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To determine whether somatostatin (SST) could be a cortico-brainstem neurotransmitter involved in producing the headache of migraine. There is evidence to support the idea that a cortico-brainstem-trigeminal nucleus neuraxis might be responsible for producing migraine headache; we have suggested that SST may be one of the neurotransmitters involved. Rats were anesthetised and prepared for recording neurons in either the periaqueductal gray matter (PAG) or nucleus raphe magnus (NRM), as well as the trigeminal nucleus caudalis (TNC). The dura mater and facial skin were stimulated electrically or mechanically. SST, the SST agonist L054264 and the SST antagonist CYN54806 were injected intravenously, by microinjection, or by iontophoresis into the PAG or NRM. Cortical neuronal activity was provoked by cortical spreading depression (CSD) or light flash (LF) and was monitored by recording cortical blood flow (CBF). Intravenous injection of SST: (a) selectively decreased the responses of TNC neurons to stimulation of the dura, but not skin, for up to 5 h; (b) decreased the ongoing discharge rate of TNC neurons while simultaneously increasing the discharge rate of neurons in either brainstem nucleus and; (c) prevented, or reversed, the effect of CSD and LF on brainstem and trigeminal neuron discharge rates. CSD and LF decreased the discharge rate of neurons in both brainstem nuclei and increased the discharge rate of TNC neurons. These effects were reversed by L054264 and mimicked by CYN54806. Injections of L054264 into the PAG or NRM reduced the response of TNC neurons to dural stimulation and skin stimulation differentially, depending on the nucleus injected. Injections of CYN54806 into either brainstem nucleus potentiated the responses of TNC neurons to dural and skin stimulation, but without a marked differential effect. These results imply that SST could be a neurotransmitter in a pathway responsible for migraine pain. [ABSTRACT FROM AUTHOR]

Objective: The opioid crisis has had devastating effects on individuals and communities, and it has rapidly increased in severity. However, we still lack nationally representative information on the diversity of comorbidity patterns among prescription opioid use disorder (P-OUD), other substance use disorders (SUDs), and psychopathology using the newest edition of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013). This impedes planning for multiple aspects of intervention, including society-wide allocation of treatment resources, program design at individual treatment centers, and personalized care to individual patients. Method: To address this critical gap in information, we evaluated clinical profiles of American adults via latent class analysis in a large, recently collected epidemiological dataset that uses structured diagnostic assessment for DSM-5 psychopathology (National Epidemiologic Survey on Alcohol and Related Conditions–III; N = 36,309). Variables considered for profiles included lifetime diagnosis for multiple SUDs, various externalizing and internalizing conditions, and demographic variables. We then associated clinical profiles with demographic variables and functional impairment. Results: Comorbid psychopathology and other SUDs were common in latent classes with elevated and very high rates of P-OUD. To illustrate, alcohol use disorder rates were greater than 45%, and posttraumatic stress disorder rates were greater than 28% in classes with higher P-OUD rates. Higher P-OUD rates were associated with White/non-Hispanic and American Indian/Alaska Native populations. Relationships between P-OUD rates and functional impairment were inconsistent. Conclusion: Many current treatment delivery systems are not designed to accommodate the heterogeneous profiles associated with high P-OUD rates. We provide specific suggestions for improvements to the mental health service system, individual clinical care programs, and future research approaches. A number of distinct clinical profiles are associated with elevated rates of prescription opioid use disorder. We highlight specific profiles that can include other substance use disorders, depression, anxiety, posttraumatic stress disorder, and externalizing conditions. These profiles can be used to guide public policy, resource allocation, and the design of personalized care strategies for patients in need. [ABSTRACT FROM AUTHOR]

