Effects of a relined fiberglass post with conventional and self-adhesive resin cement.

Objectives: This study was conducted to evaluate the mechanical properties of relined and non-relined fiberglass posts when cemented to root canal dentin using a conventional dual-cure resin cement or a self-adhesive resin cement. Materials and Methods: Two types of resin cements were utilized: conventional and self-adhesive. Additionally, 2 cementation protocols were employed, involving relined and non-relined fiberglass posts. In total, 72 bovine incisors were cemented and subjected to push-out bond strength testing (n = 10) followed by failure mode analysis. The cross-sectional microhardness (n = 5) was assessed along the root canal, and interface analyses (n = 3) were conducted using scanning electron microscopy (SEM). Data from the push-out bond strength and cross-sectional microhardness tests were analyzed via 3-way analysis of variance and the Bonferroni post-hoc test (α = 0.05). Results: For non-relined fiberglass posts, conventional resin cement exhibited higher push-out bond strength than self-adhesive cement. Relined fiberglass posts yielded comparable results between the resin cements. Type II failure was the most common failure mode for both resin cements, regardless of cementation protocol. The use of relined fiberglass posts improved the cross-sectional microhardness values for both cements. SEM images revealed voids and bubbles in the incisors with non-relined fiberglass posts. Conclusions: Mechanical properties were impacted by the cementation protocol. Relined fiberglass posts presented the highest push-out bond strength and cross-sectional microhardness values, regardless of the resin cement used (conventional dual-cure or self-adhesive). Conversely, for non-relined fiberglass posts, the conventional dual-cure resin cement yielded superior results to the self-adhesive resin cement.

[Social inequalities in the diagnosis of cervical cancer in Brazil: a hospital-based study]. / Desigualdades sociais no diagnóstico do câncer do colo do útero no Brasil: um estudo de base hospitalar.

The scope of this study is to analyze the prevalence of advanced stage diagnosis of cervical cancer and its association with individual and contextual socioeconomic and healthcare service indicators in Brazil. A cross-sectional study was conducted using cervical cancer cases in women aged 18 to 99 years, from 2006 to 2015, extracted from the Hospital Cancer Registry (HCR) Integrator. Contextual variables were collected from the Atlas of Human Development in Brazil; the National Registry of Health Institutions (NRHI); and the Outpatient Information System. Multilevel Poisson Regression with random intercept was used. The prevalence of advanced stage diagnosis was 48.4%, revealing an association with older age groups (PR 1.06; CI 1.01-1.10), black, brown, and indigenous race/skin color (PR 1.04; CI 1.01-1.07), lower levels of schooling (PR 1.28; CI 1.16-1.40), no marital partner (PR 1.10; CI 1.07-1.13), public referral to the health service (PR 1.07; CI 1.03-1.11), and lower rates of cytological examination (PR 1.08; CI 1.01-1.14). The results reinforce the need for improvements in the national cervical cancer prevention program in areas with low coverage of oncotic cytology.

O estudo visa analisar a prevalência de estadiamento avançado ao diagnóstico do câncer do colo do útero e sua associação com indicadores individuais e contextuais socioeconômicos e de oferta de serviços de saúde no Brasil. Estudo transversal, realizado com casos de câncer do colo do útero em mulheres de 18 a 99 anos, no período de 2006 a 2015, extraídos do Integrador de Registros Hospitalares de Câncer. Variáveis contextuais foram coletadas no Atlas do Desenvolvimento Humano, no Cadastro Nacional de Estabelecimentos de Saúde e no Sistema de Informações Ambulatoriais. Usou-se o modelo de regressão de Poisson multinível com intercepto aleatório. A prevalência de diagnóstico em estádio avançado foi de 48,4%, apresentando associação com idades mais avançadas (RP 1,06; IC 1,01-1,10), raça/cor da pele preta, parda e indígena (RP 1,04; IC 1,01-1,07), menores níveis de escolaridade (RP 1,28; IC 1,16-1,40), ausência de parceiro conjugal (RP 1,10; IC 1,07-1,13), encaminhamento do tipo público ao serviço de saúde (RP 1,07; IC 1,03-1,11) e menor taxa de realização de exame citopatológico (RP 1,08; IC 1,01-1,14). Os resultados reforçam a necessidade de melhorias no programa nacional de prevenção do câncer do colo do útero em áreas com baixa cobertura da citologia oncótica.

