Immune dysfunction and increased oxidative stress state in diet-induced obese mice are reverted by nutritional supplementation with monounsaturated and n-3 polyunsaturated fatty acids.

PURPOSE: Obesity is associated with impaired immune defences and chronic low levels of inflammation and oxidation. In addition, this condition may lead to premature aging. The aim of the study was to evaluate the effects of a nutritional supplementation with monounsaturated and n-3 polyunsaturated fatty acids on several functions and oxidative stress parameters in peritoneal immune cells of obese mice, as well as on the life span of these animals. METHODS: Obesity was induced in adult female ICR/CD1 by the administration of a high-fat diet (HFD) for 14 weeks. During the last 6 weeks of HFD feeding, one group of obese mice received the same HFD, supplemented with 1500 mg of 2-hydroxyoleic acid (2-OHOA) and another with 3000 mg of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Several functions and oxidative stress parameters of peritoneal leukocytes were evaluated. RESULTS: The groups of obese mice treated with 2-OHOA or with EPA and DHA showed a significant improvement in several functions such as chemotaxis, phagocytosis, digestion capacity, Natural killer activity and lymphoproliferation in response to mitogens. All of these functions, which were decreased in obese mice, increased reaching similar levels to those found in non-obese controls. Both treatments also improved oxidative stress parameters such as xanthine oxidase activity, which decreased, catalase activity and glutathione levels, which increased. CONCLUSION: These data suggest that dietary supplementation with monounsaturated and n-3 polyunsaturated fatty acids could be an effective nutritional intervention to restore the immune response and oxidative stress state, which are impaired in obese mice.

Parent and child ratings of child behaviour following mild traumatic brain injury.

BACKGROUND: Mild traumatic brain injury (mTBI) in children is most commonly associated with parent-reported child behaviour problems. The extent to which parent and child ratings align is unknown. OBJECTIVES: To examine differences in child behaviour and patterns of recovery over the first 12 months following mTBI based on parent and child self-report. METHODS: Ninety-nine children (8-15 years) with mTBI and one of their parents completed the Behavioural Assessment Scale for Children - version 2 to assess child hyperactivity, anxiety and depression at baseline, 1, 6 and 12 months post-injury. Differences between ratings from parents and children were evaluated using Bland-Altman limits of agreement analyses. Child recovery over time was examined using mixed models repeated measures analyses. RESULTS: Parent and child ratings for child hyperactivity, anxiety and depression differed significantly at baseline and these differences remained constant at each follow-up. Parents tended to report more child hyperactivity, anxiety and depression. Over time, parents and children reported fewer child hyperactivity and anxiety problems. CONCLUSIONS: Parents and children have poor agreement in ratings of child behaviour yet there is general agreement in patterns of recovery in the year following mTBI. Findings show the importance of considering both parent and self-report of child behaviour.

Oxidative stress and immunosenescence in spleen of obese mice can be reversed by 2-hydroxyoleic acid.

