Search

Introduction Darier-White disease (DD) is a rare genodermatosis of dominant autosomic inheritance characterized by the keratinization of epidermis, nails and mucous membrane. It leads to the formation of papules and brown hyperkeratotic plaques, mainly in seborrheic areas. The disease is associated with a mutation on the ATP2A2 gene, mapped in the 12q23-24 chromosome. There is known a relationship between DD and neuropsychiatric diseases, such as bipolar disorder, depression and schizophrenia. Objectives To discuss the relationship between DD and neuropshychiatric disorders. Methods We report the case of a patient with diagnosed schizophrenia, alcohol and cannabis dependence who presented skin lesions. Results The physical exploration of our patient revealed cutaneous lesions and we pointed the diagnostic towards DD. Afterwards, a cross-consultation was done with the dermatology experts. During the physical exploration, the patient shows confluent hyperkeratotic papules, dominant on the sides and center of back and hands, together with nail injuries (see images). The diagnostic was confirmed through anatomic pathology. The patient was treated with 10 mg/day of Acitretin together with emollients twice a day, which improved the patient clinical status and signs. The patient remained stable at a psychiatric standpoint. After 3 years of treatment, the patient keeps the same medication but with a reduced dose of 5 mg/day, with a 70% decrease of the initial hyperkeratotic lesions. Conclusions Previous studies concludes that mutations in the ATP2A2 gene, in addition to causing DD, confer susceptibility to neuropsychiatric features.These case report highlight the need for clinicians to asses and recognize neuropsychiatric symptoms in DD. Disclosure No significant relationships.

Introduction Clozapine is the most effective antipsychotic for treatment resistant schizophrenia but adverse reactions to clozapine include neutropenia. Patients with COVID-19 infection frequently experience lymphopenia, but not neutropenia.The impact of clozapine treatment in the presence of COVID-19 is unknown Objectives Show 2 cases of neutropenia in patients treated with long-term clozapine during COVID-19 infection. Methods Subjects: 48 admitted patients to a long-stay psychiatric unit. COVID-19 infection confirmed by positive nasopharyngeal swab for viral ribonucleic acid of SARS-CoV-2. Hematological controls between March and April 2020. Results 16 patients (33%) treated with clozapine.18 patients (37’5%) had COVID-19 infection, of which 5 (10’4%) were treated with clozapine; 2 presented neutropenia. 1- 56-year-old woman diagnosed with schizophrenia on clozapine since 2009. Begins to have a dry cough and fever with positive COVID-19 swab (day 0). Slight leukopenia without neutropenia was observed on day 1. On day 7, neutropenia was observed with an absolute neutrophil count (ANC) of 1100. We decided to suspend clozapine and to initiate daily hematological controls. The ANC on day 8 was 970. Over the next few days the ANC will progressively improve until neutropenia resolved (day 22). 2- 55-year-old woman who required a transfer to a general hospital because of respiratory complications from COVID-19. She presented significant leukopenia (1’01x 10^3/uL) and neutropenia (ANC 100). Clozapine was not withdrawn. She was treated with granulocyte colony-stimulating factor. Conclusions An urgent full blood count will be required to exclude neutropenia with appropriate action. Further research will be needed to clarify the possible relationship between COVID-19, clozapine and neutropenia. Disclosure No significant relationships.

Introduction Clozapine is the most effective antipsychotic for treatment resistant schizophrenia. In patients treated with clozapine, COVID-19 infection may result in complications including an increased risk of pneumonia, clozapine toxicity, and disruption to clozapine treatment by COVID-19 induced lymphopenia. Objectives We report 5 cases of elevated clozapine levels occurring in patients with COVID-19 infection who had been previously managed for several years on stable doses. Methods Subjects: 48 admitted patients to a long-stay psychiatric unit. COVID-19 infection confirmed by positive nasopharyngeal swab for viral ribonucleic acid of SARS-CoV-2. Hematological controls between March and April 2020. Results 16 patients (33%) treated with clozapine.18 patients (37’5%) had COVID-19 infection, of which 5 (10’4%) were treated with clozapine. Results are presented in table 1. Increases in plasma clozapine levels were observed in all cases (49’38 to 307.5%). We don’t have the clozapine levels of a patient who presented a pneumonia requiring admission and treatment in the general hospital. Two cases of neutropenia were observed, of which one had to discontinue treatment with clozapine. In the other three patients the dose of clozapine was reduced and they did not present haematological or intoxication complications that required further adjustments. Conclusions Covid-19 infection is associated with increased serum clozapine levels by probably multifactorial mechanisms (systemic infection, reduced smoking). Importance of full clinical assessment of suspected COVID-19 infection in clozapine treated patients, including assessment clozapine level, and full blood count. The general recommendation is to reduce the dose of clozapine in this patients.

