Confidence and authority through new knowledge: An evaluation of the national educational programme in paediatric oncology nursing in Sweden.
There is a lack of nurse specialists in many paediatric hospitals in Sweden. This lack of competence is devastating for childhood cancer care because it is a highly specialised area that demands specialist knowledge. Continuing education of nurses is important to develop nursing practice and also to retain them. The aim of this study was to evaluate a Swedish national educational programme in paediatric oncology nursing. The nurses who participated came from all of the six paediatric oncology centres as well as from general paediatric wards. At the time of the evaluation, three groups of registered nurses (n=66) had completed this 2year, part-time educational programme. A study specific questionnaire, including closed and open-ended questions was sent to the 66 nurses and 54 questionnaires were returned. Answers were analysed using descriptive statistics and qualitative content analysis. The results show that almost all the nurses (93%) stayed in paediatric care after the programme. Furthermore, 31% had a position in management or as a consultant nurse after the programme. The vast majority of the nurses (98%) stated that the programme had made them more secure in their work. The nurses were equipped, through education, for paediatric oncology care which included: knowledge generating new knowledge; confidence and authority; national networks and resources. They felt increased confidence in their roles as paediatric oncology nurses as well as authority in their encounters with families and in discussions with co-workers. New networks and resources were appreciated and used in their daily work in paediatric oncology. The programme was of importance to the career of the individual nurse and also to the quality of care given to families in paediatric oncology. The national educational programme for nurses in Paediatric Oncology Care meets the needs of the highly specialised care.


Pharmacotherapy of tetanus--a review.
With adequate immunization, tetanus caused by the gram-positive anaerobic cocci, clostridium tetani, is a preventable disease. In treating C. tetani infection, Metronidazole as an antibiotic is more effective than Penicillin G since it is a GABA antagonist. Agents used to control spasm and rigidity should have little effect on the level of consciousness, respiration and blood pressure. The drug of choice for treating spasm and rigidity is benzodiazepine, a GABA agonists. Large doses of benzodiazepines may be required to overcome the spasm and are safe. Baclofen is another GABA agonist, which has been tried as an alternative to benzodiazepine with moderate success. Clinical experience with dantrolene sodium is limited. Magnesium with its unique properties on the neuromuscular junction and sympathetic system has been used to treat both spasms and autonomic dysfunction with limited success. Neuromuscular blocking drugs are indicated depending on the severity of spasms. Neuromuscular blocking drugs with steroid molecule should be avoided in view of prolonged weakness. No drug has consistently proven to be effective in the treatment of autonomic dysfunction. Beta-blockers, variation of and beta blockers, opioids, clonidine, magnesium, spinal and epidural anaesthesia have been tried with varying success. Beta-blockers should be used with caution as they have been implicated in the deaths of some patients with autonomic dysfunction.


Study of gamma-interferon in schistosomiasis mansoni, autoimmune diseases and schistosomal arthropathy.
IFN-gamma, a Th1 cytokine was quantitatively estimated using EASIA in the sera of patients with different stages of schistosomiasis mansoni autoimmune diseases and schistosomal arthropathy. Level of IFN-gamma was significantly elevated in all the test groups compared to the control group. The highest level of IFN-gamma observed was in RA and SLE, with insignificant statistical difference (P > 0.05) between them. Cases with early S. mansoni infection showed significant higher level (P < 0.05) of IFN-gamma compared to hepatosplenic schistosomiasis with and without ascites. A significant statistical difference (P < 0.05) concerning IFN-gamma level was observed when comparing RA and SLE to different stages of S. mansoni infection and schistosomal arthropathy. This might lead to a conclusion that IFN-gamma estimation in sera of patients having joint complaint could be a good marker for differentiation between autoimmune collagen induced arthritis and schistosomiasis induced arthropathy.


Binned progressive quantization for compressive sensing.
Compressive sensing (CS) has been recently and enthusiastically promoted as a joint sampling and compression approach. The advantages of CS over conventional signal compression techniques are architectural: the CS encoder is made signal independent and computationally inexpensive by shifting the bulk of system complexity to the decoder. While these properties of CS allow signal acquisition and communication in some severely resource-deprived conditions that render conventional sampling and coding impossible, they are accompanied by rather disappointing rate-distortion performance. In this paper, we propose a novel coding technique that rectifies, to a certain extent, the problem of poor compression performance of CS and, at the same time, maintains the simplicity and universality of the current CS encoder design. The main innovation is a scheme of progressive fixed-rate scalar quantization with binning that enables the CS decoder to exploit hidden correlations between CS measurements, which was overlooked in the existing literature. Experimental results are presented to demonstrate the efficacy of the new CS coding technique. Encouragingly, on some test images, the new CS technique matches or even slightly outperforms JPEG.


Medical malpractice arbitration: a primer for Texas physicians.
The medical malpractice crises and ensuing tort reform efforts, including methods of alternative dispute resolution (ADR), are generally reviewed. Arbitration in the context of medical malpractice is examined from the perspective of other states' experiences. Michigan has one of the nation's oldest medical malpractice arbitration programs, but it suffers from underutilization. California's experience derives from the use of arbitration in the managed care setting. While Texas has statutory provisions for medical malpractice arbitration, in light of public policy favoring ADR, the statute could be perceived as antipublic policy, resulting in underuse. The National Practitioner Data Bank also serves to discourage physician participation. Policy options are offered to address these concerns.


A Neural Circuit from Thalamic Paraventricular Nucleus to Central Amygdala for the Facilitation of Neuropathic Pain.
As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVTGlu+-CeA-vlPAGGlu+ circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.SIGNIFICANCE STATEMENT Studies have shown that the interactions between the posterior portion of the thalamic paraventricular nucleus (pPVT) and central amygdala (CeA) play a critical role in pain-related emotional regulation. However, most reports have associated this circuit with fear and anxiety behaviors. Here, an integrative approach of behavioral tests, electrophysiology, and immunohistochemistry was used to advance the novel concept that the pPVT-CeA pathway activation facilitates neuropathic pain processing. Using rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques, we found that glutamatergic neurons in the vlPAG were the target of the pPVT-CeA pathway. Thus, this study indicates the involvement of a pPVTGlu+-CeA-vlPAGGlu+ pathway in a descending facilitatory mechanism underlying neuropathic pain.


Exposure of emergency medical responders to methicillin-resistant Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) infections result in 19,000 deaths a year in the United States. Epidemiologic studies have shown that community-acquired infections are increasing dramatically, and strains typical of community infections are increasingly detected in hospital populations. Emergency medical responders (EMR) are exposed to both community and hospital MRSA patients, which, combined with their communal lifestyles in fire stations, results in higher risk of exposure. This study determined the occurrence and frequency of MRSA and other bacterial indicators on environmental surfaces in fire stations, training sites, and offices of EMR. Handled sponges were used for collection of targeted bacteria from commonly contacted environmental surfaces at EMR facilities. Biochemical tests confirmed isolates as S aureus, and MRSA was confirmed by growth on selective and differential media. An initial set of 500 samples was collected at 9 fire-related facilities to identify areas of increased exposure. Subsequent studies targeted sites (n = 160) for repeat sampling that were MRSA positive. S aureus was isolated from 10.6% (17/160) of the sampled sites. The couch and the classroom desks were the most contaminated at 20% (4/20 and 2/10, respectively). Of the S aureus isolated, 64.7% (11/17) were confirmed as MRSA. EMR have a high potential for exposure to MRSA, not only through patient and hospital contacts but also in the fire station environment. MRSA was isolated with the highest frequency on the couches and the class desks. Although the true health significance of these exposures is unknown, improved infection control practices, such as routine handwashing and surface disinfection, are warranted to reduce MRSA exposures.


Indigenous women's voices: marginalization and health.
Marginalization may affect health care delivery. Ways in which indigenous women experienced marginalization were examined. Data from 57 indigenous women (18 to 65 years) were analyzed for themes. Three themes emerged: historical trauma as lived marginalization, biculturalism experienced as marginalization, and interacting within a complex health care system. Experienced marginalization reflected participants' unique perspective and were congruent with previous research. It is necessary for health care providers to assess the detrimental impact of marginalization on the health status of individuals and/or communities.


Education Mediates Racial Disparities in Cognitive Impairment Among Older Adults With Schizophrenia.
In the general population, the construct of race is associated with disparities in cognitive aging. There are notable racial group disparities and inequities among people living with schizophrenia (PLWSz). Despite the salience of the construct of race in schizophrenia, there remains a knowledge gap about racial disparities in cognitive impairment among older adults in this vulnerable population. Our study uses mediation analysis to examine racial disparities in cognitive impairment among older adults with schizophrenia. We assess global cognition in PLWSz over age 55 with the Measurement and Treatment Research to Improve Cognition in Schizophrenia cognitive test battery in our "all-comer" sample (N = 64). The primary exposure is self-reported racial group. We examine mediation of cognitive impairment through educational attainment, adjusting for psychiatric illness severity, history of substance use, and vascular risk factors. There was a Black/non-Black group racial disparity in global cognitive score (-2.8, 95% CI: -4.4, -1.3) after adjusting for confounding and interaction. This disparity was significantly mediated by years of education. There are notable racial disparities in cognitive impairment among older adults with schizophrenia; however, differences in cognitive scores between racial groups are mediated by level of education. Social determinants of health, particularly educational attainment, are important risk factors for cognitive impairment in PLWSz and should be considered by clinicians. Early screening and assessment of cognitive symptoms is essential to addressing health disparities/inequalities among older adults living with schizophrenia. Controlled Direct EffectsHIV: Human Immunodeficiency VirusMATRICS: Measurement and Treatment Research to Improve Cognition in SchizophreniaMCCB: MATRICS Consensus Cognitive BatteryMTE: Marginal Total EffectsNDE: Natural Direct EffectsPANSS: Positive and Negative Symptom ScalePLWSz: People with schizophrenia.


