Incobotulinum Toxin-A in Professional Musicians with Focal Task-Specific Dystonia: A Double Blind, Placebo Controlled, Cross-Over Study.

Background: Musician's focal task-specific dystonia is a complex disorder of fine motor control, with incomplete understanding of its etiology. There have been relatively few trials of botulinum toxin in upper limb task-specific dystonia, and prior studies have yielded variable results, leading to skepticism regarding the utility of this approach in elite performers. Methods: We conducted a double-blind, placebo-controlled, randomized, cross-over study of incobotulinum toxin-A in 21 professional musicians with focal upper extremity task-specific dystonia affecting performance on their instrument, using a novel paradigm of initial injections followed by booster injections at two- and four-week intervals. The primary outcome measure was the change in blinded dystonia rating of the active arm by two expert raters using a Clinical Global Impression numeric scale at week 8 compared to enrollment. Findings: 19 men and 2 women with musicians' dystonia were enrolled over a six-year period. Nineteen patients completed the study. Analysis of the primary outcome measure in comparison to baseline revealed a change in dystonia severity of P = 0.04 and an improvement in overall musical performance of P = 0.027. No clinically significant weakness was observed, and neutralizing antibodies to toxin were not found. Interpretation: Despite its small sample size, our study demonstrated a statistically significant benefit of incobotulinum toxin-A injections as a treatment for musicians' task-specific dystonia. Tailoring the use of toxin with booster injections allowed refinement of dosing strategy and outcomes, with benefits that were meaningful to patients clearly visible on videotaped evaluations. In addition to its application to musicians' dystonia, this approach may have relevance to optimize application of botulinum toxin in other forms of focal dystonia such as blepharospasm, cervical dystonia, writer's cramp, and spasmodic dysphonia.

Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer.

Cancer cells exhibit rewired transcriptional regulatory networks that promote tumor growth and survival. However, the mechanisms underlying the formation of these pathological networks remain poorly understood. Through a pan-cancer epigenomic analysis, we found that primate-specific endogenous retroviruses (ERVs) are a rich source of enhancers displaying cancer-specific activity. In colorectal cancer and other epithelial tumors, oncogenic MAPK/AP1 signaling drives the activation of enhancers derived from the primate-specific ERV family LTR10. Functional studies in colorectal cancer cells revealed that LTR10 elements regulate tumor-specific expression of multiple genes associated with tumorigenesis, such as ATG12 and XRCC4. Within the human population, individual LTR10 elements exhibit germline and somatic structural variation resulting from a highly mutable internal tandem repeat region, which affects AP1 binding activity. Our findings reveal that ERV-derived enhancers contribute to transcriptional dysregulation in response to oncogenic signaling and shape the evolution of cancer-specific regulatory networks.

Applying process dissociation to self-sacrificial moral dilemmas: Extending the dual-process model.

There is considerable evidence linking cognitive reflection with utilitarian judgments in dilemmas that involve sacrificing someone else for the greater good. However, the evidence is mixed on the question of whether cognitive reflection is associated with utilitarian judgments in self-sacrificial dilemmas. We employed process dissociation to extract a self-sacrificial utilitarian (SU) parameter, an altruism (A) parameter, an other-sacrificial (OU) utilitarian parameter, and a deontology (D) parameter. In Study 1, the cognitive reflection test (CRT) positively correlated with both SU and OU (replicated in Studies 2 and 4, pre-registered). In Study 2, we found that instructing participants to rely on reason increased SU and OU (replicated in Study 4, pre-registered). In Study 3, we found that SU and OU positively correlated with giving in the single-game version of the public goods game (replicated in Study 4, pre-registered), which provides behavioral validation that they are genuine moral tendencies. Together, these studies constitute strong cumulative evidence that SU and OU are both valid measures that are associated with reliance on cognitive reflection.

Neural rhythms of narcissism: Facets of narcissism are associated with different neural sources in resting-state EEG.