Desigualdades sociais no diagnóstico do câncer do colo do útero no Brasil: um estudo de base hospitalar / Social inequalities in the diagnosis of cervical cancer in Brazil: a hospital-based study

Resumo O estudo visa analisar a prevalência de estadiamento avançado ao diagnóstico do câncer do colo do útero e sua associação com indicadores individuais e contextuais socioeconômicos e de oferta de serviços de saúde no Brasil. Estudo transversal, realizado com casos de câncer do colo do útero em mulheres de 18 a 99 anos, no período de 2006 a 2015, extraídos do Integrador de Registros Hospitalares de Câncer. Variáveis contextuais foram coletadas no Atlas do Desenvolvimento Humano, no Cadastro Nacional de Estabelecimentos de Saúde e no Sistema de Informações Ambulatoriais. Usou-se o modelo de regressão de Poisson multinível com intercepto aleatório. A prevalência de diagnóstico em estádio avançado foi de 48,4%, apresentando associação com idades mais avançadas (RP 1,06; IC 1,01-1,10), raça/cor da pele preta, parda e indígena (RP 1,04; IC 1,01-1,07), menores níveis de escolaridade (RP 1,28; IC 1,16-1,40), ausência de parceiro conjugal (RP 1,10; IC 1,07-1,13), encaminhamento do tipo público ao serviço de saúde (RP 1,07; IC 1,03-1,11) e menor taxa de realização de exame citopatológico (RP 1,08; IC 1,01-1,14). Os resultados reforçam a necessidade de melhorias no programa nacional de prevenção do câncer do colo do útero em áreas com baixa cobertura da citologia oncótica.

Abstract The scope of this study is to analyze the prevalence of advanced stage diagnosis of cervical cancer and its association with individual and contextual socioeconomic and healthcare service indicators in Brazil. A cross-sectional study was conducted using cervical cancer cases in women aged 18 to 99 years, from 2006 to 2015, extracted from the Hospital Cancer Registry (HCR) Integrator. Contextual variables were collected from the Atlas of Human Development in Brazil; the National Registry of Health Institutions (NRHI); and the Outpatient Information System. Multilevel Poisson Regression with random intercept was used. The prevalence of advanced stage diagnosis was 48.4%, revealing an association with older age groups (PR 1.06; CI 1.01-1.10), black, brown, and indigenous race/skin color (PR 1.04; CI 1.01-1.07), lower levels of schooling (PR 1.28; CI 1.16-1.40), no marital partner (PR 1.10; CI 1.07-1.13), public referral to the health service (PR 1.07; CI 1.03-1.11), and lower rates of cytological examination (PR 1.08; CI 1.01-1.14). The results reinforce the need for improvements in the national cervical cancer prevention program in areas with low coverage of oncotic cytology.

Seroprevalence of Protective Antibodies Against Influenza and the Reduction of the Influenza Incidence Rate: An Annual Repeated Cross-Sectional Study From 2014 to 2019.

BACKGROUND: Seroepidemiological studies provide estimates of population-level immunity, prevalence/incidence of infections, and evaluation of vaccination programs. We assessed the seroprevalence of protective antibodies against influenza and evaluated the correlation of seroprevalence with the cumulative annual influenza incidence rate. METHODS: We conducted an annual repeated cross-sectional seroepidemiological survey, during June-August, from 2014 to 2019, in Portugal. A total of 4326 sera from all age groups, sex, and regions was tested by hemagglutination inhibition assay. Seroprevalence and geometric mean titers (GMT) of protective antibodies against influenza were assessed by age group, sex, and vaccine status (65+ years old). The association between summer annual seroprevalence and the difference of influenza incidence rates between one season and the previous one was measured by Pearson correlation coefficient (r). RESULTS: Significant differences in seroprevalence of protective antibodies against influenza were observed in the population. Higher seroprevalence and GMT for A(H1N1)pdm09 and A(H3N2) were observed in children (5-14); influenza B seroprevalence in adults 65+ was 1.6-4.4 times than in children (0-4). Vaccinated participants (65+) showed significant higher seroprevalence/GMT for influenza. A strong negative and significant correlation was found between seroprevalence and ILI incidence rate for A(H1N1)pdm09 in children between 5 and 14 (r = -0.84; 95% CI, -0.98 to -0.07); a weak negative correlation was observed for A(H3N2) and B/Yamagata (r ≤ -0.1). CONCLUSIONS: The study provides new insight into the anti-influenza antibodies seroprevalence measured in summer on the ILI incidence rate in the next season and the need for adjusted preventive health care measures to prevent influenza infection and transmission.

