Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis

Langerhans cell histiocytosis is a rare group of proliferative disorders. Beside cutaneous involvement, other internal organs can be affected. The treatment of cutaneous lesions is difficult and relies on topical corticosteroids, carmustine, nitrogen mustard, and photochemotherapy. Systemic steroids and vinblastine are used for recalcitrant skin lesions. However, some cases fail to respond. An 18-month old boy presented a CD1a+, S100a+ Langerhans cell histocytosis with cutaneous and severe scalp involvement. Topical corticosteroids and nitrogen mustard failed to improve the skin lesions. Systemic corticosteroids and vinblastine improved the truncal involvement but had no effect on the scalp lesions. Methylaminolevulinate (MAL) based photodynamic therapy (PDT) resulted in a significant regression of the scalp lesions. Control histology revealed an almost complete clearance of the tumor infiltrate. Clinical follow-up after six months showed no recurrence

Validation of the PHQ-9 as a screening instrument for depression in diabetes patients in specialized outpatient clinics

Background. For the treatment of depression in diabetes patients, it is important that depression is recognized at an early stage. A screening method for depression is the patient health questionnaire (PHQ-9). The aim of this study is to validate the 9-item Patient Health Questionnaire (PHQ-9) as a screening instrument for depression in diabetes patients in outpatient clinics. Methods. 197 diabetes patients from outpatient clinics in the Netherlands filled in the PHQ-9. Within 2 weeks they were approached for an interview with the Mini Neuropsychiatric Interview. DSM-IV diagnoses of Major Depressive Disorder (MDD) were the criterion for which the sensitivity, specificity, positive- and negative predictive values and Receiver Operator Curves (ROC) for the PHQ-9 were calculated. Results. The cut-off point of a summed score of 12 on the PHQ-9 resulted in a sensitivity of 75.7% and a specificity of 80.0%. Predictive values for negative and positive test results were respectively 93.4% and 46.7%. The ROC showed an area under the curve of 0.77. Conclusions. The PHQ-9 proved to be an efficient and well-received screening instrument for MDD in this sample of diabetes patients in a specialized outpatient clinic. The higher cut-off point of 12 that was needed and somewhat lower sensitivity than had been reported elsewhere may be due to the fact that the patients from a specialized diabetes clinic have more severe pathology and more complications, which could be recognized by the PHQ-9 as depression symptoms, while instead being diabetes symptom

RNA profiling of cyclooxygenases 1 and 2 in colorectal cancer

Cyclooxygenases (particularily Cox-2) are involved in carcinogenesis and metastatic cancer progression. The expression profiles of the cyclooxygenases and the roles they play in established tumours of similar stage remains unclear. We report that Cox-1 and Cox-2 expression is highly variable in Dukes' C tumours, and changes in Cox-1 expression may be of importance

Application of dense offshore tsunami observations from Ocean Bottom Pressure Gauges (OBPGs) for tsunami research and early warnings

We introduce a new data source of dense deep-ocean tsunami records 7 from Ocean Bottom Pressure Gauges (OBPGs) which are attached to Ocean Bottom 8 Seismometers (OBS) and apply them for far-field and near-field tsunami warnings. 9 Tsunami observations from OBPGs are new sources of deep-ocean tsunami 10 observations which, for the first time, provide dense tsunami data with spacing 11 intervals in the range of 10–50 km. Such dense data are of importance for tsunami 12 research and warnings and are capable of providing new insights into tsunami 13 characteristics. Here, we present a standard procedure for the processing of the 14 OBPG data and extraction of tsunami signals out of these high-frequency data. 15 Then, the procedure is applied to two tsunamis of 15 July 2009 Mw 7.8 Dusky 16 Sound (offshore New Zealand) and 28 October 2012 Mw 7.8 Haida Gwaii (offshore 17 Canada). We successfully extracted 30 and 57 OBPG data for the two aforesaid 18 tsunamis, respectively. Numerical modeling of tsunami was performed for both 19 tsunamis in order to compare the modeling results with observation and to use the 20 modeling results for the calibration of some of the OBPG data. We successfully 21 employed the OBPG data of the 2012 Haida Gwaii tsunami for tsunami forecast by 22 applying a data assimilation technique. Our results, including two case studies, 23 demonstrate the high potential of OBPG data for contribution to tsunami research 24 and warnings. The procedure developed in this study can be readily applied for the 2526 extraction of tsunami signals from OBPG data

Genetic Disruption of Both Tryptophan Hydroxylase Genes Dramatically Reduces Serotonin and Affects Behavior in Models Sensitive to Antidepressants

The neurotransmitter serotonin (5-HT) plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2). We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO) and Tph1/Tph2 double knockout (DKO) mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders

Spatial variation and hot-spots of district level diarrhea incidences in Ghana: 2010–2014

