The Diagnostic Value of Biomarkers in Acute Mesenteric Ischaemia Is Insufficiently Substantiated: A Systematic Review.

OBJECTIVE: There is an urgent need for accurate biomarkers to support timely diagnosis of acute mesenteric ischaemia (AMI) and thereby improve clinical outcomes. With this systematic review, the aim was to substantiate the potential diagnostic value of biomarkers for arterial occlusive AMI. DATA SOURCES: The Pubmed, Embase, and the Cochrane Library electronic databases were searched. REVIEW METHODS: A systematic review of the literature has been conducted to define the potential diagnostic value of biomarkers for arterial occlusive AMI. All studies including ≥ 10 patients describing biomarkers for macrovascular occlusive AMI between 1950 and 17 February 2023 were identified within the Pubmed, Embase, and the Cochrane Library electronic databases. There were no restrictions to any particular study design, but letters and editorials were excluded. The QUADAS-2 tool was used for the critical appraisal of quality. The study protocol was registered on Prospero (CRD42021254970). RESULTS: Fifty of 4334 studies were eligible for inclusion in this review. Ninety per cent of studies were of low quality. A total of 60 biomarkers were identified, with 24 in two or more studies and 15 in five or more studies. There was variation in reported units, normal range, and cut off values. Meta-analysis was not possible due to study heterogeneity. Biomarkers currently recommended by the European Journal of Vascular and Endovascular Surgery, European Society for Trauma and Emergency Surgery 2016, and World Society of Emergency Surgery 2017 guidelines also had heterogeneous low quality data for use in the diagnosis of AMI. CONCLUSION: This systematic review demonstrates high heterogeneity and low quality of the available evidence on biomarkers for arterial occlusive AMI. No clinical conclusions can be drawn on a biomarker or combination of biomarkers for patients suspected of arterial occlusive AMI. Restraint is advised when rejecting or determining AMI solely based on biomarkers.

Structural and functional properties of the Kunitz-type and C-terminal domains of Amblyomin-X supporting its antitumor activity.

Amblyomin-X is a Kunitz-type FXa inhibitor identified through the transcriptome analysis of the salivary gland from Amblyomma sculptum tick. This protein consists of two domains of equivalent size, triggers apoptosis in different tumor cell lines, and promotes regression of tumor growth, and reduction of metastasis. To study the structural properties and functional roles of the N-terminal (N-ter) and C-terminal (C-ter) domains of Amblyomin-X, we synthesized them by solid-phase peptide synthesis, solved the X-Ray crystallographic structure of the N-ter domain, confirming its Kunitz-type signature, and studied their biological properties. We show here that the C-ter domain is responsible for the uptake of Amblyomin-X by tumor cells and highlight the ability of this domain to deliver intracellular cargo by the strong enhancement of the intracellular detection of molecules with low cellular-uptake efficiency (p15) after their coupling with the C-ter domain. In contrast, the N-ter Kunitz domain of Amblyomin-X is not capable of crossing through the cell membrane but is associated with tumor cell cytotoxicity when it is microinjected into the cells or fused to TAT cell-penetrating peptide. Additionally, we identify the minimum length C-terminal domain named F2C able to enter in the SK-MEL-28 cells and induces dynein chains gene expression modulation, a molecular motor that plays a role in the uptake and intracellular trafficking of Amblyomin-X.

Systematic Review of the Efficacy of Treatment for Median Arcuate Ligament Syndrome.

