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Evidence strongly suggests that antibiotic prophylaxis should not be used routinely for transoesophageal echocardiography for any indication. [ABSTRACT FROM AUTHOR]

A substudy of the Lovastatin Restenosis Trial in patients with elevated cholesterol (>200 mg/dl) showed no evidence of an effect of aggressive lipid lowering on restenosis, confirming the results of the main trial. [ABSTRACT FROM AUTHOR]

Background: Epithelial ovarian cancer (EOC) remains a significant challenge in gynecologic oncology, particularly in the context of platinum-resistant disease. Mirvetuximab soravtansine (MIRV), was approved after trials revealed favorable response and survival outcomes. MIRV targets folate receptor alpha (FRα), a cell-surface receptor that is overexpressed in EOC and has been associated with aggressive disease phenotypes., Methods: This retrospective study analyzed 425 patient samples tested for FRα using the VENTANA® FOLR1 RxDx immunohistochemical assay. The patient cohort included cases with high grade serous carcinoma predominantly, tested across various anatomical sites. Statistical analysis examined the correlation between FRα positivity and clinical parameters such as tumor site and histology., Results: FRα was highly expressed in 36.3 % of the cases, with a significant association between FRα positivity and high grade serous ovarian histology. Tumor samples from the ovary, fallopian tube, adnexa, and dominant pelvic masses showed higher FRα positivity compared to metastatic sites (positive rates of 44.4 % vs 32.5 %, p = 0.02), highlighting the potential influence of tumor origin on expression of FRα. Time between sample collection and testing did not impact FRα expression, with sample testing spread over a median of 19.5 months post-collection. Eight patients had more than one specimen tested, of which 3 (37.5 %) had discordant results when a subsequent specimen was tested., Conclusion: Our results highlight a need for standardized protocols for FRα testing to ensure accurate biomarker evaluation across varied clinical settings. The heterogeneity in FRα expression, influenced by tumor histology and anatomical origin, warrant further investigation to optimize therapeutic outcomes., Prior Presentation: Preliminary findings from this study were previously presented in poster format at the Society of Gynecologic Oncology 2024 Annual Metting. We confirm that the submission complies with the journal requirements., Competing Interests: Declaration of competing interest This manuscript was funded by Labcorp. Rebecca A. Previs is a current employee of Labcorp, owns Labcorp stock, and receives travel support from Labcorp. Kyle C. Strickland is a current employee of Labcorp, owns Labcorp stock, and consulting fees from Foundation Medicine, Almac Pharmaceuticals, OncoQuest Pharmaceuticals, and CanariaBio. Zachary Wallen is a current employee of Labcorp, owns Labcorp stock, and receives travel support from Labcorp. Heidi Ko is a current employee of Labcorp and owns Labcorp stock. Michelle Green is a current employee of Labcorp. Maureen Cooper was a former employee of Labcorp and owns Labcorp stock. Elizabeth Lyon is a current employee of Labcorp and owns Labcorp stock. Michael Biorn is a current employee of Labcorp and owns Labcorp stock. Jennifer Armetta is a current employee of Labcorp and owns Labcorp stock. Rennie Quarles is a current employee of Labcorp and owns Labcorp stock. Catherine H Watson has no disclosures. Kari Ring received speakers' bureau honoraria from Ethicon. Jonathan L. Klein is a current employee of Labcorp and owns Labcorp stock. Brian Caveney is a board member of the Personalized Medicine Coalition, a current employee of Labcorp and owns Labcorp stock. Eric A. Severson is a current employee of Labcorp and owns Labcorp stock. Shakti Ramkissoon is a current employee of Labcorp and owns Labcorp stock., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to investigate the feasibility of using ground soybean hulls and white oat grains to finish steers reared exclusively on concentrated feed. We used 33 steers, predominantly of Charolais or Nellore breeds, and randomly assigned the animals to the treatments, blocking them according to genetic predominance. The diets were isonitrogenous, and the treatments consisted of soybean hulls, white oats, and mix these in equal parts, supplemented with calcitic limestone and a protein nucleus. The study measured variables related to the dry matter intake (DMI) and bromatological fractions of diets, as well as performance of steers. No significant differences were observed between treatments in terms of DMI during the experimental period. Although DMI intake was similar across treatments, steers receiving the mixed diet exhibited significantly higher weight gain than those on the soybean hull diet (1.300 vs. 0.972 kg day-1). However, both these treatments showed comparable results to the white oat grain diet (1.203 kg day-1), achieving a similar final weight (387.22 kg). Implementing 100% concentrate diets is technically feasible for steers fed with white oat grain and the mixture of soybean hull and white oat grain, which also demonstrated superior performance compared to the soybean hull treatment.

