Syphilitic Stomatitis: Raising Awareness on an Often-Overlooked Presentation of Secondary Syphilis.

Syphilis, a disease caused by the bacteria Treponema pallidum, has a multitude of clinical manifestations and is classified into primary syphilis, secondary syphilis and tertiary syphilis, based on clinical presentations and the time elapsed since the primary infection. The secondary stage of the disease can affect multiple organs and systems, and some of these involvements may be general and non-specific, justifying its name as 'the great imitator'. We present a case of a 30-year-old woman with a history of painful neck lymph nodes with progressive enlargement, persistent headache, weight loss, myalgia and alopecia. During investigations, stomatitis on the dorsal face of the tongue developed. A secondary study showed serum positive for rapid plasma reagin (RPR) and T. pallidum haemagglutination (TPHA), negative RPR in cerebrospinal fluid and normal MRI, thus the diagnosis of secondary syphilis was made. The patient was treated with a single dose of penicillin with complete resolution of symptoms. The case highlights the need for an exhaustive clinical examination, especially in cases presenting with non-specific and general symptoms, and raises awareness for this disease which has increased its prevalence in the last decades. LEARNING POINTS: Syphilis is a resurgent infection with increasing prevalence, and its manifestations in the secondary stage of the disease are general and non-specific, being able to affect every organ system.The oral mucosa may be involved at any stage of the disease and the tongue, often a neglected organ, can be particularly affected and should be routinely observed.The internist, integrating a cornerstone speciality able to manage and diagnose systemic diseases, must be aware of the individual aspects of the physical examination, notably the appreciation and interpretation of each clue and sign found.

Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models.

Combinations of the topoisomerase II inhibitor doxorubicin and the poly (ADP-ribose) polymerase inhibitor olaparib offer potential drug-drug synergy for the treatment of triple negative breast cancers (TNBC). In this study we performed in vitro screening of combinations of these drugs, administered directly or encapsulated within polymer nanoparticles, in both 2D and in 3D spheroid models of breast cancer. A variety of assays were used to evaluate drug potency, and calculations of combination index (CI) values indicated that synergistic effects of drug combinations occurred in a molar-ratio dependent manner. It is suggested that the mechanisms of synergy were related to enhancement of DNA damage as shown by the level of double-strand DNA breaks, and mechanisms of antagonism associated with mitochondrial mediated cell survival, as indicated by reactive oxygen species (ROS) generation. Enhanced drug delivery and potency was observed with nanoparticle formulations, with a greater extent of doxorubicin localised to cell nuclei as evidenced by microscopy, and higher cytotoxicity at the same time points compared to free drugs. Together, the work presented identifies specific combinations of doxorubicin and olaparib which were most effective in a panel of TNBC cell lines, explores the mechanisms by which these combined agents might act, and shows that formulation of these drug combinations into polymeric nanoparticles at specific ratios conserves synergistic action and enhanced potency in vitro compared to the free drugs.

From synaptic dysfunction to atypical emotional processing in autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition mainly characterized by social impairments and repetitive behaviors. Among these core symptoms, a notable aspect of ASD is the presence of emotional complexities, including high rates of anxiety disorders. The inherent heterogeneity of ASD poses a unique challenge in understanding its etiological origins, yet the utilization of diverse animal models replicating ASD traits has enabled researchers to dissect the intricate relationship between autism and atypical emotional processing. In this review, we delve into the general findings about the neural circuits underpinning one of the most extensively researched and evolutionarily conserved emotional states: fear and anxiety. Additionally, we explore how distinct ASD animal models exhibit various anxiety phenotypes, making them a crucial tool for dissecting ASD's multifaceted nature. Overall, to a proper display of fear response, it is crucial to properly process and integrate sensorial and visceral cues to the fear-induced stimuli. ASD individuals exhibit altered sensory processing, possibly contributing to the emergence of atypical phobias, a prevailing anxiety disorder manifested in this population. Moreover, these individuals display distinctive alterations in a pivotal fear and anxiety processing hub, the amygdala. By examining the neurobiological mechanisms underlying fear and anxiety regulation, we can gain insights into the factors contributing to the distinctive emotional profile observed in individuals with ASD. Such insights hold the potential to pave the way for more targeted interventions and therapies that address the emotional challenges faced by individuals within the autism spectrum.

