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CPPD disease can affect patients' quality of life through its various clinical presentations. This mini-review discusses the evolution of CPPD from its discovery to current knowledge of its pathogenesis, genetic associations, diagnostics, and treatment options. Despite extensive research, the exact mechanisms of CPPD are not well understood, and there is a notable lack of knowledge about psychosocial impacts and patient experiences. This study aims to present a CPPD Disease Timeline identifying gaps in current knowledge and potential directions for future research. These findings contribute to a broader understanding of CPPD disease and emphasize the importance of continued research and innovation in this field.

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Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

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Pauli channels are fundamental in the context of quantum computing as they model the simplest kind of noise in quantum devices. We propose a quantum algorithm for simulating Pauli channels and extend it to encompass Pauli dynamical maps (parametrized Pauli channels). A parametrized quantum circuit is employed to accommodate for dynamical maps. We also establish the mathematical conditions for an N-qubit transformation to be achievable using a parametrized circuit where only one single-qubit operation depends on the parameter. The implementation of the proposed circuit is demonstrated using IBM's quantum computers for the case of one qubit, and the fidelity of this implementation is reported.

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Transforming the orthopedic landscape, hip arthroscopy pioneers a minimally invasive surgical approach for diagnosing and addressing hip pathologies. With its origins dating back to Burman's 1931 cadaveric study, this groundbreaking technique gained clinical relevance in 1939 through Takagi's report. However, the 1980s marked the actual emergence of hip arthroscopy for treating a wide range of hip disorders. Now, a staple in modern orthopedics, hip arthroscopy empowers patients with previously undiagnosed and untreated hip conditions, enabling them to obtain relief and reclaim their lives. By employing a compact camera and specialized tools, surgeons expertly navigate the hip joint, performing procedures from excising loose bodies and mending labral tears to addressing femoroacetabular impingement and tackling other intricate issues. This innovative approach has dramatically elevated patients' quality of life, allowing them to embrace targeted treatments and resume daily activities without resorting to lifestyle alterations.

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Takayasu arteritis (TAK) is a rare systemic vasculitis primarily affecting the aorta and its major branches. Early diagnosis is critical to prevent severe vascular complications, yet current biomarkers are insufficient. This proof-of-concept study explores the potential of long non-coding RNAs (lncRNAs) in TAK, an area largely unexplored. In this cross-sectional study, 53 TAK patients, 53 healthy controls, and 10 rheumatoid arthritis (RA) patients were enrolled. Clinical evaluations, disease activity assessments, and lncRNA expression levels were analyzed. TAK patients exhibited significant dysregulation in several lncRNAs, including THRIL (19.4, 11.1-48.8 vs. 62.5, 48.6-91.4 arbitrary units [a.u.]; p < 0.0001), HIF1A-AS1 (4.5, 1.8-16.6 vs. 26.5, 19.8-33.7 a.u.; p < 0.0001), MALAT-1 (26.9, 13.8-52.5 vs. 92.1, 58.5-92.1 a.u.; p < 0.0001), and HOTAIR (8.0, 2.5-24.5 vs. 36.0, 30.0-43.8 a.u.; p < 0.0001), compared to healthy controls. Notably, HOTAIR (area under the ROC curve [AUC] = 0.825), HIF1A-AS1 (AUC = 0.820), and THRIL (AUC = 0.781) demonstrated high diagnostic potential with superior specificity (approximately 95%). While lncRNAs showed diagnostic promise, no significant correlations with TAK activity were observed. Comparative analysis with RA patients revealed distinct lncRNA expression patterns. This study unveils significant dysregulation of lncRNAs THRIL, HIF1A-AS1, and HOTAIR in TAK patients, underscoring their potential as biomarkers and opening avenues for further research into the mechanistic roles of these lncRNAs in TAK pathogenesis.