OBJECTIVE: Since the first description of the median arcuate ligament syndrome (MALS), the existence for the syndrome and the efficacy of treatment for it have been questioned. METHODS: A systematic review conforming to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was conducted, with a broader view on treatment for MALS including any kind of coeliac artery release, coeliac plexus resection, and coeliac plexus blockage, irrespective of age. Online databases were used to identify papers published between 1963 and July 2021. The inclusion criteria were abdominal symptoms, proof of MALS on imaging, and articles reporting at least three patients. Primary outcomes were symptom relief and quality of life (QoL). RESULTS: Thirty-eight studies describing 880 adult patients and six studies describing 195 paediatric patients were included. The majority of the adult studies reported symptom relief of more than 70% from three to 228 months after treatment. Two adult studies showed an improved QoL after treatment. Half of the paediatric studies reported symptom relief of more than 70% from six to 62 months after laparoscopic coeliac artery release, and four studies reported an improved QoL. Thirty-five (92%) adult studies and five (83%) paediatric studies scored a high or unclear risk of bias for the majority of the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) items. The meaning of coeliac plexus resection or blockage could not be substantiated. CONCLUSION: This systematic review suggests a sustainable symptom relief of more than 70% after treatment for MALS in the majority of adult and paediatric studies; however, owing to the heterogeneity of the inclusion criteria and outcome parameters, the risk of bias was high and a formal meta-analysis could not be performed. To improve care for patients with MALS the next steps would be to deal with reporting standards, outcome definitions, and consensus descriptions of the intervention(s), after which an appropriate randomised controlled trial should be performed.

Association between CACNG2 polymorphisms (rs4820242, rs2284015 and rs2284017) and chronic peripheral neuropathic pain risk in a Mexican population.

OBJECTIVE: In animal models and humans, mutations in voltage-dependent calcium channel gamma-2 subunit gene (CACNG2) have been associated with neuronal hyperexcitability, including neuropathic pain. The objective of this study was to determine the allelic and genotypic frequencies of CACNG2 polymorphisms (rs4820242, rs2284015 and rs2284017) and their association with the risk of chronic peripheral neuropathic pain (CPNP) in the Mexican population. PATIENTS AND METHODS: Single nucleotide polymorphisms (SNPs) were determined by real-time PCR, and allelic and genotypic frequencies were compared between healthy Mexican subjects and CPNP patients. The risk of association of CACNG2 SNPs with the presence of CPNP and its characteristics was evaluated. RESULTS: The allele G (OR 2.08, p = 0.01) of rs2284015 was observed as a risk factor for developing CPNP. The allele A of rs4820442 showed a risk of association with a history of surgery (OR 3.92, p = 0.04), radiculopathy (OR 4.29, p = 0.0001), bilateral presentation of pain (OR 3.15, p = 0.003), and neuropraxia (OR 0.36, p = 0.01). The allele C of rs2284015 was associated with an increased risk of burning and allodynia. In the analysis of the association of genotype frequencies and inheritance patterns, as well as in the analysis of interaction with sex, a modification of risk was observed. CONCLUSIONS: The allele G of rs2284015 and the AGC haplotype of CACNG2 rs4820242, rs2284015 and rs2284017, regardless of sex and etiology could contribute to the risk of CPNP. Certain alleles and genotypes could constitute severity markers in CPNP with sex-biased effects; however, further studies are required to confirm these observations.

How we approach the treatment of patients with high-risk neuroblastoma with naxitamab: experience from the Hospital Sant Joan de Déu in Barcelona, Spain.

Naxitamab [humanized 3f8 (hu3F8)] is a humanized monoclonal antibody (mAb) targeting the disialoganglioside GD2. It was approved in 2020 by the United States Food and Drug Administration (FDA) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for treatment of pediatric and adult patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow (BM). The team at Sant Joan de Déu Children's Hospital in Barcelona, Spain, have been using naxitamab to treat neuroblastoma under clinical trial protocols [e.g. Trial 201, and hu3F8, irinotecan, temozolomide, and sargramostim (GM-CSF) (HITS) study] and compassionate use since 2017. The team has experience with two primary regimens: naxitamab with GM-CSF only, or naxitamab in combination with irinotecan, temozolomide, and GM-CSF (chemoimmunotherapy). This article aims to provide a practical overview of the team's experience with naxitamab to date, including preparing the treatment room and selecting the team. Adverse event management, including the use of ketamine to manage pain during anti-GD2 mAb infusions, is also discussed. We hope this will provide practical information for other health care providers considering offering this treatment.

[The methodology of calculation of indices of provision of population with beds of palliative medical care].

