Sexual experiences and knowledge of people with moderate intellectual disability.

BACKGROUND: This study addresses the sexuality of people with moderate intellectual disabilities (PMID), a topic that has been little studied. Understanding romantic and sexual experiences is highly relevant for reducing stigma and prejudice related to their sexuality. Additionally, comprehending the level of sexual knowledge of PMID contributes to the development of preventive and sexual health education programmes tailored for this group. Our aim is to explore the sexual history (relationships, sexual behaviour, condom use and sexual abuse), sex education received and the level of sexual knowledge of PMID. METHOD: The total of 142 PMID completed questionnaires about sexual knowledge and experiences, and their support staff provided additional information. Data were analysed using chi-square test (χ2) and descriptive statistical analysis. RESULTS: Masturbation was the most common sexual behaviour (75.7%), especially among men (χ2 = 5.81, P < 0.05). Sexual intercourse was rare, and only 30.5% reported using condoms. Women reported a higher prevalence of self-reported sexual abuse (27.3% vs. 6% in men). The study also highlighted misconceptions about sexual intercourse risks and contraceptive methods. CONCLUSION: The results suggest that PMID need sexual education to ensure healthy sexual experiences and prevent risky behaviour.

Hepatocellular adenoma subtyping by qualitative MRI features and machine learning algorithm of integrated qualitative and quantitative features: a proof-of-concept study.

AIM: To evaluate hepatocellular adenoma (HCA) subtyping using qualitative magnetic resonance imaging (MRI) features and feasibility of differentiating HCA subtypes using machine learning (ML) of qualitative and quantitative MRI features with histopathology as the reference standard. MATERIALS AND METHODS: This retrospective study included 39 histopathologically subtyped HCAs (13 hepatocyte nuclear factor (HNF)-1-alpha mutated [HHCA], 11 inflammatory [IHCA], one beta-catenin-mutated [BHCA], and 14 unclassified [UHCA]) in 36 patients. HCA subtyping by two blinded radiologists using the proposed schema of qualitative MRI features and using the random forest algorithm was compared against histopathology. For quantitative features, 1,409 radiomic features were extracted after segmentation and reduced to 10 principle components. Support vector machine and logistic regression was applied to assess HCA subtyping. RESULTS: Qualitative MRI features with proposed flow chart yielded diagnostic accuracies of 87%, 82%, and 74% for HHCA, IHCA, and UHCA respectively. The ML algorithm based on qualitative MRI features showed AUCs (area under the receiver operating characteristic curve [ROC] curve) of 0.846, 0.642, and 0.766 for diagnosing HHCA, IHCA, and UHCA, respectively. Quantitative radiomic features from portal venous and hepatic venous phase MRI demonstrated AUCs of 0.83 and 0.82, with a sensitivity of 72% and a specificity of 85% in predicting HHCA subtype. CONCLUSIONS: The proposed schema of integrated qualitative MRI features with ML algorithm provided high accuracy for HCA subtyping while quantitative radiomic features provide value for diagnosis of HHCA. The key qualitative MRI features for differentiating HCA subtypes were concordant between the radiologists and the ML algorithm. These approaches appear promising to better inform clinical management for patients with HCA.

Modified-dropless protocol (nil intraocular) for micro-incision vitrectomy surgery (MIVS): a retrospective pilot study.

