Med Diet 4.0: the Mediterranean diet with four sustainable benefits.

OBJECTIVE: To characterize the multiple dimensions and benefits of the Mediterranean diet as a sustainable diet, in order to revitalize this intangible food heritage at the country level; and to develop a multidimensional framework - the Med Diet 4.0 - in which four sustainability benefits of the Mediterranean diet are presented in parallel: major health and nutrition benefits, low environmental impacts and richness in biodiversity, high sociocultural food values, and positive local economic returns. DESIGN: A narrative review was applied at the country level to highlight the multiple sustainable benefits of the Mediterranean diet into a single multidimensional framework: the Med Diet 4.0. Setting/subjects We included studies published in English in peer-reviewed journals that contained data on the characterization of sustainable diets and of the Mediterranean diet. The methodological framework approach was finalized through a series of meetings, workshops and conferences where the framework was presented, discussed and ultimately refined. RESULTS: The Med Diet 4.0 provides a conceptual multidimensional framework to characterize the Mediterranean diet as a sustainable diet model, by applying principles of sustainability to the Mediterranean diet. CONCLUSIONS: By providing a broader understanding of the many sustainable benefits of the Mediterranean diet, the Med Diet 4.0 can contribute to the revitalization of the Mediterranean diet by improving its current perception not only as a healthy diet but also a sustainable lifestyle model, with country-specific and culturally appropriate variations. It also takes into account the identity and diversity of food cultures and systems, expressed within the notion of the Mediterranean diet, across the Mediterranean region and in other parts of the world. Further multidisciplinary studies are needed for the assessment of the sustainability of the Mediterranean diet to include these new dimensions.

Clostridium difficile colitis acquired in the intensive care unit: outcome and prognostic factors.

PURPOSE: We assessed factors associated with mortality and complicated course in the case of Clostridium difficile infection (CDI) acquired in the intensive care unit (ICU). METHOD: Retrospective cohort study conducted from 1 January 2002 through 1 January 2012. All patients who acquired CDI in our ICU were included. RESULTS: Thirty-one patients were included. Twenty patients (65 %) had mild colitis, 8 (25 %) moderate colitis, and 3 (10 %) severe colitis. Initial antibiotherapy was metronidazole (n = 30, 97 %) and vancomycin (n = 1, 3 %). Seventeen patients (55 %) experienced at least one complication: failure of initial treatment (n = 16, 52 %), shock (n = 11, 34 %), need for surgery (n = 1, 3 %) or renal replacement (n = 4, 13 %), or death (n = 8, 26 %). Risk factors of ICU mortality were history of corticosteroids prescription, prolonged ICU stay, low serum albumin level, and high Sequential Organ Failure Assessment (SOFA) score at the time of CDI diagnosis. Factors associated with a complicated course were high Simplified Acute Physiology Score (SAPS II), high SOFA score, and low serum albumin level at the time of CDI onset. CONCLUSION: Risk factors of poor outcome in patients with CDI acquired in the ICU are different from those in the general population suffering from CDI. The implementation of treatment algorithms taking into account these factors may reduce complication rates in this specific population.

Clinical spectrum and outcome of critically ill patients suffering from prosthetic joint infections.

PURPOSE: To report the clinical characteristics and prognosis of prosthetic joint infections (PJIs) in Intensive care units (ICUs). METHODS: Forty-one patients consecutively admitted to ICUs for PJIs between January 2004 and June 2011 were included in a retrospective case series. RESULTS: A majority of patients (73 %) had severe underlying disease. Acute infection affected 26 patients (63 %). Blood cultures were positive in 16 patients (39 %). Staphylococcus species were the most commonly implicated causative organisms (n = 36, 88 %). The surgical strategy was two-stage replacement in 25 cases (61 %). The surgical procedure leading to ICU admission was mainly prosthesis removal with spacer implantation (n = 13, 32 %). Initial antibiotherapy was a broad-spectrum beta-lactam antibiotic combined with a glycopeptide, linezolid, or daptomycin in 26 cases (63 %). Mortality in the ICU was 20 %. In nonsurvivors, diabetes, acute infection, and American Society of Anesthesiologists (ASA) score >3 were more frequent. The distribution of surgical strategies and procedures was not statistically different in survivors and nonsurvivors. The proportion of patients treated with antibiotherapy adjusted according to previous microbiological findings was higher in nonsurvivors (50 vs. 12 %, p = 0.02). CONCLUSIONS: In our case series of critically ill patients suffering from PJI, factors associated with a poor outcome were diabetes mellitus, ASA score >3, and acute infection. Surgical strategies and surgical procedures had no significant impact on the ICU mortality. Adjustment of initial antibiotherapy according to previous microbiological findings should be made with caution.

