A miniaturized additive-manufactured carbon black/PLA electrochemical sensor for pharmaceuticals detection.

Additive manufacturing is a technique that allows the construction of prototypes and has evolved a lot in the last 20 years, innovating industrial fabrication processes in several areas. In chemistry, additive manufacturing has been used in several functionalities, such as microfluidic analytical devices, energy storage devices, and electrochemical sensors. Theophylline and paracetamol are important pharmaceutical drugs where overdosing can cause adverse effects, such as tachycardia, seizures, and even renal failure. Therefore, this paper aims at the development of miniaturized electrochemical sensors using 3D printing and polylactic acid-based conductive carbon black commercial filament for theophylline and paracetamol detection. Electrochemical characterizations of the proposed sensor were performed to prove the functionality of the device. Morphological characterizations were carried out, in which chemical treatment could change the surface structure, causing the improvement of the analytical signal. Thus, the detection of theophylline at a linear range of 5.00-150 µmol L-1 with a limit of detection of 1.2 µmol L-1 was attained, and the detection of paracetamol at a linear range of 1.00-200 µmol L-1 with a limit of detection of 0.370 µmol L-1 was obtained, demonstrating the proposed sensor effectively detected pharmaceutical drugs.

Effect of antihypertensive agents on sleep apnea and ambulatory blood pressure in patients with hypertension: A randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). METHODS: In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10-40 apneas/hour of sleep) and BP within the systolic range of 140-159 mmHg or diastolic range of 90-99 mmHg. RESULTS: The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24-h, and nighttime ABP, but the two groups had no significant difference. CONCLUSION: Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01896661.

Using historical habitat loss to predict contemporary mammal extirpations in Neotropical forests.

Understanding which species will be extirpated in the aftermath of large-scale human disturbance is critical to mitigating biodiversity loss, particularly in hyperdiverse tropical biomes. Deforestation is the strongest driver of contemporary local extinctions in tropical forests but may occur at different tempos. The 2 most extensive tropical forest biomes in South America-the Atlantic Forest and the Amazon-have experienced historically divergent pathways of habitat loss and biodiversity decay, providing a unique case study to investigate rates of local species persistence on a single continent. We quantified medium- to large-bodied mammal species persistence across these biomes to elucidate how landscape configuration affects their persistence and associated ecological functions. We collected occurrence data for 617 assemblages of medium- to large-bodied mammal species (>1 kg) in the Atlantic Forest and the Amazon. Analyzing natural habitat cover based on satellite data (1985-2022), we employed descriptive statistics and generalized linear models (GLMs) to investigate ecospecies occurrence patterns in relation to habitat cover across the landscapes. The subregional erosion of Amazonian mammal assemblage diversity since the 1970s mirrors that observed since the colonial conquest of the Atlantic Forest, given that 52.8% of all Amazonian mammals are now on a similar trajectory. Four out of 5 large mammals in the Atlantic Forest were prone to extirpation, whereas 53% of Amazonian mammals were vulnerable to extirpation. Greater natural habitat cover increased the persistence likelihood of ecospecies in both biomes. These trends reflected a median local species loss 63.9% higher in the Atlantic Forest than in the Amazon, which appears to be moving toward a turning point of forest habitat loss and degradation. The contrasting trajectories of species persistence in the Amazon and Atlantic Forest domains underscore the importance of considering historical habitat loss pathways and regional biodiversity erosion in conservation strategies. By focusing on landscape configuration and identifying essential ecological functions associated with large vertebrate species, conservation planning and management practices can be better informed.

