De Winter's ECG: Not your usual STEMI.

We report a 39-year-old male who presented with severe chest pain and diaphoresis who suffered from pulseless polymorphic ventricular tachycardia en route to the hospital. His initial electrocardiogram showed De Winter's Pattern (dWP). Coronary angiography revealed 100% thrombotic ostial occlusion of the left anterior descending artery. In young males presenting with chest pain and diaphoresis, dWP should be part of a clinician's differential diagnosis when analyzing the initial electrocardiogram. The medical community needs increased awareness to prevent delay of revascularization because dWP is an ST-segment elevation myocardial infarction (STEMI) equivalent and does not present like a typical STEMI on electrocardiogram.

Cleavage and Polyadenylation-Specific Factor 4 (CPSF4) Expression Is Associated with Enhanced Prostate Cancer Cell Migration and Cell Cycle Dysregulation, In Vitro.

Potential oncogene cleavage and polyadenylation specific factor 4 (CPSF4) has been linked to several cancer types. However, little research has been conducted on its function in prostate cancer (PCa). In benign, incidental, advanced, and castrate resistant PCa (CRPCa) patient samples, protein expression of CPSF4 was examined on tissue microarray (TMAs) of 353 PCa patients using immunohistochemistry. Using the 'The Cancer Genome Atlas' Prostate Adenocarcinoma (TCGA PRAD) database, significant correlations were found between high CPSF4 expression and high-risk genomic abnormalities such as ERG-fusion, ETV1-fusion, and SPOP mutations. Gene Set Enrichment Analysis (GSEA) of CPSF4 revealed evidence for the increase in biological processes such as cellular proliferation and metastasis. We further examined the function of CPSF4 in vitro and confirmed CPSF4 clinical outcomes and its underlying mechanism. Our findings showed a substantial correlation between Gleason groups and CPSF4 protein expression. In vitro, CPSF4 knockdown reduced cell invasion and migration while also causing G1 and G2 arrest in PC3 cell lines. Our findings demonstrate that CPSF4 may be used as a possible biomarker in PCa and support its oncogenic function in cellular proliferation and metastasis.

Glycyl-tRNA Synthetase (GARS) Expression Is Associated with Prostate Cancer Progression and Its Inhibition Decreases Migration, and Invasion In Vitro.

Glycyl-tRNA synthetase (GARS) is a potential oncogene associated with poor overall survival in various cancers. However, its role in prostate cancer (PCa) has not been investigated. Protein expression of GARS was investigated in benign, incidental, advanced, and castrate-resistant PCa (CRPC) patient samples. We also investigated the role of GARS in vitro and validated GARS clinical outcomes and its underlying mechanism, utilizing The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) database. Our data revealed a significant association between GARS protein expression and Gleason groups. Knockdown of GARS in PC3 cell lines attenuated cell migration and invasion and resulted in early apoptosis signs and cellular arrest in S phase. Bioinformatically, higher GARS expression was observed in TCGA PRAD cohort, and there was significant association with higher Gleason groups, pathological stage, and lymph nodes metastasis. High GARS expression was also significantly correlated with high-risk genomic aberrations such as PTEN, TP53, FXA1, IDH1, SPOP mutations, and ERG, ETV1, and ETV4 gene fusions. Gene Set Enrichment Analysis (GSEA) of GARS through the TCGA PRAD database provided evidence for upregulation of biological processes such as cellular proliferation. Our findings support the oncogenic role of GARS involved in cellular proliferation and poor clinical outcome and provide further evidence for its use as a potential biomarker in PCa.

Downregulation of BUD31 Promotes Prostate Cancer Cell Proliferation and Migration via Activation of p-AKT and Vimentin In Vitro.

