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Background: Assessing the risk of measles outbreaks and identifying the susceptible parts of the population is essential to timely intervention. Infants between 6–12 months are increasingly susceptible to measles but evaluating the performance of high throughput enzyme immunoassays (ELISAs) in infants

Abstract Studies examining the association between type 1 diabetes (T1D) and atopic diseases, i.e., atopic dermatitis, allergic rhinitis and asthma have yielded conflicting results due to different algorithms for classification, sample size issues and risk of referral bias of exposed cohorts with frequent contact to health care professionals. Using Danish national registries and well-established disease algorithms, we examined the bidirectional association between T1D and atopic diseases in childhood and adolescence using Cox Proportional Hazard regression compared to two different unexposed cohorts from a population of 1.5 million Danish children born from 1997 to 2018. We found no associations between T1D and atopic dermatitis, allergic rhinitis, or asthma (defined after age five). However, in multivariable analysis we found an increased risk of persistent wheezing (defined as asthma medication before age five) after T1D with an adjusted hazard ratio (aHR) of 1.70 [1.17–2.45]. We also identified an increased risk of developing T1D after persistent wheezing with aHR of 1.24 [1.13–1.36]. This study highlights similar risks of atopic diseases in children with T1D and of T1D in children with atopic disease after age of five years versus healthy controls. However, more research is needed to understand the possible early immunological effects of the link between persistent wheezing and T1D.

The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose monitoring (CGM) in our center and analyze their association with various factors. As part of the international ISPAD JENIOUS-initiated SKIN-PEDIC project, we interviewed and examined patients who visited the regional pediatric diabetes center in Opole (Poland) for four weeks regarding the use of IP and/or CGM and the presence of skin problems. Body mass index (BMI) and glycemic parameters were obtained retrospectively from medical records. Among 115 individuals (45.2% girls, 83.5% IP users, 96.5% CGM users), old scars were the most common skin problem (IP users 53.1%; CGM users 66.4%), while ≥2 types of skin problems co-occurred (IP users 40.6%; CGM users 27.3%). Longer IP use was associated with a higher prevalence of skin problems (50% for IP < 1 year, 98.1%-IP 1–3 years, 100% for IP > 3 years; p < 0.001), pointing out extra attention with IP use > 1 year. No significant associations were found between skin problems and gender, age, BMI centile and glycemic parameters. Dermatological complications were common among children using IP and CGM in our center, highlighting the need for vigilant monitoring and early intervention to manage these skin-related issues effectively.

Summary: Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods: Healthy 5–7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.gov NCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks.Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). Findings: 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4–5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3–1.9) after routine MMR.Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9–1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8–4.0); none deemed vaccine related. Interpretation: Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5–7 months was safe and not associated with higher rates of reactogenicity than placebo. Funding: Innovation Fund Denmark.

Contact dermatitis because of use of diabetes devices is frequent in individuals with type 1 diabetes (TD1), especially in the pediatric age group, but the putative role of a constitutional impaired skin barrier in persons with TD1 is unclear. This study examined the skin barrier function by the measurement of natural moisturizing factor and free cytokines collected through skin tape strips, as well as biophysical markers and the skin microbiome, in persons with TD1 than to age- and sex-matched healthy controls. All measurements were done in nonlesional skin. We found that the skin barrier function was similar in children and adolescents with TD1 than to controls but found that the beta-diversity of skin microbiome at the buttock differed between the two groups. We conclude that individuals with TD1 have normal skin barrier function, and that the increased occurrence of contact dermatitis following pump and sensor use is explained by exogenous factors.