Uso de la pérdida histórica de hábitat para predecir la desaparición de mamíferos contemporáneos en los bosques neotropicales Resumen Tener conocimiento de cuáles especies desaparecerán después de una perturbación humana es de suma importancia para mitigar la pérdida de la biodiversidad, particularmente en los biomas híper diversos. La deforestación es la principal causante de las extinciones locales contemporáneas en los bosques tropicales, aunque puede ocurrir en diferentes tiempos. Los dos bosques tropicales más extensos de América del Sur - el Bosque Atlántico y la Amazonia - han experimentado formas históricamente divergentes de pérdida de hábitat y decadencia de biodiversidad, lo que proporciona un caso único de estudio para investigar las tasas de persistencia de las especies locales en un solo continente. Cuantificamos la persistencia de las especies de mamíferos de talla mediana a grande en estos dos bosques para aclarar cómo la configuración del paisaje afecta su persistencia y las funciones ecológicas asociadas. Recolectamos datos de presencia de 617 ensambles de especies de mamíferos de talla mediana a grande (>1 kg) en el Bosque Atlántico y en la Amazonia. Analizamos la cobertura natural del hábitat con base en datos satelitales (1985-2022) y empleamos estadística descriptiva y modelos lineales generalizados (MLG) para investigar los patrones de presencia de las eco especies en relación con la cobertura del hábitat en los distintos paisajes. La erosión subregional de la diversidad de ensambles de mamíferos en la Amazonia desde los 70s es igual a la observada en el Bosque Atlántico desde la conquista colonial, dado que 52.8% de todos los mamíferos amazónicos se encuentran en una trayectoria similar. Cuatro de los cinco grandes mamíferos en el Bosque Atlántico estaban propensos a desaparecer, mientras que el 53% de los mamíferos amazónicos estaban vulnerables a desaparecer. Una mayor cobertura natural del hábitat incrementó la probabilidad de persistencia de las eco especies en ambos bosques. Estas tendencias reflejaron una pérdida mediana de especies locales 63.9% mayor en el Bosque Atlántico que en la Amazonia, lo cual parece dirigirse hacia un momento decisivo para la degradación y pérdida del hábitat del bosque. Las trayectorias contrastantes de la persistencia de especies en el Bosque Atlántico y la Amazonia destacan la importancia de considerar dentro de las estrategias de conservación las maneras en las que se ha perdido históricamente el hábitat y la erosión de la biodiversidad regional. Si nos enfocamos en la configuración del paisaje y en la identificación de las funciones ecológicas esenciales asociadas con las especies grandes de vertebrados, podemos informar de mejor manera a la planeación de la conservación y las prácticas de manejo.

The historical ecology of the world's largest tropical country uniquely chronicled by its municipal coat-of-arms symbology.

Coats-of-arms representing municipal counties express local patterns of rural economics, natural resource and land use, features of the natural capital, and the cultural heritage of either aborigines or colonists. We reconstruct the subnational economic and political timeline of the world's largest tropical country using municipal coats-of-arms to reinterpret Brazil's historical ecology. We assessed all natural resource, biophysical, agricultural, and ethnocultural elements of 5,197 coats-of-arms (93.3%) distributed throughout Brazil. We extracted socioenvironmental co-variables for any municipality to understand and predict the relationships between social inequality, environmental degradation, and the historical ecology symbology. We analyzed data via ecological networks and structural equation models. Our results show that the portfolio of political-administrative symbology in coats-of-arms is an underutilized tool to understand the history of colonization frontiers. Although Brazil is arguably Earth's most species-rich country, generations of political leaders have historically failed to celebrate this biodiversity, instead prioritizing a symbology depicted by icons of frontier conquest and key natural resources. Brazilian historical ecology reflects the relentless depletion of the natural resource capital while ignoring profound social inequalities. Degradation of natural ecosystems is widespread in Brazilian economy, reflecting a legacy of boom-and-bust rural development that so far has failed to deliver sustainable socioeconomic prosperity.

Investigation of the impact of AXL, TLR3, and STAT2 in congenital Zika syndrome through genetic polymorphisms and protein-protein interaction network analyses.

