Polyphenolic profile, processing impact, and bioaccessibility of apple fermented products.

Health-promoting foods have become increasingly popular due to intensified consumer interest and awareness of illnesses. There is a global market for apple fruits, which are affordable, nutritious, tasty, and produced in large quantities for direct consumption as well as food processing to make derived products. The food matrix of apples is suitable for fermentation, besides containing a high amount of phenolics and polyphenols. Fermentation of apples is one of the most common methods of preserving apple fruit and its byproducts. With different fermentation techniques, apple fruit can be used to make a wide range of products, such as fermented apple juice, cider, liqueurs, apple cider, apple vinegar and fermented apple solids, because it is not only a low-cost and simple method of processing the fruit, but it can also sometimes increase the bioavailability of nutrients and the levels of components that can improve health and sensory quality. To understand the health benefits of food products and how the fermentation process impacts polyphenols, it is also crucial to observe the effects of digestion on polyphenol bioaccessibility. Polyphenolic profile changes can be observed via both in vitro and in vivo digestion methods; however, in vitro digestion methods have the advantage of observing every step of gastrointestinal track effects and have less cost as well. In this review, the polyphenolic profile, processing impact, and bioaccessibility of apple-fermented products is assessed, with most available studies showing polyphenol profiles and bioaccessibility in apple varieties and fermented apple products.

Exploring Rhodospirillum rubrum response to high doses of carbon monoxide under light and dark conditions.

Environmental concerns about residues and the traditional disposal methods are driving the search for more environmentally conscious processes, such as pyrolysis and gasification. Their main final product is synthesis gas (syngas) composed of CO, CO2, H2, and methane. Syngas can be converted into various products using CO-tolerant microorganisms. Among them, Rhodospirillum rubrum is highlighted for its biotechnological potential. However, the extent to which high doses of CO affect its physiology is still opaque. For this reason, we have studied R. rubrum behavior under high levels of this gas (up to 2.5 bar), revealing a profound dependence on the presence or absence of light. In darkness, the key variable affected was the lag phase, where the highest levels of CO retarded growth to more than 20 days. Under light, R. rubrum ability to convert CO into CO2 and H2 depended on the presence of an additional carbon source, such as acetate. In those conditions where CO was completely exhausted, CO2 fixation was unblocked, leading to a diauxic growth. To enhance R. rubrum tolerance to CO in darkness, a UV-accelerated adaptive laboratory evolution (UVa-ALE) trial was conducted to isolate clones with shorter lag phases, resulting in the isolation of clones 1.4-2B and 1.7-2A. The adaptation of 1.4-2B was mainly based on mutated enzymes with a metabolic function, while 1.7-3A was mostly affected at regulatory genes, including the anti-repressor PpaA/AerR. Despite these mutations having slight effects on biomass and pigment levels, they successfully provoked a significant reduction in the lag phase (-50%). KEYPOINTS: • CO affects principally R. rubrum lag phase (darkness) and growth rate (light) • CO is converted to CO2/H2 during acetate uptake and inhibits CO2 fixation (light) • UVa-ALE clones showed a 50% reduction in the lag phase (darkness).

A new active packaging system based on chickpea-based edible coatings added with microcapsules of Cosmos sulphureus Cav. flower extract.

