Brexpiprazole: A Review in Schizophrenia.
Brexpiprazole (Rxulti®, Rexulti®) is an oral atypical antipsychotic agent approved for the treatment of schizophrenia in the EU (in adult patients) and the USA, as well as in some other countries, including Japan. Like aripiprazole, it is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors. However, brexpiprazole displays less intrinsic activity at D2 receptors and, coupled with actions at 5HT1A, 5HT2A and noradrenaline α1B receptors that are at least as potent as its action at D2 receptors, is predicted to demonstrate a lower propensity for activating adverse events and extrapyramidal symptoms than aripiprazole. Brexpiprazole 2-4 mg/day produced statistically significant and clinically meaningful improvements in overall symptomatology and psychosocial functioning compared with placebo in adults with acute exacerbation of schizophrenia. As maintenance treatment, brexpiprazole 1-4 mg/day significantly delayed the time to relapse compared with placebo in patients who were already stabilized on the drug and was associated with stabilization or continued improvement in patients' symptoms and functioning. Brexpiprazole was generally well tolerated, exhibiting an adverse event profile characterized by a relatively low incidence of activating and sedating adverse effects, small changes in QT interval and metabolic parameters that were not clinically significant, and moderate weight gain. Clinical evidence to date suggests it usefully extends the range of therapeutic options for schizophrenia.


Immunosuppression and Aberrant T Cell Development in the Absence of N-Myristoylation.
N-myristoylation refers to the attachment of myristic acid to the N-terminal glycine of proteins and substantially affects their intracellular targeting and functions. The thymus represents an organ with a prominent N-myristoylation activity. To elucidate the role of protein N-myristoylation for thymocyte development, we generated mice with a T cell lineage-specific deficiency in N-myristoyl transferase (Nmt)1 and 2. Depletion of Nmt activity in T cells led to a defective transmission of TCR signals, a developmental blockage of thymocytes at the transition from double-negative 3 to 4 stages, and a reduction of all the following stages. We could demonstrate that Lck and myristoylated alanine-rich C kinase substrate, two main myristoylated kinases in T cells, were mislocalized in the absence of Nmt activity. N-myristoylation was also indispensable for early and distal TCR signaling events such as CD3ζ, Zap70, and Erk activation and for release of cytokines such as IFN-γ and IL-2. As a consequence, the initiation and propagation of the TCR signaling cascade was severely impaired. Furthermore, we showed that the absence of myristoylation had an immunosuppressive effect on T cells in vivo after treatment with CpG and stimulation of the TCR with the staphylococcal enterotoxin B superantigen. Therefore, protein myristoylation is indispensable in T cell development and activation and its inhibition might offer a novel strategy to achieve immunosuppression.


The DMB promoter: delineation, in vivo footprint, trans-activation, and trans-dominant suppression.
The HLA-DM loci encode the heterodimeric unconventional class II MHC molecules that are coexpressed with conventional class II MHC molecules. DM molecules are essential for the proper formation and function of conventional class II MHC molecules. This report characterizes the DMB promoter both by in vivo footprint and by in vitro functional analysis and reveals a promoter structure similar to that of conventional class II MHC genes. DR-negative mutant cell lines selectively defective in the transcription factor or class II trans-activator (CIITA) were used to reveal a requirement for both these factors in DMB promoter activation. Complementation of defective cell lines with the appropriate transcription factor reconstituted DMB promoter activation. Further analysis with CIITA identified several mutant forms of CIITA that are trans-dominant-negative mutants, i.e., they suppressed DMB promoter activation by transfected and endogenous CIITA. These mutants may be used in abiological setting to down-regulate the function of DM in Ag processing.


Is preoperative intracranial hemorrhage a surgical contraindication in infective endocarditis with stroke?
The optimal timing for surgery in infective endocarditis (IE) with hemorrhagic stroke and neurologic deficits is difficult to decide because of the risk of exacerbating the stroke and provoking intracranial hemorrhagic conversion after surgery using cardiopulmonary bypass (CPB). This retrospective study aimed to investigate the impact of the presence or absence of preoperative intracranial hemorrhage (ICH) on surgical outcomes in IE with recent stroke. The medical records of all patients who underwent open heart surgery for active IE from February 2009 to December 2020 were retrospectively reviewed. Among 164 patients who had surgery for left-sided IE, 71 cases in which the period from stroke onset to surgery was <4 weeks were divided into two groups for analysis. Group A consisted of 49 patients without preoperative ICH and group B consisted of 22 patients with preoperative ICH. There was no significant difference in underlying conditions between the two groups. The two groups had similar rates of postoperative ICH (10.2%, group A vs. 13.6%, group B, P=0.696). The 30-day mortality rate was 8.2% in group A and 4.5% in group B (P=1.000), and the one-year survival was 86.8% in group A and 95.5% in group B (P=0.320). Univariate analysis was performed to identify risk factors for exacerbation of postoperative ICH in the 71 patients, but none of the factors tested showed statistically significant association with the exacerbation of ICH. Preoperative ICH did not appear to increase the risk of exacerbation of postoperative ICH or the early mortality rate after open heart surgery in patients with infectious endocarditis accompanied by recent septic cerebral embolism.


Impaired thiol-disulphide homeostasis in patients with axonal polyneuropathy.
The objective of this study is to examine thiol-disulphide homeostasis in patients with polyneuropathy dominated by diabetic or non-diabetic axonal degeneration. Fifty-four patients diagnosed with polyneuropathy dominated by axonal damage and 41 healthy subjects were included in the study. The patients were grouped into two groups according to whether or not they had diabetes. The native thiol and total thiol concentrations were measured with the newly developed automated method. While there was no significant difference between the patients with diabetic and non-diabetic polyneuropathy in terms of native thiol and total thiol levels (p > 0.05), the native thiol and total thiol levels of the groups with both diabetic polyneuropathy and non-diabetic polyneuropathy were significantly low compared to the control group (p < 0.01). The level of disulphides in the patients with diabetic polyneuropathy was significantly higher than that of the patients with non-diabetic polyneuropathy and the healthy individuals (p < 0.05). The loss in the sural nerve sensory neural action potential amplitude was positively correlated with the decrease in the levels of both native thiol and total thiol (p < 0.05). In our study, we observed that the thiol-disulphide balance was also impaired in patients with non-diabetic polyneuropathy similar to patients with diabetic polyneuropathy, and we therefore considered that impaired the thiol-disulphide homeostasis could be the last common path in patients with polyneuropathy with axonal damage, regardless of the aetiology. Therefore, fortification of thiol deficiency with N-acetyl cysteine or alpha-lipoic acid can fix the thiol-disulphide balance and help decelerate the axonal damage.


Staging of arterial complications of cervical rib: guidelines for surgical management.
Subclavian artery compression by a cervical rib is an uncommon but potentially disabling condition. A series of 12 patients with 15 arterial lesions is reviewed and a staging system proposed to provide guidelines for managing patients with this condition. Stage I lesions have only arterial stenosis and minor poststenotic dilatation and are managed by thoracic outlet decompression, usually consisting of cervical rib resection. Stage II lesions have intrinsic arterial damage usually with subclavian aneurysm formation and require rib resection, aneurysmectomy, and arterial reconstruction. Stage III lesions present with distal thromboembolic complications and require thrombectomy or embolectomy in addition to thoracic outlet decompression and arterial reconstruction. The anatomic and pathophysiologic bases of the syndrome are reviewed and clinical and angiographic examples of each stage are presented.


Catalytic Oxygenative Allylic Transposition of Alkenes into Enones with an Azaadamantane-Type Oxoammonium Salt Catalyst.
The first catalytic oxygenative allylic transposition of unactivated alkenes into enones has been developed using an oxoammonium salt as the catalyst. This reaction converts various tri- and trans-disubstituted alkenes into their corresponding enones with transposition of their double bonds at ambient temperature in good yields. The use of a less-hindered azaadamantane-type oxoammonium salt as the catalyst and a combination of two distinct stoichiometric oxidants, namely, iodobenzene diacetate and magnesium monoperoxyphthalate hexahydrate (MMPP⋅6 H2 O) are essential to facilitate the enone formation efficiently.


Development of stealth liposome formulation of 2'-deoxyinosine as 5-fluorouracil modulator: in vitro and in vivo study.
The aims of this study were to develop a stealth, pegylated liposomal formulation of 2'-deoxyinosine (d-Ino), a 5-fluorouracil (5-FU) modulator, to evaluate its efficacy in vitro and in tumor-bearing mice, and to study its pharmacokinetics in rats. After designing a pegylated liposome encapsulating d-Ino (L-d-Ino), we evaluated its efficacy as 5-FU modulator in vitro. Antiproliferative assays, thymidylate synthase (TS) inhibition, and apoptosis studies were carried out to check whether an optimization of 5-FU action was achieved on the 5-FU-resistant SW620 cell line. Animal pharmacokinetic and ex vivo studies were next performed to confirm that L-d-Ino displayed a slower plasma elimination pattern than free d-Ino. Finally, effects on tumor growth of L-d-Ino + 5-FU combination was evaluated in xenografted mice. We developed a stable, sterile, and homogenous 100-nm population of pegylated liposomes encapsulating 30% of d-Ino. Liposomal d-Ino exhibited a strong potential as 5-FU modulator in vitro by enhancing TS inhibition and subsequent apoptosis induction, while displaying a better pharmacokinetic profile in animals, with a near seven times clearance reduction as compared with the free form. When used in tumor-bearing mice in combination with 5-FU, our results showed next that the association led to 70% of tumor reduction with a doubling median survival time as compared with untreated animals, whereas 5-FU alone was ineffective. Our data show that liposomal d-Ino, through an optimized pharmacokinetic profile, displays a potent effect as fluoropyrimidines modulator, both in vitro and in xenografted mice. Besides, we showed here that it is possible to reverse a resistant phenotype to 5-FU, a major drug extensively described in clinical oncology.


