[Automated exchange transfusion in premature and newborn infants with hyperbilirubinemia using a peripheral arteriovenous vascular access device].
The technique of exchange transfusion using a plastic catheter in the umbilical vein developed by Diamond and modified by Allen was instrumental in decreasing the mortality and morbidity in newborn infants with jaundice. Allen et al. demonstrated that the development of kernicterus in infants with erythroblastosis with indirect hyperbilirubinemia could be prevented by this method. Since that time numerous modifications of this "single site, push pull technique" have been described to further reduce the risk of morbidity and mortality. On the basis of the successful use of percutaneous radial artery catheters for arterial blood gas monitoring, we developed a technique for exchange transfusion using a peripheral arterial catheter inserted in the radial artery for blood withdrawal and a peripheral venous catheter for replacement of heparinized compatible donor blood. For simultaneous withdrawal and replacement we used two volumetric infusion pumps, one aspirating patients' arterial blood, the other replacing equal volumes of donor blood at exactly the same time. We evaluated our new procedure in 19 newborn infants (group 1) with hyperbilirubinemia who required exchange transfusion. Retrospectively we analysed the data in 18 newborn infants (group 2) treated over a previous period by means of the conventional "one site, push pull" technique using the umbilical vein, and compared the data. Mean birth weights, gestational ages and Apgar scores were similar in both groups, as were volumes of blood used for exchange transfusions. The results were superior in group 1 infants, as reflected by the significantly greater percentage decreases in serum bilirubin concentration and fewer complications. No baby died.(ABSTRACT TRUNCATED AT 250 WORDS)


Radiation protection of radiosensitive populations.
Radiosensitive populations (defined as subpopulations with increased radiogenic risk for cancer) may include individuals with known genetic predispositions for cancer (e.g., breast cancer), and persons with certain diseases, such as ataxia telangiectasia, which are characterized by enhanced radiation sensitivity and increased risk for cancer. Although approximately 10% of the population may be radiosensitive, current radiological protection limits, based on the "average" individual, should be retained. Radiation is a weak environmental carcinogen. Diet and cigarette smoking each account for 15-18 times more cancer deaths. Radiosensitivity is a much less important host factor than age and genetic predisposition. Workers should be allowed to "declare" a predisposition for cancer. Workers who have declared radiosensitivities should be provided with additional information regarding job-related risks and strategies to reduce dose. "Declared" employees should not be subjected to different terms and conditions of employment.


Evaluation of Time to Onset and Outcome of Lung Adverse Events Related to Pembrolizumab Using Marketing Surveillance.
Pembrolizumab has been widely used in patients since its release, but detailed information on lung-specific adverse events (AEs) from post-marketing monitoring has not been reported. This study was undertaken to determine the risk of pembrolizumab-induced lung AEs, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2022. Data on lung AEs were extracted and the relative risks of AEs were estimated using reporting odds ratios. We analyzed 2,021,907 reports and identified 15,306 reports of AEs caused by pembrolizumab, including 3,004 lung AEs. Signals were detected for 14 lung AEs. Interstitial lung disease was the most frequently reported (62.3%) and included fatal cases. A histogram of median time to onset showed occurrence ranging from 2 to 73 days, but some cases of interstitial lung disease occurred after 2 years of administration. The AEs showing the highest fatality rates were interstitial lung disease, respiratory failure, and pneumonia aspiration. This study focused on lung AEs caused by pembrolizumab as post-marketing AEs. Some cases could potentially involve serious outcomes, so patients should be monitored for signs of AE onset not only at the start of administration but also over an extended period, especially for interstitial lung disease.


Fluorescent probes for organelle-targeted bioactive species imaging.
Bioactive species, including reactive oxygen species (ROS, including O2˙-, H2O2, HOCl, 1O2, ˙OH, HOBr, etc.), reactive nitrogen species (RNS, including ONOO-, NO, NO2, HNO, etc.), reactive sulfur species (RSS, including GSH, Hcy, Cys, H2S, H2S n , SO2 derivatives, etc.), ATP, HCHO, CO and so on, are a highly important category of molecules in living cells. The dynamic fluctuations of these molecules in subcellular microenvironments determine cellular homeostasis, signal conduction, immunity and metabolism. However, their abnormal expressions can cause disorders which are associated with diverse major diseases. Monitoring bioactive molecules in subcellular structures is therefore critical for bioanalysis and related drug discovery. With the emergence of organelle-targeted fluorescent probes, significant progress has been made in subcellular imaging. Among the developed subcellular localization fluorescent tools, ROS, RNS and RSS (RONSS) probes are highly attractive, owing to their potential for revealing the physiological and pathological functions of these highly reactive, interactive and interconvertible molecules during diverse biological events, which are rather significant for advancing our understanding of different life phenomena and exploring new technologies for life regulation. This review mainly illustrates the design principles, detection mechanisms, current challenges, and potential future directions of organelle-targeted fluorescent probes toward RONSS.


An Intervention Utilizing the Salience Principle to Reduce Pharmacy Students' Psychological Attraction to Smartphones.
Objective. To determine pharmacy student reactions to and experiences with an intervention based on the principle of salience to reduce psychological attraction and attention to smartphones.Method. For a period of three weeks, participants were directed to change their smartphone's color setting to grayscale mode, turn off social media notifications, remove social media icons from smartphone home screen, and place the device away from their bed when sleeping. A thematic analysis was performed on responses to an anonymous, open-ended survey question that asked participants to record any positive/negative changes to their life and well-being as a result of participating in the study.Results. Thematic analysis revealed 20 unique themes and a variety of notable observations, including a reduction in both smartphone and social media use, reduced allure because of grayscale mode, frustrations caused by grayscale mode, increased productivity, and general improvements in sleep, face-to-face interactions, and overall well-beingConclusion. Results of this study provide initial evidence that changes to smartphone settings and physical placement at night may lead to positive outcomes. Participants reported primarily positive effects regarding well-being and reduced smartphone usage as a result of participating in the study. In many cases, less time on smartphones meant improved sleep, more productivity, more time for social/leisure activities, improved face-to-face interactions, and/or improvement in well-being.


Fitness of a gas mask for the face of a worker handling organic solvents.
The fitness of the half facepiece of a gas mask to the face of a worker handling organic solvents was evaluated through the quantitative determination of the concentrations of both organic solvent vapors and airborne dust inside and outside the facepiece. Leakage rates for dust were measured using a mask-fitting tester on a facepiece with a dust filter-covered respirator cartridge of organic solvents. The same facepiece was evaluated for the leakage rate for organic solvent vapors through the determination of the concentrations of the air inside and outside the facepiece. Highly significant correlations were found between the leakage rates obtained for dust and those for organic solvent vapors. The leakage rates for organic solvents were found to be slightly higher than those for dust. The present finding suggested that the leakage of organic solvent vapors from the interstice between the facepiece of gas masks and workers' faces can be evaluated using the leakage rate for dust for the same facepiece of the gas mask attached with the cartridge covered with a high efficiency particulate air (HEPA) filter.


Identifying and analyzing diagnostic paths: a new approach for studying diagnostic practices.
Diagnostic error is a serious public health problem to which knowledge gaps and associated cognitive error contribute significantly. Identifying diagnostic approaches to common problems in ambulatory care associated with more timely and accurate diagnosis and lower cost and harm associated with diagnostic evaluation is an important priority for health care systems, clinicians, and of course patients. Unfortunately, guidance on how best to approach diagnosis in patients with common presenting complaints such as abdominal pain, dizziness, and fatigue is lacking. Exploring diagnostic practice variation and patterns of diagnostic evaluation is a potentially valuable approach to identifying best current diagnostic practices. A "diagnostic path" is the sequence of actions taken to evaluate a new complaint from first presentation until a diagnosis is established, or the evaluation ends for other reasons. A "big data" approach to identifying diagnostic paths from electronic health records can be used to identify practice variation and best practices from a large number of patients. Limitations of this approach include incompleteness and inaccuracy of electronic medical record data, the fact that diagnostic paths may not represent clinician thinking, and the fact that diagnostic paths may be used to identify best current practices, rather than optimal practices.


Mitochondrial clearance by the STK38 kinase supports oncogenic Ras-induced cell transformation.
Oncogenic Ras signalling occurs frequently in many human cancers. However, no effective targeted therapies are currently available to treat patients suffering from Ras-driven tumours. Therefore, it is imperative to identify downstream effectors of Ras signalling that potentially represent promising new therapeutic options. Particularly, considering that autophagy inhibition can impair the survival of Ras-transformed cells in tissue culture and mouse models, an understanding of factors regulating the balance between autophagy and apoptosis in Ras-transformed human cells is needed. Here, we report critical roles of the STK38 protein kinase in oncogenic Ras transformation. STK38 knockdown impaired anoikis resistance, anchorage-independent soft agar growth, and in vivo xenograft growth of Ras-transformed human cells. Mechanistically, STK38 supports Ras-driven transformation through promoting detachment-induced autophagy. Even more importantly, upon cell detachment STK38 is required to sustain the removal of damaged mitochondria by mitophagy, a selective autophagic process, to prevent excessive mitochondrial reactive oxygen species production that can negatively affect cancer cell survival. Significantly, knockdown of PINK1 or Parkin, two positive regulators of mitophagy, also impaired anoikis resistance and anchorage-independent growth of Ras-transformed human cells, while knockdown of USP30, a negative regulator of PINK1/Parkin-mediated mitophagy, restored anchorage-independent growth of STK38-depleted Ras-transformed human cells. Therefore, our findings collectively reveal novel molecular players that determine whether Ras-transformed human cells die or survive upon cell detachment, which potentially could be exploited for the development of novel strategies to target Ras-transformed cells.


