Distonija kao manifestacija korea-akantocitoze

The aim of this article is to present two Slovenian chorea-acanthocytosis (ChAc) siblings with an unusual predominantly dystonic ChAc phenotype. For diagnostic purposes, the genomic DNA was screened for VPS13A mutations. Movement disorder was evaluated and scored according to the Dystonia Movement and Disability Scale (DMDS) in order to evaluate the effects of L-dopa on dystonia. Brain imaging was performed with the use of magnetic resonance imaging scan and 99m Tc-ethyl cysteinate dimmer single photon emission computed tomography (Tc-ECD SPECT). Clinical neurological examination disclosed gait dystonia. Marked swallowing difficulty due to tongue and feeding dystonia was observed. Both siblings were found to be heterozygous for a substitution in exon 22 (c.2191C>T) and for a deletion in exon 35 (c.3995_3996delinsA) leading to mutation in VPS13A. After being administered L-dopa for three months, both subjects showed significant symptomatic improvement documented by reduced DMDS scores. It is concluded that VPS13A mutation testing may improve diagnosis of dystonia and recognition of atypical ChAc phenotypes. It seems that L-dopa could be effective in the treatment of dystonia due to VPS13A mutations.Prikazuje se dvoje slovenskih bolesnika, brat i sestra, s koreom-akantocitozom, s neuobičajenim pretežito distoničnim fenotipom korea-akantocitoze. Proveden je dijagnostički probir genomske DNA na mutacije VPS13A. Poremećaj kretanja procijenjen je i ocijenjen prema Dystonia Movement and Disability Scale (DMDS) kako bi se procijenili učinci L-dopa na distoniju. Slikovni prikazi mozga napravljeni su pomoću magnetske rezonance i Tc-ECD SPECT (99m Tc-ethyl cysteinate dimmer single photon emission computed tomography). Klinički neurološki pregled otkrio je distoniju hoda. Zapažene su znatne teškoće pri gutanju zbog distonije jezika i distonija hranjenja. I brat i sestra bili su heterozigotni za supstituciju u eksonu 22 (c.2191C>T) i za deleciju u eksonu 35 (c.3995_3996delinsA), koje uzrokuju mutaciju u VPS13A. Nakon davanja L-dopa kroz tri mjeseca oboje je pokazalo značajno poboljšanje simptoma, što je dokumentirano sniženim zbirom na DMDS. Zaključuje se da testiranje na mutaciju VPS13A može pomoći u dijagnosticiranju distonije i prepoznavanju atipičnih fenotipova korea-akantocitoze. Čini se da bi L-dopa mogla biti učinkovita u liječenju distonije uzrokovane mutacijama VPS13A

Alternativní zemědělství - informační bulletin č.7

Témata informačního bulletinu č.7 jsou: Vyhodnocení výnosů zemědělských plodin v roce 1991 u organicky hospodařících zemědělců svazu PRO-BIO. Nutnost moření osiva z hlediska alternativního zemědělství. Využití přirozených surovin v alternativním zemědělství. Mechanická regulace plevelů. Možnosti realizace alternativního zemědělství z hlediska ochrany rostlin. Regulace hraboše polního bez chemie. Úvod k připravované knize "Ekologická východiska zemědělství". Stáj s hlubokou podestýlkou pro dojnice z hlediska etologie a ekonomiky. Zelené hnojení. Organické vinohradnictví

The impact of noradrenergic neurotoxin DSP-4 and noradrenaline transporter knockout (NET-KO) on the activity of liver cytochrome P450 3A (CYP3A) in male and female mice

Background Our earlier studies have shown that the brain noradrenergic system regulates cytochrome P450 (CYP) in rat liver via neuroendocrine mechanism. In the present work, a comparative study on the effect of intraperitoneal administration of the noradrenergic neurotoxin DSP-4 and the knockout of noradrenaline transporter (NET-KO) on the CYP3A in the liver of male and female mice was performed. Methods The experiments were conducted on C57BL/6J WT and $NET^{–/–}$ male/female mice. DSP-4 was injected intraperitoneally as a single dose (50 mg/kg ip.) to WT mice. The activity of CYP3A was measured as the rate of 6β-hydroxylation of testosterone in liver microsomes. The CYP3A protein level was estimated by Western blotting. Results DSP-4 evoked a selective decrease in the noradrenaline level in the brain of male and female mice. At the same time, DSP-4 reduced the CYP3A activity in males, but not in females. The level of CYP3A protein was not changed. The NET knockout did not affect the CYP3A activity/protein in both sexes. Conclusions The results with DSP-4 treated mice showed sex-dependent differences in the regulation of liver CYP3A by the brain noradrenergic system (with only males being responsive), and revealed that the NET knockout did not affect CYP3A in both sexes. Further studies into the hypothalamic–pituitary–gonadal hormones in DSP-4 treated mice may explain sex-specific differences in CYP3A regulation, whereas investigation of monoaminergic receptor sensitivity in the hypothalamic/pituitary areas of $NET^{–/–}$ mice will allow for understanding a lack of changes in the CYP3A activity in the NET-KO animals

