Mental Health Providers' Perspectives on What Helps and Hinders in Psychotherapy for Autistic Adults with Co-occurring Mental Health Problems.
Autistic adults experience disproportionate rates of co-occurring mental health problems. Psychotherapy has been recognized as an appropriate treatment approach, but evidence is limited. Researchers used a qualitative research paradigm to explore the experiences of mental health providers who provide psychotherapy to autistic adults. The Enhanced Critical Incident Technique was used to interview 13 mental health providers regarding perceptions of facilitating therapy with autistic adults. This research highlights challenges to providing psychotherapy to autistic adults while also illuminating ways that mental health providers have worked to ameliorate such challenges and create positive experiences in therapy. This research also contrasts therapy for autistic adults relative to the general population. Practice recommendations and suggestions for future research are offered.


Associative learning of likes and dislikes: Some current controversies and possible ways forward.
Evaluative conditioning (EC) is one of the terms that is used to refer to associatively induced changes in liking. Many controversies have arisen in the literature on EC. Do associatively induced changes in liking actually exist? Does EC depend on awareness of the fact that stimuli are associated? Is EC resistant to extinction? Does attention help or hinder EC? As an introduction to this special issue, we will discuss the extent to which the papers that are published in this issue help to resolve some of the controversies that surround EC. We also speculate about possible boundary conditions of EC and attempt to reconcile conflicting results on the functional properties of EC.


Binge-type eating attenuates corticosterone and hypophagic responses to restraint stress.
Binge eating has been associated with stress responses. Data in rats suggest that activation of the hypothalamic-pituitary-adrenal (HPA) axis is suppressed by consumption of a high sucrose diet, and is increased with exposure to a high fat diet. Additionally, the choice to consume a highly palatable food following exposure to a stressor results in reduced corticosterone levels. To test the effects of intermittent access to a high sugar/high fat food on stress hormone levels, rats were given either unrestricted (UR) access to a sucrose-vegetable shortening mixture (SVS) or 2 hour SVS access 7 days (7D) or 3 days (3D) per week for 4 weeks. Rats on the UR and 3D schedules consumed significantly more calories per day than did controls with no access to SVS, and the 7D and 3D rats consumed as many SVS calories in the 2 hour access period as did the UR rats with 24 hour access to SVS. After 4 weeks of access to SVS (UR, 7D, and 3D), rats were briefly restrained. Control and UR rats had elevated corticosterone during and following restraint, whereas there were no differences in corticosterone levels of 7D and 3D rats in response to restraint, as compared to baseline. Post-restraint consumption of chow was significantly decreased in all groups, and consumption of SVS was reduced in the UR, but not the 7D and 3D rats. These data demonstrate that intermittent access to SVS dampens the corticosterone response to restraint stress and that stressful events do not induce bingeing in non-bingeing animals with access to a high sucrose/high fat food.


Dissolution enhancement of tadalafil by liquisolid technique.
This study aimed to enhance the dissolution of tadalafil, a poorly water-soluble drug by applying liquisolid technique. The effects of two critical formulation variables, namely drug concentration (17.5% and 35%, w/w) and excipients ratio (10, 15 and 20) on dissolution rates were investigated. Pre-compression tests, including particle size distribution, flowability determination, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and scanning electron microscopy (SEM), were carried out to investigate the mechanism of dissolution enhancement. Tadalafil liquisolid tablets were prepared and their quality control tests, dissolution study, contact angle measurement, Raman mapping, and storage stability test were performed. The results suggested that all the liquisolid tablets exhibited significantly higher dissolution rates than the conventional tablets and pure tadalafil. FT-IR spectrum reflected no drug-excipient interactions. DSC and XRD studies indicated reduction in crystallinity of tadalafil, which was further confirmed by SEM and Raman mapping outcomes. The contact angle measurement demonstrated obvious increase in wetting property. Taken together, the reduction of particle size and crystallinity, and the improvement of wettability were the main mechanisms for the enhanced dissolution rate. No significant changes were observed in drug crystallinity and dissolution behavior after storage based on XRD, SEM and dissolution results.


Postoperative vomiting and fever following tonsillectomy in Enugu, Nigeria.
To determine the incidence of postoperative vomiting and fever in patients that had tonsillectomy in our centre over a five year period. The hospital records (case files) of patients that had tonsillectomy with or without adenoidectomy under general anaesthesia at the University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria from January 2004 to December 2008 were retrieved and analyzed. Patients that had an adenoidectomy only were excluded. The patients were of the American Society of Anesthesiologists (ASA) I to III status. There were fifty two (52) patients that had tonsillectomy and adenotonsillectomy under general anaesthesia during the period under review. Forty one (41) patients were between the ages of 1-13 years (78%) and eleven (11) patients between the ages of 18-62 years (12%). There were 32 males and 20 females. The average age for all the patients was 9.03 years. There were seven (7) patients with post operative vomiting (13.4%). These included four (4) patients in the paediatric population (9.75%) and three (3) in the adult population (27.2%). Twenty one (21) patients (40.3%) developed postoperative fever. There were no deaths The other significant morbidity was postoperative pain. The number of patients that had tonsillectomy in our center was small compared to other studies. The incidence of postoperative vomiting in this study is lower than that reported from Western World, showing possible racial variations, a trend that has been reported in some earlier studies in Black populations.


Gold derivatives of scorpionates: comparison with the other coinage metal poly(pyrazolyl)borate analogues.
Gold derivatives [Au(Tpx)(PR3)](Tpx = Tp, hydrotris(pyrazol-1-yl)borate or Tp*, hydrotris(3,5-dimethylpyrazol-1-yl)borate; R = Ph or tBu) and [Au(pzTp)(PR3)x](pzTp = tetrakis(pyrazol-1-yl)borate, x = 1 or 2, R = Ph or tBu) have been synthesised and characterized both in solution (1H- and 31P[1H]-NMR) and in the solid state (IR, single crystal X-ray structure analysis, 31P CPMAS). 31P [1H] NMR solution data suggest greater stability of the tetrakis(pyrazolyl)borate relative to those of tris(pyrazolyl)borate. All compounds are fluxional at room temperature. In order to compare [Au(Tp*)(PPh3)] with analogous coinage metal adducts we have synthesized and structurally characterized [Cu(Tp*)(PPh3)] x PPh3 and [Ag(Tp*)(PPh3)] x 2MeCN. In [Au(Tp*)(PPh3)] the gold atom adopts a distorted tetrahedral geometry with <Au-P> 2.181(5) and <Au-N> 2.37(2) angstroms (cf. <Cu-P,N> 2.166(6), 2.098(1) in [Cu(Tp*)PPh3], 2.156(2), 2.075(7) in [Cu(Tp*)(PPh3)] x PPh3; and <Ag-P,N> in [Ag(Tp*)PPh3] x MeCN 2.347(12), 2.35(5) angstroms). There are three independent [Au(Tp*)(PPh3)] molecules in the asymmetric unit of the structure with their PAu...B axes lying on the cell diagonal of a cubic P213 cell, two with the same chirality aligned opposed in direction to the third which is of opposite chirality. A number of Cu, Ag and Au complexes containing scorpionate ligands have also been investigated by 31P cross-polarization magic-angle-spinning (CPMAS) NMR spectroscopy.


Laryngeal and tracheobronchial cough in anesthetized dogs.
Tussigenic sensitivity of laryngeal and tracheobronchial regions to mechanical and chemical stimuli was compared in 22 urethan-alpha-chloralose-anesthetized dogs. In addition, the contribution of myelinated and unmyelinated vagal fibers in mediating laryngeal and tracheobronchial cough was investigated. The intensity of cough was evaluated from changes in esophageal pressure. Whereas all mechanical stimulations and citric acid inhalations into tracheobronchial region elicited cough, only 56.7% of mechanical stimulation and 33.3% of citric acid challenges to larynx were effective. The intensity of tracheobronchial cough was significantly higher than that of laryngeal cough. When mechanical stimulation was conducted under visual control (bronchofiberscope), cough elicitability was found to be higher from tracheal bifurcation and main stem bronchi (62.5-87.5%) than from any laryngeal structure (0-42.9%). During partial block of vagal conduction (cooling to 6 degrees C), mechanical and citric acid tracheobronchial stimulations failed to elicit cough and mechanical laryngeal stimulation was effective only in 1 of 10 dogs. Intensity of cough was strongly decreased when mechanical stimulation followed capsaicin administration into trachea (0.3 ml; 100 micrograms/ml) or intravenously (10 micrograms/kg). We conclude that, in anesthetized dogs, stimulation of tracheobronchial region is more effective and prompt in eliciting cough than stimulation of larynx, myelinated vagal afferent fibers play an important role in mediating mechanically and citric acid-induced tracheobronchial cough and mechanically induced laryngeal cough, and stimulation of tracheobronchial and pulmonary capsaicin-sensitive receptors strongly inhibits mechanically induced cough.


Upregulation of estrogen receptor beta protein but not mRNA predicts poor prognosis and may be associated with enhanced translation in non-small cell lung cancer: a systematic review and meta-analysis.
An increasing number of original studies suggest that estrogen receptor beta (ERβ) expression may be related to non-small cell lung cancer (NSCLC) prognosis; however, the evidence remains inconclusive and conflicting. We aimed to systematically evaluate the expression and prognostic value of ERβ in NSCLC, and to explain the inconsistency between ERβ protein and mRNA level. PubMed, Embase, and Web of Science databases were searched for studies (published before October 6, 2020) reporting the prognostic value of ERβ protein expression in NSCLC. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) were calculated. Transcriptome and survival data of lung adenocarcinoma patients were obtained from public databases for differential expression and survival analyses. Immunohistochemistry (IHC) was performed to examine the ERβ protein expression in 39 NSCLC patients. Western blotting and RT-qPCR were performed to analyze ERβ expression in two paired NSCLC and normal adjacent tissue samples. The effect of methyltransferase-like 13 (METTL3) on ERβ expression was investigated in a lung cancer cell line. Meta-analysis of 23 studies with a total of 3744 patients demonstrated that high protein expression of overall ERβ and cytoplasmic ERβ indicated poor OS (HR: 1.05, 95% CI: 1.00 to 1.10; HR: 1.48, 95% CI: 1.13 to 1.95) in NSCLC. For lung adenocarcinoma especially, high protein expression of both overall/cytoplasmic ERβ and nuclear ERβ suggested poor OS (HR: 1.54, 95% CI: 1.05 to 2.25; HR: 1.36, 95% CI: 1.03 to 1.80). Bioinformatics analysis indicated the expression of ERβ mRNA was not associated with the prognosis of lung adenocarcinoma. Analysis of public databases showed that ERβ mRNA is not highly expressed in tumor tissues, however, IHC results revealed that ERβ protein is highly expressed in NSCLC tissues. We validated this inconsistency in ERβ expression in paired tumors and normal adjacent tissues from patients. Moreover, METTL3 knockdown in the A549 cell line downregulated ERβ protein expression but not ERβ mRNA expression. Our study elucidated the inconsistency between ERβ protein and mRNA expression levels and their prognostic values. The results indicated that METTL3-driven enhanced translation in NSCLC may cause this inconsistency.


