Concurrence of hyperinsulinemia and hyperuricemia significantly augmented all-cause mortality.

BACKGROUND AND AIMS: Hyperinsulinemia and hyperuricemia are known to increase the risk of mortality due to certain complications, such as Type 2 Diabetes and cardiovascular disease. However, despite their common comorbidities, their combined effect has not been evaluated. The study's aim was to evaluate the combine effect of hyperinsulinemia and hyperuricemia on all-cause mortality. METHODS AND RESULTS: NHANES datasets (cycles 2003-2018) were examined. Differences between groups were evaluated using Rao-Scott Chi-square and General Linear Model for categorical and continuous data, respectively. Hazard Ratios (HR) were calculated using Cox regression with 95% confidence intervals (95%CI). There was significant difference (p < 0.05) in the mortality rate between the control group (2.3 ± 0.2%), the hyperinsulinemia only group (3.1 ± 0.3%), the hyperuricemia only group (4.0 ± 0.8%), and both conditions (5.1 ± 0.8%). Individually, when compared to the control group, there was a significant increase in mortality risk for hyperinsulinemia (HR: 1.50, 95%CI: 1.12-2.01, p = 0.007) and hyperuricemia (HR: 1.80, 95%CI:1.18-2.75, p = 0.006). However, when both conditions were present, there appeared an additive effect in the mortality risk (HR: 2.32, 95%CI: 1.66-3.25, p < 0.001). When stratified by BMI class, only normal weight participants presented with a significant risk (HR: 7.00, 95%CI: 2.50-20.30, p < 0.001). Also, when stratified by age, only participants older than 40 years presented a risk (HR: 2.22, 95%CI: 1.56-3.16, p < 0.001). CONCLUSION: Alone, hyperuricemia and hyperinsulinemia significantly increased the mortality rate; however, the combined presence of both pathologies was associated with a significantly augmented mortality rate. Normal weight participant or that were >40 years old had a greater risk for mortality.

Metformin does not improve insulin sensitivity over hypocaloric diets in women with polycystic ovary syndrome: a systematic review of 12 studies.

OBJECTIVE: To improve insulin action, most clinicians prescribe Metformin in patients with insulin resistance (IR). Women with polycystic ovary syndrome (PCOS), in which IR is an important physiopathological mechanism, treatment with Metformin and specialized diets have been suggested to reduce the patient's IR. However, numerous studies have demonstrated conflicting results with respect to supplementing a diet with Metformin. Therefore, we conducted a meta-analysis to determine if Metformin provides a benefit in conjunction with hypocaloric diets to improve insulin sensitivity in PCOS women. METHODS: PubMed, SCOPUS, LILACS, and EBSCO databases and retrieved studies' bibliographies were searched for prospective studies that investigated the effect between Metformin and hypocaloric diets in PCOS women until April 2020. Pre- and post-intervention values for fasting plasma glucose (FPG), fasting plasma insulin (FPI), and IR indices (HOMA1-IR, ISI, and QUICKI) were extracted. Using Comprehensive Meta-Analysis software, the pooled standard difference in the means (SDM) and 95%CIs were calculated. RESULTS: 11 publications (12 studies) were selected. There was not a benefit of adding Metformin to a hypocaloric diet with respect to FPG (SDM= -0.17; 95%CI: -0.48-0.14, p = .28) and FPI (SDM = 0.16; 95%CI: -0.24-0.55, p = .45). None of the IR indices also demonstrated any benefit of using Metformin when a diet intervention was implemented (HOMA1-IR: SDM = 0.28; 95%CI: -0.27-0.84, p = .315; ISI: SDM = 0.344; 95%CI: -0.17-0.85, p = .186; QUICKI: SDM= -0.01; 95%CI: -0.42-0.41, p = .968). CONCLUSION: Here, we determined that adding Metformin to hypocaloric diets did not improve serum glucose or insulin concentrations as well as IR in PCOS women.

Validation of a non-laboratorial questionnaire to identify Metabolic Syndrome among a population in central Mexico.

