Stress indicators in minorities with multiple sclerosis.

Black Americans with multiple sclerosis (MS) experience higher levels of disease-related disability compared to White Americans (Marrie et al., 2006). Comorbidities such as depression and anxiety, which are underdiagnosed and undertreated in this population, negatively impact quality of life and treatment outcomes for people living with multiple sclerosis (plwMS) (D'Alisa et al., 2006; Marrie et al., 2009; Stepleman et al., 2014). Acts of discrimination toward Black Americans is associated with stress, which is a contributing factor for depression (Carter, 2017; Nadimpalli, 2015; Williams and Mohammed, 2009). This study compared the severity of multiple sclerosis symptoms amongst Black Americans and White Americans, and whether worsened MS symptoms in Black Americans are associated with increased experiences of discrimination. Data was analyzed from 143 plwMS in the Stress Indicators in Minorities with Multiple Sclerosis (SiMMS) study. Using the Mann-Whitney U test, significant differences were found on the NIH Emotional Distress - Anxiety measure (U = 1466.500, p = 0.045) and NIH Sleep Disturbance measure (U = 1467.000, p = 0.044) between the Black participant and the White participant groups. Discrimination was significantly correlated with both NIH Emotional Distress - Anxiety (r = 0.677, p < .001) and NIH Sleep Disturbance (r = 0.446, p = .007) in Black MS individuals. Additionally, several physiological condition and psychological outcome measures were correlated with the NIH Emotional Distress - Anxiety and NIH Sleep Disturbance measures. This study contributes to literature highlighting the negative impacts of discrimination and race related stress on the physical and mental health of Black Americans.

CERKL is upregulated in cutaneous squamous cell carcinoma and maintains cellular sphingolipids and resistance to oxidative stress.

BACKGROUND: Ceramide kinase-like protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism. OBJECTIVES: To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress. METHODS: CERKL expression was determined by RNA-Seq, quantitative polymerase chain reaction and immunohistochemistry. CERKL was knocked down in cSCC cells using small interfering RNA. Sphingolipid content was analysed by liquid chromatography-mass spectrometry. Oxidative stress was induced by treatment with H2 O2 , and apoptosis was measured using flow cytometry to determine annexin V binding. RESULTS: CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL is also expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress. CONCLUSIONS: These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC.

CERKL is Upregulated in Cutaneous Squamous Cell Carcinoma and Maintains Cellular Sphingolipids and Resistance to Oxidative Stress.

BACKGROUND: Ceramide Kinase-Like Protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease, retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism. OBJECTIVES: To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress. METHODS: CERKL expression was determined by RNA-Seq, qPCR and immunohistochemistry. CERKL was knocked down in cSCC cells using siRNA. Sphingolipid content was analyzed by liquid chromatography-mass spectrometry (LC-MS). Oxidative stress was induced by treatment with H2 O2 , and apoptosis was measured using flow cytometry to determine annexin v binding. RESULTS: CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL also is expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress. CONCLUSIONS: These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC.

[Physiological hydronephrosis in pregnancy: Occurrence and possible causes. An MRI study]. / L'hydronéphrose physiologique durant la grossesse : prévalences et causes possibles. Une étude basée sur l'IRM.

INTRODUCTION: The etiology of the uretero-hydronephrosis in pregnancy is just hypothesis: hormonal or mechanical hypothesis, only investigated by echographic studies. MRI permits to visualize the entirety of the urinary tract, which can be helpful to find out a mechanical cause. METHODOLOGY: We have analysed the MRI of 100 asymptomatic pregnant women. We have determined the number and locations of the uretero-hydronephroses and researched whether there is any relationship between the uretero-hydronephrosis and certain abdominal structures. We focused on the psoas muscle and measured its depth, width and calculated its surface by a reproducible method. RESULTS: The analysis revealed that the uretero-hydronephrosis was predominantly at the right side (63%) and in the majority of the cases limited to the kidney (42%) and/or the proximal third of the ureter (42%). We were able to rule out some proposed etiologies: a compression of the ureter between the uterus and the iliac or ovarian vessels; a protective effect of the left intestinal structures. A link was observed between the psoas muscle and the physiological uretero-hydronephrosis: the ipsilateral psoas muscle seemed smaller in pregnant women presenting a uretero-hydronephrosis. CONCLUSION: We have highlighted a link between a physiological uretero-hydronephrosis during pregnancy and a lesser developped psoas muscle. The hypothesis proposed is that a smaller psoas muscle would have a less protective effect of the ureter due to a lesser development. This study offers a practical conclusion: a left sided uretero-hydronephrosis during pregnancy and/or including the entirety of the ureter is more probably a pathological hydronephrosis. LEVEL OF EVIDENCE: 4.