While pregnancy is a time of relative immunosuppression, infective endocarditis and bacterial meningitis remain rare. We present a case of a pregnant woman with Streptococcus oralis endocarditis and meningitis. This is the first reported case of Streptococcus oralis meningitis in a patient without predisposing risk factors. This case highlights the importance of collecting blood cultures in febrile illness during pregnancy and illustrates that effective management plans can be formulated without performing invasive diagnostic tests such as transesophageal echocardiography., (© The Author(s) 2022.)

A novel bacterial strain, GSTT-20 T was isolated from an infected, prosthetic endovascular graft explanted from a shepherd in London, United Kingdom. This strain was an aerobic, catalase-positive, oxidase-negative, Gram-stain-negative, motile, curved rod. It grew on blood agar, chocolate agar and MacConkey agar incubated at 37 °C in an aerobic environment after 48 h, appearing as yellow, mucoid colonies. Analysis of the complete 16S rRNA gene sequence showed closest similarity to Variovorax paradoxus with 99.6 % identity and Variovorax boronicumulans with 99.5 % identity. Phylogenetic analysis of the 16S rRNA gene sequence and phylogenomic analysis of single nucleotide polymorphisms within 1530 core genes showed GSTT-20 T forms a distinct lineage in the genus Variovorax of the family Comamonadaceae . In silico DNA-DNA hybridization assays against GSTT-20 T were estimated at 32.1 % for V. boronicumulans and 31.9 % for V. paradoxus . Genome similarity based on average nucleotide identity was 87.50 % when comparing GSTT-20 T to V. paradoxus . Based on these results, the strain represented a novel species for which the name Variovorax durovernensis sp. nov. was proposed. The type strain is GSTT-20 T (NCTC 14621 T =CECT 30390 T ).

This work examines differences in chromatin accessibility, methylation, and response to DNA hypomethylating agents between mismatch repair-deficient and non-mismatch repair-deficient endometrial cancer. Next-generation sequencing of a stage 1B, grade 2 endometrioid endometrial cancer tumor revealed microsatellite instability and a variant of unknown significance in POLE along with global and MLH1 hypermethylation. Inhibition of viability by decitabine in the study and comparison tumors was minimal, as shown by an inhibitory effect of 0 and 17.9, respectively. Conversely, the inhibitory effect of azacitidine on the study tumor was more pronounced, at 72.8 versus 41.2. In vitro , mismatch repair-deficient endometrial cancer with MLH1 hypermethylation respond better to DNA methyltransferase inhibition by azacytidine (DNA/RNA inhibition), than to decitabine (DNA-only inhibition). Additional large studies are needed to substantiate our findings.

The aim was to identify the predominant variables in the differentiation of meat quality of cattle submitted to surgical castration, immunocastration, or non-castration and finished in a tropical pasture. Thirty-nine crossbred cattle were used and distributed in three treatments: i) surgical castration; ii) immunocastration; and iii) non-castration, with an initial mean age of 14.06±0.72 months and a mean weight of 284.10±31.40 kg. We used the principal component analysis to differentiate the qualitative meat characteristics between the treatments. Based on that analysis, we found that the first three principal components explained 71.44% of the total variation in the meat quality data, which ensures that the variation found is associated with the effect of the treatments. The characteristics correlated with the first three principal components and responsible for the discrimination between sexual conditions were subcutaneous fat thickness, instrumental meat color, cooking loss and shear force. These characteristics were similar among castrated animals, regardless of the methods. Therefore, immunological castration preserves the attributes of the meat and prevents possible damage to the physical and mental integrity of the animals. Finally, principal component analysis is an important methodology in the objective investigation of beef meat attributes.

