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Competing Interests: Competing interests: None declared.

Although considerable research has been done on memory for temporal information, as well as on the relationship between context and cognition, not much is known about the influence of temporal context on memory formation and retention. In this study, given that our sample comes from a largely Roman Catholic population, we used religious practices that occur throughout the calendar year to operationalize temporal context into two religious seasons (Lent and Ordinary Time). In addition, we used religious art to assess experience and memory as a function of whether there was temporal congruity or incongruity. This allowed us to explore different levels of memory representation; namely, memory for perceptual details of the art, memory for more inferential understanding of the art, and autobiographical memory for the initial experience of the art. Participants viewed 22 representational and abstract artworks during either Lent or Ordinary Time. After viewing, memory was tested at immediate, 1-day, and 7-day delays. We expected that the congruent temporal context (i.e., Lent) would lead to more activated semantic knowledge, which would then aid memory encoding and retention. This was the case only for perceptual details of the art. In addition, during Lent, forgetting followed a more linear pattern. These results suggest that priming semantic knowledge through temporal context leads encoding to focus on low-level information, as opposed to the processing of more complex information. Overall, these findings suggest that temporal context can influence cognition, but to a limited extent., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Coaching interventions in graduate medical education have proven successful in increasing technical and communication skills, reducing errors, and improving patient care. Effective stakeholder engagement enhances the relevance, value, and long-term sustainability of interventions, yet specific strategies for stakeholder engagement remain uncertain. The purpose of this article is to identify strategies to foster engagement of diverse stakeholder groups in coaching interventions., Material and Methods: We conducted 35 semi-structured interviews between November 2021 and April 2022 with purposively sampled key stakeholders that captured participants' perspectives on physicians' communication training needs, roles, and involvement in, as well as contextual factors, facilitators, barriers, and improvement strategies of the multi-departmental Communication Coaching Program at our institution. We utilized the Consolidated Framework of Implementation Research to guide data collection and analysis. An analytic approach relied on team-based thematic analysis with high inter-coder agreement between three raters (Cohen's kappa coefficient 0.83). Several validation techniques were used to enhance the credibility and trustworthiness of the study., Results: Analysis of transcribed interviews with stakeholders directly involved in the Communication Coaching Program, including 10 residents, 10 faculty coaches, 9 medical education leaders, and 8 programmatic sponsors, revealed five key engagement strategies: (1) embrace collaborative design, (2) enable flexible adjustments and modifications, (3) secure funding, (4) identify champions, and (5) demonstrate outcomes. Additionally, a patient-centered approach to delivering the best possible patient care emerged as a primary objective that linked all stakeholder groups., Discussion: Evaluating the experiences of key stakeholders in the Communication Coaching Program helped identify targetable strategies to facilitate participant engagement across all organizational levels. The analysis also revealed universal alignment around the importance of providing high-quality patient care. Insights from this work provide guidance for clinical training programs moving toward the implementation of coaching interventions.

Background A national survey of general surgery residents revealed significant self-assessed deficits in preparation for independent practice, with only 7.7% of graduating postgraduate year 5 residents (n=1145) reporting self-efficacy for all 10 commonly performed operations surveyed. Objective We sought to understand why this phenomenon occurs. We hypothesized that self-efficacy would be positively correlated with both operative independence and case volume. Methods We compared 3 independent datasets: case information for the same 10 previously surveyed operations for residents graduating in 2020 (dataset 1), operative independence data obtained through the SIMPL OR app, an operative self-assessment tool (dataset 2), and case volume data obtained through the Accreditation Council for Graduate Medical Education National Data Report (dataset 3). Operations were categorized into high, middle (mid), and low self-efficacy tiers; analysis of variance was used to compare operative independence and case volume per tier. Results There were significant differences in self-efficacy between high (87.7%), mid (68.3%), and low (25.4%) tiers ( P =.008 [95% CI 6.2, 32.7] for high vs mid, P <.001 for high vs low [49.1, 75.6], and P <.001 for mid vs low [28.7, 57.1]). The percentage of cases completed with operative independence followed similar trends (high 32.7%, mid 13.8%, low 4.9%, P =.006 [6.4, 31.4] for high vs mid, P <.001 [15.3, 40.3] for high vs low, P =.23 [-4.5, 22.3] for mid vs low). The total volume of cases decreased from high to mid to low self-efficacy tiers (average 91.8 to 20.8 to 11.1) but did not reach statistical significance on post-hoc analysis. Conclusions In this analysis of US surgical residents, operative independence was strongly correlated with self-efficacy.