Among men, prostate cancer (PCa) is the second most frequently diagnosed cancer subtype and has demonstrated a high degree of prevalence globally. BUD31, also known as Functional Spliceosome-Associated Protein 17, is a protein that works at the level of the spliceosome; it is functionally implicated in pre-mRNA splicing as well as processing, while also acting as a transcriptional regulator of androgen receptor (AR) target genes. Clinically, the expression of BUD31 and its functions in the development and progression of PCa is yet to be elucidated. The BUD31 expression was assessed using IHC in a tissue microarray (TMA) constructed from a cohort of 284 patient samples. In addition, we analyzed the prostate adenocarcinoma (TCGAPRAD-) database. Finally, we used PCa cell lines to knockdown BUD31 to study the underlying mechanisms in vitro.Assesment of BUD31 protein expression revealed lower expression in incidental and advanced PCa, and significantly lower expression was observed in patients diagnosed with castrate-resistant prostate cancer. Additionally, bioinformatic analysis and GSEA revealed that BUD31 increased processes related to cancer cell migration and proliferation. In vitro results made evident that BUD31 knockdown in PC3 cells led to an increase in the G2 cell population, indicating a more active and proliferative state. Additionally, an investigation of metastatic processes revealed that knockdown of BUD31 significantly enhanced the ability of PC3 cells to migrate and invade. Our in vitro results showed BUD31 knockdown promotes cell proliferation and migration of prostate cancer cells via activation of p-AKT and vimentin. These results support the clinical data, where low expression of BUD31 was correlated to more advanced stages of PCa.

The Expression of Proto-Oncogene ETS-Related Gene (ERG) Plays a Central Role in the Oncogenic Mechanism Involved in the Development and Progression of Prostate Cancer.

The ETS-related gene (ERG) is proto-oncogene that is classified as a member of the ETS transcription factor family, which has been found to be consistently overexpressed in about half of the patients with clinically significant prostate cancer (PCa). The overexpression of ERG can mostly be attributed to the fusion of the ERG and transmembrane serine protease 2 (TMPRSS2) genes, and this fusion is estimated to represent about 85% of all gene fusions observed in prostate cancer. Clinically, individuals with ERG gene fusion are mostly documented to have advanced tumor stages, increased mortality, and higher rates of metastasis in non-surgical cohorts. In the current review, we elucidate ERG's molecular interaction with downstream genes and the pathways associated with PCa. Studies have documented that ERG plays a central role in PCa progression due to its ability to enhance tumor growth by promoting inflammatory and angiogenic responses. ERG has also been implicated in the epithelial-mesenchymal transition (EMT) in PCa cells, which increases the ability of cancer cells to metastasize. In vivo, research has demonstrated that higher levels of ERG expression are involved with nuclear pleomorphism that prompts hyperplasia and the loss of cell polarity.

The Association between Cyclin Dependent Kinase 2 Associated Protein 1 (CDK2AP1) and Molecular Subtypes of Lethal Prostate Cancer.

Prostate cancer (PCa) is one of the most commonly diagnosed types of malignancy and is the second leading cause of cancer-related death in men in developed countries. Cyclin dependent kinase 2 associate protein 1(CDK2AP1) is an epigenetic and cell cycle regulator gene which has been downregulated in several malignancies, but its involvement in PCa has not yet been investigated in a clinical setting. We assessed the prognostic value of CDK2AP1 expression in a cohort of men diagnosed with PCa (n = 275) treated non-surgically by transurethral resection of the prostate (TURP) and studied the relationship between CDK2AP1 expression to various PCa molecular subtypes (ERG, PTEN, p53 and AR) and evaluated the association with clinical outcome. Further, we used bioinformatic tools to analyze the available TCGA PRAD transcriptomic data to explore the underlying mechanism. Our data confirmed increased expression of CDK2AP1 with higher Gleason Grade Group (GG) and metastatic PCa (p <0.0001). High CDK2AP1 expression was associated with worse overall survival (OS) (HR: 1.62, CI: 1.19−2.21, p = 0.002) and cause-specific survival (CSS) (HR: 2.012, CI 1.29−3.13, p = 0.002) using univariate analysis. When compared to each sub-molecular type. High CDK2AP1/PTEN-loss, abnormal AR or p53 expression showed even worse association to poorer OS and CCS and remained significant when adjusted for GG. Our data indicates that CDK2AP1 directly binds to p53 using the Co-Immunoprecipitation (Co-IP) technique, which was validated using molecular docking tools. This suggests that these two proteins have a significant association through several binding features and correlates with our observed clinical data. In conclusion, our results indicated that the CDK2AP1 overexpression is associate with worse OS and CSS when combined with certain PCa molecular subtypes; interaction between p53 stands out as the most prominent candidate which directly interacts with CDK2AP1.

