Timectomía toracoscópica en pacientes con Miastenia Gravis juvenil

Objetivo: Describir la evolución clínica postquirúrgica de una serie de casos de pacientes con Miastenia Gravis juvenil (MGJ) tratados con timectomía por toraoscópica videoasistida (TVA) derecha. Materiales y Métodos: Estudio retrospectivo que incluyó 13 pacientes pediátricos con diagnóstico de MGJ sometidos a timectomía toracoscópica derecha en la Unidad Médica de Alta Especialidad Hospital de Pediatría, Centro Médico Nacional Siglo XXI de México, entre marzo de 2016 y abril de 2022. Los pacientes fueron caracterizados clínicamente y la enfermedad fue clasificada de acuerdo a los criterios de Osserman. La evolución postquirúrgica se evaluó con la clasificación de DeFilippi para determinar la proporción de pacientes con mejoría y la remisión completa. Resultados: Los pacientes incluidos fueron, en su mayoría, mujeres (84,6%) con edad promedio al diagnóstico fue de 11,1 ± 3,1 años. Las cuatro clasificaciones de MG fueron incluidas, con mayor proporción de MG generalizada leve (38,5%), seguida de ocular (23,1%) y generalizada moderada grave (23,1%). La evaluación de la progresión postquirúrgica demostró que a los tres meses de seguimiento 92,3% presentó mejorías, incluyendo la disminución del uso de medicamentos. La remisión total solo se registró en uno de los pacientes. Los pacientes que tuvieron cirugía antes de los 12 meses de evolución de la MGJ presentaron mejores resultados post timectomía por TVA. Conclusión: Se demostró la utilidad de timectomía por TVA en pacientes pediátricos mexicanos con MGJ. Nuestra experiencia agrega evidencia de que los pacientes pediátricos se benefician de la timectomía, mejorando su estado clínico y disminuyendo el uso de medicamentos y complicaciones e la enfermedad.

Objective: To describe the post-surgical clinical evolution of a case series of patients with juvenile myasthenia gravis (JMG) treated with right video-assisted thoracoscopic (TVA) thymectomy. Materials and Methods: Retrospective study that included 13 pediatric patients with JMG who underwent right TVA thymectomy at the Siglo XXI National Medical Center of Mexico between March 2016 and April 2022. Patients were clinically characterized, and the disease was classified according to Osserman's criteria. Post-surgical evolution was evaluated using the DeFilippi classification to determine the proportion of patients with improvement and complete remission. Results: The included patients were mostly women (84.6%) with a mean age at diagnosis of 11.1 ± 3.1 years. The four MG classifications were included, with the highest proportion of mild generalized MG (38.5%), followed by ocular (23.1%) and moderate-severe generalized (23.1%). The evaluation of post-surgical progression showed that after three months of follow-up, 92.3% presented improvements, including a decrease in the use of medications. Complete remission was only recorded in one of the patients. Patients who underwent surgery before 12 months of evolution of JMG had better results after TVA thymectomy. Conclusion: The usefulness of TVA thymectomy in Mexican pediatric patients with JMG was demonstrated. Our experience adds evidence that pediatric patients benefit from thymectomy by improving their clinical status and decreasing the use of medications and complications of the disease.

The COVID-19 epidemic curve and vaccine acceptance among patients with rheumatic diseases: an ecological study.

The attitudes toward emerging COVID-19 vaccines have been of great interest worldwide, especially among vulnerable populations such as patients with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to analyze the relationship between the nationwide number of COVID-19 cases and deaths, and vaccine acceptance or hesitancy of patients with RMDs from four patient care centers in Mexico. Furthermore, we explored differences in acceptance according to specific diagnoses: rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This ecological study was a secondary analysis of a cross-sectional study using a validated questionnaire to measure vaccine acceptance. We generated a global Likert scale to evaluate overall attitudes toward the COVID-19 vaccine. We analyzed data from 1336 patients from March to September 2021: 85.13% (1169) were women, with a mean age of 47.87 (SD 14.14) years. The most frequent diagnoses were RA (42.85%, 559) and SLE (27.08%, 393). 635(47.52%) patients were unvaccinated, 253(18.93%) had one dose and 478(35.77%) had two doses. Of all participating patients, 94% were accepting toward the COVID-19 vaccine. Vaccine acceptance remained consistently high throughout the study. However, differences in vaccine acceptance are identified when comparing diagnoses. The peak of the national epidemic curve coincided with an increase in hesitancy among patients with RA. Contrastingly, patients with SLE became more accepting as the epidemic curve peaked. Mexican patients show high acceptance of the COVID-19 vaccine, influenced in part by a patient's specific diagnosis. Furthermore, vaccine acceptance increased mirroring the curve of COVID-19 cases and deaths in the country. This should be taken into consideration when updating recommendations for clinical practice.

