New perspectives on frailty in light of the Global Leadership Initiative on Malnutrition, the Global Leadership Initiative on Sarcopenia, and the WHO's concept of intrinsic capacity: A narrative review.

This review gathered the evidence on the epidemiology of frailty, as well as on screening and diagnostic tools, and new perspectives, in light of the latest global frameworks in malnutrition, sarcopenia, and the World Health Organization's concept of intrinsic capacity. Frailty is a worldwide health challenge and highly prevalent in older adults and the population with chronic diseases independent of age. Regardless of the particular concept of frailty, many screening and diagnostic tools are able to identify frailty in older people, but none of them has shown superiority in every population and healthcare setting. Physical, cognitive, and social components are part of the larger context of frailty. The latest evidence-based initiatives on frailty recommend the use of validated tools to identify frailty's different components, tailored to the needs of specific populations and healthcare systems. Unintentional weight loss is a shared criterion between physical frailty and malnutrition according to the Global Leadership Initiative on Malnutrition criteria. A new definition of sarcopenia by the Global Leadership Initiative on Sarcopenia is awaited, but at present physical frailty shares with sarcopenia the criteria of low muscle function and physical performance (severity grading) according to the revised consensus of the European Working Group on Sarcopenia in Older People (EWGSOP2). The EWGSOP2 includes both muscle mass and function, with most scientific groups agreeing that function is a key hallmark of sarcopenia. The concept of intrinsic capacity features the reserves and positive aspects of aging, and responds to ageism by addressing the deficit model approach. Intrinsic capacity is an emerging, person-centered and public health indicator, aimed at preserving health at mid-life and beyond, to move towards a better aging process in the Decade of Healthy Aging 2020-2030.

A novel expert-driven methodology to develop thermal response curves and project habitat thermal suitability for cetaceans under a changing climate.

Over the last decades, global warming has contributed to changes in marine species composition, abundance and distribution, in response to changes in oceanographic conditions such as temperature, acidification, and deoxygenation. Experimentally derived thermal limits, which are known to be related to observed latitudinal ranges, have been used to assess variations in species distribution patterns. However, such experiments cannot be undertaken on free-swimming large marine predators with wide-range distribution, like cetaceans. An alternative approach is to elicit expert's knowledge to derive species' thermal suitability and assess their thermal responses, something that has never been tested in these taxa. We developed and applied a methodology based on expert-derived thermal suitability curves and projected future responses for several species under different climate scenarios. We tested this approach with ten cetacean species currently present in the biogeographic area of Macaronesia (North Atlantic) under Representative Concentration Pathways 2.6, 4.5 and 8.5, until 2050. Overall, increases in annual thermal suitability were found for Balaenoptera edeni, Globicephala macrorhynchus, Mesoplodon densirostris, Physeter macrocephalus, Stenella frontalis, Tursiops truncatus and Ziphius cavirostris. Conversely, our results indicated a decline in thermal suitability for B. physalus, Delphinus delphis, and Grampus griseus. Our study reveals potential responses in cetaceans' thermal suitability, and potentially in other highly mobile and large predators, and it tests this method's applicability, which is a novel application for this purpose and group of species. It aims to be a cost-efficient tool to support conservation managers and practitioners.

MONICET: The Azores whale watching contribution to cetacean monitoring.

Background: The Azores islands have been historically linked to cetaceans, becoming an example of a successful transition from whaling to whale watching. Twenty-eight cetacean species have been sighted in these waters, making the archipelago one of the most recognised whale and dolphin watching destinations worldwide. The business is well-established in the region, operates in four of the nine islands year-round or seasonally and provides an excellent opportunity to collect long term information on cetacean distribution and abundance in an affordable way. Continuous monitoring is indeed essential to establish baseline knowledge and to evaluate cetacean response to potential natural or anthropogenic impacts. Opportunistic data greatly complement traditional dedicated surveys, providing additional support for appropriate management plans. New information: The MONICET platform has been running continuously since 2009 as a collaborative instrument to collect, store, organise and disseminate cetacean data voluntarily collected by whale watching companies in the Azores. In the period covered by this dataset (2009-2020), 11 whale watching companies have voluntarily provided data from the four islands of the archipelago where whale watching takes place. The dataset contains more than 37,000 sightings of 25 species (22 cetaceans and three turtles). This manuscript presents the first long-term whale watching cetacean occurrence dataset openly available for the Azores. We explain the methodology used for data collection and address the potential biases and limitations inherent to the opportunistic nature of the dataset to maximise its usability by external users.

