Molecular identification of the invasive subterranean termite Reticulitermes grassei (Blattodea: Rhinotermitidae) outside its known distribution: introduction routes and implications for pest management strategies.

Despite providing important ecosystem services, termites are also serious pests of wooden structures. Termites are highly adaptive organisms that cause concern as an invasive species. Predictions of the future spread of their distribution range due to factors such as climate change, urban growth, and global trade present new challenges to our capacity to protect our wood and wood-based materials and structures effectively. Reticulitermes grassei Clément, 1978 (Blattodea: Rhinotermitidae) is a subterranean termite native to the Iberian Peninsula and France, whose global distribution has widened over recent years. This article updates the distribution range of this species, confirming its identification in the Azores, Madeira, and Morocco through molecular analysis. The origin and consequences of these putative invasive populations are discussed in light of previously available data. The resulting network showed a highly structured base consisting of many haplotypes from the southern and southwestern Iberian Peninsula (Spain and Portugal), including those from Morocco (in natural landscapes) and Switzerland (in infrastructures). The more derived part of the network includes the haplotypes from southwest France, the northwest Iberian Peninsula, the United Kingdom, Azores, and Madeira, the last 3 being linked probably to human-mediated transportation events. The potential impacts of invasive subterranean termite populations expanding into new regions are concerning, especially in urban environments, and remain uncertain in natural areas. The challenges posed by these termites could be especially worrying in island ecosystems. Hence, it is crucial to implement early warning systems and monitoring programs in regions susceptible to subterranean termite invasions.

Graft-derived neurons and bystander effects are maintained for six months after human iPSC-derived NESC transplantation in mice's cerebella.

Machado-Joseph disease (MJD) is a neurodegenerative disorder characterized by widespread neuronal death affecting the cerebellum. Cell therapy can trigger neuronal replacement and neuroprotection through bystander effects providing a therapeutic option for neurodegenerative diseases. Here, human control (CNT) and MJD iPSC-derived neuroepithelial stem cells (NESC) were established and tested for their therapeutic potential. Cells' neuroectodermal phenotype was demonstrated. Brain organoids obtained from the Control NESC showed higher mRNA levels of genes related to stem cells' bystander effects, such as BDNF, NEUROD1, and NOTCH1, as compared with organoids produced from MJD NESC, suggesting that Control NESC have a higher therapeutic potential. Graft-derived glia and neurons, such as cells positive for markers of cerebellar neurons, were detected six months after NESC transplantation in mice cerebella. The graft-derived neurons established excitatory and inhibitory synapses in the host cerebella, although CNT neurons exhibited higher excitatory synapse numbers compared with MJD neurons. Cell grafts, mainly CNT NESC, sustained the bystander effects through modulation of inflammatory interleukins (IL1B and IL10), neurotrophic factors (NGF), and neurogenesis-related proteins (Msi1 and NeuroD1), for six months in the mice cerebella. Altogether this study demonstrates the long-lasting therapeutic potential of human iPSC-derived NESC in the cerebellum.

Anaphylactic Shock After Cervical Conization Hemostasis With a Packing Soaked in Monsel's Solution.

