Heavy menstrual bleeding in women with inherited bleeding disorders in use of LNG-IUS: A systematic review and single-arm meta-analysis.

OBJECTIVES: Inherited bleeding disorders may cause heavy menstrual bleeding in women, impacting quality of life and impairing daily and social activities. The levonorgestrel-releasing intrauterine system is a potential treatment for these women, which might reduce menstrual blood loss. STUDY DESIGN: We performed a systematic review and single-arm meta-analysis to examine the levonorgestrel-releasing intrauterine system in women with inherited bleeding disorders and heavy menstrual bleeding. RESULTS: A systematic search on PubMed, Embase and Cochrane yielded 583 results, of which six observational studies (n = 156) met inclusion criteria. Levonorgestrel-releasing intrauterine system use in patients with inherited bleeding disorders and heavy menstrual bleeding was associated with amenorrhea in 60% of patients and a significant increase of 1.40 g/dL in hemoglobin and of 19.75 ng/mL in ferritin levels when comparing post- and pre-treatment levels. The post-treatment mean hemoglobin was 13.32 g/dL and the mean ferritin was 43.22 ng/dL. The rate of intrauterine device expulsion or removal due to mal position was low (13%), as was the need for intrauterine device removal due to lack of efficacy (14%). CONCLUSION: The levonorgestrel-releasing intrauterine system may improve bleeding patterns and quality of life in patients with inherited bleeding disorders and heavy menstrual bleeding. IMPLICATIONS: Women with inherited bleeding disorders could benefit from levonorgestrel-releasing intrauterine system, so its use should be an option for this women.

The Influence of IL-11 on Cardiac Fibrosis in Experimental Models: A Systematic Review.

Fibrosis is one of the main factors that impair the function of many organs. In the heart, fibrosis leads to contractile dysfunction and arrhythmias, which are important in the development of heart failure. Interleukin (IL)-11 is regulated in various heart diseases and has recently been reported to be an important cytokine in fibrosis in this organ. However, this topic has been little explored, and many questions persist. Thus, this systematic review aimed to report on possible IL-11 therapies evaluated in rodent model-induced cardiac fibrosis. Inclusion criteria were experimental in vivo studies that used different rodent models for cardiac fibrosis associated with IL-11 interventions, without year and language restrictions. The search in PubMed, Web of Science, and Embase databases was performed in October 2022. The risk of bias assessment of the studies was based on the guidelines of the SYRCLE tool, and data from the selected articles were also presented in a table as a narrative description. This review was based on eight studies in which five different interventions were used: recombinant human IL-11 (rhIL-11), anti-IL11 (X203), recombinant mouse IL-11 (rmIL-11), lentivirus (LV)-IL-11 + lutein, and anti-IL11RA (X209). Based on the included studies, the results were variable, with IL-11 overexpression inducing cardiac fibrosis, while inhibition protected against this process, preserving the function of this organ. Therefore, IL-11 stands out as a promising therapeutic target for cardiac fibrosis. However, further studies are needed to understand the mechanisms triggered by each treatment, as well as its safety and immunogenicity.

The Multifarious Functions of Leukotrienes in Bone Metabolism.