Implementation of bactericidal topographies on biomimetic calcium phosphates and the potential effect of its reactivity.

Since the discovery that nanostructured surfaces were able to kill bacteria, many works have been published focusing on the design of nanopatterned surfaces with antimicrobial properties. Synthetic bone grafts, based on calcium phosphate (CaP) formulations, can greatly benefit from this discovery if adequate nanotopographies can be developed. However, CaP are reactive materials and experience ionic exchanges when placed into aqueous solutions which may in turn affect cell behaviour and complicate the interpretation of the bactericidal results. The present study explores the bactericidal potential of two nanopillared CaP prepared by hydrolysis of two different sizes of α-tricalcium phosphate (α-TCP) powders under biomimetic or hydrothermal conditions. A more lethal bactericidal response toward Pseudomonas aeruginosa (~75% killing efficiency of adhered bacteria) was obtained from the hydrothermally treated CaP which consisted in a more irregular topography in terms of pillar size (radius: 20-60 nm), interpillar distances (100-1500 nm) and pillar distribution (pillar groups forming bouquets) than the biomimetically treated one (radius: 20-40 nm and interpillar distances: 50-200 nm with a homogeneous pillar distribution). The material reactivity was greatly influenced by the type of medium (nutrient-rich versus nutrient-free) and the presence or not of bacteria. A lower reactivity and superior bacterial attachment were observed in the nutrient-free medium while a lower attachment was observed for the nutrient rich medium which was explained by a superior reactivity of the material paired with the lower tendency of planktonic bacteria to adhere on surfaces in the presence of nutrients. Importantly, the ionic exchanges produced by the presence of materials were not toxic to planktonic cells. Thus, we can conclude that topography was the main contributor to mortality in the bacterial adhesion tests.

The Path to UVCB Ecological Risk Assessment: Grappling with Substance Characterization.

Substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) pose a unique challenge to regulators and to product registrants, who are required to characterize their fate, exposure, hazard, and potential risks to human health and the environment. To address these challenges and ensure an efficient and fit-for-purpose process, it is proposed that the ecological risks of UVCBs be assessed following a tiered strategy. The development of this approach required exploring how substance composition ties into hazard and exposure information and determining the extent to which a UVCB needs to be characterized to ensure a robust risk assessment. The present study highlights the key aspects of this new method. It presents how a tiered substance characterization approach can be integrated into broader UVCB risk-assessment schemes to encourage an examination of data needs before a full substance characterization is performed. The first tier of the characterization process, Tier 0, is a fundamental step that includes data from basic, lower-resolution compositional analyses. Tier 0 assessments can be used to inform hazard and exposure for any substance of interest. The need for more sophisticated, higher-tier characterization is determined by the level of uncertainty of the risk assessment. The next step will integrate a tiered exposure assessment into the characterization scheme featured in the present study, to create a more complete risk-assessment framework. Environ Toxicol Chem 2022;41:2649-2657. © 2022 Her Majesty the Queen in Right of Canada, Health and Environmental Sciences Institute and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada.

The Next Frontier of Environmental Unknowns: Substances of Unknown or Variable Composition, Complex Reaction Products, or Biological Materials (UVCBs).

Substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs) are over 70 000 "complex" chemical mixtures produced and used at significant levels worldwide. Due to their unknown or variable composition, applying chemical assessments originally developed for individual compounds to UVCBs is challenging, which impedes sound management of these substances. Across the analytical sciences, toxicology, cheminformatics, and regulatory practice, new approaches addressing specific aspects of UVCB assessment are being developed, albeit in a fragmented manner. This review attempts to convey the "big picture" of the state of the art in dealing with UVCBs by holistically examining UVCB characterization and chemical identity representation, as well as hazard, exposure, and risk assessment. Overall, information gaps on chemical identities underpin the fundamental challenges concerning UVCBs, and better reporting and substance characterization efforts are needed to support subsequent chemical assessments. To this end, an information level scheme for improved UVCB data collection and management within databases is proposed. The development of UVCB testing shows early progress, in line with three main methods: whole substance, known constituents, and fraction profiling. For toxicity assessment, one option is a whole-mixture testing approach. If the identities of (many) constituents are known, grouping, read across, and mixture toxicity modeling represent complementary approaches to overcome data gaps in toxicity assessment. This review highlights continued needs for concerted efforts from all stakeholders to ensure proper assessment and sound management of UVCBs.

Anthropogenic pressures enhance the deleterious effects of extreme storms on rocky shore communities.

Climate change is not only changing the mean values of environmental parameters that modulate ecosystems, but also the regime of disturbances. Among them, extreme events have a key role in structuring biological communities. Ecosystems are frequently suffering multiple anthropogenic pressures which can cause effects that are not additive. Thus, the effects of extreme events need to be studied in combination with other pressures to adequately evaluate their consequences. We performed a manipulative approach in two rocky shores in the Mediterranean with contrasting levels of anthropogenic pressure (mainly eutrophication) simulating storms with different disturbance regimes in the intertidal and subtidal zones. In the short-term, an extreme storm had a greater impact on the species assemblage than other disturbance regimes, being especially notable in the area suffering from a high anthropogenic pressure. In this area, the species assemblages that suffered from an extreme storm took a longer time to recover than the ones affected by other disturbance regimes and were generally more affected after the disturbance. The intertidal zone, having more variable environmental conditions than the subtidal zone, was more resistant and able to recover from extreme storms. Our results suggest that the effects of extreme events on biological communities could be strengthened when co-occurring with anthropogenic pressures, especially ecosystems adapted to less variable environmental conditions. Thus, limiting other anthropogenic pressures that ecosystems are suffering is crucial to maintain the natural resistance and recovery capacity of ecosystems towards extreme events such as storms.

Autoimmune encephalitis in a tertiary hospital in the Philippines.

BACKGROUND: Autoimmune encephalitis (AE) is an emerging disorder in adults and children. Due to its potentially reversible nature, prompt recognition and intervention are of utmost importance. OBJECTIVE: To describe the clinical and paraclinical features, as well as treatment outcomes of patients with AE admitted in a Philippine tertiary hospital. METHODS: Retrospective case series of patients with definite AE. RESULTS: Eighteen (18) patients were included (12 adults, 6 children), majority of whom had anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. The median age of onset was 32 (IQR: 10.8) years old and 13 (IQR: 4.8) years old in the adult and pediatric population, respectively. In both age groups, most presented with psychiatric symptoms and normal imaging findings. Cerebrospinal fluid (CSF) pleocytosis was detected in 8/12 (66.7%) adults and 2/6 (33.3%) children, while CSF protein elevation was only seen in 6/12 (50%) adults. Most patients presented with seizures, and the most frequent electroencephalography (EEG) abnormality detected was slow activity (70.5%). A high proportion of patients received high dose steroids, alone (35.3%) or in combination with intravenous immunoglobulin (IVIG, 52.9%). Overall, 66.7% had improved outcomes, mostly seen in the pediatric population. CONCLUSION: This study highlighted the broad clinical phenotype, as well as the similarities and differences of AE manifestations in adults and children. It demonstrated the limited but supportive role of laboratory investigations in the diagnosis of AE. It also underscored the importance of early intervention in AE and highlighted factors influencing treatment practices and discharge outcomes in the local setting.