The Role of Task Difficulty in Learning a Visuomotor Skill.
Task difficulty affects the amount of interpretable information from a task, which is thought to interfere with motor learning. However, it is unclear whether task difficulty in itself is a stimulus for motor learning because the experimental evidence is mixed in support of the optimal challenge point framework that predicts one specific level of task difficulty to produce the greatest magnitude of motor learning. We determined the effects of functional task difficulty on motor skill acquisition, retention, and transfer. Healthy young participants (N = 36) learned a mirror star-tracing task at a low, medium, or hard difficulty level defined by the bandwidth of the star. We measured skill acquisition, retention, and transfer to untrained difficulty levels, as well as the perceived mental workload during the task. Task difficulty affected motor performance, but did not affect motor learning and transfer. For the groups that practiced the task at the medium and hard but not at the low difficulty level, initial skill level correlated with the magnitude of learning. The optimal challenge point framework does not capture the complex relationship between task difficulty and motor learning. Previously reported effects of task difficulty on the magnitude of motor learning are probably mediated by perceived mental workload. Task difficulty did not affect the magnitude of visuomotor skill learning but it affected how learning occurred. The data have implications on how athletes learn new motor skills and patients relearn injury-impaired motor skills during rehabilitation.


Characteristics, prognosis and outcome of patients with oesophageal varices in a university hospital in Sweden 1994-1999.
Patients with liver cirrhosis, portal hypertension and oesophageal varices are known to have high morbidity and mortality. The knowledge of incidence, aetiology and outcome in Sweden in recent years is limited. All patients with oesophageal varices diagnosed for the first time at Sahlgrenska University Hospital during the 6-year period 1994-1999 were retrospectively studied. Information about the aetiology of liver cirrhosis and oesophageal varices, as well as about the proportion of bleeding and non-bleeding varices, endoscopic and pharmacological treatment and outcome, was analyszed. 312 patients were retrieved, 297 with liver cirrhosis (197 diagnosed before first bleeding (P), 92 after bleeding (B) and 8 at autopsy) and 15 with portal vein thrombosis without cirrhosis. Fifty-four percent had alcoholic liver disease. Fifty-five percent in group B and 13% in group P had at least one bleeding episode during follow-up (p<0.001). There was no significant difference in survival between groups B and P. Twenty-six percent of the cirrhotics died of liver failure and 19% from variceal bleeding. In a multivariate analysis, variables predicting mortality were: Child-Pugh class, group B, age and bilirubin levels. Variceal bleeding is still a strong risk factor for recurrent bleeding, but few die from their first bleeding. This concurs with studies indicating declining mortality from variceal bleeding. However, this patient group still has a high mortality from other causes.


Metabolism, pharmacokinetics, tissue distribution, and stability studies of the prodrug analog of an anti-hepatitis B virus dinucleoside phosphorothioate.
The alkoxycarbonyloxy dinucleotide prodrug R(p), S(p)-2 is an orally bioavailable anti-hepatitis B virus agent. The compound is efficiently metabolized to the active dinucleoside phosphorothioate R(p), S(p)-1 by human liver microsomes and S9 fraction without cytochrome P450-mediated oxidation or conjugation. The conversion of R(p), S(p)-2 to R(p), S(p)-1 appears to be mediated by liver esterases, occurs in a stereospecific manner, and is consistent with our earlier reported studies of serum-mediated hydrolytic conversion of R(p), S(p)-2 to R(p), S(p)-1. However, further metabolism of R(p), S(p)-1 does not occur. The presence of a minor metabolite, the desulfurized product 10 was noted. The prodrug R(p), S(p)-2 was quite stable in simulated gastric fluid, whereas the active R(p), S(p)-1 had a half-life of <15 min. In simulated intestinal fluid, the prodrug 2 was fully converted to 1 in approximately 3 h, whereas 1 remained stable. To ascertain the tissue distribution of the prodrug 2 in rats, the synthesis of (35)S-labeled R(p), S(p)-2 was undertaken. Tissue distribution studies of orally and intravenously administered radiolabeled [(35)S]2 demonstrated that the radioactivity concentrates in the liver, with the highest liver/plasma ratio in the intravenous group at 1 h being 3.89 (females) and in the oral group at 1 h being 2.86 (males). The preferential distribution of the dinucleotide 1 and its prodrug 2 into liver may be attributed to the presence of nucleoside phosphorothioate backbone because phosphorothioate oligonucleotides also reveal a similar tissue distribution profile upon intravenous administration.


[Tardy ulnar palsy treated by anterior subcutaneous transposition].
Twenty cases of tardy ulnar palsy were treated by anterior subcutaneous transposition in the past 6 years at the Veterans General Hospital-Taichung. These cases were followed up for at least 9 months after operation. Mean duration of follow up was 39.5 months. Age distribution was from 40y/o to 72y/o, mean age was 54.5y/o. Duration of symptoms was from 2 months to 72 months, mean was 20.3 months. Eight cases were attributed to the idiopathic type. 16 cases (80%) improved after operation. Four factors were analyzed to evaluate their status as a prognostic guide: age, duration of syndrome, severity before operation and precipitating factors. Only severity before operation correlated with prognosis, but good recovery can be achieved in severe cases. Anterior subcutaneous transposition is a good method for treating tardy ulnar palsy.


Characteristics of new adult users of mepolizumab with asthma in the USA.
In the USA, over 25 million people have asthma; 5%-10% of cases are severe. Mepolizumab (Nucala) is an interleukin-5 antagonist monoclonal antibody; it was approved by the FDA in 2015 as add-on maintenance treatment of severe asthma for patients aged ≥12 years with an eosinophilic phenotype. (1) Describe baseline demographic and clinical characteristics of new US adult mepolizumab users 2015-2019, (2) describe asthma medication use in the 12 months preceding initiation of and concomitant with mepolizumab and (3) assess mepolizumab adherence, persistence and discontinuation patterns in 12 months postinitiation. We conducted a new-user observational cohort study using data from Aetna, a CVS Health Company, HealthCore (Anthem), Harvard Pilgrim Healthcare, and IBM MarketScan Research Databases. Curated administrative claims data in the FDA Sentinel System common data model format and publicly available Sentinel analytical tools were used to query the databases. We included adults who initiated mepolizumab in 2015-2019 with an asthma diagnosis in the preceding 12 months and no evidence of cystic fibrosis. We examined age, sex, comorbid conditions, asthma medication use and severe asthma exacerbations. We identified 3496 adults (mean age 54.2 years, SD 12.5 years) who initiated mepolizumab. In the 12 months before mepolizumab initiation, 22% had received inhaled corticosteroids, 46% had inhaled corticosteroid/long-acting beta agonists, 72.6% had leukotriene antagonists, 38% had long-acting muscarinic antagonist, 18% had omalizumab,<1% had reslizumab, dupilumab or benralizumab. In the previous 12 months, 70% had a diagnosis of allergic rhinitis, 32% had chronic obstructive pulmonary disease, 17% eosinophilia and 3% eosinophilic granulomatosis with polyangiitis. Further, 56% had an asthma-related ambulatory visit, 73%≥1 course of oral corticosteroids lasting 3-27 days, 10% an asthma-related emergency department visit and 22% an asthma-related hospitalisation. In the 12 months following initiation, the mean proportion of days covered was 70%, and reductions in the average mean dispensings of rescue oral corticosteriods (35%) and omalizumab (61%) were observed. Adults with asthma treated with mepolizumab had varying levels of healthcare utilisation and we observed evidence of mepolizumab use in patients without severe asthma.


Use of complementary and alternative medicine by cancer patients at Zhejiang University Teaching Hospital Zhuji Hospital, China.
Complementary and alternative medicine (CAM) is garnering increasing interest and acceptance among the general population throughout the world. The use of CAM by cancer patients is very common in China. The referenced English literature has no rural community-based study from China on this subject. This study was conducted to define the prevalence, pattern of use, and reasons for using CAM by cancer patients at Zhejiang University Teaching Hospital Zhuji Hospital (ZUTH-ZJH), China. Face-to-face interviews using a structured questionnaire were used to determine the use of CAM by cancer patients. All consenting cancer patients were interviewed as they presented at the Department of Surgical Oncology of ZUTH-ZJH, from September 2009 to February 2010. One hundred and twenty one patients were interviewed; 64 (52.9%) were males and 57 (47.1%) were females. One hundred and thirteen patients (93.4%) have used CAM at some time during their current cancer illness, fifty two (46.0%) are female and sixty one (54.0%) are male patients; 8 (6.6%) patients have not used any form of CAM. Chinese medicine (73.5.0%) was the most commonly reported CAM modality. Over 71.7% of those who used CAM were satisfied, only 28.3% were disappointed. Twenty eight users (24.8%) did not see any benefit from the CAM, but eighty one patients (71.7%) could describe some specific benefits. Only one patient will use orthodox medicine instead of CAM in the future, almost all patients will continue to use CAM in the future. CAM use is very common among cancer patients in local area of China. Most users obtain the expected benefits, and adverse events are uncommon. It is imperative that oncologists should explore the use of CAM with their cancer patients and work towards an integrated model of health-care provision. This knowledge will enable oncologists to better counsel the patients.


Image acquisition: ultrasound, computed tomography, and magnetic resonance imaging.
As the transition toward total digital image acquisition continues, radiology is transcending the current standard of two-dimensional (2-D) cross-sectional anatomic imaging to more complex models. Among these are three-dimensional (3-D) anatomic images, constructed either from a synthesis of traditional 2-D data sets, or directly from volumetrically acquired data. However, current trends are moving beyond mere anatomic imaging to include physiological data once mainly obtained via nuclear medicine. Recent magnetic resonance pulse sequences, in addition to Doppler and harmonic ultrasound methods, are providing insight into blood flow, oxygenation, and metabolite concentrations non-invasively. Through image registration techniques, these data (even from differing modalities) are being assembled into 2-D and 3-D "fusion" images that promise to revolutionize diagnosis. Furthermore, with improvements in miniaturization, reliability, speed, built-in intelligence, and ease of use, these new developments are finding their way into use by nonspecialists. For instance, a new hand-held ultrasound unit will likely become a common tool among emergency medical teams, military medical teams, and in NASA's manned space program. Portable computed tomography (CT) scanners are already being used in the operating room. The increasing sophistication of imaging instruments will bring about a complementary increase in ease of use for both scanning and data interpretation, bringing diagnostic imaging and therapeutic capabilities closer to the patient, rather than the converse.