Introduction Horticultural therapy is a professional practice that is increasingly used in a lot of mental health rehabilitation programs. This therapy was introduced in the Comunitary Rehabilitation Service of INAD, considering its beneficial results in patients with severe mental disorder in combination with the usual rehabilitation program. Objectives We would like to study the benefits of this therapy compared to the usual in our patients. Methods This is an explanatory study for the purpose of establishing the association between the application of a Therapeutic Horticulture Program and the Clinical Symptomatology of Schizophrenia. A research with an experimental design Pre and Post-Test was carried out, by applying a Horticulture Program and evaluating with PANSS after 6 months its effects on the Clinical Symptomatology. The participants of the experimental group were selectively chosen. The only selection criteria were to attend the orchard at least once a week and be diagnosed with a schizophrenic disorder. The control group was chosen according to the number of members that made up the other group, with the criterion that they did not perform any outdoor activities and also had a diagnosis of schizophrenia. Results The comparison of the Pre and Post-Test measures in the case of the experimental group reports the presence of statistically significant differences in the scale of positive symptomatology composite scale and general scale. Conclusions This psychopathological improvement of those participants open a door to possible applications of this therapy as a psychosocial treatment.

This paper includes part of the ethnobotanical work carried out in the Alt Emporda region (Catalonia, Iberian Peninsula), in which the compilation of medicinal plants in popular therapeutics and folk food plants in traditional diets have been the outstanding objectives. We report here a total of 211 food plants, both wild and cultivated, used for human alimentation in the study area. From these species, there are 13 which have no previous references in the bibliography consulted. These species are mainly used to prepare a house-made drink very common among our informants called 'ratafia'. Several of these edible plants are also referred as medicinal for local people, so they could be classified as nutraceuticals or food medicines. A significant number of other most commonly reported species also have this double use, as food and medicinal. A great proportion of the alimentary plants reported are wild or minor crops. Some of these plants are used quite frequently. being normal in the diet, and they are prepared with the same variation of methods as common crops.

In this letter an experimental method is introduced that allows detection of terahertz (THz) radiation from arrays of joule-heated Single-Walled Carbon Nanotubes (SWCNTs), by coupling this radiation through integrated antennas and a silicon lens. The radiation forms a diffraction-limited beam with a total maximum radiated power of 450 nW, significantly greater than the power estimated from Nyquist thermal noise (8 nW). The physical radiation process is unknown at this stage, but possible explanations for the high radiated power are discussed briefly. The emission has a typical bandwidth of 1.2 THz and can be tuned to different frequencies by changing the dimensions of the antennas. Arrays of the devices could be integrated in CMOS integrated circuits, and find application in THz systems, such as in near-range medical imaging.

Ethnopharmacological Relevance: The discovery of the antimalarial agent artemisinin is considered one of the most significant success stories of ethnopharmacological research in recent times. The isolation of artemisinin was inspired by the use of Artemisia annua in traditional Chinese medicine (TCM) and was awarded a Nobel Prize in 2015. Antimalarial activity has since been demonstrated for a range of other Artemisia species, suggesting that the genus could provide alternative sources of antimalarial treatments. Given the stunning diversity of the genus (c. 500 species), a prioritisation of taxa to be investigated for their likely antimalarial properties is required., Materials and Methods: Here we use a phylogenetic approach to explore the potential for identifying species more likely to possess antimalarial properties. Ethnobotanical data from literature reports is recorded for 117 species. Subsequent phylogenetically informed analysis was used to identify lineages in which there is an overrepresentation of species used to treat malarial symptoms, and which could therefore be high priority for further investigation of antimalarial activity., Results: We show that these lineages indeed include several species with documented antimalarial activity. To further inform our approach, we use LC-MS/MS analysis to explore artemisinin content in fifteen species from both highlighted and not highlighted lineages. We detected artemisinin in nine species, in eight of them for the first time, doubling the number of Artemisia taxa known to content this molecule., Conclusions: Our findings indicate that artemisinin may be widespread across the genus, providing an accessible local resource outside the distribution area of Artemisia annua., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Malaria is caused by Plasmodium parasites that proliferate in the bloodstream. During each replication cycle, some parasites differentiate into gametocytes, the only forms able to infect the mosquito vector and transmit malaria. Sexual commitment is triggered by activation of AP2-G, the master transcriptional regulator of gametocytogenesis. Heterochromatin protein 1 (HP1)-dependent silencing of ap2-g prevents sexual conversion in proliferating parasites. In this study, we identified Plasmodium falciparum gametocyte development 1 (GDV1) as an upstream activator of sexual commitment. We found that GDV1 targeted heterochromatin and triggered HP1 eviction, thus derepressing ap2-g Expression of GDV1 was responsive to environmental triggers of sexual conversion and controlled via a gdv1 antisense RNA. Hence, GDV1 appears to act as an effector protein that induces sexual differentiation by antagonizing HP1-dependent gene silencing., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

