Unusual presentation of jejunal adenocarcinoma and ovarian metastasis

It is rare to find a small bowel tumour presenting as intestinal obstruction. This type of cancer is an extremely unusual condition often misdiagnosed until late stages. We report the case of a patient with persistent vomiting secondary to an obstructing jejunal adenocarcinoma not related to intestinal bowel disease. After resection and chemotherapy treatment a huge mass was detected in the left ovary. The anatomopathological findings confirmed a metastatic cancer consequent to the jejunal adenocarcinoma previously resected. This case illustrates a successful outcome of a jejunal adenocarcinoma with very poor prognosis after a extremely unusual ovarian metastasis. It is highly important to suspect other causes than intestinal bowel disease when doing a differential diagnosis in a young patient presenting with clinical symptoms of intestinal obstruction. (AU)

Pancreatic intraductal papillary mucinous neoplasm evolving into adenocarcinoma. Continual follow-up necessary.

We report a 62-year-old female with chronic pancreatitis after three episodes of severe acute pancreatitis. In 2008, an uneven main pancreatic duct (MPD) of 16 mm was found during an abdominal ultrasound. The follow-up was not continued until 2020, when a dilation of 27 mm of the MPD was discovered at magnetic resonance imaging (MRI). In 2022, another radiological test was carried out showing a dilation of the MPD of 40 mm with an intraductal tumoral lesion of 30 mm at the head of the pancreas). An echo-endoscopy was carried out and a pancreatic-duodenal tumour with a mixed pattern was discovered. Atypic cells were observed at the fine needle punction. A total duodenopancreatectomy was successfully carried out. In the anatomopathological macroscopic study a 14 cm-multi-cystic neoformation was seen and a solid tumour was discovered at the head of the pancreas that infiltrated the wall of the duodenum. In the longitudinal cross-section of the pancreatic body the MPD was seen to be severely dilated. A focal adenocarcinoma in a intraductal papillary mucinous neoplasm (IPMN) was finally diagnosed. Pancreatic lesions are usually asymptomatic and are detected by chance during other imaging tests. The IPMN rates of malignancy have been reported of between 19 to 30%. The management of pancreatic cystic lesions still represents a clinical challenge. As always, the multi-disciplinary management is mandatory in this type of tumour.

Unusual presentation of jejunal adenocarcinoma and ovarian metastasis.

It is rare to find a small bowel tumour presenting as intestinal obstruction. This type of cancer is an extremely unusual condition often misdiagnosed until late stages. We report the case of a patient with persistent vomiting secondary to an obstructing jejunal adenocarcinoma not related to intestinal bowel disease. After resection and chemotherapy treatment a huge mass was detected in the left ovary. The anatomopathological findings confirmed a metastatic cancer consequent to the jejunal adenocarcinoma previously resected. This case illustrates a successful outcome of a jejunal adenocarcinoma with very poor prognosis after a extremely unusual ovarian metastasis. It is highly important to suspect other causes than intestinal bowel disease when doing a differential diagnosis in a young patient presenting with clinical symptoms of intestinal obstruction.

Severe outbreak of ulcerative colitis and cerebral neoplasia. Difficult management in COVID time.

A 61-year-old male diabetic patient, diagnosed with ulcerative colitis (UC) 30 years ago, currently under treatment with mesalazine is presented. He was admitted to the emergency department due to a severe outbreak of UC, with 15 depositions daily, rectal bleeding and poor general condition. A brain CT-scan was carried out in the emergency department due to a sudden self-limited aphasia. A left frontal lesion of 45x38 mms with a prominent perilesional edema and with a displacement of the midline was reported. This was believed to be a meningioma (figure 1A). Urgent neurosurgery was not performed, prioritizing the severe flare-up UC. Based on this, full-dose metilprednisolone was administered.

Stigma related to breast cancer among women and men: The case of the Druze minority in Israel.

