Late diagnosis of intraplacental choriocarcinoma co-existing with fetomaternal haemorrhage causing fetal demise: A case report.

Intraplacental choriocarcinoma (IC) is a rare disease, occurring in approximately 1 in 50,000 pregnancies. A 33-year-old woman, gravida 2 para 0, sustained an intrauterine fetal death due to fetomaternal haemorrhage (FMH) at 36 weeks of gestation after presenting with decreased fetal movements in the days prior. The placenta macroscopically appeared normal. However, histological examination revealed an intraplacental choriocarcinoma. Assessment of this woman's quantitative beta human chorionic gonadotropin (bHCG) level was negative and a computerized tomography scan of her chest, abdomen and pelvis revealed no metastatic disease yet a bulky uterus. After discussion at a multidisciplinary tumour board meeting, the patient had endometrial curettings to rule out any uterine pathology and serial bHCG tests until one year post-partum. Following this, the patient successfully carried and delivered a live female term infant. Although FMH is a rare clinical manifestation of IC it should always alert clinicians to investigate the cause further, through urgent and careful histopathological examination of the placenta. This will allow for appropriate management with chemotherapy if indicated and a reduction in maternal morbidity and mortality.

Candida chorioamnionitis associated with late stillbirth: A case report.

Vulvovaginal candidiasis during pregnancy is common, but serious complications, including chorioamnionitis, are infrequent. A 41-year-old woman presented at 37 weeks of gestation with reduced fetal movements, and fetal death in utero was subsequently confirmed on ultrasound. Histopathology of the cord and placenta revealed Candida infection and microabscesses on the umbilical cord. Overall, these features are suggestive of ascending infection, consistent with Candida as the causative organism. To the best of our knowledge, this is the first reported case of late stillbirth due to Candida chorioamnionitis. More research is needed to determine the mechanism whereby Candida becomes pathogenic in pregnancy. There is also no clear consensus on how to manage such patients in a subsequent pregnancy.

Home-based crisis team in North Cork service description and patient-related outcomes.

OBJECTIVE: Home-based crisis team (HBCT) in North Cork was established in 2013 to provide short term, intensive home treatment to people who are experiencing acute mental health problems, with the aim of averting hospital admission wherever possible or supporting patients discharged from hospital. METHODS: A retrospective descriptive study design was adopted to describe the activities of the North Cork HBCT over a 1 year period. Data were analysed using R version 3.4.0 for Windows. RESULTS: A total of 388 patients were referred to the HBCT in 2015, of which 328 required assessments. General practitioners (GPs) made 56% of all referrals. The most common referral reason was low mood (40%). Stepped-up care to the psychiatric inpatient unit was required for 12.4% of patients, 62% were discharged to the outpatient clinic for routine follow-up. CONCLUSION: Many common psychiatric presentations can be managed at home with the support of the HBCT although hospital admission is required for significant numbers.

Sex-dependent influences of morphine and its metabolites on pain sensitivity in the rat.

Preclinical studies report that the effective dose for morphine is approximately 2-fold higher in females than males. Following systemic administration, morphine is metabolized via Phase II glucuronidation in the liver and brain into two active metabolites: morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), each possessing distinct pharmacological profiles. M6G binds to µ opioid receptors and acts as a potent analgesic. In contrast, M3G binds to toll-like receptor 4 (TLR4), initiating a neuroinflammatory response that directly opposes the analgesic effects of morphine and M6G. M3G serum concentrations are 2-fold higher in females than males, however, sex-specific effects of morphine metabolites on analgesia and glial activation in vivo remain unknown. The present studies test the hypothesis that increased M3G, and subsequent TLR4-mediated activation of glia, is a primary mechanism driving the attenuated response to morphine in females. We demonstrate that intra-PAG M6G results in a greater analgesic response in females than morphine alone. M6G analgesia was reversed with co-administration of (-)-naloxone, but not (+)-naloxone, suggesting that this effect is µ opioid receptor mediated. In contrast, intra-PAG administration of M3G significantly attenuated the analgesic effects of systemic morphine in males only, increasing the 50% effective dose of morphine two-fold (5.0 vs 10.3mg/kg) and eliminating the previously observed sex difference. An increase in IL-1ß, IL-6 and TNF was observed in females following intra-PAG morphine or M6G. In males, only IL-1ß levels increased following morphine. Changes in cytokine levels following M3G were limited to TNF in females. Together, these data implicate sex differences in morphine metabolism, specifically M3G, as a contributing factor in the attenuated response to morphine observed in females.