BACKGROUND: The Cosmos sulphureus Cav. plant is studied for its high polyphenolic content with antioxidant properties. Its flowers, rich in phenolic acids, flavonoids, and tannins, hold promise as antioxidants in food preservation. The inclusion of these compounds in chickpea-based coatings with a previously studied preservative effect would be an excellent option as a food preservation method and microencapsulation addresses challenges like dispersion and degradation of polyphenols in the coating. The objective of this research was to evaluate the in vitro antioxidant activity of Cosmos sulphureus leaves, seed, and flower extracts and explore the protective effects of chickpea-based coatings containing microcapsules of flower polyphenolic extract on the chemical quality of stored roasted sunflower seeds during storage. RESULTS: The ethanolic leaf extract exhibited the highest antiradical activity, followed by the aqueous flower extract. After a storage period of 15 days, at 40 °C, the chickpea-based coatings effectively delayed lipid oxidation in the roasted sunflowers seeds, and the inclusion of polyphenolic microcapsules with 0.01% extract (SMC 0.01%) in the coating significantly improved the protective effect. By day 15 of storage, SMC 0.01% showed comparable peroxide value, conjugated dienes, and linoleic acid content to samples containing the synthetic antioxidant BHT (butylated hydroxytoluene). Samples that only contained chickpea-based coating and coating with polyphenolic microcapsules with 0.005% extract exhibited significantly greater reduction in fatty acid content compared to the 0.01% SMC treatment. CONCLUSION: The chickpea-based coating with polyphenolic microcapsules demonstrated antioxidant activity akin to synthetic BHT, offering a promising biopackaging solution for lipid-rich foods like roasted sunflower seeds. © 2024 Society of Chemical Industry.

Seaweed polysaccharides: Emerging extraction technologies, chemical modifications and bioactive properties.

Nowadays, consumers are increasingly aware of the relationship between diet and health, showing a greater preference of products from natural origin. In the last decade, seaweeds have outlined as one of the natural sources with more potential to obtain bioactive carbohydrates. Numerous seaweed polysaccharides have aroused the interest of the scientific community, due to their biological activities and their high potential on biomedical, functional food and technological applications. To obtain polysaccharides from seaweeds, it is necessary to find methodologies that improve both yield and quality and that they are profitable. Nowadays, environmentally friendly extraction technologies are a viable alternative to conventional methods for obtaining these products, providing several advantages like reduced number of solvents, energy and time. On the other hand, chemical modification of their structure is a useful approach to improve their solubility and biological properties, and thus enhance the extent of their potential applications since some uses of polysaccharides are still limited. The present review aimed to compile current information about the most relevant seaweed polysaccharides, available extraction and modification methods, as well as a summary of their biological activities, to evaluate knowledge gaps and future trends for the industrial applications of these compounds.Key teaching pointsStructure and biological functions of main seaweed polysaccharides.Emerging extraction methods for sulfate polysaccharides.Chemical modification of seaweeds polysaccharides.Potential industrial applications of seaweed polysaccharides.Biological activities, knowledge gaps and future trends of seaweed polysaccharides.

Aerobic-anaerobic transition boosts poly(3-hydroxybutyrate-co-3-hydroxyvalerate) synthesis in Rhodospirillum rubrum: the key role of carbon dioxide.

BACKGROUND: Microbially produced bioplastics are specially promising materials since they can be naturally synthesized and degraded, making its end-of-life management more amenable to the environment. A prominent example of these new materials are polyhydroxyalkanoates. These polyesters serve manly as carbon and energy storage and increase the resistance to stress. Their synthesis can also work as an electron sink for the regeneration of oxidized cofactors. In terms of biotechnological applications, the co-polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate), or PHBV, has interesting biotechnological properties due to its lower stiffness and fragility compared to the homopolymer poly(3-hydroxybutyrate) (P3HB). In this work, we explored the potentiality of Rhodospirillum rubrum as a producer of this co-polymer, exploiting its metabolic versatility when grown in different aeration conditions and photoheterotrophically. RESULTS: When shaken flasks experiments were carried out with limited aeration using fructose as carbon source, PHBV production was triggered reaching 29 ± 2% CDW of polymer accumulation with a 75 ± 1%mol of 3-hydroxyvalerate (3HV) (condition C2). Propionate and acetate were secreted in this condition. The synthesis of PHBV was exclusively carried out by the PHA synthase PhaC2. Interestingly, transcription of cbbM coding RuBisCO, the key enzyme of the Calvin-Benson-Bassham cycle, was similar in aerobic and microaerobic/anaerobic cultures. The maximal PHBV yield (81% CDW with 86%mol 3HV) was achieved when cells were transferred from aerobic to anaerobic conditions and controlling the CO2 concentration by adding bicarbonate to the culture. In these conditions, the cells behaved like resting cells, since polymer accumulation prevailed over residual biomass formation. In the absence of bicarbonate, cells could not adapt to an anaerobic environment in the studied lapse. CONCLUSIONS: We found that two-phase growth (aerobic-anaerobic) significantly improved the previous report of PHBV production in purple nonsulfur bacteria, maximizing the polymer accumulation at the expense of other components of the biomass. The presence of CO2 is key in this process demonstrating the involvement of the Calvin-Benson-Bassham in the adaptation to changes in oxygen availability. These results stand R. rubrum as a promising producer of high-3HV-content PHBV co-polymer from fructose, a PHBV unrelated carbon source.

