Data Processing Techniques Impact Quantification of Cortico-Cortical Evoked Potentials.

BACKGROUND: Cortico-cortical evoked potentials (CCEPs) are a common tool for probing effective connectivity in intracranial human electrophysiology. As with all human electrophysiology data, CCEP data are highly susceptible to noise. To address noise, filters and re-referencing are often applied to CCEP data, but different processing strategies are used from study to study. NEW METHOD: We systematically compare how common average re-referencing and filtering CCEP data impacts quantification. RESULTS: We show that common average re-referencing and filters, particularly filters that cut out more frequencies, can significantly impact the quantification of CCEP magnitude and morphology. We identify that high cutoff high pass filters (> 0.5Hz), low cutoff low pass filters (< 200Hz), and common average re-referencing impact quantification across subjects. However, we also demonstrate that the presence of noise may impact CCEP quantification, and preprocessing is necessary to mitigate this. We show that filtering is more effective than re-referencing or averaging across trials for reducing most common types of noise. COMPARISON WITH EXISTING METHODS: These results suggest that existing CCEP processing methods must be applied with care to maximize noise reduction and minimize changes to the data. We do not test every available processing strategy; rather we demonstrate that processing can influence the results of CCEP studies. We emphasize the importance of reporting all processing methods, particularly re-referencing methods. CONCLUSIONS: We propose a general framework for choosing an appropriate processing pipeline for CCEP data, taking into consideration the noise levels of a specific dataset. We suggest that minimal gentle filtering is preferable.

Medical students' perceptions on preparedness and care delivery for patients with autism or intellectual disability.

Introduction: To provide competent care to patients with autism spectrum disorder (ASD) or intellectual developmental disorder (IDD), healthcare professionals must recognize the needs of neurodivergent populations and adapt their clinical approach. We assessed the perceived preparedness of medical students to adapt care delivery for patients with ASD/IDD, as well as their perceptions on neurodiversity education. Methods: We conducted a sequential explanatory mixed-methods study on undergraduate medical students at McGill University during the academic year 2020-2021. We administered an online survey, followed by semi-structured interviews. We analyzed data using descriptive statistics and thematic analysis. We integrated findings at the interpretation level. Results: We included two-hundred-ten survey responses (~29% of class), and 12 interviews. Few students felt prepared to adjust care for patients with ASD/IDD despite most indicating doing so was important. Ninety-seven percent desired more training regarding care accommodation for neurodivergent patients. Thematic analysis unveiled the perception of current insufficient education, and the value of experiential learning. Discussion/Conclusions: This study highlights low perceived preparedness of medical students to accommodate care for neurodivergent patients, and a desire for more instruction. Incorporating interactive training in medical school curricula regarding modifying care delivery for neurodivergent individuals may improve the perceived preparedness of medical trainees to work with these patients and care quality.

Introduction: Pour fournir des soins compétents aux patients atteints d'un trouble du spectre de l'autisme (TSA) ou d'un trouble du développement intellectuel (TDI), les professionnels de la santé doivent reconnaître les besoins des populations neurodivergentes et adapter leur approche clinique. Nous avons évalué le degré perçu de préparation des étudiants en médecine à adapter la prestation de soins aux patients atteints de TSA/TDI, ainsi que leurs perceptions de la formation relative à la neurodiversité. Méthodes: Nous avons mené une étude séquentielle explicative à méthodes mixtes auprès d'étudiants en médecine de premier cycle de l'Université McGill au cours de l'année universitaire 2020-2021. Nous avons administré un sondage en ligne, suivi d'entretiens semi-structurés. Nous avons analysé les données en faisant appel à la statistique descriptive et à une analyse thématique. Nous avons intégré les résultats sur le plan interprétatif. Résultats: Nous avons inclus deux cent dix réponses à l'enquête (~29% de la classe), et 12 entretiens. Peu d'étudiants se sentaient préparés à adapter les soins aux patients atteints de TSA/TDI, bien que la plupart d'entre eux aient indiqué qu'il était important de le faire. Quatre-vingt-dix-sept pour cent d'entre eux souhaitaient davantage de formation sur l'adaptation des soins aux patients neurodivergents. L'analyse thématique a révélé que les participants considéraient la formation actuelle insuffisante et jugeaient utile l'apprentissage par l'expérience. Discussion/Conclusions: Cette étude met en évidence le faible niveau de préparation perçu par les étudiants en médecine en ce qui concerne l'adaptation des soins aux patients neurodivergents, ainsi que le désir d'une formation plus poussée. L'intégration dans les programmes des facultés de médecine d'une formation interactive portant sur la modification de la prestation des soins pour les personnes neurodivergentes pourrait améliorer la perception des étudiants en médecine de leur degré de préparation à travailler avec ce type de patients et de la qualité des soins.