Lead-Induced Atypical Parkinsonism in Rats: Behavioral, Electrophysiological, and Neurochemical Evidence for a Role of Noradrenaline Depletion.
Background: Lead neurotoxicity is a major health problem known as a risk factor for neurodegenerative diseases, including the manifestation of parkinsonism-like disorder. While lead is known to preferentially accumulate in basal ganglia, the mechanisms underlying behavioral disorders remain unknown. Here, we investigated the neurophysiological and biochemical correlates of motor deficits induced by sub-chronic injections of lead. Methods: Sprague Dawely rats were exposed to sub-chronic injections of lead (10 mg/kg, i.p.) or to a single i.p. injection of 50 mg/kg N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a drug known to induce selective depletion of noradrenaline. Rats were submitted to a battery of behavioral tests, including the open field for locomotor activity and rotarod for motor coordination. Electrophysiological recordings were carried out in three major basal ganglia nuclei, the subthalamic nucleus (STN), globus pallidus (GP), and substantia nigra pars reticulata (SNr). At the end of experiments, post-mortem tissue level of the three monoamines (dopamine, noradrenaline, and serotonin) and their metabolites has been determined using HPLC. Results: Lead intoxication significantly impaired exploratory and locomotor activity as well as motor coordination. It resulted in a significant reduction in the level of noradrenaline in the cortex and dopamine and its metabolites, DOPAC, and HVA, in the striatum. The tissue level of serotonin and its metabolite 5-HIAA was not affected in the two structures. Similarly, DSP-4, which induced a selective depletion of noradrenaline, significantly decreased exploratory, and locomotor activity as well as motor coordination. L-DOPA treatment did not improve motor deficits induced by lead and DSP-4 in the two animal groups. Electrophysiological recordings showed that both lead and DSP-4 did not change the firing rate but resulted in a switch from the regular normal firing to irregular and bursty discharge patterns of STN neurons. Neither lead nor DSP-4 treatments changed the firing rate and the pattern of GP and SNr neurons. Conclusions: Our findings provide evidence that lead represents a risk factor for inducing parkinsonism-like deficits. As the motor deficits induced by lead were not improved by L-DOPA, we suggest that the deficits may be due to the depletion of noradrenaline and the parallel disorganization of STN neuronal activity.


Application of clinical decision analysis to audiological tests.
This paper is the first in a series of three concerning audiological tests and test batteries designed to differentiate cochlear from retrocochlear site-of-lesion. This paper concentrates on the techniques of clinical decision analysis with particular application to audiology. Those principles of clinical decision analysis which are most relevant for the audiologist are presented. Several techniques for measuring test performance are described and evaluated. In addition, this paper considers the problem of comparing test performance to determine the superior test.


[Transthoracic pacing in a very low birth weight infant with congenital complete atrioventricular block - Case report].
We report our experience of pacemaker treatment in a premature infant of 832 grams with congenital complete atrioventricular block due to maternal Sjögren's Syndrome. She was delivered by cesarean section at an estimated gestational age of 26 weeks because of fetal bradycardia, decreasing fetal movements and hydrops. Immediate postnatal transesophageal ventricular pacing was not successful, whereas transthoracic pacing with self-adhesive patch electrodes adapted to body size resulted in an effective increase of the infant's heart rate until operative application of temporary epimyocardial pacing wires ensured the external stimulation of the heart.


Development of oesophageal tissue structures in human embryogenesis.
The authors investigated human embryos and fetuses of 4 to 40 weeks old, their evolution and oesophageal histodifferentiation characteristics. The terms used to describe oesophageal tissue structure formation are defined more accurately. A detailed analysis of the sequence of oesophageal histogenesis processes is given, special attention being paid to the development of muscle element evolution in different oesophagus sections.


Substance P exacerbates dopaminergic neurodegeneration through neurokinin-1 receptor-independent activation of microglial NADPH oxidase.
Although dysregulated substance P (SP) has been implicated in the pathophysiology of Parkinson's disease (PD), how SP affects the survival of dopaminergic neurons remains unclear. Here, we found that mice lacking endogenous SP (TAC1(-/-)), but not those deficient in the SP receptor (neurokinin-1 receptor, NK1R), were more resistant to lipopolysaccharide (LPS)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigral dopaminergic neurodegeneration than wild-type controls, suggesting a NK1R-independent toxic action of SP. In vitro dose-response studies revealed that exogenous SP enhanced LPS- and 1-methyl-4-phenylpyridinium (MPP(+))-induced dopaminergic neurodegeneration in a bimodal manner, peaking at submicromolar and subpicomolar concentrations, but was substantially less effective at intermediate concentrations. Mechanistically, the actions of submicromolar levels of SP were NK1R-dependent, whereas subpicomolar SP-elicited actions required microglial NADPH oxidase (NOX2), the key superoxide-producing enzyme, but not NK1R. Subpicomolar concentrations of SP activated NOX2 by binding to the catalytic subunit gp91(phox) and inducing membrane translocation of the cytosolic subunits p47(phox) and p67(phox). The importance of NOX2 was further corroborated by showing that inhibition or disruption of NOX2 blocked subpicomolar SP-exacerbated neurotoxicity. Together, our findings revealed a critical role of microglial NOX2 in mediating the neuroinflammatory and dopaminergic neurodegenerative effects of SP, which may provide new insights into the pathogenesis of PD.


A Siglec-like sialic-acid-binding motif revealed in an adenovirus capsid protein.
Sialic-acid-binding immunoglobulin-like lectins (Siglecs) are a family of transmembrane receptors that are well documented to play roles in regulation of innate and adaptive immune responses. To see whether the features that define the molecular recognition of sialic acid were found in other sialic-acid-binding proteins, we analyzed 127 structures with bound sialic acids found in the Protein Data Bank database. Of these, the canine adenovirus 2-fiber knob protein showed close local structural relationship to Siglecs despite low sequence similarity. The fiber knob harbors a noncanonical sialic-acid recognition site, which was then explored for detailed specificity using a custom glycan microarray comprising 58 diverse sialosides. It was found that the adenoviral protein preferentially recognizes the epitope Neu5Acα2-3[6S]Galβ1-4GlcNAc, a structure previously identified as the preferred ligand for Siglec-8 in humans and Siglec-F in mice. Comparison of the Siglec and fiber knob sialic-acid-binding sites reveal conserved structural elements that are not clearly identifiable from the primary amino acid sequence, suggesting a Siglec-like sialic-acid-binding motif that comprises the consensus features of these proteins in complex with sialic acid.


[Complete urethral rupture caused by pelvic fracture in females].
Complete urethral rupture caused by pelvic fracture in females is rare. In China except 6 cases treated at other institutions, we encountered 3 case of this kind injury from 1987 to 1989. Reviewing the etiology, diagnosis and treatment of the injury of 9 cases, we suggest that urethral reunion, traction by Foley's catheter and cystostomy should be performed routinely to raise the cure rate.


In vitro studies of prolactin inhibition of luteinizing hormone action on Leydig cells of rats and mice.
Previous in vivo studies have shown that in male rabbits prolactin inhibits the testosterone production stimulated by luteinizing hormone (LH) or human chorionic gonadotropin (hCG). This inhibition has now been studied in vitro using both mouse and rat testicular interstitial cells. First, the dose response of human LH (hLH) stimulation of testosterone was studied in detail using testicular interstitial cells from both species. Next, a small but stimulatory dose of hLH was selected and extensive prolactin doses were studied in vitro. NIH B-6 (bovine) prolactin in varying doses was added to the interstitial cells 30 min prior to the addition of a constant dose of hLH. Under these circumstances prolactin inhibited LH action over a wide range of doses. In both species a biphasic dose-response curve existed: large doses of 100 to 1000 ng/ml produced less inhibition or augmented LH action, compared to smaller doses. Next, entire hLH dose-response curves were produced in the presence of three doses of prolactin (0.33, 33, and 1000 ng/ml) as well as in the absence of prolactin. The addition of prolactin shifted the hLH dose-response curve to the right and depressed the maximal response in comparison to the curve without prolactin. Finally, inhibitory doses of prolactin resulted in no detectable change in LH receptor number as estimated from Scatchard plots. It is concluded that prolactin inhibits LH action on interstitial cells as determined by rate of testosterone production except at very large doses of prolactin where LH action is less inhibited or augmented. The inhibitory action of prolactin in this in vitro interstitial cell assay was not accompanied by a decrease in LH receptor number. Thus, a postreceptor action is likely to be involved.


Flexible sigmoidoscopy: screening for colorectal cancer.
Flexible sigmoidoscopy is an important screening procedure because of its ability to detect early changes in the distal colon. The 60-cm flexible sigmoidoscope provides excellent visualization with minimal discomfort to patients. Successful sigmoidoscopy requires adequate patient preparation, proper equipment and an experienced examiner who can recognize both normal and abnormal findings. Complications arising from sigmoidoscopy are rare, but patients may experience some cramping, gas or watery stools. Screening and primary preventive measures, including regular exercise and increased dietary fiber intake, can lower the morbidity and mortality associated with colorectal cancer.


Relevance of Frequency-Domain Analyses to Relate Shoe Cushioning, Ground Impact Forces and Running Injury Risk: A Secondary Analysis of a Randomized Trial With 800+ Recreational Runners.
Cushioning systems in running shoes are used assuming that ground impact forces relate to injury risk and that cushioning materials reduce these impact forces. In our recent trial, the more cushioned shoe version was associated with lower injury risk. However, vertical impact peak force was higher in participants with the Soft shoe version. The primary objective of this study was to investigate the effect of shoe cushioning on the time, magnitude and frequency characteristics of peak forces using frequency-domain analysis by comparing the two study groups from our recent trial (Hard and Soft shoe group, respectively). The secondary objective was to investigate if force characteristics are prospectively associated with the risk of running-related injury. This is a secondary analysis of a double-blinded randomized trial on shoe cushioning with a biomechanical running analysis at baseline and a 6-month follow-up on running exposure and injury. Participants (n = 848) were tested on an instrumented treadmill at their preferred running speed in their randomly allocated shoe condition. The vertical ground reaction force signal for each stance phase was decomposed into the frequency domain using the discrete Fourier transform. Both components were recomposed into the time domain using the inverse Fourier transform. An analysis of variance was used to compare force characteristics between the two study groups. Cox regression analysis was used to investigate the association between force characteristics and injury risk. Participants using the Soft shoes displayed lower impact peak force (p < 0.001, d = 0.23), longer time to peak force (p < 0.001, d = 0.25), and lower average loading rate (p < 0.001, d = 0.18) of the high frequency signal compared to those using the Hard shoes. Participants with low average and instantaneous loading rate of the high frequency signal had lower injury risk [Sub hazard rate ratio (SHR) = 0.49 and 0.55; 95% Confidence Interval (CI) = 0.25-0.97 and 0.30-0.99, respectively], and those with early occurrence of impact peak force (high frequency signal) had greater injury risk (SHR = 1.60; 95% CI = 1.05-2.53). Our findings may explain the protective effect of the Soft shoe version previously observed. The present study also demonstrates that frequency-domain analyses may provide clinically relevant impact force characteristics. Clinical Trial Registration: https://clinicaltrials.gov/, identifier: 9NCT03115437.