Transcriptomic alterations in hypertrophy of the ligamentum flavum: interactions of Rho GTPases, RTK, PIK3, and FGF.

PURPOSE: To analyze the differential transcriptome expression in hypertrophic ligaments flavum (HLF) compared to normal ligaments. METHODS: A case-control study was conducted that included 15 patients with hypertrophy of LF and 15 controls. Samples of LF were obtained through a lumbar laminectomy and analyzed by DNA microarrays and histology. The dysregulated biological processes, signaling pathways, and pathological markers in the HLF were identified using bioinformatics tools. RESULTS: The HLF had notable histological alterations, including hyalinosis, leukocyte infiltration, and disarrangement of collagen fibers. Transcriptomic analysis showed that up-regulated genes were associated with the signaling pathways of Rho GTPases, receptor tyrosine kinases (RTK), fibroblast growth factors (FGF), WNT, vascular endothelial growth factor, phosphoinositide 3-kinase (PIK3), mitogen-activated protein kinases, and immune system. The genes PIK3R1, RHOA, RPS27A, CDC42, VAV1, and FGF5, 9, 18, and 19 were highlighted as crucial markers in HLF. The down-expressed genes in the HLF had associations with the metabolism of RNA and proteins. CONCLUSION: Our results suggest that abnormal processes in hypertrophied LF are mediated by the interaction of the Rho GTPase, RTK, and PI3K pathways, which have not been previously described in the HLF, but for which there are currently therapeutic proposals. More studies are required to confirm the therapeutic potential of the pathways and mediators described in our results.

Low-Intensity Physical Exercise Decreases Inflammation and Joint Damage in the Preclinical Phase of a Rheumatoid Arthritis Murine Model.

Lifestyle modifications in preclinical Rheumatoid Arthritis (RA) could delay the ongoing pathogenic immune processes and potentially prevent its onset. Physical exercise (PE) benefits RA patients; however, its impact in reducing the risk of developing RA has scarcely been studied. The objective was to describe the effects of low-intensity PE applied at the disease's preclinical phase on the joints of DBA/1 mice with collagen-induced arthritis (CIA). Twelve mice with CIA were randomly distributed into two groups: the CIA-Ex group, which undertook treadmill PE, and the CIA-NoEx, which was not exercised. The effects of PE were evaluated through clinical, histological, transcriptomics, and immunodetection analyses in the mice's hind paws. The CIA-Ex group showed lower joint inflammation and damage and a decreased expression of RA-related genes (Tnf Il2, Il10, Il12a, IL23a, and Tgfb1) and signaling pathways (Cytokines, Chemokines, JAK-STAT, MAPK, NF-kappa B, TNF, and TGF-beta). TNF-α expression was decreased by PE in the inflamed joints. Low-intensity PE in pre-arthritic CIA reduced the severity through joint down-expression of proinflammatory genes and proteins. Knowledge on the underlying mechanisms of PE in preclinical arthritis and its impact on reducing the risk of developing RA is still needed.

Complete Freund's Adjuvant Induces a Fibroblast-like Synoviocytes (FLS) Metabolic and Migratory Phenotype in Resident Fibroblasts of the Inoculated Footpad at the Earliest Stage of Adjuvant-Induced Arthritis.