Objectives: Masked hypertension - a blood pressure (BP) phenotype characterized by a clinic BP in the normal range but elevated BP outside the office - is associated with early hypertension-mediated organ damage. This study examined early target organ manifestations of masked hypertension diagnosed by home (HBPM) and ambulatory (ABPM) BP monitoring., Methods: Left ventricular (LV) structure and diastolic function measured by echocardiography, microalbuminuria, and coronary artery calcification were evaluated in 420 patients with high clinic BP (SBP 120-150 mmHg or DBP 80-95 mmHg). Evidence of hypertension-mediated organ damage was compared in patients with sustained normotension, masked hypertension, and sustained hypertension based on measurements by HBPM, daytime ABPM, and 24-h ABPM., Results: The 420 participants averaged 48 (12) [mean (SD)] years of age; the average clinic BP was 130 (13)/81 (8) mmHg. In individuals with masked hypertension diagnosed by HBPM, indexed LV mass, relative wall thickness, and e' and E/e' (indices of LV relaxation), were generally intermediate between values observed in normotensives and sustained hypertensive patients, and were significantly greater in masked hypertension than normotensives. Similar trends were observed when masked hypertension was diagnosed by ABPM but a diagnosis of masked hypertension was not as reliably associated with LV remodeling or impaired LV relaxation in comparison to normotensives. There were trends towards greater likelihoods of detectable urinary microalbumin and coronary calcification in masked hypertension than in normotensives., Conclusion: These results support previous studies demonstrating early hypertension-mediated organ damage in patients with masked hypertension, and suggest that HBPM may be superior to ABPM in identifying patients with masked hypertension who have early LV remodeling and diastolic LV dysfunction., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease., Methods and Materials: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high., Results: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm 3 (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively., Conclusions: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: There are no reliable blood biomarkers for monitoring endometrial cancer patients in the current clinical practice. Circulating tumor DNA (ctDNA) is emerging as a promising non-invasive method to measure tumor burden, define prognosis and monitor disease status in many solid cancers. In this pilot study, we investigated if unique tumor-specific DNA junctions can be used to detect ctDNA levels in patients with endometrial cancer., Methods: Chromosomal rearrangements in primary tumors of eleven patients with high-grade or advanced stage endometrial cancer were determined by whole-genome Mate-Pair sequencing. Identified unique tumor-specific junctions were evaluated in pre- and six-week post-surgery patient plasma using individualized quantitative polymerase chain reaction (qPCR) assays. The relationship between clinicopathological features and detection of ctDNA was investigated., Results: CtDNA was detected in 60% (6/10) of cases pre-surgery and in 27% (3/11) post-surgery. The detection of ctDNA pre-surgery was consistent with clinical indicators of aggressive disease such as advanced stage (80% - 4/5), lymphatic spread of disease (100% - 3/3), serous histology (80% - 4/5), deep myometrial invasion (100% - 3/3), lympho-vascular space invasion (75% - 3/4). All patients in which ctDNA was detected post-surgically had type II endometrial cancer., Discussion: This pilot study demonstrates the feasibility of using personalized tumor-specific junction panels for detecting ctDNA in the plasma of endometrial cancer patients. Larger studies and longer follow-up are needed to validate the potential association between pre-surgical ctDNA detection and the presence of cancers with aggressive pathologic tumor characteristics or advanced stage observed in this study., Competing Interests: The authors declare no competing financial interests.

