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Abstract Most patients with advanced ovarian cancer (AOC) ultimately relapse after platinum-based chemotherapy. Combining bevacizumab, olaparib, and durvalumab likely drives synergistic activity. This open-label phase 2 study (NCT04015739) aimed to assess activity and safety of this triple combination in female patients with relapsed high-grade AOC following prior platinum-based therapy. Patients were treated with olaparib (300 mg orally, twice daily), the bevacizumab biosimilar FKB238 (15 mg/kg intravenously, once-every-3-weeks), and durvalumab (1.12 g intravenously, once-every-3-weeks) in nine French centers. The primary endpoint was the non-progression rate at 3 months for platinum-resistant relapse or 6 months for platinum-sensitive relapse per RECIST 1.1 and irRECIST. Secondary endpoints were CA-125 decline with CA-125 ELIMination rate constant K (KELIM-B) per CA-125 longitudinal kinetics over 100 days, progression free survival and overall survival, tumor response, and safety. Non-progression rates were 69.8% (90%CI 55.9%-80.0%) at 3 months for platinum-resistant relapse patients (N = 41), meeting the prespecified endpoint, and 43.8% (90%CI 29.0%-57.4%) at 6 months for platinum-sensitive relapse (N = 33), not meeting the prespecified endpoint. Median progression-free survival was 4.1 months (95%CI 3.5–5.9) and 4.9 months (95%CI 2.9–7.0) respectively. Favorable KELIM-B was associated with better survival. No toxic deaths or major safety signals were observed. Here we show that further investigation of this triple combination may be considered in AOC patients with platinum-resistant relapse.

Summary: Melanoma is the deadliest form of skin cancer due to its propensity to metastasize. It arises from melanocytes, which are attached to keratinocytes within the basal epidermis. Here, we hypothesize that, in addition to melanocyte-intrinsic modifications, dysregulation of keratinocyte functions could initiate early-stage melanoma cell invasion. We identified the lysolipid sphingosine 1-phosphate (S1P) as a tumor paracrine signal from melanoma cells that modifies the keratinocyte transcriptome and reduces their adhesive properties, leading to tumor invasion. Mechanistically, tumor cell-derived S1P reduced E-cadherin expression in keratinocytes via S1P receptor dependent Snail and Slug activation. All of these effects were blocked by S1P2/3 antagonists. Importantly, we showed that epidermal E-cadherin expression was inversely correlated with the expression of the S1P-producing enzyme in neighboring tumors and the Breslow thickness in patients with early-stage melanoma. These findings support the notion that E-cadherin loss in the epidermis initiates the metastatic cascade in melanoma.

The autonomic nervous systems densely innervate the pancreas, but its contribution to pancreatic ductal adenocarcinoma (PDAC) progression is not fully understood. Here, the authors characterize the pattern of sympathetic innervation by 3D imaging in a murine model of PDAC and show that sympathectomy aggravates cancer progression.

