A Two-Faced Gut Microbiome: Butyrogenic and Proinflammatory Bacteria Predominate in the Intestinal Milieu of People Living with HIV from Western Mexico.

HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. Our objective was to determine the GM composition and functions in people living with HIV (PLWHIV) under ART in comparison to seronegative controls (SC). Fecal samples from 21 subjects (treated with integrase strand-transfer inhibitors, INSTIs) and 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled with PICRUSt2 and fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (p < 0.001) compared to the SC group, at the expense of increased amounts of Pseudomonadota (Proteobacteria), Segatella copri, Lactobacillus, and Gram-negative bacteria. Concurrently, we observed an enrichment in Megasphaera and Butyricicoccus, both SCFA-producing bacteria, and significant elevations in fecal butyrate in this group (p < 0.001). Interestingly, gut dysbiosis in PLWHIV was characterized by a proinflammatory environment orchestrated by Pseudomonadota and elevated levels of butyrate associated with bacterial metabolic pathways, as well as the evident presence of butyrogenic bacteria. The role of this unique GM in PLWHIV should be evaluated, as well as the use of butyrate-based supplements and ART regimens that contain succinate, such as tenofovir disoproxil succinate. This mixed profile is described for the first time in PLWHIV from Mexico.

Phytochemicals and Their Usefulness in the Maintenance of Health.

Inflammation is the immune system's first biological response to infection, injury, or irritation. Evidence suggests that the anti-inflammatory effect is mediated by the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ, as well as the non-cytokine mediator, prostaglandin E2. Currently, the mechanism of action and clinical usefulness of phytochemicals is known; their action on the activity of cytokines, free radicals, and oxidative stress. The latter are of great relevance in the development of diseases, such that the evidence collected demonstrates the beneficial effects of phytochemicals in maintaining health. Epidemiological evidence indicates that regular consumption of fruits and vegetables is related to a low risk of developing cancer and other chronic diseases.

Pilot study on the efficacy and safety of berberine in people with metabolic syndrome and human immunodeficiency virus infection.

BACKGROUND: Antiretroviral therapy has increased the life expectancy of people living with HIV. However, this increase is not free of comorbidities, and metabolic syndrome is one of the most prevalent. Berberine is an alkaloid nutraceutical that has been shown to ameliorate metabolic disorders such as prediabetes, polycystic ovary syndrome, and non-alcoholic fatty liver disease. However, it has not been tested in HIV infection. Therefore, we conducted a randomized controlled trial to evaluate the efficacy of berberine in improving metabolic syndrome. METHODS AND RESULTS: In this double-blind, placebo-controlled trial, adults living with HIV under virological suppression and metabolic syndrome received either berberine 500 mg TID or placebo for 20 weeks. The primary outcomes were a composite of weight reduction, insulin resistance decrease, and lipid profile improvement. A total of 43 participants were randomized (22 in the berberine group and 21 in the placebo group); 36 participants completed the follow-up and were analyzed. The berberine group showed a reduction in weight and body mass index, lower insulin resistance, and a reduction in TNF-alpha. The control group had higher total cholesterol, c-LDL, and IL-6 concentration. CONCLUSION: In people living with HIV under virological suppression, berberine was safe and improves clinical and biochemical components of metabolic syndrome. However, further studies with more participants and longer intervention periods need to be explored.

Gut Bacterial Communities in HIV-Infected Individuals with Metabolic Syndrome: Effects of the Therapy with Integrase Strand Transfer Inhibitor-Based and Protease Inhibitor-Based Regimens.