Purpose: Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy adults, but has also become an increasing cause of invasive infection. The aims of this study were to describe the incidence and factors associated with the occurrence of invasive GBS disease in adults in Norway., Methods: We performed a nationwide retrospective case-control study of invasive GBS infections during 1996-2019, with two control groups; invasive Group A streptococcal disease (GAS) to control for changes in surveillance and diagnostics, and a second representing the general population., Results: A total of 3710 GBS episodes were identified. The age-standardized incidence rate increased steadily from 1.10 (95% CI 0.80-1.50) in 1996 to 6.70 (95% CI 5.90-7.50) per 100,000 person-years in 2019. The incidence rate had an average annual increase of 6.44% (95% CI 5.12-7.78). Incidence rates of GAS varied considerably, and there was no evidence of a consistent change over the study period. GBS incidence was highest among adults > 60 years of age. Cardiovascular disease, cancer, and diabetes were the most common comorbid conditions. There was a shift in the distribution of capsular serotypes from three dominant types to more equal distribution among the six most common serotypes., Conclusions: The incidence of invasive GBS disease in adults increased significantly from 1996 to 2019. The increasing age of the population with accompanying underlying comorbid conditions might contribute to the increasing burden of invasive GBS disease. Interestingly, type 1 diabetes was also associated with the occurrence of invasive GBS disease., (© 2024. The Author(s).)

Background: Studies suggest that there are key differences in operative experience based on a trainee's gender. A large-scale self-efficacy (SE) survey, distributed to general surgery residents after the American Board of Surgery In-Training Examination in 2020, found that female gender was associated with decreased SE in graduating PGY5 residents for all 4 laparoscopic procedures included on the survey (cholecystectomy, appendectomy, right hemicolectomy, and diagnostic laparoscopy). We sought to determine whether these differences were reflected at the case level when considering operative performance and supervision using an operative assessment tool (SIMPL OR)., Methods: Supervision and performance data reported through the SIMPL OR platform for the same 4 laparoscopic procedures included in the SE survey were aggregated for residents who were PGY5s in 2020. Independent t-tests and multiple linear regression were used to determine the relationship between trainee gender and supervision/performance ratings., Results: For laparoscopic cases in aggregate (n = 2708), male residents rated their performance higher than females (3.57 vs. 3.26, p < 0.001, 1 = critical deficiency, 5 = exceptional performance) and reported less supervision (3.15 vs. 2.85, p < 0.001, 1 = show and tell, 4 = supervision only); similar findings were seen when looking at attending reports of resident supervision and performance. A multiple linear regression model showed that attending gender did not significantly predict resident-reported supervision or performance levels, while case complexity and trainee gender significantly affected both supervision and performance (p < 0.001)., Discussion: Female residents perceive themselves to be less self-efficacious at core laparoscopic procedures compared to their male colleagues. Comparison to more case-specific data confirm that female residents receive more supervision and lower performance ratings. This may create a domino effect in which female residents receive less operative independence, preventing the opportunity to establish SE. Further research should identify opportunities to break this cycle and consider gender identity beyond the male/female construct., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: A 2020 survey of post-graduate year 5 (PGY5) general surgery residents linked to the American Board of Surgery In-Training Examination (ABSITE) revealed significant deficits in self-efficacy (SE), or personal judgment of one's ability to complete a task, for 10 commonly performed operations. Identifying whether this deficit is similarly perceived by program directors (PDs) has not been well established. We hypothesized that PDs would perceive higher levels of operative SE compared to PGY5s., Methods: A survey was distributed through the Association of Program Directors in Surgery listserv; PDs were queried about their PGY5 residents' ability to perform the same 10 operations independently and their accuracy of patient assessments and operative plans for components of several core entrustable professional activities (EPAs). Results of this survey were compared to PGY5 residents' perception of their SE and entrustment based on the 2020 post-ABSITE survey. Chi-squared tests were used for statistical analysis., Results: 108 responses were received, representing ∼32% (108/342) of general surgery programs. Perceptions from PDs of PGY5 residents' operative SE were highly concordant with resident perceptions; no significant differences were observed for 9 of 10 procedures. Both PGY5 residents and PDs perceived adequate levels of entrustment; no significant differences were observed for 6 of 8 EPA components., Conclusions: These findings show concordance between PDs and PGY5 residents in their perceptions of operative SE and entrustment. Though both groups perceive adequate levels of entrustment, PDs corroborate the previously described operative SE deficit, illustrating the importance of improved preparation for independent practice.

