Uncovering moderators of pain perception by women with endometriosis from Latin America and Spain: the roles of sociodemographics, racial self-identity, and pain catastrophizing.

ABSTRACT: A cross-sectional multinational collaborative study on women with endometriosis from Latin America and Spain uncovered high levels of painful symptomatology and high pain catastrophizing scores. Associations between pain perception/catastrophizing and race/ethnicity have been documented. This study was conducted to uncover factors moderating pelvic pain severity, including socioeconomic variables, self-identified race, and pain catastrophizing in women with endometriosis from Latin America and Spain, a population encompassing diverse racial and sociocultural contexts. Self-reported data on demographics, clinical history, Ob-Gyn history, pelvic pain intensity, and pain catastrophizing were collected with the Spanish World Endometriosis Research Foundation (WERF) Endometriosis Phenome Project (EPhect) Clinical Questionnaire (ECQ). Multiple logistic regression was conducted to analyze effects of self-identified race, demographic clusters (defined as countries with similar racial population distribution), socioeconomic factors, and pain catastrophizing on reporting severe vs moderate-mild levels of dysmenorrhea, dyspareunia, and pelvic pain. Self-identified race did not affect the likelihood of reporting severe pelvic pain; however, there were significant differences in reporting severe dysmenorrhea at worst among demographic clusters. Older age was associated with severe dyspareunia at worst and recent pelvic pain. Pain catastrophizing score was highly predictive of reporting most types of severe pelvic pain, regardless of race and demographic cluster. These results negate a role of racial categories as moderator of pain in women from Latin America and Spain and support integration of pain catastrophizing assessments and psychological interventions into the pain management plan to enhance therapeutic outcomes and QoL for patients with endometriosis.

An Observational Study in the Real Clinical Practice of the Treatment of Noninfectious Uveitis.

BACKGROUND: The aim of this study was to describe the characteristics of patients with uveitis associated with an immunologic or idiopathic disease that requires immunosuppressive treatment and the response to such treatments in real clinical practice. METHODS: An observational, descriptive, longitudinal, and retrospective study of a cohort of patients diagnosed with noninfectious uveitis was performed. To assess the response to treatment, we evaluated the change in visual acuity, vitritis, and the presence of macular edema. RESULTS: We included 356 patients. Overall, 12% required treatment with systemic corticosteroids, and 66 patients (18.5%) required immunosuppressive/biological treatment, with methotrexate being the most used (55%). Immunosuppressive drugs were used in 59 cases (in 56 patients, as the first choice of treatment and for 3 patients as the second choice after treatment with biologics). Treatment with biologics was the first choice in 10 patients out of 66 (15%), and 34 (48%) required them at some time during the disease, with adalimumab being the most commonly used. Thirty-five patients (53%) needed to switch drugs due to a lack of response to the first one. There were no differences between different drugs in the resolution of vitritis and improvement in vision. CONCLUSIONS: The use of systemic corticosteroids and immunosuppressive/biologics was necessary for a high number of patients with noninfectious uveitis. In our series, tocilizumab was significantly more effective in the resolution of macular edema.

Hypofractionated whole breast IMRT with HDR brachytherapy boost in early-stage breast cancer: Long-term results from a single-center.

INTRODUCTION/OBJECTIVES: The addition of a boost to the lumpectomy bed after whole-breast (WB) radiotherapy plays a key role in the treatment of patients with breast cancer (BC). The clinical benefits of a boost with high-dose-rate brachytherapy (HDR-BT) after conventional fractionation is supported by a large body of evidence. However, few studies have described its outcomes after a hypofractionated scheme. MATERIALS AND METHODS: We included all patients treated with adjuvant WB-IMRT in 15 sessions followed by a single-session HDR-BT boost with local anesthesia on an outpatient basis. RESULTS: Between 2009 and 2017, 638 patients with early-stage BC were treated according to the aforementioned protocol after breast-conserving surgery. Median follow-up was 6 years (4-11). Despite the low incidence of side effects and their slightness, we did identify an impact of breast volume on the risk of acute radiodermatitis, fibrosis, pain and edema. However, we did not identify any relationship between the volume in cubic centimeters of the BT-implant with acute or long-term side effects. 2.2% patients had an actual local relapse, 2.4% a 2nd primary in the same breast and 2.39% were diagnosed with contralateral BC. Event-free survival at 11 years was 85.5% with an overall survival of 95.7%. CONCLUSION: Adjuvant hypofractionated whole-breast IMRT followed by a single dose HDR-BT boost has a low incidence of acute and chronic toxicity and excellent oncological outcomes. However, it may be worthwhile to intensify self-care protocols and surveillance in women with large breasts who may be at increased risk of side effects.