Antiretroviral therapies (ART) are strongly associated with weight gain and metabolic syndrome (MetS) development in HIV-infected patients. Few studies have evaluated the association between gut microbiota and integrase strand transfer inhibitor (INSTI)-based and protease inhibitor (PI)-based regimens in HIV-infected patients with MetS. To assess this, fecal samples were obtained from HIV-infected patients treated with different regimens (16 PI + MetS or 30 INSTI + MetS) and 18 healthy controls (HCs). The microbial composition was characterized using 16S rRNA amplicon sequencing. The INSTI-based and PI-based regimens were associated with a significant decrease in α-diversity compared to HCs. The INSTI + MetS group showed the lowest α-diversity between both regimens. A significant increase in the abundance of short-chain fatty acid (SCFA)-producing genera (Roseburia, Dorea, Ruminococcus torques, and Coprococcus) was observed in the PI + MetS group, while Prevotella, Fusobacterium, and Succinivibrio were significantly increased in the INSTI + MetS group. Moreover, the Proteobacteria/Firmicutes ratio was overrepresented, and functional pathways related to the biosynthesis of LPS components were increased in the INSTI + MetS group. The gut microbiota of patients receiving INSTIs showed a more pronounced dysbiosis orchestrated by decreased bacterial richness and diversity, with an almost complete absence of SCFA-producing bacteria and alterations in gut microbiota functional pathways. These findings have not been previously observed.

Effect of antiretroviral therapy on decreasing arterial stiffness, metabolic profile, vascular and systemic inflammatory cytokines in treatment-naïve HIV: A one-year prospective study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: One year of ART had a positive effect on reducing inflammatory and vascular cytokines and arterial stiffness.

[Gastric pull-up in caustic stenosis: presentation of a complex clinical case]. / Ascenso gástrico en estenosis por cáusticos: presentación de un caso clínico complejo.

Introduction: Chemical substances are important causes of gastrointestinal tract injuries and usually affect two groups of patients: children under 5 years of age and adults who attempt suicide. Its effects can range from necrosis to perforation of the digestive tract, which can affect the mouth, pharynx, esophagus and stomach. The main complication of accidental caustic ingestion is esophageal stricture. The frequency with which esophageal strictures appear ranges from 15% to 35% and is related to the degree of injury induced by the ingested agent. They may become symptomatic by the second or third week after a latent repair phase or, in other cases, months or years after ingestion. Different forms of treatment have been applied to treat caustic esophageal strictures, and endoscopic dilation is the first line, with successful results in 60% to 80% of patients. If these are not effective, surgical treatment for esophageal replacement is indicated. Clinical Case: A clinical case of a 48-year-old male patient with no chronic degenerative history is presented, who began suffering after accidental ingestion of caustic substance 4 months ago with dysphagia to liquids and solids, for which he is protocolized in our unit for definitive surgical resolution by gastric pull-up. Conclusions: Although associated with high rates of anastomotic stricture, transhiatal esophagectomy and gastric pull-up with cervical anastomosis are safe procedures for the treatment of caustic esophageal strictures.

Introducción: las sustancias químicas son causas importantes de lesiones del tracto gastrointestinal y suelen afectar a dos grupos de pacientes: los niños menores de 5 años y los adultos que intentan el suicidio. Sus efectos pueden variar, desde la necrosis hasta la perforación del tubo digestivo, que puede afectar la boca, faringe, esófago y estómago. La principal complicación de la ingesta accidental de cáusticos es la estenosis esofágica. La frecuencia con la que aparecen las estenosis esofágicas oscila entre el 15 y el 35% y se relaciona con el grado de lesión inducida por el agente ingerido. Pueden hacerse sintomáticas hacia la segunda o tercera semanas después de una fase latente de reparación o, en otros casos, meses o años después de la ingesta. Diferentes formas de tratamiento se han aplicado para tratar las estenosis esofágicas por cáusticos, y en primera línea está la dilatación endoscópica, con resultados exitosos en el 60 a 80% de los pacientes. Si estas no son efectivas se indica el tratamiento quirúrgico de reemplazo esofágico. Caso clínico: se presenta el caso clínico de un paciente masculino de 48 años de edad sin antecedentes crónico-degenerativos, el cual inicia padecimiento tras la ingesta accidental de sustancia cáustica hacía 4 meses, con disfagia a líquidos y sólidos, por lo que es protocolizado en nuestra unidad para resolución quirúrgica definitiva mediante ascenso gástrico. Conclusiones: aunque se asocia con tasas altas de estenosis anastomótica, la esofagectomía transhiatal y el ascenso gástrico con anastomosis cervical son procedimientos seguros para el tratamiento de estenosis esofágicas por sustancias cáusticas.

