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Objectives:To compare and contrast the definitions of primary treatment endpoints in randomized studies of dose-fractionation schedules for treating bone metastases and to identify basic characteristics of treatment endpoint that may require consensus among investigators. Methods:Randomized controlled trials (RCTs) of various dose-fractionation schedules for painful bone metastases, published between 1980 and 1999, and on-going trials whose protocols were available, were systematically reviewed based on the following features of the primary treatment endpoint: (i) degree of pain relief; (ii) timing of the pain response assessment; (iii) effect of co-interventions on pain relief; (iv) the reduction of analgesic as a treatment response; and (v) quantification of response duration. Results:Ten published RCTs (each sampled over 100 patients), plus two current trial protocols were reviewed. Five of the 12 studies defined any reduction in pain score as the primary endpoint. Three trials defined response at pre-determined time points, whereas eight studies attributed pain improvement at any time during follow-up to the effect of radiotherapy. No trial incorporated effect of systemic treatments on response. Only two trials incorporated analgesic scores into the primary endpoint criteria, although several trials reported results of combined pain and analgesic relief. Eight trials reported duration of response. Three provided some estimation of duration with respect to survival: two of them employing actuarial time to pain progression, and one calculated the ratio of pain response to median survival duration (percent net relief). Quality of life was measured in four of 12 studies, as secondary endpoint. Conclusion:Although available data suggest similarity in pain relief among various dose-fractionation scedules, accurate and consistent description of the degree of benefit from radiotherapy is lacking. While pain relief is a consistent primary treatment goal among randomized trials, a consensus on several important features of treatment endpoint is needed in order to establish common grounds for future trials in palliative radiotherapy. [Copyright &y& Elsevier]

Rab GTPases and their effectors regulate membrane traffic by determining, along with cognate SNAREs, the specificity of transport vesicle docking and fusion steps. Recent studies have also implicated Rabs in the movement of these transport vesicles from their site of formation to their site of fusion, and several Rabs have been linked to specific microtubule- or actin-based motor proteins. Analyses of Rab and motor protein mutants, coupled with advanced imaging techniques, have led to the suggestion that certain Rabs function as essential components of the vesicle receptor for specific motor proteins. [ABSTRACT FROM AUTHOR]

We report the dynamic third-order nonlinear optical susceptibilities χ(3) using the INDO/SDCI method coupled with the SOS method for the different forms of PcTiO films. The calculated values of χ(3) at a low frequency are found to decrease in the order α-PcTiO>Y-PcTiO>β-PcTiO, and well corresponded to the varied trends in the measurements. A low space symmetrical structure of α-PcTiO film has the largest magnitude of χ(3), which is the contribution from the intermolecular interaction. The electron transfers from macrocycle π orbitals to metal Ti 3d orbital make a substantial contribution to the third-order NLO response for the PcTiO. [Copyright &y& Elsevier]

Three main patterns of aortic sinus rotation were defined on 517 lateral angiograms of tetralogy of Fallot with 14 cases of anomalous coronary artery pattern occurring only in patients with a right anterior or right lateral aorta. The significant dependence of coronary artery types on the aortic sinus pattern made it possible to predict the predisposing coronary artery pattern in tetralogy of Fallot based on the aortic sinus pattern. [ABSTRACT FROM AUTHOR]

In this paper, the elastic fields of a wedge disclination in a functionally graded cylinder are obtained in closed-form by directly solving the equilibrium equations. The cylinder material is graded radially according to a power law characterized by a gradient index. The disclination has a small fixed core of nanometer dimension. The results show that: (1) the displacement, radial and transverse stresses vary with the radial coordinate according to a sum of power laws, (2) the gradient index changes the elastic fields through modification of the elastic parameters, and modification of the power law indices of the field dependence on (i) the radial coordinate and (ii) the cylinder dimensions, (3) the stresses at and near the disclination core are generally reduced by both positive and negative gradients, (4) the transverse stress at the disclination core can be reduced to zero and even compressive for small negative gradients, (5) a significant size effect exists for the disclination stresses, and the effect is influenced strongly by the gradient index, (6) the energy of the disclination is a strong, non-monotonic function of the gradient. These results suggest that various relaxation phenomena such as crack nucleation and disclination splitting may be controlled by selecting a suitable gradient for the material variation. • Obtains elasticity solutions for a wedge disclination in a functionally graded cylinder. • A radial gradient is used to tailor the displacement and stresses. • Helps to understand disclination relaxations, e.g., crack nucleation and disclination splitting. • Helps to understand the size effect of critical disclination strengths. • Development of strong and tough materials for critical applications. [ABSTRACT FROM AUTHOR]