• Neurofilament measurement has become a promising biomarker in MS. • In relapsing MS, predictors were cortical lesions and previous clinical activity. • In progressive MS, T1-hypointense lesion volume was the only predictor. A major aim in MS field has been the search for biomarkers that enable accurate detection of neuronal damage. Besides MRI, recent studies have shown that neuroaxonal damage can also be tracked by neurofilament detection. Nevertheless, before widespread implementation, a better understanding of the principal contributors for this biomarker is of paramount importance. Therefore, we analyzed neurofilament light chain (NfL) in relapsing (RMS) and progressive MS (PMS), addressing which MRI and clinical variables are better related to this biomarker. Forty-seven MS patients underwent MRI (3T) and cerebrospinal fluid (CSF) sampling. We measured NfL concentrations using ELISA (UmanDiagnostics) and performed multivariable regression analysis to assess the contribution of clinical and MRI metrics to NfL. NfL correlated with previous clinical activity in RMS (p < 0.001). In RMS, NfL also correlated with Gad+ and cortical lesion volumes. However, after multivariable analysis, only cortical lesions and relapses in previous 12 months remained in the final model (R 2 = 0.610; p = 0.009 and p = 0.00008, respectively). In PMS, T1-hypointense lesion volume was the only predictor after multivariate analysis (R 2 = 0.564; p = 0.012). CSF NfL levels are increased in RMS and associated with relapses and cortical lesions. Although NfL levels were correlated with Gad+ lesion volume, this association did not persist in multivariable analysis after controlling for previous clinical activity. We encourage controlling for previous clinical activity when testing the association of NfL with MRI. In PMS, the major contributor to NfL was T1-hypointense lesion volume. [ABSTRACT FROM AUTHOR]

Highlights • Good "real world" outcomes are achievable in stroke patients treated with EVT > 6 h. • Predictors of outcome include initial and 24 h clinical severity and large vessel occlusion site. • Widespread access to perfusion imaging should improve patient selection and outcomes. Abstract Two recent randomized controlled trials (RCTs) showed selected patients treated with endovascular thrombectomy (EVT) more than 6 h from acute ischemic stroke (AIS) onset had significant improvement in functional outcome at 90 days compared with standard care alone. Our aim is to determine the outcome and predictors of good outcome in AIS patients undergoing EVT with unknown-onset, or late presentation, stroke after 6 h from time last seen well, or witnessed stroke onset, at two Australian comprehensive stroke centres. A retrospective analysis of functional outcome and mortality at 90-days from a prospective cohort of 56 consecutive patients with unknown-onset, or late presentation, stroke with large vessel occlusion (LVO) in the anterior cerebral circulation undergoing EVT over a 15-month period (2016–2017). We evaluated factors which correlated with good functional outcome defined as a 90-day modified Rankin scale (mRS) 0–2. Recanalization times and symptomatic intracranial haemorrhage (sICH) rates were also examined. A good functional outcome was achieved in 35 patients (62%). Eight patients died (14%). Median time-to-recanalization was 7.6 h. SICH occurred in four patients (7%). Factors which predicted good 90-day functional outcome included baseline National Institutes of Health Stroke Scale (NIHSS) < 16, 24 h NIHSS < 10, baseline Alberta Stroke Program Early CT Score (ASPECTS) ≥ 8, pre-procedural CT perfusion imaging and LVO lesion location. This study shows good 'real world' outcomes, comparable to published RCTs, in patients with unknown-onset, or late presentation, stroke treated with EVT more than 6 h from stroke onset. [ABSTRACT FROM AUTHOR]

Background The mechanisms of action of dimethyl fumarate (DMF), and its metabolite, monomethyl fumarate (MMF), for the treatment of multiple sclerosis are not completely elucidated. Objectives To discuss the role of DMF/MMF-induced hydroxycarboxylic acid receptor 2 (HCA 2 /GPR109A) pathway activation in the immune response and treatment of MS. Methods A narrative (traditional) review of the current literature. Results Studies have shown that binding of DMF/MMF to HCA 2 on dendritic cells inhibits the production of pro-inflammatory cytokines in vitro and in MS murine models. Evidence suggests that activation of HCA 2 expressed in immune cells and gut epithelial cells by DMF/MMF, may induce anti-inflammatory responses in the intestinal mucosa. Conclusion Although the DMF/MMF mechanism of action remains unclear, evidence suggests that the activation of HCA 2 /GPR109A pathway downregulates the immune response and may activate anti-inflammatory response in the intestinal mucosa, possibly leading to reduction in CNS tissue damage in MS patients. [ABSTRACT FROM AUTHOR]