The fibroblast-like synoviocytes (FLS) have a crucial role in the pathogenesis of Rheumatoid Arthritis (RA); however, its precise mechanisms remain partially unknown. The involvement of the fibroblast in activating adjuvant-induced arthritis (AA) has not been previously reported. The objective was to describe the participation of footpads' fibroblasts in the critical initial process that drives the AA onset. Wistar rats were injected with Complete Freund's Adjuvant (CFA) or saline solution in the hind paws' footpads and euthanized at 24 or 48 h for genetic and histological analyses. Microarrays revealed the differentially expressed genes between the groups. The CFA dysregulated RA-linked biological processes at both times. Genes of MAPK, Jak-STAT, HIF, PI3K-Akt, TLR, TNF, and NF-κB signaling pathways were altered 24 h before the arrival of immune cells (CD4, CD8, and CD68). Key markers TNF-α, IL-1ß, IL-6, NFκB, MEK-1, JAK3, Enolase, and VEGF were immunodetected in fibroblast in CFA-injected footpads at 24 h but not in the control group. Moreover, fibroblasts in the CFA inoculation site overexpressed cadherin-11, which is linked to the migration and invasion ability of RA-FLS. Our study shows that CFA induced a pathological phenotype in the fibroblast of the inoculation site at very early AA stages from 24 h, suggesting a prominent role in arthritis activation processes.

Prevalence of Polymorphism and Post-Training Expression of ACTN3 (R/X) and ACE (I/D) Genes in CrossFit Athletes.

BACKGROUND: CrossFit is known as a functional fitness training high-intensity exercise to improve physical performance. The most studied polymorphisms are the ACTN3 R577X gene, known for speed, power, and strength, and ACE I/D, related to endurance and strength. The present investigation analyzed the effects of training on ACTN3 and ACE gene expression in CrossFit athletes for 12 weeks. METHODS: the studies included 18 athletes from the Rx category, where ACTN3 (RR, RX, XX) and ACE (II, ID, DD) characterization of genotypes and tests of maximum strength (NSCA), power (T-Force), and aerobic endurance (Course Navette) were performed. The technique used was the reverse transcription-quantitative PCR real-time polymerase chain reaction (RT-qPCR) for the relative expression analysis. RESULTS: the relative quantification (RQ) values for the ACTN3 gene increased their levels 2.3 times (p = 0.035), and for ACE, they increased 3.0 times (p = 0.049). CONCLUSIONS: there is an overexpression of the ACTN3 and ACE genes due to the effect of training for 12 weeks. Additionally, the correlation of the expression of the ACTN3 (p = 0.040) and ACE (p = 0.030) genes with power was verified.

Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process.

To analyze the effect of levofloxacin-induced intestinal microbiota modifications on intestinal, joint, and systemic inflammation in the DBA/1 mice with spontaneous arthritis. The study included two groups of mice, one of which received levofloxacin. The composition and structure of the microbiota were determined in the mice's stool using 16S rRNA sequencing; the differential taxa and metabolic pathway between mice treated with levofloxacin and control mice were also defied. The effect of levofloxacin was evaluated in the intestines, hind paws, and spines of mice through DNA microarray transcriptome and histopathological analyses; systemic inflammation was measured by flow cytometry. Levofloxacin decreased the pro-inflammatory bacteria, including Prevotellaceae, Odoribacter, and Blautia, and increased the anti-inflammatory Muribaculaceae in mice's stool. Histological analysis confirmed the intestinal inflammation in control mice, while in levofloxacin-treated mice, inflammation was reduced; in the hind paws and spines, levofloxacin also decreased the inflammation. Microarray showed the downregulation of genes and signaling pathways relevant in spondyloarthritis, including several cytokines and chemokines. Levofloxacin-treated mice showed differential transcriptomic profiles between peripheral and axial joints and intestines. Levofloxacin decreased the expression of TNF-α, IL-23a, and JAK3 in the three tissues, but IL-17 behaved differently in the intestine and the joints. Serum TNF-α was also reduced in levofloxacin-treated mice. Our results suggest that the microbiota modification aimed at reducing pro-inflammatory and increasing anti-inflammatory bacteria could potentially be a coadjuvant in treating inflammatory arthropathies.

Abortion as an Essential Health Service in Latin America During the COVID-19 Pandemic.