[Medical Big Data Analysis Using Machine Learning Algorithms in the Field of Clinical Pharmacy].
Industrial reforms utilizing artificial intelligence (AI) have been progressing remarkably around the world in recent years. In medical informatics, the application of medical big data analytics using AI is also being promoted, and it is expected to provide screening methods for predicting potential adverse drug reactions (ADRs) and discovering new effects. Previously, we developed a unique ADRs analysis system that incorporates Accord.NET, an open-source machine learning (ML) framework written in the programming language C#, and uses the Japanese Adverse Drug Event Report (JADER) database. By using this system to analyze ADRs and screening the cause and severity of ADRs, information can be obtained to evaluate efficacy as well as ADRs. Although both statistical methods and ML are commonly used for prediction, a characteristic difference between them is that the former emphasizes causal relationships and the latter emphasizes prediction results. Therefore, it is important to distinguish between cases where decisions must be made with an emphasis on causality and those where decisions must be made by focusing on unknown risks, and statistical methods and ML should be selected and used as appropriate. Against this backdrop, this paper describes a use case and suggests that the proper use of AI tools to analyze medical big data will help clinical pharmacists practice optimal drug management for each patient.


Deciphering the Functional Composition of Fusogenic Liposomes.
Cationic liposomes are frequently used as carrier particles for nucleic acid delivery. The most popular formulation is the equimolar mixture of two components, a cationic lipid and a neutral phosphoethanolamine. Its uptake pathway has been described as endocytosis. The presence of an aromatic molecule as a third component strongly influences the cellular uptake process and results in complete membrane fusion instead of endocytosis. Here, we systematically varied all three components of this lipid mixture and determined how efficiently the resulting particles fused with the plasma membrane of living mammalian cells. Our results show that an aromatic molecule and a cationic lipid component with conical molecular shape are essential for efficient fusion induction. While a neutral lipid is not mandatory, it can be used to control fusion efficiency and, in the most extreme case, to revert the uptake mechanism back to endocytosis.


Efficacy and safety of once-daily, extended-release hydrocodone in individuals previously receiving hydrocodone/acetaminophen combination therapy for chronic pain.
Hydrocodone/acetaminophen combination analgesics are frequently prescribed for chronic pain management; however, acetaminophen presents potential hepatotoxicity to patients and thus dose limitations. These opioid medications are also widely abused. Once-daily, single-entity hydrocodone (Hysingla™ ER tablets [HYD]) is a novel formulation with abuse-deterrent properties for the management of chronic pain and represents a suitable option for those patients receiving analgesics containing the same opioid analgesic, hydrocodone. This post-hoc analysis evaluated the efficacy and safety of HYD in patients whose primary pre-study analgesic was hydrocodone/acetaminophen analgesics (23-31% of the study populations). Data were analyzed from two Phase III trials, a 12-week randomized, placebo-controlled trial (RCT) and an open-label, 52-week trial. In both trials, a dose-titration period with HYD was followed by respective periods of fixed-dose double-blind (randomized controlled trial [RCT]) or open-label, flexible-dose maintenance treatment. Pain intensity was assessed using a numerical rating scale (0-10, 0 = no pain). For the RCT, primary and sensitivity analyses of pain scores used different approaches to handle missing data. Safety data for both studies were summarized. In the RCT, the mean baseline pain score was 7.3. Pain relief was greater with HYD than placebo during double-blind treatment. In the open-label, flexible-dose trial, the majority of patients were maintained on their titrated dose. Mean baseline pain score was 6.3, about 57% of patients completed the 1-year maintenance period, and mean pain scores were between 3.6 and 4.1 during the maintenance period. Use of supplemental pain medication decreased or was maintained during the maintenance treatment with HYD. Adverse events in both trials were typical of those associated with opioid analgesics. In patients whose primary pretrial analgesic was hydrocodone/acetaminophen combination tablets, single-entity HYD was effective in reducing pain intensity and in maintaining analgesia over time without need for continued dose increase. HYD's safety and tolerability profiles were similar to other opioid analgesics.


Effects of streptozotocin-induced diabetes on taste buds in rat vallate papillae.
Some studies have documented taste changes in patients with diabetes mellitus (DM). In order to understand the relationships between taste disorders caused by DM and the innervation and morphologic changes in the taste buds, we studied the vallate papillae and their taste buds in rats with DM. DM was induced in these rats with streptozotocin (STZ), which causes the death of beta cells of the pancreas. The rats were sacrificed and the vallate papillae were dissected for morphometric and quantitative immunohistochemical analyses. The innervations of the vallate papillae and taste buds in diabetic and control rats were detected using immunohistochemistry employing antibodies directed against protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP). The results showed that PGP 9.5- and CGRP-immunoreactive nerve fibers in the trench wall of diabetic vallate papillae, as well as taste cells in the taste buds, gradually decreased both intragemmally and intergemmally. The morphometry revealed no significant difference in papilla size between the control and diabetic groups, but there were fewer taste buds per papilla (per animal). The quantification of innervation in taste buds of the diabetic rats supported the visual assessment of immunohistochemical labeling, that the innervation of taste cells was significantly reduced in diabetic animals. These findings suggest that taste impairment in diabetic subjects may be caused by neuropathy defects and/or morphological changes in the taste buds.


Distinct requirements for interleukin-6 in airway inflammation induced by diesel exhaust in mice.
To clarify the possible role of interleukin-6 in aggravation of inflammatory responses in diesel exhaust-exposed mice, we compared the infiltration of inflammatory cells and the production of chemokines between interleukin-6-deficient and wild-type mice following 0, 1.0, or 3.0 mg diesel particles/m3 diesel exhaust inhalation for 4 weeks. Exposure to diesel exhaust significantly increased the number of inflammatory cells and the amount of CCL17 and CXCL3 in bronchoalveolar lavage fluids from wild-type mice, but not in interleukin-6-deficient mice. These findings suggest that interleukin-6 plays a critical role in airway inflammatory responses induced by diesel exhaust inhalation.


Antibiotic cement was associated with half the risk of re-revision in 1,154 aseptic revision total knee arthroplasties.
Aseptic revisions comprise 80% of revision total knee arthroplasties (TKAs). We determined the incidence of re-revision TKA, the reasons for re-revision, and risk factors associated with these procedures. We conducted a retrospective cohort study of 1,154 patients who underwent aseptic revision TKA between 2002 and 2013 and were followed prospectively by a total joint replacement registry in the USA. Revision was defined as any operation in which an implanted component was replaced. Patient-, surgeon-, and procedure-related risk factors were evaluated. Survival analyses were conducted. There were 114 re-revisions (10%) with a median time to reoperation of 3.6 years (interquartile range (IQR): 2.6-5.2). The infection rate was 2.9% (34/1,154) and accounted for 30% of re-revisions (34 of 114). In adjusted models, use of antibiotic-loaded cement was associated with a 50% lower risk of all-cause re-revision surgery (hazard ratio (HR) = 0.5, 95% CI: 0.3-0.9), age with a 20% lower risk for every 10-year increase (HR = 0.8, CI: 0.7-1.0), body mass index (BMI) with a 20% lower risk for every 5-unit increase (HR = 0.8, CI: 0.7-1.0), and a surgeon's greater cumulative experience (≥ 20 cases vs. < 20 cases) with a 3 times higher risk of re-revision (HR = 2.8, CI: 1.5-5). Revised TKAs were at high risk of subsequent failure. The use of antibiotic-loaded cement, higher age, and higher BMI were associated with lower risk of further revision whereas a higher degree of surgeon experience was associated with higher risk.


Immunohistochemical localization of the glucocorticoid receptor in pancreatic beta-cells of the rat.
We used a monoclonal antibody against an epitope located in the N-terminal moiety of the rat glucocorticoid receptor to identify the glucocorticoid receptor-containing cells in the rat pancreas. Monospecific polyclonal antisera against insulin, glucagon, somatostatin, and amylase were applied to serial sections in colocalization studies to identify the respective endocrine and exocrine cells. Glucocorticoid receptor immunoreactivity was exclusively present in nuclei and cytoplasm of the beta-cells of pancreatic islets. Western blots using the glucocorticoid receptor antibody resulted in identical 94K immunoreactive proteins in both liver and pancreas. After adrenalectomy, the glucocorticoid receptor immunoreactivity of beta-cells decreased significantly. A computer-assisted method of semiquantitative evaluation of the glucocorticoid receptor immunoreactivity demonstrated a significant decrease in the staining intensity of the beta-cells by 23.5% and in that of insulin antibodies by 10.4%, while amylase immunoreactivity was only slightly decreased. Serum levels of corticosterone determined by RIA decreased from 225 micrograms/ml in sham-operated animals to 55 micrograms/ml in animals 14 days after adrenalectomy, while the tissue content of amylase decreased by 45%. The immunohistochemical findings give circumstantial evidence of the presence of glucocorticoid receptor in beta-cells. We interpret our data as indicating an indirect effect of glucocorticoids on amylase synthesis via a glucocorticoid-insulin-exocrine cell pathway.