BACKGROUND: Perioperative infection and inflammation prophylaxis after ocular surgery has evolved over the years along with improvements in surgical equipment and a growing interest in alternatives to the standard topical eye drops. The purpose of this study is to evaluate the outcomes of a novel, modified-dropless protocol for 23-gauge (23-G), 25-gauge (25-G) and 27-gauge (27-G) micro-incision vitrectomy surgery (MIVS) that omits any intraocular injections of antibiotics or steroids. METHODS: This Institutional Review Board-approved, single-surgeon retrospective study reviewed MIVS post-surgical outcomes in patients who received a modified-dropless protocol from February 2020 to March 2021. A total of 158 charts were reviewed, of which 150 eyes met the eligibility criteria. After each case, patients were administered a 0.5 cc subconjunctival injection of a 1:1 Cefazolin (50 mg/cc):Dexamethasone (10 mg/cc) in the inferior fornix and 0.5 cc of posterior Sub-Tenon's Kenalog (STK). No intravitreal injections were administered, and no pre- or postoperative antibiotic or steroid eye drops were prescribed. For patients allergic to penicillin, separate subconjunctival injections of 0.25 cc each of Vancomycin (10 mg/cc) and Dexamethasone (10 mg/cc) were administered. The primary safety parameter was postoperative cases of endophthalmitis. Secondary endpoints consisted of Best-Corrected Distance Visual Acuity (BCVA), intraocular pressure (IOP), and postoperative complications (retinal detachments, inflammation, need for additional surgery) within three months of surgery. Statistical analysis was performed using chi-square (χ²) tests for categorical values, and a Student's t-test to compare continuous outcomes. RESULTS: The majority of surgeries (96%) were performed with the 27G MIVS platform. There were no cases of postoperative endophthalmitis. Mean logMAR BCVA improved from 0.71 (± 0.67) to 0.61 (± 0.60) post-operatively (p = 0.02). Excluding patients who had silicone oil tamponade, postoperative BCVA improved from 0.67 (± 0.66) to 0.54 (± 0.55) (p = 0.003). Mean IOP increased from 14.6 (± 3.8) to 15.3 (± 4.1) (p = 0.05). Ten patients required further medication therapy for an increase in IOP, one had inflammatory signs, and 14 required a second surgical intervention mostly due to recurrences of initial surgical indication. CONCLUSION: A modified-dropless postoperative protocol involving subconjunctival and posterior sub-Tenon's injections only may be a safe and convenient alternative to topical eye drops for patients undergoing MIVS, but additional and larger studies are needed.

Nanostructured fibrin-based hydrogel membranes for use as an augmentation strategy in Achilles tendon surgical repair in rats.

Hydrogels are polymeric biomaterials characterised by their promising biological and biomechanical properties, which make them potential alternatives for use in tendon repair. The aim of the present study was to generate in vitro, and determine the therapeutic efficacy in vivo, of novel nanostructured fibrin-based hydrogels to be used as an augmentation strategy for the surgical repair of rat Achilles tendon injuries. Fibrin, fibrin-agarose and fibrin-collagen nanostructured hydrogels (NFH, NFAH and NFCH, respectively) were generated and their biomechanical properties and cell-biomaterial interactions characterised ex vivo. Achilles tendon ruptures were created in 24 adult Wistar rats, which were next treated with direct repair (control group) or direct repair augmented with the generated biomaterials (6 rats/group). After 4 and 8 weeks, the animals were euthanised for macroscopical and histological analyses. Biomechanical characterisation showed optimal properties of the biomaterials for use in tendon repair. Moreover, biological analyses confirmed that tendon-derived fibroblasts were able to adhere to the surface of the generated biomaterials, with high levels of viability and functionality. In vivo studies demonstrated successful tendon repair in all groups. Lastly, histological analyses disclosed better tissue and extracellular matrix organisation and alignment with biomaterial-based augmentation strategies than direct repair, especially when NFAH and NFCH were used. The present study demonstrated that nanostructured fibrin-collagen hydrogels can be used to enhance the healing process in the surgical repair of tendon ruptures.

TAT-Beclin-1 induces severe synovial hyperplasia and does not protect from injury-induced osteoarthritis in mice.

