CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) appearing in non-coding genomic regions in CVDs. The SNPs may alter gene expression by modifying transcription factor (TF) binding sites and lead to functional consequences in cardiovascular traits or diseases. To understand the underlying molecular mechanisms, it is crucial to identify which variations are involved and how they affect TF binding. METHODS: The SNEEP (SNP exploration and analysis using epigenomics data) pipeline was used to identify regulatory SNPs, which alter the binding behavior of TFs and link GWAS SNPs to their potential target genes for six CVDs. The human-induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs), monoculture cardiac organoids (MCOs) and self-organized cardiac organoids (SCOs) were used in the study. Gene expression, cardiomyocyte size and cardiac contractility were assessed. RESULTS: By using our integrative computational pipeline, we identified 1905 regulatory SNPs in CVD GWAS data. These were associated with hundreds of genes, half of them non-coding RNAs (ncRNAs), suggesting novel CVD genes. We experimentally tested 40 CVD-associated non-coding RNAs, among them RP11-98F14.11, RPL23AP92, IGBP1P1, and CTD-2383I20.1, which were upregulated in hiPSC-CMs, MCOs and SCOs under hypoxic conditions. Further experiments showed that IGBP1P1 depletion rescued expression of hypertrophic marker genes, reduced hypoxia-induced cardiomyocyte size and improved hypoxia-reduced cardiac contractility in hiPSC-CMs and MCOs. CONCLUSIONS: IGBP1P1 is a novel ncRNA with key regulatory functions in modulating cardiomyocyte size and cardiac function in our disease models. Our data suggest ncRNA IGBP1P1 as a potential therapeutic target to improve cardiac function in CVDs.

The endothelial-enriched lncRNA LINC00607 mediates angiogenic function.

Long non-coding RNAs (lncRNAs) can act as regulatory RNAs which, by altering the expression of target genes, impact on the cellular phenotype and cardiovascular disease development. Endothelial lncRNAs and their vascular functions are largely undefined. Deep RNA-Seq and FANTOM5 CAGE analysis revealed the lncRNA LINC00607 to be highly enriched in human endothelial cells. LINC00607 was induced in response to hypoxia, arteriosclerosis regression in non-human primates, post-atherosclerotic cultured endothelial cells from patients and also in response to propranolol used to induce regression of human arteriovenous malformations. siRNA knockdown or CRISPR/Cas9 knockout of LINC00607 attenuated VEGF-A-induced angiogenic sprouting. LINC00607 knockout in endothelial cells also integrated less into newly formed vascular networks in an in vivo assay in SCID mice. Overexpression of LINC00607 in CRISPR knockout cells restored normal endothelial function. RNA- and ATAC-Seq after LINC00607 knockout revealed changes in the transcription of endothelial gene sets linked to the endothelial phenotype and in chromatin accessibility around ERG-binding sites. Mechanistically, LINC00607 interacted with the SWI/SNF chromatin remodeling protein BRG1. CRISPR/Cas9-mediated knockout of BRG1 in HUVEC followed by CUT&RUN revealed that BRG1 is required to secure a stable chromatin state, mainly on ERG-binding sites. In conclusion, LINC00607 is an endothelial-enriched lncRNA that maintains ERG target gene transcription by interacting with the chromatin remodeler BRG1 to ultimately mediate angiogenesis.

Microaggressions and general health among Black and Asian Americans: The moderating role of cognitive reappraisal.