ObjectiveTo assess the efficacy and safety of a dual-hormone (DH [insulin and glucagon]) closed-loop system compared to a single-hormone (SH [insulin only]) closed-loop system in adolescents with type 1 diabetes.MethodsThis was a 26-hour, two-period, randomized, crossover, inpatient study involving 11 adolescents with type 1 diabetes (nine males [82%], mean ± SD age 14.8 ± 1.4 years, diabetes duration 5.7 ± 2.3 years). Except for the treatment configuration of the DiaCon Artificial Pancreas: DH or SH, experimental visits were identical consisting of: an overnight stay (10:00 pm until 7:30 am), several meals/snacks, and a 45-minute bout of moderate intensity continuous exercise. The primary endpoint was percentage of time spent with sensor glucose values below range (TBR [10.0 mmol/L]) 28.1 [18.1, 49.8] vs. 23.3 [12.3, 27.2]%, p=0.10. Mean ( ± SD) glucose was higher during DH than SH (8.7 ( ± 3.2) vs. 8.1 ( ± 3.0) mmol/L, p

Among the types of different particulates, silica is a standout as one of the the cheapest and low-density particulates accessible in substantial amounts. The present study has been centered around the synthesis and study of aluminum matrix composite strengthened with nano-sized SiO2 particles of various weight percentage by means of the stir casting technique. The EDX emphasized the presence of various elements and augmented the in situ reaction. The tensile strength and wear studies were also carried out. The reinforcement materials percentage variation was one of the important factors for the present studies. The Aluminum Alloy 5083 and 2024, which are magnesium and copper-based alloys, had a significant effect on the material characterization. [ABSTRACT FROM AUTHOR]

[This corrects the article DOI: 10.1371/journal.pmed.1003977.].

Abstract Background Measles is a highly contagious and serious infection. Before the introduction of vaccination, measles caused yearly epidemics putting vulnerable children at risk of brain damage and death. Despite safe and cost-effective vaccines, measles remains a leading cause of death in children globally. Due to insufficient vaccine coverage and low levels of in utero transferred antibodies from vaccinated mothers, outbreaks of measles in Denmark and other high-income countries are observed at increasing frequency. The current vaccine was introduced in Denmark in 1987 as a one-shot measles-mumps-rubella vaccine at 15 months, a timing chosen to avoid inhibition of the infant’s immune response by maternal antibodies. One generation later, the MMR vaccinated mothers have lower antibody levels compared to the naturally infected, and their infants are already susceptible at 6 months of age or earlier, thus increasing the risk of epidemics. Methods The Danish MMR trial is a double-blind randomized clinical trial recruiting between March 2019 and December 2021 with last patient last visit in February 2022. Altogether N = 6500 infants aged 6 months will be randomly assigned to intramuscular vaccination with routine MMR (M-M-R VaxPro) or placebo (solvent only). According to the Danish Childhood vaccination program, all infants will receive a routine MMR vaccination at 15 months of age. At randomization, 1 month later, and 1 month after routine MMR vaccination at 15 months of age, a blood sample is drawn from app. 10% (N = 600) of the population. Additionally, hair, saliva, and urine are sampled at randomization. The co-primary study outcomes are immunogenicity 1 month after MMR vaccination at 6 months of age assessed as plaque-reduction neutralization test, and incidence of infectious disease hospitalizations from randomization to 12 months of age. Six weeks post randomization, all participants are interviewed regarding adverse events. Trial registration The trial is registered in the EU Clinical Trials Registry. EudraCT registration number: 2016-001901-18 . Registered on 14 February 2017.