Microwave synthesis of molybdenene from MoS2.
Dirac materials are characterized by the emergence of massless quasiparticles in their low-energy excitation spectrum that obey the Dirac Hamiltonian. Known examples of Dirac materials are topological insulators, d-wave superconductors, graphene, and Weyl and Dirac semimetals, representing a striking range of fundamental properties with potential disruptive applications. However, none of the Dirac materials identified so far shows metallic character. Here, we present evidence for the formation of free-standing molybdenene, a two-dimensional material composed of only Mo atoms. Using MoS2 as a precursor, we induced electric-field-assisted molybdenene growth under microwave irradiation. We observe the formation of millimetre-long whiskers following screw-dislocation growth, consisting of weakly bonded molybdenene sheets, which, upon exfoliation, show metallic character, with an electrical conductivity of ~940 S m-1. Molybdenene when hybridized with two-dimensional h-BN or MoS2, fetch tunable optical and electronic properties. As a proof of principle, we also demonstrate applications of molybdenene as a surface-enhanced Raman spectroscopy platform for molecular sensing, as a substrate for electron imaging and as a scanning probe microscope cantilever.


Tc-99m DTPA renography in children following renal transplantation: its value in the evaluation of rejection.
A retrospective analysis of the value of Tc-99m DTPA DRS in children requiring renal biopsy following transplantation. Thirty-one children following renal transplantation with possible rejection underwent thirty-nine DRS and biopsy within a 72-h period and clinical followed up for 12 months. The biopsy was classified according to the Banff 97. The DRS assessed semi-quantitatively images of renal perfusion and filtration, and the balance between these two images. The clinical notes were reviewed. Based on the biopsy results 15 children had acute rejection, three children chronic rejection, nine children a mixed appearance of both acute and chronic rejection while 12 children had no rejection. Based on the long-term clinical outcome, the DRS had an overall sensitivity of 76% and specificity of 86%. While renal biopsy remains the gold standard for the diagnosis of rejection, if the perfusion and filtration phases of the DRS are analysed separately and the results integrated, there is a possibility of suggesting that acute rejection is not the cause of the increase in creatinine. The DRS provides useful information to the nephrologist when taken in conjunction with the biopsy result and other investigations.


Elastic stiffness of the nuclear-spin system in tetragonal U2D2 nuclear-ordered solid (3)He.
We have measured temperature dependences of sound velocity for both longitudinal and transverse sound in nuclear-ordered U2D2 solid 3He with several crystal orientations along the melting curve. The sound velocity change was proportional to T4 for all sound modes and crystal orientations and was attributed to the nuclear-spin part of the internal energy. We extracted six-independent elastic stiffness of the nuclear-spin part and obtained Grüneisen constants of the spin wave velocity for four-independent strains. Grüneisen constants for compressional strain were larger than those for shear strain. Using the multiple-spin-exchange model, we explain the anisotropy of Grüneisen constants in tetragonal symmetry.


A rare case report of teen-onset pica in a female patient with a clinical high risk for psychosis.
We aimed to further elucidate the under-researched, underdiagnosed and misunderstood comorbid pica in the context of psychosis. We report a case of teen-onset plastophagia in an antipsychotic-naïve girl at ultra-high risk (UHR) for psychosis. HA is a 17-year-old unmarried girl who had a history of good premorbid functioning, no personal psychiatric history and an uncle with schizophrenia. She was referred to our psychiatry department with the complaint of having the habit of eating plastic for about 2 years. A thorough clinical history revealed that she developed, since more than a year, difficulty in school and interpersonal functioning. After clinical evaluation, a diagnosis of UHR with major depressive disorder, iron deficiency anaemia and pica was made. We draw attention to the possibility of an overlap between the pathogenesis of pica and psychosis, and we highlight the importance of early diagnosis and management of both pica and UHR since they can lead to serious medical and mental consequences.


Trehalose Alleviated Salt Stress in Tomato by Regulating ROS Metabolism, Photosynthesis, Osmolyte Synthesis, and Trehalose Metabolic Pathways.
Trehalose plays a critical role in plant response to salinity but the involved regulatory mechanisms remain obscure. Here, this study explored the mechanism of exogenous trehalose-induced salt tolerance in tomato plants by the hydroponic test method. Our results indicated that 10 mM trehalose displayed remarkable plant biomass by improving growth physiology, which were supported by the results of chlorophyll fluorescence and rapid light-response curve. In the salinity environment, trehalose + NaCl treatment could greatly inhibit the decrease of malondialdehyde level, and it increases the contents of other osmotic substances, carbohydrates, K+, and K+/Na+ ratio. Meanwhile, trehalose still had similar effects after recovery from salt stress. Furthermore, trehalose pretreatment promoted trehalose metabolism; significantly increased the enzymatic activity of the trehalose metabolic pathway, including trehalose-6-phosphate synthase (TPS), trehalose-6-phosphate phosphatase (TPP), and trehalase (TRE); and upregulated the expression of SlTPS1, SlTPS5, SlTPS7, SlTPPJ, SlTPPH, and SlTRE under saline conditions. However, the transcriptional levels of SlTPS1, SlTPS5, and SlTPS7 genes and the activity of TPS enzyme were reversed after recovery. In addition, we found that hydrogen peroxide (H2O2) and superoxide anion (O2 -) were accumulated in tomato leaves because of salt stress, but these parameters were all recovered by foliar-applied trehalose, and its visualization degree was correspondingly reduced. Antioxidant enzyme activities (SOD, POD, and CAT) and related gene expression (SlCu/Zn-SOD, SlFe-SOD, SlMn-SOD, SlPOD, and SlCAT) in salt-stressed tomato leaves were also elevated by trehalose to counteract salt stress. Collectively, exogenous trehalose appeared to be the effective treatment in counteracting the negative effects of salt stress.


COVID-19 and Long-Term Outcomes: Lessons from Other Critical Care Illnesses and Potential Mechanisms.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that is currently causing a pandemic and has been termed coronavirus disease (COVID-19). The elderly or those with preexisting conditions like diabetes, hypertension, coronary heart disease, chronic obstructive pulmonary disease, cerebrovascular disease, or kidney dysfunction are more likely to develop severe cases when infected. Patients with COVID-19 admitted to the ICU have higher mortality than non-ICU patients. Critical illness has consistently posed a challenge not only in terms of mortality but also in regard to long-term outcomes of survivors. Patients who survive acute critical illness including, but not limited to, pulmonary and systemic insults associated with acute respiratory distress syndrome, pneumonia, systemic inflammation, and mechanical ventilation, will likely suffer from post-ICU syndrome, a phenomenon of cognitive, psychiatric, and/or physical disability after treatment in the ICU. Post-ICU morbidity and mortality continue to be a cause for concern when considering large-scale studies showing 12-month mortality risks of 11.8-21%. Previous studies have demonstrated that multiple mechanisms, including cytokine release, mitochondrial dysfunction, and even amyloids, may lead to end-organ dysfunction in patients. We hypothesize that COVID-19 infection will lead to post-ICU syndrome via potentially similar mechanisms as other chronic critical illnesses and cause long-term morbidity and mortality in patients. We consider a variety of mechanisms and questions that not only consider the short-term impact of the COVID-19 pandemic but its long-term effects that may not yet be imagined.


Development of a Participatory Health Communication Intervention: An Ecological Approach to Reducing Rural Information Inequality and Health Disparities.
A strong and diverse communication infrastructure is essential for communication to improve health. When that infrastructure is weak, health information fails to reach appropriate audiences; this is a component of information inequality that contributes to health disparities. Approaches to addressing information inequality have either focused on individual-level barriers or exclusively on changing the information environment. Largely missing from information inequality interventions is a multilevel, ecological approach consistent with the ways in which information inequality affects health. This study addresses that gap by describing a participatory intervention in a rural, majority-Latino community. Previous work identified a weak information infrastructure as a major barrier to health: Residents struggled to find timely, relevant information, while stakeholders faced challenges knowing how to reach diverse audiences with critical health-related information. We employed participatory health communication asset mapping to identify health communication resources - safe, trusted spaces, and places - that served three distinct communication functions: informational (i.e., where health information can be provided), conversational (i.e., where residents feel comfortable discussing health issues), and connection (i.e., where a relationship exists). Through a six-step process, community leaders and residents identified communication resources and collaborated to create a communication resource map. We discuss how this study advances the theoretical understanding of integration of culture-centered and ecological approaches for communication to reduce health disparities.


[Analysis of epidemiological features of pelvic fracture].
To investigate the epidemiological features of patients with pelvic fractures. The data of patients with pelvic fractures treated between 2003 and 2007 at our hospital were collected and analyzed through the PACS system and case reports checking system. And analytic items included gender, age, injured sites and type of AO or Young-Burgess classification. A total of 1953 pelvic fractures including 917 males and 930 females were selected and 379 patients hospitalized. The high-risk age of all patients was between 31 and 40 years old. And 81 cases were combined with acetabular fractures and 312 cases other parts fracture. The 61-A type fractures are the most common type fractures of AO classification including 766 males and 853 females. The 61-A2 fracture was one of the most common subtype fractures including 562 males and 433 females. In the Young-Burgess classification, the most common fracture was of APC type including 119 males and 70 females. The APC-I fracture was the most common subtype fractures including 68 males and 41 females. The current investigation has implied the epidemiological features of pelvic fractures treated between 2003 - 2007 in our hospital.


Rates of protein synthesis in different regions of the normotensive and hypertrophied heart in response to acute alcohol toxicity.
The objective of study was (a) to investigate whether protein synthesis in different regions of the heart (i.e. left and right atria, left and right ventricles) expressed equal sensitivity to acute ethanol dosage, and (b) to ascertain whether concomitant cardiac abnormalities (i.e. experimental hypertrophic heart disease) exacerbated these responses. Acute ethanol dosage (75 mmol/kg body weight, i.p.) to mature male Wistar rats reduced the fractional rate of protein synthesis (ks, %/day) in all regions (atria and ventricles) of the normal and overloaded (30 days aortic constricted) hearts. The responses in ks were variable. In normal heart, the atrial tissues showed a slightly greater decrease in ks (approx. -30%) when compared to the ventricular regions (approx -20%). The most pronounced effects occurred in the hypertrophied left ventricular tissues where the depressive effects of ethanol on the rate of protein synthesis were potentiated in the presence of hypertrophy (ks reduced by approx 40%). Other regions of the overloaded heart did not show additional sensitivity to the effects of ethanol on protein synthesis in the presence of chronic hypertension. In conclusion, the deleterious effects of ethanol on the left ventricle are additive in the presence of chronic hypertrophy. These results may have important implications for other cardiac abnormalities where there is also concomitant ethanol exposure.