Leukotrienes (LTs) are derived from arachidonic acid metabolism by the 5-lipoxygenase (5-LO) enzyme. The production of LTs is stimulated in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis, and periodontitis, with a relevant contribution to bone resorption. However, its role in bone turnover, particularly the suppression of bone formation by modulating the function of osteoclasts and osteoblasts, remains unclear. We investigated the effects of LTs on bone metabolism and their impact on osteogenic differentiation and osteoclastogenesis using a 5-LO knockout (KO) mouse model. Results from micro-computed tomography (µCT) analysis of femur from 8-week-old 5-LO-deficient mice showed increased cortical bone and medullary region in females and males and decreased trabecular bone in females. In the vertebra, we observed increased marrow area in both females and males 5-LO KO and decreased trabecular bone only in females 5-LO KO. Immunohistochemistry (IHC) analysis showed higher levels of osteogenic markers tissue-nonspecific alkaline phosphatase (TNAP) and osteopontin (OPN) and lower expression of osteoclastogenic marker tartrate-resistant acid phosphatase (TRAP) in the femurs of 5-LO KO mice versus wild-type (WT). Alkaline phosphatase activity and mineralization assay results showed that the 5-LO absence enhances osteoblasts differentiation and mineralization but decreases the proliferation. Alkaline phosphatase (ALP), Bglap, and Sp7 gene expression were higher in 5-LO KO osteoblasts compared to WT cells. Eicosanoids production was higher in 5-LO KO osteoblasts except for thromboxane 2, which was lower in 5-LO-deficient mice. Proteomic analysis identified the downregulation of proteins related to adenosine triphosphate (ATP) metabolism in 5-LO KO osteoblasts, and the upregulation of transcription factors such as the adaptor-related protein complex 1 (AP-1 complex) in long bones from 5-LO KO mice leading to an increased bone formation pattern in 5-LO-deficient mice. We observed enormous differences in the morphology and function of osteoclasts with reduced bone resorption markers and impaired osteoclasts in 5-LO KO compared to WT osteoclasts. Altogether, these results demonstrate that the absence of 5-LO is related to the greater osteogenic profile. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Dentoalveolar Alterations in an Adenine-Induced Chronic Kidney Disease Mouse Model.

Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD-MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hormone (PTH) secretion, skeletal abnormalities, and vascular calcification. CKD-MBD impacts the oral cavity, with effects including salivary gland dysfunction, enamel hypoplasia and damage, increased dentin formation, decreased pulp volume, pulp calcifications, and altered jaw bones, contributing to clinical manifestations of periodontal disease and tooth loss. Underlying mechanisms are not fully understood, and CKD mouse models commonly require invasive procedures with high rates of infection and mortality. We aimed to characterize the dentoalveolar effects of an adenine diet (AD)-induced CKD (AD-CKD) mouse model. Eight-week-old C57BL/6J mice were provided either a normal phosphorus diet control (CTR) or adenine and high-phosphorus diet CKD to induce kidney failure. Mice were euthanized at 15 weeks old, and mandibles were collected for micro-computed tomography and histology. CKD mice exhibited kidney failure, hyperphosphatemia, and hyperparathyroidism in association with porous cortical bone in femurs. CKD mice showed a 30% decrease in molar enamel volume compared to CTR mice. Enamel wear was associated with reduced ductal components, ectopic calcifications, and altered osteopontin (OPN) deposition in submandibular salivary glands of CKD mice. Molar cusps in CKD mice were flattened, exposing dentin. Molar dentin/cementum volume increased 7% in CKD mice and pulp volume decreased. Histology revealed excessive reactionary dentin and altered pulp-dentin extracellular matrix proteins, including increased OPN. Mandibular bone volume fraction decreased 12% and bone mineral density decreased 9% in CKD versus CTR mice. Alveolar bone in CKD mice exhibited increased tissue-nonspecific alkaline phosphatase localization, OPN deposition, and greater osteoclast numbers. AD-CKD recapitulated key aspects reported in CKD patients and revealed new insights into CKD-associated oral defects. This model has potential for studying mechanisms of dentoalveolar defects or therapeutic interventions. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

[Hereditary bradykinin angioedema. Case report]. / Angioedema hereditario por bradicinina. Reporte de Caso.

INTRODUCTION: Hereditary angioedema is an autosomal dominant genetic disease, associated with increased levels of bradykinin. It is classified into 3 types according to the C1-INH enzyme. The diagnosis is clinical and laboratory. Its treatment is divided into short- and long-term and crisis prophylaxis. CASE REPORT: 40-year-old female patient who came to the emergency service for labial edema without resolution with corticosteroids. The tests for IgE, C4 and C1 esterase inhibitors had a low result. She currently uses danazol prophylactically and fresh frozen plasma in crises. CONCLUSIONS: Since it is a disease that considerably affects the quality of life, hereditary angioedema must be diagnosed and an effective treatment plan made to prevent or reduce its complications.

