A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

Developmental plasticity and variability in the formation of egg-spots, a pigmentation ornament in the cichlid Astatotilapia calliptera.

Vertebrate pigmentation patterns are highly diverse, yet we have a limited understanding of how evolutionary changes to genetic, cellular, and developmental mechanisms generate variation. To address this, we examine the formation of a sexually-selected male ornament exhibiting inter- and intraspecific variation, the egg-spot pattern, consisting of circular yellow-orange markings on the male anal fins of haplochromine cichlid fishes. We focus on Astatotilapia calliptera, the ancestor-type species of the Malawi cichlid adaptive radiation of over 850 species. We identify a key role for iridophores in initializing egg-spot aggregations composed of iridophore-xanthophore associations. Despite adult sexual dimorphism, aggregations initially form in both males and females, with development only diverging between the sexes at later stages. Unexpectedly, we found that the timing of egg-spot initialization is plastic. The earlier individuals are socially isolated, the earlier the aggregations form, with iridophores being the cell type that responds to changes to the social environment. Furthermore, we observe apparent competitive interactions between adjacent egg-spot aggregations, which strongly suggests that egg-spot patterning results mostly from cell-autonomous cellular interactions. Together, these results demonstrate that A. calliptera egg-spot development is an exciting model for investigating pigment pattern formation at the cellular level in a system with developmental plasticity, sexual dimorphism, and intraspecific variation. As A. calliptera represents the ancestral bauplan for egg-spots, these findings provide a baseline for informed comparisons across the incredibly diverse Malawi cichlid radiation.

Nutritional composition of ultra-processed plant-based foods in the out-of-home environment: a multi-country survey with plant-based burgers.

Ultra-processed plant-based foods, such as plant-based burgers, have gained in popularity. Particularly in the out-of-home (OOH) environment, evidence regarding their nutritional profile and environmental sustainability is still evolving. Plant-based burgers available at selected OOH sites were randomly sampled in Amsterdam, Copenhagen, Lisbon and London. Plant-based burgers (patty, bread and condiment) (n 41) were lab analysed for their energy, macronutrients, amino acids and minerals content per 100 g and serving and were compared with reference values. For the plant-based burgers, the median values per 100 g were 234 kcal, 20·8 g carbohydrates, 3·5 g dietary fibre and 12·0 g fat, including 0·08 g TFS and 2·2 g SFA. Protein content was 8·9 g/100 g, with low protein quality according to amino acid composition. Median Na content was 389 mg/100 g, equivalent to 1 g salt. Compared with references, the median serving provided 31% of energy intake based on a 2000 kcal per day and contributed to carbohydrates (17-28%), dietary fibre (42%), protein (40%), total fat (48%), SFA (26%) and Na (54%). One serving provided 15-23% of the reference values for Ca, K and Mg, while higher contributions were found for Zn, Mn, P and Fe (30-67%). The ultra-processed plant-based burgers provide protein, dietary fibre and essential minerals and contain relatively high levels of energy, Na and total fats. The amino acid composition indicated low protein quality. The multifaceted nutritional profile of plant-based burgers highlights the need for manufacturers to implement improvements to better support healthy dietary habits, including reducing energy, Na and total fats.

Applying a heat transfer mathematical model for the cryopreservation of rainbow trout (Oncorhynchus mykiss) sperm: How straw location over liquid nitrogen level affects freezing rate and fertilization yield.

Cryopreservation of rainbow trout semen under field conditions was analyzed. Straw location over liquid nitrogen level is a crucial variable that affects freezing rate and fertilization yield due to changes in nitrogen vapor external temperature. The objectives were: to analyze cryopreservation protocols by experimentally measuring the cooling rates and fertilization yield of 0.5 ml plastic straws located in nitrogen vapor at different heights corresponding to different external temperatures; to numerically simulate the freezing process, by solving the heat transfer partial differential equations with the corresponding thermo-physical properties of the biological system and the plastic straw; to evaluate and analyze the surface heat transfer coefficient (h) during the freezing process of the straws; to introduce a new variable, the characteristic freezing time (tc), that enables comparison between protocols; this variable was defined as the elapsed period between the initial freezing temperature and a final reference temperature of -40 °C (temperature in which more than 80 % of the water is in a frozen state). The mathematical model predicted the temperature distribution inside the straw, showing a low effect of straw plastic materials (polyethylene-terephthalate glycol, polyvinyl-chloride, and polypropylene) on freezing rates. The average h value obtained from numerical simulations was 25.5 W/m2 K, close to that obtained from the analytical Nusselt correlation for natural convection. An improvement on fertilization trials was observed when the average external nitrogen temperature was -129.6 °C (temperature range: -94 to -171 °C) with an average tc of 56.8 s (ranging between 47 and 72 s). These results corresponded to a height above the level of liquid nitrogen of 2 cm. Comparison with literature reported data showed satisfactory results. Applying mathematical models in the cryobiology field achieved results that are relevant for cryopreservation activities.