The use of layer-by-layer (LbL) deposition technique allows materials, such as drugs, to be self-assembled in multilayers with other electrolytes by combining their properties in a nanostructured system. Triclosan (TCS) is commonly used as a drug because of its bactericidal action, while erythrosine (ERY) has been used as a photosensitizer in photodynamic therapies because of its high light absorptivity in the visible region of the electromagnetic spectrum. The major advantage of investigating systems immobilized in LbL films is the benefit of characterizing the interaction through available substances in solid state techniques. It was possible to immobilize in LbL films, ERY, and ERY + TCS. The results show that the growth of the films was linear, indicating the deposition of the same amount of material from the first bilayer without substrate interference. The release analysis showed slow kinetics, which occurred more rapidly for ERY LbL films, probably due to apparent activation energy, which were higher for films with TCS. The combination of TCS, ERY, and laser light (532 nm) for photodynamic inactivation of the fungus Candida albicans was analyzed, and the results were promising for future studies in applications, such as coating surfaces of dental implants. [ABSTRACT FROM AUTHOR]

Migraine is a condition without apparent pathology. Its cardinal symptom is the prolonged excruciating headache. Theories about this pain have posited pathologies which run the gamut from neural to vascular to neurovascular, but no observations have detected a plausible pathology. We believe that no pathology can be found for migraine headache because none exists. Migraine is not driven by pathology – it is driven by neural events produced by triggers – or simply by neural noise- noise that has crossed a critical threshold. If these ideas are true, how does the pain arise? We hypothesise that migraine headache is a consequence of withdrawal of descending pain control, produced by “noise” in the cerebral cortex. Nevertheless, there has to be a neural circuit to transform cortical noise to withdrawal of pain control. In our hypothesis, this neural circuit extends from the cortex, synapses in two brainstem nuclei (the periaqueductal gray matter and the raphe magnus nucleus) and ultimately reaches the first synapse of the trigeminal sensory system. The second stage of this circuit uses serotonin (5HT) as a neurotransmitter, but the neuronal projection from the cortex to the brainstem seems to involve relatively uncommon neurotransmitters. We believe that one of these is somatostatin (SST). Temporal changes in levels of circulating SST mirror the temporal changes in the incidence of migraine, particularly in women. The SST 2 receptor agonist octreotide has been used with some success in migraine and cluster headache. A cortical to PAG/NRM neural projection certainly exists and we briefly review the anatomical and neurophysiological evidence for it and provide preliminary evidence that SST may the critical neurotransmitter in this pathway. We therefore suggest that the withdrawal of descending tone in SST-containing neurons, might create a false pain signal and hence the headache of migraine. [ABSTRACT FROM AUTHOR]

The present study examined concordance between the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) and its self-report version (Y-BOCS-SR), as well as theoretically derived moderators. Sixty-seven adults (ages 18–67) with obsessive–compulsive disorder (OCD) were administered the Y-BOCS prior to completing self-report measures. The Y-BOCS-SR generated lower scores relative to the clinician-administered Y-BOCS (5.3 points lower). Strong correspondence was shown between the Y-BOCS and Y-BOCS-SR; however, many items exhibited fair to moderate agreement, particularly the resistance and control against obsessions/compulsions items. Depression significantly moderated correspondence such that Y-BOCS-SR scores significantly predicted Y-BOCS scores in the presence of low and average depression levels in our sample, but not for patients with high levels of depression relative to the rest of our sample; gender, generalized anxiety and obsessionality did not significantly impact agreement. Synthesizing the present data, the Y-BOCS-SR demonstrates modest agreement with the Y-BOCS and may underestimate clinical severity especially for those with high levels of depression. [ABSTRACT FROM AUTHOR]