We are the multi-institutional organization known as the Collaboration of Surgical Education Fellows (CoSEF). We've collectively reflected on our range of experiences across the country and identified 3 principles which promote a successful intern experience: (1) Own your patients; (2) Treat people like people; and (3) Take care of yourself., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

We describe inflammatory vaginitis as a potential side effect of long-term rituximab treatment for multiple sclerosis in the absence of any other systemic disease or underlying malignancy.More studies are needed to characterise the incidence of inflammatory vaginitis among women on long-term rituximab therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Implementation of the Fundamentals of Laparoscopic Surgery (FLS) by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) has served a need for educational structure for laparoscopic skill within General Surgery training since 2004. This study looks at how FLS affects resident self-efficacy (SE) with laparoscopic procedures., Methods: We conducted a national survey, linked to the 2020 American Board of Surgery In-Training Examination (ABSITE), in which 9275 residents from 325 US General Surgery Training Programs participated. The online survey included multimodal questions that analyzed whether participants felt they could perform the most commonly-logged laparoscopic operations among residents [Laparoscopic Appendectomy (LA), Laparoscopic Cholecystectomy (LC), Laparoscopic Right Hemicolectomy (LRH), Diagnostic Laparoscopy (DL)] without faculty assistance. This used a 5-point scaled assessment, ranging from "not able to" to "definitely able to." Multivariate analyses determined if completion of FLS made a difference for resident self-efficacy, stratified by post-graduate year (PGY)., Results: At the time of the survey, 2300 reported completion of FLS. The percentage of FLS completion increased from PGY1 to PGY5 (4.2% n = 59 vs 85.8% n = 893). PGY1 residents who completed FLS, from 48 diverse institutions, demonstrated the most significant increases in SE (p < 0.05) with significantly higher perceived self-efficacy in LA (p = 0.001) and LRH (p = 0.012). PGY2 and PGY3 residents indicated increased SE in DL (p = 0.037, p = 0.015, respectively), based on FLS completion. These FLS effects were less evident in the more senior classes., Conclusions: Completion of FLS arguably has the greatest benefits for more junior residents, as it establishes a foundation of laparoscopic knowledge and skill, upon which further residency training can build. Successful completion of the curriculum and assessment offered by the Fundamentals of Laparoscopic Surgery leads to greater sense of ability in early trainees., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Our aim was to identify gender and racial disparities in presidential leadership for national medical and surgical organizations., Methods: We located publicly sourced information on national medical organizations. Years between or since the first diverse presidents were analyzed using descriptive statistics and Mann Whitney U tests., Results: Sixty-seven national medical and surgical organizations were surveyed. 70.8% (n = 34) diversified via gender first (White-female), whereas 26.1% (n = 14) had racial diversity first. Organizations with gender diversity first followed with an African American male president sooner than organizations who first diversified by race (14.7 ± 11.8 v. 27.6 ± 11.3 years, p = 0.018). No significant difference was observed for the third tier of diversification., Conclusions: Significant gender and racial leadership disparities in national medical organizations are still present. It is notable that organizations with female leaders had a shorter timeline to racial diversity. These findings help to inform strategies to promote and increase diversity, equity, and inclusion in national leadership., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Tandem mass tag spectrometry (TMT labeling-LC-MS/MS) was utilized to examine the global proteomes of Atlantic halibut eggs at the 1-cell-stage post fertilization. Comparisons were made between eggs judged to be of good quality (GQ) versus poor quality (BQ) as evidenced by their subsequent rates of survival for 12 days. Altered abundance of selected proteins in BQ eggs was confirmed by parallel reaction monitoring spectrometry (PRM-LC-MS/MS). Correspondence of protein levels to expression of related gene transcripts was examined via qPCR. Potential mitochondrial differences between GQ and BQ eggs were assessed by transmission electron microscopy (TEM) and measurements of mitochondrial DNA (mtDNA) levels., Results: A total of 115 proteins were found to be differentially abundant between GQ and BQ eggs. Frequency distributions of these proteins indicated higher protein folding activity in GQ eggs compared to higher transcription and protein degradation activities in BQ eggs. BQ eggs were also significantly enriched with proteins related to mitochondrial structure and biogenesis. Quantitative differences in abundance of several proteins with parallel differences in their transcript levels were confirmed in egg samples obtained over three consecutive reproductive seasons. The observed disparities in global proteome profiles suggest impairment of protein and energy homeostasis related to unfolded protein response and mitochondrial stress in BQ eggs. TEM revealed BQ eggs to contain significantly higher numbers of mitochondria, but differences in corresponding genomic mtDNA (mt-nd5 and mt-atp6) levels were not significant. Mitochondria from BQ eggs were significantly smaller with a more irregular shape and a higher number of cristae than those from GQ eggs., Conclusion: The results of this study indicate that BQ Atlantic halibut eggs are impaired at both transcription and translation levels leading to endoplasmic reticulum and mitochondrial disorders. Observation of these irregularities over three consecutive reproductive seasons in BQ eggs from females of diverse background, age and reproductive experience indicates that they are a hallmark of poor egg quality. Additional research is needed to discover when in oogenesis and under what circumstances these defects may arise. The prevalence of this suite of markers in BQ eggs of diverse vertebrate species also begs investigation., (© 2022. The Author(s).)