Residents' views on landscape and ecosystem services during a wind farm proposal in an island protected area

Industrial wind farms are being developed within many protected areas, such as in EU Natura 2000 sites; this includes proposals on small Mediterranean islands, such as Samothraki in Greece. Scarce wild land areas on islands may be particularly vulnerable to landscape-scale degradation; this may have serious negative societal impacts. Samothraki's resident perceptions were surveyed in the wake of such a proposal, in June 2018. Of 98 respondents, 48% reported they were against the wind farm plan, while 22% did not take sides. We compare for-and-against sub-group perceptions of the proposed wind farm with potential impacts on the landscape and explore residents' opinions on ecosystem services and environmental pressures and threats. Conflict over the wind farm was prevalent; residents most frequently reported that the proposal threatens aesthetic and landscape qualities. Aesthetic qualities were also the second highest ranked ecosystem services, after freshwater provision. However, other threats, such as livestock overgrazing, top residents' opinion of major environmental problems on the island. The questionnaire survey used provides a scoping assessment, which may assist in identifying "conflict hotspots" for wind farm development. A critical review of wind farm planning in protected areas is presented in light of insights gained from this survey and other relevant studies

Case report: Filarial infection of a parti-coloured bat: Litomosa sp. adult worms in abdominal cavity and microfilariae in bat semen

BackgroundFilarial infections have been understudied in bats. Likewise, little is known about pathogens associated with the reproductive system in chiropterans. While semen quality is critical for reproductive success, semen-borne pathogens may contribute to reproductive failure.MethodsFor the first time we performed electroejaculation and used computer-assisted semen analysis to provide baseline data on semen quality in a parti-coloured bat (Vespertilio murinus).ResultsThe semen quality values measured in the V. murinus male appeared high (semen concentration = 305.4 × 106/mL; progressive and motile sperm = 46.58 and 60.27%, respectively). As an incidental finding, however, microfilariae were observed in the bat semen examined. At necropsy, eight adult filarial worms, later genetically identified as Litomosa sp., were found in the peritoneal cavity, close to the stomach, of the same particoloured bat male dying as a result of dysmicrobia and haemorrhagic gastroenteritis in a wildlife rescue centre. Histopathology revealed microfilariae in the testicular connective tissue and the epidydimal connective and fat tissues. A PCR assay targeting cytochrome c oxidase subunit 1 confirmed that adult worms from the peritoneal cavity and testicular microfilariae were of the same filarial species. Mildly engorged argasid mite larvae attached to the bat skin proved negative for filarial DNA and the adult filarial worms proved negative for endosymbiont Wolbachia.ConclusionWhile the standard filarial life cycle pattern involves a vertebrate definitive host and an invertebrate vector, represented by a blood-sucking ectoparasite, our finding suggests that microfilariae of this nematode species may also be semen-borne, with transmission intensity promoted by the polygynous mating system of vespertilionid bats in which an infected male mates with many females during the autumn swarming. Presence of microfilariae may be expected to decrease semen quality and transmission via this route may challenge the success of reproductive events in females after mating. Further investigation will be necessary to better understand the bat-parasite interaction and the life cycle of this filarial worm

Agentes de mudança na biodiversidade e serviços ecossistêmicos na APA Sistema Cantareira: Uma análise prospectiva da implementação de políticas públicas