OBJECTIVE: To determine the reliability of a non-laboratorial questionnaire, the Encuesta de Identificación de Sujetos Metabólicamente Comprometidos en Fase-I (ESF-I) for identifying Metabolic Syndrome among a population in central Mexico. METHODS: Clinical and biochemical parameters were collected for 232 participants from 1 June 2012 - 31 August 2013. Three definitions of Metabolic Syndrome (Harmonizing, National Cholesterol Education Program Expert Panel and Adult Treatment Panel III [ATPIII], and International Diabetes Federation [IDF]) were used to allocate subjects to either the normal or Metabolic Syndrome positive (MetS+) group. The predictability of the questionnaire was determined by the Area-Under-the-Receiver-Operating Characteristic curve (AUC). Youden's index was calculated and the highest score was considered the optimal cutoff value. Cohen´s kappa (κ) was calculated to determine the level of agreement between the ESF-I questionnaire (max score: 15 based on 15 items) and Metabolic Syndrome. RESULTS: From 53.8% - 60.7% of the participants were determined to be MetS+. The average questionnaire score was significantly higher in the MetS+ group for each definition (4.0 vs. 8.0, P < 0.05). The ESF-I questionnaire was predictive for the Harmonizing definition (AUC = 0.841, 95%CI: 0.790 - 0.892), the ATPIII definition (AUC = 0.827, 95%CI: 0.774 - 0.880), and the IDF definition (AUC = 0.836, 95%CI: 0.785 - 0.887). A cutoff value of 7 was determined for each definition; therefore, the cohort was re-categorized based on questionnaire results. There was a strong agreement between the ESF-I questionnaire and MetS (Harmonizing: accuracy = 77.6%, κ = 0.554; ATPIII: accuracy = 74.1%, κ = 0.489; IDF: accuracy = 74.6%, κ = 0.495, P < 0.001). CONCLUSION: The ESF-I questionnaire can identify MetS+ patients, and therefore, lead to earlier diagnoses, reduced number of consultations, and lower costs with easier application.

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease.

Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels.

Visceral and subcutaneous abdominal fat is associated with non-alcoholic fatty liver disease while augmenting Metabolic Syndrome's effect on non-alcoholic fatty liver disease: A cross-sectional study of NHANES 2017-2018.

BACKGROUND: The aim was to evaluate the effect different types of abdominal fat have on NAFLD development and the effects of abdominal fat has on the association between Metabolic Syndrome (MetS) and NALFD. METHODS: Data was collected from the cross-sectional NHANES dataset (2017-2018 cycle). Using the controlled attenuation parameter (USG CAP, dB/m), which measures the level of steatosis, the cohort was stratified into two groups: NAFLD(+) (≥274 dB/m) and NAFLD(-). Using complex samples analyses, associations between liver steatosis or NAFLD and types of abdominal fat area [Total abdominal (TAFA), subcutaneous (SAT), and visceral (VAT)] were determined. Pearson's correlation coefficient (r) was calculated to evaluate the associations between adipose tissues and NAFLD. Logistic regression was used to determine the risk [odds ratio (OR) and 95% confidence interval (95%CI)]. Participants were also classified by MetS, using the Harmonizing Definition criteria. RESULTS: Using 1,980 participants (96,282,896 weighted), there was a significant (p<0.001) correlation between USG CAP and TAFA (r = 0.569), VAT (r = 0.645), and SAT (r = 0.479). Additionally, the risk of developing NAFLD was observed for total abdominal obesity (OR = 19.9, 95%CI: 5.1-77.8, p<0.001), visceral obesity (OR = 9.1, 95%CI: 6.2-13.5, p<0.001) and subcutaneous obesity (OR = 4.8, 95%CI: 3.2-6.9, p<0.001). Using 866 participants (44,399,696 weighted), for visceral obesity, participants with MetS and visceral obesity (OR = 18.1, 95%CI: 8.0-41.3, p<0.001) were shown to have a greater risk than participants with MetS only (OR = 6.3, 95%CI: 2.6-15.2, p<0.001). For subcutaneous obesity, again, participants with MetS and subcutaneous obesity (OR = 18.3, 95%CI: 8.0-41.9, p<0.001) were shown to have a greater risk than the MetS-only group (OR = 10.3, 95%CI: 4.8-22.4, p<0.001). CONCLUSION: TAFA, VAT, and SAT were positively associated with USG CAP values and increased the risk of developing NAFLD. Also, the type of abdominal fat depots did affect the association between MetS and NAFLD.

Obesity attenuates the beneficial effect of an intrauterine infusion of autologous platelet-rich plasma during in vitro fertilization.

