Face in collision: emotional looming stimuli modulate interpersonal space across development and gender.

Basic visual functions have evolved to allow for rapid detection of dynamic stimuli in our surrounding environment. In particular, looming stimuli are of relevance because they are expected to enter the individual's interpersonal space representing a potential threat. Different studies showed that emotions can modulate the perception of visual looming stimuli and the borders of interpersonal space, defined as the area around the body that individuals maintain between themselves and others during social interactions. Here, we investigated how emotions modulate the perception and the physiological correlates of interpersonal space and whether such indexes change across age and gender. Children and adults were asked to quickly react to emotional looming stimuli while measuring their skin conductance response (SCR). We found that emotional looming stimuli shrink the borders of interpersonal space of males more than females, and that this pattern does not change with age. In addition, adults reacted faster to angry than happy and neutral faces, which is in line with the notion that threatening stimuli capture attention more quickly than other types of emotional stimuli. However, this was not observed in children, suggesting that experience with negative stimuli, rather than the evolutionary meaning they possess, may influence the boundaries of interpersonal space. Overall, our study suggests that interpersonal space is modulated by emotions, but this appears to be modulated by gender and age: while behavioural responses to emotional looming stimuli refine with age, physiological responses are adult-like as early as 5 years of age.

Pre-diagnostic DNA methylation patterns differ according to mammographic breast density amongst women who subsequently develop breast cancer: a case-only study in the EPIC-Florence cohort.

PURPOSE: Mammographic breast density (MBD) is a marker of increased breast cancer (BC) risk, yet much remains to be clarified about the underlying mechanisms. We investigated whether DNA methylation patterns differ between high- vs. low-MBD women who developed BC during an 8.9-year median follow-up in the Florence section of the European Prospective Investigation into Cancer and Nutrition. METHODS: We analysed 96 pairs of women with BC arising on high- vs. low-MBD breasts (BI-RADS category III-IV vs. I). DNA methylation was determined on pre-diagnostic blood samples using the Illumina Infinium MethylationEPIC BeadChip assay. The statistical analysis was conducted by performing an epigenome-wide association study (EWAS), by searching differentially methylated regions (DMRs) in gene promoters (followed by functional enrichment and gene annotation analysis); and through a "candidate pathways" approach focusing on pre-defined inflammation-related pathways. RESULTS: In EWAS, no single CpG site was differentially methylated between high- and low-MBD women after correction for multiple testing. A total of 140 DMRs were identified, of which 131 were hyper- and 9 hypo-methylated amongst high-MBD women. These DMRs encompassed an annotation cluster of 35 genes coding for proteins implicated in transcription regulation and DNA binding. The "apoptosis signalling" was the only inflammation-related candidate pathway differentially methylated between high- and low-MBD women. CONCLUSION: Pre-diagnostic methylation patterns differ between high- vs. low-MBD women who subsequently develop BC, particularly, in genes involved in the regulation of DNA transcription and cell apoptosis. Our study provides novel clues about the mechanisms linking MBD and BC.

Compressed sensing real-time cine imaging for assessment of ventricular function, volumes and mass in clinical practice.

OBJECTIVES: This study was conducted in order to evaluate the accuracy of a compressed sensing (CS) real-time single-breath-hold cine sequence for the assessment of left and right ventricular functional parameters in daily practice. METHODS: Cardiac magnetic resonance (CMR) cine images were acquired from 100 consecutive patients using both the reference segmented multi-breath-hold steady-state free precession (SSFP) acquisition and a prototype single-breath-hold real-time CS sequence, providing the same slice number, position, and thickness. For both sequences, the left (LV) and right ventricular (RV) ejection fractions (EF) and end-diastolic volumes (EDV) were assessed as well as LV mass (LVM). The visualization of wall-motion disorders (WMD) and signal void related to mitral or tricuspid regurgitation was also analyzed. RESULTS: The CS sequence mean scan time was 23 ± 6 versus 510 ± 109 s for the multi-breath-hold SSFP sequence (p < 0.001). There was an excellent correlation between the two sequences regarding mean LVEF (r = 0.995), LVEDV (r = 0.997), LVM (r = 0.981), RVEF (r = 0.979), and RVEDV (r = 0.983). Moreover, inter- and intraobserver agreements were very strong with intraclass correlations of 0.96 and 0.99, respectively. On CS images, mitral or tricuspid regurgitation visualization was good (AUC = 0.85 and 0.81, respectively; ROC curve analysis) and wall-motion disorder visualization was excellent (AUC ≥ 0.97). CONCLUSION: CS real-time single-breath-hold cine imaging reduces CMR scan duration by almost 20 times in daily practice while providing reliable measurements of both left and right ventricles. There was no clinically relevant information loss regarding valve regurgitation and wall-motion disorder depiction. KEY POINTS: • Compressed sensing single-breath-hold real-time cine imaging is a reliable sequence in daily practice. • Fast CS real-time imaging reduces CMR scan time and improves patient workflow. • There is no clinically relevant information loss with CS regarding heart valve regurgitation or wall-motion disorders.

