Entropic potential field formed for a linear-motor protein near a filament: Statistical-mechanical analyses using simple models.
We report a new progress in elucidating the mechanism of the unidirectional movement of a linear-motor protein (e.g., myosin) along a filament (e.g., F-actin). The basic concept emphasized here is that a potential field is entropically formed for the protein on the filament immersed in solvent due to the effect of the translational displacement of solvent molecules. The entropic potential field is strongly dependent on geometric features of the protein and the filament, their overall shapes as well as details of the polyatomic structures. The features and the corresponding field are judiciously adjusted by the binding of adenosine triphosphate (ATP) to the protein, hydrolysis of ATP into adenosine diphosphate (ADP)+Pi, and release of Pi and ADP. As the first step, we propose the following physical picture: The potential field formed along the filament for the protein without the binding of ATP or ADP+Pi to it is largely different from that for the protein with the binding, and the directed movement is realized by repeated switches from one of the fields to the other. To illustrate the picture, we analyze the spatial distribution of the entropic potential between a large solute and a large body using the three-dimensional integral equation theory. The solute is modeled as a large hard sphere. Two model filaments are considered as the body: model 1 is a set of one-dimensionally connected large hard spheres and model 2 is a double helical structure formed by two sets of connected large hard spheres. The solute and the filament are immersed in small hard spheres forming the solvent. The major findings are as follows. The solute is strongly confined within a narrow space in contact with the filament. Within the space there are locations with sharply deep local potential minima along the filament, and the distance between two adjacent locations is equal to the diameter of the large spheres constituting the filament. The potential minima form a ringlike domain in model 1 while they form a pointlike one in model 2. We then examine the effects of geometric features of the solute on the amplitudes and asymmetry of the entropic potential field acting on the solute along the filament. A large aspherical solute with a cleft near the solute-filament interface, which mimics the myosin motor domain, is considered in the examination. Thus, the two fields in our physical picture described above are qualitatively reproduced. The factors to be taken into account in further studies are also discussed.


Occurrence and ecotoxicological risk assessment of non-steroidal anti-inflammatory drugs in South African aquatic environment: What is known and the missing information?
Non-steroidal anti-inflammatory drugs (NSAIDs) are medications used individually or as mixtures with other pharmaceuticals for the treatment of various illnesses. Their easy accessibility and high human consumption have resulted to their detection at high concentrations in South African water resources. In the present work, an extensive review of the occurrence and ecotoxicological risk assessment of NSAIDs in South African aquatic environment is provided. Reviewed literature suggested ibuprofen, naproxen, diclofenac, ketoprofen and fenoprofen as the most prominent NSAIDs in the South African aquatic environment. Among these NSAIDs, higher concentrations of ibuprofen are common in South African waters. As a result, this drug was found to pose high ecotoxicological risks towards the aquatic organisms with the highest risk quotients of 14.9 and 11.9 found for algae in surface water and wastewater, respectively. Like in other parts of the world, NSAIDs are not completely removed in wastewater treatment plants. Removal efficiencies below 0% due to higher concentrations of NSAIDs in wastewater effluents rather than influents were observed in certain instances. The detection of NSAIDs in sediments and aquatic plants could serve as the important starting step to investigate other means of NSAIDs removal from water. In conclusion, recommendations regarding future studies that could paint a clearer picture regarding the occurrence and ecotoxicological risks posed by NSAIDs in South African aquatic environment are provided.


Self-coacervation of modular squid beak proteins - a comparative study.
The beak of the Humboldt squid is a biocomposite material made solely of organic components - chitin and proteins - which exhibits 200-fold stiffness and hardness gradients from the soft base to the exceptionally hard tip (rostrum). The outstanding mechanical properties of the squid beak are achieved via controlled hydration and impregnation of the chitin-based scaffold by protein coacervates. Molecular-based understanding of these proteins is essential to mimic the natural beak material. Here, we present detailed studies of two histidine-rich beak proteins (HBP-1 and -2) that play central roles during beak bio-fabrication. We show that both proteins have the ability to self-coacervate, which is governed intrinsically by the sequence modularity of their C-terminus and extrinsically by pH and ionic strength. We demonstrate that HBPs possess dynamic structures in solution and achieve maximum folding in the coacervate state, and propose that their self-coacervation is driven by hydrophobic interactions following charge neutralization through salt-screening. Finally, we show that subtle differences in the modular repeats of HBPs result in significant changes in the rheological response of the coacervates. This knowledge may be exploited to design self-coacervating polypeptides for a wide range of engineering and biomedical applications, for example bio-inspired composite materials, smart hydrogels and adhesives, and biomedical implants.


Diagnostic value of antibody-induced procoagulant platelets in heparin-induced thrombocytopenia: Communication from the ISTH SSC Subcommittee on Platelet Immunology.
Heparin-induced thrombocytopenia (HIT) is an immune-mediated prothrombotic disorder characterised by a drop in platelet count and an increased risk of thromboembolic events. The accurate diagnosis of HIT involves clinical assessment and laboratory testing with well characterized functional tests. Recent research has shown the potential of investigating procoagulant platelet formation induced by HIT antibodies. To successfully implement these assays in clinical laboratories, careful consideration of technical and preanalytical factors is crucial. In this Communication from the SSC Platelet Immunology, we provide a consensus from experts on the use of flow cytometry in HIT diagnosis, highlighting the importance of standardized protocols.


Intimate partner violence during pregnancy and the first year postpartum in an Australian pregnancy cohort study.
To assess intimate partner violence (IPV) in a longitudinal cohort study during and after pregnancy, and examine social and economic factors encouraging or inhibiting violence. Nulliparous women were recruited from 6 public hospitals in Melbourne, Australia. Self-administered questionnaires included standardised measures assessing fear of an intimate partner at enrolment, 6 and 12 months postpartum; and period prevalence of physical and emotional abuse in the first 12 months postpartum. 1,507 women completed baseline data (mean gestation 15 weeks). Response fractions at 3, 6 and 12 months postpartum were 95, 93 and 90%, respectively. 5.1 and 5.4% of women reported fear in pregnancy and the first year postpartum, respectively. 17% experienced physical and/or emotional abuse in the first year postpartum. Most women who reported fear of an intimate partner in the first year after the index birth reported fear before and/or during pregnancy. Women working in early pregnancy who qualified for paid maternity leave had significantly reduced odds of reporting combined physical and emotional IPV in the first 12 months postpartum compared with women not working (Adj. OR 0.21, 95% CI 0.08-0.55). Women working but not eligible for paid leave had reduced odds compared with women not working (Adj. OR 0.49, 95% CI 0.24-1.00). Models adjusted for maternal age, relationship status, income and education level. Few first time mothers reported fear for the first time after childbirth suggesting that IPV more commonly commences prior to the first birth. Paid maternity leave may have broader social benefits beyond immediate financial benefits to women and families.


Contribution to laboratory diagnostics of neuroborreliosis.
Neuroborreliosis affects peripheral and central nervous system. Point out on possibilities of laboratory diagnostics of neuroborreliosis. During 1997-2001 we tested 666 pair samples of CSF and serum from 661 patients with different neurological diagnosis by ELISA, Westernblot, PCR, completed by biochemical and cytological investigations. We confirmed intrathecal specific IgG antibodies production by AI in 14 cases (2.1%) of total 666 samples tested. From those in 7 cases there were present also IgM antibodies in CSF. We found borderline AI values in 3 cases (0.5%) and isolated intrathecal production, antibodies present only in CSF, in 1 case (0.15%). There were normal AI values found in 25 cases (3.8%). Specific antibody possitivity by WB method was detected only in one case. DNA positivity by PCR was detected in one CSF from 43 samples during 2 years period. The microbiological test results should not be used in isolation but used in correlation with the biochemical and cytologic tests and also with clinical symptoms and epidemiological data to produce an overall clinical diagnosis. (Tab. 7, Fig. 1, Ref. 21)


[Molecular aspects of congenital heart diseases].
Significant advances in the understanding of the molecular and genetic basis of congenital heart disease have emerged from gene inactivation studies in mice and from human genetic investigations. The identification of genes for heart defects have led to a clinical approach of these malformations in children and their families. These progresses have been made with the help of molecular biology as well as with the analysis of mouse models. Paediatric cardiologists have improved their efficiency in defining cardiac phenotypes but the genetic heterogeneity has made the molecular approach of a given defect difficult. In this review, we summarize different genetic causes for congenital heart disease and we highlight relevant genetic data for cardiac development in animal models.


Extensive Alternative Splicing Patterns in Systemic Lupus Erythematosus Highlight Sexual Differences.
Substantial evidence highlights divergences in immune responses between men and women. Women are more susceptible to autoimmunity, whereas men suffer from the more severe presentation of autoimmune disorders. The molecular mechanism of this sexual dimorphism remains elusive. Herein, we conducted a comprehensive analysis of sex differences in whole-blood gene expression focusing on alternative splicing (AS) events in systemic lupus erythematosus (SLE), which is a prototype sex-biased disease. This study included 79 SLE patients with active disease and 58 matched healthy controls who underwent whole-blood RNA sequencing. Sex differences in splicing events were widespread, existent in both SLE and a healthy state. However, we observed distinct gene sets and molecular pathways targeted by sex-dependent AS in SLE patients as compared to healthy subjects, as well as a notable sex dissimilarity in intron retention events. Sexually differential spliced genes specific to SLE patients were enriched for dynamic cellular processes including chromatin remodeling, stress and inflammatory responses. Remarkably, the extent of sexual differences in AS in the SLE patients and healthy individuals exceeded those in gene expression. Overall, this study reveals an unprecedent variation in sex-dependent splicing events in SLE and the healthy state, with potential implications for understanding the molecular basis of sexual dimorphism in autoimmunity.