The enhancement of organization of palliative medical care to increase life quality of terminally ill patients is one of directions of development of health care system. To elaborate measures of improving accessibility and quality of palliative medical care, it is necessary to apply single unified methodology of calculating indices and criteria. One of them is provision of bed capacity. The purpose of the study is to elaborate methodology of calculating control indices of provision population with beds to render palliative medical care. The indices are calculated on the basis of statistical processing of monitoring corresponding data in the subjects of the Russian Federation.

Development of Monitoring and Mating Disruption against the Chilean Leafroller Proeulia auraria (Lepidoptera: Tortricidae) in Orchards.

The leafroller Proeulia auraria (Clarke) (Lepidoptera: Tortricidae) is a native, polyphagous, and growing pest of several fruit crops in Chile; it also has quarantine importance to several markets, thus tools for management are needed. Using synthetic pheromone compounds, we conducted field trials to optimize the blend for monitoring, and to determine the activity period of rubber septa aged under field conditions. We concluded that septa loaded with 200 µg of E11-14:OAc + 60 µg E11-14:OH allowed for efficient trap captures for up to 10 weeks. Using this blend, we studied the phenology of adult males in vineyards, apple, and blueberry orchards, identifying two long flight cycles per season, lasting from September to May and suggesting 2-3 generations during the season. No or low adult activity was observed during January and between late May and late August. Furthermore, mating disruption (MD) field trials showed that application of 250 pheromone point sources using the dispenser wax matrix SPLAT (Specialized Pheromone and Lure Application Technology, 10.5% pheromone) with a total of 78 g/ha of the blend described above resulted in trap shutdown immediately after application, and mating disruption >99% in all orchards for at least 5 months. We concluded that MD is feasible for P. auraria, needing now the development of a commercial product and the strategy (and protocols) necessary to control this pest in conventional and organic orchards in Chile. As far as we know, this is the first report on MD development against a South American tortricid pest.

Quantification of the radiosensitization effect of high-Znanoparticles on photon irradiated cells: combining Monte Carlo simulations and an analytical approach to the local effect model.

In vitroexperiments show significant reduction in the survival fraction of cells under irradiation treatments assisted with high-Znanoparticles (NPs). In order to predict the radiosensitization effect of NPs, a modification of the local effect model (LEM), in which the energy deposition from NPs is assessed by Monte Carlo (MC) radiation transport codes, has been employed in the past. In this work, a combined framework that splits the consideration of the radiosensitization effect into two steps is proposed. The first step is the evaluation of the radial dose distribution (RDD) around a single NP ionized by a photon beam with given energy spectrum using MC simulation. Thereafter, an analytical approach based of the LEM and the calculated RDD is used for evaluation of the average dose and the average number of lethal lesions in a cell target due to a set of ionized NPs. The explicit expressions were derived for the case of a spherical cell target and the RDD describing by the power law function. RDDs around gold NPs (GNPs) of different radii were simulated using the MC technique and fitted by a power law function. The fitted RDD and the derived expressions were applied for calculation of the survival curves and relative biological effectiveness of a spherical MDA-MB-231 cell loaded with GNPs and irradiated with monoenergetic photons of 10-150 keV. The proposed framework provides a practical alternative to time-consuming MC simulations, enabling the assessment of the response of cell cultures to an irradiation treatment assisted with NPs for a wide variety of cell geometries, NP distributions and irradiation schemes.

Wnt/ß-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties.

The Wnt/ß-catenin pathway plays an important role in tumor progression and chemotherapy resistance and seems to be essential for the maintenance of cancer stem cells (CSC) in several tumor types. However, the interplay of these factors has not been fully addressed in bladder cancer. Here, our goal was to analyze the role of the Wnt/ß-catenin pathway in paclitaxel resistance and to study the therapeutic efficacy of its inhibition in bladder cancer cells, as well as to determine its influence in the maintenance of the CSC-like phenotype in bladder cancer. Our results show that paclitaxel-resistant HT1197 cells have hyperactivation of the Wnt/ß-catenin pathway and increased CSC-like properties compared with paclitaxel-sensitive 5637 cells. Paclitaxel sensitivity diminishes in 5637 cells after ß-catenin overexpression or when they are grown as tumorspheres, enriched for the CSC-like phenotype. Additionally, downregulation of ß-catenin or inhibition with XAV939 sensitizes HT1197 cells to paclitaxel. Moreover, a subset of muscle-invasive bladder carcinomas shows aberrant expression of ß-catenin that associates with positive expression of the CSC marker ALDH1A1. In conclusion, we demonstrate that Wnt/ß-catenin signaling contributes to paclitaxel resistance in bladder cancer cells with CSC-like properties.

