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Psoriasis is a skin disease characterized by hyperproliferation of keratinocytes and chronic inflammation. Mesenchymal stem/stromal cells (MSCs) exhibit an immunoregulatory function that can be altered in the skin of these patients. However, to date, the presence and functional capacity of MSCs in the dermis and epidermis of patients with psoriasis have not been fully established. In the present study, we evaluated the presence of MSCs in the skin of patients by obtaining adherent cells from the dermis and epidermis of lesional and nonlesional areas and characterizing them in a comparative manner with corresponding cells obtained from the dermis (HD-MSCs) and epidermis (HE-MSCs) of healthy donors. We determined whether the adherent cells had immunophenotypic profiles and differentiation potentials that were characteristic of MSCs. In addition, we analyzed their immunosuppression function by evaluating their capacity to decrease T cell proliferation. Our results indicate the presence of MSCs in the dermis and epidermis of healthy donors and patients with psoriasis; adherent cells from all skin sources exhibited MSC characteristics, such as expression of CD73, CD90, and CD105 markers and a lack of hematopoietic and endothelial marker expression. However, the cell populations obtained showed differences in differentiation potential toward adipogenic, osteogenic, and chondrogenic lineages. In addition, we observed a low MSC obtention frequency in nonlesional epidermal samples (NLE-MSCs), which also showed alterations in morphology and proliferation rate. Interestingly, MSCs from both the nonlesional dermis (NLD-MSCs) and lesional dermis (LD-MSCs) showed higher HLA class I antigen (HLA-I) expression than HD-MSCs. Moreover, NLD-MSCs showed a low T cell proliferation suppression capacity. In summary, this study demonstrates the presence of MSCs in the epidermis and dermis of patients with psoriasis and suggests that such cells may favor the inflammatory process and thus psoriatic lesion development through high HLA-I expression and low immunosuppression capacity. [ABSTRACT FROM AUTHOR]

Aims. To evaluate the factors that predict reulceration beneath the hallux in people with a history of diabetic foot ulceration. Methods. A prospective study conducted between January 2012 and December 2014 was performed in a diabetic foot unit to assess the risk factors associated with hallux reulceration. Sixty patients with diabetic neuropathy and a history of previous ulcer were consecutively included. Sociodemographic factors and comorbidities plus the biomechanical and radiographic factors were obtained. Follow-up on participants was conducted every month, and they wore offloading therapeutic footwear and custom-made insoles. Hallux reulceration during the follow-up period was assessed as the main outcome measure in the study. Results. Patients were followed up during 29 (14.2-64.4) months. Twenty-nine patients (52%) developed a new ulceration: 9 patients (31%) in the hallux and 20 (69%) in other locations. Functional hallux limitus (p=0.005, 95% CI (2.097–73.128), HR 12.384) and increased body mass index (p=0.044, 95% CI (1.003-1.272), HR 1.129) were associated with the hallux ulceration-free survival time in the multivariate Cox model. Conclusions. Obesity and the presence of functional hallux limitus increase the probability of developing hallux reulceration in patients with diabetic neuropathy and a history of ulcers. [ABSTRACT FROM AUTHOR]

