Association of TLR8 Variants in Sex-Based Clinical Differences in Patients with COVID-19.

The host immune response might confer differential vulnerability to SARS-CoV-2 infection. The Toll-like receptor 8 (TLR8), could participated for severe COVID-19 outcomes. To investigated the relationship of TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G with COVID-19 outcomes and with biochemical parameters. A cross-sectional study of 830 laboratory-confirmed COVID-19 patients was performed, and classified into mild, severe, critical, and deceased outcomes. The TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G polymorphisms were genotyped. A logistic regression analysis was performed to determinate the association with COVID-19. A stratified analysis was by alleles was done with clinical and metabolic markets. In all outcomes, men presented the highest ferritin levels compared to women (P < 0.001). LDH levels were significantly different between sex in mild (P = 0.003), severe (P < 0.001) and deceased (P = 0.01) COVID-19 outcomes. The GGG haplotype showed an Odds Ratio of 1.55 (Interval Confidence 95% 1.05-2.32; P = 0.03) in men. Among patients with severe outcome, we observed that the carriers of the GGG haplotype had lower Ferritin, C-reactive protein and LDH levels than the CAA carriers (P < 0.01). After further stratified by sex, these associations were also seen in the male patients, except for D-dimer. Interestingly, among men patients, we could observe associations between TLR8 haplotypes and Ferritin (P < 0.001), D-dimer (P = 0.04), C-reactive protein, and Lactate dehydrogenase in mild (P = 0.04) group. Our results suggest that even though TLR8 haplotypes show a significant association with COVID-19 outcomes, they are associated with clinical markers in COVID-19 severity.

Characterisation of crevicular fluid microbiota in primary Sjögren's syndrome.

OBJECTIVES: To describe the taxonomy of the microbiota in crevicular fluid of primary Sjögren's syndrome (pSS) patients, and evaluate its association with clinical/serological variables, and oral quality of life. METHODS: Observational study that included 48 pSS without diabetes mellitus, no active neoplasia, no antibiotic use in the previous two weeks, and no current active infection. We registered demographics, oral/ocular sicca symptoms, parotid enlargement and anti-Ro/La serology. We assessed the non-stimulated whole salivary flow (NSWSF), the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), and the Xerostomia-related Quality of Life Scale (XeQoLS). Two periodontists determined the presence of periodontal disease and collected crevicular fluid from 6 teeth using filter paper. Samples were frozen at -86°C until processing. We included 17 sex- and age-matched control subjects. Bacterial DNA was extracted from the crevicular fluid sample using a commercial kit. 16SrRNA V3-V4 region was sequenced using reversible adaptor technology. Sequences were pre-processed and analysed using QIIME2 and phyloseq software programs. Functionality profiles were predicted using the Tax4Fun2 package. RESULTS: PSS patients had more bacteria of the genera Prevotella, Streptococcus, Veillonella, Fusobacterium, and Leptotrichia and fewer bacteria of the genus Selenomonas than controls. The pSS microbiota contained more genes encoding accessory secretory proteins. Microbiota also differed between patients with anti-Ro/La status, parotid gland enlargement, and periodontal disease severity, but did not correlate with NSWSF and XeQoLS. CONCLUSIONS: The crevicular fluid microbiota of pSS patients and controls differed significantly, even in SSP patients depending on their serology, parotid gland enlargement, and periodontal disease status.

Inflammasome genes polymorphisms and susceptibility to gout. Is there a link?

Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1ß release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1ß rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

OBJECTIVE: To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. METHODS: Hypervariable V3-V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profiles using bioinformatics in order to identify differences in taxonomy and metabolic pathways. RESULTS: We identified a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifidobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabolism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed differences in key bacterial enzymes involved in urate synthesis, degradation, and elimination. CONCLUSION: Our findings revealed that taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

Risk of Wnt/ß-catenin signalling pathway gene polymorphisms in primary Sjögren's syndrome.