Cancer mortality and radioactive fallout in southwestern Utah.
Cancer mortality was compared between a three-county region in southwestern Utah and the remainder of Utah in an investigation of reported excess cancer risks associated with residence in southwestern Utah during the period of above-ground nuclear tests at the Nevada Test Site. Because most of the fallout in southwestern Utah was deposited during 1953-1957, comparisons were limited to persons born before 1958, and deaths from leukemia and bone cancer during 1955-1980 and from other cancers during 1964-1980. There was no excess risk of cancer mortality in southwestern Utah, for single or grouped sites, with the single exception of leukemia which showed statistically significant odds ratios of 1.45 based on 62 deaths at all ages, and 2.84 based on nine deaths at ages 0-14. The finding for childhood leukemia was based on different time periods and geographic comparisons from those of two earlier studies in which no such excess was found. Mortality from all cancer sites combined was significantly lower in southwestern Utah than in the remainder of the state, even after adjustment for the higher proportion of (lower risk) Mormons in southwestern Utah. The present results, including the positive association for leukemia, are inconsistent with the high excess risks reported by Johnson (JAMA 1984;251:230-6) based on an interview survey of cancer incidence among long-term Mormon residents of southwestern Utah.


Ultrasound Measurement of Rectus Femoris Muscle Parameters for Discriminating Sarcopenia in Community-Dwelling Adults.
Sarcopenia patients require more medical attention and caretaking. As such, early detection of sarcopenia and appropriate interventions are crucial for decreasing medical costs and meeting the challenges of aging populations. The aim of the present study was to develop a reliable and accurate model to estimate muscle mass using ultrasound-derived parameters from the rectus femoris (RF), referenced by dual-energy X-ray absorptiometry. Cross-sectional study was performed. The study patients were recruited by Taipei Veterans General Hospital (No. 2016-07-013C) between 2016 and 2019. A total of 91 community-dwelling adults (35 men and 56 women) were enrolled in this study. Ultrasound measurements of RF muscle thickness (MT), cross-sectional area (CSA), and muscle volume (MV) were performed in B-mode. Muscle strength and physical performance were also examined. Multivariate linear regression was used to build models for the prediction of appendicular skeletal muscle index (ASMI) based on MT, CSA, and MV values. The accuracy of ultrasound RF measurements for predicting sarcopenia was evaluated by using receiver operating characteristic (ROC) curve analysis. The regression equations used for ASMI prediction (adjusted body mass index, sex, and leg length) had high precision and low error. Moreover, the MV model results were close to those of the CSA model and higher than those of the MT model. The ROC analysis showed that both MV and CSA had excellent discrimination when assessing sarcopenia (AUC = 0.83 and 0.81, respectively), whereas MT showed acceptable discrimination (AUC = 0.73). Ultrasound-derived RF MV was accurate when predicting ASMI and diagnosing sarcopenia in community-dwelling adults.


Association between fast-food consumption and lifestyle characteristics in Greek children and adolescents; results from the EYZHN (National Action for Children's Health) programme.
To examine the prevalence of fast-food consumption and the association between fast food and lifestyle factors in a representative sample of children and adolescents. Cross-sectional, observational study. Fast-food consumption and dietary habits were evaluated using questionnaires (KIDMED index). Anthropometric and physical fitness measurements were obtained by trained investigators. Physical activity (PA) status, sedentary activities and sleeping habits were assessed through self-completed questionnaires. Greece. Population data derived from a school-based health survey (EYZHN programme) carried out in 2015 on 177 091 (51 % boys) children aged 8-17 years. A greater proportion of boys v. girls (23·3 v. 15·7 %, P1 time/week. Frequent fast-food consumption was strongly correlated with unhealthy dietary habits such as skipping breakfast and consuming sweets/candy regularly. Adjusting for several covariates, insufficient dietary habits, insufficient (<8-9 h/d) sleep, inadequate PA levels and increased screen time increased the odds (95 % CI) of being a frequent fast-food consumer by 77 % (0·218, 0·234), 30 % (1·270, 1·338), 94 % (1·887, 1·995) and 32 % (1·287, 1·357), respectively. Being overweight/obese or centrally obese did not correlate with frequency of fast-food consumption. Frequent fast-food consumption was associated with an unhealthy lifestyle profile among children and adolescents. The findings support the development of interventions to help children adopt healthier dietary habits.


A randomized controlled trial of cognitive behavioral therapy (CBT) for adjusting to multiple sclerosis (the saMS trial): does CBT work and for whom does it work?
The aims were (a) to test the effectiveness of a nurse-led cognitive behavioral therapy (CBT) program to assist adjustment in the early stages of multiple sclerosis (MS) and (b) to determine moderators of treatment including baseline distress, social support (SS), and treatment preference. Ninety-four ambulatory people with MS within 10 years of diagnosis were randomized to receive 8 individual sessions of CBT (n = 48) or supportive listening (n = 46), most delivered on the telephone, in a multicenter randomized controlled trial. The primary outcomes were distress and functional impairment. Secondary outcomes included global improvement, acceptance of illness, and dysfunctional cognitions. Assessments were completed at home and were coordinated by a blind assessor. Data were analyzed by intention-to-treat using multilevel models. The CBT group was significantly less distressed at the end of treatment (estimated General Health Questionnaire group difference = 3.2 points, 95\% CI 1.1 to 5.4 points) and at the 12-month follow-up (estimated group difference = 2.2 points, 95\% CI 0.01 to 4.4 points). There were no differences between the groups on functional impairment. The CBT group also demonstrated significantly greater improvements on secondary outcomes at the end of treatment but not at the 12-month follow-up. CBT participants with poor SS and/or clinically defined levels of distress at baseline showed significantly greater gains on both primary outcomes. Treatment preference did not moderate treatment effects. CBT is more effective than supportive listening in reducing distress in people with MS. CBT appears most effective for patients with poor SS and high levels of distress. The loss of gains in the secondary outcomes by 12 months suggests further follow-up sessions may be warranted.


Immunosuppression in men with bowenoid papulosis.
The immune status of four men with bowenoid papulosis was evaluated. Each case had been refractory to multiple methods of treatment. Three of the men had other infections and demonstrated a depletion of T4-helper cells. Two of these patients were anergic on skin testing, and the third showed weak reactivity. The fourth patient, who had no evidence of additional infections, had a normal T4 value and T4/T8 ratio, but was anergic on skin testing. All the men were serologically negative for human immunodeficiency virus antibodies. One of the immunosuppressed patients developed squamous cell carcinoma of the tongue, which, along with his bowenoid papulosis, contained human papillomavirus 16 DNA. We suggest that patients with persistent bowenoid papulosis be investigated for altered immune status and followed up as potential candidates for the development of epithelial malignant neoplasms.


Evaluation of video-assisted thoracoscopic surgery lobectomy requiring emergency conversion to thoracotomy.
Video-assisted thoracoscopic surgery (VATS) lobectomy has been employed for the treatment of lung cancer. Many investigators have reported that the outcomes of VATS lobectomy for lung cancer are comparable to those of thoracotomy; however, several controversial issues remain. One of the critical concerns is the safety. VATS lobectomy often requires an emergency conversion to thoracotomy, for example, in the event of massive bleeding. In this study, cases in which VATS lobectomy for lung cancer was converted to thoracotomy intra-operatively (converted VATS lobectomy) were identified. The safety of the converted VATS lobectomy was evaluated. Between 2003 and 2007, VATS lobectomy was converted to thoracotomy in 24 out of 492 cases. Information regarding the patients' characteristics, reasons for the conversion and perioperative complications as well as the recurrence and survival data were carefully reviewed. The reasons for the conversion were classified into two groups: (1) problems related to the VATS procedure (VATS-related problems) and (2) problems not related to the VATS procedure (non-VATS-related problems). Of the 24 converted cases, 19 (79%) had a history of smoking. Nine patients (38%) had a history of lung disease. Left upper lobectomy was the most frequently associated with conversion (11/24, 46%), followed by right lower lobectomy and right upper lobectomy. The most frequent reasons for the conversion were hilar lymphadenopathy and bleeding (seven patients each), followed by fused fissure. Eight of the conversions were considered to be attributable to VATS-related problems. Perioperative complications were observed in four patients, consisting of prolonged air leak in three patients and transient recurrent laryngeal nerve palsy in one patient. However, there were no life-threatening complications. The median follow-up period was 26 months. Recurrence occurred in two patients: pleural dissemination in one and bone metastasis in the other. Two deaths were observed during the follow-up period: one related to lung cancer and another related to other type of cancer. The safety of the conversion was acceptable. Our findings suggest that VATS lobectomy for lung cancer is feasible from the viewpoint of safety, even after taking into account the potential need for conversion to thoracotomy in some patients.


E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells.
Extravasation of circulating tumor cells (CTCs) from the vasculature is a key step in cancer metastasis. CTCs bind to cell adhesion molecules (CAMs) expressed by endothelial cells (ECs) for flow arrest prior to extravasation. While a number of EC-expressed CAMs have been implicated in facilitating CTC binding, this work investigated the efficacy of inhibiting cancer cell binding to human lung microvascular ECs via antibody blocking of E-selectin using antibody-functionalized gold nanoshells (NS). The antibody-functionalized gold NS were synthesized using both directional and non-directional antibody conjugation techniques with variations in synthesis parameters (linker length, amount of passivating agents, and ratio of antibodies to NS) to gain a better understanding of these properties on the resultant hydrodynamic diameter, zeta potential, and antibody loading density. We quantified the ability of E-selectin antibody-functionalized NS to bind human lung microvascular endothelial cells (HMVEC-Ls) under non-inflamed and inflamed (TNF-α) conditions to inhibit binding of triple-negative MDA-MB-231s. E-selectin-targeted NS prepared using non-directional conjugation had higher antibody loading than those prepared via directional conjugation, resulting in the conjugates having similar overall binding to HMVEC-Ls at a given antibody concentration. E-selectin-targeted NS reduced MDA-MB-231 binding to HMVEC-Ls by up to 41% as determined using an in vitro binding assay. These results provide useful insights into the characteristics of antibody-functionalized NS prepared under different conditions while also demonstrating proof of concept that these conjugates hold potential to inhibit CTC binding to ECs, a critical step in extravasation during metastasis.