HOW I DO IT: Cushing's disease-selective adenomectomy via an endoscopic transsphenoidal approach.

BACKGROUND: An ACTH-secreting pituitary adenoma is the most common cause of excessive endogenous glucocorticoid production resulting in Cushing's Syndrome. A multidisciplinary approach is paramount. Selective adenomectomy is the treatment of choice. METHOD: Endoscopic transnasal transsphenoidal approach to the tumour, along with techniques for resection, are demonstrated. CONCLUSION: Endoscopic transsphenoidal approaches with its magnified view of the pituitary gland allows precise microsurgical dissection during selective adenomectomy. This technique increases the possibility of proving a gross total resection, leading to clinical and biochemical cure in these patients.

Use of rumination time in health risk assessment of prepartum dairy cows.

The objectives of this observational cohort study were to evaluate the associations of rumination time (RT) in the last week of pregnancy with transition cow metabolism, inflammation, health, and subsequent milk production, reproduction, and culling. Pregnant nulliparous (n = 199) and parous (n = 337) cows were enrolled 21 d before the expected calving. RT and physical activity were monitored automatically by sensors from d -21 to 15 relative to calving. Blood samples were collected on d -14, -5, 4, 8, and 12 ± 1 relative to calving. Diagnoses of clinical health problems were performed by researchers from calving to 15 d in milk (DIM). In classification 1, cows were ranked based on average daily RT in the last week of pregnancy and classified into terciles as short RT (SRT), moderate RT (MRT), or long RT (LRT) for association analyses. In classification 2, RT deviation from the parity average was used in a receiver operating characteristic curve to identify the best threshold to predict postpartum clinical disease. Cows were then classified as above the threshold (AT) or below the threshold (BT). Compared with cows with LRT, cows with SRT had greater serum concentrations of NEFA (0.47 vs 0.40 ± 0.01 mmol/L), BHB (0.58 vs 0.52 ± 0.01 mmol/L), and haptoglobin (0.22 vs 0.18 ± 0.008 g/L) throughout the transition period, and reduced concentrations of glucose, cholesterol, albumin, and magnesium in a time-dependent manner. Parous cows with SRT had higher odds of postpartum clinical disease (adjusted odds ratio [AOR]: 3.7; 95% confidence interval [CI]: 2.1-6.4), lower odds of pregnancy by 210 DIM (AOR: 0.34; CI: 0.15-0.75), and lower milk production (46.9 vs 48.6 ± 0.5 kg/d) than parous cows with LRT. Deviation in prepartum RT had good predictive value for clinical disease in parous cows (area under the curve [AUC]: 0.65; CI: 0.60-0.71) but not in nulliparous (AUC: 0.51; CI: 0.42-0.59). Separation of parous cows according to the identified threshold (≤-53 min from the parity average) resulted in differences in serum concentrations of NEFA (AT = 0.31 ± 0.006, BT = 0.38 ± 0.014 mmol/L), BHB (AT = 0.49 ± 0.008, BT = 0.53 ± 0.015 mmol/L), and globulin (AT = 32.3 ± 0.3, BT = 34.8 ± 0.5 g/L) throughout the transition period, as well as in serum cholesterol, urea, magnesium, albumin, and haptoglobin in a time-dependent manner. BT parous cows had higher odds of clinical disease (AOR: 3.7; CI: 2.1-6.4), reduced hazard of pregnancy (AHR: 0.64, CI: 0.47-0.89), greater hazard of culling (AHR: 2.1, CI: 1.2-3.6), and lower milk production (46.3 ± 0.7 vs 48.5 ± 0.3 kg/d). External validation using data from 153 parous cows from a different herd and the established threshold in RT deviation (≤-53 min) resulted in similar predictive value, with the odds of postpartum disease 2.4 times greater in BT than AT (37.5 vs 20.1%). In conclusion, RT in the wk preceding calving was a reasonable predictor of postpartum health and future milk production, reproduction, and culling in parous cows but not in nulliparous cows.