Hoarding symptoms frequently emerge in early adulthood and can result in considerable impairments. Hoarding is related to many other psychological symptoms; however, greater study of hoarding within its context as an obsessive compulsive spectrum disorder, as well the role of attention-deficit/hyperactivity symptoms amongst these disorders, warrants investigation. As such, this study explored the extent and nature of hoarding symptoms, as well as their relationship with other psychopathology, in a college sample. Participants were 578 undergraduate students who completed a series of measures assessing the presence and severity of hoarding, anxiety, depression, stress, obsessive-compulsive, body dysmorphic, trichotillomania, skin picking, and attention-deficit hyperactivity symptoms. Independent samples t -tests did not detect significant differences in frequency of hoarding symptoms among men versus women, or those living alone versus with others; however, hoarding symptoms were significantly more common in individuals with a self-reported family history of hoarding. Correlational analyses found positive relationships between hoarding and all other symptom areas. Results from path analyses suggest that contrary to prior investigations, ADHD symptoms were not uniquely related to hoarding relative to anxiety and other obsessive-compulsive-spectrum pathology. This research may aid in developing a more thorough clinical profile of hoarding symptoms, potentially leading to more effective treatment strategies. [ABSTRACT FROM AUTHOR]

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This Viewpoint highlights several notable consequences of data pollution and identifies actionable steps that can be taken to address it. [ABSTRACT FROM AUTHOR]

Recently, cellulose nanofibers (CNFs) have attracted considerable attention as natural, abundant polymers with excellent mechanical properties and biodegradability. CNFs provide a new materials platform for the sustainable production of high-performance nano-enable products for various applications. Given the increasing rates of CNF production, the potential for their release to the environment and the subsequent impact on ecosystem is becoming an increasing concern that needs to be addressed. Here, we used the Klebsormidium flaccidum as a bioindicator organism of terrestrial and freshwater habitats pollution using a battery of biomarkers. Our results show that cotton CNFs inhibit the proliferation of algae and induce morphological changes in them. The two main toxicity mechanisms induced by cotton CNFs are: (i) a direct contact of CNFs with the cell wall and cellular membrane and (ii) an indirect effect through the generation of reactive oxygen species (ROS). [ABSTRACT FROM AUTHOR]

Objective: The Yale--Brown Obsessive--Compulsive Scale (Y-BOCS) is the most commonly used instrument to assess the clinical severity of obsessive--compulsive symptoms. Treatment determinations are often based on Y-BOCS score thresholds. However, these benchmarks are not empirically based, which may result in non-evidence based treatment decisions. Accordingly, the present study sought to derive empirically-based benchmarks for defining obsessive--compulsive symptom severity. Method: Nine hundred fifty-four adult patients with obsessive--compulsive disorder (OCD), recruited through the Brazilian Research Consortium on Obsessive--Compulsive Spectrum Disorders, were evaluated by experienced clinicians using a structured clinical interview, the Y-BOCS, and the Clinical Global Impressions--Severity scale (CGI-Severity). Results: Similar to results in treatment-seeking children with OCD, our findings demonstrated convergence between the Y-BOCS and global OCD severity assessed by the CGI-Severity (Nagelkerke R² = .48). Y-BOCS scores of 0-13 corresponded with 'mild symptoms' (CGI-Severity = 0-2), 14-25 with 'moderate symptoms' (CGI-Severity = 3), 26-34 with 'moderate-severe symptoms' (CGI-Severity = 4) and 35-40 with 'severe symptoms' (CGI-Severity = 5-6). Neither age nor ethnicity was associated with Y-BOCS scores, but females demonstrated more severe obsessive--compulsive symptoms than males (d = .34). Time spent on obsessions/compulsions, interference, distress, resistance, and control were significantly related to global OCD severity although the symptom resistance item pairing demonstrated a less robust relationship relative to other components of the Y-BOCS. Conclusions: These data provide empirically-based benchmarks on the Y-BOCS for defining the clinical severity of treatment seeking adults with OCD, which can be used for normative comparisons in the clinic and for future research. [ABSTRACT FROM AUTHOR]