Multilevel analysis of social determinants of advanced stage colorectal cancer diagnosis.

The advanced stage at diagnosis of colorectal cancer (CRC) may be related to individual factors, socioeconomic conditions, and healthcare service availability. The objective of the study was to analyze the prevalence of advanced stage CRC at the time of diagnosis and its association with individual, contextual, socioeconomic, and healthcare service indicators. An observational, cross-sectional study was conducted, analyzing cases of malignant neoplasms of the colon and rectum in individuals of both sexes, aged between 18 and 99 years, diagnosed between 2010 and 2019 in Brazil (n = 69,047). Data were collected from the Hospital Cancer Registry (HCR), Atlas of Human Development in Brazil, and from the National Registry of Health Institutions (NRHI). A Multilevel Poisson Regression model with random intercept was used. The prevalence of advanced stage CRC at diagnosis was 65.6%. Advanced stage was associated with older age groups prevalence ratio (PR) 4.40 and younger age groups (PR 1.84), low Human Development Index (HDI) (PR 1.22), and low density of family health strategy teams (PR 1.10). The study highlights the unequal distribution of social determinants of health in the diagnosis CRC in Brazil, revealing the need to evaluate and redirect public policies aimed at improving early detection and prevention of CRC in the country.

Structured wound angiogenesis instructs mesenchymal barrier compartments in the regenerating nerve.

Organ injury stimulates the formation of new capillaries to restore blood supply raising questions about the potential contribution of neoangiogenic vessel architecture to the healing process. Using single-cell mapping, we resolved the properties of endothelial cells that organize a polarized scaffold at the repair site of lesioned peripheral nerves. Transient reactivation of an embryonic guidance program is required to orient neovessels across the wound. Manipulation of this structured angiogenic response through genetic and pharmacological targeting of Plexin-D1/VEGF pathways within an early window of repair has long-term impact on configuration of the nerve stroma. Neovessels direct nerve-resident mesenchymal cells to mold a provisionary fibrotic scar by assembling an orderly system of stable barrier compartments that channel regenerating nerve fibers and shield them from the persistently leaky vasculature. Thus, guided and balanced repair angiogenesis enables the construction of a "bridge" microenvironment conducive for axon regrowth and homeostasis of the regenerated tissue.

Usefulness of three vessel-trachea view and parasagittal plan for prenatal diagnosis of interrupted aortic arch.

BACKGROUND: Interrupted aortic arch (IAA) is a rare congenital heart disease characterized by loss of continuity between the ascending and the descending aorta. Prenatal diagnosis of IAA by echocardiography is challenging but nonetheless can be accomplished via a systematization of cardiac fetal evaluation. CASE PRESENTATION: We report a case of fetal IAA type A prenatally diagnosed through two-dimensional echocardiography using both a three vessel-trachea view and a sagittal view. CONCLUSION: Prenatal counseling regarding the diagnosis and prognosis about this anomaly is still challenging nowadays due to associated anomalies/chromosomal abnormalities who may impact the prognosis. Fetal autopsy in all cases of pregnancy termination after abnormal ultrasound findings is important in order to make a full diagnosis and characterize the anomaly.

Intrinsic factors and CD1d1 but not CD1d2 expression levels control invariant natural killer T cell subset differentiation.