INTRODUCCIÓN: El angioedema hereditario es una enfermedad genética autosómica dominante, asociada con aumento de las concentraciones de bradicinina. Se clasifica en tres tipos, de acuerdo con la enzima C1-INH. El diagnóstico se establece por las manifestaciones clínicas y los estudios de laboratorio. El tratamiento consiste profilaxis a corto y largo plazo, y protocolo para el control de las crisis. REPORTE DEL CASO: Paciente femenina de 40 años, que acudió al servicio de Urgencias por edema labial, sin reacción al tratamiento con corticosteroides. Se detectaron concentraciones bajas de IgE, C4 e inhibidores de la esterasa C1. Se estableció el diagnóstico de angioedema hereditario. Actualmente se mantiene en tratamiento profiláctico con danazol y plasma fresco congelado para el control de las crisis. CONCLUSIONES: El angioedema hereditario es una enfermedad que afecta considerablemente la calidad de vida; por tanto, debe diagnosticarse de forma oportuna y establecer un plan de tratamiento eficaz, con la intención de prevenir o reducir las complicaciones.

Gene Therapy Using Recombinant AAV Type 8 Vector Encoding TNAP-D10 Improves the Skeletal Phenotypes in Murine Models of Osteomalacia.

Hypophosphatasia (HPP), caused by loss-of-function mutations in the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNAP), is characterized by skeletal and dental hypomineralization that can vary in severity from life-threatening to milder manifestations only in adulthood. PHOSPHO1 deficiency leads to early-onset scoliosis, osteomalacia, and fractures that mimic pseudo-HPP. Asfotase alfa, a life-saving enzyme replacement therapy approved for pediatric-onset HPP, requires subcutaneous injections 3 to 6 times per week. We recently showed that a single injection of an adeno-associated virus vector serotype 8 harboring TNAP-D10 (AAV8-TNAP-D10) effectively prevented skeletal disease and prolonged life in Alpl -/- mice phenocopying infantile HPP. Here, we aimed to determine the efficacy of AAV8-TNAP-D10 in improving the skeletal and dental phenotype in the Alpl Prx1/Prx1 and Phospho1 -/- mouse models of late-onset (adult) HPP and pseudo-HPP, respectively. A single dose of 3 × 1011 vector genomes per body (vg/b) was injected intramuscularly into 8-week-old Alpl Prx1/Prx1 and wild-type (WT) littermates, or into 3-day-old Phospho1 -/- and WT mice, and treatment efficacy was evaluated after 60 days for late-onset HPP mice and after 90 days for Phospho1 -/- mice. Biochemical analysis showed sustained serum alkaline phosphatase activity and reduced plasma PPi levels, and radiographic images, micro-computed tomography (micro-CT) analysis, and hematoxylin and eosin (H&E) staining showed improvements in the long bones in the late-onset HPP mice and corrected scoliosis in the Phospho1 -/- mice. Micro-CT analysis of the dentoalveolar complex did not reveal significant changes in the phenotype of late-onset HPP and pseudo-HPP models. Moreover, alizarin red staining analysis showed that AAV8-TNAP-D10 treatment did not promote ectopic calcification of soft organs in adult HPP mice after 60 days of treatment, even after inducing chronic kidney disease. Overall, the AAV8-TNAP-D10 treatment improved the skeletal phenotype in both the adult HPP and pseudo-HPP mouse models. This preclinical study will contribute to the advancement of gene therapy for the improvement of skeletal disease in patients with heritable forms of osteomalacia. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

SOX3 duplication in a boy with 46,XX ovotesticular disorder of sex development and his 46,XX sister with atypical genitalia: Probable germline mosaicism.