OBJECTIVE: To assess how obesity, normal weight (NW) versus overweight/obese (OW/OB), impacts platelet-rich plasma's (PRP) effectiveness during in vitro fertilization and how obesity affects platelets during the menstrual cycle. METHODS: Endometrial mean thickness (EMT), embryo implantation, and clinical pregnancy were assessed using a self-controlled retrospective study that enrolled 59 patients with two failed cycles and treated with autologous PRP (three-dose scheme). The NHANES dataset was used to assess platelet changes during the menstrual cycle, using the mean platelet volume to platelet count ratio (MPR) index. The COSINOR packages for R were used to determine rhythmicity. RESULTS: PRP treatments significantly improved the EMT (2.5 ± 1.4 mm, P<0.001), unaffected by obesity. After the PRP treatment, one patient spontaneously became pregnant; therefore, 58 patients underwent embryo transfer (62 cycles), of which in 39 cycles the embryos implanted (63.9%). This was a significant improvement from their previous cycle (vs. 22.6%, P<0.001). Clinical pregnancy also improved with the PRP treatment over the previous cycle (57.4% vs. 16.1%, P<0.001). When stratified by obesity, there was an appreciable decrease in embryo implantation and clinical pregnancy rates for the OW/OB group; nevertheless, the PRP treatment significantly improved embryo implantation and clinical pregnancy (P<0.05). A rhythm was observed with the MPR index (P<0.05) only for the NW group, suggesting that the platelets normally fluctuate during the menstrual cycle. CONCLUSION: PRP improved embryo implantation and clinical pregnancy rates; however, these beneficial effects were attenuated by obesity. PRP presumptively promoted a change in the uterine environment to mimic the normal findings associated with normal-weight women.

The Effect of Microbiome Therapies on Waist Circumference, a Measure of Central Obesity, in Patients with Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Microbiome therapies (probiotic, prebiotic, and synbiotics) have been proposed as adjuvants in the control of central obesity; however, their results for patients with type 2 diabetes (T2D) remain inconclusive. OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the effect of microbiome therapies on central obesity as measured by waist circumference (WC), and to evaluate the effect of microbiome therapies for glycemic parameters (fasting glucose [FPG], fasting insulin [FPI], hemoglobin A1c [HbA1c], and insulin resistance [HOMA1-IR]) in patients with T2D. METHODS: SCOPUS, Pubmed, EBSCO, and LILACS databases were searched for studies that investigated the effect of microbiome therapies on WC up to June 1, 2022. Heterogeneity was determined using Cochran's Q test and quantified using the inconsistency index. The random effects model was used to calculate the pooled difference in means (DM) and 95% confidence intervals (95%CI). Egger's test and Beggs-Muzamar's test were used to assess publication bias. RESULTS: Fifteen reports were included (443 treated and 387 controls). Overall, a significant decrease in WC was found (DM = -0.97 cm; 95% confidence interval [95%CI] = -1.74 to -0.20; P = 0.014); however, when stratified by type of microbiome therapy, only probiotics significantly decreased WC (DM = -0.62 cm; 95%CI = -1.00 to -0.24; P = 0.002). No effect was observed for prebiotics and synbiotics. With respect to glycemic parameters, HbA1c, FPG, and HOMA1-IR significantly decrease with microbiome therapies (P ≤ 0.001). When stratified by the type of therapy, for probiotic treatments, HbA1c, FPG, and HOMA1-IR scores decrease (P < 0.001). For prebiotic treatments, HbA1c and FPG (P ≤ 0.001) levels decrease, whereas FPI increased (P = 0.012). Synbiotic treatments were only associated with an increase in FPI (P = 0.031). CONCLUSION: Findings indicate that using probiotics alone improved WC in patients with T2D. Both probiotics and prebiotics decreased HbA1c and FPG; however, prebiotics and synbiotics resulted in an increase in FPI. The formulation of the therapy (single vs multi) had no difference on the effect.

Probiotics' effect on visceral and subcutaneous adipose tissue: a systematic review of randomized controlled trials.