Abstract Background Lymphopenia is a hallmark of severe coronavirus disease 19 (COVID-19). Similar alterations have been described in bacterial sepsis and therapeutic strategies targeting T cell function such as recombinant human interleukin 7 (rhIL-7) have been proposed in this clinical context. As COVID-19 is a viral sepsis, the objectives of this study were to characterize T lymphocyte response over time in severe COVID-19 patients and to assess the effect of ex vivo administration of rhIL-7. Results Peripheral blood mononuclear cells from COVID-19 patients hospitalized in intensive care unit (ICU) were collected at admission and after 20 days. Transcriptomic profile was evaluated through NanoString technology. Inhibitory immune checkpoints expressions were determined by flow cytometry. T lymphocyte proliferation and IFN-γ production were evaluated after ex vivo stimulation in the presence or not of rhIL-7. COVID-19 ICU patients were markedly lymphopenic at admission. Mononuclear cells presented with inhibited transcriptomic profile prevalently with impaired T cell activation pathways. CD4 + and CD8 + T cells presented with over-expression of co-inhibitory molecules PD-1, PD-L1, CTLA-4 and TIM-3. CD4 + and CD8 + T cell proliferation and IFN-γ production were markedly altered in samples collected at ICU admission. These alterations, characteristic of a T cell exhaustion state, were more pronounced at ICU admission and alleviated over time. Treatment with rhIL-7 ex vivo significantly improved both T cell proliferation and IFN-γ production in cells from COVID-19 patients. Conclusions Severe COVID-19 patients present with features of profound T cell exhaustion upon ICU admission which can be reversed ex vivo by rhIL-7. These results reinforce our understanding of severe COVID-19 pathophysiology and opens novel therapeutic avenues to treat such critically ill patients based of immunomodulation approaches. Defining the appropriate timing for initiating such immune-adjuvant therapy in clinical setting and the pertinent markers for a careful selection of patients are now warranted to confirm the ex vivo results described so far. Trial registration ClinicalTrials.gov identifier: NCT04392401 Registered 18 May 2020, http:// clinicaltrials.gov/ct2/show/NCT04392401.

We report a case of metastatic pancreatic neuroendocrine carcinoma associated with paraneoplastic Cushing’s syndrome, successively treated with five lines of treatment (platin-etoposide, LV5FU2-dacarbazine, FOLFIRINOX, pembrolizumab, and paclitaxel) and anti-secretory treatment. Circulating-free DNA (cfDNA) was analysed at each morphological evaluation starting from the second-line treatment. cfDNA changes were well correlated with the disease course, and cfDNA may be used as a predictive marker and/or as an early marker of response. In addition, the absolute count of atypical cells was elevated upon disease progression.

Microsatellite instability (MSI) is a molecular signature of mismatch repair deficiency (dMMR), a predictive marker of immune checkpoint inhibitor therapy response. Despite its recognized pan-cancer value, most methods only support detection of this signature in colorectal cancer. In addition to the tissue-specific differences that impact the sensitivity of MSI detection in other tissues, the performance of most methods is also affected by patient ethnicity, tumor content, and other sample-specific properties. These limitations are particularly important when only tumor samples are available and restrict the performance and adoption of MSI testing. Here we introduce MSIdetect, a novel solution for NGS-based MSI detection. MSIdetect models the impact of indel burden and tumor content on read coverage at a set of homopolymer regions that we found are minimally impacted by sample-specific factors. We validated MSIdetect in 139 Formalin-Fixed Paraffin-Embedded (FFPE) clinical samples from colorectal and endometrial cancer as well as other more challenging tumor types, such as glioma or sebaceous adenoma or carcinoma. Based on analysis of these samples, MSIdetect displays 100% specificity and 96.3% sensitivity. Limit of detection analysis supports that MSIdetect is sensitive even in samples with relatively low tumor content and limited microsatellite instability. Finally, the results obtained using MSIdetect in tumor-only data correlate well (R=0.988) with what is obtained using tumor-normal matched pairs, demonstrating that the solution addresses the challenges posed by MSI detection from tumor-only data. The accuracy of MSI detection by MSIdetect in different cancer types coupled with the flexibility afforded by NGS-based testing will support the adoption of MSI testing in the clinical setting and increase the number of patients identified that are likely to benefit from immune checkpoint inhibitor therapy.

Abstract Parental care has been shown to reduce the magnitude of inbreeding depression in some species with facultative care. However, parents often vary in the quality or amount of care they provide to their offspring, and it is less clear whether this variation also impacts the magnitude of inbreeding depression. Here, we tested whether age‐related changes in parental care modulate the expression of inbreeding depression in the burying beetle, Nicrophorus orbicollis. Consistent with previous studies, we found that older parents produced larger broods of offspring than younger parents without sacrificing mean larval mass. Inbreeding depression was evident in several fitness‐related traits: brood size at dispersal, the proportion of the brood that survived to eclosion, and mean age at death were all reduced in inbred broods compared with outbred broods. Surprisingly, inbred offspring were heavier at dispersal than outbred offspring. This was likely due to reduced sibling competition in inbred broods. Despite evidence for age‐related changes in parental investment and the existence of inbreeding depression, there was no evidence that an interaction between the two influenced any of the traits we measured. Our results suggest that age‐related changes in parental care may be too slight to influence the expression of inbreeding depression.

