IL-4 in vitro production is upregulated in Alzheimer's disease patients treated with acetylcholinesterase inhibitors

Cytokines appear to be involved in the pathogenesis of Alzheimer's Disease (AD). Their modulation by treatment has been investigated only in a few studies. The aim of our study was to evaluate the effect of acetylcholinesterase inhibitors (AChEI) on Interleukin-4 (IL-4) production in AD patients. IL-4 levels were measured by ELISA on peripheral blood mononuclear cell cultures in the presence or absence of Concanavalin A or Phytohaemagglutinin. Linear regression analysis shows that patients who have been treated, have higher levels of IL-4 independently from age, gender and comorbidity. The increased production of IL-4 in AChEI treated patients might represent an additional mechanism through which AChEI act on AD progression.     

Accurate estimate of pancreatic T2* values: how to deal with fat infiltration

Purpose

We examined different approaches aimed to deal with the signal fluctuation of pancreatic T2* values due to fat infiltration in order to obtain accurate estimates of iron overload.

Methods

Pancreatic T2* values were assessed in 20 patients (13 females, 37.24 ± 9.12 years) enrolled in the Myocardial Iron Overload in Thalassemia network without and with the application of fat suppression-FS (T2*-NoFS and T2*-FS). T2* values were assessed in three different ways: (1) from the immediate fit (original T2*); (2) discarding the echoes until the achievement of a good visual concordance between the signal and the model (final_vis T2*); (3) eliminating the echoes until the achievement of a fitting error (known) <5% (final_thres T2*).

Results

For the T2*-NoFS sequence the original T2* values were significantly higher than the final_vis T2* values (difference:4.8 ± 6.1 ms; P < 0.0001) and the final_thres T2* values (difference:4.3 ± 6.1 ms; P = 0.006). For the T2*-FS sequence the original T2* values were comparable to final_vis and final_thres T2* values. The original T2*-FS values were significantly different from the original T2*-NoFS values. The final_vis T2*-FS values were comparable to the final_vis T2*-NoFS values and the final_thresh T2*-FS values were comparable to the final_thresh T2*-NoFS values. For both T2*-FS and T2*-NoFS sequences, the final_thres T2* values were not significantly different from the final_vis T2* values and no bias was present.

Conclusions

In the clinical practice, an accurate pancreatic iron overload assessment should be done by applying FS and, when needed, by discarding the TEs until the fitting error goes below 5%.

     

Artificial intelligence technologies for the detection of colorectal lesions: The future is now

Several studies have shown a significant adenoma miss rate up to 35% during screening colonoscopy, especially in patients with diminutive adenomas. The use of artificial intelligence(AI) in colonoscopy has been gaining popularity by helping endoscopists in polyp detection, with the aim to increase their adenoma detection rate(ADR) and polyp detection rate(PDR) in order to reduce the incidence of interval cancers. The efficacy of deep convolutional neural network(DCNN)-based AI system for polyp detection has been trained and tested in ex vivo settings such as colonoscopy still images or videos. Recent trials have evaluated the real-time efficacy of DCNN-based systems showing promising results in term of improved ADR and PDR. In this review we reported data from the preliminary ex vivo experiences and summarized the results of the initial randomized controlled trials.     

Insecure Attachment Attitudes in the Onset of Problematic Internet Use Among Late Adolescents

Studies on the role played by attachment attitudes among late adolescents who show Problematic Internet Use (PIU) are still lacking. Three self-report measures concerning attachment attitudes, childhood experiences of abuse, and Internet addiction were administered to 310 students (49 % males) aged 18–19 attending the last year of high school. Students who screened positive for PIU were more likely to be male and to have suffered childhood experiences of physical and sexual abuse; they also scored higher than the other participants on scales assessing anxious and avoidant attachment attitudes. A logistic regression showed that the classification of participants in the PIU group was predicted by male gender, having suffered from physical and sexual abuse in childhood, and preoccupation with relationships. Keeping constant the effects of gender and childhood experiences of abuse in the equation model, increasing values of preoccupation with relationships were reflected by an exponential growth in the probability curve for PIU classification. Findings of the study support the hypothesis that insecure attachment attitudes (particularly the preoccupation with relationships) are involved in the development of PIU among late adolescents.     

Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation

The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs), for which hematopoietic cell transplantation (HCT) is applied to repopulate the recipient myeloid compartment, including microglia, with cells expressing the defective functional hydrolase. By studying wild-type and LSD mice at diverse time-points after HCT, we showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. However, only the use of a conditioning regimen capable of ablating functionally defined brain-resident myeloid precursors allowed turnover of microglia with the donor, mediated by local proliferation of early immigrants rather than entrance of mature cells from the circulation.     

Endocrine orbitopathy: 11 years retrospective study and review of 102 patients & 196 orbits

BackgroundEndocrine Orbitopathy (EO) is the most frequent and important extrathyroidal stigma of Graves’ disease. In the active stage of the orbitopathy fibrosis and hypertrophy of the extra-ocular muscles can lead to visual impairment and diplopia. In the stable phase of the disease surgical treatment by orbital expansion and/or orbital decompression can improve the quality of life and it is indicated for morpho-aesthetic and functional reasons.MethodsFrom 1998 to 2009 a consecutive series of 131 patients (251 orbits) with endocrine orbitopathy underwent surgery by different techniques.The medical records of 102 patients (78%) and 196 orbits were available to be assessed retrospectively.Ninety-four patients had bilateral involvement of the orbits and eight unilateral. A total of 556 operations were performed.ResultsMean pre-operative exophthalmos was 24.7 ± 2.5 mm (max–min 20–34), mean post-operative exophthalmos was 21 ± 1.8 mm (max–min 18–26), and mean differential exophthalmos was 3.9 ± 1.7 mm (max–min 1–9).The reduction in exophthalmos after surgery had a mean value of 3.8 mm (min 1, max 9).Kaplan Meier algorithm demonstrates that intra-operative cortisone injection had an adverse effect on post-operative diplopia.ConclusionsThe surgical technique used should be adapted to the individual patients’ needs. In severe cases intraorbital fat removal and bony decompression can be and carried out in one surgical procedure. An integrated global approach by a multidisciplinary team is strongly recommended.Strabismus surgery is a significant part of the overall treatment. The Authors suggest general surgical guidelines and an algorithm of treatment in EO.     

Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation

Hairy cell leukemia (HCL) is a distinct clinicopathologic entity that responds well to purine analogs but is sometimes difficult to differentiate from HCL-like disorders (e.g., splenic marginal zone lymphoma and HCL variant). We recently identified the BRAF-V600E mutation as the disease-defining genetic event in HCL. In this study, we describe a new, simple, and inexpensive test for genetics-based diagnosis of HCL in whole-blood samples that detects BRAF-V600E through a sensitive allele-specific PCR qualitative assay followed by agarose-gel electrophoresis. This approach detected BRAF-V600E in all 123 leukemic HCL samples investigated containing as few as 0.1% leukemic cells. BRAF-V600E was detected at different time points during the disease course, even after therapy, pointing to its pivotal role in HCL pathogenesis and maintenance of the leukemic clone. Conversely, 115 non-HCL chronic B-cell neoplasms, including 79 HCL-like disorders, were invariably negative for BRAF-V600E. This molecular assay is a powerful tool for improving the diagnostic accuracy in HCL.     

Body mass index correlates with waist circumference in school aged Italian children

This study demonstrates the existence of a linear correlation between Body Mass Index (BMI) and waist circumference in Italian school aged children and suggests an indirect method (from weight and height) to estimate waist circumference, whose increase may be indicative for the diagnosis of the metabolic syndrome.