Large-scale movements of common bottlenose dolphins in the Atlantic: dolphins with an international courtyard.

Wide-ranging connectivity patterns of common bottlenose dolphins (Tursiops truncatus) are generally poorly known worldwide and more so within the oceanic archipelagos of Macaronesia in the North East (NE) Atlantic. This study aimed to identify long-range movements between the archipelagos of Macaronesia that lie between 500 and 1,500 km apart, and between Madeira archipelago and the Portuguese continental shelf, through the compilation and comparison of bottlenose dolphin's photo-identification catalogues from different regions: one from Madeira (n = 363 individuals), two from different areas in the Azores (n = 495 and 176), and four from different islands of the Canary Islands (n = 182, 110, 142 and 281), summing up 1791 photographs. An additional comparison was made between the Madeira catalogue and one catalogue from Sagres, on the southwest tip of the Iberian Peninsula (n = 359). Results showed 26 individual matches, mostly between Madeira and the Canary Islands (n = 23), and between Azores and Madeira (n = 3). No matches were found between the Canary Islands and the Azores, nor between Madeira and Sagres. There were no individuals identified in all three archipelagos. The minimum time recorded between sightings in two different archipelagos (≈ 460 km apart) was 62 days. Association patterns revealed that the individuals moving between archipelagos were connected to resident, migrant and transient individuals in Madeira. The higher number of individuals that were re-sighted between Madeira and the Canary Islands can be explained by the relative proximity of these two archipelagos. This study shows the first inter-archipelago movements of bottlenose dolphins in the Macaronesia region, emphasizing the high mobility of this species and supporting the high gene flow described for oceanic dolphins inhabiting the North Atlantic. The dynamics of these long-range movements strongly denotes the need to review marine protected areas established for this species in each archipelago, calling for joint resolutions from three autonomous regions belonging to two EU countries.

Cerebellar ataxia as a primary manifestation of neuropsychiatric systemic lupus erythematosus.

Acute cerebellar ataxia is a rare primary manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE). We report a case of a 22-year-old woman who presented with gait instability, behavioural changes and new-onset seizures. The tempo of disease progression was explained by an autoimmune cause, eventually fulfilling the criteria for systemic lupus erythematosus. The patient's neurological symptoms improved markedly following administration of steroids and immunomodulators. A review of literature on cerebellar ataxia in NPSLE and a summary of all reported cases to date are also presented.

Treatment gaps and challenges in epilepsy care in the Philippines.

OBJECTIVE: Epilepsy is a neurologic disease that carries a high disease burden and likely, a huge treatment gap especially in low-to-middle income countries (LMIC) such as the Philippines. This review aimed to examine the treatment gaps and challenges that burden Philippine epilepsy care. MATERIALS & METHODS: Pertinent data on epidemiology, research, health financing and health systems, pharmacologic and surgical treatment options, cost of care, and workforce were obtained through a literature search and review of relevant Philippine government websites. RESULTS: The estimated prevalence of epilepsy in the Philippines is 0.9%. Epilepsy research in the Philippines is low in quantity compared with the rest of Southeast Asia (SEA). Inequities in quality and quantity of healthcare services delivered to local government units (LGUs) have arisen because of devolution. Programs for epilepsy care by both government and nongovernment institutions have been implemented. Healthcare expenditure in the Philippines is still largely out-of-pocket, with only partial coverage from the public sector. There is limited access to antiseizure medications (ASMs), mainly due to cost. Epilepsy surgery is an underutilized treatment option. There are only 20 epileptologists in the Philippines, with one epileptologist for every 45,000 patients with epilepsy. In addition, epilepsy care service delivery has been further impeded by the coronavirus disease of 2019 (COVID-19) pandemic. CONCLUSION: There is a large treatment gap in epilepsy care in the Philippines in terms of high epilepsy disease burden, socioeconomic limitations and inadequate public support, sparse clinico-epidemiologic research on epilepsy, inaccessibility of health care services and essential pharmacotherapy, underutilization of surgical options, and lack of specialists capable of rendering epilepsy care. Acknowledgment of the existence of these treatment gaps and addressing such are expected to improve the overall survival and quality of life of patients with epilepsy in the Philippines.