Effect of swamp cultivation on distribution of anopheline larval habitats in Western Kenya.
Malaria resurgence in highland regions of East Africa has been on increase. The spatio-temporal distribution of larval habitats of malaria vectors determines the distribution of adult vectors, hence, disease transmission. Vector's ecology is necessary for strategic vector control through effective plan for source reduction. Mapping of the larval habitats is necessary for targeted control measures. The purpose of this study is to assess and compare the spatial and seasonal variations in anopheline larval habitats in Western Kenya. A comparative study was conducted on spatial distribution of GPS geo-located anopheline larval habitats in relation to highland and lowland environments. Land use types were categorized and all potential aquatic habitats of malaria vectors were examined in February, May, August and November 2004. Data analyses were performed using SAS JMP software. Results showed a higher percentage of Anopheles gambiae s.s. (70.9%) than An. funestus (29.1%) in highland. In the lowland, An. gambiae s.l. comprised 60.1% while An. funestus represented 39.9%. The distribution of larval breeding is confined to the valley bottom in the highland while it was dispersed in the lowland. Land use type influenced the occurrence of positive breeding habitats in the highland. In the lowland, distribution was due to seasonality. We found high proportion of potential and positive breeding sites in cultivated swamps and farmlands at the highland site. These results suggest that swamp cultivation increases the availability and suitability of larval breeding habitats of malaria vectors, thus malaria transmission in the Western Kenya highlands environment.


Evolution of marine mammals: back to the sea after 300 million years.
The fossil record demonstrates that mammals re-entered the marine realm on at least seven separate occasions. Five of these clades are still extant, whereas two are extinct. This review presents a brief introduction to the phylogeny of each group of marine mammals, based on the latest studies using both morphological and molecular data. Evolutionary highlights are presented, focusing on changes affecting the sensory systems, locomotion, breathing, feeding, and reproduction in Cetacea, Sirenia, Desmostylia, and Pinnipedia. Aquatic adaptations are specifically cited, supported by data from morphological and geochemical studies. For example, analysis of oxygen isotopes incorporated into fossil tooth enamel indicates whether these mammals foraged in (and, therefore, ingested) fresh water or sea water. Comparisons between groups are made to see if there are any common patterns, particularly relating to adaptations to aquatic life. Results show that aquatic characteristics evolved in mosaic patterns and that different morphological solutions to aquatic conditions were achieved separately in each of these groups. Changes in the axial and appendicular skeleton assist with locomotion for aquatic foraging. Nostril and eye placement modifications accommodate wading versus underwater foraging needs. All groups exhibit aquatic adaptations directly related to feeding, particularly changes in the dentition and rostrum. The earliest representatives of these clades all show morphological features that indicate they were feeding while in the water, suggesting that feeding ecology is a key factor in the evolution of marine mammals.


Ultra-high performance liquid chromatography-mass spectrometry analysis of plant apocarotenoids.
Apocarotenoids (APOs) are a class of carotenoid oxidation products with high structural and functional diversity. Apart from serving as precursors of phytohormones, fungal pheromones and vitamin A, several APOs act as signaling molecules involved in stress response and growth as regulators in plants. To comprehensively profile plant APOs, we established an improved ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometer (UHPLC-Q-Orbitrap MS) analytical platform. The improved APO analytical platform consists of an optimized sequential APO sample preparation and multiple UHPLC-MS detection methods and was successfully used to identify and quantify multiple subclasses of APOs from tomato fruits. By integrating ultrasound-assisted extraction, solid phase extraction, and chemical derivatization, the improved sequential APOs sample preparation facilitates the simultaneous preparation of different subclasses of APOs from plant materials. In addition, multiple UHPLC-MS detection methods enables high throughput analysis of APOs. Application of this analytical strategy can make important contributions to understanding the function of these compounds and significantly facilitate the elucidation of plant APO metabolism.


Effects of sphingolipid extracts on the morphological structure and lipid profile in an in vitro model of canine skin.
Ceramides (CER) are essential sphingolipids of the stratum corneum (SC) that play an important role in maintaining cutaneous barrier function. Skin barrier defects occur in both human beings and dogs affected with atopic dermatitis, and have been associated with decreased CER concentrations and morphological alterations in the SC. The aim of the present study was to investigate the changes induced by three different sphingolipid extracts (SPE-1, SPE-2 and SPE-3) on the morphological structure and lipid composition of canine skin, using an in vitro model, whereby keratinocytes were seeded onto fibroblast-embedded collagen type I matrix at the air-liquid interface. Cell cultures were supplemented with SPE-1, SPE-2, SPE-3 or vehicle (control) for 14 days. The relative concentrations of lipids were determined by ultra-performance liquid chromatography coupled to mass spectrometry. The ultrastructural morphology of samples was examined by transmission electron microscopy. SPE-1 induced significant elevation in total CERs, CER[NS], CER[NDS], CER[NP], CER[AS], CER[AP], CER[EOS] and CER[EOP] subclasses, whereas SPE-2 induced a significant elevation in total CER, CER[AP] and CER[EOS] compared with control conditions. Ultrastructural analysis revealed an increase in lamellar-lipid structures in the SC of SPE-1-treated samples. The findings demonstrated that SPE-1 stimulates production of CERs, as shown by changes in lipid composition and ultrastructural morphology. Thus, SPE-1 contributes to the formation of a well-organised SC and represents a potential therapeutic target for improving skin barrier function in atopic dermatitis.


[Value of transtracheobronchial ultrasonography in the assessment of mediastinal lymphadenopathy in patients with lung cancer].
In patients with lung cancer, decisions regarding treatment can depend on the diagnosis of hilar and mediastinal nodal involvement. We prospectively compared the diagnostic value of computed tomography (CT) with that of transtracheobronchial ultrasonography (TUS) in the evaluation of lymphadenopathy. Five patients with resectable lung cancer were studied. TUS was done with EU-M 20 or M 30 and lymph nodes located at #3, #4, #7, ipsilateral #10, and #11 were observed and measured. TUS findings, CT findings, and histological findings were evaluated and compared. The sizes of lymph nodes as measured by TUS were similar to or slightly smaller than their sizes as measured by CT. Hilar lymph nodes and lymph nodes located at right #4 were clearly observed with TUS, but were sometimes unclear with CT. Diagnosis of model involvement by TUS needs further study.


Correlation between the methylation of LIVIN gene and the pathogenesis of bone tumor.
We investigated the correlation between the methylation of LIVIN gene and the pathogenesis of bone tumor at the molecular level, in order to improve the treatment method and enhance the cure rate of bone tumor. The expression level of Livin protein was detected using Western blot analysis, and its expressions in control group and patients were detected by immunohistochemistry. The methylation frequency of LIVIN gene was calculated by direct sequencing. Finally, the prognosis of treatment was investigated by follow-up. The experiment found that Livin protein was not expressed in normal cells, while its expression rate was about 71.4% in 112 patients. The methylation frequency of LIVIN gene was gradually decreased with the increase of clinical stage, and had no significant relationship with age and sex. The prognosis experiment indicated that the lower the methylation frequency of LIVIN gene was, the shorter the survival time would be. The methylation of LIVIN gene was closely related to the pathogenesis of bone tumor, which may be one of the important factors to induce the formation of a bone tumor. In addition, the methylation frequency of LIVIN gene could be used as a biomarker for the prognosis of bone tumor treatment.


[Diagnostic difficulties in pulmonary tuberculosis].
The pronounced pathomorphosis complicates the diagnosis of pulmonary tuberculosis, especially with round growths in lungs. In the author's opinion the reasons that lead to the errors in the diagnosis of pulmonary tuberculosis are the following: as a rule, the diagnosis is made only on the basis of clinico-roentgenological data; lack of oncological anxiety; overestimation of trial chemotherapy by means of tuberculostatic medications. In cases of the indeterminate diagnosis it is recommended to arrive at the decision on operation within the shortest possible time.


Evidence for the role of fibronectin in amphibian gastrulation.
In amphibian embryos, fibronectin (FN) assembles as a fibrillar network on the roof of the blastocoel cavity, preceding mesodermal cell migration. Local inversion of the ectoderm to produce a site where no FN is available prevents mesodermal cell migration. Microinjection of monovalent antibodies to FN arrests gastrulation. A complete inhibition of mesodermal cell migration is obtained after microinjection of a synthetic peptide containing the cell binding site sequence of FN. Prevention of interactions between receptors and FN appears to be the primary cause for blockage of gastrulation.


Hypertonic saline activates lipid-primed human neutrophils for enhanced elastase release.
Ongoing clinical trials have revived interest in hypertonic saline (HTS) for postinjury resuscitation; these studies have documented serum Na+ concentrations > or = 170 mmol/L. Recent animal studies have shown that HTS enhances T-cell and monocyte function, but effects on the polymorphonuclear neutrophil (PMN) remain unclear. The postinjury lipid mediators platelet-activating factor (PAF) and leukotriene B4 (LTB4) have been implicated in PMN priming for cytotoxicity, which is believed to be important in the pathogenesis of multiple organ failure. We hypothesized that HTS would stimulate PMN superoxide (O2-) and elastase release from PAF- and LTB4-primed PMNs. Isolated PMNs from five donors were primed for 5 minutes with 200 nmol/L PAF or 1 micromol/L LTB4 in Kreb's-Ringer's phosphate with dextrose at a Na+ concentration of 140 mmol/L (normal serum Na+ concentration), pelleted, and resuspended in Kreb's-Ringer's phosphate with dextrose for 10 minutes at a Na+ concentration of 130 to 170 mmol/L. O2- generation was measured by superoxide dismutase-inhibitable reduction of cytochrome c and elastase release by cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide. HTS with Na+ concentration up to 170 mmol/L had no significant effect on O2- production or elastase release from quiescent cells. Na+ concentration of 160 and 170 mmol/L, however, activated PAF- and LTB4-primed PMNs for enhanced elastase release with no effect on O2- production. In clinically relevant concentrations, elevated Na+ activates lipid-primed neutrophils for enhanced elastase degranulation. Consequently, the administration of HTS in the early postinjury resuscitation period, when PMNs are maximally primed, may activate PMN elastase release and thereby promote the development of multiple organ failure.