Diagnosis, Course, and Management of Angioedema in Patients With Acquired C1-Inhibitor Deficiency.
Acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) is a rare disease with no prevalence data or approved therapies. To report data on patients with C1-INH-AAE followed at Angioedema Center, Milan (from 1976 to 2015). Diagnostic criteria included history of recurrent angioedema without wheals; decreased C1-INH antigen levels and/or functional activity of C1-INH and C4 antigen less than 50% of normal; late symptom onset (>40 years); no family history of angioedema and C1-INH deficiency. In total, 77 patients (58% females; median age, 70 years) were diagnosed with C1-INH-AAE and 675 patients with hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) (1 patient with C1-INH-AAE/8.8 patients with C1-INH-HAE). Median age at diagnosis was 64 years. Median time between symptom onset and diagnosis was 2 years. Sixteen patients (21%) died since diagnosis, including 1 because of laryngeal edema. Angioedema of the face was most common (N = 63 [82%]), followed by abdomen (N = 51 [66%]), peripheries (N = 50 [65%]), and oral mucosa and/or glottis (N = 42 [55%]). Forty-eight of 71 patients (68%) had autoantibodies to C1-INH. In total, 56 patients (70%) used on-demand treatment for angioedema including intravenous pdC1-INH 2000 U (Berinert, CSL Behring, Marburg, Germany) (N = 49) and/or subcutaneous icatibant 30 mg (Firazyr, Shire; Milano, Italy) (N = 27). Eventually, 8 of 49 patients receiving pdC1-INH became nonresponsive; all had autoantibodies. Thirty-four patients received long-term prophylaxis with tranexamic acid (effective in 29) and 20 with androgens (effective in 8). The incidence of C1-INH-AAE was 1 for every 8.8 patients with C1-INH-HAE. Thirty percent of the deaths were related to the disease. Treatments approved for C1-INH-HAE are effective in C1-INH-AAE, although with minimal differences.


Function of cardiac M3 receptors.
1. Since the initial identification of the M3 subtype of muscarinic acetylcholine receptors (M3-mAChR) in the heart, there have been increasing interest and advances in studies on the pathophysiological roles of M3-mAChR in the heart. Recent studies from several laboratories have provided compelling and solid evidence in support of the important roles of M3-mAChR in regulation and maintenance of cardiac function and in generation and progression of heart disease as well. 2. The functions of the cardiac M3-mAChR revealed thus far include (i) M3-mAChR regulation of heart rate and cardiac repolarization, (ii) modulation of inotropic effects, (iii) cytoprotection against ischaemic injuries of myocardium, (iv) regulation of cell-to-cell communication, and (v) participation in generation and maintenance of atrial fibrillation. 3. Signal transduction mechanisms underlying these pathophysiological functions have also been studied, which have allowed us to get insight into the following mechanistic aspects. (i) M3-mAChR activates a delayed rectifying K+ current I(KM3) to participate in cardiac repolarization, negative chronotropic actions, and anti-dysrhythmic (suppresses ischaemic dysrhythmias) as well as pro-dysrhythmic (facilitates atrial fibrillation) actions. (ii) M3-mAChR interacts with gap-junctional channel connexin 43 to maintain cell-cell communication and excitation propagation. (iii) M3-mAChR regulates intracellular phosphoinositide hydrolysis to improve cardiac contraction and haemodynamic function. (iv) M3-mAChR activate anti-apoptotic signalling molecules, enhances endogenous antioxidant capacity, and diminishes intracellular Ca2+ overload, all of which contribute to protecting the heart against ischaemic injuries. 4. This article provides an overview of the potential roles of the M3-mAChR in parasympathetic control of heart function under normal physiological conditions and in the setting of a variety of pathological processes including heart failure, myocardial ischaemia and dysrhythmias.


Microsomal glutathione transferase 1 attenuated ROS-induced lipid peroxidation in Apostichopus japonicus.
Microsomal glutathione transferase (mGST) is a membrane bound glutathione transferase in multifunctional detoxification isoenzymes family and also plays crucial roles in innate immunity. In the present study, a novel microsomal GST homology was identified from Apostichopus japonicus (designated as AjmGST1) by RACE approaches. The full-length cDNA of AjmGST1 was of 1296 bp encoded a protein of 169 amino acids residues. Multiple sequence alignment and phylogenetic analysis together supported that AjmGST1 belonged to a new member in invertebrates mGST family. Spatial expression analysis revealed that AjmGST1was ubiquitously expressed in all examined tissues with the larger magnitude in tentacle. Time-course expression of AjmGST1 mRNA in coelomocytes was up-regulated after Vibrio splendidus challenge from 6 h until 72 h with the peak expression in 24 h, compared with that in the control group. Similarly, the induced expression of AjmGST1 expression was also detected in lipopolysaccharide (LPS) exposed primary coelomocytes. The purified recombinant protein of AjmGST1 showed high activity with GST substrate at pH of 7.0 and temperature of 35 °C. Meantime, the recombinant AjmGST1 depressed H2O2-induced MDA production both in vivo and in vitro. All of these results indicated that AjmGST1 was an important regulator in elimination of lipid peroxidation under immune response.


Selected contribution: estrogen receptor-alpha gene transfer inhibits proliferation and NF-kappaB activation in VSM cells from female rats.
Epidemiological studies have demonstrated that hormone replacement therapy with estrogen (E2) or E2 plus progesterone in postmenopausal women decreases the age-associated risk of cardiovascular disease by 30-50%. Treatment of vascular smooth muscle (VSM) cells with physiological concentrations of E2 has been shown to inhibit growth factor-stimulated cell proliferation. In this study, we tested the hypothesis that E2 inhibits the age-associated increase in VSM cell proliferation by inhibiting nuclear factor (NF)-kappaB pathway. We investigated the effects of E2 treatment and adenovirus-mediated estrogen receptor (ER)-alpha gene transfer on cell proliferation and NF-kappaB activation using VSM cells cultured from 3-mo-old and 24-mo-old Fischer 344 female rats. Our results demonstrate that VSM cell proliferation was significantly increased (P < 0.05) in aged compared with young adult female rats. Treatment of VSM cells with physiological concentrations of E2 inhibited VSM cell proliferation, and this inhibition was significantly greater (P < 0.05) in cells from aged female rats compared with young adults. The inhibitory effects of E(2) on cell proliferation in aged female rats were significantly potentiated by overexpression of the human ER-alpha gene into VSM cells. Constitutive and interleukin (IL)-1beta-stimulated NF-kappaB activation was significantly greater (P < 0.05) in VSM cells from aged compared with young female rats. E2 treatment of VSM cells from aged female rats inhibited both constitutive and IL-1beta-stimulated NF-kappaB activation. ER-alpha gene transfer into VSM cells from aged female rats further augmented the inhibitory effects of E2. In conclusion, our data demonstrate that constitutive and IL-1beta-stimulated NF-kappaB activation is increased in VSM cells from aged female rats due to loss of E2 and this can be restored back to normal levels by ER-alpha gene transfer and E2 treatment. In addition, increased NF-kappaB signaling may be responsible for increased incidence of cardiovascular disease in postmenopausal females.


Neurothekeoma of the eyelid: a case report.
The purpose of this article is to describe a rare benign tumor of nerve sheath origin arising from the eyelid in an elderly male. Local excision was done and histopathological examination revealed a neurothekeoma. Six months later the patient was doing well with no recurrence. The case was unique in that the patient was an elderly male while neurothekeoma is commonly seen on the face of young adults, especially females.


Significantly Enhanced Hydrogen Evolution Activity of Freestanding Pd-Ru Distorted Icosahedral Clusters with less than 600 Atoms.
Freestanding metal nanoclusters can tune, precisely and effectively, the Gibbs free energy (ΔGH ) of atomic hydrogen on the surface of materials. This enables the enhancement of hydrogen evolution activity. In this paper, we report a study of freestanding Pd-Ru distorted icosahedral clusters (ico-clusters) with less than 600 atoms by using a simple one-pot synthesis method. This Pd-Ru ico-cluster can be used as an efficient electrocatalyst for the hydrogen evolution reaction (HER) in acidic water, which is a promising alternative to Pt. The experimental and theoretical results suggest that the face-centered cubic (fcc) freestanding Pd-Ru distorted ico-clusters with less than 600 atoms ensure increased active edges and distorted defect sites, which reduce the coordination number for the atoms on the catalyst surface. Furthermore, Ru is a more effective hydrogen dissociation source, whereas Pd has a better hydrogen storage function. Pd-Ru can tune the ΔGH of atomic hydrogen adsorbed on a catalyst and reach an optimal equilibrium state that improves the HER performance. Our studies represent a robust approach towards the development of freestanding Pd-Ru distorted ico-clusters and advanced catalysts with non-Pt content for HER and many other heterogeneous reactions.


Using a Human-Centered Design Approach to Determine Consumer Preferences for Long-Lasting Insecticidal Nets in Ghana.
A human-centered design approach, paired with traditional research methods, was used to explore consumer preferences of middle-class Ghanaians for a long-lasting insecticidal net (LLIN) to be designed for the private-sector retail market. In March 2017, we conducted 9 focus groups with urban and rural middle-class Ghanaians across Ashanti, Greater Accra, and Western regions. A total of 78 participants (51 adults and 27 boarding school students) were involved in the focus groups. Participants were asked for their input on topics related to malaria prevention, LLIN perceptions and use behavior, as well as general consumer preferences related to the home and bedroom. They participated in a variety of exercises, such as rank ordering their preferences of various accessories that might be bundled with an LLIN and interacting with actual LLINs of different sizes and designs. The data were gathered and analyzed, using micro-interlocutor analysis framework to capture emergent themes. LLINs are currently available through free distribution channels, but in most accounts, participants reported that the nets were inconvenient, uncomfortable, and not aesthetically pleasing, thus they were undesirable to use. For example, several participants described the process of hanging as well as entering and exiting the LLIN as challenging, stressful, and/or tedious. In addition, use of LLINs was considered to make people feel even hotter in an already warm climate as well as to leave users feeling confined within a small space. Finally, many participants discussed how to improve the look of LLINs including suggestions for additional colors, shapes, and hanging mechanisms to make the LLINs more compatible with their desired bedroom and home décor. Based on the participants' responses, we concluded that they would prefer LLINs that better reflect contemporary sensibilities. We devised and tested different LLIN attributes to address these points, focusing on a more convenient way to hang the net, a more attractive silhouette, and a zipper that allows the user to enter and exit with ease while still maintaining a sealed, mosquito-free space. A separate discrete choice experiment confirmed the attractiveness of these attributes by capturing the target population's willingness to pay for LLINs with said preference-congruent attributes. Our human-centered design approach yielded consumer insights and preferences for novel LLIN designs for the private-sector retail market in Ghana. If this net design is successful, it could increase LLIN use among the middle class and catalyze the purchase of LLINs to support ongoing malaria control efforts.