Psychological safety is known to improve team performance and organizational learning. The related concept of "educational safety" has recently emerged to describe an environment in which learners can unreservedly focus on learning and professional growth, without worrying about the potential repercussions of interpersonal risk-taking. Educational safety is crucial for optimal learning in clinical environments, and yet is difficult to establish due to constant performance assessment, fear of failure, and pervasive hierarchies. In this perspective, we propose a framework for conceptualizing educational safety in surgical learning environments, and explore current threats to educational safety. We also discuss strategies for combating these threats, as well as the importance of further research to evaluate the impact of educational safety on surgical learning outcomes., (Published by Elsevier Inc.)

Background: Local needs assessments in our institution's surgery and neurology residency programs identified barriers to effective communication, such as no shared communication framework and limited feedback on nontechnical clinical skills. Residents identified faculty-led coaching as a desired educational intervention to improve communication skills. Three university departments (Surgery, Neurology, and Pediatrics) and health-care system leaders collaborated closely to develop an innovative communication coaching initiative generalizable to other residency programs., Innovation: Coaching program development involved several layers of collaboration between health-care system leaders, faculty educators, and departmental communication champions. The efforts included: (1) creating and delivering communication skills training to faculty and residents; (2) hosting frequent meetings among various stakeholders to develop program strategy, discuss opportunities and learnings, and engage other medical educators interested in coaching; (3) obtaining funding to implement the coaching initiative; (4) selecting coaches and providing salary and training support., Evaluation: A multi-phased mixed-methods study utilized online surveys and virtual semi-structured interviews to assess the program's quality and impact on the communication culture and the satisfaction and communication skills of residents. Quantitative and qualitative data have been integrated during data collection and analysis using embedding, building, and merging strategies., Discussion and Implications: Establishing a multi-departmental coaching program may be feasible and can be adapted by other programs if similar resources and focus are present. We found that stakeholders' buy-in, financial support, protected faculty time, flexible approach, and rigorous evaluation are crucial factors in successfully implementing and sustaining such an initiative., Competing Interests: None

The Enterobacteriales order is composed of Gram-negative bacteria that range from harmless symbionts to well-studied pathogens. We announce complete genome sequences of five related SO-1-like Enterobacteriales bacteriophages (also known as the Dhillonvirus genus) isolated from wastewater that infect Escherichia coli (Opt-212, Over9000, Pubbukkers, and Teewinot) or Shigella boydii (StarDew).