Enabling genome editing in tropical maize lines through an improved, morphogenic regulator-assisted transformation protocol.

The recalcitrance exhibited by many maize (Zea mays) genotypes to traditional genetic transformation protocols poses a significant challenge to the large-scale application of genome editing (GE) in this major crop species. Although a few maize genotypes are widely used for genetic transformation, they prove unsuitable for agronomic tests in field trials or commercial applications. This challenge is exacerbated by the predominance of transformable maize lines adapted to temperate geographies, despite a considerable proportion of maize production occurring in the tropics. Ectopic expression of morphogenic regulators (MRs) stands out as a promising approach to overcome low efficiency and genotype dependency, aiming to achieve 'universal' transformation and GE capabilities in maize. Here, we report the successful GE of agronomically relevant tropical maize lines using a MR-based, Agrobacterium-mediated transformation protocol previously optimized for the B104 temperate inbred line. To this end, we used a CRISPR/Cas9-based construct aiming at the knockout of the VIRESCENT YELLOW-LIKE (VYL) gene, which results in an easily recognizable phenotype. Mutations at VYL were verified in protoplasts prepared from B104 and three tropical lines, regardless of the presence of a single nucleotide polymorphism (SNP) at the seed region of the VYL target site in two of the tropical lines. Three out of five tropical lines were amenable to transformation, with efficiencies reaching up to 6.63%. Remarkably, 97% of the recovered events presented indels at the target site, which were inherited by the next generation. We observed off-target activity of the CRISPR/Cas9-based construct towards the VYL paralog VYL-MODIFIER, which could be partly due to the expression of the WUSCHEL (WUS) MR. Our results demonstrate efficient GE of relevant tropical maize lines, expanding the current availability of GE-amenable genotypes of this major crop.

Paradoxical Immune Reconstitution Inflammatory Syndrome in SARS-CoV-2 Infection After Improvement of Chemotherapy-Induced Aplasia.

Severe coronavirus disease 2019 (COVID-19) is known to manifest in two phases, with a potential worsening in the second week. The pathophysiology of the first phase is expected to be heavily influenced by viral replication while the second phase is thought to be primarily characterized by systemic inflammation. We present the case of a 42-year-old man hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with a history of Philadelphia-positive chronic myeloid leukemia, diagnosed seven months earlier, proposed to bone marrow allotransplantation after refractory imatinib and dasatinib treatment. After an initial clinical and laboratory improvement, the patient got worse. A pulmonary CT scan showed worsening ground-glass opacities and multiple bilateral consolidations. Neutropenia was resolved, and on the same day, the patient developed progressive respiratory failure with rapidly increasing oxygen demand and distributive shock, requiring mechanical ventilation. Acute respiratory distress syndrome (ARDS) induced by paradoxical COVID-19 immune reconstitution inflammatory syndrome (IRIS) following chemotherapy-induced aplasia was equated. High-dose corticosteroid therapy was rapidly effective. IRIS occurs in patients with severe immunosuppression in response to rapid immune reconstitution and results in an uncontrolled inflammatory response to infectious agents that cause tissue damage. The inflammation associated with both IRIS and COVID-19 shares a common path in terms of immunological response. We hypothesize that in our patient, a hyperinflammation overlap exerted a synergistic effect, leading to the worsening of the disease.

Chronic treatment with D2-antagonist haloperidol leads to inhibitory/excitatory imbalance in striatal D1-neurons.