NoDe: a fast error-correction algorithm for pyrosequencing amplicon reads.
The popularity of new sequencing technologies has led to an explosion of possible applications, including new approaches in biodiversity studies. However each of these sequencing technologies suffers from sequencing errors originating from different factors. For 16S rRNA metagenomics studies, the 454 pyrosequencing technology is one of the most frequently used platforms, but sequencing errors still lead to important data analysis issues (e.g. in clustering in taxonomic units and biodiversity estimation). Moreover, retaining a higher portion of the sequencing data by preserving as much of the read length as possible while maintaining the error rate within an acceptable range, will have important consequences at the level of taxonomic precision. The new error correction algorithm proposed in this work - NoDe (Noise Detector) - is trained to identify those positions in 454 sequencing reads that are likely to have an error, and subsequently clusters those error-prone reads with correct reads resulting in error-free representative read. A benchmarking study with other denoising algorithms shows that NoDe can detect up to 75% more errors in a large scale mock community dataset, and this with a low computational cost compared to the second best algorithm considered in this study. The positive effect of NoDe in 16S rRNA studies was confirmed by the beneficial effect on the precision of the clustering of pyrosequencing reads in operational taxonomic units. NoDe was shown to be a computational efficient denoising algorithm for pyrosequencing reads, producing the lowest error rates in an extensive benchmarking study with other denoising algorithms.


Leishmania major glycosylation mutants require phosphoglycans (lpg2-) but not lipophosphoglycan (lpg1-) for survival in permissive sand fly vectors.
Sand fly species able to support the survival of the protozoan parasite Leishmania have been classified as permissive or specific, based upon their ability to support a wide or limited range of strains and/or species. Studies of a limited number of fly/parasite species combinations have implicated parasite surface molecules in this process and here we provide further evidence in support of this proposal. We investigated the role of lipophosphoglycan (LPG) and other phosphoglycans (PGs) in sand fly survival, using Leishmania major mutants deficient in LPG (lpg1(-)), and the phosphoglycan (PG)-deficient mutant lpg2(-). The sand fly species used were the permissive species Phlebotomus perniciosus and P. argentipes, and the specific vector P. duboscqi, a species resistant to L. infantum development. The lpg2(-) mutants did not survive well in any of the three sand fly species, suggesting that phosphoglycans and/or other LPG2-dependent molecules are required for parasite development. In vitro, all three L. major lines were equally resistant to proteolytic activity of bovine trypsin, suggesting that sand fly-specific hydrolytic proteases or other factors are the reason for the early lpg2(-) parasite killing. The lpg1(-) mutants developed late-stage infections in two permissive species, P. perniciosus and P. argentipes, where their infection rates and intensities of infections were comparable to the wild type (WT) parasites. In contrast, in P. duboscqi the lpg1(-) mutants developed significantly worse than the WT parasites. In combination with previous studies, the data establish clearly that LPG is not required for Leishmania survival in permissive species P. perniciosus and P. argentipes but plays an important role in the specific vector P. duboscqi. With regard to PGs other than LPG, the data prove the importance of LPG2-related molecules for survival of L. major in the three sand fly species tested.


[Risk of infection through use of selective immunomodulating drugs for rheumatoid arthritis].
New drugs for rheumatoid arthritis (RA) have resulted in an improvement in patients' functioning and morbidity, but are linked with increased risk of infections. Traditional immunosuppressant drugs are often used in combination with anti-tumour necrosis factor-alpha (TNF-α) inhibitors or anti-CD20 (rituximab). The review is based on a search in PubMed and on the authors' own experience of treating infections in patients who receive immunosuppressant treatment. Traditional immunomodulating treatment results in an increased risk of infection. The disease RA in itself increases the risk of infections. There is evidence of an increased incidence of infections with both extracellular bacteria and intracellular microorganisms such as mycobacteria, including Mycobacterium tuberculosis, and viruses in patients who are treated with TNF-α inhibitors. Patients who are about to start taking TNF-α inhibitors must therefore undergo a tuberculosis-risk assessment. Rituximab may increase the incidence of infection, but long-term observations are limited. Combination therapy involving different drugs that selectively modulate immune response is normally contraindicated because of the increased risk of infection. The benefit of TNF-α inhibitors and rituximab treatment for RA must be weighed up against the increased risk of infections. Symptoms, findings and laboratory test results pertaining to serious infections may be influenced by immunomodulation therapy and thereby make clinical assessment difficult.


Fluorescence modulation via photoinduced spin crossover switched energy transfer from fluorophores to FeII ions.
Molecular materials possessing phototunable fluorescence properties have attracted great interest owing to their potential applications in optical switches and storage. However, most fluorescence modulation is realized through light-responsive structural isomerization in solution. It is a formidable challenge to achieve phototunable fluorescence emission with high fatigue resistance and a fast response rate in the solid state for the development of devices. Here, a mononuclear compound was constructed via the coordination of fluorophores with FeII ions, whose electronic configuration changed from low spin to high spin upon light irradiation. The photoinduced spin crossover of FeII ions was accompanied by a 20% increase in the fluorescence emission intensity. A temperature-dependent spectroscopic study together with time-dependent density functional theory calculations revealed that the effective spectral overlap between the emission of the fluorophores and the absorption band of the FeII ions differed between the low spin and high spin states. The photoinduced spin crossover switched the energy transfer from the fluorophore to the FeII ion, resulting in fluorescence modulation. The presented results provide a novel approach for developing optical memory and sensors via electron rearrangement of photoinduced spin crossover.


[Capgras syndrome: open perspectives for cognitive neuropsychology].
To examine the way in which certain concepts regarding the physiopathology of Capgras' syndrome (1) have been tested neuropsychologically. Data consist of approximately 30 studies selected for their relevance to the cerebral stages of face processing in patients with schizophrenia, patients with Capgras' syndrome and normal subjects. Study of this work shows: a) that with respect to patients, authors have focused on the stage of treatment corresponding to the facial recognition phase per se; b) but that it is also possible to study the phase corresponding to knowledge and beliefs relative to individuals and to evaluate the existence of the cleavage proposed by numerous psychodynamicians. Views from the field of neuropsychology, like those from the field of psychodynamics, can therefore be tested. By offering a means of developing testable predictions in experimental protocols, cognitive neuropsychology methods will, in short, make it possible to reject erroneous concepts and demonstrate accurate ones. Limited here to the example of Capgras' syndrome, we advocate that the same methods be applied to Capgras' syndrome as to each symptom of schizophrenia.


Incidence of adenocarcinoma among patients with Barrett's esophagus.
Accurate population-based data are needed on the incidence of esophageal adenocarcinoma and high-grade dysplasia among patients with Barrett's esophagus. We conducted a nationwide, population-based, cohort study involving all patients with Barrett's esophagus in Denmark during the period from 1992 through 2009, using data from the Danish Pathology Registry and the Danish Cancer Registry. We determined the incidence rates (numbers of cases per 1000 person-years) of adenocarcinoma and high-grade dysplasia. As a measure of relative risk, standardized incidence ratios were calculated with the use of national cancer rates in Denmark during the study period. We identified 11,028 patients with Barrett's esophagus and analyzed their data for a median of 5.2 years. Within the first year after the index endoscopy, 131 new cases of adenocarcinoma were diagnosed. During subsequent years, 66 new adenocarcinomas were detected, yielding an incidence rate for adenocarcinoma of 1.2 cases per 1000 person-years (95% confidence interval [CI], 0.9 to 1.5). As compared with the risk in the general population, the relative risk of adenocarcinoma among patients with Barrett's esophagus was 11.3 (95% CI, 8.8 to 14.4). The annual risk of esophageal adenocarcinoma was 0.12% (95% CI, 0.09 to 0.15). Detection of low-grade dysplasia on the index endoscopy was associated with an incidence rate for adenocarcinoma of 5.1 cases per 1000 person-years. In contrast, the incidence rate among patients without dysplasia was 1.0 case per 1000 person-years. Risk estimates for patients with high-grade dysplasia were slightly higher. Barrett's esophagus is a strong risk factor for esophageal adenocarcinoma, but the absolute annual risk, 0.12%, is much lower than the assumed risk of 0.5%, which is the basis for current surveillance guidelines. Data from the current study call into question the rationale for ongoing surveillance in patients who have Barrett's esophagus without dysplasia. (Funded by the Clinical Institute, University of Aarhus, Aarhus, Denmark.).


Association of anemia and hypoalbuminemia in German geriatric inpatients: Relationship to nutritional status and comprehensive geriatric assessment.
Anemia and hypoalbuminemia (HA) are acknowledged independent risk factors for morbidity and mortality in geriatric patients and are associated with nutritional status and frailty. Data exist regarding the association between albumin and frailty, anemia and frailty as well as frailty and nutritional status; however, there is a lack of information on the association between HA, anemia and nutritional status in older people. This study retrospectively analyzed 626 patients admitted to a German geriatrics department (average age 81.1 years, 68.2% female and 31.8% male) for anemia and HA. Data from the comprehensive geriatric assessment (CGA) and from the mini-nutritional assessment (MNA) were available in all patients. Patients with anemia suffered significantly more often from HA (p<0.001) than patients without anemia, with an odds ratio (OR) of 1.99 (95% confidence interval CI: 1.2-3.2) and of 5.41 (CI 95%: 2.3-12.6) in patients at risk for malnutrition and in malnourished patients, respectively. A moderately significant association was seen between hemoglobin (Hb) and albumin values (Pearson's correlation r=0.330; p<0.001) as well as between albumin values and the Barthel index (Spearman's correlation r=0.210; p<0.001). Anemia appears to be a risk factor for HA in inpatients with malnutrition and the observed association between albumin and Hb warrants further research. Geriatric inpatients with anemia should be evaluated in terms of the presence of malnutrition risk and HA.