INTRODUCTION: Zika virus (ZIKV) is a human teratogen that causes congenital Zika syndrome (CZS). AXL, TLR3, and STAT2 are proteins involved in the ZIKV's entry into cells (AXL) and host's immune response (TLR3 and STAT2). In this study, we evaluated the role of genetic polymorphisms in these three genes as risk factors to CZS, and highlighted which proteins that interact with them could be important for ZIKV infection and teratogenesis. MATERIALS AND METHODS: We evaluate eighty-eight children exposed to ZIKV during the pregnancy, 40 with CZS and 48 without congenital anomalies. The evaluated polymorphisms in AXL (rs1051008), TLR3 (rs3775291), and STAT2 (rs2066811) were genotyped using TaqMan® Genotyping Assays. A protein-protein interaction network was created in STRING database and analyzed in Cytoscape software. RESULTS: We did not find any statistical significant association among the polymorphisms and the occurrence of CZS. Through the analyses of the network composed by AXL, TLR3, STAT2 and their interactions targets, we found that EGFR and SRC could be important proteins for the ZIKV infection and its teratogenesis. CONCLUSION: In summary, our results demonstrated that the evaluated polymorphisms do not seem to represent risk factors for CZS; however, EGFR and SRC appear to be important proteins that should be investigated in future studies.

Effects of chlorthalidone plus amiloride compared with amlodipine on short-term blood pressure variability in individuals with hypertension and obstructive sleep apnea: a randomized controlled trial.

OBJECTIVE: To compare the effects of chlortalidone plus amiloride and amlodipine on blood pressure (BP) variability in patients with hypertension and obstructive sleep apnea syndrome (OSA). METHODS: A randomized, controlled, double-blind trial enrolled men and women aged 40 years or older with a diagnosis of OSA (apnea-hypopnea index 10-40 apneas/h of sleep) confirmed by overnight laboratory polysomnography and systolic BP 140-159 mmHg or diastolic BP 90-99 mmHg. Participants were randomized to receive chlortalidone 25 mg plus amiloride 5 mg daily or amlodipine 10 mg daily for 8 weeks. BP variability was calculated from 24-hour ambulatory BP monitoring at baseline and follow-up using the following indices: SD, coefficient of variation, average real variability (ARV), time-rate index, and variability independent of the mean (VIM). RESULTS: The study included 65 patients, with 33 assigned to the chlortalidone plus amiloride group and 32 to the amlodipine group. Participants in both groups had similar baseline characteristics. Short-term BP variability decreased within groups for SD and ARV indexes for 24-hour systolic BP and daytime systolic BP, but statistically significant time*group interactions were found for sleep systolic SD and VIM, with greater reduction in patients treated with amlodipine. CONCLUSION: In brief, our study has shown that the use of chlorthalidone in combination with amiloride and amlodipine produces comparable effects on short-term BP variability in patients with hypertension and OSA. Therefore, our findings suggest that BP variability may not be a significant factor when choosing between these medications for the treatment of hypertension and OSA.

Effects of Antihypertensive Treatment on Left and Right Ventricular Global Longitudinal Strain and Diastolic Parameters in Patients with Hypertension and Obstructive Sleep Apnea: Randomized Clinical Trial of Chlorthalidone plus Amiloride vs. Amlodipine.

Hypertension is highly prevalent in patients with obstructive sleep apnea (OSA), and fluid retention with its nighttime rostral distribution is one potential mechanism. We tested whether or not diuretics differ from amlodipine in their impact on echocardiographic parameters. Patients with moderate OSA and hypertension were randomized to receive diuretics (chlorthalidone plus amiloride) or amlodipine daily for 8 weeks. We compared their effects on left and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively), on LV diastolic parameters, and on LV remodeling. In the 55 participants who had echocardiographic images feasible for strain analysis, all echocardiographic parameters were within normal ranges. After 8 weeks, the 24 h blood pressure (BP) reduction values were similar, while most echocardiographic metrics were kept unchanged, except for LV-GLS and LV mass. In conclusion, the use of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension, suggesting that they do not have important effects on mediating the interaction between OSA and hypertension.

Circular Economy Electrochemistry: Recycling Old Mixed Material Additively Manufactured Sensors into New Electroanalytical Sensing Platforms.