Anaphylactic shock is a life-threatening medical emergency, and its successful approach depends on early recognition and treatment. We present a case report of a 54-year-old female, with the American Society of Anesthesiology (ASA) Physical Status Classification III, admitted for cervical conization. She presented with known allergies to paracetamol, diclofenac, and nimesulide, and a history of nickel contact dermatitis, with no reports of complicated anesthesia. During conization, adrenaline was infiltrated in the cervix, and hemostasis was performed with packing soaked in Monsel's solution. The immediate postoperative period in the post-anesthesia care unit was uneventful, and no drugs were administered during this period. Three hours after discharge to the ward, the patient had progressive dyspnea with desaturation and maculopapular exanthema. Anesthesia medical emergency was activated. Upon arrival of the emergency team, the patient presented: marked edema of the lips and tongue, respiratory distress, SpO2 82% (under non-rebreathing high concentration oxygen mask), audible vesicular murmur but diminished in all lung fields (without bronchospasm), blood pressure of 60/40 mmHg, increased capillary refill time (4-5 seconds), Glasgow Coma Scale score of 14, as well as generalized maculopapular exanthema and eyelid edema. Gas analysis revealed the following: pH 7.36, pO2 150, pCO2 33, HCO3 22, and lactate 2.2 mmol/L. Anaphylactic shock was immediately diagnosed without an identified causative agent. Intramuscular adrenaline (0.5mg), endovenous hydrocortisone (200 mg), clemastine (2 mg), and profuse fluid therapy were administered. There was an initial slight improvement followed by subsequent worsening. Additional administration of 0.5 mg intramuscular adrenaline and endovenous methylprednisolone (125 mg) provided similar results. Considering that no other drugs were administered in the ward, the emergency team and the attending gynecologist assumed an association between nickel allergy and the chemical composition of Monsel's solute. Thus, it was decided to remove the packing soaked in Monsel's solute from the vaginal cavity and wash it with saline solution. After removing the packing and further administration of 0.5 mg intramuscular adrenaline, there was progressive improvement in the blood pressure and SpO2. Tryptase samples collected one hour later were increased (23.9 ug/L; normal: <11.4 ug/L). The patient was shifted to the intensive care unit for surveillance, from which she was discharged after 2 days, with scheduled immunoallergology consultation, which is waiting. This case highlights the importance of causative agent identification as a key point for anaphylactic shock resolution, as well as a multidisciplinary discussion among professionals.

When the Conception of Symmetry Deceives Us: A Case Report on the Perioperative Diagnosis of Subclavian Artery Stenosis.

Subclavian artery stenosis is a relatively uncommon manifestation of peripheral artery disease with significant morbidity. We describe a case of left subclavian artery stenosis that became apparent in the intraoperative setting, in a patient who presented for emergency surgery after a fall and subsequent left femoral neck fracture. Initial non-invasive blood pressure readings on the left upper extremity were in the normal range but after placement of the arterial line on the right upper extremity, the discrepancy was evident pointing towards a structural abnormality as the causative factor. CT angiography was found to confirm the diagnosis of left subclavian artery stenosis of an atherosclerotic nature. A thorough physical examination can point to the presence of subclavian stenosis through pulse amplitude and blood pressure asymmetries. This study highlights the importance of obtaining blood pressure readings ideally on all four limbs to avoid misinterpretation of blood pressure values that could ultimately lead to the use of unnecessary and inadequate interventions and possible complications in the perioperative setting.

Quality of Sexuality during Pregnancy, We Must Do Something-Survey Study.

BACKGROUND: The main aim of this study was to describe the changes in sexual desire in pregnant women during the gestation period. We also sought to analyze their sexual habits, how they perceive their partners' attitudes, and determine if they know the importance of sex education during pregnancy. METHODS: A cross-sectional descriptive observational study was conducted using an existing 32-item questionnaire among pregnant women attending the Fetal Welfare Clinic of a reference hospital. Univariate and bivariate analyses were performed. RESULTS: One hundred seventeen women participated. 50.4% stated that their sexual interest decreased. Aspects like the number of coitus, feeling orgasm with penetration or with masturbation, or the frequency of oral sex, were significantly reduced during pregnancy. 90.6% of the women stated that they would like to receive more sex education during pregnancy. There were no differences according to their education level, their partners' education level, or whether they believed that sexual intercourse could harm the baby. CONCLUSIONS: Several advances have been achieved in the healthcare that physicians and midwives provide pregnant women. However, the quality of women's sex lives still declines during pregnancy. Healthcare providers should assume a proactive role, essential in helping future parents to enjoy their sexuality and dispel myths about sexuality, regardless of their education level.

Using QR Codes as a Form of eHealth to Promote Health Among Women in a Pandemic: Cross-sectional Study.