OBJECTIVE: To explore genetic polymorphisms of the Wnt/ß-catenin signalling pathway in primary SS (PSS). METHODS: We included 98 patients with PSS and 165 healthy volunteers. Genomic DNA was extracted from peripheral blood samples. Through an open-array platform of low density, we genotyped 25 polymorphisms from 14 genes (WISP1, DKK1, SOST, FRZB, LRP1, LRP4, LRP5, LRP6, GSKB, ADAMTS5, GDF5, FMN2, ADIPOQ and COL11A1) involved in the Wnt/ß-catenin signalling pathway. We compared the allelic and genotypic frequencies with Fisher's exact test and logistic regression analysis adjusted by age, gender and individual admixture, as well as bootstrap-resampling analysis. We assessed the gene-gene interaction by the multifactor dimensionality reduction method. RESULTS: We found a positive significant association with four polymorphisms: LRP5 rs606989, FRZB rs409238, GSK3B rs2037547 and ADIPOQ rs2241766. All of them conferred risk for PSS, being the highest among subjects carrying three to four risk alleles (P < 0.001). According to a multifactor dimensionality reduction analysis, the best models included the LRP5 (rs606989), FRZB (rs409238) and ADIPOQ (rs2241766) polymorphisms. CONCLUSION: LRP5, FRZB and ADIPOQ genes related in the Wnt/ß-catenin signalling pathway increased the risk of PSS. Further research is needed to establish their functional role in this clinical entity.

Common gene variants interactions related to uric acid transport are associated with knee osteoarthritis susceptibility.

BACKGROUND: The presence of genetic variants in uric acid (UA) transporters can be associated with hyperuricemia, and therefore with an increased risk of monosodium urate (MSU) crystal precipitation. The inflammatory process triggered by these crystals leads to cartilage damage, which, in turn, could promote knee osteoarthritis (KOA). OBJECTIVE: To determine whether genetic polymorphisms of the UA transporters and their interactions are associated with KOA. MATERIALS AND METHODS: Two hundred forty-three unrelated Mexican-mestizo individuals were recruited for this case-control study. Ninety-three of them were KOA patients but without gout, and one hundred and fifty healthy individuals with no symptoms or signs of KOA were recruited as controls. Forty-one single-nucleotide polymorphisms (SNPs) involved in the UA transporters were genotyped with OpenArray technology in a QuantStudio 12K flex-System with both cases and controls. RESULTS: After adjusting by age, gender, BMI, and ancestry, significant associations were found for eight SNPs: rs1260326 (GCKR), rs780093 (GCKR), rs17050272 (INHBB), rs1471633 (PDZK1), rs12129861 (PDZK1), rs7193778 (IGF1R), rs17786744 (STC1), and rs1106766 (R3HDM2). With respect to gene-gene interactions, the pairwise interactions of rs112129861 (PDZK1) and rs7193778 (IGF1R); rs17050272 (INHBB) and rs1106766 (R3HDM2); rs1106766 (R3HDM2) and rs780093 (GCKR); rs1260326 (GCKR) and rs17786744 (STC1); and rs17786744 (STC1) and rs1106766 (R3HDM2) make it possible to visualize the synergistic or antagonistic effect of their genotypes or alleles on KOA development. CONCLUSIONS: Our preliminary results show that the common gene variants related to UA transport are associated with KOA in the Mexican population. Further studies must be carried out to corroborate it.

Gene-gene interactions of the Wnt/ß-catenin signaling pathway in knee osteoarthritis.

This study was designed to investigate whether genetic polymorphisms of the Wnt/ß-catenin signaling pathway and its interactions are involved in the development of knee osteoarthritis (KOA). Patients with KOA (n = 131) and healthy individuals (n = 190) with different ancestry from two Mexican populations (Mexico City and Guadalajara City) were analyzed. Twenty-five SNPs from thirteen genes (WISP1, DKK1, SOST, FRZB, LRP1, LRP4, LRP5, LRP6, GSKB, ADAMTS5, GDF5, FMN2 and COL11A1) involved in the Wnt/ß-catenin signaling pathway were genotyped. Genetic and allelic frequencies and gene-gene interactions were performed for this study. After adjusting for age, sex, BMI and admixture, significant associations were found for five SNPs in Mexico City: LRP6 rs12314259 (G/G genotype OR 0.22, P = 0.029; and G allele OR 0.48, P = 0.022), SOST rs851054 (C/T genotype OR 0.42, P = 0.027; and T allele OR 0.62, P = 0.026), FMN2 rs986690 (G/A genotype OR 0.42, P = 0.034; and A allele OR 0.50, P = 0.015), FRZB rs409238 (A/G genotype, OR 2.41, P = 0.022), and COL11A1 rs2615977 (A/C genotype OR 2.39, P = 0.024); no associations for Guadalajara City were found. With respect to gene-gene interactions, the pairwise interactions of WISP1-COL11A1, COL11A1-FRZB, FRZB-SOST and WISP1-FMN2 make it possible to visualize the synergistic or antagonistic effect of their genotypes or alleles in both populations. These results suggest that gene-gene interactions in the Wnt/ß-catenin signaling pathway play a role in the etiology of KOA.