Model-based identifiable parameter determination applied to a simultaneous saccharification and fermentation process model for bio-ethanol production.
In this work, a methodology for the model-based identifiable parameter determination (MBIPD) is presented. This systematic approach is proposed to be used for structure and parameter identification of nonlinear models of biological reaction networks. Usually, this kind of problems are over-parameterized with large correlations between parameters. Hence, the related inverse problems for parameter determination and analysis are mathematically ill-posed and numerically difficult to solve. The proposed MBIPD methodology comprises several tasks: (i) model selection, (ii) tracking of an adequate initial guess, and (iii) an iterative parameter estimation step which includes an identifiable parameter subset selection (SsS) algorithm and accuracy analysis of the estimated parameters. The SsS algorithm is based on the analysis of the sensitivity matrix by rank revealing factorization methods. Using this, a reduction of the parameter search space to a reasonable subset, which can be reliably and efficiently estimated from available measurements, is achieved. The simultaneous saccharification and fermentation (SSF) process for bio-ethanol production from cellulosic material is used as case study for testing the methodology. The successful application of MBIPD to the SSF process demonstrates a relatively large reduction in the identified parameter space. It is shown by a cross-validation that using the identified parameters (even though the reduction of the search space), the model is still able to predict the experimental data properly. Moreover, it is shown that the model is easily and efficiently adapted to new process conditions by solving reduced and well conditioned problems.


Local control of polymicrobial infections via a dual antibiotic delivery system.
Contaminated traumatic open orthopedic wounds are frequently complicated by polymicrobial contamination and infection. In high-risk wounds, the standard of care comprises debridement and irrigation combined with antibiotics which can be applied directly or combined with systemic antibiotics. Recently, bioabsorbable chitosan sponges have been shown to be an effective single-agent delivery device for local antibiotics with and without negative pressure wound therapy (NPWT). Severely contaminated orthopedic wounds, however, are often complicated by polymicrobial infections, necessitating multiple antibiotic agents. As such, the purpose of this study was to determine if a chitosan sponge would provide a suitable delivery vehicle for multiple antibiotics for the treatment of a polymicrobial infection in a large animal polytraumatic extremity wound model. A complex polytraumatic extremity wound was created in 11 adult male Boer goats. Each wound was contaminated with a bioluminescent strain of S. aureus (1 ml of 108 colony forming units/ml) and of P. aeruginosa (1 ml of 108 CFU/ml) which are genetically engineered to allow quantification with a photon-counting camera. Six hours following initial wound creation and contamination, wounds were debrided and irrigated with low-pressure normal saline. The animals were randomized into one of two treatments: wet-to-dry dressings alone or a commercially available chitosan sponge loaded with 1 g vancomycin and 1.2 g of tobramycin. Each animal was then recovered and reimaged 48 h later for total bacteria content; tissue samples were taken from the wound bed to determine relative bacterial colonization. All animals in the chitosan sponge group saw significant reductions in overall bacterial load of S. aureus and P. aeruginosa (p = 0.001). The bioluminescence was also significantly reduced compared to the wet-to-dry dressing group (p = 0.0001). Furthermore, whereas the antibiotic sponge group displayed near complete eradication of bacteria, the wounds treated with the wet-to-dry dressings alone displayed a significant 2-log increase in total bacteria at 48 h p = 0.0001). S. aureus was the predominant species found in the wounds, comprising 95 and 99% of all bacteria found in the chitosan sponge and wet-to-dry, respectively. Dual antimicrobial therapy loaded in a chitosan sponge is an effective way to reduce polymicrobial infections traumatic extremity wound.


High blood pressure trends in children and adolescents in national surveys, 1963 to 2002.
Secular trend data on hypertension in children and adolescents are scarce and inconsistent. In the face of growing obesity, we sought to assess high blood pressure (HBP) secular trends in children and adolescents enrolled in national surveys and to determine whether the HBP trend reversed its course with the rise in obesity. National survey data obtained from multistage probability sampling of the US noninstitutionalized population from 1963 to 2002 were examined; 8- to 17-year-old non-Hispanic blacks and whites and Mexican Americans were included. HBP ascertainment was based on age-, gender-, and height percentile-specific systolic and diastolic BPs. Weighted analyses were performed to account for the complex design. The BP, pre-HBP, and HBP trends were downward from 1963 to 1988 and upward thereafter. Pre-HBP and HBP increased 2.3% (P=0.0003) and 1% (P=0.17), respectively, between 1988 and 1999. Obesity increase, more so abdominal than general obesity, partially explained the rise in HBP and pre-HBP from 1988 to 1999. BP and HBP reversed their downward trends 10 years after the increase in the prevalence of obesity. Additionally, an ethnic and gender gap appeared in 1988 for pre-HBP and in 1999 for HBP; non-Hispanic blacks and Mexican Americans had a greater prevalence of HBP and pre-HBP than non-Hispanic whites, and males had a greater prevalence than females. HBP and pre-HBP in children and adolescents are on the rise. These new findings have implications for the cardiovascular disease public health burden, particularly the risk of a new cardiovascular disease transition. They reinforce the urgent call for early prevention of obesity and HBP and illustrate racial/ethnic disparities in this age group.


Characterization of antigens recognized by new monoclonal antibodies raised against culture filtrate proteins of Mycobacterium bovis bacillus Calmette-Guérin.
Effective protection against Mycobacterium tuberculosis may be achieved in experimental animals by immunization with proteins secreted by tuberculous bacilli in the extracellular milieu during growth. In this study, monoclonal antibodies were raised against Mycobacterium bovis bacillus Calmette-Guérin (BCG) culture filtrate proteins or live BCG, in an attempt to identify novel mycobacterial secretion antigens: the localization of the antigens recognized by the monoclonal antibodies within the mycobacterial cell was studied and interspecies reactivity was also investigated. The monoclonal antibodies obtained recognized proteins of molecular mass ranging from 5 to 82 kDa, with a prevailing frequency in the 30 kDa region. Three of the monoclonal antibodies recognized proteins present only in culture filtrates, one reacted with a cytoplasmic antigen, while the remaining antibodies recognized components which were mainly associated with the cell wall and the cytoplasmic membrane. The chemical nature and possible identity of the antigens was checked. Three monoclonal antibodies are likely to react with novel mycobacterial antigens of 5, 42 and 82 kDa, respectively.


The cell line data base and the new catalogue: Detailed information on 2650 human and animal cell lines.
The Cell Line Data Base (CLDB), set up within the Interlab Project, is a relational database containing data on 2650 Human and animal cell lines which are available in labs and cell banks all over Europe. The second edition of the catalogue, directly generated from the database, has been produced, and will be published in the first months of 1993. Furthermore, the electronic catalogue is available for IBM-compatible personal computers and the version for MacIntosh is under preparation.


Dietary carbohydrates alter the fecal composition and pH and the ammonia emission from slurry of growing pigs.
We investigated the effects of dietary carbohydrates on the composition and pH of fecal material and on the ammonia emission from the slurry of growing pigs. Thirty-four barrows (BW approximately 40 kg) were randomly allotted to 1 of 10 diets. A basal diet was formulated to meet all requirements for protein, amino acids, minerals, and vitamins. The control diet was composed of the basal diet plus heat-treated cornstarch. In the other diets, the cornstarch in the control diet was replaced with three levels of either coconut expeller, soybean hulls, or dried sugar beet pulp. Feces were collected separately from urine in a balance experiment. Feces were mixed with a standardized urine (ratio of 1:2.5, wt/wt) to form a slurry. A sample of this slurry was placed in an in vitro system to determine the pH and the ammonia emission for 16 d at 20 degrees C. The fecal and slurry DM contents decreased (P < .001) and the total VFA concentrations increased (P < .001) when the level of dietary carbohydrates increased. The pH and the ammonia emission decreased as the level of carbohydrates increased (P < .001). The addition of soybean hulls to the diet had the greatest effect on reducing the pH and ammonia emission (P < .001), and the effects of sugar beet pulp and coconut expeller were approximately the same. A linear relationship was found between the intake of dietary nonstarch polysaccharides (NSP) and the ammonia emission (P < .001). For each 100-g increase in the intake of dietary NSP, the slurry pH decreased by approximately .12 unit and the ammonia emission from slurry decreased by 5.4%. We conclude that replacing cornstarch in the diet with components that have a high concentration of fermentable carbohydrates increases the VFA concentration of feces and slurry and reduces the pH and ammonia emission from the slurry of growing pigs.


Guidelines versus clinical practice in antimicrobial therapy for COPD.
Limited information is available about current practice patterns involving the use of antibiotics in the inpatient management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We sought to characterize current patterns of antibiotic use and to compare them to evidence-based guidelines. This study is a retrospective case series of patients at a regional tertiary care medical center. Charts were reviewed to identify patients admitted between January 2006 and 2008 with an initial diagnosis of AECOPD who had no evidence of another infectious process and who were not immunocompromised. Relevant data extracted from charts included initial clinical presentation, antibiotic administration, microbiological studies, and hospital course. One hundred sixteen admissions meeting inclusion criteria were identified. There was no statistically significant relationship between the presence of an established indication for antibiotic administration and the use of antibiotics, with roughly 75% of patients in all groups receiving therapy. A significant fraction of patients received combination therapy that was more appropriate for the management of pneumonia than for AECOPD. There were significant deviations between practice patterns and guidelines regarding the use and selection of antibiotics. Some of these may reflect areas of uncertainty in the primary literature and varying sets of guidelines.