OBJECTIVES: The present study has two aims: (a) to examine the frequency of various microaggression types experienced by Asian and Black Americans and (b) to examine cognitive reappraisal as a moderator of the relationship between microaggression types and general health. METHOD: Two hundred seventy-one Black and Asian American participants recruited from Amazon Mechanical Turk completed a cross-sectional online survey. The Racial and Ethnic Microaggressions Scale was used to assess the frequency with which participants experienced six different types of microaggressions. Cognitive reappraisal was assessed by the cognitive reappraisal subscale of the Emotion Regulation Questionnaire. General health was assessed by the RAND 36-item Short Form Health Survey. RESULTS: We found that Black Americans experienced higher levels of Inferiority, Criminality, Workplace/School Microaggressions and Microinvalidations than Asian Americans. In contrast, Asian Americans experienced greater Exoticization and Environmental Microaggressions. There were ethnic/racial group differences in whether cognitive reappraisal moderated the relationships between microaggression types and general health. CONCLUSIONS: Our findings highlight important differences in the types of microaggressions experienced across ethnic/racial groups, and the role of cognitive reappraisal in influencing the detrimental effects of microaggressions on general health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The relationship between team dynamics with healthcare coordination and clinical work satisfaction among Commune Health Workers: A Bayesian model averaging study.

OBJECTIVE: To determine the relationship between team dynamics with healthcare coordination and clinical job satisfaction of the community health workers (CHWs). METHODS: A cross-sectional study was conducted among 133 health workers (including doctors, nurses, or midwives) at 21 Commune Health Cent in Quoc Oai District, Vietnam, from July 2015 to May 2017. A self-administered questionnaire consisting of 5-Likert items regarding team dynamics and healthcare coordination clinical work satisfaction was utilised. Descriptive statistics and correlation matrix were applied for seven factors of team dynamic, clinical work satisfaction, and patient care coordination queried by primary care providers. Bayesian model averaging (BMA) was used to identify the predictors of the level of team dynamics and healthcare coordination. RESULTS: The mean score of overall team dynamics among the study participants was 4.08. Clinical work satisfaction and patient care coordination scores among resident physicians were higher than those of attending clinicians; however, the differences were not statistically significant. The results of BMA analysis indicated that team dynamics significantly associated with clinical work satisfaction, and it explains 9% of the total variance in clinical work satisfaction. Team dynamics level was also positively associated with patient care coordination. Patient care coordination was not a significant mediator between team dynamics and clinical work satisfaction. CONCLUSION: Team dynamics is a potential contributor to improving patient care coordination and clinical job satisfaction of CHWs. As no significant correlation between patient care coordination and clinical job satisfaction was observed, to improve team performance, providing conditions that facilitate team building and teamwork should be conducted for CHWs in CHCs.

"Are you a homophobic racist?": Applying lay theory of generalized prejudice to the discrimination-distress link.

OBJECTIVES: The present research aimed to examine, among lesbian, gay, bisexual, transgender, and queer (LGBTQ +) people of color, whether experiencing discrimination rooted in one stigmatized identity (e.g., racial/ethnic minority identity) would be positively associated with expecting discrimination rooted in both the same (e.g., racial/ethnic minority identity) and different (e.g., sexual/gender minority identity) stigmatized identities, and whether such expectations would be positively associated with psychological distress. Endorsement of a lay theory of generalized prejudice (LTGP) was expected to moderate the relationship between experience of discrimination in one identity dimension and expectation of it in another. METHOD: We recruited 246 LGBTQ + people of color (48.4% cisgender women, 24.8% transgender/gender-variant; Mage = 23.84, SD = 4.73) to complete an online survey. RESULTS: As hypothesized, more frequent heterosexism/cisgenderism was associated with greater racial/ethnic discrimination, which was associated with greater psychological distress. Likewise, experience of racism was positively associated with expectation of heterosexism/cisgenderism; however, expecting heterosexism/cisgenderism was not associated with psychological distress. Contrary to the hypothesis, only among people low (but not high) in LTGP was experience of racism or heterosexism/cisgenderism associated with the expectation of discrimination rooted in the other identity. CONCLUSIONS: People high in LTGP may habitually expect discrimination regardless of their discriminatory experiences. By demonstrating the different pathways via which discrimination is linked with distress, this study highlights the benefit of intersectional research and underscores the need for systemic change to reduce discrimination. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Dissection of heterocellular cross-talk in vascularized cardiac tissue mimetics.

