Antiviral Potential of Algal Metabolites—A Comprehensive Review

Historically, algae have stimulated significant economic interest particularly as a source of fertilizers, feeds, foods and pharmaceutical precursors. However, there is increasing interest in exploiting algal diversity for their antiviral potential. Here, we present an overview of 50-years of scientific and technological developments in the field of algae antivirals. After bibliometric analysis of 999 scientific references, a survey of 16 clinical trials and analysis of 84 patents, it was possible to identify the dominant algae, molecules and viruses that have been shaping and driving this promising field of research. A description of the most promising discoveries is presented according to molecule class. We observed a diverse range of algae and respective molecules displaying significant antiviral effects against an equally diverse range of viruses. Some natural algae molecules, like carrageenan, cyanovirin or griffithsin, are now considered prime reference molecules for their outstanding antiviral capacity. Crucially, while many algae antiviral applications have already reached successful commercialization, the large spectrum of algae antiviral capacities already identified suggests a strong potential for future expansion of this field

Doença Hepática Crónica Agudizada: Revisão da Experiência de um Centro Português de Referenciação

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of a patient with cirrhosis, frequently associated with multi-organ failure and a high short-term mortality rate. We present a retrospective study that aims to characterize the presentation, evolution, and outcome of patients diagnosed with ACLF at our center over the last 3 years, with a comparative analysis between the group of patients that had ACLF precipitated by infectious insults of bacterial origin and the group of those with ACLF triggered by a nonbacterial infectious insult; the incidence of acute kidney injury and its impact on the prognosis of ACLF was also analyzed. Twenty-nine patients were enrolled, the majority of them being male (89.6%), and the mean age was 53 years. Fourteen patients (48.3%) developed ACLF due to a bacterial infectious event, and 9 of them died (64.2%, overall mortality rate 31%); however, no statistical significance was found (p < 0.7). Of the remaining 15 patients (51.7%) with noninfectious triggers, 11 died (73.3%, overall mortality rate 37.9%); again there was no statistical significance (p < 0.7). Twenty-four patients (83%) developed acute kidney injury (overall mortality rate 65.5%; p < 0.022) at the 28-day and 90-day follow-up. Twelve patients had acute kidney injury requiring renal replacement therapy (41.37%; overall mortality rate 37.9%; p < 0.043). Hepatic transplant was performed in 3 patients, with a 100% survival at the 28-day and 90-day follow-up (p < 0.023). Higher grades of ACLF were associated with increased mortality (p < 0.02; overall mortality 69%). CONCLUSIONS: ACLF is a heterogeneous syndrome with a variety of precipitant factors and different grades of extrahepatic involvement. Most cases will have some degree of renal dysfunction, with an increased risk of mortality. Hepatic transplant is an efficient form of therapy for this syndrome.info:eu-repo/semantics/publishedVersio

Brain atrophy accelerates cognitive decline in cerebral small vessel disease: The LADIS study

Objective: To examine the independent contributions and combined interactions of medial temporal lobe atrophy (MTA), cortical and subcortical atrophy, and white matter lesion (WML) volume in longitudinal cognitive performance. Methods: A total of 477 subjects with age-relatedWMLwere evaluated with brain MRI and annual neuropsychological examinations in 3-year follow-up. Baseline MRI determinants of cognitive decline were analyzed with linear mixed models controlling for multiple confounders. Results: MTA and subcortical atrophy predicted significantly steeper rate of decline in global cognitive measures as well as compound scores for psychomotor speed, executive functions, and memory after adjusting for age, gender, education, lacunes/infarcts, and WML volume. Cortical atrophy independently predicted decline in psychomotor speed. WML volume remained significantly associated with cognitive decline even after controlling for the atrophy scores. Moreover, significant synergistic interactions were found between WML and atrophy measures in overall cognitive performance across time and the rate of cognitive decline. Synergistic effects were also observed between baseline lacunar infarcts and all atrophy measures on change in psychomotor speed. The main results remained robust after exclusion of subjects with clinical stroke or incident dementia, and after additional adjustments for progression of WML and lacunes. Conclusions: Brain atrophy and WML are independently related to longitudinal cognitive decline in small vessel disease. MTA, subcortical, and cortical atrophy seem to potentiate the effect ofWML and lacunes on cognitive decline

Impacto das Infeções Respiratórias Viricas Múltiplas na Evolução de Crianças Gravemente Doentes

Introdução: As infecções respiratórias baixas são a principal causa de mortalidade em crianças até aos 5 anos. A utilização do painel rápido multiplex por PCR melhora a identificação do diagnóstico etiológico. Objetivos: Comparar a evolução de infecções respiratórias víricas com um ou mais agente isolado em crianças admitidas por insuficiência respiratória aguda (IRA) em cuidados intensivos. Métodos: Estudo retrospetivo (39 meses, dezembro 2014 a fevereiro 2018) de doentes com IRA e identificação de pelo menos um vírus por PCR multiplex. Estudou-se a idade, género, PCR multiplex e evolução. Consideraram-se dois grupos: A um vírus e B mais do que um vírus. Utilizaram-se os testes Qui-quadrado ou Exato de Fisher para testar associações entre variáveis. Resultados: Obtiveram-se 54 IRA com agente identificado: grupo A=42 e B=12. Mediana de idade de 4 e 5 meses (A/B), género masculino 57% e 50% (A/B). No mesmo período, verificaram-se 1149 internamentos, com PRISM médio de 2,68 e mortalidade de 2,78%. No grupo A, o PRISM médio foi de 7,50 e no B de 5,17. Não se registaram óbitos. A doença crónica e a falência de órgão foram mais frequentes no grupo A (33% e 8%, p=0,088; 83% e 67%, p=0,206). Os vírus mais frequentes foram: A - Vírus Sincicial Respiratório (43%), B - Rhinovírus (58%), com coinfecção bacteriana em 21% e 8% (A/B, p=0,303). O grupo B necessitou mais de ventilação (A - 67%, B - 75%, p=0,512), sem diferença no modo (não invasiva p=0,571, invasiva p=0,571). Houve necessidade de acesso central em 24% e 25% (A/B, p=0,932) e vasopressores em 10% e 0% (A/B, p=0,564). A demora média foi 11 e 10 dias (A/B). Conclusão: O estudo sugere que a coexistência de vários vírus no mesmo doente não alterou significativamente a evolução e o prognóstico.info:eu-repo/semantics/publishedVersio