Probiotics are shown to alter the microbiota, leading to a favorable environment, in which weight loss and metabolic parameters are improve. However, the results on probiotics' effect on specific types of central adipose tissues, mainly visceral (VAT) and subcutaneous adipose tissue (SAT), are conflicting. Therefore, we conducted a systematic review, aimed to evaluate the effects of probiotics on VAT and SAT. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of probiotics on VAT and SAT. Fixed effects were used to calculate the pooled difference in means (DM) and 95% confidence intervals (95%CI). Fourteen publications met the inclusion criteria, which consisted of 1523 participants. For VAT, overall, there was a significant decrease (DM = -3.63 cm2, 95% CI: -5.08 to -2.17, p < 0.001). When stratified by type of probiotic, single Bifidobacterium (DM = -4.49 cm2, 95% CI:-7.37 to -1.61, p = 0.002) and single Lactobacillus probiotics (DM = -3.84 cm2, 95% CI:-5.74 to -1.93, p < 0.001) resulted in significant reductions. Mixed probiotics had no effect. For SAT, overall, there was a significant decrease (DM = -2.91 cm2, 95% CI:-4.82 to -1.01, p = 0.003), and when stratified by type of probiotic, single Lactobacillus (DM = -3.39 cm2, 95% CI:-5.90 to -0.88, p = 0.008) and mixed probiotics (DM = -5.97 cm2, 95% CI:-10.32 to -1.62, p = 0.007) resulted in a significant decrease. Single Bifidobacterium probiotics had no effect. Using meta-regression, no association was observed between the total daily probiotic dose and VAT or SAT reduction. This study shows that probiotics have a beneficial effect on central adiposity. Single Lactobacillus-based probiotics reduced VAT and SAT, whereas Bifidobacterium-based probiotics reduce VAT.

Endometrial preparation with etanercept increased embryo implantation and live birth rates in women suffering from recurrent implantation failure during IVF.

Recurrent implantation failure (RIF), defined as ≥3 failed in vitro fertilization (IVF) cycles with the accumulated transfer of at least five embryos, plague many infertile women. The exact cause is unknown; however, evidence supports the immune system, specifically the Tumor Necrosis Factor (TNF) pathway. Etanercept (a TNFα antagonist) has been shown to improve pregnancy rates in women with rheumatoid arthritis or endometriomas; therefore, this study aimed to determine the effectiveness of etanercept for IVF in RIF women. Eighty-three RIF women were recruited from the Ingenes Institute in Mexico City for this single-arm, prospective study. All patients underwent a similar IVF protocol and received etanercept (4 × 25 mg every 72 h) after endometrial preparation, if applicable, and at embryo transfer. IVF endpoints assessed were embryo implantation (h-ßCG >10 mg/dL at Day 14), the presence of a gestational sac, live birth, and birth weight. All women reported no side-effects associated with the etanercept treatment. 75.9 % of the cohort achieved embryo implantation, 74.7 % developed gestational sacs, and the ongoing pregnancy/live birth rate was at 62.7 %. However, 56.7 % of the live births were preterm (<37 weeks) and 60.5 % of the births were underweight (<2500 g). When stratified by fresh or frozen cycles or by the ova source (patient versus donor), the results were not significantly different with respect to the implantation rate, formation of gestational sacs, and the live birth rate. Here, we showed that using etanercept during endometrial preparation improves IVF outcomes in RIF women.

Association between Osteoprotegerin and Charcot Neuroarthropathy: a systematic review.

AIMS: Osteoprotegerin (OPG) has been associated with Charcot Neuroarthropathy (CN); however, three studied OPG polymorphisms (1181C > G, 245A > C and 950 T > C) have yielded conflicting results. Therefore, this meta-analysis was conducted to determine the difference in serum OPG concentrations between healthy controls and diabetics with and without CN and the effect OPG polymorphisms have on CN development. METHODS: PubMed, LILAC, SCOPUS, and EBSCO databases and retrieved publications' bibliographies were searched for studies that examined for OPG and CN. Depending on the heterogeneity, fixed or random effects were used to calculate the pooled odds ratio (OR) or standard difference in means (SDM) with 95% confidence intervals (95%CI) for 5 genetic models (heterozygous, homozygous, dominant, recessive, and allelic) and serum concentrations, respectively. RESULTS: Seven publications (12 studies) demonstrated that serum OPG concentrations were more elevated in subjects with CN (SDM = 0.719, 95%CI = 0.555-0.883, p < 0.001). When CN was compared to healthy controls or diabetics, the difference was more prominent for healthy controls (SDM = 1.043, 95%CI = 0.676-1.409, p < 0.001) than diabetics (SDM = 0.639, 95%CI = 0.456-0.821, p < 0.001) and the SDM difference was significant (p = 0.013). Using 6 publications (9 studies), neither the 1181C > G or the 950 T > C polymorphisms showed any significant associations for any genetic model. For the 245A > C polymorphism, only the homozygous genetic model showed a significant association between the polymorphism and CN (OR = 2.850, 95%CI: 1.051-7.729, p = 0.040). CONCLUSIONS: Here, we determined a potential correlation between the CN and serum OPG concentrations and that only the CC genotype of the 245A > C polymorphism showed an increased risk of developing CN.