Ghrelin level as a biomarker for knee osteoarthritis severity and appearance in HIV + patients.

BACKGROUND: Knee Osteoarthritis (KOA) is a multifactorial disease with several mechanisms to promote articular cartilage damage. New molecules, such as ghrelin, have been recently reported to participate in the pathogenesis and progression of KOA. In HIV + patients, arthralgias are the most frequent musculoskeletal manifestations, mainly affecting joints such as the knee. Also, it has been reported that HIV + patients have a reduction of ghrelin even with treatment compared to HIV- patients. However, there is no report in the literature evaluating ghrelin and KOA in the HIV + population. We aimed to evaluate whether serum ghrelin levels can function as a biomarker for OA in HIV + patients. METHODS: We recruited 40 patients, 20 HIV+, and 20 HIV- controls, and grouped as follows: HIV+/KOA+; HIV+/KOA-; HIV-/KOA+; HIV-/KOA-. Clinical features were obtained during clinical visits. Peripheral blood samples were acquired to measure serum ghrelin levels. RESULTS: The HIV+/KOA + group significantly reduced serum ghrelin levels when compared with the other groups. Comparing the ghrelin levels with the patients' nadir of CD4+ T-cells count, we identified a statistically significant negative correlation in the KOA- group (r = -0.80, P < 0.007). An ROC curve analysis, for the accuracy of ghrelin levels to identified HIV+/KOA + from HIV+/KOA- patients, found an area under the curve of 0.83 (95 % CI 0.65-0.10; P = 0.017), with a cut-off < 4026 pg/mL serum ghrelin levels, with a sensitivity of 0.62 (95 % CI 0.32-0.86), and a specificity of 0.10 (95 % CI 0.59-0.10). CONCLUSION: This study shows the potential use of ghrelin levels as a biomarker for KOA in the high-risk HIV population that should be further analyzed.

In vitro Azole antifungals susceptibility of Candida spp. isolates from HIV-infected patients with periodontitis.

OBJECTIVE: The objective of the present study was to determine the in vitro Azole antifungals susceptibility of Candida spp. strains isolated from HIV-positive patients with periodontitis. METHODS: Oral examination was performed in 500 HIV-positive patients, of which 228 were included in the study for having periodontitis which and separated in two groups based on their TCD4+ T-cells: (A) n = 110 (≤200 CD4+); (B) n = 118 (>200 CD4+). Candida spp. were isolated from the subgingival biofilm and crevicular fluid by seeding on CHROMagar plates and confirmed by endpoint PCR and MALDI-TOF. The susceptibility test in vitro for five antifungals was performed using the disc diffusion method. RESULTS: From the 228 HIV-positive patients with periodontitis, 174 were positive to Candida spp., and 204 isolations were obtained. 138 (67.64%) were C. albicans, and 66 (32.35%) were Candida non-albicans species. The most frequent Candida non-albicans species in order of frequency were C. glabrata with 48 (23.52%), C. tropicalis with 10 (4.9%), C. krusei with 7 (3.43%), and C. dubliniensis with 1 (0.49%). All species presented resistance to any antifungal: 149 to 5-fluorocytosine (73.0%), 149 to fluconazole (73.0%), and 144 to voriconazole (70.7%). Miconazole and econazole presented the highest susceptibility rates with 129 (63.2%) and 130 (63.7%) isolations, respectively. CONCLUSION: The Candida spp. involved in periodontitis of HIV-positive patients have a multi-resistant feature. It is necessary to implement recurrent research regarding the antifungal resistance of the Candida spp. that take part in periodontitis pathogenesis to promote an effective treatment in HIV patients.