Ovotesticular disorders of sex development (OT-DSD) are characterized by ovarian follicles and seminiferous tubules in the same individual, with a wide range of atypical genitalia. We report on two sibs with atypical genitalia and SRY-negative 46,XX DSD, OT-DSD was confirmed only in the boy, while the girl had bilateral ovaries. Chromosome microarray analysis (CMA) showed a 737-kb duplication at Xq27.1 including the entire SOX3 gene in both sibs, which was confirmed by quantitative real time PCR. Also, X chromosome inactivation assay showed random inactivation in both sibs. Whole exome sequencing revealed no pathogenic or likely pathogenic variant. CMA of the parents showed normal results for both, suggesting that germline mosaicism could be the reason of recurrence of this duplication in the siblings. Our results support a pathogenic role of SOX3 overexpression in 46,XX subjects leading to variable DSD phenotypes.

Duchenne muscular dystrophy progression induced by downhill running is accompanied by increased endomysial fibrosis and oxidative damage DNA in muscle of mdx mice.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle necrosis. One of the major challenges for prescribing physical rehabilitation exercises for DMD patients is associated with the lack of a thorough knowledge of dystrophic muscle responsiveness to exercise. This study aims to understand the relationship between myogenic regulation, inflammation and oxidative stress parameters, and disease progression induced by downhill running in the skeletal muscle of an experimental model of DMD. Six-month-old C57BL/10 and C57BL/10-DMDmdx male mice were distributed into three groups: Control (C), mdx, and mdx + Exercise (mdx + Ex). Animals were trained in a downhill running protocol for seven weeks. The gastrocnemius muscle was subjected to histopathology, muscle regeneration (myoD and myogenin), inflammation (COX-2), oxidative stress (8-OHdG) immunohistochemistry markers, and gene expression (qPCR) of NF-kB and NADP(H)Oxidase 2 (NOX-2) analysis. In the mdx + Ex group, the gastrocnemius muscle showed a higher incidence of endomysial fibrosis and a lower myonecrosis percentage area. Immunohistochemical analysis revealed decreased myogenin immunoexpression in the mdx group, as well as accentuated immunoexpression of nuclear 8-OHdG in both mdx groups and increase in cytoplasmic 8-OHdG only in the mdx + Ex. COX-2 immunoexpression was related to areas of regeneration process and inflammatory infiltrate in the mdx group, while associated with areas of muscle fibrosis in the mdx + Ex. Moreover, the NF-kB gene expression was not influenced by exercise; however, a NAD(P)HOxidase 2 increase was observed. Oxidative stress and oxidative DNA damage play a significant role in the DMD phenotype progression induced by exercise, compromising cellular patterns resulting in increased endomysial fibrosis.

The Increased Alcohol and Marijuana Use Associated with the Quality of Life and Psychosocial Aspects: a Study During the Covid-19 Pandemic in a Brazilian University Community.

The primary practice adopted to reduce Covid-19 contamination is social distancing (SD). SD had significant consequences on alcohol/drug use, quality of life, and psychosocial aspects. In the university community specifically, SD produces a collective traumatic event with changes in the work routine by the suspension of presence. This study aims to identify and analyze the associations of increased alcohol and marijuana consumption on the quality of life and psychosocial aspects of the university community (students, professors, and technical and administrative staff) at a Brazilian public university during SD due to Covid-19 pandemic. This descriptive and cross-sectional study used an online questionnaire to obtain information from 2790 university community participants. Data were analyzed using IBM SPSS Statistics version 22. The analysis included descriptive associations performed using Spearman's correlation coefficient and p < 0.05 was taken as statistically significant. The participants' majority was 62% female, 95.4% students, 73% were 17-25 years old, 33.4% had income between 1 and 3 minimum wage, and 48% of the university community "totally adhered to SD." The increased alcohol consumption during SD was associated with a worsening in quality of life (p = 0.001), health satisfaction (p = 0.015), the meaning of life (p = 0.040), ability to concentrate (p = 0.001), satisfaction with yourself (p = 0.029), and frequency of negative feelings (p = 0.001); in contrast, increased alcohol use improved satisfaction with peer support (p = 0.042), as well as increased marijuana use improved satisfaction with sex life (p < 0.001). The increased alcohol use was higher in women (30.5%) than in men (26.7%) and was negatively associated with more quality of life and psychosocial aspects among women than men. Students were the segment that presented the highest frequency of associations with increased alcohol and/or marijuana use in the three domains analyzed. This study innovated by associating increased alcohol and/or marijuana use with worsening quality of life and psychosocial aspects rather than evaluating them apart. Future studies must identify whether this association between increased alcohol use, mainly, and the worsening quality of life and psychosocial aspects during the SD period is maintained or improved with the return to face-to-face activities at the university, with particular attention to women and students. Psychologists and other mental health professionals should be called upon to develop interventions to meet emerging mental health needs.

Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia?

Mineralization of the skeleton occurs by several physicochemical and biochemical processes and mechanisms that facilitate the deposition of hydroxyapatite (HA) in specific areas of the extracellular matrix (ECM). Two key phosphatases, phosphatase, orphan 1 (PHOSPHO1) and tissue-non-specific alkaline phosphatase (TNAP), play complementary roles in the mineralization process. The actions of PHOSPHO1 on phosphocholine and phosphoethanolamine in matrix vesicles (MVs) produce inorganic phosphate (Pi) for the initiation of HA mineral formation within MVs. TNAP hydrolyzes adenosine triphosphate (ATP) and the mineralization inhibitor, inorganic pyrophosphate (PPi), to generate Pi that is incorporated into MVs. Genetic mutations in the ALPL gene-encoding TNAP lead to hypophosphatasia (HPP), characterized by low circulating TNAP levels (ALP), rickets in children and/or osteomalacia in adults, and a spectrum of dentoalveolar defects, the most prevalent being lack of acellular cementum leading to premature tooth loss. Given that the skeletal manifestations of genetic ablation of the Phospho1 gene in mice resemble many of the manifestations of HPP, we propose that Phospho1 gene mutations may underlie some cases of "pseudo-HPP" where ALP may be normal to subnormal, but ALPL mutation(s) have not been identified. The goal of this perspective article is to compare and contrast the loss-of-function effects of TNAP and PHOSPHO1 on the dentoalveolar complex to predict the likely dental phenotype in humans that may result from PHOSPHO1 mutations. Potential cases of pseudo-HPP associated with PHOSPHO1 mutations may resist diagnosis, and the dental manifestations could be a key criterion for consideration.

Ultrasensitive Diamond Microelectrode Application in the Detection of Ca2+ Transport by AnnexinA5-Containing Nanostructured Liposomes.

This report describes the innovative application of high sensitivity Boron-doped nanocrystalline diamond microelectrodes for tracking small changes in Ca2+ concentration due to binding to Annexin-A5 inserted into the lipid bilayer of liposomes (proteoliposomes), which could not be assessed using common Ca2+ selective electrodes. Dispensing proteoliposomes to an electrolyte containing 1 mM Ca2+ resulted in a potential jump that decreased with time, reaching the baseline level after ~300 s, suggesting that Ca2+ ions were incorporated into the vesicle compartment and were no longer detected by the microelectrode. This behavior was not observed when liposomes (vesicles without AnxA5) were dispensed in the presence of Ca2+. The ion transport appears Ca2+-selective, since dispensing proteoliposomes in the presence of Mg2+ did not result in potential drop. The experimental conditions were adjusted to ensure an excess of Ca2+, thus confirming that the potential reduction was not only due to the binding of Ca2+ to AnxA5 but to the transfer of ions to the lumen of the proteoliposomes. Ca2+ uptake stopped immediately after the addition of EDTA. Therefore, our data provide evidence of selective Ca2+ transport into the proteoliposomes and support the possible function of AnxA5 as a hydrophilic pore once incorporated into lipid membrane, mediating the mineralization initiation process occurring in matrix vesicles.

Combined use of systemic quercetin, glutamine and alpha-tocopherol attenuates myocardial fibrosis in diabetic rats.

This study aimed to analyze the effects of the quercetin (100 mg/kg), 1% glutamine and 1% α-tocopherol antioxidants in the myocardium of rats with streptozotocin-induced diabetes mellitus. Twenty male rats were subdivided into four groups (n = 5): N (normoglycemic); D (diabetic); NT (normoglycemic treated with antioxidants); and DT (diabetic treated with antioxidants) treated for 60 days. Clinical parameters, oxidative stress markers, inflammatory cytokines, myocardial collagen fibers and immunoexpression of superoxide dismutase 1 (SOD-1), glutathione peroxidase-1 (GPx-1), interleukin-1ß (IL-1-ß), transforming growth factor-beta (TGF-ß), and fibroblast growth factor-2 (FGF-2) were evaluated. Results showed reduced body weight, hyperphagia, polydipsia and hyperglycemic state in groups D and DT. The levels of glutathione (GSH) were higher in NT and DT compared to N (p < 0.01) and D (p < 0.001) groups, respectively. Greater GSH levels were found in DT when compared to N animals (p < 0.001). In DT, there was an increase in IL-10 in relation to N, D and NT (p < 0.05), while GPx-1 expression was similar to N and lower compared to D (p < 0.001). TGF-ß expression in DT was greater than N (p < 0.001) group, whereas FGF-2 in DT was higher than in the other groups (p < 0.001). A significant reduction in collagen fibers (type I) was found in DT compared to D (p < 0.05). The associated administration of quercetin, glutamine and α-tocopherol increased the levels of circulating interleukin-10 (IL-10) and GSH, and reduced the number of type I collagen fibers. Combined use of systemic quercetin, glutamine and alpha-tocopherol attenuates myocardial fibrosis in diabetic rats.

COVID-19 and Lung Mast Cells: The Kallikrein-Kinin Activation Pathway.

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein-kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.

The Colombian Strain of Trypanosoma cruzi Induces a Proinflammatory Profile, Neuronal Death, and Collagen Deposition in the Intestine of C57BL/6 Mice Both during the Acute and Early Chronic Phase.

The objective of this study was to evaluate the histopathological changes caused by infection with the Colombian strain of Trypanosoma cruzi (T. cruzi) in the acute and chronic experimental phases. C57Bl/6 mice were infected with 1000 trypomastigote forms of the Colombian strain of T. cruzi. After 30 days (acute phase) and 90 days (early chronic phase) of infection, the animals were euthanized, and the colon was collected and divided into two parts: proximal and distal. The distal portion was used for histopathological analysis, whereas the proximal portion was used for quantification of pro- and anti-inflammatory cytokines. In addition, the weight of the animals and parasitemia were assessed. The infection induced gradual weight loss in the animals. In addition, the infection induced an increase in interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α) in the intestine in the acute phase, in which this increase continued until the early chronic phase. The same was observed in relation to the presence of intestinal inflammatory infiltrates. In relation to interleukin (IL)-10, there was an increase only in the early chronic phase. The Colombian strain infection was also able to induce neuronal loss in the myenteric plexus and deposition of the collagen fibers during the acute phase. The Colombian strain of T. cruzi is capable of causing histopathological changes in the intestine of infected mice, especially in inducing neuronal destructions. Thus, this strain can also be used to study the intestinal form of Chagas disease in experimental models.

Living with an enemy: Invasive sun-coral (Tubastraea spp.) competing against sponges Desmapsamma anchorata in southeastern Brazil.