NEW FINDINGS: What is the central question of this study? Evidence is growing for the link between obesity, immune dysfunction and oxidative stress, but it is still not known how the properties and functions of the spleen and splenic leucocytes are affected. What is the main finding and its importance? Obesity led to premature immunosenescence, manifested as oxidative stress and changes in leucocyte functions in mouse spleen. The oleic acid derivative 2-hydroxyoleate and, to a lesser extent, a combination of eicosapentaenoic and docosahexaenoic acids could reverse most of the observed alterations, suggesting a potential therapeutic tool for obesity-related immune dysfunction and redox imbalance. We aimed to investigate the effects of obesity on oxidative stress and leucocyte function in the mouse spleen and to assess whether supplementation with 2-hydroxyoleic acid (2-OHOA) or n-3 polyunsaturated fatty acids (PUFAs) could reverse those effects. Female ICR/CD1 mice (8 weeks old, n = 24) received an obesogenic diet (22% fat for 4 weeks and 60% fat for 14 weeks). After 6 weeks, mice were divided into the following three groups (n = 8 per group): no supplementation; 2-OHOA supplementation (1500 mg kg-1 of diet); and n-3 PUFA supplementation (eicosapentaenoic acid and docosahexaenoic acid, 1500 + 1500 mg kg-1 of diet). Eight mice were fed the standard diet for the whole duration of the study (control group). At the end of the experiment, the following variables were assessed in spleens: levels of reduced (GSH) and oxidized glutathione (GSSG), GSH/GSSG, xanthine oxidase activity, lipid peroxidation, lymphocyte chemotaxis, natural killer activity and mitogen (concanavalin A and lipopolysaccharide)-induced lymphocyte proliferation. Obese animals presented higher GSSG levels (P = 0.003), GSSG/GSH ratio (P = 0.013), lipid peroxidation (P = 0.004), xanthine oxidase activity (P = 0.015) and lymphocyte chemotaxis (P < 0.001), and lower natural killer activity (P = 0.003) and proliferation in response to concanavalin A (P < 0.001) than control mice. 2-Hydroxyoleic acid totally or partly reversed most of the changes (body weight, fat content, GSSG levels, GSH/GSSG, lipid peroxidation, chemotaxis and proliferation, all P < 0.05), whereas n-3 PUFAs reversed the increase in xanthine oxidase activity (P = 0.032). In conclusion, 2-OHOA or, to a lesser extent, n-3 PUFAs could ameliorate the oxidative stress and alteration of leucocyte function in the spleens of obese mice. Our findings support a link between obesity and immunosenescence and suggest a potential therapeutic tool for obesity-related immune dysfunction.

[Pathology of the vitreomacular interface]. / Aspecte patologice ale interfetei vitreomaculare.

Vitreous role in the pathophysiology of retinal diseases has increased importantly over the recent years. This was possible using Optical Coherence Tomography which reviewed the way the vitreoretinal interface should be looked at and defined and classified new pathologies such as Vitreoretinal Traction Syndrome. Vitreous is not an empty space but an important anatomical structure with role in ocular physiology. With age biochemical changes occur so that vitreous starts to liquefy. Once the vitreous is liquefied (sinchisis) it collapses and passes in the retrohialoid space (sineresis). In complete PVD besides sinchisis there is a weakness of the adherence between the posterior cortex and ILM with total detachment of posterior cortex. Abnormal adhesions are associated with incomplete PVD. The definition and understanting of vitreoretinal pathology is an active and continuous process, PVD being the trigger of a lot of retinal pathologies: epiretinal membrane, macular hole, tractional macular oedema, VMTS, myopic traction maculopathy, exacerbations of exudative ARMD.

The surgical management of a patient with Fuchs endothelial dystrophy and cataracts.

Objective: To report the two different surgical approaches in the case of a patient with Fuchs endothelial dystrophy with low endothelial cell count and advanced cataracts. Methods: The chosen surgical approach differed between eyes, with the right eye undergoing a combined approach consisting of cataract surgery, intraocular lens implantation, and penetrating keratoplasty in 2022. One year later, for the left eye, a different approach was decided: cataract surgery followed by Descemet membrane endothelial keratoplasty (DMEK). The Descemet membrane graft was prepared by the surgeon using the liquid bubble technique. AS-OCT was used to monitor the patient before and after surgery. Results: Visual recovery was excellent for both eyes, however, visual acuity improved quickly in the left eye (DMEK), while, in the right eye (PK), the best corrected visual acuity was reached after several months post-surgery. Conclusion: Advanced stages of Fuchs dystrophy patients will most likely need corneal transplantation. Each type of corneal transplantation procedure comes with unique challenges, both intraoperative and postoperative. DMEK is a very good treatment option for patients with Fuchs endothelial dystrophy, with excellent visual recovery and good graft survival at the 10-year mark. Abbreviations: DMEK = Descemet membrane endothelial keratoplasty, PK = penetrating keratoplasty, AS-OCT = anterior segment optical coherence tomography, FECD = Fuchs endothelial corneal dystrophy, BCVA = best corrected visual acuity, US = ultrasound, CDE = cumulative dissipated energy, IOL = intraocular lens.

Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice.

