Biallelic somatic inactivation of the mismatch repair gene MLH1 in a primary skin melanoma

Inactivation of mismatch repair (MMR) genes has been linked to the hereditary nonpolyposis colon cancer syndrome and to a subset of sporadic cancers. A phenotypic characteristic of tumors with defective MMR is microsatellite instability (MSI). Although MSI has been reported in a proportion of cutaneous melanomas, inactivation of MMR genes in this tumor type has not been detected thus far. We recently described a human melanoma cell line, PR-Mel, and a cutaneous metastasis from the same patient, which displayed a MMR defect, and showed high MSI. Here we report that in the PR-Mel cell line both MLH1 alleles are somatically inactivated. One allele is lost through a chromosomal deletion of the region 3p21-24, whereas the remaining allele harbors a G --> A transition at position -1 of the acceptor splice site of intron 15, leading to the in-frame skipping of exon 16. The primary melanoma of the PR patient shows loss of heterozygosity at the BAT21 microsatellite marker, located in the MLH1 gene, and does not express the MLH1 and PMS2 proteins. Moreover, it harbors the same mutation detected in the PR-Mel cells. These results demonstrate that biallelic inactivation of MLH1 had occurred in the primary melanoma of the PR patient and suggest that disruption of MMR might have had a role in the development of the melanoma. This is the first report in which genetic defects leading to disruption of MMR function in a human melanoma have been identified.     

Protective role of endothelial nitric oxide synthase

Nitric oxide is a versatile molecule, with its actions ranging from haemodynamic regulation to anti-proliferative effects on vascular smooth muscle cells. Nitric oxide is produced by the nitric oxide synthases, endothelial NOS (eNOS), neural NOS (nNOS), and inducible NOS (iNOS). Constitutively expressed eNOS produces low concentrations of NO, which is necessary for a good endothelial function and integrity. Endothelial derived NO is often seen as a protective agent in a variety of diseases.This review will focus on the potential protective role of eNOS. We will discuss recent data derived from studies in eNOS knockout mice and other experimental models. Furthermore, the role of eNOS in human diseases is described and possible therapeutic intervention strategies will be discussed.     

The Frequency and Context of Snacking among Children: An Objective Analysis Using Wearable Cameras

Snacking is a common eating behaviour, but there is little objective data about children’s snacking. We aimed to determine the frequency and context of children’s snacking (n = 158; mean age = 12.6 years) by ethnicity, gender, socioeconomic deprivation and body mass index (BMI) children. Participants wore wearable cameras that passively captured images of their surroundings every seven seconds. Images (n = 739,162) were coded for snacking episodes, defined as eating occasions in between main meals. Contextual factors analysed included: snacking location, food source, timing, social contact and screen use. Rates of total, discretionary (not recommended for consumption) and healthful (recommended for consumption) snacking were calculated using negative binomial regression. On average, children consumed 8.2 (95%CI 7.4, 9.1) snacks per day, of which 5.2 (95%CI 4.6, 5.9) were discretionary foods/beverages. Children consumed more discretionary snacks than healthful snacks in each setting and at all times, including 15.0× more discretionary snacks in public spaces and 2.4× more discretionary snacks in schools. Most snacks (68.9%) were sourced from home. Girls consumed more total, discretionary and healthful snacks than boys, and Māori and Pacific consumed fewer healthful snacks than New Zealand (NZ) Europeans. Results show that children snack frequently, and that most snacking involves discretionary food items. Our findings suggest targeting home buying behaviour and environmental changes to support healthy snacking choices.     

Social Inequalities in Changes in Diet in Adolescents during Confinement Due to COVID-19 in Spain: The DESKcohort Project

Adolescence is a critical period in the consolidation of healthy lifestyles that can last into adulthood. To analyze changes in food consumption and eating behaviors in high-school adolescents during the first confinement, a cross-sectional study was conducted at the end of confinement in Spain. Changes in the frequency or quantity of consumption of different types of food and food-related behaviors were analyzed. Socioeconomic and health-related variables were also considered. To determine whether dietary changes were related to socioeconomic position (SEP), Poisson regression models with robust variance were estimated. Overall, there were some changes towards a healthier diet such as an increase in fruit consumption (38.9%) and a decrease in the consumption of soft drinks (49.8%), sweets and pastries (39.3%), and convenience foods (49.2%). Some changes, however, were related to less healthy behaviors, such as a more irregular pattern of meal distribution (39.9%) or an increase in snacking between meals (56.4%). Changes towards less healthy eating were also related to students’ SEP. The risk of worsening the diet was found to be 21% higher in adolescents from a more disadvantaged SEP. Future public policies could be adapted to avoid increasing nutritional and health inequalities.     