Laboratory analogue of a supersonic accretion column in a binary star system.

Astrophysical flows exhibit rich behaviour resulting from the interplay of different forms of energy-gravitational, thermal, magnetic and radiative. For magnetic cataclysmic variable stars, material from a late, main sequence star is pulled onto a highly magnetized (B>10 MG) white dwarf. The magnetic field is sufficiently large to direct the flow as an accretion column onto the poles of the white dwarf, a star subclass known as AM Herculis. A stationary radiative shock is expected to form 100-1,000 km above the surface of the white dwarf, far too small to be resolved with current telescopes. Here we report the results of a laboratory experiment showing the evolution of a reverse shock when both ionization and radiative losses are important. We find that the stand-off position of the shock agrees with radiation hydrodynamic simulations and is consistent, when scaled to AM Herculis star systems, with theoretical predictions.

Improving the finite element model accuracy of tissue engineering scaffolds produced by selective laser sintering.

In bone tissue engineering, both geometrical and mechanical properties of a scaffold play a major part in the success of the treatment. The mechanical stresses and strains that act on cells on a scaffold in a physiological environment are a determining factor on the subsequent tissue formation. Computational models are often used to simulate the effect of changes of internal architectures and external loads applied to the scaffold in order to optimise the scaffold geometry for the prospective implantation site. Finite element analysis (FEA) based on computer models of the scaffold is a common technique, but would not take into account actual inaccuracies due to the manufacturing process. Image based FEA using CT scans of fabricated scaffolds can provide a more accurate analysis of the scaffold, and was used in this work in order to accurately simulate and predict the mechanical performance of bone tissue engineering scaffolds, fabricated using selective laser sintering (SLS), with a view to generating a methodology that could be used to optimise scaffold design. The present work revealed that an approach that assumes isotropic properties of SLS fabricated scaffolds will lead to inaccurate predictions of the FE model. However, a dependency of the grey value of the CT scans and the mechanical properties was discovered, which may ultimately lead to accurate FE models without the need of experimental validation.

Optical Thomson scattering measurements of plasma parameters in the ablation stage of wire array Z pinches.

A Thomson scattering diagnostic has been used to measure the parameters of cylindrical wire array Z pinch plasmas during the ablation phase. The scattering operates in the collective regime (α>1) allowing spatially localized measurements of the ion or electron plasma temperatures and of the plasma bulk velocity. The ablation flow is found to accelerate towards the axis reaching peak velocities of 1.2-1.3×10(7) cm/s in aluminium and ∼1×10(7) cm/s in tungsten arrays. Precursor ion temperature measurements made shortly after formation are found to correspond to the kinetic energy of the converging ablation flow.

Observation of a velocity domain cooling instability in a radiative shock.

We report on experimental investigations into strong, laser-driven, radiative shocks in cluster media. Cylindrical shocks launched with several joules of deposited energy exhibit strong radiative effects including rapid deceleration, radiative preheat, and shell thinning. Using time-resolved propagation data from single-shot streaked Schlieren measurements, we have observed temporal modulations on the shock velocity, which we attribute to the thermal cooling instability, a process which is believed to occur in supernova remnants but until now has not been observed experimentally.

Gold nanoparticles and oxidative stress in Mytilus edulis.

Little is known about potential environmental impact of nanoparticles. Gold nanoparticles can cause unexpected biological responses. Here, Mytilus edulis were exposed (24h) to gold-citrate nanoparticles (GNP), menadione and both compounds simultaneously (GNP/menadione). Protein ubiquitination and carbonylation were determined in gill, mantle and digestive gland, along with traditional oxidative stress biomarkers; catalase activity and neutral red retention time assay (haemolymph). 2DE gels were performed on gill proteins (menadione; GNP/menadione). Our results reveal that GNP may induce oxidative stress.

Changes in serum electrolytes during treatment of patients in liver failure with molecular adsorbent recirculating system.