In general, calf production occurs in less intensive systems. The limitation of nutrients during the gestation phase of beef cows can have negative impacts on the consequent productivity of females. Therefore, this study aimed to evaluate the effects of nutritional levels in the third trimester of pregnancy on the productive performance of beef cows kept in a natural pasture (NP). Eighty-three Charolais × Nelore cows were used, ranging in age from 4 to 12 years, which were divided according to their nutritional levels during the third trimester of pregnancy: NP, cows supplemented with 100% of their energy and protein requirements (SP100) and cows supplemented with 150% of their energy and protein requirements (SP150). The experimental design was completely randomized with three treatments and a varied number of repetitions. The SP100 and SP150 cows presented better body condition at calving (2.92 and 2.99 vs 2.81 points) and at the start of the breeding season (2.90 and 2.95 vs 2.80 points) than did NP cows. The nutritional level of the cows in the third trimester of gestation did not influence the blood metabolite concentrations. The plasma levels of albumin and total proteins were 3.11 and 8.18 g/dl, respectively. Glucose and cholesterol showed values of 74.96 and 166.50 mg/dl. The lowest concentration of blood metabolites was observed in the first postpartum weeks. The SP100 and SP150 cows showed faster follicular growth and, consequently, a higher percentage of females with ovulatory follicles at 21 days postpartum than did NP cows (45.68, 41.11, and 11.00%, respectively). The SP150 cows had a higher pregnancy rate (40.74%), total calf production (295.88 kg/cow), and consequently, offspring sale value. An increased nutritional level in the third trimester of pregnancy improves the postpartum metabolic condition and productive efficiency of beef cows kept on NP., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

No consensus exists regarding the definition of ventilator-associated pneumonia (VAP) in neonates and reliability of chest X-ray (CXR) is low. Lung ultrasound (LU) is a potential alternative diagnostic tool. The aim was to define characteristics of VAP in our patient population and propose a multiparameter score, incorporating LU, for VAP diagnosis. Between March 25, 2018, and May 25, 2019, infants with VAP were identified. Clinical, laboratory and microbiology data were collected. CXRs and LU scans were reviewed. A multiparameter VAP score, including LU, was calculated on Day 1 and Day 3 for infants with VAP and for a control group and compared with CXR. VAP incidence was 10.47 episodes/1000 ventilator days. LU and CXR were available for 31 episodes in 21 infants with VAP, and for six episodes in five patients without VAP. On Day 1, a VAP score of > 4, and on Day 3 a score of > 5 showed sensitivity of 0.94, and area under the curve of 0.91 and 0.97, respectively. AUC for clinical information only was 0.88 and for clinical and CXR 0.85.Conclusion: The multiparameter VAP score including LU could be useful in diagnosing VAP in neonates with underlying lung pathology. What is Known: • Ventilator associated pneumonia (VAP) is common in infants on the neonatal unit and is associated with increased use of antibiotics, prolonged ventilation and higher incidence of chronic lung disease. • Commonly used definitions of VAP are difficult to apply in neonates and interpretation of chest X-ray is challenging with poor inter-rater agreement in patients with underlying chronic lung disease. What is New: • The multiparameter VAP score combining clinical, microbiology and lung ultrasound (LU) data is predictive for VAP diagnosis in preterm infants with chronic lung disease. • LU findings of VAP in neonates showed high inter-rater agreement and included consolidated lung areas, dynamic bronchograms and pleural effusion.

The pharmaceutical industry is continuing to face high research and development (R&D) costs and low overall success rates of clinical compounds during drug development. There is an increasing demand for development and validation of healthy or disease-relevant and physiological human cellular models that can be implemented in early-stage discovery, thereby shifting attrition of future therapeutics to a point in discovery at which the costs are significantly lower. There needs to be a paradigm shift in the early drug discovery phase (which is lengthy and costly), away from simplistic cellular models that show an inability to effectively and efficiently reproduce healthy or human disease-relevant states to steer target and compound selection for safety, pharmacology, and efficacy questions. This perspective article covers the various stages of early drug discovery from target identification (ID) and validation to the hit/lead discovery phase, lead optimization, and preclinical safety. We outline key aspects that should be considered when developing, qualifying, and implementing complex in vitro models (CIVMs) during these phases, because criteria such as cell types (e.g., cell lines, primary cells, stem cells, and tissue), platform (e.g., spheroids, scaffolds or hydrogels, organoids, microphysiological systems, and bioprinting), throughput, automation, and single and multiplexing endpoints will vary. The article emphasizes the need to adequately qualify these CIVMs such that they are suitable for various applications (e.g., context of use) of drug discovery and translational research. The article ends looking to the future, in which there is an increase in combining computational modeling, artificial intelligence and machine learning (AI/ML), and CIVMs.