Association of blood manganese concentrations with 24-h based brachial and central blood pressure, and pulse-wave velocity.

Potential environmental determinants of BP and hypertension in older adults are far less known than their lifestyle risk factors. Manganese (Mn) is an essential element for life that may induce changes in blood pressure (BP), but the direction of the association is unclear. We aimed to examine the association of blood manganese (bMn) with 24-h-based brachial, central BP (cBP), and pulse-wave velocity (PWV). With this purpose, we analyzed data from 1009 community-living adults aged >65 years without BP medication. bMn was measured using inductively-coupled plasma-mass spectrometry and 24-h BP with validated devices. The association of bMn (median: 6.77 µg/L; IQR: 5.59-8.27) with daytime brachial and central systolic (SBP) and with diastolic BP (DBP) was non-linear, with BP increases up to around the median of Mn and then stabilization or slight rightward decrease. Mean BP differences (95% confidence interval) comparing Mn Q2 to Q5 (vs Q1 quintile) for brachial daytime SBP were 2.56 (0.22; 4.90), 3.59 (1.22; 5.96), 3.14 (0.77; 5.51) and 1.72 (-0.68; 4.11) mmHg, respectively; and 2.22 (0.70, 3.73), 2.55 (1.01, 4.08), 2.45 (0.91; 3.98), and 1.68 (0.13; 3.24), respectively, for DBP. Daytime central-pressures showed a similar dose-response relationship with bMn as daytime brachial-pressures. The association with nighttime BP was linearly positive for brachial BPs, and only increasing for Q5 for cBP. Regarding PWV, a tendency to significant linear increase along bMn levels was observed (p-trend = 0.042). The present findings extend the scarce evidence on the association between Mn and brachial BP to 2 other vascular parameters, suggesting Mn levels as a candidate risk factor for increasing levels of both brachial and cBPs in older adults, yet further research is needed with larger cohort studies in adults at all age ranges.

Satisfaction and medication adherence in women with vulvovaginal atrophy: the CRETA.

OBJECTIVE: This study aimed to evaluate the self-reported satisfaction of Spanish postmenopausal women currently treated for vulvovaginal atrophy (VVA) symptoms. METHODS: The CRETA (CRoss sectional European sTudy on Adherence) is a multicenter cross-sectional study conducted in 29 public and private hospitals in Spain, which enrolled postmenopausal women receiving treatment with ospemifene, local hormone therapy (HT) or vaginal moisturizers for VVA. After the prior informed consent of the patients, sociodemographic and treatment perception data were collected using a structured questionnaire. RESULTS: Among 752 women who completed the survey, the satisfaction score was significantly higher for the group treated with ospemifene (mean 8.3 ± 1.4) compared with the local HT group (7.2 ± 1.7) and the vaginal moisturizer group (6.5 ± 2.1) according to a 10-point Likert scale (p < 0.0001). Compared to vaginal moisturizers and local HT, participants treated with ospemifene reported the highest adherence (96.7% vs. 70.2% and 78.6%, respectively) and the lowest number of missed doses in the last month (0.6 ± 1.3 standard deviation [SD] vs. 3.5 ± 4.3 SD and 2.0 ± 2.8 SD, respectively) (p < 0.0001). Ospemifene was significantly perceived as easy to use (83.9% vs. 44.9% and 58.6%, respectively; p < 0.0001), efficacious in reducing the time to relieve symptoms (17.1% vs. 7.0% and 6.7%, p = 0.0005 and p = 0.0006, respectively) and convenient for sexual life (53.1% vs. 25.6% and 42.3%, p < 0.0001 and p = 0.0234, respectively). CONCLUSIONS: Among postmenopausal women with VVA, treatment with ospemifene has the most positive perceptions and the highest overall satisfaction level and could be an optimal therapeutic approach, maximizing patient adherence.