The objective of this study was to explore stigma related to breast cancer among Druze women and men and identify factors associated with low screening rates among Druze women. A sample of 270 Druze women and men completed an online questionnaire adapted to detect breast cancer stigma and internalized breast cancer stigma. Independent samples t-test results showed higher scores for men compared to women, at a significant level, on four of the Breast Cancer Stigma scales: awkwardness, avoidance, policy opposition, and personal responsibility. Independent samples t-test results also showed higher scores for men compared to women, at a significant level, on two of the Internalized Breast Cancer Stigma scales: stereotype endorsement and discrimination experience. These results suggest a need for psychoeducation about breast cancer screening for minority groups such as the Druze, with male partners of women who are diagnosed with breast cancer being the main target recipients.

High-Quality Contact With Fellow Majority Group Students Is Associated With Better Academic Performance of Minority Group Students.

We examined the association between intergroup contact and academic performance at university among minority students in a context with a segregated pre-university school system. Study 1 tested whether participation in a group dynamics course, which involves intimate interpersonal contact between Israeli Arab (n = 125) and Jewish students, was associated with better grade point average (GPA). As expected, Arab students who participated in the course had a higher GPA than those who did not, even when controlling for pre-university achievements. The corresponding difference among Jews was substantially smaller. Study 2 (N = 90), a longitudinal study, revealed that the quality of contact with Jewish students at university was associated with Arab students' subsequent higher GPA, even when controlling for pre-university contact, proxies of academic achievements, and perceptions of intergroup relations. The quality of contact with Jewish students was also associated with Arab students' sense of academic belonging. Theoretical and practical implications are discussed.

The relationship between non-suicidal self-injury, identity conflict, and risky behavior among Druze adolescents.

Objectives: This study aimed to explore the prevalence of non-suicidal self-injury (NSSI) among Druze adolescents in Israel, an ethnic minority, and examine the influence of identity conflict, depression, and performance of risky behaviors on such adolescents' engagement in NSSI. This investigation is important because little is known about NSSI among adolescents from ethnic minorities. Methods: Overall, 290 Druze adolescents aged 16-18 (mean = 16.26, standard deviation = 0.9) years (63.9% female) participated in this study. They were recruited through snowball sampling from three Druze schools that agreed to participate in the study. All participants completed self-report measures for NSSI, depression, anxiety, engagement in risky behaviors, emotion regulation, sleep problems, and identity integration. Results: Almost 20% of the total sample engaged in NSSI. Those who engaged in NSSI reported more significant depression, anxiety, sleep problems, and engagement in risky behaviors when compared with those who did not engage in NSSI. Moreover, those who engaged in NSSI reported experiencing a higher level of identity conflict. Further analysis revealed an indirect effect of identity conflict on NSSI through engagement in risky behaviors. Conclusions: This study's findings clarify the prevalence of NSSI among Druze adolescents, as well as contributing factors, and also highlights the importance of developing interventions that specifically target this unique ethnic group.

New vistas unfold: Chicken MHC molecules reveal unexpected ways to present peptides to the immune system.

The functions of a wide variety of molecules with structures similar to the classical class I and class II molecules encoded by the major histocompatibility complex (MHC) have been studied by biochemical and structural studies over decades, with many aspects for humans and mice now enshrined in textbooks as dogma. However, there is much variation of the MHC and MHC molecules among the other jawed vertebrates, understood in the most detail for the domestic chicken. Among the many unexpected features in chickens is the co-evolution between polymorphic TAP and tapasin genes with a dominantly-expressed class I gene based on a different genomic arrangement compared to typical mammals. Another important discovery was the hierarchy of class I alleles for a suite of properties including size of peptide repertoire, stability and cell surface expression level, which is also found in humans although not as extreme, and which led to the concept of generalists and specialists in response to infectious pathogens. Structural studies of chicken class I molecules have provided molecular explanations for the differences in peptide binding compared to typical mammals. These unexpected phenomena include the stringent binding with three anchor residues and acidic residues at the peptide C-terminus for fastidious alleles, and the remodelling binding sites, relaxed binding of anchor residues in broad hydrophobic pockets and extension at the peptide C-terminus for promiscuous alleles. The first few studies for chicken class II molecules have already uncovered unanticipated structural features, including an allele that binds peptides by a decamer core. It seems likely that the understanding of how MHC molecules bind and present peptides to lymphocytes will broaden considerably with further unexpected discoveries through biochemical and structural studies for chickens and other non-mammalian vertebrates.