Comparison of healthy blood donor Greyhounds and non-Greyhounds using a novel point-of-care viscoelastic coagulometer.
To measure and compare viscoelastic coagulation in 2 canine blood donor populations using a novel, point-of-care device (VCM Vet Analyzer, VCM). Cohort study. Academic and commercial veterinary blood banks. Non-Greyhounds from community-based blood donor program and Greyhounds from a blood bank colony. Blood was collected from all dogs via direct venipuncture for a complete hemogram, biochemistry, and point-of-care viscoelastic coagulation. All biochemical measurements for all dogs in Group NG (n = 38, non-Greyhounds) and Group G (n = 53, Greyhounds) were within local reference intervals. Hematology data showed significant statistical differences between groups in hemoglobin, RBC, platelet, and WBC concentrations. Group G demonstrated lower maximum clot firmness (MCF) with 17 VCM units (26 VCM units in Group NG), increased lysis with 30 VCM units at 30 minutes (LI30) and 27 VCM units at 45 minutes (LI45) (86 VCM units LI30 and 85 VCM units LI45 in Group NG), and decreased amplitude of 13 VCM units 10 minutes (A10) after clot time (CT) and 6 VCM units 20 minutes after CT (A20) (18 VCM units [A10] and 22 VCM units [A20] in Group NG). This study found differences between healthy Greyhound and non-Greyhound blood donors in measures of clot strength and fibrinolysis as measured by the VCM. Whereas Greyhound have unique hematologic and hemostatic profiles, these measured viscoelastic differences are important to note prior to and following surgical intervention to aid in clinical decision-making if bleeding complications develop.


Solvent Degradation and Polymerization in the Li-Metal Battery: Organic-Phase Formation in Solid-Electrolyte Interphases.
The products of solvent polymerization and degradation are crucial components of the Li-metal battery solid-electrolyte interphase. However, in-depth mechanistic studies of these reactions are still scarce. Here, we model the polymerization of common lithium battery electrolyte solvents─ethylene carbonate (EC) and vinylene carbonate (VC)─near the anode surface. Being consistent with the molecular calculation, ab initio molecular dynamic (AIMD) simulations reveal fast solvent decompositions upon contact with the Li anode. Additionally, we assessed the thermochemical impacts of decarboxylation reactions as well as the lithium bonding with reaction intermediates. In both EC and VC polymerization pathways, lithium bonding demonstrated profound catalytic effects while different degrees of decarboxylation were observed. The VC polymerization pathways with and without ring-opening events were evaluated systematically, and the latter one which leads to poly(VC) formation was proven to dominate the oligomerization process. Both the decomposition and polymerization reactivities of VC are found to be higher than EC, while the cross-coupling between EC and VC has an even lower-energy barrier. These findings are in good agreement with experimental evidence and explanatory toward the enhanced performance of VC-added lithium-metal batteries.


Lung Edema Clearance: Relevance to Patients with Lung Injury.
Pulmonary edema clearance is necessary for patients with lung injury to recover and survive. The mechanisms regulating edema clearance from the lungs are distinct from the factors contributing edema formation during injury. Edema clearance is effected via vectorial transport of Na(+) out of the airspaces which generates an osmotic gradient causing water to follow the gradient out of the cells. This Na(+) transport across the alveolar epithelium is mostly effected via apical Na(+) and chloride channels and basolateral Na,K-ATPase. The Na,K-ATPase pumps Na(+) out of the cell and K(+) into the cell against their respective gradients in an ATP-consuming reaction. Two mechanisms contribute to the regulation of the Na,K-ATPase activity:recruitment of its subunits from intracellular compartments into the basolateral membrane, and transcriptional/translational regulation. Na,K-ATPase activity and edema clearance are increased by catecholamines, aldosterone, vasopressin, overexpression of the pump genes, and others. During lung injury, mechanisms regulating edema clearance are inhibited by yet unclear pathways. Better understanding of the mechanisms that regulate pulmonary edema clearance may lead to therapeutic interventions that counterbalance the inhibition of edema clearance during lung injury and improve the lungs' ability to clear fluid, which is crucial for patient survival.


Success and reliability of extrafemoral Exoseal vascular closure device: "Off-label" usage.
The aim of this study is to present the reliability and efficacy of Exoseal vascular closure device (EVCD) for closure of extrafemoral punctures. All patients who were treated with EVCD following arterial endovascular treatment involving an extrafemoral puncture between April 2013 and January 2014 were examined retrospectively. This study included 11 patients (4 women and 7 men between the ages of 48 and 87 years; average age = 65 years). A total of 13 procedures were performed in 11 patients involving the following access routes: brachial artery (n = 5), popliteal artery (n = 4), and polytetrafluoroethylene graft (n = 4). Twelve out of 13 EVCD procedures achieved technical success and procedural success. One minor and one major complications occurred. Both complications were revealed to be pseudoaneurysms, both in the brachial artery. Pseudoaneurysm of the minor complication was treated by Fibrin Sealant (Tisseel) injection guided by ultrasonography and the other pseudoaneurysm was treated by covered stent placement. The femoral artery is an essential access route of arterial endovascular procedures; however, in some cases, the extrafemoral arterial route is necessary. In this study, EVCD was found to be useful for closing extrafemoral arterial routes. This study had a limited number of cases and more large-scale studies are needed.


Epigenetic Signatures in Breast Cancer: Clinical Perspective.
There is now a compelling body of evidences sustaining the importance of epigenetic mechanisms in the development and progression of cancer. DNA methylation, post-translational histone and other protein modifications, microRNA expression, and nucleosome positioning, all act together to exert their cellular effects. The epigenome is responsible for controlling gene expression thus defining cell differentiation and tissue specificity. This review will focus on DNA methylation and histone modification because these epigenetic events are widely implicated in cancer development and progression. We will in particular address the translational aspects of breast cancer epigenomics including the development of biomarkers and the prospects for epigenetic based pharmacologic treatments. The analysis of DNA methylation has the advantage over other molecular methods (e.g. single gene mutation, microsatellite analysis) that it can be detected with a very high degree of specificity even in the presence of excess unmethylated DNA. Furthermore, the presence of specific CpG methylation signatures makes methylation-based markers attractive diagnostic, prognostic, and predictive tools for better management of breast cancer patients.


The common murre (Uria aalge), an auk seabird, reacts to underwater sound.
Marine mammals have fine-tuned hearing abilities, which makes them vulnerable to human-induced sounds from shipping, sonars, pile drivers, and air guns. Many species of marine birds, such as penguins, auks, and cormorants, find their food underwater where light is often limited, suggesting sound detection may play a vital role. Yet, for most marine birds, it is unknown whether they are using, and can thereby be affected by, underwater sound. The authors conducted a series of playback experiments to test whether Alcid seabirds responded to and were disrupted by, underwater sound. Underwater broadband sound bursts and mid-frequency naval 53 C sonar signals were presented to two common murres (Uria aalge) in a quiet pool. The received sound pressure levels varied from 110 to 137 dB re 1 μPa. Both murres showed consistent reactions to sounds of all intensities, as compared to no reactions during control trials. For one of the birds, there was a clearly graded response, so that more responses were found at higher received levels. The authors' findings indicate that common murres may be affected by, and therefore potentially also vulnerable to, underwater noise. The effect of man-made noise on murres, and possibly other marine birds, requires more thorough consideration.


Recommended antimicrobial therapy for common inpatient infections: a comparative review of guidelines across 51 hospital trusts in England.
The number of different antimicrobial recommendations between hospital trusts for the same indication in England is unknown. We aimed to evaluate the heterogeneity of antimicrobial recommendations for seven common inpatient infections across hospital trusts in England and evaluate changes to recommendations following introduction of national (National Institute for Healthcare and Excellence, NICE) and international (WHO) antimicrobial guidelines. Guidelines published on the MicroGuide smartphone application were collected from December 2017 to February 2018 and re-evaluated between December 2019 and February 2020. The following indications were assessed: community-acquired pneumonia (CAP) CURB65 score ≥3, hospital-acquired pneumonia (HAP), infective exacerbation of chronic obstructive pulmonary disease (iCOPD), cellulitis, uncomplicated urinary tract infection (uUTI), intra-abdominal infection (IAI) and sepsis of unknown source (SUS). On follow-up, compliance against WHO WATCH antibiotic and NICE recommendations was evaluated. Guidelines were obtained predominantly from England. Antibiotic regimens between hospitals became increasingly diverse across indications in the following order: uUTI, cellulitis, iCOPD, CAP, HAP, IAI and SUS. A piperacillin/tazobactam-based regimen was recommended in HAP (59%), SUS (39%) and IAI (30%). After 2 years, 107 changes were made to 357 antibiotic regimen recommendations; the overall number of regimens using piperacillin-tazobactam and WHO WATCH antibiotics remained similar. Compliance of recommendations with NICE guidelines as follows: iCOPD (100% adherent), uUTI (98%), cellulitis (90%), CAP (43%) and HAP (27%). The heterogeneity of antibiotic recommendations increased as the indicated infection was more severe, with broader underlying bacterial causes. Piperacillin-tazobactam remains favoured in antibiotic regimens, despite not recommended in WHO and NICE guidance.


Secondhand Aerosol Exposure From Heated Tobacco Products and Its Socioeconomic Inequalities in Japan: The JASTIS Study 2017-2020.
The growing use of heated tobacco products (HTPs) has raised concerns about secondhand aerosol (SHA) from HTPs, but few studies have been reported on it. This study aimed to investigate the trends in SHA exposure and their socioeconomic inequalities in Japan. The prevalence of SHA exposure from 2017 to 2020 was estimated using longitudinal internet survey data of 5221 participants, aged 20-69 years in 2017 (baseline), with adjustments using inverse probability weighting for "being a participant in an internet survey". Multivariable modified Poisson regression models were applied to examine the association between socioeconomic status (ie, educational attainment and equivalent income) at baseline and SHA exposure in 2020 with adjustments for sex and age. The estimated prevalence of SHA exposure has consistently increased from 4.5% in 2017 to 10.8% in 2020. Lower educational attainment was associated with a higher risk of SHA exposure (p for trend = 0.010). The covariate-adjusted risks of SHA exposure in participants with a low-education and middle-education level were 1.57 and 1.34 times higher, respectively, than in those with a high-education level. However, significant differences in risks of SHA exposure between participants with low-, middle-, and high-income levels were not observed. Meanwhile, participants with a low-education and middle-education level also had 1.87 and 1.61 times higher risks of secondhand smoke (SHS) exposure from combustible cigarettes than those with a high-education level, respectively. Our study revealed a rapid increase in SHA exposure and the existence of educational inequalities in both SHA and SHS exposure. Using longitudinal internet cohort survey data, we found that the prevalence of exposure to secondhand aerosol (SHA) from heated tobacco products (HTPs) rapidly increased to 10.8% in 2020 in Japan. Furthermore, people with lower educational attainment were at higher risk of SHA exposure, suggesting that extensive educational interventions may be necessary to inform the public that although emissions from HTPs contain significantly lesser amounts of harmful and potentially harmful constituents and these compounds than cigarette smoke, they are not harmless and still entail risks, and its long-term effects are unknown. Therefore, future extensive monitoring of SHA exposure is needed.


