A review of peristaltic micropumps.
This report presents a review of progress on peristaltic micropumps since their emergence, which have been widely used in many research fields from biology to aeronautics. This paper summarizes different techniques that have been used to mimic this elegant physiological transport mechanism that is commonly found in nature. The analysis provides definitions of peristaltic micropumps and their different features, distinguishing them from other mechanical micropumps. Important parameters in peristalsis are presented, such as the operating frequency, stroke volume, and various actuation sequences, along with introducing design rules and analysis for optimizing actuation sequences. Actuation methods such as piezoelectric, motor, pneumatic, electrostatic, and thermal are discussed with their advantages and disadvantages for application in peristaltic micropumps. This review evaluates research efforts over the past 30 years with comparison of key features and outputs, and suggestions for future development. The analysis provides a starting point for researchers designing peristaltic micropumps for a broad range of applications.


The Epidemiology of Injuries in Football at the London 2012 Paralympic Games.
The epidemiology of injury in Paralympic football has received little attention. A study of all sports at the London 2012 Paralympic Games identified football 5-a-side as the sport with the highest injury rate, meriting further detailed analysis, which may facilitate the development of strategies to prevent injuries. To examine the injury rates and risk factors associated with injury in Paralympic football. Secondary analysis of a prospective cohort study of injuries to football 5-a-side and football 7-a-side athletes. London 2012 Paralympic Games. Participants included 70 football 5-a-side athletes and 96 football 7-a-side athletes. Athletes from all but one country chose to participate in this study. The Paralympic Injury and Illness Surveillance System was used to track injuries during the Games, with data entered by medical staff. Injury incidence rate (IR) and injury incidence proportion (IP). The overall IR for football 5-a-side was 22.4 injuries/1000 athlete-days (95% confidence interval [CI], 14.1-33.8) with an IP of 31.4 injuries per 100 athletes (95% CI, 20.9-43.6). In 5-a-side competition, 62.5% of injuries were associated with foul play. The overall IR for football 7-a-side was 10.4 injuries/1000 athlete-days (95% CI, 5.4-15.5), with an IP of 14.6 injuries per 100 athletes (95% CI, 7.5-21.6). The most commonly injured body region in both sports was the lower extremity. To our knowledge, this study is the first to examine IR and risk factors associated with injury in Paralympic football. Future studies are needed to determine mechanisms of injury and independent risk factors for injury, thus informing prevention strategies.


Germ cell tumors of the head and neck: report from the MAKEI Study Group.
Germ cell tumors (GCTs) of the head and neck region are rare but may pose significant problems for perinatal management as well as surgical and adjuvant therapy. Thirty-two prospectively reported patients from the German MAKEI studies (Maligne Keimzelltumoren) were analyzed with regard to perinatal management and long-term survival. Twenty-three tumors were diagnosed around birth and four during the first 3 months of life. All were primarily diagnosed as teratomas, but in two tumors, yolk sac tumor (YST) foci were identified. Another pure teratoma was diagnosed at 12 months. Four tumors were diagnosed after the first year of life and showed YST as leading histology. Most neonates presented with huge tumors causing external airway obstruction. All tumors were resected (complete resection, 16/26 patients with complete surgical information; incomplete resection, 10/26 patients). Eight tumors including five of six YSTs were treated with chemotherapy. In total, six patients relapsed. Relapse rate was higher after incomplete (5/10 patients) than after complete resection (1/16 patients). Accordingly, more relapses were observed in pharyngeal than in neck tumors due to incomplete resection. Nevertheless, half of the patients with incomplete resection remained in remission. One patient with YST died after multiple relapses. GCTs of the head and neck region require a multidisciplinary approach in specialized centers. Most patients with antenatal tumor growth are identified by ultrasound and delivered preterm by cesarian section. After delivery, immediate intubation and ventilation aim for respiratory stabilization, followed by elective resection. With this approach, outcome was favorable.


Migration from HL7 CDA to FHIR in Infectious Disease System of Estonia.
On the basis of the Estonian National Health System, we propose a universal and reusable methodology for migrating HL7 CDA documents or their components.


Home nocturnal hemodialysis in children.
To describe the effect of home nocturnal hemodialysis (NHD) in North American children. Four teenagers underwent NHD for 8 hours, 6 to 7 nights/week, using either central venous lines or fistulae for periods of 6 to 12 months. Blood flow approximated 200 mL/min, and dialysate flow was 300 mL/min; the dialysate contained potassium and phosphate. The procedure was remotely monitored. The children had unrestricted diets and fluid allowance and did not require phosphate binders. Persistent relative hypotension developed in 2 of 4 children. Weekly Kt/V urea values were consistently >10; other biochemical measures varied. Quality of life and school attendance improved in 3 of 4 children. The workload and reported emotional burden of NHD was substantial. No significant complications occurred. Dialysate losses of calcium, phosphate and carnitine required supplementation. The annual cost per patient was dollar 64,000 Canadian, which represented a 27% savings compared with thrice weekly in-center hemodialysis. NHD is feasible in selected children, allows free dietary and fluid intake, and improves patient wellbeing. The burden on the family is substantial, and NHD requires support of a dedicated multidisciplinary team.