• The flow and heat transfer of a channel with a twisted-tape pin-fin array were studied. • The multiple vortical flows induced by the twisted-tape pin-fin array increased the heat transfer rate. • The Nu value of the designed channel was 5.26–4.73 times higher than that of a plain tube. • The TPF value of the designed channel was 1.55–1.39 times higher than that of the plain tube. • The Nu and f correlations of the designed channel were determined. In this study, an innovative twisted-tape pin-fin array was proposed for passive heat transfer enhancement (HTE) to improve the aerothermal performance of channel flows. The full-field Nusselt number distributions, Fanning friction coefficients and thermal performance factors of an improved channel were measured at Reynolds numbers of 5000, 7500, 10,000, 12,500, and 15,000. The turbulent channel flows were numerically explored using the ANSYS-Fluent code to perform correlative analysis between the aerothermal measurements and numerical flow results. A set of aerothermal data and numerical flow results was selected to illustrate the properties of HTE and the responsive flow mechanisms. Because of the vortical flows induced by each twisted tape in the array, the average measured Nusselt numbers and Fanning friction coefficients of the improved channel were 5.26–4.73 and 39.4–38.5 times higher than those of a plain tube, respectively; thus, the thermal performance factor (TPF) of the improved channel was 1.55–1.39 when 5000 < Re < 15,000. Compared with the pin-fin channels with different geometries reported in the literature, the twisted-tape pin-fin channel designed in this study provided a higher degree of HTE and thus a higher TPF at the same pressure drop penalty and pumping power. On the basis of the experimental results, two empirical correlations that were used to evaluate the average endwall Nusselt number and Fanning friction coefficient of the designed pin-fin channel were proposed for relevant applications. [ABSTRACT FROM AUTHOR]

Highlights: [•] Dedifferentiated endometrioid adenocarcinoma is characterized by the coexistence of an undifferentiated carcinoma and a low-grade endometrioid adenocarcinoma. [•] Given its histological appearance, this tumor can be mistaken for other less aggressive tumors. [•] The possibility of undifferentiated carcinoma should be considered in endometrioid carcinoma with patterns of solid growth without appreciable glandular differentiation [Copyright &y& Elsevier]

Abstract: Background: Ventriculopleural shunts have been utilized in the management of hydrocephalus since the early 1900s. Shunt malfunctions can lead to fluid accumulation in the pleural space and a tension hydrothorax can develop. Improved diagnostic and therapeutic resources have led to an increasing number of ventriculopleural shunts being utilized in patients with symptomatic hydrocephalus. Emergency physicians are being called upon more frequently to diagnose and help manage many of the critical complications that can arise with ventricular shunts. Objectives: Very little literature exists concerning the evaluation and treatment of patients with a suspected tension hydrothorax secondary to a ventriculopleural shunt malfunction. If left unrecognized and untreated, tension pneumothoraces can progress and result in hemodynamic decompensation and cardiopulmonary arrest. Patient survival depends on early diagnosis and prompt fluid drainage in this clinically challenging scenario. Case Report: This is the first article in the emergency medicine literature to describe the presentation and management of a pediatric patient who presents to the Emergency Department with a rare diagnosis of a tension hydrothorax secondary to a defective ventriculopleural shunt. Conclusion: The increasing number of ventriculopleural shunts being utilized requires emergency physicians to become familiar with the life-threatening complications that can be associated with these types of shunts. Correctly identifying this complication and initiating immediate treatment can lead to improved patient outcomes. [Copyright &y& Elsevier]

