, a flavonoid with potent antioxidant capacity. The aim of this study was to compare the phenolic quantities, antioxidant activities, anthocyanin, sugar and phenolic compounds of blueberries produced in Turkey with those of similar blueberry varieties produced around the world. As a result of the conducted analysis, the total phenolic content (TPC) amount found in the berries was 77.26-215.12 mg GAE/100 g, the total flavonoid content (TFC) was 30.44-91.69 mg QE/100 g and the total anthocyanin content (TAC) was 43.03-295.06 mg c3-GE/100 g. Examining the antioxidant activities of the berries, DPPH between 1.10-5.65 mg/ml, FRAP between 454.93-36832.96 µmol troloks/100 g, β-Carotene between 40.66-86.48%. It was determined that the natural berries contained much more phenolic compounds and higher antioxidant activity than that of the cultivars The result of HPLC analysis, chlorogenic acid is determined to be the dominant compound in all berries. Furthermore, fructose and glucose are found in all fruits in different quantities while sucrose is found in certain varieties of berries as well. At the end of the performed study the data indicate that wild and cultivars of blueberries are rich sources of antioxidants for local as well international industries importing this fruit for food processing and enormous products

Evaluation of the physical and emotional effects of the COVID-19 pandemic on patients with fibromyalgia and chronic low back pain: A multicenter cross-sectional controlled study

Objectives: This study aimed to investigate the physical and emotional effects of the coronavirus disease 2019 pandemic in patients with fibromyalgia syndrome (FMS) and chronic low back pain (CLBP) patients.Patients and methods: The cross-sectional controlled study was performed with 1,360 participants (332 males, 1,028 females; mean age: 42.3 +/- 12.5 years; range, 18 to 65 years) between September 2020 and February 2021. The participants were evaluated in three groups: the FMS group (n=465), the CLBP group (n=455), and the healthy control group (n=440). Physical activity, pain levels, and general health status before and during the pandemic were evaluated in all participants. Stress levels were analyzed with the perceived stress scale (PSS) in all groups, and disease activity was analyzed with the fibromyalgia impact questionnaire (FIQ) in patients with FMS.Results: Patients with FMS had worsened general health status and pain levels during the pandemic compared to the other groups (p<0.01). The FMS group showed significantly higher PSS scores than those in other groups (p<0.01). There was a weak-positive correlation between FIQ and PSS parameters in patients with FMS (p<0.05, r=0.385).Conclusion: The general health status, pain, and stress levels of the patients with FMS and CLBP tended to worsen during the pandemic. This high-stress level appeared to affect disease activity in patients with FMS

Bladder Wall Telangiectasia in a Patient with Ataxia-Telangiectasia and How to Manage?

Ataxia-telangiectasia (A-T) is a rare neurodegenerative, inherited disease causing severe morbidity. Oculocutaneous telangiectasias are almost constant findings among the affected cases as telangiectasia is considered the main clinical finding for diagnosis. Vascular abnormalities in organs have been reported infrequently but bladder wall telangiectasias are extremely rare. We aimed to report recurrent hemorrhage from bladder wall telangiectasia in a 9-year-old boy with A-T who had received intravenous cyclophosphamide for non-Hodgkin’s lymphoma. Since A-T patients are known to be more susceptible to chemical agents, we suggested that possibly cyclophosphamide was the drug which induced bladder wall injury in this patient