Manuka honey enhanced sensitivity of HepG2, hepatocellular carcinoma cells, for Doxorubicin and induced apoptosis through inhibition of Wnt/ß-catenin and ERK1/2.

BACKGROUND: Recently, there is increasing awareness focused on the identification of naturally occurring anticancer agents derived from natural products. Manuka honey (MH) has been recognized for its biological properties as antimicrobial, antioxidant, and anticancer properties. However, its antiproliferative mechanism in hepatocellular carcinoma is not investigated. The current study focused mainly on investigating the molecular mechanism and synergistic effect of anticancer properties of MH on Doxorubicin (DOX)-mediated apoptotic cell death, using two different p53 statuses (HepG2 and Hep3B) and one non-tumorigenic immortalized liver cell line. RESULTS: MH treatment showed a proliferative inhibitory effect on tested cells in a dose-dependent manner with IC50 concentration of (6.92 ± 0.005%) and (18.62 ± 0.07%) for HepG2 and Hep3B cells, respectively, and induced dramatic morphological changes of Hep-G2 cells, which considered as characteristics feature of apoptosis induction after 48 h of treatment. Our results showed that MH or combined treatments induced higher cytotoxicity in p53-wild type, HepG2, than in p53-null, Hep3B, cells. Cytotoxicity was not observed in normal liver cells. Furthermore, the synergistic effect of MH and Dox on apoptosis was evidenced by increased annexin-V-positive cells and Sub-G1 cells in both tested cell lines with a significant increase in the percentage of Hep-G2 cells at late apoptosis as confirmed by the flow cytometric analysis. Consistently, the proteolytic activities of caspase-3 and the degradation of poly (ADP-ribose) polymerase were also higher in the combined treatment which in turn accompanied by significant inhibitory effects of pERK1/2, mTOR, S6K, oncogenic ß-catenin, and cyclin D1 after 48 h. In contrast, the MH or combined treatment-induced apoptosis was accompanied by significantly upregulated expression of proapoptotic Bax protein and downregulated expression of anti-apoptotic Bcl-2 protein after 48 h. CONCLUSIONS: Our data showed a synergistic inhibitory effect of MH on DOX-mediated apoptotic cell death in HCC cells. To our knowledge, the present study provides the first report on the anticancer activity of MH and its combined treatment with DOX on HCC cell lines, introducing MH as a promising natural and nontoxic anticancer compound.

Therapeutic strategies for stricturing Crohn's disease in childhood: a systematic review.

PURPOSE: Childhood stricturing Crohn's disease (CD) has significant morbidity. Interventions including resection, stricturoplasty and endoscopic balloon dilatation (EBD) are often required. Optimal intervention modality and timing, and use of adjuvant medical therapies, remains unclear. We aim to review the therapies used in paediatric stricturing CD. METHODS: A systematic review in accordance with PRISMA was performed (PROSPERO: CRD42020164464). Demographics, stricture features, interventions and outcomes were extracted. RESULTS: Fourteen studies were selected, including 177 patients (183 strictures). Strictures presented at 40.6 months (range 14-108) following CD diagnosis. Medical therapy was used in 142 patients for an average of 20.4 months (2-36), with a complete response in 11 (8%). Interventions were undertaken in 138 patients: 53 (38%) resections, 39 (28%) stricturoplasties, and 17 (12%) EBD. Complications occurred in 11% of resections, versus 15% stricturoplasties, versus 6% EBD (p = 0.223). At a median follow-up of 1.9 years (interquartile range 1.2-2.4) pooled stricture recurrence was 22%. Resection had 9% recurrence, versus 38% stricturoplasty, versus 47% EBD (p < 0.001). CONCLUSIONS: Resection is associated with a low incidence of recurrence and complications. There remains a paucity of evidence regarding adjuvant medical therapy and the role of EBD. We propose a minimum reported dataset for interventions in paediatric stricturing CD.