To evaluate apparent diffusion coefficient (ADC) and its standard deviation (SD ADC) in preoperative predicting liver invasion by T3-staged gallbladder carcinoma (GBC). Forty-one consecutive patients with T3-staged resectable GBC were included and divided into two sets with (n= 27) and without (n= 14) liver invasion. All patients underwent DWI at b-values of 0, 20, 50, 80, 100, 200, 400, 600, 800, and 1,000 s/mm2 with a 3 T magnetic resonance imaging scanner before surgery. ADC and SD ADC of tumour-adjacent and tumour-distant liver tissues were measured on DWI, and were compared by Mann–Whitney U -tests. If there was a significant difference in any derived parameter, the area under the receiver operating characteristic curve (AUC) was used to assess performance of this parameter to predict liver invasion. DWI could differentiate between patients with and without liver invasion when b = 0, 1,000 s/mm2 (AUCs of ADC and SD ADC were 0.697 and 0.714, respectively). In patients with liver invasion, mean ADC and SD ADC of tumour-adjacent liver tissue were lower than of tumour-distant liver tissue when b = 0, 800 s/mm2, and = 0, 1,000 s/mm2 (all p -values <0.05). To differentiate tumour-adjacent from tumour-distant liver tissues in patients with liver invasion, AUCs of ADC were 0.687 (b = 0, 800 s/mm2) and 0.680 (b = 0, 1,000 s/mm2), and AUCs of SD ADC were 0.673 (b = 0, 800 s/mm2) and 0.731 (b = 0, 1,000 s/mm2). DWI could have potential value in preoperative predicting liver invasion by T3-staged GBC. • DWI can preoperatively predict liver invasion by T 3 -staged gallbladder carcinoma. • For liver invasion, DWI can help identify tumor-adjacent and -distant liver tissues. • DWI shows no difference between tumor-adjacent and -distant tissues without invasion. [ABSTRACT FROM AUTHOR]

Introduction: Rehabilitation therapies are critical for optimizing quality-of-life and daily functions for individuals living with Parkinson's disease (PD). Thus, understanding the patterns of and under what conditions physicians make rehabilitation referrals is important for optimizing care.Method: We analyzed data from 5020 participants (4 countries) collected from 1/3/2016 to 4/20/2018 as part of the Parkinson's Foundation Quality Improvement Initiative (PF QII). Data were analyzed for single discipline and multidiscipline referrals to speech language pathology (SLP), physical therapy (PT), and occupational therapy (OT). Group comparisons (referred vs. not-referred) and regression procedures were implemented to determine demographic and clinical variables that were associated with an increased likelihood of rehabilitation referral.Results: 35.3% of participants were referred to rehabilitation services. Of these, 25.1% received a multidiscipline referral. There was a statistically significant effect of disease stage on both single discipline (χ2(2) = 45.1, p < 0.0001) and multidiscipline (χ2(2) = 74.2, p < 0.0001) referrals, with higher rates in later stages. Referred vs. not-referred participants differed significantly on a number of variables; however, only falls in the 6-months prior, advanced- and moderate-stage disease, older age, hospital admissions, and higher caregiver burden were associated with an increased likelihood of rehabilitation referral (adjusted odds ratios ≥ 1, Range = 1.08 to 1.62).Conclusions: Despite evidence supporting multidiscipline and proactive rehabilitation in PD, the majority of referrals were made to a single service and may be reactions to falls or advancing disease. Data suggest there may be missed opportunities for optimizing care through proactive rehabilitation interventions. [ABSTRACT FROM AUTHOR]

Background: Malnutrition affects body growth, size, and composition of children. Yet, few functional biomarkers are known to be associated with childhood morphology.Objective: This cross-sectional study examined associations of anthropometric indicators of height, musculature, and fat mass with plasma proteins by using proteomics in a population cohort of school-aged Nepalese children.Methods: Height, weight, midupper arm circumference (MUAC), triceps and subscapular skinfolds, upper arm muscle area (AMA), and arm fat area (AFA) were assessed in 500 children 6-8 y of age. Height-for-age z scores (HAZs), weight-for-age z scores (WAZs), and body mass index-for-age z scores (BAZs) were derived from the WHO growth reference. Relative protein abundance was quantified by using tandem mass spectrometry. Protein-anthropometry associations were evaluated by linear mixed-effects models and identified as having a false discovery rate (q) <5%.Results: Among 982 proteins, 1, 10, 14, and 17 proteins were associated with BAZ, HAZ, MUAC, and AMA, respectively (q < 0.05). Insulin-like growth factor (IGF)-I, 2 IGF-binding proteins, and carnosinase-1 were associated with both HAZ and AMA. Proteins involved in nutrient transport, activation of innate immunity, and bone mineralization were associated with HAZ. Several extracellular matrix proteins were positively associated with AMA alone. The proteomes of MUAC and AMA substantially overlapped, whereas no proteins were associated with AFA or triceps and subscapular skinfolds. Myosin light-chain kinase, possibly reflecting leakage from muscle, was inversely associated with BAZ. The proteome of WAZ was the largest (n = 33) and most comprehensive, including proteins involved in neural development and oxidative stress response, among others.Conclusions: Plasma proteomics confirmed known biomarkers of childhood growth and revealed novel proteins associated with lean mass in chronically undernourished children. Identified proteins may serve as candidates for assessing growth and nutritional status of children in similar undernourished settings. The antenatal micronutrient supplementation trial yielding the study cohort of children was registered at clinicaltrials.gov as NCT00115271. [ABSTRACT FROM AUTHOR]