Acute presentation of immunotherapy-related diabetes mellitus without ketoacidosis, low C-peptide or elevated HbA1c.
The rapid rise in the use of immune checkpoint inhibitors as systemic cancer therapy has seen the emergence of immunotherapy-induced diabetes, a severe irreversible immunotherapy-related adverse event. Affected patients typically present with diabetic ketoacidosis (DKA) and low C-peptide consistent with insulin deficiency secondary to autoimmune β-cell destruction. We present the unusual case of a 61-year-old female with metastatic ampullary duodenal adenocarcinoma with primary tumour adjacent to the pancreatic head. She was commenced on immunotherapy after conventional systemic chemotherapy. Acute-onset hyperglycaemia was detected after 7 weeks on weekly blood glucose monitoring, with no glucocorticoid use or prior history of diabetes. On presentation, there was no evidence of DKA, and her glycated haemoglobin level was within the normal non-diabetic range at 5.3%, reflecting the acuity of her presentation. Initial serum C-peptide was preserved; however, it became undetectable a few weeks later, confirming insulin deficiency. We describe a case of atypical presentation of immunotherapy-induced diabetes, review the existing literature on this emerging clinical entity and discuss the differential diagnosis for new-onset diabetes mellitus in patients with metastatic cancer. Regular proactive glycaemic monitoring in patients receiving immunotherapy, particularly antibodies against programmed death ligand 1 and PD1, can facilitate very early detection of immunotherapy-induced diabetes, prompting insulin commencement and avoiding life-threatening presentations of diabetic ketoacidosis. Glycated haemoglobin can be within the normal range in patients diagnosed acutely with immunotherapy-induced diabetes. Serum C-peptide can be preserved initially in patients diagnosed with immunotherapy-induced diabetes but is likely to become undetectable during their illness. New-onset diabetes in patients with metastatic cancer carries a broad differential diagnosis.


MiR-155 affects proliferation and apoptosis of bladder cancer cells by regulating GSK-3β/β-catenin pathway.
GSK-3β negatively regulates Wnt/β-catenin signaling pathway. The abnormal miR-155 expression is associated with bladder cancer. Bioinformatics analysis revealed a complementary binding site between miR-155 and GSK-3β mRNA. This study investigated the role of miR-155 in the proliferation and apoptosis of bladder cancer cells. The dual luciferase reporter gene assay validated the targeted regulation between miR-155 and GSK-3β. Tumor tissues and adjacent tissues were collected from bladder cancer patients and the expression of miR-155 and GSK-3β mRNA was detected by RT-PCR. Bladder cancer cell line BIU-87 cells were cultured in vitro and divided into miR-NC group and miR-155 inhibitor group. The expressions of miR-155, GSK-3β and β-catenin were compared, cell apoptosis was detected by flow cytometry, and cell proliferation was detected by EdU staining. Compared with adjacent tissues, miR-155 expression was significantly increased in bladder cancer tissues, and GSK-3β mRNA expression was significantly decreased. There was a targeted regulatory relationship between miR-155 and GSK-3β. Compared with SV-HUC-1 cells, miR-155 expression in bladder cancer BIU-87 and 5637 cells was significantly increased, and GSK-3β expression was significantly decreased. Transfection of miR-155 inhibitor significantly increased GSK-3β expression in BIU-87 and 5637 cells, decreased β-catenin expression, increased cell apoptosis, and decreased cell proliferation. The increased expression of miR-155 plays a role in reducing the expression of GSK-3β and in promoting the pathogenesis of bladder cancer. Inhibition of miR-155 can up-regulate the expression of GSK-3β, inhibit the activity of Wnt/β-catenin pathway, attenuate proliferation and promote apoptosis of bladder cancer cells.


Biochemical and virologic parameters in patients co-infected with hepatitis C and HIV versus patients with hepatitis C mono-infection.
Previous studies of patients with hepatitis C virus (HCV) infection looking at the effect of human immunodeficiency virus (HIV) co-infection on biochemical parameters and HCV RNA level have shown conflicting results. Accurate characterization of the effect of HIV is important for evaluation and treatment of HCV in co-infected persons. We studied 315 HCV mono-infected and 75 HCV-HIV co-infected subjects to determine the effect of HIV on biochemical parameters and HCV RNA and to determine the predictors of elevated serum alanine aminotransferase (ALT) levels and HCV RNA levels. The co-infected subjects were more likely to be African-American (55% vs 26%, P < 0.0005), have used injection drugs (68% vs 60%, P = 0.02), have detectable HCV RNA (84% vs 70.5%, P = 0.018), have HCV RNA levels >6 log10 IU/mL (60% vs 38%, P = 0.001), and have lower mean serum ALT levels (50.4 IU/mL vs 73.7 IU/mL, P = 0.006). In multivariable analyses, the following factors predicted an ALT level >50 IU/mL: log10 HCV RNA (OR, 1.15; 95% CI, 1.00 to 1.32); HIV co-infection (OR, 0.48; 95% CI, 0.25 to 0.89); and having ever been treated for HCV (OR, 1.92; 95% CI, 1.16 to 3.18). The only significant predictor of HCV RNA level >6 log10 IU/mL was HIV co-infection (OR, 2.75; 95% CI, 1.46 to 5.15). Significant predictors of having a detectable HCV RNA level were female sex (OR, 3.81; 95% CI, 1.18 to 12.25); HIV co-infection (2.45; 95% CI, 1.14 to 5.26); and ever being treated for HCV (OR, 1.96; 95% CI, 1.10 to 3.48). HCV-HIV co-infected persons have higher HCV RNA levels but lower serum ALT levels than HCV mono-infected patients. Criteria for performing liver biopsy and treating HCV infection in co-infected patients may need to be revisited.


Osteogenesis Stimulator Devices Reduce Surgical Intervention, Opioid Utilization, and Overall Costs in Patients with Fracture Nonunions.
Approximately 10% of fractures result in delayed union or nonunion. These cases result in pain and disability as well as increased utilization of healthcare resources such as pain medication, physical therapy, and subsequent surgery. Osteogenesis stimulator devices are a safe and low-cost, non-invasive option to aid healing in nonunion cases. Study objectives aimed to evaluate real-world data of osteogenesis stimulator device usage in a variety of healthcare utilization endpoints including surgical intervention for nonunion, pain medication use, and overall healthcare costs. Data were stratified into three groups: the Stim Device group and the No Stim and Surgical control groups. A retrospective analysis of a large claims-based database was conducted. The database was queried for adult patients having a diagnosis of nonunion, with evidence of a prior fracture in the previous 180 days (n = 11,010). The osteogenesis stimulator group (Stim Device group, n = 1,628) was defined as those patients having at least one claim for an osteogenesis stimulator in the period 90 to 180 days following fracture and up to 60 days following the nonunion diagnosis. The control group (No Stim group, n = 9,382) had a nonunion diagnosis with evidence of a fracture in the prior 180 days but did not receive a device. A total of 1,751 patients from the No Stim group were sub-grouped into surgical/operative controls (No Stim - Surgical group). Stim Device patients showed lower rates of surgical intervention for their bone nonunion compared to the No Stim patients (214/1,628, 13.1% vs. 1,751/9,382, 18.7%, p < 0.001). Stim Device patients had lower rates of opioid utilization post-index compared to No Stim patients (948/1,628, 58.2% vs. 6,359/9,382, 67.8%, p < 0.001). Overall healthcare costs were significantly reduced in the Stim Device group ($21,654) compared with No Stim ($29,101; p < 0.001) and Surgical ($35,914; p < 0.001) control groups. The results show that bone growth stimulator devices have a positive individual and societal impact on treating patients with fracture nonunions.


Stramenopile microorganisms associated with the massive coral Favia sp.
The surfaces of massive corals of the genus Favia from Eilat, Red Sea, and from Heron Island, Great Barrier Reef, are covered by a layer of eukaryotic microorganisms. These microorganisms are embedded in the coral mucus and tissue. In the Gulf of Eilat, the prevalence of corals covered by patches of eukaryotic microorganisms was positively correlated with a decrease in water temperatures (from 25-28 degrees C in the summer to 20-23 degrees C in winter). Comparisons carried out using transmission and scanning electron microscopy showed morphological similarities between the microorganisms from the two geographically distant reefs. The microorganisms found on and in the tissues were approximately 5-15 microm in diameter, surrounded by scales in their cell wall, contained a nucleus, and included unique auto-florescent coccoid bodies of approximately 1 mum. Such morphological characters suggested that these microorganisms are stramenopile protists and in particular thraustochytrids. Molecular analysis, carried out using specific primers for stramenopile 18S rRNA genes, revealed that 90% (111/123) of the clones in the gene libraries were from the Thraustochytriidae. The dominant genera in this family were Aplanochytrium sp., Thraustochytrium sp., and Labyrinthuloides sp. Ten stramenopile strains were isolated and cultured from the corals. Some strains showed > or =97% similarity to clones derived from libraries of mucus-associated microorganisms retrieved directly from these corals. Fatty acid characterization of one of the prevalent strains revealed a high percentage of polyunsaturated fatty acids, including omega-3. The possible association of these stramenopiles in the coral holobiont appeared to be a positive one.