Gut microbiota from Mexican patients with metabolic syndrome and HIV infection: An inflammatory profile.

AIM: A remarkable increase in metabolic syndrome (MetS) has occurred in HIV-infected subjects. Gut dysbiosis is involved in the pathogenesis of metabolic disorders. Therefore, the aim is to explore the profile of the gut microbiota in Mexican population with HIV infection and MetS. METHODS AND RESULTS: In all, 30 HIV-infected patients with MetS were compared to a group of 30 patients without MetS, treated with integrase inhibitors and undetectable viral load were included in the study. Stool samples were analysed by 16S rRNA next-generation sequencing. High-sensitivity C-reactive protein >3 mg L-1 and higher scores in cardiometabolic indices were associated with MetS. The group with MetS was characterized by a decrease in α-diversity, higher abundance of Enterobacteriaceae and Prevotella, as well as a dramatic decrease in bacteria producing short-chain fatty acids. Prevotella negatively correlated with Akkermansia, Lactobacillus and Anaerostipes. Interestingly, the group without MetS presented higher abundance of Faecalibacterium, Ruminococcus, Anaerofilum, Oscillospira and Anaerostipes. Functional pathways related to energy metabolism and inflammation were increased in the group with MetS. CONCLUSIONS: HIV-infected patients with MetS present a strong inflammatory microbiota profile; therefore, future strategies to balance intestinal dysbiosis should be implemented.

Clinical features associated with neurosyphilis in people living with HIV and late latent syphilis.

BACKGROUND: The diagnosis of neurosyphilis is a challenge, and the criteria for deciding when to perform a lumbar puncture are still controversial, especially in people living with HIV with a late latent syphilis diagnosis. METHODS: Retrospective analysis of demographic, clinical, and laboratory data of people with HIV and documented late latent syphilis or syphilis of unknown duration with a cerebrospinal fluid VDRL test. RESULTS: 122 patients were evaluated, of whom 52 had the diagnosis of neurosyphilis. Patients with and without neurosyphilis presented a similar viral load and lymphocyte CD4+ T-cell count. Neurological symptoms (OR 6.4, 95% CI 2.1-22.4; p < 0.01), serum VDRL titers of 1:32 (p<0.01), 1:64 (p = 0.055), and ≥1:128 (p < 0.001) were associated with neurosyphilis. Furthermore, serum VDRL ≥1:32 were associated with (OR 24.9, 95% CI 5.45-154.9; p < 0.001) or without (OR 6.5, 95% CI 2.0-29.2; p = 0.004) neurological symptoms with neurosyphilis; however, VDRL ≤1:16 with neurological symptoms can be associated with neurosyphilis (OR 7.6, 95% CI 1.03-64.3; p = 0.046). CONCLUSION: Neurological symptoms, particularly headache, were predictors of neurosyphilis in people with HIV irrespective of their viral load and lymphocyte CD4+ T-cell count in late latent syphilis. A serum VDRL ≥1:32 increased the risk of neurosyphilis in patients with or without any symptoms.

Prevalence and risk factors of chronic kidney disease in an HIV positive Mexican cohort.

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.

ZBTB gene expression in HIV patients: a possible new molecular mechanism of viral control.

HIV infects its target cell and integrates into its genome as an essential step in its replication cycle. Proviral DNA is also subjected to the same transcriptional regulation as the host cell genome by its own transcriptional factors, with activating or repressive activity. There is a clear interaction between the presence of transcriptional repressors and a decrease in the rate of HIV replication, promoting gene silencing in infected cells, which serve as viral reservoirs. This represents a major obstacle for HIV eradication. The ZBTB gene family comprises 49 genes that encode transcription factors that have a repressor function in differentiation and development of cells of the lymphopoietic lineage, including the main target cells of HIV, CD4+ T cells. In this cross-sectional study, we evaluated the expression profile of ZBTB genes in CD4+ T cells of HIV-positive individuals with different levels of infection control. We found upregulation of gene expression of ZBTB4 (p < 0.01), ZBTB7B (p < 0.001), and ZBTB38 (p < 0.05) and downregulation of ZBTB16 (p < 0.01) in HIV-positive patients compared to HIV-negative individuals. Interestingly, in a deeper analysis, we observed that elite controllers had the highest levels of expression of the ZBTB38, ZBTB2, HIC1, ZBTB7A, ZBTB7B (ThPOK) and ZBTB4 genes, showing 2.56- to 7.60-fold upregulation compare to the ART-naïve group. These results suggest a possible contribution of these ZBTB transcriptional repressors in HIV-positive patients and a possible new molecular mechanism of viral control.

