Outcomes of direct and indirect medical intensive care unit admissions from the emergency department of an acute care hospital: a retrospective cohort study.
This study aimed to determine if the risk of adverse outcomes (in-hospital and 60-day mortality, intensive care unit (ICU) and total hospital length of stay (LOS)) was greater for medical ICU (MICU) or high dependency unit (HDU) patients indirectly admitted from the emergency department (ED) than for directly admitted patients. This study was conducted at a large public acute care hospital in Singapore. In this retrospective cohort study, hospital records of patients who were admitted directly from the ED, or initially admitted to the general wards from the ED and subsequently transferred to the MICU/HDU within 24 h, were reviewed. Patients were included if they were: (A) discharged from the MICU/HDU in 2009 and were admitted from the ED and (B) transferred to the MICU/HDU within 24 h of presentation at the ED. Data from 706 patients were analysed; 58.4% were men with a median age of 61 years. The following outcomes were compared: in-hospital mortality, 60-day mortality, LOS at the MICU/HDU, as well as total hospital LOS. Of the 706 patients, 491 (69.5%) were directly admitted to the MICU/HDU. After adjusting for demographics, comorbidities, interventions at the ED and clinical parameters at the ED (heart rate, respiration, oxygen saturation, mean arterial pressure), as well as the Apache II score on arrival at the MICU/HDU, indirectly admitted patients had a higher risk of in-hospital mortality (OR=3.07, 95% CI 1.39 to 6.80), death within 60 days (OR=3.09, 95% CI 1.40 to 6.83) and risk of staying >1 day at the MICU/HDU (OR=2.54, 95% CI 1.48 to 4.36). There was no significant difference in total in-hospital LOS. Indirectly admitted MICU/HDU patients had generally poorer outcomes. As the magnitude of effect may vary across settings, context-specific studies may be useful for improving outcomes.


Carbohydrate recognition systems in autoimmunity.
The immune system is a complex functional network of diverse cells and soluble molecules orchestrating innate and adaptive immunity. Biological information, to run these intricate interactions, is not only stored in protein sequences but also in the structure of the glycan part of the glycoconjugates. The spatially accessible carbohydrate structures that contribute to the cell's glycome are decoded by versatile recognition systems in order to maintain the immune homeostasis of an organism. Microbial carbohydrate structures are recognized by pathogen associated molecular pattern (PAMP) receptors of innate immunity including C-type lectins such as MBL, the tandem-repeat-type macrophage mannose receptor, DC-SIGN or dectin-1 of dendritic cells, certain TLRS or the TCR of NKT cells. Natural autoantibodies, a long known effector branch of this network-based operation, are effective to home in on non-self and self-glycosylation also. The recirculating pool of mammalian immune cells is recruited to inflammatory sites by a reaction pathway involving the self-carbohydrate-binding selectins as initial recognition step. Galectins, further key sensors reading the high-density sugar code, exert regulatory functions on activated T cells, among other activities. Autoimmune diseases are being associated with defined changes of glycosylation. This correlation deserves to be thoroughly studied on the levels of structural mimicry and dysregulation as well as effector molecules to devise innovative anti-inflammatory strategies. This review briefly summarizes data on sensor systems for carbohydrate epitopes and implications for autoimmunity.


Refractory period of single motor nerve fibres in man.
Electromyographic single motor unit recordings were used to study the axonal refractory period of 28 accessory nerve innervated motor units in young normal subjects and 10 reinnervated motor units in elderly subjects. The refractory period was measured after a conditioning antidromic propagated nerve impulse and after a conditioning electrical nerve stimulus delivered through the same electrode as the test stimulus. The refractory period after a propagated impulse was 1.83 +/- 0.26 ms when test stimulus strength was 10% above the axonal threshold at rest and 0.88 +/- 0.26 ms when test stimulus strength was 100% above threshold. Corresponding data after an electrical stimulus were 2.38 +/- 0.32 ms and 1.28 +/- 0.22 ms. The difference between the methods was partially due to the effect of stimulus spread when the refractory period was measured after an antidromic propagated nerve impulse. Different properties of the nerve fibre membrane and the surrounding tissues after a propagated nerve impulse and after an electrical stimulus might also contribute. For further studies of motor unit pathology both methods seem equally reliable when proper normal data are available.


Smooth muscle antibody in patients with warts.
Sera from fifty-four patients with warts were tested for the presence of commonly found autoantibodies. Smooth muscle antibody (SMA) was detected at a significantly higher level than in a control group of healthy blood donors matched for age and sex, and was in the IgM class. The SMA-positive sera gave a microfilamentous staining pattern also in the IgM class, on fixed HEp2 tissue culture cells. Absorption of positive sera with smooth muscle removed both SMA staining and the anti-cellular staining.


Three legacies of humanitarianism in China.
The rise of China has altered the context of the international humanitarian community of donors and aid agencies. China is becoming one of the key actors in this grouping, undertaking infrastructure projects in areas in which paramount humanitarian challenges exist. The literature discusses how the Chinese approach differs from that of Western donors, but it does not pay much attention to why China concentrates on its state-centric and infrastructure-based approach. This paper seeks to shed some light on this subject by examining the historical evolution of the concept of humanitarianism in China. This evolution has produced three legacies: (i) the ideal of a well-ordered state; (ii) anti-Western sentiment; and (iii) the notion of comprehensive development based on a human-oriented approach. China's policies and discourses on assistance in humanitarian crises today rest on these three legacies. Traditional donors would be well advised to consider carefully the implications of the Chinese understanding of humanitarianism when engaging with the country.


Health care directives for the elderly.
The treatment of incompetent older people presents physicians and family members with complex medical, ethical, moral, and legal problems. This article explores the use of advance health care directives in the decision-making process, the qualities of the "ideal" directive, practical and legal issues relating to directives, and the role of the family physician in their implementation.


Effects of Diamond Steps Exercises on Balance Improvement in Healthy Young and Older Adults: A Protocol Proposal.
Diamond step (DS) exercises are associated with multiple components of postural control and, thus, have the potential to efficiently improve balance ability. This study aimed to verify whether DS exercises contribute to improving balance ability. This study included 35 healthy young people and 29 older adults. DS exercises were performed continuously for 3 min, four times a week, for 1 month. Balance ability was assessed at baseline and after 1 and 2 months; eight items in total were examined: 30 s chair stand test, functional reach test, standing on one leg with eyes closed, time required for five rounds of DS, left-right DS, Y balance test, open-close stepping test, and finger-to-floor distance. The difficulty, achievement, and lightness/enjoyment of DS exercises were measured after the first practice and 1 month after beginning the exercises as subjective evaluations. Older adults showed improvement in seven of the eight items, with the exception being the one-legged stance with closed eyes. The subjective evaluation showed a decrease in the level of difficulty of DS exercises for older adults. DS exercises may improve balance by effectively utilizing various postural control strategies. These exercises can be effective and easy to implement, given their moderate difficulty level and self-efficacy.


Ultrafast switching of an electrochromic device based on layered double hydroxide/Prussian blue multilayered films.
Electrochromic materials are the most important and essential components in an electrochromic device. Herein, we fabricated high-performance electrochromic films based on exfoliated layered double hydroxide (LDH) nanosheets and Prussian blue (PB) nanoparticles via the layer-by-layer assembly technique. X-ray diffraction and UV-vis absorption spectroscopy indicate a periodic layered structure with uniform and regular growth of (LDH/PB)n ultrathin films (UTFs). The resulting (LDH/PB)n UTF electrodes exhibit electrochromic behavior arising from the reversible K(+) ion migration into/out of the PB lattice, which induces a change in the optical properties of the UTFs. Furthermore, an electrochromic device (ECD) based on the (LDH/PB)n-ITO/0.1 M KCl electrolyte/ITO sandwich structure displays superior response properties (0.91/1.21 s for coloration/bleaching), a comparable coloration efficiency (68 cm(2) C(-1)) and satisfactory optical contrast (45% at 700 nm), in comparison with other inorganic material-based ECDs reported previously. Therefore, this work presents a facile and cost-effective strategy to immobilize electrochemically active nanoparticles in a 2D inorganic matrix for potential application in displays, smart windows and optoelectronic devices.


Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light.
Photodynamic therapy (PDT) is a promising strategy to promote antitumor immunity by inducing immunogenic cell death (ICD) in tumor cells. However, practical PDT uses an intense visible light owing to the shallow penetration depth of the light, resulting in immunosuppression at the tumor tissues. Herein, we propose an implantable micro-scale light-emitting diode device (micro-LED) guided PDT that enables the on-demand light activation of photosensitizers deep in the body to potentiate antitumor immunity with mild visible light. The micro-LED is prepared by stacking one to four micro-scale LEDs (100 μm) on a needle-shape photonic device, which can be directly implanted into the core part of the tumor tissue. The photonic device with four LEDs efficiently elicits sufficient light output powers without thermal degradation and promotes reactive oxygen species (ROS) from a photosensitizer (verteporfin; VPF). After the intravenous injection of VPF in colon tumor-bearing mice, the tumor tissues are irradiated with optimal light intensity using an implanted micro-LED. While tumor tissues under intense visible light causes immunosuppression by severe inflammatory responses and regulatory T cell activation, mild visible light elicits potent ICD in tumor cells, which promotes dendritic cell (DC) maturation and T cell activation. The enhanced therapeutic efficacy and antitumor immunity by micro-LED guided PDT with mild visible light are assessed in colon tumor models. Finally, micro-LED guided PDT in combination with immune checkpoint blockade leads to 100% complete tumor regression and also establishes systemic immunological memory to prevent the recurrence of tumors. Collectively, this study demonstrates that micro-LED guided PDT with mild visible light is a promising strategy for cancer immunotherapy.