Crop forcing technique and irrigation strategy modified the content and phenolic profile of cv. Tempranillo grape berries grown in a semi-arid climate.

BACKGROUND: Climate change modifies the content and phenolic profiles of grapes and wines. It is known that high temperatures, related to climate change, reduce anthocyanins and procyanidin (catechin and tannin) compounds accumulated in the berries. In recent years, with the aim of improving the phenolic composition of the berries, the technique of crop forcing has been proposed to delay grape ripening to a more favourable period of temperatures. RESULTS: In this study, crop forcing was applied to cv. Tempranillo vines on two different dates, after flowering (F1) and after fruit set (F2), and compared to a treatment control (NF, without forcing). Additionally, as a secondary factor, two irrigation strategies were established in each treatment: irrigation with no water stress, and a pre-veraison deficit irrigation. The study was carried out in three consecutive years (2017-2019). For most of the parameters analysed, no interaction was found. Therefore, for these parameters, the effect of each of these techniques was investigated independently. Regardless of the irrigation strategy, F2 berries achieved higher contents of catechins and anthocyanins than NF berries. Each year, regardless of the irrigation strategy, crop forcing increased the content of monoglucoside forms, and had a positive effect on the total content of malvidin, petunidin, delphinidin, peonidin and malvidin derivatives, but only affected acetyl and coumaryl forms in 2017. However, the effect of irrigation strategy was less significant and consistent, being more dependent on the vintage. CONCLUSION: Regardless of vine water status, crop forcing technique applied after fruit set could be used by vine growers to delay ripening of the grapes and thus achieve an increase in the anthocyanin characteristics of the grapes. © 2023 Society of Chemical Industry.

Biological properties and potential of compounds extracted from red seaweeds.

Macroalgae have been recently used for different applications in the food, cosmetic and pharmaceutical industry since they do not compete for land and freshwater against other resources. Moreover, they have been highlighted as a potential source of bioactive compounds. Red algae (Rhodophyta) are the largest group of seaweeds, including around 6000 different species, thus it can be hypothesized that they are a potential source of bioactive compounds. Sulfated polysaccharides, mainly agar and carrageenans, are the most relevant and exploited compounds of red algae. Other potential molecules are essential fatty acids, phycobiliproteins, vitamins, minerals, and other secondary metabolites. All these compounds have been demonstrated to exert several biological activities, among which antioxidant, anti-inflammatory, antitumor, and antimicrobial properties can be highlighted. Nevertheless, these properties need to be further tested on in vivo experiments and go in-depth in the study of the mechanism of action of the specific molecules and the understanding of the structure-activity relation. At last, the extraction technologies are essential for the correct isolation of the molecules, in a cost-effective way, to facilitate the scale-up of the processes and their further application by the industry. This manuscript is aimed at describing the fundamental composition of red algae and their most studied biological properties to pave the way to the utilization of this underused resource.

Solutions for the sustainability of the food production and consumption system.

Due to the increasing population, there is high concern about whether the current food system will be able to provide enough healthy food for 10 billion people by 2050. The general opinion is that it is possible to feed this population, but the food system requires major transformations on behalf of promoting sustainability, reducing food waste and stimulating a change toward diets healthy for humans and also sustainable for the planet. This article will review some detected problems in food production and consumption. In food production, current problems like destruction of land ecosystems, overfishing or generation of high amounts of residues stand out. Some solutions have been described, such as implement the agroecology, improve productivity of aquaculture or re-valorization of by-products. In food consumption, the main problems are the food fraud and the unhealthy dietary patters, whose main solutions are the standardization along food chain and education on healthy lifestyles. Concluding, food system should change toward more sustainable practices and behaviors in other to ensure the subsistence of the present and the future generations.