A human IgE bispecific antibody shows potent cytotoxic capacity mediated by monocytes.

The generation of bispecific antibodies (bsAbs) targeting two different antigens opens a new level of specificity and, compared to mAbs, improved clinical efficacy in cancer therapy. Currently, the different strategies for development of bsAbs primarily focus on IgG isotypes. Nevertheless, in comparison to IgG isotypes, IgE has been shown to offer superior tumor control in preclinical models. Therefore, in order to combine the promising potential of IgE molecules with increased target selectivity of bsAbs, we developed dual tumor-associated antigen-targeting bispecific human IgE antibodies. As proof of principle, we used two different pairing approaches - knobs-into-holes and leucine zipper-mediated pairing. Our data show that both strategies were highly efficient in driving bispecific IgE formation, with no undesired pairings observed. Bispecific IgE antibodies also showed a dose-dependent binding to their target antigens, and cell bridging experiments demonstrated simultaneous binding of two different antigens. As antibodies mediate a major part of their effector functions through interaction with Fc receptors (FcRs) expressed on immune cells, we confirmed FcεR binding by inducing in vitro mast cell degranulation and demonstrating in vitro and in vivo monocyte-mediated cytotoxicity against target antigen-expressing Chinese hamster ovary cells. Moreover, we demonstrated that the IgE bsAb construct was significantly more efficient in mediating antibody-dependent cell toxicity than its IgG1 counterpart. In conclusion, we describe the successful development of first bispecific IgE antibodies with superior antibody-dependent cell toxicity-mediated cell killing in comparison to IgG bispecific antibodies. These findings highlight the relevance of IgE-based bispecific antibodies for clinical application.

The dominantly expressed class II molecule from a resistant MHC haplotype presents only a few Marek's disease virus peptides by using an unprecedented binding motif.

Viral diseases pose major threats to humans and other animals, including the billions of chickens that are an important food source as well as a public health concern due to zoonotic pathogens. Unlike humans and other typical mammals, the major histocompatibility complex (MHC) of chickens can confer decisive resistance or susceptibility to many viral diseases. An iconic example is Marek's disease, caused by an oncogenic herpesvirus with over 100 genes. Classical MHC class I and class II molecules present antigenic peptides to T lymphocytes, and it has been hard to understand how such MHC molecules could be involved in susceptibility to Marek's disease, given the potential number of peptides from over 100 genes. We used a new in vitro infection system and immunopeptidomics to determine peptide motifs for the 2 class II molecules expressed by the MHC haplotype B2, which is known to confer resistance to Marek's disease. Surprisingly, we found that the vast majority of viral peptide epitopes presented by chicken class II molecules arise from only 4 viral genes, nearly all having the peptide motif for BL2*02, the dominantly expressed class II molecule in chickens. We expressed BL2*02 linked to several Marek's disease virus (MDV) peptides and determined one X-ray crystal structure, showing how a single small amino acid in the binding site causes a crinkle in the peptide, leading to a core binding peptide of 10 amino acids, compared to the 9 amino acids in all other reported class II molecules. The limited number of potential T cell epitopes from such a complex virus can explain the differential MHC-determined resistance to MDV, but raises questions of mechanism and opportunities for vaccine targets in this important food species, as well as providing a basis for understanding class II molecules in other species including humans.

Ingroup Bias in Healthcare Contexts: Israeli-Jewish Perceptions of Arab and Jewish Doctors.