Detection and Profiling of Antibiotic Resistance among Culturable Bacterial Isolates in Vended Food and Soil Samples.
The emergence and persistence of antibiotic resistance remain formidable health challenges. This study aimed at detecting and profiling antibiotic resistance of bacterial contaminants in vended food and the environment. Seventy antibiotic-resistant bacterial isolates were isolated from fried fish, African sausages, roasted meat, smokies, samosa, chips (potato fries), vegetable salads, and soil samples collected from Embu Town and Kangaru Market in Embu County, Kenya. The antibiotic susceptibility test, morphological and biochemical characterization, antibiosis assay, polymerase chain reaction-based detection of antibiotic resistance genes, and sequencing of the 16S rRNA gene were done. Analysis of variance on all measured data was done, and Tukey's honest test was used to compare and separate mean diameters of zones inhibition. Resistance of bacterial isolates to antibiotics was chloramphenicol (90%), cefotaxime (84.29%), nalidixic acid (81.43%), tetracycline (77.14%), amoxicillin (72.86%), gentamycin (48.57%), streptomycin (32.86%), and trimethoprim + sulphamethoxazole (30%). Isolate KMP337, Salmonella spp., exhibited highly significant antibiosis against S. aureus recording a mean inhibition diameter and standard error (SE) of 16.33 ± 0.88 mm, respectively, at P=0.001. The 70 bacterial isolates belonged to Bacillus, Paraclostridium, Lysinibacillus, Virgibacillus, and Serratia genera. The study isolated Bacillus wiedmannii (KC75) which is a risk group 2 as well as Serratia marcescens (KMP95) and Bacillus anthracis (KS606) which are risk group 3 organisms. The presence of antibiotic resistance genes Tet A, Bla TEM, StrB, Dfr A, Amp, and FloR genes was confirmed by a polymerase chain reaction. Samples from Kangaru Market recorded a higher (88.57%) proportion of resistant isolates as compared to isolates from Embu Town (11.43%). The study confirmed the presence of antibiotic-resistant bacteria in vended fast food and the soil in Embu Town and Kangaru Market. This study calls for continuous monitoring of bacterial status and hygienic handling of vended food.


Program changes are effective and cost-effective in increasing the amount of oil used in preparing corn soy blend porridge for treatment of moderate acute malnutrition in Malawi.
Corn Soy Blend (CSB) porridge is commonly prepared with oil for treatment of moderate acute malnutrition (MAM). A recent review recommended that 30 g of oil be used with 100 g of CSB to increase energy density and micronutrient absorption. This study assessed the effectiveness and cost-effectiveness of program changes aimed at achieving that target oil:CSB ratio in prepared porridge. Caregivers of children in MAM supplementary feeding programs were assigned to three groups: a control group received monthly rations of 1 L oil, 8 kg CSB in bulk, and social and behavior change communication (SBCC); intervention groups received 2.6 L oil, 8 kg CSB provided either in bulk (Group 1) or four 2-kg packages with printed messages (Group 2), and enhanced SBCC emphasizing the target oil:CSB ratio. Compared to the control, both intervention groups had higher mean added oil per 100 g CSB (18 g, p < 0.01, and 13 g, p= 0.04, higher in groups 1 and 2, respectively), and greater odds of meeting or exceeding the target ratio (28.4, p< 0.01, and 12.7, p= 0.02, in groups 1 and 2, respectively). Cost per caregiver reaching the target ratio was most favorable in Group 1 ($391 in Group 1, $527 in Group 2, and $1,666 in the control). Enhanced SBCC combined with increased oil ration resulted in increased use of oil in CSB porridge in a supplementary feeding program. Modified packaging did not improve effectiveness. However, both interventions were more cost-effective than standard programming.


Characterization and localization of the even-skipped protein of Drosophila.
On the basis of homeo box cross-homology we have isolated the pair-rule gene even-skipped (eve) of Drosophila. The eve transcription unit appears to be less than 1.5 kb in length, and encodes a single mRNA of approximately 1.4 kb. The nucleotide sequence of genomic and cDNA clones indicates that the eve protein is composed of 376 amino acid residues, and that its homeo domain shares only approximately 50% amino acid identity with the homeo domains of previously characterized genes. Using antibodies raised against a beta-galactosidase fusion protein we show that the eve protein is distributed in a series of seven transverse stripes at the cellular blastoderm stage, and is localized primarily within the nuclear regions of those embryonic cells that express the gene. After gastrulation, seven weakly stained stripes of eve expression appear, resulting in a transient pattern that consists of a total of 14 evenly spaced stripes. Both the original and new stripes gradually disappear during germ band elongation. A second expression pattern emerges during neurogenesis, whereby eve protein is detected in discrete subsets of neurons in each of the ventral ganglia.


Decreased axial bone mineral density in perimenopausal women with rheumatoid arthritis--a population based study.
Although periarticular osteoporosis is a well-recognised phenomenon in rheumatoid arthritis (RA), there is considerable controversy over whether RA is associated with more generalised osteoporosis. The aetiology of this bone loss is probably multifactorial, including both life-style risk factors and disease-related determinants. Population-based studies on bone mineral density (BMD) in RA have not previously been conducted, and the purpose of the present cross-sectional population-based study was to determine whether patients with RA are at an increased risk of having osteoporosis. Furthermore, the determinants of BMD in RA patients were investigated. BMD at the spine and femoral neck was measured in 143 women with RA. The control group consisted of 1611 women with no disease or taking any drugs known to affect bone metabolism. The study population was a random stratified sample from the Kuopio Osteoporosis Study, which included all perimenopausal women aged 47-56 years residing in Kuopio Province, Eastern Finland in 1989 (n = 14,220). The mean age of the patients at the time of densitometry was 53.7 years. The mean (SD) spinal and femoral neck BMD was significantly lower in patients with RA compared with controls [spine: 1.067 (0.161) v 1.129 (0.157) g/cm2, p < 0.001; femoral neck: 0.851 (0.136) v 0.932 (0.123) g/cm2, p < 0.001]. Analysis of variance showed that at the spine the difference was significant only in patients having corticosteroid treatment, whereas at the femoral neck patients with non-steroid treatment also had significantly lower BMD. When confounding factors were corrected, no significant difference could be found between non-steroid and corticosteroid treated patients with RA, suggesting that the independent effect of corticosteroids on BMD is only minimal. Multiple regression analysis found age, weight and functional grade to be significant predictors of spinal BMD (R2 = 0.403, p < 0.001). In the femoral neck weight, cumulative corticosteroid dose and functional grade were significant predictors of BMD (R2 = 0.410, p < 0.001). RA is associated with generalised osteoporosis. The physical impairment and body weight are the major determinants of both spinal and femoral bone mass in RA patients. The cumulative corticosteroid dose was also a significant determinant of femoral neck BMD. However, the independent effect of corticosteroids is questionable because the use of corticosteroids may be an indicator of more severe disease.


[Eye symptoms in hypophyseal adenomas, craniopharyngiomas and meningiomas of the anterior and middle cranial fossa].
Among 181 inpatients suffering from pituitary adenoma, craniopharyngioma, or meningioma of the anterior or middle cranial fossa, 112 had ocular symptoms initially or during the course of the disease. Patients' histories were analyzed with regard to ophthalmological, neurological, and radiological diagnostic procedures carried out, and the conclusions drawn from these. Initial symptoms and signs were often misinterpreted and appropriate investigations consequently delayed. The mean duration of the history was 2.67 years (0-13 years) for the pituitary adenomas, 1.44 years (3 months-6 years) for the craniopharyngiomas and 3.73 years (1 month-24 years) for the meningiomas. Typical initial eye symptoms were progressive loss of vision with or without optic nerve atrophy, visual field defects, extraocular nerve palsies, and exophthalmus, the last two occurring if parasellar extension of the tumor was present. Plain skull X-rays were abnormal in nearly all cases of pituitary adenomas, but the incidence of abnormalities was less frequent with cases of craniopharyngiomas and meningiomas. The tumor was demonstrated by computerized tomography in all cases of pituitary adenomas, in 5 out of 6 cases with craniopharyngiomas and, where the examination was performed before and after administration of contrast medium, in all cases of meningiomas. Introduction of CT, however, shortened the duration of the history only in the meningioma group; the mean dropped from 4.38 years to 3.04 years. The chance of achieving a cure by surgical intervention lessened with both increasing length of history and tumor size. Out of 90 patients (15.6%) operated on, 14 died in the postoperative period. Vision improved postoperatively in only 26 patients whereas it remained unchanged or decreased further in 40 patients. In 10 cases there were no postoperative data available. These results emphasize the necessity of making an early diagnosis. This can nearly always be achieved if a careful clinical examination and adequate additional diagnostic procedures are carried out.


Frequency of genomic rearrangements involving the SHFM3 locus at chromosome 10q24 in syndromic and non-syndromic split-hand/foot malformation.
Split-hand/foot malformation (SHFM), or ectrodactyly, is characterized by underdeveloped or absent central digital rays, clefts of the hands and feet, and variable syndactyly of the remaining digits. SHFM occurs as both an isolated finding and a component of many syndromes. SHFM is a heterogeneous condition caused by multiple loci, including SHFM1 (chromosome region 7q21-q22), SHFM2 (Xq26), SHFM3 (10q24), SHFM4 (3q27), and SHFM5 (2q31). Mutations in TP63 at the SHFM4 locus are known to underlie both syndromic and non-syndromic forms SHFM, but the causes of most non-syndromic SHFM cases remain unknown. The recent identification of submicroscopic tandem chromosome duplications affecting the SHFM3 locus in seven families with non-syndromic SHFM has helped to further unravel the molecular basis of this malformation. In our ongoing studies of the SHFM3 locus in 44 additional cases of syndromic and non-syndromic SHFM, we have identified similar chromosome rearrangements in eight additional cases (18%), using pulsed-field gel electrophoresis (PFGE). We have also utilized real-time quantitative PCR (qPCR) to test for the duplications. Seven of the cases with rearrangements were non-syndromic. The current findings bring the total of SHFM3-associated cases with chromosome rearrangements to 15, which constitute 29% (15 of 51) of the cases screened to date. This includes 9 of 9 cases (100%) with known linkage to the SHFM3 locus, all of whom have non-syndromic SHFM, and 6 of 42 additional cases (14%), four of whom have non-syndromic SHFM. Thus, SHFM3 abnormalities underlie a substantial proportion of SHFM cases and appear to be a more frequent cause of non-syndromic SHFM than mutations in TP63.