An animal model for teaching subfacial ligation of perforator veins to treat venous stasis ulcers.
Endoscopic subfacial ligation of perforator veins in the lower limb has been described in the treatment of venous stasis ulcer. An animal model to enable surgeons to become familiar with the surgical technique is presented. The model uses the porcine abdominal wall and allows practice in endoscopic dissection and ligation using appropriate instrumentation in an environment that is a reasonable surrogate for the human calf.


The first international leprosy conference, Berlin, 1897: the politics of segregation.
The present paper examines the first attempts to internationalize the problem of leprosy, a subject hitherto overlooked by historians of imperialism and disease. The last decade of the nineteenth century saw many in the 'civilized countries' of the imperialist West gripped by a paranoia about an invasion of leprosy via germ-laden immigrants and returning expatriates who had acquired the infection in leprosy-endemic colonial possessions. Such alarmists clamoured for the adoption of vigorous leper segregation policies in such colonies. But the contagiousness of leprosy did not go unquestioned by other westerners. The convocation in Berlin of the first international meeting on leprosy revealed the interplay of differing and sometimes incompatible views about the containment of leprosy by segregation. The roles of officials from several countries, as well as the roles of five protagonists (Albert Ashmead, Jules Goldschmidt, Edvard Ehlers, Armauer Hansen, and Phineas Abraham) in the shaping of the Berlin Conference are here examined.


Transversus abdominis plane block to ameliorate postoperative pain outcomes after laparoscopic surgery: a meta-analysis of randomized controlled trials.
Transversus abdominis plane (TAP) block has been used as a multimodal strategy to optimize postoperative pain outcomes; however, it remains unclear which type of surgical procedures can benefit from the administration of a TAP block. Several studies have examined the effect of the TAP block on postoperative pain outcomes after laparoscopic surgical procedures and generated conflicting results. Our main objective in the current investigation was to evaluate the effect of TAP block on postoperative analgesia outcomes for laparoscopic surgical procedures. A search was performed to identify randomized controlled trials that evaluated the effects of the TAP block compared with an inactive group (placebo or "no treatment") on postoperative pain outcomes in laparoscopic surgical procedures. Primary outcomes included early (0-4 hours) and late (24 hours) postoperative pain at rest and on movement and postoperative opioid consumption (up to 24 hours). Meta-analysis was performed using a random-effects model. Publication bias was evaluated by examining the presence of asymmetric funnel plots using Egger regression test. Meta-regression analysis was performed to establish an association between the local anesthetic dose and the evaluated outcomes. Ten randomized clinical trials with 633 subjects were included in the analysis. The weighted mean difference (99% confidence interval) of the combined effects favored TAP block over control for pain at rest (≤4 hours, -2.41 [-3.6 to -1.16]) and (at 24 hours, -1.33 [-2.19 to -0.48]) (0-10 numerical scale). Postoperative opioid consumption was decreased in the TAP block group compared with control, weighted mean difference (99% confidence interval) of -5.74 (-8.48 to -2.99) mg morphine IV equivalents. Publication bias was not present in any of the analysis. Preoperative TAP block administration resulted in greater effects on early pain and opioid consumption compared with postoperative administration. Meta-regression analysis revealed an association between local anesthetic dose and the TAP block effect on late pain at rest and postoperative opioid consumption. None of the studies reported symptoms of local anesthetic toxicity. TAP block is an effective strategy to improve early and late pain at rest and to reduce opioid consumption after laparoscopic surgical procedures. In contrast, the TAP block was not superior compared with control to reduce early and late pain during movement. Preoperative administration of a TAP block seems to result in greater effects on postoperative pain outcomes. We also detected a local anesthetic dose response on late pain and postoperative opioid consumption.


Systemic absorption and adverse ocular and systemic effects after topical ophthalmic administration of 0.1% diclofenac to healthy cats.
To quantify plasma concentrations and determine adverse ocular, renal, or hepatic effects associated with repeated topical ophthalmic application of 0.1% diclofenac to healthy cats. 8 healthy sexually intact male cats. A randomized, placebo-controlled crossover study was conducted. A topical formulation of 0.1% diclofenac was administered 4 times/d for 7 days to 4 cats, and artificial tear (control) solution was administered to the other 4 cats. After a 12-day washout period, cats received the other treatment. Ophthalmic examinations were performed daily. Plasma samples were obtained on days 1 and 7 for pharmacokinetic analysis. A CBC, serum biochemical analysis, urinalysis, determination of urine protein-to-creatinine ratio, and determination of glomerular filtration rate were performed before the start of the study and after each 7-day treatment period. Mild conjunctival hyperemia was the only adverse ocular effect detected. Maximal drug concentration and area under the curve were significantly higher on day 7 than on day 1. Diclofenac-treated cats had a significantly lower glomerular filtration rate than did control-treated cats after the second but not after the first treatment period, presumably associated with iatrogenic hypovolemia. Topical ophthalmic administration of 0.1% diclofenac was well tolerated in healthy cats, with only mild signs of ocular irritation. Detectable systemic concentrations of diclofenac were achieved with accumulation over 7 days. Systemic absorption of diclofenac may be associated with reduced glomerular filtration rate, particularly in volume-contracted animals. Topical ophthalmic 0.1% diclofenac should be used with caution in volume-contracted or systemically ill cats.


EAN consensus review on prevention, diagnosis and management of tick-borne encephalitis.
Tick-borne encephalitis (TBE) is an infection of the central nervous system (CNS) caused by tick-borne encephalitis virus (TBEV) and transmitted by ticks, with a variety of clinical manifestations. The incidence of TBE in Europe is increasing due to an extended season of the infection and the enlargement of endemic areas. Our objectives are to provide recommendations on the prevention, diagnosis and management of TBE, based on evidence or consensus decisions. For systematic evaluation, the literature was searched from 1970 to 2015 (including early online publications of 2016), and recommendations were based on evidence or consensus decisions of the Task Force when evidence-based data were not available. Vaccination against TBE is recommended for all age groups above 1 year in highly endemic areas (≥5 cases/100 000/year), but also for individuals at risk in areas with a lower incidence. Travellers to endemic areas should be vaccinated if their visits will include extensive outdoor activities. Post-exposure prophylaxis after a tick bite is not recommended. A case of TBE is defined by the presence of clinical signs of meningitis, meningoencephalitis or meningoencephalomyelitis with cerebrospinal fluid (CSF) pleocytosis (>5 × 106 cells/l) and the presence of specific TBEV serum immunoglobulin M (IgM) and IgG antibodies, CSF IgM antibodies or TBEV IgG seroconversion. TBEV-specific polymerase chain reaction in blood is diagnostic in the first viremic phase but it is not sensitive in the second phase of TBE with clinical manifestations of CNS inflammation. Lumbar puncture should be performed in all patients with suspected CNS infection unless there are contraindications. Imaging of the brain and spinal cord has a low sensitivity and a low specificity, but it is useful for differential diagnosis. No effective antiviral or immunomodulating therapy is available for TBE; therefore the treatment is symptomatic. Patients with a potentially life threatening meningoencephalitis or meningoencephalomyelitis should be admitted to an intensive care unit. In the case of brain oedema, analgosedation should be deepened; osmotherapy and corticosteroids are not routinely recommended. If intracranial pressure is increased, therapeutic hypothermia or decompressive craniectomy might be considered. Seizures should be treated as any other symptomatic epileptic seizures. Tick-borne encephalitis is a viral CNS infection that may result in long-term neurological sequelae. Since its incidence in Europe is increasing due to broadening of endemic areas and prolongation of the tick activity season, the health burden of TBE is enlarging. There is no effective antiviral treatment for TBE, but the disease may be effectively prevented by vaccination.


MiMiR--an integrated platform for microarray data sharing, mining and analysis.
Despite considerable efforts within the microarray community for standardising data format, content and description, microarray technologies present major challenges in managing, sharing, analysing and re-using the large amount of data generated locally or internationally. Additionally, it is recognised that inconsistent and low quality experimental annotation in public data repositories significantly compromises the re-use of microarray data for meta-analysis. MiMiR, the Microarray data Mining Resource was designed to tackle some of these limitations and challenges. Here we present new software components and enhancements to the original infrastructure that increase accessibility, utility and opportunities for large scale mining of experimental and clinical data. A user friendly Online Annotation Tool allows researchers to submit detailed experimental information via the web at the time of data generation rather than at the time of publication. This ensures the easy access and high accuracy of meta-data collected. Experiments are programmatically built in the MiMiR database from the submitted information and details are systematically curated and further annotated by a team of trained annotators using a new Curation and Annotation Tool. Clinical information can be annotated and coded with a clinical Data Mapping Tool within an appropriate ethical framework. Users can visualise experimental annotation, assess data quality, download and share data via a web-based experiment browser called MiMiR Online. All requests to access data in MiMiR are routed through a sophisticated middleware security layer thereby allowing secure data access and sharing amongst MiMiR registered users prior to publication. Data in MiMiR can be mined and analysed using the integrated EMAAS open source analysis web portal or via export of data and meta-data into Rosetta Resolver data analysis package. The new MiMiR suite of software enables systematic and effective capture of extensive experimental and clinical information with the highest MIAME score, and secure data sharing prior to publication. MiMiR currently contains more than 150 experiments corresponding to over 3000 hybridisations and supports the Microarray Centre's large microarray user community and two international consortia. The MiMiR flexible and scalable hardware and software architecture enables secure warehousing of thousands of datasets, including clinical studies, from microarray and potentially other -omics technologies.