Trait narcissism is characterized by significant heterogeneity across individuals. Despite advances in the conceptualization of narcissism, including the increasing recognition that narcissism is a multidimensional construct, the sources of this heterogeneity remain poorly understood. Here, we used a neural trait approach to help better understand "how," and shed light on "why," individuals vary in facets of trait narcissism. Participants (N = 58) first completed personality measures, including the Narcissistic Personality Inventory (NPI), and then in a second session sat passively while resting-state electroencephalography (rs-EEG) was recorded. We then regressed source-localized rs-EEG activity on the distinct facets of narcissism: Grandiose Exhibitionism (GE), Entitlement/Exploitativeness (EE), and Leadership/Authority (LA). Results revealed that each facet was associated with different (though sometimes overlapping) neural sources. Specifically, GE was associated with reduced activation in the dorsomedial prefrontal cortex (DMPFC). EE was associated with reduced activation in the DMPFC and right lateral PFC. LA was associated with increased activation in the left anterior temporal cortex. These findings support the idea that trait narcissism is a multidimensional construct undergirded by individual differences in neural regions related to social cognition (the DMPFC), self-regulation (right lateral PFC), and self-referential processing (left anterior temporal cortex).

The TGFß Induced MicroRNAome of the Trabecular Meshwork.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor ß (TGFß) in the anterior segment of the eye. Understanding how TGFß affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-ß1 and -ß2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFß-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

Optimization of microbial fuel cell performance application to high sulfide industrial wastewater treatment by modulating microbial function.

Microbial fuel cells (MFCs) are innovative eco-friendly technologies that advance a circular economy by enabling the conversion of both organic and inorganic substances in wastewater to electricity. While conceptually promising, there are lingering questions regarding the performance and stability of MFCs in real industrial settings. To address this research gap, we investigated the influence of specific operational settings, regarding the hydraulic retention time (HRT) and organic loading rate (OLR) on the performance of MFCs used for treating sulfide-rich wastewater from a canned pineapple factory. Experiments were performed at varying hydraulic retention times (2 days and 4 days) during both low and high seasonal production. Through optimization, we achieved a current density generation of 47±15 mA/m2, a COD removal efficiency of 91±9%, and a sulfide removal efficiency of 86±10%. Microbiome analysis revealed improved MFC performance when there was a substantial presence of electrogenic bacteria, sulfide-oxidizing bacteria, and methanotrophs, alongside a reduced abundance of sulfate-reducing bacteria and methanogens. In conclusion, we recommend the following operational guidelines for applying MFCs in industrial wastewater treatment: (i) Careful selection of the microbial inoculum, as this step significantly influences the composition of the MFC microbial community and its overall performance. (ii) Initiating MFC operation with an appropriate OLR is essential. This helps in establishing an effective and adaptable microbial community within the MFCs, which can be beneficial when facing variations in OLR due to seasonal production changes. (iii) Identifying and maintaining MFC-supporting microbes, including those identified in this study, should be a priority. Keeping these microbes as an integral part of the system's microbial composition throughout the operation enhances and stabilizes MFC performance.

Is the persistence of Listeria monocytogenes in food processing facilities and its resistance to pathogen intervention linked to its phylogeny?

The foodborne pathogen Listeria monocytogenes is differentiated into four distinct lineages which differ in their virulence. It remains unknown, however, whether the four lineages also differ with respect to their ability to persist in food processing facilities, their resistance to high pressure, a preservation method that is used commercially for Listeria control on ready-to-eat meats, and their ability to form biofilms. This study aimed to determine differences in the pressure resistance and biofilm formation of 59 isolates of L. monocytogenes representing lineages I and II. Furthermore, the genetic similarity of 9 isolates of L. monocytogenes that were obtained from a meat processing facility over a period of 1 year and of 20 isolates of L. monocytogenes from food processing facilities was analyzed to assess whether the ability of the lineages of L. monocytogenes to persist in these facilities differs. Analysis of 386 genomes with respect to the source of isolation revealed that genomes of lineage II are over-represented in meat isolates when compared with clinical isolates. Of the 38 strains of Lm. monocytogenes that persisted in food processing facilities (this study or published studies), 31 were assigned to lineage II. Isolates of lineage I were more resistant to treatments at 400 to 600 MPa. The thickness of biofilms did not differ between lineages. In conclusion, strains of lineage II are more likely to persist in food processing facilities while strains of lineage I are more resistant to high pressure.IMPORTANCEListeria monocytogenes substantially contributes to the mortality of foodborne disease in developed countries. The virulence of strains of four lineages of L. monocytogenes differs, indicating that risks associated with the presence of L. monocytogenes are lineage specific. Our study extends the current knowledge by documentation that the lineage-level phylogeny of L. monocytogenes plays a role in the source of isolation, in the persistence in food processing facilities, and in the resistance to pathogen intervention technologies. In short, the control of risks associated with the presence of L. monocytogenes in food is also lineage specific. Understanding the route of contamination L. monocytogenes is an important factor to consider when designing improved control measures.