Patricide (killing the father) is uncommon form of homicide. Usually the assaults occur at home in the absence of witnesses and adult sons are frequently involved. Homicides in a domestic context usually do not tend to recurrence, because the motivation for the crime ends with the death of the parent. However, this is not what was observed in the present case study dealing with the death of a 70 years old white man originally misclassified as accident and discovered three years later only after an additional homicide in a family context of a 60 years old white lady. Multiple stab wounds to the neck and thorax were misinterpreted at the external male body examination as blunt trauma falling down stairs. No forensic autopsy was requested and no comparison of medical findings with the results from the death scene, such as a bloodstain analysis was performed by the police officers nor required by the judicial authority. This was quite surprising because an additional but preliminary post-mortem external examination performed by a general practitioner on the male body already raised the suspicion that the external lesions were stab wounds thus requiring a forensic autopsy. Only the exhumation of the elderly body, performed years later, confirmed the diagnostic hypothesis raised by the first physician. The present case is quite representative of a death investigation not run professionally and performed by individuals with no specific training where most of the medico-legal investigations (especially for traumatic and violent deaths) are restricted to an external body examination without subsequent autopsy. Although misinterpretation of external lesions is inevitable and significant discrepancies between external body examination and forensic autopsy are not rare, in the case of contradictory results of post-mortem external examination or unclear/suspicious cause and manner of death, investigation should proceed necessarily with a forensic autopsy. [ABSTRACT FROM AUTHOR]

The article presents a study which aimed to evaluate the most relevant sheep husbandry practices and determine the technological level of farms in Minas Gerais, Southeastern Brazil. Topics covered include technological status of farms in the sampling area which includes twelve mesoregions in Minas Gerais, Brazil, details relating to the sheep population in the sheep farms included in the sampling area, and the importance of regular technical assistance to ensure successful sheep farming.

Obsessive-compulsive disorder (OCD) is marked by the presence of obsessions and/or compulsions that cause significant interference in an individual's life. Insight regarding symptoms in youth with OCD may affect accurate assessment, acceptance and motivation for treatment, tolerance of negative valence states (i.e., fear) and treatment outcome, so assessment of this construct and associated clinical characteristics is important. Accordingly, the current study sought to expand the literature on symptom insight by examining multi-informant ratings of insight from children, parents, and clinicians simultaneously and its relationship to varied clinical characteristics. One-hundred and ten treatment-seeking youth with a primary diagnosis of OCD, aged 6-17, participated in the study along with a parent/guardian. The nature of symptom conviction, fixity of ideas, and perceptions about the cause of the problems were important indicators in assessing child insight and resulted in a comprehensive, psychometrically-sound measure of insight. Insight was generally not strongly associated with clinical characteristics. Poor insight was moderately associated with less resistance of obsessive-compulsive symptoms, increased externalizing symptoms, and ordering symptoms. Overall, this study contributes further information into the nature and correlates of insight in youth with OCD, and provides a psychometrically sound approach for its assessment. [ABSTRACT FROM AUTHOR]

The article presents a study which determined the technological level and the level of knowledge of farmers on management practices to control gastrointestinal parasites in sheep in Minas Gerais state, southeastern Brazil. Questionnaires were applied by official veterinarians of the State Government Agency for Animal Health. The management practices adopted by the farmers to reduce parasitism included split young and adult animals, change pasture after deworming the animals and deworming newly arrived sheep. The need for strong technology-transfer programs to support good management practices to minimize the potential risk factors contributing to the development of anthelmintic resistance is emphasized.