BACKGROUND: QR codes have played an integral role during the pandemic in many sectors, but their use has been limited in the health care sector, especially by patients. Although some authors have stated that developing specific content for women on how to cope with health problems could be an effective way to prevent problems, especially during pandemics, there is little research regarding the use of QR codes to promote health during a pandemic, and even fewer studies are focused on women. Moreover, although the importance of assessing these interventions from the users' perspective has been stated, research carried out from this point of view is still scarce. OBJECTIVE: This study aimed to assess the usefulness of using QR codes with information to promote women's health in the context of a pandemic. We also sought to design and validate a questionnaire to assess this. METHODS: A cross-sectional study was conducted among women in the gynecology waiting rooms of a reference hospital. Exploratory factorial analysis with the split-half method and Cronbach α values was performed for questionnaire validation. Univariant and bivariant analyses were performed to analyze the data obtained. RESULTS: In total, 186 women took part in the study. Exploratory factor analysis identified 2 domains: usability and applicability in medical practice. The Cronbach α value was .81. Overall, 83.7% of the answers to the first domain and 56.4% of those to the second were favorable. Women with university education or those who had used QR codes before scored better in the usability domain, while no differences were observed in the applicability scores. CONCLUSIONS: Using QR codes in the gynecology clinics' waiting rooms can help promote women's health during a pandemic, regardless of their education level or whether they have used QR codes before. The questionnaire developed herein is a helpful tool to assess this. These findings are important for clinical practice. This research can be performed in other ambits, specialties, or countries.

Antifungal Activity of Benzoquinones Produced by Tribolium castaneum in Maize-Associated Fungi.

Tribolium castaneum (Herbst) adults produce 1,4-benzoquinone (BQ), methyl-1,4-benzoquinone (MBQ), and ethyl-1,4-benzoquinone (EBQ). These components are chemical defenses used as repellents and irritants, and BQ has a negative impact on the growth of some fungal species. In this work, the inhibitory and/or lethal effects of these benzoquinones on the development of six fungi identified in maize, namely Aspergillus flavus, A. fumigatus, A. niger, Fusarium sp., Penicillium sp., and Trichoderma sp., were evaluated. Ten-day-long disk diffusion trials were performed using benzoquinones. The experiments simulated the activity of BQ (B1) or "EBQ + MBQ" (B2) released by 40-day-old insect adults (n = 200), considering a total average release of 45 µg per adult. Inhibition halos imposed by benzoquinones on fungal growth showed a significant effect when compared with the controls (water and solvent). Mycelial growth was decreased for all fungi, with the level of response depending on the fungal species. B1 and B2 displayed an inhibitory effect against all fungi, but Trichoderma sp. and A. niger showed rapid recoveries. B2 showed a lethal effect on Penicillium sp. The inhibitory and lethal activities of benzoquinones released by T. castaneum adults may contribute to regulate fungal growth, and understanding their interaction is important to develop innovative control strategies.

miRNA-Mediated Knockdown of ATXN3 Alleviates Molecular Disease Hallmarks in a Mouse Model for Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by the expansion of a CAG repeat in the ATXN3 gene. This mutation leads to a toxic gain of function of the ataxin-3 protein, resulting in neuronal dysfunction and atrophy of specific brain regions over time. As ataxin-3 is a dispensable protein in rodents, ataxin-3 knockdown by gene therapy may be a powerful approach for the treatment of SCA3. In this study, we tested the feasibility of an adeno-associated viral (AAV) vector carrying a previously described artificial microRNA against ATXN3 in a striatal mouse model of SCA3. Striatal injection of the AAV resulted in good distribution throughout the striatum, with strong dose-dependent ataxin-3 knockdown. The hallmark intracellular ataxin-3 inclusions were almost completely alleviated by the microRNA-induced ATXN3 knockdown. In addition, the striatal lesion of dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) in the SCA3 mice was rescued by ATXN3 knockdown, indicating functional rescue of neuronal signaling and health upon AAV treatment. Together, these data suggest that microRNA-induced ataxin-3 knockdown is a promising therapeutic strategy in the treatment of SCA3.

