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BackgroundInflammatory bowel diseases (IBD) are multifactorial disorders affecting millions of people worldwide with alarmingly increasing incidences every year. Dysfunction of the intestinal epithelial barrier is associated with IBD pathogenesis, and therapies include anti-inflammatory drugs that enhance intestinal barrier function. However, these drugs often have adverse side effects thus warranting the search for alternatives. Compatible solutes such as bacterial ectoines stabilize cell membranes and proteins.AimTo unravel whether ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and homoectoine (4,5,6,7-tetrahydro-2-methyl-1H-(1,3)-diazepine-4-carboxylic acid), a synthetic derivative of ectoine, have beneficial effects during dextran sulfate sodium (DSS)-induced colitis in mice.Methods/ResultsWe found that the disease activity index was significantly reduced by both ectoines. DSS-induced edema formation, epithelial permeability, leukocyte recruitment and tissue damage were reduced by ectoine and homoectoine, with the latter having stronger effects. Interestingly, the claudin switch usually observed during colitis (decreased expression of claudin-1 and increased expression of the leaky claudin-2) was completely prevented by homoectoine, whereas ectoine only reduced claudin-2 expression. Concomitantly, only homoectoine ameliorated the drop in transepithelial electrical resistance induced by IFN-γ and TNF-α in Caco-2 cells. Both ectoines inhibited loss of ZO-1 and occludin and prevented IFN-γ/TNF-α-induced increased paracellular flux of 4 kDa FITC-dextran in vitro. Moreover, both ectoines reduced expression of pro-inflammatory cytokines and oxidative stress during colitis.ConclusionWhile both ectoine and homoectoine have protective effects on the epithelial barrier during inflammation, only homoectoine completely prevented the inflammatory claudin switch in tight junctions. Thus, homoectoine may serve as diet supplement in IBD patients to reach or extend remission.

Background HIV subjects have several kidney pathologies, like HIV-associated nephropathy or antiretroviral therapy injury, among others. The global prevalence of Chronic Kidney Disease (CKD) is 8–16%; however, in HIV subjects, the prevalence varies between geographic regions (2–38%). The aim was to determine the prevalence of CKD and identify the associated risk factors. Methods A longitudinal descriptive study was carried out at the 'Hospital Civil de Guadalajara' Feb'18 – Jan'19. Basal clinical, demographic, opportunistic infections (OI), and laboratory data were obtained at months 0 and 3; inclusion criteria were ≥ 18 years old, naïve HIV + , urine albumin/creatinine ratio, serum creatinine & urine test, and signed informed consent. Descriptive and multiple logistic regression statistical analyses were made. Results One hundred twenty subjects were included; 92.5% were male, 33 ± 9.5 years, 60% consumed tobacco, 73% alcohol, and 59% some type of drug. The CKD prevalence was 15.8%. CKD patients had a higher risk of hepatitis C virus coinfection, Relative Risk (RR):5.9; HCV infection, RR:4.3; ≥ 30 years old, RR:3.9; C clinical-stage, RR:3.5; CD4 +  T cells count < 200 cells/μL, RR: 2.4; and HIV-1 viral load ≥ 100,000 cop/mL, RR: 2.7. Conclusions Our study showed a higher CKD prevalence in patients with HIV; higher CKD development with coinfections as Hepatitis C Virus and Mycobacterium tuberculosis . The identification and prompt management of CKD and coinfections should be considered to avoid the progression and to delay renal replacement therapy as long as possible.

Biodiesels are mostly produced from lipid transesterification of vegetable oils, including those from soybean, jatropha, palm, rapeseed, sunflower, and others. Unfortunately, transesterification of oil produces various unwanted side products, including steryl glucosides (SG), which precipitate and need to be removed to avoid clogging of filters and engine failures. So far, efficient and cost-effective methods to remove SGs from biodiesel are not available. Here we describe for the first time the identification, characterization and heterologous production of an enzyme capable of hydrolyzing SGs. A synthetic codon-optimized version of the lacS gene from Sulfolobus solfataricus was efficiently expressed and purified from Escherichia coli , and used to treat soybean derived biodiesel containing 100 ppm of SGs. After optimizing different variables, we found that at pH 5.5 and 87 °C, and in the presence of 0.9 % of the emulsifier polyglycerol polyricinoleate, 81 % of the total amount of SGs present in biodiesel were hydrolyzed by the enzyme. This remarkable reduction in SGs suggests a path for the removal of these contaminants from biodiesel on industrial scale using an environmentally friendly enzymatic process.