Paradoxical Psoriasis Induced by Anti-TNFα Treatment: Evaluation of Disease-Specific Clinical and Genetic Markers.

Paradoxical psoriasis (PP) may occur during treatment with anti-tumor necrosis factor-alpha (TNF-α) drugs in various chronic immune-mediated diseases, mainly inflammatory bowel diseases (IBD) and psoriasis. In this study, clinical and genetic characteristics of PP arising in IBD and psoriatic patients were investigated to identify disease-specific markers of the paradoxical effect. A total of 161 IBD and psoriatic patients treated with anti-TNF-α drugs were included in the study. Of these patients, 39 developed PP. All patients were characterized for the main clinical-pathologic characteristics and genotyped for six candidate single nucleotide polymorphisms (SNPs) selected for their possible role in PP susceptibility. In IBD patients, the onset of PP was associated with female sex, presence of comorbidities, and use of adalimumab. IBD patients with PP had a higher frequency of the TNF-α rs1799964 rare allele (p = 0.006) compared with cases without the paradoxical effect, and a lower frequency of the human leucocyte antigen (HLA)-Cw06 rs10484554 rare allele (p = 0.03) compared with psoriatic patients with PP. Overall, these findings point to specific clinical and genetic characteristics of IBD patients with PP and provide data showing that genetic variability may be related to the paradoxical effect of anti-TNF-α drugs with possible implications into clinical practice.

Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy.

Breast cancer (BC) in men is rare and genetic predisposition is likely to play a relevant role in its etiology. Inherited mutations in BRCA1/2 account for about 13% of all cases and additional genes that may contribute to the missing heritability need to be investigated. In our study, a well-characterized series of 523 male BC (MBC) patients from the Italian multicenter study on MBC, enriched for non-BRCA1/2 MBC cases, was screened by a multigene custom panel of 50 cancer-associated genes. The main clinical-pathologic characteristics of MBC in pathogenic variant carriers and non-carriers were also compared. BRCA1/2 pathogenic variants were detected in twenty patients, thus, a total of 503 non-BRCA1/2 MBC patients were examined in our study. Twenty-seven of the non-BRCA1/2 MBC patients were carriers of germline pathogenic variants in other genes, including two APC p.Ile1307Lys variant carriers and one MUTYH biallelic variant carrier. PALB2 was the most frequently altered gene (1.2%) and PALB2 pathogenic variants were significantly associated with high risk of MBC. Non-BRCA1/2 pathogenic variant carriers were more likely to have personal (p = 0.0005) and family (p = 0.007) history of cancer. Results of our study support a central role of PALB2 in MBC susceptibility and show a low impact of CHEK2 on MBC predisposition in the Italian population. Overall, our data indicate that a multigene testing approach may benefit from appropriately selected patients with implications for clinical management and counseling of MBC patients and their family members.

Smyd3 open & closed lock mechanism for substrate recruitment: The hinge motion of C-terminal domain inferred from µ-second molecular dynamics simulations.