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Anti-carbamylated protein (anti-CarP) antibodies are promising biomarkers in rheumatoid arthritis (RA), although their significance in seronegative disease (SNRA) remains uncertain. To assess the influence of anti-CarP antibodies on disease activity and erosive joint damage in SNRA patients. In RA patients, rheumatoid factor (RF), anti-citrullinated protein antibodies, and anti-CarP antibodies were measured. Disease activity was assessed using DAS28-CRP and SDAI indices, while musculoskeletal ultrasound identified bone erosions. A total of 77 patients were enrolled, comprising 49 with seropositive RA (SPRA) and 28 with SNRA. Notably, 28% of SPRA and 10% of SNRA patients were positive to anti-CarP antibodies. Anti-CarP-positive patients exhibited elevated C-reactive protein (median 10.6, interquartile range 4.6-20.0 vs. 3.4, 1.7-9.9 mg/L; p = 0.005), erythrocyte sedimentation rate (34, 19-46 vs. 16, 7-25 mm/h; p = 0.002), DAS28-CRP (3.2, 2.6-4.2 vs. 2.6, 1.9-3.5; p = 0.048), and SDAI (19.9, 6.3-32.1 vs. 10.9, 5.5-18.1; p = 0.034) indices. Multivariate analysis revealed RF positivity as the sole predictor for anti-CarP antibodies (odds ratio [OR] = 5.9). Musculoskeletal ultrasound revealed bone erosions in 36% of RA patients; 35% among anti-CarP-negative patients and 40% among anti-CarP-positive patients. Notably, RF presence (OR = 44.3) and DAS28-CRP index (OR = 2.4) emerged as predictors of musculoskeletal ultrasound-confirmed erosive joint disease. Anti-CarP antibodies are detected at similar frequencies among both SPRA and SNRA patients. While associated with increased disease activity, these antibodies did not correlate with increased erosive joint damage.

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Robotic-assisted orthopedic surgery (RAOS) is revolutionizing the field, offering the potential for increased accuracy and precision and improved patient outcomes. This comprehensive review explores the historical perspective, current robotic systems, advantages and limitations, clinical outcomes, patient satisfaction, future developments, and innovation in RAOS. Based on systematic reviews, meta-analyses, and recent studies, this article highlights the most significant findings and compares RAOS to conventional techniques. As robotic-assisted surgery continues to evolve, clinicians and researchers must stay informed and adapt their practices to provide optimal patient care. Evidence from published studies corroborates these claims, highlighting superior component positioning, decreased incidence of complications, and heightened patient satisfaction. However, challenges such as costs, learning curves, and technical issues must be resolved to fully capitalize on these advantages.

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Monoclonal antibodies are among the most effective tools for detecting tumor-associated antigens. The U.S. Food and Drug Administration (FDA) has approved more than 36 therapeutic antibodies for developing novel alternative therapies that have significant success rates in fighting cancer. However, some functional limitations have been described, such as their access to solid tumors and low interaction with the immune system. Single-chain variable fragments (scFv) are versatile and easy to produce, and being an attractive tool for use in immunotherapy models. The small size of scFv can be advantageous for treatment due to its short half-life and other characteristics related to the structural and functional aspects of the antibodies. Therefore, the main objective of this review was to describe the current situation regarding the mechanisms of action, applications, and limitations of monoclonal antibodies and scFv in the treatment of cancer.

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Syntenin-1 is a 298 amino acid protein codified by the melanoma differentiation-associated gene-9 (MDA-9). Structurally, it is composed of four domains: N-terminal, PDZ1, PDZ2, and C-terminal. The PDZ domains of syntenin-1 are involved in the stability and interaction with other molecules such as proteins, glycoproteins, and lipids. Domains are also associated with several biological functions such as the activation of signaling pathways related to cell-to-cell adhesion, signaling translation, and the traffic of intracellular lipids, among others. The overexpression of syntenin-1 has been reported in glioblastoma, colorectal, melanoma, lung, prostate, and breast cancer, which promotes tumorigenesis by regulating cell migration, invasion, proliferation, angiogenesis, apoptosis, and immune response evasion, and metastasis. The overexpression of syntenin-1 in samples has been associated with worst prognostic and recurrence, whereas the use of inhibitors such as shRNA, siRNA, and PDZli showed a diminution of the tumor size and reduction in metastasis and invasion. Syntenin-1 has been suggested as a potential biomarker and therapeutic target in cancer for developing more effective diagnostic/prognostic tests or passive/active immunotherapies.