The association of AKNA gene polymorphisms with knee osteoarthritis suggests the relevance of this immune response regulator in the disease genetic susceptibility.

Recent studies have identified AKNA as a potential susceptibility gene for several inflammatory diseases. Here, we aimed to assess the potential association of AKNA polymorphisms with knee osteoarthritis (KOA) susceptibility in a Mexican population, following STREGA recommendations. From a DNA bank of 181 KOA patients and 140 healthy controls, two AKNA SNPs were genotyped using TaqMan probes. The association between KOA susceptibility and AKNA polymorphisms genotypes was evaluated by multivariated logistic regression analysis. Information regarding patients' inflammatory biomarkers levels was obtained and their association with AKNA polymorphisms genotypes was assessed by lineal regression. We found a positive association with the recessive inheritance model of both AKNA polymorphisms (A/A genotype for both) and KOA susceptibility adjusting by age, body mass index (BMI), gender and place of birth (OR = 2.48, 95% CI 1.09-5.65 for rs10817595 polymorphism; and OR = 4.96; 95% CI 2.421-10.2 for rs3748176 polymorphism). Additionally these associations were also seen after stratifying patients by KOA severity and age. Furthermore the total leukocyte count was positively associated with rs10817595 AKNA polymorphism (ß = 1.39; 95% CI 0.44-2.34) adjusting by age, BMI, gender, place of birth and disease severity. We suggest that regulatory and coding polymorphisms of the inflammatory modulator gene AKNA can influence the development of KOA. Further structural and functional studies might reveal the role of AKNA in OA and other rheumatic diseases.

Fast Morphological Gallbladder Changes Triggered by a Hypercholesterolemic Diet.

INTRODUCTION AND AIM: Obesity is a worldwide epidemic problem, described as a risk factor for hepatic diseases, such as non-alcoholic fatty liver disease and other pathologies related to development of cholesterol crystals and cholesterol gallbladder stones. It has been reported that cholesterol overload may cause hepatic damage; however, little is known about the effects of an acute hypercholesterolemic diet on the gallbladder. The aim of this manuscript was to evaluate the impact of a cholesterol-rich diet on the gallbladder. MATERIAL AND METHODS: The study included ten eight-week-old C57BL6 male mice, which were divided into two study groups and fed different diets for 48 h: a hypercholesterolemic diet and a balanced Chow diet. After 48 h, the mice were analyzed by US with a Siemens Acuson Antares equipment. Mice were subsequently sacrificed to carry out a cholesterol analysis with a Refloton System (Roche), a crystal analysis with a Carl Zeiss microscope with polarized light, and a histological analysis with Hematoxylin-eosin staining. RESULTS: The hypercholesterolemic diet induced an increase in gallbladder size and total cholesterol content in the bile, along with important histological changes. CONCLUSION: Cholesterol overloads not only trigger hepatic damage, but also affect the gallbladder significantly.

Hyperlipidemic microenvironment conditionates damage mechanisms in human chondrocytes by oxidative stress.

