A comparison of the antischistosomal effect of levo- and dextro-praziquantel on Schistosoma japonicum and S. mansoni in mice.
Praziquantel (PZQ) is a racemic compound composed of equal proportions of its optical isomers, levo- and dextro-PZQ. The efficacy of these compounds was compared with that of PZQ in mice infected with Schistosoma japonicum or S. mansoni. Mice were given 50, 2 x 50 (on consecutive days), 500, or 2 x 250 mg/kg of each compound orally 5 weeks after infection. Significant reduction of worm recovery was observed in S. japonicum infection 30 days after treatment with 2 x 50, 500, or 2 x 250 mg/kg of levo-PZQ, whereas no therapeutic effect was demonstrated with dextro-PZQ. Percent reduction in worm burden in mice treated with levo-PZQ was significantly higher than in those with PZQ at a dosage of 2 x 50 mg/kg (67.9% vs. 34.5%). Neither eggs in feces nor miracidial hatching of eggs from the livers and intestines were observed in mice treated with levo-PZQ. In S. mansoni infection, levo-PZQ showed no significant schistosomicidal effect compared with PZQ and dextro-PZQ, although there was reduction in egg counts.


Relatives' experience of intensive care: the other side of hospitalization.
This study aims at understanding the experience concerning family members of patients in the Intensive Care Unit (ICU), with the purpose of contributing to care humanization in this context. Considering the nature of the research object, this research was carried out to understand the phenomenon Being a family that experiences the hospitalization of a family member in ICU. Phenomenology was used as a methodological reference framework. Seventeen family members of adult patients in the Intensive Care Unit (ICU) at the Santa Casa in Londrina were interviewed from September to December 2004. Through analysis of these interviews, some theme categories emerged: difficult, painful, speechless experience; experiencing and recognizing somebody's life: approaching the patient's suffering; break-up of the family's daily routine; fear of having a family member die; ICU: a fearsome scene, but necessary; concern with family care. Some issues related to the family's attendance in the ICU were discussed, contributing to the establishment of humanized care delivery to critical patients and their families' uniqueness.


Non-infusional 5-fluorouracil, doxorubicin and cisplatin in the treatment of locally advanced or metastatic gastro-oesophageal adenocarcinoma.
To reduce the Hickman line-associated morbidity of continuous infusion 5-fluorouracil combined with epirubicin and cisplatin (ECF) and to investigate the need for infusional regimens, we conducted a retrospective study in patients with advanced gastro-oesophageal adenocarcinoma. Thirty-six patients, with histologically proven irresectable gastro-oesophageal adenocarcinoma were given: 60 mg/m2 cisplatin on day 1, 35 mg/m2 doxorubicin on day 1 and 500 mg/m2 5-fluorouracil on days 1 and 8 (NIACF) every 3-weeks. A median of 3 cycles was administered. The principal toxicity was myelosuppression with grade III/IV neutropenia in 47% of cycles. Neutropenic fever occurred in 5% of the cycles: non-haematological toxicity was mild and there were no treatment-related deaths. Administered dose intensity was 96.1% for doxorubicin, 93.6% for cisplatin and 90.5% for 5-fluorouracil. There were 16 partial responses and 1 complete response (overall response rate 47%, 95% confidence interval CI 31-63%); 8 patients had stable disease. Median progression-free and overall survival rates were 5 months (95% CI 4-6) and 8 months (95% CI 6-10), respectively. NIACF is a well-tolerated regimen in advanced gastro-oesophageal adenocarcinoma that precludes the need for central venous access, with activity similar to that observed with ECF.


Pixel-Oriented Adaptive Apodization for Plane-Wave Imaging Based on Recovery of the Complete Dataset.
In theory, coherent plane-wave compounding (CPWC) enables ultrafast ultrasound imaging while maintaining a high imaging quality that is comparable to conventional B-mode imaging based on focused beam transmissions. However, in practice, due to the imperfect synthetization of transmit focusing (e.g., heterogeneous speed of sound in tissue and limited range of steering angle), CPWC suffers from a variety of imaging artifacts resulting from side lobes, grating lobes, and axial lobes. This study focuses on addressing the issues of axial lobes for CPWC, which constitutes an important source of clutter that leads to the degradation of contrast ratio and contrast-to-noise ratio (CR and CNR) of CPWC. We first investigated the source of the axial lobes based on plane-wave propagation and the delay-and-sum (DAS) beamforming. We then proposed a new method that is based on pixel-oriented adaptive apodization (POAA) to eliminate the axial lobes throughout the entire field of view (FOV). POAA was first validated in a simulation study, followed by in vitro phantom experiments and an in vivo case study on a carotid artery from a healthy volunteer. In the simulation study, suppression of axial lobes by 120 dB was observed from wire targets, and an improvement of CNR by up to 60% was found in a cyst-mimicking digital phantom. In the phantom experiment, POAA showed an improvement in CNR by around 20% over conventional methods. The effectiveness of axial lobe suppression was finally demonstrated in vivo, where POAA showed a substantial suppression of clutters throughout the entire FOV.


[The surgical treatment of malignant stomach ulcers].
The authors analyse the specific features of the clinical picture, diagnosis, pathomorphological changes and surgical treatment in 52 patients with gastric ulcer which underwent malignant degeneration. It is noted that malignancy occurs most frequently in close vicinity to the ulcerative defect and rarely in the mucosa beyond the ulcer. The morphostructural reorganizations are determined to a certain degree by the peculiarities of extension of the tumor along the mucosa and the organ as a whole. The authors discuss the principles of the choice of the method for treatment according to the findings of pathomorphological examination of biopsy material and the results of emergency intraoperative examination. Even if the merest suspicion of malignancy of the ulcer arises, the operation should be conducted with observance of all oncological principles. Postoperative mortality was 3.8%, complications occurred in 7.7% of cases. Five-year survival was 84.6% in the absence of metastases and the presence of carcinoma cells within the limits of the mucosa and 12.5% among cases in which metastases were found during the operation. Attention is drawn to the principles of regular medical surveillance over patients receiving nonoperative treatment for gastric ulcer.


Tetrakis(imino)pyracene complexes exhibiting multielectron redox processes.
The differences in redox behavior of the monofunctional bis(imino)acenaphthene (BIAN) and bifunctional tetrakis(imino)pyracene (TIP) ligands have been explored by treatment of the latter with PI(3), TeI(4), or BI(3). These reactions result in the formation of products involving the transfer of three or four electrons. Accompanying DFT calculations reveal that in each case the extent of electron transfer from each p-block element into the TIP ligand is dependent upon the element-TIP bonding interactions.


Detection and quantification of proviral HIV-1 184 M/V in circulating CD4(+) T cells of patients on HAART with a viremia less than 1,000 copies/ml.
Highly active anti-retroviral therapy (HAART) effectively reduces HIV replication but does not completely hinder it. Sub-optimal therapy leads to HIV resistance to the drugs administered. However, the role of low-level viremia (viral-load less than 1,000 copies/ml) on mutation genesis and incorporation of resistant forms in the long-lived CD4(+) T cellular DNA compartment is not clear. To investigate the relationship between lamivudine associated mutant-type 184 V and the wild-type 184 M proviral forms in the circulating CD4(+) T cells of patients and low-level viremia. Cross-sectional study of 50 patients on long-term HAART, with a viremia of less than 1 000 copies/ml. Patients were stratified into three groups; on lamivudine, group I (viral load <20 copies/ml), group II (viral load 20-1000 copies/ml) and as lamivudine experienced, group III (viral load <1000 copies/ml). 184 M and 184 V proviral HIV-1 was detected and quantified by a specific and sensitive assay combining a TaqMan real-time PCR analysis with the amplification-refractory mutation system (ARMS) principle. Fifty-six percent of patients with low-level viremia had 184 V in the CD4(+) T cellular DNA compartment as compared to only 8% in those with undetectable viremia. The presence of 184 V was significantly associated with a higher viral load (P=0.001). Patients with low-level viremia without 184 V in the CD4(+) T cellular DNA compartment, had a median plasma viral load of 135 copies/ml, while patients harbouring 184 V had a median viral load of 498 copies/ml (P=0.006). No significant differences between the groups were observed in proviral HIV-1 DNA load. The frequency of the 184 V mutation was significantly lower, in the CD4(+) T cellular compartment of patients with a viral load of less than 20 copies/ml as compared to patients with a viremia of 20-1,000 copies/ml. Viremia, sustained below 20 copies/ml may prevent the appearance of 184 V mutation in this reservoir and therefore should be the objective of treatment.


Hemidemethylation is sufficient for chromatin relaxation and transcriptional activation of methylated aprt gene in mouse P19 embryonal carcinoma cell line.
A series of clones displaying a high-frequency "switching" phenotype for expression of the adenine phosphoribosyltransferase (aprt) gene was previously isolated from the P19 mouse embryonal carcinoma stem cell line. In a subset of these clones, loss of aprt expression was correlated with increased DNA methylation, a nuclease-resistant chromatin conformation, and loss of RNA transcription; reactivation was associated with a reversal of these parameters. In this report, the role of DNA methylation in transcriptional inactivation was studied in the H22D3 clone. The cells of this clone contain a single inactive aprt allele that is methylated. Mass cultures of H22D3 were treated with 2-deoxy-5'-azacytidine (5aCdr) and found to reactivate aprt at frequencies ranging from 60 to 90%. Treated cultures were then assayed over time for aprt mRNA, chromatin conformation, and DNA methylation of the aprt gene. These studies demonstrated that 5aCdr treatment resulted in promoter region-specific hemidemethylation and chromatin relaxation starting at 12 h. This was followed by the appearance of RNA transcripts at 18 h and increasing levels of APRT enzymatic activity at 36 h after treatment. Complete demethylation occurred significantly later. Experiments in which cells were treated with 5aCdr for varying periods of time demonstrated that a single round of analog incorporation was sufficient for transcriptional reactivation of aprt in H22D3.