Denosumab improves glucose parameters in patients with impaired glucose tolerance: a systematic review and meta-analysis.

OBJECTIVE: Receptor activator of NF-κß ligand (RANKL) is crucial for the development of hepatic insulin resistance and poor glucose uptake; therefore, inhibiting RANKL with Denosumab could improve fasting plasma glucose (FPG) and insulin (FPI). METHODS: A systematic review was conducted to evaluate the effects of Denosumab on glycemic parameters. PubMed, SCOPUS, EBSCO, and LILACS databases were searched for studies that investigated the effect of Denosumab on FPG, glycated hemoglobin (HbA1c), FPI, and Homeostatic Model Assessment for Insulin Resistance (HOMA1-IR). The pooled standard difference in means (SDM) and 95% confidence intervals (95%CI) were calculated. The results were stratified into (1) Normal Glucose Tolerance (NGT) and (2) Impaired Glucose Tolerance (IGT). RESULTS: Six publications (1203 participants) were included. There was a significant association between Denosumab and FPG (SDM = -0.388, 95%CI: -0.705 to -0.070, p = .017) and with HOMA1-IR (SDM = -0.223, 95%CI: -0.388 to -0.058, p = .008), but not for HbA1c and FPI. When stratified by glucose tolerance, the association between Denosumab and FPG, HbA1c, and HOMA1-IR was present for the IGT group. Lastly, Denosumab had a time-dependent effect on HbA1c (slope = -0.037, 95%CI: -0.059 to -0.015, p < .005). CONCLUSIONS: Denosumab significantly improved glycemic parameters. This outcome was more prominent for subjects with compromised glucose tolerance, positing that Denosumab can be used as a treatment to improve glucose metabolism for persons with pre-diabetes and diabetes.

The association between interleukin-6 promoter polymorphisms and rheumatoid arthritis by ethnicity: A meta-analysis of 33 studies.

OBJECTIVE: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. MATERIAL AND METHODS: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28-25.14, ORhomozygous=5.84, 95%CI: 2.06-16.56, ORdominant=7.21, 95%CI: 2.30-22.63, ORrecessive=5.04, 95%CI: 1.78-14.28, ORallelic=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10-4.81, ORdominant=2.27, 95%CI: 1.22-4.22, ORallelic=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08-.82, ORrecessive=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16-2.09, ORrecessive=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. CONCLUSIONS: Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.

Association between the L55M and Q192R polymorphisms of the paraoxonase-1 gene and age-related macular degeneration: a meta-analysis.

PURPOSE: Paraoxonase-1 activity is associated with age-related macular degeneration. Two polymorphisms (L55M and Q192R) were shown to increase paraoxonase-1 activity and have been implicated in the development of age-related macular degeneration. The results of studies that have examined these polymorphisms are conflicting, showing no effect, as well as increased or decreased risk. Therefore, this meta-analysis was conducted to determine the effect of these polymorphisms on age-related macular degeneration. METHODS: PubMed, EBSCO, LILACS, and Scopus databases, as well as and the retrieved bibliographies of publications were searched for case-control studies that examined for paraoxonase-1 polymorphisms and age-related macular degeneration. Data were analyzed using the Comprehensive Meta-Analysis Version 2.2 and the NCSS Statistical Version 2020 software. Genotype distributions were extracted and, depending on the level of heterogeneity, fixed effects or random effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: Overall, for the L55M polymorphism, none of the genetic models demonstrated a significant association. However, for non-Asian populations, a significant association was determined for the heterozygous and dominant genetic models (ORrange=1.24-1.27, p<0.05). For the Asian population, the heterozygous, dominant, and allelic genetic models demonstrated a benefit/protective factor (ORrange=0.29-0.35, p<0.05). For the Q192R polymorphism, none of the genetic models demonstrated a significant association. However, when the cohort was grouped by ethnicity, a significant association was determined in the Asian population for the recessive and allelic genetic models (ORrange=1.63-2.08, p<0.05). However, for the non-Asian population, there was no association observed. Also, there was no identifiable risk when the cohort was stratified into exudative and non-exudative cases. CONCLUSIONS: The paraoxonase-1L55M polymorphism increases the risk of developing age-related macular degeneration in non-Asian populations, whereas in Asian populations, the polymorphism exerts a protective effect. However, for the paraoxonase-1 Q192R polymorphism, only the Asian population demonstrated a risk of developing age-related macular degeneration.

Whole-genome amplification/preimplantation genetic testing for propionic acidemia of successful pregnancy in an obligate carrier Mexican couple: A case report.