Recycling used mixed material additively manufactured electroanalytical sensors into new 3D-printing filaments (both conductive and non-conductive) for the production of new sensors is reported herein. Additively manufactured (3D-printed) sensing platforms were transformed into a non-conductive filament for fused filament fabrication through four different methodologies (granulation, ball-milling, solvent mixing, and thermal mixing) with thermal mixing producing the best quality filament, as evidenced by the improved dispersion of fillers throughout the composite. Utilizing this thermal mixing methodology, and without supplementation with the virgin polymer, the filament was able to be cycled twice before failure. This was then used to process old sensors into an electrically conductive filament through the addition of carbon black into the thermal mixing process. Both recycled filaments (conductive and non-conductive) were utilized to produce a new electroanalytical sensing platform, which was tested for the cell's original application of acetaminophen determination. The fully recycled cell matched the electrochemical and electroanalytical performance of the original sensing platform, achieving a sensitivity of 22.4 ± 0.2 µA µM-1, a limit of detection of 3.2 ± 0.8 µM, and a recovery value of 95 ± 5% when tested using a real pharmaceutical sample. This study represents a paradigm shift in how sustainability and recycling can be utilized within additively manufactured electrochemistry toward promoting circular economy electrochemistry.

Impending anthropogenic threats and protected area prioritization for jaguars in the Brazilian Amazon.

Jaguars (Panthera onca) exert critical top-down control over large vertebrates across the Neotropics. Yet, this iconic species have been declining due to multiple threats, such as habitat loss and hunting, which are rapidly increasing across the New World tropics. Based on geospatial layers, we extracted socio-environmental variables for 447 protected areas across the Brazilian Amazon to identify those that merit short-term high-priority efforts to maximize jaguar persistence. Data were analyzed using descriptive statistics and comparisons of measures of central tendency. Our results reveal that areas containing the largest jaguar densities and the largest estimated population sizes are precisely among those confronting most anthropogenic threats. Jaguars are threatened in the world's largest tropical forest biome by deforestation associated with anthropogenic fires, and the subsequent establishment of pastures. By contrasting the highest threats with the highest jaguar population sizes in a bivariate plot, we provide a shortlist of the top-10 protected areas that should be prioritized for immediate jaguar conservation efforts and 74 for short-term action. Many of these are located at the deforestation frontier or in important boundaries with neighboring countries (e.g., Peruvian, Colombian and Venezuelan Amazon). The predicament of a safe future for jaguars can only be ensured if protected areas persist and resist downgrading and downsizing due to both external anthropogenic threats and geopolitical pressures (e.g., infrastructure development and frail law enforcement).

Retrospective Analysis of the Association of a Small Vestibular Aqueduct with Cochleovestibular Symptoms in a Large, Single-Center Cohort Undergoing CT.

BACKGROUND AND PURPOSE: Temporal bones in some patients with Ménière disease have demonstrated small vestibular aqueducts; however, the prevalence and clinical importance of small vestibular aqueducts remain unclear in patients without Ménière disease. This study correlates the presence of a small vestibular aqueduct with cochleovestibular symptoms. MATERIALS AND METHODS: Consecutive temporal bone CTs in adults from January to December 2020 were reviewed. The midpoint vestibular aqueduct size in the 45°-oblique Pöschl view was measured by 2 reviewers independently in 684 patients (1346 ears). Retrospective chart review for the clinical diagnosis of Ménière disease, the presence of cochleovestibular symptoms, and indications for CT was performed. RESULTS: Fifty-two of 684 patients (7.6% of patients, 62/1346 ears) had small vestibular aqueducts. Twelve patients (15/1346 ears) had Ménière disease. Five of 12 patients with Ménière disease (5 ears) had a small vestibular aqueduct. There was a significant correlation between a small vestibular aqueduct and Ménière disease (P < .001). There was no statistical difference between the small vestibular aqueduct cohort and the cohort with normal vestibular aqueducts (0.3-0.7 mm) regarding tinnitus (P = .06), hearing loss (P = .88), vertigo (P = .26), dizziness (P = .83), and aural fullness (P = .61). CONCLUSIONS: While patients with Ménière disease were proportionately more likely to have a small vestibular aqueduct than patients without Ménière disease, the small vestibular aqueduct was more frequently seen in patients without Ménière disease and had no correlation with hearing loss, vertigo, dizziness, or aural fullness. We suggest that the finding of a small vestibular aqueduct on CT could be reported by radiologists as a possible finding in Ménière disease, but it remains of uncertain, and potentially unlikely, clinical importance in the absence of symptoms of Ménière disease.