DNA methylation is an essential epigenetic modification for mammalian development and is crucial for the establishment and maintenance of cellular identity. Traditionally, DNA methylation has been considered as a permanent repressive epigenetic mark. However, the application of genome-wide approaches has allowed the analysis of DNA methylation in different genomic contexts, revealing a more dynamic regulation than originally thought, as active DNA methylation and demethylation occur during cell fate commitment and terminal differentiation. Recent data provide insights into the contribution of different epigenetic factors, and DNA methylation in particular, to the establishment of cellular memory during embryonic development and the modulation of cell type-specific gene regulation programs to ensure proper differentiation. This review summarizes published data regarding DNA methylation changes along lineage specification and differentiation programs. We also discuss the current knowledge about DNA methylation alterations occurring in physiological and pathological conditions such as aging and cancer., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Ethnobotanical academic research, particularly in European industrialised countries, has been, and is, mostly focused on folk uses of food and medicinal plants. Nevertheless, other uses, as may well be supposed, account for a significant portion of these folk uses. In the Catalan linguistic domain, a considerable amount of ethnobotanical work has been produced, but to date almost nothing has been published on these other plant uses., Methods: We basically used the method of semistructured interviews to collect data on names, knowledge and use of plants in the above-mentioned fields from 759 informants in three Catalonian (Alt Empordà, Montseny and Ripollès) and two Balearic (Formentera and Mallorca) areas. We identified the plants quoted by the informants and prepared herbarium vouchers. We analysed and compared the results obtained., Results: Information has been collected on 401 genera, 552 species, 81 subspecies and four varieties, belonging to 122 families, totalling 4137 use reports for popular non-food and non-medicinal uses (classified in 14 modalities), and designated with 1303 folk Catalan names. The informant consensus factor is 0.87, accounting for a consistent and robust dataset., Conclusion: Contrarily to what could be thought a priori, and irrespective of the fact that some uses are declining or changing, non-medicinal and non-food folk plant uses strongly persist in the territories considered, are highly considered by their practitioners, and may even imply some economic revenues.

Background: Skeletal muscle stem cells enable the formation, growth, maintenance, and regeneration of skeletal muscle throughout life. The regeneration process is compromised in several pathological conditions, and muscle progenitors derived from pluripotent stem cells have been suggested as a potential therapeutic source for tissue replacement. DNA methylation is an important epigenetic mechanism in the setting and maintenance of cellular identity, but its role in stem cell determination towards the myogenic lineage is unknown. Here we addressed the DNA methylation dynamics of the major genes orchestrating the myogenic determination and differentiation programs in embryonic stem (ES) cells, their Pax7-induced myogenic derivatives, and muscle stem cells in proliferating and differentiating conditions., Results: Our data showed a common muscle-specific DNA demethylation signature required to acquire and maintain the muscle-cell identity. This specific-DNA demethylation is Pax7-mediated, and it is a prime event in muscle stem cells gene activation. Notably, downregulation of the demethylation-related enzyme Apobec2 in ES-derived myogenic precursors reduced myogenin-associated DNA demethylation and dramatically impaired the expression of differentiation markers and, ultimately, muscle differentiation., Conclusions: Our results underscore DNA demethylation as a key mechanism driving myogenesis and identify specific Pax7-mediated DNA demethylation signatures to acquire and maintain the muscle-cell identity. Additionally, we provide a panel of epigenetic markers for the efficient and safe generation of ES- and induced pluripotent stem cell (iPS)-derived myogenic progenitors for therapeutic applications.