HIV continues to be a public health concern in Mexico and Latin America due to an increase in new infections, despite a decrease being observed globally. Treatment adherence is a pillar for achieving viral suppression. It prevents the spread of the disease at a community level and improves the quality and survival of people living with HIV. Thus, it is important to implement strategies to achieve sustained treatment adherence. The objective of this study is to evaluate the effectiveness of a mobile health (mHealth) intervention based on SMS text messages to increase antiretroviral therapy (ART) adherence for HIV-positive adults. A randomized controlled trial was performed at the Hospital Civil de Guadalajara - Fray Antonio Alcalde on HIV-positive adults who had initiated ART. The mHealth intervention included the use of SMS text messages as a reminder system for upcoming medical examinations and ART resupply to increase adherence. This intervention was provided to 40 participants for a 6-month period. A control group (n=40) received medical attention by the standard protocol used in the hospital. Intervention effectiveness was assessed by quantifying CD4+ T cells and viral load, as well as a self-report of adherence by the patient. The intervention group had greater adherence to ART than the control group (96% vs 92%; P<.001). In addition, the intervention group had better clinical characteristics, including a lower viral load (141 copies/mL vs 2413 copies/mL; P<.001) and a trend toward higher CD4+ T cells counts (399 cells/μL vs 290 cells/μL; P=.15). These results show that an mHealth intervention significantly improves ART adherence. Implementing mHealth programs could enhance the commitment of HIV-positive adults to their treatment.

Background Hemophagocytic lymphohistiocytosis syndrome (HLS) is an immune-mediated life-threatening disease considered as a medical emergency, with a potentially fatal multisystem inflammatory outcome. We present a patient that developed HLS and was able to be diagnosed efficiently with the help of an academic research institute of immunology. Case presentation A 21 years old male Mexican with human immunodeficiency virus (HIV), late presenter; who developed cytomegalovirus (CMV) infection and a disseminated histoplasmosis-related HLS, as part of an immune reconstitution inflammatory syndrome (IRIS). The patient required a long course of corticotherapy, intravenous immunoglobulin and massive transfusions (more than 10 units in 24 h, and a total of 83 units), besides amphotericin-B and ganciclovir treatment. An academic research institute of immunology aided in the accurate diagnosis of HLS with the implementation of tests not available within the hospital, thus improving the care provided to the patient. The patient recovered, was discharged, and continue to improve. Conclusion The objective of this report is to highlight the importance of having multidisciplinary support, including basic medical sciences groups providing specific tests that are sometimes very difficult to get, which provides a benefit to patients in the well-aimed diagnosis as part of applied translational medicine.

Susceptibility to inflammatory bowel diseases (IBDs), Crohn's disease (CD), and ulcerative colitis (UC) is linked with loss of intestinal epithelial barrier integrity and mitochondria dysfunction. Steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain-containing protein 7 (STARD7) is a phosphatidylcholine-specific (PC-specific) lipid transfer protein that transports PC from the ER to the mitochondria, facilitating mitochondria membrane stabilization and respiration function. The aim of this study was to define the contribution of STARD7 in the regulation of the intestinal epithelial mitochondrial function and susceptibility to colitis. In silico analyses identified significantly reduced expression of STARD7 in patients with UC, which was associated with downregulation of metabolic function and a more severe disease phenotype. STARD7 was expressed in intestinal epithelial cells, and STARD7 knockdown resulted in deformed mitochondria and diminished aerobic respiration. Loss of mitochondria function was associated with reduced expression of tight junction proteins and loss of intestinal epithelial barrier integrity that could be recovered by AMPK activation. Stard7+/- mice were more susceptible to the development of DSS-induced and Il10-/- spontaneous models of colitis. STARD7 is critical for intestinal epithelial mitochondrial function and barrier integrity, and loss of STARD7 function increases susceptibility to IBD.

Chronic periodontitis (CP), caused by bacteria and fungi, appears in up to 66% of HIV-patients. The impact and association of HIV-treatment (HAART) and itself has not been properly evaluated in the development and progression of CP. The immunopathogenesis is characterized by CD4 T-cells activation and the balance between the T-helper 1 (Th1) and T-helper 2 (Th2) or a mixed cytokine profile. Currently, the associated causes of an immune response in HIV-patients with CP is controversial. Our aims were the determination of spp. and cytokine profile in oral samples from HIV-positive patients with CP, considering the CD4 T cells levels and HAART use. From 500 HIV-positive patients evaluated, 228 patients were enrolled. Patients were separated in groups: (A) = 53 (≤200 CD4 T-cells on HAART); (B) = 57 (≤200 CD4 T-cells without HAART); (C) = 50 (>200 CD4 T-cells without HAART); (D) = 68 (>200 CD4 T-cells on HAART). spp. were isolated from the oral biofilm and crevicular fluid in CHROMagar and confirmed by endpoint PCR. Cytokine levels were measured by beads-based immunoassay in saliva by flow cytometry. 147 patients (64.5%) were positive to . and 204 strains were isolated; 138 (67.6%) were and the remaining species ( > > > . In this study, CHROMagar showed good sensitivity (95%) but poor specificity (68%); since of the 152 samples identified as , only 131 were confirmed by PCR; from the 10 samples identified as , only six were confirmed. Finally, of the 42 samples detected as , only five were confirmed. When evaluating spp. presence, group A and D had higher isolation, while group B had the highest species diversity. Whereas, group C had a significant reduction of spp. Despite the presence of and HAART, we found a Th1/Th2 hybrid profile in the saliva of patients with low CD4 T-cell count (group A). Abundance and diversity of the spp. detected in HIV-patients with CP could be related to HAART and low CD4 T-cells levels. Also, the immunosuppression might promote a local Th1/Th2 hybrid cytokine profile.