Antifungal properties of 5-hydroxytryptamine (serotonin) against Aspergillus spp. in vitro.
This study shows that 5-hydroxytrypatmine (5-HT, serotonin) is fungicidal towards conidia and hyphae of clinical isolates of Aspergillus (A.) fumigatus, A. flavus and A. terreus. The minimal fungicidal concentrations for Aspergillus conidia and hyphae ranged between 14.68 to 117.5 mM and 29.37 to 235 mM during 24 and 48 h of incubation. Several serotonin receptor antagonists (5-HT2, 5-HT3) studied in vitro did not influence antifungal activity.


Cu-catalyzed efficient construction of S (Se)-containing functional organosilicon compounds.
A Cu-catalyzed cascade reaction of four-membered silacyclobutanes (SCBs) and thiosulfonates to construct S (Se)-containing organosilicon compounds was developed. The protocol shows a wide range of substrate scope, high functional group compatibility and mild reaction conditions. New C-S (Se) and Si-O bonds were constructed in one step.


Receptor binding of osteoblast-specific factor 1 (OSF-1/HB-GAM) to human osteosarcoma cells promotes cell attachment.
OSF-1/HB-GAM is a member of developmentally regulated growth factors and cytokines. High expression levels of this factor are found in different tissues, e.g., in brain and in bone. We have analyzed the biological function and binding properties of natural OSF-1 to human osteoblasts. Using antibodies raised against the entire OSF-1 molecule or a synthetic carboxy-terminal peptide (amino acids (aa) 110-140) we have investigated the binding sites of rat OSF-1 on human osteoblast-like osteosarcoma cell lines: HOS(TE85) and MG-63. Immunofluorescence microscopic studies and flow cytometric data revealed that OSF-1 is specifically bound to the surface of these cells. Further characterization of the binding sites showed that both osteosarcoma cells express two different kinds of binding sites: Besides binding to a specific OSF-1 receptor, OSF-1 also significantly binds to cell surface heparan sulfates. Using the peptide specific polyclonal antibody we show that the carboxy-terminal domain, aa 110 to 140 of OSF-1, seems to be involved in ligand binding. Studies on the biological function of OSF-1 revealed a strong cell attachment promoting activity in vitro. This activity is not diminished after digestion of cell surface heparan sulfates by heparinase I and heparitinase I, demonstrating that the OSF-1 receptor mediates the cell attachment of osteoblasts. Our results indicate that one biological function of OSF-1 is the promotion of osteoblast attachment to the extracellular bone matrix.


Totally Robotic Reversal of Omega-Loop Gastric Bypass to Normal Anatomy.
Gastric bypass procedures can potentially lead to middle and long-term complications (Podnos et al. Arch Surg 138(9):957-61, 2003). For several years, Roux-en-Y gastric bypass reversal procedures performed by laparotomy or laparoscopic way have been described in literature (Moon et al. Surg Obes Relat Dis 11(4):821-6, 2015). Major complications are anastomotic ulcers, anastomotic complications or functional disorder such as dumping syndrome, hypocalcemia, severe hypoglycemia, and malnutrition (Moon et al. Surg Obes Relat Dis 11(4):821-6, 2015; Campos et al. Surg Obes Relat Dis 10(1):36-43, 2014). One-anastomosis gastric bypass (OAGB) also called omega-loop gastric bypass (OLGB) or mini-gastric bypass (MGB) is a technique that has demonstrated similar results to traditional Roux-en-Y procedures in terms of weight loss and postoperative quality of life (Lee et al. Ann Surg 242(1):20-8, 2005). However, in a recent description of 1000 patients, the percentage of malnutrition was 0.2 % (two patients) with an indication to revert omega-loop gastric bypass back into normal anatomy (Chevallier et al. Obes Surg 25(6):951-8, 2015), but technical details have not been exposed yet. The first robotic gastric bypass was published by Horgan and Vanuno in 2001 (Horgan and Vanuno J Laparoendosc Adv Surg Tech A 11(6):415-9, 2001). The present work describes for the first time a robotic procedure to reverse OLGB into normal anatomy. We present the video report of a 69-year-old woman suffering of severe malnutrition (weight of 42 kg, body mass index of 15.8 kg/m(2), albumin 21 g/l) who had undergone laparoscopic omega-loop gastric bypass 2 years ago (initial weight of 104 kg and initial body mass index of 39.6 kg/m(2)). She was referred to our Bariatric Surgery Unit, and after a period of parenteral nutrition support to improve nutritional status (albumin 32 g/l), we decided in a multidisciplinary staff to perform a reversal omega-loop gastric bypass back into normal anatomy using the DaVinci Si™ system by Intuitive Surgical Inc ®, Sunnyvale, CA. In this high definition video, we present step-by-step robotic reversal of the omega-loop gastric bypass. The procedure began with a careful adhesiolysis of the left lobe of the liver, small gastric pouch, and omega-loop. Then, the gastro-jejunostomy was transected with a 45-mm Endo GIA endocutter with purple staples. The key-point was the creation of a gastro-gastric anastomosis between the small gastric pouch and the excluded stomach. Omega-loop jejunum was resected and the anastomosis was performed in order to avoid intestinal stenosis. The operative time was 232 min. Postoperative course was uneventful and the patient was discharged in postoperative day 8. One month after the procedure, she has gained 10 kg (albumin 34 g/l) and stabilized her nutritional status without further nutritional support. This is the first case described in the literature of a reversal omega-loop gastric bypass into normal anatomy and the first description of the use of a robotic approach. This intervention is challenging, but a feasible procedure. This technology may increase the number of surgeons who are able to provide the benefits of minimal invasive surgery to their patients without the increased risks of complications associated with initial learning curves. The three-dimensional robotic vision, a stable camera, and the multiples degrees of freedom of the robotic instruments are the features that seem to provide greater surgical precision for these complex laparoscopic operations.


Gastric inhibitory polypeptide (GIP) stimulated by fat ingestion in man.
Ten normal volunteers ingested emulsified corn oil and the immunoreactive GIP, insulin (IRI) and nonesterified fatty acid (NEFA) responses were measured. Serum GIP levels increased after the ingestion of corn oil in all subjects, rising from a mean fasting level of 272 pg/ml to 856 +/- 272 pg/ml (P less than 0.05) by 30 minutes. The peak mean serum GIP concentration of 1,345 +/- 291 pg/ml occurred at 60 minutes; and mean serum GIP levels at 180 minutes remained significantly elevated over fasting values. Serum IRI, glucose and NEFA concentrations did not change during the 180 minutes of study. No changes in serum GIP concentrations occurred when, for control purposes, six volunteers ingested water on another day. We conclude: 1) Fat is a potent stimulus for the release of GIP in normal individuals. 2) Endogenously released GIP is not insulinotropic under the conditions of this study.


[Image processing method based on prime number factor layer].
In sport games, since the human body movement data are mainly drawn from the sports field with the hues or even interruptions of commercial environment, some difficulties must be surmounted in order to analyze the images. It is obviously not enough just to use the method of grey-image treatment. We have applied the characteristics of the prime number function to the human body movement images and thus introduce a new method of image processing in this article. When trying to deal with certain moving images, we can get a better result.


USA aid policy and induced abortion in sub-Saharan Africa: an analysis of the Mexico City Policy.
The Mexico City Policy, first announced by US President Ronald Reagan and since lifted and reinstated by presidents along partisan lines, prohibits US foreign assistance to any organisation that performs or provides counselling on abortion. Many organisations affected by this policy are also providers of modern contraception. If the policy reduces these organisations' ability to supply modern contraceptives, it could have the unintended consequence of increasing abortion rates. We empirically examined patterns of modern contraception use, pregnancies, and abortion among women in 26 countries in sub-Saharan Africa in response to the reinstatement and subsequent repeal of the Mexico City Policy across three presidential administrations (William Clinton, George W Bush, and Barack Obama). We combine individual-level data on pregnancies and abortions from 743 691 women, country-year data on modern contraception use, and annual data on development assistance for family planning and reproductive health in a difference-in-difference framework to examine relative changes in use of modern contraception, pregnancy, and abortion in response to the policy. We found that when the Mexico City Policy was in effect (2001-08), abortion rates rose among women in countries highly exposed to the policy by 4·8 abortions per 10 000 woman-years (95% CI 1·5 to 8·1, p=0·0041) relative to women in low-exposure countries and relative to periods when the policy was rescinded in 1995-2000 and 2009-14, a rise of approximately 40%. We found a symmetric reduction in use of modern contraception by 3·15 percentage points (relative decrease of 13·5%; 95% CI -4·9 to -1·4; p=0·0006) and increase in pregnancies by 3·2 percentage points (relative increase of 12%; 95% CI 1·6 to 4·8; p<0·0001) while the policy was enacted. Our findings suggest that curbing US assistance to family planning organisations, especially those that consider abortion as a method of family planning, increases abortion prevalence in sub-Saharan African countries most affected by the policy. The William and Flora Hewlett Foundation, the Doris Duke Charitable Foundation, the David and Lucile Packard Foundation, and the Stanford Earth Dean's Fellowship.


How should diuretic-refractory, volume-overloaded heart failure patients be managed?
Hospitalization is often required for patients with decompensated heart failure, usually with volume overload. Intravenous diuretics are recommended to optimize volume status; however, the management of patients refractory to diuretic therapy is not addressed in American Heart Association/American College of Cardiology, European Society of Cardiology or Heart Failure Society of America guidelines. This review focuses the invasive/interventional cardiologist on the rationale for greater involvement in the care of patients admitted to the hospital with decompensated volume overload, in particular when such patients are diuretic refractory.


