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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Input-Output Relationship of CA1 Pyramidal Neurons Reveals Intact Homeostatic Mechanisms in a Mouse Model of Fragile X Syndrome.

Cellular hyperexcitability is a salient feature of fragile X syndrome animal models. The cellular basis of hyperexcitability and how it responds to changing activity states is not fully understood. Here, we show increased axon initial segment length in CA1 of the Fmr1-/y mouse hippocampus, with increased cellular excitability. This change in length does not result from reduced AIS plasticity, as prolonged depolarization induces changes in AIS length independent of genotype. However, depolarization does reduce cellular excitability, the magnitude of which is greater in Fmr1-/y neurons. Finally, we observe reduced functional inputs from the entorhinal cortex, with no genotypic difference in the firing rates of CA1 pyramidal neurons. This suggests that AIS-dependent hyperexcitability in Fmr1-/y mice may result from adaptive or homeostatic regulation induced by reduced functional synaptic connectivity. Thus, while AIS length and intrinsic excitability contribute to cellular hyperexcitability, they may reflect a homeostatic mechanism for reduced synaptic input onto CA1 neurons.

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.

Individual and Combined Components of Metabolic Syndrome with Chronic Kidney Disease in Individuals with Hypertension and/or Diabetes Mellitus Accompanied by Primary Health Care.

PURPOSE: To identify the associations between MetS and its components and chronic kidney disease (CKD) in a population with arterial hypertension (AH), or diabetes mellitus (DM) accompanied by the Primary Health Care (PHC). PATIENTS AND METHODS: A cross-sectional study with 788 individuals diagnosed with AH and/or DM followed by PHC of Viçosa, Brazil. Anthropometric, biochemical and clinical measures were performed for the diagnosis of MetS and CKD. MetS was identified using the NCEP-ATPIII criteria. CKD was identified by estimating the glomerular filtration rate using the CKD-EPI equation. Logistic regression models were used to estimate the chances of CKD associated with MetS and its components and specific combinations of components. RESULTS: The prevalence of MetS reported in the population was 65.4%, that of hidden CKD was 15.4%. The prevalence of CKD among participants with MetS was 75.2%. The most prevalent component of MetS in the population was AH (96.7%). Elevated fasting blood glucose, central obesity, and reduced HDL-c were significantly associated with an increased chance of CKD (OR = 2.80, 95% CI 1.76-4.45, OR = 1.68, 95% CI, 05-2.71, OR = 1.61, CI 95% 1.03-2.50, respectively). For the multivariate adjustment, the participants with MetS were 2 times more likely to have CKD than those without MetS (OR = 2.07; 95% CI, 1.25-3.44). The combination of three components of MetS high blood pressure, abdominal obesity and elevated fasting blood glucose and the combination of four components of MetS high blood pressure, reduced HDL-c, high fasting blood glucose and abdominal obesity were associated with increased odds of CKD (OR = 2.67, CI 95% 1.70-4.20, OR = 2.50, CI 95% 1.55-4.02, respectively). CONCLUSION: MetS, as well as its individual or combined components were independently associated with CKD in the population with AH and/or DM accompanied by PHC.

Prevalence of chronic kidney disease in Brazilians with arterial hypertension and/or diabetes mellitus.

The present study aimed to evaluate the prevalence of chronic kidney disease (CKD) in individuals with arterial hypertension (AH) and/or diabetes mellitus (DM) accompanied by Primary Health Care (PHC) in Brazil. The estimated glomerular filtration rate (eGFR) based on creatinine, and urinary albumin-to-creatinine ratio (ACR) were measured in 841 subjects with AH and/or DM, followed by PHC in the city of Viçosa. The CKD was diagnosed according to KDIGO criteria. Sociodemographic, clinical, and anthropometric factors related to the prevalence of CKD were investigated through multiple logistic regression. The prevalence of hidden CKD was 15.4%. Of these, 7.5% were identified by albuminuria (ACR ≥30 mg/g) with slightly decreased eGFR. Age, baseline disease, waist circumference (WC), and systolic blood pressure remained associated with CKD after multivariate analysis. The two major risk factors for hidden CKD were the presence of AH in association with DM and an increase in age. Hidden CKD was more common within people with AH and DM, and with high WC, glycosylated hemoglobin, and serum phosphorus as well as male gender and decreased serum albumin. This knowledge of risk associations can help avoid progression to CKD.

