Atopic dermatitis pediatric patients show high rates of nasal and intestinal colonization by methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci.

BACKGROUND: Atopic dermatitis (AD) patients have high rates of colonization by Staphylococcus aureus, which has been associated with worsening of the disease. This study characterized Staphylococcus spp isolates recovered from nares and feces of pediatric patients with AD in relation to antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec) type, presence of pvl genes and clonality. Besides, gut bacterial community profiles were compared with those of children without AD. RESULTS: All 55 AD patients evaluated had colonization by Staphylococcus spp. Fifty-three (96.4%) patients had colonization in both clinical sites, whereas one patient each was not colonize in the nares or gut. Staphylococcus aureus was identified in the nostrils and feces of 45 (81.8%) and 39 (70.9%) patients, respectively. Methicillin-resistant Staphylococcus spp. isolates were found in 70.9% of the patients, and 24 (43.6%) had methicillin-resistant S. aureus (MRSA). S. aureus (55.6%) and S. epidermidis (26.5%) were the major species found. The prevalent lineages of S. aureus were USA800/SCCmecIV (47.6%) and USA1100/SCCmecIV (21.4%), and 61.9% of the evaluated patients had the same genotype in both sites. Additionally, gut bacterial profile of AD patients exhibits greater dissimilarity from the control group than it does among varying severities of AD. CONCLUSIONS: High rates of nasal and intestinal colonization by S. aureus and methicillin-resistant staphylococci isolates were found in AD patients. Besides, gut bacterial profiles of AD patients were distinctly different from those of the control group, emphasizing the importance of monitoring S. aureus colonization and gut microbiome composition in AD patients.

Is it all the RAGE? Defining the role of the receptor for advanced glycation end products in Parkinson's disease.

The receptor for advanced glycation end products (RAGE) is a transmembrane receptor that belongs to the immunoglobulin superfamily and is extensively associated with chronic inflammation in non-transmissible diseases. As chronic inflammation is consistently present in neurodegenerative diseases, it was largely assumed that RAGE could act as a critical modulator of neuroinflammation in Parkinson's disease (PD), similar to what was reported for Alzheimer's disease (AD), where RAGE is postulated to mediate pro-inflammatory signaling in microglia by binding to amyloid-ß peptide. However, accumulating evidence from studies of RAGE in PD models suggests a less obvious scenario. Here, we review physiological aspects of RAGE and address the current questions about the potential involvement of this receptor in the cellular events that may be critical for the development and progression of PD, exploring possible mechanisms beyond the classical view of the microglial activation/neuroinflammation/neurodegeneration axis that is widely assumed to be the general mechanism of RAGE action in the adult brain.

Pharmacological Approaches to the Treatment of Dementia in Down Syndrome: A Systematic Review of Randomized Clinical Studies.

Down Syndrome (DS) is considered the most frequent form of Intellectual Disability, with important expressions of cognitive decline and early dementia. Studies on potential treatments for dementia in this population are still scarce. Thus, the current review aims to synthesize the different pharmacological approaches that already exist in the literature, which focus on improving the set of symptoms related to dementia in people with DS. A total of six studies were included, evaluating the application of supplemental antioxidant therapies, such as alpha-tocopherol; the use of acetylcholinesterase inhibitor drugs, such as donepezil; N-methyl-d-aspartate (NMDA) receptor antagonists, such as memantine; and the use of vitamin E and a fast-acting intranasal insulin. Two studies observed important positive changes related to some general functions in people with DS (referring to donepezil). In the majority of studies, the use of pharmacological therapies did not lead to improvement in the set of symptoms related to dementia, such as memory and general functionality, in the population with DS.

Pain Characteristics and Their Relationship With Motor Dysfunction in Individuals With Parkinson Disease-A Cross-Sectional Study.