Context: This scoping review maps the existing literature on narrative interventions within a palliative care and end-of-life context.Objectives: A scoping review was performed to address the following research question: What observational or randomized controlled trials have been performed to evaluate narrative interventions in the palliative care setting?Methods: A search across multiple electronic databases was performed. The search results were screened. Relevant articles were reviewed for the identification of common themes and challenges.Results: After reviewing 495 citations from electronic searches, and 44 articles from author archives or from manual review of article reference lists, we identified 34 articles for inclusion. Narrative interventions have focused on reflection or communication, and have been studied among providers, students, patients, and caregivers. Only patient/caregiver studies used randomized controlled design. Most studies were small and at the level of evaluating feasibility. Challenges include a high degree of heterogeneity among interventions and heterogeneity among parameters for evaluating those interventions.Conclusion: Narrative interventions are actively being evaluated with the intention of improving communication and well-being among all parties within the palliative care and end-of-life experience. The field would benefit from selecting a subset of outcomes that are comparable across studies, and a common framework for describing narrative interventions. Scant literature exists regarding narrative interventions to assist providers in communication. [ABSTRACT FROM AUTHOR]

Abstract Purpose The purpose of the study was to evaluate the association between a nationwide introduction of robotic minimally invasive surgery (RMIS) and survival in women with early-stage endometrial cancer. Materials and methods Prospective data on consecutive women with early-stage endometrial cancer who underwent surgery during January 2005 to June 2015 in Denmark were identified in the nationwide Danish Gynaecological Cancer Database. Data were linked with national registries regarding comorbidity, education, income and death. The cohort was divided according to the time they underwent surgery: Group 1 before RMIS introduction in their respective region and Group 2 after RMIS introduction. Five-year overall survival was compared by multivariate Cox proportional hazards models stratified by histopathological risk between Groups 1 and 2 and between surgical modalities within Group 2: total abdominal hysterectomy (TAH), laparoscopic minimally invasive surgery (LMIS) and RMIS. Results Women in Group 1 (N = 3091) had significantly lower overall survival compared with those in Group 2 (N = 2563; hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.05–1.42). Age, smoking, socioeconomic status, American Society of Anaesthesiologists (ASA) score, comorbidity and histopathological risk influenced the overall survival. Following RMIS adoption, TAH was associated with higher mortality compared with LMIS and RMIS (HR, 1.42; 95% CI 1.02–1.97 and HR, 1.70; 95% CI 1.31–2.19 for LMIS and RMIS, respectively). There was no significant survival difference between RMIS and LMIS (HR, 1.19; 95% CI 0.85–1.68). Conclusion The national introduction of robotic surgery for early-stage endometrial cancer was associated with improved survival irrespective of age, body mass index, ASA score, comorbidity, smoking, socioeconomic status and histopathological risk. Highlights • A national adoption of minimally invasive surgery for endometrial cancer is associated with improved survival. • Minimally invasive techniques yield similar survival in endometrial cancer. • Survival benefit was found independent of histopathological risk group. [ABSTRACT FROM AUTHOR]

Objective: To develop and examine the psychometric properties of the Children's Yale-Brown Obsessive-Compulsive Scale Second Edition (CY-BOCS-II) in children and adolescents with obsessive-compulsive disorder (OCD).Method: Youth with OCD (N = 102; age range 7-17 years), who were seeking treatment from 1 of 2 specialty OCD treatment centers, participated in the study. The CY-BOCS-II was administered at an initial assessment, and measures of OCD symptom severity, anxiety and depressive symptoms, behavioral and emotional problems, and global functioning were administered. Inter-rater and test-retest reliabilities were assessed on a subsample of participants (n = 50 and n = 31, respectively) approximately 1 week after intial assessment.Results: The CY-BOCS-II demonstrated moderate-to-strong internal consistency (α = 0.75-0.88) and excellent inter-rater (intraclass correlation coefficient = 0.86-0.92) and test-retest (intraclass correlation coefficient = 0.95-0.98) reliabilities across all scales. Construct validity was supported by strong correlations with clinician-rated measures of OCD symptom severity and moderate correlations with measures of anxiety symptoms. Exploratory factor analysis showed a 2-factor structure, which was generally inconsistent with its adult counterpart, the Yale-Brown Obsessive-Compulsive Scale Second Edition.Conclusion: Initial findings support the CY-BOCS-II as a reliable and valid measure of obsessive-compulsive symptoms in youth. [ABSTRACT FROM AUTHOR]