Role of hydroxyl group and R/S configuration of isostere in binding properties of HIV-1 protease inhibitors.
The crystal structure of the complex between human immunodeficiency virus type 1 (HIV-1) protease and a peptidomimetic inhibitor of ethyleneamine type has been refined to R factor of 0.178 with diffraction limit 2.5 A. The peptidomimetic inhibitor Boc-Phe-Psi[CH2CH2NH]-Phe-Glu-Phe-NH2 (denoted here as OE) contains the ethyleneamine replacement of the scissile peptide bond. The inhibitor lacks the hydroxyl group which is believed to mimic tetrahedral transition state of proteolytic reaction and thus is suspected to be necessary for good properties of peptidomimetic HIV-1 protease inhibitors. Despite the missing hydroxyl group the inhibition constant of OE is 1.53 nm and it remains in the nanomolar range also towards several available mutants of HIV-1 protease. The inhibitor was found in the active site of protease in an extended conformation with a unique hydrogen bond pattern different from hydroxyethylene and hydroxyethylamine inhibitors. The isostere nitrogen forms a hydrogen bond to one catalytic aspartate only. The other aspartate forms two weak hydrogen bridges to the ethylene group of the isostere. A comparison with other inhibitors of this series containing isostere hydroxyl group in R or S configuration shows different ways of accommodation of inhibitor in the active site. Special attention is devoted to intermolecular contacts between neighbouring dimers responsible for mutual protein adhesion and for a special conformation of Met46 and Phe53 side chains not expected for free protein in water solution.


[The first report of 2 imported AIDS cases in Guangzhou].
In March and May 1991, two imported AIDS cases were reported for the first time in Guangzhou. We investigated the cases and found that they have been misdiagnosed, because the doctors were not well familiar with this disease. The investigation showed that clinicians must improve their diagnostic ability. And the surveillance on AIDS must be carried out.


Analysis of Moving-Coil Actuator Jet Injectors for Viscous Fluids.
A jet injector is a device that can be used to deliver liquid drugs through the skin using a fluid jet, without the use of a needle. Most jet injectors are designed and used for the delivery of inviscid liquids, and are not optimized for the delivery of viscous drug compounds. To better understand the requirements for delivering viscous drugs, we have developed a mathematical model of the electromechanics of a moving-coil actuated jet injector as it delivers viscous fluids. The model builds upon previous work by incorporating the nonlinear electrical properties of the motor, compliant elements of the mechanical piston and ampoule system, and the effect of viscosity on injector characteristics. The model has been validated by monitoring the movement of the piston tip and measurements of the jet force. The results of the model indicate that the jet speed is diminished with increasing fluid viscosity, but overshoot and ringing in the jet speed is unaffected. However, a stiffer ampoule and piston will allow for a better control of the jet speed profile during an injection, and reduce ringing. We identified that the piston friction coefficient, the compliance of the injector components, and the viscous properties of the fluid are important determinants of performance when jet-injecting viscous fluids. By expanding upon previous jet injector models, this study has provided informative simulations of jet injector characteristics and performance. The model can be used to guide the design of future jet injectors for viscous fluids.


Systemic lupus erythematosus (SLE): changing concepts and challenges for the new millennium.
SLE is still the prototype experimental animal and human autoimmune disease. The clinical manifestations are so diverse that some have come to regard it as the incumbent 'luetic heir apparent' of the late 20th century. The aberrations of the immune disturbance have up until now defied clear explanation but have certainly generated a level of academic and research interest far greater than the frequency of the disease would initially suggest. The clear understanding of the immune derangements in SLE will probably lead to the understanding of the core mechanisms of the immune system and thus to better ways of its specific manipulation in the management of many other conditions including cancer. Research currently being undertaken on the mechanisms of control of immunologically mediated inflammation and the possible use of immunogenetic therapy in the treatment of various forms of SLE will hopefully further improve SLE related morbidity and mortality.


Evaluation of the Safety and Efficacy of Resection of Endometrial Polyps and Submucosal Fibroids in an Outpatient Setting in a Large District General Hospital in the UK.
Conventionally, endometrial pathologies of varying complexity have been surgically treated as inpatients under a general or regional anesthetic. In this paper, we evaluate the safety and efficacy of hysteroscopic morcellation of endometrial pathology in the form of endometrial polyps (EPs) and submucosal fibroids in an outpatient setting for both simple and complex lesions using the Myosure™ device. Two hundred and forty-nine hysteroscopic resections were performed in an outpatient setting at the < BLINDED FOR REVIEW > from May 2014 to March 2021. The median age of the patients was 54 years. More than half of the patients presented with postmenopausal bleeding; 64% were diagnosed with EPs and 24% with submucous fibroids (SMFs). The size, topography, extension, penetration, and wall classification system scoring system were used to grade them as simple (≤4) or complex (≥5) pathologies. 90% of pathologies were simple (≤4), of which complete resection was carried out in 95% of patients; 10% of the pathologies were complex (≥5), of which 63% had complete resection. Two patients with complex pathologies returned for completion surgery as a two-step procedure. No procedure was abandoned due to the patient intolerance. The median intraprocedure pain score visual analog scale was 5/10 and immediate postprocedure pain score was 1/10. Notably, there was no intra- or post-procedure complications. Outpatient resection of endometrial pathology, both simple and complex, can be safely and effectively performed using hysteroscopic morcellator (Myosure™) and is accepted and well tolerated by patients.


Fructose supports energy metabolism of some, but not all, axons in adult mouse optic nerve.
We used transmission electron microscopy (TEM) and electrophysiological techniques to characterize the morphology and stimulus-evoked compound action potential (CAP), respectively, of the adult mouse optic nerve (MON). Electrophysiological recordings demonstrated an identical CAP profile for each MON. An initial peak, smallest in area and presumably composed of the fastest-conducting axons displayed the lowest threshold for activation as expected for large axons. The second peak, the largest, was presumably composed of axons of intermediate diameter and conduction velocity, and the third peak was composed of the slowest and presumably smallest axons. In 10 mM fructose, the first CAP peak area was reduced by 78%, but the second and third peaks were unaffected. Histological analysis revealed a cross-sectional area of 33,346 microm2, containing 24,068 axons per MON. All axons were myelinated and axon diameter ranged from 0.09 to 2.58 microm, although 80 +/- 6% of the axons were <0.75 microm in diameter and only 0.6 +/- 0.3% of the axons were >2 microm in diameter. After bathing in fructose for 2 h 94 +/- 2% of normal appearing axons were <0.75 microm in diameter and none were >1.5 microm-all of the larger axons being grossly abnormal in structure. We conclude that fructose is unable to support function of the larger axons contributing to the first CAP peak, thus enabling us to identify a distinct population of axons that contributes to that peak.


Extracorporeal shock wave lithotripsy for bladder stones.
Between December 1989 and July 1991, 29 patients with bladder stones were treated on the MPL 9000 extracorporeal shock wave lithotriptor using ultrasound for localisation. The mean stone dimensions were 22.65 x 15.17 mm (< 400 mm2 in 20 patients); 75% of patients required only 1 ESWL session but the largest stone (2025 mm2) required 3. Whilst larger stones tended to require more shock waves, linear regression analysis showed a poor fit and factors other than size (operator experience and stone hardness) may determine the number of shock waves required. Satisfactory fragmentation was obtained in all patients. All were treated under intravenous analgesia without anaesthesia. Three patients also had outflow obstruction and were treated by transurethral resection of the prostate (TURP) on the day after completing ESWL. ESWL prior to TURP reduces the morbidity and operating time associated with endoscopic therapy of bladder stones. Macroscopic fragments remaining after ESWL can be washed out at TURP.


Sexual Violence and Abuse Against Children: A First Review Through the Lens of Environmental Criminology.
Most criminal justice responses to address sexual violence and abuse against children are aimed at identifying and incarcerating offenders or at best, trying to prevent them from reoffending. This policy situation, primarily characterized by tertiary intervention strategies, is exacerbated by a lack of evidence-based knowledge about the circumstances in which this phenomenon occurs. This specific information can inform certain types of primary and secondary prevention strategies. In this study, we are taking the first steps to address this situation by (a) organising and reviewing for the first time the empirical knowledge on this phenomenon according to questions asked by environmental criminologists and crime analysts, that is, the who, what, where, when, and how this phenomenon occurs, and (b) discussing directions for future research. By engaging in this exercise, we argue that environmental criminology can substantially contribute to understanding and informing prevention practices in the field of sexual violence and abuse against children.


Distinguishing between aerobic and anaerobic appearance of dissolved CO2 in intestine during low flow.
Increased intestinal mucosal PCO2 is used to detect the condition of inadequate O2 delivery, i.e., "dysoxia." However, mucosal PCO2 (PmCO2) can arise from oxidative phosphorylation, in which case it would detect metabolism that persists as blood stagnates, and/or from HCO3- neutralization by anaerobically produced metabolic acid, in which event it could represent dysoxia. We measured portal venous PCO2 (PVCO2) directly and PmCO2 indirectly with saline-filled CO2-permeable Silastic balloon tonometers in the intestinal lumen during progressive lethal cardiac tamponade in six pentobarbital-anesthetized dogs. PVCO2 and PmCO2 were relatively constant, differing by approximately 10 Torr until an O2 delivery (DO2) of approximately 1.3 ml.kg-1.min-1 was reached, below which PVCO2 and PmCO2 diverged strikingly, achieving a final difference of 78.7 +/- 35.81 (SD) Torr. To determine whether PCO2 arose from aerobic or anaerobic metabolism, we used the Dill nomogram to predict venous oxyhemoglobin (HbO2v) saturation (%HbO2v) from PVCO2. Portal venous %HbO2 predicted by the Dill nomogram agreed well with measured portal venous %HbO2 during all but the final values, indicating primarily aerobic appearance of PCO2 in venous blood, suggesting that portions of intestine that remained perfused at very low flow produced dissolved CO2 mainly by oxidative phosphorylation. As PmCO2 increased below critical DO2, however, predicted mucosal %HbO2v became strikingly negative, achieving a final value of -192 +/- 106.1%, indicating anaerobic dissolved CO2 production in mucosa. We conclude that PCO2 measured in intestinal lumen can be used to detect dysoxia.


Dichroic filters to protect milliwatt far-infrared detectors from megawatt ECRH radiation.
Dichroic filters have been used to shield effectively the far infrared (FIR) detectors at the interferometer/polarimeter on TEXTOR. The filters consist of metal foils with regular holes, the hole diameter, the mutual spacing and the thickness of the foils are chosen to transmit radiation at the design frequency with transmission >90%. The attenuation at the low frequency end of the bandpass filter is about 30 dB per octave, the high frequency transmission is between 20% and 40%. The filters have been used to block the stray radiation from the megawatt microwave heating beam to the detectors of the FIR interferometer, operating with power on the detector in the milliwatt range. If required, the low frequency attenuation can be still enhanced, without compromising the transmission in the passband. The FIR interferometer used for plasma density and position control is no longer disturbed by electromagnetic waves used for plasma heating.