Inheritance of genomic regions and genes associated with number of oocytes and embryos in Gir cattle through daughter design.

Over the past decades, daughter designs, including genotyped sires and their genotyped daughters, have been used as an approach to identify QTL related to economic traits. The aim of this study was to identify genomic regions inherited by Gir sire families and genes associated with number of viable oocytes (VO), total number of oocytes (TO), and number of embryos (EMBR) based on a daughter design approach. In total, 15 Gir sire families were selected. The number of daughters per family ranged from 26 to 395, which were genotyped with different SNP panels and imputed to the Illumina BovineHD BeadChip (777K) and had phenotypes for oocyte and embryo production. Daughters had phenotypic data for VO, TO, and EMBR. The search for QTL was performed through GWAS based on GBLUP. The QTL were found for each trait among and within families based on the top 10 genomic windows with the greatest genetic variance. For EMBR, genomic windows identified among families were located on BTA4, BTA5, BTA6, BTA7, BTA8, BTA13, BTA16, and BTA17, and they were most frequent on BTA7 within families. For VO, genomic windows were located on BTA2, BTA4, BTA5, BTA7, BTA17, BTA21, BTA22, BTA23, and BTA27 among families, being most frequent on BTA8 within families. For TO, the top 10 genomic windows were identified on BTA2, BTA4, BTA5, BTA7, BTA17, BTA21, BTA22, BTA26, and BTA27, being most frequent on BTA7 and BTA8 within families. Considering all results, the greatest number of genomic windows was found on BTA7, where the VCAN, XRCC4, TRNAC-ACA, HAPLN1, and EDIL3 genes were identified in the common regions. In conclusion, 15 Gir sire families with 26 to 395 daughters per family with phenotypes for oocyte and embryo production helped to identify the inheritance of several genomic regions, especially on BTA7, where the EDIL3, HAPLN1, and VCAN candidate genes were associated with number of oocytes and embryos in Gir cattle families.

Molecular sensitization profile to grass and olive pollens in Portugal.

Summary: Background. Grass and olive pollens have overlapping pollination periods and are common allergens in the Iberian Peninsula. The objective is to determine the sensitization pattern to major Phleum pratense and Olea europaea pollens in the Portuguese population with pollen allergic rhinitis (AR) using molecular allergen diagnosis (MAD). Methods. Seasonal AR patients (≥ 12 years), with positive skin prick tests (SPT) to Phleum and Olea were recruited from 16 centers. Using ALEX2, specific IgE to Phl p1, Phl p2, Phl p5, Phl p6, Phl p7, Phl p 12, Ole e1, Ole e7 and Ole e9 were determined. Immunoblotting of Olea allergic patients was performed. Results. Included 175 patients (55.4% female; mean age 31.6 ± 13.3 years; 85.7% adults; 40% asthmatic, Coast 28%/Inland 72% and North 29.1%/Centre 20.6%/South 50.3%). Considering Phleum MAD, 85.7% were sensitized to Phl p1, 45.7% to Phl p2, 50.3% to Phl p5, 45.7%, to Phl p6, 10.9% to Phl p7 and 22.9% to Phl p12. Sensitization to Ole e1 was found in 56.6%, to Ole e7 in 1.7% and Ole e9 in 3.4% patients. Sensitization to Phl p7 was more frequent in asthmatics (17.4% vs 6.6%; p = 0.044). Sensitization to Phl p5, Phl p6, Phl p12 and Ole e1 was more frequent in inland. Regarding sensitization patterns: 53.1% patients were sensitized to both species genuine´ sIgE, 38.3% to Phleum and 3.4% only to Olea species' sIgE. Immunoblotting of Olea allergic patients showed a high intensity band that may correspond to Ole e12. Conclusions. MAD showed "genuine" Grass and Olea sensitization in approximately 50% of our patients.

Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

Validation of a 3D Local-Scale Adaptive Solar Radiation Model by Using Pyranometer Measurements and a High-Resolution Digital Elevation Model.

The result of the multidisciplinary collaboration of researchers from different areas of knowledge to validate a solar radiation model is presented. The MAPsol is a 3D local-scale adaptive solar radiation model that allows us to estimate direct, diffuse, and reflected irradiance for clear sky conditions. The model includes the adaptation of the mesh to complex orography and albedo, and considers the shadows cast by the terrain and buildings. The surface mesh generation is based on surface refinement, smoothing and parameterization techniques and allows the generation of high-quality adapted meshes with a reasonable number of elements. Another key aspect of the paper is the generation of a high-resolution digital elevation model (DEM). This high-resolution DEM is constructed from LiDAR data, and its resolution is two times more accurate than the publicly available DEMs. The validation process uses direct and global solar irradiance data obtained from pyranometers at the University of Salamanca located in an urban area affected by systematic shading from nearby buildings. This work provides an efficient protocol for studying solar resources, with particular emphasis on areas of complex orography and dense buildings where shadows can potentially make solar energy production facilities less efficient.

Hierarchical Zeolites Prepared Using a Surfactant-Mediated Strategy: ZSM-5 vs. Y as Catalysts for Friedel-Crafts Acylation Reaction.

Hierarchical ZSM5 and Y zeolites were prepared through a surfactant-mediated strategy with NH4OH changing the duration of the treatment and the amount of CTAB surfactant and taking as reference multiples of the critical micellar concentration (CMC). The materials were characterized using powder X-ray diffraction, N2 adsorption isotherms at -196 °C, and SEM and TEM microscopy. The catalytic performance was evaluated in Friedel-Crafts acylation of furan with acetic anhydride at 80 °C. The alkaline surfactant-mediated treatment had different effects on the two zeolites. For ZSM5, the CTAB molecular aggregates can hardly diffuse inside the medium-size pores, leading mainly to intercrystalline mesoporosity and increased external surface area, with no positive catalytic impact. On the other hand, for large-pore Y zeolite, the CTAB molecular aggregates can easily diffuse and promote the rearrangement of crystal units around micelles, causing the enlargement of the pores, i.e., intracrystalline porosity. The optimized Y-based sample, treated for 12 h with a CTAB amount 32 times the CMC, shows an increase in product yield and rate constant that was not observed when a higher amount of surfactant was added. The reuse of spent catalysts upon thermal treatment at 400 °C shows a regeneration efficiency around 90%, showing good potentialities for the modified catalysts.

Identification of runs of homozygosity (ROHs) in Curraleiro Pé-Duro and Pantaneiro cattle breeds.

This study aimed to identify and characterize runs of homozygosis (ROHs), genes involved in production characteristics and adaptation to tropical systems and to estimate the inbreeding coefficient of Curraleiro Pé-Duro (CPD) and Pantaneiro (PANT), two brazilian locally adapted cattle breeds. The results demonstrated that 79.25% and 54.29% of ROH segments were bigger than 8 Mb in CPD and PANT, respectively, indicating recent inbred matings in the studied population. Six homozygosis islands were identified simultaneously in both breeds, where 175 QTLs and 1072 genes previously described as associated with production traits are located. The inbreeding coefficient (FROH) estimated based on ROHs (FROH) showed that inbreeding is low (2 to 4%), which is different from expected for small populations such as locally adapted ones.

Morphological and temporal variation in early embryogenesis contributes to species divergence in Malawi cichlid fishes.

The cichlid fishes comprise the largest extant vertebrate family and are the quintessential example of rapid "explosive" adaptive radiations and phenotypic diversification. Despite low genetic divergence, East African cichlids harbor a spectacular intra- and interspecific morphological diversity, including the hyper-variable, neural crest (NC)-derived traits such as coloration and craniofacial skeleton. Although the genetic and developmental basis of these phenotypes has been investigated, understanding of when, and specifically how early, in ontogeny species-specific differences emerge, remains limited. Since adult traits often originate during embryonic development, the processes of embryogenesis could serve as a potential source of species-specific variation. Consequently, we designed a staging system by which we compare the features of embryogenesis between three Malawi cichlid species-Astatotilapia calliptera, Tropheops sp. 'mauve' and Rhamphochromis sp. "chilingali"-representing a wide spectrum of variation in pigmentation and craniofacial morphologies. Our results showed fundamental differences in multiple aspects of embryogenesis that could underlie interspecific divergence in adult adaptive traits. First, we identified variation in the somite number and signatures of temporal variation, or heterochrony, in the rates of somite formation. The heterochrony was also evident within and between species throughout ontogeny, up to the juvenile stages. Finally, the identified interspecific differences in the development of pigmentation and craniofacial cartilages, present at the earliest stages of their overt formation, provide compelling evidence that the species-specific trajectories begin divergence during early embryogenesis, potentially during somitogenesis and NC development. Altogether, our results expand our understanding of fundamental cichlid biology and provide new insights into the developmental origins of vertebrate morphological diversity.

Nicotiana hairy roots for recombinant protein expression, where to start? A systematic review.

BACKGROUND: Hairy roots are a plant-tissue culture raised by Rhizobium rhizogenes infection (formerly known as Agrobacterium rhizogenes). Nowadays, these roots have been gaining more space in biotechnology due to their benefits for the recombinant expression of valuables proteins; it includes simplified downstream processing, protein rhizosecretion, and scalability in bioreactors. However, due to methodological inconsistency among reports, the tissue platform is still a promising technology. METHODS AND RESULTS: In the current paper, we propose the first step to overcome this issue through a systematic review of studies that employ Nicotiana hairy roots for recombinant expression. We conducted a qualitative synthesis of 36 out of 387 publications initially selected. Following the PRISMA procedure, all papers were assessed for exclusion and inclusion criteria. Multiple points of root culture were explored, including transformation methods, root growth curve, external additives, and scale-up with bioreactors to determine which approaches performed best and what is still required to achieve a robust protocol. CONCLUSION: The information presented here may help researchers who want to work with hairy roots in their laboratories trace a successful path to appraisal the literature status.

Neuroimaging findings in paediatric patients with sickle cell disease.

Sickle cell disease (SCD) is an autosomal recessive haemoglobinopathy, which manifests as multisystem ischaemia and infarction, as well as haemolytic anaemia. The morphological changes of red blood cells (RBCs) that promote ischaemia/infarction as the main multi-systemic manifestation, with associated vasculopathy, may also lead to haemorrhage and fat embolisation. Bone infarctions, whether of the skull or spine, are relatively common with subsequent increased infectious susceptibility. We present a broad spectrum of brain and spine imaging findings of SCD from a level III paediatric hospital in Lisbon, between 2010 and 2022. Our aim is to highlight brain and spine imaging findings from a serial review of multiple patients with SCD and respective neuroimaging characterisation.

Frequency of non-aureus staphylococci and mammaliicocci species isolated from quarter clinical mastitis: a six-year retrospective study.

Non-aureus staphylococci and mammaliicocci (NASM) are the most frequently isolated bacterial group from bovine milk samples. Most studies focus on subclinical mastitis caused by NASM, however NASM can cause clinical mastitis (CM) as well. We evaluated retrospective data from 6 years (2017-2022) to determine the species and frequency of NASM isolated from quarter bovine CM. The data comprised of microbiological results from quarter CM samples routinely submitted to Quality Milk Production Services (QMPS), Cornell University, NY, US, for microbial identification by MALDI-TOF MS. A total of 9,909 microbiological results from 410 dairy herds were evaluated. Our results showed that 29 distinct NASM species were identified, with the 8 most prevalent NASM species being Staphylococcus chromogenes, S. haemolyticus, S. simulans, S. epidermidis, S. sciuri (now Mammaliicoccus sciuri), S. agnetis/S. hyicus, S. borealis, and S. xylosus. The NASM distribution remained similar among seasons, but the frequency of NASM CM cases was higher during the summer. Our results showed different patterns of variations in the isolation frequency over time, depending on the bacterial species: increasing or decreasing trends, cyclic fluctuations, and except for S. borealis, a significant seasonality effect for our study's most prevalent NASM was observed. This study showed that S. chromogenes remains the most frequent (43%) NASM species identified from bovine CM, followed by S. haemolyticus (18%), and S. simulans (12%).

Molecular detection of Babesia spp. and Rickettsia spp. in coatis (Nasua nasua) and associated ticks from midwestern Brazil.

Procyonids are reservoirs of many zoonotic infectious diseases, including tick-borne pathogens. The role of coatis (Nasua nasua) in the epidemiology of piroplasmids and Rickettsia has not been fully addressed in Brazil. To molecularly study these agents in coatis and associated ticks, animals were sampled in two urban areas in Midwestern Brazil. Blood (n = 163) and tick (n = 248) DNA samples were screened by PCR assays targeting the 18S rRNA and gltA genes of piroplasmids and Rickettsia spp., respectively. Positive samples were further molecularly tested targeting cox-1, cox-3, ß-tubulin, cytB, and hsp70 (piroplasmid) and ompA, ompB, and htrA 17-kDa (Rickettsia spp.) genes, sequenced and phylogenetically analyzed. All coatis' blood samples were negative for piroplasmids, whereas five pools of ticks (2%) were positive for two different sequences of Babesia spp.. The first from Amblyomma sculptum nymphs was close (i.e., ≥ 99% nucleotide identity) to a Babesia sp. previously found in capybaras (Hydrochoerus hydrochaeris); the second from Amblyomma dubitatum nymphs and Amblyomma spp. larvae was identical (100% nucleotide identity) to a Babesia sp. detected in opossums (Didelphis albiventris) and associated ticks. Four samples (0.8%) were positive by PCR to two different Rickettsia spp. sequences, being the first from Amblyomma sp. larva identical to Rickettsia belli and the second from A. dubitatum nymph identical to Rickettsia species from Spotted Fever Group (SFG). The detection of piroplasmids and SFG Rickettsia sp. highlights the importance of Amblyomma spp. in the maintenance of tick-borne agents in urban parks where humans and wild and domestic animals are living in sympatry.