Striatal dysfunction has been implicated in the pathophysiology of schizophrenia, a disorder characterized by positive symptoms such as hallucinations and delusions. Haloperidol is a typical antipsychotic medication used in the treatment of schizophrenia that is known to antagonize dopamine D2 receptors, which are abundantly expressed in the striatum. However, haloperidol's delayed therapeutic effect also suggests a mechanism of action that may go beyond the acute blocking of D2 receptors. Here, we performed proteomic analysis of striatum brain tissue and found more than 400 proteins significantly altered after 30 days of chronic haloperidol treatment in mice, namely proteins involved in glutamatergic and GABAergic synaptic transmission. Cell-type specific electrophysiological recordings further revealed that haloperidol not only reduces the excitability of striatal medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) but also affects D1-MSNs by increasing the ratio of inhibitory/excitatory synaptic transmission (I/E ratio) specifically onto D1-MSNs but not D2-MSNs. Therefore, we propose the slow remodeling of D1-MSNs as a mechanism mediating the delayed therapeutic effect of haloperidol over striatum circuits. Understanding how haloperidol exactly contributes to treating schizophrenia symptoms may help to improve therapeutic outcomes and elucidate the molecular underpinnings of this disorder.

Chronic stress promotes basal ganglia disinhibition by increasing the excitatory drive of direct-pathway neurons.

Chronic stress (CS) is a well-recognized triggering factor in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS), two neuropsychiatric disorders characterized by the presence of stereotypic motor symptoms. Planning and execution of motor actions are controlled by the dorsal striatum, a brain region that promotes or suppresses motor movement by activating striatal neurons from the direct- or indirect-pathway, respectively. Despite the dorsal striatum being affected in motor disorders and by CS exposure, how CS affects the two opposing pathways is not fully understood. Here, we report that CS in mice selectively potentiates the direct-pathway, while sparing the indirect-pathway. Specifically, we show that CS both increases excitation and reduces inhibition over direct-pathway neurons in the dorsomedial striatum (DMS). Furthermore, inhibitory interneurons located in the DMS also display reduced excitatory drive after chronic stress, thus amplifying striatal disinhibition. Altogether, we propose a model where both increased excitatory drive and decreased inhibitory drive in the striatum causes disinhibition of basal ganglia's motor direct pathway - a mechanism that might explain the emergence of motor stereotypies and tic disorders under stress.

The Shank3-InsG3680(+/+) mouse model of autism spectrum disorder displays auditory avoidance in a novel behavioral test.

Introduction: Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, repetitive behaviors, and sensory alterations, with auditory hypersensitivity being one of the most commonly reported sensory-perceptual abnormalities. Several candidate genes for involvement in this disorder have emerged from patient studies, including SHANK3, a gene that encodes a protein (SHANK3) in the postsynaptic density of excitatory synapses. Previous work has shown that mutant mice carrying a human ASD mutation in the Shank3 gene (InsG3680) exhibit repetitive behaviors and social interaction deficits, indicating important construct and face validity for this genotype as an animal model of ASD. Methods: To further address whether these mice also present auditory sensory-perceptual alterations, we developed a novel behavioral test in which mice can choose between different soundscapes. Results: Our results reveal that, in comparison to wild-type mice, Shank3 mutants display a strong behavioral preference toward silent regions of the arena. Discussion: These data suggest that Shank3- mutant mice might express an auditory hypersensitivity phenotype, further adding to the face validity of this genotype as an animal model of ASD.

Fracture Resistance of Fiber-Reinforced Composite Restorations: A Systematic Review and Meta-Analysis.

Composite resin is universally used for posterior teeth restorations. Fibers have been suggested for the mechanical improvement of the restorations. This study assessed the fracture resistance of class II fiber-reinforced composite restorations and compared it with the fracture resistance of three control groups: (1) healthy teeth, (2) non-fiber-reinforced restorations and (3) unrestored cavities. A search was performed using PubMed, Web of Science and Google Scholar from 15 May to 12 June 2023. Only in vitro studies from the last 10 years were included for this systematic analysis. This study was registered in the PROSPERO database, it followed PRISMA guidelines and the risk of bias was assessed using the QUIN tool. Fracture resistance median values, in Newtons (N), were calculated for the experimental and control groups (95% confidence interval). For pairwise comparison, nonparametric tests (p < 0.05) were applied. Twenty-four in vitro studies met the inclusion criteria. The fracture resistance of the experimental group was 976.0 N and differed (p < 0.05) from all controls. The experimental group showed lower values of fracture resistance than healthy teeth (1459.9 N; p = 0.048) but higher values than non-fiber-reinforced restorations (771.0 N; p = 0.008) and unrestored cavities (386.6 N; p < 0.001). In vitro systematic outcomes evidenced that glass and/or polyethylene fibers improved the fracture resistance of composite restorations.