The effects of strabismus on motor development.
Blindness in young children has been shown to lead to significant motor delay. Few studies to date have evaluated the effects of strabismus and its treatment on motor development. We evaluated nine children prior to and post eye alignment via strabismus surgery to determine the effect of this treatment on motor development. Developmental milestones using the Bayley and modified Denver developmental scale were recorded prior to and post surgery. It was found that in this study sample there was developmental advancement within days of surgery in every case. We feel that eye alignment at an early age in strabismic children is an important factor contributing to age appropriate motor development as measured by developmental milestones. A method for a larger scale objective study to better define the effect of strabismus surgery on motor development is currently being planned.


Enrichment and immunoprecipitation of 22 kDa human growth hormone spiked into human urine.
Approaches to detect whether an athlete has used growth hormone have been intensely investigated by sport organizations for 20 years. This effort has led to a human growth hormone (hGH) isoform ratio test in serum that has been approved by WADA and deployed at three Olympic Games, although a positive case has yet to be reported. We set out to determine whether the ratio test could be applied to urine. First we investigated various ways to extract hGH from spiked urine. We were able to recover 95% using selective centrifugal concentration. This fraction was then subjected to four different commercially available immunoprecipitation kits. The highest yield was obtained with the Invitrogen Dynabeads Protein G kit. Nevertheless it is apparent that these methods do not recover enough hGH for subsequent analysis by mass spectrometry. With further effort greater recovery of the 22 kDa isoform might be achieved, however it is very unlikely that the 20 kDa isoform could be detected. This method may be significantly improved by the application of both nanoparticle and aptamer technology.


A novel point variant in NTRK3, R645C, suggests a role of this gene in the pathogenesis of Hirschsprung disease.
Hirschsprung disease (HSCR) is a developmental disorder characterized by the absence of ganglion cells in the myenteric and submucosal plexuses due to a defect in the migration process of neural crest neuroblasts. Manifestation of the disease has been linked to the dysfunction of two principal signalling pathways involved in the enteric nervous system (ENS) formation: the RET-GDNF and the EDN3-EDNRB receptor systems. However, the NTF3/NTRK3 signalling pathway plays an essential role in the development of the ENS suggesting a potential role for those genes in the pathogenesis of HSCR. We have sought to evaluate the candidature of the NTRK3 gene, which encodes the TrkC receptor, as a susceptibility gene for Hirschsprung disease. Using dHPLC technology we have screened the NTRK3 coding region in 143 Spanish HSCR patients. A total of four previously described polymorphisms and 12 novel sequence variants were detected. Of note, the novel R645C mutation was detected in 2 affected siblings of a HSCR family also carrying a RET splicing mutation. Using bioinformatics tools we observed that the presence of an additional cysteine residue might implicate structural alterations in the mutated protein. We propose haploinsufficiency as the most probable mechanism for the NTRK3 R645C mutation. NTRK3 and RET mutations in this family only appear together in the HSCR patients, suggesting that they per se are necessary but not sufficient to produce the phenotype. In addition, it is quite probable that the contribution of other still unidentified modifier genes, may be responsible for the different phenotypes (length of aganglionosis) in the two affected members.


Abiotrophia defectiva endocarditis.
A previously healthy 27-year-old Jamaican man presented to the University Hospital of the West Indies with recurrent joint pain, remitting and relapsing fever, and shortness of breath. He was subsequently found to have Abiotrophia defectiva endocarditis. This was the first time this organism had been isolated at our institution. Despite culture directed antibiotics, his clinical course was quite severe with mitral regurgitation and congestive cardiac failure requiring mitral valve replacement. He recovered well postoperatively and is currently being followed at our outpatient cardiology clinic. This report highlights the severe presentation and often poor outcome associated with A. defectiva endocarditis and stresses that the outcome may be improved by early and appropriate surgical intervention.


Frozen State of Sephadex® Gels of Different Crosslink Density Analyzed by X-ray Computed Tomography and X-ray Diffraction.
Water in Sephadex® (crosslinked dextran) gels is known to indicate different freezing behavior which is dependent on the density of the crosslinks, and water in a Sephadex® G25 gel remains partially unfrozen during cooling and crystallizes during rewarming. The mechanism of anomalous ice crystallization during rewarming is still unclear. The objective of this study is to observe the ice grains that form in Sephadex® beads and to comprehend their frozen state with a focus on the ice crystallization during rewarming. Sephadex® beads containing 50 wt % water were prepared and used for the measurements. The observation of the ice grains was carried out by using synchrotron radiation-sourced X-ray CT (computed tomography). XRD (X-ray diffraction) analysis was also conducted to investigate the frozen state. As a result, ice grains that were larger than ~1 μm were hardly observed after the slow cooling of Sephadex® beads, except in the G25 beads. However, at the occurrence of ice crystallization during rewarming, ice grains that were larger than 10 μm appeared in the G25 beads. Using XRD, it was found that small incomplete ice crystals were formed in G25 beads and the presence of glassy water was indicated in the gel. In conclusion, the size and distribution of ice grains that formed in Sephadex® beads were different depending on the density of the crosslinks.


Endovenous ablation of incompetent truncal veins and their perforators with a new radiofrequency system. Mid-term outcomes.
This is a prospective trial investigating endovenous radiofrequency ablation with the EVRF system for the treatment of symptomatic varicose veins. Primary endpoints include one-year anatomical and clinical success and procedure-related complications. Secondary endpoints include adjunctive procedures and recanalization rates, periprocedural pain assessment, and time return to normal activities. In 60 patients with 74 limbs, 58 great saphenous vein, 11 small saphenous vein, 2 anterior accessory saphenous vein, and 3 perforators were ablated. Additional ablations for further improvement were necessary in 28.4%. Clinical success was 94.6%. Anatomical success was 96.0% at one month and 89.2% at one year. Primary ablation success was 77%. Revascularization occurred in 12.1%. Clinically driven repeat ablation rate was 4.0%. Perforator ablation due to segmental revascularization was performed in 5.4%. Complications included one puncture-site infection, three scars, two cases of transient paresthesia, and one skin pigmentation. Periprocedural mean pain score was 2.4 ± 2.6. In 27.0% cases, the patients used analgesics and mean time return was 1.2 ± 0.5 days. The EVRF system yields satisfactory clinical and anatomical midterm outcomes with very low complication rates.


Redundant use of luminance and flashing with shape and color as highlighting codes in symbolic displays.
Three visual search experiments evaluated the benefits and distracting effects of using luminance and flashing to highlight subclasses of symbols coded by shape and color. Each of three general shape/color classes (circular/blue, diamond/red, square/yellow) was divided into three subclasses by presenting the upper half, lower half, or entire symbol. Increasing the luminance of a subclass by a factor of two did not result in a significant improvement in search performance. Flashing a subclass at a rate of 3 Hz resulted in a significantly shorter mean search time (48% improvement). Increasing the luminance of one subclass (by a factor of five) while simultaneously flashing another significantly improved search times by 31% and 43% respectively, compared with nonhighlighted search conditions. In each experiment, the search times for nonhighlighted target subclasses were not affected by the presence of brighter and flashing targets. The failure of the initial experiment to find a significant performance improvement caused by increasing symbol luminance suggested that a larger luminance increase was necessary for this code to be effective. The overall results suggest that using luminance and flashing to highlight subclasses of color- and shape-coded symbols can reduce search times for these subclasses without producing a distraction effect by way of a concomitant increase in the search times for unhighlighted symbols.


Tebentafusp: First Approval.
Tebentafusp (tebentafusp-tebn; Kimmtrak®) is a first-in-class, bispecific gp100 peptide-HLA-A*02:01 directed T cell receptor (TCR) CD3 T cell engager being developed by Immunocore for the treatment of uveal melanoma and malignant melanoma. The TCR arm of tebentafusp binds to HLA-A*02:01-positive uveal melanoma cells and activates polyclonal T cells, through CD3, to release inflammatory cytokines and cytolytic proteins, resulting in the direct lysis of tumour cells. In January 2022, tebentafusp received its first approval in the USA for the treatment of HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma, and in February 2022 received a Positive Opinion from the EU Committee for Medicinal Products for Human Use for the treatment of uveal melanoma. Tebentafusp is under regulatory review for the treatment of metastatic uveal melanoma in the UK, Australia and Canada. Clinical studies of tebentafusp are underway for uveal melanoma and cutaneous melanoma in several countries worldwide. This article summarizes the milestones in the development of tebentafusp leading to this first approval for unresectable or metastatic uveal melanoma.


Psychosis in Parkinson's disease without dementia: common and comorbid with other non-motor symptoms.
Psychosis in Parkinson's disease (PD) is common and associated with a range of negative outcomes. Dementia and psychosis are highly correlated in PD, but the frequency and correlates of psychosis in patients without cognitive impairment are not well understood. One hundred and ninety-one non-demented PD patients at two movement disorders centers participated in a study of neuropsychiatric complications in PD and completed a detailed neurological and neuropsychiatric assessment, including the rater-administered Parkinson Psychosis Rating Scale for hallucinations, delusions, and minor symptoms of psychosis (illusions and misidentification of persons). Psychotic symptoms were present in 21.5% of the sample. Visual hallucinations were most common (13.6%), followed by auditory hallucinations (6.8%), illusions or misidentification of people (7.3%), and paranoid ideation (4.7%). Visual hallucinations and illusions or misidentification of people were the most common comorbid symptoms (3.1%). Depression (P = 0.01) and rapid eye movement behavior disorder symptoms (P = 0.03) were associated with psychosis in a multivariable model. The odds of experiencing psychotic symptoms were approximately five times higher in patients with comorbid disorders of depression and sleep-wakefulness. Even in patients without global cognitive impairment, psychosis in PD is common and most highly correlated with other non-motor symptoms. Screening for psychosis should occur at all stages of PD as part of a broad non-motor assessment. In addition, these findings suggest a common neural substrate for disturbances of perception, mood, sleep-wakefulness, and incipient cognitive decline in PD.