Dimensional stability of short fibre reinforced flowable dental composites.
Fibre-reinforced dental composites are proven to have superior mechanical properties in comparison with micro/nano/hybrid filled composites. However, the addition of small quantities of short glass fibres could affect the dimensional stability of the restoration both during initial stages as well as through the life of the restoration. This in-vitro study aims at evaluating the physical properties of short S-Glass reinforced flowable dental composites. Two S-Glass short fibre-particulate reinforced (5 wt% of aspect ratios 50 and 70) and one particulate only reinforced flowable dental composites were prepared with UDMA-TEGDMA based dental monomer systems. Samples were photopolymersied for 60 s and stored in distilled water at 37 °C for 24 h before testing. Depth of cure (through-thickness microhardness), volumetric shrinkage (Archimedes technique), polymerisation stress (cantilever based tensometer), curing exotherm (thermocouple), water sorption and solubility (ISO 4049) and thermal expansion coefficient (dilatometer) were determined. The test results were statistically analysed using one-way ANOVA (p < 0.05). Depth of cure increased by 41%, volumetric shrinkage increased by 8.3%, shrinkage stress increased by 37.6%, exotherm increased by 20.2%, and thermal expansion reduced by 6.4% while water sorption and solubility had a negligible effect with the inclusion of short glass fibres. The study demonstrates that within the same organic resin system and quantity, a small replacement of fillers with short fibres could significantly affect the dimensional stability of the composite system. In conjunction with mechanical properties, this study could help clinicians to gain confidence in fibre reinforced dental composite restorative system.


Upregulation of miR-92a contributes to blocking goblet cell metaplasia by targeting MUC5AC in asthma.
As a chronic airway disease, asthma has two characteristics, tissue remodeling and airway inflammation. This research focused on miR-92a to explore how it works in asthma. We revealed that the expressions of miR-92a were decreased in both serum and lung tissues from ovalbumin-induced asthma mouse. Bioinformatics analysis, quantitative polymerase chain reaction (qPCR) and dual luciferase assay revealed that miR-92a targets MUC5AC, which was linked to mucus hypersecretion in the pulmonary tracts. By injecting miR-92a-mimics into the trachea, both the airway hyper-reactivity and airway inflammation can be alleviated in an asthma mouse model which is induced by ovalbumin. Moreover, the goblet cell phenotype of asthmatic mice is significantly reduced by the action of miR-92a. Furthermore, miR-92a blocked interleukin (IL)-13-induced MUC5AC luciferase activity in 16HBE. Together, upregulation of miR-92a expression in asthmatic mice plays a role in blocking goblet cell metaplasia by targeting MUC5AC, and thus in the treatment of chronic airway diseases, miR-92a can prevent epithelial remodeling, which is a reasonable method.


Perceptions and experiences of community-based healthcare professionals in the state of Qatar having do not attempt resuscitation discussions during the COVID-19 pandemic.
The values and attitudes of healthcare professionals influence their handling of "do-not-attempt-resuscitation" (DNAR) orders, as does that of the families they interact with. The aim of this study was to describe attitudes, perceptions, and practices among community-based medical practitioners towards discussing cardiopulmonary resuscitation and DNAR orders with patients and their relatives, and to investigate if the COVID-19 pandemic affected their practice in having these discussions. This is a researcher-developed online survey-based study which aimed to recruit a convenience sample of respondents from a total population of 106 healthcare professionals working for the Mobile Healthcare Service (MHS), Hamad Medical Corporation Ambulance Service in the State of Qatar. 33 family physicians, 38 nurses, and 20 paramedics (n = 91) responded to the questionnaire, of who around 40, 8, and 50%, respectively, had engaged in Do Not Attempt Resuscitation discussions during their work with MHS. 15% of physicians who had experience with Do Not Attempt Resuscitation discussions in Qatar felt that the family or patient were not open to having such discussions. 90% of paramedics thought that Do Not Attempt Resuscitation was a taboo topic for their patients in Qatar, and this view was shared by 75% of physicians and 50% of nurses. Per the responses, the COVID-19 pandemic had not affected the likelihood of most of the physicians or nurses (and 50% of the paramedics) identifying patients with whom having a Do Not Attempt Resuscitation discussion would be clinically appropriate. Overall, for all three groups, the COVID-19 pandemic did not affect the likelihood of identifying patients with whom a Do Not Attempt Resuscitation discussion would be clinically appropriate. We found that the greatest barriers in having Do Not Attempt Resuscitation discussions were perceived to be the religious or cultural beliefs of the patient and/or their family, along with the factor of feeling the staff member did not know the patient or their family well enough. All three groups said they would be more likely to have a conversation about Do Not Attempt Resuscitation if barriers were addressed.


Frequency analysis of ultrasonic echo intensities of the skeletal muscle in elderly and young individuals.
The skeletal muscle echo intensity (EI) during ultrasound imaging has been investigated to evaluate the muscle quality. However, EI fluctuates according to the scanning conditions. The motor functions and ultrasound images of 19 elderly (73 ± 3.2 years) and 19 young (22 ± 1.5 years) individuals were investigated and an EI frequency component was assessed for more reliable evaluations. Healthy elderly and young subjects participated in this study. The motor functions were assessed during walking and according to the knee extension muscle strength. The muscle thicknesses of rectus femoris (RF), vastus intermedius (VI), and quadriceps femoris (QF) were investigated. EIs were calculated and the mean frequencies of the regions of interest (MFROIs) for RF and VI were analyzed. EIs and MFROIs were greater in elderly subjects than in young subjects (P<0.01 for RF, and P<0.001 for VI, in EIs; and P<0.01 for RF, and P<0.05 for VI, in MFROIs). In young subjects, EI of RF was greater than that of VI; however, there was no difference between the RF and VI MFROIs in both elderly and young subjects. EIs of VI exhibited a significantly negative correlation with the QF thickness in both elderly and young subjects. RF MFROIs negatively correlated with the QF thickness and positively correlated with EI of VI in elderly subjects alone. These findings suggest that MFROIs of elderly individuals would have a larger value than those of young individuals; moreover, MFROIs did not fluctuate greatly with the tissue depth and scanning conditions. MFROIs might be thus useful for further investigations of muscle quality and applications for the early prevention of age-related motor functional decline.


In what clinical settings should Cushing's syndrome be suspected?
Despite its low frequency, endogenous Cushing's syndrome is not an exceptional clinical entity. A growing number of cases are currently derived to specialized centers suggesting an increasing knowledge of the clinical features of hypercortisolism by specialists of diverse branches of clinical medicine. Clinical signs derive from an exaggeration of the physiological actions of cortisol inducing protein breakdown, hyperglycemia, fat mobilization, dyslipidemia, hydrosaline retention, immunosuppression and increased susceptibility to infection. Despite its low specificity, symptoms such as unexplained development of central obesity, mood changes, fatigue, weakness, myopathy, easy bruisability, red striae, arterial hypertension, diabetes and hyperlipidemia, are suggestive of the diagnosis. From an epidemiological point of view, Cushing's syndrome is to be suspected and consequently searched for among patients with uncontrolled high blood pressure or diabetes mellitus, metabolic syndrome, polycystic ovarian syndrome, osteoporosis, depression or adrenal incidentaloma. True Cushing's syndrome has to be differentiated from pseudo syndromes. Most sensitive physical signs for discriminating Cushing's syndrome from pseudo-Cushing states are the presence of supraclavicular fat pads, myopathy, thin skin and easy bruising. The recognition of the clinical manifestations of Cushing's syndrome and of the sub-populations at risk of contracting the disease should be improved through medical education at the medical school and at postgraduate levels. Clinical detection of Cushing's syndrome must be performed mainly by non-endocrinologists, yet its etiological diagnosis and therapeutic management is to be carried out in highly experienced and specialized centers, to ensure the best results in the treatment of this really challenging endocrine disturbance.


Histopathological and Inflammatory Features of Chronically Discharging Open Mastoid Cavities: Secondary Analysis of a Randomized Clinical Trial.
Many patients with an open radical mastoid cavity experience therapy-resistant otorrhea. Little is known about the underlying histopathological substrate of unstable cavities and the correlation with treatment failure. To study the histopathological and inflammatory features of chronically discharging open radical mastoid cavities and the influence of different treatments. This secondary analysis of a randomized clinical trial was a histopathology study of tissue samples of a cohort of 30 patients with a chronically discharging open mastoid cavity. Samples were taken from the cavities, which were treated with either honey gel or conventional eardrops in a tertiary center between 2012 and 2013. Tissue staining was performed in May 2014; final computer analysis/correlation studies were performed in June 2016. Differences of epithelial tissue coverage, infiltration of T cells (CD3, CD4, CD8) and macrophage (CD68, isoenzyme nitric oxide synthase, arginase 1) (sub-)populations, infection status, and the correlation with clinical presentation. There were 30 patients (24 [80%] male; mean [SD] age, 59 [14] years). Cavities were covered with either stratified squamous (keratinized) epithelium (n = 10), respiratory columnar epithelium (n = 9), or granulation tissue (n = 10). The presence of respiratory epithelium was associated with lower treatment success (posttreatment VAS improvement of 3.1 [95% CI, 0.5 to 5.8] for discomfort and 3.6 [95% CI, 0.2 to 6.9] for otorrhea in the group with granulation tissue coverage vs 4.9 [95% CI, 0.2 to 9.6] and 5.8 [95% CI, -0.1 to 11.6] in the group with squamous [keratinized] epithelium coverage and 1.4 [95% CI, -1.2 to 4.1] and 2.5 [95% CI, -1.3 to 6.2] in the group with respiratory columnar epithelium coverage). In all 3 tissue types of cavity-covering tissues, T-cell infiltrates consisted of helper T cells and cytotoxic T cells, together with a lower number of macrophages. The immunopositivity for isoenzyme nitric oxide synthase and arginase 1 was high and not restricted to a macrophage subpopulation, but seen in various cell types. Inflammatory infiltrations varied strongly in all 3 tissue modalities. Discharging open mastoid cavities can be classified histologically into 3 different types, based on their coverage: squamous epithelium, respiratory epithelium, or granulation tissue. Treatment is less successful in cavities covered with respiratory epithelium, possibly explained by the status of bacterial infection and local immunological differences.