[Histopathologic study of the frontolateral laryngectomy specimen: topics of clinical interest].
Frontolateral laryngectomy is a surgical procedure that allows removal of a vocal cord, anterior commissure, one third of the healthy vocal cord and the thyroid cartilage keel. It is indicated in patients with T1a and T1b glottic-located carcinomas with adverse prognosis factors and selected T2 cases. The success relies on appropriate tumor excision. In order to make an assessment, we need to know the critical topics of clinic interest in the histopathologic study of the specimen. The objective is to analyze which are the significant factors to histologically assess in frontolateral laryngectomy and to report the histological study technique conducted at the Oncology Hospital of the National Medical Center of the Mexican Social Security Institute. According to the critical sites in the surgical technique and significant for local tumor recurrence, we report the histological study technique followed for the frontolateral laryngectomy specimens. The factors to assess in the frontolateral laryngectomy specimen are the anterior third part of the healthy cord, the paraglottic space and the crico-vocal ligament. The pathologic study technique reported herein allows us to satisfactorily assess these risk factors. Macroscopic tumor excision is not sufficient, and a satisfactory histological analysis is required that will allow us to assess the critical sites where there may be residual tumor. These may translate into a higher possibility of tumor recurrence for the patient. Communication between pathologists and surgeons is essential to achieve success in this procedure.


Visualization and quantitation of the expression of microRNAs and their target genes in neuroblastoma single cells using imaging cytometry.
MicroRNAs (miRNAs) are regulatory molecules that play an important role in many physiological processes, including cell growth, differentiation, and apoptosis. In addition to modulating normal cellular functions, it has also been reported that miRNAs are involved in the development of many pathologies, including cardiovascular diseases, cancer, inflammation, and neurodegeneration. Methods for the sensitive detection and measurement of specific miRNAs and their cellular targets are essential for both basic research endeavours, as well as diagnostic efforts aimed at understanding the role of miRNAs in disease processes. In this study, we describe a novel, imaging cytometry-based protocol that allows for simultaneous visualisation and quantification of miRNAs and their putative targets. We validated this methodology in a neuronal cell line by examining the relationship of the miRNA miR-124 and its known target, cyclin dependent kinase 6 (CDK6). We found that ectopic overexpression of miR-124 resulted in the downregulation of CDK6, decreased cellular proliferation, and induced cellular morphological changes. This method is suitable for analysing the expression and cellular localisation of miRNAs and target proteins in small cell subsets within a heterogeneous cell suspension. We believe that our cytometry-based methodology will be easily adaptable to miRNA studies in many areas of biomedical research including neuroscience, stem cell biology, immunology, and oncology.


First human Cerenkography.
Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues with a velocity greater than the speed of light. We present the first human Cerenkography obtained by detecting Cerenkov radiation escaping the thyroid gland of a patient treated for hyperthyroidism. The Cerenkov light was detected using an electron multiplied charge coupled device and a conventional C-mount lens. The system set-up has been tested by using a slab of ex vivo tissue equal to a 1 cm slice of chicken breast in order to simulate optical photons attenuation. We then imaged for 2 min the head and neck region of a patient treated orally 24 h before with 550 MBq of I-131. Co-registration between photographic and Cerenkov images showed a good localization of the Cerenkov light within the thyroid region. In conclusion, we showed that it is possible to obtain a planar image of Cerenkov photons escaping from a human tissue. Cerenkography is a potential novel medical tool to image superficial organs of patients treated with beta minus radiopharmaceuticals and can be extended to the imaging of beta plus emitters.


Mental Simulation of Painful Situations Has an Impact on Posture and Psychophysiological Parameters.
Embodiment is made possible by the ability to imagine ourselves in a particular situation (mental simulation). Postural changes have been demonstrated in response to painful situations, but the effect of an implicit instruction has not been studied. The present study was designed to record differential responses according to whether or not subjects were instructed to imagine themselves in a painful or non-painful situation. Painful stimuli and instructions to mentally simulate the displayed situation were hypothesized to induce postural changes that could be demonstrated by changes in the center of pressure (COP) trajectory compared to viewing the same stimuli with no instructions. We hypothesized that mental simulation of a painful situation would induce embodiment of the emotional situation as reflected by posterior displacement of the COP and physiological responses as compared to passive observation of the same visual scene. Thirty-one subjects participated in this study while standing quietly on a posturographic platform with presentation of visual stimuli depicting scenes defining three experimental conditions (painful, non-painful and neutral situations) for 12 s. Physiological measurements [heart rate (HR) and electrodermal activity] and postural responses (COP displacements) were recorded in response to the stimuli with or without instructions to imagine themselves in the situation. Time-course analyses (1 s sliding window) were conducted for several postural parameters, HR and electrodermal response. An interaction effect (instruction × stimuli × time) demonstrated that mental simulation induced posterior displacement of the mean position of the COP at different times during presentation of visual stimuli (4 s; 9-12 s). An effect of instruction was reported for HR (HR was higher in the mental simulation condition), while a stimulation effect was reported only for HR (lower for painful stimuli than for non-painful stimuli). The results of time-course analyses demonstrated embodiment of painful situations by postural control modulations and physiological changes depending on whether or not the participants were instructed to imagine themselves in the situation.


Assessment of a traditional acupuncture therapy for chronic neck pain: a pilot randomised controlled study.
This study is aimed to assess the efficacy of traditional acupuncture for chronic neck pain in patients by comparing the differences in symptoms, dysfunctions and quality of life. The study used a two-arm, single-blinded, randomised controlled design. The patients were randomised to the study group and control group, who respectively received traditional acupuncture and placebo treatment. The Northwick Park Neck Pain Questionnaire (NPQ), visual analogue scale (VAS), Short Form (36) Health Survey (SF-36) and doctor's judgement were applied for measuring effectiveness. The patients' effectiveness outcome was assessed, respectively, before the intervention, immediately after the intervention, at the end of the first month of follow-up and at the end of the third month of follow-up. The statistical analysis was done on Statistical Package for Social Sciences (SPSS) v13, which included comparison of demographic and clinical homogeneity, the repeated measures approach based on the general linear model (GLM) for effectiveness assessment and the sum rank test for doctors' subjective efficacy judgement. Totally, 190 patients were recruited and 178 patients (88 in the study group and 90 in the control group) completed the intervention and follow-up assessment. The scores of NPQ, VAS and SF-36 were improved after the intervention and during follow-up (P<0.01 vs. before the intervention). The patients in the study group had better effectiveness outcome in NPQ, VAS and in the VT, SF and MH domains of SF-36 (P<0.05). Traditional acupuncture can relieve pain intensity and improve the quality of daily life with a relative long-term clinical efficacy in patients with chronic neck pain.


Experimental manipulations of perspective taking and perspective switching in expressive writing.
Previous studies suggest that those who naturally vary their pronoun use over the course of expressive writing subsequently report the greatest improvements in physical and mental health. To explore possible perspective taking or perspective switching effects, two studies manipulated writing perspectives about emotional events from either a first-person, second-person, or third-person perspective. In Study 1, 55 students were randomly assigned to one of the three writing perspectives and were asked to write from the same perspective for three 5-minute writing sessions. In Study 2, 129 students wrote for three 5-minute sessions, one from each perspective in a counterbalanced order. The results showed that writing from a first-person perspective conferred more perceived benefits and was associated with using more cognitive mechanism words, whether engaged in perspective taking or perspective switching.


Reduced risk of prostate cancer in U.S. Men with AIDS.
Previous studies describe decreased prostate cancer risk in HIV-infected men. In the United States, prostate-specific antigen (PSA) screening is common and increases the detection of prostate cancer. We evaluated whether the prostate cancer deficit among men with AIDS reflects differential PSA screening. Data from the U.S. HIV/AIDS Cancer Match Study were used to calculate standardized incidence ratios (SIR) for prostate cancer, comparing men with AIDS (N = 287,247) to the general population. Furthermore, we estimated PSA testing rates in the Johns Hopkins HIV Clinical Cohort. Prostate cancer rates increased over time in the general population and, beginning in the 1990s, were consistently higher than among men with AIDS. Men with AIDS had the same prostate cancer risk as the general population in the pre-PSA era (<1992, SIR = 1.00), but significantly reduced risk during the PSA era overall (1992-2007, SIR = 0.50) and across age, race, HIV risk group, antiretroviral therapy era, and CD4 counts. Local and regional stage prostate cancer risk was lower among men with AIDS (SIRs, 0.49 and 0.14, respectively), but distant stage cancer risk did not differ (SIR = 0.85). Among HIV-infected men ≥40 years old, PSA testing was uncommon (18.7% per year), but increased 2.4-fold from 2000 to 2008, after age adjustment. Prostate cancer risk was decreased by 50% among men with AIDS compared with the general population. This deficit was limited to the PSA era and early stage cancers. Our findings suggest that the prostate cancer deficit in HIV-infected men is largely due to differential PSA screening.


Anemia risk in relation to lead exposure in lead-related manufacturing.
Lead-exposed workers may suffer adverse health effects under the currently regulated blood lead (BPb) levels. However, a probabilistic assessment about lead exposure-associated anemia risk is lacking. The goal of this study was to examine the association between lead exposure and anemia risk among factory workers in Taiwan. We first collated BPb and indicators of hematopoietic function data via health examination records that included 533 male and 218 female lead-exposed workers between 2012 and 2014. We used benchmark dose (BMD) modeling to estimate the critical effect doses for detection of abnormal indicators. A risk-based probabilistic model was used to characterize the potential hazard of lead poisoning for job-specific workers by hazard index (HI). We applied Bayesian decision analysis to determine whether BMD could be implicated as a suitable BPb standard. Our results indicated that HI for total lead-exposed workers was 0.78 (95% confidence interval: 0.50-1.26) with risk occurrence probability of 11.1%. The abnormal risk of anemia indicators for male and female workers could be reduced, respectively, by 67-77% and 86-95% by adopting the suggested BPb standards of 25 and 15 μg/dL. We conclude that cumulative exposure to lead in the workplace was significantly associated with anemia risk. This study suggests that current BPb standard needs to be better understood for the application of lead-exposed population protection in different scenarios to provide a novel standard for health management. Low-level lead exposure risk is an occupational and public health problem that should be paid more attention.