Extramammary Paget's Disease : Case Report of a Penoscrotal Presentation.

We report the case of a 72 year old male with penoscrotal extramammary Paget's disease (EMPD). The patient presented with an eczematous lesion on the scrotum extending on to the base of the penis. Given the persistent and progressive nature of the lesion a biopsy was taken which revealed a malignant lesion suggestive of extramammary Paget's disease. After performing a CAT-scan of the lower abdomen and inguinal region, which was negative, a primary surgical approach with curative intentions was taken. One year after surgery the patient is doing well and shows no sign of local recurrence.

Iron-regulated metabolites produced by Pseudomonas fluorescens WCS374r are not required for eliciting induced systemic resistance against Pseudomonas syringae pv. tomato in Arabidopsis.

The plant growth-promoting rhizobacterium Pseudomonas fluorescens WCS374r produces several iron-regulated metabolites, including the fluorescent siderophore pseudobactin (Psb374), salicylic acid (SA), and pseudomonine (Psm), a siderophore that contains a SA moiety. After purification of Psb374 from culture supernatant of WCS374r, its structure was determined following isoelectrofocusing and tandem mass spectrometry, and found to be identical to the fluorescent siderophore produced by P. fluorescens ATCC 13525. To study the role of SA and Psm production in colonization of Arabidopsis thaliana roots and in induced systemic resistance (ISR) against Pseudomonas syringae pv. tomato (Pst) by strain WCS374r, mutants disrupted in the production of these metabolites were obtained by homologous recombination. These mutants were further subjected to transposon Tn5 mutagenesis to generate mutants also deficient in Psb374 production. The mutants behaved similar to the wild type in both their Arabidopsis rhizosphere-colonizing capacity and their ability to elicit ISR against Pst. We conclude that Psb374, SA, and Psm production by P. fluorescens WCS374r are not required for eliciting ISR in Arabidopsis.

Anderson localization in a periodic photonic lattice with a disordered boundary.

We investigate experimentally the light evolution inside a two-dimensional finite periodic array of weakly coupled optical waveguides with a disordered boundary. For a completely localized initial condition away from the surface, we find that the disordered boundary induces an asymptotic localization in the bulk, centered around the initial position of the input beam.

Chemical Characterization, Crossfeeding and Uptake Studies on Hydroxamate Siderophore of Alcaligenes faecalis.

We report the production of two types of siderophores namely catecholate and hydroxamate in modified succinic acid medium (SM) from Alcaligenes faecalis. Two fractions of siderophores were purified on amberlite XAD, major fraction was hydroxamate type having a λ(max) at 224 nm and minor fraction appeared as catecholate with a λ(max) of 264 nm. The recovery yield obtained from major and minor fractions was 297 and 50 mg ml(-1) respectively. The IEF pattern of XAD-4 purified siderophore suggested the pI value of 6.5. Cross feeding studies revealed that A. faecalis accepts heterologous as well as self (hydroxamate) siderophore in both free and iron complexed forms however; the rate of siderophore uptake was more in case of siderophores complexed to iron. Siderophore iron uptake studies indicated the differences between hydroxamate siderophore of A. faecalis and Alc E, a siderophore of Alcaligenes eutrophus.

A comparison of the peri-operative data after open radical retropubic prostatectomy or robotic-assisted laparoscopic prostatectomy.