Background: Local, regional, and national diversity, equity, and inclusion (DEI) initiatives have been established to combat barriers to entry and promote retention in surgery residency programs. Our study evaluates changes in diversity in general surgery residency programs. We hypothesize that diversity trends have remained stable nationally and regionally., Materials and Methods: General surgery residents in all postgraduate years were queried regarding their self-reported sex, race, and ethnicity following the 2020 ABSITE. Residents were then grouped into geographic regions. Data were analyzed utilizing descriptive statistics, Kruskal-Wallis test, and chi-square analyses., Results: A total of 9276 residents responded. Nationally, increases in female residents were noted from 38.0 to 46.0% ( P < .001) and in Hispanic or Latinx residents from 7.3 to 8.3% ( P = .031). Across geographic regions, a significant increase in female residents was noted in the Northwest (51.9 to 58.3%, P = .039), Midwest (36.9 to 43.3%, P = .006), and Southwest (35.8 to 47.5%, P = .027). A significant increase in black residents was only noted in the Northwest (0 to 15.8%, P = .031). The proportion of white residents decreased nationally by 8.9% and in the Mid-Atlantic, Southeast, and Southwest between 5.5 and 15.9% ( P < .05)., Discussion: In an increasingly diverse society, expanding the numbers of underrepresented surgeons in training, and ultimately in practice, is a necessity. This study shows that there are region-specific increases in diversity, despite minimal change on a national level. This finding may suggest the need for region-specific DEI strategies and initiatives. Future studies will seek to evaluate individual programs with DEI plans and determine if there is a correlation to changing demographics.

Aims: To evaluate the analytical performance of 32 rapid tests for detection of antibodies against coronavirus SARS-CoV-2., Materials and Methods: We used at total of 262 serum samples (197 pre-pandemic and 65 convalescent COVID-19), and three criteria to evaluate the rapid tests under standardized and optimal conditions: (i) Immunoglobulin G (IgG) specificity "good" if lower limit of the 95% confidence interval was ≥ 97.0%, "acceptable" if point estimate was ≥ 97.0%, otherwise "not acceptable". (ii) IgG sensitivity "good" if point estimate was ≥ 90.0%, "acceptable" if ≥ 85.0%, otherwise "not acceptable". (iii) User-friendliness "not acceptable" if complicated to perform or difficult to read result, otherwise "good". We also included partial evaluations of three automated immunoassay systems., Results: Sensitivity and specificity varied considerably; IgG specificity between 90.9% (85.9-94.2) and 100% (97.7-100.0), and IgG sensitivity between 53.8% (41.9-65.4) and 98.5% (91.0-100.0). Combining our evaluation criteria, none of the 28 rapid tests that detected IgG had an overall performance considered "good", seven tests were considered "acceptable", while 21 tests were considered "not acceptable". Four tests detected only total antibodies and were not given an overall evaluation. IgG sensitivity and/or specificity of the automated immunoassays did not exceed that of many rapid tests., Conclusion: When prevalence is low, the most important analytical property is a test's IgG specificity, which must be high to minimize false positive results. Out of 32 rapid tests, none had a performance classified as "good", but seven were classified as "acceptable"., (Copyright © 2021. Published by Elsevier B.V.)

Background: The purpose of this study was to investigate the effect of advising sleep health optimization on anthropomorphic variables following 10 weeks resistance exercise training., Methods: Thirty untrained healthy men were recruited for the study and 23 were included in the final analysis. Participants were randomly assigned to exercise and sleep optimization: ExS (N.=10) or exercise only: Ex (N.=12). Both groups performed a whole-body resistance exercise program twice a week for 10 weeks. The ExS group received sleep health (SH) education on how to improve both sleep quantity and quality., Results: After 10 weeks of training both groups had increased lean body mass by a similar amount. The ExS group experienced an increase of 1.7±1.1 kg while the Ex group experienced an increase of 1.3±0.8 kg (P=0.29 for difference between groups). The men in the ExS group reduced fat mass significantly (-1.8±0.8 kg) while the Ex group did not (0.8±1.0 kg). P value was 0.02 for difference between groups., Conclusions: This randomized controlled trial suggests that combining regular resistance exercise training with optimization of sleep health provide significant added benefits to body composition. This optimization provides a simple and cheap tool, applicable to the general healthy population.