Clinical features and outcomes of nonconvulsive status epilepticus in a developing country: A 5-year retrospective study.

BACKGROUND: This study aimed to determine the frequency of electrographically confirmed nonconvulsive status epilepticus (NCSE) in a cohort suspected with this condition and to determine the demographic/clinical profile, treatment, and outcomes of these patients in the context of a developing country, the Philippines. METHODS: We conducted a retrospective study among patients with suspected with NCSE admitted in the Philippine General Hospital from 2014 to 2019. Using the Salzberg 2013 criteria to diagnose NCSE, three electroencephalographers independently reviewed the electroencephalogram (EEG) tracings of suspected patients and were blinded from the clinical information. Then, we obtained pertinent clinical data from the medical records of EEG-confirmed NCSE cases. RESULTS: Out of 89 patients suspected with NCSE and with available EEG tracings, information from a total of 14 patients (15.7%) with electrographically confirmed cases were included in the analysis. Median age was 52 ranging from 22 to 77 and female-to-male ratio was 1.3:1. The following conditions were associated with NCSE: intracranial tumor (n = 4), metabolic encephalopathy (n = 4), autoimmune encephalitis (n = 3), intracranial hemorrhage (n = 3), sepsis (n = 3), cardiac arrest (n = 2), hypoxic-ischemic injury (n = 2), antiepileptic withdrawal (n = 1), intracranial abscess (n = 1), head trauma (n = 1), and meningitis (n = 1). Three patients (21.4%) had relatively good clinical outcomes (mRS 0-2) while 6 patients (42.8%) had poor outcomes (mRS 3-5) at discharge. Five patients (35.7%) died due to medical/neurological complications. Our review of the literature showed that the profile of NCSE cases identified in our resource-limited institution strengthens the findings in other populations. CONCLUSION: Our data showed that approximately 1 in 6 patients who are suspected with NCSE may have electrographic evidence of NCSE in our setting. The most common etiologies associated with NCSE were intracranial tumors and metabolic conditions. Further studies may entail a prospective collection of data to validate the estimates of our study.

Electroencephalographic findings in antileucine-rich glioma-inactivated 1 (LGI1) autoimmune encephalitis: A systematic review.

BACKGROUND: Antileucine-rich glioma-inactivated 1 (LGI1) autoimmune encephalitis is a distinct syndrome of early onset faciobrachial dystonic seizures (FBDS) and other focal seizures followed by neuropsychiatric symptoms. The electroclinical syndrome of this condition is yet to be fully understood. The main objective of this study was to determine the frequencies of electroencephalogram (EEG) findings in patients diagnosed with anti-LGI1 autoimmune encephalitis through a systematic review of published relevant articles. METHODS: Major electronic healthcare databases were searched for relevant published articles until July 2020. RESULTS: From 327 articles, 23 case reports and 14 case series were included in the review after satisfying the eligibility criteria. Data from a total of 151 cases of definite anti-LGI1 encephalitis were analyzed in this systematic review. Epileptiform discharges were the most frequent finding at 57.3%. Focal electroencephalographic abnormalities including slow wave (59.3%) and epileptiform activities (53.5%) most commonly arise from the temporal region. Faciobrachial dystonic seizures often have no ictal electroencephalographic correlate but would show electrodecremental events when seizure duration is prolonged. CONCLUSION: Electroencephalogram abnormalities are seen in anti-LGI1 autoimmune encephalitis with epileptiform discharges as the most common finding followed by focal slowing. These findings were most frequently seen arising in the temporal region. Further studies using a standardized protocol focusing on electroencephalographic findings in anti-LGI1 encephalitis with clinical correlation to disease stage and treatment outcomes in terms of seizure control and memory and cognitive function are needed. Particular attention on ictal electrodecremental activity during FBDS should be done in studies with a larger sample size.