PURPOSE: To study the effect of MARS on serum electrolytes during liver failure. DESIGN: Twenty-three patients admitted to a quaternary health care facility from September 2000 to May 2002, 22 adults and 1 child, 11 males (48%) and 12 females (52%), age 15-70 (median 53), treated with MARS for: 12 acute-on-chronic liver failure (52%); 4 fulminant hepatic failure (17%); 3 intractable pruritus (13%); 2 primary-non-function (9%); 2 following major liver resection (9%). PROCEDURES: Sodium, potassium, chloride, phosphorus, calcium, and magnesium were measured in the serum, ultrafiltrate and albumin circuit before and after MARS. STATISTICAL METHODS: A comparison of electrolyte concentrations, before and after MARS, was performed using a paired t test. MAIN FINDINGS: Serum electrolyte concentrations before and after MARS, while statistically significant in some cases, were very small, and of no clinical relevance. CONCLUSION: MARS exchanges potassium, chloride, calcium, and magnesium by ultrafiltration; sodium by the albumin dialysis.

Lupus autoantigens: their origins, forms, and presentation.

The immune system has developed a number of mechanisms by which to distinguish self from foreign proteins. These mechanisms are found throughout the ontogeny of B and T cell development and include the deletion of autoreactive cells in central lymphoid organs and the induction of self-tolerance in the periphery. However, any failure of these mechanisms for self-tolerance may result in autoimmune disease. Efforts in our laboratory have been directed at understanding how autoimmunity is initiated and maintained in both the B and T cell compartment, with particular interest in the autoimmunity of systemic lupus erythematosus (SLE). This review will focus on our studies on the forms of self-antigens that may be involved in the original "antigenic sin" of SLE and in the role of B lymphocytes as autoantigen presenting cells. We will also discuss whether costimulation is a formal requirement for the induction and maintenance of autoimmunity. Finally, we have provided a model for how all of these individual elements may contribute to the autoimmune processes leading to pathology.

Structural integrity of histone H2B in vivo requires the activity of protein L-isoaspartate O-methyltransferase, a putative protein repair enzyme.

Protein L-isoaspartate O-methyltransferase (PIMT) is postulated to repair beta-aspartyl linkages (isoaspartyl (isoAsp)) that accumulate at certain Asp-Xaa and Asn-Xaa sites in association with protein aging and deamidation. To identify major targets of PIMT action we cultured rat PC12 cells with adenosine dialdehyde (AdOx), a methyltransferase inhibitor that promotes accumulation of isoAsp in vivo. Subcellular fractionation of AdOx-treated cells revealed marked accumulation of isoAsp in a 14-kDa nuclear protein. Gel electrophoresis and chromatography of nuclei (3)H-methylated in vitro by PIMT revealed this protein to be histone H2B. The isoAsp content of H2B in AdOx-treated cells was approximately 18 times that in control cells, although no isoAsp was seen in other core histones, regardless of treatment. To confirm the relevance and specificity of this effect, we measured isoAsp levels in histones from brains of PIMT knockout mice. IsoAsp was found at near stoichiometric levels in H2B extracted from knockout brains and was at least 80 times greater than that in H2B from normal mice. Little or no isoAsp was detected in H2A, H3, or H4 from mice of either genotype. Accumulation of isoAsp in histone H2B may disrupt normal gene regulation and contribute to the reduced life span that characterizes PIMT knockouts. In addition to disrupting protein function, isoAsp has been shown to trigger immunity against self-proteins. The propensity of H2B to generate isoAsp in vivo may help explain why this histone in particular is found as a major antigen in autoimmune diseases such as lupus erythematosus.

Post-translational protein modifications in antigen recognition and autoimmunity.

It is estimated that 50-90% of the proteins in the human body are post-translationally modified. In the proper context, these modifications are necessary for the biological functions of a vast array of proteins and the effector functions of the cells in which they reside. However, it is now clear that some post-translational modifications can create new self antigens (Ags) or even mask Ags normally recognized by the immune system. In either case, they profoundly affect the recognition of Ag by bone marrow-derived cells, as well as their effector functions. How do post-translational protein modifications affect the processing of foreign and self Ags and what is their role in the origin of autoimmune responses?

Malignant fibrous histiocytoma of the gallbladder: case report and review of the literature.