Consumption of a high-fat diet (HFD), which is associated with chronic 'low-grade' systemic inflammation, alters the gut microbiota (GM). The aim of the present study was to investigate the ability of an oleic acid-derived compound (S1) and a combination of n-3 fatty acids (EPA and DHA, S2) to modulate both body weight and the GM in HFD-induced obese mice. A total of eighty mice were fed either a control diet or a HFD, non-supplemented or supplemented with S1 or S2. At week 19, faeces were collected in order to analyse the GM. Group-specific primers for accurate quantification of several major bacterial groups from faecal samples were assayed using quantitative PCR. The HFD induced an increase in body weight, which was reduced by supplementation with S1. Furthermore, S1 supplementation markedly increased total bacterial density and restored the proportions of bacteria that were increased (i.e. clostridial cluster XIVa and Enterobacteriales) or decreased (i.e. Bifidobacterium spp.) during HFD feeding. S2 supplementation significantly increased the quantities of Firmicutes (especially the Lactobacillus group). Correlation analysis revealed that body weight correlated positively with the phylum Firmicutes and clostridial cluster XIVa, and negatively with the phylum Bacteroidetes. In conclusion, the consumption of a HFD induced changes in the faecal microbiota, which were associated with the appearance of an obese phenotype. Supplementation of the HFD with S1 counteracted HFD-induced gut dysbiosis, together with an improvement in body weight. These data support a role for certain fatty acids as interesting nutrients related to obesity prevention.

Ocular Complications of Radiotherapy in Uveal Melanoma.

Uveal melanoma is the most common primary malignant intraocular tumor in adults. Radiation therapy has replaced enucleation and is now the preferred treatment in most cases. Nonetheless, around 70% of patients develop radiation-related complications, some of which are vision-threatening. The objective of this review is to present the most important complications associated with radiotherapy in the treatment of uveal melanoma and their pathogenesis, incidence, risk factors, and available preventive and therapeutic measures. The most common complications are cataracts, with a reported incidence ranging from 4% to 69%, and radiation retinopathy, reported in 5-68% of cases. Radiation-related complications are responsible for approximately half of secondary enucleations, the leading cause being neovascular glaucoma. A poor visual outcome is mainly associated with the presence of radiation retinopathy and radiation optic neuropathy. Therapeutic options are available for the majority of complications with the notable exception of optic neuropathy. However, many studies report a final visual acuity of less than 20/200 in more than 60% of treated eyes. Reducing complication rates can be achieved by lowering the dose of radiation, with the use of eccentric, customized plaques and careful planning of the irradiation delivery in order to protect structures vital to vision and by associating radiation therapy with other methods with the aim of reducing tumor volume.

Intraocular Pressure Measurement after Penetrating Keratoplasty.

Assessing the intraocular pressure is a difficult but crucial task in the follow-up of patients that have undergone penetrating keratoplasty. Early recognition of elevated intraocular pressure and/or glaucoma and establishment of the appropriate treatment is essential to ensure the best possible visual outcome for patients dealing with this feared complication. Although Goldmann applanation tonometry is still the gold standard for measuring the intraocular pressure, its limitations in postkeratoplasty eyes, due to postoperative modified corneal morphology, have led to the search for more suitable alternatives. This review is the result of a comprehensive literature search in the MEDLINE database that aims to present glaucoma in the context of perforating keratoplasty, the corneal properties with impact on ocular pressure measurement, and the results achieved with the most important tonometers that have been studied in this pathology. Goldmann applanation tonometry remains the reference for intraocular pressure assessment even in corneas after penetrating keratoplasty. However, some promising alternatives have emerged, the most important of which are the Pascal dynamic contour tonometry, the Tono-Pen XL, the ocular response analyzer, and the iCare. All have advantages and disadvantages but have proved to be appropriate alternatives, especially in cases in which Goldmann applanation tonometry cannot be used.

A systematic review of euthyroid Graves' disease (Review).