OBJECT: Autophagy maintains cartilage homeostasis and is compromised during osteoarthritis (OA), contributing to cartilage degeneration. We sought to determine if D-isomer TAT-Beclin-1, a potent inducer of autophagy, could attenuate post-traumatic OA in mice. METHODS: 10-week-old mice underwent destabilization of the medial meniscus (DMM) surgery to induce post-traumatic OA, or sham surgery (control), and injected intra-articularly with D-isomer TAT-Beclin-1 (0.5-2 mg/kg) or PBS 1 week post-surgery for up to 9 weeks. Mice were sacrificed at 2 or 10 weeks post-surgery. Knee joint sections were evaluated by histopathology for cartilage degeneration and synovitis, and immunostaining for key markers of autophagy (LC3B), cell proliferation (nuclear Ki67), activated fibroblasts (αSMA), and cells of hematopoietic origin (CD45). RESULTS: All D-isomer TAT-Beclin-1-treated DMM mice had no difference in the degree of cartilage degeneration compared to PBS-injected DMM mice. Surprisingly, all D-isomer TAT-Beclin-1-treated mice exhibited substantial synovial hyperplasia, with increased cellularity and ECM deposition (fibrosis-like phenotype), as compared to PBS-injected mice. Synovial effects of D-isomer TAT-Beclin-1 were dose- and injection frequency-dependent. An increased percentage of cells positive for LC3B and nuclear Ki67 were found in the synovial intima early after injection, which persisted after frequent injections. CONCLUSIONS: D-isomer TAT-Beclin-1 did not attenuate cartilage degeneration, but rather induced synovial hyperplasia associated with increased expression of key markers of autophagy and cell proliferation and a fibrosis-like phenotype, independent of markers of fibroblast activation or persistent hematopoietic-origin cell infiltration. These data suggest that, if not tissue-targeted, caution should be taken using autophagy activators due to diverse cellular responses in the joint.

Suppression of circadian clock protein cryptochrome 2 promotes osteoarthritis.

OBJECTIVES: Abnormal chondrocyte gene expression promotes osteoarthritis (OA) pathogenesis. A previous RNA-sequencing study revealed that circadian rhythm pathway and expression of core clock gene cryptochrome 2 (CRY2) are dysregulated in human OA cartilage. Here we determined expression patterns and function CRY1 and CRY2. METHODS: CRY mRNA and protein expression was analyzed in normal and OA human and mouse cartilage. Mice with deletion of Cry1 or Cry2 were analyzed for severity of experimental OA and to determine genes and pathways that are regulated by Cry. RESULTS: In human OA cartilage, CRY2 but not CRY1 staining and mRNA expression was significantly decreased. Cry2 was also suppressed in mice with aging-related OA. Cry2 knock out (KO) but not Cry1 KO mice with experimental OA showed significantly increased severity of histopathological changes in cartilage, subchondral bone and synovium. In OA chondrocytes, the levels of CRY1 and CRY2 and the amplitude of circadian fluctuation were significantly lower. RNA-seq on knee articular cartilage of wild-type and Cry2 KO mice identified 53 differentially expressed genes, including known Cry2 target circadian genes Nr1d1, Nr1d2, Dbp and Tef. Pathway analysis that circadian rhythm and extracellular matrix remodeling were dysregulated in Cry2 KO mice. CONCLUSIONS: These results show an active role of the circadian clock in general, and of CRY2 in particular, in maintaining extracellular matrix (ECM) homeostasis in cartilage. This cell autonomous network of circadian rhythm genes is disrupted in OA chondrocytes. Targeting CRY2 has potential to correct abnormal gene expression patterns and reduce the severity of OA.

Sequencing identifies a distinct signature of circulating microRNAs in early radiographic knee osteoarthritis.

OBJECTIVE: MicroRNAs act locally and systemically to impact osteoarthritis (OA) pathophysiology, but comprehensive profiling of the circulating miRNome in early vs late stages of OA has yet to be conducted. Sequencing has emerged as the preferred method for microRNA profiling since it offers high sensitivity and specificity. Our objective was to sequence the miRNome in plasma from 91 patients with early [Kellgren-Lawrence (KL) grade 0 or 1 (n = 41)] or late [KL grade 3 or 4 (n = 50)] symptomatic radiographic knee OA to identify unique microRNA signatures in each disease state. DESIGN: MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq 550. Counts were produced for microRNAs captured in miRBase and for novel microRNAs. Statistical, bioinformatics, and computational biology approaches were used to refine and interpret the final list of microRNAs. RESULTS: From 215 differentially expressed microRNAs (FDR < 0.01), 97 microRNAs showed an increase or decrease in expression in ≥85% of samples in the early OA group as compared to the median expression in the late OA group. Increasing this threshold to ≥95%, seven microRNAs were identified: hsa-miR-335-3p, hsa-miR-199a-5p, hsa-miR-671-3p, hsa-miR-1260b, hsa-miR-191-3p, hsa-miR-335-5p, and hsa-miR-543. Four novel microRNAs were present in ≥50% of early OA samples and had 27 predicted gene targets in common with the prioritized set of predicted gene targets from the 97 microRNAs, suggesting common underlying mechanisms. CONCLUSION: Sequencing of well-characterized patient cohorts produced unbiased profiling of the circulating miRNome and identified a unique panel of 11 microRNAs in early radiographic knee OA.