Providing office workers with height-adjustable workstation to reduce and interrupt workplace sitting time: protocol for the Stand Up for Healthy Aging (SUFHA) cluster randomized controlled trial.

BACKGROUND: Sedentary behavior (SB) has been linked to several negative health outcomes. Therefore, reducing SB or breaking up prolonged periods of SB improves functional fitness, food consumption, job satisfaction, and productivity. Reducing SB can be achieved by introducing a health-enhancing contextual modification promoted by a sit-stand desk in the workplace. The primary goal will be to test the effectiveness of this intervention in reducing and breaking up SB, while improving health outcomes in office-based workers during a 6-month intervention. METHODS: A two-arm (1:1), superiority parallel-group cluster RCT will be conducted to evaluate the effectiveness of this intervention in a sample of office-based workers from a university in Portugal. The intervention will consist of a psychoeducation session, motivational prompts, and contextual modification promoted by a sit-stand desk in the workplace for 6 months. The control group will work as usual in their workplace, with no contextual change or prompts during the 6-month intervention. Three assessment points will be conducted in both groups, pre-intervention (baseline), post-intervention, and a 3-month follow-up. The primary outcomes include sedentary and physical activity-related variables, which will be objectively assessed with 24 h monitoring using the ActivPAL for 7 days. The secondary outcomes include (a) biometric indices as body composition, body mass index, waist circumference, and postural inequalities; and (b) psychosocial variables such as overall and work-related fatigue, overall discomfort, life/work satisfaction, quality of life, and eating behavior. Both the primary and secondary outcomes will be assessed at each assessment point. DISCUSSION: This study will lean on the use of a sit-stand workstation for 6 months, prompted by an initial psychoeducational session and ongoing motivational prompts. We will aim to contribute to this topic by providing robust data on alternating sitting and standing postures in the workplace. TRIAL REGISTRATION: The trial was prospectively registered, and the details are at: https://doi.org/10.17605/OSF.IO/JHGPW ; Registered 15 November 2022. OSF Preregistration.

Autism Spectrum Disorder and auditory sensory alterations: a systematic review on the integrity of cognitive and neuronal functions related to auditory processing.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with a wide spectrum of symptoms, mainly characterized by social, communication, and cognitive impairments. Latest diagnostic criteria according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, 2013) now include sensory issues among the four restricted/repetitive behavior features defined as "hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of environment". Here, we review auditory sensory alterations in patients with ASD. Considering the updated diagnostic criteria for ASD, we examined research evidence (2015-2022) of the integrity of the cognitive function in auditory-related tasks, the integrity of the peripheral auditory system, and the integrity of the central nervous system in patients diagnosed with ASD. Taking into account the different approaches and experimental study designs, we reappraise the knowledge on auditory sensory alterations and reflect on how these might be linked with behavior symptomatology in ASD.

Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries.

Approximately 15 million babies are born prematurely every year and many will face lifetime motor and/or cognitive deficits. Children born prematurely are at higher risk of developing perinatal brain lesions, especially white matter injuries (WMI). Evidence in humans and rodents demonstrates that systemic inflammation-induced neuroinflammation, including microglial and astrocyte reactivity, is the prominent processes of WMI associated with preterm birth. Thus, a new challenge in the field of perinatal brain injuries is to develop new neuroprotective strategies to target neuroinflammation to prevent WMI. Serotonin (5-HT) and its receptors play an important role in inflammation, and emerging evidence indicates that 5-HT may regulate brain inflammation by the modulation of microglial reactivity and astrocyte functions. The present study is based on a mouse model of WMI induced by intraperitoneal (i.p.) injections of IL-1ß during the first 5 days of life. In this model, certain key lesions of preterm brain injuries can be summarized by (i) systemic inflammation, (ii) pro-inflammatory microglial and astrocyte activation, and (iii) inhibition of oligodendrocyte maturation, leading to hypomyelination. We demonstrate that Htr7 mRNA (coding for the HTR7/5-HT7 receptor) is significantly overexpressed in the anterior cortex of IL-1ß-exposed animals, suggesting it as a potential therapeutic target. LP-211 is a specific high-affinity HTR7 agonist that crosses the blood-brain barrier (BBB). When co-injected with IL-1ß, LP-211 treatment prevented glial reactivity, the down-regulation of myelin-associated proteins, and the apparition of anxiety-like phenotypes. Thus, HTR7 may represent an innovative therapeutic target to protect the developing brain from preterm brain injuries.