Subtle Malformation of the Cochlear Apex and Genetic Abnormalities: Beyond the "Thorny" Cochlea.

With the routine use of high-resolution heavily T2-weighted sequences to evaluate patients with hearing deficits, new, subtle phenotypes of cochlear malformations are being discovered and an increasing number of genotype-phenotype correlations are being found through a reverse phenotype approach, which can help guide geneticists. In this brief report, we present subtle malformations of the apical turn of the cochlea related to 3 genetic mutations, emphasizing the importance of a careful assessment of the cochlear apex.

Molecular Mechanisms of ZIKV-Induced Teratogenesis: A Systematic Review of Studies in Animal Models.

Zika virus (ZIKV) is a teratogen that causes congenital anomalies, being linked to microcephaly in children exposed during pregnancy. Animal studies have been conducted to investigate the molecular mechanisms related to ZIKV teratogenesis. Although animal models can mimic the effects of ZIKV in human embryo development, few in vivo studies have addressed molecular changes following ZIKV infection in embryos. Moreover, few literature reviews have been conducted with these studies. The aim of this systematic review is to evaluate the molecular mechanisms of ZIKV teratogenesis determined from studies in animal models. PubMed/MEDLINE, EMBASE, Web of Science, and Scopus as well as grey literature were searched for studies that evaluated molecular alterations related to ZIKV teratogenesis which occurred during embryonic development. Nine studies were included: six with mice, one with mice and guinea pigs, one with pigs and one with chickens. In general, studies presented an unclear or high risk of bias for methodological criteria. Most of studies reported embryos exposed to ZIKV presenting microcephaly, reduced cortex thickness, and growth restriction. Different techniques were used to evaluated molecular changes in the animals following ZIKV infection: RNA sequencing, RT-qPCR, and in situ hybridization. It was found that common pathways are changed in most studies, being pathways related to immune response upregulated and those involved to neurodevelopment downregulated.

Sensing performances of spinel ferrites MFe2O4 (M = Mg, Ni, Co, Mn, Cu and Zn) based electrochemical sensors: A review.

The history of ferrites comes from many centuries and was fundamental in many fields. Initially, ferrites were extracted directly from nature, but in the last century, scientists learned to produce ferrites with different properties that gave origin to many advances in industrial and instrumental applications. More recently, the designed preparation of ferrites with nanometric size revealed remarkable characteristics. In the last years, different spinel ferrites were used as electroactive layers to build high-performance modified electrodes. In this review, it is presented a critical overview of the utilization of spinel ferrites (with a general formula MFe2O4, where M2+ = Mg2+, Ni2+, Co2+, Cu2+, Mn2+ and Zn2+) to create differentiated voltammetric sensors. The association of these materials with graphene, glassy carbon, carbon nitride, ionic liquids, nanoparticles of noble metals, oxides of transition metals and other materials can produce notable synergic responses towards electrochemical activity. Some of these sensors can produce very sensitive signals and ample concentration ranges for compounds such hydrogen peroxide, glucose and bisphenol A, and present potential for many other applications. Along this review, all these aspects will be discussed and the main results are organized in tables, using as a base the metal associated with the ferrite.

The Cochlea in Branchio-Oto-Renal Syndrome: An Objective Method for the Diagnosis of Offset Cochlear Turns.