Cellular specialization and interaction with other cell types in cardiac tissue is essential for the coordinated function of cell populations in the heart. The complex interplay between cardiomyocytes, endothelial cells and fibroblasts is necessary for adaptation but can also lead to pathophysiological remodeling. To understand this complex interplay, we developed 3D vascularized cardiac tissue mimetics (CTM) to study heterocellular cross-talk in hypertrophic, hypoxic and fibrogenic environments. This 3D platform responds to physiologic and pathologic stressors and mimics the microenvironment of diseased tissue. In combination with endothelial cell fluorescence reporters, these cardiac tissue mimetics can be used to precisely visualize and quantify cellular and functional responses upon stress stimulation. Utilizing this platform, we demonstrate that stimulation of α/ß-adrenergic receptors with phenylephrine (PE) promotes cardiomyocyte hypertrophy, metabolic maturation and vascularization of CTMs. Increased vascularization was promoted by conditioned medium of PE-stimulated cardiomyocytes and blocked by inhibiting VEGF or upon ß-adrenergic receptor antagonist treatment, demonstrating cardiomyocyte-endothelial cross-talk. Pathophysiological stressors such as severe hypoxia reduced angiogenic sprouting and increased cell death, while TGF ß2 stimulation increased collagen deposition concomitant to endothelial-to-mesenchymal transition. In sum, we have developed a cardiac 3D culture system that reflects native cardiac tissue function, metabolism and morphology - and for the first time enables the tracking and analysis of cardiac vascularization dynamics in physiology and pathology.

Inhibition of the Hypoxia-Inducible Factor 1α-Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease.

BACKGROUND: Enhancers are genomic regulatory elements conferring spatiotemporal and signal-dependent control of gene expression. Recent evidence suggests that enhancers can generate noncoding enhancer RNAs, but their (patho)biological functions remain largely elusive. METHODS: We performed chromatin immunoprecipitation-coupled sequencing of histone marks combined with RNA sequencing of left ventricular biopsies from experimental and genetic mouse models of human cardiac hypertrophy to identify transcripts revealing enhancer localization, conservation with the human genome, and hypoxia-inducible factor 1α dependence. The most promising candidate, hypoxia-inducible enhancer RNA ( HERNA)1, was further examined by investigating its capacity to modulate neighboring coding gene expression by binding to their gene promoters by using chromatin isolation by RNA purification and λN-BoxB tethering-based reporter assays. The role of HERNA1 and its neighboring genes for pathological stress-induced growth and contractile dysfunction, and the therapeutic potential of HERNA1 inhibition was studied in gapmer-mediated loss-of-function studies in vitro using human induced pluripotent stem cell-derived cardiomyocytes and various in vivo models of human pathological cardiac hypertrophy. RESULTS: HERNA1 is robustly induced on pathological stress. Production of HERNA1 is initiated by direct hypoxia-inducible factor 1α binding to a hypoxia-response element in the histoneH3-lysine27acetylation marks-enriched promoter of the enhancer and confers hypoxia responsiveness to nearby genes including synaptotagmin XVII, a member of the family of membrane-trafficking and Ca2+-sensing proteins and SMG1, encoding a phosphatidylinositol 3-kinase-related kinase. Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. In vitro and in vivo inactivation of SMG1 and SYT17 revealed overlapping and distinct roles in modulating cardiac hypertrophy. Finally, in vivo administration of antisense oligonucleotides targeting HERNA1 protected mice from stress-induced pathological hypertrophy. The inhibition of HERNA1 postdisease development reversed left ventricular growth and dysfunction, resulting in increased overall survival. CONCLUSIONS: HERNA1 is a novel heart-specific noncoding RNA with key regulatory functions in modulating the growth, metabolic, and contractile gene program in disease, and reveals a molecular target amenable to therapeutic exploitation.

COVID-19 in Africa: care and protection for frontline healthcare workers.