MDM2 and BET inhibitors have shown efficacy in AML treatment. Here, the authors show that the two compounds can synergize through both p53 protein stabilization and inhibition of BRD4-mediated repression of p53 target genes.

Background The efficacy of immunotherapies in metastatic melanoma depends on a robust T cell infiltration. Oncogenic alterations of tumor cells have been associated to T cell exclusion. Identifying novel cancer cell-intrinsic non-genetic mechanisms of immune escape, the targeting of which would reinstate T cell recruitment, would allow to restore the response to anti-programmed cell death protein 1 (PD-1) antibody therapy. The epithelial-to-mesenchymal transition (EMT)-inducing transcription factor ZEB1 is a major regulator of melanoma cell plasticity, driving resistance to mitogen-activated protein kinase (MAPK) targeted therapies. We thus wondered whether ZEB1 signaling in melanoma cells may promote immune evasion and resistance to immunotherapy.Methods We evaluated the putative correlation between ZEB1 expression in melanoma cells and the composition of the immune infiltrate in a cohort of 60 human melanoma samples by combining transcriptomic (RNA-sequencing) and seven-color spatial multi-immunofluorescence analyses. Algorithm-based spatial reconstitution of tumors allowed the quantification of CD8+, CD4+ T cells number and their activation state (PD-1, Ki67). ZEB1 gain-of-function or loss-of-function approaches were then implemented in syngeneic melanoma mouse models, followed by monitoring of tumor growth, quantification of immune cell populations frequency and function by flow cytometry, cytokines secretion by multiplex analyses. Chromatin-immunoprecipitation was used to demonstrate the direct binding of this transcription factor on the promoters of cytokine-encoding genes. Finally, the sensitivity to anti-PD-1 antibody therapy upon ZEB1 gain-of-function or loss-of-function was evaluated.Results Combined spatial and transcriptomic analyses of the immune infiltrates in human melanoma samples demonstrated that ZEB1 expression in melanoma cells is associated with decreased CD8+ T cell infiltration, independently of β-catenin pathway activation. ZEB1 ectopic expression in melanoma cells impairs CD8+ T cell recruitment in syngeneic mouse models, resulting in tumor immune evasion and resistance to immune checkpoint blockade. Mechanistically, we demonstrate that ZEB1 directly represses the secretion of T cell-attracting chemokines, including CXCL10. Finally, Zeb1 knock-out, by promoting CD8+ T cell infiltration, synergizes with anti-PD-1 antibody therapy in promoting tumor regression.Conclusions We identify the ZEB1 transcription factor as a key determinant of melanoma immune escape, highlighting a previously unknown therapeutic target to increase efficacy of immunotherapy in melanoma.Trial registration number NCT02828202.

Background: ICIs have dramatically improved patient outcomes in different malignancies. However, the impact of liver metastases (LM) and number of metastatic sites (MS) remains unclear in patients treated with single-agent anti-PD(L)1. Methods: We aimed to assess the prognostic impact of LM and MS number on progression-free survival (PFS) and overall survival (OS) in a large single-arm retrospective multicentric cohort (IMMUCARE) of patients treated with anti-PD(L)-1 for different solid tumors. Results: A total of 759 patients were enrolled from January 2012 to October 2018. The primary tumor types were non-small cell lung cancer (71%), melanoma (19%), or urologic cancer (10%). At the time of ICI initiation, 167 patients (22%) had LM and 370 patients (49%) had more than MS. LM was associated with a shorter median PFS of 1.9 months (95% CI: 1.8–2.5) vs. 4.0 months (95% CI: 3.6–5.4) in patients without LM (p < 0.001). The median OS of patients with LM was of 5.2 months (95% CI: 4.0–7.7) compared with 12.8 months (95% CI: 11.2–15.1) (p < 0.001). Interestingly, LM were not associated with shorter PFS, or OS compared to other MS types (brain, bone, or lung) in patients with only one MS. Patients with multiple MS also had poor clinical outcomes compared to patients with only one MS. The presence of LM and MS number were independent prognostic factors on overall survival. Conclusion: The presence of LM or multiple MS were associated with poorer survival outcomes in patients treated with anti-PD(L)-1.