BACKGROUND: Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities' current methodology for screening, which focuses on the detecting multiple genetic disorders at once. Here, we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects (PGT-M) approach for detecting propionic acidemia (PA) in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit (PCCA) couple. CASE SUMMARY: A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling. They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit (PCCB) genotype. Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant (c.2041-1G>T, ClinVar:RCV000802701.1; dbSNP:rs1367867218) in both parents. The couple requested in vitro fertilization (IVF) and PGT-M for PA. From IVF, 12 oocytes were collected and fertilized, of which two resulted in high-quality embryos. Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid. End-point polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female embryo. Both embryos were transferred, resulting in a clinical pregnancy and the delivery of a healthy male newborn (38 wk, weight: 4080 g, length: 49 cm, APGAR 9/9). The absence of PA was confirmed by expanded newborn screening. CONCLUSION: We show that using PGT-M with Whole Genome Amplification templates, coupled with IVF, can reduce the transmission of a pathogenic variant of the PCCA gene.

Metabolic Age, an Index Based on Basal Metabolic Rate, Can Predict Individuals That are High Risk of Developing Metabolic Syndrome.

INTRODUCTION: Every 10 years, an adult's basal metabolic rate (BMR), independent of their BMI, decreases 1-2% due to skeletal muscle loss, thus decreasing an adult's energy requirement and promoting obesity. Increased obesity augments the risk of developing Metabolic Syndrome (MetS); however, an adult's healthy lifestyle, which increases BMR, can mitigate MetS development. To compare different BMRs for certain ages, Metabolic age (Met-age) was developed. AIM: To assess the association between Met-age and MetS and to determine if Met-age is an indicator of high-risk individuals for MetS. METHODS: Four hundred thirty-five attendees at 2 clinics agreed to participate and gave signed informed consent. MetS risk was assessed by the ESF-I questionnaire. Met-age was determined using a TANITA bio-analyzer. Strengthen of association was determined by calculating Spearman's rho and predictability was evaluated by the area-under-a-receiver-operating characteristic curve (AUC). Difference-in-age (DIA) = [chronological age - Met-age]. RESULTS: There was a difference between the low-risk (n = 155) and the high-risk (n = 280) groups' Met-age (37.8±16.7 v. 62.9±17.3) and DIA (1.3±17.4 v. - 10.5±20.8, p < 0.001). There was a positive correlation between the ESF-I questionnaire and Met-age (rho = - 0.624, p < 0.001) and a negative correlation for DIA (rho = - 0.358, p < 0.001). Met-age was strongly predictive (AUC = 0.84, 95% CI 0.80-0.88), suggesting a 45.5 years cutoff (sensitivity = 83.2%, specificity = 72.3%). DIA was a good predictor (AUC = 0.68, 95% CI 0.63-0.74) with a - 11.5 years cutoff (sensitivity = 52.5%, specificity = 82.8%). CONCLUSION: Met-age highly associated with and is an indicator of high-risk individuals for MetS. This would suggest that increases in Met-age are associated with augmented MetS severity, independent of the individual's chronological age.

[Association between metabolic syndrome, socioeconomic status and quality of life in mexicans]. / Asociación entre síndrome metabólico, nivel socioeconómico y calidad de vida en mexicanos.

Background: In Mexico there is little information regarding the link between metabolic syndrome (MetS), socioeconomic status (SES) and quality of life (QoL). Objective: To assess the association between subjects who are at high risk of developing MetS with SES and QoL. Material and methods: Patients attending UMF-2 IMSS or Centro Urbano-SSA Clínica-1 were asked to participate. Anthropometric measures were collected, the AMAI, SF12, and ESF-I questionnaire where apply for SES, QoL, and MetS, respectively. Association were determined by calculating Spearman's rho and the risk (odds ratio and 95% confidence-interval) was assessed using logistic regression. Results: The difference of SES (193 ± 53 vs. 124 ± 50) and QoL (86.3 ± 14.8 vs. 56.0±25.4) questionnaires were significantly between low-risk and high-risk groups, respectively (p < 0.001). There was a negative correlation between ESF-I and SES (rho = -0.623, p < 0.001) as well as the QoL (rho = -0.719, p < 0.001). MetS risk was augmented by decreasing SES (C+: OR = 6.4, 95%IC: 3.2-13.0; D: OR = 66.1, 95%IC: 23.2-188.3), whereas increasing QoL attenuated it (OR = 0.93, 95%CI: 0.91-0.94). However, QoL mitigated the effect of SES (C+: OR = 4.5, 95%IC: 2.1-9.6; D: OR = 11.9, 95%IC: 3.8-37.6). Conclusions: Lower QoL and SES increased the risk of MetS in Central Mexico; however, improving the QoL can mitigated the effect SES has on developing MetS.