Objective: We previously reported associations between preeclampsia and the occurrence of metabolic and respiratory diseases in the offspring. In this article we examine whether the associations were due to preeclampsia or factors leading to preeclampsia. Study Design: From 1978 through 2004, we identified 22,264 discordant sib-pairs in Denmark according to prenatal exposure to preeclampsia. Exposed children were compared to their unexposed siblings by using stratified Cox regression to estimate hazard ratios and 95% confidence intervals for metabolic and respiratory diseases. Results: Exposed children had rather similar risks for metabolic disorders compared to their unexposed siblings. However, when the second child within each sib-pair was exposed, this child had an increased risk for respiratory diseases (hazard ratio, 1.55; 95% confidence interval, 1.20–2.01). Conclusion: Factors leading to preeclampsia may shape susceptibility to metabolic or respiratory diseases in the offspring but a programming effect on respiratory diseases induced by preeclampsia cannot be ruled out. [ABSTRACT FROM AUTHOR]

Objective: We assessed whether preeclampsia correlates with the long-term postnatal health of the offspring. Study Design: We conducted a population-based cohort study of 1,618,481 singletons born in Denmark (1978-2004) with up to 27 years of follow-up. We used Cox regression to estimate the associations between preeclampsia and long-term health outcomes of the offspring. Results: Children born at term exposed to preeclampsia had an increased risk of a variety of diseases, such as endocrine, nutritional, and metabolic diseases (incidence rate ratio, 1.6; 95% confidence interval, 1.5–1.7), and diseases of the blood and blood-forming organs (incidence rate ratio, 1.5; 95% confidence interval, 1.3–1.8). Children born preterm exposed to preeclampsia had a similar pattern of hospitalizations compared with the children born preterm unexposed to preeclampsia, although they had a decreased risk of cerebral palsy (incidence rate ratio, 0.7; 95% confidence interval, 0.6–0.9). Conclusion: Preeclampsia was associated with an increased risk of being hospitalized for a number of diseases, especially in the children born at term. [Copyright &y& Elsevier]

Recent advances in pollution control and monitoring technologies, improved analytical capability, changes in government priorities and results of scientific studies have substantially changed our views and perceptions towards marine pollution in the last two decades. Globally, the problems caused by eutrophication, water borne pathogens and xenobiotic compounds are likely to be exacerbated and pose significantecological and/or public health risks in the coming years, especially in developing countries. The large amount of anthropogenic input ofnutrients has caused major changes in the structure and function of phytoplankton, zooplankton, benthic and fish communities over large areas, and such a trend is likely to continue in many coastal waters. Escalated public health risks associated with the increases in frequency and severity of toxic algal blooms are also of growing concern. Reduction of nutrient input through changes in land-use and farming practises, and the development of cost-effective methods for nutrient removal are required. Water borne pathogens affect large numbers of people through consumption of contaminated seafood and direct contact with contaminated water, and such problems are much more serious in developing countries. Current techniques in monitoring bacterial indicators in water and shellfish have clear limitations and cannot afford adequate protection to safeguard public health. Emerging molecular techniques, such as multiplex PCR and specific gene probes, are likely to provide new and cost effective tools for monitoring water borne pathogens in the coming years. Nowadays, xenobiotic compounds can be found almost everywhere in any marine ecosystems. Although these compounds normally occur at very low concentrations and their effects are not well understood, there is growing concern about the chronic exposure and bioconcentration/biomagnification of xenobiotic compounds. In particular, endocrine disrupters which may cause reproductive dysfuncti [ABSTRACT FROM AUTHOR]