Multichannel high noise level ECG denoising based on adversarial deep learning.

This paper proposes a denoising method based on an adversarial deep learning approach for the post-processing of multi-channel fetal electrocardiogram (ECG) signals. As it's well known, noise leads to misinterpretations of fetal ECG signals and thus limits the use of fetal electrocardiography for healthcare applications. Therefore, denoising algorithms are essential for the exploitation of non-invasive fetal ECG. The proposed method is based on the combination of three end-to-end trained sub-networks to convert noisy fetal ECG signals into clean signals. The first two sub-networks are linked by skip connections and form a deep convolutional network that downsamples the noisy signals into a latent representation and subsequently upsamples this latent representation to recover clean signals. The third sub-network aims to boost the decoder sub-network to generate realistic clean signals. Experiments carried out on synthetic and real data showed that the proposed method improved by the signal-to-noise (SNR) of fetal ECG signals with input SNR ranging from [Formula: see text] to 0 dB by an average of 20 dB, and improve fetal signal quality by significantly increasing the number of true detected QRS complexes and halving QRS complex detection errors.

[Distribution features of gunshot residue from hunting Steyr Mannlicher AUG-Z3 carbine on targets]. / Osobennosti raspredeleniya na mishenyakh produktov vystrela iz okhotnich'ego karabina Steyr Mannlicher AUG-Z3.

OBJECTIVE: To study the morphology of distribution of shot factors on white targets made of coarse calico at different distances. MATERIAL AND METHODS: The study was conducted on 57 experimental damages of targets made of cotton fabric, caused by shots from hunting self-loading Steyr Mannlicher AUG-Z3 carbine of.223 Rem caliber. The number of experimental firings equal 19 was done by 3 shots at the distance from close range to 250 cm. The examination of shot targets was carried out using the visual, metric, stereoscopic (Leica 125M microscope) methods, in ultraviolet rays (LUMATEC SUPERLITE M Series light). RESULTS: The nature and morphology of distribution of gunshot residue on targets' surfaces made it possible to establish close range firing zones. The nature in which soot is deposited during shot under the conditions of point-blank range and in the first zone of close range (up to 8 cm) allows to establish the position of weapon's transverse plane relative to the target basing on a specific blowout of a gas-powder jet from special design of flame arrestor. The performed experimental shooting from hunting self-loading Steyr Mannlicher AUG-Z3 carbine made it possible to determine the metric and morphological characteristics of the close range firing zones: 1 zone is equal a distance up to 8 cm; 2 zone - up to 30 cm; 3 zone - up to 100 cm from muzzle of weapon. The design features of Steyr Mannlicher AUG-Z3 carbine's flame arrestor allow to identify the type of weapon according to the morphological pattern of target's damage. The complex of obtained data makes it possible to determine the firing distance with high accuracy.

A Qualitative Study on Dentists' Communication Approaches in Managing Fluoride-Hesitant Caregivers.