Differences between individuals in high-Mr glycoproteins from human mammary epithelia.
SDS-polyacrylamide gel electrophoretic analysis of high molecular mass glycoproteins from human milk fat globules revealed that the pattern of bands is unique for each milk donor. The number, position, width and intensity of bands varied between donors. A difference in the pattern of sisters could be discerned. There is evidence that these mucin-like glycoproteins, which originate from the plasma membrane of the mammary epithelial cell, occur in other cells and tissues. They may function in the immunorecognition system because of their individual-specific character and cell surface location.


Mediated biosensors.
Direct electrode transfer between enzyme and the electrode in biosensors requires high efficiency therefore, synthetic replacement for oxygen led to the development of enzyme mediators and modified electrodes in biosensor fabrication. In this context, a number of electron acceptors and complexes have been used. Present paper gives an overview of various methodologies involved in the mediated systems, their merits and wide applications.


Successful surgical management of a rare esophageal inflammatory myofibroblastic tumour: a case report.
Inflammatory myofibroblastic tumour (IMT) is an uncommon mesenchymal tumour, which can occur anywhere in the body, rarely in esophagus. Mostly, the diagnosis is postoperative, after the hispathological evaluation of the specimen. There are no definite guidelines regarding the diagnosis and management. Here, we report a 60 year old lady presenting with dysphagia, diagnosed to have a submucosal esophageal tumor with Barium esophagogram and contrast enhanced computed tomography. She was managed successfully with surgical enucleation with the final histopathological diagnosis of IMT. Surgical excision is not only therapeutic but also diagnostic in such cases.


Investigating the effects of low intensity visible light on human keratinocytes using a customized LED exposure system.
Photobiomodulation (PBM) refers to the use of light to modulate cellular processes, and has demonstrated utility in improving wound healing outcomes, and reducing pain and inflammation. Despite the potential benefits of PBM, the precise molecular mechanisms through which it influences cell behavior are not yet well understood. Inconsistent reporting of key light parameters has created uncertainty around optimal exposure profiles. In addition, very low intensities of light, < 0.1 J/cm2, have not been thoroughly examined for their use in PBM. Here, we present a custom-made compact, and modular LED-based exposure system for studying the effects of very low-intensity visible light (cell proliferation, migration, ROS production, and mitochondrial membrane potential) of three different wavelengths in a parallel manner. The device allows for six repeats of three different exposure conditions plus a non-irradiated control on a single 24-well plate. The immortalised human keratinocyte cell line, HaCaT, was selected as a major cellular component of the skin epidermal barrier. Furthermore, an in vitro wound model was developed by allowing the HaCaT to form a confluent monolayer, then scratching the cells with a pipette tip to form a wound. Cells were exposed to yellow (585 nm, 0.09 mW, ~ 3.7 mJ/cm2), orange (610 nm, 0.8 mW, ~ 31 mJ/cm2), and red (660 nm, 0.8 mW, ~ 31 mJ/cm2) light for 10 min. 48 h post-irradiation, immunohistochemistry was performed to evaluate cell viability, proliferation, ROS production, and mitochondrial membrane potential. The results demonstrate increased proliferation and decreased scratch area for all exposure conditions, however only red light increased the mitochondrial activity. Oxidative stress levels did not increase for any of the exposures. The present exposure system provides opportunities to better understand the complex cellular mechanisms driven by the irradiation of skin cells with visible light.


Conformational Control of Organocatalyst in Strongly Brønsted-Acidic Metal-Organic Frameworks for Enantioselective Catalysis.
Chiral imidodiphosphates (IDPs) have emerged as strong Brønsted acid catalysts for many enantioselective processes. However, the dynamic transformation between O,O-syn and O,O-anti conformers typically results in low enantioselectivity. Here we demonstrate that topologies of metal-organic frameworks (MOFs) can be exploited to control IDP conformations and local chiral microenvironments for enantioselective catalysis. Two porous Dy-MOFs with different topologies are obtained from an enantiopure 1,1'-biphenol IDP-based tetracarboxylate ligand. While the ligand adopts a 4- or 3-connected (c) binding mode, all IDPs are rigidified to get only a single O,O-syn conformation and display greatly enhanced Brønsted acidity relative to the free IDP. The MOF with the 4-c IDP that has a relatively less compact shape than the 3-c IDP can be an efficient and recyclable heterogeneous Brønsted acid catalysing the challenging asymmetric O,O-acetalization reaction with up to 96 % enantiomeric excess.