Medical staff caring for COVID-19 patients face mental stress, physical exhaustion, separation from families, stigma, and the pain of losing patients and colleagues. Many of them have acquired SARS-CoV-2 and some have died. In Africa, where the pandemic is escalating, there are major gaps in response capacity, especially in human resources and protective equipment. We examine these challenges and propose interventions to protect healthcare workers on the continent, drawing on articles identified on Medline (Pubmed) in a search on 24 March 2020. Global jostling means that supplies of personal protective equipment are limited in Africa. Even low-cost interventions such as facemasks for patients with a cough and water supplies for handwashing may be challenging, as is 'physical distancing' in overcrowded primary health care clinics. Without adequate protection, COVID-19 mortality may be high among healthcare workers and their family in Africa given limited critical care beds and difficulties in transporting ill healthcare workers from rural to urban care centres. Much can be done to protect healthcare workers, however. The continent has learnt invaluable lessons from Ebola and HIV control. HIV counselors and community healthcare workers are key resources, and could promote social distancing and related interventions, dispel myths, support healthcare workers, perform symptom screening and trace contacts. Staff motivation and retention may be enhanced through carefully managed risk 'allowances' or compensation. International support with personnel and protective equipment, especially from China, could turn the pandemic's trajectory in Africa around. Telemedicine holds promise as it rationalises human resources and reduces patient contact and thus infection risks. Importantly, healthcare workers, using their authoritative voice, can promote effective COVID-19 policies and prioritization of their safety. Prioritizing healthcare workers for SARS-CoV-2 testing, hospital beds and targeted research, as well as ensuring that public figures and the population acknowledge the commitment of healthcare workers may help to maintain morale. Clearly there are multiple ways that international support and national commitment could help safeguard healthcare workers in Africa, essential for limiting the pandemic's potentially devastating heath, socio-economic and security impacts on the continent.

Mapping of research on maternal health interventions in low- and middle-income countries: a review of 2292 publications between 2000 and 2012.

BACKGROUND: Progress in achieving maternal health goals and the rates of reductions in deaths from individual conditions have varied over time and across countries. Assessing whether research priorities in maternal health align with the main causes of mortality, and those factors responsible for inequitable health outcomes, such as health system performance, may help direct future research. The study thus investigated whether the research done in low- and middle-income countries (LMICs) matched the principal causes of maternal deaths in these settings. METHODS: Systematic mapping was done of maternal health interventional research in LMICs from 2000 to 2012. Articles were included on health systems strengthening, health promotion; and on five tracer conditions (haemorrhage, hypertension, malaria, HIV and other sexually transmitted infections (STIs)). Following review of 35,078 titles and abstracts in duplicate, data were extracted from 2292 full-text publications. RESULTS: Over time, the number of publications rose several-fold, especially in 2004-2007, and the range of methods used broadened considerably. More than half the studies were done in sub-Saharan Africa (55.4 %), mostly addressing HIV and malaria. This region had low numbers of publications per hypertension and haemorrhage deaths, though South Asia had even fewer. The proportion of studies set in East Asia Pacific dropped steadily over the period, and in Latin America from 2008 to 2012. By 2008-2012, 39.1 % of articles included health systems components and 30.2 % health promotion. Only 5.4 % of studies assessed maternal STI interventions, diminishing with time. More than a third of haemorrhage research included health systems or health promotion components, double that of HIV research. CONCLUSION: Several mismatches were noted between research publications, and the burden and causes of maternal deaths. This is especially true for South Asia; haemorrhage and hypertension in sub-Saharan Africa; and for STIs worldwide. The large rise in research outputs and range of methods employed indicates a major expansion in the number of researchers and their skills. This bodes well for maternal health if variations in research priorities across settings and topics are corrected.

Black Americans suppress emotions when prejudice is believed to stem from shared ignorance.

Past research examining lay theories of the origins of prejudice has focused on white Americans and has not considered how Black Americans' lay theories of prejudice may impact emotion regulation following discrimination. Across three samples of Black Americans (N = 419), the present research examined relationships between endorsement of two lay theories of prejudice origins (1, beliefs that prejudice stems from shared social ignorance and 2, that prejudice stems from malice). Stronger beliefs that prejudice stems from shared ignorance were associated with greater expression suppression following experiences of racial discrimination (studies 1b and 2), which was, in turn, associated with psychological distress (study 2). By centering the beliefs and experiences of Black Americans in response to discrimination events, the present research has implications for understanding how emotion regulation following racial discrimination is impacted by marginalized groups' conceptualizations of prejudice. Future research should investigate how these factors impact health disparities.

