Non-invasive MR assessment of macroscopic and microscopic vascular abnormalities in the rectal tumour-surrounding mesorectum

Objectives

To evaluate the MRI macroscopic and microscopic parameters of mesorectal vasculature in rectal cancer patients.

Methods

Thirteen patients with rectal adenocarcinoma underwent a dynamic contrast-enhanced MRI at 1.5 T using a blood pool agent at the primary staging. Mesorectal macrovascular features, i.e., the number of vascular branches, average diameter and length, were assessed from baseline-subtracted post-contrast images by two independent readers. Mesorectal microvascular function was investigated by means of area under the enhancement-time curve (AUC). Histopathology served as reference standard of the tumour response to CRT.

Results

The average vessel branching in the mesorectum around the tumour and normal rectal wall was 8.2?±?3.8 and 1.7?±?1.3, respectively (reader1: p?=?0.001, reader2: p?=?0.002). Similarly, the tumour-surrounding mesorectum displayed circa tenfold elevated AUC (p?=?0.01). Interestingly, patients with primary node involvement had a twofold higher number of macrovascular branches compared to those with healthy nodes (reader1: p?=?0.005 and reader2: p?=?0.03). A similar difference was observed between good and poor responders to CRT, whose tumour-surrounding mesorectum displayed 10.7?±?3.4 and 5.6?±?1.5 vessels, respectively (reader1/reader2: p?=?0.02).

Conclusions

We showed at baseline MRI of rectal tumours a significantly enhanced macrovascular structure and microvascular function in rectal tumour-surrounding mesorectum, and the association of primary mesorectal macrovascular parameters with node involvement and therapy response.

Key Points

? Vascular MRI reveals macrovascular and microvascular abnormalities in the rectal tumour-surrounding mesorectum. ? Formation of highly vascular stroma precedes the actual tumour invasion. ? High macrovascular parameters are associated with node involvement. ? Mesorectal vascular network differs for good and poor responders.

     

High Frequency of Pathogenic Rearrangements in SPG11 and Extensive Contribution of Mutational Hotspots and Founder Alleles

Biallelic loss‐of‐function mutations in SPG11 cause a wide spectrum of recessively inherited, neurodegenerative disorders including hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis, and Charcot‐Marie‐Tooth disease. By comprehensive screening of three large cohorts of HSP index patients, we identified 83 alleles with “small” mutations and 13 alleles that carry large genomic rearrangements. Including relevant data from previous studies, we estimate that copy number variants (CNVs) account for ～19% of pathogenic SPG11 alleles. The breakpoints for all novel and some previously reported CNVs were determined by long‐range PCR and sequencing. This revealed several Alu‐associated recombination hotspots. We also found evidence for additional mutational mechanisms, including for a two‐step event in which an Alu retrotransposition preceded the actual rearrangement. Apparently independent samples with identical breakpoints were analyzed by microsatellite PCRs. The resulting haplotypes suggested the existence of two rearrangement founder alleles. Our findings widen the spectra of mutations and mutational mechanisms in SPG11, underscore the pivotal role played by Alus, and are of high diagnostic relevance for a wide spectrum of clinical phenotypes including the most frequent form of recessive HSP.     

Active Double-Layered Films Enriched with AgNPs in Great Water Dock Root and Pu-Erh Extracts

A novel, eco-friendly, and biocompatible method was applied to form silver nanoparticles (AgNPs) in great water dock (Lapathi radix) (KB) and pu-erh (Camellia sinensis) (PE) extracts. The surface plasma resonance peak of green synthesized AgNPs at 451.8 nm for AgNPs+KB and 440.8 nm for AgNPs+PE was observed via spectral analysis of UV absorbance. In this study, double-layered biopolymer films (FUR/CHIT+HGEL) with AgNPs incorporated in KB solution (AgNPs+KB) and AgNPs in PE solution (AgNPs+PE), were successfully prepared using the casting method. The SEM, XRD, zeta potential and size analyses confirmed the presence of AgNP in the films. The addition of AgNPs in plant extracts improved antimicrobial and antioxidant activity and thermal stability, whereas WVTR experienced a decrease. The nanocomposite films’ orange-brown colour may aid in the protection of food products against UV rays. The composite films demonstrated antibacterial activity against food-borne pathogens and may offer potential in food packaging applications.     

