Macrophages, IL-10, and nitric oxide increase, induced by hyperglycemic conditions, impact the development of murine melanoma B16F10-Nex2.

Epidemiological studies show a strong correlation between diabetes and the increased risk of developing different cancers, including melanoma. In the present study, we investigated the impact of a streptozotocin (STZ)-induced hyperglycemic environment on B16F10-Nex2 murine melanoma development. Hyperglycemic male C57Bl/6 mice showed increased subcutaneous tumor development, partially inhibited by metformin. Tumors showed increased infiltrating macrophages, and augmented IL-10 and nitric oxide (NO) concentrations. In vivo neutralization of IL-10, NO synthase inhibition, and depletion of macrophages reduced tumor development. STZ-treated TLR4 KO animals showed delayed tumor development; the transfer of hyperglycemic C57Bl/6 macrophages to TLR4 KO reversed this effect. Increased concentrations of IL-10 present in tumor homogenates of hyperglycemic mice induced a higher number of pre-angiogenic structures in vitro, and B16F10-Nex2 cells incubated with different glucose concentrations in vitro produced increased levels of IL-10. In summary, our findings show that a hyperglycemic environment stimulates murine melanoma B16F10-Nex2 primary tumor growth, and this effect is dependent on tumor cell stimulation, increased numbers of macrophages, and augmented IL-10 and NO concentrations. These findings show the involvement of tumor cells and other components of the tumor microenvironment in the development of subcutaneous melanoma under hyperglycemic conditions, defining novel targets for melanoma control in diabetic patients.

Potentialities and limitations of Interprofessional Education during graduation: a systematic review and thematic synthesis of qualitative studies.

BACKGROUND: Rapid demographic, epidemiological, technological, cultural/behavioural, and educational transitions, as they become more complex, demand new integrated and complementary professional skills and abilities. Interprofessional Education (IPE) is a promising alternative to deal with these changes, especially in courses in the health area. This systematic review was to explore the potentialities and limitations of IPE, from the perspective of undergraduate students, through a thematic synthesis of qualitative studies. METHODS: A thematic synthesis of qualitative studies was conducted. The question elaborated for this review was: "What is the impact of interprofessional education on the teaching and learning of students in the health area inserted in Higher Education Institutions?". The search strategy was performed in the electronic databases PubMed, Latin American and Caribbean Literature in Health Sciences (LILACS), Cochrane Library, and Scientific Electronic Library Online (SciELO). In addition, searches were carried out in grey literature on the ERIC platforms, ProQuest Disserts and Theses, and Academic Google. The assessment of the quality of the studies was carried out using the Critical Appraisal Skills Programme tool. Data were summarized through thematic synthesis. From the databases, 8,793 studies were identified. After standardized filters procedures, critical summaries, and assessment of relevance to the eligibility criteria, 14 articles were included. RESULTS: The synthesis of the studies revealed the potential of this teaching approach, arranged in three analytical themes: learning from each other and about them; the value of education and interprofessional practice; patient-centred health care. On the other hand, some limitations were also identified, such as barriers related to EIP; the difficulties related to teaching methodologies. CONCLUSION: Overcoming the identified limitations can enhance the results of the IPE, in view of its impact on the education of students and on the health care of the population.

[Unsafe practices fostering cutaneous abscesses in people who inject substances : Results from the ANRS-OUTSIDER study]. / Des pratiques à risque favorisant la survenue d'abcès cutanés chez les personnes qui injectent des substances : résultats de l'étude ANRS-OUTSIDER.