Outcomes of urgent versus nonurgent transcatheter aortic valve replacement.

BACKGROUND: There is a paucity of data regarding the outcomes of transcatheter valve replacement (TAVR) performed in an urgent clinical setting. METHODS: The Nationwide Inpatient Sample (NIS) database years 2011-2014 was used to identify hospitalizations for TAVR in the urgent setting. Using propensity score matching, we compared patients who underwent TAVR in nonurgent versus urgent settings. RESULTS: Among 42,154 hospitalizations in which TAVR was performed, 10,114 (24%) underwent urgent TAVR. There was an uptrend in the rate of urgent TAVR procedures (p = .001). The rates of in-hospital mortality among this group did not change during the study period (p = .713). Nonurgent TAVR was associated with lower mortality (odds ratio [OR] = 0.78; 95% confidence interval [CI]: 0.69-0.89, p < .001) compared with urgent TAVR. Nonurgent TAVR was associated with lower incidence of cardiogenic shock (OR = 0.46; 95%CI: 0.40-0.53 p < .001), use of mechanical circulatory support devices (OR = 0.69; 95%CI: 0.59-0.82, p < .001), AKI (OR = 0.60; 95%CI: 0.56-0.64 p < .001), hemodialysis (OR = 0.67; 95%CI: 0.56-0.80 p < .001), major bleeding (OR = 0.94; 95%CI: 0.89-0.99 p = .045) and shorter length of stay (7.08 ± 6.317 vs. 12.39 ± 9.737 days, p < .001). There was no difference in acute stroke (OR = 0.96; 95%CI: 0.81-1.14, p = .636), vascular complications (OR = 1.07; 95%CI: 0.89-1.29, p = .492), and pacemaker insertions (OR = 0.92; 95%CI: 0.84-1.01, p = .067) between both groups. Among those undergoing urgent TAVR, subgroup analysis showed higher mortality in patients ≤80 years (p = .033), women (p < .001), chronic kidney disease (p = .001), heart failure (p < .001), and liver disease (p = .003). CONCLUSION: In this large nationwide analysis, almost a quarter of TAVR procedures were performed in the urgent settings. Although urgent TAVR was associated with higher mortality and increased complications compared with nonurgent TAVR, the absolute difference in in-hospital mortality was not remarkably higher. Thus, urgent TAVR can be considered as a reasonable approach when indicated.

Fetal abdominal cysts: antenatal course and postnatal outcomes.

Background There is little information on which to base the prognostic counselling as to whether an antenatally diagnosed fetal abdominal cyst will grow or shrink, or need surgery. This study aims to provide contemporary data on prenatally diagnosed fetal abdominal cysts in relation to their course and postnatal outcomes. Methods Fetal abdominal cysts diagnosed over 11 years in a single centre were identified. The gestational age at diagnosis and cyst characteristics at each examination were recorded (size, location, echogenity, septation and vascularity) and follow-up data from postnatal visits were collected. Results Eighty abdominal cysts were identified antenatally at 28+4 weeks (range 11+0-38+3). Most (87%) were isolated and the majority were pelvic (52%), simple (87.5%) and avascular (100%). Antenatally, 29% resolved spontaneously; 29% reduced in size; 9% were stable and 33% increased in size. Forty-one percent of cysts under 20 mm diameter increased in size, while only 20% of cysts with a diameter of over 40 mm increased in size. The majority of cysts were ovarian in origin (n=45, 56%), followed by intestinal (n=15, 18%), choledochal (n=3, 4%), liver (n=2, 3%) and renal/adrenal origins (n=2, 3%), respectively. In 16% (n=13), the antenatal diagnosis was not obvious. Seventy-five percent of the cysts that persisted postnatally required surgical intervention. Conclusion Most antenatally diagnosed fetal abdominal cysts were ovarian in origin. Though most disappeared antenatally, nearly three quarters required surgical intervention when present after birth. Cysts of intestinal origin are more difficult to diagnose antenatally and often require surgery.