Euthyroid Graves' Disease (EGD) is a challenging pathology, due to its atypical clinical manifestations and the absence of abnormal thyroid function. Typically, thyroid ophthalmopathy is associated with elevated thyroid hormone levels and with the presence of thyrotropin receptor antibodies (TRAb) but a low percentage of patients remain euthyroid without developing hyperthyroidism during long-term follow-up periods. Although it is considered a different pathology, it shares a lot of similarities with Graves' disease, rendering the diagnosis more difficult. It is also important to note that ophthalmopathy may be the first clinical manifestation of Graves' disease and that thyroid function examinations do not present abnormalities over a long period. Treatment choices for euthyroid disease do not differ from those described in Graves' ophthalmopathy. However, it is considered that since euthyroid patients develop milder ophthalmic symptoms and their clinical activity score is lower, they tend to have better responses to treatment. Moreover, atypical sight-threatening cases such as exposure keratopathy and dysthyroid optic neuropathy with variable responses to therapy also exist. Disease management consists of a favorable collaboration between ophthalmologists and endocrinologists because patients with EGD can develop thyroid abnormalities over time. In conclusion, the diagnosis of EGD is difficult, clinical manifestations and evolution are variables depending on several factors, including the heterogeneity of TRAb. This review aimed to identify the characteristics of this disease by reviewing the clinical studies and case reports published in previous years.

Adipokines, cortisol and cytokine alterations in recent onset anorexia nervosa. A case-control study.

INTRODUCTION: Psychological and neuroendocrine alterations are typical characteristics in anorexia nervosa patients. The role of adipokines and cytokines as mediators of body systems' adaptations to the patients' abnormal eating behavior is not well understood. The duration of disease seems to be a determinant of nutritional status and associated hormone changes. We aimed to assess whether alterations in adipokines, cytokines and cortisol do already exist in patients with a recent disease onset by means of a case-control study. METHODS: Forty-one adolescent female patients on their first-episode and diagnosed with anorexia nervosa, were matched by age and socioeconomic status (SES) (1:1) with healthy girls. Leptin, soluble leptin receptor (sOB-R), adiponectin, cortisol, and the cytokines IL-1ß, IL-2, IL-6 and TNF-α were examined. RESULTS: The results showed reduced leptin and increased sOB-R and cortisol levels in AN patients. Adiponectin was also increased but opposite to the previous biomarkers did not correlate with BMI Z-score. Serum TNF-α and IL-2 showed significantly lower and higher values, respectively, in the AN patients than in the controls. Cortisol showed the strongest correlation with sOB-R (r=0.436; P=0.005). CONCLUSIONS: Our study confirms previous findings on adipokine and cortisol alterations in AN patients, while overall cytokine results did not show a clear disruption in AN patients with short disease duration. The results highlight the need to disentangle the role of the sOB-R in the interactions between leptin and cortisol secretion.

Associations of Probiotic Fermented Milk (PFM) and Yogurt Consumption with Bifidobacterium and Lactobacillus Components of the Gut Microbiota in Healthy Adults.

The current study investigates whether probiotic fermented milk (PFM) and yogurt consumption (YC) are related to both the ingested bacteria taxa and the overall gut microbiota (GM) composition in healthy adults. PFM and YC habits were analyzed in 260 subjects (51% male) by specific questionnaires, and the following groups were considered: (1) PFM groups: nonconsumers (PFM-NC, n = 175) and consumers (PFM, n = 85), divided as follows: Bifidobacterium-containing PFM (Bif-PFM; n = 33), Lactobacillus-containing PFM (Lb-PFM; n = 14), and mixed Bifidobacterium and Lactobacillus-containing PFM (Mixed-PFM; n = 38); (2) PFM-NC were classified as: yogurt nonconsumers (Y-NC; n = 40) and yogurt consumers (n = 135). GM was analyzed through 16S rRNA sequencing. PFM consumers showed higher Bifidobacteria taxa levels compared to NC, from phylum through to species. Specifically, Bif-PFM consumption was related to higher B. animalis levels (p < 0.001), whereas Lb-PFM consumption was associated to higher levels of Bifidobacterium (p < 0.045) and B. longum (p = 0.011). YC was related to higher levels of the yogurt starter Streptococcus thermophilus (p < 0.001). Lactobacilli and the overall GM were not related either to YC or PFM consumption. According to these results, healthy adults might benefit from PFM intake by increasing Bifidobacterium levels.