Introducción: en México existe escasa información respecto al vínculo entre el síndrome metabólico (MetS), el nivel socioeconómico (NSE) y la calidad de vida (CdV) de la población. Objetivo: evaluar la asociación entre sujetos que tienen alto riesgo de desarrollar MetS con NSE y CdV. Material y métodos: se invitó a participar a pacientes de la UMF-2 del IMSS y del Centro Urbano-SSA Clínica-1. Se recolectaron medidas antropométricas y se aplicaron los cuestionarios AMAI, SF12 y ESF-I para NSE, CdV y MetS, respectivamente. La asociación se determinó calculando rho de Spearman. El riesgo se evaluó mediante regresión logística (razon de momios e intervalo de confianza del 95%). Resultados: la diferencia entre NSE (193 ± 53 frente a 124 ± 50) y CdV (86.3 ± 14.8 frente a 56.0 ± 25.4) fue significativa entre los grupos de bajo y alto riesgo, respectivamente (p < 0.001). Hubo una fuerte correlación negativa entre las puntuaciones de la ESF-I y NSE (rho = -0.623, p < 0.001) así como con la CdV (rho = -0.719, p < 0.001). El riesgo de MetS aumentó al disminuir el NSE (C+: OR = 6.4, IC95%: 3.2 - 13.0; D: OR = 66.1, IC95%: 23.2 - 188.3), mientras que el aumento de la CdV lo atenuó (OR = 0.93, IC95%: 0.91 - 0.94). Interesantemente, la CdV mitigó el efecto del NSE (C+: OR = 4.5, IC95%: 2.1 - 9.6; D: OR = 11.9, IC95%: 3.8 - 37.6). Conclusión: Una menor CdV y NSE aumentan el riesgo de MetS en la región centro de México; sin embargo, el aumento en la CdV podría disminuir el efecto que tiene el NSE en el desarrollo de MetS.

Metabolic age correlates better than chronological age with waist-to-height ratio, a cardiovascular risk index.

OBJECTIVES: Chronological age confers an increased risk for cardiovascular disease; however, chronological age does not reflect the subject's current health status. Therefore, we assessed whether Metabolic age (Met-age), based on free fat mass, is a predictor of cardiovascular risk (CVR). METHODS: Subjects attending either IMSS UMF-2 or CUSC-1 were asked to participate. CVR was assessed using the waist-to-height ratio (WHtR), whereas Met-age was determined using the TANITA bio-analyser (model: BC-545F Fitscan). The strengthen of association was determined by calculating Pearson's r and predictability was determined by the area-under-a-receiver-operating characteristic curve (AUC). RESULTS: 284 subjects participated in this study, of which 61.6% had increased CVR. As expected, the chronological age was significantly higher in the CVR(+) group than the CVR(-) group (47.3±14.4 v. 35.2±12.7, respectively, p<.001) as well as Met-age (59.3±15.5 v. 34.3±14.3, respectively, p<.001). There was a strong association between WHtR and Met-age (r=.720, p<.001) and a moderate association for chronological age (r=.407 p<.001); however, the correlation between WHtR and Met-age was significantly better than chronological age (Z=-5.91, p<.01). Met-age was a good predictor of CVR (AUC=.88, 95%CI: .83-.92, p<.001), whereas chronological age was a fair predictor (AUC=.72, 95%CI: .66-.78, p<.001). However, Met-age showed a higher discriminatory capacity for CVR than chronological age (z=-4.597, p<.001). CONCLUSIONS: Here, we determined that Met-age correlated with a CVR index, WHtR, and was able to predict subjects with increased CVR better than chronological age.