Background: The rapid increase in demand for health services as a result of the COVID-19 outbreak has created significant challenges for health systems. National and international health authorities have declared reproductive health services as essential, particularly those related to prevention, care during pregnancy, delivery and postpartum, as well as abortion services. This research was conducted by a regional team in cooperation with nine local organizations that are members of the Latin American Consortium against Unsafe Abortion (Consorcio Latinoamericano Contra el Aborto Inseguro, CLACAI). Objectives: Our research aimed to examine the provision of reproductive healthcare services, with a focus on abortion, in nine countries during the first few months of the pandemic (March to September 2020). Methods: Our research design developed a set of quantitative and qualitative indicators to monitor the availability and accessibility of abortion services during the COVID-19 pandemic. Researchers collected the quantitative data by reviewing regulations and other documents, government and civil society reports, and official statistics; the qualitative data was acquired through interviews with key actors, and non-representative surveys completed by healthcare professional and end users of reproductive services. Results: Although six of the nine countries we researched deemed reproductive health services essential, only two of these six countries considered abortion services to be essential, and all nine countries reported difficulties in accessing abortion services. Restrictive abortion laws remained in place in the majority of countries (seven), and as a result access to abortion services became even more limited than it had been before the pandemic. At the same time, good practices to facilitate access to abortion services in healthcare facilities, updated regulatory frameworks, and collaboration between civil society and government agencies were identified and should continue to be promoted even after the pandemic crisis has subsided. Conclusions: The pandemic catalyzed what was already happening in each country, and as such abortion services have become more accessible in countries like Argentina, where the so-called green wave has been generating social, legal and policy changes, whereas in countries such as Ecuador, where abortion is legally restricted and opposed to by the government, access to safe abortion became even more difficult than it was before the pandemic. However, the general trend has been a lack of adequate adaptation in order to guarantee quality in abortion care. That said, there have also been some interesting and positive service provision initiatives, such as telemedicine, implemented in at least two countries, which, if maintained long-term, could improve access to safe abortion.

Treatment with silica-gold nanostructures decreases inflammation-related gene expression in collagen-induced arthritis.

Gold salts have been used to treat rheumatoid arthritis (RA) since the 1940s, and, with advances in nanotechnology, the use of nanogold provides multiple options for anti-inflammatory therapies. This paper presents the synthesis and characterization of silica-gold nanostructures (SGNs) and their therapeutic effect in collagen-induced arthritis (CIA) in DBA/1 mice. At the end of the treatment, the synovial membranes, kidneys, livers, and spleens were dissected and analyzed by inductively coupled plasma mass spectroscopy (ICP) showing less than 0.0001 and 0.1% of the administered doses of Au and Si, respectively. Remains of the SGNs were visually identified in the synovial membrane by scanning electron microscopy (SEM), and the bone density of the hind paws was observed by computerized tomography (CT) indicating a reduction of porosity in the CIA-experimental group. The DNA microarray analysis carried out with RNA obtained from the hind paws showed 2628 differentially expressed genes (DEGs) by SGNs. The bioinformatic analysis showed that DEGs were significantly associated with several inflammatory signalling pathways including chemokines, cytokine-cytokine receptor interaction, PI3K-Akt, TNF, IL-17, NFκß, MAPK, and RA. SGNs downregulated relevant inflammatory genes in the arthritic joints, including Tnf, Ifng, Il6, and Cxcl5; immunohistochemistry (IHC) confirmed the reduction of TNFα, IL-6, NFκß, and VEGF in the joints due to the effect of SGNs. TNFα and IL-6 were also reduced in the serum of DBA/1 mice treated with SGNs.

Dynamics of DNA damage response markers, RAD51 and XRCC1, throughout the menstrual cycle and pregnancy in healthy women. Increment during pregnancy and relation to a low titer of antinuclear antibodies.

PROBLEM: Antinuclear antibodies (ANA) potentially play a role in the pathogenesis of connective tissue diseases (CTDs); however, they are also detected in healthy individuals. Our understanding of the physiological and pathological origin of ANA is incomplete. Both; female reproductive processes and deficiencies in DNA damage response (DDR) have been independently associated with ANA production. However, the link between these two factors and the presence of ANA is unclear METHOD OF STUDY: A cohort study was conducted on 87 non-pregnant and 51 healthy pregnant women. ANA and the DDR markers X-ray repair cross-complementing 1 (XRCC1) and recombinase (RAD51) were quantified in sera by enzyme-linked immunosorbent assay. Additionally, ANA was detected by indirect immunofluorescence in HEp-2 cells in 1:40 diluted sera during the three phases of the menstrual cycle in non-pregnant women and every trimester in pregnant women RESULTS: The prevalence of ANA+ in healthy women was 26.1%, with no significant differences between pregnant and non-pregnant women. ANA and DDR marker levels did not vary among the three phases of the menstrual cycle or the three trimesters of pregnancy. However, DDR marker levels were higher in pregnant women than in non-pregnant women (p < .001) and were found to be higher in ANA+ women (XRCC1, p = .025; RAD51, p = .006) CONCLUSIONS: The menstrual cycle and pregnancy did not influence the levels of DDR markers or ANA in healthy women; however, the DDR was higher in pregnancy and ANA+ women. The results suggest a potential role of DDR in the pathophysiology of ANA.