BACKGROUND: Currently, two pathogenic pathways describe the role of obesity in osteoarthritis (OA); one through biomechanical stress, and the other by the contribution of systemic inflammation. The aim of this study was to evaluate the effect of free fatty acids (FFA) in human chondrocytes (HC) expression of proinflammatory factors and reactive oxygen species (ROS). METHODS: HC were exposed to two different concentrations of FFA in order to evaluate the secretion of adipokines through cytokines immunoassays panel, quantify the protein secretion of FFA-treated chondrocytes, and fluorescent cytometry assays were performed to evaluate the reactive oxygen species (ROS) production. RESULTS: HC injury was observed at 48 h of treatment with FFA. In the FFA-treated HC the production of reactive oxygen species such as superoxide radical, hydrogen peroxide, and the reactive nitrogen species increased significantly in a at the two-dose tested (250 and 500 µM). In addition, we found an increase in the cytokine secretion of IL-6 and chemokine IL-8 in FFA-treated HC in comparison to the untreated HC. CONCLUSION: In our in vitro model of HC, a hyperlipidemia microenvironment induces an oxidative stress state that enhances the inflammatory process mediated by adipokines secretion in HC.

Polymorphic variation of hypoxia inducible factor-1 A (HIF1A) gene might contribute to the development of knee osteoarthritis: a pilot study.

BACKGROUND: Osteoarthritis (OA) is a multifactorial degenerative condition of the whole joint with a complex pathogenesis whose development and progression is significantly mediated by interactions between the joint cartilage and articular tissues, particularly, proinflammatory mediators and oxidative stress, which results in cartilage deterioration and subchondral bone destruction. HIF-1 alpha regulates oxygen homeostasis in hypoxic tissues such as joint cartilage; efficiency of transcriptional activity of the HIF1A gene is strongly influenced by the presence of polymorphic variants. Given the loss of articular cartilage and with intention to restore damaged tissue, WISP-1 participates in the development of subchondral bone; further, its expression is highly increased in chondrocytes of OA patients. The aim of this study was to evaluate gene frequencies of HIF1A and WISP1 polymorphisms in Mexican patients suffering from knee OA. METHODS: We determined HIF1A rs11549465 (P582S), rs11549467 (A588T), and rs2057482 (C191T), and WISP1 rs2929970 (A2364G) polymorphisms in 70 Mexican patients with knee OA and compare them to those present in 66 ethnically matched healthy controls. Genotyping for these polymorphisms was performed by Real-Time PCR using TaqMan probes. RESULTS: Gene frequencies exhibited a significant increase of the CC genotype of rs11549465 polymorphism in knee OA patients as compared with those present in controls (P = 0.003 OR = 5.7, 95% CI = 1.7-21.6); CT genotype and T allele showed decreased frequency in the knee OA group vs. the controls (P = 0.003 OR = 0.2, CI = 0.05-0.6; and P = 0.004 OR = 0.2, CI = 0.05-0.65, respectively). Allele frequencies of the other polymorphic variants were similar in both patients and controls. CONCLUSIONS: These results suggest that the presence of the rs11549465 SNP (HIF1A) plays a role protective in the loss of articular cartilage in our population, and offers the possibility to further study the molecular mechanisms within cartilage and subchondral bone.

[Cholesterol overload in hepatocytes affects nicotinamide adenine dinucleotide phosphate oxidase (NADPH) activity abrogating hepatocyte growth factor (HGF) induced cellular protection]. / La acumulación de colesterol en hepatocitos sobreactiva el fosfato de dinucleótido de adenina y nicotinamida (NADPH) oxidasa pero abroga la respuesta de protección del factor de crecimiento de hepatocitos (HGF).

The increment in the prevalence of obesity incidence in Mexico is leading to the increase in many chronic maladies, including liver diseases. It is well known that lipid-induced liver sensitization is related to the kind of lipid rather than the amount of them in the organ. Cholesterol overload in the liver aggravates the toxic effects of canonical liver insults. However, the status on the repair and survival response elicited by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the hepatocyte growth factor (HGF) is not completely understood. In the present, work we aimed to figure out the HGF/NADPH oxidase-induced cellular protection in the hepatocyte with a cholesterol overload. Our results show that a hypercholesterolemic diet induced liver damage and steatosis in mice. The hepatocytes isolated from these animals exhibited an increase in basal NADPH oxidase activity, although transcriptional levels of some of its components were decreased. No effect on the oxidase activity was observed in HGF treatments. The protective effect of HGF was abrogated as a result of cholesterol cellular overload, calculated by a survival assay. In conclusion, the cholesterol overload in hepatocytes impairs the HGF/NADPH oxidase-induced cellular protection.