Background Human immunodeficiency virus (HIV) infection is associated with a greater risk of cardiovascular disease (CVD). HIV infection causes a chronic inflammatory state and increases oxidative stress which can cause endothelial dysfunction and arterial stiffness. Aortic stiffness measured by carotid femoral-pulse wave velocity (cfPWV) and central hemodynamics are independent cardiovascular risk factors and have the prognostic ability for CVD. We assessed cfPWV and central hemodynamics in young individuals with recent HIV infection diagnosis and without antiretroviral therapy. We hypothesized that individuals living with HIV would present greater cfPWV and central hemodynamics (central systolic blood pressure and pulse pressure) compared to uninfected controls. Methods We recruited 51 treatment- naïve individuals living with HIV (HIV(+)) without previous CVD and 51 age- and sex-matched controls (HIV negative (−)). We evaluated traditional CVD risk factors including metabolic profile, blood pressure (BP), smoking, HIV viral load, and CD4 + T-cells count. Arterial stiffness and central hemodynamics were evaluated by cfPWV, central systolic BP, and central pulse pressure (cPP) via applanation tonometry. Results HIV(+) individuals presented a greater prevalence of smoking, reduced high-density lipoprotein cholesterol, and body mass index. 65.9% of HIV(+) individuals exhibited lymphocyte CD4 + T-cells count < 500 cells/μL. There was no difference in brachial or central BP between groups; however, HIV(+) individuals showed significantly lower cPP. We observed a greater cfPWV (mean difference = 0.5 m/s; p  < 0.01) in HIV(+) compared to controls, even after adjusting for heart rate, mean arterial pressure and smoking. Conclusion In the early stages of infection, non-treated HIV individuals present a greater prevalence of traditional CVD risk factors, arterial stiffness, and normal or in some cases central hemodynamics.

Cardiovascular disease is a major cause of death among people living with HIV (PLH). Non-treated PLH show increased levels of inflammation and biomarkers of vascular activation, and arterial stiffness as a prognostic cardiovascular disease risk factor. We investigated the effect of one year of ART on treatment-naïve HIV(+) individuals on arterial stiffness and inflammatory and vascular cytokines. We cross-sectionally compared aortic stiffness via tonometry, inflammatory, and vascular serum cytokines on treatment-naïve (n = 20) and HIV (-) (n = 9) matched by age, sex, metabolic profile, and Framingham score. We subsequently followed young, treatment-naïve individuals after 1-year of ART and compared aortic stiffness, metabolic profile, and inflammatory and vascular serum biomarkers to baseline. Inflammatory biomarkers included: hs-CRP, D-Dimer, SAA, sCD163s, MCP-1, IL-8, IL-18, MRP8/14. Vascular cytokines included: myoglobin, NGAL, MPO, Cystatin C, ICAM-1, VCAM-1, and MMP9. Treatment-naïve individuals were 34.8 years old, mostly males (95%), and with high smoking prevalence (70%). Baseline T CD4+ was 512±324 cells/mcL. cfPWV was similar between HIV(-) and treatment-naïve (6.8 vs 7.3 m/s; p = 0.16) but significantly decreased after ART (-0.52 m/s; 95% CI -0.87 to -0.16; p0.006). Almost all the determined cytokines were significantly higher compared to controls, except for MCP-1, myoglobin, NGAL, cystatin C, and MMP-9. At follow-up, only total cholesterol and triglycerides increased and all inflammatory cytokines significantly decreased. Regarding vascular cytokines, MPO, ICAM-1, and VCAM-1 showed a reduction. D-Dimer tended to decrease (p = 0.06) and hs-CRP did not show a significant reduction (p = 0.17). One year of ART had a positive effect on reducing inflammatory and vascular cytokines and arterial stiffness.

Background. Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory and demyelinating disorder of the central nervous system, with a distinct tendency to a perivenous localization of pathological changes. Children are the most affected population and frequently presented after exanthematous viral infections or vaccination. Due to the rarity of this disease, the annual incidence rate in the population is not precisely known. Case Presentation. Here, we present a 28-year-old male HIV-1 positive patient with an acute confusional state, a diminished alert status characterized by somnolence, hypoprosexia, and complex visual hallucinations. Neuroimages reported white matter demyelinating lesions, mainly affecting the semioval centers, the frontal lobe, and the left parietal lobe; hypointense on T1-weighted images, hyperintense on T2-weighted images and fluid-attenuated inversion recovery weighted images, DWI with restricted diffusion, and a parietal ring-enhancing lesion after IV gadolinium administration. Discussion. In HIV positive patients, the demyelinating disorders have a broader clinical spectrum that could be explained by the immunosuppressed state of the patients, the evolution of the disease, the use of medications, the opportunistic infections, and the environment. Due to this highly variable clinical spectrum, ADEM is a significant challenge for the physicians in HIV positive patients, causing a delay in the diagnosis and treatment. Conclusion. We suggest that ADEM should be considered among the differential diagnosis in HIV-infected patients with focal or multifocal neurological symptoms, particularly in encephalopathies with multifocal central nervous system involvement without severe immunosuppression.