2-OHOA supplementation reduced adiposity and improved cardiometabolic risk to a greater extent than n-3 PUFA in obese mice.

OBJECTIVE: We aimed to assess whether 2-hydroxyoleic acid (2-OHOA) and n-3 polyunsaturated fatty acids (PUFA) could counteract changes on adipokine secretion and cardiometabolic risk biomarkers associated with high-fat diet-induced obesity in mice. METHODS: Female ICR/CD1 mice (8 weeks old) were divided into four groups receiving different diets (n=8/group): (1) standard chow (control) for 18 weeks; (2) 22% fat for 4 weeks + 60% fat for 14 weeks (obesogenic diet, OD); 3) OD + 2-OHOA (1500mgkg-1 diet) for the last 6 weeks (ODHO); and 4) OD+n-3 PUFA (eicosapentaenoic+docosahexaenoic acids, 1500+1500mgkg-1 diet) for the last 6 weeks (OD-N3). After 18 weeks, body weight, periovarian visceral fat, heart and liver weights were measured, as well as cardiometabolic parameters (systolic and diastolic blood pressure, blood glucose, insulin, HOMA index, triglycerides, total cholesterol, apolipoproteins A1 and E), plasma adipokines and inflammatory proteins (leptin, adiponectin, plasminogen activator inhibitor 1 [PAI1], soluble E-selectin [sE-selectin], matrix metalloproteinase-9 [MMP-9], fibrinogen, soluble intercellular adhesion molecule [sICAM] and soluble vascular adhesion molecule [sVCAM]), and secretion of pro-inflamatory cytokines and inflammatory biomarkers from periovarian adipocytes. RESULTS: OD mice had greater body and heart weights, and plasma leptin, and lower adiponectin and resistin secretion from adipocytes. Supplementation with 2-OHOA reduced body and heart weights, blood pressure, triglycerides and leptin, and restored adiponectin and resistin secretion, while n-3 PUFA only reduced triglyceride levels (all P<0.05). CONCLUSION: 2-OHOA supplementation was more effective in reducing adiposity, modulating adipokine secretion and ameliorating cardiometabolic risk than n-3 PUFA.

Various therapies for ocular surface diseases.

This paper aims to discuss various therapeutical strategies (corneal cross-linking, amniotic membrane transplantation with or without autologous serum application, medical regenerative therapy) for treating ocular surface diseases according to medical indications, etiology, local and general status of the patient. Besides the evolution and treatment of the lesions induced by corneal foreign body, ocular burns, neurotrophic keratitis, pterygium removal, Mooren's ulcer, this paper also follows and evaluates the migration, stratification and development of corneal epithelium. Of course, the success of the treatment depended on the therapeutic approach, the cause of the disease, the status of the eye and the patients' compliance. All cases presented had good results, proving once again, that a well-chosen therapeutic approach ensures the improvement or cure for many ocular surface diseases nowadays. ABBREVIATIONS: BVCA = best corrected visual acuity, OCT = optical coherence tomography, CLX = corneal cross-linking.

Increased naive CD4+ and B lymphocyte subsets are associated with body mass loss and drive relative lymphocytosis in anorexia nervosa patients.

Anorexia nervosa (AN) is an atypical form of malnutrition with peculiar changes in the immune system. We hypothesized that different lymphocyte subsets are differentially affected by malnutrition in AN, and thus, our aim was to investigate the influence of body mass loss on the variability of lymphocyte subsets in AN patients. A group of 66 adolescent female patients, aged 12-17 years, referred for their first episode of either AN or feeding or eating disorders not elsewhere classified were studied upon admission (46 AN-restricting subtype, 11 AN-binge/purging subtype, and 9 feeding or eating disorders not elsewhere classified). Ninety healthy adolescents served as controls. White blood cells and lymphocyte subsets were analyzed by flow cytometry. Relationships with the body mass index (BMI) z score were assessed in linear models adjusted by diagnostic subtype and age. Leukocyte numbers were lower in AN patients than in controls, and relative lymphocytosis was observed in AN-restricting subtype. Lower CD8+, NK, and memory CD8+ counts were found in eating disorder patients compared with controls. No differences were found for CD4+ counts or naive and memory CD4+ subsets between the groups. Negative associations between lymphocyte percentage and the BMI z score, as well as between the B cell counts, naive CD4+ percentage and counts, and the BMI z score, were found. In conclusion, increased naive CD4+ and B lymphocyte subsets associated with body mass loss drive the relative lymphocytosis observed in AN patients, which reflects an adaptive mechanism to preserve the adaptive immune response.