Microorganisms act both as drivers and indicators of perturbations in the marine environment. In an effort to establish baselines to predict the response of marine habitats to environmental change, here we report a broad survey of microbial diversity across the Indian Ocean, including the first microbial samples collected in the pristine lagoon of Salomon Islands, Chagos Archipelago. This was the first large-scale ecogenomic survey aboard a private yacht employing a 'citizen oceanography' approach and tools and protocols easily adapted to ocean going sailboats. Our data highlighted biogeographic patterns in microbial community composition across the Indian Ocean. Samples from within the Salomon Islands lagoon contained a community which was different even from adjacent samples despite constant water exchange, driven by the dominance of the photosynthetic cyanobacterium Synechococcus. In the lagoon, Synechococcus was also responsible for driving shifts in the metatranscriptional profiles. Enrichment of transcripts related to photosynthesis and nutrient cycling indicated bottom-up controls of community structure. However a five-fold increase in viral transcripts within the lagoon during the day, suggested a concomitant top-down control by bacteriophages. Indeed, genome recruitment against Synechococcus reference genomes suggested a role of viruses in providing the ecological filter for determining the β-diversity patterns in this system.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits.

Competing Interests: The authors have declared that no competing interests exist.

Background: The use of Deep Brain Stimulation (DBS) as a potential therapy for treatment resistant epilepsy remains an area of active clinical investigation. We recently reported the first chronic evaluation of an implantable, clinical-grade system that permits concurrent stimulation and recording, in a large animal (ovine) model developed to study DBS for epilepsy., Objective: In this study we extended this work to compare the effects of remote (anterior thalamic) and direct (hippocampal) stimulation on local field potential (LFP) activity and network excitability, and to assess closed-loop stimulation within this neural network., Methods: Following anesthesia and 1.5T MRI acquisition, unilateral anterior thalamic and hippocampal DBS leads were implanted in three subjects using a frameless stereotactic system. Chronic, awake recordings of evoked potentials (EPs) and LFPs in response to thalamic and hippocampal stimulation were collected with the implanted device and analyzed off-line., Results: Consistent with earlier reports, thalamic DBS and direct stimulation of the hippocampus produced parameter-dependent effects on hippocampal activity. LFP suppression could be reliably induced with specific stimulation parameters, and was shown to reflect a state of reduced network excitability, as measured by effects on hippocampal EP amplitudes and after-discharge thresholds. Real-time modulation of network excitability via the implanted device was demonstrated using hippocampal theta-band power level as a control signal for closed-loop stimulation., Conclusions: The results presented provide evidence of network excitability changes induced by stimulation that could underlie the clinical effects that have been reported with both thalamic and direct cortical stimulation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A bi-directional neural interface (NI) system was designed and prototyped by incorporating a novel neural recording and processing subsystem into a commercial neural stimulator architecture. The NI system prototype leverages the system infrastructure from an existing neurostimulator to ensure reliable operation in a chronic implantation environment. In addition to providing predicate therapy capabilities, the device adds key elements to facilitate chronic research, such as four channels of electrocortigram/local field potential amplification and spectral analysis, a three-axis accelerometer, algorithm processing, event-based data logging, and wireless telemetry for data uploads and algorithm/configuration updates. The custom-integrated micropower sensor and interface circuits facilitate extended operation in a power-limited device. The prototype underwent significant verification testing to ensure reliability, and meets the requirements for a class CF instrument per IEC-60601 protocols. The ability of the device system to process and aid in classifying brain states was preclinically validated using an in vivo non-human primate model for brain control of a computer cursor (i.e. brain-machine interface or BMI). The primate BMI model was chosen for its ability to quantitatively measure signal decoding performance from brain activity that is similar in both amplitude and spectral content to other biomarkers used to detect disease states (e.g. Parkinson's disease). A key goal of this research prototype is to help broaden the clinical scope and acceptance of NI techniques, particularly real-time brain state detection. These techniques have the potential to be generalized beyond motor prosthesis, and are being explored for unmet needs in other neurological conditions such as movement disorders, stroke and epilepsy.

A slight predominance of cluster pain on the right side has been reported in several studies. The aim of this large retrospective Nordic multicenter study was to estimate the prevalence of right- and left-sided pain in cluster headache (CH) patients with side-locked pain, the prevalence of side shifts in episodic and chronic CH patients, and the occurrence of cranial autonomic symptoms related to pain side. Among 383 cluster patients, 55 (14%) had experienced pain side shift. Of the remaining 328 individuals without side shift, there was no significant difference between the occurrence of right-sided and left-sided pain (54 vs. 46%). The prevalence of side shift was similar for episodic and chronic CH and the occurrence of cranial autonomic symptoms was not influenced by the pain side. In conclusion, previous reports of a side difference in location of cluster pain could not be confirmed in this large Nordic sample.