Noncoding RNAs as potential biomarkers for DIPG diagnosis and prognosis: XIST and XIST-210 involvement.

PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) are the most fatal primary brainstem tumors in pediatric patients. The identification of new molecular features, mediating their formation and progression, as non-coding RNAs (ncRNAs), would be of great importance for the development of effective treatments. METHODS: We analyzed the DIPGs transcriptome with the HTA2.0 array and it was compared with pediatric non-brainstem astrocytoma expression profiles (GSE72269). RESULTS: More than 50% of the differentially expressed transcripts were ncRNAs and based on this, we proposed a DIPGs ncRNA signature. LncRNAs XIST and XIST-210, and the HBII-52 and HBII-85 snoRNA clusters were markedly downregulated in DIPGs. qPCR assays demonstrated XIST downregulation in all non-brainstem astrocytomas, in a gender, age, and brain location-independent manner, as well as in DIPGs affecting boys; however, DIPGs affecting girls showed both downregulation and upregulation of XIST. Girls' with longer survival positively correlated with XIST expression. CONCLUSIONS: The involvement of ncRNAs in DIPGs is imminent and their expression profile is useful to differentiate them from non-neoplastic tissues and non-brain stem astrocytomas, which suggests their potential use as DIPG biomarkers. In fact, XIST and XIST-210 are potential DIPG prognostic biomarkers.

Opsoclonus-myoclonus-ataxia syndrome associated with central nervous system HIV-1 escape phenomenon. / Síndrome opsoclono-mioclono-ataxia asociado a fenómeno de escape viral por virus de la inmunodeficiencia humana en el sistema nervioso central.

INTRODUCTION: Opsoclonus-myoclonus-ataxia (OMA) syndrome is a rare neurological disorder characterized by involuntary conjugate saccadic eye movements, myoclonus, and ataxia. Few reports exist on patients with HIV and OMA. CASE REPORT: A 41-year-old man diagnosed with HIV-1 infection in 1997 coursed with multiple anti-retroviral schemes as a consequence of poor adherence. In 2008 he presented an HIV-1 viral load of 100,000 copies/mL and a CD4+ T cell count of 10 cells/mm3. In 2013 our patient arrived with an 11-month history of progressive opsoclonus and ataxia. He had undetectable plasma HIV-1 RNA load and CD4+ of 606 cells/mm3. No opportunistic infections were found. Cerebrospinal fluid analysis showed mildly elevated protein concentration and HIV-1 viral load of 534 copies/mL. Cerebrospinal fluid co-receptor tropism test showed selective CCR5 usage. A brain magnetic resonance imaging showed hippocampal atrophy and T2-weighted hyperintensities. Our patient exhibited a dramatic recovery and cerebrospinal fluid HIV clearance after adjustment of anti-retroviral treatment based on genotyping resistance and tropism analyses. CONCLUSIONS: In patients with HIV presenting cengral nervous system dysfunction without opportunistic infections, cerebro-spinal fluid and plasma HIV-1 viral load, resistance and tropism tests should be performed to assess a potential viral escape and to design the appropriate anti-retroviral therapy in an individual patient basis.