Single-Cell RNA Sequencing Reveals Cardiac Fibroblast-Specific Transcriptomic Changes in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset. Differential gene expression was detected primarily in the cardiac fibroblast population. Bulk RNA sequencing was performed on an independent cohort of human cardiac tissue and compared with scRNA-seq gene alterations to generate a stratified list of higher-confidence, fibroblast-specific expression candidates for further validation. Concordant gene dysregulation was confirmed in TGFß-induced fibroblasts. Functional assessment of gene candidates showed that AEBP1 may play a significant role in fibroblast activation. This unbiased approach enabled improved resolution of cardiac cell-type-specific transcriptomic alterations in DCM.

Time-domain methods for quantifying dynamic cerebral blood flow autoregulation: Review and recommendations. A white paper from the Cerebrovascular Research Network (CARNet).

Cerebral Autoregulation (CA) is an important physiological mechanism stabilizing cerebral blood flow (CBF) in response to changes in cerebral perfusion pressure (CPP). By maintaining an adequate, relatively constant supply of blood flow, CA plays a critical role in brain function. Quantifying CA under different physiological and pathological states is crucial for understanding its implications. This knowledge may serve as a foundation for informed clinical decision-making, particularly in cases where CA may become impaired. The quantification of CA functionality typically involves constructing models that capture the relationship between CPP (or arterial blood pressure) and experimental measures of CBF. Besides describing normal CA function, these models provide a means to detect possible deviations from the latter. In this context, a recent white paper from the Cerebrovascular Research Network focused on Transfer Function Analysis (TFA), which obtains frequency domain estimates of dynamic CA. In the present paper, we consider the use of time-domain techniques as an alternative approach. Due to their increased flexibility, time-domain methods enable the mitigation of measurement/physiological noise and the incorporation of nonlinearities and time variations in CA dynamics. Here, we provide practical recommendations and guidelines to support researchers and clinicians in effectively utilizing these techniques to study CA.

Individual Patient Data Meta-Analysis of Dynamic Cerebral Autoregulation and Functional Outcome After Ischemic Stroke.

BACKGROUND: The relationship between dynamic cerebral autoregulation (dCA) and functional outcome after acute ischemic stroke (AIS) is unclear. Previous studies are limited by small sample sizes and heterogeneity. METHODS: We performed a 1-stage individual patient data meta-analysis to investigate associations between dCA and functional outcome after AIS. Participating centers were identified through a systematic search of the literature and direct invitation. We included centers with dCA data within 1 year of AIS in adults aged over 18 years, excluding intracerebral or subarachnoid hemorrhage. Data were obtained on phase, gain, coherence, and autoregulation index derived from transfer function analysis at low-frequency and very low-frequency bands. Cerebral blood velocity, arterial pressure, end-tidal carbon dioxide, heart rate, stroke severity and sub-type, and comorbidities were collected where available. Data were grouped into 4 time points after AIS: <24 hours, 24 to 72 hours, 4 to 7 days, and >3 months. The modified Rankin Scale assessed functional outcome at 3 months. Modified Rankin Scale was analyzed as both dichotomized (0 to 2 versus 3 to 6) and ordinal (modified Rankin Scale scores, 0-6) outcomes. Univariable and multivariable analyses were conducted to identify significant relationships between dCA parameters, comorbidities, and outcomes, for each time point using generalized linear (dichotomized outcome), or cumulative link (ordinal outcome) mixed models. The participating center was modeled as a random intercept to generate odds ratios with 95% CIs. RESULTS: The sample included 384 individuals (35% women) from 7 centers, aged 66.3±13.7 years, with predominantly nonlacunar stroke (n=348, 69%). In the affected hemisphere, higher phase at very low-frequency predicted better outcome (dichotomized modified Rankin Scale) at <24 (crude odds ratios, 2.17 [95% CI, 1.47-3.19]; P<0.001) hours, 24-72 (crude odds ratios, 1.95 [95% CI, 1.21-3.13]; P=0.006) hours, and phase at low-frequency predicted outcome at 3 (crude odds ratios, 3.03 [95% CI, 1.10-8.33]; P=0.032) months. These results remained after covariate adjustment. CONCLUSIONS: Greater transfer function analysis-derived phase was associated with improved functional outcome at 3 months after AIS. dCA parameters in the early phase of AIS may help to predict functional outcome.