Systematic management of graft-versus-host disease (GVHD).
Patients with graft-versus-host disease (GVHD) develop multiple organ failure (MOF), so systematic management is needed. First, patients should be kept in a clean room. Antibiotics, anti-fungal drugs and gamma-globulins are essential for the prevention and treatment of infections. If patients are hypoxic for the nasal cannula or the mask, continuous positive airway pressure (CPAP) or artificial ventilation must be used. In the treatment of hepatic dysfunction, lactulose, branched chain amino acid, glucagon-insulin, and Prostaglandin E1 (PGE1) are given. If plasma exchanges are ineffective, a bilirubin absorption therapy may remain partially effective. In the treatment of renal failure, diuretics, PGE1 and dopamine are given. Hemofiltration and hemodialysis will be effective. But the effective treatment for post-transfusion GVHD is unavailable, so systematic management of GVHD is no more than allopathic treatment.


Hypertensive emergencies in old age: effects of angiotensin converting enzyme inhibition.
Hypertensive emergencies, and to a certain extent their treatment, contribute to morbidity and mortality in elderly patients. We studied 22 hospitalized patients, aged 70-90 years, all of whom had moderate essential hypertensive. During acute hypertension, mean systolic and diastolic blood pressure rose to 230 +/- 24 and 120 +/- 22 mmHg, respectively. Symptoms of reduced tissue perfusion/oxygenation and/or organ failure occurred, forcing us to begin antihypertensive therapy. We administered 50 mg of the angiotensin converting enzyme (ACE) inhibitor captopril sublingually, and within 15 min, systolic blood pressure decreased by an average 60 +/- 16 mmHg and diastolic blood pressure by an average 25 +/- 14 mmHg. There was no significant change in the heart rate. In addition, we treated 22 comparable patients with 10 mg nifedipine sublingually and observed, in four cases, a greater fall in blood pressure (up to 90 mmHg) together with tachycardia. These results show the beneficial effects of captopril in the treatment of hypertensive emergencies in elderly patients. The absence of dangerous side effects indicates that ACE inhibitors can be used as first-choice drugs for the treatment of acute hypertensive crises, even in old age.


Papillary cystadenoma of the epididymis.
Papillary cystadenoma is a rare benign neoplasm of the epididymis, occurring mainly in young adult males. More than one-third of the cases reported in the literature have occurred in patients with von Hippel-Lindau disease. Conversely, epididymal nodules presumed to be papillary cystadenomas are found in one-third of males with von Hippel-Lindau disease. The association is stronger for bilateral tumors. The pathogenesis involves loss of the von Hippel-Lindau gene resulting in overexpression of the angiogenic protein "hypoxia-inducible factor." Papillary cystadenoma is of mesonephric derivation. It originates in the efferent ductules of the head of the epididymis in the form of tiny precursor lesions. Histologically, papillary cystadenoma is characterized by cystic spaces with intracystic papillary projections lined by clear cells, with a resultant resemblance to renal cell carcinoma. Immunohistochemical markers may facilitate the distinction between the 2 tumors. Treatment consists of surgical excision and the prognosis is excellent.


Outcome of myasthenia gravis mothers and their infants.
The aim of this retrospective study was to assess neonatal outcomes of pregnant women with myasthenia gravis (MG). Pregnant women with MG who were treated in our hospital over an 8-year period were enrolled. Data relating to the course of the mother's MG (including the anti-acetylcholine receptor antibody (anti-AchR) titer and drug dosage), delivery mode, delivery course, puerperium period, and neonatal outcomes were obtained from the medical records. Twelve women with MG had 13 pregnancies in our hospital from January 1997 to December 2005. None of the mothers needed intensive care. Two patients delivered vaginally, and ten delivered by cesarean section. Fourteen infants were born at an average gestational age of 37.2 +/- 2.0 weeks; their average birth weight was 2838.6 +/- 724.2 g. Two neonates (14.2%) had a congenital anomaly. Transitory neonatal myasthenia gravis (NMG) was diagnosed in one infant (7.1%). In our study, MG exacerbations occurred in 38.5% of the patients. Postpartum, all MG patients experienced deterioration except one patient who deteriorated in the first trimester with a concomitant upper airway tract infection. Only 1 of the 14 neonates developed transient NMG; the incidence of transient NMG was lower than that previously reported. There was no correlation between the occurrence of NMG and the maternal anti-AChR titer. The cesarean section rate was approximately 33%; this high rate of elective cesarean sections in these MG patients could have prevented the occurrence of some of the complications related to vaginal delivery.


The passive, human calf muscles in relation to standing: the non-linear decrease from short range to long range stiffness.
During human standing, tonic ankle extensor torque is required to support the centre of mass (CoM) forward of the ankles, and dynamic torque modulation is required to maintain unstable balance. Passive mechanisms contribute to both but the extent is controversial. Some groups have revealed a substantial intrinsic stiffness (65-90%) normalized to load stiffness, 'mgh'. Others regard their methodology as unsuitable for the low-frequency conditions of quiet standing and believe the passive contribution to be small (10-15%). Here we applied low-frequency ankle rotations to upright subjects who were supported at the waist allowing the leg muscles to be passive and we report normalized stiffness. The passive calf muscles provided: (i) an extensor torque capable of sustaining unstable balance without tonic activity at a mean CoM-ankle angle of 1.6 deg, (ii) a long range stiffness of 13 +/- 2% and (iii) a short range (< 0.2 deg) stiffness of 67 +/- 8%. Chordal ankle stiffness, derived from the torque versus angle relationship for 7 deg rotations, shows a non-linear decrease (stiffness alpha rotation(-0.33+/-0.04)) from 101 +/- 9% to 19 +/- 5% for rotations of 0.03-7 deg, respectively. Thus, passive stiffness is well adapted for the continuum of postural and movement activity and has a substantial postural role eliminating the need for continuous muscle activity and increasing the unstable time constant of the human inverted pendulum. Ignoring the non-linear dependence of passive stiffness on sway size could lead to serious misinterpretation of experiments using perturbations and sensory manipulations such as eye closure, sway referencing and altered support surfaces.


Screening and Validation of Highly-Efficient Insecticidal Conotoxins from a Transcriptome-Based Dataset of Chinese Tubular Cone Snail.
Most previous studies have focused on analgesic and anti-cancer activities for the conotoxins identified from piscivorous and molluscivorous cone snails, but little attention has been devoted to insecticidal activity of conotoxins from the dominant vermivorous species. As a representative vermivorous cone snail, the Chinese tubular cone snail (Conus betulinus) is the dominant Conus species inhabiting the South China Sea. We sequenced related venom transcriptomes from C. betulinus using both the next-generation sequencing and traditional Sanger sequencing technologies, and a comprehensive library of 215 conotoxin transcripts was constructed. In our current study, six conotoxins with potential insecticidal activity were screened out from our conotoxin library by homologous search with a reported positive control (alpha-conotoxin ImI from C. imperialis) as the query. Subsequently, these conotoxins were synthesized by chemical solid-phase and oxidative folding for further insecticidal activity validation, such as MTT assay, insect bioassay and homology modeling. The final results proved insecticidal activities of our achieved six conotoxins from the transcriptome-based dataset. Interestingly, two of them presented a lot of high insecticidal activity, which supports their usefulness for a trial as insecticides in field investigations. In summary, our present work provides a good example for high throughput development of biological insecticides on basis of the accumulated genomic resources.


Expression of murine Fc receptors for IgG.
There are two distinct genes that encode murine low affinity Fc gamma RII, murine Fc gamma RII alpha, and murine Fc gamma RII beta, which are transcribed in specific cell lineages. Fc gamma RII alpha transcripts are present in macrophages, NK cells, and mesangial cells; Fc gamma RII beta transcripts are expressed in Fc gamma R-bearing B cells, T cells, and macrophages. We have devised a sandwich ELISA to quantify the expression of Fc gamma RII alpha protein. The ELISA is specific for Fc gamma RII alpha, and does not detect the closely related Fc gamma RII beta protein. Upon stimulation with IFN-gamma the Fc gamma RII beta- macrophage cell line J774a expressed a twelvefold enhanced level of Fc gamma RII alpha protein. Peritoneal macrophages synthesized varying amounts of Fc gamma RII alpha. High levels of Fc gamma RII alpha were observed in resident and thioglycollate-elicited peritoneal macrophages, but no Fc gamma RII alpha was detected in Bacillus Calmette Guérin-elicited macrophages. J774a cells stimulated with rIL-6 bound approximately twice as much anti-Fc gamma RII mAb 2.4G2 IgG as did unstimulated controls. However, the Fc gamma RII alpha-specific ELISA showed no change in the amount of Fc gamma RII alpha expressed. A probe encompassing the extracellular coding sequence of Fc gamma RII beta hybridized to two distinct transcripts that were elevated in rIL-6-stimulated J774a cells. One of these transcripts had the same mobility in electrophoresis as Fc gamma RII alpha mRNA and hybridized to an Fc gamma RII alpha-specific probe, whereas the other transcript was larger and did not hybridize to probes specific for either Fc gamma RII alpha or Fc gamma RII beta. Moreover, we confirmed, with an Fc gamma RII beta-specific probe, that J774a cells do not make Fc gamma RII beta mRNA. Thus, the larger transcript appears to encode a novel Fc gamma RII. We suggest that the increased level of binding of the anti-Fc gamma RII mAb 2.4G2 to rIL-6-induced cells represents translation of a Fc gamma R distinct from Fc gamma RII alpha or Fc gamma RII beta.


[ASC-J9 for castration-resistant prostate cancer].
Androgen deprivation therapy has been the standard treatment for the patients with advanced prostate cancer. Androgen deprivation therapy initially suppresses the growth of prostate cancer. However, most patients eventually progress to castration-resistant prostate cancer. Novel drugs, including enzalutamide and abiraterone acetate, are recently able to be used for the patients with castration-resistant prostate cancer. Even so, the therapeutic options for castration-resistant prostate cancer are not enough. Interestingly, androgen receptor degradation enhancer ASC-J9 is reported to degrade the androgen receptor, resulting in the suppression of the growth in castration-resistant prostate cancer cells. In this chapter, ASC-J9 for prostate cancer is reviewed.


The investigated case of etiology of chylous pleural effusion: Ataxia-telangiectasia.
Ataxia-telangiectasia is an autosomal recessive, rare, neurodegenerative multisystem disorder characterized by ataxia-telangiectasia, cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure associated with increased malignancy risk. Clinical diagnosis is made with ataxia-telangiectasia mutated (ATM) gene. Our case, who was diagnosed as ataxia-telangiectasia while investigating the etiology of chylous pleural effusion, is presented because of its rare occurrence.