TITLE: Síndrome opsoclono-mioclono-ataxia asociado a fenómeno de escape viral por virus de la inmunodeficiencia humana en el sistema nervioso central.Introducción. El síndrome opsoclono-mioclono-ataxia (OMA) es un trastorno neurológico infrecuente caracterizado por movimientos oculares conjugados sacádicos involuntarios, mioclonías y ataxia. Existen pocos casos en la bibliografía de pacientes con virus de la inmunodeficiencia humana (VIH) y OMA. Caso clínico. Varón de 41 años y diagnóstico de infección por el VIH-1 desde 1997, que cursó con múltiples esquemas antirretrovirales debido a una pobre adhesión al tratamiento. En 2008 presentó una carga viral de 100.000 copias/mL y una cuenta linfocitaria CD4+ de 10 células/mm3. En 2013 sufrió un cuadro progresivo de 11 meses de evolución caracterizado por opsoclonía y ataxia. En ese momento, su carga viral era indetectable, y la cuenta de CD4+, de 606 células/mm3. Se descartaron infecciones oportunistas. El examen del líquido cefalorraquídeo demostró hiperproteinorraquia leve y una carga viral de 534 copias/mL. El examen del tropismo de correceptor en el líquido cefalorraquídeo demostró un uso selectivo de CCR5. La resonancia magnética cerebral objetivó atrofia hipocámpica e hiperintensidades en las secuencias ponderadas en T2. El paciente mostró una recuperación clínica franca y un aclaramiento de la carga viral en el líquido cefalorraquídeo tras el ajuste de antirretrovirales basado en la resistencia de genotipo y el análisis de tropismo. Conclusiones. En pacientes con infección por el VIH y disfunción del sistema nervioso central sin infecciones oportunistas, debería llevarse a cabo una determinación de la carga viral en el plasma y el líquido cefalorraquídeo para descartar un potencial fenómeno de escape viral, así como exámenes de resistencia y tropismo para diseñar el tratamiento antirretroviral adecuado.

EDIL3 promotes epithelial-mesenchymal transition and paclitaxel resistance through its interaction with integrin αVß3 in cancer cells.

Epithelial-mesenchymal transition (EMT) has recently been associated with tumor progression, metastasis, and chemotherapy resistance in several tumor types. We performed a differential gene expression analysis comparing paclitaxel-resistant vs. paclitaxel-sensitive breast cancer cells that showed the upregulation of EDIL3 (EGF Like Repeats and Discoidin I Like Domains Protein 3). This gene codifies an extracellular matrix protein that has been identified as a novel regulator of EMT, so we studied its role in tumor progression and paclitaxel response. Our results demonstrated that EDIL3 expression levels were increased in paclitaxel-resistant breast and prostate cancer cells, and in subsets of high-grade breast and prostate tumors. Moreover, we observed that EDIL3 modulated the expression of EMT markers and this was impaired by cilengitide, which blocks the EDIL3-integrin αVß3 interaction. EDIL3 knockdown reverted EMT and sensitized cells to paclitaxel. In contrast, EDIL3 overexpression or the culture of cells in the presence of EDIL3-enriched medium induced EMT and paclitaxel resistance. Adding cilengitide resensitized these cells to paclitaxel treatment. In summary, EDIL3 may contribute to EMT and paclitaxel resistance through autocrine or paracrine signaling in cancer cells. Blockade of EDIL3-integrin αVß3 interaction by cilengitide restores sensitivity to paclitaxel and reverts EMT in paclitaxel-resistant cancer cells. Combinations of cilengitide and taxanes could be beneficial in the treatment of subsets of breast and prostate cancers.

Nicotinamide reduces inflammation and oxidative stress via the cholinergic system in fructose-induced metabolic syndrome in rats.