Objective: Independent evaluators (IE) are used widely in clinical trials to make unbiased determinations of treatment response. By virtue of being kept blind to treatment condition, however, IEs are also kept unaware of many pertinent clinical details that are relevant for decisions about clinical improvement. In this study, agreement among raters (children, parents, therapists, and IEs) about treatment response over the course of a 14-week clinical trial for pediatric obsessive-compulsive disorder (OCD) was examined in order to determine the utility of nonblind clinician and patient ratings of treatment response. Method: Participants were 71 youth (mean age = 12.2 years; 63.4% female) with a primary diagnosis of OCD and their parents participating in a psychotherapy trial. IEs provided response ratings (Clinician's Global Impressions-Improvement Scale; CGI-I) at Weeks 4, 8, and 14, and therapists, children, and parents completed independent CGI-I ratings at Weeks 2, 4, 8, and 14. Results: Nonlinear mixed models revealed differences in rating parties, with therapists and IEs slower to rate treatment improvement compared with children and parents, and growth curve models suggested that therapists and IEs produced generally consistent ratings. In addition, no evidence was found for an Evaluator x Treatment interaction, indicating that raters displayed these differences consistently across both active and placebo conditions. Conclusions: Youth and parents may be able to provide accurate ratings of global improvement; nonblinded treating clinicians (with training in research-oriented assessment) can offer global improvement ratings commensurate with blinded IEs. Findings suggest that alternatives (or additions) to the blinded-IE model may be appropriate for assessing global improvement, especially with the growing emphasis on dissemination and effectiveness trials. [ABSTRACT FROM AUTHOR]

The article discusses migraine headache, deemed the most common neurological problem with which patients present to general practitioners and neurologists in Australia. It notes that the second edition of "The International Classification of Headache Disorders" provides a comprehensive description of the many types of headaches. It talks about recognising the features of migraine headache, differential diagnoses, and migraine aura. Also detailed are migraine complications and management.

Background: Surgery for acute aortic dissection (AAD) is frequently complicated by excessive postoperative bleeding and blood product transfusion. Blood flow through the nonendothelialized false lumen is a potential trigger for the activation of the hemostatic system; however, the physiopathology of the aortic dissection induced coagulopathy has never been precisely studied. The aim of the present study is the evaluation of the coagulation and fibrinolytic systems and platelet activation in patients undergoing surgery for AAD. Methods: Eighteen patients undergoing emergent surgery for Stanford type A AAD were enrolled in the study. The activation of the coagulation and fibrinolytic systems and platelet activation were evaluated at 6 different time points before, during, and after the operation, measuring prothrombin fragment 1.2 (F1.2), plasmin-antiplasmin complex, and platelet factor 4, respectively. Results: All measured biomarkers were increased before, during, and after the operations indicating a systemic activation of coagulation, fibrinolysis, and platelets. These changes were pronounced even preoperatively (T0), and soon after the beginning of cardiopulmonary bypass (T1) when the influence of hypothermia and prolonged cardiopulmonary bypass time were not yet involved. Time from symptom onset to intervention inversely correlated with preoperative F1.2 (r = −0.75; p = 0.002) and plasmin-antiplasmin levels (r = −0.57; p = 0.034). Conclusions: Blood flow through the false lumen is a powerful activator of the hemostatic system even before the operation. This remarkable activation may influence postoperative outcome of AAD patients. [Copyright &y& Elsevier]

Abstract: Sex differentiation process, determination of sexual strategy, and gametogenesis of the annual fish Austrolebias charrua are established. Evidence of histological sex differentiation in an antero-posterior gradient was observed in pre-hatching stages. Sexual strategy corresponds to the “differentiated gonochoric” pattern. Histological analyses of adult gonads showed an asynchronous spawning mode for females and continuous spawning for males. Mature oocytes presented fluid yolk. Testis organization corresponded to a restricted spermatogonial model. Herein, we report the ultrastructural organization of the vitelline envelope and the main features of the sperm of A. charrua. Taking together these results also contribute to phylogenetic studies and provide base line data to propose A. charrua as a biomonitor of contamination in a protected area. [Copyright &y& Elsevier]