Objective: To compare the utility of routine third-trimester ultrasound examination at 36 weeks' gestation with that at 32 weeks in detecting fetal growth restriction (FGR).Methods: This was an open-label parallel randomized trial (ROUTE study) conducted at a single general hospital serving a geographically well-defined catchment area in Barcelona, Spain, between May 2011 and April 2014. Women with no adverse medical or obstetric history and a singleton pregnancy without fetal abnormalities at routine second-trimester scan were assigned randomly to undergo a scan at 32 weeks' gestation (n = 1272) or at 36 weeks' gestation (n = 1314). Primary outcome measures were detection rates of FGR (customized birth weight < 10(th) centile) and severe FGR (customized birth weight < 3(rd) centile).Results: There were no significant differences in perinatal outcome between those who underwent a scan at 32 weeks' gestation and those who underwent a scan at 36 weeks' gestation. Severe FGR at birth was associated significantly with emergency Cesarean delivery for fetal distress (odds ratio (OR), 3.4 (95% CI, 1.8-6.7)), neonatal admission (OR, 2.23 (95% CI, 1.23-4.05)), hypoglycemia (OR, 9.5 (95% CI, 1.8-49.8)) and hyperbilirubinemia (OR, 9.0 (95% CI, 4.6-17.6)). Despite similar false-positive rates (FPRs) (6.4% vs 8.2%), FGR detection rates were superior at 36 vs 32 weeks' gestation (sensitivity, 38.8% vs 22.5%; P = 0.006), with positive and negative likelihood ratios of 6.1 vs 2.7 and 0.65 vs 0.84, respectively. In cases of severe FGR, FPRs for both scans were also similar (8.5% vs 8.7%), but detection rates were superior at 36 vs 32 weeks' gestation (61.4% vs 32.5%; P = 0.008). Positive and negative likelihood ratios were 7.2 vs 3.7 and 0.4 vs 0.74, respectively.Conclusion: In low-risk pregnancies, routine ultrasound examination at 36 weeks' gestation was more effective than that at 32 weeks' gestation in detecting FGR and related adverse perinatal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Gel permeation chromatography (GPC), also known as size exclusion chromatography (SEC), is the technique routinely used at high temperature to analyze the molar mass distribution in polyolefins. The distribution of comonomer along the molar mass distribution in a copolymer is a key microstructural feature that determines the macroscopic properties of the material, and thus, its range of possible applications and performance. The direct coupling of a modern filter-based infrared (IR) detector to a high temperature GPC instrument, by means of a heated flow-through cell, is here described. The analyses are carried out by recording the continuous IR absorbance chromatograms at selected bands, which show different sensitivities to the different monomer units. A slice-by-slice ratio of the IR bands is further calculated to determine the average chemical composition of each molar mass fraction, after GPC separation. The high sensitivity of this IR detection method allows the injection of low concentrations of sample and the use of standard GPC analysis conditions, so that chromatographic quality is not compromised even in cases where very high molar mass fractions are present. The analysis of comonomer variations along the molar mass distribution in polyolefin copolymers is discussed. Selected applications of the method to polyethylene and poly(propylene) copolymers are presented. [ABSTRACT FROM AUTHOR]

Aims To analyse the risk of reulceration caused by the transfer of lesions in patients with diabetes, undergoing resection of at least one metatarsal head. Methods A total of 119 patients with diabetes from the Diabetic Foot Unit (Complutense University, Madrid, Spain), who underwent resection of at least one metatarsal head were analysed prospectively from November 2006 to December 2011 to assess reulceration in the other metatarsal head. Results Seven patients were excluded for being subjected to a pan-metatarsal head resection and 11 patients dropped out. During a median follow-up period of 13.1 months (interquartile range 6.1-22.8 months), 41% of patients suffered from reulcerations. Reulceration frequency in patients operated on the 1st, 2nd, 3rd, 4th, 5th and several metatarsal heads was 9 (69%), 8 (44%), 12 (52%), 2 (25%), 6 (19%) and 4 (50%) events, respectively. The Cox regression model showed hazard ratios that were significant for the location of the metatarsal resection. The first metatarsal showed the highest risk for reulceration (hazard ratio 3.307; 1.472-7.430) and the fifth metatarsal showed the lowest risk (hazard ratio 0.339; 0.138-0.832). Conclusions Reulceration is a frequent event following resection of a metatarsal head and should be regarded as an implicit complication of the intervention. The location of the resection determines the risk of reulceration, which is highest for patients operated on the first metatarsal head and lowest for patients operated on the fifth metatarsal head. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to compare the outcomes of surgical treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) with cases caused by methicillin-sensitive Staphylococcus aureus (MSSA). Methods We abstracted data of a series of 185 consecutive patients with diabetes and foot osteomyelitis undergoing surgery within the first 12 h after admission at a single hospital. Bone infection was confirmed by histopathological studies. Only cases where Staphylococcus aureus was isolated from bone specimens were included in this analysis. We analysed several variables between the two groups: MRSA vs. MSSA. Results MRSA bone infection was associated with higher body temperature ( P = 0.02) and white blood cell count ( P = 0.02) than MSSA. Patients with MRSA infections underwent a greater number of surgical procedures ( P = 0.03). Limb salvage was achieved in 93.6% of the patients, with no statistically significant difference in limb salvage rates between MRSA and MSSA-related osteomyelitis. Conclusions From our experience, where treatment is based on early and aggressive surgical treatment, MRSA bone infections are not associated with worse prognosis. [ABSTRACT FROM AUTHOR]

Diabet. Med. 28, 1238-1240 (2011) Abstract Aims The objectives of our study were (i) to analyse the inter-observer reproducibility or diagnostic variability of the probing-to-bone test, depending on the training of the professional involved, and (ii) to assess whether the probing-to-bone test can be extrapolated to any professional specialty that deals with these patients. Methods This was a cross-sectional study, involving 75 patients with diabetic foot ulcer and clinical suspicion of osteomyelitis. A registration sheet was completed for all patients involved in the research study, gathering data relative to the results of the probing-to-bone test performed by three observers. Observer 1 was a very experienced professional with several years of experience in the treatment of the diabetic foot; observer 2 was a medium-experienced professional whose experience ranges from 6 to 12 months in the treatment of the diabetic foot; observer 3 was a healthcare professional without experience in the treatment of the diabetic foot. Data were gathered confidentially by a fourth researcher. Results The results showed a kappa index of 0.593 (95% CI 0.407-0.778) between observer 1 and observer 2, 0.397 (95% CI 0.188-0.604) between observer 1 and observer 3 and 0.53 (95% CI 0.335-0.725) between observer 2 and observer 3. Conclusions The probing-to-bone test demonstrated moderate to fair concordance with an experienced examiner, although the degree of concordance is not significant between groups. [ABSTRACT FROM AUTHOR]