AIMS: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been associated with risk factors for metabolic syndrome (MetS). Our objective was to evaluate the effect of nicotinamide (NAM) on the activities, expression and protein content of cholinesterases in a MetS model. MAIN METHODS: MetS was induced in male rats administrating 40% fructose to the drinking water for 16 weeks. Additionally, from 5th week onward, the carbohydrate solution was replaced by NAM, at several concentrations for 5 h each morning for the next 12 weeks. In the 15th week, the glucose tolerance test was conducted, and blood pressure was measured. After the treatment period had concluded, the biochemical profile; oxidant stress; proinflammatory markers; and the activity, quantity and expression of cholinesterases were evaluated, and molecular docking analysis was performed. KEY FINDINGS: The MetS group showed anthropometric, hemodynamic and biochemical alterations and increased cholinesterase activity, inflammation and stress markers. In the liver, cholinesterase activity and mRNA, free fatty acid, tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid-reactive substance (TBARS) levels were increased, while reduced glutathione (GSH) levels were decreased. NAM partially or totally decreased risk factors for MetS, markers of stress and inflammation, and the activity (serum and liver) and expression (liver) of cholinesterases. Molecular docking analysis showed that NAM has a greater affinity for cholinesterases than acetylcholine (ACh), suggesting NAM as an inhibitor of cholinesterases. SIGNIFICANCE: Supplementation with 40% fructose induced MetS, which increased the activity and expression of cholinesterases, oxidative stress and the inflammation. NAM attenuated these MetS-induced alterations and changes in cholinesterases.

Age, Gleason Score, and PSA are important prognostic factors for survival in metastatic castration-resistant prostate cancer. Results of The Uroncor Group (Uro-Oncological Tumors) of the Spanish Society of Radiation Oncology (SEOR).

INTRODUCTION: The treatment of metastatic castration-resistant prostate cancer (mCRPC) has changed significantly in recent years. Inhibitors of androgen receptors have shown especially significant benefits in overall (OS) and progression-free survival (PFS), with a good toxicity profile. Treatment selection depends on the patient's individual clinical, radiological, and biological characteristics. OBJECTIVE: To describe treatment outcomes (efficacy, toxicity) in a cohort of patients with mCRPC in Spain. MATERIALS AND METHODS: Multicenter, retrospective study of patients with mCRPC included in a database of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR). Metastatic CRPC was defined according to the prostate cancer working group 3 (PCWG3) criteria. The Kaplan-Meier technique was used to evaluate OS and the Common Terminology Criteria for Adverse Events (CTCAE, v.4.0) were used to assess toxicity. Univariate and multivariate Cox regression analyses were performed to identify the factors significantly associated with OS. RESULTS: A total of 314 patients from 17 hospitals in Spain diagnosed with mCRPC between June 2010 and September 2017 were included in this study. Mean age at diagnosis was 68 years (range 45-89). At a median follow-up of 35 months, OS at 1, 3, and 5 years were 92%, 38%, and 28%, respectively. Grades 1-2 and grade 3 toxicity rates were, respectively, 68% and 19%. No grade 4 toxicities were observed. On the multivariate analysis, the following factors were significantly associated with OS: age (hazard ratio [HR] 0.42, p = 0.010), PSA value at diagnosis of mCRPC (HR 0.55, p = 0.008), and Gleason score (HR 0.61, p = 0.009). CONCLUSIONS: Age, Gleason score, and PSA at diagnosis of mCRPC are independently associated with overall survival in patients with mCRPC. The efficacy and toxicity outcomes in this patient cohort treated in radiation oncology departments in Spain are consistent with previous reports.

Factors associated with infection of primary total knee prosthesis in older adults in a referral hospital in Peru. 2012-2015. / Factores asociados a infección de prótesis total de rodilla primaria en adultos mayores en un hospital de referencia en Perú. 2012-2015.

OBJECTIVE: To determine the risk factors associated with prosthetic knee infection in elderly patients in a referral hospital in Peru. PATIENTS AND METHODS: A case and control study was performed. The calculated sample was 44 cases and 132 controls. The data were collected retrospectively from clinical records. U-Mann Whitney and Chi-square tests were performed in the comparison of cases and controls. Odds ratios (OR) were calculated in a binary logistic regression analysis to identify the risk factors, a P<.05 and a 95% confidence interval (CI) were considered significant. RESULTS: Significant (P<.05) risk factors evidenced in the bivariate analysis were obesity (OR=9.72; 95%CI: 4.47-21.14), smoking (OR=4.06; 95%CI: 1.59-10.39), rheumatoid arthritis (OR=4.66; 95%CI: 1.52-14.32), diabetes mellitus type2 (OR=5.63; 95%CI: 2.69-11.78), persistent drainage (OR=9.27; 95%CI: 3.85-22.31), superficial infection (OR=6.87; 95%CI: 3.25-14.49) and prolonged hospital stay (OR=4.67; 95%CI: 2.26-9.64). In the multivariate analysis where it was adjusted for confounding variables, it was determined that risk factors were obesity (ORa=9.14; 95%CI: 3.28-25.48), diabetes mellitus (ORa=3.77; 95%CI: 1.38-10.32), persistent drainage (ORa=4.64; 95%CI: 1.03-20.80) and superficial wound infection (ORa=27.35; 95%CI: 2.57-290.64). CONCLUSIONS: Risk factors for prosthetic knee infection identified in this study are preventable. The main risk factors were obesity, diabetes mellitus type2, superficial wound infection and persistent drainage, which were considered together or separately to be risk factors in the population studied.