Young adults presenting with an acute myelopathy often represent a diagnostic challenge. We present the case of a 20-year-old man who demonstrated many of the diagnostic issues involved in the evaluation of this syndrome.

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura and transient hemiplegia. FHM mutations are known in three genes, the CACNA1A (FHM1) gene, the ATP1A2 (FHM2) and the SCN1A (FHM3) gene and seem to have an autosomal-dominant mode of inheritance. The aim of this study was to search for FHM mutations in FHM families identified through a screen of the Danish population of 5.2 million people. FHM patients were diagnosed according to the International Classification of Headache Disorders and all FHM patients had a physical and neurological examination by a physician. A total of 147 FHM patients from 44 different families were identified; 43 FHM families participated in this study. Linkage analysis of these families shows clear linkage to the FHM locus (FHM1) on chromosome 19, supportive linkage to the FHM2 locus whereas no linkage was found to the FHM3 locus. Furthermore, we sequenced all exons and promoter regions of the CACNA1A and ATP1A2 genes and screened for the Q1489K mutation in the SCN1A gene. CACNA1A gene mutations were identified in three of the FHM families, two known FHM mutations, R583Q and T666M and one novel C1369Y mutation. Three FHM families were identified with novel mutations in the ATP1A2 gene; a family with a V138A mutation, a family with a R202Q mutation and a family with a R763C mutation. None of the Danish FHM families have the Q1489K mutation in the SCN1A gene. Our study shows that only 14% (6/42) of FHM families in the general Danish population have exonic FHM mutations in the CACNA1A or ATP1A2 gene. The families we identified with FHM mutations in the CACNA1A and ATP1A2 genes were extended, multiple affected families whereas the remaining FHM families were smaller. The existence of many small families in the Danish FHM cohort may reflect less bias in FHM family ascertainment and/or more locus heterogeneity than described previously.

Invasive lobular and ductal breast tumors have distinct histologies and clinical presentation. Other than altered expression of E-cadherin, little is known about the underlying biology that distinguishes the tumor subtypes. We used cDNA microarrays to identify genes differentially expressed between lobular and ductal tumors. Unsupervised clustering of tumors failed to distinguish between the two subtypes. Prediction analysis for microarrays (PAM) was able to predict tumor type with an accuracy of 93.7%. Genes that were significantly differentially expressed between the two groups were identified by MaxT permutation analysis using t tests (20 cDNA clones and 10 unique genes), significance analysis for microarrays (33 cDNA clones and 15 genes, at an estimated false discovery rate of 2%), and PAM (31 cDNAs and 15 genes). There were 8 genes identified by all three of these related methods (E-cadherin, survivin, cathepsin B, TPI1, SPRY1, SCYA14, TFAP2B, and thrombospondin 4), and an additional 3 that were identified by significance analysis for microarrays and PAM (osteopontin, HLA-G, and CHC1). To validate the differential expression of these genes, 7 of them were tested by real-time quantitative PCR, which verified that they were differentially expressed in lobular versus ductal tumors. In conclusion, specific changes in gene expression distinguish lobular from ductal breast carcinomas. These genes may be important in understanding the basis of phenotypic differences among breast cancers.

In an effort to expand the spectrum of activity of the oxazolidinone class of antibacterial agents to include Gram-negative bacteria, a series of new carbon-carbon linked pyrazolylphenyl analogues has been prepared. The alpha-N-substituted methyl pyrazole (10alpha) in the C3-linked series exhibited very good Gram-positive activity with MICs

The heterogeneity of the Ixodes persulcatus population in the vicinity of Saint Petersburg was estimated by using malate dehydrogenase (MDH) isoenzyme. There are six MDH genotypes carrying 3 alleles in the Ixodes persulcatus population. The prevalence of Borrelia and Ehrlichia species in the study genotypes was analyzed. There was a difference in the prevalence and intensity of infection. The greatest abundance of Borrelia was described in the genotypes to Genogroup 1 (with allele 1). Among them, heterozygous ticks were most intensively infected. Polymerase chain reaction identified species pathogenic for man. These included 3 species of Borrelia: B. afzelii, B. garinii, and B. burgdorferi sensu stricto and 2 species of Ehrlichia muris and HGE agent. The author are the first to describe HGE agent and B. burgdorfei ss encountered in Russia.