Impact of combination therapy with aminoglycosides on the outcome of ICU-acquired bacteraemias.

Pharmacodynamic studies report on the rapid bactericidal activity of aminoglycosides, conferring them as being of theoretical interest for bacteraemia treatment. We assessed this issue in a retrospective study of patients with intensive care unit (ICU)-acquired bacteraemias. To determine the impact of aminoglycosides in antimicrobial combination on the outcome of patients with bacteraemia, we performed a monovariate analysis and a logistic regression analysis comparing patients treated with or without aminoglycosides. Forty-eight bacteraemias in 48 patients were included. Eighteen patients received aminoglycosides. Baseline characteristics as well as adaptation and adequation of antibiotherapy did not differ in patients who did or did not receive aminoglycosides. Patients who received aminoglycosides had longer time alive away from the ICU (11.3 ± 8.9 (10 [0-20]) vs. 3.2 ± 6.6 (0 [0-2] days; p = 0.002) and free from mechanical ventilation (12.5 ± 9.3 (14 [0-21] vs. 5.5 ± 9.2 (0 [0-10] days; p = 0.02) on day 28. The ICU mortality was 16% in the aminoglycoside group versus 46% (p = 0.03). In the multivariate analysis, patients treated with aminoglycosides were 6 times less likely to die than those treated without aminoglycosides (confidence interval [CI] = [1.3-28.9]; p = 0.02). Our study supports the hypothesis that combination short-term antibiotherapy with an aminoglycoside for ICU-acquired bacteraemias could increase survival.

Factors of loss to follow-up during tuberculosis treatment in a low-incidence region.

OBJECTIVE: The proportion of successfully treated tuberculosis (TB) patients remains below the WHO target in France, because of a high proportion of loss to follow-up. We aimed to identify factors associated with loss to follow-up in northern France, a low-incidence area. METHODS: Between 1997 and 2017, all consecutive patients diagnosed with TB at the Tourcoing Hospital, except those infected with multidrug-resistant or extensively drug-resistant strains, were included in a retrospective cohort study. A logistic regression analysis was performed to determine factors associated with loss to follow-up. RESULTS: One hundred and ninety patients were included. Previous TB treatment was reported in 32 patients (17%), extrapulmonary TB in 107 (56%), and HIV infection in 44 (23%). The proportion of loss to follow-up was 15%. In multivariate analysis, the risk of loss to follow-up decreased in case of first TB treatment (OR 0.36; 95% CI: 0.14-0.92, P=0.03) and increased in non-HIV-infected patients (OR 7.67; 95% CI: 1.00-59.0, p=0.05). Support for compliance was more frequent in HIV-infected patients (23% vs. 7%, p=0.005). CONCLUSION: The proportion of loss to follow-up was high. HIV infection was associated with a lower risk of loss to follow-up, likely to be due to more frequent support for compliance.

Multidrug-resistant tuberculous meningitis in an HIV-positive patient: a challenging disease.

We report two cases of disseminated multidrug-resistant tuberculosis with meningitis in HIV-positive patients, who were both recent emigrants from sub-Saharan Africa. Our two cases highlight new challenges in the care of HIV and tuberculosis coinfection including early diagnosis and treatment of multidrug-resistant tuberculosis that is spreading.

Induction of the skin endogenous protective mitochondrial MnSOD by Vitreoscilla filiformis extract.