Very low density lipoprotein receptor, a negative regulator of the wnt signaling pathway and choroidal neovascularization.
Choroidal neovascularization (CNV) in age-related macular degeneration is a leading cause of blindness. Very low density lipoprotein receptor gene knock-out (Vldlr(-/-)) mice have been shown to develop subretinal neovascularization (NV) with an unknown mechanism. The present study showed that in Vldlr(-/-) mice, NV initiated in the choroid and progressed to penetrate the retinal pigment epithelium layer, proliferating in the subretinal space. This phenotype recapitulated what is seen in wet age-related macular degeneration, suggesting that this is a CNV model. The CNV correlated with overexpression of vascular endothelial growth factor in Vldlr(-/-) eyecups and was blocked by a neutralizing antibody against vascular endothelial growth factor receptor-2. The wnt co-receptor LRP5/6 expression was significantly up-regulated in Vldlr(-/-) eyecups compared with that in wild-type mice. Significantly, Vldlr(-/-) mice showed impaired phosphorylation of downstream effectors of the wnt signaling pathway, glycogen synthase kinase-3beta (GSK-3beta), and beta-catenin, concomitant with increased levels of free GSK-3beta and beta-catenin, suggesting an increased activity of the wnt pathway. Down-regulation of VLDLR by small interference RNA resulted in up-regulation of LRP5/6 expression and activation of beta-catenin in cultured endothelial cells. Furthermore, Dickkopf-1, a specific inhibitor of the wnt pathway, effectively decreased vascular endothelial growth factor and beta-catenin levels in the retinal pigment epithelium of Vldlr(-/-) mice and in cells transfected with the VLDLR small interference RNA. These results suggest that VLDLR functions as a negative regulator of CNV, and this function is mediated through the wnt pathway.


[Effect of irradiation from a personal computer video terminal on estrus function, melatonin level, and free radical processes in laboratory rodents].
Chronic irradiation by the video terminal of a personal computer leads to the acceleration of sexual maturation and premature termination of the reproductive function, decreases the nocturnal level of melatonin, the content of diene conjugates and schiff bases in blood serum of female rats and does not affect the intensity of blood serum chemiluminescence in male rats. The data obtained indicate that the irradiation by the personal computer video terminal has a marked biological effect and may affect adversely the health of users.


Outcomes of BDSF technique for osteosynthesis of femoral neck fractures.
Femoral neck fractures present a significant challenge for orthopedic surgeons, especially in young patients who want to preserve their natural femoral head. Conventional methods for fixing these fractures often lead to poor outcomes and high complication rates. The Biplane Double-supported Screw Fixation (BDSF) technique is a novel approach that involves placing screws in two planes simultaneously, creating a two-point support for the screws in the neck and head of the femur. This study aimed to evaluate the effectiveness of the BDSF technique in treating femoral neck fractures in patients aged 20-60 years. A total of 28 patients with fresh femoral neck fractures (less than three weeks old) were treated with closed reduction and internal fixation using the BDSF method. The patients' functional outcomes were evaluated using the Harris hip score, and the radiographic outcomes of union, femoral neck shortening, screw back-out, and femoral head avascular necrosis (AVN) were also evaluated. The results showed that the BDSF technique is a safe and effective method for treating femoral neck fractures in young adults. Out of the 25 patients who were followed up for a mean time of 18 months (range 6-24 months), 20 (80%) achieved fracture union in a mean time of 5.2 months. Non-union occurred in five patients (20%), and AVN of the femoral head was observed in three patients (12%). Two patients experienced varus collapse, but their fractures united successfully. The BDSF technique offers several advantages over conventional methods, including increased stability and improved fixation strength. It can be considered as an alternative to conventional methods for managing femoral neck fractures in young adults, with a low incidence of non-union and avascular necrosis and no cases of fixation failure or varus collapse.


A homolog of interleukin-10 is encoded by the poxvirus orf virus.
A gene encoding a polypeptide with homology to interleukin-10 (IL-10) has been discovered in the genome of orf virus (OV) strain NZ2, a parapoxvirus that infects sheep, goats, and humans. The predicted polypeptide sequence shows high levels of amino acid identity to IL-10 of sheep (80%), cattle (75%), humans (67%), and mice (64%), as well as IL-10-like proteins of Epstein-Barr virus (63%) and equine herpesvirus (67%). The C-terminal region, comprising two-thirds of the OV protein, is identical to ovine IL-10, which suggests that this gene has been captured from its host sheep during the evolution of OV. The IL-10-like gene is transcribed early. Conditioned medium from COS cells transfected with a eukaryotic expression vector containing the OV IL-10-like gene showed the same biological activity as ovine IL-10 in a murine thymocyte proliferation assay. OV IL-10 is likely to be important in immune evasion by OV, since IL-10 is a multifunctional cytokine that has inhibitory effects on nonspecific immunity and Th1 effector function.


Formation of oligopeptides in high yield under simple programmable conditions.
Many high-yielding reactions for forming peptide bonds have been developed but these are complex, requiring activated amino-acid precursors and heterogeneous supports. Herein we demonstrate the programmable one-pot dehydration-hydration condensation of amino acids forming oligopeptide chains in around 50% yield. A digital recursive reactor system was developed to investigate this process, performing these reactions with control over parameters such as temperature, number of cycles, cycle duration, initial monomer concentration and initial pH. Glycine oligopeptides up to 20 amino acids long were formed with very high monomer-to-oligomer conversion, and the majority of these products comprised three amino acid residues or more. Having established the formation of glycine homo-oligopeptides, we then demonstrated the co-condensation of glycine with eight other amino acids (Ala, Asp, Glu, His, Lys, Pro, Thr and Val), incorporating a range of side-chain functionality.


Some morphological aspects of Cylicocyclus brevicapsulatus (Nematoda: Cyathostominae) parasite of horse.
This paper describes some morphological aspects of Cylicocyclus brevicapsulatus (Ihle, 1920) (Nematoda: Cyathostominae) from Equus caballus in Brazil. The worms were studied using an optical microscope (measurements and illustrations) and a scanning electron microscope for a more detailed examination of the external morphology. The buccal capsule is very short, with a very thin wall, and the dorsal gutter is absent. Other morphological aspects are described including measurement of the spicules and gubernaculum.


Angiography in giant-cell tumours of bone.
The angiographic appearance of 9 cases of genuine giant-cell tumour of bone, 6 cases of aneurysmal bone cyst and one case of non-ossifying fibroma is described. Differential diagnosis would appear to be possible to a certain extent. The non-ossifying fibroma was poorly vascularized. The genuine giant-cell tumours were hypervascularized as well as some of the aneurysmal bone cysts making a differential diagnosis in these cases impossible. On the other hand, a poorly vascularized tumour devoid of soft tissue component and arteriovenous fistulas is probably an aneurysmal bone cyst. A hypervascular soft tissue component is of great prognostic value in cases of geniune giant-cell tumour.


The New Concept of Physiological "Riolan's Arch" and the Reconstruction Mechanism of Pathological Riolan's Arch After High Ligation of the Inferior Mesenteric Artery by CT Angiography-Based Small Vessel Imaging.
Due to the complexity of anatomical relationship between superior mesenteric artery (SMA) and left colic artery (LCA), there is no unified anatomical concept of "Riolan's arch." There is no consensus as to tie off the inferior mesenteric artery (IMA) at its origin or just below the origin of the left colic artery during radical surgery of sigmoid colon and rectal cancers. The aim of the study is to investigate the anatomy of shortcut anastomotic branches (adjacent branches) of SMA at splenic flexure and to explore how the shortcut pathway (Riolan's arch) was formed, as the compensation of anastomotic branches between MCA and LCA under pathological conditions and the reconstruction and the mechanism of pathological Riolan's arch after high ligation of the inferior mesenteric artery. Between January 2018 and May 2020, patients with colorectal cancer who underwent CTA before surgery were enrolled in the study. The anatomy of shortcut anastomotic branch of SMA and LCA was investigated by volume rendering technique (VR) and maximum-intensity projection (MIP). GE's small vessel extraction technology (selected VR) was used to directly display these shortcut anastomotic branches on a map and to establish their three-dimensional anatomical classification. Then, we used the axonometric drawing to make the model more exact. Next, combining with some cases of pathological Riolan's arch and basing on hydrodynamic principle, we speculate the mechanism of collateral circulation. Finally, based on the retrospective study of high ligation cases and combined principles of fluid mechanics, we show how these shortcut anastomotic branches evolved into Riolan's arch. We report the classification of the ascending branch of LCA (which approaches the splenic flexure) and the left branch of MCA, display these shortcut anastomotic branches on a map, and establish their three-dimensional anatomical classification. We found that Riolan's arch is a shortcut pathway for the compensation of anastomotic branches, between MCA and LCA under pathological conditions, and that the formation mechanism of shortcut path accords with the principle of hydrodynamics. Our results show the mechanism of pathological Riolan's arch formation and provide new anatomic thinking for the battle between high and low ligation of IMA in colorectal cancer surgery.


It's no laughing matter: An exploratory study of the use of ironic versus sarcastic humor in health-related advertising messages.
We examined the persuasive effects of ironic and sarcastic versus no humor appeals in health messages and the potential differential effects of ironic versus sarcastic humor. Findings of a controlled experiment (N = 303) suggested that sarcastic messages, as compared to no humor messages, resulted in less negative affect, more counterarguing, and decreased perceived argument strength. Ironic messages led to more counterarguing than no humor messages. Significant differences in counterarguing, perceived argument strength, and attitudes toward the risky behavior were detected between the two humor types. Counterarguing mediated the indirect effect of message type on attitudes toward the risky behavior.


Helping clients understand pets' needs.
During National Pet Month in April the Veterinary Animal Welfare Coalition launched its second public-facing campaign to improve pet owners' understanding of their animals' welfare, writes Felicity Quick, BVA media officer.


Tourette syndrome.
This survey of recent literature addressing Tourette syndrome reflects clinical and laboratory findings of investigations of behavioral, neuropsychological, imaging, genetic, neurobiological and treatment considerations. Tourette syndrome is a prototypic neuropsychiatric disorder manifesting a full range of objectively describable phenomena from different scientific vantage points and serves as a model for study and integrative understanding of brain and behavior.


Microsatellite marker analysis of peach-potato aphids (Myzus persicae, Homoptera: Aphididae) from Scottish suction traps.
The peach-potato aphid Myzus persicae (Sulzer) is an important vector of plant viruses. A network of suction traps collects aerial samples of this aphid in order to monitor and help predict its spatial distribution and likely impact on virus transmission in crops. A suction trap catch is thought to be a good representation of the total aphid pool. Sensitive molecular markers have been developed that determine the genetic composition of the M. persicae population. In Scotland, UK, these were applied to field collections revealing a limited number of clones. Molecular markers are less successful when applied to specimens that have been preserved in an ethanol-based trap fluid designed to preserve morphology. An assessment of different DNA extraction and PCR techniques is presented and the most efficient are used to analyse M. persicae specimens caught in the Dundee suction trap in 2001, a year when exceptionally high numbers were caught. The results reveal that the majority of the M. persicae caught belonged to two highly insecticide resistant clones. In addition, it was possible to compare the relative frequencies of genotypes caught in the trap with those collected at insecticide treated and untreated field sites in the vicinity. These results indicate that, in addition to suction trap data, the ability to sample field sites provides valuable early warning data which have implications for pest control and virus management strategies.