Lesion location associated with balance recovery and gait velocity change after rehabilitation in stroke patients.
Impaired gait function after stroke contributes strongly to overall patient disability. However, the response to rehabilitation varies between individuals. The aims of this study were to identify predictors of gait velocity change and to elucidate lesion location associated with change of balance and gait function. We reviewed 102 stroke patients. The patients were divided into two groups according to gait ability post-rehabilitation, and we analyzed differences in their characteristics, such as demographic information, lesion factors, and initial balance function. Multivariate regression analyses were performed to examine the predictors of rehabilitation response. Lesion location and volume were measured on brain magnetic resonance images. We generated statistical maps of the lesions related to functional gains in gait and balance using voxel-based lesion symptom mapping (VLSM). The group of patients who regained independent ambulation function showed a smaller lesion size, a shorter duration from stroke onset, and higher initial balance function. In the regression model, gait velocity changes were predicted with the initial Berg balance scale (BBS) and duration post-onset. Absolute BBS changes were also correlated with the duration post-onset and initial BBS, and relative BBS changes were predicted by the baseline BBS. Using VLSM, lesion locations associated with gait velocity changes and balance adjusting for other factors were the insula, internal capsule, and adjacent white matter. Initial balance function as well as the interval between stroke onset and the initiation of therapy might influence balance recovery and gait velocity changes. Damage to the insula and internal capsule also affected gait velocity change after rehabilitation.


[Coxiella burnetii and Q fever in Brazil: a public health issue].
Q fever is a zoonosis that is broadly distributed worldwide, despite few reports associated with its occurrence in Brazil. Coxiella burnetii, namely the causative agent of Q fever is a gram-negative coccobacillus and an obligate intracellular bacterial parasite of the order of Legionellales. The microorganism is generally present in the urine and feces of infected animals and can be found in large quantities in placental membranes of at-term or aborted animals. The inhalation of particles suspended in the air or contaminated aerosols is the most common form of bacterial contact. Q Fever is a self-limited disease, and often progresses in a benign way. In cases where the disease progresses to the chronic form, endocarditis is the most prevalent manifestation. Clinical diagnosis is difficult since the symptoms are similar to many other diseases. In confirmed cases, antibiotic therapy is the treatment indicated. Given the lack of knowledge about the disease and the difficulty of diagnosis, it is believed that Q fever is more common than generally believed in Brazil.


Molecular functions of nuclear actin in transcription.
Actin is not only a major cytoskeletal component in all eukaryotic cells but also a nuclear protein that plays a role in gene transcription. We put together data from in vitro and in vivo experiments that begin to provide insights into the molecular mechanisms by which actin functions in transcription. Recent studies performed in vitro have suggested that actin, in direct contact with the transcription apparatus, is required in an early step of transcription that is common to all three eukaryotic RNA polymerases. In addition, there is evidence from in vivo studies that actin is involved in the transcription elongation of class II genes. In this case, actin is bound to a specific subset of premessenger RNA binding proteins, and the actin-messenger RNP complex may constitute a molecular platform for recruitment of histone-modifying enzymes. We discuss a general model for actin in RNA polymerase II transcription whereby actin works as a conformational switch in conjunction with specific adaptors to facilitate the remodeling of large macromolecular assemblies at the promoter and along the active gene.


Interfacial rheological properties of recombinant spider-silk proteins.
Freestanding protein films are interesting for many applications ranging from microencapsulation to tissue engineering. Here, the authors use interfacial rheology to characterize the adsorption kinetics and the rheology of spider-silk films formed at an oil water interface. The high surface activity of the engineered spider-silk proteins results in a fast formation of highly stable films, which can be modified by the addition of phosphate ions to the solution.


Identification and characterization of a novel follistatin-like protein as a binding protein for the TGF-beta family.
Follistatin is an activin-binding protein that prevents activin from binding to its receptors and neutralizes its activity. Follistatin also binds bone morphogenetic proteins (BMPs). In this study, we report the identification of a novel follistatin-like protein from mouse. The mouse cDNA encodes a 256-residue precursor and most likely a mouse homologue of human FLRG, which was found at the breakpoint of the chromosomal rearrangement in a B-cell line. Whereas follistatin has three follistatin domains, which are presumed to be growth factor binding motifs, FLRG possesses only two follistatin domains. Northern blotting revealed that mRNAs for FLRG were abundantly expressed in heart, lung, kidney, and testis in mouse. The recombinant mouse FLRG proteins were found to have binding activity for both activin and bone morphogenetic protein-2. Like follistatin, FLRG has higher affinity for activin than for BMP-2. The FLRG protein inhibited activin-induced and BMP-2-induced transcriptional responses in a dose-dependent manner. Glutathione S-transferase fusion proteins encoding various regions of FLRG were produced and studied. Ligand blotting using (125)I-activin revealed that the COOH-terminal region containing the second follistatin domain was able to bind activin. Our finding implies that cellular signaling by activin and BMPs is tightly regulated by multiple members of the follistatin family.


GABA alterations in pediatric sport concussion.
To evaluate whether frontal-lobe magnetic resonance spectroscopy measures of γ-aminobutyric acid (GABA) would be altered in a sample of adolescents scanned after sport concussion because mild traumatic brain injury is often associated with working memory problems. Eleven adolescents (age 14-17 years) who had sustained a first-time sport concussion were studied with MRI/magnetic resonance spectroscopy within 23 to 44 days after injury (mean 30.4 ± 6.1 days). Age- and sex-matched healthy controls, being seen for sports-related injuries not involving the head and with no history of concussion, were also examined. GABA/creatine + phosphocreatine (Cre) was measured in left-sided frontal lobe and central posterior cingulate regions. The frontal voxel was positioned to overlap with patient-specific activation on a 1-back working memory task. Increased GABA/Cre was shown in the frontal lobe for the concussed group. A decreased relationship was observed in the parietal region. High correlations between GABA/Cre and task activation were observed for the control group in the frontal lobe, a relationship not shown in the concussed participants. GABA/Cre appears increased in a region colocalized with working memory task activation after sport concussion. Further work extending these results in larger samples and at time points across the injury episode will aid in refining the clinical significance of these observations.


[Mild head injury in children and adults. Diagnostic challenges in the emergency department].
Mild head injuries are one of the most frequent reasons for attending emergency departments and are particularly challenging in different ways. While clinically important injuries are infrequent, delayed or missed injuries may lead to fatal consequences. The initial mostly inconspicuous appearance may not reflect the degree of intracranial injury and computed tomography (CT) is necessary to rule out covert injuries. Furthermore, infants and young children with a lack of or rudimentary cognitive and language development are challenging, especially for those examiners not familiar with pediatric care. Established check lists of clinical risk factors for children and adults regarding traumatic brain injuries allow specific and rational decision-making for cranial CT imaging. Clinically important intracranial injuries can be reliably detected and unnecessary radiation exposure avoided at the same time.


Circulation of Zoonotic Arboviruses in Equine Populations of Mallorca Island (Spain).
The presence of major arbovirus vector species, climate change that promotes the expansion and increase of their populations, and potential animal reservoirs mean that vector-borne diseases represent a significant health risk for Mallorca's inhabitants. Microbiological monitoring of circulating arboviruses, particularly flaviviruses causing encephalitis, was initiated using domestic horses from localities near wetlands as "sentinel" hosts. A total of 291 blood samples were taken from 172 horses between 2011 and 2012, using paired samples to highlight seroconversion events. A multiplex immunoassay and confirmatory reference serological assays were used to screen sera for immunoglobulin G antibodies against West Nile (WNV), Usutu (USUV), and tick-borne encephalitis (TBEV) viruses. The seroprevalence was 6.4% (confidence interval [95% CI] 3.2%-11.0%) for WNV, 1.2% (95% CI 0.1%-4.1%) for USUV, and 0.6% (95% CI 0.0%-3.2%) for TBEV. In addition, eight horses (4.6%; 95% CI 2.0%-8.9%) were found positive for unidentified flaviviruses. Seroconversion events were detected for WNV and USUV, reflecting recent arboviral infections. These results highlight the active transmission of zoonotic arboviruses in Mallorca wetlands.


Contact X-ray microscopy of living cells by using LiF crystal as imaging detector.
In this paper, the use of lithium fluoride (LiF) as imaging radiation detector to analyse living cells by single-shot soft X-ray contact microscopy is presented. High resolved X-ray images on LiF of cyanobacterium Leptolyngbya VRUC135, two unicellular microalgae of the genus Chlamydomonas and mouse macrophage cells (line RAW 264.7) have been obtained utilizing X-ray radiation in the water window energy range from a laser plasma source. The used method is based on loading of the samples, the cell suspension, in a special holder where they are in close contact with a LiF crystal solid-state X-ray imaging detector. After exposure and sample removal, the images stored in LiF by the soft X-ray contact microscopy technique are read by an optical microscope in fluorescence mode. The clear image of the mucilaginous sheath the structure of the filamentous Leptolyngbya and the visible nucleolus in the macrophage cells image, are noteworthiness results. The peculiarities of the used X-ray radiation and of the LiF imaging detector allow obtaining images in absorption contrast revealing the internal structures of the investigated samples at high spatial resolution. Moreover, the wide dynamic range of the LiF imaging detector contributes to obtain high-quality images. In particular, we demonstrate that this peculiar characteristic of LiF detector allows enhancing the contrast and reveal details even when they were obscured by a nonuniform stray light.


Effects of Collagenase Digestion and Stromal Vascular Fraction Supplementation on Volume Retention of Fat Grafts.
The use of autologous fat as a soft tissue filler has increased over the past decade in both reconstructive and aesthetic surgeries. Enhancement of autologous fat grafts with the addition of the stromal vascular fraction (SVF) has been reported to improve long-term volume retention. Stromal vascular fraction is most commonly isolated using enzymatic digestion, but it is unknown what effect the digestion process has on the adipocytes and SVF cells that comprise the graft. Some clinicians have reported use of enzymatically digested fat grafts to alter the physical properties of the tissue in specialized applications. We have previously reported that increasing collagenase digestion duration adversely affects the viability of adipocytes and SVF cells. Here, we aimed to determine if collagenase digestion of adipocytes before grafting is detrimental to long-term graft retention and if SVF supplementation can abrogate these potential deleterious effects. We used a published xenograft model in which human lipoaspirate was implanted into the scalp of immunocompromised mice to study the effects of collagenase digestion on in vivo graft survival after 12 weeks. We used 4 experimental groups: grafts composed of collagenase-digested and nondigested adipocytes (50-minute digestion) and grafts with and without SVF supplementation. We used microcomputed tomography to serially and noninvasively quantify graft volume, in conjunction with hematoxylin-eosin staining of histological cross-sections of implanted and excised grafts to assess overall tissue viability. We found that adipocytes that were collagenase-digested before implantation had significantly lower retention rates at 12 weeks and poorer tissue health, which was assessed by quantifying the number of intact adipocytes, the number of cystic formations, and by scoring the degree of inflammation and fibrosis. Further, we found that SVF supplementation of the digested grafts improved graft survival, but not to the level observed in undigested grafts. We conclude that collagenase digestion adversely affects the long-term volume retention of fat grafts, but that graft retention is improved by SVF supplementation. These experimental results can serve as an initial framework to further elucidate the reported efficacy and safety of using collagenase-digested fat grafts and SVF in the clinical setting.