Risk of a Second Skin Cancer in a Cohort of Patients With Nonmelanoma Skin Cancer -Basal Cell Carcinoma or Squamous Cell Carcinoma-Treated With Mohs Micrographic Surgery: A National Prospective Cohort Study. / Riesgo de aparición de segundas neoplasias cutáneas en una cohorte de pacientes diagnosticados de carcinoma queratinocítico (carcinoma basocelular y carcinoma epidermoide) tratados con cirugía de Mohs. Estudio de cohortes prospectivo nacional.

OBJECTIVE: Patients with nonmelanoma skin cancer (NMSC)-ie, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)-have an increased risk of developing a second skin cancer. The aim of this study was to describe the frequency, incidence per 1000 person-years, and predictors of a second skin cancer in a cohort of patients with NMSC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: Prospective study of a national cohort of patients with NMSC who underwent MMS at 22 Spanish hospitals between July 2013 and February 2020; case data were recorded in the REGESMOHS registry. The study variables included demographic characteristics, frequency and incidence per 1000 person-years of second skin cancers diagnosed during the study period, and risk factors identified using mixed-effects logistic regression. RESULTS: We analyzed data for 4768 patients who underwent MMS; 4397 (92%) had BCC and 371 (8%) had SCC. Mean follow-up was 2.4 years. Overall, 1201 patients (25%) developed a second skin cancer during follow-up; 1013 of the tumors were BCCs (21%), 154 were SCCs (3%), and 20 were melanomas (0.4%). The incidence was 107 per 1000 person-years (95% CI, 101-113) for any cancer, 90 per 1000 person-years (95% CI, 85-96) for BCC, 14 (95% CI, 12-16) per 1000 person-years for SCC, and 2 (95% CI, 1-3) per 1000 person-years for melanoma. More men than women developed a subsequent skin cancer (738 [61%] vs 463 [39%]). The main risk factors were a history of multiple tumors before diagnosis (relative risk [RR], 4.6; 95% CI, 2.9-7.1), immunosuppression (RR, 2.1; 95% CI, 1.4-3.1), and male sex (RR, 1.6; 95% CI, 1.4-1.9). CONCLUSION: Patients have an increased risk of developing a second tumor after MMS treatment of NMSC. Risk factors are a history of multiple tumors at diagnosis, immunosuppression, and male sex.

Providing new insights on the biphasic lifestyle of the predatory bacterium Bdellovibrio bacteriovorus through genome-scale metabolic modeling.

In this study we analyze the growth-phase dependent metabolic states of Bdellovibrio bacteriovorus by constructing a fully compartmented, mass and charge-balanced genome-scale metabolic model of this predatory bacterium (iCH457). Considering the differences between life cycle phases driving the growth of this predator, growth-phase condition-specific models have been generated allowing the systematic study of its metabolic capabilities. Using these computational tools, we have been able to analyze, from a system level, the dynamic metabolism of the predatory bacteria as the life cycle progresses. We provide computational evidences supporting potential axenic growth of B. bacteriovorus's in a rich medium based on its encoded metabolic capabilities. Our systems-level analysis confirms the presence of "energy-saving" mechanisms in this predator as well as an abrupt metabolic shift between the attack and intraperiplasmic growth phases. Our results strongly suggest that predatory bacteria's metabolic networks have low robustness, likely hampering their ability to tackle drastic environmental fluctuations, thus being confined to stable and predictable habitats. Overall, we present here a valuable computational testbed based on predatory bacteria activity for rational design of novel and controlled biocatalysts in biotechnological/clinical applications.

[The effects of quarantine on anxiety and emotional symptoms. Results of an online survey]. / Trastornos de la salud mental en personas sometidas a cuarentena, estudio transversal durante pandemia por COVID-19 en población chilena.