Carcinomas of the thyroid gland invading larynx and trachea.
Twenty-nine patients with a thyroid carcinoma invading the larynx and trachea were treated over a 25-yr period. Eight patients had invasion of the walls of the trachea or larynx and 21 had invasion into the lumen. Of the 15 patients who underwent limited surgery, i.e. total thyroidectomy, tracheostomy and neck dissection, 8 had intraluminal invasion and 7 suffered from bleeding into the trachea or airway obstruction. In contrast, none of the 13 who underwent extensive surgery, i.e. thyroidectomy, laryngectomy, partial resection of the trachea and one resection of the pharynx, (12 of whom had intraluminal invasion) showed either bleeding into the trachea or airway obstruction. Although the prognosis was no better in the group undergoing extensive operation there is the feeling that in cases with intraluminal invasion extensive surgery is indicated to prevent the severe airway difficulties which often develop in such patients.


Effects of Muscone on Random Skin Flap Survival in Rats.
The necrosis of a distal area of random skin flap remains challenging. Muscone can increase blood flow and reduce ischemia-reperfusion injury, this study was undertaken to investigate the effects of muscone on random skin flap survival. McFarlane flaps were established in 72 rats and divided into two groups. The test group received intraperitoneal injections of muscone (0.64 mg/kg/d); control rats received intraperitoneal injections of saline. The percentage flap survival area and tissue water content were measured after 7 days. Flap angiogenesis was assessed via lead oxide-gelatin angiography, hematoxylin and eosin staining, and immunohistochemistry and western blotting for vascular endothelial growth factor (VEGF). The extent of apoptosis was evaluated by immunohistochemistry for cleaved caspase 3 and western blotting for cleaved caspase 3, Bax, and Bcl2. Oxidative stress status was assessed by measuring the activity of tissue superoxide dismutase (SOD) and malondialdehyde (MDA) content. Compared with controls, muscone-treated flaps displayed greater survival area lower tissue water content. Muscone increased skin flap angiogenesis and activated VEGF expression. SOD activity and MDA content indicated lower oxidative stress in muscone-treated flaps than controls, and western blotting and immunohistochemistry revealed significantly lower apoptosis. Muscone have a positive effect to promote the survival of random skin flap.


Guidewire-assisted infundibular tilt: a technique for access into another calix during percutaneous nephrolithotomy.
Sometimes, during percutaneous nephrolithotomy, a stone fragment migrates into a parallel calix, necessitating a separate puncture. We describe a simple technique for removing such fragments. This technique is especially useful for patients who have moderate to severe hydronephrosis where the intercaliceal parenchyma is thin.


The M2 haplotype in the ANXA5 gene is an independent risk factor for idiopathic small-for-gestational age newborns.
Hereditary thrombophilias can impair vascular placental functions and predispose to the birth of small-for-gestational age (SGA) babies. The placental anticoagulant protein annexin A5 (ANXA5) may contribute to this process. A functional haplotype (M2) within the ANXA5 gene is associated with fetal loss and venous thrombosis. This study investigated the prevalence of the M2 haplotype in a group of women with idiopathic SGA newborn babies. Seventy-eight women with at least one previous unexplained SGA birth and 195 controls all from Southern Italy were investigated. Hereditary thrombophilia was found in 13 (16.5%) cases and 21 (11%) controls (P < 0.05.). The M2 haplotype was found in 29% of cases (n = 23) and 15% of controls [n = 30; P = 0.001; OR = 2.3, 95% CI (1.17-4.48)]. Within the case group, 82.5% of the M2 haplotype carriers gave birth to babies with a birthweight below the 3rd percentile [P = 0.01; OR = 2.4, 95% CI (1.26-4.73)]. A logistic regression, corrected for age, parity and gravity showed that the M2 haplotype was independently associated with the delivery of an SGA new born [P = 0.029; OR = 2.6, 95% CI (1.1-6.0)]. In conclusion, the M2 haplotype of the ANXA5 gene confers a risk of delivering SGA babies.


Thrombosis and a hypercoagulable state in HIV-infected patients.
Human immunodeficiency virus infection is an illness with protean manifestations including hematological abnormalities. Thromboembolic complications in HIV-infected patients have been described. Recent literature describes an incidence ranging from 0.26% to 7.6%; higher incidence is seen in patients with active opportunistic infections or malignancy, and in patients with the acquired immunodeficiency syndrome. A variety of potential mechanisms have been proposed to account for the observed hypercoagulability in HIV-infected patients. These include the presence of antiphospholipid-anticardiolipin antibodies, decreased activities of natural anticoagulants (especially protein S), and increased platelet activation. Recent epidemiological studies emphasize the increased incidence of thromboembolic events including myocardial infarction in the HIV-infected population after the introduction of highly active antiretroviral therapy. The use of protease inhibitors in particular is implicated. A hypercoagulable state and especially thromboses are emerging as clinical issues in HIV-infected patients. Further studies are in order to more clearly delineate the pathophysiologic mechanism(s) of thromboses in HIV-infected patients.


[Culture media for the detection and the identification of Streptococcus agalactiae].
Streptococcus agalactiae, a Group B streptococcus, is the main cause of bacterial perinatal infection and is also an important opportunistic pathogen. Detection and identification of S. agalactiae are straight forward with special culture media, where Group B streptococci show a specific, typical pink or red pigment. To quickly and easily detect the pigment, culture media should contain: (i) starch; (ii) an inhibitor of the folate pathway; (iii) animal serum; (iv) a pepsic proteic hydrolysate; and (v) glucose, together with a high-capacity buffer. When selective antibiotics are added to culture media designed in this way, it is possible to detect S. agalactiae directly from clinical samples by observation of its pigment after less than 12 hours of aerobic incubation.


Computational reconstruction of transcriptional regulatory modules of the yeast cell cycle.
A transcriptional regulatory module (TRM) is a set of genes that is regulated by a common set of transcription factors (TFs). By organizing the genome into TRMs, a living cell can coordinate the activities of many genes and carry out complex functions. Therefore, identifying TRMs is helpful for understanding gene regulation. Integrating gene expression and ChIP-chip data, we develop a method, called MOdule Finding Algorithm (MOFA), for reconstructing TRMs of the yeast cell cycle. MOFA identified 87 TRMs, which together contain 336 distinct genes regulated by 40 TFs. Using various kinds of data, we validated the biological relevance of the identified TRMs. Our analysis shows that different combinations of a fairly small number of TFs are responsible for regulating a large number of genes involved in different cell cycle phases and that there may exist crosstalk between the cell cycle and other cellular processes. MOFA is capable of finding many novel TF-target gene relationships and can determine whether a TF is an activator or/and a repressor. Finally, MOFA refines some clusters proposed by previous studies and provides a better understanding of how the complex expression program of the cell cycle is regulated. MOFA was developed to reconstruct TRMs of the yeast cell cycle. Many of these TRMs are in agreement with previous studies. Further, MOFA inferred many interesting modules and novel TF combinations. We believe that computational analysis of multiple types of data will be a powerful approach to studying complex biological systems when more and more genomic resources such as genome-wide protein activity data and protein-protein interaction data become available.


Vitamin D receptor agonist VS-105 improves cardiac function in the presence of enalapril in 5/6 nephrectomized rats.
Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to manage hyperparathyroidism secondary to chronic kidney disease (CKD). Patients with CKD experience extremely high risks of cardiovascular morbidity and mortality. Clinical observations show that VDRA therapy may be associated with cardio-renal protective and survival benefits in patients with CKD. The 5/6 nephrectomized (NX) Sprague-Dawley rat with established uremia exhibits elevated serum parathyroid hormone (PTH), hypertension, and abnormal cardiac function. Treatment of 5/6 NX rats with VS-105, a novel VDRA (0.05 and 0.5 μg/kg po by gavage), once daily for 8 wk in the presence or absence of enalapril (30 mg/kg po via drinking water) effectively suppressed serum PTH without raising serum calcium. VS-105 alone reduced systolic blood pressure (from 174 ± 6 to 145 ± 9 mmHg, P < 0.05) as effectively as enalapril (from 174 ± 6 to 144 ± 7 mmHg, P < 0.05). VS-105 improved cardiac functional parameters such as E/A ratio, ejection fraction, and fractional shortening with or without enalapril. Enalapril or VS-105 alone significantly reduced left ventricular hypertrophy (LVH); VS-105 plus enalapril did not further reduce LVH. VS-105 significantly reduced both cardiac and renal fibrosis. The lack of hypercalcemic toxicity of VS-105 is due to its lack of effects on stimulating intestinal calcium transport and inducing the expression of intestinal calcium transporter genes such as Calb3 and TRPV6. These studies demonstrate that VS-105 is a novel VDRA that may provide cardiovascular benefits via VDR activation. Clinical studies are required to confirm the cardiovascular benefits of VS-105 in CKD.


Morphology, density and distribution of tyrosine hydroxylase immunoreactive cells in the retina in the gerbil Meriones shawi. Relationships with horizontal cells.
Dopamine neurons have been demonstrated with the use of tyrosine hydroxylase (TH)-immunohistochemistry in the retina of Meriones shawi, a wild species of pigmented sand rat, in order to compare their morphology, density, and distribution with those in albino laboratory rat. The morphology and density of TH-immunoreactive cells were quite comparable in the two species: the dopamine cell population was composed of amacrine cells, displaced amacrine cells, and interplexiform cells, these latter being more numerous in the albino rat. The distribution of dopamine cells was more homogeneous in the sand rat retina where a peak density in the area centralis was not observed. The relationships between TH-immunoreactive cells and horizontal cells, demonstrated by their immunoreactivity to calbindin, have been observed in view of the dopamine action driven by scleral processes of interplexiform cells. A close vicinity occurred between 40% of the TH-immunoreactive cell and horizontal cell somata within the inner nuclear layer.