Lymph node harvesting after laparoscopic complete mesocolic excision colectomy in colon cancer with practical application of glacial acid, absolute ethanol, water, and formaldehyde solution: A prospective cohort study.

Objectives: Quality of surgery has recently become an essential topic in the prognosis of colon cancer. Complete mesocolic excision for colon cancer has recently gained popularity with high-quality surgery. Patient specimens after complete mesocolic excision with central vessel ligation procedures have an integrity of the mesocolon and the yield of three fields of lymph node harvest. We apply the glacial acid, absolute ethanol, water, and formaldehyde solution to each specimen based on the Japanese classification of lymph node groups and station numbers. We aim to identify the distribution and status of lymph node metastasis according to each tumor site and some pathological characteristics related to this disease. Methods: A prospective cohort study was performed on 45 laparoscopic complete mesocolic excision surgery patients. Results: 2791 lymph nodes were harvested after complete mesocolic excision surgery. The average number was 62.0 ± 22.3 nodes. The mean tumor size (in the largest dimension) was 4.2 ± 1.8 cm. The average length of the resected bowel segments was 29.1 ± 7.7 cm. There are 63 (2.3%) node metastases in 2791 lymph nodes, in which 17/45 (37.8%) patients had pN(+). The minimum positive node size was 1 mm. The positive pericolic lymph nodes (station 1) accounted for the highest rate, with 53 nodes (1.9%). The number of lymph nodes in young age ⩽60 is more significant than in older. The results were similar, with a more significant node retrieval in the group with a tumor size >4.5 cm and specimen length >25 cm. The number of lymph nodes in lower tumor invasive (pT1,3) was smaller than pT4. Our research shows that the cecum, ascending, and descending colon had greater nodes than others, with a mean number of 78.6, 74.2, and 71.3, respectively. Conclusions: The metastasis and harvested lymph nodes accounted for the highest rate of colon cancer in station 1 and the lowest rate in station 3. The number of retrieved lymph nodes was significantly associated with tumor location, size, specimen length, and patient age.

Splenic lymphangioma in adult patient treated with laparoscopic splenectomy: A rare case report.

Splenic lymphangioma is a benign cystic tumor that develops as a result of lymphatic vessels' congenital abnormalities. It is a rare condition that mostly occurs in children and young adults. Due to the lack of typical symptoms and signs, splenic lymphangioma is difficult to diagnose and often incidentally revealed during radiological examinations. We report a case of a 55-year-old Asian female, who presented with left upper quadrant abdominal pain in the past 3 days. She had mild upper abdominal tenderness, with no other specific findings. Abdominal contrast material-enhanced computed tomography revealed three hypodense lesions arising from a normal-sized spleen. The histologic findings after laparoscopic splenectomy demonstrated a 3-cm-diameter yellowish-white tumor made up of multiple cystic structures. Primary benign splenic tumors are exceedingly rare, especially in adults over 20. While small lesions are mostly asymptomatic, bigger lesions can cause organ compression or even rupture. Therefore, even in adults with pain in the left upper quadrant abdomen or enlarged spleen, splenic lymphangioma should be taken into account in the differential diagnosis. The case serves as an example of a rare congenital splenic tumor. Treatment of this benign splenic abnormality with laparoscopic splenectomy is a good, safe approach.

The effect of the Xpert HIV-1 Qual test on early infant diagnosis of HIV in Myanmar and Papua New Guinea: a pragmatic, cluster-randomised, stepped-wedge, open-label trial.