[Display omitted] • Cell damage on paraprobiotics (PB) varies among the tested probiotic strains. • PB Lactobacillus casei PB obtained by ultrasound shows active enzymatic metabolism. • Ultrasound drastically affects L. acidophilus PB cell morphology and surface. • Inactivation method defines paraprobiotic physiology and morphology. • Ultrasound is a viable method to obtain paraprobiotics with active metabolism. This study aimed to determine the suitable inactivation conditions of ultrasound and other five methods [heat, low pH, high pH, gamma irradiation and supercritical carbon dioxide (CO 2)] to obtain paraprobiotics from Lactobacilus acidophilus , Lacticaseibacillus casei and Bifidobacterium animalis. The impact of each method at distinct conditions of inactivation was assessed by plate culturing and, the physiological and morphological aspects of the inactivated cells were assessed by a combined approach of flow cytometry and field-emission scanning electron microscopy analysis. The ability to grow on culture media after exposure to distinct processes or different conditions of the same process largely varied among the tested strains. The exposure to the best conditions defined for the distinct processes for inactivation of each strain resulted in distinct (p < 0.05) percentages of cells with active enzymatic metabolism and integrity of membranes. After the ultrasound treatment, L. casei presented the highest and lowest percentages of enzymatic activity (86.2%) and damage to membrane integrity (4.6%) among the tested strains, respectively. Morphological characteristics of L. casei were similar after exposure to the distinct processes tested. Otherwise, ultrasound deeply affected the morphological aspects of L. acidophilus and B. animalis , and compromised the enzymatic activity in a great percentage of cells of these bacteria (>80%). The extension of damage to the cell surface, changes in cell roughness, lysed cells and cell debris varied with the tested strain and the inactivation method. Results indicate that the inactivation method defines the physiological and morphological conditions in each derived paraprobiotic that must be optimized for each strain. Findings suggest ultrasound as a feasible method to obtain L. casei paraprobiotics with an active metabolism. [ABSTRACT FROM AUTHOR]

Recently, it was shown that highly effective anti-CD20 therapies used for MS patients not only deplete CD20+ B cells, but also a small subset of T cells expressing CD20 surface marker (CD3+CD20+ T cells). Here we demonstrated that, in progressive MS patients, CD3+CD20+ T cells share the ability to express cytotoxic factors such as perforin and serine-protease granzyme-B (GzmB), classically associated with CD8+ T cells functionality. Beyond it, cluster analyses show that a set of activation markers and transcriptional factors related with CD8 effector program are also expressed in CD3+CD20+ T cells. Further characterization of surface and functional markers from CD3+CD20+ T subsets may be helpful for development of new therapeutic strategies mainly for progressive MS patients, as well as for assessing pathophysiological effects of highly effective anti-CD20 therapies. [ABSTRACT FROM AUTHOR]

• Symptom patterns in multiple sclerosis are seemingly heterogeneous • Latent profile analysis can identify subgroups with similar impairments across measures • The most impaired cluster was less likely to be White Americans or of high economic standing • Age, sex, or disease duration did not differ between the least and most impaired clusters Multiple sclerosis (MS) patients experience wide-ranging symptoms with varied severity, and approaches that integrate patient-reported outcomes and objective quantitative measures will present opportunities for advancing clinical profiling. The primary objective of the current study was to conduct exploratory data analysis using latent variable modeling to empirically identify clusters of relapsing remitting (RR) MS patients with shared impairment patterns across three patient-reported outcomes and two timed task measures. Latent profile analyses and impairment data for 2,012 RRMS patients identified distinct patient clusters using timed task measures of upper and lower limb performance, and patient-reported outcomes measuring quality of life, depression symptom severity, and perceived global disability. Multinomial logistic regression models were used to characterize associations between socio-demographic attributes and assignment to the patient clusters. There were 6 distinct clusters of RRMS patients that differed by symptom patterns, and by their socio-demographic attributes. Most notable were were no differences in age, sex, or disease duration between the least and most impaired classes, representing 14% and 4% of patients, respectively. Patients in the most impaired class were much more likely to be Black American, have a history of smoking, have a higher body mass index, and be of lower socioeconomic status than the least impaired class. There were positive relationships between age and classification to clusters of increasing moderately severe impairment but not the most severe clusters. We present a framework for discerning phenotypic impairment clusters in RRMS. The results demonstrate opportunities for advancing clinical profiling, which is necessary for optimizing personalized MS care models and clinical research. [ABSTRACT FROM AUTHOR]