INTRODUCTION: Cutaneous abscesses are a common complication of intravenous substance use. Although these skin and soft tissue infections represent one of the main causes of emergency room visits and hospitalizations in people who inject drugs (PWID), data on their prevalence and causes are scarce. The present study was part of the larger ANRS-OUTSIDER project and aimed to study the factors associated with skin abscesses in PWID, focusing in particular on the different stages of injection. METHOD: Analyses were based on data of the 164 persons who regularly injected psychoactive substances participating in the French ANRS-OUTSIDER project. A face-to-face questionnaire collected data on sociodemographics, substance use, injection practices, and experience of skin abscesses in the previous six months. Factors associated with skin abscesses were studied using a logistic regression model. RESULTS: Of the 140 participants for whom abscess data were recorded at inclusion, 35% reported having a skin abscess in the previous six months. Factors associated with skin abscesses were: benefiting from universal health coverage (PUMA/CMU/AME) (Odd ratio (OR) = 0.28, confidence interval (CI) à 95%=0.08-0.99), finding the vein to inject by touch (OR=3.44, 95% CI=1.41-8.43) and licking the needle before injection (OR=5.16, 95% CI=1.10-24.30). CONCLUSION: Our results highlight that skin abscesses were very frequent among the complications observed in our sample of French PWID, and that certain injection practices fostered their occurrence. These data will provide stakeholders with useful information to improve prevention and harm reduction messages for PWID.

Home-based is as effective as centre-based rehabilitation for improving upper limb motor recovery and activity limitations after stroke: A systematic review with meta-analysis.

OBJECTIVE: This systematic review aimed to examine the effects of home-based exercises in comparison with centre-based exercises for improving the paretic upper limb after stroke. DATA SOURCES: AMED, MEDLINE, EMBASE CINAHL, Cochrane, PsycINFO, and PEDro databases. REVIEW METHODS: Only randomized clinical trials were included. Participants in the reviewed studies were adults at any time after stroke. The experimental intervention was home-based exercises compared with centre-based exercises. Outcome data related to strength, motor recovery, dexterity, activity, and participation were extracted from the eligible trials and combined in meta-analyses. The quality of included trials was assessed by the PEDro scores. The quality of evidence was determined according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Eight trials, involving 488 participants, were included. Most trials (63%) delivered semi-supervised interventions (amount of supervision 3-43%), and three trials provided full supervision. Random-effects meta-analyses provided moderate- to high-quality evidence that home- and centre-based exercises provide similar effects on motor recovery (MD 1.4 points; 95% CI -0.9 to 3.8), dexterity (MD -0.01 pegs/s; 95% CI -0.04 to 0.05), upper limb activity performance (SMD -0.04; 95% CI -0.25 to 0.18), and quality of movement (0.1 points; 95% CI -0.2 to 0.4). Effects on strength were also similar but the quality of the evidence was rated as low. No trials examined effects on participation. CONCLUSION: Effects of home-based prescribed exercises on upper limb motor recovery, dexterity, and activity are likely to be similar to improvements obtained by centre-based exercises after stroke.

Cellular Model of Malignant Transformation of Primary Human Astrocytes Induced by Deadhesion/Readhesion Cycles.

Astrocytoma is the most common and aggressive tumor of the central nervous system. Genetic and environmental factors, bacterial infection, and several other factors are known to be involved in gliomagenesis, although the complete underlying molecular mechanism is not fully understood. Tumorigenesis is a multistep process involving initiation, promotion, and progression. We present a human model of malignant astrocyte transformation established by subjecting primary astrocytes from healthy adults to four sequential cycles of forced anchorage impediment (deadhesion). After limiting dilution of the surviving cells obtained after the fourth deadhesion/readhesion cycle, three clones were randomly selected, and exhibited malignant characteristics, including increased proliferation rate and capacity for colony formation, migration, and anchorage-independent growth in soft agar. Functional assay results for these clonal cells, including response to temozolomide, were comparable to U87MG-a human glioblastoma-derived cell lineage-reinforcing malignant cell transformation. RNA-Seq analysis by next-generation sequencing of the transformed clones relative to the primary astrocytes revealed upregulation of genes involved in the PI3K/AKT and Wnt/ß-catenin signaling pathways, in addition to upregulation of genes related to epithelial-mesenchymal transition, and downregulation of genes related to aerobic respiration. These findings, at a molecular level, corroborate the change in cell behavior towards mesenchymal-like cell dedifferentiation. This linear progressive model of malignant human astrocyte transformation is unique in that neither genetic manipulation nor treatment with carcinogens are used, representing a promising tool for testing combined therapeutic strategies for glioblastoma patients, and furthering knowledge of astrocytoma transformation and progression.

Seroprevalence of hepatitis B and C among domestic and healthcare waste handlers in Belo Horizonte, Brazil.

Infection with the hepatitis B and C viruses may occur through contact with infected body fluids, including injury with infected sharps. Collectors of domestic or healthcare wastes are potentially exposed to these infections. The aim of this article is to investigate the risk factors associated with the prevalence of hepatitis B and C viruses (HBV and HCV) infection among domestic and healthcare waste workers in Belo Horizonte, Brazil. A cross-sectional study of hepatitis B and C infection was conducted from November 2014 to January 2015, through blood sample collection and interviews about socio-demographic factors with 61 workers exposed to healthcare waste ('exposed') and 461 exposed only to domestic wastes ('unexposed'). The prevalence of antibodies to HCV (Anti-HCV) antibodies was 3.3% in 'exposed' workers and 0.9% in 'unexposed', and of antibody to hepatitis B core antigen (Anti-HBc) was 9.8% and 5.6% in 'exposed' and 'unexposed' workers, respectively. Only 207 (44.9%) of those exposed to domestic waste and 45 (73.8%) of those handling healthcare waste were effectively immunised against hepatitis B virus (HBV). Exposures to domestic waste and to healthcare wastes were associated with similar risks of infection with HBV. The risk of hepatitis C virus (HCV) infection was marginally higher among healthcare waste workers compared with domestic waste workers, probably because of needlestick accidents owing to deficient sharps management systems. Immunisation against hepatitis B and screening tests to ensure the success of vaccination should be a condition for recruitment for both groups of waste workers.

Effect of low-intensity pulsed ultrasound on bone regeneration: biochemical and radiologic analyses.

OBJECTIVES: The purpose of this study was to evaluate the effects of low-intensity pulsed ultrasound at 1.0 MHz on the healing process of fractures with bone loss in the rat fibula by alkaline phosphate level measurement and radiologic analyses. METHODS: Thirty 70-day-old male Wistar rats underwent a bone resection of 2.5 to 3.0 mm between the proximal and middle third of the right fibular diaphysis. The animals were randomly divided into 3 experimental groups: reference (uninjured), control (injured only), and treated (injured and treated with 5 applications of ultrasound, interspersed by 2 days of rest, beginning 24 hours after the osteotomy). Euthanasia was performed at experimental periods of 7 and 14 days. The right hind limb was removed for radiologic analysis. The blood was collected via cardiac puncture to determine the serum alkaline phosphatase activity. RESULTS: The bone fractures had not been completely consolidated in the treated and control group when analysis of the bone took place. At day 7, the serum alkaline phosphatase activity was higher in the treated group (mean ± SD, 72.17 ± 7.02 U/L) compared to the control (65.26 ± 8.41 U/L) and reference (67.21 ± 7.86 U/L) groups. At day 14, higher alkaline phosphatase activity was seen in the control group (68.96 ± 8.12 U/L) compared to the treated (66.09 ± 8.46 U/L) and reference (67.14 ± 7.96 U/L) groups. CONCLUSIONS: The biochemical and radiologic results suggest that low-intensity pulsed ultrasound can be used as an auxiliary method to consolidate fractures and probably reduces the bone healing time, offering clinical benefits.

Gender and Drug Use Discrimination Among People Who Inject Drugs: An Intersectional Approach Using the COSINUS Cohort.

Purpose: Injection drug use is strongly associated with stigmatization by loved ones, healthcare providers, and society in general. This stigmatization can have negative consequences on the health of people who inject drugs (PWID) and limit their access to care. Women who inject drugs face greater stigma than men because of gendered social norms and the intersectional effect between gender and drug use identities. For this analysis, we aimed to study discrimination - which is closely linked to stigmatization - experienced by PWID, considering the intersectionality between drug use discrimination and gender discrimination in the French context. Methods: We used data from the COSINUS cohort study, conducted between June 2016 and May 2019 in four French cities. We selected 427 of the 665 PWID who regularly injected drugs enrolled in COSINUS, at three months of follow-up, and performed multivariable logistic regression to identify factors associated with self-reported drug use discrimination. Results: Women comprised 20.6% of the study sample. Sixty-nine percent of the participants declared drug use discrimination and 15% gender discrimination. In the multivariable regression analysis, PWID who had hurried injection out of fear of being seen were almost twice as likely to have experienced drug use discrimination (OR [95% CI]: 1.77 [1.15, 2.74], p = 0.010). Likewise, women experiencing gender discrimination were almost three times as likely to have experienced drug use discrimination (OR [95% CI]: 2.84 [1.07,7.56], p=0.037). Conclusion: Women who inject drugs experienced gender and drug use intersectional discrimination. This could be a reason for the low attendance rates of women in healthcare settings. In addition, discrimination negatively impacted injection drug use practices (eg, hurried injection), particularly for people with unstable housing who injected in public spaces. We recommend introducing adapted services in healthcare facilities for women who inject drugs, and creating a favorable social and physical environment for all PWID in order to improve their health and access to care.

Mycobacterium leprae is able to infect adipocytes, inducing lipolysis and modulating the immune response.

Leprosy is a chronic infectious disease caused by the intracellular bacillus Mycobacterium leprae (M. leprae), which is known to infect skin macrophages and Schwann cells. Although adipose tissue is a recognized site of Mycobacterium tuberculosis infection, its role in the histopathology of leprosy was, until now, unknown. We analyzed the M. leprae capacity to infect and persist inside adipocytes, characterizing the induction of a lipolytic phenotype in adipocytes, as well as the effect of these infected cells on macrophage recruitment. We evaluated 3T3-L1-derived adipocytes, inguinal adipose tissue of SWR/J mice, and subcutaneous adipose tissue biopsies of leprosy patients. M. leprae was able to infect 3T3-L1-derived adipocytes in vitro, presenting a strong lipolytic profile after infection, followed by significant cholesterol efflux. This lipolytic phenotype was replicated in vivo by M. leprae injection into mice inguinal adipose tissue. Furthermore, M. leprae was detected inside crown-like structures in the subcutaneous adipose tissue of multibacillary patients. These data indicate that subcutaneous adipose tissue could be an important site of infection, and probably persistence, for M. leprae, being involved in the modulation of the innate immune control in leprosy via the release of cholesterol, MCP-1, and adiponectin.

Sleep and memory complaints in long COVID: an insight into clustered psychological phenotypes.

This study evaluated clinical features of individuals with long COVID (5-8 months after diagnosis) who reported sleep and memory problems (62 cases) compared to those without (52 controls). Both groups had a similar mean age (41 vs. 39 years). Around 86% of the participants were non-hospitalized at the time of infection, and none of them were vaccinated at that point. Subsequently, both cases and controls received the vaccine; however, the vaccination rates differed significantly between the groups (30.7% vs. 51.0%). Cases and controls had similar rates of symptoms at acute COVID phase. However, cases were more likely to experience coryza, dyspnea, headache, and nausea/vomiting during long COVID. Regarding new-onset symptoms in long COVID, 12.9% of cases had dyspnea, and 14.5% experienced nausea/vomiting, whereas in the control group there were only 1.9% and 0.0%, respectively. Cases also had a significantly higher prevalence of persistent headache (22.6% vs. 7.7%), and dyspnea (12.9% vs. 0.0). In addition, cases also showed an increased rate of mental health complaints: disability in daily activities (45.2% vs. 9.6%; P < 0.001); concentration/sustained attention difficulties (74.2% vs. 9.6%; P < 0.001); anxiety-Generalized Anxiety Disorder 2-item scale (GAD-2) ≥ 3 (66.1% vs. 34.6%; P = 0.0013); and "post-COVID sadness" (82.3% vs. 40.4%; P < 0.001). We observed a significant correlation between sadness and anxiety in cases, which was not observed in controls (P=0.0212; Spearman correlation test). Furthermore, the frequency of concomitant sadness and anxiety was markedly higher in cases compared to controls (59.7% vs. 19.2%) (P < 0.0001; Mann-Whitney test). These findings highlight a noteworthy association between sadness and anxiety specifically in cases. In conclusion, our data identified concurrent psychological phenotypes in individuals experiencing sleep and memory disturbances during long COVID. This strengthens the existing evidence that SARS-CoV-2 causes widespread brain pathology with interconnected phenotypic clusters. This finding highlights the need for comprehensive medical attention to address these complex issues, as well as major investments in testing strategies capable of preventing the development of long COVID sequelae, such as vaccination.

Is transcranial direct current stimulation (tDCS) effective to improve cognition and functionality after severe traumatic brain injury? A perspective article and hypothesis.

Severe traumatic brain injury (sTBI) is an important cause of disability and mortality and affects people of all ages. Current scientific evidence indicates that motor dysfunction and cognitive impairment are the main limiting factors in patients with sTBI. Transcranial direct current stimulation (tDCS) seems to be a good therapeutic option, but when it comes to patients with sTBI, the results are inconclusive, and some protocols have not yet been tested. In addition, there is still a lack of information on tDCS-related physiological mechanisms, especially during the acute phase. In the present study, based on current evidence on tDCS mechanisms of action, we hypothesized that performing tDCS sessions in individuals with sTBI, especially in the acute and subacute phases, together with conventional therapy sessions, could improve cognition and motor function in this population. This hypothesis presents a new possibility for treating sTBI, seeking to elucidate the extent to which early tDCS may affect long-term clinical outcomes.

Comparative evaluation of vegetable matter involved lesions with oral parasitic infections in the oral cavity.

The current research aims to perform a comparative evaluation of vegetable matter involved lesions with oral parasitic infections found in oral mucosa, presenting histochemical methods to differentiate their microscopic similarities. Eight cases were selected out of a sample of 1.975 reports from a single Oral and Maxillofacial Pathology Service of the author's institution from 2012 to 2019. Specimens were examined by hematoxylin and eosin staining (HE), periodic acid-Schiff (PAS) staining, Gomori-Grocott staining, Ziehl-Neelsen staining, Giemsa, and mucicarmine staining. Microscopic analysis included fluorescence, polarized light, and confocal microscopy. Microscopically, in HE coloration, hookworm eggs showed as eosinophilic. Inflammatory multinucleated giant cells and lymphocytes, were usually related to the nematode eggs, forming an intense inflammatory infiltrate. Biofluorescent properties of eggs and larvae revealed to be sensitive in the detection of parasitic structures contrasting with the inflamed connective tissue. Vegetable presence was confirmed by polarized light microscopy and it was found to be associated with microbial biofilms. Confocal microscopy has showed to be an excellent method for morphotype differentiation of parasitic eggs. Parasitic infection and vegetable matter displayed similarities in the inflammatory response, but the latter can rot and agglomerate biofilms. The microscopic diagnosis of such infections requires the interpretation of challenging morphological features since the parasites are usually sectioned and mixed with an inflammatory reaction. These histochemical approaches proved to be excellent to distinguish both lesions.

Quality of biosafety guidelines for dental clinical practice throughout the world in the early COVID-19 pandemic: a systematic review.

OBJECTIVES: To conduct a systematic review of coronavirus disease 2019 (COVID-19)-related biosafety guidelines for dental clinical practice in the early stage of the pandemic, focusing on quality assessment. METHODS: Electronic (via PubMed, Scopus, Web of Science, Latin American and Caribbean Health Sciences Literature database, Brazilian Library in Dentistry, and Cochrane Library) and gray literature searches were performed for documents published up to May 12, 2020. Guidelines updated until April 17, 2021 were identified. Documents were included as guidelines if they (1) consisted of a set of statements, directions, or principles presenting current or future rules or policy; (2) were developed by government agencies, institutions, organizations, or expert panels; and (3) were related to the general conduct of healthcare activities rather a particular condition. Two researchers, using the Appraisal of Guidelines for Research & Evaluation II, independently extracted the recommendations and evaluated the quality of the guidelines. RESULTS: Twenty-seven documents from 19 countries were included in the review. These documents presented 122 recommendations related to (1) professional biosafety; (2) patients'/companions' safety; (3) the organization and biosafety of the physical dental facility environment; and (4) the work process in dental care. Overall, the scientific quality of the guidelines was considered low. Some recommendations presented in these guidelines would require further research to establish their effectiveness. CONCLUSIONS: We found a wide variety of biosafety guidelines for dental practice regarding COVID-19 in the early months of the pandemic, but their quality was low. Biosafety recommendations should be frequently updated.

Impact of interprofessional education on the teaching and learning of higher education students: A systematic review.

AIM: This systematic review was to explore the potentialities and limitations of Interprofessional Education (IPE), from the perspective of undergraduate students. BACKGROUND: The increasing complexity in health increasingly demand professionals with the capacity to act in the face of new global challenges. Thus, this pedagogical approach presents itself as one of the most promising choices in facing these new obstacles. DESIGN: A synthesis of quantitative studies and mixed methods. METHODS: Studies involving quantitative analyzes were included, with no restriction on the date of publication and language. The search strategy was carried out in the electronic databases: PubMed, Latin American and Caribbean Literature in Health Sciences (LILACS), Cochrane Library and Scientific Electronic Library Online (SciELO). In addition, searches were carried out in gray literature on the ERIC platforms (ProQuest), ProQuest Disserts and Theses Full text and Academic Google. The assessment of the quality of the studies was carried out using the instrument by Downs and Black. The risks of bias in the studies were examined with the aid of the adapted version of the Cochrane Collaboration tool, with the domains of the Downs and Black instrument. RESULTS: After standardized filter procedures, critical summaries and assessment of relevance to the eligibility criteria, 11 articles were included. The results showed that most students have a positive perception of IPE, with different factors influencing this research finding. The need to develop more robust assessment instruments is highlighted, in view of the insufficiency of tools with sufficient methodological rigor to measure real changes in attitudes among different groups of students. CONCLUSION: More consistent research is needed, which assesses, in a longitudinal way, the effects that the IPE has on the teaching and learning of undergraduate students and its impact after professional training.

Decitabine limits escape from MEK inhibition in uveal melanoma.

MEK inhibitors (MEKi) demonstrate anti-proliferative activity in patients with metastatic uveal melanoma, but responses are short-lived. In the present study, we evaluated the MEKi trametinib alone and in combination with drugs targeting epigenetic regulators, including DOT1L, EZH2, LSD1, DNA methyltransferases, and histone acetyltransferases. The DNA methyltransferase inhibitor (DNMTi) decitabine effectively enhanced the anti-proliferative activity of trametinib in cell viability, colony formation, and 3D organoid assays. RNA-Seq analysis showed the MEKi-DNMTi combination primarily affected the expression of genes involved in G1 and G2/2M checkpoints, cell survival, chromosome segregation and mitotic spindle. The DNMTi-MEKi combination did not appear to induce a DNA damage response (as measured by γH2AX foci) or senescence (as measured by ß-galactosidase staining) compared to either MEKi or DNMTi alone. Instead, the combination increased expression of the CDK inhibitor p21 and the pro-apoptotic protein BIM. In vivo, the DNMTi-MEKi combination was more effective at suppressing growth of MP41 uveal melanoma xenografts than either drug alone. Our studies indicate that DNMTi may enhance the activity of MEKi in uveal melanoma.

Long-term single-cell passaging of human iPSC fully supports pluripotency and high-efficient trilineage differentiation capacity.

OBJECTIVES: To establish a straightforward single-cell passaging cultivation method that enables high-quality maintenance of human induced pluripotent stem cells without the appearance of karyotypic abnormalities or loss of pluripotency. METHODS: Cells were kept in culture for over 50 passages, following a structured chronogram of passage and monitoring cell growth by population doubling time calculation and cell confluence. Standard procedures for human induced pluripotent stem cells monitoring as embryonic body formation, karyotyping and pluripotency markers expression were evaluated in order to assess the cellular state in long-term culture. Cells that underwent these tests were then subjected to differentiation into keratinocytes, cardiomyocytes and definitive endoderm to evaluate its differentiation capacity. RESULTS: Human induced pluripotent stem cells clones maintained its pluripotent capability as well as chromosomal integrity and were able to generate derivatives from the three germ layers at high passages by embryoid body formation and high-efficient direct differentiation into keratinocytes, cardiomyocytes and definitive endoderm. CONCLUSIONS: Our findings support the routine of human induced pluripotent stem cells single-cell passaging as a reliable procedure even after long-term cultivation, providing healthy human induced pluripotent stem cells to be used in drug discovery, toxicity, and disease modeling as well as for therapeutic approaches.