BACKGROUND AND PURPOSE: An "unwound" or "offset" cochlea has been described as a characteristic imaging feature in patients with branchio-oto-renal syndrome, and recently recognized to be associated in particular to those with EYA1 gene mutations. Determination of this feature has traditionally relied on subjective visual assessment. Our aim was to establish an objective assessment method for cochlear offset (the cochlear turn alignment ratio) and determine an optimal cutoff turn alignment ratio value that separates individuals with EYA1-branchio-oto-renal syndrome from those with SIX1-branchio-oto-renal syndrome and healthy controls. MATERIALS AND METHODS: Temporal bone CT or MR imaging from 40 individuals with branchio-oto-renal syndrome and 40 controls was retrospectively reviewed. Cochlear offset was determined visually by 2 independent blinded readers and then quantitatively via a standardized technique yielding the cochlear turn alignment ratio. The turn alignment ratio values were compared between cochleae qualitatively assessed as "not offset" and "offset." Receiver operating characteristic analysis was used to determine the ability of the turn alignment ratio to differentiate between these populations and an optimal cutoff turn alignment ratio value. Cochlear offset and turn alignment ratio values were analyzed for each branchio-oto-renal syndrome genotype subpopulation and for controls. RESULTS: The turn alignment ratio can accurately differentiate between cochleae with and without an offset (P < .001). The optimal cutoff value separating these populations was 0.476 (sensitivity = 1, specificity = 0.986, J = 0.986). All except 1 cochlea among the EYA1-branchio-oto-renal syndrome subset and all with unknown genotype branchio-oto-renal syndrome had a cochlear offset and a turn alignment ratio of <0.476. All except 1 cochlea among the SIX1-branchio-oto-renal syndrome subset and all controls had no offset and a turn alignment ratio of >0.476. CONCLUSIONS: There is a statistically significant difference in turn alignment ratios between offset and nonoffset cochleae, with an optimal cutoff of 0.476. This cutoff value allows excellent separation of EYA1-branchio-oto-renal syndrome from SIX1-branchio-oto-renal syndrome and from individuals without branchio-oto-renal syndrome or sensorineural hearing loss. The turn alignment ratio is a reliable and objective metric that can aid in the imaging evaluation of branchio-oto-renal syndrome.

The ABCD stop signal data: Response to Bissett et al.

This paper responds to a recent critique by Bissett et al. of the fMRI Stop task used in the Adolescent Brain Cognitive Development℠ Study (ABCD Study®). The critique focuses primarily on a task design feature related to race model assumptions (i.e., that the Go and Stop processes are fully independent). In response, we note that the race model is quite robust against violations of its assumptions. Most importantly, while Bissett raises conceptual concerns with the task we focus here on analyzes of the task data and conclude that the concerns appear to have minimal impact on the neuroimaging data (the validity of which do not rely on race model assumptions) and have far less of an impact on the performance data than the critique suggests. We note that Bissett did not apply any performance-based exclusions to the data they analyzed, a number of the trial coding errors they flagged were already identified and corrected in ABCD annual data releases, a number of their secondary concerns reflect sensible design decisions and, indeed, their own computational modeling of the ABCD Stop task suggests the problems they identify have just a modest impact on the rank ordering of individual differences in subject performance.

UVA Light-promoted Catalyst-free Cyclization of Vinyl Selenides: Green and Efficient Synthesis of C3-Unsubstituted 2-Selanyl Benzochalcogenophenes.

A metal- and catalyst-free photo-promoted cyclization of properly substituted vinyl selenides was developed using UVA irradiation. A total of eighteen new C3-unsubstituted 2-selanyl benzochalcogenophenes (benzofurans, benzothiophenes and benzoselenophenes) were prepared in 30-86% yield after irradiation with UVA at room temperature. The usefulness of the title compounds was demonstrated in the easy functionalization of the remaining free C-H bond of the benzochalcogenophenes to form new C-Se and C-Br bonds by simple procedures. Furthermore, the reaction can be performed under natural sunlight irradiation and the solvent is easily reused further in several subsequent runs.