Results of R-ESHAP as salvage therapy in refractory/relapsed follicular lymphoma: a real-world experience on behalf of GELCAB group.

There is no standard treatment for relapsed follicular lymphoma (FL). Although platinum-based combinations are one of the most used treatments, few data have been reported in this setting. Our aim was to analyse R-ESHAP efficacy in relapsed FL patients. We retrospectively analysed 80 FL patients treated with R-ESHAP in the first or successive relapses. Responding patients received a stem cell transplantation following R-ESHAP. Seventeen histologically transformed patients were included. Median age was 50 years. At R-ESHAP initiation, 85% of the patients were in an advanced stage, 28% had a bulky disease and 40% had increased LDH. There were no statistically significant differences between POD24 and non-POD24 patients in terms of response to R-ESHAP (ORR 72% vs. 93%, p = 0.109). When analyzing R-ESHAP efficacy according to the response to the immediately previous line, patients achieving CR or PR had better CR rates to R-ESHAP than those who did not respond (CR of 57% vs. 15%, respectively, p = 0.009), as well as differences in OS (7.2 vs. 1.4 years, p < 0.0001) and in PFS (2.1 vs. 0.3 years, p < 0.0001). R-ESHAP is an effective treatment in relapsed FL patients who respond to the previous line and has to be considered as an adequate alternative for some patients.

Psychosocial repercussion of migraine: is it a stigmatized disease?

INTRODUCTION: Stigma manifests both in prejudices and rejection from society towards patients who suffer from a specific pathology, and by patient's internalization of this discrimination, with the consequent repercussions on their state of mind and quality of life. The aim of the study was to quantify the stigma associated with migraine and analyze whether it is related to the clinical-demographic characteristics of the patients, as well as the possible impact on their daily lives. MATERIALS AND METHODS: The stigma scale for chronic illness (SSCI) and other questionnaires were administered to 56 patients with episodic migraine (EM), 18 with chronic migraine (CM), and 21 with epilepsy, as a control group. RESULTS: The mean SSCI score was higher (51.6 ± 15.0) in the CM group than in the EM (45.0 ± 13.5) and epilepsy (47.6 ± 15.5) groups, without reaching statistical significance. In addition, the score was higher in patients who were unemployed, divorced, and in those who had migraine with aura. A statistically significant correlation was found between the SSCI score and the impact of migraine on daily life, the presence of stress, anxiety and depression, and low self-esteem. CONCLUSIONS: There is a stigma around migraine in our society, which seems to be more prevalent in patients with certain socio-demographic characteristics, and that is related to stress, mood alterations, and low self-esteem. Trying to reduce stigma could contribute to improve the control of migraine and reduce the impact of the disease at a socio-economic level.

Stopping cannabis use benefits outcome in psychosis: findings from 10-year follow-up study in the PAFIP-cohort.