Uptake and loss of cobalt-57 were investigated in the starfish Asterias rubens, in order to assess its value as a sentinel organism for nearshore radionuclide contamination. Whole-body uptake from sea waterwas linear over a 32-day exposure period and reached wet weight concentration factor (CF) of 23 +/- 5. Bioaccumulation of 57Cowas dependent upon body compartment, the aboral part of the body wall concentrating cobalt to the greatest degree (wet weight CF: 77 +/- 16). After restoration of uncontaminated conditions, radiocobalt was released following an exponential loss kinetics characterized by a biological half-life (T b1/2) of 27 +/- 6 day. Dietary radiocobalt (taken up during a short-term feeding for 24 h on radiolabelled mussels) showed a much more rapid turnover time (T b1/2:14 +/- 4 d), suggesting that A. rubens accumulates this radionuclidepredominantly from sea water. A. rubens, and more particularly the aboral part of its body wall, would readily reveal the presence of an environmental contamination by radiocobalt and could preserve this information over a period of few months. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the relationship between peer pressure and the health risk behaviors of secondary school students. Study design: Cross-sectional study using a self-completed questionnaire. Methods: Secondary school students in Year 3 were the target population of this study. Information was solicited from students on their perceptions of peer pressure using a questionnaire employing the Peer Pressure Inventory and their involvement in risk behaviors using a modified global school-based student health survey. Results: A total of 840 secondary students from Hong Kong completed the questionnaires. The prevalence of secondary students who had ever smoked was 6.4%, consumed alcohol 39.2%, ever used drugs 0.5%, were sexually active 3.9%, and involved in bullying 20.5%. A higher proportion of secondary students involved in risk behaviors were affiliated with peers who were involved in the same activities: smoking (48.9%), drinking alcohol (86.5%), using drugs (18.2%), engaged in sexual activity (34.5%), and bullying (82.6%). The perception of peer conformity and peer involvement was found to be significantly correlated with the students' health risk behaviors, particularly with regard to smoking, drinking alcohol, and bullying. A logistic regression analysis showed that having friends who are involved in the same risk behaviors is the single most important factor associated with the participation of secondary students in those specific risk behaviors. Conclusions: The results of this study provided a better understanding of the association between peer pressure and the adoption of health behaviors. The development of effective peer-led prevention programs to reduce the uptake of health risk behaviors should therefore be promoted to prevent adolescents from developing serious health problems. [ABSTRACT FROM AUTHOR]

To compare the indications, specimen quality, and cost of CT versus non-image guided bone marrow aspirate and biopsy (BMAB). All CT and non-image guided BMAB performed from January 2013–July 2022 were studied. Body-mass-index (BMI), skin-to-bone distance, aspirate, and core specimen quality, and core sample length were documented. Indications for CT guided BMAB were recorded. Categorical variables were compared using chi-squared test and continuous variables using Mann-Whitney test. Analysis of per-biopsy factors used linear mixed-effect models to adjust for clustering. Cost of CT and non-image guided BMAB was taken from patient billing data. There were 301 CT and 6535 non-image guided BMABs studied. All CT guided BMAB were studied. A subset of 317 non-image guided BMAB was selected randomly from the top ten CT BMAB referrers. BMI (kg/m2) and skin-to-bone distance (cm) was higher in the CT versus the non-image guided group; 34.4 v 26.8, p < 0.0001; 4.8 v 2.5, p < 0.0001, respectively. Aspirate and core sample quality were not different between groups, p = 0.21 and p = 0.12, respectively. CT guided core marrow samples were longer, p < 0.0001. The most common CT BMAB referral indications were large body habitus (47.7 %), failed attempt (18.8 %) and not stated (17.4 %). Cost of a CT guided BMAB with conscious sedation was $3945 USD versus $310 USD for non-image guided. CT guided BMAB are commonly performed in patients with large body habitus and failed attempt. However, the cost is 12.7 fold higher with no increase in specimen quality. These findings can help referrers be cost conscious. • Requests for CT guided BMAB are increasing. • Patients undergoing CT guided BMAB have higher BMI and longer skin-to-bone distance compared to bedside BMAB. • Large body habitus, failed bedside attempt, and pain control were the most common reasons for CT guided BMAB. • There was no difference in specimen quality; however, CT guided BMAB costs 12.7 times more than non-imaged guided BMAB. [ABSTRACT FROM AUTHOR]

Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes as top dependencies specific to POU2F3-positive SCLC. Notably, chemical disruption of mSWI/SNF ATPase activity attenuates proliferation of all POU2F3-positive SCLCs, while disruption of non-canonical BAF (ncBAF) via BRD9 degradation is effective in pure non-neuroendocrine POU2F3-SCLCs. mSWI/SNF targets to and maintains accessibility over gene loci central to POU2F3-mediated gene regulatory networks. Finally, clinical-grade pharmacologic disruption of SMARCA4/2 ATPases and BRD9 decreases POU2F3-SCLC tumor growth and increases survival in vivo. These results demonstrate mSWI/SNF-mediated governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy for POU2F3-positive SCLCs. [Display omitted] • A positive selection genome-wide CRISPR-Cas9 screen identifies POU2F3 regulators • The mSWI/SNF complex maintains POU2F3 and its oncogenic program • Neuroendocrine (NE) status demarcates two subclasses of POU2F3+ SCLC • Non-NE POU2F3+ SCLCs are highly sensitive to SMARCA4/2 inhibitors and BRD9 degraders Duplaquet et al. use positive-selection CRISPR screening to identify that mSWI/SNF chromatin remodeler complexes regulate POU2F3 and its oncogenic program in SCLC and are required for POU2F3+ SCLC survival. Clinical-grade SMARCA4/2 inhibitors or BRD9 degraders demonstrate efficacy in POU2F3+ patient-derived and cell line xenograft models. [ABSTRACT FROM AUTHOR]