Profile of the Users and the Most Visited Topics of a Pediatric eHealth Website.

Parents need information about their children's health, and the Internet has become an essential repository for this information. However, there is almost no information about which topics are the most searched, consulted, or shared, or about the main characteristics of pediatric website users. The main aim of this research was to describe the profile of the users of a pediatric website, which topics they searched for, which topics were the most consulted, and which were the most shared. Users' demographic data were analyzed regarding their use of the Internet to search for information about health. A pediatric website for parents was analyzed. A 26-item questionnaire collected demographical features of the users of the website. Descriptive and analytical analyses were performed. Most participants used general search engines for their health searches, and the most searched keywords were prurigo, barking cough, and laryngitis. The most visited topics were unexplained fever, snots, and laryngitis. The most shared were snots, lipotomy, and dizziness. The users were mainly women (67.8%), with an average age of 38.8 years, and one or two children (89%) with a mean age of 4.6 years. The users who mainly used the Internet for health purposes were women of younger age, and with a higher educational level.

Users evaluation of a Spanish eHealth pediatric website.

BACKGROUND: Parents use the Internet to take decisions about their children's health, but few resources have focused on eHealth technology evaluations from their point of view. OBJECTIVE: The main aim of this research was to evaluate a Spanish eHealth pediatric website for parents. METHODS: A previously validated web questionnaire was used to evaluate five domains: usability, utility, trust and confidence, well-child section and accessibility of the website. Univariate, bivariate and multiple linear regression analyses were performed. RESULTS: 516 users participated in the research and rated the website as usable, useful, trustworthy and accessible. Higher scores were given by the participants who relied most on the Internet for taking decisions about health; by the participants who used a smartphone to access the pediatric website; by the participants who knew the website the longest; and by the participants who had accessed it more times. No differences in the evaluations of the website were found regarding age, education level or household income of the participants. CONCLUSIONS: eHealth pediatric websites, written by a pediatrician in an easy to understand language, can be perceived as usable, trustworthy, useful and accessible by their users and consequently help them with their decisions making. Some characteristics of the users are associated with a better perception of these websites.

The Interaction between Tribolium castaneum and Mycotoxigenic Aspergillus flavus in Maize Flour.

Tribolium castaneum is one of the most common insect pests of stored products. Its presence makes cereals more susceptible to the spread of the fungi Aspergillus flavus, which may produce mycotoxins. The aim of this work was to evaluate the influence of T. castaneum adults on the development of a mycotoxigenic A. flavus strain in maize flour as well as the influence of this fungus on the insects. Maize flour was exposed to T. castaneum, spores of A. flavus or to both. The results revealed an interaction between T. castaneum and A. flavus as the flour exposed to both organisms was totally colonized by the fungus whereas almost all the insects were killed. Aflatoxin B1 (AFB1) revealed a significantly higher concentration in the flour inoculated with both organisms (18.8 µg/kg), being lower when exposed only to A. flavus, suggesting that the presence of insects may trigger fungal development and enhance mycotoxin production. The ability of these organisms to thrive under the same conditions and the chemical compounds they release makes the interaction between them a subject of great importance to maintain the safety of stored maize. This is the first work evaluating the interaction between T. castaneum and A. flavus mycotoxin production.

Influence of Zwitterionic Buffer Effects with Thermal Modification Treatments of Wood on Symbiotic Protists in Reticulitermes grassei Clément.