Gastric leiomyosarcoma: a clinicopathological review.
To report our experience of eight patients with primary gastric leiomyosarcoma. Retrospective study. Teaching hospital, Taiwan. 8 patients who presented with primary gastric leiomyosarcoma between 1986 and 1990. Endoscopic, radiological, and histopathological features, DNA ploidy, and outcome. Abdominal pain and gastrointestinal bleeding were the most common presenting symptoms. In 5 of the 7 patients who had endoscopy preoperatively a diagnosis of submucosal tumour was made, but a definite diagnosis of leiomyosarcoma was made in only 3. A provisional diagnosis of leiomyosarcoma was made in 3 of the 4 patients who had computed tomography. All patients underwent some form of gastric resection ranging from palliative resection to total gastrectomy. Patients in whom the tumour had invaded adjacent organs had a poor prognosis. Histopathological grading of tumours correlated well with DNA ploidy. Both histopathological grading and DNA ploidy could be helpful objective prognostic criteria in patients with primary gastric leiomyosarcoma.


Patients' experience of return to work rehabilitation following traumatic brain injury: a phenomenological study.
Many persons with traumatic brain injury (TBI) are young adults who, prior to their TBI, were in paid employment. Psychosocial outcome after TBI, for many, remains poor. This includes low rates of return to pre-injury work or education, among others. This qualitative study explored the experience of return to work (RTW) rehabilitation with 10 individuals who sustained TBI. Data were collected from semi-structured interviews. Transcripts were analysed using interpretative phenomenological analysis (IPA). Some of the main findings from this study included the following: Individuals find the RTW experience difficult and painful. They experience a distinct grief reaction in the process of exploring re-engagement in occupation following TBI. In view of these and other findings, changes to RTW rehabilitation should be considered to facilitate the optimal support for patients with TBI engaging in the RTW rehabilitation process.


Assessment and prevalences of diabetic complications in 722 Thai type 2 diabetes patients.
The purpose of this study is to determine the percent of patients who have been assessed as having diabetic complications as recommended by American Diabetes Association. The secondary goals were to determine factor(s) associated with reduced assessment of diabetic complication and to determine the prevalence of diabetic complications in Thai type 2 diabetes patients. We conducted a retrospective review of medical records of Thai type 2 diabetes patients who were followed up at the out-patient department (OPD) of Department of Internal Medicine at Siriraj Hospital Mahidol University Thailand during 1st January to 31st December 2006. Of 722 diabetes patients who were recruited, 7.5% were treated by general practitioners (GP), 10.4% by internal medicine residents (Res), 49.9% by internist (Int), 11.8% by endocrinologist (Endo) and 20.5% was indeterminate because they could not identify the field of the health care provider. 38.4% of patients received an eye examination by an ophthalmologist. 42% were screened for diabetic nephropathy. Serum creatinine level was measured in 83.5%. Foot examination was done in only 125 patients (17.3%). We founded that patients taken care by GP and Int received less intensive and less extensive assessment for diabetic complications than those taken care by Res and Endo. The prevalences of diabetic nephropathy and chronic kidney disease of at least stage 3 were 37 and 48.2%, respectively. Diabetic retinopathy occurred in 31.2%, cardiovascular disease in 28.9%, cerebrovascular disease in 10.6% and diabetic foot in 40%. There was a high prevalence rate of diabetic complications in patients with type 2 diabetes. Screening for diabetic complications will help to identify patients at high risk of concomitant complications eventhough some practitioners are not initially aware of the importance of the diabetic complication screening. These data may help the physician decide to modify treatment to prevent disabilities.


New magnifying laryngeal and nasopharyngeal mirrors.
Indirect laryngoscopy and nasopharyngoscopy have been a part of every routine examination by the otolaryngologist and others who choose to use this technique. However, some early lesions of the nasopharynx and laryngopharynx are not detected by the naked eye through the plain mirror. New magnifying laryngeal and nasopharyngeal mirrors are described, which help to visualize the small lesions of the larynx and nasopharynx more easily.


Fat Mass Index Better Identifies Metabolic Syndrome: Insights from Patients in Early Outpatient Cardiac Rehabilitation.
Body mass index (BMI) does not differentiate fat and lean mass or the distribution of adipose tissue. The purpose of this study was to examine the prevalence of metabolic syndrome (MetS) among patients entering outpatient cardiac rehabilitation (CR) across fat mass index (FMI) categories compared with BMI. This retrospective cross-sectional study evaluated dual-energy x-ray absorptiometry in 483 CR patients from 1 January 2014, through 31 December 2017. Clinical data were extracted from the electronic health record. Patients were grouped by FMI and BMI categories. Mean (SD) age of patients was 64.3 (14) years. The normal FMI category had 15 patients; excess fat, 74; and obese, 384. In contrast, 93, 174, and 216 were in the normal, overweight, and obese BMI categories, respectively. Prevalence of MetS was 0 (0%) in normal, 5 (1%) in excess fat, and 167 (54%) in obese FMI, with 97% in the obese category. MetS prevalence was 4 patients (0.8%) in normal, 39 (8%) in overweight, and 129 (27%) in obese BMI categories, with 75% of MetS in the obese category. FMI more accurately classified CR patients with metabolically abnormal fat (p < 0.001). FMI is a more sensitive index than BMI for metabolically abnormal fat of outpatient CR patients.


Pushing Critical Thinking Skills With Multiple-Choice Questions: Does Bloom's Taxonomy Work?
Medical school assessments should foster the development of higher-order thinking skills to support clinical reasoning and a solid foundation of knowledge. Multiple-choice questions (MCQs) are commonly used to assess student learning, and well-written MCQs can support learner engagement in higher levels of cognitive reasoning such as application or synthesis of knowledge. Bloom's taxonomy has been used to identify MCQs that assess students' critical thinking skills, with evidence suggesting that higher-order MCQs support a deeper conceptual understanding of scientific process skills. Similarly, clinical practice also requires learners to develop higher-order thinking skills that include all of Bloom's levels. Faculty question writers and examinees may approach the same material differently based on varying levels of knowledge and expertise, and these differences can influence the cognitive levels being measured by MCQs. Consequently, faculty question writers may perceive that certain MCQs require higher-order thinking skills to process the question, whereas examinees may only need to employ lower-order thinking skills to render a correct response. Likewise, seemingly lower-order questions may actually require higher-order thinking skills to respond correctly. In this Perspective, the authors describe some of the cognitive processes examinees use to respond to MCQs. The authors propose that various factors affect both the question writer and examinee's interaction with test material and subsequent cognitive processes necessary to answer a question.


A combination of cytomorphology, cytogenetic analysis, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for establishing clonality in cases of persisting hypereosinophilia.
To evaluate the frequency of clonal abnormalities in patients with unexplained persisting eosinophilia we analyzed 40 patients (27 males, 13 females) using cytomorphology, cytogenetic analysis, interphase fluorescence in situ hybridization (FISH), and reverse transcriptase polymerase chain reaction (RT-PCR). Cytogenetic analysis revealed clonal abnormalities in five patients (four of whom were males) including t(8;9)(p21;p24), ins(9;4)(q34;q12q31), del(6)(q24), and trisomy 8 (n=2). RT-PCR confirmed a PCM1-JAK2 fusion underlying the t(8;9). FISH analysis suggested a rearrangement involving PDGFRA in the ins(9;4). A FIP1L1-PDGFRA fusion gene was identified in four male patients by interphase FISH and RT-PCR. These methods in combination demonstrated clonality in 8/40 patients (20%) with a male predominance (6/8; 75%).


Ten Essential Practices for Developing or Reforming a Biostatistics Core for a NCI Designated Cancer Center.
There are 69 National Cancer Institute (NCI) designated Cancer Centers (CCs) in the United States. Biostatistical collaboration is pivotal in cancer research, and support for a cancer biostatistics shared resource facility (C-BSRF) is included in the award. Although the services and staff needed in a C-BSRF have been outlined in general terms and best practices for biostatistical consultations and collaboration in an academic health center have been agreed upon, implementing these practices in the demanding setting of cancer centers interested in pursuing or maintaining NCI designation remains challenging. We surveyed all C-BSRF websites to assess their organizational charts, governance, size, services provided, and financial models and have identified 10 essential practices for the development of a successful C-BSRF. Here, we share our success with, and barriers to, implementation of these practices. Showcasing development plans for these essential practices resulted in an NCI score of "Excellent to Outstanding" for our C-BSRF in 2015, and performance metrics in 2016-2017 demonstrated notable improvement since our original Cancer Center Support Grant (CCSG) application in 2014. We believe that the essential practices described here can be adapted and adjusted, as needed, for CCs of various sizes and with different types of cancer research programs.


Parenteral methods of supplementation with copper and selenium.
Parenteral treatments can provide a rapid successful method of supplementing ruminants with copper and selenium, and avoid the possible interactions between an oral supplement and other dietary constituents. The copper preparations studied contained copper complexed with calcium edetate (EDTA) or copper methionate , copper oxide or copper oxyquinoline sulphonate. The recommended doses of these commercial preparations contain different amounts of copper only part of which is transferred to the liver stores from which it can be released during the following months. The recommended dose of copper oxyquinoline sulphonate contains only 12 mg copper and the duration of its protective effect is short. Only a small proportion of the copper in copper methionate and copper oxide is transferred to the liver whereas nearly all the copper in a single dose of the EDTA complex (50 mg copper for sheep) is transferred to the liver stores. Although no longer recommended for use in sheep the copper EDTA complex can be administered to cattle to provide up to 1 mg copper/kg bodyweight. Selenium deficiency in both cattle and sheep can be corrected by the subcutaneous administration of up to 0.15 mg selenium/kg bodyweight as sodium selenate. However, if a dietary deficiency persists copper and selenium treatments are effective for only a few months. To avoid the need for repeated treatments, slowly dissolving or controlled release systems have been developed. Subcutaneous depots of barium selenate have been used (1 mg selenium/kg bodyweight) but large residues remained at the site of injection for up to three months. Initial trials with controlled release glasses containing copper have shown that they maybe useful for routine parenteral therapy.


Identification and analysis of a new tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol.
A new tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) was isolated from snuff tobacco. Structural characterization of this N-nitrosamine was confirmed by mass spectral analysis. Five popular US brands of moist snuff and three popular US brands of dry snuff tobacco were analyzed for moisture, nicotine and tobacco-specific N-nitrosamines. The moisture content varied from 20 to 53% in moist snuff and from 4.7 to 5.6% in dry snuff. The nicotine levels in these samples varied from 0.6 to 3.2%. The newly identified iso-NNAL was present in concentrations ranging from 0.07 to 2.5 p.p.m. whereas other tobacco-specific N-nitrosamines, N-nitrosonornicotine, N-nitrosoanatabine, N-nitrosoanabasine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone were found to range from 0.1 to 178 p.p.m. Iso-NNAL was not detected in mainstream and sidestream smoke of cigarettes. Iso-NNAL is genotoxic in primary rat hepatocytes; its tumorigenic properties are currently being tested in mice and rats.