Domestic Dogs as Sentinels for West Nile Virus but not Aedes-borne Flaviviruses, Mexico.

We tested 294 domestic pet dogs in Mexico for neutralizing antibodies for mosquito-borne flaviviruses. We found high (42.6%) exposure to West Nile virus in Reynosa (northern Mexico) and low (1.2%) exposure in Tuxtla Gutierrez (southern Mexico) but very limited exposure to Aedes-borne flaviviruses. Domestic dogs may be useful sentinels for West Nile virus.

Factors associated to COVID-19 vaccine acceptance in Mexican patients with rheumatic diseases: A cross-sectional and multicenter study.

COVID-19 vaccination is recommended in patients with rheumatic diseases (RDs) to prevent hospitalized COVID-19 and worse outcomes. However, patients' willingness to receive a SARS-CoV-2 vaccine and the associated factors vary across populations, vaccines, and time. The objective was to identify factors associated with COVID-19 vaccine acceptance (VA) in Mexican outpatients with RDs. This multicenter study was performed between March 1 and September 30, 2021, and four national centers contributed with patients. Participants filled out a questionnaire, which included 32 items related to patients' perception of the patient-doctor relationship, the COVID-19 vaccine component, the pandemic severity, the RD-related disability, comorbid conditions control, immunosuppressive treatment impact on the immune system, and moral/civil position of COVID-19 vaccine. Sociodemographic, disease-related, and treatment-related variables and previous influenza record vaccination were also obtained. Multiple logistic regression analyses identified factors associated with VA, which was defined based on a questionnaire validated in our population. There were 1439 patients whose data were analyzed, and the most frequent diagnoses were Rheumatoid Arthritis in 577 patients (40.1%) and Systemic Lupus Erythematosus in 427 (29.7%). Patients were primarily middle-aged women (1235 [85.8%]), with (mean±SD) 12.1 (±4.4) years of formal education. Years of education, corticosteroid use, patient perceptions about the vaccine and the pandemic severity, patient civil/moral position regarding COVID-19 vaccine, and previous influenza vaccination were associated with VA. In Mexican patients with RDs, COVID-19 VA is associated with individual social-demographic and disease-related factors, patient´s perceptions, and previous record vaccination. This information is crucial for tailoring effective vaccine messaging in Mexican patients with RDs.

Exercise-driven exacerbation of inflammation: contribution of animal models of rheumatoid arthritis and spondyloarthritis.

PURPOSE: To describe the observations of studies that have explored the effects of exercise on inflammation and tissue remodeling in animal models of inflammatory arthropathies including Rheumatoid Arthritis and Spondyloarthritis. METHODS: A search was performed at Pubmed, Scopus and Web of Science databases from 2010 to 2021. The selected articles were classified into those who reported positive and negative effects of exercise, and the characteristics of their experimental designs, including the animal model, the study groups, the exercise intervention and the evaluation techniques, were detailed. RESULTS: Thirteen original articles that met the selection criteria were included. The effects of exercise on the joint biology of mice with inflammatory arthritis were controversial. Although exercise benefits have been observed in some experimental designs, the majority of them have shown that exercise leads to exacerbation of inflammation, tissue remodeling, and processes associated with arthritis such as oxidative stress and hypoxia. CONCLUSION: Further research is necessary as the existing guidelines do not consider the negative effects of the exercise evidenced in animal models. The potential risks of exercise for patients should be considered.

Prevalence of complementary and alternative medicine despite limited perceived efficacy in patients with rheumatic diseases in Mexico: Cross-sectional study.