The azooxanthellate corals Tubastraea coccinea and T. tagusensis invaded the Brazilian coast in the 1980s and is still in expansion, favored by lower predation and competition pressure in their new habitats. Interestingly, the native sponge Desmapsamma anchorata has been observed overgrowing these corals. Considering that competitive displacement is expected to play a major role in the successful outcome of an invasion, the present study tested the physical and chemical mechanisms possibly involved in the competition between D. anchorata and the Tubastraea corals through field and aquaria experiments as well as the Raman spectroscopy technique for chemical analysis. Our results showed that the sponge grew in all directions including over Tubastraea colonies and regardless of its presence. There was no evidence of a specific chemical response among sponges or corals. However, we observed the extrusion of mesenteric filaments and tentacles of corals and the projection of sponge tissue during interspecific interaction, which suggests that physical imposition plays a key role for space competition at micro scales. Given the interspersed nature of benthic species distributions and the fast expansion of Tubastraea, it is unlikely that D. anchorata or any other sponges could serve a biological control against these invasive corals at larger scales, but our results showed that at a microscale they can withstand the corals presence and even outgrow them locally.

Articular cartilage degeneration and bone adaptation due to lack of dystrophin in mice.

INTRODUCTION: Duchenne muscular dystrophy is caused by the absence of dystrophin. This study aimed to investigate femoral morphological characteristics of lack of dystrophin in MDX mice, considering that this model, different from DMD patient, is not influenced by corticosteroids administration and limited ambulation. MATERIALS AND METHODS: Proximal femur of male 16-week-old Control and MDX mice were submitted to histological, morphometric (volume density of articular cartilage, compact bone, trabecular bone and bone marrow; articular cartilage layers area; articular cartilage cell area), and immunohistochemistry analysis for RUNX-2, RANK-L, MMP-2, MMP-9, Caspase-3 and KI-67. RESULTS: MDX showed loss of linearity of articular cartilage with subchondral bone transition and elevation of this subchondral bone to the articular surface when compared with control. In addition, MDX presented morphological difference in the pantographic network of collagen fibers. Volume density of trabecular bone tissue was higher in the MDX than Control, but volume density of articular cartilage was lower in MDX (p < 0.05). The articular cartilage layers and chondrocytes area were significantly smaller in MDX than Control. These results associated to MMPs and osteogenic markers of proximal femur revealed an adaptation process as a consequence of lack of dystrophin. CONCLUSIONS: The morphological changes observed in the bone tissue of the MDX may be not only secondary to muscle weakness or chronic use of corticosteroids but also our results indicate connections between decrease of cartilage thickness, collagen network alteration and consequent subchondral changes that may lead to articular cartilage degeneration and bone adaptation mechanism in MDX mice.

Uberização: precarização do trabalho e ação política dos trabalhadores no Brasil de 2020 / Uberisation: precarisation of work and political action of workers in 2020 Brazil

Este artigo tem por objetivo geral debater o que é trabalhar no Brasil de 2020, a partir do processo de precarização em sua versão mais atualizada: a uberização. Em específico, nosso objetivo é discutir as estratégias e reinvenções desenvolvidas por uma categoria de trabalhadores uberizados para minimizar ou conter o avanço da precarização. Seguindo a tradição teórico-metodológica da psicologia social do trabalho, conduzimos uma análise temática a partir do perfil oficial do movimento dos Entregadores Antifascistas na rede social Instagram. O material para análise compreende postagens, entrevistas e reportagens em formato escrito e audiovisual, de acesso público. Nossa análise é apresentada a partir de três temas que emergem como fundamentais para o debate proposto: a precarização e seu aprofundamento na pandemia; o empreendedorismo funcionando para a precarização do trabalho; e o encontro da política com o trabalho dos entregadores. Concluímos que acompanhar a emergência e o desenvolvimento de movimentos de trabalhadores no enfrentamento à uberização nos mundos do trabalho permite identificar e compreender as implicações psicossociais dessas novas modalidades de organização do trabalho