COL1A1, CCDC170, and ESR1 single nucleotide polymorphisms associated with distal radius fracture in postmenopausal Mexican women.

Objective: The aim of this study was to analyze the genetic association of five ESR1 single nucleotide polymorphisms (SNPs) (rs3020331, rs851982, rs1999805, rs2234693, rs3020404), four COL1A1 SNPs (rs1800012, rs2075555, rs2412298, rs1107946), and two SNPs on the CCDC170 gene (rs9479055, rs4870044) with distal radius fracture (DRF) in a group of postmenopausal Mexican women.Methods: A case-control study was conducted. Cases (n = 182) were women above the age of 38 years with low-energy DRF, and controls (n = 201) were women without. Analysis was done through real-time polymerase chain reaction. Frequencies and Hardy-Weinberg equilibrium were calculated. A multivariate analysis including bone mass index, age, menarche, and menopause as covariables was carried out. Finally, haplotype and linkage disequilibrium (LD) analyses were performed.Results:COL1A1 rs1107946 was strongly associated with DRF. Both CCDC170 SNPs showed strong association with DRF. For the ESR1 gene, four SNPs (rs2234693, 3020404, rs3020331, and rs851982) showed very strong association with DRF. Additionally, the region between the latter two showed strong LD.Conclusions: A strong association of DRF with variants in these genes was found, including haplotypes and a region with strong LD on ESR1. The results suggest that these SNPs could be useful to detect the population at risk of presenting DRF among Mexican perimenopausal women.

High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymes.

An imbalance in the redox state, increased levels of lipid precursors and overactivation of de novo lipogenesis determine the development of fibrosis during nonalcoholic steatohepatitis (NASH). We evaluated the modulation of NADPH-producing enzymes associated with the antifibrotic, antioxidant and antilipemic effects of nicotinamide (NAM) in a model of NASH induced by excess fructose consumption. Male rats were provided drinking water containing 40% fructose for 16 weeks. During the last 12 weeks of fructose administration, water containing NAM was provided to some of the rats for 5 h/day. The biochemical profiles and the ghrelin, leptin, lipoperoxidation and TNF-α levels in serum and the glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and NADP+-dependent isocitric dehydrogenase (IDP) levels, the reduced/oxidized glutathione (GSH/GSSG) and reduced/oxidized nicotinamide adenine dinucleotide (phosphate) (NAD(P)H/NAD(P)+) ratios, and the levels of various lipogenic and fibrotic markers in the liver were evaluated. The results showed that hepatic fibrosis induced by fructose consumption was associated with weight gain, hunger-satiety system dysregulation, hyperinsulinemia, dyslipidemia, lipoperoxidation and inflammation. Moreover, increased levels of hepatic G6PD and ME activity and expression, the NAD(P)H/NAD(P)+ ratios, and GSSG concentration and increased expression of lipogenic and fibrotic markers were detected, and these alterations were attenuated by NAM administration. Specifically, NAM diminished the activity and expression of G6PD and ME, and this effect was associated with a decrease in the NADPH/NADP+ ratios, increased GSH levels and decreased lipoperoxidation and inflammation, ameliorating fibrosis and NASH development. NAM reduces liver steatosis and fibrosis by regulating redox homeostasis through a G6PD- and ME-dependent mechanism.