Mild hypothermia decreases GSK3beta expression following global cerebral ischemia.
The serine/threonine kinase glycogen synthase kinase 3beta (GSK3beta) is abundant in the central nervous system and is neuron-specific. GSK3beta plays a pivotal role in the regulation of numerous cellular functions (including phosphorylation) and, thereby, regulation of many metabolic, signaling, and structural proteins as well as transcription factors that can influence cell survival. This article reports that GSK3beta expression following global cerebral ischemia (GCI) is altered by the neuroprotectant, mild hypothermia (33 degrees C). Male Sprague-Dawley rats were anesthetized and subjected to GCI; arterial blood pressure was reduced to 30 mmHg by blood withdrawal via the jugular vein, and both common carotid arteries were occluded with aneurysm clips for 8 minutes. Hypothermia (33 degrees C) was induced in half the rats 10 minutes prior to GCI and was maintained for 3 hours. Rats were killed 24 or 72 hours later to assess cell death and GSK3beta expression. At 72 hours post-GCI, levels of GSK3beta expression were significantly lower in hypothermic rats than in normothermic rats. This reduction in GSK3beta correlated with marked neuroprotection and reduced terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining in hippocampal CA1 neurons. No significant changes in phosphorylated GSK3beta expression were observed. These data suggest that GSK3beta plays a role in GCI pathology that can be altered by mild hypothermia.


HELZ2 Is an IFN Effector Mediating Suppression of Dengue Virus.
Flaviviral infections including dengue virus are an increasing clinical problem worldwide. Dengue infection triggers host production of the type 1 IFN, IFN alpha, one of the strongest and broadest acting antivirals known. However, dengue virus subverts host IFN signaling at early steps of IFN signal transduction. This subversion allows unbridled viral replication which subsequently triggers ongoing production of IFN which, again, is subverted. Identification of downstream IFN antiviral effectors will provide targets which could be activated to restore broad acting antiviral activity, stopping the signal to produce endogenous IFN at toxic levels. To this end, we performed a targeted functional genomic screen for IFN antiviral effector genes (IEGs), identifying 56 IEGs required for antiviral effects of IFN against fully infectious dengue virus. Dengue IEGs were enriched for genes encoding nuclear receptor interacting proteins, including HELZ2, MAP2K4, SLC27A2, HSP90AA1, and HSP90AB1. We focused on HELZ2 (Helicase With Zinc Finger 2), an IFN stimulated gene and IEG which encodes a promiscuous nuclear factor coactivator that exists in two isoforms. The two unique HELZ2 isoforms are both IFN responsive, contain ISRE elements, and gene products increase in the nucleus upon IFN stimulation. Chromatin immunoprecipitation-sequencing revealed that the HELZ2 complex interacts with triglyceride-regulator LMF1. Mass spectrometry revealed that HELZ2 knockdown cells are depleted of triglyceride subsets. We thus sought to determine whether HELZ2 interacts with a nuclear receptor known to regulate immune response and lipid metabolism, AHR, and identified HELZ2:AHR interactions via co-immunoprecipitation, found that AHR is a dengue IEG, and that an AHR ligand, FICZ, exhibits anti-dengue activity. Primary bone marrow derived macrophages from HELZ2 knockout mice, compared to wild type controls, exhibit enhanced dengue infectivity. Overall, these findings reveal that IFN antiviral response is mediated by HELZ2 transcriptional upregulation, enrichment of HELZ2 protein levels in the nucleus, and activation of a transcriptional program that appears to modulate intracellular lipid state. IEGs identified in this study may serve as both (1) potential targets for host directed antiviral design, downstream of the common flaviviral subversion point, as well as (2) possible biomarkers, whose variation, natural, or iatrogenic, could affect host response to viral infections.


Retinoic acid disturbs mouse middle ear development in a stage-dependent fashion.
The mammalian middle ear contains a chain of three ossicles, the malleus, incus, and stapes, that transmit into the inner ear the vibrations produced in the tympanic membrane by aerial sound. I show here that retinoic acid interferes with the formation of the middle ear in a stage-specific fashion. The malformations produced are derived from a retinoic acid-induced inhibition of the formation and/or migration of the cranial neural crest that generates the middle ear skeletal elements and not from a respecification of neural crest identity to more posterior fates. I have used these effects of retinoic acid to analyze the temporal sequence of events involved in the morphogenesis of the middle ear. I show that the middle ear bones develop from several primordia that originate in a typical temporal sequence from Day 8 plus 4.5 hr to Day 8 plus 7.5 hr of pregnancy. Moreover, interactions between adjacent bones are not required for their proper formation. My results also suggest a Hoxa-2-mediated patterning of the otic capsule in the region where the oval window is located.


The effect of heat exposure and bacterial endotoxin on plasma zinc concentration and the body temperature in the broiler.
The effect of heat exposure and bacterial endotoxins on plasma zinc levels and mean rectal temperature of 8 week old broilers and investigated. Broilers exposed for 2 hours to 35-35 degrees C. had higher (P less than 0.01) mean rectal temperatures (42.8 vs 41.7 degrees C.) than sham treated broilers maintained at 22-24 degrees C. Likewise, endotoxin (E. coli, 500 mug./kg) treated broilers also had mean rectal temperatures significantly higher (P less than 0.01, 42.4 vs 41.7 degrees C.) than sham treated broilers. Plasma zinc levels in the bacterial endotoxin treated broilers were lower (P less than 0.05) than in the sham treated (173 vs 220, and 219 mug/kg./100 ml. plasma, respectively). In contrast, the plasma zinc concentration was not significantly depressed in the broilers exposed to heat for 2 hours. In summary, either endotoxin or heat exposure resulted in increased body temperature, however only the response to endotoxin resulted in a significant depression of plasma zinc concentration.


Levodopa in Parkinson's Disease: A Review of Population Pharmacokinetics/Pharmacodynamics Analysis.
Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Although levodopa remains the single effective agent in the management of Parkinson's disease, the accurate determination of this optimal dosage is complicated by marked between-subject and between-occasion variability in this population. This review presents a synthesis of the population pharmacokinetic and pharmacodynamic models of levodopa described in Parkinson's disease. A literature search was conducted from the PubMed database, from their inception through April 2016, using the following terms: levodopa, pharmacokinetic(s), pharmacodynamic(s) population, model(ling) and nonlinear mixed effect. Articles were excluded if they were not pertinent. References of all selected articles were also evaluated. A total of 12 articles were finally retained. The following covariates were selected as interindividual variability factors: body weight, age, sex, creatinine clearance and levodopa dose. The clinical response versus effect site concentration relationship was described with different sigmoidal Emax models. Different pharmacodynamic effects were described: UPDRS, Tapping, Dyskinesia, CURSΣ and treatment response scale. This review allows us to realize interpretation of a patient's clinical picture and confirmed the appropriateness of the pharmacokinetic-pharmacodynamic modeling for levodopa. External evaluation of previous published models should be also continued to evaluate these previous studies. New pharmacokinetic and/or pharmacodynamic population modelling studies could be consider to improve future models and decrease variability, to better understand the evolution of patients with Parkinson's disease treated by levodopa. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.


Structural Manipulation of Ruthenium(II) Polypyridine Nitrone Complexes to Generate Phosphorogenic Bioorthogonal Reagents for Selective Cellular Labeling.
We report a new class of ruthenium(II) polypyridine complexes functionalized with a nitrone group as phosphorogenic bioorthogonal probes. These complexes were very weakly emissive owing to rapid C=N isomerization of the nitrone moiety, but exhibited significant emission enhancement upon strain-promoted alkyne-nitrone cycloaddition (SPANC) reaction with bicyclo[6.1.0]nonyne (BCN)-modified substrates. The modification of nitrone with a dicationic ruthenium(II) polypyridine unit at the α-C-position and a phenyl ring at the N-position led to remarkably accelerated reaction kinetics, which are substantially greater (up to ≈278 fold) than those of other acyclic nitrone-BCN systems. Interestingly, the complexes achieved specific cell membrane/cytosol staining upon specific labeling of an exogenous substrate, BCN-modified decane (BCN-C10), in live cells. Importantly, the in situ generation of the more lipophilic isoxazoline adduct in the cytoplasm resulted in increased cytotoxicity, highlighting a novel approach to apply the SPANC labeling technique in drug activation.


The inhibition of low density lipoprotein metabolism by transforming growth factor-beta mediates its effects on steroidogenesis in bovine adrenocortical cells in vitro.
Transforming growth factor-beta (TGF beta) has a differential effect on the growth and function of bovine adrenocortical cells in vitro. TGF beta inhibits basal as well as ACTH- or angiotensin II-stimulated steroid formation, with no evidence of change in cell growth. The major inhibitory effect of TGF beta occurs at a step before cholesterol formation, since treatment of adrenocortical cells with TGF beta decreased not only delta 4-steroid levels but also delta 5-steroid levels. The addition of cholesterol reverses the suppression of steroidogenesis induced by TGF beta. To determine the mechanism of this inhibition, the effect of TGF beta on low density lipoprotein (LDL) metabolism was investigated. Cells treated with TGF beta showed a significant suppression of [125I]iodohuman LDL ([125I]LDL) binding to the cell surface, followed by decreases in internalization and proteolytic degradation of [125I]LDL. Maximal inhibition of LDL metabolism was observed at a concentration of 1 ng/ml (4 X 10(-11) M) TGF beta. The stimulation of LDL metabolism by ACTH was also inhibited by TGF beta, and the inhibition observed correlated well with the inhibition of steroidogenesis. The inhibitory effect of TGF beta on [125I]LDL binding results from the decrease in the maximal LDL-binding capacity. The stimulation of LDL uptake induced by Bu2cAMP, cholera toxin, forskolin, and Ang II was also decreased by treatment with 1 ng/ml TGF beta. The specificity of this effect is quite high, since the inhibitory effects of TGF beta on LDL metabolism were not observed with either inhibin A or activin, two molecules that have considerable structural homology to TGF beta. We conclude that TGF beta specifically suppresses LDL metabolism in bovine adrenocortical cell cultures and that this step may mediate, at least in part, its role as a potent inhibitor of steroidogenesis.


Diagnosis and prevention of atherosclerotic cerebral infarction.
Atherosclerotic disease accounts for approximately 25% of ischemic strokes. Atherosclerotic stroke is caused mainly by embolic events from the carotid artery bifurcation or the aortic arch, although intracranial thrombosis can occur, more often in African Americans, Asians, and diabetes patients. Primary prevention of stroke is critical for patients with risk factors for atherosclerosis, including hypertension, diabetes, smoking and hypercholesterolemia. Stroke can be prevented in patients with established atherosclerotic disease by identification and management of patients with carotid artery stenosis by non-invasive testing. Particular attention must be paid to patients with transient symptoms of brain ischemia.