Background: Diarrhea is a public health menace, especially in developing countries. Knowledge of the biological and anthropogenic characteristics is abundant. However, little is known about its spatial patterns especially in developing countries like Ghana. This study aims to map and explore the spatial variation and hot-spots of district level diarrhea incidences in Ghana. Methods: Data on district level incidences of diarrhea from 2010 to 2014 were compiled together with population data. We mapped the relative risks using empirical Bayesian smoothing. The spatial scan statistics was used to detect and map spatial and space-Time clusters. Logistic regression was used to explore the relationship between space-Time clustering and urbanization strata, i.e. rural, peri-urban, and urban districts. Results: We observed substantial variation in the spatial distribution of the relative risk. There was evidence of significant spatial clusters with most of the excess incidences being long-Term with only a few being emerging clusters. Space-Time clustering was found to be more likely to occur in peri-urban districts than in rural and urban districts. Conclusion: This study has revealed that the excess incidences of diarrhea is spatially clustered with peri-urban districts showing the greatest risk of space-Time clustering. More attention should therefore be paid to diarrhea in peri-urban districts. These findings also prompt public health officials to integrate disease mapping and cluster analyses in developing location specific interventions for reducing diarrhea

Detection and characteristics of microvascular obstruction in reperfused acute myocardial infarction using an optimized protocol for contrast-enhanced cardiovascular magnetic resonance imaging

Several cardiovascular magnetic resonance imaging (CMR) techniques are used to detect microvascular obstruction (MVO) after acute myocardial infarction (AMI). To determine the prevalence of MVO and gain more insight into the dynamic changes in appearance of MVO, we studied 84 consecutive patients with a reperfused AMI on average 5 and 104 days after admission, using an optimised single breath-hold 3D inversion recovery gradient echo pulse sequence (IR-GRE) protocol. Early MVO (2 min post-contrast) was detected in 53 patients (63%) and late MVO (10 min post-contrast) in 45 patients (54%; p = 0.008). The extent of MVO decreased from early to late imaging (4.3 ± 3.2% vs. 1.8 ± 1.8%, p < 0.001) and showed a heterogeneous pattern. At baseline, patients without MVO (early and late) had a higher left ventricular ejection fraction (LVEF) than patients with persistent late MVO (56 ± 7% vs. 48 ± 7%, p < 0.001) and LVEF was intermediate in patients with early MVO but late MVO disappearance (54 ± 6%). During follow-up, LVEF improved in all three subgroups but remained intermediate in patients with late MVO disappearance. This optimised single breath-hold 3D IR-GRE technique for imaging MVO early and late after contrast administration is fast, accurate and allows detection of patients with intermediate remodelling at follow-up

Solution conformation and flexibility of capsular polysaccharides from Neisseria meningitidis and glycoconjugates with the tetanus toxoid protein

The structural integrity of meningococcal native, micro-fluidized and activated capsular polysaccharides and their glycoconjugates – in the form most relevant to their potential use as vaccines (dilute solution) - have been investigated with respect to their homogeneity, conformation and flexibility. Sedimentation velocity analysis showed that the polysaccharide size distributions were generally bimodal with some evidence for higher molar mass forms at higher concentration. Weight average molar masses Mw where lower for activated polysaccharides. Conjugation with tetanus toxoid protein however greatly increased the molar mass and polydispersity of the final conjugates. Glycoconjugates had an approximately unimodal log-normal but broad and large molar mass profiles, confirmed by sedimentation equilibrium “SEDFIT MSTAR” analysis. Conformation analysis using HYDFIT (which globally combines sedimentation and viscosity data), “Conformation Zoning” and Wales-van Holde approaches showed a high degree of flexibility – at least as great as the unconjugated polysaccharides, and very different from the tetanus toxoid (TT) protein used for the conjugation. As with the recently published finding for Hib-TT complexes, it is the carbohydrate component that dictates the solution behaviour of these glycoconjugates, although the lower intrinsic viscosities suggest some degree of compaction of the carbohydrate chains around the protein

Dual requirement of cytokine and activation receptor triggering for cytotoxic control of murine cytomegalovirus by NK cells

Natural killer (NK) cells play a critical role in controlling murine cytomegalovirus (MCMV) and can mediate both cytokine production and direct cytotoxicity. The NK cell activation receptor, Ly49H, is responsible for genetic resistance to MCMV in C57BL/6 mice. Recognition of the viral m157 protein by Ly49H is sufficient for effective control of MCMV infection. Additionally, during the host response to infection, distinct immune and non-immune cells elaborate a variety of pleiotropic cytokines which have the potential to impact viral pathogenesis, NK cells, and other immune functions, both directly and indirectly. While the effects of various immune deficiencies have been examined for general antiviral phenotypes, their direct effects on Ly49H-dependent MCMV control are poorly understood. To specifically interrogate Ly49H-dependent functions, herein we employed an in vivo viral competition approach to show Ly49H-dependent MCMV control is specifically mediated through cytotoxicity but not IFNγ production. Whereas m157 induced Ly49H-dependent degranulation, efficient cytotoxicity also required either IL-12 or type I interferon (IFN-I) which acted directly on NK cells to produce granzyme B. These studies demonstrate that both of these distinct NK cell-intrinsic mechanisms are integrated for optimal viral control by NK cells

Expression of COX-2, NF-κB-p65, NF-κB-p50 and IKKα in malignant and adjacent normal human colorectal tissue

Peer reviewedPublisher PD