Purpose To determine changes in lamina cribrosa ( LC) and prelaminar tissue in patients with unilateral non-arteritic anterior ischemic optic neurophaty ( NAION) using enhanced depth imaging ( EDI) spectral domain optical coherence tomography ( SD- OCT). Methods Seventeen eyes of 17 patients with NAION were prospectively studied. SD- OCT scans using EDI technology were obtained at the acute episode and at two and six months after the ischemic event. The OCT device was set to image a 15x10 degree vertical rectangle centered on the optic disc. The scan in LC was seen clearliest was selected for analysis. The vertical distances from three equidistant points on the reference line (Bruch's membrane opening- BMO) to the anterior prelaminar tissue surface, and to the anterior and posterior surfaces of the LC were measured. Results At diagnosis, mean prelaminar tissue was significantly thicker and anterior LC surface more posteriorly placed in NAION eyes than in non-involved eyes. During the follow-up, in NAION eyes there was a significant prelaminar thinning and an anterior LCreversal (P = 0.001 and P = 0.002 at 2 and 6 months respectively). BMO significantly reduced during follow-up (P = 0.008 and P = 0.034 at 2 and 6 months respectively). Both prelaminar tissue thickness and BMO changes correlated with retinal nerve fiber layer thickness measurements. Conclusions OHN is a dynamic structure that undergoes biomechanical changes in eyes suffering NAION. A significant prelaminar tissue thickening and posterior lamina cribrosa displacement occurred during the acute ischemic optic neuropathy, that reverse as the edema resolves. [ABSTRACT FROM AUTHOR]

Heavy binge drinking in adolescence can cause long-term cognitive and behavioral dysfunctions. Recent experimental evidence indicates the participation of immune system activation in the effects of ethanol in the adolescent brain and suggests gender differences. The present study aims to assess plasma cytokine and chemokine levels in male and female adolescents and young adults during acute alcohol intoxication and to correlate these results with the toll-like receptor 4 (TLR4) response. The potential role of the TLR4 signaling response was also assessed in plasma and prefrontal cortex (PFC) of adolescent wild-type and TLR4-knockout male and female mice with binge ethanol treatment. The results showed that alcohol intoxication increased the plasma levels of several cytokine and chemokine [interferon-γ, interleukin (IL)-10, IL-17A, IL-1β, IL-2, IL-4, IL-6, IL-8, fractalkine, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1α (MIP-1α)] and the upregulation of TLR4 mRNA levels occurred in intoxicated females, while elevation of colony-stimulating factor was only observed in the plasma of males. In wild-type female adolescent mice, intermittent ethanol treatment increased the levels of several cytokines (IL-17A and IL-1β) and chemokines (MCP-1, MIP-1α and fractalkine) in PFC and in serum (IL-17A, MCP-1 and MIP-1α), but significant differences in the fractalkine levels in PFC were observed only in male mice. No changes in serum or prefrontal cortex cytokine and chemokine levels were noted in ethanol-treated male or female TLR4-knockout mice. Our findings revealed that females are more vulnerable than males to inflammatory effects of binge ethanol drinking and suggested that TLR4 is an important target of ethanol-induced inflammation and neuroinflammation in adolescence., (© 2016 Society for the Study of Addiction.)