The influence of group membership on perceptions of outgroup members has been extensively studied in various contexts. This research has indicated a strong tendency for ingroup bias - preferring the ingroup over the outgroup. We seek to further expand on the growing literature regarding the effects of group membership within healthcare contexts. Focusing on the Arab-Jewish context in Israel, the present study explored the influence of group membership on Israeli-Jewish participants' evaluations when exposed to potential malpractice. Specifically, participants (n = 165) read a description of an Israeli-Jewish or Israeli-Arab physician who was either culpable or non-culpable of malpractice. Consistent with our predictions, findings generally indicated more negative evaluations of the Israeli-Arab physician, regardless of objective culpability. We conclude by discussing the study's limitations and implications.

The Underlying Process of Prosocial Behavior Among Soldiers: A Terror Management Theory Perspective.

The mortality salience (MS) hypothesis postulates that anxiety elicited by mortality awareness leads people to develop negative emotions toward those who hold values inconsistent with their worldview faith. We explored this hypothesis in a sample of 76 Israeli combat soldiers, who were asked to reflect on either their mortality or dental pain. Subsequently, participants reported their motivation to help a father in need who was either an Arab (outgroup) or a Jewish Israeli (ingroup), as well as their perceptions of threat by Arab Israelis. Regression analysis indicated that mortality reminders intensified soldiers' perception of threat by the outgroup, leading to an increased desire to assist a Jewish-Israeli father, and a decreased motivation to help an Arab-Israeli one. The findings demonstrate the pronounced effects of MS on soldiers involved in frequent combat actions in terms of evoking negative emotions leading to reluctance to help unarmed civilian outgroup members. Recommendations for soldiers' pre-deployment psychoeducation sessions are provided.

Phosphorylation of the multifunctional signal transducer B-cell adaptor protein (BCAP) promotes recruitment of multiple SH2/SH3 proteins including GRB2.

B-cell adaptor protein (BCAP) is a multimodular, multifunctional signal transducer that regulates signal transduction pathways in leukocytes, including macrophages, B-cells, and T-cells. In particular, BCAP suppresses inflammatory signaling by Toll-like receptors (TLRs). However, how BCAP itself is regulated and what its interaction partners are is unclear. Here, using human immune cell lines, including THP-1 cells, we characterized the complex phosphorylation patterns of BCAP and used a novel protein complex trapping strategy, called virotrap, to identify its interaction partners. This analysis identified known interactions of BCAP with phosphoinositide 3-kinase (PI3K) p85 subunit and NCK adaptor protein (NCK), together with previously unknown interactions of BCAP with Src homology 2 (SH2) and SH3 domain-containing adaptor proteins, notably growth factor receptor-bound protein 2 (GRB2) and CRK-like proto-oncogene, adaptor protein (CRKL). We show that the SH3 domain of GRB2 can bind to BCAP independently of BCAP phosphorylation status, suggesting that the SH2 domains mediate interactions with activated receptor tyrosine kinase complexes including the CD19 subunit of the B-cell receptor. Our results also suggested that the PI3K p85 subunit binds to BCAP via SH3 domains forming an inactive complex that is then activated by sequential binding with the SH2 domains. Taken together, our results indicate that BCAP is a complex hub that processes signals from multiple pathways in diverse cell types of the immune system.

Power matters: The role of power and morality needs in competitive victimhood among advantaged and disadvantaged groups.

Competitive victimhood denotes group members' efforts to establish that their ingroup has suffered greater injustice than an adversarial outgroup. Previous research in contexts of structural inequality has stressed the role of the need to defend the ingroup's moral identity, rather than the need for power, in leading advantaged and disadvantaged group members to engage in competitive victimhood. Focusing on the structural inequality between Jewish and Arab citizens of Israel (Study 1) and Israeli women and men (Study 2), we found that across all groups and contexts, power needs predicted competitive victimhood. Also, the need to protect the ingroup's moral reputation (i.e., defensive moral needs) positively predicted competitive victimhood, whereas among advantaged group members, the need to protect the ingroup's moral essence negatively predicted competitive victimhood. Finally, exploratory analyses revealed that competitive victimhood correlated, positively for advantaged and negatively for disadvantaged group members, with support for policies securing realistic and symbolic resources for the disadvantaged group. Theoretical and practical implications of these results, which are consistent with the logic of the needs-based model of reconciliation, are discussed.