Downregulation of the mitochondrial phosphatase PTPMT1 is sufficient to promote cancer cell death.
Protein Tyrosine Phosphatase localized to the Mitochondrion 1 (PTPMT1) is a dual specificity phosphatase exclusively localized to the mitochondria, and has recently been shown to be a critical component in the cardiolipin biosynthetic pathway. The downregulation of PTPMT1 in pancreatic beta cells has been shown to increase cellular ATP levels and insulin production, however, the generalized role of PTPMT1 in cancer cells has not been characterized. Here we report that downregulation of PTPMT1 activity is sufficient to induce apoptosis of cancer cells. Additionally, the silencing of PTPMT1 decreases cardiolipin levels in cancer cells, while selectively increasing ATP levels in glycolytic media. Additionally, sublethal downregulation of PTPMT1 synergizes with low doses of paclitaxel to promote cancer cell death. Our data suggest that inhibition of PTPMT1 causes a metabolic crisis in cancer cells that induces cell death, and may be a mechanism by which cancer cells can be sensitized to currently available therapies.


Read carefully, because this is important! How value-driven strategies impact sentence memory.
Little is understood about how people strategically process and remember important but complex information, such as sentences. In the current study, we asked whether people can effectively prioritize memory for sentences as a function of their relative importance (operationalized as a reward point value) and whether they do so, in part, by changing their sentence processing strategies when value information is available in advance. We adapted the value-directed remembering paradigm (Castel, Psychol Learn Motiv 48:225-270, 2007) for sentences that varied in constraint and predictability. Each sentence was associated with a high or low value for subsequent free recall (whole sentence) and recognition (sentence-final words) tests. Value information appeared after or before each sentence as a between-subject manipulation. Regardless of condition, we observed that high-value sentences were recalled more often than low-value sentences, showing that people can strategically prioritize their encoding of sentences. However, memory patterns differed depending on when value information was available. Recall for high-value sentences that ended unexpectedly (and therefore violated one's predictions) was reduced in the Before compared to the After condition. Before condition participants also showed a greater tendency to false alarm to lures (words that were the predicted - but not obtained - ending) from strongly constraining sentences. These observations suggest that when people try to prioritize sentence-level information that they know is valuable, the reading strategies they employ may paradoxically lead to worse memory.


Performance analysis and optimization of inverted inorganic CsGeI3 perovskite cells with carbon/copper charge transport materials using SCAPS-1D.
Organic-inorganic perovskite solar cells (PSCs) have achieved the power conversion efficiencies (PCEs) of more than 25%. However, the organic compound in the material is causing structural degradation of the PSC owing to heat (thermal instability), humidity and moisture. This has led to the exploration of only inorganic perovskite materials. Inorganic PSCs such as caesium have seen a breakthrough by achieving highly stable PSC with PCE exceeding 15%. In this work, the inorganic non-toxic PSC of caesium germanium tri-iodide (CsGeI3) is numerically modelled in SCAPS-1D with two carbon-based electron transport layers (ETLs) and two copper-based hole transport layers (HTLs). This study introduces in-depth numerical modelling and analysis of CsGeI3 through continuity and Poisson equations. Cu HTLs are selected to increase the electric conductivity of the cell, while carbon-based ETL is used to increase the thermal conductivity of the PSC. A total of four unique PSC structures are designed and presented. A systematic approach is adopted to obtain the optimized PSC design parameters for maximum performance. From the optimized results, it is observed that the C60/CsGeI3/CuSCN structure is the highest performance PSC, with open-circuit voltage (V oc) of 1.0169 V, short-circuit current density (J sc) of 19.653 mA cm-2, fill factor of 88.13% and the PCE of 17.61%. Moreover, the effect of quantum efficiency, electric field, interface recombination, interface defects, layer thickness, defect density, doping concentration, working temperature and reflection coating on the cell performance are studied in detail.


Recent ruling on ADA and the value of early intervention.
Early intervention in a disability case can make all the difference. Two cases of carpal tunnel syndrome in the workplace are compared. Frequent communication, good documentation and an inclusive approach that blends medical expertise with objectivity and employer policy are essential.


Mutations that alter a repeated ACCA element located at the 5' end of the Potato virus X genome affect RNA accumulation.
The repeated ACCA or AC-rich sequence and structural (SL1) elements in the 5' non-translated region (NTR) of the Potato virus X (PVX) RNA play vital roles in the PVX life cycle by controlling translation, RNA replication, movement, and assembly. It has already been shown that the repeated ACCA or AC-rich sequence affect both gRNA and sgRNA accumulation, while not affecting minus-strand RNA accumulation, and are also required for host protein binding. The functional significance of the repeated ACCA sequence elements in the 5' NTR region was investigated by analyzing the effects of deletion and site-directed mutations on PVX replication in Nicotiana benthamiana plants and NT1 protoplasts. Substitution (ACCA into AAAA or UUUU) mutations introduced in the first (nt 10-13) element in the 5' NTR of the PVX RNA significantly affected viral replication, while mutations introduced in the second (nt 17-20) and third (nt 20-23) elements did not. The fourth (nt 29-32) ACCA element weakly affected virus replication, whereas mutations in the fifth (nt 38-41) significantly reduced virus replication due to the structure disruption of SL1 by AAAA and/or UUUU substitutions. Further characterization of the first ACCA element indicated that duplication of ACCA at nt 10-13 (nt 10-17, ACCAACCA) caused severe symptom development as compared to that of wild type, while deletion of the single element (nt 10-13), DeltaACCA) or tripling of this element caused reduced symptom development. Single- and double-nucleotide substitutions introduced into the first ACCA element revealed the importance of CC located at nt positions 11 and 12. Altogether, these results indicate that the first ACCA element is important for PVX replication.


Erysipelas Outbreaks in Flocks of Geese in Poland--Biochemical and Genetic Analyses of the Isolates.
Erysipelothrix rhusiopathiae causes erysipelas in many vertebrate species. Severe disease outbreaks have been noted in many poultry species--chickens, ducks, emus, pheasants, pigeons, and geese. This article describes the biochemical and genetic analyses of six E. rhusiopathiae strains isolated from geese for meat production. The isolates came from birds kept in different poultry houses on one farm, and were collected during two erysipelas outbreaks. We analyzed and compared the isolates by random amplified polymorphic DNA with the use of NK6 primer and pulsed-field gel electrophoresis, with the restriction enzyme SmaI. Biochemical examination was performed with API Coryne test. Analyses showed that the three strains isolated during the first outbreak differed, whereas the three isolates from the second outbreak were identical to one another, but distinct from the isolates from the first outbreak. The results of biochemical and genetic analyses of E. rhusiopathiae strains isolated from geese suggest different sources of infection for the erysipelas outbreaks.


Clinical consequences of activating germline mutations of TSH receptor, the concept of toxic hyperplasia.
Activating mutations of TSH-R have been described in toxic nodules and more recently in familial nonautoimmune thyrotoxicosis. This last entity is still confused with familial Graves' disease and the aim of this study is to define its phenotype. Based on 49 patients coming from our first family and on the 4 other kindreds secondarily described in the literature, the phenotypic expression is: a high incidence of hyperthyroidism, an early onset of disease, a higher men/women ratio (17/32) than in Graves, disease, the absence of ophthalmopathy and of circulating and intrathyroid signs of immunity, a pathology similar to toxic nodule, the need for a total destruction of thyroid tissue to cure the patients. The total analogy with toxic nodule leads us to name this new entity "toxic hyperplasia'. Among 92 successive diffuse nonfamilial thyrotoxicosis cases (initially considered as Graves) we isolated 5 cases without extra- and intrathyroidal autoimmunity, raising the question of the existence of an apparent "sporadic' form of toxic hyperplasia (neomutation?).


What Factors Correlate With Length of Stay and Readmission After Limb Lengthening Procedures? A Large-database Study.
Indications and techniques for limb lengthening procedures have evolved over the past two decades. Although there are several case series reporting on the complications and efficacy of these techniques, limited data are available on length of stay and hospital readmission rates after these procedures. (1) What is the median length of stay after lower limb lengthening procedures, and is variability in patient demographics, preoperative diagnosis, and surgical technique associated with length of stay? (2) What is the 1-year readmission rate after lower limb lengthening procedures? (3) Is variability in patient demographics, preoperative diagnosis, and surgical technique associated with varying rates of hospital readmission? Patients who underwent femoral or tibial lengthening from 2005 to 2015 in seven states were identified using the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases. These databases include a large, diverse group of patients across a wide range of hospitals and socioeconomic backgrounds with inclusion of patients regardless of payer. Between 2005 and 2015, there were 3979 inpatient admissions that were identified as involving femoral and/or tibial lengthening procedures based on ICD-9 procedure codes; of those, 2% (97 of 3979) of the inpatient admissions were excluded from analysis because they had ICD-9 procedure codes for primary or revision hip or knee arthroplasty, and 10% (394 of 3979) of the inpatient admissions were excluded because they involved repeated admissions of patients with previous hospitalization data within the database. This yielded 3488 patients for analysis. The median (interquartile range) age of patients was 18 years (12 to 41), and 42% (1481 of 3488) of patients were women. A total of 49% (1705 of 3469) of patients were children (younger than 18 years), 19% (675 of 3469) were young adults (18 to 34 years), 24% (817 of 3469) were adults (35 to 59 years), and 8% (272 of 3469) were seniors (60 years and older). Length of stay and rates of readmission at 1 year after the lengthening procedure were calculated. Univariate analysis was performed to examine associations between age, race, payment method, underlying diagnosis, bone lengthened, and lengthening technique with length of stay and readmission rate. Factors found to be significantly associated with the outcome variables (p < 0.05) were further examined with a multivariate analyses. Included patients had a median (IQR) length of hospital stay of 3 days (2 to 4). Given the poor explanatory power of the multivariate model for length of stay (R 2 = 0.03), no meaningful correlations could be drawn between age, race, underlying diagnosis, lengthening technique, and length of stay. The overall 1-year readmission rate was 35% (1237 of 3488). There were higher readmission rates among adult patients compared with pediatric patients (odds ratio 1.78 [95% confidence interval 1.46 to 2.18]; p < 0.001), patients with government insurance compared with commercial insurance (OR 1.28 [95% CI 1.05 to 1.54]; p = 0.01), and patients undergoing lengthening via external fixation (OR 1.61 [95% CI 1.29 to 2.02]; p < 0.001) or hybrid fixation (OR 1.81 [95% CI 1.38 to 2.37]; p < 0.001) compared with lengthening with internal fixation only. When counseling patients who may be candidates for limb lengthening, providers should inform individual patients and their caretakers on the anticipated length of hospital stay and likelihood of hospital readmission based on our findings. Adult patients, those with government insurance, and patients undergoing hybrid or external fixator limb lengthening procedures should be advised that they are at greater risk for hospital readmission. The relationship of specific patient-related factors (such as severity of deformity or associated comorbidities) and treatment-related variables (such as amount of lengthening, compliance with physical therapy, or surgeon's experience) with clinical outcomes after lower limb lengthening and the burden of care associated with hospital readmission needs further study. Level III, therapeutic study.