Evaluation of LIPS (luciferase immunoprecipitation system) for serodiagnosis of Toxoplasmosis.
Development of reliable, quantitative technologies for serodiagnosis of Toxoplasma gondii infection remains desirable. The luciferase immunoprecipitation system (LIPS) is a relatively simple, highly sensitive, and rapid quantitative immunoassay. The major advantages of this assay over ELISA are a wider dynamic range, shorter overall assay time, and less sample volume. In this study, we aimed to use this method for the serodiagnosis of toxoplasmosis. Recombinant Toxoplasma antigens (dense granule antigens GRA6, GRA7, and GRA8 and bradyzoite antigen BAG1) fused with nanoluciferase (Nluc, a small luciferase enzyme) were expressed in Escherichia coli, purified, and tested in LIPS assays with sera from experimental mice infected with T. gondii and a WHO standard anti-Toxoplasma human immunoglobulin (TOXM). In the experimentally infected mice, LIPS assays detected antibodies against Nluc-GRA6, Nluc-GRA7, and Nluc-GRA8 as early as day 14, whereas antibodies against Nluc-BAG1 remained undetected until day 21 and then showed significant elevation on day 60. In TOXM sera, LIPS assays with each Nluc recombinant protein produced reliable standard curves with a coefficient of determination (R2) of 0.980-0.989 for GRA6, 0.986-0.990 for GRA7, 0.998-0.999 for GRA8, and 0.942-0.987 for BAG1. The detection limits were estimated to be 3.9, 2, 1, and 1 IU/ml for rGRA6, rGRA7, rGRA8, and rBAG1, respectively. The LIPS assay for toxoplasmosis could detect antibodies against T. gondii in the mouse and human sera with a reasonably high sensitivity. We consider the LIPS assay to be a promising alternative tool for screening, diagnosing, and monitoring toxoplasmosis. In particular, detection of antibodies against BAG1 may be useful for a longitudinal seroprevalence study in suspected high-risk areas on the basis of its elevated serum concentration in the chronic phase.


TlR expression profile of human gingival margin-derived stem progenitor cells.
Gingival margin-derived stem/progenitor cells (G-MSCs) show remarkable periodontal regenerative potential in vivo. During regeneration, G-MSCs may interact with their inflammatory environment via toll-like-receptors (TLRs). The present study aimed to depict the G-MSCs TLRs expression profile. Cells were isolated from free gingival margins, STRO-1-immunomagnetically sorted and seeded to obtain single colony forming units (CFUs). G-MSCs were characterized for CD14, CD34, CD45, CD73, CD90, CD105, CD146 and STRO-1 expression, and for multilineage differentiation potential. Following G-MSCs' incubation in basic or inflammatory medium (IL-1β, IFN-γ, IFN-α, TNF-α) a TLR expression profile was generated. G-MSCs showed all stem/progenitor cells' characteristics. In basic medium G-MSCs expressed TLRs 1, 2, 3, 4, 5, 6, 7, and 10. The inflammatory medium significantly up-regulated TLRs 1, 2, 4, 5, 7 and 10 and diminished TLR 6 (p≤0.05, Wilcoxon-Signed-Ranks-Test). The current study describes for the first time the distinctive TLRs expression profile of G-MSCs under uninflamed and inflamed conditions.


Angiotensin II facilitates the potassium-evoked release of 3H-noradrenaline from the rabbit hypothalamus.
Antiotensin II facilitated in a concentration-dependent manner the potassium-evoked 3H-noradrenaline over-flow from the rabbit hypothalamus. This effect which is probably mediated through presynaptic angiotensin facilitatory receptors on noradrenergic nerve terminals was blocked by the specific angiotensin receptor antagonist, saralasin. These results demonstrate that angiotensin II also facilitates the stimulation-evoked release of noradrenaline in the central nervous system.


Imaging of the carotid artery.
In the study of carotid arteries, modern techniques of imaging allow to analyze various alterations beyond simple luminal narrowing, including the morphology of atherosclerotic plaques, the arterial wall and the surrounding structures. By using CTA and MRI it is possible to obtain three-dimensional rendering of anatomic structures with excellent detail for treatment planning. This paper will detail the role of various imaging methods for the assessment of carotid artery pathology with emphasis on the detection, analysis and characterization of carotid atherosclerosis.


Identification of cellular target proteins for signaling cyclic phosphates.
Cyclic glycerophosphates and their deoxy analogs were previously found to induce intracellular tyrosine and threonine phosphorylation in Chinese hamster ovary (CHO) cells. Further studies have indicated that these compounds induce neuronal outgrowth in PC-12 cells, as well as elevation of the state of cellular differentiation in human breast cancer cell lines. The mechanism by which these cyclic phosphates operate is not yet fully delineated. Using an affinity labeling approach we probed for possible cyclic phosphate target proteins in CHO cells. A 170 kDa protein that was labeled by an affinity cyclic phosphate reagent was identified by mass spectrometry as the largest subunit of the eukaryotic initiation factor 3 (eIF3). Using In-Gel kinase assays allowed the detection of a approximately 70 kDa target kinase directly activated by cyclic phosphates. Identification of these proteins may provide a basis for deciphering the mechanisms, by which cyclic phosphates exert their effects.


Brca2, Rad51 and Mre11: performing balancing acts on replication forks.
Homologous recombination (HR) is required for faithful repair of double strand breaks (DSBs) and is believed to be important for DNA replication under stressful conditions in unicellular organisms. However, its role during DNA replication in high eukaryotes has always been elusive. In particular, due to the essential nature of its main players it has been difficult to dissect the direct role of HR in DNA replication. Recent studies revealed that some key HR factors such as Rad51 and BRCA2 play unexpected functions during DNA replication by protecting nascent DNA from Mre11 mediated degradation, which takes place at stalled replication forks. These novel functions appear to be essential to ensure smooth progression of DNA replication and to promote maintenance of genome stability.