Malignant fibrous histiocytoma is a soft tissue sarcoma of mesenchymal origin. It can rarely present as a primary gallbladder tumor with only five cases having been reported to date in the English literature. Here we report the sixth documented case of malignant fibrous histiocytoma of the gallbladder, and we review all other cases reported. The outcome of the visceral sarcomas is poor when compared with tumors arising from the soft tissues. The treatment of primary malignant fibrous histiocytomas of the gallbladder is surgery. However, tumor recurrence is the norm even if wide clean margins are obtained. In contrast to tumors arising from the extremities the role of adjuvant radiotherapy and chemotherapy is less clear in the case of retroperitoneal and visceral sarcomas. Our patient is still alive and free of disease 46 weeks after surgery. The fact that this is the longest survival reported to date underscores the dismal prognosis of this disease.

The impact of liver dysfunction on outcome in patients with multiple injuries.

Multiple organ dysfunction syndrome (MODS) is the leading cause of late deaths after traumatic injury. The relative importance of dysfunction of individual organ systems in determining outcome from MODS has not been clearly defined. Some studies have suggested that hepatic dysfunction associated with MODS increases mortality, whereas others have suggested that it contributes little to outcome in trauma patients. To clarify the role of the hepatic dysfunction after traumatic injury we retrospectively reviewed all trauma patients with an Injury Severity Score > or = 14 admitted from January 1, 1994 through June 30, 1997 for the presence of hepatic dysfunction defined as a serum bilirubin > or = 2.0 mg/dL. Of the 1962 patients who met the entry criteria 154 developed hepatic dysfunction during their hospital stay. Patients with hepatic dysfunction were older (46 +/- 2 versus 41 +/- 1 years), were more severely injured (Injury Severity Score 31.5 +/- 0.9 versus 23.3 + 0.2), and had a lower prehospital blood pressure (102 +/- 3 versus 117 +/- 1 mm Hg) compared with patients who did not develop hepatic dysfunction. Patients with hepatic dysfunction were more likely to present with shock as reflected in a lower initial emergency room blood pressure (109 +/- 3 versus 128 +/- 1 mm Hg) and base deficit (-6.9 +/- 0.6 versus -3.5 +/- 0.1 mEq/L). Patients who developed hyperbilirubinemia had longer lengths of stay in the intensive care unit (15.8 +/- 1.2 versus 3.4 +/- 0.2 days) and the hospital (27.4 +/- 1.7 versus 11.1 +/- 0.2 days) and a higher in-hospital mortality (16.2% versus 2.5%). These data demonstrate that the development of hepatic dysfunction reflects the severity of injury and is associated with a significantly worse outcome after traumatic injury.

Applying split-thickness skin grafts: a step-by-step clinical guide and nursing implications.

Wounds in the lower extremities represent a complex medical dilemma and a significant financial burden on the healthcare system. Often, skin grafts and flaps must be incorporated into the treatment of complex defects. Wound management has developed from a multidisciplinary to a collaborative forum, blurring treatment lines among the specialties. Various clinicians and specialists are playing an increasingly larger role in the healing algorithm of wounds in the lower extremities, including the application of skin grafts. This allows the plastic surgeon to deal with the more complex free flaps and microscopic surgical procedures. A patient's status following skin grafting can be an issue in many nursing care environments. This paper provides a pictorial review of a reliable split-thickness skin graft technique that fosters imbibition and inosculation. The points relevant to nursing care include nursing implications (for the graft and donor site), complications, and what to expect in patients who have undergone the procedure.

Recurrent neural networks for predicting outcomes after liver transplantation: representing temporal sequence of clinical observations.

OBJECTIVES: This paper investigates a version of recurrent neural network with the backpropagation through time (BPTT) algorithm for predicting liver transplant graft failure based on a time series sequence of clinical observations. The objective is to improve upon the current approaches to liver transplant outcome prediction by developing a more complete model that takes into account not only the preoperative risk assessment, but also the early postoperative history. METHODS: A 6-fold cross-validation procedure was used to measure the performance of the networks. The data set was divided into a learning set and a test set by maintaining the same proportion of positive and negative cases in the original set. The effects of network complexity on overfitting were investigated by constructing two types of networks with different numbers of hidden units. For each type of network, 10 individual networks were trained on the learning set and used to form a committee. The performance of the networks was measured exhaustively with respect to both the entire training and test sets. RESULTS: The networks were capable of learning the time series problem and achieved good performances of 90% correct classification on the learning set and 78% on the test set. The prediction accuracy increases as more information becomes progressively available after the operation with the daily improvement of 10% on the learning set and 5% on the test set. CONCLUSIONS: Recurrent neural networks trained with BPTT algorithm are capable of learning to represent temporal behavior of the time series prediction task. This model is an improvement upon the current model that does not take into account postoperative temporal information.