Linking genomics and ecology to investigate the complex evolution of an invasive Drosophila pest.
Drosophilid fruit flies have provided science with striking cases of behavioral adaptation and genetic innovation. A recent example is the invasive pest Drosophila suzukii, which, unlike most other Drosophila, lays eggs and feeds on undamaged, ripening fruits. This not only poses a serious threat for fruit cultivation but also offers an interesting model to study evolution of behavioral innovation. We developed genome and transcriptome resources for D. suzukii. Coupling analyses of these data with field observations, we propose a hypothesis of the origin of its peculiar ecology. Using nuclear and mitochondrial phylogenetic analyses, we confirm its Asian origin and reveal a surprising sister relationship between the eugracilis and the melanogaster subgroups. Although the D. suzukii genome is comparable in size and repeat content to other Drosophila species, it has the lowest nucleotide substitution rate among the species analyzed in this study. This finding is compatible with the overwintering diapause of D. suzukii, which results in a reduced number of generations per year compared with its sister species. Genome-scale relaxed clock analyses support a late Miocene origin of D. suzukii, concomitant with paleogeological and climatic conditions that suggest an adaptation to temperate montane forests, a hypothesis confirmed by field trapping. We propose a causal link between the ecological adaptations of D. suzukii in its native habitat and its invasive success in Europe and North America.


Driving position field study, differences with the whiplash protocol and biomechanics experimental responses.
Rear-impact collisions at low speed are a leading cause of economic costs among motor vehicle accidents. Recently, EuroNCAP has incorporated in its protocol the whiplash test, to reproduce a low-speed rear impact. This paper presents a field driving study to assess the potential differences between the EuroNCAP dummy tests and actual drivers in the field, focusing on occupant position and biomechanics experimental results. A total of 182 drivers were randomly selected in two geographical areas in Spain. The driving position of each driver was recorded with a focus on the most relevant measurements for rear impact. Statistical analysis was performed to obtain means, standard deviations and density functions to compare observational seating position with that of the EuroNCAP testing protocol. The observational data showed a similar seatback angle to that used in the EuroNCAP protocol (24° in front of 25° for the protocol), a greater distance between the head vertex and the top of the head restraint (53mm compared to 39.5mm), and less distance between the occipital bone of the head and the headrest (67.9 compared to 89.3mm). Based on these data, 4 dummy tests were conducted using the dummy BioRID IIg. The baseline test was designed to reproduce the dummy position according to EuroNCAP 3.0 whiplash protocol. Three different additional tests were defined to reproduce the actual observed driving position as well as to assess a "worst case" scenario in terms of reduced seatback angle. These variations in initial driver position, comparing the EuroNCAP protocol to the observational study results, were not observed to cause significant differences in the biomechanical values measured in the BioRID IIg, The T1 acceleration was reduced less than 8%, the NIC was increased about 8%, and the NKm presented a reduction of 20%. Reducing the seat angle was observed to be more harmful in terms of NIC.


Effects of different luting agents on bond strengths of fiber-reinforced composite posts to root canal dentin.
To evaluate the bond strength between two fiber posts (FRC Postec and DT Light Post) and different composite resins following different surface treatments of the posts. One hundred sixty extracted teeth were divided into sixteen groups (n = 10). After pretreatment of the post surface with (1) no treatment, (2) silanization, (3) sandblasting + silanization or (4) tribochemical coating, the posts were either luted with the resin cements provided by the manufacturers of the post system or with a core buildup material. Push-out tests were performed in a universal testing machine until the post segment was dislodged from the root section. Data were analyzed using ANOVA. Multiple comparisons were performed using Tukey's test. FRC Postec achieved significantly higher bond strengths than DT Light Post (p < 0.0001). Cementation with the core buildup material showed significantly higher bond strengths than the resin cement provided by the post manufacturers (p < 0.0001). Post type, type of surface treatment and type of resin cement were significant factors for bond strength. Luting with a core buildup material significantly increased the bond strengths.


Diffractive lens design for optimized focusing.
We utilized nonlinear optimization to design phase-only diffractive lenses that focus light to a spot, whose width is smaller than that dictated by the far-field diffraction limit. Although scalar-diffraction theory was utilized for the design, careful comparisons against rigorous finite-difference time-domain simulations confirm the superfocusing effect. We were able to design a lens with a focal spot size that is 25% smaller than that formed by a conventional lens of the same numerical aperture. An optimization strategy that allows one to design such lenses is clearly explained. Furthermore, we performed careful simulations to elucidate the effects of fabrication errors and defocus on the performance of such optimized lenses. Since these lenses are thin, binary, and planar, large uniform arrays could be readily fabricated enabling important applications in microscopy and lithography.


Interaction of blood components with heparin-immobilized polyurethanes prepared by plasma glow discharge.
The blood compatibility of poly(ethylene oxide) (PEO)-grafted and heparin (Hep) immobilized polyurethanes was investigated using in vitro plasma recalcification time (PRT), activated partial thromboplastin time (APTT), platelet adhesion and activation, and peripheral blood mononuclear cell (PBMC) adhesion and activation. In the experiment with plasma proteins, the PRT of the polyurethane (PU) surface was prolonged by PEO grafting and further prolonged by heparin immobilization. The APTT was prolonged on PU-Hep, suggesting the binding of immobilized heparin to antithrombin III. The percentage of platelet adhesion on PU was not much different from that on acrylic acid- and PEO-grafted PUs (PU-C, PU-6, PU-33), yet was substantially decreased by heparin immobilization (PU-6-Hep, PU-33-Hep). The release of serotonin from adhering platelets was slightly suppressed on PEO-grafted PUs yet significantly suppressed on heparin-immobilized PUs. In the PBMC experiments, the adhesion and activation of the cells were significantly suppressed on heparin-immobilized PUs, and the amount of interleukin-6 (IL-6) released from PBMCs stimulated with surface-modified PUs decreased with a decrease in PBMC adhesion.


A receptor-mediated mechanism of nicotine toxicity in oral keratinocytes.
Smoking and smokeless tobacco cause morbidity that originates from the epithelium lining of the skin and upper digestive tract. Oral keratinocytes (OKC) express nicotinic acetylcholine receptors (nAChRs) that bind nicotine (Nic). We studied the mechanism of the receptor-mediated toxicity of tobacco products on OKC. Preincubation of normal human OKC with Nic altered the ligand-binding kinetics of their nAChRs, suggesting that the nAChRs underwent structural changes. This hypothesis was confirmed by the finding that exposure of OKC to Nic causes transcriptional and translational changes. Through RT-PCR and immunoblotting, we found a 1.5- to 2.9-fold increase in the mRNA and protein levels of alpha3, alpha5, alpha7, beta2, and beta4 nAChR subunits. Exposure of OKC to Nic also changed the mRNA and protein levels of the cell cycle and cell differentiation markers Ki-67, PCNA, p21, cyclin D1, p53, filaggrin, loricrin, and cytokeratins 1 and 10. The nicotinic antagonist mecamylamine prevented these changes, which indicates that the Nic-induced changes in the expression of both the nAChR and the cell cycle and cell differentiation genes resulted from pharmacologic stimulation of nAChRs with Nic. To establish the relevance of these findings to the pathobiologic effects of tobacco products in vivo, we studied the above parameters in the oral tissue of rats and mice after their exposure for 3 weeks to environmental cigarette smoke or drinking water containing equivalent concentrations of Nic that are pathophysiologically relevant. The changes of the nAChRs and the cell cycle and cell differentiation genes were similar to those found in vitro. The results of indirect immunofluorescence assay of tissue specimens validated these findings. Thus, some pathobiologic effects of tobacco products in oral tissues may stem from Nic-induced alterations of the structure and function of keratinocyte nAChRs responsible for the physiologic regulation of the cell cycle by the cytotransmitter acetylcholine.


Hypertension and quality of life issues.
A number of lifestyle modifications and a variety of highly effective and reasonably safe classes of antihypertensive agents can satisfactorily control elevated blood pressure in most patients. As clinicians evaluated their patients' response to antihypertensive regimens, in addition to measurement of the level of blood pressure and review of laboratory test values, there should be assessment of quality of life outcomes. These include the impact of therapy on the patients' daily routine; on fatigue or activity limitation; on sexual dysfunction; on impairment of memory, alertness, mood, or cognitive ability; on sleep dysfunction; work performance and satisfaction; and satisfaction with family, social, and leisure time activities.


Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiation.
MicroRNAs (miRNAs) play important roles in differentiation of stem cells. However, the precise dynamics of miRNA induction during stem cell differentiation have not been visualized and molecular mechanisms through which miRNAs execute their function remain unclear. Using high-resolution in situ hybridization together with cell lineage and proliferation markers in mouse skin, we show that miR-203 is transcriptionally activated in the differentiating daughter cells upon the asymmetric cell division of interfollicular progenitor cells. Once induced, miR-203 rapidly promotes the cell cycle exit within 6 hours and abolishes self-renewal of the progenitor cells. With an inducible mouse model, we identify numerous miR-203 in vivo targets that are highly enriched in regulation of cell cycle and cell division, as well as in response to DNA damage. Importantly, co-suppression of individual targets, including p63, Skp2 and Msi2 by miR-203 is required for its function of promoting the cell cycle exit and inhibiting the long-term proliferation. Together, our findings reveal the rapid and widespread impact of miR-203 on the self-renewal program and provide mechanistic insights into the potent role of miR-203 during the epidermal differentiation. These results should also contribute to understanding the role of miR-203 in the development of skin cancer.