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To characterize CD4+CD28null cells in chronic hyperuricemia and investigate whether allopurinol could restore CD28 expression and the balance of T helper phenotypes. Asymptomatic individuals with chronic hyperuricemia and ultrasonographic findings evocative of urate deposition in the joints. Age- and gender-matched normouricemic individuals were also studied. Oral allopurinol at 150 mg/day for 4 weeks, followed by 300 mg/day through week 12. Color-flow cytometry on peripheral blood mononuclear cells (PBMC) with antibodies against CD4, CD28, T-bet (Th1), GATA-3 (Th2), and RORγt (Th17). Six patients (five men, median age of 53 years) and seven controls were studied. At baseline, hyperuricemic patients had more CD4+CD28null/CD4+ cells than normouricemic subjects (36.8% vs. 6.1%; p = 0.001), with a predominance of T-bet+ cells (98.5% vs. 6.6%; p = 0.001) and few RORγt+ cells (0.7% vs. 89.4%; p = 0.014). In hyperuricemic patients, the number of CD4+ cells/10,000 PBMC was similar before and after allopurinol (3378 vs. 3954; p = 0.843). Conversely, CD4+CD28null cells decreased from 36.8% (23.0-43.7) to 15.8% (4.7-28.1; p = 0.031). CD4+CD28nullT-bet+ cells decreased from 98.5% (95.0-99.4) to 88.3% (75.2-98.9; p = 0.062), CD4+CD28nullGATA-3+ cells increased from 0% (0-4.0) to 2.8% (0.1-15.6; p = 0.156), and CD4+CD28nullRORγt+ cells increased from 0.7% (0.4-7.0) to 4.5% (1.3-28.1; p = 0.031). The CD4+CD28null cell subset is abnormally expanded in chronic hyperuricemia, despite the absence of overt urate-related disease. Allopurinol may partially restore CD28 expression on CD4+ cells while enhancing the homeostatic balance of T helper phenotypes. ClinicalTrials.gov, number NCT04012294.

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Background and Objectives: REST (RE1-silencing transcription factor) diminution is associated with transcriptional relaxation, neuropeptide overexpression, and phenotype redefinition in neuroendocrine cancers, but this effect has barely been studied in cervical cancer (CC). We previously reported reduced expressions of REST in samples with premalignant lesions and CC; however, the transcriptional consequences for neural genes associated with reduced REST expression in CC are unknown. Therefore, the objective of this work was to evaluate the expression of neuronal genes in cancerous cells with reduced expression levels of REST. Materials and Methods: Here, we monitored levels of REST by immunostaining along the premalignant lesions and in invasive cervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma (ADC) in tissue samples from female patients from southern Mexico and the derivative cell lines SiHa and HeLa, respectively. Next, we selected REST target genes in silico and explored the effect of REST silencing by RT-PCR in siRNA-treated HeLa cells. Results: The results show a REST diminution in premalignant lesions, SCC, ADC, and cancerous cell lines. Further REST silencing in HeLa cells altered the expression of genes containing the RE1 (Restrictive Element 1) sequence, including CgA (chromogranin A), CHRNß2 (cholinergic receptor nicotinic ß 2 subunit), BDNF (brain-derived neurotrophic factor), CRF (corticotropin-releasing factor), and RASSF1A (Ras association domain family 1). Conclusions: This work provides preliminary evidence of the role of REST loss in the transcriptional regulation of its target genes in HeLa cells, which could have positive implications for the search for new biomarkers of cervical cancer.

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ZO-1α+ and ZO-1α- proteins are expressed in hermetic and leaky tight junctions, respectively. Two cis-acting distant exonic elements partly activate the 240 nucleotide-long α exon producing the ZO-1α+ isoform. However, the elements within and around the α exon and their respective factors involved in its splicing are unknown. To study the dynamic interaction between SRSF3 and its bioinformatically predicted target sites around the 3'ss upstream of the α exon during its activation, we performed EMSA, crosslinking, and in vivo splicing assays by ZO-1 minigene expression and siRNA-mediated silencing in transfected cells. Using V1 RNase, we probed the possible formation of a hairpin RNA structure between the intronic and proximal exonic SRSF3 binding sites. The hairpin sufficed for complex formations in the EMSA. The interaction of SRSF3 with the intronic site promoted the cooperative binding of SRSF3 to the exonic site. Finally, SRSF3 restored α exon activation in SRSF3 knockdown transfectants. Altogether, our results show that SRSF3-hairpin RNA interaction is crucial in the early recognition of 3'ss for α exon activation. It remains to be explored whether SRSF3 recruits or stabilizes the binding of other factors or brings separate splice sites into proximity.