Impact of Host DNA and Sequencing Depth on the Taxonomic Resolution of Whole Metagenome Sequencing for Microbiome Analysis.
The amount of host DNA poses a major challenge to metagenome analysis. However, there is no guidance on the levels of host DNA, nor on the depth of sequencing needed to acquire meaningful information from whole metagenome sequencing (WMS). Here, we evaluated the impact of a wide range of amounts of host DNA and sequencing depths on microbiome taxonomic profiling using WMS. Synthetic samples with increasing levels of host DNA were created by spiking DNA of a mock bacterial community, with DNA from a mouse-derived cell line. Taxonomic analysis revealed that increasing proportions of host DNA led to decreased sensitivity in detecting very low and low abundant species. Reduction of sequencing depth had major impact on the sensitivity of WMS for profiling samples with 90% host DNA, increasing the number of undetected species. Finally, analysis of simulated datasets with fixed depth of 10 million reads confirmed that microbiome profiling becomes more inaccurate as the level of host DNA increases in a sample. In conclusion, samples with high amounts of host DNA coupled with reduced sequencing depths, decrease WMS coverage for characterization of the microbiome. This study highlights the importance of carefully considering these aspects in the design of WMS experiments to maximize microbiome analyses.


Marine Bacteria with Antiyeast Activity.
Various marine substrates were examined quantitatively and qualitatively for marine bacteria. Of 132 isolates, 20 (six genera) showed some degree of inhibitory activity against 12 assay microorganisms. Inhibition was most frequent and most pronounced against terrestrial and marine-occurring yeasts.


Tryptophan mutants of human C5a anaphylatoxin: a fluorescence anisotropy decay and energy transfer study.
Three mutants of the anaphylatoxin C5a were prepared with positions 2, 64 and 70, respectively, substituted by tryptophan. The last mutant was additionally labelled at Cys27 for fluorescence energy transfer (FET) measurements. The structural integrity and biological activity of the molecules were not affected. Fluorescence anisotropy decay (FAD) measurements showed that the rotational correlation time for tryptophan decreases in the order: [Trp2]rhC5a > [Trp64]rhC5a > [Trp70]rhC5a, indicating an increasing mobility of the side chain. Measurements of the fluorescence energy transfer from Trp70 to the 1,5-AEDANS group at Cys27 yielded a distance distribution of 2.4 +/- 0.8 nm. This value is compatible with the C-terminal chain being arranged as a slightly stretched helix pointing away from the body of the molecule.


Analysis of bacterial exopolysaccharides.
Extracellular polysaccharides have been isolated from cultures of freshwater and marine bacteria originally isolated from material adhering to surfaces and underivatized hydrolysates have been analyzed by high-performance liquid chromatography methods. A scheme has been developed whereby the uronic acids can be identified on strong anion-exchange columns, while neutral monosaccharides can be separated and identified using aminobonded columns or cation-exchange adsorbent loaded with a heavy metal ion. The methods permit rapid and accurate comparison of polysaccharides with differing chemotype. The strains studied show a range of different chemotypes, all containing a uronic acid and several neutral monosaccharides. Some of the polysaccharides isolated from marine bacteria possessed a very high acetyl content.


Multiple arterial and venous thromboembolic complications in AL amyloidosis and cardiac involvement: a case report and literature review.
A 41-year-old woman with immunoglobulin light chain (AL) systemic amyloidosis with cardiac and gastrointestinal involvement developed multiple arterial and venous thromboembolic complications. Treatment with unfractionated heparin was complicated by life-threatening gastrointestinal bleeding. Work up for hereditary thrombophilia was unrevealing. Treatment with cyclophosphamide, bortezomib and dexamethasone combination regimen led to hematologic response without further thromboembolic complications. While thromboembolic complications have been reported in AL amyloidosis and cardiac involvement, this unique case highlights the complexity of the disease, the various pathogenic mechanisms at play and the difficult management decisions necessary in caring for these complex patients. A literature review of thrombembolic complications in patients with amyloidosis is presented.


Upregulated HSPA2 predicts early relapse of pancreatic cancer after surgery.
Heat shock protein A2 (HSPA2) is known to relate to the pathogenesis and progress of cancer. This study aimed to investigate the connection between HSPA2 and early postsurgical relapse of pancreatic cancer (PC). Expression of HSPA2 in 85 pairs of cancerous and matched noncancerous samples was determined by immunostaining method. The relationship between HSPA2 expression and early postsurgical recurrence was assessed using logistic regression. The performance and potential application of HSPA2 expression to predict early postsurgical recurrence was evaluated by receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). HSPA2 expression in tumor specimens was markedly elevated compared with non-tumor specimens. Logistic regression analysis indicated that HSPA2 upregulation was an independent risk marker for early postsurgical recurrence of PC. ROC curve analysis and DCA demonstrated that both the area under the curve (AUC) and the net benefit of HSPA2 expression were higher than those of other clinicopathologic features in predicting early postsurgical relapse of PC. The combination of HSPA2 expression with other malignant clinicopathologic characteristics had greater AUC and net benefit relative to them alone in predicting early postsurgical recurrence. Upregulated HSPA2 independently predicts early postsurgical recurrence of PC and has superior predictive performance and potential application value when combined with malignant clinicopathologic features. Our findings reveal that HSPA2 is a promising predictor for early postoperative relapse of PC.


Identification of diacylated ureas as a novel family of fungus-specific leukocyte-activating pathogen-associated molecules.
Polymorphonuclear leukocytes represent primary components of the host's innate immune defenses against fungal infection, suggesting involvement of fungal leukocyte attractants. We have found in various fungi, but not in bacteria or host cells, unstable lipid-like leukocyte chemoattractants, which also induced adherence and degranulation in human neutrophils. Purification from bakers' yeast and structural analyses by electrospray mass spectrometry, (1)H NMR spectroscopy, and chemical synthesis revealed these inflammatory mediators as diacylated ureas, a novel class of unstable lipoids. The N,N'-dipalmitoleyl urea appeared to be the most potent innate immune responses inducing compound eliciting half-maximum neutrophil chemotactic activity at 140 nm. The all-trans isomer, N,N'-dipalmitelaidyl urea, was found to be inactive with respect to stimulation of degranulation in neutrophils, which indicates a Delta(9) cis-double bond to be essential for bioactivity of these diacyl ureas. N,N'-Dipalmitoleyl urea elicited Ca(2+) mobilization in neutrophils, which was found to be pertussis toxin-sensitive and sensitive toward a carboxylmethyltransferase inhibitor, indicating that these diacyl ureas activate leukocytes via a putative Galpha(i)-protein-coupled receptor. Their isolation exclusively from fungi suggests that these lipoids are fungus-specific pathogen-associated molecules that may alert the human innate immunity system to the presence of a fungal infection.


Effective interventions for pressure ulcer prevention.
This article examines the causes of pressure ulcers and provides an overview of the best advice available in preventing them in the clinical setting. This should enable nurses to provide more effective interventions for preventing patients from developing pressure ulcers.


High-dose chemotherapy with autologous haematopoietic stem cell support for relapsed or refractory primary CNS lymphoma: a prospective multicentre trial by the German Cooperative PCNSL study group.
To investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL), we conducted a single-arm multicentre study for immunocompetent patients (<66 years) with PCNSL failing high-dose methotrexate)-based chemotherapy. Induction consisted of two courses of rituximab (375 mg/m2), high-dose cytarabine (2 × 3 g/m2) and thiotepa (40 mg/m2) with collection of stem cells in between. Conditioning for HCT-ASCT consisted of rituximab 375 mg/m2, carmustine 400 mg/m2 and thiotepa (4 × 5 mg/kg). Patients commenced HCT-ASCT irrespective of response after induction. Patients not achieving complete remission (CR) after HCT-ASCT received whole-brain radiotherapy. Primary end point was CR after HCT-ASCT. We enrolled 39 patients; median age and Karnofsky performance score are 57 years and 90%, respectively. About 28 patients had relapsed and 8 refractory disease. About 22 patients responded to induction and 32 patients commenced HCT-ASCT. About 22 patients (56.4%) achieved CR after HCT-ASCT. Respective 2-year progression-free survival (PFS) and overall survival (OS) rates were 46.0% (median PFS 12.4 months) and 56.4%; median OS not reached. We recorded four treatment-related deaths. Thiotepa-based HCT-ASCT is an effective treatment option in eligible patients with r/r PCNSL. Comparative studies are needed to further scrutinise the role of HCT-ASCT in the salvage setting.


An ERK-p38 subnetwork coordinates host cell apoptosis and necrosis during coxsackievirus B3 infection.
The host response to a virus is determined by intracellular signaling pathways that are modified during infection. These pathways converge as networks and produce interdependent phenotypes, making it difficult to link virus-induced signals and responses at a systems level. Coxsackievirus B3 (CVB3) infection induces death of cardiomyocytes, causing tissue damage and virus dissemination, through incompletely characterized host cell signaling networks. We built a statistical model that quantitatively predicts cardiomyocyte responses from time-dependent measurements of phosphorylation events modified by CVB3. Model analysis revealed that CVB3-stimulated cytotoxicity involves tight coupling between the host ERK and p38 MAPK pathways, which are generally thought to control distinct cellular responses. The kinase ERK5 requires p38 kinase activity and inhibits apoptosis caused by CVB3 infection. By contrast, p38 indirectly promotes apoptosis via ERK1/2 inhibition but directly causes CVB3-induced necrosis. Thus, the cellular events governing pathogenesis are revealed when virus-host programs are monitored systematically and deconvolved mathematically.


Computing hubs in the hippocampus and cortex.
Neural computation occurs within large neuron networks in the dynamic context of varying brain states. Whether functions are performed by specific subsets of neurons and whether they occur in specific dynamical regimes remain poorly understood. Using high-density recordings in the hippocampus, medial entorhinal, and medial prefrontal cortex of the rat, we identify computing substates where specific computing hub neurons perform well-defined storage and sharing operations in a brain state-dependent manner. We retrieve distinct computing substates within each global brain state, such as REM and nonREM sleep. Half of recorded neurons act as computing hubs in at least one substate, suggesting that functional roles are not hardwired but reassigned at the second time scale. We identify sequences of substates whose temporal organization is dynamic and stands between order and disorder. We propose that global brain states constrain the language of neuronal computations by regulating the syntactic complexity of substate sequences.