The lack of implementation of well-designed public policies aimed at the conservation of natural ecosystems has resulted, at a global level, in the decline of ecosystem functioning and, consequently, of the contributions they make to people. The poor enforcement of important environmental legislation in Brazil-for instance, the “Atlantic Forest Law” (Law n.11.428/2006) and the “Forest Code” (Law n.12.651/2012)-could compromise the overall maintenance of ecosystems and the services they provide. To explore the implications of different levels of federal laws’ enforcement within the Cantareira System Protected Area (PA)-a PA in southeastern Brazil that provides fresh water for 47% of the Sao Paulo Metropolitan Area-, we developed a conceptual framework to identify indirect and direct drives of biodiversity and ecosystem changes. We also projected four land-use scenarios to 2050 to test the effects of deforestation control and forest restoration practices on biodiversity and ecosystem services maintenance: the “business-as-usual” scenario (BAU), which assumes that all trends in land-use cover changes observed in the past will continue in the future, and three alternative exploratory scenarios considering the Atlantic Forest Law implementation, the partial implementation of the Forest Code and the full implementation of the Forest Code. Using the land-use maps generated for each scenario, we assessed the impacts of land-use changes on biodiversity conservation and soil retention. Our results revealed all alternative scenarios could increase biodiversity conservation (by 7%; 12%; and 12%, respectively), reduce soil loss (by 24.70%; 34.70%; and 38.12%, respectively) and sediment exportation to water (by 27.47%; 55.06%; and 59.28%, respectively), when compared to the BAU scenario. Our findings highlight the importance of restoring and conserving native vegetation for the maintenance and improvement of biodiversity conservation and for the provision of ecosystem services.A falta de implementação de políticas públicas voltadas para a conservação ambiental, tem resultado, em nível global, em impactos sobre a biodiversidade e o funcionamento dos ecossistemas e, consequentemente, na contribuição da natureza para as pessoas. A aplicação inadequada de importantes de leis ambientais no Brasil, como por exemplo, a “Lei da Mata Atlântica” (Lei nº 11.428 / 2006) e o “Código Florestal” (Lei nº 12.651 / 2012), podem comprometer a manutenção dos ecossistemas e dos serviços que eles fornecem. Neste estudo, nós desenvolvemos um mapa conceitual que busca identificar causas diretas e indiretas de mudanças – agentes de mudança – na biodiversidade e na provisão de serviços ecossistêmicos relacionados ao solo e à água, na Área de Proteção Ambiental (APA) Sistema Cantareira. A APA Sistema Cantareira, localizada no sudeste do Brasil, fornece água potável para 47% da Região Metropolitana de São Paulo. Além da abordagem conceitual, nós projetamos quatro cenários de mudança no uso da terra para o ano de 2050, a fim de analisar o impacto de diferentes níveis de aplicação de leis federais: o cenário “business-as-usual” (BAU), que pressupõe que as tendências na mudança de uso da terra observadas no passado continuarão no futuro, e três cenários alternativos, considerando a implementação da Lei da Mata Atlântica, a implementação parcial do Código Florestal e a implementação completa do Código Florestal. A partir dos mapas de uso da terra gerados, avaliamos os impactos de cada cenário na conservação da biodiversidade, na retenção de solos e na exportação de sedimentos para os corpos d’água. Nossos resultados mostraram que os três cenários alternativos podem aumentar a conservação da biodiversidade (em 7%; 12%; e 12%, respectivamente), reduzir a perda de solo (em 24,70%; 34,70%; e 38,12%, respectivamente) e reduzir a exportação de sedimentos para a água (em 27,47 %; 55,06%; e 59,28%, respectivamente), quando comparados ao cenário BAU. Este estudo destaca a importância da restauração e conservação da vegetação nativa para a manutenção da biodiversidade e melhoria na provisão de serviços ecossistêmicos relacionados ao solo e à água, em uma região estratégica para o abastecimento de água no Brasil.Fil: Dib, Viviane. Universidade Federal do Rio de Janeiro; BrasilFil: Nalon, Marco Aurélio. Estado de São Paulo. Secretaria de Infraestrutura e Meio ambiente. Instituto Florestal; BrasilFil: Amazonas, Nino Tavares. Universidade de Sao Paulo; BrasilFil: Vidal, Cristina Yuri. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Ortiz Rodríguez, Iván A.. Scuola Normale Superiore. Classe di Scienze; ItaliaFil: Danek, Jan. Czech Academy of Sciences; República ChecaFil: Oliveira, Maíra Formis de. Estado de São Paulo. Secretaria de Agricultura e Abastecimento; BrasilFil: Alberti, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Biodiversidad Neotropical. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Biodiversidad Neotropical. Instituto de Biodiversidad Neotropical; ArgentinaFil: Silva, Rafaela Aparecida da. Universidade Federal de Goiás; BrasilFil: Precinoto, Raíza Salomão. Universidade Federal do Rio de Janeiro; BrasilFil: Gomes, Taciana Figueiredo. Universidade de Sao Paulo; Brasi

Candidate genes for obstructive sleep apnea in non-syndromic children with craniofacial dysmorphisms – a narrative review