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Fibromyalgia is characterised by widespread musculoskeletal pain, which may present with fatigue, depression, anxiety, sleep and cognitive disturbances. It is the second most prevalent rheumatic disease. An accurate diagnosis is challenging, since its symptoms may resemble diverse conditions such as carpal tunnel syndrome, Raynaud syndrome, Sjögren syndrome, amongst others. Neuropathic pain and autonomic dysfunction in fibromyalgia suggest the involvement of the nervous system. Ion channels, neurotransmitters and neuromodulators may play a role. Small fibre neuropathy (SFN) may also cause chronic widespread pain. SFN may occur in 50% of fibromyalgia patients, but its role in the disease is unknown. Despite several efforts to synthesise the evidence on the mechanisms for pain in fibromyalgia, there are few studies applying an integrative perspective of neurochemical, immunological, and neuroanatomical characteristics, and their relevance to the disease. This protocol aims to clarify the mechanisms of the central and peripheral nervous system associated with pain in fibromyalgia. We will retrieve published studies from Web of Science, MEDLINE, Scopus, EBSCOhost, Ovid and Google Scholar. All clinical studies or experimental models of fibromyalgia reporting imaging, neurophysiological, anatomical, structural, neurochemical, or immunological characteristics of the central or peripheral nervous systems associated with pain will be included. Exclusion criteria will eliminate studies evaluating pain without a standardised measure, studies written in languages different from Spanish or English that could not be appropriately translated, and studies whose full-text files could not be retrieved after all efforts made. A narrative synthesis will be performed.

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Abstract The erector spinae plane (ESP) block is an interfascial block described in 2016 by Forero and collaborators, with wide clinical uses and benefits when it comes to analgesic control in different surgeries. This block consists of the application of local anesthetic (LA) in a deep plane over the transverse process, anterior to the erector spinae muscle in the anatomical site where dorsal and ventral branches of the spinal nerve roots are located. This review will cover its clinical uses according to different surgical models, the existing evidence and complications described to date.

Resumen El bloqueo del plano del músculo erector de la espina (ESP, por sus siglas en inglés) es un bloqueo interfascial descrito en 2016 por Forero y colaboradores, con amplios usos clínicos y beneficios en relación con el control analgésico de diferentes modelos quirúrgicos. Este consiste en la aplicación de anestésico local (AL) en un plano profundo sobre apófisis transversa anterior al músculo erector de la espina, sitio anatómico donde se encuentra la bifurcación de los ramos dorsal y ventral de las raíces nerviosas espinales. En esta revisión, se expondrán los usos clínicos según diferentes modelos quirúrgicos, la evidencia que existe de ellos y las complicaciones descritas hasta la actualidad.

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Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

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Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype due to its greater invasive capacity and non-response to hormone therapy. Several species of the Ficus genus have been used as an alternative to traditional medicine against malignant diseases. Previously, leaf extracts from Ficus crocata (Miq.) Mart. ex Miq. (F. crocata) showed antiproliferative activity in vitro against breast and cervical tumor cells without having a cytotoxic effect on non-tumor cell lines. The purpose of the study was to evaluate the effect of hexane (Hex-EFc), dichloromethane (Dic-EFc), and acetone (Ace-EFc) extracts from F. crocata on the proliferative and invasive capacity of breast cancer cells MCF-7 and MDA-MB-231. Materials and methods: The phytochemical profile was carried out by gas chromatography-mass spectrometry (GC-MS). Cell proliferation, migration, and invasion were determined by MTT, wound closure, and transwell assays, respectively. MMPs activity was analyzed using gelatin zymography, and fluorescence microscopy was used to visualize F-actin distribution. Results: Hex-EFc, Dic-EFc, and Ace-EFc showed cytotoxic activity on MDA-MB-231 tumor cells and, to a lesser extent, on MCF-7 cells, without presenting cytotoxicity at the same concentrations in MCF-10A non-tumor cells. Dic-EFc and Ace-EFc (5-10 µg/mL) reduced the migration capacity of MCF-7 and MDA-MB-231 cells. Interestingly, exposure to Dic-EFc and Ace-EFc (5-10 µg/mL) inhibited the invasive ability of MDA-MB-231 cells, reducing the secretion and activity of MMP-2 and MMP-9, as well as the F-actin distribution. Conclusions: Dic-EFc and Ace-EFc at low concentrations decreased breast cancer cell proliferation and invasiveness, mainly of MDA-MB-231 cells. The above supports the potential use of compounds from leaf extracts of F. crocata in neoadjuvant therapy to reduce the progression of breast cancer tumors, mainly triple-negative tumors.