Evidence of high compliance and fatigue in mask adherence in two mandates in Barcelona, Spain: a naturalistic observational study.

OBJECTIVE: We investigated a possible pandemic fatigue effect, comparing adherence to compulsory mask use outdoors in Barcelona during the fourth and sixth waves of the pandemic. STUDY DESIGN: We used naturalistic observation to determine the degree of pedestrians' compliance. METHODS: We assessed mask use outdoors in a sample of pedestrians in Barcelona between 28 December 2021 and 9 February 2022 (during the sixth wave in Spain), and compared it with the fourth wave (which was between 5 April 2021 and 29 April 2021). Masks were compulsory in both periods. RESULTS: The population studied amounted to 45,116 people (21,246 in the fourth wave and 23,870 in the sixth wave). In the sixth wave, only 67.3% wore a mask correctly, 18.6% did so incorrectly and 14.1% did not wear a mask, while the figures for the fourth wave were 78.2%, 16.3% and 5.5%, respectively (P = 0.001). CONCLUSION: Our results suggest that adherence was high in the population studied, but with an evident fatigue effect when the two waves were compared, as the proportion of individuals wearing a mask correctly declined compared to the fourth wave. These results suggest that policymakers need guidance on adopting clear and enforceable guidelines during future mask mandates, assessing advantages and drawbacks in terms of the population's behavior to prevent the fatigue effect.

Rivastigmine-Benzimidazole Hybrids as Promising Multitarget Metal-Modulating Compounds for Potential Treatment of Neurodegenerative Diseases.

With the goal of combating the multi-faceted Alzheimer's disease (AD), a series of Rivastigmine-Benzimidazole (RIV-BIM) hybrids was recently reported by us as multitarget-directed ligands, thanks to their capacity to tackle important hallmarks of AD. In particular, they exhibited antioxidant activity, acted as cholinesterase inhibitors, and inhibited amyloid-ß (Aß) aggregation. Herein, we moved forward in this project, studying their ability to chelate redox-active biometal ions, Cu(II) and Fe(III), with widely recognized roles in the generation of oxidative reactive species and in protein misfolding and aggregation in both AD and Parkinson's disease (PD). Although Cu(II) chelation showed higher efficiency for the positional isomers of series 5 than those of series 4 of the hybrids, the Aß-aggregation inhibition appears more dependent on their capacity for fibril intercalation than on copper chelation. Since monoamine oxidases (MAOs) are also important targets for the treatment of AD and PD, the capacity of these hybrids to inhibit MAO-A and MAO-B was evaluated, and they showed higher activity and selectivity for MAO-A. The rationalization of the experimental evaluations (metal chelation and MAO inhibition) was supported by computational molecular modeling studies. Finally, some compounds showed also neuroprotective effects in human neuroblastoma (SH-SY5Y cells) upon treatment with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxic metabolite of a Parkinsonian-inducing agent.

Wasted leg syndrome: An atypical slowly-progressive form of lower motor neuron disease.

We describe four male patients with wasted-leg syndrome, with predominant asymmetric thigh atrophy and weakness that stabilized after a period of slow progression (follow-up 7-18 years). Two patients had an Indian ethnic background and two were Portuguese, without known Indian ancestry. Other mimicking disorders were excluded, but one Indian patient was later diagnosed with CADASIL. Electromyography (EMG) revealed severe chronic neurogenic changes in proximal leg muscles, and mild changes in distal leg muscles, but EMG of the upper limbs was normal. Upper motor neuron signs were absent clinically and on transcranial magnetic stimulation. This seems to represent a variant of the common wasted-leg syndrome presentation.