Background Conflicting results have been reported concerning possible adverse effects on the cognitive function of offspring of mothers with type 1 diabetes (O-mT1D). Previous studies have included offspring of parents from the background population (O-BP), but not offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group. Methods and findings This is a population-based retrospective cohort study from 2010 to 2016. Nationally standardized school test scores (range, 1 to 100) were obtained for public school grades 2, 3, 4, 6, and 8 in O-mT1D and compared with those in O-fT1D and O-BP. Of the 622,073 included children, 2,144 were O-mT1D, and 3,474 were O-fT1D. Multiple linear regression models were used to compare outcomes, including the covariates offspring with type 1 diabetes, parity, number of siblings, offspring sex, smoking during pregnancy, parental age, and socioeconomic factors. Mean test scores were 54.2 (standard deviation, SD 24.8) in O-mT1D, 54.4 (SD 24.8) in O-fT1D, and 56.4 (SD 24.7) in O-BP. In adjusted analyses, the mean differences in test scores were −1.59 (95% CI −2.48 to −0.71, p < 0.001) between O-mT1D and O-BP and −0.78 (95% CI −1.48 to −0.08, p = 0.03) between O-fT1D and O-BP. No significant difference in the adjusted mean test scores was found between O-mT1D and O-fT1D (p = 0.16). The study’s limitation was no access to measures of glycemic control during pregnancy. Conclusions O-mT1D achieved lower test scores than O-BP but similar test scores compared with O-fT1D. Glycemic control during pregnancy is essential to prevent various adverse pregnancy outcomes in women with type 1 diabetes. However, the present study reduces previous concerns regarding adverse effects of in utero hyperglycemia on offspring cognitive function. Anne Lærke Spangmose and colleagues examine the association between school performance and exposure to maternal or paternal type 1 diabetes in utero in Denmark. Author summary Why was this study done? The influence of maternal diabetes during pregnancy on offspring cognition has been widely explored because high blood sugar levels in pregnant women are suspected to affect fetal development, including the brain. Limited evidence is available on how different subtypes of maternal diabetes are associated with offspring cognition (e.g., gestational diabetes and type 1 and type 2 diabetes). Limited data are available on the association between maternal type 1 diabetes during pregnancy and offspring cognition using offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group, which allows for adjustments of potentially shared genes and familial stress of having a parent suffering from a serious chronic disease like diabetes. What did the researchers do and find? Data were identified from Danish registers, and test scores in math (grades 3 and 6) and reading (grades 2, 4, 6, and 8) were obtained on all Danish children attending public schools from 2010 to 2016. We included 2,144 offspring of mothers and 3,474 O-fT1D and 616,455 from the background population, including 1,704,447 test scores. Offspring of mothers with type 1 diabetes (O-mT1D) achieved lower test scores than offspring in the background population but similar test scores compared with O-fT1D. What do these findings mean? The lower test scores in the O-mT1D appear to reflect a negative association of having a parent with type 1 diabetes rather than a specific adverse effect of maternal type 1 diabetes during pregnancy on the fetus. This study presents evidence of an alternative explanation for the previously observed adverse effect of maternal type 1 diabetes during pregnancy on offspring cognitive development.

Clinical outpatient visits comprise a relatively small part of the lives of children with diabetes and their families, but there is evidence that these visits have a strong impact on the long-term management of diabetes. Because children with diabetes are looking at frequent hospital visits for the rest of their lives, it is important to explore their experiences to ensure visits meet their needs. This study aimed to investigate families’ experiences with outpatient visits at a pediatric diabetes clinic. Thirteen semi-structured family interviews were conducted. Systematic text condensation was used to analyze the data. With an analytical focus on communication and social relations, nine themes were identified: 1. Discrepancies in perception of diabetes tasks, 2. Talking about adult things, but the children listen, 3. The importance of spoken and written words, 4. Confusion about division of responsibilities, 5. Relief when someone eases the burden, 6. Courtesy when visiting the clinic, 7. Understanding of the family context, 8. Importance of continuous personal relations, and 9. Need for a facilitated peer network. The findings encourage reflection on how to improve communication and underline the importance of establishing a continuous and personal relation between families and health care professionals to improve families’ experience with pediatric outpatient visits.

OBJECTIVES:Several studies suggest a relationship between gestational age at birth and risk of school difficulties. Our study aimed to investigate the association between the entire range of gestational ages and significant school difficulties measured as 1) More than nine hours per week special educational support and 2) Failing to complete compulsory school. METHODS:A population-based register study including all children attending the Danish compulsory school in 2015/2016 and all live-born infants born in Denmark from 1992 to 1997. Data were collected and linked using multiple registers held by Statistic Denmark. Multiple logistic regression analyses were used to estimate the association between gestational age and significant school difficulties, adjusted for explanatory variables. RESULTS:For measurement 1) "Special educational support" 615,789 children entered the analyses after exclusion of those with missing neonatal data. The risk of special educational support increased gradually across the entire range of gestation from 40 to ≤24 weeks: The adjusted odds ratio was 1.07 (95% confidence interval 1.03-1.12) at 39 weeks of gestational and 6.18 (95% confidence interval 5.17-7.39) at gestational ages < 28 weeks. For measurement 2) "Failing to complete compulsory school" the cohort consisted of 374,798 children after exclusion of those who died, had emigrated and/or had missing neonatal data. The risk of failing to complete compulsory school increased across the entire range of gestational ages: The adjusted odds ratio was 1.07 (95% confidence interval 1.04-1.10) at 39 weeks of gestation and 2.99 (95% confidence interval 2.41-3.71) at gestational ages < 28 weeks. In both sets of analyses GA = 40 weeks was used as reference. CONCLUSIONS:We confirm a clear association between the degree of prematurity and significant school difficulties across the entire range of gestational ages from ≤ 24 to 40 weeks.

The predominant tautomeric forms of N1–H, N2–H of 5-(2,6-dimethyl- and 5-(2,6-diisopropylphenoxy)-(1H)-tetrazoles were analyzed at B3LYP method using 6-311G(d,p) basis set in the gas phase. The N1–H form of tetrazoles was found to be more stable than N2–H form in both solid and gas phases. Crystal structures of both tetrazoles show an intermolecular H-bond between N1-H and N4 atom of other tetrazole space. The hydrogen bonds between each tautomer of tetrazoles were evaluated at B3LYP/6-311G(d,p) level. The geometrical parameters and spectral data of tetrazoles and their variation were studied in both solid and gas phases.

Aims. A new perspective on autoantibodies as pivotal players in the pathogenesis of type 1 diabetes (T1D) has recently emerged. Our key objective was to examine whether increased levels of autoantibodies against the β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma associated antigen-2A (IA-2A) mirrored the 3.4% annual increase in incidence of T1D. Methods. From the Danish Childhood Diabetes Register, we randomly selected 500 patients and 500 siblings for GADA and IA-2A analysis (1997 through 2005). Blood samples were taken within three months after onset. A robust log-normal regression model was used. Nine hundred children and adolescents had complete records and were included in the analysis. Cochran-Armitage test for trend was used to evaluate changes in prevalence of autoantibody positivity by period. Results. No significant changes in levels of GADA and IA-2A were found over our 9-year study period. No trends in autoantibody positivity—in either patients or siblings—were found. Levels of GADA and IA-2A were significantly associated with HLA risk groups and GADA with age. Conclusion. The prevalence of positivity and the levels of GADA and IA-2A have not changed between 1997 and 2005 in newly diagnosed patients with T1D and their siblings without T1D.

The purpose of the present study is to explore the progression of type 1 diabetes (T1D) in Danish children 12 months after diagnosis using Latent Factor Modelling. We include three data blocks of dynamic paraclinical biomarkers, baseline clinical characteristics and genetic profiles of diabetes related SNPs in the analyses. This method identified a model explaining 21.6% of the total variation in the data set. The model consists of two components: (1) A pattern of declining residual β-cell function positively associated with young age, presence of diabetic ketoacidosis and long duration of disease symptoms (P = 0.0004), and with risk alleles of WFS1, CDKN2A/2B and RNLS (P = 0.006). (2) A second pattern of high ZnT8 autoantibody levels and low postprandial glucagon levels associated with risk alleles of IFIH1, TCF2, TAF5L, IL2RA and PTPN2 and protective alleles of ERBB3 gene (P = 0.0005). These results demonstrate that Latent Factor Modelling can identify associating patterns in clinical prospective data--future functional studies will be needed to clarify the relevance of these patterns.

Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule causing permanent neonatal diabetes. All three were diagnosed before 29 weeks of age, were born at term with near-normal birth weight, and were negative for GAD, ICA, IA-2, and IAA autoantibodies. The daily insulin requirement the first six months after diagnosis was

Surface composites are viable choices for various applications in the aerospace and automotive industries. Friction Stir Processing (FSP) is a promising method for fabricating surface composites. Aluminum Hybrid Surface Composites (AHSC) are fabricated using the FSP to strengthen a hybrid mixture prepared with equal parts of Boron carbide (B 4 C), Silicon Carbide (SiC), and Calcium Carbonate (CaCO 3 ) particles. Different hybrid reinforcement weight percentages (reinforcement content of 5% (T1), 10% (T2), and 15% (T3)) were used in fabricating AHSC samples. Furthermore, different mechanical tests were performed on hybrid surface composite samples with different weight percentages of the reinforcements. Dry sliding wear assessments were performed in standard pin-on-disc apparatus as per ASTM G99 guidelines to estimate wear rates. The presence of reinforcement contents and dislocation behavior was investigated using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) studies. The results indicated that the Ultimate Tensile Strength (UTS) of sample T3 exhibited 62.63% and 15.17% higher than that of samples T1 and T2, respectively, while the Elongation (%) of T3 exhibited 38.46% and 15.38% lower than that of samples T1 and T2, respectively. Moreover, it was found that the hardness of sample T3 increased in the stir zone compared to samples T1 and T2, owing to its higher brittle response. The higher brittle response of sample T3 compared to samples T1 and T2 was confirmed by the higher value of Young's modulus and the lower value of Elongation (%).

Melanoma is the most aggressive among all types of skin cancers. The current strategies against melanoma utilize BRAF V600E , as a focal point for targeted therapy. However, therapy resistance developed in melanoma patients against the conventional anti-melanoma drugs hinders the ultimate benefits of targeted therapies. A major mechanism by which melanoma cells attain therapy resistance is via the activation of microphthalmia-associated transcription factor-M (MITF-M), the key transcription factor and oncogene aiding the survival of melanoma cells. We demonstrate that tryptanthrin (Tpn), an indole quinazoline alkaloid, which we isolated and characterized from Wrightia tinctoria, exhibits remarkable anti-tumor activity towards human melanoma through the down-regulation of MITF-M. Microarray analysis of Tpn-treated melanoma cells followed by a STRING protein association network analysis revealed that differential expression of genes in melanoma converges at MITF-M. Furthermore, in vitro and in vivo studies conducted using melanoma cells with differential MITF-M expression status, endogenously or ectopically, demonstrated that the anti-melanoma activity of Tpn is decisively contingent on its efficacy in down-regulating MITF-M expression. Tpn potentiates the degradation of MITF-M via the modulation of MEK1/2-ERK1/2-MITF-M signaling cascades. Murine models demonstrate the efficacy of Tpn in attenuating the migration and metastasis of melanoma cells, while remaining pharmacologically safe. In addition, Tpn suppresses the expression of mutated BRAF V600E and inhibits Casein Kinase 2α, a pro-survival enzyme that regulates ERK1/2 homeostasis in many tumor types, including melanoma. Together, we point to a promising anti-melanoma drug in Tpn, by virtue of its attributes to impede melanoma invasion and metastasis by attenuating MITF-M., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

We previously reported the remarkable potency of uttroside B (Utt-B), saponin-isolated and characterized in our lab from Solanum nigrum Linn, against HCC. Recently, the U.S. FDA approved Utt-B as an 'orphan drug' against HCC. The current study validates the superior anti-HCC efficacy of Utt-B over sorafenib, the first-line treatment option against HCC. The therapeutic efficacies of Utt-B vs. sorafenib against HCC were compared in vitro, using various liver cancer cell lines and in vivo, utilizing NOD.CB17-Prkdcscid/J mice bearing human HCC xenografts. Our data indicate that Utt-B holds an augmented anti-HCC efficacy over sorafenib. Our previous report demonstrated the pharmacological safety of Utt-B in Chang Liver, the normal immortalized hepatocytes, and in the acute and chronic toxicity murine models even at elevated Utt-B concentrations. Here, we show that higher concentrations of sorafenib induce severe toxicity, in Chang Liver, as well as in acute and chronic in vivo models, indicating that, apart from the superior therapeutic benefit over sorafenib, Utt-B is a pharmacologically safer molecule, and the drug-induced undesirable effects can, thus, be substantially alleviated in the context of HCC chemotherapy. Clinical studies in HCC patients utilizing Utt-B, is a contiguous key step to promote this drug to the clinic.

Background: Nutrition education is central to pediatric type 1 diabetes management. Dietary management guidelines for type 1 diabetes are evidence based, but implementation may be challenging and inconsistent. We describe variation in the practice of nutrition education across pediatric diabetes centers globally and explore associations with A1c and BMI., Methods: In 2018, 77 pediatric diabetes clinics in the SWEET network received a survey about nutrition education. Using data submitted to the registry, regression analysis corrected for age, diabetes duration, BMI, and sex was used to compare survey parameters with A1c and BMI., Results: Fifty-three centers who collectively cared for 22,085 patients aged 0 to 18 with type 1 diabetes responded. Median A1c was 7.68% [IQR 7.37-8.03], age 13.13 y [12.60-13.54], insulin pump use 39.1%, and continuous glucose monitor use 37.3%. 34% reported screening for disordered eating, but only 15.1% used validated screening tools. Recommending insulin boluses for snacks in patients taking insulin via injection varied, with 23% of the clinics giving this recommendation to half or fewer patients. In regression analysis, instructing patients to take insulin for snacks was the only survey parameter associated with the percent of clinic percent of patients attaining A1c <7.5% (<58 mmol/mol, P = 0.018) and < 7.0% (<53 mmol/mol, P = 0.026)., Conclusions: There is considerable variation in nutrition education for pediatric patients with type 1 diabetes across this international registry. Consistently recommending independent of treatment modality (insulin pump or injections) that patients take insulin for snacks and more uniformity in screening for disordered eating are improvement opportunities., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Bullous fixed drug eruption (BFDE) is a rare and particular adverse drug reaction characterized by localized or generalized blisters and erosions, which can be confused with Stevens-Johnson syndrome, toxic epidermal necrolysis, major erythema multiforme and autoimmune bullous dermatosis., Objective: The aim of our study was to assess the epidemiological, clinical and therapeutic features and outcome of BFDE., Methods: A retrospective and descriptive study collecting all observations of BFDE was conducted in the dermatology department of Habib Thameur Hospital in Tunisia, over an 18-year period (2000-2017). The diagnosis of BFDE was confirmed by histopathological examination and all the patients underwent pharmacovigilance investigation., Results: Totally, 18 cases were enrolled in our study with BFDE. The mean age was 57.9 years with a sex ratio M/F of 1. BFDE was localized in 8 cases and generalized in 10 cases. It was the first episode of BFDE in 11 patients and a recurrence in 7 patients. Drugs involved in the genesis of BFDE in our study were mainly non-steroidal anti-inflammatory drugs in 10 patients and antibiotics in 5 cases. Drug patch tests were performed in four patients on the residual plaques of FDE (fixed drug eruption) and were positive to the suspected drug. A favorable outcome was observed in all our patients under treatment and after suspected drug withdrawal., Conclusion: BFDE is a rare adverse drug reaction and could be severe especially when it presents as a generalized eruption. Drugs involved are mainly non-steroidal anti-inflammatory drugs followed by antibiotics., (Copyright © 2019 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