Vision in Alzheimer's disease: a focus on the anterior afferent pathway.
Visual dysfunction has long been recognized as a manifestation of Alzheimer's disease (AD), particularly in the form of visuospatial impairment during all stages of disease. However, investigations have revealed findings within the anterior (i.e., pregeniculate) afferent visual pathways that rely on retinal imaging and electrophysiologic methodologies for detection. Here we focus on the anterior afferent visual pathways in AD and the measures used for assessment, including optical coherence tomography, electrophysiology, color vision testing and threshold visual field perimetry. A brief summary of higher order visual dysfunction is also included to allow the reader to keep in context the broader findings of afferent visual dysfunction in AD.


Immunohistochemical and ultrastructural examination of smooth muscle cells in aortocoronary saphenous vein grafts.
In this study, phenotypic modulation and remodulation of smooth muscle cells and associated intermediate filament expression were demonstrated by means of immunohistochemistry and ultrastructure to understand the development of intimal hyperplasia in aortocoronary saphenous vein grafts. In nongrafted saphenous veins, all smooth muscle cells expressed vimentin and desmin and were of a contractile form. In saphenous vein grafts showing stenotic intimal hyperplasia (luminal stenosis < 75%), expression of desmin was notably lower, whereas that of vimentin was higher. The cells were shown to be of a synthetic phenotype, suggesting modulation from the original contractile form. In saphenous vein grafts showing occlusive intimal hyperplasia (luminal stenosis > 76%), desmin expression in smooth muscle cells was increased again, and such cells were of a contractile form, suggesting remodulation from the synthetic phenotype. Some of the smooth muscle cells of the synthetic phenotype were positive for an antibody against proliferation cell nuclear antigen. Smooth muscle cells of the contractile form were negative for this antibody. The study suggests that smooth muscle cells of synthetic phenotype are highly responsible for "growing" intimal hyperplasia of aortocoronary saphenous vein grafts.


Comparison of gene expression profiles in the blood, hippocampus and prefrontal cortex of rats.
The comparability of gene expression between blood and brain tissues is a central issue in neuropsychiatric research where the analysis of molecular mechanisms in the brain is of high importance for the understanding of the diseases and the discovery of biomarkers. However, the accessibility of brain tissue is limited. Therefore, knowledge about how easily accessible peripheral tissue, e. g. blood, is comparable to and reflects gene expression of brain regions will help to advance neuropsychiatric research. Gene expression in the blood, hippocampus (HC) and prefrontal cortex (PFC) of genetically identical rats was compared using a genome-wide Affymetrix gene expression microarray covering 29,215 expressed genes. A total of 56.8% of 15,717 expressed genes were co-expressed in blood and at least one brain tissue, while 55.3% of all genes were co-expressed in all three tissues simultaneously. The overlapping genes included a set of genes of relevance to neuropsychiatric diseases, in particular bipolar disorder, schizophrenia and alcohol addiction. These genes included CLOCK, COMT, FAAH, NPY, NR3C1, NRGN, PBRM1, TCF4, and SYNE. This study provides baseline data on absolute gene expression and differences between gene expression in the blood, HC and PFC brain tissue of genetically identical rats. The present data represents a valuable resource for future studies as it might be used for first information on gene expression levels of genes of interest in blood and brain under baseline conditions. Limitations of our study comprise possible contamination of brain tissue with blood and the non-detection of genes with very low expression levels. Genes that are more highly expressed in the brain than in the blood are of particular interest since changes in their expression, e.g. due to disease status, or treatment, are likely to be detected in an experiment. In contrast, genes with higher expression in the blood than in the brain are less informative since their higher baseline levels could superimpose variation in brain.


Metabolic syndrome in chronic hepatitis C infection: does it still matter in the era of directly acting antiviral therapy?
Metabolic syndrome is prevalent in patients with hepatitis C virus (HCV) infection. Given the pandemic spread of HCV infection and metabolic syndrome, the burden of their interaction is a major public health issue. The presence of metabolic syndrome accelerates the progression of liver disease in patients with HCV infection. New drug development in HCV has seen an unprecedented rise in the last year, which resulted in better efficacy, better tolerance, and a shorter treatment duration. This review describes the underlying mechanisms and clinical effects of metabolic syndrome in HCV infection, as well as their importance in the era of new directly acting antiviral therapy.


Solvent-controlled stereoselective formation of a cyclic ether in the lewis acid-mediated allylation of an alpha-chloroacetoxy acyclic ether. Very high stereoselectivity in CH3CN vs low stereoselectivity in CH2Cl2.
The MgBr2.OEt2-mediated intramolecular allylation of a 4:1 diastereoisomeric mixture of the alpha-chloroacetoxyl ether 1a bearing the A-G/JK ring system of brevetoxin B in CH2Cl2 gave a 1:1 diastereoisomeric mixture of the trans- and cis-cyclization products 4a and 5a having the A-G/I-K ring system, while that in CH3CN afforded the trans-isomer 4a nearly as the single product. To help clarify a reason for this marked solvent effect in the cyclization of the brevetoxin B precursor, DFT computations for the starting materials, intermediates, transition states, and products were carried out. The cyclization would proceed through a carbocation intermediate 3a having sp2 flat structure (SN1 type mechanism) in CH2Cl2, in which the activation energies leading to both diastereoisomers are approximately identical, while in CH3CN alkylnitrilium salts 6a would be formed through the coordination of CH3CN to the carbocation leading to an sp3-type intermediate in which sever steric hindrance takes place in the transition state leading to the undesired diastereoisomer. The scope of this novel solvent-controlled stereoselectivity was tested for simple compounds. In small model compounds the marked solvent dependence was absent, but the model bearing two consecutive cyclic ether rings 1b exhibited a remarkable solvent effect similar to that observed in the brevetoxin B system.


HLA-DPB1 matching status has significant implications for recipients of unrelated donor stem cell transplants.
Studies in unrelated donor (UD) hematopoietic stem cell transplantations (HSCT) show an effect of the matching status of HLA-DPB1 on complications. We analyzed 423 UD-HSCT pairs. Most protocols included T-cell depletion (TCD). All pairs had high-resolution tissue typing performed for 6 HLA loci. Two hundred eighty-two pairs were matched at 10 of 10 alleles (29% were DPB1 matched). In 141 HLA-mismatched pairs, 28% were matched for DPB1. In the 10 of 10 matched pairs (n = 282), the 3-year probability of relapse was 61%. This was significantly higher in DPB1-matched pairs (74%) as compared with DPB1-mismatched pairs (56%) (log rank, P = .001). This finding persisted in multivariate analysis. In the group overall (n = 423), relapse was also significantly increased if DPB1 was matched (log rank; P < .001). These results were similar in chronic myeloid leukemia (CML; P < .001) and acute lymphoblastic leukemia (ALL; P = .013). In ALL, DPB1-matched pairs had a significantly worse overall survival (log rank; P = .025). Thus, in recipients of TCD UD-HSCT, a match for DPB1 is associated with a significantly increased risk of disease relapse, irrespective of the matching status for the other HLA molecules. It is possible that this effect is especially apparent following TCD transplantations and invites speculation about the function of DPB1 within the immune system.


A Cross-Sectional Study on Intestinal Parasitic Infections in Children in Suburban Public Primary Schools, Saraburi, the Central Region of Thailand.
Intestinal parasitic infection rate among school-aged children in Thailand has been decreasing. However, certain intestinal parasites remain problematic in some regions. This cross-sectional study was conducted between February and September 2016 in three suburban government primary schools (KK, BR, and HK), Saraburi, Thailand. Stool was collected from 263 asymptomatic subjects (4-15 years old), using simple direct smear, formalin-ether concentration, Boeck and Drbohlav's Locke-Egg-Serum (LES) medium culture, and agar plate culture. A self-administered questionnaire was used to collect data about lifestyle and socioeconomic status. The overall rate of intestinal parasites was 22.1% (15.6% single infection and 6.5% multiple infections). The helminths involving the digestive system found were Strongyloides stercoralis (1.5%) and Opisthorchis viverrini (0.4%). For protozoan infection, the major cause was Blastocystis hominis (17.5%). The other protozoa included Endolimax nana (4.6%), Entamoeba coli (3.4%), Entamoeba histolytica/Entamoeba dispar (1.1%), and Giardia intestinalis (0.8%). The sensitivity for the detection of B. hominis increased with the LES culture technique. The infection rate of each organism was not significantly different among the three schools except for B. hominis which showed the highest prevalence in the HK school (P = 0.001). This was correlated with the questionnaire results in which the HK school showed the highest risk of drinking contaminated water (P = 0.004). The present study emphasized the persistent problems of protozoan infections among suburban school-aged children. Lifestyle was still an important factor for intestinal parasitic infections among suburban school-aged Thai children in this study. Health education as well as routine surveillance was necessary to control the infections.


Scanning electron microscopic, transmission electron microscopic, and confocal laser scanning microscopic observation of fibroblasts cultured on microgrooved surfaces of bulk titanium substrata.
During this study, microtechnology and plasma etching were used to produce gratings 1.0 (TiD01), 2.0 (TiD02), 5.0 (TiD05), and 10.0 microns wide (TiD10) into commercially pure titanium wafers. After incubation of rat dermal fibroblast (RDFs) on these surfaces for 3 days, the cells were observed with scanning electron (SEM), transmission electron (TEM), and confocal laser scanning microscopy (CLSM). Results showed that the RDFs as a whole and their stress fibers oriented strictly parallel to the surface pattern on the TiD01 and TiD02 surfaces. On the TiD05 and TiD10 surfaces, this orientation was not observed. In addition, TEM and CLSM demonstrated that the focal adhesion points (FAP) were located mainly on the surface pattern ridges. TEM revealed that FAP were wrapped occasionally around the edges of the ridges. Only the RDFs on both the TiD05 and TiD10 surfaces protruded into the grooves and possessed FAP on the walls of the grooves. Attachment to the groove floor was observed only on the TiD10 textures. Comparison of these results with earlier observations on microtextured silicone rubber substrata suggests that material-specific properties do not influence the orientational effect of the surface texture on the observed RDF cellular behavior. The proliferation rate of the RDFs, however, seems to be much higher on titanium than on silicone rubber substrata.