Selective T‐cell depletion targeting CD45RA reduces viremia and enhances early T‐cell recovery compared with CD3‐targeted T‐cell depletion

1 Background

T‐cell depletion (TCD) effectively reduces severe graft‐versus‐host disease in recipients of HLA‐mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory‐immunity in the allografts and confer protection against important viral infections in the early post‐transplant period.

2 Methods

Sixty‐seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed.

3 Results

Patients receiving CD45RA‐depleted donor grafts had 2000‐fold more donor T cells infused, significantly higher T‐cell counts at Day +30 post transplant (550/μL vs 10/μL; P < .001), and higher T‐cell diversity by Vbeta spectratyping at Day +100 (P < .001). Importantly, these recipients experienced a significant reduction in both the incidence (P = .002) and duration (P = .02) of any viremia (cytomegalovirus, Epstein‐Barr virus, or adenovirus) in the first 6 months post transplant. Specifically, recipients of CD3‐depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P = .02).

4 Conclusion

CD45RA‐depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T‐cell recovery and protection against viremia.     

Neurocognitive Mechanisms in Compulsive Sexual Behavior Disorder

Purpose of Review

The current review summarizes the latest findings concerning neurobiological mechanisms of compulsive sexual behavior disorder (CSBD) and provides recommendations for future research specific to the diagnostic classification of the condition.

Recent Findings

To date, most neuroimaging research on compulsive sexual behavior has provided evidence of overlapping mechanisms underlying compulsive sexual behavior and non-sexual addictions. Compulsive sexual behavior is associated with altered functioning in brain regions and networks implicated in sensitization, habituation, impulse dyscontrol, and reward processing in patterns like substance, gambling, and gaming addictions. Key brain regions linked to compulsive sexual behavior features include the frontal and temporal cortices, amygdala, and striatum, including the nucleus accumbens.

Summary

Despite much neuroscience research finding many similarities between CSBD and substance and behavioral addictions, the World Health Organization included CSBD in the ICD-11 as an impulse-control disorder. Although previous research has helped to highlight some underlying mechanisms of the condition, additional investigations are needed to fully understand this phenomenon and resolve classification issues surrounding CSBD.

     

Which Dimensions of Human Sexuality Are Related to Compulsive Sexual Behavior Disorder (CSBD)? Study Using a Multidimensional Sexuality Questionnaire on a Sample of Polish Males

IntroductionHuman sexuality is a multidimensional phenomenon related to several factors, such as self-esteem, awareness of sexual needs, and ability to communicate them to others.AimTo examine the sexual characteristics of patients seeking treatment for compulsive sexual behavior disorder (CSBD)—a clinical diagnosis recently included in the 11th edition of the International Classification of Diseases classification.MethodsWe have investigated the sexual characteristics of 72 Polish men seeking treatment for CSBD compared with 208 men from the Polish general population.Main Outcome MeasuresThe Multidimensional Sexual Questionnaire–PL was used to examine 12 sexual aspects of human sexuality. The severity of CSBD symptoms was assessed using Sexual Addiction Screening Test–PL, and the severity of problematic pornography use was measured by Brief Pornography Screener.ResultsResults show that CSBD patients (when compared with the general population) exhibit higher sexual anxiety, sexual depression, external sexual control, and fear of sexual relationship. Furthermore, CSBD severity is negatively related to sexual esteem, internal sexual control, sexual consciousness, sexual assertiveness, and sexual satisfaction.Clinical ImplicationsOur findings suggest that the impairment of the abovementioned dimensions warrant attention during clinical work and future studies on CSBD.Strengths & LimitationsThis study was limited to men, most of whom self-identified as heterosexual. Future research should include women and non-heterosexual identified individuals.ConclusionSexual esteem, consciousness, assertiveness, satisfaction and internal sexual control are commonly affected among CSBD individuals and should be properly addressed during the clinical interview and treatment intervention.Kowalewska E, Kraus SW, Lew-Starowicz M, et al. Which Dimensions of Human Sexuality Are Related to Compulsive Sexual Behavior Disorder (CSBD)? Study Using a Multidimensional Sexuality Questionnaire on a Sample of Polish Males. J Sex Med 2019;16:1264–1273.