INTRODUCTION: Complementary and alternative medicine (CAM) is frequently used by patients with rheumatic diseases (RD) to improve their symptoms; however, its diversity and availability have increased notably while scientific support for its effectiveness and adverse effects is still scarce. OBJECTIVE: To describe the prevalence and diversity of CAM in patients with RD in Chihuahua, Mexico. METHODS: A cross-sectional study was conducted in 500 patients with RD who were interviewed about the use of CAM to treat their disease. The interview included sociodemographic aspects, characteristics of the disease, as well as a description of CAM use, including type, frequency of use, perception of the benefit, communication with the rheumatologist, among others. RESULTS: The prevalence of CAM use was reported by 59.2% of patients, which informed a total of 155 different therapies. The herbal CAM group was the most used (31.4%) and included more than 50 different therapies. The use of menthol-based and arnica ointments was highly prevalent (35%). Most patients (62.3%) reported very little or no improvement in their symptoms. Only a fourth of the patients informed the rheumatologist of the use of CAM. The use of CAM was influenced by female sex, university degree, diagnosis delay, lack adherence to the rheumatologist's treatment, family history of RD, and orthopedic devices. CONCLUSION: The use of CAM in our population is highly prevalent and similar to reports in different populations suggesting a widespread use in many different societies. We found high use of herbal remedies; however, there were many different types suggesting a lack of significant effect. Patients continue using CAM despite a perception of no-effectiveness. Recurrent use of CAM is explained by factors other than its efficacy.

Cu2+-dependent stereoselective hydrolysis of a chiral organophosphonothioate insecticide for domestic mammals' sera and its albumins.

Acute toxicity of organophosphate (OPs) pesticides is a public health problem. The adverse effects are associated with the inhibition and aging of nervous system B-esterases such as acetyl cholinesterase (AChE) and neuropathic target esterase (NTE). Treatment based on A-esterases such as mammal serum paraoxonase-1 has been suggested. This ex vivo study shows the Cu2+-dependent hydrolysis of trichloronate (TCN), a racemic organophosphonothioate insecticide, in human and domestic mammal serum (dog, goat, pig, sheep and cow). Ca2+-dependent (2.5 mM) or EDTA-resistant (5 mM) activity (1-6%) was not significant (p>0.05) in all samples, except goat serum and its albumin, which showed higher levels of TCN hydrolysis (38-58%) than other mammals with 100 and 300 µM copper sulfate at physiological conditions for 60 min. Goat serum albumin (GSA) showed significant (p˂0.05) stereoselective hydrolysis (+)-TCN ˃ (-)-TCN (45% versus 33%). This suggests that GSA is the protein responsible for Cu2+-dependent TCNase activity in goat serum. This is the first report on Cu2+-dependent A-esterase activity in mammalian tissues. This goat serum cuproprotein could be considered as an alternative in future biotechnological applications including enantiomeric synthesis, bioremediation and antidotal treatment of organophosphonothioate pesticide poisoning.

Stability of housekeeping genes in inflamed joints of spontaneous and collagen-induced arthritis in DBA/1 mice.

BACKGROUND: DBA/1 mice arthritis models have contributed to our understanding of human rheumatoid arthritis (RA) and spondyloarthritis (SpA) pathogenesis, as well as the exploration of therapeutic targets for treatment. Quantitative polymerase chain reaction (qPCR) is an indispensable tool in molecular research, which requires reference gene validation to obtain consistent and reliable results. OBJECTIVE: To determine the stability of candidate reference genes for qPCR in the joint of collagen-induced arthritis (CIA) and spontaneous arthritis (SpAD) DBA/1 mice. METHODS: The expression of eleven commonly used reference genes (ACTB, B2M, EF1a, GAPDH, HMBS, HPRT, PPIB, RPL13A, SDHA, TBP, and YWHAZ) was assessed by qPCR and the data were compared using delta-Ct methods and the geNorm, NormFinder, and RefFinder software packages. Genes identified as stable in each model were used for the quantification of inflammatory cytokines RESULTS: The gene stabilities differed between the two arthritis models in the DBA/1 mice. EF1a and RPL13A were the best reference genes for SpAD, while RPL13A and TBP were the best for the CIA. These genes allowed the data normalization for the quantification of the inflammatory cytokines in both models; these results showed an increase in the expression of IL-1B, IL-12B, IL-17A, and IL-6 in the inflamed joints. The use of different primer sequences for the same reference gene resulted in different relative quantification values. CONCLUSION: This study demonstrates that commonly used reference genes may not be suitable for arthritic tissues from DBA/1 mice, and strengthening the principle that meticulous validation of reference genes is essential before each experiment to obtain valid and reproducible qPCR data for analysis or interpretation.