Aortic stiffness and central hemodynamics in treatment-naïve HIV infection: a cross-sectional study.

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.

Correction to: Alterations in bacterial communities, SCFA and biomarkers in an elderly HIV-positive and HIV-negative population in western Mexico.

An amendment to this paper has been published and can be accessed via the original article.

Association of intestinal and systemic inflammatory biomarkers with immune reconstitution in HIV+ patients on ART.

BACKGROUND: HIV infection is characterized by CD4+ T-cells depletion related to gut damage, microbial translocation, immune activation and intestinal and systemic low-grade inflammation. With the use of antiretroviral treatment, these alterations in HIV+ patients reach similar levels to HIV- controls. However, almost 20% patients have deficient immune reconstitution of CD4+ T-cells, which make them more susceptible to develop non-AIDS and AIDS comorbidities. METHODS: HIV+ patients on ART, with sustained virologic control were grouped according to their immune reconstitution as: immunological responders (n = 18) and immunological non-responders (n = 18); also, HIV- controls were enrolled (n = 14). CD4+ and CD8+ T-cell activation (HLA-DR+ and CD38+ single and co-expression) were measured by flow cytometry. Serum levels of sCD14, sCD163, lipopolysaccharide, I-FABP, sST2, as well as fecal levels of calprotectin, lactoferrin and secretory IgA were evaluated by ELISA. Levels of C-reactive protein were determined by a high sensibility singleplex bead-based immunoassay. Serum and fecal concentrations of proinflammatory cytokines were quantified by multiplex bead-based immunoassay. RESULTS: HLA-DR+ and CD38+ co-expression, as well as median fluorescence intensity in CD4+ and CD8+ T-cells subpopulations was greater in immunological non-responders group, after normalization and fold change calculation. Similarly, this group presented higher levels of sCD14, C-reactive protein, as well as fecal calprotectin and lactoferrin. Furthermore, both HIV+ groups showed elevated levels of proinflammatory cytokines in stool. CONCLUSIONS: Our data suggests that despite the virologic control, HIV+ patients under treatment with deficient immune reconstitution showed elevation of both innate and T-cells immune activation, as well as intestinal and systemic inflammation. However, some patients with CD4+ T-cells count above 350 cells/µL also presented these alterations. Future studies are necessary to evaluate the dynamics of multiple systemic and intestinal biomarkers in diverse types of HIV+ patients, as such as their clinical impact.

Cytomegalovirus and disseminated histoplasmosis-related hemophagocytic lymphohistiocytosis syndrome in an HIV-patient late presenter with IRIS: a case report.

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.

Candida spp. Determination and Th1/Th2 Mixed Cytokine Profile in Oral Samples From HIV+ Patients With Chronic Periodontitis.