Primary pure squamous cell carcinoma of the duodenum: a case report.
Primary pure squamous cell carcinoma of the duodenum is a very rare type of duodenal neoplasm and is more likely to be presented as a metastatic tumor. The literature offers little information on this subject and includes very few articles and case reports. Laboratory tests, CT and ultrasound examinations, x-rays and immunohistochemical markers assisted us in making this rare diagnosis of primary squamous cell carcinoma of the duodenum in a 47 year old female patient, who presented with weight loss and melena. The 8 cm duodenal tumor with pancreas invasion was resected by a cephalic duodenopancreatectomy. The pathology examination revealed a primary duodenal squamous cell carcinoma moderately differentiated (G2), invasive in the head of the pancreas, with keratinization, stage II B (pT4N0MxL0V0R0). Positive outcome after surgery was highlighted, no recurrence being registered at the 6 month CT scan follow-up.


The Ventilatory and Diffusion Dysfunctions in Obese Patients with and without Obstructive Sleep Apnea-Hypopnea Syndrome.
To analyze the ventilatory and alveolar-capillary diffusion dysfunctions in case of obesity with or without an OSAS. It is a cross-sectional study of 48 obese adults (23 OSAS and 25 controls). Anthropometric data (height, weight, and body mass index (BMI)) were collected. All adults responded to a medical questionnaire and underwent polysomnography or sleep polygraphy for apnea-hypopnea index (AHI) and percentage of desaturation measurements. The following lung function data were collected: pulmonary flows and volumes, lung transfer factor for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FeNO). Obesity was confirmed for the two groups with a total sample mean value of BMI = 35.06 ± 4.68 kg/m2. A significant decrease in lung function was noted in patients with OSAS compared with controls. Indeed, when compared with the control group, the OSAS one had a severe restrictive ventilatory defect (total lung capacity: 93 ± 14 vs. 79 ± 12%), an abnormal DLCO (112 ± 20 vs. 93 ± 22%), and higher bronchial inflammation (18.40 ± 9.20 vs. 31.30 ± 13.60 ppb) (p < 0.05). Obesity when associated with OSAS increases the severity of pulmonary function and alveolar-capillary diffusion alteration. This can be explained in part by the alveolar inflammation.


Is the Holocaust implicated in posttraumatic growth in second-generation Holocaust survivors? A prospective study.
With the growing interest in posttraumatic growth (PTG), and the ongoing debate on the implications of transgenerational transmission of trauma, this longitudinal study examined PTG among Holocaust survivor offspring following their own exposure to trauma. Using self-report questionnaires, we assessed PTG over time in middle aged (age: M = 53 years) Israeli male combat veterans of the 1973 Yom Kippur War whose parents were (n = 43) and were not (n = 156) second-generation survivors of the Nazi Holocaust at 2 time points: 30 and 35 years following the war (in 2003 and 2008). Posttraumatic stress disorder symptoms and trauma exposure were also assessed in 1991. We hypothesized that second-generation survivors would report more PTG than controls. However, repeated measures design revealed that the second-generation veterans reported less PTG than veterans who were not second generation, which was evident in the PTG domains of relations to others, personal strength, and appreciation of life. Our findings suggest that transmission of trauma from one generation to the next is possibly implicated in the offspring's propensity for growth following subsequent trauma. Future research is warranted to examine the link between transmission of trauma and positive outcomes following trauma.


Identification of Myb-binding protein 1A (MYBBP1A) as a novel substrate for aurora B kinase.
Aurora kinases are mitotic enzymes involved in centrosome maturation and separation, spindle assembly and stability, and chromosome condensation, segregation, and cytokinesis and represent well known targets for cancer therapy because their deregulation has been linked to tumorigenesis. The availability of suitable markers is of crucial importance to investigate the functions of Auroras and monitor kinase inhibition in in vivo models and in clinical trials. Extending the knowledge on Aurora substrates could help to better understand their biology and could be a source for clinical biomarkers. Using biochemical, mass spectrometric, and cellular approaches, we identified MYBBP1A as a novel Aurora B substrate and serine 1303 as the major phosphorylation site. MYBBP1A is phosphorylated in nocodazole-arrested cells and is dephosphorylated upon Aurora B silencing or by treatment with Danusertib, a small molecule inhibitor of Aurora kinases. Furthermore, we show that MYBBP1A depletion by RNA interference causes mitotic progression delay and spindle assembly defects. MYBBP1A has until now been described as a nucleolar protein, mainly involved in transcriptional regulation. The results presented herein show MYBBP1A as a novel Aurora B kinase substrate and reveal a not yet recognized link of this nucleolar protein to mitosis.


[Hemobilia with spontaneous resolution. Sonographic diagnosis and follow-up].
We describe a case of hemobilia after liver biopsy, which resolved spontaneously. Clinical, analytical and sonographic monitoring were performed until the patient returned to normal. We highlight the particular characteristics of the onset and evolution in our case, as well as the role played by ultrasonography in diagnosing and monitoring. We conclude by pointing out the increasing frequency of hemobilia as a complication to invasive techniques.


Formulated collagen gel accelerates healing rate immediately after application in patients with diabetic neuropathic foot ulcers.
We assessed the safety and efficacy of Formulated Collagen Gel (FCG) alone and with Ad5PDGF-B (GAM501) compared with Standard of Care (SOC) in patients with 1.5-10.0 cm(2) chronic diabetic neuropathic foot ulcers that healed <30% during Run-in. Wound size was assessed by planimetry of acetate tracings and photographs in 124 patients. Comparison of data sets revealed that acetate tracings frequently overestimated areas at some sites. For per-protocol analysis, 113 patients qualified using acetate tracings but only 82 qualified using photographs. Prior animal studies suggested that collagen alone would have little effect on healing and would serve as a negative control. Surprisingly trends for increased incidence of complete closure were observed for both GAM501 (41%) and FCG (45%) vs. Standard of Care (31%). By photographic data, Standard of Care had no significant effect on change in wound radius (mm/week) from during Run-in to Week 1 (-0.06 ± 0.32 to 0.78 ± 1.53, p=ns) but both FCG (-0.08 ± 0.61 to 1.97 ± 1.77, p<0.002) and GAM501 (-0.02 ± 0.58 to 1.46 ± 1.37, p<0.002) significantly increased healing rates that gradually declined over subsequent weeks. Both GAM501 and FCG appeared to be safe and well tolerated, and alternate dosing schedules hold promise to improve overall complete wound closure in adequately powered trials.


Role of leisure sedentary behavior on type 2 diabetes and glycemic homeostasis: a Mendelian randomization analysis.
Utilize Mendelian randomization (MR) to examine the impact of leisure sedentary behavior (LSB) on the prevalence of type 2 diabetes mellitus (T2D) and glycemic homeostasis impairment, as well as to identify potential mediating pathways involved in these associations. We chose genetic variants linked to LSB from a large genome-wide association study (GWAS) to use as instrumental variables (IVs). Then, we used a two-sample MR study to investigate the link between LSB and T2D and glycemic homeostasis. Multivariate MR (MVMR) and mediation analysis were also used to look at possible mediating paths. MR analysis showed a genetical link between leisure TV watching and T2D (OR 1.64, 95% CI 1.39-1.93, P< 0.001) and impaired Glycemic Homeostasis, while leisure computer use seemed to protect against T2D prevalence (OR 0.65, 95% CI 0.50-0.84, P< 0.001). It was found that leisure TV watching increases the risk of T2D through higher BMI (mediation effect 0.23, 95% CI 0.11-0.35, P< 0.001), higher triglycerides (mediation effect 0.07, 95% CI 0.04-0.11, P< 0.001), and less education (mediation effect 0.16, 95% CI 0.08-0.24, P< 0.001). Sensitivity and heterogeneity analyses further substantiated the robustness of these findings. Reverse MR analysis did not yield significant results. This study shows LSB is linked to a higher rate of T2D and impaired glycemic homeostasis through obesity, lipid metabolism disorders, and reduced educational attainment.


Individual Differences in Patterns of Community Violence Exposure and Internalizing and Externalizing Behaviors.
Youth community violence has been linked with depressive and anxious symptoms, and aggressive behavior; however, little research has examined different combinations of emotional and behavioral adjustment among community-violence-exposed youth, or individual characteristics that may account for different patterns of emotional and behavioral adjustment in community-violence-exposed youth. This research used person-centered methods to examine how gender, temperament characteristics, and prior exposure to community violence were linked with classes of community violence exposure and internalizing and externalizing adjustment among a sample of urban African American youth. Participants were 464 African American adolescents (46.7% female; mean age = 14.83, SD = .43) who reported their community violence exposure in Grade 9 and for whom reports of depressive and anxious symptoms, and aggressive behavior were available. Latent class analysis identified four classes of adolescents distinguished by their exposure to community violence exposure and internalizing and externalizing behavior. The two classes with high community violence exposure were characterized by internalizing symptoms or aggressive behavior; the two classes with low community violence exposure had low internalizing symptoms with moderate aggression or had all moderate symptoms. These community violence adjustment classes were distinguished by gender, history of community violence exposure, behavioral inhibition, and fight-flight-freeze systems. Findings highlight heterogeneity in internalizing and externalizing responses of community-violence-exposed youth and suggest factors that explain community violence exposure, repeat exposure, and responses to community violence exposure.