OBJECTIVE: To examine the long-term (up to 10 years) patterns related to cannabis use in a sample of patients with first episode of psychosis (FEP) and the effect that consumption might have on clinical, functioning, and neurocognition at long-term. METHODS: Cannabis use was described in 209 FEP patients. Patients were divided into three groups according to cannabis use: persistent users, ex-users, and never-users. Groups were longitudinally (baseline and 10-year follow-up) compared on clinical, functional, and cognitive variables. RESULTS: Clinical differences at 10-year follow-up were observed between persistent cannabis users and the other two groups (ex-users and never-users), showing persistent users more severe symptoms (BPRS: x2  = 15.583, P ≤ 0.001; SAPS: x2  = 12.386, P = 0.002) and poorer functionality (DAS: x2  = 6.067, P = 0.048; GAF: x2  = 6.635, P = 0.033). Patients who stopped cannabis use prior to the reassessment showed a similar pattern to those who had never consumed. CONCLUSION: The use of cannabis could negatively affect the evolution of the psychotic disorder. Perhaps the negative effects caused by cannabis use could be reversed with the cessation of consumption. It is necessary to make an effort in the intervention toward an early withdrawal from the use of cannabis, since this could play an important role in the prognosis of the disease.

Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis.

OBJECTIVE: Osteoarthritis (OA) is the most prevalent joint disease. As disease-modifying therapies are not available, novel therapeutic targets need to be discovered and prioritized for their importance in mediating the abnormal phenotype of cells in OA-affected joints. Here, we generated a genome-wide molecular profile of OA to elucidate regulatory mechanisms of OA pathogenesis and to identify possible therapeutic targets using integrative analysis of mRNA-sequencing data obtained from human knee cartilage. DESIGN: RNA-sequencing (RNA-seq) was performed on 18 normal and 20 OA human knee cartilage tissues. RNA-seq datasets were analysed to identify genes, pathways and regulatory networks that were dysregulated in OA. RESULTS: RNA-seq data analysis revealed 1332 differentially expressed (DE) genes between OA and non-OA samples, including known and novel transcription factors (TFs). Pathway analysis identified 15 significantly perturbed pathways in OA with ECM-related, PI3K-Akt, HIF-1, FoxO and circadian rhythm pathways being the most significantly dysregulated. We selected DE TFs that are enriched for regulating DE genes in OA and prioritized these TFs by creating a cartilage-specific interaction subnetwork. This analysis revealed eight TFs, including JUN, Early growth response (EGR)1, JUND, FOSL2, MYC, KLF4, RELA, and FOS that both target large numbers of dysregulated genes in OA and are themselves suppressed in OA. CONCLUSIONS: We identified a novel subnetwork of dysregulated TFs that represent new mediators of abnormal gene expression and promising therapeutic targets in OA.

Intestinal parasites: Associations with intestinal and systemic inflammation.

The aim of the present study was to evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school-aged children with high rates of obesity. Plasma concentrations of C-Reactive Protein (CRP), leptin, TNF-α, IL-6 and IL-10 were measured as systemic inflammation markers and count of stool leukocytes as marker of intestinal inflammation in 291 children (6-10 years). Intestinal parasitic infection was measured by stool examination. Logistic regression analyses were performed to determine the odds of having high inflammatory markers for each parasite or group of parasites as compared to parasite-free children while adjusting for sex, age, mother's educational level and percentage of body fat. The prevalence of soil-transmitted helminths and intestinal protozoa infections was 12% and 36%, respectively. Parasitic infection was not associated with CRP, IL-6, IL-10 or TNF-α. Children infected with Ascaris lumbricoides (aOR: 5.91, 95% CI: 1.97-17.70) and Entamoeba coli (aOR: 8.46, 95% CI: 2.85-25.14) were more likely to have higher stool leucocytes than parasite-free children. Children with multiple infections (aOR: 10.60, 95% CI: 2.85-25.14) were more likely to have higher leptin concentrations than parasite-free children. Intestinal parasitic infection was not associated with systemic inflammation, but was associated with intestinal inflammation. Having multiple infections were associated with higher leptin concentrations.

Health utility scores from EQ-5D and health-related quality of life in patients with esophageal cancer: a real-world cross-sectional study.