The human placenta shares properties with solid tumors, such as rapid growth, tissue invasion, cell migration, angiogenesis, and immune evasion. However, the mechanisms that drive the evolution from premalignant proliferative placental diseases—called hydatidiform moles—to their malignant counterparts, gestational choriocarcinoma, as well as the factors underlying the increased aggressiveness of choriocarcinoma arising after term delivery compared to those developing from hydatidiform moles, are unknown. Using a 730-gene panel covering 13 cancer-associated canonical pathways, we compared the transcriptomic profiles of complete moles to those of postmolar choriocarcinoma samples and those of postmolar to post-term delivery choriocarcinoma. We identified 33 genes differentially expressed between complete moles and postmolar choriocarcinoma, which revealed TGF-β pathway dysregulation. We found the strong expression of SALL4, an upstream regulator of TGF-β, in postmolar choriocarcinoma, compared to moles, in which its expression was almost null. Finally, there were no differentially expressed genes between postmolar and post-term delivery choriocarcinoma samples. To conclude, the TGF-β pathway appears to be a crucial step in the progression of placental malignancies. Further studies should investigate the value of TGF- β family members as biomarkers and new therapeutic targets.

BCL-XL provides a survival advantage to cancer cells even in the absence of apoptotic pressures. In this study, the authors show that BCL-XL interacts with RAS in a BH4-dependent manner and regulates RAS-mediated activation of pathways involved in the stemness feature of breast cancer cells.

A. Rosenfeld [23] introduced the notion of a digitally continuous function between digital images, and showed that although digital images need not have fixed point properties analogous to those of the Euclidean spaces modeled by the images, there often are approximate fixed point properties of such images. In the current paper, we obtain additional results concerning fixed points and approximate fixed points of digitally continuous functions. Among these are several results concerning the relationship between universal functions and the approximate fixed point property (AFPP).

Apoptosis often requires mitochondrial outer membrane permeabilization, a process targeted by Bcl-2-binding BH3 mimetics. Here the authors describe and apply 'mito-priming', a method that allows triggering mitochondrial apoptosis in a synchronous manner, facilitating the investigation of mitochondrial apoptosis and its regulation by Bcl-2 proteins.

Src tyrosine kinases are deregulated in numerous cancers and may favor tumorigenesis and tumor progression. We previously described that Src activation in NIH-3T3 mouse fibroblasts promoted cell resistance to apoptosis. Indeed, Src was found to accelerate the degradation of the pro-apoptotic BH3-only protein Bik and compromised Bax activation as well as subsequent mitochondrial outer membrane permeabilization. The present study undertook a systems biomedicine approach to design optimal anticancer therapeutic strategies using Src-transformed and parental fibroblasts as a biological model. First, a mathematical model of Bik kinetics was designed and fitted to biological data. It guided further experimental investigation that showed that Bik total amount remained constant during staurosporine exposure, and suggested that Bik protein might undergo activation to induce apoptosis. Then, a mathematical model of the mitochondrial pathway of apoptosis was designed and fitted to experimental results. It showed that Src inhibitors could circumvent resistance to apoptosis in Src-transformed cells but gave no specific advantage to parental cells. In addition, it predicted that inhibitors of Bcl-2 antiapoptotic proteins such as ABT-737 should not be used in this biological system in which apoptosis resistance relied on the deficiency of an apoptosis accelerator but not on the overexpression of an apoptosis inhibitor, which was experimentally verified. Finally, we designed theoretically optimal therapeutic strategies using the data-calibrated model. All of them relied on the observed Bax overexpression in Src-transformed cells compared to parental fibroblasts. Indeed, they all involved Bax downregulation such that Bax levels would still be high enough to induce apoptosis in Src-transformed cells but not in parental ones. Efficacy of this counterintuitive therapeutic strategy was further experimentally validated. Thus, the use of Bax inhibitors might be an unexpected way to specifically target cancer cells with deregulated Src tyrosine kinase activity.