Low seroprevalence of SARS-CoV-2 antibodies in a liver transplant cohort

Solid organ transplant recipients might be at greater risk for acquisition and mortality because of SARS-CoV-2. There are no data regarding SARS-CoV-2 seroprevalence among liver transplant (LT) recipients, and whether it is different from that of the general population or other immunosuppressed groups. We evaluated the prevalence of IgG SARS-CoV-2 antibodies among LT recipients to estimate the frequency of asymptomatic SARS-CoV-2 infection using serological assays in our outpatient clinic. We conducted a cross-sectional analysis from 10 May to 26 October 2020 of all adult (>18 years) LT recipients that underwent a routine laboratory test for the outpatient clinic follow-up at the Hospital Universitari Vall d’Hebron (Barcelona) in which we included serological testing for SARS-CoV-2. Nine out of 294 LT recipients (3.1%) tested positive for anti-SARS-CoV-2 IgG antibodies. Five of them (55.5%) had suffered clinically symptomatic SARS-CoV-2 infection confirmed by RT-PCR, four (44.4%) had presented compatible symptoms but without microbiological confirmation and only one patient (1/9, 11.1%) tested positive without any previous symptom. SARS-CoV-2 seroprevalence among LT recipients in an area highly affected by the pandemic is lower than in the general population in the same area. These results render the possibility of asymptomatic infection in LT recipients very unlikely.     

Peyronie’s disease may negatively impact the sexual experience of a couple and female sexual function: a single center study

BackgroundPeyonie’s disease (PD) mostly affects males in the fifth decade of life, with a prevalence in the general population ranging between 0.5% and 20.3%. The pathology of PD is characterized by fibrosis of the tunic albuginea of the cavernous bodies of the penis, with the presence of pain in the erection and penile deformity. This is associated with decreased sexual function for both participants. The objective of the study was to investigate the influence of PD pathology on both male patients’ and their female partners’ sexual spheres, and analyze changes in sexual function and perception following penile correction surgery.MethodsProspective study, we included male patients with PD and their female partner sexually active. Patients underwent corporoplasty with multiple plications. The male and female sexuality was evaluated before surgery and three months after male treatment by the Female sexual Function Index (FSFI); International Index of Erectile Function (IIEF); Visual Analogical Scale (VAS).ResultsFrom January 2018 to November 2019 we included 35 couple. The female subjects before partner’s surgery presented dyspareunia, loss of sexual desire, inability to achieve orgasm, and sexual dissatisfaction. At three months after surgical treatment there was an improvement of sexual function in both male patients and female partners (desire P<0.0001, arousal P<0.0001, lubrification P<0.0001, orgasm P<0.0001, satisfaction P<0.0001, pain P<0.0001). As regarding male patients the pain decreased significantly (VAS score from 6 to 2.5), while there was no statistically significant improvement in erectile function (P=0.05).ConclusionsOur findings suggest that a viable approach to treatment of PD patients that involves their partners could lead to better functional and psychological results.     

Ataque de Nervios and History of Childhood Trauma

Objective: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis. It typically describes episodic, dramatic outbursts of negative emotion in response to a stressor, sometimes involving destructive behavior. Dissociation and affective dysregulation during such episodes suggested a link to childhood trauma. We therefore assessed psychiatric diagnoses, history of ataque, and childhood trauma in treatment-seeking Hispanic outpatients (N = 70). Significantly more subjects with an anxiety or affective disorder plus ataque reported a history of physical abuse, sexual abuse, and/or or a substance-abusing caretaker than those with psychiatric disorder but no ataque. In some Hispanic individuals, ataque may represent a culturally sanctioned expression of extreme affect dysregulation associated with childhood trauma. Patients with ataque de nervios should receive a thorough traumatic history assessment.     

Levels of physical activity for colon cancer prevention compared with generic public health recommendations: population prevalence and sociodemographic correlates.

BACKGROUND: The proportion of Australian adults achieving physical activity levels believed to be sufficient for colon cancer prevention was estimated, and sociodemographic correlates (age, gender, educational attainment, occupation, marital status, and children in household) of meeting these levels of activity were analyzed. METHODS: Data from the 2000 National Physical Activity Survey were used to estimate the prevalence of participation in physical activity in relation to three criteria: generic public health recommendations, weekly amount of at least moderate-intensity physical activity currently believed to reduce risk of colon cancer, and weekly amount of vigorous-intensity physical activity believed to reduce risk of colon cancer. RESULTS: Overall, 46% of adults met the generic public health criterion, 26% met the colon cancer criterion based on participation in at least moderate-intensity physical activity, and 10% met the colon cancer criterion based on vigorous-intensity physical activity. Women were less likely than men to meet the colon cancer criteria. Younger and more educated persons were more likely to meet all three criteria. The most pronounced differences between gender, age, and educational attainment groups were found for meeting the amount of vigorous-intensity physical activity believed to reduce risk of colon cancer. CONCLUSIONS: The population prevalence for meeting proposed physical activity criteria for colon cancer prevention is low and much lower than that related to the more generic public health recommendations. If further epidemiologic studies confirm that high volumes and intensities of activity are required, the public health challenges for colon cancer will be significant.     

Aberrant humoral immune reactivity in DOCK8 deficiency with follicular hyperplasia and nodal plasmacytosis

Mutations in the DOCK8 gene define the most common form of autosomal-recessive Hyper-IgE-syndrome (AR-HIES/OMIM#243700). In a patient with extensive molluscum contagiosum lesions, a homozygous DOCK8 gene deletion was demonstrated.