Invariant natural killer T (NKT) cell subsets are defined based on their cytokine-production profiles and transcription factors. Their distribution is different in C57BL/6 (B6) and BALB/c mice, with a bias for NKT1 and NKT2/NKT17 subsets, respectively. Here, we show that the non-classical class I-like major histocompatibility complex CD1 molecules CD1d2, expressed in BALB/c and not in B6 mice, could not account for this difference. We find however that NKT cell subset distribution is intrinsic to bone marrow derived NKT cells, regardless of syngeneic CD1d-ligand recognition, and that multiple intrinsic factors are likely involved. Finally, we find that CD1d expression levels in combination with T cell antigen receptor signal strength could also influence NKT cell distribution and function. Overall, this study indicates that CD1d-mediated TCR signals and other intrinsic signals integrate to influence strain-specific NKT cell differentiation programs and subset distributions.

Mosaic trisomy 5 in amniotic fluid in a live fetus with Ebstein anomaly and complete trisomy 5 in chorionic villus sampling.

Complete trisomy 5 is a rare and lethal abnormality. Mosaic trisomy 5 presents in various phenotypes, ranging from a clinically normal fetus to fetuses presenting uterine growth restriction, congenital heart anomalies, multiple dysmorphic features and psychomotor development abnormalities. Although rare, there are cases of a normal psychomotor development regardless of the associated low fetal growth frequently associated with mosaic trisomy 5. This is the first case report to date of a live fetus with complete trisomy 5 reported in chorionic villus sampling and mosaic trisomy 5 in amniotic fluid with a concomitant Ebstein anomaly. Diagnosis of mosaic trisomy 5 represents a challenge for the clinical team and patients, as the information regarding this syndrome is scarce and based mostly on case reports of liveborns, which may introduce a selection bias when counselling the parents.

Evaluating the Electromagnetic Shielding of Continuous Carbon Fiber Parts Produced by Additive Manufacturing.

Electronic devices are sensitive to electromagnetic (EM) emissions, and require electromagnetic shielding protection to ensure good operation, and prevent noise, malfunctioning, or even burning. To ensure protection, it is important to develop suitable material and design solutions for electronic enclosures. Most common enclosures are made with metal alloys using traditional manufacturing methods. However, using thermoplastic composites combined with additive manufacturing (AM) technologies emerges as an alternative that enables the fabrication of complex parts that are lightweight, consolidated, and oxidation- and corrosion-resistant. In this research, an AM technique based on material extrusion was used to print 2 mm-thick specimens with a multi-material made of micro-carbon fiber (CF)-filled polyamide that was reinforced at specific layers using continuous carbon fibers stacked with a 90° rotation to each other. The specimens' electromagnetic shielding effectiveness (EMSE) was evaluated in the frequency band of 0.03-3 GHz using the coaxial transmission line method. Depending on the number of CF layers, the EM shielding obtained can be up to 70 dB, with a specific shielding up to 60 dB.cm3/g, predominantly by the absorption mechanism, being 22 times higher than without the CF layers. These findings promote this innovative approach to lightweight customizable solutions for EM shielding applications.

What does Google Trends reveal about the proportion of waterpipe users in the Brazilian population?

OBJECTIVE: To analyze the relationship between internet search volume and the prevalence of waterpipe use among young Brazilians in 2019. METHODS: This was a descriptive study with data from Brazil in 2019, using the relative search volume on waterpipes extracted from Google Trends and the proportion of waterpipe users aged between 15 and 24 years, as measured by the National Health Survey (Pesquisa Nacional de Saúde - PNS), and aged between 13 and 17 years, as measured by the National Adolescent School-based Health Survey (Pesquisa Nacional de Saúde do Escolar - PeNSE). The relationship was assessed by means of Spearman's correlation. RESULTS: The point prevalence of waterpipe use across the Brazilian Federative Units (FUs) showed a moderate (r = 0.51; PNS) to strong correlation (r = 0.74 and r = 0.80; PeNSE) with the relative search volume (p-value < 0.05). CONCLUSION: Google Trends can support the monitoring system on waterpipe use in the FUs, providing additional information to existing population-based surveys. MAIN RESULTS: The search volume for waterpipes by states in Brazil, as measured by Google Trends, showed a moderate to high correlation with the respective proportions of current use and experimentation of waterpipe among the adolescent/young adult population. IMPLICATIONS FOR SERVICES: The use of Google Trends as a support to the monitoring system for waterpipe consumption in Brazil warrants further exploration in terms of the validity of additional information to existing population surveys. PERSPECTIVES: Expanding the use of Google Trends searches to assess its potential in monitoring other health risk products and detecting (or predicting) incidence or seasonality of health-related events.

Survey of Sensitization to Common Fungi in an Allergic Dog Population: The Need for Further Focus on Sensitization and Allergy to Fungi in Veterinary Medicine.

Most fungal species are commensals and non-pathogenic to plants, humans, or animals. However, several species of the Alternaria, Aspergillus, Trichophyton, and Microsporum genera are common causes of disease, even for immunocompetent individuals. Besides mucosal damage, fungi may contribute to a skin barrier impairment, favoring sensitization and allergy development. A total of 68 allergic dogs were selected from a veterinary dermatology and allergy outpatient consultation for conditions related to both Malassezia overgrowth and other fungal complications. The allergy diagnosis was made through anamnesis and current clinical criteria, with the involved allergenic species being identified by intradermal tests (IDTs) and allergen-specific immunoglobulin E (sIgE) determination in serum. Dermatophagoides farinae, Dactylis glomerata, and Malassezia pachydermatis showed as the higher sensitization species from house dust mites, grass pollen, and fungi, respectively. Significant correlations at p < 0.05 were found between sensitization to Dactylis glomerata and Phleum pratense grass pollens, Dermatophagoides farinae and Dermatophagoides pteronyssinus, Acarus siro, Tyrophagus putrescentiae, and Lepidoglyphus destructor dust/storage mites, and between fungi like Aspergillus mix and Penicillium or Alternaria alternata. A significant correlation was also found between sensitization to the Aspergillus mix and D. farinae, D. pteronyssinus, or A. siro. Rather severe dermatitis was observed when a positive IDT to Malassezia pachydermatis was found, regardless of the detection of circulating sIgE, allowing us to consider the usefulness of both the IDT and the sIgE for a systematic diagnosis of allergy to fungi.

Stent for life initiative in Portugal: Progress through years and Covid-19 impact.

BACKGROUND: During Stent for Life Initiative in Portugal lifetime, positive changes in ST elevation myocardial infarction treatment were observed, by the increase of Primary Angioplasty numbers and improvements in patients' behaviour towards myocardial infarction, with an increase in those who called 112 and the lower proportion attending non primary percutaneous coronary intervention centres. Despite public awareness campaigns and system educational programmes, patient and system delay did not change significantly over this period. The aim of this study was to address the public awareness campaign effectiveness on peoples' behaviour facing STEMI, and how Covid-19 has affected STEMI treatment. METHODS: Data from 1381 STEMI patients were collected during a one-month period each year, from 2011 to 2016, and during one and a half month, matching first lockdown in Portugal 2020. Four groups were constituted: Group A (2011); Group B (2012&2013); Group C (2015&2016) and group D (2020). RESULTS: The proportion of patients who called 112, increased significantly (35.2% Group A; 38.7% Group B; 44.0% Group C and 49.6% Group D, p = 0.005); significant reduction was observed in the proportion of patients who attended healthcare centres without PPCI (54.5% group A; 47.6% Group B; 43.2% Group C and 40.9% Group D, p = 0.016), but there were no differences on groups comparison. Total ischemic time, measured from symptoms onset to reperfusion increased progressively from group A [250.0 (178.0-430.0)] to D [296.0 (201.0-457.5.8)] p = 0.012, with statistically significant difference between group C and D (p = 0.034). CONCLUSIONS: During the term of SFL initiative in Portugal, patients resorted less to primary health centres and called more to 112. These results can be attributed the public awareness campaign. Nevertheless, patient and system delays did not significantly change over this period, mainly in late years of SFL, probably for low efficacy of campaigns and in 2020 due to Covid-19 pandemic.

Influence of Surface Treatment on the Physical Properties and Biofilm Formation of Zirconia- Reinforced Lithium Silicate Ceramics: In Vitro Trial.

PURPOSE: To evaluate the performance of fully crystallized zirconia-reinforced lithium silicate (Celtra Duo, ZLS-CD), partially crystallized zirconia-reinforced lithium silicate (Vita Suprinity, ZLS-VS), and partially sintered lithium disilicate-based (IPS e.max CAD, LD) glass-ceramics submitted to polishing, glazing, or no surface treatment after aging. MATERIAL AND METHODS: Samples of each glass-ceramic material were subjected to polishing with rubber cups (POL), glazing (GL), or no treatment (control: unpolished) and afterward aged with 18,000 thermal cycles (5.C to 55.C). The average roughness, 2D and 3D morphology, contact angle, multispecies biofilm formation (Streptococcus mutans and Candida albicans), and mechanical strength were evaluated with atomic force microscopy (AFM, n = 5), sessile-drop goniometry (n = 5), spectrophotometry (n = 5), and the flexural strength test (n = 10), respectively. Data were analyzed using two-way ANOVA and Tukey test (α = 5%). RESULTS: POL produced lower surface roughness than GL, and ZLS-CD presented higher roughness than LD (P < .05). Surfaces without polishing displayed higher roughness than the POL group (P < .001), greater contact angle (P < .001), and significant morphologic changes, regardless of the glass-ceramic material. Irrespective of the treatment, the contact angle was higher in the ZLS-CD group, and regardless of the material, there was higher biofilm formation and lower flexural strength of the unpolished compared to the POL or GL ceramics. CONCLUSIONS: POL promoted lower roughness and minor morphologic surface alterations, but biofilm formation and flexural strength were similar to the GL group. In general, ZLS-CD and ZLS-VS showed more similar behavior than LD, which makes ZLS glass-ceramic a good option for indirect restorations.

A novel approach for lactose determination in cow's milk exploiting smartphone-based digital-image photometry.

Lactose, the main carbohydrate in cow's milk, may cause health problems for consumers with intolerance. Lactose determination in milk is hindered by the matrix complexity and lack of chromophore groups. Chromatography, volumetric, and spectrophotometric approaches involving chemical derivatization are time-consuming and require laborious sample preparation, which is incompatible with the high analytical demand. In this context, a novel approach is presented for lactose determination in milk exploiting smartphone-based digital-image photometry. It was based on a modification of the Benedict's method, involving formation of the violet Cu(I)/2,2'-biquinoline-4,4'-dicarboxylate (BCA) complex instead of the copper(I) oxide precipitate, aiming at improvement of sensitivity and precision. Sample pretreatment and analyte derivatization were performed in Eppendorf tubes with minimal reagent amounts and a smartphone camera was used for image acquisition under controlled conditions. Measurements were based on the RGB color system, taking channel G as the analytical response because of the complementarity with the color of the complex. Under the optimized conditions, the proposed procedure yielded a linear response up to 20 mg L-1 (r = 0.999), with a limit of detection of 1.5 mg L-1, which is compatible with determination of lactose in milk and dairy products categorized with low content of the sugar. The procedure takes less than 10 min, with a coefficient of variation of 3.0% (n = 12) and consumes as low as 160 µg Cu and 430 µg BCA per determination, thus being a more practical, fast, cost-effective, and environmental friendly analytical method.

Human Papillomavirus 16 Lineage D is Associated with High Risk of Cervical Cancer in the Brazilian Northeast Region.

OBJECTIVE: Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil. METHODS: A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage (p < 0.05). RESULTS: According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer (p = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p = 0.023. CONCLUSION: HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer.

OBJETIVO: Tanto os tipos quanto as linhagens do Papilomavírus Humano (HPV) parecem ter diferentes capacidades carcinogênicas e estão associados a riscos variados para o desenvolvimento de neoplasia intraepitelial cervical (NIC) e câncer de colo do útero. O presente estudo tem como objetivo analisar a diversidade genética do genótipo HPV 16 nos casos de NIC2/NIC3 e câncer de colo de útero em mulheres da região Nordeste do Brasil. MéTODOS: Estudo transversal de base hospitalar realizado na região Nordeste do Brasil no período de 2014 a 2016. A amostra foi composta por 196 casos da variante HPV-16 (59 casos de NIC2/NIC3 e 137 de câncer do colo do útero). O teste de diferença de proporção foi usado para comparar os grupos NIC2/NIC3 e câncer de colo do útero por linhagem viral em relação à prevalência da linhagem HPV-16. Foi considerada significância estatística o valor de p < 0,05. RESULTADOS: As frequências de linhagem por diagnóstico histopatológico mostraram diferença limítrofe da linhagem A no grupo NIC2/NIC3 em relação ao grupo câncer de colo de útero (p = 0,053). Por outro lado, em relação à linhagem D, houve uma proporção maior nos casos de câncer (32,8%) quando comparado ao grupo NIC2/NIC3 (16,9%) e esta diferença se mostrou estatisticamente significante (p = 0,023). CONCLUSãO: A linhagem A do HPV-16 foi a mais frequente tanto nas amostras CIN2/CIN3 quanto nas amostras de câncer de colo de útero, enquanto a linhagem D predominou no câncer de colo do útero, sugerindo uma possível associação da linhagem D de HPV-16 com câncer de colo de útero.