OBJECTIVES: Guidelines on effective provider-led communication are available but may be underused in dentistry, even if such guidelines could help dentists manage complex clinical scenarios like topical fluoride hesitancy. The purpose of this study was to investigate current chairside communication approaches used by dentists with fluoride-hesitant caregivers. METHODS: A 27-item semistructured interview script was developed and pretested with 3 dentists, revised, and finalized. One-on-one interviews were conducted with a purposive sample of pediatric dentists and general dentists from April to June 2020. Interviews were digitally recorded, transcribed, and analyzed to identify dentists' communication approaches used during clinical interactions with fluoride-hesitant caregivers. Thematic analyses identified themes and subthemes, and exemplary quotes were provided to illustrate each theme. RESULTS: Twenty-seven dentists participated (21 pediatric dentists and 6 general dentists). The mean age of participants was 43.0 ± 8.2 y (range, 30-73). Most participants were women (88.9%), white (51.9%), and non-Hispanic (85.2%). Participants had been practicing dentistry for a mean of 13.2 ± 10.5 y (range, 2-40). There were 4 themes: leaving topical fluoride decisions completely up to the caregiver, educating the caregiver about fluoride, insisting that the caregiver accept fluoride, and engaging the caregiver and child. CONCLUSION: Most communications approaches used by interviewed dentists to manage fluoride hesitancy in clinical settings are not evidence based. Future dental education efforts should ensure that trainees are exposed to and can demonstrate competency in appropriate, evidence-based patient-provider communication strategies. KNOWLEDGE TRANSFER STATEMENT: The study highlights the need for dentists to apply evidence-based communication strategies when managing difficult clinical scenarios like fluoride hesitancy, which is important in optimizing dentist-patient trust.

Investigating two mobile just-in-time adaptive interventions to foster psychological resilience: research protocol of the DynaM-INT study.

BACKGROUND: Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience - interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms. Deep participant phenotyping at baseline serves to identify individual predictors for intervention success in terms of target engagement and stress resilience. METHODS: DynaM-INT aims to recruit N = 250 healthy but vulnerable young adults in the transition phase between adolescence and adulthood (18-27 years) across five research sites (Berlin, Mainz, Nijmegen, Tel Aviv, and Warsaw). Participants are included if they report at least three negative burdensome past life events and show increased levels of internalizing symptoms while not being affected by any major mental disorder. Participants are characterized in a multimodal baseline phase, which includes neuropsychological tests, neuroimaging, bio-samples, sociodemographic and psychological questionnaires, a video-recorded interview, as well as ecological momentary assessments (EMA) and ecological physiological assessments (EPA). Subsequently, participants are randomly assigned to one of two ecological momentary interventions (EMIs), targeting either positive cognitive reappraisal or reward sensitivity. During the following intervention phase, participants' stress responses are tracked using EMA and EPA, and JITAIs are triggered if an individually calibrated stress threshold is crossed. In a three-month-long follow-up phase, parts of the baseline characterization phase are repeated. Throughout the entire study, stressor exposure and mental health are regularly monitored to calculate stressor reactivity as a proxy for outcome resilience. The online monitoring questionnaires and the repetition of the baseline questionnaires also serve to assess target engagement. DISCUSSION: The DynaM-INT study intends to advance the field of resilience research by feasibility-testing two new mechanistically targeted JITAIs that aim at increasing individual stress resilience and identifying predictors for successful intervention response. Determining these predictors is an important step toward future randomized controlled trials to establish the efficacy of these interventions.

[Forensic medical characteristic of prevalence and structure of sudden juveniles' death in Moscow Region and St. Petersburg]. / Sudebno-meditsinskaya kharakteristika rasprostranennosti i struktury vnezapnoi smerti lits molodogo vozrasta v Moskovskoi oblasti i Sankt-Peterburge.