Ultrasensitive dopamine detection with graphene aptasensor multitransistor arrays.

Detecting physiological levels of neurotransmitters in biological samples can advance our understanding of brain disorders and lead to improved diagnostics and therapeutics. However, neurotransmitter sensors for real-world applications must reliably detect low concentrations of target analytes from small volume working samples. Herein, a platform for robust and ultrasensitive detection of dopamine, an essential neurotransmitter that underlies several brain disorders, based on graphene multitransistor arrays (gMTAs) functionalized with a selective DNA aptamer is presented. High-yield scalable methodologies optimized at the wafer level were employed to integrate multiple graphene transistors on small-size chips (4.5 × 4.5 mm). The multiple sensor array configuration permits independent and simultaneous replicate measurements of the same sample that produce robust average data, reducing sources of measurement variability. This procedure allowed sensitive and reproducible dopamine detection in ultra-low concentrations from small volume samples across physiological buffers and high ionic strength complex biological samples. The obtained limit-of-detection was 1 aM (10-18) with dynamic detection ranges spanning 10 orders of magnitude up to 100 µM (10-8), and a 22 mV/decade peak sensitivity in artificial cerebral spinal fluid. Dopamine detection in dopamine-depleted brain homogenates spiked with dopamine was also possible with a LOD of 1 aM, overcoming sensitivity losses typically observed in ion-sensitive sensors in complex biological samples. Furthermore, we show that our gMTAs platform can detect minimal changes in dopamine concentrations in small working volume samples (2 µL) of cerebral spinal fluid samples obtained from a mouse model of Parkinson's Disease. The platform presented in this work can lead the way to graphene-based neurotransmitter sensors suitable for real-world academic and pre-clinical pharmaceutical research as well as clinical diagnosis.

Chronic stress causes striatal disinhibition mediated by SOM-interneurons in male mice.

Chronic stress (CS) is associated with a number of neuropsychiatric disorders, and it may also contribute to or exacerbate motor function. However, the mechanisms by which stress triggers motor symptoms are not fully understood. Here, we report that CS functionally alters dorsomedial striatum (DMS) circuits in male mice, by affecting GABAergic interneuron populations and somatostatin positive (SOM) interneurons in particular. Specifically, we show that CS impairs communication between SOM interneurons and medium spiny neurons, promoting striatal overactivation/disinhibition and increased motor output. Using probabilistic machine learning to analyze animal behavior, we demonstrate that in vivo chemogenetic manipulation of SOM interneurons in DMS modulates motor phenotypes in stressed mice. Altogether, we propose a causal link between dysfunction of striatal SOM interneurons and motor symptoms in models of chronic stress.

Auditory Dysfunction in Animal Models of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder mainly characterized by social-communication impairments, repetitive behaviors and altered sensory perception. Auditory hypersensitivity is the most common sensory-perceptual abnormality in ASD, however, its underlying neurobiological mechanisms remain elusive. Consistently with reports in ASD patients, animal models for ASD present sensory-perception alterations, including auditory processing impairments. Here we review the current knowledge regarding auditory dysfunction in rodent models of ASD, exploring both shared and distinct features among them, mechanistic and molecular underpinnings, and potential therapeutic approaches. Overall, auditory dysfunction in ASD models seems to arise from impaired central processing. Depending on the model, impairments may arise at different steps along the auditory pathway, from auditory brainstem up to the auditory cortex. Common defects found across models encompass atypical tonotopicity in different regions of the auditory pathway, temporal and spectral processing impairments and histological differences. Imbalance between excitation and inhibition (E/I imbalance) is one of the most well-supported mechanisms explaining the auditory phenotype in the ASD models studied so far and seems to be linked to alterations in GABAergic signaling. Such E/I imbalance may have a large impact on the development of the auditory pathway, influencing the establishment of connections responsible for normal sound processing.