Re-Examining the Cochlea in Branchio-Oto-Renal Syndrome: Genotype-Phenotype Correlation.

BACKGROUND AND PURPOSE: Temporal bone imaging plays an important role in the work-up of branchio-oto-renal syndrome. Previous reports have suggested that the unwound or offset cochlea is a highly characteristic marker for branchio-oto-renal syndrome. Our goals were to examine the prevalence of this finding in a branchio-oto-renal syndrome cohort and analyze genetic-phenotypic associations not previously established. MATERIALS AND METHODS: This multicenter retrospective study included 38 ears in 19 unrelated individuals with clinically diagnosed branchio-oto-renal syndrome and confirmed mutations in the EYA1 or SIX1 genes. Two blinded neuroradiologists independently reviewed and documented temporal bone imaging findings in 13 categories for each ear. Imaging phenotypes were correlated with genotypes. RESULTS: There was excellent interrater agreement for all 13 phenotypic categories (κ ≥ 0.80). Of these, 9 categories showed statistically significant differences between patients with EYA1-branchio-oto-renal syndrome and SIX1-branchio-oto-renal syndrome. Cochlear offset was present in 100% of patients with EYA1-branchio-oto-renal syndrome, but in only 1 ear (12.5%) among patients with SIX1-branchio-oto-renal syndrome. A short thorny appearance of the cochlear apical turn was observed in most patients with SIX1-branchio-oto-renal syndrome. CONCLUSIONS: An offset cochlea is associated with the EYA1-branchio-oto-renal syndrome genotype. The SIX1-branchio-oto-renal syndrome genotype is associated with a different cochlear phenotype that almost always is without offset and has a short thorny tip as the apical turn. Therefore, cochlear offset is not a characteristic marker for all patients with branchio-oto-renal syndrome. The lack of a cochlear offset in a patient with clinically suspected branchio-oto-renal syndrome does not exclude the diagnosis and, in fact, may be predictive of the SIX1 genotype.

Multiple Reflections for Classical Particles Moving under the Influence of a Time-Dependent Potential Well.

We study the dynamics of classical particles confined in a time-dependent potential well. The dynamics of each particle is described by a two-dimensional nonlinear discrete mapping for the variables energy en and phase ϕn of the periodic moving well. We obtain the phase space and show that it contains periodic islands, chaotic sea, and invariant spanning curves. We find the elliptic and hyperbolic fixed points and discuss a numerical method to obtain them. We study the dispersion of the initial conditions after a single iteration. This study allows finding regions where multiple reflections occur. Multiple reflections happen when a particle does not have enough energy to exit the potential well and is trapped inside it, suffering several reflections until it has enough energy to exit. We also show deformations in regions with multiple reflection, but the area remains constant when we change the control parameter NC. Finally, we show some structures that appear in the e0e1 plane by using density plots.

Natural history museums and zoological collections of São Paulo State / Museus de história natural e coleções zoológicas do Estado de São Paulo

Abstract Scientific collections constitute a valuable source for contributions to scientific research and the training of human resources in systematics, but also other areas of biological knowledge. In this contribution, we intend to discuss these advancements in collections and the role played by FAPESP in sponsoring them, as well as a general overview of the zoological collections in São Paulo state. We also aim to stress the importance of zoological collections and the need for continuous logistic and financial support from institutions and research agencies to maintain and develop these unique repositories of biodiversity. From 1980 to the present, FAPESP supported 118 research projects focused on several areas of zoology that are directly or indirectly associated with collections. There is a constant growth in the number of projects, and the financial support provided by FAPESP through the Biota Program was paramount for the advancement of our knowledge of biodiversity in Brazil. Parallel to the scientific advances, but not less important, this support allowed curators to increase the number of specimens, and to organize, maintain and digitize them in these valuable and irreplaceable collections. Regarding the lack of new taxonomists, it is essential that FAPESP and universities in São Paulo encourage the formation of new academics in zoological groups where specialists are rare. Considering the investment provided by FAPESP, it is quite important that the institutions that benefited from these resources took greater responsibility to safeguard these collections, and they should consider including resources on their budgets to obtain safety certificates, ensuring their permanence for many generations to come. Zoological collections are a heritage of humanity and are essential not only for the improvement of our knowledge of biodiversity but also with direct applications, among other services provided by these biological resources. It is important that research and teaching institutions in São Paulo that house specimens under their care start to value more this important patrimony and this heritage, as these collections represent the most valuable testimony of our impressive biodiversity, records of our past, and windows to our future, essential to our academic, scientific, cultural and social sovereignty.