The progressive restriction of differentiation potential from pluripotent embryonic stem cells (ESCs) to tissue-specific stem cells involves widespread epigenetic reprogramming, including modulation of DNA methylation patterns. Skeletal muscle stem cells are required for the growth, maintenance, and regeneration of skeletal muscle. To investigate the contribution of DNA methylation to the establishment of the myogenic program, we analyzed ESCs, skeletal muscle stem cells in proliferating (myoblasts) and differentiating conditions (myotubes), and mature myofibers. About 1.000 differentially methylated regions were identified during muscle-lineage determination and terminal differentiation, mainly located in gene bodies and intergenic regions. As a whole, myogenic stem cells showed a gain of DNA methylation, while muscle differentiation was accompanied by loss of DNA methylation in CpG-poor regions. Notably, the hypomethylated regions in myogenic stem cells were neighbored by enhancer-type chromatin, suggesting the involvement of DNA methylation in the regulation of cell-type specific enhancers. Interestingly, we demonstrated the hypomethylation of the muscle cell-identity Myf5 super-enhancer only in muscle cells. Furthermore, we observed that upstream stimulatory factor 1 binding to Myf5 super-enhancer occurs upon DNA demethylation in myogenic stem cells. Taken altogether, we characterized the unique DNA methylation signature of skeletal muscle stem cells and highlighted the importance of DNA methylation-mediated regulation of cell identity Myf5 super-enhancer during cellular differentiation., (© 2015 AlphaMed Press.)

DNA methylation is an essential epigenetic modification for mammalian development and is crucial for the establishment and maintenance of cellular identity. Traditionally, DNA methylation has been considered as a permanent repressive epigenetic mark. However, the application of genome-wide approaches has allowed the analysis of DNA methylation in different genomic contexts revealing a more dynamic regulation than originally thought, since active DNA methylation and demethylation occur during cellular differentiation and tissue specification. Satellite cells are the primary stem cells in adult skeletal muscle and are responsible for postnatal muscle growth, hypertrophy, and muscle regeneration. This review outlines the published data regarding DNA methylation changes along the skeletal muscle program, in both physiological and pathological conditions, to better understand the epigenetic mechanisms that control myogenesis.

Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional genetic mouse models of aRMS to activate the pathognomonic Pax3:Foxo1 fusion oncogene and inactivate p53 in several stages of prenatal and postnatal muscle development. We reveal that lineage of origin significantly influences tumor histomorphology and sensitivity to targeted therapeutics. Furthermore, we uncovered differential transcriptional regulation of the Pax3:Foxo1 locus by tumor lineage of origin, which led us to identify the histone deacetylase inhibitor entinostat as a pharmacological agent for the potential conversion of Pax3:Foxo1-positive aRMS to a state akin to fusion-negative RMS through direct transcriptional suppression of Pax3:Foxo1., (© 2014 Abraham et al.; Published by Cold Spring Harbor Laboratory Press.)

Although a variety of methods have been optimized for the collection and storage of plant specimens, most of these are not suited for field expeditions for a variety of logistic reasons. Drying specimens with silica gel in polyethylene bags is currently the standard for field-sampling methods that are suitable for subsequent DNA extraction. However, silica-gel repositories are not readily available in remote areas, and its use is not very cost-effective for the long-term storage of collections or in developing countries with limited research budgets. Salting is an ancient and traditional drying process that preserves food samples by dehydrating tissues and inhibiting water-dependent cellular metabolism. We compared salt and silica-gel drying methods with respect to dehydration rates overtime, DNA quality and polymerase chain reaction(PCR) success to assess whether dry salting can be used as an effective plant preservation method for DNA analysis. Specimens from eleven plant species covering a variety of leaf structures, leaf thicknesses and water contents were analysed. Experimental work indicated that (i) levels of dehydration in sodium chloride were usually comparable to those obtained when silica gel was used, (ii) no spoilage, fungal or bacterial growth was observed for any of the species with all drying treatments and (iii) good yields of quality genomic DNA suitable for PCR applications were obtained in the salt-drying treatments. The preservation of plant tissues in commercial table salt appears to be a satisfactory, and versatile method that may be suitable in remote areas where cryogenic resources and silica repositories are not available., (© 2013 John Wiley & Sons Ltd.)

Knowledge about mixed mating systems can improve our understanding of the evolutionary dynamics of reproductive systems. Here we report a study of the pollination system (floral and reproductive biology, pollen limitation and stigmatic pollen load, floral visitors and inbreeding depression) of Fumana hispidula, a Mediterranean subshrub belonging to a species group with a strong selfing tendency. Autonomous self-pollination, hand self- and hand cross-pollination, open pollination and controls yielded fruits (0.28, 0.65, 0.68, 0.38, and 0.67, respectively); however, autonomous self-pollination resulted in the lowest fruit set. All individuals were fully self-compatible but we found great inter-individual variation in autonomous self-pollination ability, which was probably related to a variable expression of herkogamy degree. Inbreeding depression was low (0.040 for fruit set, 0.015 for seed set and -0.026 for seed mass). The pollen supplementation experiment did not reveal pollen limitation and pollinators were seen visiting the flowers during the observation periods. These results support the idea that F. hispidula has a mixed mating strategy, which represents a successful reproduction mode in their patchy habitats.

