An electrochemically synthesized molecularly imprinted polymer for highly selective detection of breast cancer biomarker CA 15-3: a promising point-of-care biosensor.

In this study, a molecularly imprinted polymer film (MIP) was prepared on the surface of a disposable carbon screen-printed electrode (C-SPE) using (3-acrylamidopropyl)trimethylammonium chloride (AMPTMA) as a functional monomer and the cancer biomarker carbohydrate antigen 15-3 (CA 15-3) as a template. The MIP was synthesized by in situ electropolymerization (ELP) of the AMPTMA monomer in the presence of the CA 15-3 protein on the C-SPE surface. The target was subsequently removed from the polymer matrix by the action of proteinase K, resulting in imprinted cavities with a high affinity for CA 15-3. Electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to characterize the different phases of the sensor assembly. Chemical and morphological analysis was performed using RAMAN and scanning electron microscopy (SEM). CA 15-3 was successfully detected in a wide working range from 0.001 U mL-1 to 100 U mL-1 with a correlation coefficient (R2) of 0.994 in 20 min. The MIP sensor showed minimal interference with other cancer proteins (CEA and CA 125). Overall, the developed device provides a rapid, sensitive, and cost-effective response in the detection of CA 15-3. Importantly, this comprehensive approach appears suitable for point-of-care (PoC) use, particularly in a clinical context.

An Innovative Approach for Tailoring Molecularly Imprinted Polymers for Biosensors-Application to Cancer Antigen 15-3.

This work presents a novel approach for tailoring molecularly imprinted polymers (MIPs) with a preliminary stage of atom transfer radical polymerization (ATRP), for a more precise definition of the imprinted cavity. A well-defined copolymer of acrylamide and N,N'-methylenebisacrylamide (PAAm-co-PMBAm) was synthesized by ATRP and applied to gold electrodes with the template, followed by a crosslinking reaction. The template was removed from the polymer matrix by enzymatic/chemical action. The surface modifications were monitored via electrochemical impedance spectroscopy (EIS), having the MIP polymer as a non-conducting film designed with affinity sites for CA15-3. The resulting biosensor exhibited a linear response to CA15-3 log concentrations from 0.001 to 100 U/mL in PBS or in diluted fetal bovine serum (1000×) in PBS. Compared to the polyacrylamide (PAAm) MIP from conventional free-radical polymerization, the ATRP-based MIP extended the biosensor's dynamic linear range 10-fold, improving low concentration detection, and enhanced the signal reproducibility across units. The biosensor demonstrated good sensitivity and selectivity. Overall, the work described confirmed that the process of radical polymerization to build an MIP material influences the detection capacity for the target substance and the reproducibility among different biosensor units. Extending this approach to other cancer biomarkers, the methodology presented could open doors to a new generation of MIP-based biosensors for point-of-care disease diagnosis.

Cardiac Autonomic Neuropathy in Graves' Disease: Smoking and Age as Predictive Factors.

OBJECTIVES: Hypermetabolic state in Graves' disease (GD) has a great impact on heart homeostasis, acting directly on the heart muscle and modulating the autonomic nervous system. To characterize cardiac autonomic neuropathy (CAN) as a possible complication in patients with GD. METHODS: We evaluated euthyroid GD patients and a control group of healthy euthyroid people. CAN was assessed using autonomic tests of cardiovascular reflex and heart rate variability: respiratory, Valsalva, orthostatic and orthostatic hypotension tests, high frequency, low frequency, and very low-frequency bands. Transthoracic echocardiography was performed in GD patients. RESULTS: Sixty GD patients and 50 people in control group were assessed. CAN was diagnosed in 20% of GD and 14% in the control group. Among GD, 13.3% presented incipient, and 6.7% established CAN, while in the control group, it was verified incipient in 8% and established in 6% (P = .7479). All GD patients with CAN presented an alteration in the deep breathing test. Age and smoking were evidenced as factors associated with the presence of CAN, while higher TRAb values at diagnosis decreased the chance of CAN. CONCLUSIONS: The prevalence of CAN in euthyroid GD patients was 20%. Changes in the cardiac autonomic nervous system were identified, pointing to the importance of evaluating this complication in these patients. Smoking was a predictive factor for CAN, increasing its relationship with conditions that aggravate GD.

SERS biosensor with plastic antibodies for detection of a cancer biomarker protein.

Surface-enhanced Raman scattering (SERS) is a powerful method for detecting breast cancer-specific biomarkers due to its extraordinary enhancement effects obtained by localized surface plasmon resonance (LSPR) in metallic nanostructures at hotspots. In this research, gold nanostars (AuNSs) were used as SERS probes to detect a cancer biomarker at very low concentrations. To this end, we combined molecularly imprinted polymers (MIPs) as a detection layer with SERS for the detection of the biomarker CA 15-3 in point-of-care (PoC) analysis. This required two main steps: (i) the deposition of MIPs on a gold electrode, followed by a second step (ii) antibody binding with AuNSs containing a suitable Raman reporter to enhance Raman signaling (SERS). The MPan sensor was prepared by electropolymerization of the monomer aniline in the presence of CA 15-3. The template molecule was then extracted from the polymer using sodium dodecyl sulfate (SDS). In parallel, a control material was prepared in the absence of the protein (NPan). Surface modification for the control was performed using electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The performance of the sensor was evaluated using the SERS technique, in which the MPan sensor is first incubated with the protein and then exposed to the SERS probe. Under optimized conditions, the device showed a linear response to CA 15-3 concentrations from 0.016 to 248.51 U mL-1 in a PBS buffer at pH 7.4 in 1000-fold diluted serum. Overall, this approach demonstrates the potential of SERS as an optical reader and opens a new avenue for biosensing applications.

Scalable manufacture of therapeutic mesenchymal stromal cell products on customizable microcarriers in vertical wheel bioreactors that improve direct visualization, product harvest, and cost.

BACKGROUND AIMS: Human mesenchymal stromal cells (hMSCs) and their secreted products show great promise for treatment of musculoskeletal injury and inflammatory or immune diseases. However, the path to clinical utilization is hampered by donor-tissue variation and the inability to manufacture clinically relevant yields of cells or their products in a cost-effective manner. Previously we described a method to produce chemically and mechanically customizable gelatin methacryloyl (GelMA) microcarriers for culture of hMSCs. Herein, we demonstrate scalable GelMA microcarrier-mediated expansion of induced pluripotent stem cell (iPSC)-derived hMSCs (ihMSCs) in 500 mL and 3L vertical wheel bioreactors, offering several advantages over conventional microcarrier and monolayer-based expansion strategies. METHODS: Human mesenchymal stromal cells derived from induced pluripotent cells were cultured on custom-made spherical gelatin methacryloyl microcarriers in single-use vertical wheel bioreactors (PBS Biotech). Cell-laden microcarriers were visualized using confocal microscopy and elastic light scattering methodologies. Cells were assayed for viability and differentiation potential in vitro by standard methods. Osteogenic cell matrix derived from cells was tested in vitro for osteogenic healing using a rodent calvarial defect assay. Immune modulation was assayed with an in vivo peritonitis model using Zymozan A. RESULTS: The optical properties of GelMA microcarriers permit noninvasive visualization of cells with elastic light scattering modalities, and harvest of product is streamlined by microcarrier digestion. At volumes above 500 mL, the process is significantly more cost-effective than monolayer culture. Osteogenic cell matrix derived from ihMSCs expanded on GelMA microcarriers exhibited enhanced in vivo bone regenerative capacity when compared to bone morphogenic protein 2, and the ihMSCs exhibited superior immunosuppressive properties in vivo when compared to monolayer-generated ihMSCs. CONCLUSIONS: These results indicate that the cell expansion strategy described here represents a superior approach for efficient generation, monitoring and harvest of therapeutic MSCs and their products.

Pachydysostosis of the fibula in a case of familial adenomatous polyposis.

BACKGROUND: Familial Adenomatous Polyposis (FAP) is a colorectal cancer (CRC) predisposition syndrome caused by germline APC mutations and characterised by an increased risk of CRC and colonic polyps and, in certain forms, of specific prominent extraintestinal manifestations, namely osteomas, soft tissue tumours and dental anomalies. Pachydysostosis of the fibula is a rare clinical entity defined by unilateral bowing of the distal portion of the fibula and elongation of the entire bone, without affectation of the tibia. CLINICAL REPORT: We report a 17-year-old male, who presented with a non-progressive bowing of the right leg detected at 18 months of age caused by a fibula malformation (later characterized as pachydysostosis) and a large exophytic osteoma of the left radius, noticed at the age of 15 years, without gastrointestinal symptoms. There was no relevant family history. Detailed characterisation revealed multiple osteomas, skin lesions and dental abnormalities, raising the hypothesis of FAP. This diagnosis was confirmed by genetic testing [c.4406_4409dup p.(Ala1471Serfs*17) de novo mutation in the APC gene] and endoscopic investigation (multiple adenomas throughout the colon, ileum and stomach). DISCUSSION: This case report draws attention to the phenotypic spectrum of skeletal manifestations of FAP: this patient has a congenital fibula malformation, not previously associated with this syndrome, but which is likely to have been its first manifestation in this patient. This clinical case also illustrates the challenges in the early diagnosis of FAP, especially without family history, and highlights the importance of a multidisciplinary approach and the adequate study of rare skeletal abnormalities.

Femoral fracture in the elderly: dependence on nursing care

Introduction: Due to the aging of the population, nursing processes have been adapted to these patients, who require a high level of care and guidance. Objective: Analyzing the degree of dependence on nursing care by elderly patients (65 years or older) with femur fractures. Materials and Methods: retrospective, with a quantitative approach, carried out in a private hospital from April 2021 to April 2022. The sample comprehends 41 patients, analyzed epidemiological data and degree of dependence Study of nursing care during hospitalization, environment of hospitalization and discharge, according to the SCP. Results: Composed of 41 patients, mean age of 84 years and female predominance (75.61%). With regard to fractures, there was a greater occurrence due to falls from standing height and predominance of neck fractures, with an average time until surgery of less than 16 hours. Systemic Arterial Hypertension and Diabetes Mellitus were predominant. The average of the SCP estimates presented 24.26 in the 1st, 26.12 in the 2nd and 26.24 in the 3rd. The length of hospital stay was 7 days and no deaths were reported. Discussion: The findings on sociodemographic data, reasons for falls, location, comorbidities, degree of dependence and length of hospital stay are similar to those available in databases. They differ, in better quality, under time until surgery and clinical. Conclusions: The study presents specific knowledge to carry out the care of the intra-hospital nursing process, thus allowing the systematization of the team's assistance.

What is the association of depression with clinical response to therapy in patients with psoriatic arthritis treated with biologic disease-modifying antirheumatic drugs?

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic, progressive inflammatory joint disease that is associated with higher prevalence of depression. There is limited literature about the impact of depression, particularly regarding the response to therapy. METHODS: A retrospective cohort study with PsA patients that started their first biologic disease-modifying antirheumatic drugs (bDMARD) was conducted. In the majority of cases, a cutoff score of ≥ 8 in Hospital Anxiety and Depression Scale (HADS) was used to define cases of depression. In cases where patients did not complete the questionnaire, a previous diagnosis made by a psychiatrist was used to establish the presence of depression. Response to therapy 12 months after the start of bDMARD was evaluated and the switch rate to another bDMARD due to inefficacy was assessed at month 12. RESULTS: A total of 129 patients (66 females, 51.2%; mean age of 47.7 ± 11.0 years and mean disease duration of 10.0 ± 7.7 years) with PsA were included. Thirty-two (24.8%) patients had depression. Patients with depression and peripheral involvement had a significantly lower ACR20/50/70 responses (p = 0.001, p = 0.002, and p = 0.001 respectively) after 12 months of therapy and a significantly worse EULAR response (p = 0.002). Furthermore, patients with depression and axial involvement had a significantly worse response based on ASDAS response criteria (p = 0.031). Switch due to ineffectiveness in the first 12 months was significantly higher in patients with depression (p = 0.002). CONCLUSION: Depression in PsA is a frequent yet often understudied comorbidity. The causal relationship between depression and PsA is difficult to decrypt and further research is needed. Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity. Key Points • Depression in PsA is a frequent yet often understudied comorbidity. In our study, the prevalence of depression was 24.8%. • Depression in PsA seems to be associated to lower response to therapy and higher discontinuation rates of bDMARD. • Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity.

Factors influencing COVID-19 mortality among cancer patients: A Brazilian multi-institutional study.

PURPOSE: This study aimed to describe the demographic and clinical characteristics of cancer patients with COVID-19, exploring factors associated with adverse outcomes. PATIENTS AND METHODS: This retrospective cohort study methodically extracted and curated data from electronic medical records (EMRs) of numerous healthcare institutions on cancer patients diagnosed with a confirmed SARS-CoV-2 infection between May 2020 and August 2021, to identify risk factors linked to extended hospitalization and mortality. The retrieved information encompassed the patients' demographic and clinical characteristics, including the incidence of prolonged hospitalization, acute complications, and COVID-19-related mortality. RESULTS: A total of 1446 cancer patients with COVID-19 were identified (mean [Standard deviation] age, 59.2 [14.3] years). Most patients were female (913 [63.1%]), non-white (646 [44.7%]), with non-metastatic (818 [56.6%]) solid tumors (1318 [91.1%]), and undergoing chemotherapy (647 [44.7%]). The rate of extended hospitalization due to COVID-19 was 46% (n = 665), which was significantly impacted by age (p = 0.012), sex (p = 0.003), race and ethnicity (p = 0.049), the presence of two or more comorbidities (p = 0.006), hematologic malignancies (p = 0.013), metastatic disease (p = 0.002), and a performance status ≥ 2 (p = 0.001). The COVID-19-related mortality rate was 18.9% (n = 273), and metastatic disease (<0.001), performance status ≥2 (<0.001), extended hospitalization (p = 0.028), renal failure (p = 0.029), respiratory failure (p < 0.001), sepsis (p = 0.004), and shock (p = 0.040) significantly and negatively influenced survival. CONCLUSION: The rate of extended hospitalization and COVID-19-specific death in cancer patients was notably high and could be influenced by comorbidities, cancer treatment status, and clinical fragility. These observations may aid in developing risk counseling strategies regarding COVID-19 in individuals diagnosed with cancer.

Familiares em visita ampliada e social na terapia intensiva: existem diferenças no nível de conforto? / Family members undergoing extended and social visits in intensive care: are there differences in comfort level?

Analisar comparativamente o nível de conforto de familiares que participaram da visita ampliada e da visita social em Unidade de Terapia Intensiva. Método: Estudo transversal, desenvolvido com 57 familiares dos sujeitos internados na Unidade de Terapia Intensiva, entre 2019 e 2020. O conforto foi avaliado pela Escala de Conforto para Familiares de Pessoas em Estado Crítico de Saúde. Os dados foram analisados descritivamente e a análise bivariada pelo teste de T Student. O nível de significância estatística foi de 5%. Resultados: Os familiares inclusos na visita ampliada dispõem de um nível de conforto (4,00 ±0,53) maior que os da visita social (3,57 ±0,51), com (p=0,004). Observa-se melhor comunicação entre a equipe e os familiares da visita ampliada e um maior conhecimento por parte desses sobre o quadro de saúde do enfermo. Conclusão: A visita ampliada tem proporcionado maior nível de conforto nos familiares quando comparadas com a visita social.(AU)

To comparatively analyze the comfort level of family members who participated in the extended visit and the social visit in the Intensive Care Unit. Method: A cross-sectional study was carried out with 57 family members of patients admitted to the Intensive Care Unit between 2019 and 2020. Comfort was assessed using the Comfort Scale for Relatives of People in a Critical Health Condition. Data was analyzed descriptively and bivariate analysis using the Student's t-test. The level of statistical significance was 5%. Results: Family members included in the extended visit have a higher level of comfort (4.00 ±0.53) than those in the social visit (3.57 ±0.51), with (p=0.004). There was better communication between the team and the relatives during the extended visit and greater knowledge on the part of the latter about the patient's health condition. Conclusion: The extended visit has provided a greater level of comfort for family members when compared to the social visit.(AU)

Analizar comparativamente el nivel de confort de los familiares que participaron en la visita prolongada y la visita social en la Unidad de Cuidados Intensivos. Método: Se realizó un estudio transversal con 57 familiares de pacientes ingresados en la Unidad de Cuidados Intensivos entre 2019 y 2020. Se evaluó el confort mediante la Escala de Confort para Familiares de Personas en Estado Crítico de Salud. Los datos se analizaron de forma descriptiva y análisis bivariante mediante la prueba t de Student. El nivel de significación estadística fue del 5%. Resultados: Los familiares incluidos en la visita ampliada tienen un mayor nivel de confort (4,00 ±0,53) que los de la visita social (3,57 ±0,51), con (p=0,004). Hubo mejor comunicación entre el equipo y los familiares durante la visita ampliada y mayor conocimiento por parte de estos últimos sobre el estado de salud del paciente. Conclusiones: La visita ampliada ha proporcionado un mayor nivel de confort a los familiares en comparación con la visita social.(AU)

Investigating the association between dental age and polymorphisms in genes encoding estrogen receptors.

BACKGROUND: Genetic polymorphisms have been shown to influence several physiological traits, including dental and craniofacial characteristics. Understanding the clinical relevance of genetic polymorphisms in dental practice is crucial to personalize treatment plans and improve treatment outcomes. OBJECTIVE: to evaluate the association between dental age and genetic polymorphisms in genes encoding estrogen receptors alpha and beta (ESR1 and ESR2, respectively) in a sample of Brazilian children. METHODOLOGY: This retrospective cross-sectional study was performed with children undergoing orthodontic treatment. Patients with syndromes, congenital anomalies, craniofacial deformities, under hormonal or systemic treatment, and with a previous history of facial trauma were excluded. Panoramic radiographs were used to assess dental age according to the Demirjian, Goldstein, and Tanner method. A delta [dental age-chronological age (DA-CA)] was obtained, which shows whether the patient tends to have a normal, delayed (negative values), or advanced (positive values) dental age. DNA isolated from buccal cells was used to genotype four genetic polymorphisms: rs9340799 (A>G) and rs2234693 (C>T), located in ESR1; and rs1256049 (C>T) and rs4986938 (C>T), located in ESR2. A statistical analysis was performed and values of p<0.05 indicated statistical difference. RESULTS: A total of 79 patients were included, 44 (55.70%) girls and 35 (44.30%) boys. The Demirjian, Goldstein, and Tanner method, in general, overestimated patients' age by 0.75 years. There was no difference in the delta of dental age between the sexes (p>0.05). Genetic polymorphisms in ESR1 and ESR2 were not associated with dental age (p>0.05). CONCLUSION: The studied genetic polymorphisms in ESR1 and ESR2 were not associated with dental age in Brazilian children.

Immune-mediated skin lesions related to biological disease-modifying antirheumatic drugs: a 22-year experience of a tertiary center.

INTRODUCTION: Immune-mediated skin lesions (IMSL) can be very disabling leading to treatment discontinuation. Although these lesions have rarely been previously described, the true incidence is unknown. OBJECTIVE: To explore the cumulative incidence, management and outcomes of IMSL related to bDMARD in a large cohort of patients with chronic inflammatory rheumatic diseases. To explore possible associations and risk factors for IMSL development. METHODS: A retrospective single-center study of patients with rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA) that had been treated with at least one bDMARD for at least 6 months was conducted. IMSL related to bDMARD characteristics and outcomes were collected. RESULTS: A total of 989 patients with RA, SpA and PsA were included. Twenty-seven patients (2.7%) presented IMSL potentially related to bDMARD, being psoriasis the most common IMSL (n=12, 44.4%), followed by drug-induced lupus erythematosus (n=6), alopecia areata (n=3) and leukocytoclastic vasculitis (n=2). IMSL led to withdrawal of bDMARD in 18 of the 27 patients (66.7%). Patients with IMSL had younger age at diagnosis (p=0.038), longer disease duration (p=0.018), longer duration of bDMARD treatment (p=0.008), and higher number of previous bDMARDs (p < 0.001) than patients without IMSL. In the group of patients with IMSL there was a significantly higher percentage of patients treated with adalimumab (p < 0.001). In multivariate regression model, the number of previous bDMARDs (OR 2.13, 95%CI 1.47-3.10, p < 0.001) and treatment with adalimumab (OR 4.60, 95%CI 1.96-10.80 , p < 0.001) were statistically significant predictive factors for IMSL development. CONCLUSION: In our study, IMSL related to bDMARDs had an estimated cumulative incidence of 2.7%. Younger age at diagnosis, longer disease duration, longer duration of bDMARD treatment, higher number of previous bDMARDs and treatment with adalimumab were independently associated with an increased risk of IMSL development.

Cycling versus swapping strategies in psoriatic arthritis: results from the rheumatic diseases Portuguese register.

OBJECTIVE: To compare the 2-year retention rate between a second tumor necrosis factor alpha inhibitor (TNFi) and secukinumab (SEK) or ustekinumab (UST), in Psoriatic Arthritis (PsA) patients with previous inadequate response to their first TNFi. METHODS: Prospective longitudinal cohort study with a follow-up period of 2 years using the Nationwide Portuguese Reuma.pt database. Patients with a clinical diagnosis of PsA who also fulfill the CASPAR classification criteria, with previous treatment failure to a first-line TNFi and having started a second biotechnological drug (TNFi, SEK or UST) were included. The Cycling group was defined as switching from a first TNFi to a second TNFi, and the Swapping group as switching from a first TNFi to SEK or UST. Sociodemographic data, disease characteristics, disease activity scores and physical function at baseline and after 6, 12 and 24 months were recorded. Cox-proportional hazards regression was used to compare retention rates between Cycling and Swapping groups. To obtain a predictor model of 2-year discontinuation, a multivariable Cox regression model was performed. RESULTS: In total, 439 patients were included, 58% were female, with a mean age (standard deviation) of 49 (12) years. Globally, 75.6% initiated a second TNFi (Cycling group), and 24.4% started SEK/UST (Swapping group). The retention rates after 6, 12 and 24 months were 72%/66%/59% in the Cycling group; and 77%/66%/59% in the Swapping group. There were no significant differences in retention rates between both strategies (HR: 1.06, 95% CI 0.72-1.16). After 2 years of follow-up, 34.4% of patients discontinued their second biologic, mainly due to inefficacy (72.8%), with no differences found between groups. Baseline treatment with glucocorticoids was the only predictor of discontinuation after 2 years of follow-up (HR:1.668, 95% CI 1.154-2.409). CONCLUSIONS: After failure of a first TNF inhibitor, Cycling and Swapping strategies result in similar retention rates suggesting that both are acceptable in the management of patients with psoriatic arthritis.

Is There a Role for Risk-Reducing Bilateral Breast Surgery in BRCA1/2 Ovarian Cancer Survivors? An Observational Study.

BACKGROUND: Risk-reducing surgeries are an option for cancer risk management in BRCA1/2 individuals. However, while adnexectomy is commonly recommended in breast cancer (BC) survivors, risk-reducing bilateral breast surgery (RRBBS) is controversial in ovarian cancer (OC) survivors due to relapse rates and mortality. METHODS: We conducted a retrospective analysis of BRCA1/2-OC survivors, with OC as first cancer diagnosis. RESULTS: Median age at OC diagnosis for the 69 BRCA1/2-OC survivors was 54 years. Median overall survival was 8 years, being significantly higher for BRCA2 patients than for BRCA1 patients (p = 0.011). Nine patients (13.2%) developed BC at a median age of 61 years. The mean overall BC-free survival was 15.5 years (median not reached). Eight patients (11.8%) underwent bilateral mastectomy (5 simultaneous with BC treatment; 3 RRBBS) at a median age of 56.5 years. The median time from OC to bilateral mastectomy/RRBBS was 5.5 years. CONCLUSIONS: This study adds evidence regarding a lower BC risk after BRCA1/2-OC and higher survival for BRCA2-OC patients. A comprehensive analysis of the competing risks of OC mortality and recurrence against the risk of BC should be individually addressed. Surgical BC risk management may be considered for longer BRCA1/2-OC disease-free survivors. Ultimately, these decisions should always be tailored to patients' characteristics and preferences.

The investigation of WNT6 and WNT10A single nucleotide polymorphisms as potential biomarkers for dental pulp calcification in orthodontic patients.

The aim of this study is to evaluate if single nucleotide polymorphisms (SNPs) in WNT6 and WNT10A are associated with the risk of dental pulp calcification in orthodontic patients. This cross-sectional study followed the "Strengthening the Reporting of Genetic Association Studies" (STREGA) guidelines. Panoramic radiographs (pre- and post-orthodontic treatment) and genomic DNA from 132 orthodontic patients were studied. Dental pulp calcification (pulp stones and/or pulp space narrowing) was recorded in upper and lower first molars. The SNPs in WNT6 and WNT10A (rs7349332, rs3806557, rs10177996, and rs6754599) were assessed through genotyping analysis using DNA extracted from buccal epithelial cells. The association between pulp calcification and SNPs were analyzed using allelic and genotypic distributions and haplotype frequencies (p<0.05). Prevalence of dental pulp calcification was 42.4% in the 490 studied molars. In the genotypic analysis, the SNPs in WNT10A showed a statistically significant value for molar calcification (p = 0.027 for rs1017799), upper molar calcification (p = 0.040 for rs1017799) (recessive model), and molar calcification (p = 0.046 for rs3806557) (recessive model). In the allelic distribution, the allele C of the SNP rs10177996 in WNT10A was associated with molar calcifications (p = 0.042) and with upper first molar calcification (p = 0.035). Nine combinations of haplotypes showed statistically significant value (p<0.05). The findings of this study indicates that SNPs in WNT10A and WNT6 are associated with dental pulp calcification in molars after orthodontic treatment and may be considered as biomarkers for dental pulp calcification.

Yacon (Smallanthus sonchifolius) Flour Reduces Inflammation and Had No Effects on Oxidative Stress and Endotoxemia in Wistar Rats with Induced Colorectal Carcinogenesis.

Colorectal cancer has a high worldwide incidence. The aim of this study was to determine the effect of yacon flour (YF) on oxidative stress, inflammation, and endotoxemia in rats with induced colorectal cancer (CRC). The Wistar male rats were divided and kept for 8 weeks in four groups: S (basal diet, n = 10), Y (YF flour + basal diet, n = 10), C (CRC-induced control + basal diet, n = 12), CY (CRC-induced animals + YF, n = 12). CRC was induced by intraperitoneal injections of 1,2-dimethylhydrazine (25 mg/kg body weight). Groups Y and CY received 7.5% of the prebiotic FOS from YF. The treatment with YF increased fecal secretory immunoglobulin A levels and decreased lipopolysaccharides, tumor necrosis factor alpha and interleukin-12. However, no effect was observed on the oxidative stress by the total antioxidant capacity of plasma, anion superoxide, and nitric oxide analysis of the animals (p < 0.05). The short-chain fatty acids acetate, propionate, and butyrate showed interactions with NF-κB, TLR4, iNOS, and NADPH oxidase by in silico analysis and had a correlation (by the Person analysis) with CRC markers. The yacon flour treatment reduced the inflammation in rats with induced CRC, and could be a promising food to reduce the damages caused by colorectal cancer.

Impact of genetic variations in the WNT family members and RUNX2 on dental and skeletal maturation: a cross-sectional study.

BACKGROUND: This study evaluated if genetic variations in the WNT family members and RUNX2 are associated with craniofacial maturation, investigating dental and skeletal maturity in children and teenagers. METHODS: Radiographs from pre-orthodontic treatment of Brazilian patients (7 to 17 years-old) were used to assess dental (panoramic radiographs) and skeletal maturity (cephalometric radiographs). The chronological age (CA) was calculated based on the date of birth and the time the radiographs were performed. For the dental maturity analysis, the Demirjian (1973) method was used and a delta [dental age - chronological age (DA-CA)] was calculated. For the skeletal maturity analysis, the Baccetti et al. (2005) method was used and the patients were classified as "delayed skeletal maturation", "advanced skeletal maturation" or "normal skeletal maturation". DNA isolated from buccal cells was used for genotyping of two genetic variations in WNT family genes: rs708111 (G > A) in WNT3A and rs1533767 (G > A) in WNT11; and two genetic variations in RUNX2: rs1200425 (G > A) and rs59983488 (G > T). A statistical analysis was performed and values of p < 0.05 indicated a significant difference. RESULTS: There were no associations between dental maturity and genotypes (p > 0.05). In the skeletal maturity analysis, the allele A in the rs708111 (WNT3A) was statistically more frequent in patients with delayed skeletal maturation (Prevalence Ratio = 1.6; 95% Confidence Interval = 1.00 to 2.54; p-value = 0.042). CONCLUSIONS: The rs708111 in the WNT3A gene impacts on skeletal maturation.

Hypophosphatemic osteomalacia induced by intravenous iron therapy: a case report.

OBJECTIVE: Osteomalacia is an uncommon, overlooked and debilitating metabolic bone disease with numerous aetiologies. Herein, we report an atypical cause of osteomalacia - intravenous iron therapy. METHODS: Description of a case report of hypophophatemic osteomalacia induced by ferric carboxymaltose infusions. RESULTS: A 70-year-old male with Rendu-Osler-Weber syndrome requiring repeated infusions of ferric carboxymaltose was admitted for disabling lower limb pain associated with persistent hypophosphatemia (1.6mg/dL) and increased urinary fractional excretion of phosphate (43%, UP04=118.3mg/dL), serum fibroblast growth factor 23 (324UA/mL), intact parathyroid hormone (110pg/mL) and bone alkaline phosphatase (40.1mcg/L). X-ray and CT of the feet showed severe diffuse bone demineralization. Feet MRI displayed a subchondral fracture of the cuneiform-navicular joints. Spine X-ray revealed dorsolumbar vertebral flattening. Somatostatin receptor PET scan excluded an occult tumor. Bone biopsy with histomorphometry confirmed the presence of osteomalacia. After excluding other causes, a diagnosis of hypophosphatemic osteomalacia induced by frequent ferric carboxymaltose infusions was made. The iron formulation was replaced by saccharated ferric oxide infusions and progressive titration of calcitriol up to 1.5mg/day and oral disodium phosphate up to 5740mg/day was started. After 6 months, there was a clear clinical and analytical improvement. CONCLUSION: Osteomalacia may be a consequence of prolonged hypophosphatemia induced by recurrent ferric infusions, which is an uncommon and neglected bone adverse event of this therapy. Phosphate levels and bone symptoms should be monitored during repetitive iron infusions, maintaining a high level of suspicion for osteomalacia as it is important to identify and treat it in a timely manner, minimizing its severe morbidity.

The impact of antinuclear antibodies seroconversion induced by anti-tumor necrosis factor α agents on the clinical outcomes in rheumatic patients.

INTRODUCTION: Anti-tumor necrosis factor α (anti-TNFα) agents can potentially induce the anti-nuclear antibodies (ANA) development over time. Evidence of the real impact of these autoantibodies on clinical response to treatment in rheumatic patients is still scarce. OBJECTIVES: To explore the impact of ANA seroconversion induced by anti-TNFα therapy on clinical outcomes in biologic-naïve patients with Rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: An observational retrospective cohort study enrolling biologic-naïve patients with RA, axSpA and PsA who started their first anti-TNFα agent was conducted for 24 months(M). Sociodemographic data, laboratory findings, disease activity and physical function scores were collected at baseline, 12M and 24M. To examine the differences between the groups with and without ANA seroconversion, independent samples t-tests, Mann-Whitney U-tests and chi-square tests were performed. Linear and logistic regression models were used to assess the effects of ANA seroconversion on the clinical response to treatment. RESULTS: A total of 432 patients with RA (N=185), axSpA (N=171) and PsA (N=66) were included. ANA seroconversion rate at 24M was 34.6%, 64.3% and 63.6% for RA, axSpA and PsA, respectively. Regarding sociodemographic and clinical data in RA and PsA patients, no statistically significant differences between groups with and without ANA seroconversion were found. In axSpA patients, ANA seroconversion was more frequent in patients with higher body mass index (p=0.017) and significantly less frequent in patients treated with etanercept (p=0.01). Regarding disease activity, DAS28 for RA patients and ASDAS-CRP for axSpA patients were significantly higher in ANA seroconversion group at 12M (p=0.017 and p=0.009, respectively). For PsA patients, CDAI was significantly higher in ANA seroconversion group at 24M (p=0.043). Overall switching rate of biologic disease-modifying antirheumatic drugs (bDMARD) was significantly higher in the ANA seroconversion group over time (p=0.025). For RA patients, ANA seroconversion predicted DAS28 (ß=-0.21, 95%CI[-1.86;-0.18], p=0.017) at 12M. CONCLUSIONS: ANA seroconversion induced by anti-TNFα agents could interfere in clinical response of patients with rheumatic diseases. The presence of these autoantibodies can be considered as a potential predictor of poor treatment response and higher need for bDMARD switching over time.