Alteraciones temporomandibulares y odontológicas en pacientes con artritis reumatoide / Temporomandibular and odontological abnormalities in patients with rheumatoid arthritis

OBJETIVO: Caracterizar las afecciones orofaciales en pacientes con artritis reumatoide (AR) y compararlas con las presentes en pacientes sin la enfermedad de la ciudad de Chihuahua, Chihuahua, México. MÉTODOS: El estudio incluyó a 30 pacientes con diagnóstico de AR y 30 pacientes consecutivos en una consulta de odontología. A través de una revisión clínica odontológica, se compararon entre los grupos variables relacionadas con: 1) trastornos clínicos y radiográficos de la articulación temporomandibular, 2) análisis biomecánico craneocervical, 3) estado de la dentición y necesidades de tratamiento, 4) estado periodontal, 5) estado de higiene oral y 6) dolor facial. Además se determinó la asociación entre las variables estudiadas a través de pruebas de correlación. RESULTADOS: Los pacientes con AR tuvieron una mayor prevalencia de alteraciones en la articulación temporomandibular, tanto clínicas (100 vs. 60%; p < 0,001) como radiográficas incluyendo erosiones (50 vs. 16; p = 0,010), en comparación con la población de referencia. Además los pacientes con AR tuvieron mayor cantidad de pérdidas dentales (6,9±5,7 vs. 3±2; p = 0,001), caries (13,4±5,4 vs. 4,9±6,5; p = 0,001), periodontitis (1,3±0,9 vs. 0,8±0,8; p = 0,015), higiene oral deficiente (43,3 vs. 13,3%; p = 0,005) y más dolor facial (66,7 vs. 20%; p < 0,001). El análisis de cefalometría de Rocabado mostró diferencias en el ángulo craneocervical y triángulo hioideo entre AR y controles. Se obtuvieron correlaciones significativas entre las alteraciones orales y las temporomandibulares. CONCLUSIONES: Los pacientes con AR mostraron un mayor deterioro orofacial, lo que refleja la importancia de atención multidisciplinaria incluyendo la evaluación odontológica periódica

OBJECTIVE: To characterize the orofacial abnormalities in patients with rheumatoid arthritis (RA) and compare them with those in a reference population. METHODS: The study included 30 RA patients and 30 consecutive patients in an odontology clinic in whom RA was ruled out. Patients underwent a clinical dental examination which included: 1) clinical and radiographic abnormalities of the temporomandibular joint; 2) biomechanical craniocervical analysis; 3) state of dentition and treatment needs; 4) periodontal status; 5) oral hygiene status; and 6) facial pain, which was compared among study groups. In addition, the association between the variables studied was determined through correlation tests. RESULTS: Patients with RA showed a higher prevalence of temporomandibular abnormalities, both clinical (100.0% vs. 60.0%, P<.001) and radiographic, including erosions (50.0% vs. 16.0%, P=.010), compared with individuals in the control group. Likewise, patients with RA had a greater number of missing teeth (6.9±5.7 vs. 3.0±2.0, P=.001), more caries (13.4±5.4 vs. 4.9±6.5, P=.001), periodontitis (1.3±0.9 vs. 0.8±0.8, P=.015), poorer oral hygiene (43.3% vs. 13.3%, P=.005) and greater facial pain (66.7% vs. 20.0%, P <.001). The cephalometric analysis of Rocabado showed differences in the craniocervical angle and hyoid triangle between RA and controls. Significant correlations were obtained between oral and temporomandibular abnormalities. CONCLUSIONS: Patients with RA showed a greater orofacial deterioration, which reflects the importance of multidisciplinary care, including periodic dental examination

Positive transcriptional response on inflammation and joint remodelling influenced by physical exercise in proteoglycan-induced arthritis: An animal study.