A Comprehensive Procedure to Evaluate the In Vivo Performance of Cancer Nanomedicines.
Inspired by the success of previous cancer nanomedicines in the clinic, researchers have generated a large number of novel formulations in the past decade. However, only a small number of nanomedicines have been approved for clinical use, whereas the majority of nanomedicines under clinical development have produced disappointing results. One major obstacle to the successful clinical translation of new cancer nanomedicines is the lack of an accurate understanding of their in vivo performance. This article features a rigorous procedure to characterize the in vivo behavior of nanomedicines in tumor-bearing mice at systemic, tissue, single-cell, and subcellular levels via the integration of positron emission tomography-computed tomography (PET-CT), radioactivity quantification methods, flow cytometry, and fluorescence microscopy. Using this approach, researchers can accurately evaluate novel nanoscale formulations in relevant mouse models of cancer. These protocols may have the ability to identify the most promising cancer nanomedicines with high translational potential or to aid in the optimization of cancer nanomedicines for future translation.


Plant growth promoting potential of free-living diazotrophs and other rhizobacteria isolated from Northern Indian soil.
The viable count of free-living diazotrophic bacteria in different crop rhizospheres varied from 1.11 x 10(4) to 8.5 x 10(5) CFU/g of soil. The majority of the diazotrophs phenotypically belong to either Azotobacter chroococcum, non-A. chroococcum type and to a heterogenous group tentatively named putative nitrogen-fixing (PNF) bacteria. In this study, 25 isolates of the PNF group were screened for their multiple plant growth-promoting (PGP) traits and grouped into 5 PGP types. An isolate, PNF(11) showed promising PGP potential in vitro and was characterized as a species of Achromobacter by 16S rRNA analysis. The isolate PNF(11) along with three other previously isolated PGP bacteria, Azotobacter sp. (AZS(3)), fluorescent pseudomonas (Ps(5)), Bacillus sp. (Bc(1)) were selected for crop inoculation response in green house experiment on Vigna radiata var.T44. Plants from inoculated and control pots were sampled and analyzed at 30, 45 and 60 days after sowing for various vegetative, nodule-related data and yield parameters. The findings indicated that selected isolate of PNF bacteria, and other PGP isolates with multiple activities significantly improve the plant growth parameters, yield parameters of Vigna radiata T44 over control and also show good compatibility with Bradyrhizobium inoculation.


[Uterine torsion in cattle - frequency, clinical symptoms and theories about the pathogenesis].
Aim of the present study was to summarize the available literature about the incidence, frequency, clinical symptoms and ideas as to the pathogenesis of uterine torsion in the cow. Analysis of the literature using electronic libraries (Pub Med, Medline), German veterinary medicine journals and obstetrical textbooks. Uterine torsion is a very important maternal reason for dystocia as most cases occur during parturition. The post-cervical torsion (combined uterine and vaginal torsion, Torsio uteri and vaginae) is more commonly diagnosed than an intra-cervical or pre-cervical torsion. Torsions to the left occur more frequently than to the right. Clinical symptoms clearly vary depending on the degree of torsion. The frequency in relation to all parturitions is described as between 0.5 and 1%, whereas the percentage of uterine torsions presented to the veterinarian as a reason for dystocia varies between 2.7 and 65%. The pathogenesis of uterine torsion remains unclear; however, general agreement exists that the cow is predisposed to uterine torsion due to its anatomy. It appears that the Brown Swiss is more often affected than other cattle breeds.


Association of CSF and PET markers of neurodegeneration with electroclinical progression in Lafora disease.
To evaluate the electro-clinical features in association with laboratory and instrumental correlates of neurodegeneration to detect the progression of Lafora disease (LD). We investigated the electro-clinical longitudinal data and CSF Aβ42, p-tau181 and t-tauAg, amyloid, and 18F-FDG PET of five unrelated LD families. Three progressive electro-clinical stages were identified. The early phase was characterized by rare, generalized tonic-clonic and focal visual seizures, followed by the occurrence of myoclonus after a period ranging from 2 to 12 months. The intermediate stage, usually occurring 2 years after the onset of epilepsy, is characterized by a worsening of epilepsy and myoclonus associated with progressive dementia and cerebellar signs. Finally, the late stage, evolving after a mean period of 7 ± 1.41 years from the onset of the disease, was characterized by gait ataxia resulting in bedriddenness, severe dementia, daily/pluri-daily myoclonus, drug-resistant epilepsy, clusters of seizures or status epilepticus, and medical complications. Amyloid (CSF Aβ42, amyloid PET) and neurodegenerative (CSF p-tau181 and t-tauAg, FDG-PET) biomarkers indicate a pattern of cognitive impairment of the non-Alzheimer's disease type. A total of 80% of the LD patients showed more severe hypometabolism in the second FDG-PET scan compared to the first scan performed in a lower phase; the lateral temporal lobe and the thalamus hypometabolism were associated with the presence of intermediate or late phase. Three electroclinical and 18F-FDG PET evolutive stages are useful biomarkers for the progression of LD and could help to evaluate the efficacy of new disease-modifying treatments. The combination of traditional CSF biomarkers improves the diagnostic accuracy of cognitive decline in LD patients, indicating a cognitive impairment of the non-Alzheimer's disease type.


Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to several ecological receptor groups: a short review.
Toxicity among TCDD isomers can vary significantly. Isomers containing four to six chlorine atoms possess the greatest potential for biological activity, as well as the highest acute toxicity. Information available in the literature focuses largely on fish and terrestrial mammal studies. Toxicity data for aquatic invertebrates and plants is wanting, and essentially no studies pertaining to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) accumulation in these organisms could be found. No data were procurable regarding TCDD toxicity in marine mammals or reptiles. Current knowledge is not sufficient to accurately characterize TCDD toxicity in ecological receptors, with quantification of uncertainty being particularly difficult given the limited base of knowledge.


Atrophy of the corpus callosum, cognitive impairment, and cortical hypometabolism in progressive supranuclear palsy.
Recent studies disclosed neurofibrillary degeneration in layer 3 of the association cortex in patients with progressive supranuclear palsy. This lesion may be associated with corpus callosum atrophy and may impair the function of cortical regions indispensable for complex cognitive activity. To investigate whether corpus callosum atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, we studied 10 patients with progressive supranuclear palsy using magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose as a tracer. Compared with 23 age-matched control subjects, the patients had significantly decreased callosal area-skull area ratios, with anterior predominance of the degree of atrophy. The corpus callosum atrophy was accompanied by a decreased mean cortical glucose metabolic rate, predominantly in the frontal region of the cortex, and poor performance on the picture arrangement subtest of the Wechsler Adult Intelligence Scale and the verbal fluency task. We conclude that corpus callosum atrophy with anterior predominance is present in progressive supranuclear palsy, and that this atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, especially in the frontal cortical region. Corpus callosum atrophy may reflect the pathological changes in the cerebral cortex, accentuated in the frontal region, that contribute to the development of frontal lobe dysfunction in this disease.


Long-Term Outcome of Unilateral Acoustic Neuromas With or Without Hearing Loss: Over 10 Years and Beyond After Gamma Knife Radiosurgery.
Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm3 (range, 0.10-23.30 cm3). The median marginal tumor dose was 12.5 Gy (range, 8.0-15.0 Gy) and the median follow-up duration was 153 months (range, 120-216 months). The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively. The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.


Case Report: Hyponatremia Secondary to Desmopressin Administration Prior to Percutaneous Kidney Biopsy: A Case-Based Review.
Bleeding remains the most clinically relevant complication of kidney biopsy and several prophylactic approaches were proposed, including desmopressin administration. We present the case of a 60-year-old man with a history of liver transplantation, admitted for the evaluation of a renal dysfunction. As part of our department protocol, desmopressin 60 μg was administered orally, 2 h before the percutaneous kidney biopsy. The patient developed acute, severe, symptomatic hyponatremia (i.e., headache and recurrent vomiting), followed by a life-threatening upper gastrointestinal bleeding due to a Mallory-Weiss syndrome. Although it is often used as bleeding prophylaxis prior to kidney biopsy, data regarding the efficacy and safety of desmopressin in this setting are inconsistent. Accordingly, we performed a thorough literature review of the use of desmopressin as bleeding prophylaxis prior to kidney biopsy, focusing on the incidence of hyponatremia. The reported incidence of hyponatremia (<130 mmol/l) was 7-11%, probably because serum sodium was monitored in few studies. Nevertheless, hyponatremia was rarely symptomatic but, in some cases, like the one presented here, its complications could be severe. Pre-biopsy low serum sodium and estimated glomerular filtration rate as well as high spot urine sodium and non-restricted fluid intake were reported to be associated with hyponatremia incidence. However, the current evidence cannot clearly establish which patients benefit the most from desmopressin use with respect to bleeding complications. We propose that when desmopressin is used for bleeding prophylaxis prior to kidney biopsy, measurements of serum sodium levels, before and every 6 h after, should complement ultrasound and hemoglobin as part of the patient post-procedural monitoring. Also, water intake should be restricted in the day of biopsy. However, this proposed approach should be adequately evaluated in a clinical trial.


Age-dependent changes in the relative affinity of anti-dinitrophenyl antibodies in mice.
The affinity of anti-DNP antibodies produced by mice of various ages has been studied at the cellular level by the plaque inhibition technique. The affinity of PFC produced shortly after a single injection of antigen was found to increase during the first 6 weeks of life. The responses of 1- and 2-week-old animals also showed apparently restricted heterogeneity. The difference in the affinity of anti-DNP--PFC between young and adult mice could not be attributed to different (serum) levels of antigen or to differences in the rate of maturation of affinity during the immune response. Cell transfer experiments suggested that the age-dependent increase was due to a change in the population of antibody-forming (B) cell precursors and not to a progressive improvement of T-cell function. This findings is interpreted as favouring somatic mutation theories of antibody diversity.