The HIF1A rs2057482 polymorphism is associated with risk of developing premature coronary artery disease and with some metabolic and cardiovascular risk factors. The Genetics of Atherosclerotic Disease (GEA) Mexican Study.

The aim of the present study was to establish the role of HIF1A gene polymorphisms in the risk of developing premature coronary artery disease (CAD) in a well-characterized clinical cohort. Three polymorphisms in HIF1A (rs11549465, rs11549467, rs2057482) gene were genotyped in 949 patients with premature CAD, and 676 healthy controls (with negative calcium score by computed tomography). Under a dominant model adjusted for age, visceral to subcutaneous adipose tissue (VAT/SAT) ratio, hypertension, type 2 diabetes mellitus (T2DM), HDL-C levels, hypercholesterolemia and hypertriglyceridemia, the rs2057482 T allele was associated with decreased risk of premature CAD when compared to healthy controls (OR = 0.616, P(dom) = 0.020). The effect of the studied polymorphisms on various metabolic parameters and cardiovascular risk factors was explored. In this analysis, the rs2057482 T allele was associated with decreased risk of obesity, central obesity, hypertension, hypercholesterolemia, hypertriglyceridemia and increased risk of T2DM. Under a dominant model adjusted by age, the HIF1A rs2057482 T polymorphism was associated with high VAT/SAT ratio (P = 0.009) and HDL-C levels (P = 0.04) in healthy controls. The results suggest that HIF1A rs2057482 polymorphism is involved in the risk of developing CAD and is associated with some metabolic parameters and cardiovascular risk factors.

A comprehensive review of hip arthroscopy techniques and outcomes.

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.

Two-trace two-dimensional correlation spectra (2T2D-COS) analysis using FTIR spectra to monitor the immune response by COVID-19.

There is a growing trend in using saliva for SARS-CoV-2 detection with reasonable accuracy. We have studied the responses of IgA, IgG, and IgM in human saliva by directly comparing disease with control analyzing two-trace two-dimensional correlation spectra (2T2D-COS) employing Fourier transform infrared (FTIR) spectra. It explores the molecular-level variation between control and COVID-19 saliva samples. The advantage of 2T2D spectra is that it helps in discriminating remarkably subtle features between two simple pairs of spectra. It gives spectral information from highly overlapped bands associated with different systems. The clinical findings from 2T2D show the decrease of IgG and IgM salivary antibodies in the 50, 60, 65, and 75-years COVID-19 samples. Among the various COVID-19 populations studied the female 30-years group reveals defense mechanisms exhibited by IgM and IgA. Lipids and fatty acids decrease, resulting in lipid oxidation due to the SARS-CoV-2 in the samples studied. Study shows salivary thiocyanate plays defense against SARS-CoV-2 in the male population in 25 and 35 age groups. The receiver operation characteristics statistical method shows a sensitivity of 98% and a specificity of 94% for the samples studied. The measure of accuracy computed as F score and G score has a high value, supporting our study's validation. Thus, 2T2D-COS analysis can potentially monitor the progression of immunoglobulin's response function to COVID-19 with reasonable accuracy, which could help diagnose clinical trials. KEY MESSAGES: The molecular profile of salivary antibodies is well resolved and identified from 2T2D-COS FTIR spectra. The IgG antibody plays a significant role in the defense mechanism against SARS-CoV-2 in 25-40 years. 2T2D-COS reveals the absence of salivary thiocyanate in the 40-75 years COVID-19 population. The receiver operation characteristic (ROC) analysis validates our study with high sensitivity and specificity.

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.

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.

Dynamic response antibodies SARS-CoV-2 human saliva studied using two-dimensional correlation (2DCOS) infrared spectral analysis coupled with receiver operation characteristics analysis.