BACKGROUND: Quarantines may exacerbate the presence of emotional symptoms or anxiety. AIM: To explore the relation between time spent in lockdown and development of depressive and anxiety symptoms. MATERIAL AND METHODS: A survey including the GAD anxiety and PHQ-9 depression scores was answered online by 1,488 subjects aged 36 ± 14 years (74% women), invited to participate through social networks. Both scores are validated for the Chilean population. RESULTS: Most responders had a private health insurance system. Sixty seven percent had clinically significant depressive symptoms and 39% had anxiety symptoms. Spending four or more weeks of lockdown (quarantine) was associated with 1.6 times higher risk of developing depressive symptoms and 2.9 times higher risk of developing anxiety symptoms. Difficulties in access to health care increased 3.3 times the risk of developing depression. Suffering a respiratory disease increased 2.39 times the risk of developing anxiety. CONCLUSIONS: There was a direct association between depressive and anxious symptoms, and the time spent of quarantine.

Phasin interactome reveals the interplay of PhaF with the polyhydroxyalkanoate transcriptional regulatory protein PhaD in Pseudomonas putida.

Phasin PhaF, a multifunctional protein associated with the surface of polyhydroxyalkanoate (PHA) granules that also interacts with the nucleoid, contributes significantly to PHA biogenesis in pseudomonads. As a protein present on the surface of PHA granules, PhaF participates in granule stabilization and segregation, whereas its deletion has a notable impact on overall transcriptome, PHA accumulation and cell physiology, suggesting more extensive functions besides solely being a granule structural protein. Here, we followed a systematic approach to detect potential interactions of PhaF with other components of the cell, which could pinpoint unexplored functions of PhaF in the regulation of PHA production. We determined the PhaF interactome in Pseudomonas putida KT2440 via pull-down-mass spectrometry (PD-MS) experiments. PhaF complexed with PHA-related proteins, phasin PhaI and the transcriptional regulator PhaD, interactions that were verified to be direct using in vivo two-hybrid analysis. The determination of the PHA granule proteome showed that PhaI and three other potential PhaF interacting partners, but not PhaD, were granule-associated proteins. Analysis of the interaction of PhaF and PhaD with the phaI promoter by EMSA suggested a new role for PhaF in interacting with PhaD and raises new questions on the regulatory system controlling pha gene expression.

Disentangling functional trait variation and covariation in epiphytic lichens along a continent-wide latitudinal gradient.

Characterizing functional trait variation and covariation, and its drivers, is critical to understand the response of species to changing environmental conditions. Evolutionary and environmental factors determine how traits vary among and within species at multiple scales. However, disentangling their relative contribution is challenging and a comprehensive trait-environment framework addressing such questions is missing in lichens. We investigated the variation in nine traits related to photosynthetic performance, water use and nutrient acquisition applying phylogenetic comparative analyses in lichen epiphytic communities on beech across Europe. These poikilohydric organisms offer a valuable model owing to their inherent limitations to buffer contrasting environmental conditions. Photobiont type and growth form captured differences in certain physiological traits whose variation was largely determined by evolutionary processes (i.e. phylogenetic history), although the intraspecific component was non-negligible. Seasonal temperature fluctuations also had an impact on trait variation, while nitrogen content depended on photobiont type rather than nitrogen deposition. The inconsistency of trait covariation among and within species prevented establishing major resource use strategies in lichens. However, we did identify a general pattern related to the water-use strategy. Thus, to robustly unveil lichen responses under different climatic scenarios, it is necessary to incorporate both among and within-species trait variation and covariation.

Dissecting the Polyhydroxyalkanoate-Binding Domain of the PhaF Phasin: Rational Design of a Minimized Affinity Tag.

Phasin PhaF from Pseudomonas putida consists of a modular protein whose N-terminal domain (BioF) has been demonstrated to be responsible for binding to the polyhydroxyalkanoate (PHA) granule. BioF has been exploited for biotechnological purposes as an affinity tag in the functionalization of PHA beads with fusion proteins both in vivo and in vitro The structural model of this domain suggests an amphipathic α-helical conformation with the hydrophobic residues facing the PHA granule. In this work, we analyzed the mean hydrophobicity and the hydrophobic moment of the native BioF tag to rationally design shorter versions that maintain affinity for the granule. Hybrid proteins containing the green fluorescent protein (GFP) fused to the BioF derivatives were studied for in vivo localization on PHA, stability on the surface of the PHA granule against pH, temperature, and ionic strength, and their possible influence on PHA synthesis. Based on the results obtained, a minimized BioF tag for PHA functionalization has been proposed (MinP) that retains similar binding properties but possesses an attractive biotechnological potential derived from its reduced size. The MinP tag was further validated by analyzing the functionality and stability of the fusion proteins MinP-ß-galactosidase and MinP-CueO from Escherichia coliIMPORTANCE Polyhydroxyalkanoates (PHAs) are biocompatible, nontoxic, and biodegradable biopolymers with exceptional applications in the industrial and medical fields. The complex structure of the PHA granule can be exploited as a toolbox to display molecules of interest on their surface. Phasins, the most abundant group of proteins on the granule, have been employed as anchoring tags to obtain functionalized PHA beads for high-affinity bioseparation, enzyme immobilization, diagnostics, or cell targeting. Here, a shorter module based on the previously designed BioF tag has been demonstrated to maintain the affinity for the PHA granule, with higher stability and similar functionalization efficiency. The use of a 67% shorter peptide, which maintains the binding properties of the entire protein, constitutes an advantage for the immobilization of recombinant proteins on the PHA surface both in vitro and in vivo.

Cerebellar Cognitive Affective Syndrome in Costa da Morte Ataxia (SCA36).

SCA36 is an autosomal dominant spinocerebellar ataxia (SCA) affecting many families from Costa da Morte, a northwestern region of Spain. It is caused by an intronic GGCCTG repeat expansion in NOP56. In order to characterize the cognitive and affective manifestations of this cerebellar disease, a group of 30 SCA36 mutation carriers (11 preataxic and 19 ataxic patients) were assessed with a comprehensive battery of standardized tests. Phonological verbal fluency - but not semantic fluency - was already mildly impaired in preataxic subjects. In ataxic patients, both phonological and semantic fluencies were significantly below normal. Depression, while more frequent and prominent in ataxic patients, was also often present in the preataxic stage. This is the first systematic study supporting the presence of a mild cerebellar cognitive and affective syndrome in SCA36. Routine evaluation of cognitive and emotional spheres in SCA36 patients as well as asymptomatic mutation carriers should allow early detection and timely therapeutic intervention.

Combined Therapy for Alzheimer's Disease: Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity.

Alzheimer's disease has become a public health priority, so an investigation of new therapies is required. Tacrine (TAC) was licensed for treatments; however, its oral administration caused hepatotoxicity, so it is essential to reduce the side effects. PAMAM dendrimer generation 4.0 and 4.5 (DG4.0 and DG4.5) can be used as drug delivery systems and as nanodrugs per se. Our work aims to propose a combined therapy based on TAC and PAMAM dendrimer co-administration. TAC and dendrimer interactions were studied by in vitro drug release, drug stability, and FTIR. The toxicity profile of co-administration was evaluated in human red blood cells, in Neuro-2a cell culture, and in zebrafish larvae. Also, the anti-acetylcholinesterase activity was studied in cell culture. It was possible to obtain DG4.0-TAC and DG4.5-TAC suspensions, without reducing the drug solubility and stability. FTIR and in vitro release studies confirmed that interaction between TAC and DG4.5 was of the electrostatic type. No toxicity effects on human red blood cells were observed, whereas the co-administration with DG4.5 reduced cytotoxicity of TAC on the Neuro-2a cell line. Moreover, in vivo co-administration of both DG4.0-TAC and DG4.5-TAC reduced the morphological and hepatotoxic effects of TAC in zebrafish larvae. The reduction of TAC toxicity was not accompanied by a reduction in its activity since the anti-acetylcholinesterase activity remains when it is co-administrated with dendrimers. In conclusion, the co-administration of TAC with both DG4.0 and DG4.5 is a novel therapy since it was less-toxic, was more biocompatible, and has the same effectiveness than the free drug. Graphical abstract.