Tellurotungstate-Based Organotin-Rare-Earth Heterometallic Hybrids with Four Organic Components.
A family of unprecedented tellurotungstate-based organotin-rare-earth (RE) heterometallic hybrids [H2N(CH3)2]6H12Na2 {[Sn(CH3)W2O4(IN)][(B-α-TeW8O31)RE(H2O) (Ac)]2}2·25H2O [RE = CeIII (1), PrIII (2), NdIII (3), SmIII (4), EuIII (5), GdIII (6), TbIII (7); HIN = isonicotinic acid, HAc = acetic acid] were synthesized and characterized by elemental analyses, IR spectra, UV spectra, thermogravimetric analyses, powder X-ray diffraction, and single-crystal X-ray diffraction. The polyoxoanionic skeletons {[Sn(CH3)W2O4(IN)][(B-α-TeW8O31)RE(H2O) (Ac)]2}220- of 1-7 are constructed from two symmetrical units {[Sn(CH3)W2O4(IN)][(B-α-TeW8O31)RE(H2O) (Ac)]2}10- linked by two acetate connectors, which not only represent the first inorganic-organic hybrid RE-substituted tellurotungstates involving three different organic ligands, but also stand for the first samples of organotin-RE heterometallic polyoxometalate derivatives. The solid-state luminescent emission properties of 2-5 mainly display the characteristic emission bands of REIII cations, whereas during the emission procedure of 7, [B-α-TeW8O31]10- segments make a nonignorable contribution to the PL behavior of 7 accompanying by the occurrence of the intramolecular energy transfer from O→W LMCT energy to Tb3+ centers. Furthermore, 4@CTAB composites with peanutlike and honeycombed morphologies were prepared by a surfactant cetyltrimethylammonium bromide (CTAB). The time-resolved emission spectra of the 4@CTAB composite with CTAB/4 = 0.033/0.05 consolidate the energy transfer from CTAB to REIII centers. Variable-temperature magnetic susceptibility measurements for 2, 3, and 4 were performed.


Proteins of the turkey erythrocyte membrane.
A new and simplified method is described for preparation of turkey erythrocyte membranes which are essentially devoid of supernatant or nuclear contamination, but retain catecholamine-sensitive adenylate cyclase activity. These membranes have been solubilized in sodium dodecyl sulfate and analyzed by polyacrylamide gel electrophoresis and the major protein components identified. The turkey erythrocyte membranes exhibit a protein profile very similar to that of the human erythrocyte membrane, but contain a protein component of apparent molecular weight of 50000 which is not present in the human membranes. Three surface glycoprotein components of the turkey erythrocyte membranes (apparent molecular weights of 90000, 41000, and 26000) have been identified by periodic acid-Schiff staining of polyacrylamide gels and by cell surface 125I labeling using lactoperoxidase followed by polyacrylamide gel electrophoresis. After deoxycholate solubilization of membranes prepared from iodinated cells, glycoprotein with molecular weights of 90000 and 41000 bind to an infinity column of concanavalin A-Sepharose 4B and elute upon application of methyl alpha-Dmannopyrannoside. The lowest molecular weight glycoprotein component, however does not bind to the insolubilized concanavalin A.


A magnesium-induced RNA conformational switch at the internal ribosome entry site of hepatitis C virus genome visualized by atomic force microscopy.
The 5' untranslated region of hepatitis C virus (HCV) genomic RNA contains an internal ribosome entry site (IRES) element, composed of domains II-IV, which is required for cap-independent translation initiation. Little information on the 3D structure of the whole functional HCV IRES is still available. Here, we use atomic force microscopy to visualize the HCV IRES conformation in its natural sequence context, which includes the upstream domain I and the essential, downstream domains V and VI. The 574 nt-long molecule analyzed underwent an unexpected, Mg(2+)-induced switch between two alternative conformations: from 'open', elongated morphologies at 0-2 mM Mg(2+) concentration to a 'closed', comma-shaped conformation at 4-6 mM Mg(2+). This sharp transition, confirmed by gel-shift analysis and partial RNase T1 cleavage, was hindered by the microRNA miR-122. The comma-shaped IRES-574 molecules visualized at 4-6 mM Mg(2+) in the absence of miR-122 showed two arms. Our data support that the first arm would contain domain III, while the second one would be composed of domains (I-II)+(V-VI) thanks to a long-range RNA interaction between the I-II spacer and the basal region of domain VI. This reinforces the previously described structural continuity between the HCV IRES and its flanking domains I, V and VI.


[Cushing's syndrome due to small cell lung cancer with ectopic production of adrenocorticotropic and parathyroid hormone].
A 72-year-old man was admitted to our hospital because of a tumor-like shadow on a chest X-ray film. At the initial examination, he had clinical signs of Cushing's syndrome: moon face, central obesity, and hypertension. A computed tomographic scan of chest showed an abnormal shadow in the lung (5 x 6 cm) with involvement of the right paratracheal and anterior tracheal lymph nodes, and a right-sided pleural effusion. Small cell lung cancer (extended disease; T2N2M6 stage IV) was diagnosed after a transbronchial biopsy. The concentrations of adrenocorticotropic hormone, cortisol, and parathyroid hormone in plasma were markedly elevated, and there was no circadian rhythm (336 pg/ml. more than 60.1 micrograms ml. and 805 pg/ml, respectively). Fluid obtained by thoracentasis had malignant cells, and the levels of adrenocorticotropic hormone and parathyroid hormone in the effusion (1120 pg/ml and 1810 pg/ml, respectively) were higher than those in serum, which indicates that these hormones were produced by the tumor cells. The patient received chemotherapy and responded well, but he died of respiratory failure 26 months later. The response rate to chemotherapy in elderly patients with lung cancer is said to be comparable to that in younger patients, but treatment may be difficult because of poor performance status and diminished physical capacity. Although patients with lung cancer complicated by Cushing's syndrome have a poor prognosis, this patient survived for more than 2 years after the disease was diagnosed.


The effects of trawling on the benthic fauna of the Gulf of Nicoya, Costa Rica.
Four van Veen grab replicates where collected to sample macrofauna (organism retained on a 500 micron mesh sieve) at four stations in the Gulf of Nicoya, during October 24, 1997, January 16 and April 30, 1998. This information was used to search for any effects of trawling on the benthic fauna. Two stations where located in a trawled area, and two stations where in a protected area. Diversity (H') varied from 2.01 to 3.52 in the trawled area and from 2.13 to 2.78 in the protected area. Diversity was generally higher in the trawled area, and this was in contradiction to what we would have expected from other studies where the trend has been that trawling reduces diversity. Brittlestars and lancelets seemed to be the groups mostly harmed by the trawling, while amphipods where more abundant in trawled areas. The multivariate analyses did not reveal the patterns of faunal change as well as we hoped. This is surely because of our lack of more replicate samples. The multivariate analyses are easily confounded when few sites are analyzed. We have found differences in the type of fauna found in trawled and protected areas and, considering the differences in environmental variables in our stations and our lack of replication, this indicates that there are differences and a larger investigation is in order to reveal its magnitude.


DNA tests in prolific sheep from eight countries provide new evidence on origin of the Booroola (FecB) mutation.
Recent discoveries that high prolificacy in sheep carrying the Booroola gene (FecB) is the result of a mutation in the BMPIB receptor and high prolificacy in Inverdale sheep (FecX(I)) is the result of a mutation in the BMP15 oocyte-derived growth factor gene have allowed direct marker tests to be developed for FecB and FecX(I). These tests were carried out in seven strains of sheep (Javanese, Thoka, Woodlands, Olkuska, Lacaune, Belclare, and Cambridge) in which inheritance patterns have suggested the presence of major genes affecting prolificacy and in the prolific Garole sheep of India, which have been proposed as the ancestor of Australian Booroola Merinos. The FecB mutation was found in the Garole and Javanese sheep but not in Thoka, Woodlands, Olkuska, Lacaune, Belclare, and Cambridge sheep. None of the sheep tested had the FecX(I) mutation. These findings present strong evidence to support historical records that the Booroola gene was introduced into Australian flocks from Garole (Bengal) sheep in the late 18th century. It is unknown whether Javanese Thin-tailed sheep acquired the Booroola gene directly from Garole sheep from India or via Merinos from Australia. The DNA mutation test for FecB will enable breeding plans to be developed that allow the most effective use of this gene in Garole and Javanese Thin-tailed sheep and their crosses.


[Focus on diagnosis and treatment of genetic liver disorders].
The advancement and popularization of molecular diagnostic techniques has challenged and redefined the traditional concept of genetic metabolic disease. Regardless of disease origin, all genetic defects that lead to hepatobiliary dysfunction or structural abnormalities are termed as genetic liver disorders. Online Mendelian Inheritance in Man (OMIM) is a database consisting 693 genetic diseases with clear molecular mechanism of liver related phenotypes. Moreover, the effective measures to control infectious liver disease have strengthened the importance of research in the field of (adult and children) genetic liver disorders at home and abroad by well-recognized hepatologists. Notably, all patients with unexplained hepatopathy and multiple system diseases involving liver and gallbladder needs screening for genetic liver disorders, except for factors such as infection, immunity, drug-related, and anatomical abnormalities. We hope more patients with complicated liver disorders will benefit from definitive diagnosis and effective treatment in the near future with clear explanation of clinical phenotype, genotype, and metabolomics.


Diagnosis and surgical removal of a granulosa-theca cell tumor in a mare.
An 8-year-old mare showed stallion-like behavior and aggressiveness. A granulosa-theca cell tumor was tentatively diagnosed based on history, transrectal palpation, and ultrasonography, and surgically removed. Serological levels of testosterone and inhibin were elevated. Histopathological examination confirmed the diagnosis. The mare recovered and by day 45 could be turned out with other horses.


Leprechaunism: report of two cases and review.
Two new cases of leprechaunism are reported, one of which from consanguinous parents. Both cases show the clinical picture characteristic of this syndrome: severe pre- and postnatal growth failure, psychic backwardness, lack of adipose tissue, cutis laxa; elf-like face, large ears, globular eyes, hypertelorism, micrognathia and various degrees of external genitalia hypertrophy. Endocrinologically, one of the patients shows the syndrome of low T3. The role of the endocrine alterations in the etiology of the syndrome is discussed.