Resumo As coleções científicas constituem uma fonte valiosa para contribuições à pesquisa científica e para a formação de recursos humanos em sistemática, mas também em outras áreas do conhecimento biológico. Nesta contribuição, pretendemos discutir esses avanços nas coleções e o papel desempenhado pela FAPESP no seu patrocínio, bem como um panorama geral das coleções zoológicas do estado de São Paulo. Também pretendemos enfatizar a importância das coleções zoológicas e a necessidade de apoio logístico e financeiro contínuo de instituições e agências de pesquisa para manter e desenvolver esses repositórios únicos de biodiversidade. Ao longo de 1980 até os dias atuais, a FAPESP apoiou 118 projetos de pesquisa focados em diversas áreas da zoologia, direta ou indiretamente associados a coleções. Há um crescimento constante no número de projetos, e o apoio financeiro da FAPESP por meio do Programa Biota foi fundamental para o avanço do nosso conhecimento sobre a biodiversidade no Brasil. Paralelamente aos avanços científicos, mas não menos importante, este apoio permitiu aos curadores aumentar o número de exemplares, e organizá-los, mantê-los e digitalizá-los nestas valiosas e insubstituíveis coleções. Em relação à falta de novos taxonomistas, é fundamental que a FAPESP e as universidades paulistas estimulem a formação de novos acadêmicos em grupos zoológicos onde os especialistas são raros. Considerando o investimento realizado pela FAPESP, é de suma importância que as instituições beneficiadas com esses recursos tenham maior responsabilidade na salvaguarda desses acervos, devendo considerar a inclusão de recursos em seus orçamentos para obtenção de certificados de segurança, garantindo sua permanência por muitas gerações. As coleções zoológicas são patrimônio da humanidade, e são essenciais não apenas para o aprimoramento do nosso conhecimento sobre a biodiversidade, mas também com aplicações diretas, entre outros serviços prestados por esses recursos biológicos. É importante que as instituições de pesquisa e ensino paulistas que abrigam exemplares sob seus cuidados passem a valorizar mais esse importante patrimônio e essa herança, pois essas coleções representam o testemunho mais valioso de nossa impressionante biodiversidade, registros do nosso passado e janelas para o nosso futuro, essenciais à nossa soberania acadêmica, científica, cultural e social.

Secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon mRNA vaccination.

In view of the scarcity of data to guide decision making, we evaluated how BNT162b2 and mRNA-1273 vaccines affect the immune response in lactating women and the protective profile of breastmilk. Compared with controls, lactating women had a higher frequency of circulating RBD memory B cells and higher anti-RBD antibody titers but similar neutralizing capacity. We show that upon vaccination, immune transfer to breastmilk occurs through a combination of anti-spike secretory IgA (SIgA) antibodies and spike-reactive T cells. Although we found that the concentration of anti-spike IgA in breastmilk might not be sufficient to directly neutralize SARS-CoV-2, our data suggest that cumulative transfer of IgA might provide the infant with effective neutralization capacity. Our findings put forward the possibility that breastmilk might convey both immediate (through anti-spike SIgA) and long-lived (via spike-reactive T cells) immune protection to the infant. Further studies are needed to address this possibility and to determine the functional profile of spike T cells.