Feasibility study for a novel method of dual energy x-ray analysis.
Dual energy x-ray analysis (DEXA) is investigated using a nonlinear model for the x-ray linear attenuation coefficient μ that is expressed as a function of electron density N(e) and the fourth compositional ratio R₄. Nonlinear simultaneous equations are solved using a least-squares algorithm based upon the method of Levenberg and Marquardt. Measurements of μ for low atomic number materials (containing elements hydrogen to calcium) at energies 32-66 keV are used to study DEXA accuracy as a function of sample composition, photon energy and their separation ΔE. Results are presented for ΔE = 5-30 keV, for 2% measurement precision, and the doses involved are quantified. The model is subject to propagation of error analysis and results are presented for the relationship between measurement uncertainties and those for N(e) and R₄. The analysis shows how DEXA accuracy is controlled by the fractional compositional cross-product, which represents the contribution of composition to μ, and how this can be optimized by careful selection of beam energies according to the compositional range of interest. Accurate DEXA is achieved over restricted energy and compositional ranges: soft tissues only at approximately 15-25 keV, all tissues at approximately 30-80 keV and, for situations where a higher dose can be tolerated, all tissues at approximately 4-8 MeV.


[Value and possibilities of ultrasonic screening of pregnant women for detection of fetal congenital malformations].
Ultrasonic screening was performed in 4200 pregnant females, mainly within 16-24 weeks of gestation. Various congenital abnormalities of fetal development were diagnosed in 41 females. 51 per cent of the examinees had various combinations of congenital malformations. The total detection rate of congenital malformation in the region studied was 14.7 per cent. The screening revealed the disease in 9.76 per cent of those examined. The data obtained evidenced the high performance of the technique in the prenatal diagnosis of fetal congenital malformations.


Can rhythm-mediated reward boost learning, memory, and social connection? Perspectives for future research.
Studies of rhythm processing and of reward have progressed separately, with little connection between the two. However, consistent links between rhythm and reward are beginning to surface, with research suggesting that synchronization to rhythm is rewarding, and that this rewarding element may in turn also boost this synchronization. The current mini review shows that the combined study of rhythm and reward can be beneficial to better understand their independent and combined roles across two central aspects of cognition: 1) learning and memory, and 2) social connection and interpersonal synchronization; which have so far been studied largely independently. From this basis, it is discussed how connections between rhythm and reward can be applied to learning and memory and social connection across different populations, taking into account individual differences, clinical populations, human development, and animal research. Future research will need to consider the rewarding nature of rhythm, and that rhythm can in turn boost reward, potentially enhancing other cognitive and social processes.


Using an Optimized Marijuana Purchase Task to Examine Cannabis Demand in Relation to Cannabis Misuse in Heavy Drinking Emerging Adults.
A behavioral economic approach to cannabis misuse emphasizes a crucial role of high drug demand (i.e., reinforcing value), which may be measured using a marijuana purchase task (MPT). The multiple indices from this measure have been associated with cannabis misuse, but somewhat inconsistently, possibly because of task variability across studies. Based on recent qualitative research, the current study implemented an optimized MPT to examine the underlying factor structure and the relationship between cannabis demand and both cannabis misuse and motivation to change. Participants were two independent samples of emerging adults who reported cannabis use and heavy episodic drinking in the last month, one Canadian (n = 396) and the other American (n = 275). Both were assessed using an MPT, the Cannabis Use Disorder Identification Test (CUDIT), the Marijuana Adverse Consequences Questionnaire (MACQ), and readiness to change items. Principal component analyses of the MPT indices revealed the same two-factor latent structure in both samples, interpreted as Amplitude (intensity, Omax, elasticity) and Persistence (breakpoint, Pmax). Regressions revealed that Amplitude was significantly associated with CUDIT and MACQ in both samples. In the Canadian sample, Persistence was also significantly associated with CUDIT and MACQ, and both factors were associated with motivation to change. The optimized MPT generated a two-factor latent structure that was parallel across samples, and the Amplitude factor was consistently associated with cannabis misuse. The current findings indicate the robust relevance of behavioral economic demand for cannabis in relation to cannabis misuse but suggest that links to motivation may be sample-specific.


Ureteral mast cell tumor in a dog.
A 6-year-old, castrated male, mixed-breed dog was diagnosed with partial unilateral ureteral obstruction secondary to a ureteral mass. The ureteral mass was surgically resected, and an ureteroneocystostomy was performed. Histopathology of the ureteral mass was consistent with a poorly differentiated mast cell tumor (MCT). The patient recovered well but was euthanized 5 months postoperatively for central nervous system signs. A choroid plexus tumor was diagnosed during necropsy examination. There was no evidence of recurrence or dissemination of the ureteral MCT. Extracutaneous MCTs are rare in dogs, and primary MCT associated with the urinary tract has not previously been reported in the veterinary literature.


Insects in fluctuating thermal environments.
All climate change scenarios predict an increase in both global temperature means and the magnitude of seasonal and diel temperature variation. The nonlinear relationship between temperature and biological processes means that fluctuating temperatures lead to physiological, life history, and ecological consequences for ectothermic insects that diverge from those predicted from constant temperatures. Fluctuating temperatures that remain within permissive temperature ranges generally improve performance. By contrast, those which extend to stressful temperatures may have either positive impacts, allowing repair of damage accrued during exposure to thermal extremes, or negative impacts from cumulative damage during successive exposures. We discuss the mechanisms underlying these differing effects. Fluctuating temperatures could be used to enhance or weaken insects in applied rearing programs, and any prediction of insect performance in the field-including models of climate change or population performance-must account for the effect of fluctuating temperatures.


Aspartic protease inhibitors as potential anti-Candida albicans drugs: impacts on fungal biology, virulence and pathogenesis.
Mycoses are still one of the most problematic illnesses worldwide, especially affecting immunocompromised individuals. The development of novel antifungal drugs is becoming more demanding every day, since existing drugs either have too many side effects or they tend to lose effectiveness due to the resistant fungal strains. In this scenario, Candida albicans is still the main fungal pathogen isolated in hospitals. Pathogenicity results essentially from modifications of the host defense mechanisms that secondarily initiate transformations in the fungal behavior. The pathogenesis of C. albicans is multifactorial and different virulence attributes are important during the various stages of infection. Some virulence factors, like the secreted aspartic proteases (Saps), play a role in several infection stages and the inhibition of one of the many stages may contribute to the containment of the pathogen and thus should help in the treatment of disease. Therefore, Saps are potential targets for the development of novel anti-C. albicans drugs. Herein, we review the beneficial properties of pepstatin A and aspartic-type protease inhibitors used in the anti-human immunodeficiency virus chemotherapy on C. albicans, with particular emphasis in the effects on Sap activity, proliferation, morphogenesis (yeasts into mycelia transformation), ultrastructural architecture, adhesion to mammalian cells and abiotic materials, modulation of unrelated virulence factors (e.g., surface glycoconjugates, lipases and sterol), experimental candidiasis infection as well as synergistic properties when conjugated with classical antifungals. Collectively, these positive findings have stimulated the search for novel natural and/or synthetic pharmacological compounds with anti-aspartic protease properties against the human opportunistic fungus C. albicans.


Effect of Hypercapnia, an Element of Obstructive Respiratory Disorder, on Pancreatic Cancer Chemoresistance and Progression.
Chronic obstructive respiratory disorders (ORDs) are linked to increased rates of cancer-related deaths. Little is known about the effects of hypercapnia (elevated CO2) on development of pancreatic ductal adenocarcinoma (PDAC) and drug resistance. Two PDAC cell lines were exposed to normocapnic (5% CO2) and hypercapnic (continuous/intermittent 10% CO2) conditions, physiologically similar to patients with active ORD. Cells were assessed for proliferation rate, colony formation, and chemo-/radiotherapeutic efficacy. In a retrospective clinical study design, patients with PDAC who had undergone pancreatic resection between 2002 and 2014 were reviewed. Active smokers were excluded to remove possible smoking-related protumorigenic influence. Clinical data, pathologic findings, and survival end points were recorded. Kaplan-Meier and Cox regression analyses were performed. Exposure to hypercapnia resulted in increased colony formation and proliferation rates in vitro in both cell lines (MIA-PaCa-2: 111% increase and Panc-1: 114% increase; p < 0.05). Hypercapnia exposure induced a 2.5-fold increase in oxaliplatin resistance (p < 0.05) in both cell lines and increased resistance to ionizing radiation in MIA-PaCa-2 cells (p < 0.05). Five hundred and seventy-eight patients were included (52% were male, median age was 68.7 years [interquartile range 60.6 to 76.8 years]). Cox regression analysis, assessing TNM staging, age, sex, and ORD status, identified ORD as an independent risk factor for both overall survival (hazard ratio 1.64; 95% CI, 1.2 to 2.3; p < 0.05) and disease-free survival (hazard ratio 1.68; 95% CI, 1.06 to 2.67). PDAC cells exposed to hypercapnic environments, which is common in patients with ORD, showed tumor proliferation, radioresistance, and chemoresistance. Patients with a history of ORD had a worse overall prognosis, suggesting that hypercapnic conditions play a role in the development and progression of PDAC and stressing the need for patient-tailored care.


Physical Foaming and Crosslinking of Polyethylene with Modified Talcum.
The aim of this study was the investigation of the use of modified talcum for supporting crosslinking and as novel nucleating agent for physical foaming of polyethylene. For the modification of the talcum, a thermal initiator was linked to the talcum surface. During the extrusion process, the initiator decomposes, and gas and radicals are formed. The gas generates the nucleation of cells and the radicals support the crosslinking process between the polymer chains. The modification of the talcum was performed in three steps: The first step was the grafting of alkoxysilanes onto the talcum surface. The second step was the chlorination of the thermal initiator for an easier linkage, and the last step was the linking between the initiator and the silanes grafted onto the talcum surface. For this study, two investigations were carried out. One investigation was the analysis of the crosslinking effect with the modified talcum. For this purpose, polyethylene plates were compression molded and the viscoelastic properties were measured with a parallel plate rheometer. The use of the modified talcum led to a higher crosslinking density. The second investigation was the physical foaming experiment in an extrusion process with nitrogen as blowing agent using both a pure and the modified talcum as nucleating agents. The foamed samples were characterized in terms of density, cell size and cell density, and compared with each other. The blend with the modified nucleating agent indicated a foam structure with a smaller mean cell size and a lower density compared to the use of the pristine nucleating agent.