BACKGROUND: The human lysine methyltransferase Smyd3, a member of the SET and MYND domain containing protein family, harbors methylation activity on both histone and non-histone targets in a tightly regulated manner. The mechanism of how Smyd3 dynamically regulates substrate recognition is still not fully unveiled. METHODS: Here, we employed molecular dynamics simulations on full length human Smyd3, performed to a total of 1.2 µ-second, in the presence (holo) and absence (apo) of the S-Adenosyl methionine (AdoMet) cofactor. The dynamical features of Smyd3 in apo and holo states have been examined and compared via examining geometrical and electrostatic properties. RESULTS: The results show a distinct dynamics of the C-terminal domain (CTD) in the two states. In the apo state, the CTD undergoes a large hinge like motion and samples more opened configurations, thus acting like a loosened clamp and resulting in expanded substrate binding crevice. In the holo state, the CTD exhibits a restricted motion while the overall structure remains compact, mimicking a closed clamp. This leads to a localized increase in the negative potential at the substrate binding cleft. Further, solvent accessibility of critical residues at the target lysine access channel, important for methylation activity, is increased. CONCLUSIONS: We postulate that AdoMet cofactor acts like a key and locks Smyd3 in a closed conformation. In effect, the cofactor binding restricts the elasticity of the CTD, presenting a compact substrate binding cleft with high negative potential, which may have implications on substrate recruitment via long range electrostatics. GENERAL SIGNIFICANCE: The deletion of the CTD from Smyd3 has been shown to abolish the basal histone methylation activity. Our study highlights the importance of the CTD elasticity in shaping the substrate binding site for recognition and supports the previously proposed role of the CTD in stabilizing the active site for methylation activity.

FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.

Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer.

Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene.

BACKGROUND: Male breast cancer (MBC) is a rare disease whose etiology appears to be largely associated with genetic factors. BRCA1 and BRCA2 mutations account for about 10% of all MBC cases. Thus, a fraction of MBC cases are expected to be due to genetic factors not yet identified. To further explain the genetic susceptibility for MBC, whole-exome sequencing (WES) and targeted gene sequencing were applied to high-risk, BRCA1/2 mutation-negative MBC cases. METHODS: Germ-line DNA of 1 male and 2 female BRCA1/2 mutation-negative breast cancer (BC) cases from a pedigree showing a first-degree family history of MBC was analyzed with WES. Targeted gene sequencing for the validation of WES results was performed for 48 high-risk, BRCA1/2 mutation-negative MBC cases from an Italian multicenter study of MBC. A case-control series of 433 BRCA1/2 mutation-negative MBC and female breast cancer (FBC) cases and 849 male and female controls was included in the study. RESULTS: WES in the family identified the partner and localizer of BRCA2 (PALB2) c.419delA truncating mutation carried by the proband, her father, and her paternal uncle (all affected with BC) and the N-acetyltransferase 1 (NAT1) c.97C>T nonsense mutation carried by the proband's maternal aunt. Targeted PALB2 sequencing detected the c.1984A>T nonsense mutation in 1 of the 48 BRCA1/2 mutation-negative MBC cases. NAT1 c.97C>T was not found in the case-control series. CONCLUSIONS: These results add strength to the evidence showing that PALB2 is involved in BC risk for both sexes and indicate that consideration should be given to clinical testing of PALB2 for BRCA1/2 mutation-negative families with multiple MBC and FBC cases. Cancer 2017;123:210-218. © 2016 American Cancer Society.

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.

BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)). CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

EMSY copy number variation in male breast cancers characterized for BRCA1 and BRCA2 mutations.

PURPOSE: Male breast cancer (MBC) is a rare disease that shares some similarities with female breast cancer (FBC). Like FBC, genetic susceptibility to MBC can be referred to mutations in BRCA1 and, particularly, BRCA2 genes. However, only about 10 % of MBCs are caused by BRCA1/2 germ-line mutations, while the largest part are sporadic cancers and may derive from somatic alterations. EMSY, a BRCA2 inactivating gene, emerged as a candidate gene involved in the pathogenesis of sporadic FBC, and its amplification was suggested to be the somatic counterpart of BRCA2 mutations. Considering the relevant role of BRCA2 in MBC, we aimed at investigating the role of EMSY gene copy number variations in male breast tumors. METHODS: EMSY copy number variations were analyzed by quantitative real-time PCR with TaqMan probes in a selected series of 75 MBCs, characterized for BRCA1/2 mutations. RESULTS: We reported EMSY amplification in 34.7 % of MBCs. A significant association emerged between EMSY amplification and BRCA1/2 mutations (p = 0.03). We identified two amplification subgroups characterized by low and high amplification levels, with BRCA2-related tumors mostly showing low EMSY amplification. CONCLUSIONS: Our results show a high frequency of EMSY amplification in MBC, thus pointing to a role of EMSY in the pathogenesis of this disease. EMSY amplification may be a new feature that might uncover underlying molecular pathways of MBCs and may allow for the identification of MBC subgroups with potential clinical implication for targeted therapeutic approaches.