Dynamic Hippocampal and Prefrontal Contributions to Memory Processes and Representations Blur the Boundaries of Traditional Cognitive Domains.
The hippocampus has long been known to be a critical component of the memory system involved in the formation and use of long-term declarative memory. However, recent findings have revealed that the reach of hippocampal contributions extends to a variety of domains and tasks that require the flexible use of cognitive and social behavior, including domains traditionally linked to prefrontal cortex (PFC), such as decision-making. In addition, the prefrontal cortex (PFC) has gained traction as a necessary part of the memory system. These findings challenge the conventional characterizations of hippocampus and PFC as being circumscribed to traditional cognitive domains. Here, we emphasize that the ability to parsimoniously account for the breadth of hippocampal and PFC contributions to behavior, in terms of memory function and beyond, requires theoretical advances in our understanding of their characteristic processing features and mental representations. Notably, several literatures exist that touch upon this issue, but have remained disjointed because of methodological differences that necessarily limit the scope of inquiry, as well as the somewhat artificial boundaries that have been historically imposed between domains of cognition. In particular, this article focuses on the contribution of relational memory theory as an example of a framework that describes both the representations and processes supported by the hippocampus, and further elucidates the role of the hippocampal-PFC network to a variety of behaviors.


Managing abdominal aortic aneurysms: treat the aneurysm and the risk factors.
Abdominal aortic aneurysms (AAAs) are not only a danger in themselves, they also signify underlying vascular disease that warrants intensive cardiovascular risk reduction, especially smoking cessation. Aneurysmal size and the patient's fitness for surgery are the main determinants of timing and method of elective repair. The choice of open surgery vs endovascular repair depends on the patient's condition, preference, and life expectancy, and the surgeon's experience.


Influence of dietary retinyl acetate on normal rat mammary gland development and on the enhancement of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumorigenesis by high levels of dietary fat.
The effect of high levels of dietary fat and retinyl acetate (ROA) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumor development and growth was examined. Female Sprague-Dawley rats, 51-53 days of age, were treated ig with 5 mg DMBA. At 55-57 days of age, the animals were divided into the following dietary treatment groups: A) 4.5% fat [control fat (CF)]; B) CF + 1.0 mmol ROA/kg diet (CF + ROA); C) 20.0% fat [high fat (HF)]; and D) HF + ROA. HF diets significantly increased mammary tumor multiplicity, with or without ROA, but did not significantly influence mammary tumor growth. ROA treatment reduced mammary tumor multiplicity regardless of the level of dietary fat and inhibited mammary tumor growth in the presence of normal levels of dietary fat. High levels of dietary fat did not significantly influence normal mammary gland growth and development. ROA significantly decreased normal mammary gland growth and development regardless of the level of dietary fat. Blood retinoids in rats fed ROA were primarily in the form of retinyl esters, i.e., retinyl linoleate, retinyl palmitate-oleate, and retinyl stearate. Free retinol levels in blood were not significantly influenced by ROA feeding. Blood retinyl ester levels were lower in rats fed the HF + ROA diet as compared to rats fed the CF + ROA diet.


The World Health Organization's Sixty-Eighth World Health Assembly: Updates and Opportunities.
The World Health Assembly (WHA) is the decision-making body of the World Health Organization. Delegates attending the Sixty-Eighth WHA, May 2015, covered a wide range of global challenges and agreed on several key resolutions of importance to nurse leaders. Some of the resolutions adopted relevant for nurse leaders and nursing care such as air pollution, strategies to strengthen epilepsy care, antimicrobial drug resistance, and strategies to strengthen surgical care, are highlighted. Nurse leaders should consider attending the World Health Assembly, as the topics discussed are critical for the future directions of strengthening human resources for health worldwide and, in particular, nursing and midwifery services.


Analysis of functions of delayed echolalia in autistic children.
This study was a preliminary attempt to determine how autistic children used delayed echolalia in naturalistic interactions with familiar people. Fourteen functional categories of delayed echolalia were derived based on videotape analyses of linguistic, extralinguistic, and paralinguistic features. Individual differences in functional usage were apparent across the three subjects. Delayed echolalia was found to vary along the dimensions of interactiveness, comprehension of the utterance produced, and relevance to linguistic or situational context. The diversity of delayed echolalic behavior is discussed in reference to its conventionality, the presence or absence of communicative intent, and its status as symbolic communicative activity.


Eccrine spiradenoma mimicking adenoid cystic carcinoma on fine needle aspiration. A case report.
Although the cytologic features of salivary gland tumors are well recognized, an adnexal skin tumor occurring in the same region, on occasion, may resemble and be confused with a salivary gland neoplasm. A case of eccrine spiradenoma presented as a painful mass in the region of the parotid that mimicked an adenoid cystic carcinoma on fine needle aspiration cytology. Fine needle aspirates of eccrine spiradenoma, a benign cutaneous adnexal tumor, may have findings that mimic those of adenoid cystic carcinoma. Both may have cell balls and rosettelike structures surrounding stromal matrix cores. Recognition of three cell types in eccrine spiradenomas, including epithelial cells, myoepithelial cells and lymphocytes, as compared to a single cell type in adenoid cystic carcinoma, is paramount in avoiding this potential pitfall in cytologic diagnosis.


Benign cephalic histiocytosis--study of a case.
Benign cephalic histiocytosis is a rare, benign, self-healing form of non-X histiocytosis. A case in a 3-month-old girl is reported. The papular eruption involved her face, neck, shoulders and upper trunk. Light and electron microscopic findings and clinical evolution confirmed the diagnosis. The differential diagnosis with the micronodular form of juvenile xanthogranuloma is discussed.


Method for the preparation of derivatives of heptiptycene: toward dual-cavity baskets.
We have developed a novel synthetic method that enables the preparation of functional derivatives of heptiptycene, i.e., cavitands with two juxtaposed cavities. The homocoupling of bicyclic dibromoalkenes is promoted by Pd(OAc)2 (10%) in dioxane (100 °C) to give cyclotrimers in 27-77% yield under optimized reaction conditions (Ph3P, K2CO3, n-Bu4NBr, N2, 4 Å MS). These dual-cavity baskets show a strong π → π* absorption at 241 nm (ε = 939,000 M(-1) cm(-1)), along with a subsequent fluorescence emission at 305 nm.


A novel predictive model based on preoperative blood neutrophil-to-lymphocyte ratio for survival prognosis in patients with gastric neuroendocrine neoplasms.
Evaluate the predictive value of the preoperative blood neutrophil-to-lymphocyte ratio (NLR) on the clinical outcomes of patients with gastric neuroendocrine neoplasms (g-NENs) after radical surgery. The NLR was significantly higher in patients with g-NENs than in matched normal volunteers (P < 0.05). A higher blood NLR was not significantly associated with clinical characteristics (all P > 0.05). According to the multivariate analysis, the NLR was an independent prognostic factor of RFS and OS. Nomograms, including the NLR, Ki-67 index and lymph node ratio, had superior discriminative abilities to predict clinical outcomes. The recurrence rate was 37% (55/147). The median time to recurrence was 9 months; 48 (87%) patients experienced recurrence within the first 2 years. Both the NLR and Ki-67 index were correlated with liver metastases (both P < 0.05) and were also negatively correlated with recurrence time (both P < 0.05). We enrolled 147 patients who were diagnosed with g-NENs and underwent radical surgery. Receiver operating characteristic curve analysis was used to identify the optimal value for blood NLR. Univariate and multivariate survival analysis were used to identify prognostic factors for g-NENs. A nomogram was adopted to predict RFS and OS after surgery. As an independent prognostic factor for g-NENs, blood NLR can improve the predictability of RFS and OS. We recommend that g-NEN patients with a high blood NLR or high Ki-67 index undergo surveillance during the first month and then every 3 months for 2 years post-surgery.


Cometabolic degradation kinetics of TCE and phenol by Pseudomonas putida.
Modeling of cometabolic kinetics is important for better understanding of degradation reaction and in situ application of bio-remediation. In this study, a model incorporated cell growth and decay, loss of transformation activity, competitive inhibition between growth substrate and non-growth substrate and self-inhibition of non-growth substrate was proposed to simulate the degradation kinetics of phenol and trichloroethylene (TCE) by Pseudomonas putida. All the intrinsic parameters employed in this study were measured independently, and were then used for predicting the batch experimental data. The model predictions conformed well to the observed data at different phenol and TCE concentrations. At low TCE concentrations (<2 mg l(-1)), the models with or without self-inhibition of non-growth substrate both simulated the experimental data well. However, at higher TCE concentrations (>6 mg l(-1)), only the model considering self-inhibition can describe the experimental data, suggesting that a self-inhibition of TCE was present in the system. The proposed model was also employed in predicting the experimental data conducted in a repeated batch reactor, and good agreements were observed between model predictions and experimental data. The results also indicated that the biomass loss in the degradation of TCE below 2 mg l(-1) can be totally recovered in the absence of TCE for the next cycle, and it could be used for the next batch experiment for the degradation of phenol and TCE. However, for higher concentration of TCE (>6 mg l(-1)), the recovery of biomass may not be as good as that at lower TCE concentrations.


Discovery of a most remarkable cave-specialized trechine beetle from southern China (Coleoptera, Carabidae, Trechinae).
Xuedytes bellus Tian & Huang, gen. et sp. n. is described from a limestone cave in Du'an Karst of Guangxi, a kingdom of cavernicolous trechine beetles in southern China. From a morphological point of view, Xuedytes Tian & Huang, gen. n. seems to be the most extremely cave-adapted trechines in the world. Superficially, it looks much like Giraffaphaenops Deuve, 2002 in general body shape, in particular the structure of the prothorax, but simultaneously it is similar to Dongodytes (s. str.) Deuve, 1993, based on elytral characters, including chaetotaxy. Hence the new genus seems to represent a lineage intermediate between Giraffaphaenops and Dongodytes (s. str.).


Virtual covariance matrix reconstruction-based adaptive beamforming for small aperture array.
Recently, many robust adaptive beamforming (RAB) algorithms have been proposed to improve beamforming performance when model mismatches occur. For a uniform linear array, a larger aperture array can obtain higher array gain for beamforming when the inter-sensor spacing is fixed. However, only the small aperture array can be used in the equipment limited by platform installation space, significantly weakening beamforming output performance. This paper proposes two beamforming methods for improving beamforming output in small aperture sensor arrays. The first method employs an integration algorithm that combines angular sector and gradient vector search to reconstruct the interference covariance matrix (ICM). Then, the interference-plus-noise covariance matrix (INCM) is reconstructed combined with the estimated noise power. The INCM and ICM are used to optimize the desired signal steering vector (SV) by solving a quadratically constrained quadratic programming (QCQP) problem. The second method proposes a beamforming algorithm based on a virtual extended array to increase the degree of freedom of the beamformer. First, the virtual conjugated array element is designed based on the structural characteristics of a uniform linear array, and received data at the virtual array element are obtained using a linear prediction method. Then, the extended INCM is reconstructed, and the desired signal SV is optimized using an algorithm similar to the actual array. The simulation results demonstrate the effectiveness of the proposed methods under different conditions.