Best Practice Guidelines for the Management of Patients with Post-Stroke Spasticity: A Modified Scoping Review.

This article aims to provide a concise overview of the best available evidence for managing post-stroke spasticity. A modified scoping review, conducted following the PRISMA guidelines and the PRISMA Extension for Scoping Reviews (PRISMA-ScR), involved an intensive search on Medline and PubMed from 1 January 2000 to 31 August 2023. The focus was placed on high-quality (GRADE A) medical, rehabilitation, and surgical interventions. In total, 32 treatments for post-stroke spasticity were identified. Two independent reviewers rigorously assessed studies, extracting data, and evaluating bias using GRADE criteria. Only interventions with GRADE A evidence were considered. The data included the study type, number of trials, participant characteristics, interventions, parameters, controls, outcomes, and limitations. The results revealed eleven treatments supported by GRADE A evidence, comprising 14 studies. Thirteen were systematic reviews and meta-analyses, and one was randomized control trial. The GRADE A treatments included stretching exercises, static stretching with positional orthosis, transcutaneous electrical nerve stimulation, extracorporeal shock wave therapy, peripheral magnetic stimulation, non-invasive brain stimulation, botulinum toxin A injection, dry needling, intrathecal baclofen, whole body vibration, and localized muscle vibration. In conclusion, this modified scoping review highlights the multimodal treatments supported by GRADE A evidence as being effective for improving functional recovery and quality of life in post-stroke spasticity. Further research and exploration of new therapeutic options are encouraged.

The effect of seed germination and Bacillus spp. on the ripening of plant cheese analogs.

Consumer demand for plant cheeses is increasing, but challenges of improving both flavor and quality remain. This study investigated the microbiological and physicochemical impact of seed germination and fermentation with Bacillus velezensis and Bacillus amyloliquefaciens on the ripening of plant cheese analogs. Chlorine treatment or addition of Lactiplantibacillus plantarum and Lactococcus lactis controlled microbial growth during seed germination. Lp. plantarum and Lc. lactis also served as starter cultures for the acidification of soy and lupine milk and were subsequently present in the unripened plant cheese as dominant microbes. Acidification also inhibited the growth and metabolic activity of bacilli but Bacillus spores remained viable throughout ripening. During plant cheese ripening, Lc. lactis was inactivated before Lp. plantarum and the presence of bacilli during seed germination delayed Lc. lactis inactivation. Metagenomic sequencing of full-length 16S rRNA gene amplicons confirmed that the relative abundance of the inoculated strains in each ripened cheese sample exceeded 99%. Oligosaccharides including raffinose, stachyose, and verbascose were rapidly depleted in the initial stage of ripening. Both germination and the presence of bacilli during seed germination had impact on polysaccharide hydrolysis during ripening. Bacilli but not seed germination enhanced proteolysis of plant cheese during ripening. In conclusion, the use of germination with lactic acid bacteria in combination with Bacillus spp. exhibited the potential to improve the quality of ripened plant cheeses with a positive effect on the reduction of hygienic risks. IMPORTANCE: The development of novel plant-based fermented food products for which no traditional templates exist requires the development of starter cultures. Although the principles of microbial flavor formation in plant-based analogs partially overlap with dairy fermentations, the composition of the raw materials and thus likely the selective pressure on the activity of starter cultures differs. Experiments that are described in this study explored the use of seed germination, the use of lactic acid bacteria, and the use of bacilli to reduce hygienic risks, to acidify plant milk, and to generate taste-active compounds through proteolysis and fermentative conversion of carbohydrates. The characterization of fermentation microbiota by culture-dependent and culture-independent methods also confirmed that the starter cultures used were able to control microbial communities throughout 90 d of ripening. Taken together, the results provide novel tools for the development of plant-based analogs of fermented dairy products.