The POU2F3-POU2AF2/3 transcription factor complex is the master regulator of the tuft cell lineage and tuft cell-like small cell lung cancer (SCLC). Here, we identify a specific dependence of the POU2F3 molecular subtype of SCLC (SCLC-P) on the activity of the mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. Treatment of SCLC-P cells with a proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases evicts POU2F3 and its coactivators from chromatin and attenuates downstream signaling. B cell malignancies which are dependent on the POU2F1/2 cofactor, POU2AF1, are also sensitive to mSWI/SNF ATPase degraders, with treatment leading to chromatin eviction of POU2AF1 and IRF4 and decreased IRF4 signaling in multiple myeloma cells. An orally bioavailable mSWI/SNF ATPase degrader significantly inhibits tumor growth in preclinical models of SCLC-P and multiple myeloma without signs of toxicity. This study suggests that POU2F-POU2AF-driven malignancies have an intrinsic dependence on the mSWI/SNF complex, representing a therapeutic vulnerability. [Display omitted] • mSWI/SNF complex and its ATPase subunit are epigenetic dependencies in SCLC-P • POU2F3 complex requires the mSWI/SNF complex to modulate chromatin accessibility • POU2AF1 and IRF4 function as an epigenetic complex requiring mSWI/SNF in MM • An oral mSWI/SNF ATPase degrader shows potent anti-tumor efficacy in SCLC-P and MM He et al. reveal a promising avenue of treatment for small cell lung cancer and multiple myeloma driven by POU2F/POU2AF. The study highlights the potential of targeting the mSWI/SNF complex to impede oncogenic POU2F/POU2AF signaling and tumor growth, offering hope for improved therapies in these aggressive cancer types. [ABSTRACT FROM AUTHOR]

Effects of cadmium on the fertilizing capability of spermatozoa, dynamics of the first cleavage and pluteus formation in the sea urchin, Anthocidaris crassispina, were investigated. Exposure to cadmium concentrations of 0.32, 0.56, 1.0, 1.8, 3.2, 5.6 and 10.0 mg l-1 for 30 min caused a significant adverse effect on the fertilizing capability of spermatozoa (EC50=1.7 mg l-1). For the first cleavage kinetics assay, eggs were pre-exposed to 0, 0.18, 0.32, 0.56, 1.0, 1.8, 3.2 and 5.6 mg l-1 of cadmium for 30 min. Fresh sperms of fixed concentrations were then added to the eggs and the percentage of divided zygotes estimated. Concentration-dependent toxic effects on the dynamics of the first cleavage in A. crassispina were observed between 0.18 and 5.6 mg l-1 cadmium. Calculation of EC50 values by probit analysis at different stages of the first cleavage revealed that EC50 values increased gradually from 0.37 mg l-1 at the beginning to 2.24 mg l-1 at the end of the cleavage process. Different larval classes (normal, abnormal and retarded plutei, preplutei, dead embryos/larvae) of A. crassispina obtained from eggs pre-treated withcadmium for 30 min and then exposed to cadmium throughout embryogenesis were also examined. The percentage of abnormal plutei was significantly higher than that of the control at 0.56 mg l-1 cadmium and higher. The 48 h EC50 calculated for the number ofnormal plutei was 1.5 mg l-1. A chi2-test revealed significant changes in the distribution of proportions of different larval classes only at cadmium concentrations >/=1.8 mg l-1. At 5.6 mg l-1 of cadmium, small malformed plutei, and oval embryos with rudimentary skeleton, poorly differentiated intestines and no mouth (pre-pluteus stage) were observed. The relative sensitivity of various end points to cadmium is also compared and discus [ABSTRACT FROM AUTHOR]