Objectives: To describe and validate an artificial intelligence (AI)-driven structured reporting system by direct comparison of automatically generated reports to results from actual clinical reports generated by nuclear cardiology experts., Background: Quantitative parameters extracted from myocardial perfusion imaging (MPI) studies are used by our AI reporting system to generate automatically a guideline-compliant structured report (sR)., Method: A new nonparametric approach generates distribution functions of rest and stress, perfusion, and thickening, for each of 17 left ventricle segments that are then transformed to certainty factors (CFs) that a segment is hypoperfused, ischemic. These CFs are then input to our set of heuristic rules used to reach diagnostic findings and impressions propagated into a sR referred as an AI-driven structured report (AIsR). The diagnostic accuracy of the AIsR for detecting coronary artery disease (CAD) and ischemia was tested in 1,000 patients who had undergone rest/stress SPECT MPI., Results: At the high-specificity (SP) level, in a subset of 100 patients, there were no statistical differences in the agreements between the AIsr, and nine experts' impressions of CAD (P = .33) or ischemia (P = .37). This high-SP level also yielded the highest accuracy across global and regional results in the 1,000 patients. These accuracies were statistically significantly better than the other two levels [sensitivity (SN)/SP tradeoff, high SN] across all comparisons., Conclusions: This AI reporting system automatically generates a structured natural language report with a diagnostic performance comparable to those of experts.

Objective: To select optimal therapies based on the detection of actionable genomic alterations in tumor samples is a major challenge in precision medicine., Methods: We describe an effective process (opened December 1, 2017) that combines comprehensive genomic and transcriptomic tumor profiling, custom algorithms and visualization software for data integration, and preclinical 3-dimensiona ex vivo models for drug screening to assess response to therapeutic agents targeting specific genomic alterations. The process was applied to a patient with widely metastatic, weakly hormone receptor positive, HER2 nonamplified, infiltrating lobular breast cancer refractory to standard therapy., Results: Clinical testing of liver metastasis identified BRIP1, NF1, CDH1, RB1, and TP53 mutations pointing to potential therapies including PARP, MEK/RAF, and CDK inhibitors. The comprehensive genomic analysis identified 395 mutations and several structural rearrangements that resulted in loss of function of 36 genes. Meta-analysis revealed biallelic inactivation of TP53, CDH1, FOXA1, and NIN, whereas only one allele of NF1 and BRIP1 was mutated. A novel ERBB2 somatic mutation of undetermined significance (P702L), high expression of both mutated and wild-type ERBB2 transcripts, high expression of ERBB3, and a LITAF-BCAR4 fusion resulting in BCAR4 overexpression pointed toward ERBB-related therapies. Ex vivo analysis validated the ERBB-related therapies and invalidated therapies targeting mutations in BRIP1 and NF1. Systemic patient therapy with afatinib, a HER1/HER2/HER4 small molecule inhibitor, resulted in a near complete radiographic response by 3 months., Conclusion: Unlike clinical testing, the combination of tumor profiling, data integration, and functional validation accurately assessed driver alterations and predicted effective treatment., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Infective endocarditis (IE) remains a rare condition but one with high associated morbidity and mortality. With an ageing population and increasing use of implantable cardiac devices and heart valves, the epidemiology of IE has changed. Early clinical suspicion and a rapid diagnosis are essential to enable the correct treatment pathways to be accessed and to reduce complication and mortality rates. In the current review, we detail the latest guidelines for the evaluation and management of patients with endocarditis and its prevention., (© Royal College of Physicians 2020. All rights reserved.)