In this study, two Euphorbia species (i.e. terracina and paralias) were investigated for their cytotoxic and antioxidant activities. Cytotoxicity of plant methanol and chloroform fractions was examined towards human acute myeloid leukemia (THP1) and human colon epithelial (Caco2) cancer cell lines, as well as CD 14 and IEC-6 normal cells by targeting various modulators of apoptosis or inflammation. Moreover, secondary metabolite pools (phenolic classes, alkaloids, terpenes, saponins) and antioxidant activities (DPPH, ABTS and O 2 - scavenging, as well as FRAP tests) were assessed in plant extracts. Both Euphorbia species appeared to be rich in phenolic compounds and terpenoids, Moreover, E. terracina polar and apolar fractions and E. paralias polar fraction were highly active against THP1 cells, with IC 50 values of 2.08, 14.43 and 54.58μg/mL, respectively. However, no cytotoxicity was found against normal cells (CD14 + monocytes). The results indicate that the three fractions induce apoptosis in THP1 cell line after 6h of exposure. Furthermore, apoptosis caused by apolar fraction was related to a caspase-dependent process, whereas other death pathways seemed to be involved with the polar fractions. An enhanced production of reactive oxygen species was detected upon cell treatment with plant extracts. Interestingly, they have no effect on cytokine TNF-α secretion in THP1 and normal cells compared to untreated cells, indicating that the three fractions caused no inflammation. Euphorbia terracina and E. paralias polar fractions showed strong antioxidant activity with potent scavenging capacity against DPPH, ABTS and superoxide radicals. Moreover, these fractions displayed a very high ferric reducing power. These findings confirm the strong antioxidant capacity of Euphorbia plants and suggest a targeted anti-cancer effect with a potent anti-proliferative property of E. terracina and E. paralias extracts, which induce programmed cell death in leukemia cell lines but not in normal monocytes cells., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Pruritus is an unpleasant cutaneous feeling causing the desire to scratch. Few epidemiologic studies were interested in this symptom which relates to the old subject particularly., Aim: To study the epidemiological and clinical features as well as the treatment of pruritus in this age bracket., Methods: A retrospective study over 10 years and 5 months at the dermatology department of Habib Thameur hospital concerned 208 patients, 65 years old and more presenting a pruritus without specific dermatological lesion., Results: The frequency of pruritus in the old subject was 5.14 per 1000 new consultants. Pruritus had revealed an ignored affection in 36.36% of the cases: an iron deficiency in 10 cases, a type 2 diabetes in 6 cases, a hypereosinophilia over 1000 elements/mm3 in 4 cases, a chronic renal failure in 2 cases, a hepatic cytolysis in 2 cases, a cholestasis in one case, a polycythemia vera in one case and hepatitis B one a case. Skin lubricants and antihistamines associated to topical corticosteroids in 25 cases and UVB therapy in a case were prescribed. These treatments brought an attenuation of pruritus in 62% of the cases., Conclusion: Iron deficiency anemia was the principal cause of pruritus in our series, followed by the type 2 diabetes. Our results contrast with the data of the literature considering that the traditional prevalence of the hepatic cholestasis was not noted and that diabetes is not regarded as inductive factor of pruritus.

Background: Cutaneous metastases (CMs) from carcinoma are relatively uncommon, being usually late events in the course of internal malignancies. CMs from internal tumors seen at a secondary dermatological centre in Tunis are reported., Methods: A retrospective review of the available clinical records and histological material of all patients with CMs from internal malignancies was performed over a 14-year period., Results: Fourteen cases of CMs were recorded: 8 males and 6 females. The age range was 53 to 96 years, with a mean of 63.5 years for males and 76.5 years for females. CMs represented the first indication of an internal malignancy in 64% of cases. Firm solitary or multiple nodules were the most relevant clinical presentation (93%). Preferred sites were the thorax (50%), the abdomen (29%), and the head and neck region (21%). The common sites of primary malignancy were the lungs (38%) in males and breast (33%) in females. Four out of 14 patients died within a short follow-up period (mean 9.5 months)., Discussion: CMs are relatively rare in patients with internal cancers, but they may be a presenting sign of such cancers.