[Effect of bonafton on the formation of specific suppressor cells].
Administration of an antiviral agent bonafton (1.5 mg/kg, intraperitoneally) for 5 days to mice immunized with a supraoptimal dose of ram erythrocytes (5 X 10(9)) was followed by inhibition of suppressor-cell induction in the animal spleen. An adoptive transfer of the splenic cells of these mice to syngeneic recipients caused in the latter less specific inhibition of humoral and cellular immune responses than it was during the use of splenocytes from hyperimmunized donor mice not receiving bonafton. The inhibitory effect of the drug was more manifest toward the suppressor-cells of the delayed-type hypersensitivity than the cells suppress antibody formation.


Freedom, equality, race.
This essay explores come of the reasons for the continuing power of racial categorization in our era, and thus offers some friendly amendments to the more optimistic renderings of the term post-racial. Focusing mainly on the relationship between black and white Americans, it argues that the widespread embrace of universal values of freedom and equality, which most regard as antidotes to racial exclusion, actually reinforce it. The internal logic of these categories requires the construction of the "other." In America, where freedom and equality still stand at the contested center of collective identity, a history of racial oppression informs the very meaning of these terms. Thus the irony: much of the effort exerted to transcend race tends to fuel continuing division.


Lymphocyte depletion of donor bone marrow by counterflow centrifugal elutriation: results of a phase I clinical trial.
We report here the results of a phase I clinical trial using counterflow centrifugal elutriation (CCE) for the removal of donor T lymphocytes before allogeneic bone marrow transplantation (BMT). Thirty-eight patients received lymphocyte-depleted allografts from HLA-identical, MLR-nonreactive sibling donors. The patients entered onto the study were either at high risk on the basis of age (median, 39 years) or disease status (acute leukemia in early relapse [ER], chronic myelogenous leukemia [CML] in accelerated phase [AP], or therapy resistant [RES] lymphoma). All patients received a standard lymphocyte dose of 1 x 10(6) morphologic lymphocytes per kilogram ideal body weight (BW) and were maintained on cyclosporine A (CsA) for 170 days after BMT. Prompt engraftment occurred in 37 of 38 patients with a median time to absolute neutrophil count (ANC) greater than 500/microL of 18 days. Although acute graft-v-host disease (GVHD; clinical stage I or greater) was observed in 45%, it was limited to the skin in all but five patients. Survival was related to disease status at the time of BMT. Among patients with acute leukemia in first or second remission, CML in chronic phase (CP) or lymphoma in partial remission (PR), 64% are currently alive, in contrast to 31% of patients with acute leukemia in third remission or early relapse, CML in second CP or AP, or RES lymphoma. Median follow-up for all patients was 351 days (range, 105 to 711 days). We conclude that this procedure is safe and warrants further evaluation in a randomized efficacy trial.


Histone lactylation-derived LINC01127 promotes the self-renewal of glioblastoma stem cells via the cis-regulating the MAP4K4 to activate JNK pathway.
Gliomas are the most prevalent and aggressive brain tumors, exhibiting high proliferation, abnormal glycolysis, and poor prognosis. LncRNAs act as regulatory molecules and play crucial roles in the malignant behaviors of GBM cells, including cell self-renewal. However, the regulatory mechanisms involved are largely unknown. In this study, we performed bioinformatics analysis to explore NF-κB pathway-related lncRNAs. ECAR and qRT-PCR were used to measure the relationship between glycolytic activity and lncRNA expression. Assays such as RIP-PCR and ChIP-PCR were employed to reveal the regulatory mechanisms of the lncRNA. Neurosphere formation and limiting dilution assays were performed to evaluate the self-renewal capacity of GBM cells. In our study, we identified an NF-κB pathway-related lncRNA named LINC01127 in GBM, which was found to be associated with poor progression of GBM. Functionally, the NF-κB pathway promoted warburg effect, which, in turn, induced the lactylation of H3 histone and increased the expression of LINC01127. Consequently, this enhancement of LINC01127 expression led to the promotion of self-renewal in GBM cells. Furthermore, LINC01127 regulated MAP4K4 expression in cis by directly guiding POLR2A to the MAP4K4 promoter regions, thereby leading to JNK pathway activation, and ultimately modulating the self-renewal of GBM cells. Moreover, the activated JNK pathway promoted the phosphorylation of IκBα. Overall, targeting LINC01127-mediated axis impeded orthotopic tumor growth in GBM xenografts. Taken together these results revealed that warburg effect-induced histone lactylation drives NF-κB-related LINC01127 expression, thereby promoting the self-renewal of GBM cells through the MAP4K4/JNK/NF-κB axis, and providing substantial evidence that LINC01127 might provide a novel therapeutic strategy for GBM patients.


The pathophysiology of delayed ejaculation.
Delayed ejaculation (DE) is probably least studied, and least understood of male sexual dysfunctions, with an estimated prevalence of 1-4% of the male population. Pathophysiology of DE is multifactorial and including psychosexual-behavioral and cultural factors, disruption of ejaculatory apparatus, central and peripheral neurotransmitters, hormonal or neurochemical ejaculatory control and psychosocial factors. Although knowledge of the physiology of the DE has increased in the last two decade, our understanding of the different pathophysiological process of the causes of DE remains limited. To provide a systematic update on the pathophysiology of DE. A systematic review of Medline and PubMed for relevant publications on ejaculatory dysfunction (EjD), DE, retarded ejaculation, inhibited ejaculation, and climax was performed. The search was limited to the articles published between the January 1960 and December 2015 in English. Of 178 articles, 105 were selected for this review. Only those publications relevant to the pathophysiology, epidemiology and prevalence of DE were included. The pathophysiology of DE involves cerebral sensory areas, motor centers, and several spinal nuclei that are tightly interconnected. The biogenic, psychogenic and other factors strongly affect the pathophysiology of DE. Despite the many publications on this disorder, there still is a paucity of publications dedicated to the subject.


Effects of smoking on benzo(alpha)pyrene- and glutathione-metabolizing enzymes in human lung tissue.
The influence of smoking on the metabolism of benzo(alpha)pyrene and glutathione was investigated in 190 patients with primary bronchial carcinoma and 20 patients with benign lung diseases. There were no significant differences in the activities of drug-metabolizing enzymes in the lung tissue of smokers, regardless of whether they smoked low- or high-tar and -nicotine cigarettes; former smokers; or nonsmokers; nor were there such differences between female and male patients. No significant differences existed between patients with squamous cell carcinoma and those with adenocarcinoma. Impaired detoxification due to decreased activity of glutathione S-transferases, rather induction of benzo(alpha)pyrene-metabolizing enzymes, may disturb the delicate balance between the generation and detoxification of reactive metabolites. This impairment may lead to the accumulation of these compounds in the cell.


Autism spectrum disorders: perceptions of genetic etiology and recurrence risk among Taiwanese parents of affected children.
In Taiwan, autism spectrum disorders (ASDs) are an emerging public health concern. The ongoing scientific progress for understanding the genetic etiology of ASD makes it increasingly important to examine how parents of children with ASD perceive the causes and recurrence risk of having another child with ASD. These perceptions may influence their family planning, attitudes toward genetic services, and willingness to take their children for ASD genetic testing. However, previous studies addressing this issue were conducted primarily in Western countries. As culture might shape an individual's views of genetic/genomic disorders, this first-of-its-kind study examined the perceptions of the genetic etiology for ASD and the recurrence risk among Taiwanese parents of children affected with ASD. In-depth, semi-structured interviews were conducted among 39 parents having at least one child with ASD. Although the majority of participants believed that ASD has a genetic link, less than half perceived genetic factors as the cause of their own child's ASD. Moreover, most participants articulated their recurrence risk incorrectly. Some parents were concerned about their doctors' limited genomic competencies. To provide parents with better education, counseling, and support for making reproductive decisions, ASD-related genomic education among Taiwanese physicians is needed.


Electroacupuncture Alleviates Pain-Related Emotion by Upregulating the Expression of NPS and Its Receptor NPSR in the Anterior Cingulate Cortex and Hypothalamus.
Electroacupuncture (EA) is reported effective in alleviating pain-related emotion; however, the underlying mechanism of its effects still needs to be elucidated. The NPS-NPSR system has been validated for the involvement in the modulation of analgesia and emotional behavior. Here, we aimed to investigate the role of the NPS-NPSR system in the anterior cingulate cortex (ACC), hypothalamus, and central amygdala (CeA) in the use of EA to relieve affective pain modeled by complete Freund's adjuvant- (CFA-) evoked conditioned place aversion (C-CPA). Materials and Methods. CFA injection combined with a CPA paradigm was introduced to establish the C-CPA model, and the elevated O-maze (EOM) was used to test the behavioral changes after model establishment. We further explored the expression of NPS and NPSR at the protein and gene levels in the brain regions of interest by immunofluorescence staining and quantitative real-time PCR. We observed that EA stimulation delivered to the bilateral Zusanli (ST36) and Kunlun (BL60) acupoints remarkably inhibited sensory pain, pain-evoked place aversion, and anxiety-like behavior. The current study showed that EA significantly enhanced the protein expression of this peptide system in the ACC and hypothalamus, while the elevated expression of NPSR protein alone was just confined to the affected side in the CeA. Moreover, EA remarkably upregulated the mRNA expression of NPS in CeA, ACC, and hypothalamus and NPSR mRNA in the hypothalamus and CeA. These data suggest the effectiveness of EA in alleviating affective pain, and these benefits may at least partially be attributable to the upregulation of the NPS-NPSR system in the ACC and hypothalamus.