BACKGROUND: Pain is a common symptom in Parkinson disease (PD). OBJECTIVES: To analyze the relationship between pain and motor dysfunction in individuals with PD. METHODS: Fifty-four individuals with PD were screened: Hoehn and Yahr scale score = 2.5 (1 to 4); median (range) age in the "on" period of anti-Parkinson medication was 66 (44 to 85) years. Pain was assessed using King's Parkinson's Disease Pain Scale (KPPS) and the Brief Pain Inventory (BPI). Performance in routine activities and motor function were assessed using Unified Parkinson Disease Rating Scale (UPDRS II and III); gait was assessed using the Dynamic Gait Index; and balance was assessed using the Mini-BESTest. RESULTS: Thirty-eight participants (70.3%) reported mild to moderate pain. A positive correlation was found between the total KPPS score and performance in general activities (UPDRS II) (rho = 0.29, P = 0.04); a negative correlation was found between pain intensity (BPI intensity) and motor function (UPDRS III; rho = -0.28, P = 0.04); and a negative correlation was found between pain intensity (BPI intensity) and the bradykinesia subscore of the UPDRS III (rho = -0.29, P = 0.04). There was no correlation between pain and gait performance or balance. The musculoskeletal pain was the predominant type (in 81.5% of subjects), followed by nocturnal pain (52.6%) and fluctuation-related pain (47.3%). The most painful areas were lower limbs (33.0%) and shoulders/cervical area (31.0%). Twenty-one of 38 participants (55.3%) reported pain interference in their working and walking ability and general activities. CONCLUSIONS: Pain was weakly correlated with performance in general activities and with bradykinesia but was not correlated with the remaining classic motor PD symptoms, either gait or balance performance. Pain was a prevalent symptom in the present sample, and the individuals reported its interference with functionality.

Reference Values for Human Posture Measurements Based on Computerized Photogrammetry: A Systematic Review.

OBJECTIVE: The main objective of this study was to review the literature to identify reference values for angles and distances of body segments related to upright posture in healthy adult women with the Postural Assessment Software (PAS/SAPO). METHODS: Electronic databases (BVS, PubMed, SciELO and Scopus) were assessed using the following descriptors: evaluation, posture, photogrammetry, physical therapy, postural alignment, postural assessment, and physiotherapy. Studies that performed postural evaluation in healthy adult women with PAS/SAPO and were published in English, Portuguese and Spanish, between the years 2005 and 2014 were included. RESULTS: Four studies met the inclusion criteria. Data from the included studies were grouped to establish the statistical descriptors (mean, variance, and standard deviation) of the body angles and distances. A total of 29 variables were assessed (10 in the anterior views, 16 in the lateral right and left views, and 3 in the posterior views), and its respective mean and standard deviation were calculated. Reference values for the anterior and posterior views showed no symmetry between the right and left sides of the body in the frontal plane. There were also small differences in the calculated reference values for the lateral view. CONCLUSION: The proposed reference values for quantitative evaluation of the upright posture in healthy adult women estimated in the present study using PAS/SAPO could guide future studies and help clinical practice.

Decreasing fall risk in spinocerebellar ataxia.

[Purpose] Spinocerebellar ataxia consists of a group of autosomal dominant disorders that cause progressive degeneration, mainly in the cerebellum and its connections. Falls, which are a significant concern of this condition, reduce patients' mobility, deteriorate their health and have physical and social consequences. The aim of this study was to test the effectiveness of a modified protocol for improving balance and diminishing the fall risk of spinocerebellar ataxia patients exclusively. [Subjects and Methods] Exercises aiming to improve static and dynamic balance, whole body movements, measures to prevent falls and falling strategies were performed twice per week for four weeks by 11 spinocerebellar ataxia patients. Balance was evaluated using the Berg Balance Scale. [Results] The results show that there was a significant increase in Berg Balance Scale scores after the interventions (Wilcoxon p=0.0034). [Conclusion] This study demonstrated that the modified protocol is effective at reducing the fall risk of spinocerebellar ataxia patients. This protocol may be a useful option for appropriately coping with falls caused by spinocerebellar ataxia.

Viruses as a potential environmental trigger of type 1 diabetes mellitus (Review).

The etiopathogenesis of type 1 diabetes mellitus (T1DM) is a complex multifactorial process that involves an intricate network of genetic, epigenetic, immunological, and environmental factors. Despite the advances in recent years, some aspects of the mechanisms involved in triggering the disease are still unclear. Infections with certain viruses have been suggested as possible environmental triggers for the autoimmune process that leads to selective and progressive destruction of pancreatic ß-cells and insufficiency of insulin production, which is its hallmark. In this review, advances in knowledge and evidence that suggest the participation of certain viruses in the mechanisms of disease initiation and progression are described. It has been accepted that environmental factors, including viruses, can initiate and possibly sustain, accelerate, or slow down the autoimmune process and consequently damage insulin-producing pancreatic ß-cells. Although the role of these agents, especially human enteroviruses, has been exhaustively studied as the most likely triggers of the activation of autoimmunity that destroys pancreatic islets and leads to T1DM, certain doubts remain. Clinical epidemiological and experimental studies in humans and animals provide consistent and increasing evidence that persistent viral infections, especially with human enteroviruses and rotavirus infections, are associated with an increased risk of the disease in individuals genetically predisposed to autoimmunity.

Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder.

BACKGROUND: Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5-/y rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5-/y rats. METHODS: To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology. RESULTS: Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5-/y rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca2+ permeable AMPA receptor mediated currents are unchanged in Cdkl5-/y rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses. CONCLUSIONS: Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity. LIMITATIONS: This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD.

Perspective-taking in blindness: electrophysiological evidence of altered action representations.

It is well established that the mental simulation of actions involves visual and/or somatomotor representations of those imagined actions. To investigate whether the total absence of vision affects the brain activity associated with the retrieval of motor representations, we recorded the readiness potential (RP), a marker of motor preparation preceding the execution, as well as the motor imagery of the right middle-finger extension in the first-person (1P; imagining oneself performing the movement) and in the third-person (3P; imagining the experimenter performing the movement) modes in 19 sighted and 10 congenitally blind subjects. Our main result was found for the single RP slope values at the Cz channel (likely corresponding to the supplementary motor area). No difference in RP slope was found between 1P and 3P in the sighted group, suggesting that similar motor preparation networks are recruited to simulate our own and other people's actions in spite of explicit instructions to perform the task in 1P or 3P. Conversely, reduced RP slopes in 3P compared with 1P found in the blind group indicated that they might have used an alternative, nonmotor strategy to perform the task in 3P. Moreover, movement imagery ability, assessed both by means of mental chronometry and a modified version of the Movement Imagery Questionnaire-Revised, indicated that blind and sighted individuals had similar motor imagery performance. Taken together, these results suggest that complete visual loss early in life modifies the brain networks that associate with others' action representations.

Voltammetric determination of cocaine in confiscated samples using a carbon paste electrode modified with different [UO2(X-MeOsalen)(H2O)] · H2O complexes.

A fast and non-destructive voltammetric method to detect cocaine in confiscated samples based on carbon paste electrode modified with methoxy-substituted N,N'-ethylene-bis(salcylideneiminato)uranyl(VI)complexes, [UO2(X-MeOSalen)(H2O)] · H2O, where X corresponds to the positions 3, 4 or 5 of the methoxy group on the aromatic ring, is described. The electrochemical behavior of the modified electrode and the electrochemical detection of cocaine were investigated using cyclic voltammetry. Using 0.1 mol · L(-1) KCl as supporting-electrolyte, a concentration-dependent, well-defined peak current for cocaine at 0.62 V, with an amperometric sensitivity of 6.25 × 104 µA · mol · L(-1) for cocaine concentrations ranging between 1.0 × 10(-7) and 1.3 × 10(-6) mol · L-1 was obtained. Chemical interference studies using lidocaine and procaine were performed. The position of the methoxy group affects the results, with the 3-methoxy derivative being the most sensitive.

An overview of in-home care for older people in Portugal: an empirical study about the customers.

BACKGROUND: The Portuguese in-home care services have never been adequately studied or identified. This is because of the lack of classification of variables related to the care receiver and to the demographic and organizational context in which it is inserted. METHODS: The 126 organizations in the central region of Portugal were categorized into four groups depending on whether they were located in a rural or urban environment and on whether they were large or small organizations. To obtain information, the In-Home Care Protocol (ProSAD), Elderly Assessment System (EASYcare), and the Center for Epidemiologic Studies-Depression (CES-D) scale were applied to 48 customers (6 randomly chosen customers of in-home care services of each of the 8 randomly selected organizations, 2 per group of variables). RESULTS: The rural context denoted a lack of diversity of services and the number of organizations available is reduced which implies less time spent with the customers. The more dependent customers at the time of registration (Kruskal-Wallis test [KW] = 12.79; p < .05) in large organizations (Mann-Whitney [U] = 190.5; p < .05) benefit more from the services. CONCLUSIONS: In-home care services are underused and are oriented to treat those that have a family caregiver. Overall, in-home care in Portugal still has much to achieve when compared with other European countries.

A Method to Freeze Skin Samples for Cryobanks: A Test of Some Cryoprotectants for an Endangered Deer.