The majority of thermal modification processes are at temperatures greater than 180 °C, resulting in a product with some properties enhanced and some diminished (e.g., mechanical properties). However, the durability of thermally modified wood to termite attack is recognised as low. Recent attempts at combining thermal modification with chemical modification, either prior to or directly after the thermal process, are promising. Buffers, although not influencing the reaction systems, may interact on exposure to certain conditions, potentially acting as promoters of biological changes. In this study, two zwitterionic buffers, bicine and tricine, chosen for their potential to form Maillard-type products with fragmented hemicelluloses/volatiles, were assessed with and without thermal modification for two wood species (spruce and beech), with subsequent evaluation of their effect against subterranean termites (Reticulitermes grassei Clément) and their symbiotic protists. The effect of the wood treatments on termites and their symbionts was visible after four weeks, especially for spruce treated with tricine and bicine and heat treatment (bicine HT), and for beech treated with bicine and bicine and heat treatment (bicine HT). The chemical behaviour of these substances should be further investigated when in contact with wood and also after heat treatment. This is the first study evaluating the effect of potential Maillard reactions with zwitterionic buffers on subterranean termite symbiotic fauna.

Coste y ahorro potencial generado por una web de eSalud de pediatría para padres / Cost and potential savings generated by a paediatrics e-Health web site for parents

INTRODUCCIÓN: Son pocas las intervenciones de eSalud dirigidas a padres que analizan sus costes y el ahorro potencial que pueden generar. Los objetivos de este trabajo consistieron en calcular los costes de desarrollo y mantenimiento de una web de pediatría para padres, el coste por visita y por visitante, y el ahorro potencial generado en función de las visitas médicas evitadas como consecuencia de su uso. MÉTODOS: Para los costes de la web se consideraron los costes tecnológicos y del trabajo de los profesionales. El cálculo del coste de los profesionales y de ahorro potencial se basó en los honorarios oficiales y en los precios públicos del Sistema Sanitario Público de Andalucía. RESULTADOS: Durante los 5 años y 6 meses del estudio el coste total de la web fue de 45.201,56 (Euro). El coste por visita recibida fue de 0,0155 (Euro), y por cada visitante único, de 0,0186 (Euro). Entre los 516 usuarios que participaron en el estudio se evitaron visitas presenciales a las consultas de pediatría de atención primaria y a los servicios de urgencias de pediatría por un valor de 22.263,89 (Euro). CONCLUSIONES: Los costes de desarrollo de una web de eSalud de pediatría para padres escrita en español, usando tecnología existente y gratuita, son bajos en comparación a otras formas de desarrollo de eSalud. Además, los costes son considerablemente bajos si se dividen entre el número de visitas totales o el número de visitantes. También existe un potencial considerable de ahorro económico al contribuir a evitar visitas presenciales

INTRODUCTION: There are few studies on e-Health interventions directed at parents that analyse their costs and any potential savings that may occur. The aims of this study consisted of calculating the costs of the development and maintenance of paediatric web site for parents, including the costs per visit and per visitor, and the potentially savings made as regards medical visits avoided as a result of its use. METHODS: The technology costs as well as the work of the professionals were considered as costs of the web site. The calculation of the cost of the professionals and the potential savings were based on the official fees and public prices of the Andalusian Public Health Service. RESULTS: During 5 years and 6 months of the study, the total cost of the web site was (Euro)45,201.56. The cost per visit received was (Euro) 0.0155(Euro), and (Euro) 0.0186 for each single visitor. Among the 516 users that took part in the study, face-to-face visits to Primary Care paediatric clinics were avoided, as well as those to Paediatric Emergency Department, at a savings of (Euro) 22,263.89. CONCLUSIONS: The costs of developing a paediatric e-Health website for parents written in Spanish, using existing and free technologies, are low compared to other forms of e-Health development. Furthermore, the costs are considerably low if they are divided by the total number of visits or the number of visitors. There is also a considerable potential financial saving on contributing to avoid face-to-face visits

The effects of Brazilian chitosan-based biomaterials on wound healing in rats.