Single channel properties of newly synthesized acetylcholine receptors following denervation of mammalian skeletal muscle.
We have examined the single channel properties of newly synthesized acetylcholine (ACh) receptors in denervated adult mouse muscle. Patch-clamp recordings were made on freshly isolated fibers from flexor digitorum brevis (fdb) muscles that had been denervated in vivo for periods up to 3 wk. Muscles were treated with alpha-bungarotoxin (alpha-BTX), immediately before denervation, in order to block pre-existing receptors. Denervated fibers exhibited two types of ACh receptor channels, which differed in terms of single channel conductance (45 and 70 pS) and mean channel open time (approximately 7 and 2.5 ms, respectively). In contrast to innervated muscle, where only 3% of the total openings were contributed by the low-conductance channel type, greater than 80% of the openings in the nonsynaptic membrane of denervated muscle were of this type. Importantly, a similar increase in the proportion of low-conductance channels was observed for recordings from synaptic membrane after denervation. These data argue against the proposal that, in denervated muscle, the low-conductance channels undergo continued conversion to the high-conductance type focally at the site of former synaptic contact. Rather, our findings provide additional support for the idea that the functional properties of ACh receptors are governed uniformly by the state of innervation of the fiber and not by proximity to the site of synaptic contact.


[A study on parameters to predict tumor volume for stage T1c prostate cancers of Gleason score 6 or less].
The number of cases of stage T1c prostate cancer has dramatically been increasing since the introduction of PSA as a screening test. The patients with T1c prostate cancer are usually treated by radical prostatectomy. In this group, however, some cancers are of small tumor volume and with a Gleason score of less than 7. These cancers are considered to be good candidates for watchful waiting management. We have investigated 40 patients with T1c prostate cancer treated by radical prostatectomy between 1996 and 1998. All 9 patients harboring tumors of Gleason score 7 or greater had tumors larger than 0.5 cm3. We have investigated PSA-related parameters including total PSA (PSA), PSA density (PSAD), free PSA, and % free PSA in 31 patients with T1c cancers of Gleason score 6 or less in order to clarify good preoperative predictors of tumor volume. We compared the distribution of PSA, PSAD, free PSA, and % PSA between the larger and smaller tumor groups. There was no significant difference in PSA, PSAD, or free PSA value. The small tumor group had a greater mean % free PSA than the larger tumor group (23.27 versus 11.88, p = 0.007). Areas under receiver operating characteristic curves were 0.715, 0.794, 0.636, and 0.842 for PSA, PSAD, free PSA and % free PSA. In stage T1c prostate cancer of Gleason score 6 or less, % free PSA may be the most useful preoperative predictor for tumor volume of 0.5 cm3 or greater.


Cyclophosphamide for large vessel vasculitis: assessment of response by PET/CT.
Glucocorticosteroids (GC) are the standard treatment for large vessel vasculitis, but some patients are refractory. Cyclophosphamide (CYC) has been shown to be effective in autoimmune diseases. The study consisted of a retrospective analysis of 10 patients with active large vessel arteritis who received pulse CYC after failure of GC or because of organ threatening stenosis. CYC pulse therapy was started with a dose of 750mg/m² body surface every 3 weeks and increased if necessary. Clinical response was assessed by the Birmingham Vasculitis Activity Score (BVAS), the C-reactive protein and the erythrocyte sedimentation rate (ESR). PET/CT was performed at baseline and during treatment to determine disease activity. The median BVAS at the time of the initial PET/CT was 6.5 (5-13). The median ESR was 42mm/h (6-94mm/h), and the medium CRP was 4.6mg/dl (0.18-11.8mg/dl). All but one patient experienced a complete clinical remission during CYC treatment after a median of 10 cycles. PET/CT confirmed the efficacy of the treatment by normalisation of FDG uptake during therapy. One patient with persisting inflammation was lost to follow-up. One patient experienced a relapse after 21 months. The remaining 8 patients are still in remission with low-dose GC and a maintenance therapy (azathioprine, methotrexate or mycophenolate) after a median follow-up of 45 months. Pulse cyclophosphamide is effective in patients with large vessel vasculitis resistant to glucocorticosteroids. The high rate of sustained response in our patients suggests that treatment decisions based on clinical parameters combined with PET/CT may have a beneficial effect on the clinical outcome.


Comparative cytology of mucocelelike lesion and mucinous carcinoma of the breast in fine needle aspiration.
To study the fine needle aspiration cytology (FNAC) features of mucocelelike lesion (MLL) of the breast and to compare them to those of mucinous carcinoma. The fine needle aspiration (FNA) smears of 7 cases of histologically proven MLL (2 malignant and 5 benign, including 4 associated with atypical ductal hyperplasia) were reviewed and compared to those of 14 mucinous carcinoma cases. In all cases, grossly visible thick, mucoid material was obtained from FNA. The most important features for distinguishing benign MLL from mucinous carcinoma were: (1) scant cellularity; (2) no or rare single, intact tumor cells; (3) tumor cells arranged in cohesive monolayers; and (4) absence of significant nuclear atypia. In contrast, mucinous carcinoma in general showed higher cellularity; abundant single, intact cells; three-dimensional cellular clusters in most cases; and nuclear atypia ranging from mild to severe. Mucinous lesions of the breast should be divided into MLL and frank mucinous carcinoma based on FNAC. However, FNAC diagnosis of malignant MLL has yet to be defined. Excisional biopsy is advised for all hypocellular cases for further separation into benign and malignant MLL and to rule out the possibility of hypocellular mucinous carcinoma.


Hyperpolarized 3He MR imaging: physiologic monitoring observations and safety considerations in 100 consecutive subjects.
To evaluate the safety of hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging. Local institutional review board approval and informed consent were obtained. Physiologic monitoring data were obtained before, during, and after hyperpolarized (3)He MR imaging in 100 consecutive subjects (57 men, 43 women; mean age, 52 years +/- 14 [standard deviation]). The subjects inhaled 1-3 L of a gas mixture containing 300-500 mL (3)He and 0-2700 mL N(2) and held their breath for up to 15 seconds during MR imaging. Heart rate and rhythm and oxygen saturation of hemoglobin as measured by pulse oximetry (Spo(2)) were monitored continuously throughout each study. The effects of (3)He MR imaging on vital signs and Spo(2) and the relationship between pulmonary function, number of doses, and clinical classification (healthy volunteers, patients with asthma, heavy smokers, patients undergoing lung volume reduction surgery for severe emphysema, and patients with lung cancer) and the lowest observed Spo(2) were assessed. Any subjective symptoms were noted. Except for a small postimaging decrease in mean heart rate (from 78 beats per minute +/- 13 to 73 beats per minute +/- 11, P < .001), there was no effect on vital signs. A mean transient decrease in Spo(2) of 4% +/- 3 was observed during the first minute after gas inhalation (P < .001) in 77 subjects who inhaled a dose of 1 L for 10 seconds or less, reaching a nadir of less than 90% at least once in 20 subjects and of less than 85% in four subjects. There was no correlation between the lowest Spo(2) and pulmonary function parameters other than baseline Spo(2) (r = 0.36, P = .001). The lowest mean Spo(2) varied by 1% between the first and second and second and third doses (P < .001) and was unrelated to clinical classification (P = .40). Minor subjective symptoms were noted by 10 subjects. No serious adverse events occurred. Hyperpolarized (3)He MR imaging can be safely performed in healthy subjects, heavy smokers, and those with severe obstructive airflow limitation, although unpredictable transient desaturation suggests that potential subjects should be carefully screened for comorbidities.


Transition Points for the Routine Integration of Palliative Care in Patients With Advanced Cancer.
Increasing emphases are being placed on early integration of palliative care for patients with advanced cancers, yet barriers to implementation in clinical practice remain. Criteria to standardize referral have been endorsed, but their application is yet to be tested at the population level. This study sought to establish the need for standardized referral by examining current end-of-life care outcomes of decedents with cancer and define transition points within a cancer illness course, which are associated with poor prognosis, whereby palliative care should be routinely introduced to augment clinician-based decision making. Population cohort study of admitted patients with advanced cancer diagnosed with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), prostate or breast cancer between 2000 and 2010 in Victoria, Australia, identified from routinely collected, linked, hospital discharge, emergency department, and death registration data. Descriptive statistics described quality indicators for end-of-life care outcomes for decedents. Kaplan-Meier analyses were used to test the predefined transition point that mostly accurately predicted survival of six months or lesser. About 46,700 cases (56% females) were admitted with metastatic NSCLC (n = 14,759; 31.6%), SCLC (n = 2932; 6%), prostate (n = 9445; 20.2%), and breast cancer (n = 19,564; 41.9%). Of the 29,680 decedents, most (80%) died in hospital, had suboptimal end-of-life care outcomes (83%), and 59% received a palliative approach to care, a median of 27 days before death. Transition points in the cancer illness course of all cases were identified as first admission with any metastatic disease (NSCLC: 3.8 months [interquartile range {IQR} 1.1, 16.0]; n = 14,666; and SCLC: 4.2 months [IQR 1.0, 10.6]; n = 2914); first multiday admission with any metastatic disease (prostate: 6.0 months [IQR 1.3, 26.4]; n = 7174); and first multiday admission with at least one visceral metastatic site (breast: 6.0 months [IQR 1.2, 29.8]; n = 7120). Despite calls for integrated palliative care, this occurs late or not at all for many patients with cancer. Our findings demonstrate the application of targeted cancer-specific transition points to trigger integration of palliative care as a standard part of quality oncological care and augment clinician-based referral in routine clinical practice.


European-wide policymaking at the urban level: a qualitative study.
Inter-urban area (UA) health inequalities can be as dramatic as those between high and low-income countries. Policies need to focus on the determinants of health specific to UAs to effect change. This study therefore aimed to determine the degree to which policymakers from different countries could make autonomous health and wellbeing policy decisions for their urban jurisdiction area. We conducted a cross-sectional, qualitative interview study with policymakers recruited from eight European countries (N = 37). The reported autonomy among policymakers varied considerably between countries, from little or no autonomy and strict adherence to national directives (e.g. Slovak Republic) to a high degree of autonomy and ability to interpret national guidelines to local context (e.g. Norway). The main perceived barriers to implementation of local policies were political, and the importance of regular and effective communication with stakeholders, especially politicians, was emphasized. Having qualified health professionals in positions of influence within the UA was cited as a strong driver of the public health (PH) agenda at the UA level. Local-level policy development and implementation depends strongly on the degree of autonomy and independence of policymakers, which in turn depends on the organization, structure and financial budget allocation of PH services. While high levels of centralization in small, relatively homogenous countries may enhance efficient use of resources, larger, more diverse countries may benefit from devolution to smaller geographical regions.