Safety, Reactogenicity, and Immunogenicity of Human Rotavirus Vaccine RIX4414 in Human Immunodeficiency Virus-positive Infants in South Africa.
rotavirus and human immunodeficiency virus (HIV) infections are a cause of great public health concern in developing countries. The current study evaluated the safety, reactogenicity, and immunogenicity of RIX4414 vaccine in asymptomatic or mildly symptomatic (clinical stages I and II according to WHO classification) HIV-infected South African infants. a total of 100 HIV-positive infants aged 6 to 10 weeks enrolled in this double-blind, 1:1 randomized, placebo-controlled study were allocated into 2 groups to receive 3 doses of RIX4414 vaccine/placebo according to a 0-, 1-, and 2-month schedule. Routine vaccines were concomitantly administered. Solicited and unsolicited symptoms were recorded for 15 and 31 days after each dose, respectively. Serious adverse events were recorded throughout the study period. Serum antirotavirus IgA concentrations (enzyme-linked immunosorbent assay, cut-off ≥ 20 U/mL) and the immunodeficiency status were determined at screening and 2 months post-Dose 3. Stool samples were analyzed for rotavirus using enzyme-linked immunosorbent assay at predetermined points and during diarrhea episodes. all symptoms (solicited and unsolicited) occurred at a similar frequency in both groups. Six fatal serious adverse events in RIX4414 and 9 in placebo groups were reported. At 2 months post-Dose 3, the seroconversion rates were 57.1% (95% CI: 34-78.2) in RIX4414 and 18.2% (95% CI: 5.2-40.3) in the placebo group. The mean absolute CD4 cell count, CD4 percentage, and HIV-1 viral load were comparable in both groups at screening and 2 months post-Dose 3. Rotavirus shedding peaked at Day 7 after Dose 1 of RIX4414 with prolonged shedding was observed in 1 infant only. : Three doses of RIX4414 vaccine was tolerated well by the South African HIV-positive infants. A satisfactory immune response was mounted without aggravating their immunologic or HIV condition.


Oldest record of monk seals from the North Pacific and biogeographic implications.
True seals (crown Phocidae) originated during the late Oligocene-early Miocene (approx. 27-20 Ma) in the North Atlantic/Mediterranean region, with later (middle Miocene, approx. 16-11 Ma) dispersal events to the South Atlantic and South Pacific. Contrasting with other pinnipeds, the fossil record of phocids from the North Pacific region is scarce and restricted to the Pleistocene. Here we present the oldest fossil record of crown phocids, monachines (monk seals), from the North Pacific region. The specimens were collected from the upper Monterey Formation in Southern California and are dated to 8.5-7.1 Ma, predating the previously oldest known record by at least 7 Ma. This record provides new insights into the early biogeographic history of phocids in the North Pacific and is consistent with a northward dispersal of monk seals (monachines), which has been recognized for other groups of marine mammals. Alternatively, this finding may correspond with a westward dispersal through the Central American Seaway of some ancestor of the Hawaiian monk seal. This record increases the taxonomic richness of the Monterey pinniped assemblage to five taxa, making it a fairly diverse fossil assemblage, but also constitutes the oldest record of sympatry among all three extant pinniped crown clades.


Renal leiomyoma: Case report and literature review.
Renal leiomyomas are rare benign tumours of the kidney originating from muscle cells. They are usually found by an autopsy, whether the patient is asymptomatic or has symptoms (i.e., abdominal/flank pain, hematuria, palpable mass). Today the widespread use of ultrasonography and computed tomography has increased the detection of clinically asymptomatic renal leiomyomas. The differential diagnosis between leiomyomas and other malignant lesions (above all renal cell carcinoma or leiomyosarcoma) is still possible by histological examination. Radiological examinations are not sufficient for the differential diagnosis. Renal leiomyomas have no aggressive behaviour and they usually do not metastasize. The prognosis, after surgery, is excellent without recurrence. We report a case of leiomyoma in a 31-year-old man who presented hematuria and flank pain. We also review the literature and provide a summary of clinical, radiological and histological features of renal leiomyomas.


Mental Health Identification Practices of Jails: The Unmet Needs of the "Silent" Population: Special Issue: Criminal Justice and Community Psychology: Our Values and Our Work.
The overrepresentation of individuals with mental illness in the criminal/legal system is well documented. While professional associations urge diversion towards treatment, little is known about the practices these institutions use to identify this population. One understudied space in the criminal/legal continuum is jails. This exploratory study compares two types of mental health identification at jail booking to assess jail- and community-based service outcomes by identification type (N = 2956): (a) staff observation and (b) a standardized screening instrument. Individuals identified through staff observation were significantly more likely to receive jail- and community-based services, even though current symptomology and substance misuse were both significantly higher for individuals identified only by the screening instrument. These findings point to the importance of jails in providing stabilizing services during incarceration, but further, show the impact that identification practices have on individuals as they transition to the community. Community context showed varied rates of jail staff observations of mental illness, showing greater risks for individuals in rural communities. Implications include a need for system-level changes by instituting evidence-based identification practices in jails, and improving professional collaboration practices between mental health and criminal/legal practitioners as individuals enter and exit jails.


Boosting Replication and Penetration of Oncolytic Adenovirus by Paclitaxel Eradicate Peritoneal Metastasis of Gastric Cancer.
Peritoneal metastasis is the most frequent form of distant metastasis and recurrence in gastric cancer, and the prognosis is extremely poor due to the resistance of systemic chemotherapy. Here, we demonstrate that intraperitoneal (i.p.) administration of a green fluorescence protein (GFP)-expressing attenuated adenovirus with oncolytic potency (OBP-401) synergistically suppressed the peritoneal metastasis of gastric cancer in combination with paclitaxel (PTX). OBP-401 synergistically suppressed the viability of human gastric cancer cells in combination with PTX. PTX enhanced the antitumor effect of OBP-401 due to enhanced viral replication in cancer cells. The combination therapy increased induction of mitotic catastrophe, resulting in accelerated autophagy and apoptosis. Peritoneally disseminated nodules were selectively visualized as GFP-positive spots by i.p. administration of OBP-401 in an orthotopic human gastric cancer peritoneal dissemination model. PTX enhanced the deep penetration of OBP-401 into the disseminated nodules. Moreover, a non-invasive in vivo imaging system demonstrated that the combination therapy of i.p. OBP-401 administration with PTX significantly inhibited growth of peritoneal metastatic tumors and the amount of malignant ascites. i.p. virotherapy with PTX may be a promising treatment strategy for the peritoneal metastasis of gastric cancer.


Chlorine dioxide enhances lipid peroxidation through inhibiting calcium-independent cellular PLA2 in larvae of the Indianmeal moth, Plodia interpunctella.
Polyunsaturated fatty acids usually undergo lipid peroxidation induced by reactive oxygen species (ROS). Calcium-independent cellular phospholipase A2 (iPLA2) can maintain fatty acid compositions in phospholipids depending on physiological conditions. An insect iPLA2 (Pi-iPLA2) was predicted from the transciptome of the Indianmeal moth, Plodia interpunctella. It encodes 835 amino acids. It possesses five ankyrin repeats in the N terminal and patatin lipase domain in the C terminal. Pi-iPLA2 was expressed in all developmental stages of the Indianmeal moth. In the larval stage, it was expressed in all tissues tested. RNA interference (RNAi) specific to Pi-iPLA2 was performed using specific double-stranded RNA (dsRNA). It resulted in almost 70% of reduction in gene expression. Under such RNAi condition, P. interpunctella exhibited significant accumulation of lipid peroxidation based on the amount of malondialdehyde. RNAi of Pi-PLA2 expression also impaired cellular immune response of P. interpunctella. Chlorine dioxide (ClO2), an insecticidal agent by generating ROS, increased lipid peroxidation in a dose-dependent manner. However, the addition of vitamin E (an antioxidant) reduced the formation of lipid peroxidation. ClO2 treatment significantly reduced expression of Pi-iPLA2 but increased lipid peroxidation in larval fat body of P. interpunctella. Furthermore, larvae treated with dsRNA specific to Pi-iPLA2 were significantly susceptible to ClO2 treatment. These results suggest that Pi-iPLA2 plays a crucial role in repairing damaged fatty acids from phospholipids. Our results also suggest that ClO2 can elevate lipid peroxidation through inhibiting Pi-iPLA2 expression in addition to direct ROS production.


Assessing risks--challenges posed by the European general product safety directive.
The concept of risk appears in a prominent way in the recently revised European Directive on General Product Safety (GPSD). Risk assessment is therefore an important tool for the success of the Directive; the question is how risk assessment should be carried out in a systematic manner in order to meet the aims of the Directive. In this paper, the references in the GPSD concerning the concept of risk are reviewed and compared with reported problems in European risk assessment. Existing guidelines for risk assessment are examined in order to determine what factors determine the consistency of the outcome. This leads to recommendations for a process that could be followed in order to make risk assessment successful in the context of the GPSD. On the basis of existing guidelines for risk assessment, criteria are formulated with which methods of risk assessment should comply. A stepwise process is proposed in order to develop a common method of risk assessment that can be applied in Europe to support the GPSD. The requirements for risk management in the new GPSD are rather abstract and lack specification, both for producers and for enforcement authorities. The Directive further refers to the need to develop non-binding guidelines in due course. Sources of different outcomes of the risk assessment process are outlined in this paper as well as possibilities to achieve a more consistent basis for decision, more uniformity and transparency. These are essential conditions if one wishes to avoid both undue trade barriers and unsafe products on the market. A leading role for the European Commission seems necessary to make sure that the intentions of the GPSD are accomplished.


Identification of an inactivating cleavage site for alpha-thrombin on the heavy chain of factor Va.
Previous studies of factor (F)Va inactivation on human umbilical vein endothelial cells have shown that alpha-thrombin cleaves the heavy chain near the COOH-terminus to produce a M(r) 97,000 fragment containing the NH(2)-terminal portion of the heavy chain and a M(r) 8,000 peptide containing the rest of the molecule. The alpha-thrombin cleavage appeared to occur between amino acid residues 586 and 654 of FV. This region contains a consensus sequence for alpha-thrombin cleavage located at residues 640-644 (S-S-P-R-S). To test the hypothesis that alpha-thrombin cleaves the FVa heavy chain at Arg(643) and to evaluate the functional importance of this cleavage for FVa inactivation, site-directed mutagenesis was used to create recombinant FV molecules with mutations R(643) --> Q (FV(R643Q)) and R(643) --> A (FV(R643A)). All recombinant molecules were purified to homogeneity and assayed for activity following extended activation with alpha-thrombin. Under similar experimental conditions, appearance of the M(r) 97,000 heavy chain fragment in the plasma and wild-type FVa molecules correlated with partial loss of cofactor activity, while following extended incubation of FV(R643Q) and FV(R643A) with alpha-thrombin no cleavage of the heavy chain at Arg(643) was detected and no presence of the M(r) 97,000 heavy-chain fragment was noticed. Further, no loss in cofactor activity was observed using these mutant recombinant FVa molecules. Our data demonstrate that cleavage of FVa at Arg(643) by alpha-thrombin results in a partially inactive cofactor molecule and provides for an activated protein C (APC)-independent anticoagulant effect of alpha-thrombin.