The use of natural supplies is a resource to mimic an original extracellular matrix that allows for migration, proliferation, and cellular organization. Chitosan from Brazilian Atlantic Ocean had low protein, minerals percentage and excellent antibacterial activity. The aim of this study was to evaluate and to compare the effectiveness of different types of acids as solvents with Brazilian chitosan-membrane in the healing process of skin lesions. Experimental full-thickness 2 × 2 cm wounds were created on the dorsum skin of Wistar rats. The applied different treatments were saline, collagenase®, microcrystalline chitosan salt membrane (MCSM), microcrystalline chitosan acetic acid membrane (MCAAM), and microcrystalline chitosan hydrochloric acid membrane (MCHAM). The wound repairs were measured morphologically and histologically on days 0, 3, 7, 10, and 14. The exudate formation and the final wound contractions were similar in all of the groups. There were mild exudations in the groups with chitosan-membranes, despite the formation of crust under the membrane. This configured a serum hematic aspect, but there was no impact on the healing process. The MCHAM group had more favorable aspects that histologically showed the healing phases. A significant migration of neutrophils and macrophages seen by myeloperoxidade and Beta-N-Acetylglucosaminidase activities was evident in the chitosan groups, MCHAM and MCSM, respectively. Furthermore, the MCHAM group created its histological arrangement in a dense and more consistent manner.

[Cost and potential savings generated by a paediatrics e-Health web site for parents]. / Coste y ahorro potencial generado por una web de eSalud de pediatría para padres.

INTRODUCTION: There are few studies on e-Health interventions directed at parents that analyse their costs and any potential savings that may occur. The aims of this study consisted of calculating the costs of the development and maintenance of paediatric web site for parents, including the costs per visit and per visitor, and the potentially savings made as regards medical visits avoided as a result of its use. METHODS: The technology costs as well as the work of the professionals were considered as costs of the web site. The calculation of the cost of the professionals and the potential savings were based on the official fees and public prices of the Andalusian Public Health Service. RESULTS: During 5years and 6months of the study, the total cost of the web site was €45,201.56. The cost per visit received was €0.0155€, and €0.0186 for each single visitor. Among the 516 users that took part in the study, face-to-face visits to Primary Care paediatric clinics were avoided, as well as those to Paediatric Emergency Department, at a savings of €22,263.89. CONCLUSIONS: The costs of developing a paediatric e-Health website for parents written in Spanish, using existing and free technologies, are low compared to other forms of e-Health development. Furthermore, the costs are considerably low if they are divided by the total number of visits or the number of visitors. There is also a considerable potential financial saving on contributing to avoid face-to-face visits.

Risk Assessment for Tomato Fruitworm in Processing Tomato Crop-Egg Location and Sequential Sampling.

Helicoverpa armigera is one of the key pests affecting processing tomatoes and many other crops. A three-year study was conducted to describe the oviposition preferences of this species on determinate tomato plants (mainly the stratum, leaf, leaflet, and leaf side) and the spatial pattern of the eggs in the field, to form a sequential sampling plan. Eggs were found mainly in the exposed canopy, on leaves a (upper stratum) and b (upper-middle stratum) and significantly fewer eggs on leaf c (middle-lower stratum) below flower clusters. This vertical pattern in the plant was found in all phenological growth stages. The spatial pattern was found to be aggregated, with a trend towards a random pattern at lower densities. A sequential sampling plan was developed, based on Iwao's method with the parameters of Taylor's power law, with minimum and maximum sample size of 20 and 80 sample units (plants), respectively (two leaves/plant). For its validation, operating characteristic (OC) and average sample number (ASN) curves were calculated by means of simulation with independent data sets. The ß-error was higher than desirable in the vicinity of the economic threshold, but this sampling plan is regarded as an improvement both in effort and precision, compared with the fixed sample plan, and further improvements are discussed.

Validation of a Questionnaire Developed to Evaluate a Pediatric eHealth Website for Parents.