[Neurological complications in critical patients with COVID-19]. / Complicaciones neurológicas en pacientes críticos por SARS-CoV-2.

Introduction: We analysed the neurological complications of patients with severe SARS-CoV-2 infection who required intensive care unit (ICU) admission. Patients and methods: We conducted a retrospective, observational, descriptive study of consecutive patients admitted to the ICU due to severe respiratory symptoms secondary to SARS-CoV-2 infection between 1 April and 1 June 2020. Results: We included 30 patients with neurological symptoms; 21 were men (72.40%), and mean age (standard deviation [SD]) was 57.41 years (11.61). The mean duration of ICU stay was 18.83 days (14.33). The neurological conditions recorded were acute confusional syndrome in 28 patients (93.33%), neuromuscular disease in 15 (50%), headache in 5 (16.66%), cerebrovascular disease in 4 (13.33%), and encephalopathies/encephalitis in 4 (13.33%). CSF analysis results were normal in 6 patients (20%). Brain MRI or head CT showed alterations in 20 patients (66.6%). EEG was performed in all patients (100%), with 8 (26.66%) showing abnormal findings. In 5 of the 15 patients with clinical myopathy, diagnosis was confirmed with electroneuromyography. We found a correlation between older age and duration of ICU stay (P = .002; 95% CI: 4.032-6.022; OR: 3,594). Conclusions: Severe COVID-19 mainly affects men, as observed in other series. Half of our patients presented acute myopathy, and almost all patients left the ICU with acute confusional syndrome, which fully resolved; no correlation was found with EEG or neuroimaging findings. Older age is associated with longer ICU stay.

Lipid profile is associated with treatment regimen in a large cohort of children and adolescents with Type 1 diabetes mellitus: a study from the international SWEET database.

AIMS: To examine the effect of pump vs injection therapy on the lipid profile of children with Type 1 diabetes mellitus. METHODS: A cross-sectional analysis of the lipid profile of children aged ≤ 18 years with Type 1 diabetes mellitus from SWEET, an international diabetes registry, was conducted with a focus on the effect of treatment regimen. Dyslipidaemia was defined as LDL cholesterol ≥2.6 mmol/l or non-HDL cholesterol ≥3.1 mmol/l. LDL and non-HDL cholesterol values among 14 290 children (52% boys, 51% receiving pump therapy) from 60 SWEET centres were analysed by linear and logistic regression analysis adjusted for sex, age, diabetes duration, HbA1c and BMI-standard deviation score group, region, and common interactions between age, sex, HbA1c and BMI. RESULTS: This study confirmed the established associations of increased lipids with female sex, age, diabetes duration, HbA1c and BMI. LDL and non-HDL cholesterol levels were lower in the pump therapy group compared to the injection therapy group [LDL cholesterol: injection therapy 2.44 mmol/l (95% CI 2.42 to 2.46) vs pump therapy 2.39 mmol/l (95% CI 2.37-2.41), P<0.001; non-HDL cholesterol: injection therapy 2.88 mmol/l (95% CI 2.86 to 2.90) vs pump therapy 2.80 mmol/l (95% CI 2.78-2.82), both P<0.0001]. Similarly, the odds ratios for LDL cholesterol ≥2.6 mmol/l [0.89 (95% CI 0.82-0.97)] and non-HDL cholesterol ≥3.1 mmol/l [0.85 (0.78 to 0.93)] were significantly lower in the pump therapy group, even after all adjustments. CONCLUSIONS: Our results indicate that pump therapy is associated with a better lipid profile.