THE AIM OF THE STUDY: Was to compare the prevalence and structure of sudden death from cardiovascular diseases (CVD) in the structure of nonviolent death in Moscow Region as a representative of the large region and St. Petersburg as a city of federal importance. Frequency and structure of this parameter, as well as its dynamics were analyzed. The comparison of obtained results with data of Federal State Statistics Service was done. Nonparametric analysis of the initial data has been conducted. Clustering and visualization, based on the following parameters of initial sample, have been done: «death rate from CVD in the structure of nonviolent death¼, «morbidity rate¼, «incomes¼ and «unemployment rate¼. Correlation dependences between death rate from CVD according to the Form №42 and mentioned parameters of medical and social state of the subject have been determined. Dependences between sudden death rate from CDV and a number of medical and social parameters have been established.

[Morphofunctional cerebral changes associated with development of suicidal behavior]. / Morfofunktsional'nye izmeneniya golovnogo mozga, svyazannye s razvitiem suitsidal'nogo povedeniya.

THE AIM OF THE STUDY: Was to identify the cerebral areas, which demonstrate the most significant structural changes and damaged functional activity in patients with suicidal behavior. The original studies, presented in PubMed database, were used to analyze the literature. Additional literature in the form of atlases, review articles and publications, written in related spheres, was used to interpret the results. The study identified the 69 cerebral regions, demonstrating significant changes and the structures with the most significant deviations among them were selected. The regions of cerebral grey matter, in particular basal ganglia (structures of striatum and limbic system), as well as selected regions of cerebral cortex, specifically frontal, insularis, singulate and parietal mostly were included in the list. The decrease in grey matter volume, changes of neuronal and glial density, special patterns of activity and variations of functional association with other cerebral regions are described within mentioned structures. The literature review found that there was a lack of postmortem examinations in suicidal cases. Advanced study of the described structures is required in cases of completed suicide using new research methods.

Comparison of Patients with Atrial Fibrillation Without Structural Heart Disease and Normal Population In Terms of Urine Catecholamines.

OBJECTIVE: This study aimed to compare the sympathetic nervous system activity of atrial ���brillation patients without structural heart disease and the normal population in terms of urinary metanephrine levels. METHODS: Our study was conducted with 40 paroxysmal or persistent patients without structural heart disease and CHA2DS2VASc score of 0 or 1 and 40 healthy controls. Laboratory parameters, demographic characteristics, and 24-hour urine metanephrine levels were compared between the 2 groups included in the study. RESULTS: Metanephrine value in urine was found to be signi���cantly higher in the atrial ���brillation group (atrial ���brillation group 97.50 �� 17.19 ��g/day vs. control group 74.27 �� 15.55 ��g/day; P < 0.001). The body mass index of the atrial ���brillation group was found to be signi���cantly higher than the control group (atrial ���brillation group 27.26 �� 2.97 kg/m2 vs. control group 24.05 �� 2.24 kg/m2; P < 0.001). In multivariate linear regression analysis, body mass index (beta: 0.266, P =.02) and urinary metanephrine level (beta: 0.522, P = 0.002) were found to be independent risk factors. According to receiver operating characteristic analysis, it was determined that urinary metanephrine value (area under the curve = 0.834, P < 0.001) and body mass index (area under the curve = 0.803, P < 0.001) predicted the development of atrial ���brillation. CONCLUSION: Our study found that urinary metanephrine levels were higher in patients with atrial ���brillation without structural heart disease than those without atrial ���brillation, and metanephrine values predicted the development of atrial ���brillation.

MIF is a common genetic determinant of COVID-19 symptomatic infection and severity.