Alzheimer's disease: review of hormone therapy trials and implications for treatment and prevention after menopause.
Hormonal changes associated with the menopausal transition and postmenopause have the potential to influence processes linked to Alzheimer's disease symptoms and pathogenesis, but effects of menopause on Alzheimer risk can be addressed only indirectly. Nine randomized clinical trials of estrogen-containing hormone therapy in Alzheimer's disease patients were identified by a systematic literature search. Findings suggest that hormone therapy does not improve cognitive symptoms of women with Alzheimer's disease. No clinical trials of hormone therapy address Alzheimer prevention, but one clinical trial provides moderate evidence that continuous, combined estrogen plus progestogen initiated at age 65 years or older increases the risk of dementia. The timing, or critical window, hypothesis suggests that hormone therapy initiated at a younger age in closer temporal proximity to menopause may reduce the risk of Alzheimer's disease. This hypothesis is supported by observational research but is not addressed by clinical trial data. Unrecognized confounding is of concern in interpreting observational results, and research that helps resolve this issue will have important public health implications. Well-designed cohort studies, convergent evidence from appropriate laboratory models, and long-term clinical trials using surrogate biomarkers of brain function and neural pathology could provide relevant answers. Other estrogenic compounds are of theoretical interest with respect to Alzheimer treatment and risk. Effects of selective estrogen receptor modulators such as raloxifene may differ from those of estrogens; potential effects of phytoestrogens are not well studied. This article is part of a Special Issue entitled 'Menopause'.


[The interstitial organ in weightlessness: a clinico-physiologic model].
We performed an experiment within the 1991 Austromir mission, 3 months preflight, on the 6th inflight and 4th postflight days, respectively. Primary goal was to measure changes in venous blood and plasma sound velocity (BSV, PSV) with lower body suction (LBNP). Contrasting earth-based findings, there was no increase in BSV nor PSV with LBNP inflight. Postflight, the elevation in both values was greater than expected. Taken together with LBNP data from the German 1992 Mir cosmonaut, we propose the hypothesis that the dynamics of tissue fluid exchange is profoundly influenced by m-g adaptation. A further goal of the experiment was to determine volume- and stress-sensitive hormones. The results need validation by additional flight data and might be considered as an important contribution to our understanding of the normal functioning and pathophysiology of the interstitial organ.


Fas-positive T cells regulate the resolution of airway inflammation in a murine model of asthma.
Persistent airway inflammation, mucus production, and airway hyperreactivity are the major contributors to the frequency and severity of asthma. Why lung inflammation persists in asthmatics remains unclear. It has been proposed that Fas-mediated apoptosis of inflammatory cells is a fundamental mechanism involved in the resolution of eosinophilic airway inflammation. Because infiltrating eosinophils are highly sensitive to Fas-mediated apoptosis, it has been presumed that direct ligation of Fas on eosinophils is involved. Here, we utilize adoptive transfers of T cells to demonstrate that the delayed resolution of eosinophilia in Fas-deficient mice is a downstream effect of Fas deficiency on T cells, not eosinophils. Interestingly, the mice that received Fas-deficient T cells, but not the controls, developed a persistent phase of inflammation that failed to resolve even 6 wk after the last challenge. This persistent phase correlated with decreased interferon (IFN)gamma production by Fas-deficient T cells and could be reproduced with adoptive transfer of IFNgamma-deficient T cells. These data demonstrate that Fas deficiency on T cells is sufficient for the development of long-term allergic airway disease in mice and implies that deregulation of death receptors such as Fas on human T cells could be an important factor in the development and/or chronic nature of asthma.


Laparoscopic Collis gastroplasty and Nissen fundoplication. A new technique for the management of esophageal foreshortening.
The short esophagus increases the difficulty and limits the effectiveness of laparoscopic Nissen fundoplication. In out experience, approximately 20-25% of esophagi judged by preoperative criteria to be foreshortened will, after dissection, be insufficiently long to allow 2 cm of esophagus to reside below the diaphragm without inferior distraction (i.e., tension free). Collis gastroplasty combined with Nissen fundoplication has become the standard approach for the creation of an intraabdominal neoesophagus and fundic wrap. After developing methods of performing totally laparoscopic stapled gastroplasty in the cadaver lab in 1994, we started applying the technique clinically in 1966. We performed 220 laparoscopic antireflux procedures between January 1966 and July 1997. Of these 220 patients, 26% were suspected to have esophageal foreshortening based on preoperative barium studies and/or endoscopy. After hiatal dissection, nine patients, or 16% of those suspected to have esophageal foreshortening and 4% of the entire population, required the laparoscopic Collis-Nissen procedure. There was symptomatic improvement in all patients as assessed by patient-initiated symptom scores. The management of patients with esophageal foreshortening is a complex problem. We believe that our technique of laparoscopic Collis-Nissen provides an effective means of achieving intraabdominal placement of the fundic wrap while maintaining the benefits of minimally invasive approach.


[Effects of nutritional status on the multiple sclerosis disease: systematic review].
To review the available scientific literature about the effects of nutritional status on the multiple sclerosis disease. A systematic review of the scientific literature in the Medline (PubMed), Scopus, Cochrane Library and Web of Science databases through November 2016. Search equation: ("Multiple Sclerosis"[Mesh] OR "Multiple Sclerosis"[Title/Abstract] OR "Disseminated Sclerosis"[Title/Abstract] OR "Multiple Sclerosis Acute Fulminating"[Title/Abstract]) AND ("Nutritional Status"[Mesh] OR "Nutritional Status"[Title/Abstract] OR "Nutrition Status"[Title/Abstract]). The quality of the selected articles was discussed using the STROBE questionnaire. The search was completed through experts inquiry and additional review of the bibliographic references included in the selected papers. The concordance between authors (Kappa index) had to be higher than 80% for inclusion in this review. Of the 160 references recovered, after applying inclusion and exclusion criteria, 29 articles were selected for review. Concordance between evaluators was 100.00%. The most studies established vitamin D levels. Others focused their research on finding out which nutrient deficits might be related to the multiple sclerosis development. Vitamin D may influence multiple sclerosis improvement. Sunlight and physical activity would be important factors, with nutritional status, in the course of this disease. It is necessary to produce new specific works that will delve into the subject to find out more about the relationship between nutritional status and multiple sclerosis.


Provider resistance to advance provision of oral contraceptives in Africa.
In Africa, many new family planning clients are not menstruating at the time they present for services. Where pregnancy tests are unavailable, clients are often denied their method of choice and sent home to await menses. For pill clients, one obvious solution is 'advance provision' of oral contraceptives for later use. However, this practice is rare in Africa. To assess the level of provider resistance to advance provision of oral contraceptives. We added questions about advance provision of pills to five provider surveys in three African countries. We also used simulated clients in Ghana to assess provider resistance to the practice. In Kenya, only 16% of providers thought it safe to give women oral contraceptives to be started at a later date. In Ghana and Senegal, fewer than 5% of providers mentioned advance provision as a way to manage non-menstruating pill clients. Training programmes and service delivery guidelines in developing countries should provide for advance provision of pills to appropriate clients


Cutaneous scrotal metastasis: origins and clinical characteristics of visceral malignancies that metastasize to the scrotum.
Cutaneous metastases occur in about 10% of patients with cancer, occasionally presenting as the initial sign of internal malignancy. Most often cutaneous metastases are an indicator of advanced cancer and are associated with a poor prognosis. The scrotum is a rare site of cutaneous metastasis, and metastatic tumor to the scrotum can be mistaken for other skin lesions. We reviewed the published literature regarding patients who developed cutaneous metastasis to the scrotum. We summarized the clinical characteristics of these men, including primary tumor sites, age at diagnosis, treatment regimens, interval between diagnosis of primary tumor and subsequent metastasis, and outcomes. We extensively searched the PubMed medical database for papers on visceral malignancies with metastasis to the scrotum. We limited our definition to solid organ tumors; thus lymphomas, sarcomas, and melanomas of the scrotum were excluded. We identified 29 patients who developed scrotal metastases from visceral cancers. The colon/rectum (34%), prostate (28%), and lung (14%) were the most frequent sites of tumor origin. The prognosis for these patients is poor: mean patient survival was only four months after diagnosis of metastatic skin lesions. Cutaneous metastasis to the scrotum is a rare manifestation of internal malignancies that most often represents an advanced and/or progressive cancer associated with a poor prognosis. Treatment is often unsuccessful, and the mean patient survival following scrotal metastasis is <4 months.


[The endo-exo prosthesis for patients with a problematic amputation stump].
Following lower limb amputation, quality of life is highly related to the ability to use a prosthetic limb. The conventional way to attach a prosthetic limb to the body is with a socket. Many patients experience serious discomfort wearing a conventional prosthesis because of pain, instability during walking, pressure sores, bad smell or skin irritation. In addition, sitting is uncomfortable and pelvic and lower back pain due to unstable gait is often seen in these patients. The main disadvantage of the current prosthesis is the attachment of a rigid prosthesis socket to a soft and variable body. The socket must fit tightly for stability during walking but should also be comfortable for sitting. The implantation of an osseointegrated, intramedullary, transcutaneously conducted prosthesis is a new procedure for attaching a limb prosthesis to the human body without the disadvantages of the conventional prosthesis. The intramedullary prosthesis is designed with a rough surface resembling cancellous bone to enable a secure solid integration with the long bone. We treated two patients with this new prosthesis, a 44-year-old man after a transfemoral amputation, and a 32-year-old woman after a lower leg amputation; both amputations were necessary because of trauma. Those two patients are now, more than one year after the operation, showing excellent functional results without infectious complications. We assume that endo-exo prosthesis may be a promising option for selected patients unable to use a conventional prosthesis because of a problematic amputation stump.