Levodopa infusion combined with entacapone or tolcapone in Parkinson disease: a pilot trial.
Catechol-O-methyltransferase inhibitors may be used to decrease levodopa requirement. The objective was to investigate whether the levodopa/carbidopa intestinal gel infusion dose can be reduced by 20% without worsening of motor fluctuations and levodopa concentration stability when oral catechol-O-methyltransferase inhibitors are added. A short-term, randomized, partly blinded, crossover, investigator-initiated clinical trial was performed, with levodopa/carbidopa intestinal gel combined with oral entacapone and tolcapone on two different days in 10 patients. The primary outcome measure was difference in coefficient of variation of levodopa in plasma between levodopa/carbidopa, levodopa/carbidopa/entacapone, and levodopa/carbidopa/tolcapone. The secondary outcome measures other pharmacokinetic variables, patient-reported outcome, and blinded analysis of motor performance. Variation of plasma levodopa concentrations did not differ significantly between the treatments. The treatments did not differ regarding motor performance. Levodopa concentrations were significantly higher using tolcapone. Concentrations of the metabolite 3-O-methyldopa decreased gradually during catechol-O-methyltransferase inhibition. According to this small, short-term pilot study, oral catechol-O-methyltransferase inhibitors administered in 5-h intervals may be useful in cases where levodopa/carbidopa intestinal gel dose reduction is wanted. Stability of plasma levodopa levels is not significantly altered, and off-time is not increased when decreasing the levodopa/carbidopa intestinal gel dose by 20%. Rather, the dose should probably be decreased more than 20%, especially under tolcapone co-treatment, to avoid increased dyskinesias with time.


Design and Preparation Technology of Single/Dual-Cross-Linking Copolymers Based on Swida wilsoniana Oil.
To fully utilize the forestry bioresources, a novel dual-cross-linkable resin monomer of MAHSWAGMA was prepared from Swida wilsoniana oil (SWO). FT-IR and 1H-NMR analysis demonstrated the successful synthesis of the target product. Five different cross-linking copolymers, including a polymerized vinyl ester/single-cross-linking (PVESC) polymer, a polymerized epoxy/single-cross-linking (PESC) copolymer, a thermal-photo-initiated/dual-cross-linking (TPIDC) copolymer, a photo-thermal-initiated/dual-cross-linking copolymer (PTIDC), and a thermal-initiated/dual-cross-linking copolymer (TIDC), were obtained with different preparation technologies by different initiated cross-linking processes. Thermal and mechanical properties of the five copolymers were all tested, and the effects of different preparation technologies on the properties of prepared copolymers were investigated. The prepared three dual-cross-linking copolymers had higher hardness, relative cross-linking density, glass transition temperature, and more excellent mechanical property than the other two single-cross-linking copolymers. The PTIDC copolymerized system obtained with photo first and thermal latter initiated dual-cross-linking preparation technology had the most excellent comprehensive properties. This study can provide an ideal idea for the design and preparation of dual-cross-linking copolymers based on forestry vegetable oil.


SARS-CoV-2 Kappa Variant Shows Pathogenicity in a Syrian Hamster Model.
Objectives: The emergence of SARS-CoV-2 lineage B.1.617 variants in India has been associated with a surge in the number of daily infections. We investigated the pathogenic potential of Kappa (B.1.617.1) variant in Syrian golden hamsters. Methods: Two groups of Syrian golden hamsters (18 each) were inoculated intranasally with SARS-CoV-2 isolates, B.1 (D614G) and Kappa variant, respectively. The animals were monitored daily for the clinical signs and body weight. Throat swab, nasal wash, and organ samples (lungs, nasal turbinate, trachea) were collected and screened using SARS-CoV-2-specific RT-qPCR. Histopathologic evaluation of the lung samples was performed. Results: The hamsters infected with the Kappa variant demonstrated increased body weight loss compared to the B.1 lineage isolate. The highest viral RNA load was observed in the nasal turbinate and lung specimens of animals infected with both variants. A significantly higher sgRNA load was observed in the nasal swabs (7 DPI), trachea (3 DPI), and lungs (3 DPI) of hamsters infected with the Kappa variant. Neutralizing antibody response generated in the B.1 lineage-infected hamster sera were comparable against both B.1 and Kappa variant in contrast to Kappa variant-infected hamsters, which showed lower titers against B.1 lineage isolate. Gross and microscopic evaluation of the lung specimens showed severe lung lesions in hamsters infected with Kappa variant compared to B.1. Conclusions: The study demonstrates pathogenicity of Kappa variant in hamsters evident with reduced body weight, high viral RNA load in lungs, and pronounced lung lesions. Both Kappa variant- and B.1-infected hamsters produced neutralizing antibodies against both variants studied.


A study of human serum sickness.
Twelve patients with bone marrow failure, who were undergoing therapy with daily intravenous infusions of horse antithymocyte globulin, were studied for the development of serum sickness. Eleven of 12 patients developed typical signs and symptoms of serum sickness 8-13 days after the initiation of treatment. These included fever, malaise, cutaneous eruptions, arthralgias, gastrointestinal disturbances, and lymphadenopathy. Eleven of 12 patients developed high levels of circulating immune complexes during serum sickness. All 12 patients also had concomitant decreases of serum C3 and C4 levels. In addition to urticarial and/or morbilliform eruptions, 8 of 11 patients also developed a serpiginous band of erythema along the sides of the fingers, hands, toes, or feet as an early cutaneous sign of serum sickness. Direct immunofluorescence of lesional skin biopsies during serum sickness revealed deposits of immunoglobulin or complement in the walls of small cutaneous blood vessels in 3 of 5 patients. These findings indicate that circulating immune complexes play a central role in the pathophysiology of human sickness.


Scaling law for energy-momentum spectra of atomic photoelectrons.
A scaling law which was used to classify photoelectron angular distributions (PADs) is now extended to photoelectron kinetic energy spectra. Both a theoretical proof and an independent verification are presented. Considering PADs are of photoelectron momentum spectra, this extension really extends the scaling law to the entire energy-momentum spectra. The scaling law for photoelectron energy-momentum spectra applies to both directly ionized and rescattered photoelectrons. Re-scaling experimental input parameters without loosing the physical essence with this scaling law may ease the experimental conditions and reduce the material and the energy consumptions in the experiments.


A major food web component in the orinoco river channel: evidence from planktivorous electric fishes.
Deep-water sampling of the Orinoco River main channel resulted in the collection of an unexpectedly high abundance and diversity of specialized fishes. Twenty-eight of the more than 60 species collected belong to the Gymnotiformes(New World electric or knife fishes). One of the more numerous of these, a recently described species of the genus Rhabdolichops, consumes large numbers of very small planktonic Crustacea and insect larvae. These items are captured in the very swift, turbid, and deep waters of the Orinoco. Although the strong dependence of the river food web on terrestrial and floodplain food sources is well known, the specialized capabilities of Rhabdolichops and of other fishes that occur with it indicate a significant extension of the river food web into the main channel.


Direct AKAP-mediated protein-protein interactions as potential drug targets.
A-kinase-anchoring proteins (AKAPs) are a diverse family of about 50 scaffolding proteins. They are defined by the presence of a structurally conserved protein kinase A (PKA)-binding domain. AKAPs tether PKA and other signalling proteins such as further protein kinases, protein phosphatases and phosphodiesterases by direct protein-protein interactions to cellular compartments. Thus, AKAPs form the basis of signalling modules that integrate cellular signalling processes and limit these to defined sites. Disruption of AKAP functions by gene targeting, knockdown approaches and, in particular, pharmacological disruption of defined AKAP-dependent protein-protein interactions has revealed key roles of AKAPs in numerous processes, including the regulation of cardiac myocyte contractility and vasopressin-mediated water reabsorption in the kidney. Dysregulation of such processes causes diseases, including cardiovascular and renal disorders. In this review, we discuss AKAP functions elucidated by gene targeting and knockdown approaches, but mainly focus on studies utilizing peptides for disruption of direct AKAP-mediated protein-protein interactions. The latter studies point to direct AKAP-mediated protein-protein interactions as targets for novel drugs.


Aggressive surgical resection does not improve survival in operable esophageal squamous cell carcinoma with N2-3 status.
To investigate the influence of nodal status on response and clarify the optimal treatment for operable esophageal squamous cell carcinoma (OSCC). We retrospectively analyzed 1490 OSCC patients who underwent transthoracic esophagectomy and lymphadenectomy between December 1996 and December 2009 at the Sun Yat-sen University Cancer Center. The surgical approach and the number of resected lymph nodes (LNs) were considered in the assessment of surgery. Patients were classified according to their nodal statuses (N0 vs N1 vs N2-3). Overall survival was defined as the time from the date of death or final follow-up. Survival analysis was performed using the Kaplan-Meier method and differences between curves were assessed by the log-rank test. Univariate and multivariate Cox regression analyses were used to identify factors associated with prognosis. Statistical significance was assumed at a P < 0.05. With a median time from surgery to the last censoring date for the entire cohort of 72.2 mo, a total of 631 patients were still alive at the last follow-up and the median survival time was 35.5 mo. The surgical approach (left transthoracic vs Ivor-Lewis/tri-incisional) was verified as independent prognostic significance in patients with N0 or N1 status, but not in those with N2-3 status. Similar results were also observed with the number of resected LNs (≤ 14 vs ≥ 15). Compared with surgery alone, combined therapy achieved better outcomes in patients with N1 or N2-3 status, but not in those with N0 status. For those with N2-3 status, neither the surgical approach nor the number of resected LNs reached significance by univariate analysis, with unadjusted HRs of 0.826 (95%CI: 0.644-1.058) and 0.849 (95%CI: 0.668-1.078), respectively, and aggressiveness of surgery did not influence the outcome; the longest survival was observed in those patients who received the combined therapy. Combined therapy has a positive role in OSCC with LN metastasis, and aggressive surgical resection does not improve survival in patients with N2-3 status.


Accidental ingestion of an air-water syringe tip during routine dental treatment: a case report.
Accidental ingestion of instruments or their components is a possible complication of dental treatment. Although in many cases the foreign object can pass through the gastrointestinal tract without any need for surgical intervention to retrieve it, sometimes such incidents can be life-threatening. This paper reports a case of accidental ingestion of an air-water syringe tip during routine dental treatment for which endoscopic retrieval was required. The present case highlights the need for dental professionals to be aware of the fact that dental equipment comprising multiple components may be associated with a risk of accidental detachment of a component and its ingestion or aspiration by a patient receiving treatment.