The antipsychotic medications aripiprazole, brexpiprazole and cariprazine are off-target respiratory chain complex I inhibitors.

Antipsychotic drugs are the mainstay of treatment for schizophrenia and provide adjunct therapies for other prevalent psychiatric conditions, including bipolar disorder and major depressive disorder. However, they also induce debilitating extrapyramidal syndromes (EPS), such as Parkinsonism, in a significant minority of patients. The majority of antipsychotic drugs function as dopamine receptor antagonists in the brain while the most recent 'third'-generation, such as aripiprazole, act as partial agonists. Despite showing good clinical efficacy, these newer agents are still associated with EPS in ~ 5 to 15% of patients. However, it is not fully understood how these movement disorders develop. Here, we combine clinically-relevant drug concentrations with mutliscale model systems to show that aripiprazole and its primary active metabolite induce mitochondrial toxicity inducing robust declines in cellular ATP and viability. Aripiprazole, brexpiprazole and cariprazine were shown to directly inhibit respiratory complex I through its ubiquinone-binding channel. Importantly, all three drugs induced mitochondrial toxicity in primary embryonic mouse neurons, with greater bioenergetic inhibition in ventral midbrain neurons than forebrain neurons. Finally, chronic feeding with aripiprazole resulted in structural damage to mitochondria in the brain and thoracic muscle of adult Drosophila melanogaster consistent with locomotor dysfunction. Taken together, we show that antipsychotic drugs acting as partial dopamine receptor agonists exhibit off-target mitochondrial liabilities targeting complex I.

The economic impact of cancer mortality among working-age individuals in Brazil from 2001 to 2030.

BACKGROUND: About half of cancer deaths in Brazil occur among individuals of working-age (under 65 years for men, under 60 for women), resulting in a substantial economic impact for the country. We aimed to estimate the years of potential productive life lost (YPPLL) and value the productivity lost due to premature deaths from cancer between 2001 and 2015 and the projected to 2030. METHODS: We used the Human Capital Approach to estimate the productivity losses corresponding to YPPLL for cancer deaths in working age people (15-64 years). Mortality data were obtained from the Mortality Information System from 2001 to 2015 and projected between 2016 and 2030. Economic data were obtained from the Continuous National Household Sample Survey and forecasted to 2030. Productivity lost was calculated as the monetary value arising from YPPLL in Int$(2016). RESULTS: Between 2001 and 2030, a total of 2.3 million premature deaths from all cancers combined were observed and forecasted in Brazil (57% men, 43% women), corresponding to 32 million YPPLL and Int$141.3 billion in productivity losses (men: Int$102.5 billion, women: Int$38.8 billion). Between 2001 and 2030, among men, lung (Int$ 12.6 billion), stomach (Int$ 10.6 billion) and colorectal (Int$ 9.4 billion) cancers were expected to contribute to the greatest productivity losses; and among women, it will be for breast (Int$ 10.0 billion), cervical (Int$ 6.4 billion) and colorectal (Int$ 3.2 billion) cancers. CONCLUSIONS: Many preventable cancers result in high lost productivity, suggesting measure to reduce smoking prevalence, alcohol consumption, physical inactivity and inadequate diet, improving screening programs and increasing vaccination coverage for human papillomavirus and hepatitis B would have a positive impact on the economy, as well as reducing morbidity and mortality from cancer.