Electroencephalographic findings in COVID-19 patients: A systematic review.

BACKGROUND: Growing evidence of neurologic involvement seen in COVID-19 infection necessitates the pooling of neurodiagnostic findings like electroencephalography (EEG) that may guide clinical management. The objective of this study was to review the EEG findings in patients diagnosed with COVID-19 infection through a systematic review of published articles. METHODS: We systematically searched until July 25, 2020 for published articles that reported on descriptive EEG findings in patients diagnosed with COVID-19 in PUBMED by Medline, EMBASE, and CENTRAL by the Cochrane Library. RESULTS: From a total of 94 identified records, 29 relevant articles were included in this review. A total of 177 patients with COVID-19 with descriptive EEG reports were analyzed. The most common indication for EEG was unexplained altered mental status. Disturbances of background activity such as generalized and focal slowing were seen as well epileptiform abnormalities and rhythmic or periodic discharges. There were no consistent EEG findings specific to COVID-19 infection. CONCLUSION: The EEG findings in COVID-19 appear to be non-specific. Further research on the relationship of the EEG findings to the clinical state and short- or long-term prognosis of COVID-19 patients may be conducted to help clinicians discern which patients would necessitate an EEG procedure and would eventually require treatment.

Improving the Environmental Risk Assessment of Substances of Unknown or Variable Composition, Complex Reaction Products, or Biological Materials.

Substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs) pose unique risk assessment challenges to regulators and to product registrants. These substances can contain many constituents, sometimes partially unknown and/or variable, depending on fluctuations in their source material and/or manufacturing process. International regulatory agencies have highlighted the difficulties in characterizing UVCBs and assessing their toxicity and environmental fate. Several industrial sectors have attempted to address these issues by developing frameworks and characterization methods. Based on the output of a 2016 workshop, this critical review examines current practices for UVCB risk assessment and reveals a need for a multipronged and transparent approach integrating whole-substance and constituent-based information. In silico tools or empirical measurements can provide information on discrete and/or blocks of UVCB constituents with similar hazard properties. Read-across and/or whole-substance toxicity and fate testing using adapted emerging methods can provide whole-substance information. Continued collaboration of stakeholders representing government, industry, and academia will facilitate the development of practical testing strategies and guidelines for addressing regulatory requirements for UVCBs. Environ Toxicol Chem 2020;39:2097-2108. © 2020 Health and Environmental Sciences Institute. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Efficacy and tolerability of intravenous brivaracetam for status epilepticus: A systematic review.

BACKGROUND: Status epilepticus (SE) is an emergent neurologic condition that carries a high risk of morbidity and mortality. Intravenous brivaracetam (IV BRV) may be an alternative anticonvulsant against status epilepticus, although the sparseness of controlled studies on the topic limits its recommendation for this indication. OBJECTIVES: This systematic review aimed to determine the efficacy and safety of IV BRV in the treatment of status epilepticus. METHODS: A comprehensive literature search was conducted until December 2019 through several electronic databases (PubMed, Google Scholar, Scopus, OpenGrey, ScienceDirect, HERDIN, Epistemonikos, CENTRAL, ClinicalTrials.gov) to identify relevant studies. Studies that involved adult patients with SE who were given IV BRV were considered for inclusion in this review. RESULTS: From a total of 34 studies identified, 5 uncontrolled studies with 77 patients were included in this review. Thirty-seven out of 77 patients (48%) with SE responded to IV BRV. Reported time to seizure cessation may be immediate from a few minutes to several hours after IV BRV treatment. Patients manifested with significant disability on Glasgow outcome scale (Median: 3) and modified Rankin scale (Mode: 5). Six patients [somnolence (5), worsening seizures (1)] had treatment emergent adverse events. CONCLUSIONS: Limited evidence from 5 uncontrolled studies involving a limited number of patients suggests that IV BRV may be efficacious and safe in terminating seizures among patients with SE or refractory SE. Further studies employing either prospective, controlled trials or registry-based study designs are essential to determine the definitive role of IV BRV in patients with SE.