This study aims to discuss the uberization of work as a more up-to-date version of the precarization of work. It also aims to show and debate the strategies and tactics which uberized workers developed to minimize its consequences and prevent the increase of precarious and insecure jobs. Following the theoretical-methodological perspective of the Latin American social psychology of work, we conducted a thematic analysis using documents from the official Instagram account of the movement of "Anti-Fascist Couriers." Publicly accessible written and audiovisual documents ­ such as photos, interviews, documentaries, and magazine and newspaper articles ­ compose our dataset. We show our analysis considering three main themes: the increase of precarious conditions at work after the outbreak of the COVID-19 pandemic; how entrepreneurialism enlarge precarious conditions at work; and delivery workers' political action. We conclude that monitoring the emergence and development of workers' movements in the fight against uberization in the world of work enabled us to identify and understand the psychosocial implications of these new forms of work organization

Consequences of ankle joint immobilisation: insights from a morphometric analysis about fibre typification, intramuscular connective tissue, and muscle spindle in rats.

Orthosis immobilisations are routinely used in orthopaedic procedures. This intervention is applicable in bone fractures, ligament injuries, and tendonitis, among other disorders of the musculoskeletal system. We aimed to evaluate the effects of ankle joint functional immobilisation on muscle fibre morphology, connective tissue, muscle spindle and fibre typification triggered by a novel metallic orthosis. We developed a rodent-proof experimental orthosis able to hold the tibiotalar joint in a functional position for short and long terms. The tibialis anterior muscles of free and immobilised legs were collected and stained by histology and histochemistry techniques to investigate general muscle morphology, connective tissue and muscle fibre typification. Morphometric analysis of muscle cross-section area, fibre type cross-section area, fibre type density, percentage of intramuscular connective tissue, and thickness of the muscle spindle capsule were obtained to gain insights into the experimental protocol. We found that short- and long-term immobilisation decreased the cross-section area of the muscles and induced centralisation of myonuclei. The connective tissue of immobilised muscle increased after 2 and 4 weeks mainly by deposition of type III and type I collagen fibres in the perimysium and endomysium, respectively, in addition to muscle spindle capsule thickening. Type IIB muscle fibre was severely affected in our study; the profile assumed odd shapes, and our data suggest interconversion of these fibre types within long-term immobilisation. In conclusion, our protocol has produced structural and histochemical changes in muscle biology. This method might be applied to various rodent models that enable genetic manipulation for the investigation of muscle degeneration/regeneration processes.

Proteogenomics Reveals Orthologous Alternatively Spliced Proteoforms in the Same Human and Mouse Brain Regions with Differential Abundance in an Alzheimer's Disease Mouse Model.

Alternative splicing (AS) may increase the number of proteoforms produced by a gene. Alzheimer's disease (AD) is a neurodegenerative disease with well-characterized AS proteoforms. In this study, we used a proteogenomics strategy to build a customized protein sequence database and identify orthologous AS proteoforms between humans and mice on publicly available shotgun proteomics (MS/MS) data of the corpus callosum (CC) and olfactory bulb (OB). Identical proteotypic peptides of six orthologous AS proteoforms were found in both species: PKM1 (gene PKM/Pkm), STXBP1a (gene STXBP1/Stxbp1), Isoform 3 (gene HNRNPK/Hnrnpk), LCRMP-1 (gene CRMP1/Crmp1), SP3 (gene CADM1/Cadm1), and PKCßII (gene PRKCB/Prkcb). These AS variants were also detected at the transcript level by publicly available RNA-Seq data and experimentally validated by RT-qPCR. Additionally, PKM1 and STXBP1a were detected at higher abundances in a publicly available MS/MS dataset of the AD mouse model APP/PS1 than its wild type. These data corroborate other reports, which suggest that PKM1 and STXBP1a AS proteoforms might play a role in amyloid-like aggregate formation. To the best of our knowledge, this report is the first to describe PKM1 and STXBP1a overexpression in the OB of an AD mouse model. We hope that our strategy may be of use in future human neurodegenerative studies using mouse models.