PURPOSES: To compare the peri-operative biochemical data, the postoperative need for help with hygiene and mobility, and the duration of bladder catheterization, hospitalization and ICU stay of patients undergoing radical retropubic prostatectomy (RRP) versus robotic-assisted laparoscopic prostatectomy (RALP) performed by an experienced open, yet inexperienced laparoscopic, surgical team, in a peripheral low-volume urological centre. METHODS: Over a 4-year period (2004-2008), 22 men underwent radical prostatectomy without lymphadenectomy at the study institution. The mean age of the patients was 63.9 years and the mean PSA value at the time of diagnosis was 9.2 ng/mL. RESULTS: Patients in the robotic-assisted laparoscopic prostatectomy group presented a significantly lower decrease in haemoglobin, haematocrit and total plasmatic protein and a significantly smaller need for help with hygiene and mobility and a shorter duration of bladder catheterization, hospitalization and ICU stay. CONCLUSIONS: The results of this study have shown that robotic-assisted laparoscopic prostatectomy is associated with lower peri-operative morbidity and a shorter hospital stay than radical retropubic prostatectomy, even when only considering the first performed robotic-assisted laparoscopic prostatectomies by a yet inexperienced robotic team in a peripheral low-volume urological centre.

The effect of sertindole on QTD and TPTE.

OBJECTIVE: Recent research suggests that other surrogate markers than QTc, including QTc dispersion and Tpeak-Tend, may better correlate with cardiac arrhythmia risk. While sertindole significantly prolongs the QTc interval, the effects on other markers of arrhythmia risk, such as QTc dispersion and Tpeak-Tend are unknown. METHOD: Digital 12-lead ECG was recorded at baseline and at steady-state in 37 patients switched to sertindole. ECG was analysed for Fridericia-corrected QT duration (QTcF), QT dispersion and Tpeak-Tend. RESULTS: From a baseline QTcF of 407 +/- 22 ms, mean QTcF prolongation during sertindole treatment was 20 +/- 23 ms, P < 0.01. No effect on QTc dispersion was found (-1 +/- 11 ms; P = 0.41). No increased duration of the Tpeak-Tend interval from baseline was found (+7 +/- 21 ms; P = 0.05). CONCLUSION: These findings might be related to the absence of confirmed Torsade de Pointes (TdP) cases related to sertindole exposure, despite sertindole's QTc prolonging effects.

An acute toxicology study with INGN 007, an oncolytic adenovirus vector, in mice and permissive Syrian hamsters; comparisons with wild-type Ad5 and a replication-defective adenovirus vector.

Oncolytic (replication-competent) adenoviruses as anticancer agents provide new, promising tools to fight cancer. In support of a Phase I clinical trial, here we report safety data with INGN 007 (VRX-007), an oncolytic adenovirus with increased anti-tumor efficacy due to overexpression of the adenovirus-encoded ADP protein. Wild-type adenovirus type 5 (Ad5) and a replication-defective version of Ad5 were also studied as controls. A parallel study investigating the biodistribution of these viruses is described elsewhere in this issue. The toxicology experiments were conducted in two species, the Syrian hamster, which is permissive for INGN 007 and Ad5 replication and the poorly permissive mouse. The studies demonstrated that the safety profile of INGN 007 is similar to Ad5. Both viruses caused transient liver damage upon intravenous injection that resolved by 28 days post-infection. The No-Observable-Adverse-Effect-Level (NOAEL) for INGN 007 in hamsters was 3 x 10(10) viral particles per kg. In hamsters, the replication-defective vector caused less toxicity, indicating that replication of Ad vectors in the host is an important factor in pathogenesis. With mice, INGN 007 and Ad5 caused toxicity comparable to the replication-defective adenovirus vector. Partially based on these results, the FDA granted permission to enter into a Phase I clinical trial with INGN 007.

The metabolic syndrome and schizophrenia.

OBJECTIVE: To summarize the accumulated data on metabolic syndrome prevalence in patients with schizophrenia, examine evidence for a biological contribution of the mental illness to metabolic risk and review novel options available for management of prediabetic states. METHOD: A Medline search using metabolic syndrome, insulin resistance and insulin sensitivity cross-referenced with schizophrenia was performed on articles published between 1990 and May 2008. RESULTS: Recent evidence indicates that schizophrenia increases predisposition towards metabolic dysfunction independent of environmental exposure. Both fasting and non-fasting triglycerides have emerged as important indicators of cardiometabolic risk, while metformin, thiazolidinediones and GLP-1 modulators may prove promising tools for managing insulin resistance. CONCLUSION: Because of lifestyle, disease and medication effects, schizophrenia patients have significant risk for cardiometabolic disease. Routine monitoring, preferential use of metabolically neutral antipsychotics and lifestyle education are critical to minimizing risk, with a possible role for antidiabetic medications for management of insulin resistant states that do not respond to other treatment strategies.