Although Escherichia coli is widely distributed in the marine environment, only a small percentage are pathogenic to humans. Nonetheless,the widespread occurrence of waterborne infections of E. coli originin humans has become one of the major health problems worldwide. To date, several types of enterovirulent E. coli have been recognized asthe aetiologic agents of various gastrointestinal infections in humans. The most commonly encountered are those belonging to the enterotoxigenic (ETEC), enteroinvasive (EIEC), enterohaemorrhagic (EHEC) and enteropathogenic (EPEC) subtypes. In order to better determine the health risks that are associated with exposure to some of these specific subtypes, we have developed a very sensitive multiplex PCR system for the rapid detection and typing of ETEC, EHEC and possibly EPEC strains of E. coli in the aquatic environment. The target genes chosen for this investigation included: the PHO-A housekeeping gene (present in all E. coli); the LT1, LT2 and ST1 genes of ETEC; the VT1 and VT2 verotoxin, and EAE virulence genes of EHEC and EPEC, respectively. Six pairs of oligonucleotide primers were designed to simultaneously amplify internal fragments of these genes by multiplex PCR to generate PCR products that could be analysed and confirmed with relative ease by gel electrophoresis and HincII enzyme digestion. The results showed that the six sets of PCR primers were highly specific for their target genes and produced specific amplimers of the expected size from several control strains of E. coli - ATCC 35401 (LT1+/ST1+); SA53 (LT2+/VT2+); and O157 (VT1+/VT2+/EAE+). The detection sensitivity of the multiplex PCR system for the six target genes in an E. coli cell mixture was optimized and enhanced by preincubating serially diluted cells in Luria-Bertani broth for 6 h prior to PCR analysis. The results obtained indicated a detection sensitivity of 10 deg. CFU (of each strain) per 100 mu l reaction. Multiplex PCR analysis of seawater samples [ABSTRACT FROM AUTHOR]

Aeromonads occur widely in coastal waters and wastewater; and have been associated with a wide variety of gastrointestinal infections in humans. The prevalence of Aeromonas spp. in the aquatic environment has been recognized as a potential health risk, and some countries have adopted aeromonad counts as an additional indicator of water quality. In view of the above, we have attempted to develop some species-specific primers for the rapid detection of these organisms by PCR. The16S-23S rRNA intergenic spacer regions (ISR) of seven Aeromonas species - Aeromonas hydrophila, A. caviae, A. enteropelogenes, A. trota, A. jandaei, A. veronii and A. schubertii were amplified by the Polymerase chain reaction using primers complementary to conserved regions of the 16S rRNA and 23S rRNA genes. The ISR amplimers were cloned into plasmid vectors and sequenced. Analysis of the ISR sequences showedthat aeromonads contain two types of polymorphic 16S-23S spacers - ISRGlu and ISRIA. The ISRGlu containsthe tRNA gene for glutamate while ISRIA contains the tRNAgenes for isoleucine and alanine. Multiple alignment of representative ISRGlu sequences from the seven species revealed several major regions of variability. These regions were used to design Aeromonas genus-specific and species-specific primers for PCR. The specificity of the PCR primers were validated using total DNA prepared from various Aeromonas spp. and bacterial species of other genera. Results also showed that the method can be applied efficiently for routinemonitoring of aeromonads in seawater [ABSTRACT FROM AUTHOR]

Laboratory experiments were carried out to investigate the relationship between hepatocytological changes and EROD activities in the demersal fish Solea ovato up to 7 days following intraperitoneal injection of 0.1, 0.5, 1, 5 and mg/kg benzo[a]pyrene (B[a]P). At 1 and 5 mg/kg of B[a]P, observable cytological alterations involved increase in abundance of lipofuscin granules, peroxisomes, mitochondria, lipid droplets and lysosomes, slight proliferation of the ER system, and glycogen depletion. At a higher dose (10 mg/kg) of B[a]P, condensation of cytoplasmic content was observed. Stereological analysis also showed apparent changes in hepatic lipofuscin granules, peroxisomes, mitochondria and lipids in response to B[a]P exposure. Experimental results demonstrated good dose-response relationship between exposure to B[a]P and changes in EROD activities. Numerical densities of hepatic lipofuscin granules and peroxisomes were significantly correlated with EROD activities (r = 0.84, 0.75, respectively, P< 0.1). The possible relationship between EROD induction, increases of lipofuscin granules and peroxisomes as a result of B[a]P exposure in S. ovata is discussed. The observed link between EROD induction and hepatocytological changes in response to toxicant exposure provides a more meaningful interpretation of EROD induction in ecotoxicological studies. (c) 1999 sevier Science Ltd. [ABSTRACT FROM AUTHOR]