[Optimization of the HIS process mapping of the Military Instruction Hospital Mohammed V].
Introduction: Development of process mapping is not easy, as, apart from identification of the key processes of the organization, mapping can hardly describe all of the interactions involved without becoming incomprehensible. In this context, the Rabat Military Hospital decided to review its process mapping to align it with the reference mapping proposed by the National Agency for Performance Support, which is designed to standardize and improve functional mapping of healthcare production systems. Methods: To assist the Military Hospital in this convergence process, this paper proposes the application of a convergence method on the current hospital process mapping, in order to guide hospital agents in the development of optimal process mapping, complying with guidelines for urbanization of information systems while remaining consistent with strategic guidelines. Results and discussion: The results obtained from application of this method to the initial hospital process mapping indicate a positive functional and organizational impact, particularly on optimization of the flow between processes.


Twelve years experience with radical hysterectomy and pelvic lymphadenectomy in early stage cervical cancer.
The objective of this study was to evaluate the outcome, prognostic factors and complications of early stage cervical cancer patients treated with radical hysterectomy and pelvic lymphadenectomy (RHPL). The medical records of cervical cancer patients undergoing RHPL at Chiang Mai University Hospital over 12 years, between January 1995 and December 2006 were reviewed. There were 1,253 patients in the study period. The mean age was 44 years of age. Of these, 26.9% had prior diagnostic conisation. The maximum tumour size was 8 cm. The most common histology was squamous cell carcinoma (67%) followed by adenocarcinoma (23%). The distribution of FIGO staging was: stage IA 8.7%; stage IB 15.8%; stage IB1 61%; stage IB2 6.2%; and stage IIA 8.5%. Pelvic nodes, parametrial and vaginal margin involvement were detected in 15.9%, 10.7% and 3.8% of the patients, respectively. A total of 66.5% of patients underwent RHPL without adjuvant treatment; 12.1% received neoadjuvant chemotherapy. The estimated 10-year recurrence-free survival rate was 90%. Stage IB2/IIA, non-squamous cell carcinoma, nodal involvement and positive vaginal margins were independent, significant, poor prognostic factors. The most common long-term complication was lymphoedema. It was concluded that early stage cervical cancer patients treated with RHPL have long-term favourable outcome with minimal morbidity. Stage IB2 and IIA, non-squamous cell carcinoma, nodal and vaginal involvement were independent adverse prognostic factors.


Highly efficient transfer of chirality from macrocyclic conformation in the tandem oxy-Cope/Claisen/ene reaction.
We report three highly stereoselective pericyclic reactions occurring in cascade leading to the synthesis of Decalins skeletons possessing two contiguous quaternary centers. The tandem reaction is triggered by an oxy-Cope rearrangement to create in situ a 10-membered ring enol ether macrocyle 6, which immediately rearranges via a Claisen [3,3] shift to the corresponding E-cyclodec-6-en-1-one 7. The latter spontaneously cyclizes via a transannular ene reaction to produce Decalin 5. Analysis of the mechanism with respect to the origin of the high diastereoselectivity of the tandem oxy-Cope/Claisen/ene reaction is presented.


Heterogeneity for adenosine deaminase deficiency: Expression of the enzyme in cultured skin fibroblasts and amniotic fluid cells.
Adenosine deaminase (ADA) could be quantitated and the isozyme pattern characterized in cultured amniotic fluid cells. In 20 amniotic fluid cell cultures the mean specific activity was 14.3 U/g protein +/- 6.7 (SD) and compared favorably with values of 14.6 U/g protein +/- 6.8 (SD) observed in 26 cultures of skin fibroblasts. In cultures of skin fibroblasts established from two obligate heterozygotes for ADA deficiency, the specific activity of ADA was 7.0 and 7.7 U/g protein. The ADA isozyme pattern that existed in cultures of amniotic fluid cells was the same as that observed in cultured skin fibroblasts. This identification of the same apparent enzyme may permit the prenatal diagnosis of that form of combined immunodeficiency disease caused by ADA deficiency. Residual enzyme activity of less than 1% and 10% of the mean of normal fibroblasts could be measured in cultured fibroblasts from two unrelated children with ADA deficiency and combined immunodeficiency disease. The tissue-specific enzyme from cultured skin fibroblasts from the child with 10% residual activity had a faster electrophoretic mobility and greater heat stability than normal ADA. This enzymatic evidence indicates that at least two mutant alleles exist at the locus for ADA which predispose to combined immunodeficiency disease when present in the homozygous state.


Type 1 rhizomelic chondrodysplasia punctata with a homozygous PEX7 mutation.
Rhizomelic chondrodysplasia punctata (RCDP) is a rare peroxisomal disease characterised by punctate calcifications of non-ossified cartilage epiphyseal centres. The main biochemical marker of all RCDP types is a decrease in the levels of plasmalogens. Additionally, the accumulation of phytanic acid can be used as a differential marker between types of RDCP. Due to the biochemical overlap between types 1 and 5 RCDP, a genetic analysis of these genes should be performed in patients to identify the type. A 2-month-19-day-old male child presented with symptoms of limited movement and discomfort with movement in the extremities. His sister, who had similar clinical findings, was diagnosed with tetralogy of Fallot and died at 6 months of age. A physical examination revealed an atypical facial appearance, bilateral cataracts, sensitivity to touch in the extremities, shortness in the proximal segments of the long bones, limited movement in both knees and elbows and axial hypotonicity. Laboratory analyses revealed normal ammonia, lactate, plasma and urine amino acids, long chain fatty acids and phytanic acid levels. Rhizomelia, significant metaphyseal expansion, irregularities in the cortex, loss of ossification, fragmented appearance and punctate calcifications in both elbows, both knees and in the femoral epiphysis were seen on the skeletal survey. A homozygote p.L70W (c.209T>G) mutation was found in the PEX7 gene. Plasma phytanic acid levels can be normal in a patient with type 1 RCDP that develops as a result of a PEX7 gene mutation, as in our case. A molecular genetic analysis and/or fibroblast culture must be conducted in clinically suspicious cases. While no cardiac pathology was found in our case, tetralogy of Fallot was present in his sister with similar clinical findings. The presence of different cardiological phenotypes in the sibling suggested that the genotype-phenotype correlation may not be complete in this disorder.


Cten promotes epithelial-mesenchymal transition through the post-transcriptional stabilization of Snail.
Cten promotes cell migration however the knowledge of underlying signalling pathways is sparse. We have shown that Cten downregulates E-cadherin, a feature of epithelial to mesenchymal transition (EMT). This prompted us to investigate whether Cten further contributed to EMT processes to regulate cell motility. The regulation of Snail by Cten was investigated following overexpression, knockdown (by RNA-interference) or knockout of Cten in HCT116, Caco-2 and SW620 colorectal cancer (CRC) cell lines. Subsequently, the cycloheximide (CHX) pulse chase assay was used to investigate changes in Snail protein stability and the functional relevance of Cten-Snail signalling was investigated. Snail was identified as a downstream target of Cten signalling using multiple approaches of Cten expression manipulation. Furthermore, this activity was mediated through the SH2 domain of Cten. The CHX assay confirmed that Cten was regulating Snail at a post transcriptional level and this was through the prevention of Snail degradation. Cell migration, invasion and colony formation efficiency were increased following forced expression of GFP-Cten but subsequently lost when Snail was knocked down, demonstrating a functional Cten-Snail signalling axis. In conclusion, we have described a novel Cten-Snail signaling pathway that contributes to cell motility in CRC, mediated by the stabilization of Snail protein. This finding potentially furthers the understanding of EMT regulatory networks in cancer metastasis.


Placebo-related effects: a meta-narrative review of conceptualization, mechanisms and their relevance in rheumatology.
For decades in medicine, the placebo effect has been conceptualized as a subjective psychological effect associated with an inert substance and considered to be a nuisance noise in the assessment of therapeutic effects in clinical trials. However, research on placebo has undergone substantial developments since the mid-1980s in several fields of knowledge (including methodology, psychology and neurosciences) that challenge this traditional view. Using a meta-narrative approach, this review of conceptualizations, determinants, mechanisms and models of placebo effects shows that placebo effects are genuine biopsychosocial phenomena strongly affected by context and factors surrounding the patient and treatments. Psychological experiments and neurobiological and neuroimaging studies have identified various types of placebo responses, driven by different mechanisms (especially but not only expectation and conditioning) and associated with different chemical, structural and functional features. Insights into the mechanisms involved in placebo responses have led to opportunities for ethical enhancements of these mechanisms in clinical practice, notably by improving the patient-doctor interaction and refining the therapeutic ritual. These developments should be carefully considered in rheumatology settings, in which placebo effects are both prevalent and significant, with the potential to improve patient care.


Preliminary study on the effect of oral care on recovery from surgery in elderly patients.
This study aimed to clarify the effectiveness of post-operative oral care, including tooth brushing, denture cleaning and tongue cleaning, after digestive tract surgery. Subjects included 30 elderly patients aged 60-98 years (74.9 +/- 7.8 years) who underwent digestive tract surgery. Subjects were randomly divided into an intervention group and a control group. In the intervention group, the following oral care was provided daily over a 5-min period in the morning starting at baseline (day of surgery) and continued for 5 days: gargling with povidone iodine, tooth brushing, denture cleaning using a special brush and tongue cleaning using a tongue brush. In the control group, the subjects only gargled with povidone iodine. We compared the following variables between the two groups at baseline and 5 days later: the sensation of dry mouth, intra-oral gas concentration, pulmonary sounds, body temperature and bacterial flora. The number of patients with abnormal pulmonary sounds (dry or moist rales) increased from 1 to 2 in the intervention group and from 0 to 4 in the control group (P < 0.05). The average number of bacterial species per subject for the control group was 3.64 +/- 1.34 pre-operatively and 3.50 +/- 1.74 post-operatively, whereas that for the intervention group was 3.08 +/- 0.95 pre-operatively and 2.62 +/- 0.65 post-operatively. In the intervention group, there was a significant decrease in the number of bacterial species (P < 0.05). These findings indicate that post-operative oral care in elderly patients undergoing digestive tract surgery lowers the number of bacterial species found in the oral cavity. This effect, in turn, might improve respiratory function.


[Cell saver].
The blood retrievers are instruments increasingly used in operating rooms. They are especially useful in operations where there is a high risk of bleeding and transfusion requirements are high. In paediatrics is of great importance in complex interventions in order to avoid allogeneic transfusion (blood collected from donors). The implementation of the recovery of blood in the surgical field is very simple and easy to use. This is a suction tube that collects the blood that is free, transferring it to a centrifuge where it is filtered and washed, stored in a blood collection bag for subsequent infusion. The blood is of high quality and contains a high hematocrit blood from the bank.