Inhibition of ornithine decarboxylase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the activity of rat liver ornithine decarboxylase (ODC) were investigated. Sixteen hours after partial hepatectomy, rats that had been pretreated with TCDD for 1 week exhibited a 3- to 4-fold increase in ODC activity, while vehicle controls exhibited to 8- to 10-fold increase. This inhibition of ODC induction by TCDD was time dependent since TCDD administration at the time of partial hepatectomy did not produce inhibitory effects on the subsequent ODC induction. ODC induction after either aminophylline or dexamethasone administration, agents which act via cAMP-mediated and direct nuclear events, respectively, also was inhibited by pretreatment with TCDD. It was concluded that TCDD pretreatment decreased the ability of the liver to respond to hormonal stimulation as reflected in the attenuation of ODC induction. RNA polymerase I activity, which positively correlates with ODC activity in growth and development, decreased concomitantly with decreased induction of ODC. In unstimulated liver RNA polymerase I activity, as well as protein, DNA, and RNA levels, remained unchanged 1 week after TCDD. However, TCDD administration resulted in decreased liver concentrations of putrescine and spermidine, but not spermine. This suggests that TCDD pretreatment results in a time-dependent decrease in hormone responsivity.


FoxO directly regulates the expression of TOR/S6K and vitellogenin to modulate the fecundity of the brown planthopper.
As a conserved transcription factor, FoxO plays a crucial role in multiple physiological processes in vivo, including stress resistance, longevity, growth and reproduction. Previous studies on FoxO have focused on human, mouse, Drosophila melanogaster and Caenorhabditis elegans, while there are few reports on agricultural pests and little is known about how FoxO modulates insect fecundity. In Asia, the brown planthopper (BPH) Nilaparvata lugens (Stål) is one of the most serious pests in rice production and high fecundity is the basis of the outbreak of BPH. Here, using the genome-wide ChIP-seq of NlFoxO in BPH, we found that NlFoxO binds to the promoters of ribosomal proteinS6 kinase (NlS6K) and serine/threonine-protein kinase mTOR (NlTOR) and increases their expression levels. We also found that NlFoxO directly binds to the exon of vitellogenin (NlVg) and has a specific inhibitory effect on its expression. In addition, the number of eggs laid and their hatching rate decreased significantly after injection of NlFoxO double-stranded RNA into BPH adults. Our findings provide direct evidence that FoxO modulates insect fecundity through binding to the promoters of NlS6K, NlTOR and the exon of NlVg and affecting their gene expression in the Vg network.


Development of a simple non-reduced peptide mapping method that prevents disulfide scrambling of mAbs without affecting tryptic enzyme activity.
Non-reduced peptide mapping by liquid chromatography-mass spectrometry (LC-MS) analysis is a commonly used method for disulfide linkage characterization to assess structural integrity and quality of therapeutic monoclonal antibodies (mAbs). However, disulfide scrambling artifacts induced during sample preparation are often observed when basic pH and high temperatures are used during denaturation and digestion. To minimize disulfide scrambling artifacts, methods using various acidic pH conditions have been developed by multiple groups. However, lower pH conditions increase missed and non-specific cleavages, which complicates disulfide bond analysis because the majority of enzymes used in protein characterization are most efficient at alkaline pH. Here, we developed a non-reduced peptide mapping method for mAb characterization that minimizes disulfide scrambling at basic pH by adding an oxidizing agent, cystamine, and a low concentration of iodoacetamide (IAA) alkylating agent. Two human IgG1 mAbs, one with kappa light chain and another one with lambda light chain, were used as model proteins to develop and optimize the method. Using this novel method, disulfide scrambled peptides related to light chain-heavy chain (LC-HC) inter-disulfide disruption were significantly reduced with high reproducibility compared to conventional methods. Results demonstrated that the cystamine-added method is robust and minimizes disulfide scrambling artifacts produced during sample preparation.


Blisters on the battlefield: the prevalence of and factors associated with foot friction blisters during Operation Iraqi Freedom I.
Foot friction blisters in military personnel lessen a soldier's mobility, concentration, and critical decision-making skills. To determine the prevalence of and factors associated with friction blisters during deployment in all military personnel who nonurgently presented to the 28th Combat Support Hospital. A cross-sectional survey was performed at the 28th Combat Support Hospital. Statistical tests used included descriptive statistics, chi-square tests, and logistic regression for nominal data. The response rate was 97% with 872 surveys completed. Blister prevalence was 33% (95% confidence interval [CI] = 30.0-36.4). Eleven percent of these sought treatment (p < 0.001). Factors increasing the risk of developing blisters include female sex (prevalence ratio [PR] = 1.55, 95% CI = 1.27-1.91), wearing boots not broken in (PR = 1.52, CI = 1.26-1.85), longer than 6 months in theater (PR = 1.33, CI = 1.09-1.63), and history of prior blisters (PR = 2.08, CI = 1.69-2.56). The prevalence of foot friction blisters was 33% during a 12-month block of Operation Iraqi Freedom I. Of these, 11% required medical care. The group most likely to develop blisters is women, ages 26 to 34, who are unable to break in their boots and have a past history of blisters.