COVID-19 has affected the entire world due to the rapid spread of SARS-CoV-2, mainly through airborne particles from saliva, which, being easily obtained, help monitor the progression of the disease. Fourier transform infrared (FTIR) spectra combined with chemometric analysis could increase the diagnostic efficiency of the disease. However, two-dimensional correlation spectroscopy (2DCOS) is superior to conventional spectra as it helps to resolve the minute overlapped peaks. In this work, we aimed to use 2DCOS and receiver operating characteristic (ROC) analyses to compare the immune response in saliva associated with COVID-19, which could be important in biomedical diagnosis. FTIR spectra of human saliva samples from male (575) and female (366) patients ranging from 20 to 85 ± 2 years of age were used for the study. Age groups were segregated as G1 (20-40 ± 2 years), G2 (45-60 ± 2 years), and G3 (65-85 ± 2 years). The results of the 2DCOS analysis showed biomolecular changes in response to SARS-CoV-2. 2DCOS analyses of the male G1 + (1579,1644) and -(1531,1598) cross peaks evidenced changes such as amide I > IgG. Female G1 cross peaks -(1504,1645), (1504,1545) and -(1391,1645) resulted in amide I > IgG > IgM. The asynchronous spectra in 1300-900 cm-1 of the G2 male group showed that IgM is more important in diagnosing infections than IgA. Female G2 asynchronous spectra -(1027,1242) and + (1068,1176) showed that IgA > IgM is produced against SARS-CoV-2. The G3 male group evidenced antibody changes in IgG > IgM. The absence of IgM in the female G3 population diagnoses a specifically targeted immunoglobulin associated with sex. Moreover, ROC analysis showed sensitivity (85-89 % men; 81-88 % women) and specificity (90-93 % men; 78-92 % women) for the samples studied. The general classification performance (F1 score) of the studied samples is high for the male (88-91 %) and female (80-90 %) populations. This high PPV (positive predictive value) and NPV (negative predictive value) verify our segregation of COVID-19 positive and negative sample groups. Therefore, 2DCOS with ROC analysis using FTIR spectra have the potential for a non-invasive approach to monitoring COVID-19.

Revolutionizing orthopedics: a comprehensive review of robot-assisted surgery, clinical outcomes, and the future of patient care.

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.

The impact of short-chain fatty acid-producing bacteria of the gut microbiota in hyperuricemia and gout diagnosis.

INTRODUCTION/OBJECTIVES: Persistent hyperuricemia is a key factor in gout; however, only 13.5% of hyperuricemic individuals manifest the disease. The gut microbiota could be one of the many factors underlying this phenomenon. We aimed to assess the difference in taxonomic and predicted functional profiles of the gut microbiota between asymptomatic hyperuricemia (AH) individuals and gout patients. METHODS: The V3-V4 region of the 16S rRNA gene of the gut microbiota of AH individuals, gout patients, and controls was sequenced. Bioinformatic analyses were carried out with QIIME2 and phyloseq to determine the difference in the relative abundance of bacterial genera among the study groups. Tax4fun2 was used to predict the functional profile of the gut microbiota. RESULTS: AH individuals presented a higher abundance of butyrate- and propionate-producing bacteria than gout patients; however, the latter had more bacteria capable of producing acetate. The abundance of Prevotella genus bacteria was not significantly different between the patients but was higher than that in controls. This result was corroborated by the functional profile, in which AH individuals had less pyruvate oxidase abundance than gout patients and less abundance of an enzyme that regulates glutamate synthetase activation than controls. CONCLUSION: We observed a distinctive taxonomic profile in AH individuals characterized by a higher abundance of short-chain fatty acid-producing bacteria in comparison to those observed in gout patients. Furthermore, we provide scientific evidence that indicates that the gut microbiota of AH individuals could provide anti-inflammatory mediators, which prevent the appearance of gout flares. Key Points • AH and gout patients both have a higher abundance of Prevotella genus bacteria than controls. • AH individuals' gut microbiota had more butyrate- and propionate-producing bacteria than gout patients. • The gut microbiome of AH individuals provides anti-inflammatory mediators that could prevent gout flares.

Implication of myddosome complex genetic variants in outcome severity of COVID-19 patients.

BACKGROUND/PURPOSE(S): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. METHODS: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. RESULTS: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21-4.9) with deceased outcomes. CONCLUSION: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.