Pediatric obstructive sleep apnea (POSA) is a complex disease with multifactorial etiopathogenesis. The presence of craniofacial dysmorphisms influencing the patency of the upper airway is considered a risk factor for POSA development. The craniofacial features associated with sleep-related breathing disorders (SRBD) – craniosynostosis, retrognathia and micrognathia, midface and maxillary hypoplasia – have high heritability and, in a less severe form, could be also found in non-syndromic children suffering from POSA. As genetic factors play a role in both POSA and craniofacial dysmorphisms, we hypothesize that some genes associated with specific craniofacial features that are involved in the development of the orofacial area may be also considered candidate genes for POSA. The genetic background of POSA in children is less explored than in adults; so far, only one genome-wide association study for POSA has been conducted; however, children with craniofacial disorders were excluded from that study. In this narrative review, we discuss syndromes that are commonly associated with severe craniofacial dysmorphisms and a high prevalence of sleep-related breathing disorders (SRBD), including POSA. We also summarized information about their genetic background and based on this, proposed 30 candidate genes for POSA affecting craniofacial development that may play a role in children with syndromes, and identified seven of these genes that were previously associated with craniofacial features risky for POSA development in non-syndromic children. The evidence-based approach supports the proposition that variants of these candidate genes could lead to POSA phenotype even in these children, and, thus, should be considered in future research in the general pediatric population

Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias

Objective: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. Methods: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), b-amyloid (Ab(1)-42), tau, and phosphorylated tau. The longitudinal change of blood NF-L levels was measured and analyzed for correlation with functional decline and brain atrophy. Results: Serum NF-L is increased in PPA compared to controls and discriminates between nfvPPA/svPPA and lvPPA with 81% sensitivity and 67% specificity (cutoff 31 pg/mL). CSF NF-L, pNF-H, tau, phosphorylated tau, and Ab1-42 achieved similar performance, and pNF-H was the only marker for discrimination of nfvPPA from svPPA/lvPPA. In most patients with nfvPPA and svPPA, but not lvPPA, serum NF-L increased within follow-up. The increase correlated with functional decline and progression of atrophy of the left frontal lobe of all patients with PPAs and the right middle frontal gyrus of patients with nfvPPA and svPPA. Conclusions: Blood level of NF-L can aid the differential diagnosis of PPA variants, especially in combination with CSF pNF-H. Because serum NF-L correlates with functional decline and atrophy in the disease course, it qualifies as an objective disease status marker. Extended follow-up studies with cases of known neuropathology are imperative

Cortical [18F]PI-2620 Binding Differentiates Corticobasal Syndrome Subtypes

Background Corticobasal syndrome is associated with cerebral protein aggregates composed of 4-repeat (~50% of cases) or mixed 3-repeat/4-repeat tau isoforms (~25% of cases) or nontauopathies (~25% of cases). Objectives The aim of this single-center study was to investigate the diagnostic value of the tau PET-ligand [18F]PI-2620 in patients with corticobasal syndrome. Methods Forty-five patients (71.5 ± 7.6 years) with corticobasal syndrome and 14 age-matched healthy controls underwent [18F]PI-2620-PET. Beta-amyloid status was determined by cerebral β-amyloid PET and/or CSF analysis. Subcortical and cortical [18F]PI-2620 binding was quantitatively and visually compared between β-amyloid-positive and -negative patients and controls. Regional [18F]PI-2620 binding was correlated with clinical and demographic data. Results Twenty-four percent (11 of 45) were β-amyloid-positive. Significantly elevated [18F]PI-2620 distribution volume ratios were observed in both β-amyloid-positive and β-amyloid-negative patients versus controls in the dorsolateral prefrontal cortex and basal ganglia. Cortical [18F]PI-2620 PET positivity was distinctly higher in β-amyloid-positive compared with β-amyloid-negative patients with pronounced involvement of the dorsolateral prefrontal cortex. Semiquantitative analysis of [18F]PI-2620 PET revealed a sensitivity of 91% for β-amyloid-positive and of 65% for β-amyloid-negative cases, which is in excellent agreement with prior clinicopathological data. Regardless of β-amyloid status, hemispheric lateralization of [18F]PI-2620 signal reflected contralateral predominance of clinical disease severity. Conclusions Our data indicate a value of [18F]PI-2620 for evaluating corticobasal syndrome, providing quantitatively and regionally distinct signals in β-amyloid-positive as well as β-amyloid-negative corticobasal syndrome. In corticobasal syndrome, [18F]PI-2620 may potentially serve for a differential diagnosis and for monitoring disease progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Serum neurofilament light chain in behavioral variant frontotemporal dementia

Objective To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD). Methods Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry. Results At baseline, serum NfL level correlated with CSFNfL (bvFTD r = 0.706, p < 0.0001;AD/MCI r = 0.666, p = 0.0003). Highest serum levels were observed in bvFTD (p < 0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006;[follow-up] r = 0.5629, p < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p < 0.0001;95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] r = 0.6624, p < 0.0001;[follow-up] r = 0.5659, p = 0.0003) but not with regional brain volumes. Conclusions As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials. Classification of evidence This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia