EGFR, VEGF, and angiogenesis promote the development of lipoma in the oral cavity.

This study aimed to detect, quantify and compare the immunohistochemical expression of EGFR and VEGF and microvessel count (MVC) in oral lipomas, and to correlate the findings with clinical and morphological characteristics of the cases studied. The sample consisted of 54 oral lipomas (33 classic and 21 non-classic) and 23 normal adipose tissue specimens. Cytoplasmic and/or nuclear immunohistochemical staining of EGFR and VEGF was analyzed. The angiogenic index was determined by MVC. Cells were counted using the Image J® software. The Statistical Package for the Social Sciences was used for data analysis, adopting a level of significance of 5% for all statistical tests. A statistically significant difference in EGFR immunoexpression (p=0.047), especially, between classic lipomas and normal adipose tissue. There was a significant difference in MVC between non-classic lipomas and normal adipose tissue (p=0.022). In non-classic lipomas, only VEGF immunoexpression showed a significant moderate positive correlation (r=0.607, p=0.01) with MVC. In classic lipomas, the number of EGFR-immunostained adipocytes was directly proportional to the number of VEGF-positive cells, demonstrating a significant moderate positive correlation (r=0.566, p=0.005). The results suggest that EGFR, VEGF, and angiogenesis participate in the development of oral lipomas but are not primarily involved in the growth of these tumors.

Different biological effects of exposure to far-UVC (222 nm) and near-UVC (254 nm) irradiation.

Ultraviolet C (UVC) light has long been used as a sterilizing agent, primarily through devices that emit at 254 nm. Depending on the dose and duration of exposure, UV 254 nm can cause erythema and photokeratitis and potentially cause skin cancer since it directly modifies nitrogenated nucleic acid bases. Filtered KrCl excimer lamps (emitting mainly at 222 nm) have emerged as safer germicidal tools and have even been proposed as devices to sterilize surgical wounds. All the studies that showed the safety of 222 nm analyzed cell number and viability, erythema generation, epidermal thickening, the formation of genetic lesions such as cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs) and cancer-inducing potential. Although nucleic acids can absorb and be modified by both UV 254 nm and UV 222 nm equally, compared to UV 254 nm, UV 222 nm is more intensely absorbed by proteins (especially aromatic side chains), causing photooxidation and cross-linking. Here, in addition to analyzing DNA lesion formation, for the first time, we evaluated changes in the proteome and cellular pathways, reactive oxygen species formation, and metalloproteinase (MMP) levels and activity in full-thickness in vitro reconstructed human skin (RHS) exposed to UV 222 nm. We also performed the longest (40 days) in vivo study of UV 222 nm exposure in the HRS/J mouse model at the occupational threshold limit value (TLV) for indirect exposure (25 mJ/cm2) and evaluated overall skin morphology, cellular pathological alterations, CPD and 6-4PP formation and MMP-9 activity. Our study showed that processes related to reactive oxygen species and inflammatory responses were more altered by UV 254 nm than by UV 222 nm. Our chronic in vivo exposure assay using the TLV confirmed that UV 222 nm causes minor damage to the skin. However, alterations in pathways related to skin regeneration raise concerns about direct exposure to UV 222 nm.

Effects of photobiomodulation on oxidative stress in rats with type 2 diabetes mellitus.

The present study aimed to evaluate photobiomodulation effects on oxidative stress in type 2 diabetes mellitus (DM2). Thirty-one male Wistar rats were used and divided into 4 groups: group 1 - animals without diabetes mellitus 2 without laser 21 J/cm2 (C-SHAM), group 2 - animals with diabetes mellitus 2 without laser 21 J/cm2 (C-DM2), group 3 - animals without diabetes mellitus 2 with laser 21 J/cm2 (L-SHAM), group 4 - animals with diabetes mellitus 2 with laser 21 J/cm2 (L-DM2). The protocol was performed 5 days/week, for 6 weeks. The animals that received photobiomodulation had one dose irradiated at two spots in the right gastrocnemius muscle. Twenty-four hours after the last intervention, the animals were euthanized. Heart, diaphragm, liver, right gastrocnemius, plasma, kidneys, weighed, and stored for further analysis. In rats with DM2, photobiomodulation promoted a decrease in thiobarbituric acid reactive substance assay (TBARS) in plasma levels. On the other hand, photobiomodulation demonstrated an increase in non-protein thiol levels (NPSH) in the heart, diaphragm and gastrocnemius. Moreover, photobiomodulation produced in the heart, diaphragm and plasma levels led to an increase in superoxide dismutase (SOD). Interestingly, photobiomodulation was able to increase superoxide dismutase in rats without DM2 in the heart, diaphragm, gastrocnemius and kidneys. These findings suggested that 6 weeks of photobiomodulation in rats with DM2 promoted beneficial adaptations in oxidative stress, with a decrease in parameters of oxidant activity and an increase in antioxidant activity.

Desinvestimento de tecnologias em saúde no Sistema Único de Saúde: um perfil no período 2012-2022 / Disinvestment of health technologies in the Brazilian Unified Health System: a profile between 2012-2022

O termo "desinvestimento" se refere ao processo de retirada de recursos de intervenções que oferecem pouco ou nenhum ganho em saúde frente a seu custo. O intuito deste processo é reforçar práticas comprovadamente seguras, efetivas ou mais custo-efetivas, otimizando os resultados em saúde e a sustentabilidade econômica dos sistemas de saúde. O objetivo do trabalho foi caracterizar o processo de desinvestimento de medicamentos conduzido pela Comissão Nacional de Incorporação de Tecnologias (CONITEC) no Sistema Único de Saúde (SUS) entre 2012 e 2022, de forma exploratória através de análise documental dos seus relatórios técnicos de recomendações. Foram coletados nome do medicamento; sua classificação pelo sistema ATC; indicação clínica; demandante; realização de Consulta Pública; modalidade de desinvestimento recomendada e justificativa para o desinvestimento. Também foi avaliado o alinhamento das diretrizes de tratamento com as decisões de desinvestimento e o status de registro sanitário das tecnologias desinvestidas em diferentes ocasiões. Foram avaliados 30 relatórios de recomendação, correspondentes a 90 medicamentos. Três relatórios tiveram como recomendação a manutenção de sete tecnologias de perfil diversificado no SUS. Outros três relatórios eram referentes a tecnologias que foram incorporadas sob a modalidade ad experimentum e que, portanto, foram reavaliadas após três anos no SUS. Quanto às tecnologias efetivamente desinvestidas (80), elas se dividiram principalmente pelos grupos L (agentes antineoplásicos e imunomoduladores; 29,3%), J (anti-infecciosos de uso sistêmico; 21,3%) e A (aparelho digestivo e metabolismo; 20%). As principais indicações clínicas dos medicamentos desinvestidos foram: artrite reumatoide; HIV; hepatite C; e doença de Crohn. Justificativas mais mencionadas foram a indisponibilidade de registro ativo do medicamento no país (24,1%), seguida por problemas relacionados à segurança (20,6%) e efetividade (19,9%). Todas as demandas tiveram origem interna do Ministério da Saúde. Em 31,3%, houve exclusão do medicamento para indicação específica e, em 30%, exclusão total do sistema de saúde; em 27,5%, optou-se por excluir apenas determinada apresentação farmacêutica; em 10% as exclusões foram de apresentação para indicação específica; e em 1,2% ocorreu restrição de uso. Consulta Pública foi realizada em 36% dos casos. Após a publicação da Diretriz de Avaliação de Desempenho de Tecnologias em Saúde no final de 2016, o perfil de medicamentos desinvestidos por categoria ATC e por indicações clínicas adquiriram maior diversidade; as justificativas para o desinvestimento, que antes focavam em questões relacionadas a efetividade e segurança, passaram a se concentrar na indisponibilidade do medicamento no mercado; as modalidades de desinvestimento se acumularam mais em exclusões do SUS e exclusões de apresentação, e a Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos se tornou a principal demandante; submissão a consultas públicas subiu de 11,9% para 86,8%. O máximo de adequação estrutural identificado nos relatórios em relação aos tópicos preconizados pela Diretriz foi de 46,2%. Embora as iniciativas de desinvestimento tenham avançado nos últimos anos, o tema ainda enfrenta dificuldades para estabelecer uma agenda sólida no país.

Disinvestment refers to withdrawing resources from interventions that offer little or no health gain compared to their cost, seeking to reinforce practices proven to be safe, effective or more cost-effective and to optimize health outcomes and the economic sustainability of health systems. This study aimed to characterize the drug divestment process conducted by the National Commission for Incorporation of Technologies (CONITEC) in the Brazilian Unified Health System (SUS) between 2012 and 2022, in an exploratory way through their the technical recommendations reports. Drug name and ATC classification, clinical indication, proponents, occurrence of Public Consultation, recommended divestment modality and justifications for disinvestment were evaluated. We also evaluated the agreement of treatment guidelines with disinvestment decisions and the sanitary registration status of technologies disinvested at different times. We evaluated 30 recommendations reports corresponding to 90 drugs. Three reports recommended the maintenance of seven technologies in SUS. Another three reports referred to technologies that were incorporated under the ad experimentum modality and then were reassessed after three years in SUS. As for the technologies effectively disinvested (80), the drugs mainly belonged to the ATC classes L (29.3%), J (21.3%) and A (20%). The main clinical indications of the disinvested drugs were: rheumatoid arthritis, HIV, hepatitis C, and Crohn's disease. The main justifications were absence of market approval for the drug in Brazil (24.1%) and problems related to safety (20.6%) and effectiveness (19.9%). All requests were from the Brazilian Ministry of Health. Public Consultation was carried out in 36% of the situations. There were recommendations to exclude the drug for a specific indication in 31.3% of the cases and total exclusion from the SUS in 30%; exclusion of a particular pharmaceutical presentation and exclusion of presentation for a specific indication occurred in 27.5% and 10%, respectively. After the publication of the Methodological Guideline for Performance Avaliation of Health Technologies ate the end of 2016, the profile of drugs disinvested by ATC category and by clinical indications acquired bigger diversity; the justifications for disinvestment, which previously focused on issues related to effectiveness and safety, passed to focus on the unavailability of the drug on the market; disinvestment modalities concentrated more on SUS exclusions and presentation exclusions; the Secretaria of Science, Technology, Innovation and Strategic Insums became the main proponent of disinvestment demands; submission to public consultations grow up from 11.9% to 86.8%. The maximum structural adequacy identified of the reports in relation to the topics recommended by the Guideline was 46,2%. The lack of standardization and overly simplified reporting formats stood out. Although divestment initiatives have advanced in recent years, this theme still needs to improve in establishing a solid agenda in Brazil.

Low-Intensity Electrostimulation Enhances Neuroregeneration and Improves Erectile Function in a Rat Model of Cavernous Nerve Injury.

BACKGROUND: Neurogenic erectile dysfunction (ED) following radical prostatectomy (RP) is a frequent complication often leading to erectile tissue remodeling and permanent ED. Low-intensity electrostimulation (LIES) has been shown to enhance peripheral nerve regeneration, however, its application on cavernous nerves (CN) has never been investigated. AIMS: To investigate whether LIES enhances CN regeneration, improves erectile function (EF) recovery, and prevents corpora cavernosal remodeling after CN injury, which is a principal factor for ED following RP. METHODS: Adult male Sprague-Dawley rats were divided into Sham, Bilateral Cavernous Nerve Injury (BCNI), and BCNI + LIES (1V, 0.1ms, 12Hz, 1h/day). After 7days, EF was assessed (ICP measurement). Penes and CN were collected for molecular analyses of TGF-ß1, Il-6, CRP, eNOS, ERK and AKT protein levels in corpus cavernosum (CC), and immunohistological analysis of DHE, total collagen and α-SMA in CC and S-100, Tub-III, DAPI, TUNEL, and nNOS in CN. OUTCOMES: Effects of LIES on EF, erectile tissue remodeling and CN structure. RESULTS: EF was decreased (P < .05) 7 days after BCNI and increased (P < .05) by LIES. Intracavernosal reactive oxygen species (DHE) was increased (P < .05) after BCNI and normalized by LIES. Protein expressions of TGF-ß1, IL-6, and CRP were increased in the penis (P < .05) after BCNI and normalized by LIES. The α-SMA and/or total collagen ratio was decreased (P < .05) after BCNI in the penis and normalized by LIES. Protein expression ratio of p-ERK/ERK and p-AKT/AKT did not change after BCNI but increased (P < .05) in LIES group. Myelination and number of nNOS positive cells in the CN were decreased (P < .05) after BCNI and normalized by LIES. The number of apoptotic nerve cells within the dorsal penile nerve was increased (P < .05) after BCNI and decreased (P < .05) by LIES compared to the BCNI group. There were no differences in eNOS expression in the penis between study groups. CLINICAL TRANSLATION: LIES may offer a potential new tool for penile rehabilitation and ED management following RP, potentially enhancing EF recovery and minimizing the side effects of this surgery. STRENGTHS & LIMITATIONS: This study provides evidence of the protective effect of LIES on EF and tissue remodeling following CN injury; nevertheless, this study has been conducted on animals and the translation to humans remains to be demonstrated. Further research to identify the underlying mechanisms of action is required. CONCLUSION: This study demonstrates that LIES of the CN after CN injury protects CN structure, enhances EF recovery, and prevents corpora cavernosal remodeling. Sturny M, Karakus S, Fraga-Silva R, et al. Low-Intensity Electrostimulation Enhances Neuroregeneration and Improves Erectile Function in a Rat Model of Cavernous Nerve Injury. J Sex Med 2022;19:686-696.

Air pollution influence on serum inflammatory interleukins: A prospective study in childhood-onset systemic lupus erythematous patients.

OBJECTIVE: To assess the effect of individual exposure, in real-time, to traffic-related pollutants on serum interleukin levels of childhood-onset lupus erythematous systemic (c-SLE) patients. METHODS: A longitudinal and observational design was conducted in 12 repeated measures of serum samples and clinical evaluations (totaling 108 measurements) of c-SLE patients over 30 consecutive months. Real-time, individual exposure to fine particles (PM2.5) and nitrogen dioxide (NO2) was measured with portable monitors. Generalized estimating equation was used to evaluate the association between exposure to PM2.5 and NO2 and the following serum cytokine levels on the 7 days preceding clinical assessment and serum collection: MCP1, IL-6, IL-8, IL-10, IL-17, IFN-alpha, and TNF-alpha. Disease activity and other risk factors were also controlled. RESULTS: An interquartile range (IQR) increase in PM2.5 daily concentration was significantly associated with increased levels of TNF-alpha on the third, fourth, and seventh day after exposure; IL-10 on the third and fourth day after exposure; IL-17 on the third and seventh day after exposure; and INF-alpha on the third day after exposure (p < 0.05). An IQR increase in 7-day moving average of PM2.5 was associated with a 6.2 pg/mL (95% CI: 0.5; 11.8; p = 0.04) increase in serum IFN-alpha level. An unexpected significant association was observed between an IQR increase in NO27-day cumulative concentration and a decrease of 1.6 pg/mL (95% CI: -2.6; -0.7; p < 0.001) in serum IL-17. CONCLUSION: Real-time exposure to PM2.5 prospectively associated with increased serum TNF-alpha, INF-alpha, IL-10, and IL-17 levels in c-SLE patients.

Resolvin-D1 attenuation of angiotensin II-induced cardiac inflammation in mice is associated with prevention of cardiac remodeling and hypertension.

AIMS: Despite the broad pharmacological arsenal to treat hypertension, chronic patients may develop irreversible cardiac remodeling and fibrosis. Angiotensin II, the main peptide responsible for the Renin-Angiotensin-Aldosterone-System, has been closely linked to cardiac remodeling, hypertrophy, fibrosis, and hypertension, and some of these effects are induced by inflammatory mediators. Resolvin-D1 (RvD1) elicits potent anti-inflammatory and pro-resolving effects in various pathological models. In this study, we aimed to examine whether RvD1 ameliorates cardiac remodeling and hypertension triggered by angiotensin II. METHODS AND RESULTS: Alzet® osmotic mini-pumps filled with angiotensin II (1.5 mg/kg/day) were implanted in male C57BL/6 J mice for 7 or 14 days. RvD1 (3 µg/kg/day, i.p) was administered one day after the surgery and during the complete infusion period. Blood pressure and myocardial functional parameters were assessed by echocardiography. At the end of the experimental procedure, blood and heart tissue were harvested, and plasma and histological parameters were studied. After 7 and 14 days, RvD1 reduced the increase of neutrophil and macrophage infiltration triggered by angiotensin II, and also reduced ICAM-1 and VCAM-1 expression levels. RvD1 also reduced cytokine plasma levels (IL-1ß, TNF-α, IL-6, KC, MCP-1), cardiac hypertrophy, interstitial and perivascular fibrosis, and hypertension. CONCLUSIONS: This study unveils novel cardioprotective effects of RvD1 in angiotensin II-induced hypertension and cardiac remodeling by attenuating inflammation and provides insights into a potential clinical application.

A look beyond the priority: A systematic review of the genotoxic, mutagenic, and carcinogenic endpoints of non-priority PAHs.

Knowledge of the toxic potential of polycyclic aromatic hydrocarbons (PAHs) has increased over time. Much of this knowledge is about the 16 United States - Environmental Protection Agency (US - EPA) priority PAHs; however, there are other US - EPA non-priority PAHs in the environment, whose toxic potential is underestimated. We conducted a systematic review of in vitro, in vivo, and in silico studies to assess the genotoxicity, mutagenicity, and carcinogenicity of 13 US - EPA non-priority parental PAHs present in the environment. Electronic databases, such as Science Direct, PubMed, Scopus, Google Scholar, and Web of Science, were used to search for research with selected terms without time restrictions. After analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, 249 articles, published between 1946 and 2020, were selected and the quality assessment of these studies was performed. The results showed that 5-methylchrysene (5-MC), 7,12-dimethylbenz[a]anthracene (7,12-DMBA), cyclopenta[cd]pyrene (CPP), and dibenzo[al]pyrene (Db[al]P) were the most studied PAHs. Moreover, 5-MC, 7,12-DMBA, benz[j]aceanthrylene (B[j]A), CPP, anthanthrene (ANT), dibenzo[ae]pyrene (Db[ae]P), and Db[al]P have been reported to cause mutagenic effects and have been being associated with a risk of carcinogenicity. Retene (RET) and benzo[c]fluorene (B[c]F), the least studied compounds, showed evidence of a strong influence on the mutagenicity and carcinogenicity endpoints. Overall, this systematic review provided evidence of the genotoxic, mutagenic, and carcinogenic endpoints of US - EPA non-priority PAHs. However, further studies are needed to improve the future protocols of environmental analysis and risk assessment in severely exposed populations.

IgE antibodies to hepatitis C virus core and nonstructural antigens in chronic hepatitis C patients before and after antiviral treatment.

Few studies on the immunoglobulin E (IgE) immune response in chronic hepatitis C have been reported. In this study, we tested the antigenicity of commercial recombinant hepatitis C virus (HCV) core and nonstructural protein NS3, NS4, and NS5 antigens and the IgE immune response to these antigens in chronic hepatitis C patients before and after antiviral treatment with pegylated interferon (IFN)-α plus ribavirin for 12 weeks. The effects of antiviral treatment were investigated in 20 out of 35 participants. We developed amplified immunoassays using these antigens and IgG-depleted patient sera. Seropositivity for IgE antibodies was determined, and serum IgE and cytokine levels were measured. Anti-core, anti-NS3, and anti-NS4 IgE antibodies were observed in most patients, whereas anti-NS5 antibodies were less prevalent. Antiviral treatment decreased the production of anti-core, anti-NS3, and anti-NS4 IgE antibodies, but not anti-NS5 IgE antibodies. A significant decrease in the anti-NS3 and anti-NS4 IgE antibody levels was observed in patients who presented with an early sustained virological response, but no effects on anti-core and anti-NS5 IgE antibodies was observed. The serum levels of IFN-γ, interleukin (IL)-2, IL-6, tumor necrosis factor-α, and IL-10, but not IL-4, were similar between patients before and after antiviral therapy. Thus, the immune response of IgE antibodies to HCV antigens was comparable to that of anti-HCV IgG antibodies. The usefulness of anti-NS3 IgE antibodies in diagnosing occult hepatitis C and monitoring antiviral treatment with directly acting antiviral medication must be investigated in future studies.

Bone repair assessment of critical size defects in rats treated with mineralized bovine bone (Bio-Oss®) and photobiomodulation therapy: a histomorphometric and immunohistochemical study.

This study aimed to investigate the effects of administering photobiomodulation therapy (PBM) with bovine bone matrix on critical size defects in rats. Seventy-two adult male rats (albinus, Wistar), 90 days old, were used. Defect of 5 mm in diameter was made in their calvaria. The animals were divided into 4 groups: C-blood clot, B-Bio-Oss®, L-PBM, B+L-Bio-Oss®+PBM. Each group has been subdivided into 07, 30, and 60 days of observation. For PBM, a low GaAlAs energy of 660 nm was irradiated, total energy density of 45 J/cm2 . PBM was conducted in a trans-surgical form once only. For immunohistochemistry, a semi-quantitative analysis was made of expression of osteoprotegerin (OPG), nuclear kappa B-factor ligand receptor activator (RANKL), and tartrate-resistant acid phosphatase (TRAP). All histomorphometric data were statistically analyzed by ANOVA and Tukey test, significance level of 5%. The groups that showed the highest proportion of neoformation were L (0.39% ± 0.13) and C (0.37% ± 0.97), but groups B and B+L had larger defect size (C-1.75 mm2 ± 0.40, B-3.02 mm2 ± 0.63, L-2.45 mm2 ± 0.53, B+L-3.23 mm2 ± 1.01). In immunohistochemistry, groups B and B+L had higher immunostaining scores for OPG and RANKL at 60 days, and TRAP immunostaining increased in all groups at 30 days, but group L was the only one to present specimens with score 0. Although, at 60 days, groups L and C presented the highest proportion of bone neoformation, at 30 days group B+L had more than twice as much bone neoformation as group B, the choice of treatment application should depend on the aim of the treatment.

Interaction Between Near-Infrared Radiation and Temozolomide in a Glioblastoma Multiform Cell Line: A Treatment Strategy?

Photodynamic therapy (PDT) is a potential therapeutic modality against cancer, resulting from the interaction of a photosensitizer (PS) and radiation that generates damage to tumor cells. The use of near-infrared radiation (IR-A) is relevant because presents recognized biological effects, such as antioxidant, neuroprotective and antitumor effects. Glioblastoma is the most aggressive central nervous system (CNS) neoplasm with high proliferation and tissue invasion capacity and is resistant to radio and chemotherapy. Here, we evaluated in vitro the possible interaction of temozolomide (TMZ) with IR-A in a glioblastoma cell line (C6) and in a human keratinocyte cell line (HaCat) how non-tumor cell model, in an attempt to search for a new treatment strategy. The effects of TMZ, IR-A and the interaction between TMZ and IR-A was evaluated by viability exclusion with trypan blue. To perform the interaction experiments, we have chosen 10 µM TMZ and 4.5 J/cm2 of IR-A. From this, we evaluated cytotoxicity, cell proliferation, intracellular reactive oxygen species levels (ROS), as well as the process of cell migration and the P-gp and MRP-1 activity. Cell death mainly due to apoptosis, followed by necrosis, decreased cell proliferation, increased ROS levels, decreased cell migration and decreased P-gp and MRP1 activity were observed only when there was interaction between TMZ and IR-A in the C6 cell line. The interaction between TMZ and IR-A was not able to affect cell proliferation in the HaCat non-tumor cell line. Our results suggest that this interaction could be a promising approach and that in the future may serve as an antitumor strategy for PDT application.

Prevalência da dor em estudantes universitários: uma revisão sistemática / Prevalence of pain in university students: a systematic review

Objetivo: revisar estudos sobre a prevalência e os fatores relacionados a dor em estudantes universitários brasileiros. Métodos: revisão sistemática com registro na Prospero (CRD42020204197), de artigos publicados em periódicos nacionais e internacionais, nas bases Pubmed, Ebsco, Lilacs, Medline, Portal da BVS, Google Acadêmico e SciELO. Descritores: "Pain", "Chronic Pain", Students", "Students, Health Occupations" e "Universities". Incluídos: a) estudos observacionais; b) transversais; c) publicados em periódicos nacionais ou internacionais; d) redigidos em inglês ou português; e) desenvolvidos com acadêmicos, em instituições de ensino superior brasileiras; f) que tenham avaliado a prevalência e fatores relacionados a dor; g) Tais estudos deviam estar disponíveis na íntegra. Não foram realizadas restrições quanto ao período de publicação dos estudos. Excluídos: h) estudos que não relataram a metodologia aplicada para mensuração do desfecho; i) estudos com instrumentos que não avaliaram a dor como desfecho primário, posteriormente apresentando dados insuficientes para análise dos resultados; j) estudos com acadêmicos de outros países; e k) estudos com inconsistência dos dados relacionados a amostra e seus principais resultados. O risco de viés foi avaliado com a escala Downs and Black e a proposta por Hoy. Resultados: as buscas identificaram 67 artigos, contudo, após análise, 10 foram incluídos. Esses eram estudos transversais, publicados entre 2011 e 2019, sendo cinco deles da região Nordeste. A amostra totalizou 3.268 acadêmicos, sendo 68% mulheres. A prevalência da dor variou entre 14,4% e 98% e a dor crônica entre 11,5% e 59,7%. A maior percepção da dor autorrelatada foi de 4,12 ± 2,15. As principais queixas álgicas foram nas regiões de lombar e de membros superiores. Na análise metodológica, os estudos possuem moderado a alto risco de viés. Conclusões: por fim, as evidências indicam uma alta prevalência de dor, bem como sua cronificação em universitários. Contudo, estudos com adequado rigor metodológico ainda são necessários para a confirmação dos resultados apresentados.

Objective: to review studies on the prevalence and factors related to pain in Brazilian university students. Methods: systematic review with PROSPERO record (CRD42020204197), of articles published in national and international journals, in PUBMED, EBSCO, LILACS, MEDLINE, VHL Portal, Google Scholar and SciELO. Descriptors: "Pain", "Chronic Pain", Students "," Students, Health Occupations "and" Universities ". Included: a) Observational studies; b) transversal; c) published in national or international journals; d) written in English or Portuguese; e) developed with academics, in Brazilian higher education institutions; f) who have assessed the prevalence and factors related to pain; g) Such studies should be available in full. There were no restrictions on the period of publication of the studies. Excluded: h) studies that did not report the methodology applied to measure the outcome; i) studies with instruments that did not evaluate pain as a primary outcome, subsequently presenting insufficient data to analyze the results; j) studies with academics from other countries and k) studies with inconsistent data related to the sample and its main results. The risk of bias was assessed using the Downs and Black scale and proposed by Hoy. Results: searches identified 67 articles, however, after analysis 10 were included. These were cross-sectional studies, published between 2011 and 2019, 5 of them from the Northeast region. The sample totaled 3,268 students, 68% of whom were women. The prevalence of pain varied between 14.4% and 98% and chronic pain between 11.5% and 59.7%. The highest perception of self-reported pain was 4.12 ± 2.15. The main pain complaints were in the lower back and upper limbs. In the methodological analysis, studies have a moderate to high risk of bias. Conclusions: finally, the evidence indicates a high prevalence of pain, as well as its chronicity in university students. However, studies with adequate methodological rigor are still needed to confirm the results presented.

Estrogen protects dental roots from orthodontic-induced inflammatory resorption.

OBJECTIVE: Root resorption is a side effect of orthodontic tooth movement (OTM). Despite the recognized role of estrogen on bone, there is little information about their effects on orthodontic-induced inflammatory root resorption (OIIRR). We aimed to investigate if estrogen deficiency affects OIIRR in two mice strains. METHODS: Female Balb/C (Balb) and C57BL6/J (C57) mice were ovariectomized (OVX) and replaced with estradiol (E2). Tooth samples subjected or not to OTM were collected and analyzed by microCT, histomorphometry and qPCR. RESULTS: OVX resulted in decreased root volume (RV/TV) and root mineral density (RMD) in Balb mice without OTM. In contrast, OVX did not modify physiological root structure of C57 mice. OTM and OIIRR were increased after OVX in both mice strains after 30 days. E2 replacement reversed this phenotype in Balb, but not in C57 mice. Due to the significant increase of OIIRR in OVX Balb mice, the expression of key molecules was investigated in periodontium. Accordingly, these mice showed increased expression of receptor activator of nuclear factor kappa-B ligand (RANKL), tumor necrosis factor alpha, matrix metalloproteinases-2 and -13 and decreased osteoprotegerin (OPG) and interleukin-10 expression after OTM. E2 replacement reversed the changes of these markers. CONCLUSION: The lack of estrogen in Balb mice without OTM triggered loss of root structure which was positively correlated to RANKL/OPG ratio. Regardless of mouse strain, the absence of estrogen following OTM induced OIIRR. Mechanisms involve the imbalance of RANKL/OPG system, inflammatory and osteoclastic makers.

Hardy-Weinberg Equilibrium in different mitochondrial haplogroups of four genes associated with neuroprotection and neurodegeneration / Equilíbrio de Hardy-Weinberg em diferentes haplogrupos mitocondriais de quatro genes associados à neuroproteção e neurodegeneração

ABSTRACT Background: Malfunctioning or damaged mitochondria result in altered energy metabolism, redox equilibrium, and cellular dynamics and is a central point in the pathogenesis of neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis. Therefore, it is of utmost importance to identify mitochondrial genetic susceptibility markers for neurodegenerative diseases. Potential markers include the respiratory chain enzymes Riboflavin kinase (RFK), Flavin adenine dinucleotide synthetase (FAD), Succinate dehydrogenase B subunit (SDHB), and Cytochrome C1 (CYC1). These enzymes are associated with neuroprotection and neurodegeneration. Objective: To test if variants in genes RFK, FAD, SDHB and CYC1 deviate from Hardy-Weinberg Equilibrium (HWE) in different human mitochondrial haplogroups. Methods: Sequence variants in genes RFK, FAD, SDHB and CYC1 of 2,504 non-affected individuals of the 1,000 genomes project were used for mitochondrial haplogroup assessment and HWE calculations in different mitochondrial haplogroups. Results: We show that RFK variants deviate from HWE in haplogroups G, H, L, V and W, variants of FAD in haplogroups B, J, L, U, and C, variants of SDHB in relation to the C, W, and A and CYC1 variants in B, L, U, D, and T. HWE deviation indicates action of selective pressures and genetic drift. Conclusions: HWE deviation of particular variants in relation to global populational HWE, could be, at least in part, associated with the differential susceptibility of specific populations and ethnicities to neurodegenerative diseases. Our data might contribute to the epidemiology and diagnostic/prognostic methods for neurodegenerative diseases.

RESUMO Introdução: Mitocôndrias defeituosas ou danificadas resultam em alterações do metabolismo energético, equilíbrio redox e dinâmica celular e são, portanto, identificadas como o ponto central da patogênese em muitos distúrbios neurológicos, como a doença de Alzheimer, a doença de Parkinson, a doença de Huntington e a Esclerose Lateral Amiotrófica. Portanto, é de fundamental importância identificar marcadores de susceptibilidade genética mitocondrial para doenças neurodegenerativas. Entre os potenciais marcadores relevantes estão as enzimas da cadeia respiratória riboflavina quinase (RFK), flavina adenina dinucleotídeo sintetase (FAD), succinato desidrogenase subunidade B (SDHB) e citocromo C1 (CYC1). Estas enzimas estão associadas à neuroproteção e à neurodegeneração. Objetivo: Testar se variantes nas sequências dos genes RFK, FAD, SDHB e CYC1 desviam do Equilíbrio de Hardy-Weinberg (HWE) em diferentes haplogrupos mitocondriais humanos. Métodos: Neste trabalho utilizamos os variantes nos genes RFK, FAD, SDHB e CYC1 de sequências de 2.504 indivíduos não afetados do projeto de 1.000 genomas para o cálculo dos valores de HWE em diferentes haplogrupos mitocondriais. Resultados: As variantes de RFK desviam de HWE nos haplogrupos G, H, L, V e W, variantes de FAD nos haplogrupos B, J, L, U e C, variantes de SDHB em relação às variantes C, W e A e CYC1 em B, L, U, D e T. O desvio de HWE indica a ação de pressões seletivas e desvio genético. Conclusões: O desvio do HWE de variantes particulares em relação ao HWE populacional global poderia estar, pelo menos em parte, associado à suscetibilidade diferencial de populações e etnias específicas a doenças neurodegenerativas. Nossos dados podem contribuir para a epidemiologia e métodos diagnósticos/prognósticos para doenças neurodegenerativas.

Combined effect of oxygen-scavenger packaging and UV-C radiation on shelf life of refrigerated tilapia (Oreochromis niloticus) fillets.

This study investigated the physicochemical, instrumental and bacterial parameters of tilapia fillets subjected to oxygen-scavenger packaging, alone or in combination with UV-C radiation at two doses (0.102 and 0.301 J/cm2), stored at 4 ± 1 °C for 23 days. The oxygen scavenger, both UV-C doses, and the oxygen scavenger combined with UV-C, independently of the dose, extended the shelf life in 5, 6 and 7 days, respectively, by decreasing the bacterial growth rate and the formation of degradation compounds (e.g., TVB-N and ammonia). Oxygen-scavenger packaging, alone or in combination with UV-C at 0.102 J/cm2 and 0.301 J/cm2 showed lower amounts of free amino acids (FAA; 34.39, 34.49 and 34.50 mg L-lysine/kg fish tissue, 3.63, 3.57 and 3.61 mg L- ornithine/kg fish tissue, 27.52, 27.63 and 27.67 mg L-arginine/kg fish tissue), biogenic amines (BA; 3.81, 3.87 and 3.89 mg cadaverine/kg fish tissue, 12.88, 12.91 and 12.86 mg putrescine/kg fish tissue, 2.41, 2.44 and 2.47 mg spermidine/kg fish tissue), redness (2.53, 2.55 and 2.59), yellowness (6.65, 6.69 and 6.72), lipid oxidation (1.52, 1.53 and 1.58 mg malondialdehyde/kg fish tissue) and protein oxidation (5.06, 5.11 and 5.18 nmol carbonyls/mg protein), with higher hardness (3273.41, 2652.98 and 2687.57 g) than control (air packaging; 41.97 mg L-lysine/kg fish tissue, 4.83 mg L- ornithine/kg fish tissue, 37.33 mg L-arginine/kg fish tissue, 4.82 mg cadaverine/kg fish tissue, 16.56 mg putrescine/kg fish tissue, 3.21 mg spermidine/kg fish tissue, 4.26 of redness, 8.17 of yellowness, 2.88 mg malondialdehyde/kg fish tissue, 9.44 nmol carbonyls/mg protein and 2092.58 g of hardness), respectively, on day 13 of storage when the control fillets were unfit for consumption (7 log CFU/g) (p < 0.05). However, in the same day of storage, both UV-C doses had similar values for BA (p > 0.05), higher amounts of FAA (44.28 and 44.13 mg L-lysine/kg fish tissue, 5.16 and 5.12 mg L- ornithine/kg fish tissue, 40.20 and 40.28 mg L-arginine/kg fish tissue), redness (4.86 and 5.33), yellowness (9.32 and 10.01), lipid oxidation (3.09 and 3.52 mg malondialdehyde/kg fish tissue) and protein oxidation (10.27 and 11.93 nmol carbonyls/mg protein), as well as lower hardness (1877.54 and 1767.39 g), respectively, than control fillets (p < 0.05). The combined preservation methods were the most effective in extending the shelf life and prolonging the physicochemical quality of the refrigerated tilapia fillets and the O2 scavenger proved to be a potential alternative to prevent the negative changes induced by both UV-C doses.

Photobiomodulation increases cell viability via AKT activation in an in vitro model of diabetes induced by glucose neurotoxicity.

Peripheral neuropathy (PN) is a serious complication of diabetes mellitus (DM) and is known to be resistant to conventional treatment. Photobiomodulation (PBM) is demonstrated to be effective in treating PN and in protecting nerve fiber damage. To better understand the mechanisms underlying the regenerative effects of PBM on diabetic neuropathy, we conducted a study in an in vitro model of diabetes induced by glucose neurotoxicity. Neuro 2A cells (1 × 104 cells/ well; N2A) were cultured in Minimum Essential Medium (MEM) supplemented with high glucose concentrations (100 mM) for 48 h and after the incubation period were submitted to either one or three consecutive applications of PBM, once a day (low-level InGaAlP, continuous wave mode, 660 nm, 30 mW, 1.6 J/cm2, 15 s, per well). Cell viability was measured by MTT method, neurotoxicity by LDH release, neurite outgrowth was evaluated through morphometric analysis, and AKT/ERK protein expression levels were assessed by western blotting. Results demonstrate that PBM increased N2A viability as well as induced neurogenesis observed by the increase in neurite outgrowth being this effect modulated by AKT activation. Data obtained herein reinforce the regenerative potential of PBM in the treatment of PN and strongly suggests that phototherapy should be considered adjuvant in the treatment of diabetes.

Differential expression of inflammatory and anti-inflammatory mediators by M1 and M2 macrophages after photobiomodulation with red or infrared lasers.

In response to stimuli in the microenvironment, macrophages adopt either the M1 or M2 phenotype to coordinate the tissue repair process. Photobiomodulation (PBM) plays an important role in the modulation of acute inflammation, including cellular influx, macrophage polarization, and the release of inflammatory mediators. The aim of the present study was to evaluate the effects of red and infrared PBM on the mRNA expression of cytokines and chemokines in macrophages polarized to the M1 and M2 phenotypes. J774 macrophages activated to induce M1 (lipopolysaccharide + interferon gamma) or M2 (interleukin-4) phenotypes were irradiated with red or infrared PBM (1 J). After 4 and 24 h, gene expression was analyzed by qPCR. PBM at 660 nm decreased the mRNA expression of CCL3, CXCL2, and TNF-α in M1 macrophages and CXCL2 in M2 macrophages 4 h after irradiation. Similarly, PBM at 780 nm decreased mRNA expression levels of CCL3 and IL-6 by M1 macrophages 24 h after irradiation. Moreover, PBM at 780 nm increased the mRNA expression of TGFß1 4 h after irradiation and decreased the expression of this gene after 24 h in M2 macrophages. Although red and infrared PBM were able to modulate and reduce M1/M2a-related markers, infrared laser irradiation promoted a temporal increase in the expression of TGFß1 in M2 macrophages. Thus, depending on the time PBM is used on injured tissue, different parameters can promote optimal results by modulating specific macrophage phenotypes.

A Thermotolerant Xylan-Degrading Enzyme Is Produced by Streptomyces malaysiensis AMT-3 Using by-Products From the Food Industry

Abstract This study evaluated the production of endoxylanases by Streptomyces malaysiensis AMT-3 in submerged fermentation using by-products of the food industry at 28ºC. In shake-flasks experiments, the highest endoxylanase activity of 45.8 U.mL-1 was observed within 6 days in a medium containing (w/v) 2.5% wheat bran and 1.2% corn steep liquor. The same culture conditions were used to evaluate the enzyme production in a 2 L stirred tank reactor under different agitation (300, 450 and 600 rev.min-1) and aeration (30 and 60 L.h-1) conditions. The use of 450 rev.min-1 coupled to an aeration of 90 L.h-1 resulted on 81.3 U.mL-1 endoxylanase activity within 5 days. The effect of temperature and pH on endoxylanase activity and stability showed the highest activity at 60 ºC and pH 6.0. Zymography showed the presence of three xylanolytic bands with molecular masses of 690, 180 and 142 kDa. The results showed that the thermotolerant actinobacterial endoxylanase can be produced in high titers using by-product of the food industry.

P1G10, the Proteolytic Fraction from Vasconcellea cundinamarcensis, Stimulates Tissue Repair after Acute Exposure to Ultraviolet B Radiation.

BACKGROUND: P1G10 is a cysteine proteolytic fraction from Vasconcellea cundinamarcensis latex, obtained by chromatographic separation on Sephadex-G10 and ultrafiltration. This fraction enhances healing in different models of skin lesions, and displays a protective/healing effect against gastric ulcers, where it was suggested an antioxidant role. METHODS: We evaluated here the effect of topical treatment with P1G10, in mice lesions induced by UVB. RESULTS: After single exposure to 2.4 J cm-2 UVB, P1G10 reduced erythema, increased cellularity of hypodermis, enhanced MPO activity and IL1ß, and inhibited COX2 levels. These results point to an anti-inflammatory effect by P1G10. This fraction displayed antioxidant activity by reversing the depletion of glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and reducing the catalase activity increased by UVB. These changes may be related to a reduction in MDA observed in groups treated with P1G10. P1G10 also inhibited MMP-9, caspase-3 and pkat while increasing p53 levels.

Photodynamic inactivation of S. aureus with a water-soluble curcumin salt and an application to cheese decontamination.

In this study, the optimal parameters for the photodynamic inactivation (PDI) of Staphylococcus aureus in bacterial suspensions and in cheese were assessed using a water-soluble curcumin salt as the photosensitizer (PS). The in vitro study aimed at finding the optimal concentration and light dose to promote S. aureus photokilling. Four main groups were proposed: CONTROL (L-C-), LIGHT (L+C-), CUR (L-C+) and PDI (L+C+). A fixed light dose (LED, 450 ± 10 nm, 10 J cm-2) was applied using four different PS concentrations (0.75, 1.0, 1.5 and 3.0 mg mL-1). The dose also varied from 10-100 J cm-2 for a fixed concentration. High inactivation rates were observed for all light doses, with a maximum reduction of 7.58 log10 at 100 J cm-2 (p ≪ 0.05). Saturation of the PDI effect was observed after a 10 minute illumination time, as well as a slight decrease in the S. aureus population for increasing illumination times in the L+C- group. As an application, the concentration showing the best decontamination performance in vitro (0.75 mg mL-1) was applied to decontaminate cheese in loco. PDI in two types of coalho cheese, a rennet-coagulated cheese commonly consumed in Brazil, was investigated. The results showed no significant inactivation in unpasteurized cheese, but a 4.34 log10 reduction for t > 5 min in pasteurized specimens. In conclusion, the present PDI-catalyzed curcumin photosensitizer inactivated S. aureus at statistically significant levels in vitro, in pasteurized cheese, but not in unpasteurized specimens.