BACKGROUND: Genetic predisposition to coronavirus disease 2019 (COVID-19) may contribute to its morbidity and mortality. Because cytokines play an important role in multiple phases of infection, we examined whether commonly occurring, functional polymorphisms in macrophage migration inhibitory factor (MIF) are associated with COVID-19 infection or disease severity. AIM: To determine associations of common functional polymorphisms in MIF with symptomatic COVID-19 or its severity. METHODS: This retrospective case-control study utilized 1171 patients with COVID-19 from three tertiary medical centers in the USA, Hungary and Spain, together with a group of 637 pre-pandemic, healthy control subjects. Functional MIF promoter alleles (-794 CATT5-8,rs5844572), serum MIF and soluble MIF receptor levels, and available clinical characteristics were measured and correlated with COVID-19 diagnosis and hospitalization. Experimental mice genetically engineered to express human high- or low-expression MIF alleles were studied for response to coronavirus infection. RESULTS: In patients with COVID-19, there was a lower frequency of the high-expression MIF CATT7 allele when compared to healthy controls [11% vs. 19%, odds ratio (OR) 0.54 [0.41-0.72], P < 0.0001]. Among inpatients with COVID-19 (n = 805), there was a higher frequency of the MIF CATT7 allele compared to outpatients (n = 187) (12% vs. 5%, OR 2.87 [1.42-5.78], P = 0.002). Inpatients presented with higher serum MIF levels when compared to outpatients or uninfected healthy controls (87 ng/ml vs. 35 ng/ml vs. 29 ng/ml, P < 0.001, respectively). Among inpatients, circulating MIF concentrations correlated with admission ferritin (r = 0.19, P = 0.01) and maximum CRP (r = 0.16, P = 0.03) levels. Mice with a human high-expression MIF allele showed more severe disease than those with a low-expression MIF allele. CONCLUSIONS: In this multinational retrospective study of 1171 subjects with COVID-19, the commonly occurring -794 CATT7MIF allele is associated with reduced susceptibility to symptomatic SARS-CoV-2 infection but increased disease progression as assessed by hospitalization. These findings affirm the importance of the high-expression CATT7MIF allele, which occurs in 19% of the population, in different stages of COVID-19 infection.

Optical nonlinearity of a dual-frequency nematic liquid crystal via temperature-mediated mapping of dielectric anisotropy.

Liquid crystals are of great interest in the field of nonlinear optics due to their efficient response to low intensity light fields. Here we present a new, to the best of our knowledge, mechanism of a nonlinear optical response which is observed for a dye-doped dual-frequency nematic liquid crystal. The local increase in temperature caused by the absorption of light beam in the liquid crystal medium leads to spatial variation and inversion of the sign of the dielectric anisotropy. When an alternating current electric field with a frequency close to the cross-over frequency is applied to the liquid crystal cell, the planar orientation sustains at the beam periphery, but elastic deformation occurs in the irradiation region. In the case of a dye dopant with negative absorption dichroism, a first-order orientational transition with large bistability region is obtained.

Metabolism of a New Dipeptide Neuroprotector in Rats.

Metabolism of a new neuroprotector GZK-111 (N-phenylacetylglycyl-L-proline ethyl ester) in rat blood plasma was studied by HPLC-mass spectrometry. Four biotransformation products were identified. It is concluded that the main ways of GZK-111 biotransformation are hydrolysis of the ester bond by esterases followed by degradation of the resulting metabolite, as well as reactions leading to the formation of phenylacetic acid and cycloprolylglycine that exhibits neuropsychotropic activity.

Preclinical Pharmacokinetics of GZK-111, a Dipeptide with Neuroprotective Activity.

We studied the pharmacokinetics of GZK-111 (N-phenylacetyl-glycyl-L-proline ethyl ether), a compound with neuroprotective activity, and its metabolite CPG (cyclo-L-prolylglycine) in rat blood plasma after single intravenous and intragastric administration in a dose of 20 mg/kg. It was found that the parent drug undergoes intensive biotransformation; its metabolite CPG persists in the circulation more than twice as long as GZK-111 and its plasma concentrations were higher by 50-70 times than the concentrations of the parent compound.

HCN Channel Phosphorylation Sites Mapped by Mass Spectrometry in Human Epilepsy Patients and in an Animal Model of Temporal Lobe Epilepsy.