Vitreoscilla filiformis (Vf), a filamentous bacteria living in fresh water is thought to contribute to the observed beneficial effects of Spa water on skin. An active fraction obtained from a Vf biomass was evaluated for its ability to modulate mRNA expression in cultured skin cells. cDNA array analysis was conducted first using a customized membrane including 1176 selected and fully identified genes involved in skin physiology and homeostasis then the newly developed full genome U133 plus 2.0 GeneChip from Affymetrix. The mitochondrial protective manganese superoxide dismutase (MnSOD/SOD-2) was identified as a preferentially induced mRNA target in both normal human dermal fibroblasts and keratinocytes. Induction at the transcriptional level in both cell types was confirmed using quantitative real time/polymerase chain reaction and a kinetic analysis revealed a maximal increase in mRNA expression 20 h after stimulation with Vf extract (Vfe). Using immunofluorescent (fluorescent cell sorter) analysis, an induction of MnSOD protein in both normal human dermal skin fibroblasts (x1.6; P < 0.01) and epidermal keratinocytes (x1.4; P < 0.01) was confirmed. As MnSOD is a major inducible free-radical scavenger in skin, these results suggest that the Vfe could induce skin cells to produce their own endogenous protective defences in vivo against both exogenous environmental stressors such as UV irradiation or microflora as well as to combat endogenous sources of deleterious free radicals involved in skin ageing. Finally, in order to confirm the in vivo potential of this original extract in human, we evaluated its protective activity vs. placebo on the generation of sunburn cells in epidermis under UVB stress. As expected from in vitro profiling, Vfe was indeed found to significantly inhibit the appearance of sunburn cells in UVB-exposed areas, a signature of skin alteration which has been suggested to be linked to a defect in MnSOD protective activity. Altogether, those data suggest that the combination of a suitable protective UV filter together with this bioactive Vfe might improve skin protection through complementary pathways.

Complications following intravesical bacillus Calmette-Guerin treatment for bladder cancer: a case series of 22 patients.

BACKGROUND: Intravesical bacillus Calmette-Guerin (BCG) therapy is an effective and widely used treatment for superficial bladder carcinoma. Local complications are frequent whereas systemic complications are rare but can be serious, and their management is not well known. METHODS: We describe retrospectively the records of 22 patients treated in 3 infectious disease departments, for complications related to intravesical BCG therapy as treatment of bladder cancer. RESULTS: All the patients were male, with a median age of 68 years (range 56-88). Complications occurred after a median of 5 instillations (range 1-11) and were observed within 24 h following BCG instillation for 14 patients. Common symptoms were fever (n = 20), impaired general condition (n = 14), and shortness of breath (n = 7). Six patients had a systemic septic reaction leading to transfer into the intensive care unit for five of them. Lung infiltration was the most frequent presentation (n = 11). Mycobacterium bovis was isolated from only two patients, but histology showed the presence of a granuloma in nine patients. Antimycobacterial treatment was initialized in 17 patients; the outcome was favorable in 16 patients, with a median length of symptoms resolution of 22.5 days (range 5-425 days). Eleven patients received corticosteroids in addition to specific treatment and had a more rapid improvement. One patient died with disseminated BCGitis proved by biopsy. CONCLUSIONS: Complications following intravesical BCG therapy are rare but can be severe and fatal. Histology seems to be the method that contributes most in confirmation of the diagnosis. Antimycobacterial therapy is effective, and probably more efficient when combined with corticosteroids, but the regimen and duration of the treatment are not standardized.

An extract of bovine thymus stimulates human keratinocyte growth in vitro.

An extract prepared from newborn calf thymus stimulated proliferation of human keratinocytes cultured from newborn foreskins and from skin biopsies of 26 adult volunteers aged 19 to 70 years. Growth over the 7-day assay period in the basal medium was age-dependent, with newborn cultures achieving a 10-fold increase in cell number over seeding density, old adult cultures barely maintaining their seeding density and young adult cultures intermediate in proliferative capacity. Maximally stimulatory extract concentration was 5-fold higher for newborn than for adult keratinocytes, with adult cultures experiencing toxicity at doses still growth-promoting for newborn cultures. At optimal extract concentration the maximal average increase in cell yield (66.3% for newborn, 53.6% for young adult, and 18.1% for old) indicated decreased mitogen responsiveness or increased inhibitor sensitivity with increasing donor age. Stimulation of cholera toxin-treated cultures was equally high, ranging from 39.4% to 145.9%, suggesting that the extract acts through a cyclic AMP-independent pathway. Thymic extract did not increase colony forming efficiency. Our findings provide further support for the concept of functional interactions between the skin and the immune system, in addition to the recognized morphologic similarities between thymic cells and keratinocytes. Furthermore, these data confirm earlier findings of an inverse relationship between mitogen responsiveness and donor age for cultured cells.