Background: 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 Candida 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 Candida spp. and cytokine profile in oral samples from HIV-positive patients with CP, considering the CD4+ T cells levels and HAART use. Methods: From 500 HIV-positive patients evaluated, 228 patients were enrolled. Patients were separated in groups: (A) n = 53 (≤200 CD4+ T-cells on HAART); (B) n = 57 (≤200 CD4+ T-cells without HAART); (C) n = 50 (>200 CD4+ T-cells without HAART); (D) n = 68 (>200 CD4+ T-cells on HAART). Candida 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. Results: 147 patients (64.5%) were positive to Candida spp. and 204 strains were isolated; 138 (67.6%) were C. albicans and the remaining C. non-albicans species (C. glabrata>C. tropicalis>C. krusei>C. dubliniensis). In this study, CHROMagar showed good sensitivity (95%) but poor specificity (68%); since of the 152 samples identified as C. albicans, only 131 were confirmed by PCR; from the 10 samples identified as C. glabrata, only six were confirmed. Finally, of the 42 samples detected as C. tropicalis, only five were confirmed. When evaluating Candida 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 Candida spp. Despite the presence of Candida and HAART, we found a Th1/Th2 hybrid profile in the saliva of patients with low CD4+ T-cell count (group A). Conclusion: Abundance and diversity of the Candida 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.

Alterations in bacterial communities, SCFA and biomarkers in an elderly HIV-positive and HIV-negative population in western Mexico.

BACKGROUND: The study of stool microbiota has taken great relevance in the last years, given its role in the maintenance of the intestinal metabolic, physiological, and immunological homeostasis, as well as, its effect over HIV biomarkers levels such as CD4/CD8 ratio, high sensitivity C-Reactive Protein (hs-CRP), related to poor outcomes (rapid progression to AIDS). Several efforts have been made to characterize the gut microbiome. In HIV infection, most of the studies report the presence of a dysbiotic pattern; however, few of them have made an approach in elderly HIV-positive subjects despite the fact that nowadays this subgroup is rising. In this study, we compared the composition of faecal microbiota, Short Chain Fatty Acids (SCFAs), and systemic biomarkers between elderly HIV-positive and HIV-negative subjects. METHODS: A cross-sectional study with 18 HIV-negative controls and 20 HIV-positive patients. The quantification of Bacteroidetes, Firmicutes, Proteobacteria, Actinobacteria, Lactobacillus, Enterobacteriaceae, Bifidobacterium, Escherichia coli, Clostridium leptum, Clostridium coccoides was performed in faecal samples by qPCR. The analysis was performed by calculating the ΔCq of each microorganism using 16S rDNA as a reference gene. Faecal SCFAs were measured by HPLC. The hs-CRP and sCD14 were performed by ELISA. RESULTS: An increase in the Firmicutes/Bacteroidetes ratio, coupled with a significant increase in the proteobacteria phylum was detected in HIV-positive subjects. In contrast, a decrease in the Clostridium leptum group was observed. Nevertheless, these elderly HIV-positive patients showed higher levels of total SCFAs mainly by an augmented propionic acid values, compared to HIV-negative subjects. Whereas high levels of hs-CRP were positively correlated with sCD14 in the HIV-positive group. CONCLUSIONS: Alterations in bacterial communities reveals a dysbiotic state related to an unbalance of faecal SCFAs. Therefore, these intestinal conditions might drive an increase of poor prognostic biomarkers in elderly HIV-positive subjects.

Culture supernatants of cervical cancer cells induce an M2 phenotypic profile in THP-1 macrophages.

Patients with cervical cancer (CxCa) typically present an infiltrate of tumor-associated macrophages, which is associated with a poor prognosis. We found that CxCa cell lines (HeLa, SiHa, and C-33A) secreted factors involved in regulating tumor growth including IL-6, IL-4, PDGFAA, HGF, VEGF, ANG-2, and TGF-ß3. We assessed the effects of culture supernatants from these cell lines on macrophages derived from the THP-1 cell line. Macrophages treated with culture supernatants from CxCa cells developed an M2-like phenotype with expression of CD163, low nitric oxide release, and high secretion of IL-6, PDGFAA, HGF, ANG-2, and VEGF. The macrophages continued to produce PDGFAA, PDGFBB, and VEGF 48h after the CxCa cell culture supernatants were removed. The induction of M2 macrophages in vivo favors tumor growth, angiogenesis, tissue remodeling, and metastasis. These results demonstrated that factors secreted by CxCa cells induced a stable M2 phenotype in THP-1 macrophages.