BACKGROUND: Despite proven benefits for child health, coverage of early infant diagnosis of HIV remains suboptimal in many settings. We aimed to assess the effect of a point-of-care early infant diagnosis test on time-to-results communication for infants vertically exposed to HIV. METHODS: This pragmatic, cluster-randomised, stepped-wedge, open-label trial assessed the effect of the Xpert HIV-1 Qual early infant diagnosis test (Cepheid) on time-to-results communication, compared with standard care laboratory-based testing of dried blood spots using PCR. Hospitals were the unit of randomisation for one-way crossover from control to intervention phase. Each site had between 1 month and 10 months of control phase before transitioning to the intervention, with a total of 33 hospital-months in the control phase and 45 hospital-months in the intervention phase. We enrolled infants vertically exposed to HIV at six public hospitals: four in Myanmar and two in Papua New Guinea. Infants had to have mothers with confirmed HIV infection, be younger than 28 days, and required HIV testing to be eligible for enrolment. Health-care facilities providing prevention of vertical transmission services were eligible for participation. The primary outcome was communication of early infant diagnosis results to the infant's caregiver by 3 months of age, assessed by intention to treat. This completed trial was registered with the Australian and New Zealand Clinical Trials Registry, 12616000734460. FINDINGS: In Myanmar, recruitment took place between Oct 1, 2016, and June 30, 2018; in Papua New Guinea, recruitment was between Dec 1, 2016, and Aug 31, 2018. A total of 393 caregiver-infant pairs were enrolled in the study across both countries. Independent of study time, the Xpert test reduced time to early infant diagnosis results communication by 60%, compared with the standard of care (adjusted time ratio 0·40, 95% CI 0·29-0·53, p<0·0001). In the control phase, two (2%) of 102 study participants received an early infant diagnosis test result by 3 months of age compared with 214 (74%) of 291 in the intervention phase. No safety and adverse events were reported related to the diagnostic testing intervention. INTERPRETATION: This study reinforces the importance of scaling up point-of-care early infant diagnosis testing in resource-constrained and low HIV-prevalence settings, typical of the UNICEF East Asia and Pacific region. FUNDING: National Health and Medical Research Council of Australia.

Aging impairs the neurovascular interface in the heart.

Aging is a major risk factor for impaired cardiovascular health. Because the aging myocardium is characterized by microcirculatory dysfunction, and because nerves align with vessels, we assessed the impact of aging on the cardiac neurovascular interface. We report that aging reduces nerve density in the ventricle and dysregulates vascular-derived neuroregulatory genes. Aging down-regulates microRNA 145 (miR-145) and derepresses the neurorepulsive factor semaphorin-3A. miR-145 deletion, which increased Sema3a expression or endothelial Sema3a overexpression, reduced axon density, mimicking the aged-heart phenotype. Removal of senescent cells, which accumulated with chronological age in parallel to the decline in nerve density, rescued age-induced denervation, reversed Sema3a expression, preserved heart rate patterns, and reduced electrical instability. These data suggest that senescence-mediated regulation of nerve density contributes to age-associated cardiac dysfunction.

Left behind on the path to 90-90-90: understanding and responding to HIV among displaced people.

INTRODUCTION: In 2021, the number of people affected by displacement worldwide reached the highest on record, with an estimated 30.5 million refugees and 4.6 million asylum seekers seeking safety across international borders and further 53.2 million people displaced within their countries of origin. Most forcibly displaced persons come from or relocate to lower- and middle-income countries (LMICs) and many of those countries have large HIV epidemics. In this commentary, we describe some of the challenges at the intersection of HIV and displacement vulnerabilities that cannot be easily addressed in resource-limited environments. DISCUSSION: HIV transmission and prevention and treatment efforts in the context of displacement are affected by myriad behavioural, social and structural factors across different stages of the displacement journey. For example, structural barriers faced by people experiencing displacement in relation to HIV prevention and care include funding constraints and legal framework deficiencies. Such barriers prevent all forced migrants, and particularly those whose sexual identities or practices are stigmatized against, access to prevention and care equal to local residents. Xenophobia, racism and other social factors, as well as individual risky behaviours facilitated by experiences of forced migration, also affect the progress towards 90-90-90 targets in displaced populations. Current evidence suggests increased HIV vulnerability in the period before displacement due to the effect of displacement drivers on medical supplies and infrastructure. During and after displacement, substantial barriers to HIV testing exist, though following resettlement in stable displacement context, HIV incidence and viral suppression are reported to be similar to those of local populations. CONCLUSIONS: Experiences of often-marginalized displaced populations are diverse and depend on the context of displacement, countries of origin and resettlement, and the nature of the crises that forced these populations to move. To address current gaps in responses to HIV in displacement contexts, research in LMIC, particularly in less stable resettlement settings, needs to be scaled up. Furthermore, displaced populations need to be specifically addressed in national AIDS strategies and HIV surveillance systems. Finally, innovative technologies, such as point-of-care viral load and CD4 testing, need to be developed and introduced in settings facing displacement.