In vitro biosynthesis of type I and III collagens by human dermal fibroblasts from donors of increasing age.

A quantitative study of type I and type III collagen production was carried out on primary cultures of human dermal fibroblasts. Cultures were initiated from facial and mammary skin of 29 women aged between 19 and 68 years. Secreted and cell-associated collagen levels were determined by an enzyme linked immunosorbent assay (ELISA). We found that the secretion of type I and type III collagen decreased linearly with age (r = 0.432; P = 0.0193 and r = 0.502; P = 0.0147, respectively). There was a 29% loss in secretion ability for type I and type III collagen over the 49-year period studied. Furthermore, no significant linear age-related decrease was observed for type I and type III collagen associated with the cellular fraction. The influence of body site was also analysed. We observed a significant linear age-related decrease in type I collagen secretion by mammary skin cells (P = 0.0183 and r = 0.618) as well as facial skin cells (P = 0.0037 and r = 0.699). Furthermore, only mammary skin fibroblasts showed a significant linear age-related decrease in secreted type III collagen (P = 0.106 and r = 0.513). No age-related variations in cell-associated collagen were found.

Human epidermal cells progressively lose their cardiolipins during ageing without change in mitochondrial transmembrane potential.

Mitochondria dysfunction is considered to be a major cause of the modifications that occur during cell ageing. For this reason, cardiolipin, a suitable marker of the chondriome, as well as the mitochondrial transmembrane potential were examined in keratinocytes obtained from 9- to 75-year-old women. The study was carried out by flow cytometry using two fluorescent mitochondria probes: nonyl acridine orange, which binds specifically to cardiolipin, and rhodamine 123, which is incorporated mainly in response to transmembrane potential. Cardiolipin levels in cells from elderly donors (75 years old) would be 57% lower (r = 0.540; P = 0.0002) than those in children (9 years old), while the inner transmembrane potential remained unchanged (r = 0.0394; P = 0.8017). The stability of the membrane potential may be explained by either or both of the following hypotheses: (i) the same pool of organelles able to maintain membrane potential is conserved even when cardiolipin levels decrease (ii) mitochondria membrane potential does indeed decrease with age but is compensated by glycolysis energy production. Finally, it may be stated that the fluorescent probes nonyl acridine orange and rhodamine 123 might be of interest in testing the phenotype of senescent cells and would be useful in screening the role of certain specific genes in cell ageing.

Existence of a lipid gradient in the upper stratum corneum and its possible biological significance.

The internal stratum corneum lipid composition was investigated in relation to depth in vivo in healthy human volunteers by extraction following one, three or five strippings. Automated multiple development high-performance thin-layer chromatography (AMD-HPTLC) and gas chromatography (GC) followed by normalized principal component analysis showed a decrease in the amount of lipids extracted after one, three and five strippings. Between levels 0, 1, 3 and 5 the stratum corneum lipid composition showed an increase in phospholipids and cholesterol-3-sulphate at level 3, a decrease in ceramide, cholesterol and free fatty acids after level 1, and a slight decrease in sterol esters at level 3. Lipids extracted after three strippings displayed a characteristic composition with an increase in the proportion of phospholipids and cholesterol-3-sulphate. Free fatty acid analysis in relation to depth revealed a decrease in the amounts of C14:0, C16:0, C16:1, C18:0 and C18:1 between levels 1 and 5 and an increase in the C24:0. A decrease in the unsaturated/saturated chain ratio with depth was also observed, reflecting a greater decrease in unsaturated than saturated free fatty acids. A decrease in the ratios of free fatty acids to cholesterol and free fatty acids to ceramides after three and five strippings, respectively, and previously reported results, confirm the importance of this level of stratum corneum lipids in skin barrier properties.

Cutaneous bioavailability in hairless rats of tretinoin in liposomes or gel.