AIMS: To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice. METHODS: Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways. RESULTS: Arthritic mice improved their physical fitness by 42.5% after PE intervention; it induced the differential expression of 2,554 genes. The bioinformatic analysis showed that the downregulated genes (n = 1,371) were significantly associated with cellular processes that mediate the inflammation, including Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT), Notch, and cytokine receptor interaction signalling pathways. Moreover, the protein interaction network showed that the downregulated inflammatory mediators interleukin (IL) 4, IL5, IL2 receptor alpha (IL2rα), IL2 receptor beta (IL2rß), chemokine ligand (CXCL) 9, and CXCL12 were interacting in several pathways associated with the pathogenesis of arthritis. The upregulated genes (n = 1,183) were associated with processes involved in the remodelling of the extracellular matrix and bone mineralization, as well as with the processes of aerobic metabolism. At the histological level, PE attenuated joint inflammatory infiltrate and cartilage erosion. CONCLUSION: Physical exercise influences parameters intimately linked to inflammatory arthropathies. Research on the effect of PE on the pathogenesis process of arthritis is still necessary for animal and human models.Cite this article: Bone Joint Res. 2020;9(1):36-48.

Syndemic and syndemogenesis of low back pain in Latin-American population: a network and cluster analysis.

INTRODUCTION: Although low back pain (LBP) is a high-impact health condition, its burden has not been examined from the syndemic perspective. OBJECTIVE: To compare and assess clinical, socioeconomic, and geographic factors associated with LBP prevalence in low-income and upper-middle-income countries using syndemic and syndemogenesis frameworks based on network and cluster analyses. METHODS: Analyses were performed by adopting network and cluster design, whereby interrelations among the individual and social variables and their combinations were established. The required data was sourced from the databases pertaining to the six Latin-American countries. RESULTS: Database searches yielded a sample of 55,724 individuals (mean age 43.38 years, SD = 17.93), 24.12% of whom were indigenous, and 60.61% were women. The diagnosed with LBP comprised 6.59% of the total population. Network analysis showed higher relationship individuals' variables such as comorbidities, unhealthy habits, low educational level, living in rural areas, and indigenous status were found to be significantly associated with LBP. Cluster analysis showed significant association between LBP prevalence and social variables (e.g. Gender inequality Index, Human Development Index, Income Inequality). CONCLUSIONS: LBP is a highly prevalent condition in Latin-American populations with a high impact on the quality of life of young adults. It is particularly debilitating for women, indigenous individuals, and those with low educational level, and is further exacerbated by the presence of comorbidities, especially those in the mental health domain. Thus, the study findings demonstrate that syndemic and syndemogenesis have the potential to widen the health inequities stemming from LBP in vulnerable populations. Key points • Syndemic and syndemogenesis evidence health disparities in Latin-American populations, documenting the complexity of suffering from a disease such as low back pain that is associated with comorbidities, unhealthy habits, and the social and regional context where they live. • The use of network and cluster analyses are useful tools for documenting the complexity and the multifaceted impact in health in large populations as well as the differences between countries. • The variability and impact of socioeconomic indicators (e.g., Gini index) related to low back pain and comorbidities could be felt through the use of cluster analysis, which generates evidence of regional inequality in Latin America. • Populations can be studied from different models (network and cluster analysis) and grouping, presenting new interpretations beyond geographical groupings, such as syndemic and inequity in health.

Ashwin Gene Expression Profiles in Oocytes, Preimplantation Embryos, and Fetal and Adult Bovine Tissues.

The ashwin gene, originally identified in Xenopus laevis, was found to be expressed first in the neural plate and later in the embryonic brain, eyes, and spinal cord. Functional studies of ashwin suggest that it participates in cell survival and anteroposterior patterning. Furthermore, ashwin is expressed zygotically in this species, which suggests that it participates in embryonic development. Nevertheless, the expression of this gene has not been studied in mammals. Thus, the aim of this study was to analyze the ashwin expression pattern in bovine fetal and adult tissues, as well as in three independent samples of immature and mature oocytes, and in two- to four-, and eight-cell embryos, morula, and blastocysts. Spatiotemporal expression was analyzed using real-time polymerase chain reaction (PCR); ashwin mRNA was detected in all tissues analyzed, immature and mature oocytes, and two- to eight-cell embryos. It was down-regulated in morula and blastocysts, suggesting that this expression profile is similar to that of maternal genes. Immunohistochemical localization of the ashwin protein in fetal and adult ovaries and testes reveals that this protein is consistently present during all stages of follicular development and during bovine spermatogenesis. These observations lead us to propose ashwin as an important gene involved in mammalian reproduction.