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Bursera comprises ~100 tropical shrub and tree species, with the center of the species diversification in Mexico. The genomic resources developed for the genus are scarce, and this has limited the study of the gene flow, local adaptation, and hybridization dynamics. In this study, based on ~155 million Illumina paired-end reads per species, we performed a de novo genome assembly and annotation of three Bursera species of the Bullockia section: Bursera bipinnata, Bursera cuneata, and Bursera palmeri. The total lengths of the genome assemblies were 253, 237, and 229 Mb for B. cuneata, B. palmeri, and B. bipinnata, respectively. The assembly of B. palmeri retrieved the most complete and single-copy BUSCOs (87.3%) relative to B. cuneata (86.5%) and B. bipinnata (76.6%). The ab initio gene prediction recognized between 21,000 and 32,000 protein-coding genes. Other genomic features, such as simple sequence repeats (SSRs), were also detected. Using the de novo genome assemblies as a reference, we identified single-nucleotide polymorphisms (SNPs) for a set of 43 Bursera individuals. Moreover, we mapped the filtered reads of each Bursera species against the chloroplast genomes of five Burseraceae species, obtaining consensus sequences ranging from 156 to 160 kb in length. Our work contributes to the generation of genomic resources for an important but understudied genus of tropical-dry-forest species.

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Introduction: Rheumatoid arthritis (RA) is an inflammatory disease whose clinical phenotype largely depends on the presence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Seronegative RA appears to be a less severe disease, but this remains controversial. This study aimed to assess whether seronegative patients show a less severe disease than seropositive patients. Methods: A cross-sectional study was conducted on RA outpatients from a single center. Clinical activity scales, laboratory evaluations, and cardiovascular risk scores were assessed. Musculoskeletal ultrasound (US) examinations were performed. Results: One hundred and fourteen patients were enrolled. Eighty-five were seropositive (76% women) and 29 seronegative (93% women). Seropositive patients had a younger age at disease onset (43 ± 14 vs. 54 ± 11; p = 0.001) and used sulfasalazine (47 vs. 17%; p = 0.004) and glucocorticoids (36 vs. 10%; p = 0.007) more frequently. No differences in clinical activity scales and in 10-year cardiovascular risk were observed. Pathological US data were found more frequently in seropositive patients in the 2nd metacarpophalangeal (MCP) joint, both in grayscale (71 vs. 38%; p = 0.008) and in power Doppler (PD; 53 vs. 9%; p < 0.001); erosions (36 vs. 9%; p = 0.020) were also more frequent. We found greater severity of PD signals in the 2nd MCP and 3rd MCP joints of the seropositive patients, while synovitis severity was higher only in the 2nd MCP joints. The percentage of total joints with erosions (9 vs. 1%; p < 0.001) and 2nd MCP joints with erosions (25 vs. 7%; p < 0.001) was higher in seropositive patients. Conclusion: RA patients show a differentiated phenotype according to their ACPA and RF status. In seronegative patients, RA begins later in life and has a lower requirement for antirheumatic therapies. On US evaluation, seropositive patients show more joint damage, especially in MCP joints. Despite this, long-term cardiovascular risk is similar among RA patients, regardless of their RF and ACPA status.

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Sarcopenia is generally an age-related condition that directly impacts the quality of life. It is also related to chronic diseases such as metabolic dysfunction associated with diabetes and obesity. This means that everyone will be vulnerable to sarcopenia at some point in their life. Research to find the precise molecular mechanisms implicated in this condition can increase knowledge for the better prevention, diagnosis, and treatment of sarcopenia. Our work gathered the most recent research regarding inflammation in sarcopenia and new therapeutic agents proposed to target its consequences in pyroptosis and cellular senescence. Finally, we compared dual X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and ultrasound (US) as imaging techniques to diagnose and follow up on sarcopenia, indicating their respective advantages and disadvantages. Our goal is for the scientific evidence presented here to help guide future research to understand the molecular mechanisms involved in sarcopenia, new treatment strategies, and their translation into clinical practice.

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