Characterisation of tumour microenvironment and immune checkpoints in primary central nervous system diffuse large B cell lymphomas.

Primary central nervous system diffuse large B cell lymphoma (PCNS-DLBCL) is a rare and aggressive entity of diffuse large B cell lymphoma (DLBCL). Elements of the tumour microenvironment (TME) including tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) have been associated with survival in DLBCL but their composition and prognostic impact in PCNS-DLBCL are unknown. Programmed cell death-1 (PD1)/programmed death-ligand 1 (PD-L1) immune checkpoint may represent a therapeutic option. Here, we aimed to characterise PD1/PDL1 immune checkpoints and the composition of the TME in PCNS-DLBCL. We collected tumour tissue and clinical data from 57 PCNS-DLBCL and used immunohistochemistry to examine TAMs (CD68, CD163), TILs (CD3, CD4, CD8, PD1) and tumour B cells (PAX5/PDL1 double stains, PDL1). The PDL1 gene was evaluated by fluorescence in situ hybridization (FISH). PAX5/PDL1 identified PDL1 expression by tumour B cells in 10/57 cases (17.5%). PDL1 gene translocation was a recurrent cytogenetic alteration in PNCS-DLBCL (8/47.17%) and was correlated with PDL1 positive expression in tumour B cells. The TME consisted predominantly of CD163 (+) M2 TAMs and CD8 (+) TILs. Most TAMs expressed PDL1 and most TILs expressed PD1. The density of TAMs and TILs did not associate with outcome. We showed that expression of PD1 on TILs and PDL1 on TAMs, but not the expression of PDL1 on tumour B cells was correlated with better prognosis. These findings support a significant role of TME composition and PD1/PDL1 crosstalk in PCNS-DLBCL pathogenesis and bring new insights to the targeted therapy of this aggressive lymphoma.

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.

Systemic, primary cutaneous, and breast implant-associated ALK-negative anaplastic large-cell lymphomas present similar biologic features despite distinct clinical behavior.

Despite distinct clinical presentation and outcome, systemic, primary cutaneous, and breast implant-associated anaplastic large cell lymphomas (S-, PC-, BI-ALCL) ALK-negative (ALK-) show similar histopathological features including the presence of the "hallmark" cells with horseshoe-shaped nuclei and CD30 protein expression. The purpose was to better characterize these three entities using immunohistochemistry and FISH (Fluorescent in situ hybridization) to identify biomarkers differently expressed and that might be involved in their pathogenesis. Twenty-two S-ALCL ALK-, 13 PC-ALCL, and 2 BI-ALCL were included. Cases were tested for P53, P63, MUM1, MYC, GATA3, p-STAT3, PD1, and PDL1 protein expression and DUP22, TP53, TP63, MYC, and PDL1 chromosomal aberrations. As expected, S-ALCL ALK- patients had adverse outcome compare to PC and BI-ALCL. No difference was observed between the three groups concerning protein expression except for MUM1 that was significantly more frequently expressed in S-ALCL ALK- compared to PC-ALCL. In particular, constitutive activation of the STAT3 pathway and PDL1/PD1 immune-checkpoint expression was present in the three entities. TP53 deletion and PDL1 gene amplification were the commonest cytogenetic alterations and were present in the three entities. None of the studied biological parameters was associated with prognosis. Despite distinct clinical behavior, S-ALCL ALK-, PC-ALCL, and BI-ALCL share similar biological features. Larger series should be investigated with the current approach to determine more precisely the activity and the prognostic value of these biomarkers and pathways in each group.