In this communication, we provide some basic methodological and practical ideas for plant knowledge comparisons among different predefined natural regions of the Mediterranean island of Mallorca, in the frame of an ongoing project in this area. The final goal of this work is to present a tool to find out to what extent plant knowledge is similar in the different regions. We use an uncommon approach to ethnobotanical studies in terms of multidisciplinary methodology. We base our arguments on social anthropology methods, using a diversity index (the Sorensen similarity coefficient), and we also explain the botanical part of the investigation. Our preliminary results reveal few differences among the three natural regions considered on the island, which we believe could find their explanation in geographic, botanical and cultural aspects.

Ethnopharmacological Relevance: This paper represents the first large-scale ethnobotanical study in the island of Mallorca, and provides significant information on pharmaceutical plant uses, built up from interviews with native people from this touristic hotspot, demonstrating its ethnopharmacological importance., Aim of the Study: To collect, analyse and evaluate the ethnobotanical knowledge concerning medicinal plants in a north-eastern Mallorcan area (municipalities of Artà, Capdepera and Son Servera; 298 km2, 31,764 inhabitants)., Materials and Methods: We performed semi-structured interviews with 42 informants (mean age 77; 40% women, 60% men), identified the plant taxa reported and analysed the results, comparing them with those found in the current Mallorcan ethnobotanical information and in other territories., Results: The informants reported data on 121 human medicinal plants representing 64 botanical families. Around 45 medicinal uses reported, concerning 37 species, have not or have very rarely been cited as medicinal. An index of medicinal importance is proposed., Conclusions: All efforts addressed to compiling ethnobotanical information in industrialised or touristised areas such as Eastern Mallorca are still valuable. New possibilities can be explored to give practical value to Mallorcan ethnobotanical data in the frame of considering traditional plant knowledge as part of the islanders’ lifestyle and healthy habits.

This paper presents the results of an ethnobotanical study centred in veterinarian uses in two Catalan Pyrenean regions (Alt Empordà -AE- and High River Ter Valley -AT-, Iberian peninsula) and two Balearic Islands areas (Formentera -FO- and northeastern Mallorca -MA-). In the areas studied, 97 plant species have been claimed to be useful for veterinary purposes. A total of 306 veterinary use reports have been gathered and analysed. The ten most reported plants are Tanacetum parthenium (24 use reports), Parietaria officinalis (15), Ranunculus parnassifolius (14), Meum athamanticum (13), Olea europaea (13), Quercus ilex (12), Ruta chalepensis (12), Sambucus nigra (10) and Thymus vulgaris (10). According to comprehensive reviews, a high number of novelties for plant ethnoveterinary are contributed: 34 species and one subspecies, 11 genera, and three families have not been reported in previous works in this field, and 21 species had only been mentioned once. Several ethnoveterinary uses are coincidental with those in human medicine. Although ethnoveterinary practices are less relevant than in the past in the territories considered, as in all industrialised countries, the knowledge on plant properties and applications is still rich and constitutes a large pool of evidence for phytotherapy, both in domestic animals and humans.

Ethnopharmacological Relevance: This paper provides significant ethnobotanical information on pharmaceutical plant uses from a tourist and industrialised region, where some degree of acculturation exists, so that there is urgency in recording such data., Aim of the Study: To collect, analyze and evaluate the ethnobotanical knowledge about medicinal plants in a north-eastern Iberian region (Alt Empordà, 1358 km(2), 129,160 inhabitants)., Methodology: We performed 101 semi-structured interviews with 178 informants (mean age 69; 71% women, 29% men), identified the plant taxa reported and analyzed the results, comparing them with those from other territories., Results: The informants reported data on 518 species. Of these, 335, belonging to 80 botanical families, were claimed as medicinal. This work is focused on human medicinal plant uses, which represent 98% of the pharmaceutical uses (3581 out of 3643 use reports). Around 800 medicinal uses, concerning 200 species, have not, or have very rarely been cited as medicinal; of these, 32 uses of 30 species have been reported by three or more independent informants., Conclusions: The folk knowledge about medicinal plant use is still alive in the studied region, and a number of scarcely reported plant uses has been detected, some of them with promising phytotherapeutical applications.