Effect of Abdominal Massage before In Vitro Fertilization Injection on Alleviating Pain among Infertile Women.
The purpose of this study was to evaluate the effect of abdominal massage on alleviating pain caused by the injection of recombinant gonadotropin for In Vitro Fertilization (IVF) among infertile women. This study employed a nonequivalent control group non-synchronized design. A total sample of 149 infertile women who never experienced in vitro fertilization was recruited at C fertility center. Seventy women were assigned into experimental group and 79 into controls. The experimental group had been informed to do abdominal massage prior to the injection and to record their subjective pain using visual analogue scale. The control group had been informed to record their subjective pain in the same way just after the injection. Compared to the pre-tested pain scores, the pain scores in experimental group were significantly reduced by 0.7 points, whereas the control group increased by 0.9 points (t=-4.55, p=.001). This study confirms that the use of abdominal massage prior to the injection is an effective way to alleviate pain on injection site. This massage may be a useful intervention for infertile women about pain alleviation.


Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor.
Cultured mouse peritoneal macrophages secrete a growth-promoting activity that stimulates 3 types of nonlymphoid mesenchymal cells in vitro: fibroblasts, vascular smooth muscle, and vascular endothelium. Production of this macrophage-derived growth factor (MDGF) is directly related to the number of viable macrophages and their time in culture, and is independent of platelet- or plasma-derived serum growth factors. Treatment of cultured macrophages with latex, bacterial lipopolysaccharide, or phorbol myristate acetate results in increased growth factor activity. Preliminary biochemical characterization of MDGF indicates that it is a heat labile (100 degrees C, 2 min), non-dialyzable protein, which contains at least 1 essential disulfide bond. Growth-promoting activity is not adsorbed by CM-Sephadex chromatography, under conditions that effectively remove platelet-derived growth factor(s). Serine protease activity is not required for the action of MDGF. Secretion of macrophage-derived growth factor may be relevant to the function of mononuclear phagocytes in several pathologic processes, including the neovascularization and fibroplasia of wound healing, smooth muscle hyperplasia in atherosclerosis, and proliferative glomerulonephritis.


On the formation of ozone in oxygen-rich solar system ices via ionizing radiation.
The irradiation of pure molecular oxygen (O(2)) and carbon dioxide (CO(2)) ices with 5 keV H(+) and He(+) ions was investigated experimentally to simulate the chemical processing of oxygen rich planetary and interstellar surfaces by exposure to galactic cosmic ray (GCR), solar wind, and magnetospheric particles. Deposited at 12 K under ultra-high vacuum conditions (UHV), the irradiated condensates were monitored on-line and in situ in the solid-state by Fourier transform infrared spectroscopy (FTIR), revealing the formation of ozone (O(3)) in irradiated oxygen ice; and ozone, carbon monoxide (CO), and cyclic carbon trioxide (c-CO(3)) in irradiated carbon dioxide. In addition to these irradiation products, evolution of gas-phase molecular hydrogen (H(2)), atomic helium (He) and molecular oxygen (O(2)) were identified in the subliming oxygen and carbon dioxide condensates by quadrupole mass spectrometry (QMS). Temporal abundances of the oxygen and carbon dioxide precursors and the observed molecular products were compiled over the irradiation period to develop reaction schemes unfolding in the ices. These reactions were observed to be dependent on the generation of atomic oxygen (O) by the homolytic dissociation of molecular oxygen induced by electronic, S(e), and nuclear, S(n), interaction with the impinging ions. In addition, the destruction of the ozone and carbon trioxide products back to the molecular oxygen and carbon dioxide precursors was promoted over an extended period of ion bombardment. Finally, destruction and formation yields were calculated and compared between irradiation sources (including 5 keV electrons) which showed a surprising correlation between the molecular yields (∼10(-3)-10(-4) molecules eV(-1)) created by H(+) and He(+) impacts. However, energy transfer by isoenergetic, fast electrons typically generated ten times more product molecules per electron volt (∼10(-2)-10(-3) molecules eV(-1)) than exposure to the ions. Implications of these findings to Solar System chemistry are also discussed.


Patients can provide a valid assessment of quality of life, functional status, and general health on the day they undergo knee surgery.
In the interest of efficiency, investigators often offer participants in surgical trials the option of completing baseline assessments on the day of surgery. The emotional affects of this day may, however, increase bias or random error. We studied the validity and reliability of collecting subjective ratings of health on the day of surgery. One hundred and seventy-seven patients undergoing anterior cruciate ligament reconstruction and/or knee arthroscopy completed quality-of-life, functional status, and general health instruments at four weeks preoperatively, on the day of surgery, and one year postoperatively. We evaluated results with use of three conceptual frameworks: (1) that ratings provided four weeks preoperatively provide a gold standard for preoperative ratings, (2) that there is no gold standard for preoperative ratings and that, if valid, ratings on the day of surgery should be highly correlated with ratings at four weeks preoperatively and moderately and similarly correlated with ratings at one year postoperatively, and (3) that ratings provided four weeks preoperatively and on the day of surgery are measuring identical constructs and should therefore show high reliability. Most patients (97%) had a chronic injury as the interval between the injury and surgery was more than ninety days. Data collected on the day of surgery demonstrated high predictive validity with data collected within one month before surgery. There was no significant heterogeneity between variances for data collected four weeks preoperatively and on the day of surgery. The correlation between data collected on the day of surgery and four weeks preoperatively was moderate to high (range, 0.64 to 0.93), and the correlation between preoperative ratings and the one-year postoperative ratings was moderate (range, 0.40 to 0.59) across all instruments. Agreement between the ratings provided four weeks preoperatively and on the day of surgery was excellent (intraclass correlation coefficient, 0.64 to 0.91), and the standard error of measurement was small across instruments. In the treatment of chronic knee injuries, patients can accurately rate their quality of life, general health, and functional status on the day on which they undergo surgery.


Do changes in STEC diagnostics mislead interpretation of disease surveillance data in Switzerland? Time trends in positivity, 2007 to 2016.
BackgroundLaboratory-confirmed cases of Shiga toxin-producing Escherichia coli (STEC) have been notifiable to the National Notification System for Infectious Diseases in Switzerland since 1999. Since 2015, a large increase in case numbers has been observed. Around the same time, syndromic multiplex PCR started to replace other diagnostic methods in standard laboratory practice for gastrointestinal pathogen testing, suggesting that the increase in notified cases is due to a change in test practices and numbers.AimThis study examined the impact of changes in diagnostic methods, in particular the introduction of multiplex PCR panels, on routine STEC surveillance data in Switzerland.MethodsWe analysed routine laboratory data from 11 laboratories, which reported 61.9% of all STEC cases from 2007 to 2016 to calculate the positivity, i.e. the rate of the number of positive STEC tests divided by the total number of tests performed.ResultsThe introduction of multiplex PCR had a strong impact on STEC test frequency and identified cases, with the number of tests performed increasing sevenfold from 2007 to 2016. Still, age- and sex-standardised positivity increased from 0.8% in 2007 to 1.7% in 2016.ConclusionIncreasing positivity suggests that the increase in case notifications cannot be attributed to an increase in test numbers alone. Therefore, we cannot exclude a real epidemiological trend for the observed increase. Modernising the notification system to address current gaps in information availability, e.g. diagnostic methods, and improved triangulation of clinical presentation, diagnostic and serotype information are needed to deal with emerging disease and technological advances.


Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism.
Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhibitors also potentiated cell injury induced by hydrogen peroxide (H2O2), tert-butyl-hydroperoxide, and hypoxia and reoxygenation (HR). SiRNA-mediated attenuation of GST-π but not GST-μ expression reduced cell viability and significantly enhanced stress (H2O2/HR)-induced injury. GST inhibitors also induced intracellular oxidative stress (measured by dihydrorhodamine 123 and dichlorofluorescein fluorescence), caused alterations in overall intracellular redox status (as evidenced by NAD(+)/NADH ratios), and increased protein carbonyl formation. Furthermore, the antioxidant N-acetylcysteine completely prevented EA-induced oxidative stress and cytotoxicity. Whereas EA had no effect on mitochondrial energetics, it significantly altered cellular metabolic profile. To explore the physiological impact of these cellular events, we used an ex vivo mouse-isolated perfused lung model. Supplementation of perfusate with EA markedly affected lung mechanics and significantly increased lung permeability. The results of our combined genetic, pharmacological, and metabolic studies on multiple platforms suggest the importance of GST enzymes, specifically GST-π, in the cellular and whole lung response to acute oxidative and metabolic stress. These may have important clinical implications.


Diagnosis of leprosy in Victoria--a non-endemic area of Australia.
There have been at least 70 cases of leprosy in Victoria since 1950; the occurrence of 40 of these in the last seven years indicates that the disease is no longer rare in this State. The diagnosis was delayed in most patients, the average period of time between development of symptoms and diagnosis being 28 months. The most common presentations among these patients emphasize the point that a diagnosis of leprosy should be considered in patients who are suffering either from chronic skin diseases which are atypical and have not responded to therapy, of from localized disturbances of skin sensation.


Experiences with the echo midliner in children.
Three hundred eighty-five children were examined with the Midliner echoencephalography unit. In examinations termed adequate, correct interpretations were made in 94.6% of healthy children versus 78% ill children. The incidence of adequate examinations increases with the child's age, but 58% of children with hydrocephalus had inadequate examinations, regardless of age. For the measurement of the infantile ventricle system the midliner is not appropriate.