Autosomal dominant polycystic kidney disease (ADPKD) is a leading monogenetic cause of end-stage renal disease with limited therapeutic repertoire. A targeted drug delivery strategy that directs a small molecule to renal niches around cysts could increase the safety margins of agents that slow the progression of ADPKD but are poorly tolerated due to extrarenal toxicity. Herein, we determined whether previously characterized lysine-based and glutamic acid-based megalin-binding peptides can achieve renal-specific localization in the juvenile cystic kidney (JCK) mouse model of polycystic kidney disease and whether the distribution is altered compared with control mice. We performed in vivo optical and magnetic resonance imaging studies using peptides conjugated to the VivoTag 680 dye and demonstrated that megalin-interacting peptides distributed almost exclusively to the kidney cortex in both normal and JCK mice. Confocal analysis demonstrated that the peptide-dye conjugate distribution overlapped with megalin-positive renal proximal tubules. However, in the JCK mouse, the epithelium of renal cysts did not retain expression of the proximal tubule markers aquaporin 1 and megalin, and therefore these cysts did not retain peptide-dye conjugates. Furthermore, human kidney tumor tissues were evaluated by immunohistochemistry and revealed significant megalin expression in tissues from patients with renal cell carcinoma, raising the possibility that these tumors could be treated using this drug delivery strategy. Taken together, our data suggest that linking a small-molecule drug to these carrier peptides could represent a promising opportunity to develop a new platform for renal enrichment and targeting in the treatment of ADPKD and certain renal carcinomas., (Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.)

Aim: To quantify characteristics in acute flaccid myelitis (AFM) at acute and convalescent stages., Method: This was a retrospective case series of children with AFM evaluated at a single institution in the USA (2014-2017). Acute inflammatory/ischemic myelopathies were excluded. Neurological assessments and segmental quantitative analysis of signal abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord were performed., Results: Sixteen patients (11 males, five females) were evaluated. Median age at onset was 4 years (interquartile range [IQR] 3-6y). All had parainfectious acute-onset limb weakness, lower motor neuron examination, and spinal fluid pleocytosis. On acute spinal cord MRI, longitudinally extensive T2 hyperintensities were identified throughout the spinal cord mostly within grey matter; five out of 12 patients had dorsal brainstem T2 hyperintensities. At a median of 2 months follow-up (IQR 2-3mo), spinal cord MRI improved in seven out of nine patients although focal T2 hyperintensities persisted in cervical and lumbar grey matter. At a median follow-up of 4 months (IQR 2-6mo), Medical Research Council sum score rose from a median of 29 to 32; distal muscle groups improved more than proximal ones; four out of 16 patients were ventilator-dependent; and two out of 16 patients were quadriplegic., Interpretation: While patients may show marked improvement on neuroimaging from acute to convalescent stages, the majority of children with AFM have limited motor recovery and continued disability. Clinicians should consider the timing of clinical and neuroimaging exams when assessing diagnosis and prognosis., What This Paper Adds: During the 2014 to 2017 acute flaccid myelitis outbreak in the USA, clinical recovery was better in distal than proximal muscle groups. Lumbar spinal cord showed more residual abnormalities at convalescence., (© 2018 Mac Keith Press.)

Technology has shifted some human interactions to the virtual world. For many young adults, sexual encounters now occur through virtual means, as social media, picture exchanges, sexually explicit Web sites, and video chatting have become popular alternative outlets for these activities to occur. This study used the self-report responses of 812 undergraduate students (282 men and 530 women), collected from an online survey. In addition to using 10 personal demographic control variables, this study used five sexual activity/relationship characteristics (number of sexual partners, relationship status, age to first use pornography, frequency of sexual activity/intercourse, and frequency of masturbation), and the four constructs of Akers' social learning theory (identified as differential association, differential reinforcement, imitation/modeling, and definitions favorable) to predict a seven-item count of deviant cyber-sexual activities, and two measures of "sexting" behaviors. Gender, self-esteem, sexual orientation, race, and religion were strongly significant predictors in the models, but Akers' four elements of social learning performed the strongest in predicting the two measures of sexting and the overall deviant cyber-sexual activities scale. This finding indicates that peer associations and peer reinforcements have a strong influence on individuals' willingness to engage in deviant cyber-sexual activities. This study explored different avenues for young adults' engagement in sexual deviancy and the results suggest that sexual behaviors performed in-person may not be the strongest predictors of online sexual behavior.