Cardiac MR perfusion imaging: where we are.

To date, several clinical and multicentre studies have demonstrated the accuracy of perfusion cardiac magnetic resonance to detect ischaemia in comparison with quantitative coronary angiography, other noninvasive diagnostic techniques (single photon emission computed tomography; positron-emission tomography), and invasive haemodynamic measurements (fractional flow reserve). Moreover, the favourable safety profile and increasing availability contribute to make perfusion cardiac magnetic resonance one of the modalities of choice for the detection of myocardial ischaemia. Recently, the first evidence of the prognostic value of perfusion cardiac magnetic resonance results has also become available. This review summarises the technical and interpretation key points of perfusion cardiac magnetic resonance scan, the clinical indications, the most recent available literature about its diagnostic performance and prognostic value, and how perfusion cardiac magnetic resonance compares with other noninvasive techniques.

Mutational profiling in melanocytic tumors: multiple somatic mutations and clinical implications.

In this study, we analyzed multiple somatic mutations in 10 genes relevant in melanoma tumorigenesis and targeted therapies. Overall, 45% of the tumors showed mutations and, in particular, 33% had multiple mutations. Based on our results, we conclude that the assessment of mutation status of multiple genes, including CDKN2A, could provide a genetic profile that can be useful as a prognostic and therapeutic marker in melanocytic tumors.

The role of visual spatial frequencies in newborns' processing of dynamic facial expressions of emotion.

Evidence on newborns' discrimination of emotional facial expressions is scarce, and the question of what is the nature of the visual information that newborns rely on to perform such discrimination remains open. Here, we manipulated the spatial frequency (SF) content of the stimuli by selectively removing low spatial frequency (LSF) and high spatial frequency bands using newborn-appropriate cutoffs to investigate what information newborns use when preferring and discriminating between dynamic displays showing happy and fearful expressions unfolding over time. Using a preferential looking paradigm, in Study 1 (N = 63, 59% females, 92% White), we showed that newborns looked longer to happy over fearful expressions in unfiltered (broad spatial frequency) and high-pass (high spatial frequency > 0.6 cycles per degree [cpd]) faces but not in low-pass (LSF < 0.5 cpd) faces. In Study 2 (N = 22, 59% females, 91% White), newborns tested in a visual habituation paradigm showed successful discrimination of the two LSF emotions. Results show that newborns can discriminate between dynamic images of happy and fearful facial expressions containing either extreme low SF (< 0.5 cpd) information or higher SF (> 0.6 cpd) bandwidth. Their preference for the happy expression was present for intact and high-pass filtered faces but not for low-pass faces. This SF effect is tentatively driven by an enhancement of attentional response to the LSF fearful face, whereas the response to the happy face is unaffected by the SF manipulation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Gender-Specific Genetic Predisposition to Breast Cancer: BRCA Genes and Beyond.

Among neoplastic diseases, breast cancer (BC) is one of the most influenced by gender. Despite common misconceptions associating BC as a women-only disease, BC can also occur in men. Additionally, transgender individuals may also experience BC. Genetic risk factors play a relevant role in BC predisposition, with important implications in precision prevention and treatment. The genetic architecture of BC susceptibility is similar in women and men, with high-, moderate-, and low-penetrance risk variants; however, some sex-specific features have emerged. Inherited high-penetrance pathogenic variants (PVs) in BRCA1 and BRCA2 genes are the strongest BC genetic risk factor. BRCA1 and BRCA2 PVs are more commonly associated with increased risk of female and male BC, respectively. Notably, BRCA-associated BCs are characterized by sex-specific pathologic features. Recently, next-generation sequencing technologies have helped to provide more insights on the role of moderate-penetrance BC risk variants, particularly in PALB2, CHEK2, and ATM genes, while international collaborative genome-wide association studies have contributed evidence on common low-penetrance BC risk variants, on their combined effect in polygenic models, and on their role as risk modulators in BRCA1/2 PV carriers. Overall, all these studies suggested that the genetic basis of male BC, although similar, may differ from female BC. Evaluating the genetic component of male BC as a distinct entity from female BC is the first step to improve both personalized risk assessment and therapeutic choices of patients of both sexes in order to reach gender equality in BC care. In this review, we summarize the latest research in the field of BC genetic predisposition with a particular focus on similarities and differences in male and female BC, and we also discuss the implications, challenges, and open issues that surround the establishment of a gender-oriented clinical management for BC.