BACKGROUND: The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction. METHODOLOGY/PRINCIPAL FINDINGS: Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence. Using isolated mitochondria as well as model lipid Langmuir monolayers coupled with Brewster Angle Microscopy, we explored systematically and comparatively the membrane activity and membrane-peptide interactions of fragments derived from the central helical hairpin of BAX, BCL-xL and BID. The results show a connection between the differing abilities of the assayed peptide fragments to contact, insert, destabilize and porate membranes and the activity of their cognate proteins in programmed cell death. CONCLUSION/SIGNIFICANCE: BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains.

The use of digital technologies to conduct large-scale research with limited interaction (i.e. no in-person contact) and objective endpoints (i.e. biological testing) has significant potential for the field of epidemiology, but limited research to date has been published on the successes and challenges of such approaches. We analyzed data from a cohort study of sexual minority men across the United States, collected using digital strategies during a 10-month period from 2017 to 2018. Overall, 113,874 individuals were screened, of whom 26,000 were invited to the study, 10,691 joined the study, and 7,957 completed all enrollment steps, including return of a human immunodeficiency virus–negative sample. We examined group differences in completion of the steps towards enrollment to inform future research and found significant differences according to several factors, including age and race. This study adds to prior work to provide further proof-of-concept for this limited-interaction, technology-mediated methodology, highlighting some of its strengths and challenges, including rapid access to more diverse populations but also potential for bias due to differential enrollment. This method has strong promise, and future implementation research is needed to better understand the roles of burden, privacy, access, and compensation, to enhance representativeness and generalizability of the data generated. [ABSTRACT FROM AUTHOR]

La educación para la diversidad representa una forma de planificar, enseñar y aprender de diferente manera, cambiar la mentalidad del educando, el profesor y la comunidad. La “educación inclusiva” implica tolerancia, respeto y solidaridad (UNESCO, 1990). El artículo presenta un relato de experiencia en torno al diseño de un material didáctico digital para la sistematización del Informe Psicopedagógico de las Personas con Discapacidad, como parte del Programa de Atención Psicopedagógica de la Facultad de Estudios Superiores Aragón que se desarrolla en la Universidad Nacional Autónoma de México. En este trabajo se construyeron comunidades virtuales de aprendizaje transdisciplinario, con el propósito de impulsar una participación activa entre docentes y prestadores universitarios de servicio social. La metodología empleada se basó en la investigación-acción, la cual permitió realizar una indagación reflexiva mediante actores sociales en el lapso de la pandemia provocada por el virus SARS-CoV-2/ COVID-19, contando con 7 estudiantes universitarios, 3 docentes y 7 personas con discapacidad. Los resultados obtenidos mostraron que, a través de recursos digitales interactivos alojados en una nube, se logró sistematizar el diseño de informes, lo cual incluye diagnóstico, programa, plan de acción, actividades realizadas, material didáctico y evaluación. Cada uno de ellos contiene las pruebas aplicadas, así como acciones y recursos utilizados para dar seguimiento a los avances del proceso de aprendizaje de la persona con discapacidad.