Requirement for CD4(+) T lymphocytes in host resistance against Cryptococcus neoformans in the central nervous system of immunized mice.

The importance of cell-mediated immunity (CMI) and CD4(+) T lymphocytes in host resistance against Cryptococcus neoformans is well documented and is exemplified by the high susceptibility to progressive infection with this pathogen of AIDS patients with reduced CD4(+) T-cell numbers. Although much has been learned about the role of CMI in the clearance of C. neoformans from the lungs and other internal organs, less is known about the protective mechanisms in the brain, the organ most frequently involved with a fatal outcome of cryptococcosis. We hypothesized that host resistance mechanisms against C. neoformans in the central nervous system (CNS) were similar to those outside the CNS (i.e., gamma interferon [IFN-gamma], CD4(+) T cells, and others). To test this hypothesis, we used a murine model of cryptococcal meningitis whereby cryptococci are introduced directly into the CNS. In experiments where mice were immunized to mount an anticryptococcal CMI response, our results indicate that immunization induced protective mechanisms that could be detected in the CNS by inhibition of the growth of viable yeast cells. Flow cytometric analyses of leukocytes in brain and spinal cord homogenates revealed that T lymphocytes, macrophages, and neutrophils accumulated in C. neoformans-infected brains of immune mice. In vivo depletion of CD4(+) T cells, but not CD8(+) T cells, resulted in significantly reduced leukocyte accumulation in the brains of immune mice. Furthermore, depletion of CD4(+) T cells or neutralization of IFN-gamma exacerbated CNS infection in immune mice, suggesting a critical role for CMI mechanisms in acquired protection in the CNS.

UCSF partnership to enrich science teaching for sixth graders in San Francisco's schools.

Increasing the diversity of students entering the health professions is a challenging goal for medical schools. One approach to this goal is to share the enthusiasm and energy of medical students with younger students, who may pursue medical education in the future. The MedTeach program, established in 1989 and coordinated by the Science & Health Education Partnership of the University of California, San Francisco (UCSF), does so by partnering volunteer medical students from UCSF with sixth-grade classes studying the human body. In 1997-98, around 350 sixth-graders in the San Francisco Schools benefitted from the program. Each team of medical student's visits its class ten to 12 times a year to present engaging, hands-on lessons on body systems and health. The medical students are also role models for the middle-school students. In addition, the diverse student population of San Francisco public schools provides a rich environment for the medical students to improve their communication and teaching skills.

Role of the C-C chemokine, TCA3, in the protective anticryptococcal cell-mediated immune response.

Activated T lymphocytes play a crucial role in orchestrating cellular infiltration during a cell-mediated immune (CMI) reaction. TCA3, a C-C chemokine, is produced by Ag-activated T cells and is chemotactic for neutrophils and macrophages, two cell types in a murine CMI reaction. Using a gelatin sponge model for delayed-type hypersensitivity (DTH), we show that TCA3 is a component of the expression phase of an anticryptococcal CMI response in mice. TCA3 mRNA levels are augmented in anticryptococcal DTH reactions at the same time peak influxes of neutrophils and lymphocytes are observed. Neutralization of TCA3 in immunized mice results in reduced numbers of neutrophils and lymphocytes at DTH reaction sites. However, when rTCA3 is injected into sponges in naive mice, only neutrophils are attracted into the sponges, indicating TCA3 is chemotactic for neutrophils, but not lymphocytes. We show that TCA3 is indirectly attracting lymphocytes into DTH-reactive sponges by affecting at least one other chemokine that is chemotactic for lymphocytes. Of the two lymphocyte-attracting chemokines assessed, monocyte-chemotactic protein-1 and macrophage-inflammatory protein-1alpha (MIP-1alpha), only MIP-1alpha was reduced when TCA3 was neutralized, indicating that TCA3 affects the levels of MIP-1alpha, which attracts lymphocytes into the sponges. TCA3 also plays a role in protection against Cryptococcus neoformans in the lungs and brains of infected mice, as evidenced by the fact that neutralization of TCA3 results in increased C. neoformans CFU in those two organs.