Promoting foot self-care in type 2 diabetes mellitus patients receiving hemodialysis based on the information-motivation-behavioral skills model.
This study develops and verifies the use of the foot self-care behavioral model in patients with type 2 diabetes mellitus (T2DM) receiving hemodialysis (HD) based on the information-motivation-behavioral skills model. Data were collected between June and August 2021 from 156 outpatients with type 2 diabetes who were receiving regular HD. A structured questionnaire and electronic medical records were used to collect demographic and disease-related data along with Foot Care Knowledge Questionnaires, third version of Diabetes Attitude Scale, Multidimensional Scale of Perceived Social Support, Foot Care Confidence Scale, and Foot Self-care Behavior Scale. Age, diabetic foot care knowledge, social support, and foot care self-efficacy had a direct effect on foot self-care behavior. Foot care self-efficacy had a mediating effect on foot care knowledge, diabetes-related attitudes, social support, and foot self-care behavior. The information-motivation-behavioral skills model was suitable as a foot self-care behavioral model for patients with T2DM receiving HD. Additionally, these findings suggest that it is crucial to improve foot self-care behavior through increased foot care knowledge, diabetes-related attitudes, and social support, which could contribute to enhancing foot care self-efficacy.


Fluorescence demonstration of dipeptidyl peptidase I (cathepsin C) in skeletal, cardiac, and vascular smooth muscles.
Dipeptidyl peptidase I (cathepsin C) was demonstrated histochemically in soleus, extensor digitorum longus, and cardiac muscles but not in vascular smooth muscle cells of the caudal artery of the rat. The enzyme using Pro-Arg-4-methoxy-beta-naphthylamide as the substrate was found in discrete granules in the striated muscles. The activity was greatest in the soleus muscle, with less activity observed in cardiac tissue, and only a few reactive sites observed in the extensor digitorum longus muscle. Under identical conditions no activity was observed associated with vascular smooth muscle cells. Dipeptidyl peptidase I activity was inhibited completely by 1mM HgCl2 in the incubation solutions and not preserved following conventional chemical fixation techniques.


Comparison of anthropometric indices of obesity in predicting subsequent risk of hyperglycemia among Chinese men and women in Mainland China.
Obesity is a strong risk factor for hyperglycemia. However, the performance of waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), waist circumference (WC) and body mass index (BMI) in predicting hyperglycemia was inconclusive; and ethnic differences may exist in the associations. The objective was to compare WHtR, WC, WHR and BMI in predicting hyperglycemia among Chinese adults and identify optimal cut-off points. A community-based prospective cohort study was conducted during 2004-2007 in Nanjing China. WHtR, WC, WHR, BMI, fasting capillary blood glucose, covariates and potential confounders were assessed at baseline and third year of follow-up. The overall cumulative incidence of hyperglycemia was 8.6% (8.0% in men, 9.0% in women). Relative risks across quartiles of WHtR, WHR, WC and BMI were 1.00, 1.33, 1.67, 3.40; 1.00, 2.38, 2.53, 3.87; 1.00, 1.29, 1.75, 2.90; and 1.00, 1.45, 1.49, 2.41 in men, and 1.00, 1.24, 1.99, 2.87; 1.00, 1.14, 2.28, 2.66; 1.00, 1.32, 1.80, 3.14; and 1.00, 1.39, 1.50, 2.08 in women, respectively. p for trend was <0.01 for each marker and gender. Adjustment for potential confounders did not change such dose-response relationships materially. ROC analysis indicated that WHtR had the best sum of sensitivity and specificity compared to the other measures .Optimal cut-offs for WHtR, WHR, WC and BMI were 0.51, 0.92, 85 and 24 for men, while 0.55, 0.86, 82 and 25 for women, respectively. WHtR, WHR, WC and BMI were positively associated with subsequent hyperglycemia. WHtR and WC best predicted hyperglycemia among Chinese adults.


Evaluation of the microcirculation of the equine small intestine after intraluminal distention and subsequent decompression.
Effects of intraluminal distention (25 cm of H2O, 120 minutes) and subsequent decompression (60 minutes) on intramural vascular patterns of the small intestine was evaluated in 7 anesthetized horses. Intraluminal distention (25 cm of H2O, 120 minutes) was created in 2 jejunal segments in each horse. Experimental and control segments were removed either immediately after the experimental period or after 60 minutes of decompression. The vascular system of experimental and control jejunal segments was lavaged with NaCl, then was injected with a blue-colored radiopaque medium for microangiography or with a diluted methyl methacrylate for scanning electron microscopy of microcorrosion vascular casts. After angiographic evaluation, tissue sections were prepared for light microscopic evaluation to assess vascular filling and tissue morphology. The distended segments had short villi, which were separated by expanded crypts, and had mesothelial cell loss, neutrophil infiltration, and edema in the seromuscular layer. The number of perfused vessels was significantly (P < 0.05) decreased in the seromuscular layer and, to a lesser extent, in the mucosal layer of the distended segments, compared with controls. After decompression, the morphologic lesions progressed in mucosal and serosal layers and the number of observed vessels increased in all intramural layers; however, vascular density did not return to the predistention state. These results identify altered intramural vascular patterns in the equine jejunum during luminal distention and subsequent decompression.


A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.
Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.


Do conditioning focused various-sided training games prepare elite youth male soccer players for the demands of competition?
Relative metrics (i.e. distance covered per minute of match time) are regularly used to quantify soccer player movement demands. However, limited literature is available concerning the peak player demands during training. This study aimed to compare the relative and peak demands of conditioning-focused various-sided training games (VSG) to competition matches in elite youth male soccer players according to playing position. Data from twenty-nine competition matches (national) and twenty-two VSGs (small, medium, and large) were collected for twenty-three elite under-17 soccer players using 15-Hz portable global positioning system tracking devices (GPSports, Canberra, Australia). Relative player movements were reported as total distance (TD) and high-speed running distance (HSRD) (> 5.0 m/s) per minute of total playing time. Peak player movements were calculated using a 1-minute rolling epoch length, reported as the maximum TD and HSRD. Linear mixed models demonstrated interactions between VSG type and player position for relative TD (p < 0.001) and HSRD (p < 0.001), and peak TD (p = 0.010) and HSRD (p = 0.003). The relative TD of VSGs were greater than match-play for all player positions. However, only Central Defenders demonstrated similar HSRD in MSGs and LSGs compared to match-play when analysed using relative calculations. External Attackers also replicated match-play relative HSRD demands in LSGs. No VSG type was found to replicate or supersede the peak player movements of match-play across any playing position. Consequently, VSGs should be supplemented with high-speed running training to prepare players for the peak running requirements of match-play.


United States emergency department visits for children with cerebrospinal fluid shunts.
CSF shunt placement is the primary therapy for hydrocephalus; however, shunt malfunctions remain common and lead to neurological deficits if missed. There is a lack of literature characterizing the epidemiology of children with possible shunt malfunctions presenting to United States emergency departments (EDs). A retrospective study was conducted of the 2006-2017 National Emergency Department Sample. The data were queried using an exhaustive list of Current Procedural Terminology and International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes representing children with hydrocephalus diagnoses, diagnostic imaging for shunt malfunctions, and shunt-related surgical revision procedures. In 2017, there were an estimated 16,376 ED visits for suspected shunt malfunction. Children were more commonly male (57.9%), ages 0-4 years (42.2%), and publicly insured (55.8%). Many did not undergo diagnostic imaging (37.2%), and of those who did, most underwent head CT scans (43.7%). Between 2006 and 2017, pediatric ED visits for suspected shunt malfunction increased 18% (95% CI 12.1-23.8). The use of MRI increased substantially (178.0%, 95% CI 176.9-179.2). Visits resulting in discharge home from the ED increased by 76.3% (95% CI 73.1-79.4), and those involving no surgical intervention increased by 32.9% (95% CI 29.2-36.6). Between 2006 and 2017, ED visits for children to rule out shunt malfunction increased, yet there was a decline in surgical intervention and an increase in discharges home from the ED. Possible contributing factors include improved clinical criteria for shunt evaluation, alternative CSF diversion techniques, changing indications for shunt placement, and increased use of advanced imaging in the ED. CPT = Current Procedural Terminology; ED = emergency department; ETV = endoscopic third ventriculostomy; ICD-9 = International Classification of Diseases, Ninth Revision; ICD-10 = International Classification of Diseases, Tenth Revision; NEDS = National Emergency Department Sample.


Effect of particles on the recovery of cryptosporidium oocysts from source water samples of various turbidities.
Cryptosporidium parvum can be found in both source and drinking water and has been reported to cause serious waterborne outbreaks which threaten public health safety. The U.S. Environmental Protection Agency has developed method 1622 for detection of Cryptosporidium oocysts present in water. Method 1622 involves four key processing steps: filtration, immunomagnetic separation (IMS), fluorescent-antibody (FA) staining, and microscopic evaluation. The individual performance of each of these four steps was evaluated in this study. We found that the levels of recovery of C. parvum oocysts at the IMS-FA and FA staining stages were high, averaging more than 95%. In contrast, the level of recovery declined significantly, to 14.4%, when the filtration step was incorporated with tap water as a spiking medium. This observation suggested that a significant fraction of C. parvum oocysts was lost during the filtration step. When C. parvum oocysts were spiked into reclaimed water, tap water, microfiltration filtrate, and reservoir water, the highest mean level of recovery of (85.0% +/- 5.2% [mean +/- standard deviation]) was obtained for the relatively turbid reservoir water. Further studies indicated that it was the suspended particles present in the reservoir water that contributed to the enhanced C. parvum oocyst recovery. The levels of C. parvum oocyst recovery from spiked reservoir water with different turbidities indicated that particle size and concentration could affect oocyst recovery. Similar observations were also made when silica particles of different sizes and masses were added to seeded tap water. The optimal particle size was determined to be in the range from 5 to 40 micro m, and the corresponding optimal concentration of suspended particles was 1.42 g for 10 liters of tap water.