There is a need for health professionals to provide parents with not only evidence-based child health websites but also instruments to evaluate them. The main aim of this research was to develop a questionnaire for measuring users' evaluation of the usability, utility, confidence, the well-child section, and the accessibility of a Spanish pediatric eHealth website for parents. We further sought to evaluate the content validity and psychometric reliability of the instrument. A content validation study by expert review was performed, and the questionnaire was pilot tested. Psychometric analyses were used to establish scales through exploratory and confirmatory factor analyses. Reliability studies were performed using Cronbach's alpha and two split-half methods. The content validation of the questionnaire by experts was considered as excellent. The pilot web survey was completed by 516 participants. The exploratory factor analysis excluded 27 of the 41 qualitative initial items. The confirmatory factor analysis of the resultant 14-item questionnaire confirmed the five initial domains detected in the exploratory confirmatory analysis. The goodness of fit for the competing models was established through fit indices and confirmed the previously established domains. Adequate internal consistency was found for each of the subscales as well as the overall scale.

Antisense oligonucleotide therapeutics in neurodegenerative diseases: the case of polyglutamine disorders.

Polyglutamine (polyQ) disorders are a group of nine neurodegenerative diseases that share a common genetic cause, which is an expansion of CAG repeats in the coding region of the causative genes that are otherwise unrelated. The trinucleotide expansion encodes for an expanded polyQ tract in the respective proteins, resulting in toxic gain-of-function and eventually in neurodegeneration. Currently, no disease-modifying therapies are available for this group of disorders. Nevertheless, given their monogenic nature, polyQ disorders are ideal candidates for therapies that target specifically the gene transcripts. Antisense oligonucleotides (ASOs) have been under intense investigation over recent years as gene silencing tools. ASOs are small synthetic single-stranded chains of nucleic acids that target specific RNA transcripts through several mechanisms. ASOs can reduce the levels of mutant proteins by breaking down the targeted transcript, inhibit mRNA translation or alter the maturation of the pre-mRNA via splicing correction. Over the years, chemical optimization of ASO molecules has allowed significant improvement of their pharmacological properties, which has in turn made this class of therapeutics a very promising strategy to treat a variety of neurodegenerative diseases. Indeed, preclinical and clinical strategies have been developed in recent years for some polyQ disorders using ASO therapeutics. The success of ASOs in several animal models, as well as encouraging results in the clinic for Huntington's disease, points towards a promising future regarding the application of ASO-based therapies for polyQ disorders in humans, offering new opportunities to address unmet medical needs for this class of disorders. This review aims to present a brief overview of key chemical modifications, mechanisms of action and routes of administration that have been described for ASO-based therapies. Moreover, it presents a review of the most recent and relevant preclinical and clinical trials that have tested ASO therapeutics in polyQ disorders.

Repeated Mesenchymal Stromal Cell Treatment Sustainably Alleviates Machado-Joseph Disease.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3, the most common dominant spinocerebellar ataxia (SCA) worldwide, is caused by over-repetition of a CAG repeat in the ATXN3/MJD1 gene, which translates into a polyglutamine tract within the ataxin-3 protein. There is no treatment for this fatal disorder. Despite evidence of the safety and efficacy of mesenchymal stromal cells (MSCs) in delaying SCA disease progression in exploratory clinical trials, unanticipated regression of patients to the status prior to treatment makes the investigation of causes and solutions urgent and imperative. In the present study, we compared the efficacy of a single intracranial injection with repeated systemic MSC administration in alleviating the MJD phenotype of two strongly severe genetic rodent models. We found that a single MSC transplantation only produces transient effects, whereas periodic administration promotes sustained motor behavior and neuropathology alleviation, suggesting that MSC therapies should be re-designed to get sustained beneficial results in clinical practice. Furthermore, MSC promoted neuroprotection, increased the levels of GABA and glutamate, and decreased the levels of Myo-inositol, which correlated with motor improvements, indicating that these metabolites may serve as valid neurospectroscopic biomarkers of disease and treatment. This study makes important contributions to the design of new clinical approaches for MJD and other SCAs/polyglutamine disorders.