Because hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels modulate the excitability of cortical and hippocampal principal neurons, these channels play a key role in the hyperexcitability that occurs during the development of epilepsy after a brain insult, or epileptogenesis. In epileptic rats generated by pilocarpine-induced status epilepticus, HCN channel activity is downregulated by two main mechanisms: a hyperpolarizing shift in gating and a decrease in amplitude of the current mediated by HCN channels, Ih. Because these mechanisms are modulated by various phosphorylation signaling pathways, we hypothesized that phosphorylation changes occur at individual HCN channel amino acid residues (phosphosites) during epileptogenesis. We collected CA1 hippocampal tissue from male Sprague Dawley rats made epileptic by pilocarpine-induced status epilepticus, and age-matched naïve controls. We also included resected human brain tissue containing epileptogenic zones (EZs) where seizures arise for comparison to our chronically epileptic rats. After enrichment for HCN1 and HCN2 isoforms by immunoprecipitation and trypsin in-gel digestion, the samples were analyzed by mass spectrometry. We identified numerous phosphosites from HCN1 and HCN2 channels, representing a novel survey of phosphorylation sites within HCN channels. We found high levels of HCN channel phosphosite homology between humans and rats. We also identified a novel HCN1 channel phosphosite S791, which underwent significantly increased phosphorylation during the chronic epilepsy stage. Heterologous expression of a phosphomimetic mutant, S791D, replicated a hyperpolarizing shift in Ih gating seen in neurons from chronically epileptic rats. These results show that HCN1 channel phosphorylation is altered in epilepsy and may be of pathogenic importance.

Sequential Treatment with an Immune Checkpoint Inhibitor Followed by a Small-Molecule Targeted Agent Increases Drug-Induced Pneumonitis.

PURPOSE: Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis. MATERIALS AND METHODS: In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated. RESULTS: Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031). CONCLUSION: Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.

Quantification of triiodothyronine and thyroxine in rat serum using liquid chromatography tandem mass spectrometry.

Thyroid hormones act on almost every tissue in the body to promote catabolism in cells and are important for regulating many biological processes. Accurate quantification of endogenous thyroid hormones has become essential for clinical and non-clinical applications in the development of new drugs according to the OECD Guideline (2018). However, there are difficulties in quantitative analysis of thyroid hormones because no analyte-free biological matrices are available for analysis of endogenous substances. In this study, surrogate matrix and surrogate analyte methods were compared and validated to quantify endogenous triiodothyronine (T3) and thyroxine (T4) in rat serum using LC-MS/MS. Separation of analytes was performed using an Xbridge™ C18 (2.1 × 50 mm, 2.5 µm) column. In the surrogate matrix, 3,3'5-triiodo- l-thyronine-13C6 (cT3) and l-thyroxine-13C6 (cT4) were used as the internal standard (IS), and in the surrogate analyte, l-3,3'-diiodothyronine-13C6 (cT2) was used as the IS. The mobile phases consisted of 0.1 % acetic acid in purified water (A) and 0.1 % acetic acid in acetonitrile (B). Both analytical methods were suitable for selectivity, matrix effect, carryover, lower limit of quantification, linearity, accuracy, precision, recovery, stability and parallelism. The surrogate matrix method was more accurate than using the surrogate analyte method, including evaluation of parallelism at low concentrations. Additionally, the surrogate matrix is cost-effective for T3 and T4 analysis in biological samples because it consists only of deionized water. However, surrogate analytes difficult to evaluate parallelism by obtaining response factors for mass spectrometric signal differences between the actual and surrogate analytes. Therefore, the results of this study indicate that it is more cost-effective to use the surrogate matrix method for endogenous thyroid hormone, T3 and T4, analysis in biological samples.

Seroepidemiology of Leptospira infection in slaughtered cattle in Gauteng province, South Africa.