Which comes first: atypical antipsychotic treatment or cardiometabolic risk?

OBJECTIVE: To provide an overview for practicing clinicians on the pharmacological basis of cardiometabolic risk induced by antipsychotic drugs in patients with serious mental illness, to propose hypotheses to explain these risks and to give tips for managing cardiometabolic risk during antipsychotic treatment. METHOD: A MEDLINE search using terms for atypical antipsychotics (including individual drug names), metabolic, cardiovascular, weight gain and insulin resistance, cross-referenced with schizophrenia was performed on articles published between 1990 and May 2008. RESULTS: Strong evidence exists for significant cardiometabolic risk differences among several antipsychotic agents. Histamine H1 and serotonin 5HT2C antagonism are associated with risk of weight gain, but receptor targets for dyslipidemia and insulin resistance have not yet been identified. Convincing data indicate that hypertriglyceridemia and insulin resistance may occur in the absence of weight gain with certain antipsychotics. CONCLUSION: Although lifestyle and genetics may contribute independent risks of cardiometabolic dysfunction in schizophrenia and other serious mental illness, antipsychotic treatment also represents an important contributor to risk of cardiometabolic dysfunction, particularly for certain drugs and for vulnerable patients. Mental health professionals must learn to recognize the clinical signposts indicating antipsychotic-related cardiometabolic problems to forestall progression to type II diabetes, cardiovascular events and premature death.

Comparative study of 7 fluorescent pseudomonad clinical isolates.

There is some debate about the potential survival of Pseudomonas fluorescens at temperatures above 37 degrees C and its consequences for infectious potential, owing to the heterogeneity of clinical strains. Seven clinical strains growing at 37 degrees C or more were submitted for polyphasic identification; 2 were identified as Pseudomonas mosselii and 4 were precisely characterized as P. fluorescens bv. I or II. The binding indexes on glial cells of the strains identified as P. fluorescens bv. I and P. mosselii were compared with that of a reference psychrotrophic strain, P. fluorescens MF37 (bv. V). Clinical P. fluorescens had a similar adherence potential range than strain MF37. Conversely, the binding indexes for P. mosselii strains were 3 times greater than that for strain MF37. These data, and those obtained by comparing the cytotoxic activities of P. fluorescens clinical strains, suggest the existence of different virulence mechanisms, leading either to a low infectious form or to a microorganism with cytotoxic activity in the same range as that of P. mosselii or even Pseudomonas aeruginosa.

Interactions between municipal solid waste incinerator bottom ash and bacteria (Pseudomonas aeruginosa).

Municipal solid waste incinerator bottom ash (MSWI BA) can be used in road construction where it can become exposed to microbial attack, as it can be used as a source of oligoelements by bacteria. The extent of microbial colonization of the bottom ash and the intensity of microbial processes can impact the rate of leaching of potentially toxic elements. As a consequence, our objective was to highlight the mutual interactions between MSWI bottom ash and Pseudomonas aeruginosa, a common bacteria found in the environment. Experiments were carried out for 133 days at 25 degrees C using a modified soxhlet's device and a culture medium, in a closed, unstirred system with weekly renewal of the aqueous phase. The solid products of the experiments were studied using a laser confocal microscopy, which showed that biofilms formed on mineral surfaces, possibly protecting them from leaching. Our results show that the total mass loss after 133 days is systematically higher in abiotic medium than in the biotic one in proportions going from 31 to 53% depending on element. Ca and Sr show that rates in biotic medium was approximately 19% slower than in abiotic medium during the first few weeks. However, in the longer term, both rates decreased to reach similar end values after 15 weeks. By taking into account the quantities of each tracer trapped in the layers we calculate an absolute alteration rate of MSWI BA in the biotic medium (531 microg m(-2) d(-1)) and in the abiotic one (756 microg m(-2) d(-1)).