Chronic inflammatory demyelinating polyneuropathy with tongue fasciculation: A case report.

Chronic inflammatory demyelinating polyneuropathy is one of the immune-mediated polyneuropathies responsive to immunotherapy. Its usual clinical presentation is a chronic course of symmetric sensorimotor affectation of both proximal and distal extremities with signs of demyelination on electrophysiologic studies. Cranial nerve signs in this condition is not commonly encountered, particularly involvement of the hypoglossal nerve. To date, there are only three published cases of hypoglossal involvement in this condition. This case report presents a patient with tongue fasciculation, which is an uncommon finding in chronic inflammatory demyelinating polyneuropathy. This paper highlights the importance of considering chronic inflammatory demyelinating polyneuropathy in the differential diagnoses of a patient with tongue fasciculation as it has been found to be responsive to immunotherapy in comparison to other lower motor neuron syndromes.

Boron Nitride Nanotube Addition Enhances the Crystallinity and Cytocompatibility of PVDF-TrFE.

Analysis of the cellular response to piezoelectric materials has been driven by the discovery that many tissue components exhibit piezoelectric behavior ex vivo. In particular, polyvinylidene fluoride and the trifluoroethylene co-polymer (PVDF-TrFE) have been identified as promising piezo and ferroelectric materials with applications in energy harvesting and biosensor devices. Critically, the modulation of the structural and crystalline properties of PVDF-TrFE through annealing processes and the addition of particulate or fibrous fillers has been shown to modulate significantly the materials electromechanical properties. In this study, a PVDF-TrFE/boron-nitride nanotube composite was evaluated by modulated differential scanning calorimetry to assess the effects of boron nitride nanotube addition and thermal annealing on the composite structure and crystal behavior. An increased beta crystal formation [f(ß) = 0.71] was observed following PVDF-TrFE annealing at the first crystallization temperature of 120°C. In addition, the inclusion of boron nitride nanotubes significantly increased the crystal formation behavior [f(ß) = 0.76] and the mechanical properties of the material. Finally, it was observed that BNNT incorporation enhance the adherence and proliferation of human tenocyte cells in vitro.

Autoimmune encephalitis associated with two antibodies.

•In patients presenting with clinical manifestations of encephalitis without clinical or laboratory signs of infection, an autoimmune etiology should be suspected.•Antibodies for various neural antigens may coexist, thus a complete and clinically-guided autoimmune panel must be done in suspected cases of autoimmune encephalitis.•Tumor resection, if applicable, combined with high dose steroids and immunotherapy are effective treatment strategies for autoimmune encephalitis with coexisting antibodies.

The Functional Response of Mesenchymal Stem Cells to Electron-Beam Patterned Elastomeric Surfaces Presenting Micrometer to Nanoscale Heterogeneous Rigidity.

Cells directly probe and respond to the physicomechanical properties of their extracellular environment, a dynamic process which has been shown to play a key role in regulating both cellular adhesive processes and differential cellular function. Recent studies indicate that stem cells show lineage-specific differentiation when cultured on substrates approximating the stiffness profiles of specific tissues. Although tissues are associated with a range of Young's modulus values for bulk rigidity, at the subcellular level, tissues are comprised of heterogeneous distributions of rigidity. Lithographic processes have been widely explored in cell biology for the generation of analytical substrates to probe cellular physicomechanical responses. In this work, it is shown for the first time that that direct-write e-beam exposure can significantly alter the rigidity of elastomeric poly(dimethylsiloxane) substrates and a new class of 2D elastomeric substrates with controlled patterned rigidity ranging from the micrometer to the nanoscale is described. The mechanoresponse of human mesenchymal stem cells to e-beam patterned substrates was subsequently probed in vitro and significant modulation of focal adhesion formation and osteochondral lineage commitment was observed as a function of both feature diameter and rigidity, establishing the groundwork for a new generation of biomimetic material interfaces.