The value of contrast studies in the evaluation of bowel strictures after necrotising enterocolitis.

PURPOSE: Strictures of the bowel are a frequent complication post-necrotising enterocolitis (NEC). Contrast studies are routinely performed prior to stoma closure following NEC. The aim of this study was to evaluate the ability of these studies to detect strictures and also directly compare them to operative and histological findings. METHODS: Two hundred and fourteen neonates who had a diagnosis of NEC (Bell stage 2 or greater) in a single unit (2007-2011) were analysed. Their case notes, radiology, and histology were reviewed. RESULTS: One hundred and sixteen neonates underwent an emergency laparotomy and 77 had stomas fashioned. Sixty-six patients had a contrast study prior to stoma closure (distal loopogram 18, contrast enema 37, both studies 11). Colonic strictures were reported in 18 patients and small bowel strictures were reported in two patients. Fourteen of these colonic strictures were confirmed at operation and on histology but three colonic strictures were missed on contrast studies; one patient had had both contrast studies and the other two only a distal loopogram. Two small bowel strictures reported were confirmed and an additional small bowel stricture missed on distal loopogram was also detected at the time of operation. The incidence of post-op strictures was 19 out of 68 patients (27.9 %) and 16 (84.2 %) of these strictures were found in the colon. Contrast enemas had a much higher sensitivity for detecting post-NEC colonic strictures than distal loopograms; 93 versus 50 %, respectively; however, they are more likely to give a false positive result and therefore their specificity is lower; 88 versus 95 %, respectively. CONCLUSION: Colon is the commonest site for post-NEC stricture and contrast enema is the study of choice for detecting these strictures prior to stoma closure.

Antenatally diagnosed lung malformations: a plea for long-term outcome studies.

There is a wide variation in the management of infants with antenatally diagnosed lung malformations, with many paediatric surgeons and respiratory paediatricians recommending early investigations for all infants and a surgical excision for the majority of lesions, while others favour a conservative management for all asymptomatic infants. The benefits and risks of a surgical intervention have to be compared with the natural history of the untreated malformation and cohort studies from foetal diagnosis to adult life are required to provide the relevant evidence. Careful and repeated surveillance of identified foetuses is essential as recent advances in foetal medicine and surgery have improved the outcomes for the small minority, who are at risk of developing hydrops.

New Insights Into the Treatment of Hyperlipidemia: Pharmacological Updates and Emerging Treatments.

Cardiovascular diseases are the leading causes of global mortality and morbidity. Hyperlipidemia is a significant risk factor for atherosclerosis and subsequent cardiovascular diseases. Hyperlipidemia is characterized by imbalances in blood cholesterol levels, particularly elevated low-density lipoprotein cholesterol and triglycerides, and is influenced by genetic and environmental factors. Current management consists of lifestyle modifications and pharmacological interventions most commonly consisting of statins. This review paper explores pathophysiology, management strategies, and pharmacotherapies including commonly used well-established medications including statins, fibrates, and ezetimibe, exciting novel therapies including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and RNA interference therapies (inclisiran), lomitapide, and bempedoic acid, highlighting their mechanisms of action, clinical efficacy, and safety profiles. Additionally, emerging therapies under clinical trials including ApoC-III inhibitors, DGAT2 inhibitors, ACAT2 Inhibitors, and LPL gene therapies are examined for their potential to improve lipid homeostasis and cardiovascular outcomes. The evolving landscape of hyperlipidemia management underscores the importance of continued research into both established therapies and promising new candidates, offering hope for more effective treatment strategies in the future.