The clinical manifestations and treatment of male breast cancer: a report of three cases.
Male breast cancer is an extremely rare malignancy. We treated three male breast cancer patients. All three patients showed clinical N0 and received sentinel lymph node biopsy. Because the sentinel lymph node was positive for metastasis in one patient, a total mastectomy with axillary lymph node dissection was performed. The other two patients were negative for sentinel lymph node metastasis, and a simple mastectomy was performed. Two of the patients were postoperatively treated with tamoxifen; another patient was treated with adjuvant chemotherapy using taxotere and cyclophosphamide before tamoxifen. There was no recurrence in any of the three patients during an average follow-up period of 56.7 months (range 11.8-80.3). A sentinel lymph node biopsy is recommended for node staging in both male and female breast cancer patients as it is associated with a lower incidence of complications.


Prevalence and risk factors of brain atrophy and associated confusion state among adults from three hospitals in northern Tanzania.
brain atrophy is the reduction of brain volume often accompanied with cognitive changes. Despite the availability of computerized-tomography (CT) scanners in Tanzania, little is known about the magnitude of brain atrophy, its associated confusion state and the risk factors in adults. This study aimed to fill those knowledge gaps. a retrospective cross-sectional hospital-based survey was conducted in northern Tanzania using a sample size of 384 CT images of adults who underwent brain CT scans in three referral hospitals. CT images were evaluated using a diagonal brain fraction (DBF) method to determine the presence of brain atrophy. Data for other covariates were also collected. we report a prevalence of 60.67% for brain atrophy and 35% for the associated confusion state. Association between confusion state and brain atrophy was statistically significant (χ2 = 21.954, p<0.001). Brain atrophy was prognosticated by: age (adjusted OR: 1.11; 95% CI [1.05, 1.20], p<0.001), smoking (adjusted OR: 6.97; 95% CI [2.12, 26.19], p<0.001), alcohol-consumption (adjusted OR: 11.87; 95% CI [3.44, 40.81], p<0.001), hypertension (adjusted OR: 61.21; 95 CI [15.20, 349.43], p<0.001), type-2 diabetes mellitus (adjusted OR: 15.67; 95% CI [5.32, 52.77], p<0.001) and white matter demyelination (adjusted OR: 13.45; 95% CI [4.66, 44.25], p<0.001). there is high prevalence of brain atrophy and associated confusion state among hospitalized adults in northern Tanzania. Reported prognostic factors for brain atrophy such as age, smoking, alcohol consumption, hypertension, type-2 diabetes mellitus and white matter demyelination could help focus interventions in this area.


Gamma-Aminobutyric Acid Signaling in Brown Adipose Tissue Promotes Systemic Metabolic Derangement in Obesity.
Brown adipose tissue (BAT) is a metabolically active organ that contributes to the maintenance of systemic metabolism. The sympathetic nervous system plays important roles in the homeostasis of BAT and promotes its browning and activation. However, the role of other neurotransmitters in BAT homeostasis remains largely unknown. Our metabolomic analyses reveal that gamma-aminobutyric acid (GABA) levels are increased in the interscapular BAT of mice with dietary obesity. We also found a significant increase in GABA-type B receptor subunit 1 (GABA-BR1) in the cell membranes of brown adipocytes of dietary obese mice. When administered to obese mice, GABA induces BAT dysfunction together with systemic metabolic disorder. Conversely, the genetic inactivation or inhibition of GABA-BR1 leads to the re-browning of BAT under conditions of metabolic stress and ameliorated systemic glucose intolerance. These results indicate that the constitutive activation of GABA/GABA-BR1 signaling in obesity promotes BAT dysfunction and systemic metabolic derangement.


An ELISA method for the detection of autoantibodies to adrenal cortex.
An enzyme-linked immunosorbent assay (ELISA) is described for autoantibodies to adrenal cortex. Microsomes were prepared from fresh human adrenal glands, and microtitre ELISA plates were incubated at 4 degrees C overnight with 25 micrograms antigen/ml, the optimal concentration for the system. Optimal dilution of patient's serum was 1/500. Peroxidase-labelled anti-human IgG and IgM sera were used in separate tests and o-phenylenediamine and H2O2 served as substrate. Intra-assay variance of optical density units was 4.5%, and inter-assay variance was negligible when antigen preparations from 2 different adrenal glands were compared. All sera positive or negative at first test gave the same qualitative result in a second. Non-organ-specific binding of sera containing mitochondrial or ribosomal antibodies was eliminated by a blocking ELISA system where the antigen-coated plates were incubated with test sera, and in a second step, peroxidase-labelled IgG from an adrenal antibody-positive control serum was added. In this test, optimal antigen concentration for coating of plates was 6.25 micrograms/ml and optimal serum dilution 1/50. The ELISA proved more sensitive and reproducible than indirect immunofluorescence. Adrenal antibodies detected by ELISA were usually of IgG class alone and only 1 of the 30 positives also contained IgM specificity. 30 out of 38 sera (79%) from patients with 'idiopathic' Addison's disease were positive whereas immunofluorescence revealed only 23 (61%) at first testing and another 4 positives when sera were tested on different adrenal glands. The ELISA described is useful for both scientific work and clinical diagnosis of autoimmune adrenalitis.