The genetic diversity of endangered deer species, such as Mazama jucunda, can be preserved with the help of somatic cell cryopreservation. This procedure allows obtaining several cells from the individual even after its death, which is very important for applications in reproductive biotechnologies. This study's objective was to test cryopreservation protocols of skin fragments of M. jucunda, using different cryoprotectants in slow freezing. We evaluated four treatments, composed of three cryoprotectants, dimethyl sulfoxide (DMSO), polyvinylpyrrolidone (PVP), and ethylene glycol (EG), used alone and in combination. There was also a control group where the tissue did not undergo cryopreservation. Skin fragments were collected from the medial region of the pelvic limbs of three individuals. Each fragment was divided into 10 equal parts, standardized by weight, making two pieces for each treatment and control from each animal. The collected fragments were evaluated in culture, based on the speed of occupation of the free spaces of the cell culture flask. Cell viability was also evaluated using Trypan Blue dye and the mitotic index to understand the effect of toxicity and freezing on cell membrane integrity and cell division capacity, respectively. The treatments that used association with PVP proved to be more damaging to the cells, taking longer to reach confluence. EG alone showed better results than DMSO in the slow-freezing protocol. Clinical Trial Registration Number is 1390/21.

Poststroke consequences upon optimization properties of postural sway during upright stance: a cross-sectional study.

BACKGROUND: The understanding of human postural control has advanced with the introduction of optimization process modeling. These models, however, only provide control parameters, rather than analytical descriptors of optimization processes. Here, we use a newly developed direct (pattern) search algorithm to investigate changes in postural optimization process in poststroke individuals. OBJECTIVE: This cross-sectional study investigated the optimization properties of postural stability during upright standing in poststroke individuals. METHODS: Twenty-nine poststroke and 15 healthy age-matched individuals underwent posturography with a force platform while standing for 60 s for acquisition of center-of-pressure data. Poststroke individuals were grouped depending on their weight-bearing (WB) pattern and their balance capability assessed through Berg Balance Scale (BBS). The optimization properties of postural stability were computed assuming the minimization of postural sway as cost function. RESULTS: The asymmetric WB poststroke group showed larger convergence rate toward the local minimum of postural sway than the symmetric WB group. Additionally, the low-balance capability group exhibited smaller values for averaged local minima and global minimum of postural sway coordinates compared with high-balance capability group. Significant correlations were found for BBS and the local minima and global minimum (Pearson's r ranged 0.378-0.424, P < 0.05). CONCLUSIONS: In summary, the optimization properties describing postural dynamic stability, steadiness, and global reference are altered in poststroke individuals with asymmetric WB pattern and low-balance capability.

Metarhizium anisopliae E6 secretome reveals molecular players in host specificity and toxicity linked to cattle tick infection.

Although Metarhizium anisopliae is one of the most studied fungal biocontrol agents, its infection mechanism is far from being completely understood. Using multidimensional protein identification technology (MudPIT), we evaluated the differential secretome of M. anisopliae E6 induced by the host Rhipicephalus microplus cuticle. The proteomic result showed changes in the expression of 194 proteins after exposure to host cuticle, such as proteins involved in adhesion, penetration, stress and fungal defense. Further, we performed a comparative genomic distribution of differentially expressed proteins of the M. anisopliae secretome against another arthropod pathogen, using the Beauveria bassiana ARSEF2860 protein repertory. Among 47 analyzed protein families, thirty were overexpressed in the M. anisopliae E6 predicted genome compared to B. bassiana. An in vivo toxicity assay using a Galleria mellonella model confirmed that the M. anisopliae E6 secretome was more toxic in cattle tick infections compared to other secretomes, including B. bassiana with cattle ticks and M. anisopliae E6 with the insect Dysdereus peruvianus, which our proteomic results had also suggested. These results help explain molecular aspects associated with host infection specificity due to genetic differences and gene expression control at the protein level in arthropod-pathogenic fungi.

A new species of Tricorythopsis Traver, 1958 (Ephemeroptera: Leptohyphidae) from Par state, Brazil.