Esophageal cancer and its treatment can cause serious morbidity/toxicity. These effects on health-related quality of life (HRQOL) can be measured using disease-specific scales such as FACT-E, generic scales such as EQ-5D-3L, or through symptoms. In a two-year cross-sectional study, we compared HRQOL across esophageal cancer patients treated in an ambulatory clinic and across multiple disease states, among patients with all stages of esophageal cancer. Consenting patients completed FACT-E, EQ-5D, a visual analog scale, and patient reported (PR)-ECOG. Symptom complexes were constructed from FACT-E domains. Responses were categorized by disease state: pre-, during, and post-treatment, surveillance, progression, and palliative chemotherapy. Spearman correlation and multivariable linear regression characterized these associations. In total, 199 patients completed 317 questionnaires. Mean FACT-E and subscale scores dropped from baseline through treatment and recovered during post-treatment surveillance (P < 0.001); EQ-5D health utility scores (HUS) displayed a similar pattern but with smaller differences (P = 0.07), and with evidence of ceiling effect. Among patients with stage II/III esophageal cancer, mean EQ-5D HUS varied across disease states (P < 0.001), along with FACT-E and subscales (P < 0.001). Among patients with advanced disease, there was no significant difference between baseline and on-treatment total scores, but improved esophageal cancer-specific scales were noted (P = 0.003). Strong correlation was observed between EQ-5D and FACT-E (R = 0.73), along with physical and functional subscales. In addition, the association between FACT-E and EQ-5D HUS was maintained in a multivariable model (P < 0.001). We interpret these results to suggest that in a real-world clinic setting, FACT-E, EQ-5D HUS, and symptoms were strongly correlated. Most HRQOL and symptom parameters suggested that patients had worse HRQOL and symptoms during curative therapy, but recovered well afterwards. In contrast, palliative chemotherapy had a neutral to positive impact on HRQOL/symptoms when compared to their baseline pre-treatment state.

Suppression of Sestrins in aging and osteoarthritic cartilage: dysfunction of an important stress defense mechanism.

OBJECTIVES: Aging is an important osteoarthritis (OA) risk factor and compromised stress defense responses may mediate this risk. The Sestrins (Sesn) promote cell survival under stress conditions and regulate AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signaling. This study examined Sesn expression in normal and OA cartilage and functions of Sesn in chondrocytes. METHODS: Sesn expression in human and mouse normal and OA cartilage was analyzed by quantitative polymerase chain reaction (PCR) and immunohistochemistry. Sesn function was investigated by using small interfering RNA (siRNA) mediated Sesn knockdown and overexpression with analysis of cell survival, gene expression, autophagy, and AMPK and mTOR activation. RESULTS: Sesn mRNA levels were significantly reduced in human OA cartilage and immunohistochemistry of human and mouse OA cartilage also showed a corresponding reduction in protein levels. In cultured human chondrocytes Sesn1, 2 and 3 were expressed and increased by tunicamycin, an endoplasmic reticulum (ER) stress response inducer and 2-deoxyglucose (2DG), a metabolic stress inducer. Sesn1 and 2 were increased by tBHP, an oxidative stress inducer. Sesn knockdown by siRNA reduced chondrocyte viability under basal culture conditions and in the presence of 2DG. Sesn overexpression enhanced LC3-II formation and autophagic flux, and this was related to changes in mTOR but not AMPK activation. CONCLUSION: These findings are the first to show that Sesn expression is suppressed in OA affected cartilage. Sesn support chondrocyte survival under stress conditions and promote autophagy activation through modulating mTOR activity. Suppression of Sesn in OA cartilage contributes to deficiency in an important cellular homeostasis mechanism.

Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-ß signaling in chondrocytes.