HER2-Low Expression in Male Breast Cancer: Results from a Multicenter Series in Italy.

In the field of breast cancer care, a significant breakthrough has occurred with the recognition of HER2-low expression as a target for novel anti-HER2 antibody-drug conjugates (ADC). This discovery is reshaping the treatment landscape, challenging previous perceptions that considered HER2-low as clinically insignificant. The ability to target HER2-low expression is expected to have substantial clinical implications, irrespective of gender, including in cases of male breast cancer (MBC). However, an estimate of the prevalence of the HER2-low subtype in MBC is missing. This retrospective, observational, multicenter study was aimed at characterizing the HER2-low subtype in MBC. For the purpose of this study, the three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) was used to reclassify the HER2-negative group into HER-0 or HER2-low subtypes. In the whole series of 144 invasive MBCs, 79 (54.9%) were HER2-0 (IHC scores of 0), 39 (27.1%) HER2-low (IHC scores of 1+/2+ with negative ISH), and 26 (18.0%) HER2-positive (IHC scores of 3+/2+ with positive ISH). Specifically, among hormone receptor-positive (HR+) HER2-negative invasive MBCs, 34.8% were HER2-low and 65.2% HER2-0. Compared with HER2-0, HER2-low subtype was associated with a positive lymph node involvement (p = 0.01). Other pathologic characteristics including histology, staging, and grading did not show notable variations between the two subtypes. The presence of germline BRCA1/2 pathogenic variants (PVs) did not significantly differ between HER2-0 and HER2-low MBCs. However, about 13% of HER2-low MBCs had germline PVs in BRCA1/2 genes, mainly BRCA2, a clinically relevant observation in the context of combined target therapy. Overall, our data, which focused on the largest gender-specific breast cancer series, to our knowledge, confirm that the emerging three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) can also be considered in MBC, to mitigate both the gender gap and the underrepresentation of males in clinical trials.

Expression Analysis of Circulating microRNAs in Saliva and Plasma for the Identification of Clinically Relevant Biomarkers for Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

This study aims to evaluate the expression of salivary and plasmatic miRNAs as diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A total of 25 patients were divided into three groups, according to their diagnosis: OSCC patients (n = 14); OPMDs patients (n = 6); and healthy controls (n = 5). At the time at diagnosis/enrolment, patients underwent salivary and plasmatic collection. The expression of miRNA -21, -31, -138, -145, -184, and -424 were evaluated by real-time PCR. An F-test and ANOVA test were performed to evaluate the miRNA levels (significance at p < 0.05). By comparing miRNA expression levels from saliva, a statistically significant difference emerged in the expression of miR-138 and miR-424 between the three groups (p < 0.05). In particular, these two miRNAs showed decreased expression levels in saliva samples from OSCC and OPMD patients compared to those from healthy controls. On the other hand, miRNA expression levels in plasma were low in all the groups, and no statistically significant differences were found. Overall, our results showed that liquid biopsy from saliva may be a useful tool for the identification of diagnostic molecular biomarkers in OSCC and OPMDs.

Impact of Sex on Severity Assessment and Cardiac Remodeling in Primary Mitral Regurgitation.