HIV/AIDS patients' knowledge, attitude, and practice toward anti-retroviral therapy medications' adverse effects and associated factors in Tikur Anbessa Specialized Hospital.
Adverse effects (AEs) have been reported with all antiretroviral therapy (ART) medications, and it was among the most common cause for switching or terminating therapy and drug non-adherence. Even though AEs of ART medications are common and to be expected, little study has been conducted on the understanding of patients on the AEs. Therefore, this study aimed to assess patients' knowledge, attitude, and practice (KAP) toward ART medications' AEs and associated factors. A cross-sectional study design was applied using an interviewer-administered questionnaire from June to September 2021 on human immunodeficiency virus/acquired immunodeficiency syndrome patients on follow-up at Tikur Anbessa Specialized Hospital, Ethiopia. Data was gathered, cleaned, and analyzed using SPSS version 23. Logistic regression analysis was performed to assess the relationship between the independent variable and patients' knowledge and attitude about the AEs of ART medication. A p-value of 0.05 was used to determine the statistical significance. About 230 people were enrolled in this study, with 51.3% of them female. Study participants had a mean age of 36 years (standard deviation = 14.19). Of 230 participants, 67.8% had received advice on the AEs of ART medications. Poor knowledge and attitude were observed among 47.8 and 51.3% of respondents, respectively. Prior AEs experience, lack of experiencing opportunistic infection, and lack of counseling about ART medications' AEs were associated with poor knowledge, whereas female gender and a lack of counseling regarding ART medications' AEs were associated with a negative attitude (p < 0.05). Even though most patients (81.7%) report AEs of the medication to professionals, a significant number of patients involved in malpractices such as taking other drugs to treat AEs (24.3%), not prepared to do anything (27.1%), change the suspected drug (24.3%), reduce the dose (18.7%), and use local herbal medicines to treat suspected AEs (20.2%). Overall, the study participants had poor knowledge, lack of positive attitudes, and non-adherence to the actual recommended practice toward AEs of ART medications. Lack of comorbidity, having prior AEs experience, and lack of counseling regarding ART medication AEs were associated with poor knowledge. Female gender and a lack of counseling on the AEs of ART medications were associated with a negative attitude.


Time to Reflect and Take Action on Health Disparities and Health Inequities.
The United States healthcare system underperforms in healthcare access, quality, and cost resulting in some of the poorest health outcomes among comparable countries, despite spending more of its gross national product on healthcare than any other country in the world. Within the United States, there are significant healthcare disparities based on race, ethnicity, socioeconomic status, education level, sexual orientation, gender identity, and geographic location. COVID-19 has illuminated the racial disparities in health outcomes. This article provides an overview of some of the main concepts related to health disparities generally, and in orthopaedics specifically. It provides an introduction to health equity terminology, issues of bias and equity, and potential interventions to achieve equity and social justice by addressing commonly asked questions and then introduces the reader to persistent orthopaedic health disparities specific to total hip and total knee arthroplasty.


Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling.
The tumor microbiome is increasingly implicated in cancer progression and resistance to chemotherapy. In pancreatic ductal adenocarcinoma (PDAC), high intratumoral loads of Fusobacterium nucleatum correlate with shorter survival in patients. Here, we investigated the potential mechanisms underlying this association. We found that F. nucleatum infection induced both normal pancreatic epithelial cells and PDAC cells to secrete increased amounts of the cytokines GM-CSF, CXCL1, IL-8, and MIP-3α. These cytokines increased proliferation, migration, and invasive cell motility in both infected and noninfected PDAC cells but not in noncancerous pancreatic epithelial cells, suggesting autocrine and paracrine signaling to PDAC cells. This phenomenon occurred in response to Fusobacterium infection regardless of the strain and in the absence of immune and other stromal cells. Blocking GM-CSF signaling markedly limited proliferative gains after infection. Thus, F. nucleatum infection in the pancreas elicits cytokine secretion from both normal and cancerous cells that promotes phenotypes in PDAC cells associated with tumor progression. The findings support the importance of exploring host-microbe interactions in pancreatic cancer to guide future therapeutic interventions.


Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians.
During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure.


From a dominant to an oligogenic model of inheritance with environmental modifiers in acute intermittent porphyria.
Acute intermittent porphyria (AIP) is a disease affecting the heme biosynthesis pathway caused by mutations of the hydroxymethylbilane synthase (HMBS) gene. AIP is thought to display autosomal dominant inheritance with incomplete penetrance. We evaluated the prevalence, penetrance and heritability of AIP, in families with the disease from the French reference center for porphyria (CFP) (602 overt patients; 1968 relatives) and the general population, using Exome Variant Server (EVS; 12 990 alleles) data. The pathogenicity of the 42 missense variants identified was assessed in silico, and in vitro, by measuring residual HMBS activity of the recombinant protein. The minimal estimated prevalence of AIP in the general population was 1/1299. Thus, 50 000 subjects would be expected to carry the AIP genetic trait in France. Penetrance was estimated at 22.9% in families with AIP, but at only 0.5-1% in the general population. Intrafamily correlation studies showed correlations to be strong overall and modulated by kinship and the area in which the person was living, demonstrating strong influences of genetic and environmental modifiers on inheritance. Null alleles were associated with a more severe phenotype and a higher penetrance than for other mutant alleles. In conclusion, the striking difference in the penetrance of HMBS mutations between the general population and the French AIP families suggests that AIP inheritance does not follow the classical autosomal dominant model, instead of being modulated by strong environmental and genetic factors independent from HMBS. An oligogenic inheritance model with environmental modifiers might better explain AIP penetrance and heritability.


A case of anaphylaxis to chlorhexidine during digital rectal examination.
Chlorhexidine is widely used as an antiseptic and disinfectant in medical and nonmedical environments. Although the sensitization rate seems to be low, its ubiquitous use raises the possibility of sensitization in many patients and medical care workers. We describe a patient with anaphylaxis during digital rectal examination with chlorhexidine jelly. Urticaria, angioedema, dyspnea, and hypotension developed within a few minutes of the rectal examination. The patient fully recovered after treatment with epinephrine and corticosteroids. Skin tests for chlorhexidine were undertaken 5 weeks later, showing positive prick and intradermal skin tests. Within 30 min of the skin test, the patient complained of febrile sensation, chest tightness, angioedema, and urticaria on the face and trunk. An enzyme allergosorbent test for latex was negative. We present this case to alert clinicians about hypersensitivity to chlorhexidine that could potentially be life-threatening. We suggest that chlorhexidine should be recognized as a causative agent of anaphylaxis during procedural interventions.


Re-admission rates within 28 days of total hip replacement.
The aim of the study was to identify the reasons for the higher than expected emergency re-admission to hospital within 28 days of total hip replacement (THR) for Stepping Hill Hospital, Stockport. Over a 42-month period, 65 (8.5%) of 769 patients were re-admitted within 28 days of discharge following primary THR. Case notes for 61 patients were available for retrospective review to assess premorbidity, initial postoperative complications and reason for re-admission. The main reasons for re-admission were complications related to the procedure. These included thrombo-embolic disease 2.5%, atraumatic dislocation 1.4%, wound complications 1.2% and swollen limb 1.8%. Other causes such as admission to another department for problems not related to THR accounted for 0.8%. Our findings are comparable with the published literature for early complications following THR. The three main reasons for re-admission were atraumatic dislocation, thrombo-embolic and wound complications such as superficial infection and haematoma are the commonest world-wide. The re-admission rate to hospital within the first 28 days following THR was a clinical indicator suggested by the UK Department of Health. It has subsequently been incorporated in a group of indicators used by the CASPE Healthcare Knowledge Systems (CHKS), a private healthcare consultancy and analysis company, for peer benchmarking. Our re-admission rates are inflated by admissions for non-THR-related reasons. The level of post-THR complications leading to re-admission were acceptable compared with the available published literature regarding 28-day re-admission. We anticipate that this study may act as a benchmark for other trusts.


Fos expression during the estradiol-induced gonadotropin-releasing hormone (GnRH) surge of the ewe: induction in GnRH and other neurons.
The protein product of the protooncogene c-fos was used as a marker of cellular activation in an attempt to identify those neurons in the preoptic area and hypothalamus that participate in generation of the estradiol-induced surge of GnRH in the ewe. GnRH- and Fos-expressing cells were identified immunocytochemically, and the percent of coexpression was determined in three states: mid-luteal phase (low GnRH release, n = 6); short-term ovariectomy (high episodic GnRH release, n = 6); and induced GnRH surge (high sustained release, n = 8). To induce the GnRH surge, a follicular phase rise in circulating estradiol was simulated in a physiological model for the estrous cycle. Serum LH was measured as an indicator of GnRH release. In the luteal phase, LH was basal, indicating low GnRH secretion. Few cells expressed Fos; these were not GnRH cells. Despite high intermittent GnRH release in short-term ovariectomized ewes, GnRH cells did not express Fos. During the surge (sustained high GnRH release), 41 +/- 8% of GnRH cells expressed Fos; these cells were dispersed throughout the field of distribution of GnRH neurons. In addition to Fos in GnRH-positive cells, many more non-GnRH cells in the preoptic area, anterior hypothalamus, and ventrolateral hypothalamus expressed Fos during the surge than in the luteal phase or after ovariectomy. We suggest that Fos expression in GnRH cells is markedly increased by the positive feedback action of estradiol (surge), whereas short-term removal of negative feedback (ovariectomy) has little, if any, effect, despite increased GnRH release in both states. Since estradiol induces Fos expression in far more than GnRH neurons, our results also suggest that estradiol activates other cells, some of which may be part of a neuronal chain leading to GnRH surge generation, and some of which may be related to other neural actions of estradiol, such as estrous behavior.


[Intratumoral hemorrhage associated with cystic meningioma under observation: a case report].
Cystic meningiomas are not commonly encountered and are said to account for only 1 to 2% of all types of meningioma. There have been several reports on them and most of them were discussed under the aspect of the mechanism of cystic formation. Though few reports present the process of cystic formation, here we were able to present the process of cystic formation with intratumoral hemorrhage. The case was a 56-year-old man who presented with urinary incontinence. MRI revealed a large cystic tumor in the right frontal lobe and he was admitted to another hospital. After 20 days, MRI incidentally revealed hematoma near the intratumoral cyst. Two weeks later, MRI revealed that the hematoma flowed out the cyst and the cavity of the hematoma communicated with the cyst. Angiography showed that the tumor was fed by the left anterior ethmoid artery. After surgical removal of the tumor, histopathological diagnosis was that the tumor was a transitional meningioma and there were no findings of malignancy. Commonly, intratumoral hemorrhage is unusual for a meningioma but we suspect that there are not a few cases in which small hemorrhage occurred without symptoms and the hematoma cavity joined the intratumoral cyst while the cyst grew gradually.