Fistula between the hip and the caecum.
A patient is reported who developed a fistula between the hip and the caecum 39 years after arthrodesis of her hip. She presented with a painful right hip and radiographs showed that the Smith-Petersen nail used for arthrodesis had moved up through the acetabulum and into the pelvic cavity. The nail was removed but within a week a fistula which discharged alimentary contents had developed between the hip and the caecum. The patient was treated conservatively, and three weeks later the fistula had closed.


Pillararene-Based Supramolecular Polymers for Adsorption and Separation.
Supramolecular polymers have attracted increasing attention in recent years due to their perfect combination of supramolecular chemistry and traditional polymer chemistry. The design and synthesis of macrocycles have driven the rapid development of supramolecular chemistry and polymer science. Pillar[n]arenes, a new generation of macrocyclic compounds possessing unique pillar-shaped structures, nano-sized cavities, multi-functionalized groups, and excellent host-guest complexation abilities, are promising candidates to construct supramolecular polymer materials with enhanced properties and functionalities. This review summarizes recent progress in the design and synthesis of pillararene-based supramolecular polymers (PSPs) and illustrates their diverse applications as adsorption and separation materials. All performances are evaluated and analyzed in terms of efficiency, selectivity, and recyclability. Typically, PSPs can be categorized into three typical types according to their topologies, including linear, cross-linked, and hybrid structures. The advances made in the area of functional supramolecular polymeric adsorbents formed by new pillararene derivatives are also described in detail. Finally, the remaining challenges and future perspectives of PSPs for separation-based materials science are discussed. This review will inspire researchers in different fields and stimulate creative designs of supramolecular polymeric materials based on pillararenes and other macrocycles for effective adsorption and separation of a variety of targets.


NRSF/REST regulates the mTOR signaling pathway in oral cancer cells.
The neuron-restrictive silencer factor/repressor element 1-silencing transcription factor (NRSF/REST) was originally discovered as a transcriptional repressor of neuronal genes in non-neuronal cells. However, it was recently reported to be abundantly expressed in several types of aggressive cancer cells, as well as in mature neurons. In the present study, the role of NRSF/REST in the human oral squamous cell carcinoma (SCC) KB cell line was evaluated. NRSF/REST was expressed at a higher level in KB cells when compared with that in normal human oral keratinocytes (NHOKs). Knockdown of NRSF/REST by siRNA reduced cell viability only in KB cells in a time-dependent manner, and this effect was due to the activation of apoptosis components and DNA fragmentation. In addition, knockdown of NRSF/REST disrupted the mTOR signaling pathway which is a key survival factor in many types of cancer cells. For example, the phosphorylation of elF4G, elF4E and 4E-BP1 was significantly reduced in the KΒ cells upon NRSF/REST knockdown. These results imply that NRSF/REST plays an important role in the survival of oral cancer cells by regulating the mTOR signaling pathway.


[Development and Current Status of the Health Education Curriculum of the German Pension Insurance].
The health education curriculum of the German pension insurance comprises 27 patient education programs that are mostly indication-based. The curriculum aims to support the implementation of patient-oriented patient education in German rehabilitation centers. The effectiveness of several of the educational programs was evaluated in controlled trials with heterogeneous results. Overall, the dissemination of the evaluated programs in rehabilitation practice can be recommended. They constitute an essential part of the overall treatment concept, but are often modified in clinical practice. In particular, the physician led modules are frequently conducted in larger group settings. It is currently considered how these routine working conditions might be reflected in the quality assurance system of the German pension insurance and a cross-organizational conceptual framework.


A comparative study of the temporal bone in three populations of man.
A comparative study was made to determine race and sex differences in the temporal bone, to investigate growth relationships, and to establish a basis for phylogenetic studies of the temporal bone and the temporal lobe of the brain. Data on Eskimo, Indian, and white crania were collected from radiographs and directly from the skulls. Of the 25 variables studied, only the minimum diameter of porus failed to demonstrate some difference among the races. Variation between sexes was found for all measurements except the cranial base angle (of deflection) and three angles related to the petrous pyramids. Correlation coefficients indicated that none of the angles are related in any consistent manner to the other variables studied. This is interpreted as further evidence of cranial base stability. The Indians have the lowest, longest squamae, differing most from the whites. The position of squama is more anterior in the Eskimos. Females of each race possess more anteriorly positioned squamae than males. When the squama is more anteriorly located, the porus is in a more posterior position within the squama itself. Strong race variation exists in the shape of porus. In order to establish a basis for phylogenetic studies of the temporal lobe of the brain better reference points for reflecting its size and shape must be found.


Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities.
Prostate cancer is driven by acquired genetic alterations, including those impacting the epigenetic machinery. With African ancestry as a significant risk factor for aggressive disease, we hypothesize that dysregulation among the roughly 656 epigenetic genes may contribute to prostate cancer health disparities. Investigating prostate tumor genomic data from 109 men of southern African and 56 men of European Australian ancestry, we found that African-derived tumors present with a longer tail of epigenetic driver gene candidates (72 versus 10). Biased towards African-specific drivers (63 versus 9 shared), many are novel to prostate cancer (18/63), including several putative therapeutic targets (CHD7, DPF3, POLR1B, SETD1B, UBTF, and VPS72). Through clustering of all variant types and copy number alterations, we describe two epigenetic PCa taxonomies capable of differentiating patients by ancestry and predicted clinical outcomes. We identified the top genes in African- and European-derived tumors representing a multifunctional "generic machinery", the alteration of which may be instrumental in epigenetic dysregulation and prostate tumorigenesis. In conclusion, numerous somatic alterations in the epigenetic machinery drive prostate carcinogenesis, but African-derived tumors appear to achieve this state with greater diversity among such alterations. The greater novelty observed in African-derived tumors illustrates the significant clinical benefit to be derived from a much needed African-tailored approach to prostate cancer healthcare aimed at reducing prostate cancer health disparities.


Analbuminemia: three cases resulting from different point mutations in the albumin gene.
Analbuminemia is a very rare recessive disorder in which subjects have little or no circulating albumin, although albumin is normally the most abundant plasma protein and has many functions. Analbuminemia is caused by a variety of mutations in the albumin gene and is exhibited only by subjects homozygous for the defect. Previously the mutation had been identified at the molecular level in only two human cases; in one case it resulted from an exon-splicing defect, and in the other case it was caused by a nucleotide insertion that caused a frameshift and premature stop codon. In this investigation we identified the mutations in three unrelated subjects from different countries. In each instance a single-nucleotide mutation produced a stop codon, but the mutations occurred at three different sites: (i) in an Italian male a C-->T transition at nt 2368 in the genomic sequence of albumin, (ii) a C-->T transition at nt 4446 for an American female, and (iii) a G-->A transition at nt 7708 in a Canadian male. The size of the albumin fragment that might have been produced for the three cases varied from 31- to 213-amino acid residues, but no evidence for a circulating albumin fragment was obtained. The paradox is that analbuminemia is extremely rare (frequency < 1 x 10(6)); yet the virtual absence of albumin is tolerable despite its multiple functions.


Effects on groundwater microbial communities of an engineered 30-day in situ exposure to the antibiotic sulfamethoxazole.
Effects upon microbial communities from environmental exposure to concentrations of antibiotics in the μg L(-1) range remain poorly understood. Microbial communities from an oligotrophic aquifer (estimated doubling rates of only once per week) that were previously acclimated (AC) or unacclimated (UAC) to historical sulfamethoxazole (SMX) contamination, and a laboratory-grown Pseudomonas stutzeri strain, were exposed to 240-520 μg L(-1) SMX for 30 days in situ using filter chambers allowing exposure to ambient groundwater, but not to ambient microorganisms. SMX-exposed UAC bacterial communities displayed the greatest mortality and impairment (viable stain assays), the greatest change in sensitivity to SMX (dose-response assays), and the greatest change in community composition (Terminal Restriction Fragment Length Polymorphism; T-RFLP). The sul1 gene, encoding resistance to SMX at clinically relevant levels, and an element of Class I integrons, was not detected in any community. Changes in microbial community structure and SMX resistance over a short experimental period in previously nonexposed, slow-growing aquifer communities suggest concentrations of antibiotics 2-3 orders of magnitude less than those used in clinical applications may influence ecological function through changes in community composition, and could promote antibiotic resistance through selection of naturally resistant bacteria.


Synthesis, resolution, and reactivity of benzylmesitylphenylphosphine: a new p-chiral bulky ligand.
The synthesis of P,P'-dimesityl-P,P'-diphenyldiphosphine and benzylmesitylphenylphosphine is described as well as the resolution of the latter ligand by means of homochiral organometallic complexes. The absolute configuration of the phosphine is assigned by NMR spectra, using the homochiral palladacycle as a reference point. The configuration has been confirmed by single crystal X-ray diffraction. Molecular mechanics calculations were performed in [PdCl-(R)-(+)-C10H6CH(Me)NH2(PBnMesPh)], and showed that the rotation around the Pd-P bond is restricted in this complex. [Pd(eta3-2-MeC3H4)Cl(PBnMesPh)] was obtained and used as a precursor in the catalytic hydrovinylation of styrene. Benzylmesitylphenylphosphine has a strong tendency to form phosphapalladacycles by activation of one of the ortho-methyl groups. The formation of this metallacycle from cyclopalladated N-donor derivatives by a ligand-exchange reaction is also described.


Inactivation of Cryptosporidium parvum oocysts in field soil.
Cryptosporidium parvum oocysts from dairy calves are believed to regularly contaminate watersheds. Identifying oocysts and measuring their viability in the natural environment are important elements in estimating the risk posed by this resistant organism. A 152 day field study was conducted to measure the viabilities of oocysts inoculated into 25 sampling points. Water potential, pH, and ammonium content were also measured at the same 25 sampling sites. A three-dimensional mapping program (Surfer) was used to create 3-D maps of the viabilities of C. parvum oocysts and other factors measured during the experiment. The results indicate that 3-D graphical presentation may be a useful means to identify potential sites of greatest risk of oocyst survival and could indicate areas where natural conditions are causing the most rapid oocyst inactivation, and this method can be a means for the future measurement of microorganism inactivation in the natural environment.


Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A Prospective, Single Institution Study.
Glioblastoma multiforme is a highly malignant and aggressive primary brain tumor with a dismal prognosis. We studied the association of immunohistochemical expression of hypoxia inducible factor-1 alpha (HIF-1α), telomerase reverse transcriptase (TERT), isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 with overall survival (OS) in glioblastoma patients uniformly treated by standard of care, with adequate follow-up. In 87 patient samples studied, 59 were male and 28 were female. The median age was 55 years. The median follow-up was 27.7 months and the median overall survival was 14.9 months. Nuclear staining of HIF-1α was expressed in all samples and scored as strong in 42 (48%) and weak in 45 (52%). Multivariable Cox regression revealed strong HIF-1α expression as an independent poor prognostic factor (Hazard Ratio 2.12, 95% CI 1.20 - 3.74, P = 0.01). There was a statistically significant difference in OS (9.8 months vs. 16.3 months) between the "HIF-1α - strong and TERT - strong" and the "HIF-1α - weak and TERT - weak" patient subgroups, as evaluated by Kaplan-Meier analysis (P = 0.005). In our study, HIF-1α expression was an independent predictor of OS. The subgroup of patients with strong expression of both HIF-1α and TERT had the poorest prognosis.


Endocytic pathway of scavenger receptors via trans-Golgi system in bovine alveolar macrophages.
The scavenger receptors are trimeric membrane glycoproteins present on the surface membrane of macrophages and macrophage-derived foam cells and are implicated in the deposition of cholesterol in the arterial walls during atherogenesis. This receptor mediates endocytosis of a diverse alley of negatively charged macromolecules including modified low density lipoproteins. We tried biochemical and morphologic approaches to elucidate in more detail the endocytic and intracellular pathway of the scavenger receptors during endocytosis of acetylated low density lipoproteins (AcLDL) and oxidized LDL (OxLDL) by bovine alveolar macrophages. Biochemically, cell interaction and subsequent intracellular degradation of AcLDL and OxLDL were examined using [125I]AcLDL or [125I]OxLDL. At the ultramorphologic level, the scavenger receptors were detected by a mouse monoclonal antibody against bovine macrophages, D2, with colloidal gold particles (AcLDL-Au or OxLDL-Au particles) as tracer of ligands. The biochemical studies demonstrated that after binding of AcLDL and OxLDL to the cell surface, these ligands were internalized and degraded intracellularly. Immunoelectron microscopy revealed that after a 2-hour incubation at 4 degrees C AcLDL-Au or OxLDL-Au particles were bound to the scavenger receptors present on the cell surfaces. Upon a temperature shift from 4 to 37 degrees C, these particles were concentrated in coated pits and internalized in endosomes. After subsequent dissociation of the particles from the receptors within the endosomes, the ligands were transported to secondary lysosomes, the receptors were transported to a trans-Golgi system. In the Golgi complex, the receptors were packed in secretory vesicles and recycled to the cell surface membrane. The transport and recycling of the receptors via the trans-Golgi system were completely inhibited by incubation below 18 degrees C or pretreatment with monensin. These results suggest that during endocytosis of modified low density lipoprotein, the Golgi complex plays a crucial role in sorting and recycling of the scavenger receptors in macrophages.


Phase transitions in a LiMn2O4 nanowire battery observed by operando electron microscopy.
Fast charge-discharge process has been reported to give a high capacity loss. A nanobattery consisting of a single LiMn2O4 nanowire cathode, ionic liquid electrolyte and lithium titanium oxide anode was developed for in situ transmission electron microscopy. When it was fully charged or discharged within a range of 4 V in less than half an hour (corresponding average C rate: 2.5C), Li-rich and Li-poor phases were observed to be separated by a transition region, and coexisted during whole process. The phase transition region moved reversibly along the nanowire axis which corresponds to the [011] direction, allowing the volume fraction of both phases to change. In the electron diffraction patterns, the Li-rich phase was seen to have the (100) orientation with respect to the incident electron beam, while the Li-poor phase had the (111̅) orientation. The orientation was changed as the transition region moved. However, the nanowire did not fracture. This suggests that a LiMn2O4 nanowire has the advantage of preventing capacity fading at high charge rates.


Acoustic multipole sources for the regularized lattice Boltzmann method: Comparison with multiple-relaxation-time models in the inviscid limit.
In this paper, a variant of the acoustic multipole source (AMS) method is proposed within the framework of the lattice Boltzmann method. A quadrupole term is directly included in the stress system (equilibrium momentum flux), and the dependency of the quadrupole source in the inviscid limit upon the fortuitous discretization error reported in the works of E. M. Viggen [Phys. Rev. E 87, 023306 (2013)PLEEE81539-375510.1103/PhysRevE.87.023306] is removed. The regularized lattice Boltzmann (RLB) method with this variant AMS method is presented for the 2D and 3D acoustic problems in the inviscid limit, and without loss of generality, the D3Q19 model is considered in this work. To assess the accuracy and the advantage of the RLB scheme with this AMS for acoustic point sources, the numerical investigations and comparisons with the multiple-relaxation-time (MRT) models and the analytical solutions are performed on the 2D and 3D acoustic multipole point sources in the inviscid limit, including monopoles, x dipoles, and xx quadrupoles. From the present results, the good precision of this AMS method is validated, and the RLB scheme exhibits some superconvergence properties for the monopole sources compared with the MRT models, and both the RLB and MRT models have the same accuracy for the simulations of acoustic dipole and quadrupole sources. To further validate the capability of the RLB scheme with AMS, another basic acoustic problem, the acoustic scattering from a solid cylinder presented at the Second Computational Aeroacoustics Workshop on Benchmark Problems, is numerically considered. The directivity pattern of the acoustic field is computed at r=7.5; the present results agree well with the exact solutions. Also, the effects of slip and no-slip wall treatments within the regularized boundary condition on this pure acoustic scattering problem are tested, and compared with the exact solution, the slip wall treatment can present a better result. All simulations demonstrate that the RLB scheme with the AMS method is capable of accurately simulating 2D and 3D acoustic generation, propagation, and scattering at zero viscosity.


Reversal of anticoagulant effects in patients with intracerebral hemorrhage.
Anticoagulant therapies are increasingly being used for the treatment and prevention of thromboembolic diseases. A growing incidence of anticoagulant-associated intracranial hemorrhage (AICH) has accompanied the rise in their use. Although the rate of intracerebral hemorrhage (ICH) in patients receiving anticoagulation therapies such as heparin and target-specific oral anticoagulants (TSOAs) is significantly lower than that of vitamin K antagonists (VKAs), the mortality rate remains high. TSOAs have only recently become available for use in clinical practice, and presently, there is a paucity of both clinical data and evidence-based guidelines to assist in the management of TSOA-associated intracerebral hemorrhage. In this article, we review current literature and provide physicians with diagnostic and therapeutic considerations for the management of AICH.


[A process and the prospects for the medical geographic study].
Medical geography is an edge subject crossing many other subjects. It has lately become the focus of attention for the continuously worsening of the living surroundings (earth environment) of the human beings and a series of threats it imposes on human health. This text consists of a comprehensive description of the history of medical geography, a detailed introduction of the research work done in China. What's more, we put forward the idea that disease geography and health geography will become the hotspot in recent study in our country.


Detection of a mucin marker for the adenoma-carcinoma sequence inhuman colonic mucosa by monoclonal antibody AM-3.
The monoclonal antibody AM-3 was raised against mucins extracted from human colorectal carcinomas. It reacted strongly with sections of paraffin wax embedded colorectal carcinoma. In colonic adenoma tissue the percentage of cells expressing the epitope detected by AM-3 correlated with the degree of dysplasia. In contrast to immunohistochemical staining, which did not show the presence of the antigen in histologically normal mucosa, the more sensitive enzyme linked immunosorbent assay (ELISA) and immunoblot assays showed that it was weakly expressed in this tissue. AM-3 reacted with variable frequency with several normal and malignant human tissues, indicating that the detected epitope is not restricted to colonic tissue. In colonic carcinomas it is present on a sialomucin of apparent relative molecular mass of more than 440,000. These data suggest that the antigen detectable with AM-3 may be useful in the assessment of premalignant changes in colonic adenomas.


Teaching stroke patients to dial the telephone.
Two purposes of this study were to determine what percentage of adults who had had cerebrovascular accidents were able to dial and recall telephone numbers, and whether or not the device, the Dial-a-Phone, was an effective instrument to use to teach these patients to dial the telephone. Results indicated that of 73 patients tested, 42 were unable to dial on the pretest. The Dial-a-Phone was effective in teaching 36 of the 42 patients in the mean time of 4.8 minutes of instruction. Right hemiplegics experienced no more difficulties than left hemiplegics. Those who learn to dial the telephone could use this ability as a life-saving skill, as motivation to improve development of communication skills, and as encouragement for functional independence.


The impact of seizures on epilepsy outcomes: A national, community-based survey.
The aim of this study was to examine the impact of seizures on persons living with epilepsy in a national, community-based setting. The data source was the Survey of Living with Neurological Conditions in Canada (SLNCC), a cohort derived from a national population-based survey of noninstitutionalized persons aged 15 or more years. Participants had to be on a seizure drug or to have had a seizure in the past 5 years to meet the definition of active epilepsy. The respondents were further stratified by seizure status: the seizure group experienced ≥1 seizure in the past 5 years versus the no seizure group who were seizure-free in the past ≥5 years regardless of medication status. Weighted overall and stratified prevalence estimates and odds ratios were used to estimate associations. The SLNCC included 713 persons with epilepsy with a mean age of 45.4 (standard deviation 18.0) years. Fewer people in the seizure group (42.7%) reported being much better than a year ago versus those in the no seizure group (70.1%). Of those with seizures, 32.1% (95% confidence interval [95% CI] 18.8-45.3) had symptoms suggestive of major depression (as per the Patient Health Questionnaire-9) compared to 7.7% (95% CI 3.4-11.9) of those without seizures. Driving, educational, and work opportunities were also significantly limited, whereas stigma was significantly greater in those with seizures. This community-based study emphasizes the need for seizure freedom to improve clinical and psychosocial outcomes in persons with epilepsy. Seizure freedom has an important influence on overall health, as those with at least one seizure over the prior 5 years had an increased risk of mood disorders, worse quality of life, and faced significantly more stigma.