Erratum to: Evaluation of Lactobacillus coryniformis CECT5711 strain as a coadjuvant in a vaccination process: a randomised clinical trial in healthy adults.

[This corrects the article DOI: 10.1186/s12986-017-0187-1.].

Erratum to: Evaluation of Lactobacillus coryniformis CECT5711 strain as a coadjuvant in a vaccination process: a randomised clinical trial in healthy adults.

[This corrects the article DOI: 10.1186/s12986-016-0154-2.].

Evaluation of Lactobacillus coryniformis CECT5711 strain as a coadjuvant in a vaccination process: a randomised clinical trial in healthy adults.

BACKGROUND: Although the effects of probiotics on the immune system have been extensively evaluated under disease states, their role in healthy situations remains unclear, since changes are hardly expected under immunological homeostasis. EFSA indicates that vaccination protocols could be used to evaluate the potential role of probiotics to improve the immune response against antigen challenges. The aim of the study was to evaluate the effect of Lactobacillus coryniformis CECT5711 (Lc) on the specific immunity of healthy volunteers undergoing vaccination with Hepatitis A virus (HAV). METHODS: One hundred twenty-three healthy adults were randomised into three groups to follow a 6-week (wk) intervention and all received an intramuscular HAV vaccine 2 weeks after starting the intervention: 1) PRO1 received Lc for 2weeks (1 capsule/day; 3 × 109 CFU/capsule) and placebo capsules after vaccination; 2) PRO2 received a daily capsule of Lc (3 × 109 cfu/day) before and after the challenge; 3) Control group (C) received a daily placebo capsule before and after the vaccine. Blood samples were collected at the beginning (visit 1; V1) and after 2 (V2) and 6 weeks (V3) of the intervention. At each visit, lymphocyte subset counts and cytokine levels were analysed. Specific HAV antibodies were analysed at V1 and V3. To evaluate differences between groups, one-way ANOVA with Bonferroni post-hoc test were used regarding lymphocyte subset counts and specific HAV antibodies production, and Friedman test of related samples and Kendall concordance coefficient for cytokines production. Chi square test was used to analyse seroconversion rates. RESULTS: Specific HAV antibodies were significantly higher in PRO1 (50.54 ± 29.57) compared to C (36.23 ± 16.45) (P = 0.017) and showed an intermediate value in PRO2 (41.61 ± 15.74). Seroconversion rates were similar in the three groups (97.3, 92.3 and 97.4% in C, PRO1 and PRO2 respectively). Memory T-helper lymphocytes increased in V3 vs. V1 (P = 0.032) in PRO2. No differences were found in cytokine concentrations. CONCLUSION: Mixed results have been found regarding the usefulness of Lc supplementation to increase the antigen-specific antibody response to an immune challenge. Clinical trial registration number: EudraCT Number 2016-000183-42. Registered 19 January 2016. Retrospectively registered.

Ocular surface reconstruction in limbal stem cell deficiency.

The purpose of our review was to familiarize the readers with the new concepts in ocular surface diseases and reconstruction. Limbal stem cell deficiency is characterized by the progressive invasion of conjunctival epithelial cells onto the cornea, superficial vascularisation, destruction of the corneal basement membrane, and chronic inflammatory cell infiltration. Depending on the severity of the disease and the time passed from the primary injury amniotic membrane transplantation, keratolimbal allograft and autograft are the available treatments hoping that, in the nearest future, stem cell transplantation and tissue engineering will become the usual therapeutic choices.