A new species of Tricorythopsis is described, illustrated and diagnosed based on nymphs from Par state, Brazil. Tricorythopsis similis sp. nov. is related to Tricorythopsis rondoniensis (Dias, Cruz Ferreira) based on abdominal terga IIIVII with acute tubercles medially located on posterior margins, and by the absence of the transversal line on operculate gill. However, the new species can be identified by the following combination of characteristics: general coloration yellowish brown, with blackish and purplish marks irregularly distributed; maxillary palp 1-segmented; segment II of labial palp shorter than segment I and longer than segment III; femora and tibiae with margins covered by long, pectinate setae; tarsal claws with 4 to 5 marginal denticles and 4+2 very small, submarginal denticles. This is the first species of Tricorythopsis recorded from Par state.

BCL2 and BCL6 atypical/unbalanced gene rearrangements in diffuse large B-cell lymphoma are indicators of an aggressive clinical course.

AIMS: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin's lymphoma that represents a heterogeneous group of disease that is differentially characterised by clinical, molecular and cytogenetic features. MYC, BCL2 and BCL6 gene rearrangements have been identified as prognostic factors in DLBCL, especially for MYC. Nevertheless the frequency and effect of atypical/unbalanced BCL6, BCL2 and MYC translocations in DLBCL is not fully documented. Here, we aimed to analyse those atypical/unbalanced rearrangements in DLBCL and to assess their prognostic impact. METHODS: We collected tumour tissue and clinical data from 97 DLBCL and used interphase fluorescence in situ hybridisation (FISH) with break-apart probe to characterise BCL6, BCL2 and MYC gene pattern. RESULTS: 19 of 97 (19,6%) cases of DLBCL had atypical/ unbalanced gene rearrangements (14 involving BCL6 gene, 5 involving BCL2 gene and none involving MYC gene). Compared with patients with simple gene rearrangement and patients without cytogenetic abnormality, patients with atypical/unbalanced gene rearrangement were in an unfavourable risk group by the International Prognostic Index (p=0039), died of disease (p=0012), harboured relapse or progression (p=0011) and had shorter overall (p=0,04), relapse free (p=0029) and event free (p=0026) survival. CONCLUSIONS: We showed that patients with DLBCL with BCL2 or BCL6 atypical/unbalanced rearrangements constituted a group of patients with poor outcome. We also underlined the importance of FISH analyses, easily feasible in routine practise, at diagnosis of DLBCL to detect the rather frequent and clinically significant atypical/unbalanced aberrations of these genes.

Going Online in Pandemic Time: A DivulgaMicro Workshop Experience.

DivulgaMicro is a Brazilian science communication and outreach project run by three young female scientists. In 2020, due to the COVID-19 pandemic, we promoted the first virtual edition of the DivulgaMicro Workshop. Here, we describe adaptations implemented to deliver the virtual edition and its assessment by the participants. We offered a 3-day workshop addressing manuscript writing and publishing, poster design and oral presentations, and strategies for effectively communicating with the lay public on Days 1, 2, and 3, respectively. Each daily session was divided into short lectures and active learning through interactive and cooperative activities. We applied pre- and postsession surveys daily to assess participants' learning, with an opinion questionnaire at the end of the workshop. We selected 50 of 221 applicants, but only 38 of those selected participated in the workshop. Correct answers were significantly higher (p < 0.01) in the postsession surveys each day. Most of the 34 participants who answered the opinion questionnaire (97%) would recommend the workshop to their colleagues. Participants stated that the workshop content was transmitted in a clear and straightforward manner, and they considered the online format suitable for knowledge acquisition. Participants were satisfied with the organization, dynamics, and interactivity. Topics addressed on Day 3 (61.8%) and Day 1 (23.5%) were most liked and were considered most useful in the participants' careers. We believe that the overall success of the workshop is due to the combination of short lectures with active-learning activities, the use of virtual platforms that enabled effective communication between participants and instructors, and the support of our collaborators.

Hypertriglyceridemic waist phenotype and associated factors in individuals with arterial hypertension and/or diabetes mellitus.