Accuracy of body image perception and preferred weight loss strategies in schizophrenia: a controlled pilot study.

OBJECTIVE: Obesity in severely mentally ill (SMI) populations is an increasing problem, but there is no controlled data regarding the relationship between SMI and weight perception. METHOD: Fifty patients with schizophrenia and 50 demographically matched control participants were recruited. Weight, height, and body image accuracy were assessed for all participants, and assessments of mood, psychotic symptom severity and anxiety, and preferred modes of weight loss were assessed for the schizophrenia sample. RESULTS: Patients with schizophrenia were significantly more likely to be obese than controls (46% vs. 18%, P < 0.005), and most patients expressed an interest in losing weight. Obese participants with schizophrenia underestimated their body size (11.0%) more than controls (4.9%) (P < 0.05). CONCLUSION: Patients with schizophrenia are more likely to underestimate their body size, independent of the effects of obesity. However, they also express concern about weight issues and willingness to participate in psychoeducational groups targeted at weight loss.

Relationships between biochemical markers of bone and cartilage degradation with radiological progression in patients with knee osteoarthritis receiving risedronate: the Knee Osteoarthritis Structural Arthritis randomized clinical trial.

OBJECTIVE: To investigate whether early changes in biochemical markers of bone (NTX-I) and cartilage (CTX-II [C-terminal crosslinking telopeptide of type II collagen]) degradation are associated with radiological progression in patients with knee osteoarthritis (OA) receiving risedronate. DESIGN: Two thousand four hundred and eighty three patients with medial compartment knee OA were randomized in two 24-month studies in North America (NA) and European Union (EU). Studies evaluated risedronate 5 mg/day, 35 mg/week (EU), 50 mg/week (NA), and 15 mg/day (NA and EU), compared to placebo in reducing signs and symptoms and in slowing radiographic progression. One thousand eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed. RESULTS: Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months. Patients who had CTX-II levels returned to low levels (<150 ng/mmol creatinine) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [odds-ratio (95% confidence interval): 0.57 (0.39-0.85) after adjustment for demographics and joint space width]. The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [odds-ratio 0.36 (0.21-0.63)]. No significant association between NTX-I levels and radiological progression was observed. CONCLUSION: CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months. Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression.

Correlation between bone lesion changes and cartilage volume loss in patients with osteoarthritis of the knee as assessed by quantitative magnetic resonance imaging over a 24-month period.

OBJECTIVE: To evaluate in patients with knee osteoarthritis (OA) the size changes in bone oedema and cysts over 24 months, and to contrast these changes with cartilage volume loss using quantitative magnetic resonance imaging. METHODS: 107 patients with knee OA, selected from a large trial evaluating the effect of a bisphosphonate, were analysed by magnetic resonance imaging at baseline and 24 months. Assessments of subchondral bone oedema and cysts, and cartilage volume were done. RESULTS: At baseline, 86 patients showed the presence of at least one type of bone lesion: 71 oedema, 61 cysts and 51 both. At 24 months, although not statistically significant, the oedema total size change increased by 2.09 (SD 15.03) mm, and the cyst by 1.09 (8.13) mm; mean size change for the oedema was +0.38 (2.18) mm and -0.10 (4.36) mm for the cyst. When analysed according to subregions, an increase was found for the cyst size in the trochlea (+0.67 (2.74) mm, p = 0.02) and in the lateral tibial plateau (+0.15 (0.83) mm, p = 0.09), and for the oedema size in the medial tibial plateau (+1.73 (8.11) mm, p = 0.05). At 24 months, significant correlations were seen between the loss of cartilage volume and oedema size change in the medial condyle (-0.40, p = 0.0001) and the medial tibial plateau (-0.23, p = 0.03), and the changes in cyst size in the medial condyle (-0.29, p = 0.01). A multivariate analysis showed that the oedema size change was strongly and independently associated with medial cartilage volume loss (-0.31, p = 0.0004). CONCLUSION: These data demonstrate that bone lesions are prevalent in knee OA. The correlation of the oedema and cyst size increase in the medial compartment over time with a greater loss of cartilage volume in this area underlines the importance of subchondral bone lesions in OA pathophysiology.