Future time perspective and interpersonal empathy: Implications for preferring autonomy- versus dependency-oriented helping.

We examined whether potential help givers' future time perspective (FTP) accounts for the decision to give a person in need dependency-oriented help (i.e., providing the complete solution) or autonomy-oriented help (i.e., providing the means to solve a problem). In addition, building on past research on the effects of empathy in help giving decisions, the present research explored whether helpers' willingness to offer specific type of help is predicted by the interaction between FTP and interpersonal empathy. We explored FTP as both a personal predisposition (Study 1) and an experimentally induced state of mind (Study 2). The present research provides a novel perspective on theory and research on help giving behaviour, FTP, and empathy, by showing that when interpersonal empathy is high, considerations of the future predict readiness to give help that promotes person's present and future independent coping rather than help that creates and preserves social dependence.

Structure of the Toll/Interleukin-1 Receptor (TIR) Domain of the B-cell Adaptor That Links Phosphoinositide Metabolism with the Negative Regulation of the Toll-like Receptor (TLR) Signalosome.

Ligand binding to Toll-like receptors (TLRs) results in dimerization of their cytosolic Toll/interleukin-1 receptor (TIR) domains and recruitment of post-receptor signal transducers into a complex signalosome. TLR activation leads to the production of transcription factors and pro-inflammatory molecules and the activation of phosphoinositide 3-kinases (PI3K) in a process that requires the multimodular B-cell adaptor for phosphoinositide 3-kinase (BCAP). BCAP has a sequence previously proposed as a "cryptic" TIR domain. Here, we present the structure of the N-terminal region of human BCAP and show that it possesses a canonical TIR fold. Dimeric BCAP associates with the TIR domains of TLR2/4 and MAL/TIRAP, suggesting that it is recruited to the TLR signalosome by multitypic TIR-TIR interactions. BCAP also interacts with the p85 subunit of PI3K and phospholipase Cγ, enzymes that deplete plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2), and these interactions provide a molecular explanation for BCAP-mediated down-regulation of inflammatory signaling.

When suffering begets suffering: the psychology of competitive victimhood between adversarial groups in violent conflicts.

Inter-group competitive victimhood (CV) describes the efforts of members of groups involved in violent conflicts to establish that their group has suffered more than their adversarial group. Such efforts contribute to conflicts' escalation and impede their peaceful resolution. CV stems from groups' general tendency to compete with each other, along with the deep sense of victimization resulting from conflicts. The authors point to biases that contribute to groups' engagement in CV, describe five dimensions of victimhood over which groups may compete, and contend that such competition serves various functions that contribute to the maintenance of conflicts. Drawing on the Needs-Based Model, they suggest that CV may reflect groups' motivations to restore power or moral acceptance. They then review evidence of the negative consequences of CV for inter-group forgiveness and suggest potential strategies to reduce CV. Finally, the authors discuss potential moderators and directions for future research.

Intergroup helping as status relations: Effects of status stability, identification, and type of help on receptivity to high-status group's help.

Integrating research on social identity processes and helping relations, the authors proposed that low-status group members who are high identifiers will be unwilling to receive help from the high-status group when status relations are perceived as unstable and help is dependency-oriented. The first experiment, a minimal group experiment, found negative reactions to help from a high-status outgroup when status relations were unstable. The 2nd and 3rd experiments, which used real groups of Israeli Arabs and Israeli Jews, replicated this finding and showed that high identifiers were less receptive to help from the high-status outgroup than low identifiers. The 4th experiment, a help-seeking experiment with real groups of competing high schools, found that the least amount of help was sought from a high-status group by high identifiers when status relations were perceived as unstable and help was dependency-oriented. Theoretical and applied implications are discussed.