OBJECTIVES: Circadian rhythm (CR) was identified by RNA sequencing as the most dysregulated pathway in human osteoarthritis (OA) in articular cartilage. This study examined circadian rhythmicity in cultured chondrocytes and the role of the CR genes NR1D1 and BMAL1 in regulating chondrocyte functions. METHODS: RNA was extracted from normal and OA-affected human knee cartilage (n = 14 each). Expression levels of NR1D1 and BMAL1 mRNA and protein were assessed by quantitative PCR and immunohistochemistry. Human chondrocytes were synchronized and harvested at regular intervals to examine circadian rhythmicity in RNA and protein expression. Chondrocytes were treated with small interfering RNA (siRNA) for NR1D1 or BMAL1, followed by RNA sequencing and analysis of the effects on the transforming growth factor beta (TGF-ß) pathway. RESULTS: NR1D1 and BMAL1 mRNA and protein levels were significantly reduced in OA compared to normal cartilage. In cultured human chondrocytes, a clear circadian rhythmicity was observed for NR1D1 and BMAL1. Increased BMAL1 expression was observed after knocking down NR1D1, and decreased NR1D1 levels were observed after knocking down BMAL1. Sequencing of RNA from chondrocytes treated with NR1D1 or BMAL1 siRNA identified 330 and 68 significantly different genes, respectively, and this predominantly affected the TGF-ß signaling pathway. CONCLUSIONS: The CR pathway is dysregulated in OA cartilage. Interference with circadian rhythmicity in cultured chondrocytes affects TGF-ß signaling, which is a central pathway in cartilage homeostasis.

Susceptibility to rifaximin and other antimicrobials of bacteria isolated in patients with acute gastrointestinal infections in Southeast Mexico. / Susceptibilidad a la rifaximina y otros antimicrobianos de bacterias aisladas en pacientes con infecciones gastrointestinales agudas en el sureste de México.

INTRODUCTION: Enteropathogenic bacteria isolated in Mexico City have shown a high rate of resistance to different antibiotics, with the exception of rifaximin (RIF). RIF is a nonabsorbable antibiotic that reaches high fecal concentrations (≈ 8,000µg/g). Susceptibility to antimicrobials can vary in different geographic regions. AIM: To study the susceptibility to rifaximin and other antimicrobials of enteropathogenic bacteria isolated in patients with acute diarrhea in the southeastern region of Mexico. MATERIAL AND METHODS: A total of 614 strains of bacteria isolated from patients with acute diarrhea from 4 cities in Southeast Mexico were analyzed. An antibiogram with the following antibiotics was created: ampicillin (AMP), trimethoprim/sulfamethoxazole (T-S), neomycin (NEO), furazolidone (FUR), ciprofloxacin (CIP), chloramphenicol (CHL), and fosfomycin (FOS), assessed through the agar diffusion method at the standard concentrations recommended by the Clinical and Laboratory Standards Institute (CLSI) and the American Society for Microbiology (ASM), and RIF, assessed through microdilution at 4 concentrations. RESULTS: The bacteria were Escherichia coli (55%), as the majority, in all its pathogenic variants, Shigella (16.8%), Salmonella (15.3%), Aeromonas (7.8%), and less than 5% Campylobacter, Yersinia, Vibrio, and Plesiomonas. The accumulated overall susceptibility to RIF was 69.1, 90.8, 98.9, and 100% at concentrations of 100, 200, 400, and 800µg/ml, respectively. Overall susceptibility to other antibiotics was FOS 82.8%, CHL 76.8%, CIP 73.9%, FUR 64%, T-S 58.7%, NEO 55.8%, and AMP 23.8%. Susceptibility to RIF at 400 and 800µg was significantly greater than with the other antimicrobials (P<.001). CONCLUSIONS: The data of the present study were similar to those of a previous study carried out in Mexico City: susceptibility to RIF in > 98% of the bacterial strains and a high frequency of resistance to several common antimicrobials.

MicroRNA-155 suppresses autophagy in chondrocytes by modulating expression of autophagy proteins.

OBJECTIVE: Autophagy dysfunction has been reported in osteoarthritis (OA) cartilage. The objective of this study was to investigate the role of microRNA-155 (miR-155), which is overexpressed in OA, in the regulation of autophagy in human chondrocytes. DESIGN: Rapamycin (50 nM) and 2-deoxyglucose (2-DG) (5 mM) were used to stimulate autophagy in primary human articular chondrocytes and in the T/C28a2 human chondrocyte cell line. Cells were transfected with LNA GapmeR or mimic specific for miR-155 and autophagy flux was assessed by LC3 western blotting and by Cyto-ID(®) dye quantification in autophagic vacuoles. Expression of predicted miR-155 targets in the autophagy pathway were analyzed by real-time PCR and western blotting. RESULTS: Autophagy flux induced by rapamycin and 2-DG was significantly increased by miR-155 LNA, and significantly decreased after miR-155 mimic transfection in T/C28a2 cells and in human primary chondrocytes. These effects of miR-155 on autophagy were related to suppression of gene and protein expression of key autophagy regulators including Ulk1, FoxO3, Atg14, Atg5, Atg3, Gabarapl1, and Map1lc3. CONCLUSION: MiR-155 is an inhibitor of autophagy in chondrocytes and contributes to the autophagy defects in OA.