A low-dose thrombolytic infusion protocol for safe and successful treatment of left ventricular assist device thrombosis: a case series.

Background: Pump thrombosis is a serious complication of continuous-flow left ventricular assist device (CF-LVAD) therapy. In this study, we aim to report a novel protocol of an intermittent, low-dose, and slow infusion of tissue plasminogen activator (alteplase). Case summary: We treated seven LVAD pump thrombosis events (HeartMate® II and HeartWare) in four patients with a median age of 52 years (31-63), and all were female. The protocol was applied from January 2015 to December 2018, and it consisted of an intermittent, low-dose, and slow infusion of systemic thrombolytic therapy in the intensive care unit. This therapy resulted in successful resolution of pump thrombosis in six out of seven events. Bleeding complication occurred in one patient, which included a ruptured haemorrhagic ovarian cyst and a small cerebellar intra-parenchymal haemorrhage. All patients were discharged home in a stable condition, except one patient who died during hospitalization because of severe sepsis, pump thrombosis with subsequent pump exchange, and multi-organ failure. Discussion: A low-dose, prolonged, and systemic thrombolytic infusion protocol is an effective and relatively safe treatment that can lead to a sustained resolution of pump thrombosis with low bleeding complications and failure rates.

Expansion of human amniotic epithelial cells using condition cell reprogramming technology.

Human amniotic epithelial cells (hAECs) are non-immunogenic epithelial cells that can develop into cells of all three germline lineages. However, a refined clinically reliable method is required to optimize the preparation and banking procedures of hAECs for their successful translation into clinical studies. With the goal of establishing standardized clinically applicable hAECs cultured cells, we described the use of a powerful epithelial cell culture technique, termed Conditionally Reprogrammed Cells (CRC) for ex vivo expansion of hAECs. The well-established CRC culture method uses a Rho kinase inhibitor (Y-27632) and J2 mouse fibroblast feeder cells to drive the indefinite proliferation of all known epithelial cell types. In this study, we used an optimized CRC protocol to successfully culture hAECs in a CRC medium supplemented with xenogen-free human serum. We established that hAECs thrive under the CRC conditions for over 5 passages while still expressing pluripotent stem markers (OCT-4, SOX-2 and NANOG) and non-immunogenic markers (CD80, CD86 and HLA-G) suggesting that even late-passage hAECs retain their privileged phenotype. The hAECs-CRC cells were infected with a puromycin-selectable lentivirus expressing luciferase and GFP (green fluorescent protein) and stably selected with puromycin. The hAECs expressing GFP were injected subcutaneously into the flanks of Athymic and C57BL6 mice to check the tolerability and stability of cells against the immune system. Chemiluminescence imaging confirmed the presence and viability of cells at days 2, 5, and 42 without acute inflammation or any tumor formation. Collectively, these data indicate that the CRC approach offers a novel solution to expanding hAECs in humanized conditions for future clinical uses, while retaining their primary phenotype.

Moebius Syndrome: What We Know So Far.