Risk Factors for Falls in Older Adults With Mild Cognitive Impairment and Mild Alzheimer Disease.

BACKGROUND AND PURPOSE: Understanding fall risk factors in people with mild cognitive impairment (MCI) and Alzheimer disease (AD) can help to establish specific plans for prevention of falls. The purpose of this study was to identify fall risk factors in older adults with MCI and mild AD. METHODS: A prospective study was conducted with community-dwelling older adults (40 MCI; 38 mild AD). The assessments consisted of sociodemographic and health variables, caloric expenditure, functional status, functional mobility (10-m walk test, dual-task test, and transition Timed Up and Go phases), cognitive domains, and depressive symptoms. Falls were recorded for 6 months by a falls calendar and monthly telephone calls. RESULTS: Falls were reported in 52.6% and 51.4% of people with MCI and mild AD, respectively. Among people with MCI, lower functional status, higher time spent on walk and dual task tests, and higher depressive symptom scores were associated with falls. Higher time spent on the dual-task test was independently associated with falls. Among people with mild AD, falls were associated with lower time spent on the walk test and turn-to-sit phase, and a higher visuospatial domain score. Lower time spent on the turn-to-sit phase was identified as an independent predictor of falls. CONCLUSIONS: Careful attention should be given to dual-task and turn-to-sit activities when detecting risk of falls among older people with MCI and mild AD.

Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human melanoma development.

Melanoma is the most aggressive type of cutaneous tumors due to its metastatic potential and high mortality. Increased levels of reactive oxygen species, including superoxide anion (O2-), and the consequent installation of a pro-oxidant environment are associated with melanoma development. The enzyme nitric oxide synthase (NOS), responsible for the production of nitric oxide (NO), when uncoupled is as a source of O2-, for example by the absence of its cofactor tetrahydrobiopterin (BH4). Western blot analysis showed increased expression of endothelial and inducible NOS in human melanoma cells, altering the stoichiometry between NOS levels and BH4 concentration and together with decreased BH4:BH2 ratio are contributing to NOS uncoupling. The treatment of melanoma cells with exogenous BH4 increased NO concentration and decreased O2- levels, leading to NOS coupling, which in turn reduced cell viability, cell proliferation and the ability of melanoma cells to form melanoma spheroids. Moreover, BH4 level restoration rendered melanoma cells more sensitive to apoptosis, demonstrating the role of dysfunctional NOS in melanoma genesis.

Influence of experimental alcoholism on the repair process of bone defects filled with beta-tricalcium phosphate.

This study evaluated the effect of ethanol on the repair in calvaria treated with beta-tricalcium phosphate (ß-TCP). Forty rats were distributed into 2 groups: Water group (CG, n = 20) and Alcohol Group (AG, n = 20), which received 25% ethanol ad libitum after an adaptation period of 3 weeks. After 90 days of liquid diet, the rats were submitted to a 5.0 mm bilateral craniotomy in the parietal bones; the left parietal was filled with ß-TCP (CG-TCP and AG-TCP) and the contralateral only with blood clot (CG-Clot and AG-Clot). The animals were killed after 10, 20, 40 and 60 days. The groups CG-Clot and AG-Clot showed similar pattern of bone formation with a gradual and significant increase in the amount of bone in CG-Clot (22.17 ± 3.18 and 34.81 ± 5.49) in relation to AG-Clot (9.35 ± 5.98 and 21.65 ± 6.70) in periods of 20-40 days, respectively. However, in the other periods there was no statistically significant difference. Alcohol ingestion had a negative influence on bone formation, even with the use of ß-TCP, exhibiting slow resorption and replacement by fibrous tissue, with 16% of bone formation within 60 days in AG-TCP, exhibiting immature bone tissue with predominance of disorganized collagen fibers. Defects in CG-TCP showed bone tissue with predominance of lamellar arrangement filling 39% of the original defect. It can be concluded that chronic ethanol consumption impairs the ability to repair bone defects, even with the use of a ß-TCP biomaterial.