White Matter Lesion Progression in LADIS Frequency, Clinical Effects, and Sample Size Calculations

BACKGROUND AND PURPOSE: White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. METHODS: Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale. RESULTS: WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment effects on lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm. CONCLUSIONS: WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia Assessment Scale as the primary cognitive outcome measure

Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study

Objectives: In cerebral small vessel disease, whitematter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. Methods: Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/ pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. Results: Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (b=20.61; p=0.043), and worse compound scores for speed and motor control (b=20.25; p=0.006), executive functions (b=20.19; p=0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/ pallidum and the memory compound Z score (b=20.13; p=0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. Conclusion: In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH

Confirmatory factor analysis of the Neuropsychological Assessment Battery of the LADIS study: a longitudinal analysis

WOS:000315985900004Age-related white matter changes have been associated with cognitive functioning, even though their role is not fully understood. This work aimed to test a 3-factor model of the neuropsychological assessment battery and evaluate how the model fit the data longitudinally. Confirmatory factor analysis (CFA) was used to investigate the dimensions of a structured set of neuropsychological tests administered to a multicenter, international sample of independent older adults (LADIS study). Six hundred and thirty-eight older adults completed baseline neuropsychological, clinical, functional and motor assessments, which were repeated each year for a 3-year follow-up. CFA provided support for a 3-factor model. These factors involve the dimensions of executive functions, memory functions, and speed and motor control abilities. Performance decreased in most neuropsychological measures. Results showed that executive functioning, memory and speed of motor abilities are valid latent variables of neuropsychological performance among older adults, and that this structure is relatively consistent longitudinally, even though performance decreases with time.info:eu-repo/semantics/acceptedVersio

A European Academy of Neurology guideline on medical management issues in dementia

BACKGROUND AND PURPOSE: Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow‐up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia. METHODS: A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated. RESULTS: Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk–benefit ratio should be performed at regular intervals. Regular, preplanned medical follow‐up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non‐pharmacological measures have been proven to be without benefit or in the case of severe self‐harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first‐line therapy (Good Practice statement). CONCLUSION: This GRADE‐based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas

Diffusion-Weighted Imaging and Cognition in the Leukoariosis and Disability in the Elderly Study

BACKGROUND AND PURPOSE-: The mechanisms by which leukoariosis impacts on clinical and cognitive functions are not yet fully understood. We hypothesized that ultrastructural abnormalities of the normal-appearing brain tissue (NABT) assessed by diffusion-weighted imaging played a major and independent role. METHODS-: In addition to a comprehensive clinical, neuropsychologic, and imaging work-up, diffusion-weighted imaging was performed in 340 participants of the multicenter leukoariosis and disability study examining the impact of white matter hyperintensities (WMH) on 65-to 85-year old individuals without previous disability. WMH severity was rated according to the Fazekas score. Multivariate regression analysis served to assess correlations of histogram metrics of the apparent diffusion coefficient (ADC) of whole-brain tissue, NABT, and of the mean ADC of WMH with cognitive functions. RESULTS-: Increasing WMH scores were associated with a higher frequency of hypertension, a greater WMH volume, more brain atrophy, worse overall cognitive performance, and changes in ADC. We found strong associations between the peak height of the ADC histogram of whole-brain tissue and NABT with memory performance, executive dysfunction, and speed, which remained after adjustment for WMH lesion volume and brain atrophy and were consistent among centers. No such association was seen with the mean ADC of WMH. CONCLUSIONS-: Ultrastructural abnormalities of NABT increase with WMH severity and have a strong and independent effect on cognitive functions, whereas diffusion-weighted imaging metrics within WMH have no direct impact. This should be considered when defining outcome measures for trials that attempt to ameliorate the consequences of WMH progression

Report of the expert meeting on food safety for seaweed – Current status and future perspectives

The world production of marine macroalgae, or seaweed, has more than tripled since the turn of the millennium, increasing from 10.6 million tonnes in 2000 to 32.4 million tonnes in 2018. Increased cultivation and utilization of seaweed are expected to be important pillars of sustainable food security and a robust aquatic economy in the coming years. It is important, therefore, to consider the food safety implications of (increased) seaweed use for food. Many factors can affect the presence of hazards in seaweed, including: the type of seaweed, its physiology, the season in which it is produced, production waters, harvesting methods and processing. Several hazards such as heavy metals and marine biotoxins have been reported to be (potentially) associated with seaweed. However, legislation and guidance documents on the production and utilization of seaweed are generally still lacking. FAO and the World Health Organization (WHO) have therefore developed this report to identify food safety hazards (microbiological, chemical and physical) linked to the consumption of seaweed and aquatic plants. The present analysis could therefore provide a basis for undertaking further work in this area. Moreover, both FAO and WHO believe that there would be a value in developing relevant Codex guidance on this subject.publishedVersio