High throughput sequencing (HTS) is increasingly important in determining cancer diagnoses, with subsequent prognostic and therapeutic implications. The biology of cancer is becoming increasingly deciphered and it is clear that therapy needs to be individually tailored. Whilst translational research plays an important role in lymphoid malignancies, few guidelines exist to guide biologists and routine laboratories through this constantly evolving field. In this article, we review the challenges of interpreting HTS in lymphoid malignancies and provide a toolkit to interpret single nucleotide variants obtained from HTS. We define the pre-analytical issues such as sequencing DNA obtained from formalin-fixed and paraffin-embedded tissue (FFPE), the acquisition of germline DNA, or the bioinformatic pitfalls, the analytical issues encountered and how to manage them. We describe the main constitutional and cancer databases, their characteristics and limitations, with an emphasis on variant interpretation in lymphoid malignancies. Finally, we discuss the challenges of predictions that one can make using in silico or in vitro modelling, pharmacogenomic screening, and the limits of those prediction tools. This description of the current status in genomic interpretation highlights the need for new large databases and international collaboration in the lymphoma field. [ABSTRACT FROM AUTHOR]

Evidence for beneficial effects of corticotropin releasing hormone (CRH) antagonists in abdominal and pelvic organs is emerging in preclinical studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement a compilation of preclinical studies using CRH receptor antagonists as a treatment for abdominal and pelvic disease was carried out. The Animal Research: Reporting of In Vivo Experiments (ARRIVE) essential 10 guidelines were used to determine quality of the included studies. A total of 40 studies from the last 15 years studying irritable bowel syndrome, inflammatory bowel disease, endometriosis, enteritis, stress impact on gastrointestinal processes and exogenous CRH administration effects were included. Blockage of the CRH receptor 1 was mainly associated with beneficial effects while that of CRH receptor 2 worsened studied effects. However, time of administration, route of administration and the animal model used, all had an impact on the beneficial outcomes. Frequency of drugs administered indicated that astressin-2B, astressin and antalarmin were among the most utilized antagonists. Of concern, studies included were predominantly carried out in male models only, representing a gender discrepancy in preclinical studies compared to the clinical scenario. The ARRIVE score average was 13 with ~60% of the studies failing to randomize or blind the experimental units. Despite the failure to date of the CRH antagonists in moving across the clinical trials pipeline, there is evidence for their beneficial effects beyond mood disorders. Future pre-clinical studies should be tailored towards effectively predicting the clinical scenario, including reduction of bias and randomization.

Como punto de partida, el texto ocupa dos palabras complementarias: oriundos y peregrinos, para transitar en dos tipos de migración que realizaron los españoles a México en el siglo XX, en dos obras diversas: Oriundos de Fernando Fernández y el facsímil de la revista España peregrina. El texto lleva a viajar y pensar un pasado compartido, casi desconocido en la actualidad, en el que la dualidad migración-escape permea la relación entre México y España durante el siglo XX con la efeméride de los 80 años del exilio español como señal cultural.

Antecedentes: La hipertensión arterial es considerada una enfermedad y al mismo tiempo un factor de riesgo cardiovascular, involucrada principalmente en la cardiopatía isquémica, la enfermedad cerebrovascular y la insuficiencia renal, causando una elevada mortalidad. Objetivo: Realizar seguimiento con monitoreo ambulatorio de la presión arterial de 24 horas en pacientes con hipertensión arterial pertenecientes a una población con alto riesgo cardiovascular. Método: Estudio descriptivo, observacional, retrospectivo, en el que se analizaron los monitoreos ambulatorios de presión de 24 horas de 1858 pacientes, en Cartagena, Colombia. Resultados: Se incluyeron 1173 registros. La mediana de edad fue de 66 años. El 66.8% (783) fueron mujeres y el 33.2% (390) fueron hombres. Las principales alteraciones ocurrieron durante la noche, cuando el 79.1% de los pacientes tuvieron cargas elevadas de presión sistólica, el 65.6% registraron promedios elevados de presión diastólica y el 83.7% tuvieron patrones circadianos anormales. Solo el 11% de los estudios fueron normales en todos los parámetros. Conclusiones: El monitoreo ambulatorio de la presión arterial de 24 horas demostró ser una herramienta útil para identificar a los pacientes hipertensos no controlados, detectando hipertensión nocturna y patrones circadianos anormales, los cuales son marcadores de riesgo para morbilidad y mortalidad cardiovascular.