Background: Women with severe primary mitral regurgitation (MR) have lower surgery rates than men and could suffer from delayed referral for mitral valve (MV) intervention, exposing them to an increased risk of postoperative adverse outcomes. Objectives: The purpose of this study was to assess the sex-based differences in patients with primary MR. Methods: The study sample consisted of 420 patients (median age: 62 years, 26% women) with primary MR due to valve prolapse referred for preoperative assessment who underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging. Multiple endpoints (abnormally increased left ventricular size, NYHA functional class III/IV, severe left atrial [LA] dilatation, pulmonary hypertension) were studied using areas under the curves and logistic regression models. Results: Women were older than men, had higher NYHA functional class and larger indexed LA volumes (all P ≤ 0.031), despite displaying lower MR effective regurgitant orifice area, regurgitant volumes (RegVol), and ventricular volumes than men (all P ≤ 0.002). The optimal cut-off values of RegVol associated with abnormally increased left ventricular size according to reference normal values were lower in women (TTE: 67 ml, CMR: 50 ml) than in men (TTE: 77 ml, CMR: 65 ml). MR regurgitant fraction, but not RegVol, was associated in women and men with NYHA functional class III/IV, severe LA dilatation, and pulmonary hypertension (all areas under the curves, P ≤ 0.024). Conclusions: Despite having hallmarks of more advanced valvular heart disease, women with significant primary MR demonstrate lower mitral RegVol and ventricular volumes than men. In contrast, the systematic calculation of MR regurgitant fraction could standardize MR quantification irrespective of sex.

SULT1A1 gene deletion in BRCA2-associated male breast cancer: a link between genes and environmental exposures?

SULT1A1, a member of sulfotransferase superfamily, is a drug and hormone metabolizing enzyme involved in the metabolism of a variety of potential mammary carcinogens of endogenous and exogenous origin. Interestingly, the metabolic activity of SULT1A1 can be affected by variations in gene copy number. Male Breast Cancer (MBC) is a rare disease and less investigated disease compared to female BC (FBC). As in FBC, the concurrent effects of genetic risk factors, particularly BRCA2 mutations, increased exposure to estrogens and environmental carcinogens play a relevant role in MBC. By quantitative real-time PCR with TaqMan probes, we investigated the presence of SULT1A1 gene copy number variations (CNVs) in a series of 72 MBCs. SULT1A1 gene deletion was observed in 10 of the 72 MBCs (13.9%). In a multivariate analysis association between BRCA2 mutation and SULT1A1 gene deletion emerged (p = 0.0005). Based on the evidence that the level of SULT1A1 enzyme activity is correlated with CNV, our data suggest that in male breast tumors SULT1A1 activity may be decreased. Thus, it can be hypothesized that in a proportion of MBCs, particularly in BRCA2-associated MBCs, the level of estrogens and environmental carcinogens exposure might be increased suggesting a link between gene and environmental exposure in the pathogenesis of MBC.

MDCT coronary angiography -- postprocessing, reading, and reporting: last but not least.

Significant literature on MDCT coronary angiography (MDCT-CA) has emerged in the last decade concerning patient's selection, technical aspects of different generations of CT equipment, ECG gating, contrast material and beta-blockade administration, acquisition parameters, and radiation dose. However, the literature regarding postprocessing, reading, and reporting is not so extensive. This review highlights the main elements of MDCT-CA data analysis, thereby allowing the radiologist to take full advantage of this technology and enable a structured report to be generated, promoting best practice with high-quality results.

Touch me or touch me not: Emotion regulation by affective touch in human adults.

In mammals, including humans, affective touch (AT) supports the establishment and maintenance of social connections and mitigates the effects of social conflict and ostracism. AT is used to describe slowly moving, low-forced mechanical stimulation that is frequently perceived as pleasant. In humans, AT has been addressed particularly for its role in promoting bonding and emotional regulation during early development; however, more recent studies have suggested that AT also preserves physical and emotional well-being in adulthood. Here, we investigated whether AT can buffer adults' experience of negative emotions as reflected in their behavioral and physiological responses to emotionally arousing stimuli. Participants were stimulated on their forearms using AT or tapping (T) while they viewed a series of emotionally arousing and neutral images, and we measured their skin conductance response and their explicit rating of the images' unpleasantness. We found that AT, but not T, reduced the arousal and perceived unpleasantness of the emotional stimuli but not the neutral ones, revealing the soothing role of AT in emotional contexts. The second aim of the study was to explore the possibility that AT might benefit some individuals more than others, according to their individual differences. To this aim, we assessed individuals' empathy and sensory processing sensitivity, as well as their perception of AT itself. Results revealed that while empathy did not predict changes in emotional processing irrespective of tactile stimulation, individuals with higher sensitivity reported AT as less pleasant. We discuss the possible factors mediating the observed interindividual variability in AT perception. (PsycInfo Database Record (c) 2023 APA, all rights reserved).