Impact of cigarette smoke on osteogenic and osteoclast signaling in middle palatal suture.

Considering that smoking is a public health problem that has been growing among adolescents, the aim of this study was to investigate the impact of cigarette smoke on osteogenic and osteoclastogenic signaling in middle palatal suture of rats. Male Wistar rats exposed (n = 30) or not to cigarette smoke (n = 30) were used. Exposure to smoke was carried out for two daily periods of 3 minutes each, with an interval of 12 hours between exposures. After the experimental periods of 3, 7, 14 and 21 days, the animals were euthanized. The collected tissues were analyzed using light microscopy and real-time RT-PCR was performed to investigate gene expression. The data obtained were compared using the Kruskal Wallis and Dunn tests (⍺ = 5%). Morphologically, there were no significant changes in the middle palatal suture of rats exposed or not to cigarette smoke during 3, 7, 14 and 21 days (p> 0.05). On the other hand, osteoclastogenic signaling was increased in animals exposed to smoke and was characterized by a higher production of RANKL at 3 and 14 days (p <0.05), with no change in the synthesis of RANK and osteoprotegerin (p> 0.05). Interestingly, in the exposed animals, an early increase in the synthesis of osteocalcin, bone sialoprotein and osteopontin was also identified at 3 days of exposure (p <0.05), not sustained over time (p> 0.05). Cigarette smoke modulates osteogenic and osteoclastogenic signaling in the middle palatal suture of young rats, although morphological changes have not been evidenced.

Passerini chemistries for synthesis of polymer pro-drug and polymersome drug delivery nanoparticles.

New materials chemistries are urgently needed to overcome the limitations of existing biomedical materials in terms of preparation, functionality and versatility, and also in regards to their compatibility with biological environments. Here, we show that Passerini reactions are especially suited for the preparation of drug delivery materials, as with relatively few steps, polymers can be synthesized with functionality installed enabling drug conjugation and encapsulation, self-assembly into micellar or vesicular architectures, and with facile attachment triggerable chemistries. The polymers can be made with a variety of building blocks and assemble into nanoparticles, which are rapidly internalized in triple negative breast cancer (TNBC) cells. In addition, the polymers transport drug molecules efficiently through 3D cell cultures, and when designed with chemistries allowing pH-mediated release, exhibit greater efficacy against TNBC cells compared to the parent drug.

Impact of cigarette smoke on osteogenic and osteoclast signaling in middle palatal suture

Abstract Considering that smoking is a public health problem that has been growing among adolescents, the aim of this study was to investigate the impact of cigarette smoke on osteogenic and osteoclastogenic signaling in middle palatal suture of rats. Male Wistar rats exposed (n = 30) or not to cigarette smoke (n = 30) were used. Exposure to smoke was carried out for two daily periods of 3 minutes each, with an interval of 12 hours between exposures. After the experimental periods of 3, 7, 14 and 21 days, the animals were euthanized. The collected tissues were analyzed using light microscopy and real-time RT-PCR was performed to investigate gene expression. The data obtained were compared using the Kruskal Wallis and Dunn tests (⍺ = 5%). Morphologically, there were no significant changes in the middle palatal suture of rats exposed or not to cigarette smoke during 3, 7, 14 and 21 days (p> 0.05). On the other hand, osteoclastogenic signaling was increased in animals exposed to smoke and was characterized by a higher production of RANKL at 3 and 14 days (p <0.05), with no change in the synthesis of RANK and osteoprotegerin (p> 0.05). Interestingly, in the exposed animals, an early increase in the synthesis of osteocalcin, bone sialoprotein and osteopontin was also identified at 3 days of exposure (p <0.05), not sustained over time (p> 0.05). Cigarette smoke modulates osteogenic and osteoclastogenic signaling in the middle palatal suture of young rats, although morphological changes have not been evidenced.