Glucantime is the firstline treatment for cutaneous leishmaniasis in Tunisia. Adverse effects related to systemic administration of Glucantime are frequent. The purpose of this retrospective study was to review the files of 53 patients who were treated for cutaneous leishmaniasis using meglumine antimoniate at a dose of 60 mg/kg/day for 15 days during the period between 1998 and 2007. Adverse effects were observed in 5 men and 4 women with an average age of 40.8 years. Antimony intolerance occurred in 8 patients and stibio-intoxication occurred in 4. Glucantime was considered as the most likely cause of adverse effects in 6 patients and as the plausible cause in 3 patients. Fever was the most frequent complication of antimony intolerance followed by cough, myalgia, and cutaneous lesions. Hepatic cytolysis was the most frequent sign of stibio-intoxication. Asymptomatic elevation of amylase level to 108 UI/l was observed in one case. The most serious complication was acute toxic kidney failure on the 15th day of treatment. The incidence of adverse events to Glucantime ranges from 16% to 59%. The most severe complication is acute renal failure on the 15th day of treatment, as observed in one patient in this series. Patient status must be monitored by performing laboratory tests at the beginning and end of the treatment. Since cutaneous leishmaniasis observed in Tunisia is a self-healing dermatosis that never results in sequels, treatment with Glucantime should be discontinued in any patient who develops suspicious symptoms.

Background: Acanthosis nigricans is a well-defined skin disorder with a distinctive appearance and an elective topography to the flexural areas that facilitate its diagnosis. In Tunisia, apart from isolated reports of malignant AN, few epidemiologic data are available., Aim: In order to describe the characteristics of this affection, we conducted a retrospective study in the area of Tunis over a 12-year period., Methods: Retrospective study of all the cases of AN seen in the dermatology department of Habib Thameur teaching hospital between 1991 and 2003, including the cases coming from the north and of the centre of Tunisia., Results: Sixty-nine cases were recorded with a sex-ratio H/F of 0.17. The average age was 24.1 years (extremes of 3 and 66 years) and 57.9% of the patients were aged between 9 and 22 years. The neck (98.6%) and the axillae (75.4%) represented the most common localizations. All the patients presented a benign AN, comprising 51 cases of pseudo-AN, 11 cases of AN associated with endocrine diseases, 5 cases of familial AN and 2 cases of AN associated with an auto-immune disease. Local treatments associated an hypocaloric diet (AN with obesity) were recommended with a light improvement after 3 months an average follow-up., Conclusion: The frequency of the AN is probably underestimated because of the usually asymptomatic character of this affection. AN constitutes a double cutaneous marker, being able to reveal either an hyperinsulinemia constituting a cardiovascular risk factor or an ignored subjacent neoplasm engaging the vital prognosis.

Background: Cutaneous adverse drug reactions correspond to adverse effects with cutaneous expression resulting from the systemic penetration of a drug in the body. The aim of this study is to evaluate the various clinical pictures of RCM, their epidemiologic characteristics as well as the different causative drugs, through a retrospective hospital series., Methods: It is about a retrospective study about all the patients consulting and/or hospitalized for suspicion of an adverse cutaneous drug reaction led to the service of dermatology of the teaching hospital Habib Thameur of Tunis over a 3-year period (from January 2002 to December 2004). The diagnosis was based on a beam of clinical and anamnestic arguments. Only the patients having a positive pharmacovigilance investigation were retained., Results: 28 patients were retained for this study. The macular and papular exanthema represented the most frequent clinical aspects followed by acute urticaria and fixed drug eruption. The antibiotics represented the most causative drugs followed by analgesics and non steroidal anti-inflammatory., Conclusion: We record a lower frequency of cutaneous adverse drug reactions in comparison with the literature. We also find a high frequency of severe forms and stress on the difficulties encountered in the identification of the causativele drugs. Though, a close cooperation between the various hospital structures and pharmacovigilance centers is mandatory.