Selective effects of ageing on vestibular-dependent lower limb responses following galvanic stimulation.
To examine the influence of ageing on electromyographic (EMG) responses to galvanic vestibular stimulation (GVS) in the lower limbs and to define normal values. EMG responses to 4 mA/20 ms transmastoid binaural GVS were recorded from the soleus muscles of 70 healthy adults aged 24-85 years. Short (SL) and medium latency (ML) vestibular-dependent reflex latencies and amplitudes were measured from averaged rectified EMG. Side to side differences were examined in 30 subjects, using monaural stimulation, and expressed as an asymmetry ratio (AR). SL reflexes to transmastoid binaural stimulation were absent in 10 of the 25 subjects over the age of 60. ML responses were present in all subjects. SL reflex amplitudes decreased from 24.4+/-12.4% (mean+/-SD) in the 3rd decade to 7.6+/-6.2% in the 8th and 9th decades. The ML reflex amplitudes showed a tendency to increase with age. The mean AR for SL reflex amplitudes increased from 12.1% in the 3rd decade to 80.7% in the 8th and 9th decades but that for ML amplitudes did not change significantly. The average SL and ML response onset latencies were 56.5+/-7.5 and 97.2+/-9.4 ms. SL onset latencies were significantly delayed with age. Both SL and ML responses were highly reproducible between experiments. SL and ML responses behave differently in response to age. The decrease in SL reflex amplitudes correlates well with previously described age-related morphological changes. Preservation of the ML reflex may reflect central adaptation to reduced afferent input. SL and ML responses are potentially useful measures of vestibular-spinal function, which may have a role in the assessment of older subjects with dysequilibrium. These reflexes need to be interpreted in the context of age.


Early behavioral and catecholaminergic effects of 6-hydroxydopamine and guanethidine in the neonatal rat.
New born rats received 7 consecutive daily injections of 6-hydroxydopamine (6-OHDA) or guanethidine. Locomotor activity, measured at 3 day intervals, was differentially affected by these drugs, although neither drug elimination a characteristic pattern of ontogeny of locomotor activity. Differing neurochemical effects were also observed. 6-OHDA decreased tyrosine hydroxylase activity in cortex and cerebellum, increased it in the brainstem and had no effect on the hypothalamus. Guanethidine slightly elevated enzyme levels in all four brain regions, with the elevation in brainstem significant at 16 days of age. Regional brain changes in enzyme activity after 4 daily 6-OHDA injections beginning at 1, 5 or 9 days of age indicated that toxic effect of 6-OHDA upon catecholaminergic neurons was age dependent. These data are not consistent with a simple interpretation either in terms of maturational changes in blood brain barrier permeability to 6-OHDA or neuronal uptake of the drug. Further analyses of brainstem areas indicated that the increased brainstem enzyme activity after 6-OHDA was restricted to the pons.


Reducing no flow times during automated external defibrillation.
There has recently been an increased attention focused on the importance of reducing time without blood flow from chest compressions (no flow time, NFT) during cardiopulmonary resuscitation (CPR). In this study we have analyzed and quantified the NFTs during external automatic defibrillation in 105 cardiac arrest patients. We found that for around half of the time (about 10 min), these patients were not perfused. We have proposed methods to reduce NFT in connection with analyses and shocks. The key factors were rhythm analysis during ongoing CPR, capacitor charging during analysis, 1 min of CPR immediately after a shock (with rhythm analysis during CPR at the end of the 1 min), and distinguishing between asystole and organized rhythm in analyses to skip pulse check if asystole. The potential reduction in NFT using these methods was calculated theoretically and we found a reduction in the total NFT of about 4.5 and 1 min, respectively, in the subgroups of patients having at least one shock and patients having received no shocks. In the present study, the median NFT ratio could theoretically be reduced from 51% to 34% or 49% to 39% depending on if the patient would have a shockable rhythm or not. By introducing the proposed methods into an AED, the NFT would be significantly reduced, hopefully increasing the survival.


Predicting survival of glioblastoma from automatic whole-brain and tumor segmentation of MR images.
Survival prediction models can potentially be used to guide treatment of glioblastoma patients. However, currently available MR imaging biomarkers holding prognostic information are often challenging to interpret, have difficulties generalizing across data acquisitions, or are only applicable to pre-operative MR data. In this paper we aim to address these issues by introducing novel imaging features that can be automatically computed from MR images and fed into machine learning models to predict patient survival. The features we propose have a direct anatomical-functional interpretation: They measure the deformation caused by the tumor on the surrounding brain structures, comparing the shape of various structures in the patient's brain to their expected shape in healthy individuals. To obtain the required segmentations, we use an automatic method that is contrast-adaptive and robust to missing modalities, making the features generalizable across scanners and imaging protocols. Since the features we propose do not depend on characteristics of the tumor region itself, they are also applicable to post-operative images, which have been much less studied in the context of survival prediction. Using experiments involving both pre- and post-operative data, we show that the proposed features carry prognostic value in terms of overall- and progression-free survival, over and above that of conventional non-imaging features.