Biotransformation of volatile fatty acids by oleaginous and non-oleaginous yeast species.
The possibility of utilizing volatile fatty acids (VFA)-containing waste substrates from biotechnological and industrial processes was investigated by cultivating both oleaginous (Candida sp., Rhodotorula glutinis, Trichosporon cutaneum, Yarrowia lipolytica) and non-oleaginous (Kluyveromyces polysporus, Saccharomyces cerevisiae, Torulaspora delbrueckii) yeast species on acetic acid, propionic acid and a combination of either acid with glucose as carbon and energy sources. Both oleaginous and non-oleaginous yeasts grew on VFA. Oleaginous yeasts accumulated lipids to 15-48% of dry cell weight, non-oleaginous yeasts also grew on VFA and showed comparable biomass yields but the lipid content was only 2-5%. Biomass and lipid yield increased in cultivations on VFA plus glucose. The lipid composition was comparable to plant-derived oils and therefore might be exploitable in biodiesel production; nearly all species, when cultured on propionate, showed a high content of the desirable odd-chain unsaturated FA, especially 17:1 acid. This study points at the wide array of possible applications of many yeasts, even non-oleaginous strains, for biovalorization of industrial wastes. Despite their low lipid content these species are useful because they can readily utilize VFA from waste products and, since they are not biologically hazardous, their biomass can be afterwards used, e.g. as livestock fodder.


Preoperative risk model for perioperative stroke after intracranial tumor resection: ACS NSQIP analysis of 30,951 cases.
Perioperative and/or postoperative cerebrovascular accidents (PCVAs) after intracranial tumor resection (ITR) are serious complications with devastating effects on quality of life and survival. Here, the authors retrospectively analyzed a prospectively maintained, multicenter surgical registry to design a risk model for PCVA after ITR to support efforts in neurosurgical personalized medicine to risk stratify patients and potentially mitigate poor outcomes. The National Surgical Quality Improvement Program database was queried for ITR cases (2015-2019, n = 30,951). Patients with and without PCVAs were compared on baseline demographics, preoperative clinical characteristics, and outcomes. Frailty (physiological reserve for surgery) was measured by the Revised Risk Analysis Index (RAI-rev). Logistic regression analysis was performed to identify independent associations between preoperative covariates and PCVA occurrence. The ITR-PCVA risk model was generated based on logit effect sizes and assessed in area under the receiver operating characteristic curve (AUROC) analysis. The rate of PCVA was 1.7% (n = 532). Patients with PCVAs, on average, were older and frailer, and had increased rates of nonelective surgery, interhospital transfer status, diabetes, hypertension, unintentional weight loss, and elevated BUN. PCVA was associated with higher rates of postoperative reintubation, infection, thromboembolic events, prolonged length of stay, readmission, reoperation, nonhome discharge destination, and 30-day mortality (all p < 0.001). In multivariable analysis, predictors of PCVAs included RAI "frail" category (OR 1.7, 95% CI 1.2-2.4; p = 0.006), Black (vs White) race (OR 1.5, 95% CI 1.1-2.1; p = 0.009), nonelective surgery (OR 1.4, 95% CI 1.1-1.7; p = 0.003), diabetes mellitus (OR 1.5, 95% CI 1.1-1.9; p = 0.002), hypertension (OR 1.4, 95% CI 1.1-1.7; p = 0.006), and preoperative elevated blood urea nitrogen (OR 1.4, 95% CI 1.1-1.8; p = 0.014). The ITR-PCVA predictive model was proposed from the resultant multivariable analysis and performed with a modest C-statistic in AUROC analysis of 0.64 (95% CI 0.61-0.66). Multicollinearity diagnostics did not detect any correlation between RAI-rev parameters and other covariates (variance inflation factor = 1). The current study proposes a novel preoperative risk model for PCVA in patients undergoing ITR. Patients with poor physiological reserve (measured by frailty), multiple comorbidities, abnormal preoperative laboratory values, and those admitted under high acuity were at highest risk. The ITR-PCVA risk model may support patient-centered counseling striving to respect goals of care and maximize quality of life. Future prospective studies are warranted to validate the ITR-PCVA risk model and evaluate its utility as a bedside clinical tool.


Perceptions and acceptability of co-administered albendazole, ivermectin and azithromycin mass drug administration, among the health workforce and recipient communities in Ethiopia.
Several neglected tropical diseases (NTDs) employ mass drug administration (MDA) as part of their control or elimination strategies. This has historically required multiple distinct campaigns, each targeting one or more NTDs, representing a strain on both the recipient communities and the local health workforce implementing the distribution. We explored perceptions and attitudes surrounding combined MDA among these two groups of stakeholders. Our qualitative study was nested within a cluster randomized non-inferiority safety trial of combined ivermectin, albendazole and azithromycin MDA. Using semi-structured question guides, we conducted 16 key informant interviews with selected individuals involved in implementing MDA within the participating district. To better understand the perceptions of recipient communities, we also conducted four focus group discussions with key community groups. Individuals were selected from both the trial arm (integrated MDA) and the control arm (standard MDA) to provide a means of comparison and discussion. All interviews and focus group discussions were led by fluent Afaan oromo speakers. Interviewers transcribed and later translated all discussions into English. The study team synthesized and analyzed the results via a coding framework and software. Most respondents appreciated the time and effort saved via the co-administered MDA strategy but there were some misgivings amongst community beneficiaries surrounding pill burden. Both the implementing health work force members and beneficiaries reported refusals stemming from lack of understanding around the need for the new drug regimen as well as some mistrust of government officials among the youth. The house-to-house distribution method, adopted as a COVID-19 prevention strategy, was by far preferred by all beneficiaries over central-point MDA, and may have led to greater acceptability of co-administration. Our data demonstrate that a co-administration strategy for NTDs is acceptable to both communities and health staff.


The Personal Support Worker Program Standard in Ontario: An Alternative to Self-Regulation?
Personal support workers (PSWS) provide hands-on assistance in a variety of long-term care and community settings. The question of whether psws should become regulated similar to other self-regulating health professions is a perennial concern in policy circles, especially because of the intimate nature of their work and the potential for abuse of clients and workers. This article explores a chain of policy decisions around psws in ontario culminating in the creation of a common educational standard for psw programs, titled the psw program standard. We argue that these policy developments may represent an alternative pathway to self-regulation of an essential workforce.


Growth hormone determines sexual dimorphism of hepatic cytochrome P450 3A4 expression in transgenic mice.
The impact of age and sex on the expression of hepatic cytochrome P450 3A4 (CYP3A4) was recently determined in a transgenic mouse line carrying the human CYP3A4 gene. To further investigate the physiological regulation of human CYP3A genes, a novel transgenic mouse line was generated using a bacterial artificial chromosome clone containing both CYP3A4 and CYP3A7 genes. CYP3A7 expression was observed in transgenic mouse fetal livers, whereas CYP3A4 exhibited developmental expression characterized by sexual dimorphism in postpubertal livers. Hepatic CYP3A4 protein and RNA were expressed in immature transgenic male mice and became undetectable after 6 weeks of age, whereas CYP3A4 was expressed in both immature and adult females. CYP3A4 was markedly elevated by the xenobiotic receptor activator phenobarbital in both male and female livers, demonstrating drug induction of the CYP3A4 transgene in this mouse model. Furthermore, continuous infusion of recombinant growth hormone (GH) in transgenic male mice, overriding the pulsatile male plasma GH profile, increased hepatic CYP3A4 mRNA and protein to normal female levels. Continuous GH treatment also feminized the expression of endogenous murine Cyp2b and Cyp3a44 genes. Thus, human CYP3A4 contains all of the gene regulatory sequences required for it to respond to endogenous hormonal regulators of developmental expression and sexual dimorphism, in particular GH. These findings may help elucidate the role of GH in determining the sex-dependent expression of CYP3A4 in human liver and suggest that GH therapy may alter the pharmacokinetic and pharmacodynamic properties of CYP3A4 substrates, leading to enhanced metabolism and disposition of drugs in men.


Nonalcoholic steatohepatitis in bariatric patients with a diagnosis of obstructive sleep apnea.
To study a possible association between obstructive sleep apnea (OSA) severity, managed with noninvasive ventilation, and nonalcoholic steatohepatitis (NASH) in bariatric surgical patients. Medical records of 218 bariatric surgical patients who underwent liver biopsy were reviewed. OSA severity was determined from preoperative polysomnography (apnea-hypopnea index (AHI) ≤ 15 no/mild OSA vs. AHI ≥ 16 moderate/severe OSA). Patients diagnosed with OSA were prescribed noninvasive ventilation. Patients were categorized according to liver histopathology into 3 groups: (i) no liver disease or simple steatosis, (ii) mild NASH (steatosis with necroinflammation and mild fibrosis (stage 0-1)), and iii) advanced NASH (steatosis with necroinflammation and more advanced fibrosis (stage ≥ 2)). 125 patients (57%) had no/mild OSA, and 93 (43%) had moderate/severe OSA. There was no difference in serum aminotransferases between patients by OSA severity classification. There was a high prevalence of hepatic histopathological abnormalities: 84% patients had steatosis, 57% had necroinflammation, 34% had fibrotic changes, and 14% had advanced NASH. There was no association between severity of NASH and severity of OSA. There is no association between stage of steatohepatitis and OSA severity among morbidly obese patients managed with noninvasive ventilation.


The incidence of antisperm antibodies in infertility patients with a history of cryptorchidism.
Infertility in patients with a history of cryptorchidism is usually the result of oligo-asthenospermia. In this study we analyzed the incidence of antisperm antibodies in infertility patients with a history of cryptorchidism, general infertility patients and donors of known fertility. Of the cryptorchid patients 66% tested positive for antisperm antibodies compared to 2.6% of the control group of infertile patients and 2.8% of the donors of known fertility. Sperm progressive motility was significantly (p < 0.05) decreased in the cryptorchid patients testing positive for antisperm antibodies compared to those testing negative for antisperm antibodies, and compared to both control groups. Of the patients treated for cryptorchidism by orchiopexy 52% were positive for antisperm antibodies, and the mean patient age at orchiopexy was significantly (p < 0.01) higher in the positive antibody group (14.2 +/- 1.2 years old) than the negative antibody group (8.6 +/- 0.8 years old). While decreased sperm concentration, motility and morphology are usually the primary causes of infertility in patients with a history of cryptorchidism, it appears that the presence of antisperm antibodies is also increased in these patients, which may contribute to reduced fertility.