Background: We previously showed that, by activating innate immune receptors Toll-like 4 (TLR4), adolescent intermittent ethanol (EtOH) exposure causes neuroinflammation, myelin damage, and behavioral dysfunctions. Recent findings reveal that clinically used opioid antagonists naltrexone (NT) and naloxone (NX) inhibit opioid-induced TLR4 signaling and that NT, NX, and nalmefene (NF), the 6-methylene derivative of NX, are able to reduce alcohol drinking escalation., Methods: NF (0.1 mg/kg, intraperitoneally) was injected 1 hour prior to EtOH (3 g/kg, intraperitoneally) following intermittent treatment in female (PND35) adolescent mice. Inflammatory molecules, myelin proteins, and apoptotic markers were assessed in the prefrontal cortex (PFC) and striatum/nucleus accumbens (STR/NAcc). The effect of NF on alcohol drinking preference was evaluated in both the wild-type and TLR4 knockout (KO) adolescent mice. Using astroglial cells, the inhibitory potential of NT, NX, and NF on lipopolysaccharide (LPS), or the EtOH-triggered TLR4 response, was compared., Results: Our findings indicate that NF prevents the up-regulation of cytokines (IL-1β, IL-17A, TNF-α), chemokines (MCP-1, MIP-1, KC), and pro-inflammatory mediators (iNOS, COX-2), along with myelin damage and apoptotic events, in both PFC and STR/NAcc. NF also abolishes EtOH-induced escalation of alcohol preference/consumption, but has no effect when administered to TLR4-KO mice. In vitro experiments indicate that NX and NF inhibit TLR4 activation upon LPS or EtOH stimulation. Immunofluorescence studies and lipid rafts isolation show that NF is able to prevent TLR4 translocation to lipid rafts/caveolae in astrocytes., Conclusions: These results suggest that NF prevents neuroinflammation and brain damage by blocking the TLR4 response and also support the role of central pro-inflammatory immune signaling in the modulation of alcohol consumption/addiction., (Copyright © 2017 by the Research Society on Alcoholism.)

The innate immune response in the central nervous system (CNS) participates in both synaptic plasticity and neural damage. Emerging evidence from human and animal studies supports the role of the neuroimmune system response in many actions of ethanol (EtOH) on the CNS. Research studies have shown that alcohol stimulates brain immune cells, microglia, and astrocytes, by activating innate immune receptors Toll-like receptors (TLRs) and NOD-like receptors (inflammasome NLRs) triggering signaling pathways, which culminate in the production of pro-inflammatory cytokines and chemokines that lead to neuroinflammation. This review focuses on evidence that indicates the participation of TLRs and the inflammasome NLRs signaling response in many effects of EtOH on the CNS, such as neuroinflammation associated with brain damage, cognitive and behavioral dysfunction, and adolescent brain development alterations. It also reviews findings that indicate the role of TLR4-dependent signaling immune molecules in alcohol consumption, reward, and addiction. The research data suggest that overactivation of TLR4 or NLRs increases pro-inflammatory cytokines and mediators to cause neural damage in the cerebral cortex and hippocampus, while modest TLR4 activation, along with the generation of certain cytokines and chemokines in specific brain areas (e.g., amygdala, ventral tegmental area), modulate neurotransmission, alcohol drinking, and alcohol rewards. Elimination of TLR4 and NLRP3 abolishes many neuroimmune effects of EtOH. Despite much progress being made in this area, there are some research gaps and unanswered questions that this review discusses. Finally, potential therapies that target neuroimmune pathways to treat neuropathological and behavioral consequences of alcohol abuse are also evaluated., (Copyright © 2016 by the Research Society on Alcoholism.)

The treatment for cocaine use constitutes a clinical challenge because of the lack of appropriate therapies and the high rate of relapse. Recent evidence indicates that the immune system might be involved in the pathogenesis of cocaine addiction and its co-morbid psychiatric disorders. This work examined the plasma pro-inflammatory cytokine and chemokine profile in abstinent cocaine users (n = 82) who sought outpatient cocaine treatment and age/sex/body mass-matched controls (n = 65). Participants were assessed with the diagnostic interview Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Tumor necrosis factor-alpha, chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 and chemokine (C-X-C motif) ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) were decreased in cocaine users, although all cytokines were identified as predictors of a lifetime pathological use of cocaine. Interleukin-1 beta (IL-1β), chemokine (C-X3-C motif) ligand 1 (CX3CL1)/fractalkine and CXCL12/SDF-1 positively correlated with the cocaine symptom severity when using the DSM-IV-TR criteria for cocaine abuse/dependence. These cytokines allowed the categorization of the outpatients into subgroups according to severity, identifying a subgroup of severe cocaine users (9-11 criteria) with increased prevalence of co-morbid psychiatric disorders [mood (54%), anxiety (32%), psychotic (30%) and personality (60%) disorders]. IL-1β was observed to be increased in users with such psychiatric disorders relative to those users with no diagnosis. In addition to these clinical data, studies in mice demonstrated that plasma IL-1β, CX3CL1 and CXCL12 were also affected after acute and chronic cocaine administration, providing a preclinical model for further research. In conclusion, cocaine exposure modifies the circulating levels of pro-inflammatory mediators. Plasma cytokine/chemokine monitoring could improve the stratification of cocaine consumers seeking treatment and thus facilitate the application of appropriate interventions, including management of heightened risk of psychiatric co-morbidity. Further research is necessary to elucidate the role of the immune system in the etiology of cocaine addiction., (© 2014 Society for the Study of Addiction.)