Introduction: Malignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy., Methods: We used mate-pair (n = 22), RNA (n = 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome., Results: We observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival., Conclusions: Our findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Purpose: The methods (IHC/FISH) typically used to assess ER, PR, HER2, and Ki67 in FFPE specimens from breast cancer patients are difficult to set up, perform, and standardize for use in low and middle-income countries. Use of an automated diagnostic platform (GeneXpert®) and assay (Xpert® Breast Cancer STRAT4) that employs RT-qPCR to quantitate ESR1, PGR, ERBB2, and MKi67 mRNAs from formalin-fixed, paraffin-embedded (FFPE) tissues facilitates analyses in less than 3 h. This study compares breast cancer biomarker analyses using an RT-qPCR-based platform with analyses using standard IHC and FISH for assessment of the same biomarkers., Methods: FFPE tissue sections from 523 patients were sent to a College of American Pathologists-certified central reference laboratory to evaluate concordance between IHC/FISH and STRAT4 using the laboratory's standard of care methods. A subset of 155 FFPE specimens was tested for concordance with STRAT4 using different IHC antibodies and scoring methods., Results: Concordance between STRAT4 and IHC was 97.8% for ESR1, 90.4% for PGR, 93.3% for ERBB2 (IHC/FISH for HER2), and 78.6% for MKi67. Receiver operating characteristic curve (ROC) area under the curve (AUC) values of 0.99, 0.95, 0.99, and 0.85 were generated for ESR1, PGR, ERBB2, and MKi67, respectively. Minor variabilities were observed depending on the IHC antibody comparator used., Conclusion: Evaluation of breast cancer biomarker status by STRAT4 was highly concordant with central IHC/FISH in this blinded, retrospectively analyzed collection of samples. STRAT4 may provide a means to cost-effectively generate standardized diagnostic results for breast cancer patients in low- and middle-income countries.

The clinical spectrum of human disease caused by Trueperella bernardiae is poorly described, partly as a result of historical difficulties with microbial identification. With the introduction of powerful new technologies, such as matrix-assisted desorption ionization-time of flight mass spectrometry, into routine microbiology laboratories, new insights into diseases caused by such organisms are being made. Here we report a case of septic thrombophlebitis with bacteraemia caused by this organism, together with a retrospective description of laboratory isolation of this organism over a period of 6 years in a hospital in London, UK.

The objective was to evaluate the influence of calving and postpartum characteristics, measured in different genetic predominance, on the postpartum rebreeding. Were evaluated 437 partum from cows that received feeding management consisting of a forage base of the native field and the mating season consisted of 90 days. The measurements were used from the data base (age of cow, genetic predominance, body weight, body condition score and date of calving) of the cows in the partum and postpartum period. The variables were submitted to analysis of multiple variances, multiple regression, correlation and cluster. Already the groups formed by cluster analysis were submitted to analysis of variance and F test and the means, compared by Student's t-test, α=0.05 probability. The increase in the mean at 0.14 points in the body condition score at calving and the occurrence of calving 9 days earlier at the calving season gives the Charolais genetically predominant cows repeat calves. The Nellore genetic predominance when they calved with similar body condition score (2.32 points) and showed a negative body weight gain at weaning (-3.0 kg and -2.1 kg) showed different behaviors, where they did not repeat the offspring, when they calved and weaned with smaller body weight.

Blood pressure (BP) variability is associated with progression to clinical atherosclerosis. The evidence is inconclusive if BP variability predicts cardiovascular outcomes in low-risk populations. The aim of this study was to analyze the association of 24-hour BP variability with coronary artery calcium (CAC) among a group of individuals without coronary artery disease. The Masked Hypertension Study targeted patients with borderline high BP (120-149 mm Hg systolic and/or 80-95 mm Hg diastolic). Ambulatory blood pressure monitoring (ABPM) was performed at two time-points, 8 days apart. CAC was measured at exit visit via cardiac CT and reported as Agatston Score. Weighted standard deviations and average real variability were calculated from ABPM. Of the 322 participants who underwent cardiac CT, 26% (84) had CAC present, 52% (168) were female, and 21% (64) were black. BP variability did not differ by CAC group. In this low cardiovascular risk group, CAC was not associated with 24-hour ambulatory BP variability., (©2018 Wiley Periodicals, Inc.)