[Long-term cross-circulation on galactosamine induced hepatic failure rats].
Cross-circulation was carried out in between galactosamine treated hepatic failure rats and normal rats and its efficacy was mainly evaluated by measuring mitochondrial respiratory function of the liver. Twenty-four hours after the injection of galactosamine, cross-circulation was performed at a blood flow rate of 1 ml/min for 8 hours. Survival rate of the rats in 48 hours and 60 hours after the injection of galactosamine was 86% and 57% in a cross-circulation group and 66% and 23% in a sham-circulation group, respectively. In a cross-circulation group, there showed significant increases of ATP synthesis per 100 gr. body weight, turnover number of phosphorylation and Cyt a (+a3) which were markedly reduced in a sham-circulation group. These appear to suggest that cross-circulation provides augmented mitochondrial energy supply in the liver and contributes higher survival rate of the rats.


Osteoid osteoma in older adults: clinical success rate of percutaneous image-guided thermal ablation.
To assess the clinical success rate of percutaneous radiofrequency and laser ablation of osteoid osteomas in older adults. Percutaneous radiofrequency or laser ablation was performed in 43 patients (35 years and older) with osteoid osteoma to achieve definitive cure in this retrospective study. The clinical success rate was defined as complete pain relief determined by numeric rating scale (NRS) scores (pre-procedural and post-procedural at 1-week, 6-week, and 2-year intervals). Tumour characteristics, technical success, procedural details, biopsy results, and complications were documented. Forty-four osteoid osteomas were ablated in 43 patients, and all procedures were technically successful. The clinical success rates were 95.2% (41/43), 93% (40/43), and 93.2% (41/44) at 1-week, 6-week, and 2-year post-procedural intervals. The acute complication rate was 2.3% (1/44; meningeal perforation following epidural anaesthesia). No delayed complication was documented. Osteoid osteomas are not unique to the paediatric and young population, and safe and effective definitive treatment of these benign tumours in older adults can be achieved by percutaneous radiofrequency and laser ablation with excellent patient outcomes.


Brainstem and forebrain contributions to the generation of learned motor behaviors for song.
Brainstem nuclei have well established roles in generating nonlearned rhythmic behaviors or as output pathways for more complex, forebrain-generated behaviors. However, the role of the brainstem in providing information to the forebrain that is used to initiate or assist in the control of complex behaviors is poorly understood. In this study, we used electrical microstimulation in select nuclei of the avian song system combined with recordings of acoustic and respiratory output to examine how forebrain and brainstem nuclei interact in the generation of learned vocal motor sequences. We found that brief stimulation in the forebrain nuclei HVC (used as a proper name) and RA (robust nucleus of the arcopallium) caused a short-latency truncation of ongoing song syllables, which ultimately led to a cessation of the ongoing motor sequence. Stimulation within the brainstem inspiratory-related nucleus paraambigualis, which receives input from RA and projects back to HVC via the thalamus, caused syllable truncations and interruptions similar to those observed in HVC and RA. In contrast, stimulation in the tracheosyringal portion of the hypoglossal nucleus, which innervates the syrinx (the avian vocal organ) but possesses no known projections back into the song system, did not cause any significant changes in the song motor pattern. These findings suggest that perturbation of premotor activity in any nucleus within the recurrent song system motor network will disrupt the ongoing song motor sequence. Given the anatomical organization of this network, our results are consistent with a model in which the brainstem respiratory nuclei form an integral part of the song motor programming network by providing timing signals to song control nuclei in the forebrain.


Anticoagulation Bridging in Patients With Left Ventricular Assist Device: A Regional Analysis of HeartMate 3 Recipients.
Advances in left ventricular assist device technologies have led to an improvement in pump hemocompatibility and outcomes. Because of concerns of thromboembolic complications in prior generations of left ventricular assist devices, bridging with parenteral anticoagulants was routinely. Management strategies of subtherapeutic INRs and their effects on the current generation of devices deserve review. We performed analysis of the MOMENTUM 3 trial including 6 centers in the mid-America region. Patients with subtherapeutic INRs (INR < 2) occurring after the index admission underwent chart review to determine the management strategies taken by clinicians. Strategies were divided into two groups, bridging or nonbridging. Of the 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic international normalized ratio (INR) events. Most (n = 179, 76.2%) of these INRs were not bridged (n = 100 warfarin dose adjustment, n = 79 no change in warfarin dose). Among those INRs (n = 56, 23.8%) treated with bridging, approximately half (n = 30, 53.6%) were treated with subcutaneous agents and other half (n = 26, 46.4%) were treated with intravenous agents. There was no difference in individual outcomes or composite endpoints of death, rehospitalization, CVA, or bleeding events between the groups.


Microfiltration of skim milk and modified skim milk using a 0.1-µm ceramic uniform transmembrane pressure system at temperatures of 50, 55, 60, and 65°C.
Increasing the temperature of microfiltration (MF) to >50°C may allow for operation at higher fluxes and reduce the bacterial growth during MF. However, there is a concern that operating at higher temperatures could cause calcium phosphate precipitation that would lead to membrane fouling. Our objective was to determine the effect of operating a 0.1-µm ceramic uniform transmembrane pressure MF unit at temperatures of 50, 55, 60, and 65°C on membrane fouling and serum protein (SP) removal from skim milk with and without removal of low-molecular-weight soluble milk components by ultrafiltration (UF) before MF at a flux of 54kg/m(2) per hour. For each replicate, 1,000kg of pasteurized skim milk was split into 2 batches. One batch was ultrafiltered (with diafiltration) to remove an average of 89±2% of the lactose and a percentage of the soluble calcium and phosphorus. The retentate from UF was diluted back to the protein concentration of skim milk, creating the diluted UF retentate (DUR). On subsequent days, both the DUR and skim milk were run on the MF unit with the flux maintained at 54kg/m(2) per hour and a concentration factor of 3× and the system run in recycle mode. The temperature of MF was increased in 5°C steps from 50 to 65°C, with a 1-h stabilization period after each increase. During the run, transmembrane pressure was monitored and permeate and retentate samples were taken and analyzed to determine if any changes in SP, calcium, or phosphorus passage through the membrane occurred. Increasing temperature of MF from 50 to 65°C at a flux of 54kg/m(2) per hour did not produce a large increase in membrane fouling when using either skim milk or a DUR as the MF feed type as measured by changes in transmembrane pressure. Increasing the temperature to 65°C only caused a slight reduction in calcium concentration in the permeate (11±3%) that was similar between the 2MF feed types. Increasing processing temperature reduced the percentage of SP removal by the process, but the increased temperature also caused a decrease in casein contamination in the permeate with no evidence of membrane fouling.


Employment of chiral columns with superficially porous particles in chiral separations of cobalt bis (dicarbollide) and nido-7,8-C2 B9 H12 (1-) derivatives.
Derivatives of the nido-7,8-C2 B9 H12 (1-) (dicarbollide ion) and [3,3'-Co-(1,2-C2 B9 H11 )2 ](1-) cobalt sandwich (COSAN) ion represent groups of extremely chemically and thermally stable abiotic compounds. They are being investigated in many research areas, that is, medicinal chemistry, material sciences, analytical chemistry, and electrochemistry. The chirality of these compounds remains still grossly overlooked, what is also reflected in limited number of reports on their chiral separations. Continued progress depends on reliable, fast, and cost-effective methods for such separations. Recently, chiral separations of COSAN derivatives were achieved in liquid chromatography and supercritical fluid chromatography. Only five anionic derivatives of nido-7,8-C2 B9 H12 (1-) were successfully enantioseparated in liquid chromatography. Efforts to separate anionic nido-7,8-C2 B9 H12 (1-) in supercritical chromatography have failed, and only a few dicarbollide ions were separated using liquid chromatography. Generally, all chiral separations in liquid chromatography took about 30 min. Herein, we identify a versatile column capable of separating both COSAN and nido-7,8-C2 B9 H12 (1-) derivatives and achieve faster analyses times employing commercially available superficially porous chiral stationary phases. The semisynthetic hydroxypropyl β-cyclodextrin-based column (CDShell-RSP) is identified as the column of choice from the tested columns by separating 19 of 27 compounds from each structural motifs tested mainly in less than 10 min. The dihydroxyalkyl, oxygen-bridged hydroxyalkyl, and bisphenylene-bridged COSAN derivatives were baseline separated in less than 5 min exceeding the results of supercritical fluid chromatography. Methods developed herein will aid synthetic chemists without the possession of a supercritical fluid chromatograph to achieve fast chiral separations of COSAN and derivatives of nido-7,8-C2 B9 H12 (1-) on a common liquid chromatograph without the need of dedicated instrumentation.


ZnO/CoO and ZnCo2O4 Hierarchical Bipyramid Nanoframes: Morphology Control, Formation Mechanism, and Their Lithium Storage Properties.
Mastery over the structure of nanoscale materials can effectively tailor and regulate their electrochemical properties, enabling improvement in both rate capability and cycling stability. We report the shape-controlled synthesis of novel mesoporous bicomponent-active ZnO/CoO hierarchical multilayered bipyramid nanoframes (HMBNFs). The as-synthesized micro/nanocrystals look like multilayered bipyramids and consist of a series of structural units with similar frames and uniform sheet branches. The use of an appropriate straight-chain monoalcohol was observed to be critical for the formation of HMBNFs. In addition, the structure of HMBNFs could be preserved only in a limited range of the precursor ratio. An extremely fast crystal growth process and an unusual transverse crystallization of the ZnCo-carbonate HMBNFs were newly discovered and proposed. By calcination of ZnCo-carbonate HMBNFs at the atmosphere of nitrogen and air, ZnO/CoO and ZnCo2O4 HMBNFs were obtained, respectively. Compared to the ZnCo2O4 HMBNFs, the ZnO/CoO HMBNFs with a uniform distribution of nanocrystal ZnO and CoO subunits exhibited enhanced electrochemical activity, including greater rate capability and longer cycling performance, when evaluated as an anode material for Li-ion batteries. The superior electrochemical performance of the ZnO/CoO HMBNFs is attributed to the unique nanostructure, bicomponent active synergy, and uniform distribution of ZnO and CoO phases at the nanoscale.