Topical bioavailability of drugs incorporated in liposomes is not well known. We compared the skin penetration of tretinoin in liposomes and in a classical alcoholic gel. [3H]Phosphatidylcholine dipalmitoyl (DPPC) and [14C]tretinoin (0.14%) were incorporated in the phospholipidic phase of the liposomes, and [14C]tretinoin was incorporated in a gel for comparison. Skin absorption was studied in vitro with Franz cells. In vivo distribution in cutaneous structures was studied according to Schaefer's method. Liposomes impregnated the stratum corneum, with a partial dissociation between tretinoin and phosphatidyl-choline dipalmitoyl. In dermis, tretinoin diffused alone. Tretinoin release seemed to be controlled, and steady state was reached later with liposomes than with gel. This phenomenon was linked with a significantly reduced absorption (1.60% for liposomes versus 3.09% for the gel) and higher retention in epidermis (mainly stratum corneum) and dermis (41 and 13%, respectively, with liposomal form versus 18 and 8%, respectively, with gel form). This study clearly shows that, compared with the gel, the liposome formulation tends to improve the local effect of tretinoin in the skin and decrease the systemic absorption.

Human epidermis reconstructed on synthetic membrane: influence of experimental conditions on terminal differentiation.

Cell suspensions of human keratinocytes seeded onto cell culture inserts may undergo terminal differentiation in the absence of fibroblasts. Among the parameters that control these morphogenic events, exposure to air and the composition of the culture medium were investigated. In the latter case, three media were considered DMEM:Ham's F12, MCDB 153, and keratinocyte SFM medium at equivalent calcium (1.5 mM) and fetal calf serum (5%) concentrations. Immunochemical methods and transmission electron microscopy show that cells cultured in DMEM:Ham's F12 medium, and then raised at the air-liquid interface, form a basal layer plus suprabasal cell layers corresponding to the stratum spinosum, stratum granulosum, and stratum corneum. The suprabasal keratinocyte layers show morphologies that resemble intact skin in which cells are connected by desmosomes and contain intermediate filaments and keratohyalin-filaggrin granules. When the cultures are kept submerged, the keratinocytes show occasional keratohyalin granules and are connected by fewer desmosomes. Additionally, no proper stratum corneum is formed. In keratinocyte SFM medium and MCDB 153, cultures raised at the air-liquid interface are not able to form an epithelium of normal architecture and do not express terminal differentiation markers. Differentiation is initiated, however, since desmosomes and bundles of keratin filaments appear; on the other hand, filaggrin is not expressed even after 28 d in culture. Membrane-bound transglutaminase is expressed throughout the entire suprabasal compartment in MCDB153 and DMEM:Ham's F12 media but never appears in keratinocyte SFM medium. These studies show the relative independence of epidermal differentiation program to the composition (including the calcium concentration) of the media contacting the dermis and filling the extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermotropic phase behavior of in vivo extracted human stratum corneum lipids.

The thermotropic phase behavior of lipids extracted either in vivo from inner forearm (SCLE) or plantar callus (PC) was investigated by differential scanning calorimetry and small angle X-ray diffraction. PC composition was chromatographically modified (MPC) by eliminating the more polar lipids in order to evaluate their role. Analysis of composition confirms the potential use of PC as a source of stratum corneum lipids. MPC and SCLE exhibit similar differential scanning calorimetry (DSC) profiles with a main transition around 50 degrees C attributed to the solid-to-liquid phase transition of the ceramides. The absence of a transition around 50 degrees C for PC suggests the possible perturbation of ceramide packing by the significantly high proportion of phospholipids. X-ray data suggest a high miscibility of sebum components in stratum corneum lipids with possible modification of chain packing. The MPC patterns show a lipid phase separation which underscores the role of polar lipids in cholesterol/free fatty acids/sterol esters/ceramides structural cohesion.

Paf-acether in human skin.

Paf is a phospholipid mediator present in human skin which induces inflammatory events, such as neutrophil infiltration and increased vascular permeability. Recent data suggest that cutaneous cells, such as fibroblasts and keratinocytes, produce paf and that paf is released during allergic cutaneous reactions. It is tempting to speculate that paf may contribute to the development of various skin disorders with acute and chronic skin inflammation. Paf antagonists may help in bringing answers to this hypothesis and may offer new prospects for the treatment of cutaneous inflammatory diseases.