Suppression of REDD1 in osteoarthritis cartilage, a novel mechanism for dysregulated mTOR signaling and defective autophagy.

OBJECTIVE: Aging is a main risk factor for the development of osteoarthritis (OA) and the molecular mechanisms underlying the aging-related changes in articular cartilage include increased mammalian target of rapamycin (mTOR) signaling and defective autophagy. REDD1 is an endogenous inhibitor of mTOR that regulates cellular stress responses. In this study we measured REDD1 expression in normal, aged and OA cartilage and assessed REDD1 function in human and mouse articular chondrocytes. METHODS: REDD1 expression was analyzed in human and mouse articular cartilage by qPCR, western blotting, and immunohistochemistry. For functional studies, REDD1 and TXNIP knockdown or overexpression was performed in chondrocytes in the presence or absence of rapamycin and chloroquine, and mTOR signaling and autophagy were measured by western blotting. REDD1/TXNIP protein interaction was assessed by co-immunoprecipitation experiments. RESULTS: Human and mouse cartilage from normal knee joints expressed high levels of REDD1. REDD1 expression was significantly reduced in aged and OA cartilage. In cultured chondrocytes, REDD1 knockdown increased whereas REDD1 overexpression decreased mTOR signaling. In addition, REDD1 activated autophagy by an mTOR independent mechanism that involved protein/protein interaction with TXNIP. The REDD1/TXNIP complex was required for autophagy activation in chondrocytes. CONCLUSION: The present study shows that REDD1 is highly expressed in normal human articular cartilage and reduced during aging and OA. REDD1 in human chondrocytes negatively regulates mTOR activity and is essential for autophagy activation. Reduced REDD1 expression thus represents a novel mechanism for the increased mTOR activation and defective autophagy observed in OA.

Nitroxide amide-BODIPY probe behavior in fibroblasts analyzed by advanced fluorescence microscopy.

A novel synthesized nitroxide amide-BODIPY prefluorescent probe was used to study cellular redox balance that modulates nitroxide/hydroxylamine ratio in cultured human fibroblasts. FLIM quantitatively differentiated between nitroxide states of the cytoplasm-localized probe imaged by TIRF, monitoring nitroxide depletion by hydrogen peroxide; eluding incorrect interpretation if only fluorescence intensity is considered.

Patient preference: a comparison of electronic patient-completed questionnaires with paper among cancer patients.

In this study, we compared cancer patients preference for computerised (tablet/web-based) surveys versus paper. We also assessed whether the understanding of a cancer-related topic, pharmacogenomics is affected by the survey format, and examined differences in demographic and medical characteristics which may affect patient preference and understanding. Three hundred and four cancer patients completed a tablet-administered survey and another 153 patients completed a paper-based survey. Patients who participated in the tablet survey were questioned regarding their preference for survey format administration (paper, tablet and web-based). Understanding was assessed with a 'direct' method, by asking patients to assess their understanding of genetic testing, and with a 'composite' score. Patients preferred administration with tablet (71%) compared with web-based (12%) and paper (17%). Patients <65 years old, non-Caucasians and white-collar professionals significantly preferred the computerised format following multivariate analysis. There was no significant difference in understanding between the paper and tablet survey with direct questioning or composite score. Age (<65 years) and white-collar professionals were associated with increased understanding (both P = 0.03). There was no significant difference in understanding between the tablet and print survey in a multivariate analysis. Patients overwhelmingly preferred computerised surveys and understanding of pharmacogenomics was not affected by survey format.