Visible light induced reversible extrusion of nitric oxide from a ruthenium(II) nitrosyl complex: a facile delivery of nitric oxide.
The new ruthenium compound [Ru(NO)(pysiS4)]Br (3) (pysiS4 = 2,6-bis(3-triphenylsilyl-2-sulfanylphenylthiomethyl)pyridine), containing sterically bulky SiPh3 groups ortho to the thiolate donors, has been synthesized. In solution, 3 releases NO efficiently on exposure to visible light (lambda >/= 455 nm) at room temperature to afford [Ru(Br)(pysiS4)] (4). Treatment of 4 with NO yielded exclusively 3 without any metal-bound side reaction.


Treatment of tuberculous infection and disease in children: the North American perspective.
The standard preventive therapy for paediatric patients with tuberculous infection centres on isoniazid therapy. The chosen regimen of isoniazid therapy is based on individual patient factors. In the case of known or suspected resistance, combination therapy [e.g. isoniazid and rifampicin (rifampin)] or alternative therapies (e.g. pyrazinamide, a fluoroquinolone and/or ethambutol) should be employed. The goal of treatment of tuberculous disease is to achieve sterilisation in the shortest possible time. More intensive multiple drug combination regimens (e.g. isoniazid, rifampicin and pyrazinamide) have resulted in successful 6- and 9-month treatment regimens in children. If drug resistance is suspected then a fourth drug is added to the initial treatment regimen and the length of therapy may be extended to 18 months. The paediatric information available on the commonly used antituberculous agents (e.g. isoniazid, rifampicin, pyrazinamide and ethambutol) is reviewed in this article. Agents are described with an emphasis on their formulation availability, mechanism of action, pharmacokinetic properties (e.g. absorption, distribution, metabolism and elimination), adverse effects, and interactions (e.g. drug-drug, drug-food and drug-disease).


Retained Stingray Barb and the Importance of Imaging.
Stingray envenomation is a common occurrence. X-ray evaluation of stingray wounds is an unnecessarily misunderstood diagnostic concept. We present the case of a patient stung by a stingray with a prolonged and complicated course and permanent disability due to a retained barb. The patient had undergone multiple medical evaluations before an X-ray was obtained.


[Coronary CT angiography and coronary atherosclerosis : Where do we stand today?]
Cardiac computed tomography (CT) has made substantial progress in recent years. The main field of application is CT coronary angiography for visualization of the coronary arteries and for the detection and exclusion of coronary artery stenosis. This has been included in international guidelines for the management of stable coronary artery disease or chronic coronary syndrome as well as for the diagnostic work-up of patients with acute chest pain; however, it must be taken into account that the diagnostic validity is only sufficiently high when the image quality is good and therefore alternative diagnostic procedures should be included in patients where an unrestricted good image quality is not to be expected. The fact that CT angiography enables the detection not only of coronary stenosis but also of nonobstructive atherosclerotic plaque is interesting for the estimation of the risk of atherosclerotic events. It is practically certain that in the absence of detectable atherosclerotic plaque in CT angiography, statin treatment does not lower the risk of atherosclerotic events. To what extent CT is suitable to provide indications for statin treatment and the threshold for which the presence of nonobstructive plaque should prompt initiation of statin treatment are currently the subject of intensive research.


Isolated bilateral inguinal lymphadenopathy in the absence of other symptoms, due to LGV in known HIV-positive MSM: is it more common than we think?
The current resurgence of lymphogranuloma venereum (LGV) has drawn most attention to its potential for causing proctitis; however, this case highlights the need for awareness of LGV as a cause of isolated painful bilateral inguinal lymphadenopathy in a high-risk population and the importance of routine screening for LGV. We describe a case of a 37-year-old HIV positive man, in the population of men who have sex with men (MSM) who presented with bilateral enlarged inguinal lymph nodes and no other symptoms or signs. Urine nucleic acid amplification test was positive for chlamydia LGV-specific DNA. Tests from other sites were negative.


Ultrastructural aspects of Fallisia effusa (Haemosporina: Garniidae) in thrombocytes of the lizard Neusticurus bicarinatus (Reptilia: Teiidae).
The fine structure of the different stages of the Fallisia effusa (Haemosporina: Garniidae), infecting the thrombocytes of the semi-aquatic Amazonian lizard Neusticurus bicarinatus (Reptilia: Teiidae) is described. Gametocytes, meronts, and merozoites of Fallisia effusa were found within a parasitophorous vacuole (PV). Multiple infections of micro- and macrogametocytes were observed. A circumferential coil of microtubules was seen in the cytoplasm of the infected host cell and this microtubule array was pronounced in cells harboring gametocytes. A deep invagination of the inner membrane complex of gametocytes may be involved in nutrition. The non-pigmented parasites underwent both merogony and gametogony in thrombocytes of the peripheral blood. No infection of the erythrocytes was observed. These observations confirm that Fallisia effusa displays characteristic features distinguishing it from other members of the Haemosporidian families, and that it has the ability to modulate microtubule assembly.