Resumo Considerando que a fumaça de cigarro é um problema de saúde pública que está crescendo entre os adolescentes, o objetivo deste estudo foi investigar o impacto da fumaça de cigarro na sinalização osteogênica e osteoclastogênica da sutura palatina mediana de ratos. Foram utilizados ratos Wistar machos expostos (n=30) e não expostos à fumaça de cigarro (n=30). A exposição à fumaça de cigarro foi realizada duas vezes ao dia por 3 minutos, com um intervalo de 12 horas entre as exposições. Os animais foram mortos após o período experimental de 3, 7, 14 e 21 dias. Os tecidos coletados foram analisados em microscópico de luz e pelo RT-PCR em tempo real foi realizado para investigar a expressão gênica. s dados obtidos foram comparados usando o testes de Kruskal Wallis e Dunn (⍺ = 5%). Morfoligicamente, não houve mudança significativa na sutura palatina mediana nos ratos expostos ou não à fumaça de cigarro durante os tempo de 3, 7, 14 e 21 dias (p> 0.05). Por outro lado, a sinalização osteogênica esta aumentada nos animais expostos à fumaça e foi caracterizado por um aumento da produção de RANKL aos 3 e 14 dias (p <0.05), sem mudança na síntese da produção de RANK e osteoprotegerina (p> 0.05). Curiosamente, nos animais expostos, também foi observado um aumento precoce da síntese de osteocalcina, sialoproteína óssea e de osteopontina aos 3 dias de exposição, o que não foi mantido ao longo do tempo. A fumaça de cigarro modula a sinalização osteogênica e osteoclastogênica na sutura palatina mediana de ratos jovens, apesar de não tenha sido evidenciado alterações morfológicas.

Prevalence of Dengue, Chikungunya and Zika Viruses in Blood Donors in the State of Pará, Northern Brazil: 2018-2020.

Arboviruses have been reported over the years as constant threats to blood transfusion recipients, given the high occurrence of asymptomatic cases and the fact that the presence of viremia precedes the onset of symptoms, making it possible that infected blood from donors act as a source of dissemination. This work aims to identify the prevalence of dengue virus (DENV), Zika virus (ZIKV) and Chikungunya virus (CHIKV) infection in blood donors during epidemic and non-epidemic periods; classify the donor as symptomatic or asymptomatic; and verify the need to include DENV, CHIKV and ZIKV in the nucleic acid test (NAT) platform in northern Brazil. We investigated 36,133 thousand donations in two years of collection in Northern Brazil. One donor was positive for DENV and one for CHIKV (0.002% prevalence). As the prevalence for arboviruses was low in this study, it would not justify the individual screening of samples from donors in a blood bank. Thus, DENV- and CHIKV-positive samples were simulated in different amounts of sample pools, and both were safely detected by molecular biology even in a pool of 14 samples, which would meet the need to include these three viruses in the routine of blood centers in endemic countries such as Brazil.

Double-Layer Flexible Neural Probe With Closely Spaced Electrodes for High-Density in vivo Brain Recordings.

Flexible polymer neural probes are an attractive emerging approach for invasive brain recordings, given that they can minimize the risks of brain damage or glial scaring. However, densely packed electrode sites, which can facilitate neuronal data analysis, are not widely available in flexible probes. Here, we present a new flexible polyimide neural probe, based on standard and low-cost lithography processes, which has 32 closely spaced 10 µm diameter gold electrode sites at two different depths from the probe surface arranged in a matrix, with inter-site distances of only 5 µm. The double-layer design and fabrication approach implemented also provides additional stiffening just sufficient to prevent probe buckling during brain insertion. This approach avoids typical laborious augmentation strategies used to increase flexible probes' mechanical rigidity while allowing a small brain insertion footprint. Chemical composition analysis and metrology of structural, mechanical, and electrical properties demonstrated the viability of this fabrication approach. Finally, in vivo functional assessment tests in the mouse cortex were performed as well as histological assessment of the insertion footprint, validating the biological applicability of this flexible neural probe for acquiring high quality neuronal recordings with high signal to noise ratio (SNR) and reduced acute trauma.