[Kinetics of constitutive synthesis of polymethylgalacturonases by Penicillium digitatum as a function of the carbon source and pH].
Constitutive biosynthesis of polymethylgalacturonases by Penicillium digitatum is most active at the postexponential growth phase. Under certain conditions, the enzymes are synthesized at the constant rate which does not depend on the conditions of nutrition of the producing culture. An increase in the concentration of H+ ions at pH 3.0 changes the character of the fungal growth, prolongs the lag phase, decreases the rate of growth and increases the rate of the enzyme synthesis. The growth rate of Penicillium digitatum does not determine the rate of the enzyme synthesis. The enzyme synthesis does not depend on the conditions of the cultural growth.


Computed tomography in the diagnosis of organic bowel obstruction.
This study examined the usefulness of computed tomography (CT) scan for cases of organic intestinal obstruction, with two simple criteria. One hundred and thirteen patients with clinical suspicion of bowel obstruction were referred for CT scans. A line was drawn between the dilated proximal, and the collapsed distal bowels. A careful search was conducted on this line for obstructive lesions. The results were reported to be organic obstruction if there was an abrupt change of caliber (Criterion I) or a soft tissue mass around the dilated bowel (Criterion II). The judgement based on the CT findings. Eighty-eight cases proved to have bowel obstruction. With Criterion I, the sensitivity was 59.1%, and specificity, 88% with Criterion II, the sensitivity was 56.3% and specificity 100%. If either of them was considered to be a positive sign of organic obstruction, the sensitivity was 100%, the specificity 88% and the accuracy 97.3%. The nature of the obstructions were precisely predicted in 76 patients (86%). With these two simple criteria, CT scan can achieve high accuracy and is a recommendation in virtually every instance when intestinal obstruction is suspected.


Shared strategies for β-lactam catabolism in the soil microbiome.
The soil microbiome can produce, resist, or degrade antibiotics and even catabolize them. While resistance genes are widely distributed in the soil, there is a dearth of knowledge concerning antibiotic catabolism. Here we describe a pathway for penicillin catabolism in four isolates. Genomic and transcriptomic sequencing revealed β-lactamase, amidase, and phenylacetic acid catabolon upregulation. Knocking out part of the phenylacetic acid catabolon or an apparent penicillin utilization operon (put) resulted in loss of penicillin catabolism in one isolate. A hydrolase from the put operon was found to degrade in vitro benzylpenicilloic acid, the β-lactamase penicillin product. To test the generality of this strategy, an Escherichia coli strain was engineered to co-express a β-lactamase and a penicillin amidase or the put operon, enabling it to grow using penicillin or benzylpenicilloic acid, respectively. Elucidation of additional pathways may allow bioremediation of antibiotic-contaminated soils and discovery of antibiotic-remodeling enzymes with industrial utility.


Nonalcoholic fatty liver disease is associated with increased hemoconcentration, thrombocytopenia, and longer hospital stay in dengue-infected patients with plasma leakage.
A prominent histopathological feature of fatal dengue cases is hepatic steatosis. However, the association between hepatic steatosis and dengue severity is unknown. We conducted a study to determine the associations of nonalcoholic fatty liver disease (NAFLD) with laboratory markers of dengue severity and length of hospital stay (LOS). A retrospective study was conducted at a private hospital in Jakarta, Indonesia, from December 2011 to December 2016. Bivariate analysis was performed to analyze the associations of laboratory markers of dengue severity and LOS with the presence or absence of NAFLD in no-plasma-leakage (no leakage) and plasma-leakage (leakage) groups. There were 267 dengue-infected patients included in this study. Of these patients, 115 (43.1%) were classified as belonging to the no leakage group, and 152 (56.9%) were classified as belonging to the leakage group. Of the 115 patients belonging to the no leakage group, 53 (46.1%) did not have NAFLD, and 62 (53.9%) had NAFLD. Of the 152 patients belonging to the leakage group, 85 (55.9%) did not have NAFLD, and 67 (44.1%) had NAFLD. Leakage group patients with NAFLD experienced significantly higher hemoconcentration severity (p = 0.04), lower platelet count (p = 0.004) and higher LOS (p = 0.042) than did leakage group patients without NAFLD. The presence of NAFLD in dengue-infected patients with plasma leakage was associated with more severe hemoconcentration, thrombocytopenia and prolonged hospital stay.


Sleep timing and consistency are associated with the standardised test performance of Icelandic adolescents.
Sleep has been shown to affect cognitive function in laboratory studies; however, its association to the academic performance of adolescents has largely been demonstrated using self-reported measures. Studies with objective measures of both sleep and academic performance are limited. The aim of the present study was to determine whether the free-living sleep quantity, quality, and timing of 15-year-old adolescents measured with wrist actiography are associated with their scores on national standardised examinations as an objective measure of academic achievement. We measured sleep with wrist actiography for 1 week in 253 (150 girls) Icelandic adolescents with a mean (SD) age of 15.9 (0.3) years. Multiple linear regression was used to assess associations between sleep parameters and combined standardised examination scores in mathematics, English, and Icelandic obtained from the Icelandic Directorate of Education. We found that students went to bed at 00:49 hours (± 51.8 min) and slept for a mean (SD) of 6.6 (0.7) hr/night, with a median (interquartile range) night-to-night variation in sleep duration of 1.2 (0.7) hr and an efficiency of 88.1 (5.3)%. Combined analyses adjusted for sex, demonstrated that both bedtime and night-to-night variability in total sleep time were negatively associated with the average score across all topics. Sex-specific associations did not indicate clear differences between boys and girls. These findings suggest that, in addition to appropriate sleep duration, public health guidance should also highlight the importance of early and consistent sleep schedules to academic achievement for both boys and girls.


Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors.
Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in approximately 80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody that specifically recognizes endogenous and transfected MCV large T (LT) antigen. We show expression of MCV LT protein localized to nuclei of tumor cells from MCC having PCR quantified MCV genome at an average of 5.2 (range 0.8-14.3) T antigen DNA copies per cell. Expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. In contrast, although 2.2% of 325 hematolymphoid malignancies surveyed also showed evidence for MCV infection by DNA PCR, none were positive at high viral copy numbers, and none of 173 lymphoid malignancies examined on tissue microarrays expressed MCV LT protein in tumor cells. As with some of the other human polyomaviruses, lymphocytes may serve as a tissue reservoir for MCV infection, but hematolymphoid malignancies associated with MCC are unlikely to be caused by MCV.


Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults.
Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of ALL in children. There are conflicting data on the incidence and prognosis of Ph-like ALL in adults. Patients with newly diagnosed B-cell ALL (B-ALL) who received frontline chemotherapy at MD Anderson Cancer Center underwent gene expression profiling of leukemic cells. Of 148 patients, 33.1% had Ph-like, 31.1% had Ph+, and 35.8% had other B-ALL subtypes (B-other). Within the Ph-like ALL cohort, 61% had cytokine receptor-like factor 2 (CRLF2) overexpression. Patients with Ph-like ALL had significantly worse overall survival (OS), and event-free survival compared with B-other with a 5-year survival of 23% (vs 59% for B-other, P = .006). Sixty-eight percent of patients with Ph-like ALL were of Hispanic ethnicity. The following were associated with inferior OS on multivariable analysis: age (hazard ratio [HR], 3.299; P < .001), white blood cell count (HR, 1.910; P = .017), platelet count (HR, 7.437; P = .005), and Ph-like ALL (HR, 1.818; P = .03). Next-generation sequencing of the CRLF2+ group identified mutations in the JAK-STAT and Ras pathway in 85% of patients, and 20% had a CRLF2 mutation. Within the CRLF2+ group, JAK2 mutation was associated with inferior outcomes. Our findings show high frequency of Ph-like ALL in adults, an increased frequency of Ph-like ALL in adults of Hispanic ethnicity, significantly inferior outcomes of adult patients with Ph-like ALL, and significantly worse outcomes in the CRLF2+ subset of Ph-like ALL. Novel strategies are needed to improve the outcome of these patients.


Anatomic variations of the T2 nerve root (including the nerve of Kuntz) and their implications for sympathectomy.
The aim of this study was to clarify the anatomic variations of the intrathoracic nerve of Kuntz, and this should help delineate the resection margins during video-assisted thoracic sympathectomy. Sixty-six thoracic sympathetic chains of 39 adult Korean cadavers were dissected on both sides of the thorax in 27 cadavers (54 sides) and on one side in 12 cadavers (12 sides). The intrathoracic nerve was observed in 45 (68.2%) sides and was present bilaterally in 48.1% of cadavers. No intrathoracic nerve or ascending ramus communicans arising from the second thoracic nerve was observed in only 5 (7.6%) sides. The diameter of the intrathoracic nerve was 1.25 plus minus 0.55 mm on average. The arising point of the intrathoracic nerve from the second thoracic nerve was 7.3 mm on average from the sympathetic trunk. Presence of the stellate ganglion was noted in 56 (84.8%) sides, and 6 (9.1%) sides showed a single large ganglion formed by the stellate and the second thoracic sympathetic ganglia. The second thoracic sympathetic ganglion was most commonly located (50%) in the second intercostal space. The anatomic variations of the intrathoracic nerve of Kuntz and the second thoracic sympathetic ganglion were characterized in human cadavers. It is hoped that this study will help to improve the recurrence of symptoms caused by the intrathoracic nerve in an upper thoracic sympathectomy for hyperhidrosis.


Effect of bepridil in patients with chronic stable angina: results of a multicenter trial.
The effects of bepridil, a calcium antagonist with a half-life of approximately 42 hr, were assessed in a double-blind, randomized, placebo-controlled crossover trial. Forty-four patients (39 men, five women) with exercise-induced angina pectoris and ST segment depression with exercise testing (modified Bruce protocol) were studied. Compared with placebo bepridil (400 mg daily) increased total exercise time, time to onset of angina, time to 1 mm of ST segment depression, time to 2 mm of ST segment depression, and total work achieved (all p less than or equal to .001). Both frequency of angina and nitroglycerin consumption decreased during the bepridil compared with the placebo period (p = .02 and .03, respectively). Minor side effects were noted during both the bepridil and placebo phases. Four patients experienced side effects that limited therapy (dizziness in three and abnormal results of liver function tests in one) and one patient died during the bepridil phase. This study suggests that bepridil, 400 mg daily, is effective for the treatment of exercise-induced myocardial ischemia and angina pectoris.