Impact of systemic therapies on SARS-CoV-2 antibody seroprevalence in patients with immune-mediated diseases. / Impacto de las terapias sistémicas en la seroprevalencia de anticuerpos contra el SARS-CoV-2 en pacientes con enfermedades inmunomediadas.

OBJECTIVE: To determine the seroprevalence of SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMID) treated with biologic (bDMARDs) or synthetic targeted disease-modifying antirheumatic drugs (tsDMARDs). METHODS: An observational, descriptive, prospective and cross-sectional study of analytical prevalence analysis was conducted in patients with IMID with bDMARDs or tsDMARDs. Seroprevalence was compared by measuring immunoglobulinG (IgG) against SARS-CoV-2 between October/2020 and May/2021. RESULTS: A total of 550 IMID's patients were studied, all of them on treatment with bDMARDs or tsDMARDs. The seroprevalence of the total patient group was 16% (88/550). Patients receiving therapy with tumor necrosis factor alpha inhibitors (TNFi) had a higher seroprevalence compared to other biologic and synthetic targeted therapies (OR: 1.792 [95%CI: 1.088-2.951]; P=.021). The influence on seroprevalence of concomitant use with b/tsDMARDs of conventional synthetic DMARDs (csDMARDs) was also analyzed. A lower seroprevalence was demonstrated in the group of patients treated with TNFi and methotrexate together, compared with those on TNFi monotherapy, 10.1 vs 24.1% (OR: 0.355 [95%CI: 0.165-0.764]; P=.006). No significant differences were found with the other DMARDs. Regarding IMIDs, no differences in seroprevalence were identified between the different disease groups. CONCLUSION: Patients on treatment with TNFα inhibitors have better humoral response compared to the other b/tsDMARDs. However, when associated with methotrexate the seroprevalence decreases significantly.

Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial.

Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908-8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Effectiveness of a Spectacle Lens with a Specific Asymmetric Myopic Peripheral Defocus: 12-Month Results in a Spanish Population.

BACKGROUND: Different designs of ophthalmic lenses have been studied to control the progression of myopia in children. This study aims to evaluate the short-term efficacy of a new design of ophthalmic lens with asymmetric myopic peripheral defocus (MPDL) on myopia progression in children compared to a control group wearing a single-vision lens (SVL). METHODS: Children aged 5 to 12 with myopia up to -0.50 D, astigmatism and anisometropia under 1.50 D, and corrected visual acuity over 20/20 were randomized to either the study group (MPDL) or control group (SVL). The myopia progression was evaluated by measuring axial length (AL) growth (IOL Master; Zeiss) over a period of one year. RESULTS: Ninety-two subjects were recruited. Forty-six children were randomly assigned to the control group, and 46 to the study group. In total, 83 children completed the clinical trial, with a mean age of 10.81 [9.53-11.92] years, among which 59.04% were female. After one year of treatment, there was less AL elongation in the study group compared to the control group (0.16 ± 0.16 mm vs. 0.24 ± 0.16 mm, p = 0.034). CONCLUSIONS: The MPDL significantly reduced the absolute growth of AL by 39% (p = 0.014) and relative growth of AL by 37.3% (p = 0.012) after 12 months in comparison to the control group in a Spanish population.

MicroRNAs modulate immunological and inflammatory responses in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis.

MicroRNAs (miRNAs) regulate the post-transcriptional expression of genes by binding to their target mRNAs. In this study, whole miRNA sequencing was used to compare the expression of miRNAs in ileocecal valve (ICV) and peripheral blood (PB) samples of cows with focal or diffuse paratuberculosis (PTB)-associated lesions in gut tissues versus (vs) control cows without lesions. Among the eight miRNAs differentially expressed in the PB samples from cows with diffuse lesions vs controls, three (miR-19a, miR-144, miR32) were also down-regulated in cows with diffuse vs focal lesions. In the ICV samples, we identified a total of 4, 5, and 18 miRNAs differentially expressed in cows with focal lesions vs controls, diffuse lesions vs controls, and diffuse vs focal lesions, respectively. The differential expression of five microRNAs (miR-19a, miR-144, miR-2425-3p, miR-139, miR-101) was confirmed by RT-qPCR. Next, mRNA target prediction was performed for each differentially expressed miRNA. A functional analysis using the predicted gene targets revealed a significant enrichment of the RNA polymerase and MAPK signaling pathways in the comparison of cows with focal vs no lesions and with diffuse vs focal lesions, respectively. The identified miRNAs could be used for the development of novel diagnostic and therapeutical tools for PTB control.

Beyond the Scalpel: Assessing ChatGPT's potential as an auxiliary intelligent virtual assistant in oral surgery.

AI has revolutionized the way we interact with technology. Noteworthy advances in AI algorithms and large language models (LLM) have led to the development of natural generative language (NGL) systems such as ChatGPT. Although these LLM can simulate human conversations and generate content in real time, they face challenges related to the topicality and accuracy of the information they generate. This study aimed to assess whether ChatGPT-4 could provide accurate and reliable answers to general dentists in the field of oral surgery, and thus explore its potential as an intelligent virtual assistant in clinical decision making in oral surgery. Thirty questions related to oral surgery were posed to ChatGPT4, each question repeated 30 times. Subsequently, a total of 900 responses were obtained. Two surgeons graded the answers according to the guidelines of the Spanish Society of Oral Surgery, using a three-point Likert scale (correct, partially correct/incomplete, and incorrect). Disagreements were arbitrated by an experienced oral surgeon, who provided the final grade Accuracy was found to be 71.7%, and consistency of the experts' grading across iterations, ranged from moderate to almost perfect. ChatGPT-4, with its potential capabilities, will inevitably be integrated into dental disciplines, including oral surgery. In the future, it could be considered as an auxiliary intelligent virtual assistant, though it would never replace oral surgery experts. Proper training and verified information by experts will remain vital to the implementation of the technology. More comprehensive research is needed to ensure the safe and successful application of AI in oral surgery.

LAENALS: epidemiological and clinical features of amyotrophic lateral sclerosis in Latin America.

OBJECTIVE: The Latin American Epidemiologic study of ALS (LAENALS) aims to gather data on ALS epidemiology, phenotype, and risk factors in Cuba, Chile, and Uruguay, to understand the impact of genetic and environmental factors on ALS. METHODS: A harmonized data collection protocol was generated, and a Latin-American Spanish language Register was constructed. Patient data were collected in Uruguay in 2018, in Chile from 2017 to 2019, and in Cuba between 2017 and 2018. Statistical analysis was performed using SPSS 25.0.0 software. Crude cumulative incidence, standardized incidence, and prevalence were calculated in the population aged 15 years and older. RESULTS: During 2017-2019, 90 people with ALS from Uruguay (55.6% men), 219 from Chile (54.6% men), and 49 from Cuba (55.1% men) were included. The cumulative crude incidence in 2018 was 1.73/100,000 persons in Uruguay, 1.08 in Chile and 0.195 in Cuba. Crude prevalence in 2018 was 2.19 per 100,000 persons in Uruguay, 1.39 in Chile and 0.55 in Cuba. Mean age at onset was 61.8 ± 11.96 SD years in Uruguay, 61.9 ± 10.4 SD years in Chile, and 60.21 ± 12.45 SD years in Cuba (p = 0.75). Median survival from onset was 32.43 months (21.93 - 42.36) in Uruguay, 24 months (13.5 - 33.5) in Chile, and 29 months (15 - 42.5) in Cuba (p = 0.006). CONCLUSIONS: These preliminary data from LAENALS confirm the lower incidence and prevalence of ALS in counties with admixed populations. The LAENALS database is now open to other Latin American countries for harmonized prospective data collection.

Uncovering Emotions: A Pilot Study on Classifying Moods in the Valence-Arousal Space using In-the-Wild Passive Data.

Mood classification from passive data promises to provide an unobtrusive way to track a person's emotions over time. In this exploratory study, we collected phone sensor data and physiological signals from 8 individuals, including 5 healthy participants and 3 depressed patients, for a maximum of 35 days. Participants were asked to answer a digital questionnaire three times daily, resulting in a total of 334 self-reported mood state samples. Gradient-boosting classification was applied to the collected passive data to categorize 4 mood states in the Valence-Energetic Arousal space. The cross-validation results showed better classification performance compared to a baseline model, which always predicts the majority class. The classifier using passive data had an area under the precision-recall curve of 0.39 (SD = 0.1) while the baseline had 0.26 (SD = 0.03), suggesting the presence of information in the collected features that support the classification process. The model identified the entropy of the heart rate and the average physical activity in the preceding 8 hours, along with the max normal-to-normal (NN) sinus beat interval and the NN low frequency-high frequency ratio during the questionnaire completion, as the most important features in its analysis. Additionally, the time range of data collection was considered a contextual factor.

Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos

Introducción: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. Objetivo: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. Métodos: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. Resultados: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). Conclusiones: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

Background: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. Aim: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. Methods: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. Results: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). Conclusions: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.

An update on Mycobacterium tuberculosis lipoproteins.

Almost 3% of the proteins of Mycobacterium tuberculosis (M. tuberculosis), the main causative agent of human tuberculosis, are lipoproteins. These lipoproteins are characteristic of the mycobacterial cell envelope and participate in many mechanisms involved in the pathogenesis of M. tuberculosis. In this review, the authors provide an updated analysis of M. tuberculosis lipoproteins and categorize them according to their demonstrated or predicted functions, including transport of compounds to and from the cytoplasm, biosynthesis of the mycobacterial cell envelope, defense and resistance mechanisms, enzymatic activities and signaling pathways. In addition, this updated analysis revealed that at least 40% of M. tuberculosis lipoproteins are glycosylated.

1D-Convolutional Neural Networks can Quantify Therapy Content of Children and Adolescents Walking in a Robot-Assisted Gait Trainer.

Therapy content, consisting of device parameter settings and therapy instructions, is crucial for an effective robot-assisted gait therapy program. Settings and instructions depend on the therapy goals of the individual patient. While device parameters can be recorded by the robot, therapeutic instructions and associated patient responses are currently difficult to capture. This limits the transferability of successful therapeutic approaches between clinics. Here, we propose that 1D-convolutional neural networks can be used to relate patient behavior during individual steps to the instructions given as a surrogate for the patient's intent. Our model takes the surface electromyography patterns of two leg muscles as input and predicts the given instruction as output. We tested this approach with data from 20 healthy children walking in a robot-assisted gait trainer with 5 different instructions. Our model performs well, with a classification accuracy of almost 90%, when the instruction targets specific aspects of gait, such as step length. This shows that 1D-convolutional neural networks are a viable tool for quantifying therapy content. Thus, they could help compare therapy approaches and identify effective strategies.

Cocoa Polyphenols Prevent Age-Related Hearing Loss and Frailty in an In Vivo Model.

Age-related hearing loss (ARHL) impairs the quality of life in elderly persons. ARHL is associated with comorbidities, such as depression, falls, or frailty. Frailty syndrome is related to poor health outcomes in old age. ARHL is a potentially modifiable risk factor for frailty. Oxidative stress has been proposed as a key factor underlying the onset and/or development of ARHL and frailty. Cocoa has high levels of polyphenols and provides many health benefits due to its antioxidant properties. Male and female C57Bl/6J mice were randomly assigned to two study groups: animals receiving a cocoa-supplemented diet and the other receiving a standard diet. Then, at the ages of 6, 14, and 22 months, hearing and frailty were measured in all mice. Auditory steady-state responses (ASSR) threshold shifts were measured to different frequencies. The frailty score was based on the "Valencia Score" adapted to the experimental animals. The total antioxidant capacity and total polyphenols in urine samples were also measured. Significant improvements in hearing ability are observed in the cocoa groups at 6, 14, and 22 months compared to the no cocoa group. The cocoa diet significantly retards the development of frailty in mice. Cocoa increases the concentration of polyphenols excreted in the urine, which increases the total antioxidant capacity. In conclusion, cocoa, due to its antioxidant properties, leads to significant protection against ARHL and frailty.

Efficacy of an environmental enrichment intervention for endometriosis: a pilot study.

Introduction: We have previously shown that Environmental Enrichment (EE), a multi-modal psychosocial intervention consisting of increased social interaction, novelty, and open spaces, improved disease presentation, anxiety, and immune-related disturbances in the rat model of endometriosis. However, there is a knowledge gap regarding the effects of EE interventions in patients with this painful, inflammatory chronic disease. Aim: To adapt and test the efficacy of an EE intervention on pelvic pain, mental health, perceived stress, quality of life, and systemic inflammation in endometriosis patients through a randomized clinical trial (RCT). Materials and methods: A multidisciplinary team with expertise in physiology, neuroscience, psychology, and women's health adapted and implemented a two-arm RCT comparing an EE intervention with a wait-list control group. Six EE modules administered on alternate weeks were provided to patients in the intervention (N = 29); controls received education only. Survey data and biospecimens were collected at baseline, end-of-study, and 3-months post-intervention to assess pain (Brief Pain Inventory, BPI), endometriosis-related quality of life-QoL (Endometriosis Health Profile-30, EHP30), anxiety (Generalized Anxiety Disorder 7, GAD7), depression (Patient Health Questionnaire for Depression 8, PHQ8), pain catastrophizing (Pain Catastrophizing Score, PCS), stress (Perceived Stress Scale-14, PSS14), and saliva cortisol levels (AM, PM). Results: Compared to the wait-list controls, participants in the EE intervention showed significantly decreased GAD-7 scores at the end of the intervention and 3-month follow-up. Depression, perceived stress, and QoL improved at the 3-month follow-up compared to baseline. While pain levels did not improve, they significantly correlated with anxiety, depression, QoL and pain catastrophizing scores. Conclusion: This pilot RCT demonstrated significant improvements in anxiety and depressive symptoms, QoL, and perceived stress, supporting enriched environments as an integrative psychosocial intervention to be used as adjuvant to the standard of care for endometriosis pain.

The Real-World Study of Immunogenicity and Safety of the Adjuvant Recombinant Vaccine against Varicella Zoster Virus in Patients with Immune-Mediated Inflammatory Diseases Treated with Janus Kinase Inhibitors.

Background. The risk of herpes zoster reactivation is increased in immunocompromised patients, especially in those with immune-mediated inflammatory diseases (IMIDs) on Janus kinase inhibitor (JAKi) treatment. The recombinant subunit herpes zoster vaccine (RZV) is a non-live vaccine, recently approved for this subgroup of patients, which shows high rates of vaccine effectiveness, with few adverse effects reported in clinical trials. Purpose. The aim of this real-world study was to determine the immunogenicity and safety of RZV in IMID patients on JAKi treatment. Methods. The increase in the concentration of anti-gE antibody for varicella zoster virus post-vaccination, compared to the pre-vaccination concentration, was analyzed to test the humoral immune response. Adverse effects after the first and second vaccine doses were registered. Results. In total, 49 patients were analyzed, and a fourfold increase in antibody concentration was achieved in almost 40% of subjects, with only one serious local adverse effect. Discussion. The resulting immunogenicity was lower than that observed in clinical trials, probably due to the presence of immune disease and immunosuppressive treatment, and to the fact that this was a real-world study. No differences in response according to age, previous virus zoster reactivation, or concomitant treatments were found. Conclusions. RZV was well tolerated and reached the immune response objective in 40% of patients. These results reinforce the importance of including RZV vaccination for immunosuppressed patients. Real-world studies regarding vaccine effectiveness are still needed in order to gain a full understanding of the response to RZV in this group of patients.

Proteomic Serum Profiling of Holstein Friesian Cows with Different Pathological Forms of Bovine Paratuberculosis Reveals Changes in the Acute-Phase Response and Lipid Metabolism.

The lack of sensitive diagnostic methods to detect Mycobacterium avium subsp. paratuberculosis (Map) subclinical infections has hindered the control of paratuberculosis (PTB). The serum proteomic profiles of naturally infected cows presenting focal and diffuse pathological forms of PTB and negative controls (n = 4 per group) were analyzed using TMT-6plex quantitative proteomics. Focal and diffuse are the most frequent pathological forms in subclinical and clinical stages of PTB, respectively. One (focal versus (vs.) control), eight (diffuse vs. control), and four (focal vs. diffuse) differentially abundant (DA) proteins (q-value < 0.05) were identified. Ingenuity pathway analysis of the DA proteins revealed changes in the acute-phase response and lipid metabolism. Six candidate biomarkers were selected for further validation by specific ELISA using serum from animals with focal, multifocal, and diffuse PTB-associated lesions (n = 108) and controls (n = 56). Overall, the trends of the serum expression levels of the selected proteins were consistent with the proteomic results. Alpha-1-acid glycoprotein (ORM1)-based ELISA, insulin-like growth factor-binding protein 2 (IGFBP2)-based ELISA, and the anti-Map ELISA had the best diagnostic performance for detection of animals with focal, multifocal, and diffuse lesions, respectively. Our findings identify potential biomarkers that improve diagnostic sensitivity of PTB and help to elucidate the mechanisms involved in PTB pathogenesis.

Shared decision-making quality and decisional regret in patients with low-risk superficial basal cell carcinoma: A prospective, multicenter cohort study.

Background: Many therapies are available to treat low-risk superficial basal cell carcinoma (lr-sBCC), which may complicate the shared decision-making (SDM) process. Objective: To assess the SDM process of patients and physicians when deciding lr-sBCC therapy as well as the factors that may influence the SDM process. Methods: A prospective, multicenter cohort study was conducted over 18 months, from October 2018 to April 2020, in 3 tertiary university hospitals and 1 private hospital. Results: This study included 107 patients. There was a weak positive correlation between Shared Decision-Making Questionnaire-Patient version (SDM-Q-9) and Shared Decision-Making Questionnaire-Physician version (SDM-Q-Doc) (Spearman's correlation coefficient [rs] [105] = 0.21; P = .03). Most patients (71%) chose a nonsurgical treatment after the SDM process. Patients with higher satisfaction with the SDM had lower decisional conflict and decisional regret (P < .001). Patients aged >80 years had higher rates of significant decisional conflict. When evaluating treatment decisions, the highest median score for decisional conflict (22, IQR [16]; P = .01) was observed among patients who chose a surgical excision. Limitations: Patients may have self-selected to participate. Conclusion: This study suggests that some patients may prefer less invasive therapies for lr-sBCC. The SDM process may reduce decisional conflict and decisional regret.

Summary-data based Mendelian randomization identifies gene expression regulatory polymorphisms associated with bovine paratuberculosis by modulation of the nuclear factor Kappa ß (NF-κß)-mediated inflammatory response.

Genome-wide association studies (GWAS) have identified host genetic variants associated with paratuberculosis (PTB) susceptibility. Most of the GWAS-identified SNPs are in non-coding regions. Connecting these non-coding variants and downstream affected genes is a challenge and, up to date, only a few functional mutations or expression quantitative loci (cis-eQTLs) associated with PTB susceptibility have been identified. In the current study, the associations between imputed whole-genome sequence genotypes and whole RNA-Sequencing data from peripheral blood (PB) and ileocecal valve (ICV) samples of Spanish Holstein cows (N = 16) were analyzed with TensorQTL. This approach allowed the identification of 88 and 37 cis-eQTLs regulating the expression levels of 90 and 37 genes in PB and ICV samples, respectively (False discorey rate, FDR ≤ 0.05). Next, we applied summary-based data Mendelian randomization (SMR) to integrate the cis-eQTL dataset with GWAS data obtained from a cohort of 813 culled cattle that were classified according to the presence or absence of PTB-associated histopathological lesions in gut tissues. After multiple testing corrections (FDR ≤ 0.05), we identified two novel cis-eQTLs affecting the expression of the early growth response factor 4 (EGR4) and the bovine neuroblastoma breakpoint family member 6-like protein isoform 2 (MGC134040) that showed pleiotropic associations with the presence of multifocal and diffuse lesions in gut tissues; P = 0.002 and P = 0.017, respectively. While EGR4 acts as a brake on T-cell proliferation and cytokine production through interaction with the nuclear factor Kappa ß (NF-κß), MGC134040 is a target gene of NF-κß. Our findings provide a better understanding of the genetic factors influencing PTB outcomes, confirm that the multifocal lesions are localized/confined lesions that have different underlying host genetics than the diffuse lesions, and highlight regulatory SNPs and regulated-gene targets to design future functional studies.