Evidence suggests that psychosocial stress negatively impacts immunological health in HIV-positive individuals. However, few studies have explored this association in substance-using older adults living with HIV (OALWH). We evaluated the effect of depression, loneliness, substance use problems, and HIV stigma on primary markers of immune function in a sample of 120 OALWH with substance-related issues. HIV stigma correlated with the greatest number of factors, including depression, loneliness, and substance use problems. Older age and antiretroviral adherence were associated with viral suppression, which was in turn associated with higher percentage of CD4 count. Multivariate path analyses demonstrated that lower HIV stigma and viral suppression were the only factors independently associated with higher percentage of CD4 count, with a significant indirect effect of adherence on CD4 through viral suppression. HIV stigma emerged as the most salient factor associated with both psychosocial well-being and immune health in the current study, suggesting that it is a critical factor to consider in future interventions for the rapidly growing population of OALWH.

False lateralization of ictal onset by scalp electroencephalogram (EEG) is an infrequent entity that has been reported in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (HS). In these cases, a tendency for rapid seizures that spread through the frontal-limbic system and hippocampal commissural pathways to the contralateral hemisphere has been proposed. Cerebral cavernous malformations (CCMs), which constitute a collection of abnormally configured small blood vessels with irregular structures, is a well-defined epilepsy-associated pathology. Their primary association with seizures might be explained either as a result of physiological changes affecting the cerebral cortex immediately surrounding the CCM (an epileptogenic mechanism that is relevant for both, temporal and extratemporal lesions) or as a result of promoting epileptogenicity in remote but anatomo-functionally connected brain regions, a mechanism that is particularly relevant for temporal lobe lesions. To date, there have been only two publications on falsely lateralizing ictal onsets by EEG in temporal cavernoma, but not in other regions. Here, we report a rare case of apparent false lateralization of ictal onset by scalp EEG in a patient with a left medial frontal gyrus cavernoma (supplementary motor area), and discuss some relevant pathophysiological mechanisms of false lateralization.

Predominantly Spanish-speaking Latino men who have sex with men (MSM) and their same-sex partners continue to be at high risk for HIV and STIs. Behavioral research has identified how relationship dynamics for male couples are associated with sexual risk behavior. Connect ‘n Unite (CNU), an evidence-based HIV/STI prevention intervention originally created for Black MSM and their same-sex partners, was adapted for predominantly Spanish-speaking Latino MSM and their same-sex partners on the assumption that its key elements would be translatable while its efficacy would be retained. A systematic adaptation process utilizing qualitative methods was used, including intervention adaptation sessions with 20 predominantly Spanish-speaking Latino gay couples and 10 health service providers. The process included five steps: (1) engaging community stakeholders, (2) capturing the lived experiences of Latino gay couples, (3) identifying intervention priorities, (4) integrating the original intervention’s social cognitive theory into a relationship-oriented, ecological framework for Latino gay couples, and (5) adapting intervention activities and materials. The adapted intervention, which we called Latinos en Pareja or Latinos in a Relationship, incorporates elements that effective HIV prevention interventions share, including: a solid theoretical foundation; emphasis on increasing risk reduction norms, sexual communication skills and social support for protection; and guidance on how to utilize available, culturally and linguistically appropriate services. The systematic adaptation approach used for a couples-based HIV prevention intervention also can be employed by other researchers and community stakeholders to adapt evidence-based interventions that promote wellness, linkage to care, and disease prevention for populations not originally targeted.