Moebius syndrome (MBS) is a rare congenital cranial nerve disorder characterized by unilateral, bilateral symmetrical, or asymmetrical facial (VII) and abducens (VI) nerve palsies. Genetics and rhombencephalon vascular disturbances from intrauterine environmental exposures have been attributed to its development. It can present with various orofacial abnormalities. Although the diagnosis is purely clinical, certain characteristic features are present in the brain's images. With no cure, it is essential to devise management on a personalized basis. We discuss etiology, presentation, diagnostic approaches, and effective management in the existing literature. This comprehensive review examines the clinic-pathological aspects of Moebius syndrome. The authors employed the PUBMED base index to identify pertinent literature and reference it according to research keywords. Findings suggest the most popular etiology is the theory of intrauterine vascular disruption to the brainstem during embryogenesis, followed by the genetic hypothesis. Intrauterine environmental exposures have been implicated as potential risk factors. Facial and abducens nerve palsies are the most common presenting features. However, clinical manifestations of lower cranial nerves (IX, X, XI, XII) may be present with orthopedic anomalies and intellectual deficiencies. The diagnosis is clinical with minimal defined diagnostic criteria. Characteristic radiological manifestations involving the brainstem and cerebellum can be observed in imaging studies. With no definitive treatment options, a multidisciplinary approach is employed to provide supportive care. Despite radiological manifestations, Moebius syndrome is diagnosed clinically. Although incurable, a multidisciplinary approach, with personalized rehabilitative measures, can manage physical and psychological deficits; however, standard guidelines need to be established.

Brain Abscess as a Complication of Hereditary Hemorrhagic Telangiectasia: A Case Report.

An 18-year-old male, previously diagnosed with hereditary hemorrhagic telangiectasia (HHT), presented to the outpatient department with a complaint of generalized seizures and fever for the past five days. He had a history of recurrent epistaxis, progressive shortness of breath, and cyanosis. Magnetic resonance imaging (MRI) of the brain revealed an abscess in the temporoparietal region. A computed angiogram of the pulmonary vasculature showed the presence of arteriovenous malformation (AVM). A four-weekly antibiotic regimen was initiated, which resulted in a profound improvement in symptoms. A brain abscess can arise as a complication of vascular malformation in a patient with HHT, providing a nidus for bacteria to migrate toward the brain. Early recognition of HHT is essential in these patients and their affected family members, as screening can help us prevent complications at an earlier stage.

A Case Report of Brucellosis-Associated Infective Endocarditis.

Brucellosis is a prevalent zoonotic infection that can be relatively well managed and tolerated if appropriate treatment is initiated. Unfortunately, likely secondary to decreased awareness and vague symptoms, the diagnosis can be easily missed leading to worsening complications that severely increase the mortality rate. We present a case of a 25-year-old female who presented from a rural setting with a diagnosis of brucellosis, which was delayed. She ultimately developed infective endocarditis with cardiac vegetations on imaging. Despite improvement on antibiotics and reduction in size of cardiac vegetation, she suffered a fatal cardiac arrest before undergoing surgical intervention. Better awareness regarding hygiene and sanitary food handling should be encouraged, especially in underdeveloped rural areas, to help prevent infection. More studies need to be performed to help better identify symptoms coupled with maintaining a high index of suspicion so as to expedite diagnosis, treatment, management and hopefully prevent the progression of disease and worsening complications.

Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate Cancer.

Arsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate samples including benign, incidental, advanced, and castrate-resistant patients treated by androgen deprivation therapy (ADT). We also explored the association of SRRT with common genetic aberrations in lethal PCa using immunohistochemistry (IHC) and performed a detailed analysis of SRRT expression using The Cancer Genome Atlas (TCGA PRAD) by utilizing RNA-seq, clinical information (pathological T category and pathological Gleason score). Our findings indicated that high SRRT expression was significantly associated with poor overall survival (OS) and cause-specific survival (CSS). SRRT expression was also significantly associated with common genomic aberrations in lethal PCa such as PTEN loss, ERG gain, mutant TP53, or ATM. Furthermore, TCGA PRAD data revealed that high SRRT mRNA expression was significantly associated with higher Gleason scores, PSA levels, and T pathological categories. Gene set enrichment analysis (GSEA) of RNAseq data from the TCGA PRAD cohort indicated that SRRT may play a potential role in regulating the expression of genes involved in prostate cancer aggressiveness. Conclusion: The current data identify the SRRT's potential role as a prognostic for lethal PCa, and further research is required to investigate its potential as a therapeutic target.