Leptospirosis is an important economical disease of livestock globally, especially in Asia, the Caribbean, and the African continent. Its presence has been reported in a wide range of livestock. However, information on leptospirosis in South Africa is scanty. We conducted a cross-sectional study in 11 randomly selected abattoirs to determine the seroprevalence and risk factors for leptospirosis in slaughtered cattle in Gauteng province, South Africa. During abattoir visits to selected abattoirs, blood samples were collected from 199 cattle and demographic data obtained on the slaughtered animals. The microscopic agglutination test (MAT) was performed on all sera using a 26-serotype panel using cutoff titer ≥ 1:100. Animal- and abattoir-level risk factors were investigated for their association with seropositivity for leptospirosis. The seroprevalence of leptospirosis in the cattle sampled was 27.6% (55/199). The predominant serogroups detected in seropositive cattle were Sejroe (sv. Hardjo) (38.2%) and Mini sv. Szwajizak) (14.5%) but low to Canicola (sv. Canicola) (1.8%) and Pomona (sv. Pomona) (1.8%). The differences were statistically significant (P < 0.05). Of the five variables investigated, only one (abattoirs) had statistically significantly (P < 0.001) differences in the seroprevalence of leptospirosis among abattoirs. The study documented for the first time in South Africa, the occurrence of serogroups Sejroe (Hardjo bovis strain lely 607), Tarassovi, Hebdomadis, and Medanensis in slaughtered cattle. It was concluded that six of the nine serovars (representing seven serogroups) of Leptospira spp. circulating in cattle population in South Africa are not vaccine serogroups. The clinical, diagnostic, and public health importance of the findings cannot be ignored.

Fully implanted adaptive deep brain stimulation in freely moving essential tremor patients.

OBJECTIVE: Deep brain stimulation (DBS) is a safe and established treatment for essential tremor (ET) and several other movement disorders. One approach to improving DBS therapy is adaptive DBS (aDBS), in which stimulation parameters are modulated in real time based on biofeedback from either external or implanted sensors. Previously tested systems have fallen short of translational applicability due to the requirement for patients to continuously wear the necessary sensors or processing devices, as well as privacy and security concerns. APPROACH: We designed and implemented a translation-ready training data collection system for fully implanted aDBS. Two patients chronically implanted with electrocorticography strips over the hand portion of M1 and DBS probes in the ipsilateral ventral intermediate nucleus of the thalamus for treatment of ET were recruited for this study. Training was conducted using a translation-ready distributed training procedure, allowing a substantially higher degree of control over data collection than previous works. A linear classifier was trained using this system, biased towards activating stimulation in accordance with clinical considerations. MAIN RESULTS: The clinically relevant average false negative rate, defined as fraction of time during which stimulation dropped below [Formula: see text] clinical levels during movement epochs, was 0.036. Tremor suppression, calculated through analysis of gyroscope data, was 33.2% more effective on average with aDBS than with continuous DBS. During a period of free movement with aDBS, one patient reported a slight paresthesia; patients noticed no difference in treatment efficacy between systems. SIGNIFICANCE: Here is presented the first translation-ready training procedure for a fully embedded aDBS control system for MDs and one of the first examples of such a system in ET, adding to the consensus that fully implanted aDBS systems are sufficiently mature for broader deployment in treatment of movement disorders.

Flavone inspired discovery of benzylidenebenzofuran-3(2H)-ones (aurones) as potent inhibitors of human protein kinase CK2.

In this work, we describe the design, synthesis and SAR studies of 2-benzylidenebenzofuran-3-ones (aurones), a new family of potent inhibitors of CK2. A series of aurones have been synthesized. These compounds are structurally related to the synthetic flavones and showed nanomolar activities towards CK2. Biochemical tests revealed that 20 newly synthesized compounds inhibited CK2 with IC50 values in the nanomolar range. Further property-based optimization of aurones was performed, yielding a series of CK2 inhibitors with enhanced lipophilic efficiency. The most potent compound 12m (BFO13) has CLipE = 4.94 (CLogP = 3.5; IC50 = 3.6 nM) commensurable with the best known inhibitors of CK2.