Pert analysis of endogenous retroviruses induced from K-BALB mouse cells treated with 5-iododeoxyuridine: a potential strategy for detection of inducible retroviruses from vaccine cell substrates.
The activation of an endogenous, infectious retrovirus in a cell substrate that is used for the production of biologics is an important safety concern, especially in the case of live, viral vaccines, where there are minimal purification and inactivation steps in order to preserve high vaccine potency. Extensive analysis has been done to evaluate various chemical agents for the induction of endogenous retroviruses in murine and avian cells; however, similar studies have not been done with cells of other species, especially human and non-human primates, that are used in vaccine production. To develop a strategy for optimal induction and sensitive detection of endogenous, infectious retroviruses in currently used or potential vaccine cell substrates, we have initially investigated the use of a state-of-the-art, highly-sensitive, product-enhanced reverse transcriptase (PERT) assay for evaluating the kinetics of retrovirus induction and replication in 5-iododeoxyuridine (IdU)-treated K-BALB mouse cells, where endogenous retrovirus activation has previously been described. In general, the overall kinetics of virus production were similar to those of previous studies in that two peaks of RT activity were seen on long-term culture of IdU-treated K-BALB cells; however, retrovirus activation was detected earlier under our induction conditions and with greater sensitivity using the PERT assay, where 1-10 virions were detected in 1 microl equivalent of the test sample, without concentration. Furthermore, the PERT activity corresponded to the presence of infectious, murine leukaemia viruses (MuLVs) induced from K-BALB cells. Based upon these results, a strategy is proposed using the PERT assay for detection of inducible, endogenous retroviruses in vaccine cell substrates.


Muscle Glycogen in Elite Soccer - A Perspective on the Implication for Performance, Fatigue, and Recovery.
Based on extrapolation of current trends in modern soccer, physiological loading has increased markedly, and the game will continue to become even more demanding in the future, which will exacerbate fatigue at the end of a game and between games. Soccer is a glycogen consuming activity due to its high-intensity intermittent nature, and muscle glycogen is a key factor associated with fatigue late in a game, as well as in determining recovery after a game or an intense training session. Low glycogen in individual muscle fibers and subcellular compartments in the muscle cell is likely to negatively affect several essential steps in the excitation-contraction coupling such as action potential propagation, calcium handling and cross-bridge cycling through reductions in muscle ATP which are suggested sites of muscle function impairment inducing muscle fatigue. Recovery of physical performance and muscle glycogen after a soccer game is a slow process, which challenges the reality in modern elite soccer with increased game and training frequency and physiological loading. We suggest a markedly higher prioritization of fitness training modalities, nutritional approaches and general recovery strategies that optimizes muscle glycogen storage prior to games and training sessions. Also, the soccer community including the governing bodies of the sport must acknowledge and plan according to the high and increasing demands of the modern game, as well as the consequences this has on fatigue and recovery. These aspects are paramount to consider in the planning of training and games, as well as in the process of structuring soccer tournaments and developing competitive regulations in the future to optimize performance and player health.


The expression of two novel orange-spotted grouper (Epinephelus coioides) TNF genes in peripheral blood leukocytes, various organs, and fish larvae.
The tumour necrosis factor (TNF) super-family is a group of important cytokines involved in inflammation, apoptosis, cell proliferation, and the general stimulation of the immune system. The TNF gene has been cloned in some bony fish; however, its counterparts are still unidentified in the majority of fish species. In this study, we cloned gTNF-1 and gTNF-2 from the orange-spotted grouper (Epinephelus coioides), an economically important farmed fish. Both genes include 4 exons and 3 introns and encoded 253 and 241 amino acid proteins with a molecular weight of approximately 27 and 26 kDa, respectively. The identity of the putative amino acid sequences between gTNF-1 and gTNF-2 was only 38%. The positions of cysteine residues, a protease cleavage site, and a transmembrane domain sequence derived from gTNF-1 and gTNF-2 were similar to those in other fish and mammalian TNF-α. The mRNA expression levels of the 2 gTNF molecules were evaluated in unstimulated/stimulated peripheral blood leukocytes, various organs, and fish larvae. Following lipopolysaccharide (LPS) treatment, gTNF-2 was expressed at higher levels, was up-regulated more quickly, and was more sensitive to the immune response than gTNF-1. gTNF-1 was constitutively expressed in the thymus, brain, and spleen, but it was also expressed in the heart, head kidney, and trunk kidney after LPS stimulation. gTNF-2 was constitutively expressed in the thymus, head kidney, trunk kidney, spleen, and intestine; further, gTNF-2 was highly expressed in all organs post-LPS stimulation. Finally, the gTNF expression levels were evaluated at various developmental stages in grouper larvae. A higher variation of gTNF expression levels was observed in fish larvae from a contaminated hatchery. This study revealed the different expression patterns of gTNF-1 and gTNF-2. In addition, gTNF-2 was more sensitive to pathogens than gTNF-1; therefore, it may be an appropriate marker for pathogen invasion and the evaluation of the larval rearing environment.


Randomized trials versus observational studies in adolescent pregnancy prevention.
The objective of this study is to compare the results of randomized trials and observational studies of interventions to prevent adolescent pregnancy. We identified published and unpublished reports through computerized searches of CATLINE, CINAHL, CONFERENCE PAPERS INDEX, DISSERTATION ABSTRACTS ONLINE, EMBASE, ERIC, MEDLINE, NTIS, POPLINE, PsycINFO, and SOCIOLOGICAL ABSTRACTS; manual searches of eight relevant journals; reference lists from primary articles; and contact with content experts. We included randomized trials and observational studies that evaluated the impact of primary prevention interventions including sex education classes, school-based clinics, free-standing clinics, physician/nurse practitioner practice-based service, improved access, and community-based programs on four outcomes: sexual intercourse, birth control use, responsible sexual behavior, or pregnancy in adolescents. One investigator abstracted the data and a second conducted a detailed review of the abstraction. We identified 13 randomized trials and 17 observational studies. We generated estimates of the impact of the interventions separately for males and females for all four outcomes for both observational studies and randomized trials. For six of the eight outcomes the summary odds ratios for the observational studies showed a significant intervention benefit (P<0.05) while the randomized trials did not show a benefit for any outcome in either females or males. The difference between the results of the observational studies and randomized trials was statistically significant in two of the eight outcomes (P<0.05 for initiation of intercourse and pregnancy in females). Observational studies yield systematically greater estimates of treatment effects than randomized trials of adolescent pregnancy prevention interventions. Public policy or individual patient treatment decisions should be based on observational studies only when randomized trials are unavailable and only with careful consideration of possible biases.


Modeling Contaminant Microbes in Rivers During Both Baseflow and Stormflow.
Rivers transport contaminant microorganisms (including fecal indicator bacteria and human pathogens) long distances downstream of diffuse and point sources, posing a human health risk. We present a mobile-immobile model that incorporates transport as well as immobilization and remobilization of contaminant microbes and other fine particles during baseflow and stormflow. During baseflow conditions, hyporheic exchange flow causes particles to accumulate in streambed sediments. Remobilization of stored particles from streambed sediments occurs slowly during baseflow via hyporheic exchange flow, while remobilization is vastly increased during stormflow. Model predictions are compared to observations over a range of artificial and natural flood events in the dairy contaminated Topehaehae Stream, New Zealand. The model outputs closely matched timing and magnitude of E. coli and turbidity observations through multiple high-flow events. By accounting for both state-of-flow and hyporheic exchange processes, the model provides a valuable framework for predicting particle and contaminant microbe behavior in streams.


Transient suppression of broadband gamma power in the default-mode network is correlated with task complexity and subject performance.
Task performance is associated with increased brain metabolism but also with prominent deactivation in specific brain structures known as the default-mode network (DMN). The role of DMN deactivation remains enigmatic in part because its electrophysiological correlates, temporal dynamics, and link to behavior are poorly understood. Using extensive depth electrode recordings in humans, we provide first electrophysiological evidence for a direct correlation between the dynamics of power decreases in the DMN and individual subject behavior. We found that all DMN areas displayed transient suppressions of broadband gamma (60-140 Hz) power during performance of a visual search task and, critically, we show for the first time that the millisecond range duration and extent of the transient gamma suppressions are correlated with task complexity and subject performance. In addition, trial-by-trial correlations revealed that spatially distributed gamma power increases and decreases formed distinct anticorrelated large-scale networks. Beyond unraveling the electrophysiological basis of DMN dynamics, our results suggest that, rather than indicating a mere switch to a global exteroceptive mode, DMN deactivation encodes the extent and efficiency of our engagement with the external world. Furthermore, our findings reveal a pivotal role for broadband gamma modulations in the interplay between task-positive and task-negative networks mediating efficient goal-directed behavior and facilitate our understanding of the relationship between electrophysiology and neuroimaging studies of intrinsic brain networks.


Fibrosis in Preeclamptic Placentas Is Associated with Stromal Fibroblasts Activated by the Transforming Growth Factor-β1 Signaling Pathway.
Although fibrosis is one of the most prominent pathologic features of preeclamptic (PE) placentas, its mechanism remains largely unknown. Consistent with previous reports, we observed overexpression of collagen; actin, α2, smooth muscle, aorta; connective tissue growth factor; and fibronectin in PE placentas compared with control ones. To investigate the mechanism of fibrosis in PE placentas, placental fibroblasts were isolated from PE placentas or normal pregnancies at delivery. The expression of fibrosis-related factors in fibroblasts was evaluated by real-time RT-PCR, Western blotting, enzyme-linked immunosorbent assay, and gene microarrays. An in vitro collagen gel contraction assay was also performed. Fibroblasts isolated from PE placentas showed higher expression levels of fibrosis-related factors compared with those from control ones. Global gene expression profiling of PE fibroblasts was contrasted with that of control ones and indicated an intimate association with transforming growth factor-β1 (TGFB1) signaling. Furthermore, the PE fibroblasts expressed abundant phosphorylated SMAD family member 2 and showed higher expression levels of target genes of TGFB1 signaling compared with the control ones. The PE fibroblasts also had a greater ability to contract compared with the control ones. Contractility also depended on TGFB1 signaling. Our results suggest that TGFB1 signaling is activated in the fibroblasts in PE placentas and that these active fibroblasts contribute to fibrosis.


New Evidence on the Effects of Mandatory Waiting Periods for Abortion.
Beyond a handful of studies examining early-adopting states in the early 1990s, little is known about the causal effects of mandatory waiting periods for abortion. In this study we evaluate the effects of a Tennessee law enacted in 2015 that requires women to make an additional trip to abortion providers for state-directed counseling at least 48 hours before they can obtain an abortion. Our difference-in-differences and synthetic-control estimates indicate that the introduction of the mandatory waiting period caused a 53-69 percent increase in the share of abortions obtained during the second trimester. Our analysis examining overall abortion rates is less conclusive but suggests a reduction caused by the waiting period. To put these estimates into context, we provide back-of-the-envelope calculations on the additional monetary costs that Tennessee's MWP imposes on women seeking abortions.