Peptidyl deformylase (PDF) is a metallo protease that catalyzes the removal of a formyl group from the N-termini of prokaryotic prepared polypeptides, an essential step in bacterial protein synthesis. Screening of our compound collection using Staphylococcus aureus PDF afforded a very potent inhibitor with an IC(50) in the low nanomolar range. Unfortunately, the compound that contains a hydroxamic acid did not exhibit antibacterial activity (MIC). In order to address the lack of activity in the MIC assay and to determine what portion of the molecule was responsible for binding to PDF, we prepared several analogues. This paper describes our findings that the hydroxamic acid functionality found in 1 is mainly responsible for the high affinity to PDF. In addition, we identified an alternative class of PDF inhibitors, the N-hydroxy urea 18, which has both PDF and antibacterial activity.

Oxazolidinones are a novel class of synthetic antibacterial agents active against gram-positive organisms including methicillin-resistant Staphylococcus aureus as well as selected anaerobic organisms. Important representatives of this class include the morpholine derivative linezolid 2, which is currently in phase III clinical trials, and the piperazine derivative eperezolid 3. As part of an investigation of the structure-activity relationships of structurally related oxazolidinones, we have prepared and evaluated the antibacterial properties of a series of piperazinyl oxazolidinones in which the distal nitrogen of the piperazinyl ring is substituted with a six-membered heteroaromatic ring. Compounds having MIC values

Subjects were presented with briefly exposed visual displays of words that were common first names with a length of four to six letters. In the main experiment, each display consisted of four words: two names shown in red and two shown in white. The subject's task was to report the red names (targets), but ignore the white ones (distractors). On some trials the subject's own name appeared as a display item (target or distractor). Presentation of the subject's name as a distractor caused no more interference with report of targets than did presentation of other names as distractors. Apparently, visual attention was not automatically attracted by the subject's own name.

An investigation of the scope and mechanism of a new synthesis of cyclopentenes from 3,6-dihydro-2H-thiopyrans is described. Alkyl halides substituted with an electron-withdrawing group in the alpha-position were reacted with sodium thiosulfate, yielding the corresponding Bunte salts, which could be transformed to reactive thiocarbonyl compounds by elimination of the elements of bisulfite with mild base treatment. In situ trapping by 1,3-dienes afforded in good yields a variety of 3,6-dihydro-2H-thiopyrans substituted with electron-withdrawing groups at the 2-position. Exposure of these cycloadducts to strong base at low temperature effected a novel ring contraction, affording 2-(methylthio)-3-cyclopentenes after quenching with methyl iodide. The level of diastereoselectivity exhibited during the generation of these cyclopentenes was found to be dependent on the nature of the electron-withdrawing group at the 2-position of the dihydrothiopyran as well as the substitution pattern originally present in the diene component. In some cases, reducing the temperature during the ring contraction resulted in the isolation of good yields of vinyl cyclopropanes of high isomeric purity. With one substrate, highly diastereoselective rearrangement of a vinyl cyclopropane to a cyclopentene was unambiguously demonstrated, suggesting that this might be a key feature of the overall ring contraction mechanism.

The binding of the antitumor drug CC-1065 has been studied with nuclear magnetic resonance (NMR) spectroscopy. This study involves two parts, the elucidation of the covalent binding site of the drug to DNA and a detailed investigation of the noncovalent interactions of CC-1065 with a DNA fragment through analysis of 2D NOE (NOESY) experiments. A CC-1065-DNA adduct was prepared, and an adenine adduct was released upon heating. NMR (1H and 13C) analysis of the adduct shows that the drug binds to N3 of adenine by reaction of its cyclopropyl group. The reaction pathway and product formed were determined by analysis of the 13C DEPT spectra. An octamer duplex, d(CGATTAGC.GCTAATCG), was synthesized and used in the interaction study of CC-1065 and the oligomer. The duplex and the drug-octamer complex were both analyzed by 2D spectroscopy (COSY, NOESY). The relative intensity of the NOEs observed between the drug (CC-1065) and the octamer duplex shows conclusively that the drug is located in the minor groove, covalently attached to N3 of adenine 6 and positioned from the 3'----5' end in relation to strand A [d(CGATTA6GC)]. A mechanism for drug binding and stabilization can be inferred from the NOE data and model-building studies.