Heterotopic Pancreas in the Duodenum Diagnosed after Laparoscopic Biopsy.

Heterotopic pancreas is defined as the presence of ectopic pancreatic tissue outside boundaries of the pancreas without vascular and duct system connection with the pancreas. Ectopic locations are mostly found anywhere in the gastrointestinal tract such as the stomach (24-38%), the duodenum (9-36%), and the jejunum (0.5-27%). Clinical manifestations are not specific, vague, and misdiagnosed another digestive disease. Most cases are incidentally detected by histological examination of specimens resected for different pathologies during endoscopy, surgery, or even autopsy. We report a case of a 31-year-old man who admitted to the hospital with the reason of epigastric pain for 3 days. Clinical examination showed mild epigastric tenderness. The past medical history of patient was unremarkable. A submucosal lesion was observed in the first part of the duodenum during endoscopy. Computed tomography and endoscopic ultrasonography findings were suspected to be heterotopic pancreatic tissue. After laparoscopic surgery for biopsy, it was histologically confirmed duodenal ectopic pancreas. It is difficult to differentiate gastrointestinal pancreatic heterotopia from gastrointestinal stromal tumors, leiomyoma, or lymphomas by using endoscopy because ectopic tissue is mostly located in the submucosal layer. In addition, rare cases of ectopic pancreatic tissue transform malignancy. Surgical treatment should be considered to take adequate tissue samples for biopsy or resect the lesions in symptomatic patients. Duodenal pancreatic heterotopia is an uncommon congenital malformation and most patients are asymptomatic. Histological examination is essential to exclude malignant lesions and to have an appropriate treatment.

Long non-coding RNA PCAT19 safeguards DNA in quiescent endothelial cells by preventing uncontrolled phosphorylation of RPA2.

In healthy vessels, endothelial cells maintain a stable, differentiated, and growth-arrested phenotype for years. Upon injury, a rapid phenotypic switch facilitates proliferation to restore tissue perfusion. Here we report the identification of the endothelial cell-enriched long non-coding RNA (lncRNA) PCAT19, which contributes to the proliferative switch and acts as a safeguard for the endothelial genome. PCAT19 is enriched in confluent, quiescent endothelial cells and binds to the full replication protein A (RPA) complex in a DNA damage- and cell-cycle-related manner. Our results suggest that PCAT19 limits the phosphorylation of RPA2, primarily on the serine 33 (S33) residue, and thereby facilitates an appropriate DNA damage response while slowing cell cycle progression. Reduction in PCAT19 levels in response to either loss of cell contacts or knockdown promotes endothelial proliferation and angiogenesis. Collectively, PCAT19 acts as a dynamic guardian of the endothelial genome and facilitates rapid switching from quiescence to proliferation.

Processing SPARQL queries with regular expressions in RDF databases.

