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.

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.

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.

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.

Analysis of the misfit of dental implant-supported prostheses made with three manufacturing processes.

STATEMENT OF PROBLEM: The microgap between implant components has been associated with complications such as screw loosening or adverse biologic responses. PURPOSE: The purpose of this study was to quantify the microroughness of the mating surfaces of implant components manufactured with different processes, to quantify the microgap between implant components, and to determine whether a correlation exists between microroughness and the microgap. MATERIAL AND METHODS: Nine dental implants with a standard external connection were paired with 3 milled, 3 cast, and 3 sintered compatible cobalt-chromium alloy abutments. The abutment surface was examined, and the roughness parameter Sz was measured by using a white-light interferometric microscope at ×10 to ×100 magnification. The abutment surface and the microgap of the implant-abutment connection were observed with scanning electron microscopy, and the microgap width was quantified from micrographs made of each implant-abutment pair. The mean and standard deviation of roughness and microgap were evaluated. A 1-way ANOVA (α=.05) was used to assess the influence of the manufacturing process on roughness and microgap. The Pearson correlation was used to check dependence between roughness and microgap. RESULTS: The milled abutments possessed a connection geometry with defined edges and a mean roughness of 29 µm, sintered abutments showed a blurred but functional connection with a roughness of 115 µm, and cast abutments showed a connection with a loss of axial symmetry and a roughness of 98 µm. A strong correlation was found between the roughness values on the mating surfaces and the microgap width. CONCLUSIONS: The milled components were smoother than the cast or sintered components. A correlation was found between surface roughness and microgap width.

Acoustic fish community in the Madeira Archipelago (North Atlantic Ocean): Characterization of sound diversity and daily patterns.

Marine ecosystems are increasingly subjected to anthropogenic pressures, which demands urgent monitoring plans. Understanding soundscapes can offer unique insights into the ocean status providing important information and revealing different sounds and their sources. Fishes can be prominent soundscape contributors, making passive acoustic monitoring (PAM) a potential tool to detect the presence of vocal fish species and to monitor changes in biodiversity. The major goal of this research was to provide a first reference of the marine soundscapes of the Madeira Archipelago focusing on fish sounds, as a basis for a long-term PAM program. Based on the literature, 102 potentially vocal and 35 vocal fish species were identified. Additionally 43 putative fish sound types were detected in audio recordings from two marine protected areas (MPAs) in the Archipelago: the Garajau MPA and the Desertas MPA. The Garajau MPA exhibited higher fish vocal activity, a greater variety of putative fish sound types and higher fish sound diversity. Lower abundance of sounds was found at night at both MPAs. Acoustic activity revealed a clear distinction between diurnal and nocturnal fish groups and demonstrated daily patterns of fish sound activity, suggesting temporal and spectral partitioning of the acoustic space. Pomacentridae species were proposed as candidates for some of the dominant sound types detected during the day, while scorpionfishes (Scorpaena spp.) were proposed as sources for some of the dominant nocturnal fish sounds. This study provides an important baseline about this community acoustic behaviour and is a valuable steppingstone for future non-invasive and cost-effective monitoring programs in Madeira.

Isotope-based inferences of the trophic niche of short-finned pilot whales in the Webbnesia.

Knowledge of predator-prey interactions is key in ecological studies and understanding ecosystem function, yet this is still poorly explored in the deep-sea environment. Carbon (δ13C: 13C/12C) and nitrogen (δ15N: 15N/14N) stable isotope ratios of a deep-diving species, the short-finned pilot whale (Globicephala macrorhynchus), were used to explore knowledge gaps on its ecological niche and foraging habitats in the Webbnesia marine ecoregion (Tenerife Island, n = 27 animals vs. Madeira, n = 31; 500 km apart) where animals display distinct levels of site fidelity. Specifically, we tested whether intraspecific isotopic variation results from differences between geographic areas (due to possible foraging plasticity between regions), sexes, and/or years (2015-2020) using Generalized Linear Models. In general, significant differences (p < 0.05) were found in the stable isotope profiles of pilot whales between the two archipelagos, which were also reflected in their isotopic niche. The higher mean and wider range of δ15N values in Tenerife suggest that pilot whales consume prey of higher trophic levels and more diverse than Madeira. The higher mean and wider range of δ13C values in Madeira suggest that in that island, pilot whales rely on prey from more diverse habitats. There was significant variation between some years, but not between sexes. Finally, we discuss pilot whales' foraging strategies worldwide and infer the reliance on benthic or benthopelagic food sources in the Webbnesia.

Plasmodium vivax spleen-dependent protein 1 and its role in extracellular vesicles-mediated intrasplenic infections.

Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by Plasmodium vivax. Previous studies have demonstrated that extracellular vesicles (EVs) secreted from infected reticulocytes facilitate binding to human spleen fibroblasts (hSFs) and identified parasite genes whose expression was dependent on an intact spleen. Here, we characterize the P. vivax spleen-dependent hypothetical gene (PVX_114580). Using CRISPR/Cas9, PVX_114580 was integrated into P. falciparum 3D7 genome and expressed during asexual stages. Immunofluorescence analysis demonstrated that the protein, which we named P. vivax Spleen-Dependent Protein 1 (PvSDP1), was located at the surface of infected red blood cells in the transgenic line and this localization was later confirmed in natural infections. Plasma-derived EVs from P. vivax-infected individuals (PvEVs) significantly increased cytoadherence of 3D7_PvSDP1 transgenic line to hSFs and this binding was inhibited by anti-PvSDP1 antibodies. Single-cell RNAseq of PvEVs-treated hSFs revealed increased expression of adhesion-related genes. These findings demonstrate the importance of parasite spleen-dependent genes and EVs from natural infections in the formation of intrasplenic niches in P. vivax, a major challenge for malaria elimination.

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.

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.