Diets with lower carbohydrate concentrations improve insulin sensitivity in women with polycystic ovary syndrome: A meta-analysis.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) are associated with increased levels of insulin resistance (IR). Other than treatment with insulin-sensitizing drugs, specialized diets have also been implemented to reduce the patient's IR. However, the capacity of certain diets, concerning with the severity of the patient's IR, to improve insulin sensitivity has not fully been explored. Therefore, we conducted a meta-analysis to determine in PCOS subjects from low to severe IR, if hypocaloric diets improve insulin sensitivity. STUDY DESIGN: PubMed, SCOPUS, EBSCO, and LILACS databases and retrieved studies' bibliographies were searched for prospective studies that investigated the association between diets and IR in PCOS women until October 2018. Diet was defined as a modification of the patients' nutrition intake according to caloric restriction, change in protein intake, or by using a specialized diet. IR measures (HOMA1-IR), pre- and post-intervention were extracted. Using Comprehensive Meta-Analysis software, depending on the level heterogeneity, determined by the ψ2-based Q-test and the I2-test, fixed-effects or random-effects models were used to calculate the pooled standard paired differences (SPD) and 95 %CI. RESULTS: 20 publications (25 studies) fulfilled the inclusion criteria. Due to the heterogeneity of the diets, the random-effects model was used. In 48 % of the studies, the diets led to a decrease of IR, where 44 % had no effect. In 2 studies, the diets increased IR. Overall, the diets decreased IR (SPD=-0.58; 95 %CI: -0.81 to -0.36). Subjects with severe IR (HOMA1-IR>4.2) had a marked improvement (SPD=-1.22; 95 %CI: -1.61 to -0.84). Moreover, diets low in carbohydrate (<50 %) was also determined to improve IR (SPD=-0.86; 95 %CI: -1.23 to -0.50). CONCLUSIONS: Here, we demonstrate that diets are more likely to improve IR in PCOS women with severe IR. Therefore, it is crucial to determine a subject's IR status before considering any intervention containing a diet.

Embryos derived from donor or patient oocytes are not different for in vitro fertilization outcomes when PGT allows euploid embryo selection: a retrospective study.

BACKGROUND: At our facilities, patients that received embryos using donor oocyte during in vitro fertilization (IVF), usually have had at least one failed attempt to produce at least one euploid embryo with their own oocytes; however, the current debate between using donor over patient oocytes remains inconclusive. We examined the aneuploidy rate and IVF clinical outcomes from embryos derived from either donor or patient oocytes. METHODS: Retrospectively, 973 cycles were examined of patients who underwent a standard IVF protocol. Chromosomal content was determined using Pre-implantation Genetic Testing (PGT) by either microarray-comparative genomic hybridization or Next-generation sequencing from either Day 3 (blastocysts) or Day 5 (trophectoderm) embryo biopsies, respectively. Embryo implantation was confirmed by serum ß-hCG (> 10 m IU/mL/Day 14), whereas clinical pregnancy by a fetal heartbeat (Week 6.5-8). RESULTS: Embryos derived from donor oocytes presented with more monosomies than embryos derived from patient oocytes (41.2% vs. 25.4%, p < 0.05, respectively); however, only Trisomy 7 (0.4% vs. 2.3%, p < 0.05) and Trisomy in X (0.7% vs. 2.3%, p < 0.05) were significantly less present when compared to patient oocyte derived embryos. Interestingly, rates for embryo implantation (46.7% vs. 50.8%, p = 0.35), clinical pregnancy (38.5% vs. 43.1%, p = 0.30), and live birth (30.5% vs. 30.5%, p = 0.99) were similar for embryos derived from donor and patient oocytes. These results did not change when adjusted for the number of embryos implanted. CONCLUSION: Here, we show no significant differences in achieving pregnancy when using donor oocytes. Taking into consideration that aneuploidy rates are > 30% in embryos, independent of the oocyte origin, PGT should be recommended with donor oocytes as well.

The Association Between Interleukin-6 Promoter Polymorphisms and Rheumatoid Arthritis by Ethnicity: A Meta-Analysis of 33 Studies.

OBJECTIVE: We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (-174 G>C, -572 G>C, and -597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity. MATERIAL AND METHODS: PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. RESULTS: From 708 identified publications, 33 were used in this analysis. For the -174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28-25.14, ORhomozygous=5.84, 95%CI: 2.06-16.56, ORdominant=7.21, 95%CI: 2.30-22.63, ORrecessive=5.04, 95%CI: 1.78-14.28, ORallelic=6.60, 95%CI: 2.26-19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10-4.81, ORdominant=2.27, 95%CI: 1.22-4.22, ORallelic=2.29, 95%CI: 1.24-4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08-.82, ORrecessive=.25, 95%CI: .08-.80, p<.05). For the -572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16-2.09, ORrecessive=1.63, 95%CI: 1.08-2.45, p<.05). For the -597 polymorphism, no association was observed. CONCLUSIONS: Here, the -174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the -572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.