Health risks of ozone from long-range transboundary air pollution

Ozone is a highly oxidative gas formed in the lower atmosphere (from gases originating to a large extent from anthropogenic sources) by photochemistry driven by solar radiation. Owing to its highly reactive chemical properties, ozone is harmful to vegetation, materials and human health. In the troposphere, ozone is also an efficient greenhouse gas. This report summarizes the results of a multidisciplinary analysis to assess the effects of ozone on health. The analysis indicates that ozone pollution affects the health of most of the populations of the WHO European Region, leading to a wide range of health problems. The effects include some 21 000 premature deaths each year in 25 countries in the European Union on and after days with high ozone levels. Current policies are not sufficient to reduce ozone levels in the Region or their impact in the next decade.

Resoluçäo espacial em mapas cerebrais após derivaçäo da fonte / Spatial resolution in brain map after source derivation

As interpolações, planar spline (PS) e 4-vizinhos-mais-próximos (NN), foram investigadas para o mapeamento cerebral após Derivação da Fonte. Distribuições simuladas com componentes de alta freqüência espacial (dipolos próximos ao scalpo) e 28 eletrodos resultaram em melhor localização de dipolos ao empregar-se a NN, em paarticipar para dipolos subjacentes aos pontos de captação. Entretanto, aumento na confiabilidade da localização de fontes depende de uma maior densidade de eletrodos.

Comparaçäo de técnicas de interpolaçäo para mapeamento topográfico cerebral / Comparison between interpolationfot brain for brain topography mapping

Utilizando distribuição de potencial simulada, técnicas de interpolação (4-vizinhos, Spline Planar e Spline Esférica) foram usadas na reconstrução de mapas topográficos cerebrais. Os resultados quantitativos indicam que o desempenho destas técnicas depende fortemente da profundidade das fontes cerebrais e de sua localização em relação aos eletrodos.

Estudo comparativo entre a coerência parcial e a derivaçäo da fonte no EEG / Comparative study between partial coherence and the EEG source derivation

Tanto a correlação/coerência após a Derivação da Fonte (DP) quanto a Coerência Parcial (CP) têm sido empregadas na quantificação da similaridade entre dois sinais EEG de regiões cerebrais distintas, após remoção da contribuição de regiões vizinhas. Apesar de poderem ser aplicadas para fins semelhantes, estas técnicas diferem conceitualmente, podendo levar a resultados diferentes. Este trabalho objetiva mostrar algumas das diferenças destas técnicas na análise do EEG.

Análise de discriminante de padröes eletrográficos do ciclo sono-vigília neonatal / Discriminant analysis of electromyographic patterns of neonatal sleep-awake cicle

Trinta componentes espectrais (selecionados da coerência e da potência) e a potência agrupada em seis bandas foram submetidos à Análise Discriminante para distinção entre os padrões Low Voltage Irregular, High Voltage Slow e Misto das fases de sono-vigília neonatais. Para o segundo conjunto de varáveis obteve-se classificação correta global de 69,7 por cento resultado próximo ao repostado na literatura - 68 por cento - para fases de sono de adultos.

Identificaçäo objetiva no domínio da frequência de resposta à fotoestimulaçäo repetitiva / Objective identification in response frequency domain by repetitive photostimulation

Visando a detecção de mudanças no EEG em resposta a estimulação visual através de métodos estatísticos, três técnicas baseadas na transformada discreta de Fourier são descritas. Estas são avaliadas em simulações e aplicadas a trechos de EEG de adultos normais sob fotoestimulação repetitiva, demonstrando a sua potencialidade.