Measurement properties of the Portuguese version of the rheumatoid arthritis patient-reported experience measure (CQRA-PREM): a cross-sectional single center study.

AIMS: to test the measurement properties of the Portuguese version of the Commissioning for Quality in Rheumatoid Arthritis Patient-Reported Experience Measure (CQRA-PREM) for patients with rheumatoid arthritis (RA). METHODS: This cross-sectional clinical field study recruited adult patients with RA during rheumatology appointments of a Portuguese rheumatology center. Patients completed the Portuguese version of CQRA-PREM, composed of 7 domains and 24 questions. Sociodemographic characteristics, symptoms/disease duration, current treatment, Pain-Visual Analog Scale (VAS), Patient Global Assessment (PGA)-VAS and Health Assessment Questionnaire (HAQ) were also collected from the patient. Disease Activity Score for 28 joints with C-reactive Protein (DAS28-CRP) was recorded by the rheumatologist. The assessment of CQRA-PREM measurement properties followed the Consensus-based Standards for the Selection of Health Status Measurement Instruments (COSMIN) recommendations. RESULTS: A total of 61 patients with RA were included. The domains in which patients showed better experience were the "Needs and preferences", followed by "Coordination and Communication". The domain "Information, education and self-care" was an identified area of improvement for providing patient-centered care. Ceiling effects were found in four domains of the CQRA-PREM. Internal consistency of all domains was considered good (α>0.7). Homogeneity was considered good for each question in all domains analyzed (0.30≤rp≤0.70). The divergent validity of the PREM was good, revealing that the domains were not correlated (Pain-VAS, HAQ, DAS28-CRP) or only weakly (PGA-VAS) correlated with clinical outcomes. CONCLUSIONS: The CQRA-PREM showed acceptable measurement properties and is a useful tool for evaluating quality of healthcare provided in daily practice, as perceived by RA patients in Portugal.

Portuguese Recommendations for the management of Raynaud's phenomenon and digital ulcers in systemic sclerosis and other connective tissue diseases.

OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological and pharmacological management of Raynaud's phenomenon (RP) and digital ulcers (DUs) in patients with systemic sclerosis and other immune-mediated connective tissue diseases (CTDs). METHODS: A task force comprising 21 rheumatologists, two surgeons (vascular and plastic), two nurses, and one patient representative was established. Following a systematic literature review performed to inform the recommendations, statements were formulated and discussed during two meetings (one online and one in-person). Levels of evidence, grades of recommendation (GoR), and level of agreement (LoA) were determined. RESULTS: Five overarching principles and 13 recommendations were developed. GoR ranged from A to D. The mean ± standard difference (SD) LoA with the overarching principles and recommendations ranged from 7.8±2.1 to 9.8±0.4. Briefly, the management of RP and DUs in patients with CTDs should be coordinated by a multidisciplinary team and based on shared decisions with patients. Nifedipine should be used as first-line therapy for RP and/or DUs. Sildenafil, tadalafil, and/or iloprost IV are second-line options for severe and/or refractory patients with RP and/or DUs. Sildenafil, tadalafil and/or Iloprost IV, should be prescribed for healing and prevention (also including bosentan) of DUs. In patients with RP and/or DUs, non-pharmacological interventions might be considered as add-ons, but there is limited quality and quantity of scientific evidence supporting their use. CONCLUSIONS: These recommendations will inform rheumatologists, specialist nurses, other healthcare professionals, and patients about a comprehensive and personalized management of RP and DUs. A research agenda was developed to address unmet needs, particularly for non-pharmacologic interventions.

Prevalence of condylar morphological changes in individuals with class II malocclusion.

This observational, cross-sectional study with retrospective collection was aimed to evaluate the prevalence of morphological changes in mandibular condyles in individuals with class II malocclusion, classified according to different vertical growth patterns (brachyfacial, mesofacial, and dolichofacial), through cone beam computed tomography (CBCT). Seventy CBCT images (140 mandibular condyles) were selected from individuals without orthodontic treatment, of both sexes, aged between 25 and 50 years. No statistically significant differences were found between facial patterns; however, there was a higher relative prevalence of bone changes in dolichofacial individuals with flattening (62%), sclerosis (44%), and subchondral bone cyst (20%). Erosion and osteophytes prevailed in mesofacial (39%), and brachyfacial individuals (32%), respectively. Thus, there was no statistically significant difference in the prevalence of degenerative changes between the vertical skeletal patterns. Flattening was the most prevalent change, whereas subchondral bone cyst was the least prevalent among the three groups studied. The observational design of this study makes it possible to analyze image banks to verify the correlation of morphological changes in the temporomandibular joint in different facial patterns in patients with class II malocclusion. A limitation of the study is that clinical characteristics were not evaluated.

Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype.

Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between ADNP and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype-specific episignature. A distinct episignature was shared by 15 individuals with BIS-causing SMARCA2 pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic ADNP variants. This represents first evidence of a sensitive phenotype-specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene-specific episignatures.

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

[This corrects the article DOI: 10.1371/journal.pone.0288782.].

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.

Is There Variation in the Morphology of the Frontal Sinus in Individuals with Different Craniofacial Patterns? A Systematic Review with Meta-Analysis.

To evaluate differences in the morphology of the frontal sinus in adolescents and adults with different craniofacial patterns, searches up to April 2024 were conducted in six databases and other information sources to identify observational studies. Study selection, data extraction, and quality assessment using the NOS scale were performed independently by two reviewers. Random effects meta-analyses were conducted to estimate the difference in frontal sinus measurements between different craniofacial skeletal patterns (α = 0.05). The certainty of the evidence was evaluated according to GRADE. Fourteen studies were included in the review. All studies had methodological limitations that affected their quality. The syntheses showed that skeletal Class II subjects presented a significantly smaller width of the frontal sinus than skeletal Class I subjects (MD = 0.56; 95% CI: 0.38, 0.74; p < 0.0001; I2 = 3%). Skeletal Class III subjects showed a frontal sinus width (MD = -0.91; 95% CI: -1.35, -0.47; p < 0.0001; I2 = 36%) and area (MD = -28.13; 95% CI: -49.03, -7.23; p = 0.0084; I2 = 66%) significantly larger than those of the skeletal Class I subjects. The available evidence suggests a positive relationship between mandibular and frontal sinus size. There is limited evidence to make reliable estimates of the association of other craniofacial patterns and frontal sinus characteristics. These reported results are not conclusive and should be evaluated carefully due to the very low certainty of the evidence. The current evidence is scarce and consists of studies with methodological limitations; the results of the studies are often inconsistent, and the pooled estimates are imprecise. New high-quality research is still necessary.

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.

An industrialized diet as a determinant of methylation in the 1F region of the NR3C1 gene promoter.

Background: Dietary composition can modify gene expression, favoring the development of chronic diseases via epigenetic mechanisms. Objective: Our study aimed to investigate the relationship between dietary patterns and NR3C1 gene methylation in users of the Brazilian Public Unified Health System (SUS). Methods: We recruited 250 adult volunteers and evaluated their socioeconomic status, psychosocial characteristics, lifestyle, and anthropometrics. Peripheral blood was collected and evaluated for cortisol levels, glycemia, lipid profile, and insulin resistance; methylation of CpGs 40-47 of the 1F region of the NR3C1 gene was also measured. Factors associated with degree of methylation were evaluated using generalized linear models (p < 0.05). Lifestyle variables and health variables were included as confounding factors. Results: The findings of our cross-sectional study indicated an association between NR3C1 DNA methylation and intake of processed foods. We also observed relevant associations of average NR3C1 DNA across the segment analyzed, methylation in component 1 (40-43), and methylation in component 2 (44-47) with a pattern of consumption of industrialized products in relation to BMI, serum cortisol levels, and lipid profile. These results may indicate a relationship between methylation and metabolic changes related to the stress response. Conclusion: These findings suggest an association of methylation and metabolic alterations with stress response. In addition, the present study highlights the significant role of diet quality as a stress-inducing factor that influences NR3C1 methylation. This relationship is further linked to changes in psychosocial factors, lifestyle choices, and cardiometabolic variables, including glucose levels, insulin resistance, and hyperlipidemia.

A direct spinal cord-computer interface enables the control of the paralysed hand in spinal cord injury.

The paralysis of the muscles controlling the hand dramatically limits the quality of life of individuals living with spinal cord injury (SCI). Here, with a non-invasive neural interface, we demonstrate that eight motor complete SCI individuals (C5-C6) are still able to task-modulate in real-time the activity of populations of spinal motor neurons with residual neural pathways. In all SCI participants tested, we identified groups of motor units under voluntary control that encoded various hand movements. The motor unit discharges were mapped into more than 10 degrees of freedom, ranging from grasping to individual hand-digit flexion and extension. We then mapped the neural dynamics into a real-time controlled virtual hand. The SCI participants were able to match the cue hand posture by proportionally controlling four degrees of freedom (opening and closing the hand and index flexion/extension). These results demonstrate that wearable muscle sensors provide access to spared motor neurons that are fully under voluntary control in complete cervical SCI individuals. This non-invasive neural interface allows the investigation of motor neuron changes after the injury and has the potential to promote movement restoration when integrated with assistive devices.

An Uncommon Presentation of Secondary Syphilis.

Syphilis is a chronic venereal disease caused by Treponema pallidum (TP). Destructive arthritis is rare in its primary and secondary stages but can occur in the tertiary stage and its congenital form.

Systematic literature review to inform the Portuguese recommendations for the management of Raynaud's phenomenon and digital ulcers in systemic sclerosis and other connective tissue diseases.

OBJECTIVE: To perform a systematic literature review (SLR) aimed at evaluating the efficacy and safety of pharmacological and non-pharmacological treatments for Raynaud's phenomenon (RP) and digital ulcers (DU) in patients with systemic sclerosis (SSc) and other connective tissue diseases (CTD), in order to inform the Portuguese recommendations for managing RP and DU in these patients. METHODS: A SLR was conducted until May 2022 to identify studies assessing the efficacy and safety of pharmacological and non-pharmacological interventions for RP and DU in SSc and other CTD. Eligible study designs included randomized controlled trials (RCTs), controlled clinical trials, and their extensions for assessing efficacy and safety of interventions. Observational studies with a comparator were included for evaluating the efficacy and safety of non-pharmacological interventions and safety of pharmacological interventions. The risk of bias of each study was assessed using standard tools. RESULTS: Out of 71 publications meeting the inclusion criteria, 59 evaluated pharmacological and 12 non-pharmacological interventions. We found moderate quality evidence supporting the efficacy of calcium channel blockers, phosphodiesterase-5 inhibitors, and intravenous prostacyclin analogues in reducing RP frequency, severity, and duration. Intravenous iloprost had a small to moderate effect size in improving DU healing. Phosphodiesterase-5 inhibitors were effective in reducing total DU count, new DU occurrence, and enhancing DU healing. Bosentan effectively prevented new DU in SSc patients. No new safety concerns were associated with these treatments. The studies on non-pharmacological interventions were, in general, of low quality, and had a small sample size. Warming measures decreased frequency and duration of RP attacks; laser therapy improved RP-related outcomes; local oxygen-ozone therapy improved RP outcomes as an add-on therapy; bone marrow mononuclear cell implantation improved DU-associated pain; periarterial sympathectomy and vascular bypass reduced DU number and finger amputation risk. CONCLUSION: The available evidence supports the efficacy and safety of pharmacological interventions, namely nifedipine, sildenafil, iloprost, and bosentan in treating RP and DU in patients with SSc and other CTD. Scarce and low-quality evidence does support the use of some non-pharmacological interventions but with only a modest effect size. This SLR underscores the limited availability of high-quality evidence for determining the optimal treatment.

Erythropoietin effects on cryopreserved/transplanted cat ovarian tissue: A comparison of two incubation methods.

Many feline species are currently threatened with extinction. Therefore, germplasm bank establishment has become imperative. However, cryoinjury and ischemia-reperfusion injury pose significant obstacles to both cryopreservation and xenotransplantation. In this regard, erythropoietin (Epo) represents a potential alternative strategy due to its properties. This study aimed to assess the incubation of domestic cat ovarian tissue in Epo, both before and after cryopreservation, and investigate its effectiveness in promoting revascularization following xenotransplantation. Sixteen ovaries from 8 healthy cats were sliced following elective bilateral ovariohysterectomy (OHE). Subsequently, 8 fragments measuring 3 mm³ each were obtained from the cortical region of each ovary. The fragments were allocated into 3 treatment groups: Cryo group, fragments were cryopreserved, thawed and immediately transplanted; Cryo + Epo group, fragments were first cryopreserved in nitrogen, thawed, incubated in Epo (100 IU) for 2h and transplanted; and the Epo + Cryo group, in which fragments were first incubated in Epo (100 IU) for 2h, cryopreserved, thawed and immediately transplanted. The fragments were then xenotransplanted into the dorsal subcutaneous region of ovariectomized female nude mice and retrieved at 7, 14, 21, and 28 days post-transplantation. The results indicated that Epo effectively enhanced follicular survival, preservation of viability, and tissue revascularization. The Epo + Cryo group displayed better revascularization rates on D14 and D21 post-transplantation and an increase in primordial and growing follicles on D28, the Cryo + Epo group exhibited significantly more follicles on D14 and D21, with fewer degenerated follicles.