Cardiovascular diseases are among the main causes of death in Brazil and worldwide. The literature indicates the hypertriglyceridemic waist phenotype (HTWP) as an accessible alternative for the identification of cardiovascular and metabolic risk. The present study aimed to identify the prevalence and factors associated with HTWP in individuals diagnosed with arterial hypertension (AH) and/or diabetes mellitus type 2 (DM2). A cross-sectional study was conducted with individuals diagnosed with AH and/or DM2. The study data were collected through semi-structured interviews containing socio-demographic information, lifestyle, health care, in addition to anthropometric assessment, blood pressure measurement and biochemical blood tests. The prevalence of HTWP was estimated and bivariate and multivariate logistic regression was used to assess the factors associated with HTWP. Of the 788 individuals analysed, 21⋅5 % had the HTWP. In the adjusted model, the following variables remained associated with a greater chance of presenting HTWP: sex, age, body mass index (BMI) and very-low-density lipoprotein (VLDL). Being female increased the chance of HTWP by 7⋅7 times (OR 7⋅7; 95 % CI 3⋅9, 15⋅2). The one-year increase in age increased the chance of HTWP by 4 % (OR 1⋅04; 95 % CI 1⋅02, 1⋅06). The addition of 1 mg/dl of VLDL-c increased the chance of HTWP by 15 % (odds ratio (OR) 1⋅15; 95 % confidence interval (CI) 1⋅12, 1⋅18), as well as the increase of 1 kg/m2 in the BMI increased the chance of this condition by 20 % (OR 1⋅20; 95 % CI 1⋅15, 1⋅27). The prevalence of HTWP was associated with females, older age, higher BMI, higher VLDL-c and risk waist/height ratio.

SARSCOVIDB-A New Platform for the Analysis of the Molecular Impact of SARS-CoV-2 Viral Infection.

The COVID-19 pandemic caused by the new coronavirus (SARS-CoV-2) has become a global emergency issue for public health. This threat has led to an acceleration in related research and, consequently, an unprecedented volume of clinical and experimental data that include changes in gene expression resulting from infection. The SARS-CoV-2 infection database (SARSCOVIDB: https://sarscovidb.org/) was created to mitigate the difficulties related to this scenario. The SARSCOVIDB is an online platform that aims to integrate all differential gene expression data, at messenger RNA and protein levels, helping to speed up analysis and research on the molecular impact of COVID-19. The database can be searched from different experimental perspectives and presents all related information from published data, such as viral strains, hosts, methodological approaches (proteomics or transcriptomics), genes/proteins, and samples (clinical or experimental). All information was taken from 24 articles related to analyses of differential gene expression out of 5,554 COVID-19/SARS-CoV-2-related articles published so far. The database features 12,535 genes whose expression has been identified as altered due to SARS-CoV-2 infection. Thus, the SARSCOVIDB is a new resource to support the health workers and the scientific community in understanding the pathogenesis and molecular impact caused by SARS-CoV-2.

The molecular landscape and microenvironment of salivary duct carcinoma reveal new therapeutic opportunities.

Purpose: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland cancer subtype with poor prognosis. The mutational landscape of SDC has already been the object of several studies, however little is known regarding the functional genomics and the tumor microenvironment despite their importance in oncology. Our investigation aimed at describing both the functional genomics of SDC and the SDC microenvironment, along with their clinical relevance. Methods: RNA-sequencing (24 tumors), proteomics (17 tumors), immunohistochemistry (22 tumors), and multiplexed immunofluorescence (3 tumors) data were obtained from three different patient cohorts and analyzed by digital imaging and bioinformatics. Adjacent non-tumoral tissue from patients in two cohorts were used in transcriptomic and proteomic analyses. Results: Transcriptomic and proteomic data revealed the importance of Notch, TGF-ß, and interferon-γ signaling for all SDCs. We confirmed an overall strong desmoplastic reaction by measuring α-SMA abundance, the level of which was associated with recurrence-free survival (RFS). Two distinct immune phenotypes were observed: immune-poor SDCs (36%) and immune-infiltrated SDCs (64%). Advanced bioinformatics analysis of the transcriptomic data suggested 72 ligand-receptor interactions occurred in the microenvironment and correlated with the immune phenotype. Among these interactions, three immune checkpoints were validated by immunofluorescence, including CTLA-4/DC86 and TIM-3/galectin-9 interactions, previously unidentified in SDC. Immunofluorescence analysis also confirmed an important immunosuppressive role of macrophages and NK cells, also supported by the transcriptomic data. Conclusions: Together our data significantly increase the understanding of SDC biology and open new perspectives for SDC tumor treatment. Before applying immunotherapy, patient stratification according to the immune infiltrate should be taken into account. Immune-infiltrated SDC could benefit from immune checkpoint-targeting therapy, with novel options such as anti-CTLA-4. Macrophages or NK cells could also be targeted. The dense stroma, i.e., fibroblasts or hyaluronic acid, may also be the focus for immune-poor SDC therapies, e.g. in combination with Notch or TGF-ß inhibitors, or molecules targeting SDC mutations.