Myosin VIIA regulates microvillus morphogenesis and interacts with cadherin Cad99C in Drosophila oogenesis.
Microvilli and related actin-based protrusions permit multiple interactions between cells and their environment. How the shape, length and arrangement of microvilli are determined remains largely unclear. To address this issue and explore the cooperation of the two main components of a microvillus, the central F-actin bundle and the enveloping plasma membrane, we investigated the expression and function of Myosin VIIA (Myo7A), which is encoded by crinkled (ck), and its interaction with cadherin Cad99C in the microvilli of the Drosophila follicular epithelium. Myo7A is present in the microvilli and terminal web of follicle cells, and associates with several other F-actin-rich structures in the ovary. Loss of Myo7A caused brush border defects and a reduction in the amount of the microvillus regulator Cad99C. We show that Myo7A and Cad99C form a molecular complex and that the cytoplasmic tail of Cad99C recruits Myo7A to microvilli. Our data indicate that Myo7A regulates the structure and spacing of microvilli, and interacts with Cad99C in vivo. A comparison of the mutant phenotypes suggests that Myo7A and Cad99C have co-dependent and independent functions in microvilli.


The neural substrates of cognitive control deficits in autism spectrum disorders.
Executive function deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive function deficits in ASDs, and only one in adolescents. The current study examined cognitive control - the ability to maintain task context online to support adaptive functioning in the face of response competition - in 22 adolescents aged 12-18 with autism spectrum disorders and 23 age, gender, and IQ matched typically developing subjects. During the cue phase of the task, where subjects must maintain information online to overcome a prepotent response tendency, typically developing subjects recruited significantly more anterior frontal (BA 10), parietal (BA 7 and BA 40), and occipital regions (BA 18) for high control trials (25% of trials) versus low control trials (75% of trials). Both groups showed similar activation for low control cues, however the ASD group exhibited significantly less activation for high control cues. Functional connectivity analysis using time series correlation, factor analysis, and beta series correlation methods provided convergent evidence that the ASD group exhibited lower levels of functional connectivity and less network integration between frontal, parietal, and occipital regions. In the typically developing group, fronto-parietal connectivity was related to lower error rates on high control trials. In the autism group, reduced fronto-parietal connectivity was related to attention deficit hyperactivity disorder symptoms.


Effect of 2-bromo-alpha-ergocryptine (CB-154) on estrogen induced growth of the rat prostate.
Castrate male Sprague-Dawley rats were treated with either testosterone; testosterone and estradiol; testosterone, estradiol and 2-Bromo-alpha-Ergocryptine (CB-154), an inhibitor of prolactin secretion; or testosterone and CB-154. Estradiol potentiated testosterone-induced growth of the dorsal, lateral, and ventral prostate and this effect was not counteracted by CB-154. Estradiol only induced hypertrophy of the dorsal and ventral prostate, however, hyperplastic changes occurred in the lateral prostate.


A fluorescence decay study of parinaroyl-phosphatidylinositol incorporated into artificial and natural membranes.
Phosphoinositide metabolism in the plasma membrane is linked to transmembrane signal transduction. In this study we have investigated some physical properties (e.g. molecular order and dynamics) of phosphatidylinositol (PI) in various membrane preparations by time-resolved fluorescence techniques, using a synthetic PI derivate with a cis-parinaroyl chain on the sn-2 position. Phospholipid vesicles, normal and denervated rat skeletal muscle sarcolemmal membranes, and acetylcholine receptor rich membranes from Torpedo marmorata were investigated both at 4 degrees C and 20 degrees C. For comparison we have also included 2-parinaroyl-phosphatidylcholine (PC) in this study. The fluorescent lipids were incorporated into the membrane preparations by way of specific phospholipid transfer proteins, to ensure an efficient and non-perturbing insertion of the lipid-probes. In the Torpedo membranes the order parameters measured for the parinaroyl derivatives of both PC and PI were higher than in phospholipid vesicles. For the Torpedo membrane preparations the acyl chain order for the PI was lower than that for PC, whereas the opposite was true for the vesicles. This inversion strongly suggests that PI has different interactions with certain membrane components as compared to PC. This is also suggested by the significantly higher rate of restricted rotation of PI as compared to PC. In contrast to the order parameters, the correlation times were almost identical for both probes and showed little difference between vesicles and the Torpedo membranes. In contrast to Torpedo membranes, the time-dependent fluorescence anisotropy of the two lipid probes in the sarcolemmal membranes showed, after an initial fast decay, a subsequent gradual increase. This phenomenon was satisfactorily analyzed by assuming two populations of probe lipids with distinct lifetimes, rotational correlation times and molecular order. The order parameter of the population with a short lifetime compared with that of phospholipid vesicles, whereas the population with a long lifetime agreed with that of the Torpedo membranes.


Roles of interleukin 1 beta and tumor necrosis factor in lipopolysaccharide fever in rats.
The roles of interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF) in lipopolysaccharide (LPS)-induced fever were investigated in the rat. We used antisera against IL-1 beta and TNF to determine whether we could alter the fever by blocking the action of these cytokines. The intravenous injection of antiserum IL-1 beta 3.5 days before the intraperitoneal injection of LPS resulted in a mean fever that was significantly lower than that seen in rats that had been injected with control serum (0.36 +/- 0.11 vs. 0.82 +/- 0.16 degrees C, P = 0.016). The intravenous injection of antiserum against TNF 3.5 days before the intraperitoneal injection of LPS did not block the fever but significantly enhanced it (1.31 +/- 0.16 vs. 0.82 +/- 0.16 degrees C, P = 0.027). These data support the hypotheses that IL-1 beta is responsible for a significant part of LPS fever and that TNF acts as an endogenous antipyretic to limit the magnitude of LPS fever in the rat.


Thoracolumbar fractures without neurosurgical involvement: surgical or conservative treatment?
The decision whether to treat amyelic thoracolumbar fractures conservatively or by surgical approach depends mainly on radiographic and clinical evaluation of their potential stability. An angle of kyphosis of 20 degrees or more evaluated using the sagittal index (s.i.) described by Farcy et al. in 1990, may be a valid indication for invasine treatment using pedicular systems for correction and stabilization; on the other hand, conservative treatment may be adequate for ensuring satisfactory results in fractures with an angle of less than 20 degrees, which are less likely to become unstable in clinically negative patients. This study confronts the immediate and long-term radiographic and clinical results in 2 groups of patients treated for amyelic thoracolumbar fractures, one treated conservatively, the other surgically; in particular, angle of kyphosis, vertebral compression and clinical conditions (pain and functional impairment) at long-term follow-up were assessed. The study was extended to include an assessment of outcome in relation to the angle of post-traumatic kyphosis in both operated and non-operated patients. Thirty-one patients with a diagnosis of non-neurological thoracolumbar trauma of the segment between D11 and L3 were studied. Twenty patients (group A) were treated conservatively (reduction on Cotrel bed and plaster vest) and 11 (group B) surgically (Diapason instrumentation). The 31 patients were subdivided into 2 groups according to the initial angle of kyphosis calculated using the s.i.: the first consisted of 16 patients (group C) with a s.i. of 20 degrees or more and the other of 15 patients (group D) with a s.i. less than 20 degrees. Six of the 16 group C patients and 5 of the 15 group D patients had been surgically treated. On the basis of the case-material considered, we found that satisfactory short-term radiographic results may be obtained by both conservative and surgical treatment. However, long-term outcome is less favorable in patients treated conservatively because maintainance of the initial improvement of the deformity in the injured segment is not as good as in those treated surgically. This limitation of conservative treatment does not however appear to negatively influence clinical conditions in patients with a s.i. of less than 20 degrees. In other words, although conservative treatment is not as effective as surgery for maintaining radiographic improvement, this does not necessarily signify clinical deterioration in cases with a s.i. of less than 20 degrees in whom the two types of treatment gave similar results.


Mechanism of bicarbonate exit across basolateral membrane of rabbit proximal straight tubule.
To clarify the mechanism(s) of HCO3- (or related base) transport across the basolateral membrane, rabbit proximal straight tubules were perfused in vitro, and intracellular pH (pHi) and Na+ activity (aiNa) were measured by double-barreled ion-selective microelectrodes. Lowering bath HCO3- from 25 to 5 mM at constant PCO2 depolarized basolateral membrane potential (Vbl), and reduced pHi. Most of these changes were inhibited by adding 1 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) to the bath. Total replacement of bath Na+ with choline also depolarized Vbl and reduced pHi, and these changes were also inhibited by SITS. Reduction in aiNa was observed when bath HCO3- was lowered. Taken together, these findings suggest that HCO3- exists the basolateral membrane with Na+ and negative charge. Calculation of the electrochemical driving forces suggests that the stoichiometry of HCO3-/Na+ must be larger than two for maintaining HCO3- efflux. Total replacement of bath Cl- with isethionate depolarized Vbl gradually and increased pHi slightly, implying the existence of a Cl(-)-related HCO3- exit mechanism. The rate of decrease in pHi induced by lowering bath HCO3- was slightly reduced (20%) by the absence of bath Cl-. Therefore, the importance of Cl(-)-related HCO3- transport is small relative to total basolateral HCO3- exit. Accordingly, these data suggest that most of HCO3- exits the basolateral membrane through the rheogenic Na+/HCO3- cotransport mechanism with a stoichiometry of HCO3-/Na+ of more than two.


Skull base chondroblastoma presenting as a deep lobe parotid tumour.
Chondroblastomas are rare, benign cartilage-producing primary bone tumours that account for 1% of all primary bone tumours. They are usually seen in young adult males and affect long tubulous bones such as the femur or humerus. Occurrences in non-tubular flat bones such as the craniofacial skeleton do occur but are seen in older adults. With only around 100 cases reported in the English literature, 'Temporal Bone Chondroblastomas' can present a diagnostic challenge for both surgeon and histopathologist. Clinical presentation can be subtle and patients may have longstanding symptoms due to compression of surrounding structures. Imaging in the form of contrast CT and/or MRI is recommended to assess size, proximity to neurovascular structures and plan operative approach. Definitive treatment is surgical excision, with radiotherapy reserved for recurrence or unfit surgical patients. Long-term follow-up is recommended for surveillance due to high recurrence rates. We present our experience managing this rare entity.