BACKGROUND: As the Resource Description Framework (RDF) data model is widely used for modeling and sharing a lot of online bioinformatics resources such as Uniprot (dev.isb-sib.ch/projects/uniprot-rdf) or Bio2RDF (bio2rdf.org), SPARQL - a W3C recommendation query for RDF databases - has become an important query language for querying the bioinformatics knowledge bases. Moreover, due to the diversity of users' requests for extracting information from the RDF data as well as the lack of users' knowledge about the exact value of each fact in the RDF databases, it is desirable to use the SPARQL query with regular expression patterns for querying the RDF data. To the best of our knowledge, there is currently no work that efficiently supports regular expression processing in SPARQL over RDF databases. Most of the existing techniques for processing regular expressions are designed for querying a text corpus, or only for supporting the matching over the paths in an RDF graph. RESULTS: In this paper, we propose a novel framework for supporting regular expression processing in SPARQL query. Our contributions can be summarized as follows. 1) We propose an efficient framework for processing SPARQL queries with regular expression patterns in RDF databases. 2) We propose a cost model in order to adapt the proposed framework in the existing query optimizers. 3) We build a prototype for the proposed framework in C++ and conduct extensive experiments demonstrating the efficiency and effectiveness of our technique. CONCLUSIONS: Experiments with a full-blown RDF engine show that our framework outperforms the existing ones by up to two orders of magnitude in processing SPARQL queries with regular expression patterns.

Ileal mucosa-associated lymphoid tissue lymphoma diagnosed after emergency surgery: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, also called MALT lymphoma, is one of the entities of marginal zone lymphomas. These lymphomas are originated from indolent B-cell lymphomas and involve many organs such as the gastrointestinal tract, salivary gland, skin, lung, thyroid or breast. Ileal MALT lymphoma is relatively rare and clinical symptoms are usually atypical. CASE PRESENTATION: We report a case of a 99-year-old man who admitted to the emergency department with increasing and colicky periumbilical pain, vomiting and constipation. Non-contrast-enhanced computed tomography suggested small bowel obstruction due to phytobezoar. Intraoperatively, surgeon discovered the tumor at the site of phytobezoar. Histologically, there was a diffuse infiltration comprised of small to medium sized lymphocytes with monocytoid features. Immunohistochemical result confirmed CD20 positive B-lymphocytes and the Ki-67 proliferation index was 10%. Ileal mucosa-associated lymphoid tissue lymphoma was diagnosed based on histological findings and immunohistochemistry. DISCUSSION: MALToma of the gastrointestinal tract is related to chronic antigenic, inflammatory bowel disease and malabsorption syndromes. However, the etiology of ileal MALToma is unclear. Moreover, symptom of ileal MALToma is really not typical and overleaped in the context of small intestinal obstruction. It should be differentiated small intestinal MALToma from immunoproliferative small intestinal disease and an alpha heavy chain disease. CONCLUSION: Ileal MALT lymphoma remains little known in many previous studies. It is really difficult to preoperatively diagnose. The combination of clinical presentation, postoperative histology and immunohistochemistry contribute to diagnosis and carry out appropriate management.

A rare congenital anomaly of the duodenal shape incidentally found at duodenopancreatectomy: A case report and literature review.

INTRODUCTION: An anomaly of the duodenal shape is one of the rare congenital anomalies and remains poorly known in many previous studies and the literature. The duodenum is formed by developing the terminal foregut and proximal midgut through four stages in the embryonic period. According to the anatomy, the duodenum is typically described as C-shaped, U-shaped, or even horseshoe-shaped. PRESENTATION OF CASE: The patient was hospitalized for abdominal pain and jaundice and diagnosed with ampullary carcinoma. During surgery, we incidentally discovered that the duodenum was not a C-shape. The first part of the duodenum and proximal half of the second part descended the head of the pancreas. However, the distal half of the second part bent to the right and ascended upwards to the upper-right margin of the pancreatic head. After that, the third part ran slantingly downward to the left and posterior of the pancreas and portal vein. DISCUSSION: During the fifth week, the ventral pancreatic bud moves around the duodenum's posterior side and unites the dorsal pancreatic bud at the sixth week. The place of the distal half of D2 migrated abnormally after ventral pancreatic bud rotation finished. The rapid and premature elongation of the proximal midgut, the influence of a very fast enlarged liver, or the early return of the umbilical loop combine with insufficiently developed abdominal space. These reasons may have led to the abnormal folding of the D2 position. CONCLUSION: Knowledge about this anomaly helps clinicians know the duodenal-anatomical abnormalities.