Purpose: Campylobacter species are a well-recognized but rare cause of bloodstream infection., Methods: Here we reviewed 41 cases of Campylobacter bloodstream infection occurring at a single center in London over 44years, comprising 0.2% of all recorded episodes during this time period., Results: Patients had a mean age of 46years and, contrasting with previous reports, nearly 50% of our patients did not have significant comorbidities. Ciprofloxacin resistance increased over the study period with 35% of isolates overall being resistant compared with only 3% exhibiting macrolide resistance. Despite a minority of patients receiving appropriate empirical antibiotic therapy, overall mortality was only 7%., Conclusion: Campylobacter bacteremia remains a rare but significant cause of morbidity with a low associated mortality. Underlying immunosuppressive conditions are common but by no means universal. In our setting, macrolides would be favored as empirical agents to treat suspected Campylobacter enteritis, including cases with associated bacteremia., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Two cases of Bartonella prosthetic valve endocarditis were cured when treated for 2 weeks with gentamicin and 3 months with doxycycline. Clinical cure correlated with decreased Bartonella antibody titers. This report suggests a strategy to monitor, treat, and cure Bartonella prosthetic valve endocarditis.

The phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal β-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%; P = 0.27), 6-month mortality (31.6% versus 25.9%; P = 0.58), and survival time after discharge (P = 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7; P = 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

This case series demonstrates a novel clinical phenotype of gait disturbance as an initial symptom in children <3 years old with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Anti-NMDAR encephalitis is one of the most common causes of encephalitis in children, more common than any of the viral encephalitides and the second most common autoimmune cause after acute disseminated encephalomyelitis. Anti-NMDAR encephalitis in children often presents with disrupted speech and sleep patterns followed by progression to motor dysfunction, dyskinesias, and seizures. Because this condition can present initially with vague symptoms, diagnosis and treatment of anti-NMDAR encephalitis are often delayed. Although nearly 40% of all reported patients are <18 years old, few infants and toddlers have been reported with this disease. Four children <3 years old were diagnosed with anti-NMDAR encephalitis at our institution. Interestingly, each child presented initially with the chief concern of gait disturbance. One child presented with unsteady walking and slurred speech, suggestive of cerebellar ataxia, and 3 had inability to bear weight on a unilateral lower extremity, resulting in unsteady gait. Two of these children had seizures at the time of hospital presentation. All developed classic behavioral changes, insomnia, dyskinesias, or decreased speech immediately before or during hospitalization. When seen in the setting of other neurologic abnormalities, gait disturbance should raise the concern for anti-NMDAR encephalitis in young children. The differential diagnosis for gait disturbance in toddlers and key features suggestive of anti-NMDAR encephalitis are reviewed., (Copyright © 2016 by the American Academy of Pediatrics.)

Background: Increasing attention is focused on polyp-related features that may contribute to the operator-dependent nature of colonoscopy. Few data on polyps are available from high-yield colonoscopies, which may serve as a benchmark for quality control., Objectives: Describe regional distribution, histology, size and shape of polyps, and the influence of patient age and gender, in colonoscopies performed by a colonoscopist with high lesion detection rate., Methods: Analysis of 698 consecutive patients with diagnostic, screening or surveillance colonoscopies., Results: In 704 colonoscopies, 1908 polyps were removed (360 were protruded and 1548 flat; 1313 were hyperplastic, 562 adenomas, 5 serrated adenomas and 8 mixed). There were 232 adenomas in female patients and 343 in male patients; 39% of the adenomas were protruded and 61% were flat. The peak adenoma detection rate (ADR) was 51% in patients beyond age 79 years. Men older than 49 years had a higher ADR than women. In men and women, respectively: 40% and 32% of adenomas were in the right colon, 31% and 22% were in the transverse colon, and 30% and 47% were in the left colon. Beyond age 59 years, the majority of adenomas were in the proximal colon., Conclusions: An excess of adenomas in the proximal colon started at age 60 and this was more pronounced in men than in women. In all colonic regions, the majority of adenomas had a shape that was flat and smaller than 6 mm.