Molecular Vises for Precisely Positioning Ligands near Catalytic Metal Centers in Metal-Organic Frameworks.
We report the construction of a molecular vise by pairing a tritopic phenylphosphorus(III) linker and a monotopic linker in opposite positions within a metal-organic framework. The angle between these linkers at metal sites is fixed upon changing the functionality in the monotopic linker, while the distance between them is precisely tuned. This distance within the molecular vise is accurately measured by 1H-31P solid-state nuclear magnetic resonance spectroscopy. This unveils the impact of the distance on catalytic performance without interference from electrostatic effects or changes in the angle of the ligand, which is unprecedented in classic organometallic complexes.


Minimal sulfated carbohydrates for recognition by L-selectin and the MECA-79 antibody.
Sulfated forms of sialyl-Le(X) containing Gal-6-SO(4) or GlcNAc-6-SO(4) have been implicated as potential recognition determinants on high endothelial venule ligands for L-selectin. The optimal configuration of sulfate esters on the N-acetyllactosamine (Galbeta1-->4GlcNAc) core of sulfosialyl-Le(X), however, remains unsettled. Using a panel of sulfated lactose (Galbeta1-->4Glc) neoglycolipids as substrates in direct binding assays, we found that 6',6-disulfolactose was the preferred structure for L-selectin, although significant binding to 6'- and 6-sulfolactose was observed as well. Binding was EDTA-sensitive and blocked by L-selectin-specific monoclonal antibodies. Surprisingly, 6', 6-disulfolactose was poorly recognized by MECA-79, a carbohydrate- and sulfate-dependent monoclonal antibody that binds competitively to L-selectin ligands. Instead, MECA-79 bound preferentially to 6-sulfolactose. The difference in preferred substrates between L-selectin and MECA-79 may explain the variable activity of MECA-79 as an inhibitor of lymphocyte adhesion to high endothelial venules in lymphoid organs. Our results suggest that both Gal-6-SO(4) and GlcNAc-6-SO(4) may contribute to L-selectin recognition, either as components of sulfosialyl-Le(X) capping groups or in internal structures. By contrast, only GlcNAc-6-SO(4) appears to contribute to MECA-79 binding.


Biological confounders for the values of cerebrospinal fluid proteins in Parkinson's disease and related disorders.
Cerebrospinal fluid (CSF) has been extensively studied to explore biochemical alterations in subjects with neurodegenerative disorders. In Alzheimer's disease, levels of increased CSF tau protein and decreased levels of β-amyloid 1-42 (Aβ42) have been shown to correlate with brain plaque formation and tangle pathology. Intracellular Lewy inclusions containing aggregated α-synuclein (α-syn) represent a pathological hallmark of Parkinson's disease (PD). In most - but not all - studies published to date total CSF α-syn concentrations have been found to be decreased in disorders related to α-syn pathology, that is, PD, dementia with Lewy bodies and multiple system atrophy. However, these reports show extensive signal overlap among tested individuals, thereby diminishing its potential for routine use in clinical practice. To investigate potential biological (i.e., non-technical) confounders of reported CSF levels for α-syn, Aβ42, and tau in PD and related disorders, we carried out a methodical review of known factors that underlie signal variability and speculate on those that have not yet been tested. We discuss several biological factors, such as neuropathology, demographics, clinical phenotype, progression and duration of disease, concomitant illnesses and, last but not least, pharmacotherapy, which in isolation or combination can substantially alter values for CSF proteins of interest. Enhanced implementation of standardized clinical protocols, streamlined operating procedures, and further progress in the development of validated assays for CSF proteins have the potential to (i) inform us as to the pathogenesis of disease, (ii) support the laboratory-based diagnosis for symptomatic subjects in the future, and (iii) facilitate breakthrough therapies to alter the course of neurodegenerative disorders, such as PD and Alzheimer's disease. Cerebrospinal fluid (CSF) has been extensively studied to explore biochemical alterations in subjects with neurodegenerative disorders. To investigate potential biological confounders of reported CSF levels for α-synuclein (α-Syn), amyloid-β 1-42(Aβ42) and tau protein in Parkinson's disease and related disorders, we reviewed the current literature for known factors that underlie signal variability and speculate on those that have not yet been tested. This article is part of a special issue on Parkinson disease.


Neural network-based detection of esophageal intubation in anesthetized patients.
To test whether a neural network-based method could differentiate between tracheal and esophageal intubation in anesthetized patients by recognizing breathing circuit pressure and flow waveform patterns. Tracheal tubes were placed in the trachea and in the esophagus of adult patients undergoing elective operations. After ensuring for proper oxygenation, ventilator settings were changed to 5 ml/kg tidal volume (VT) and 15 cpm and circuit pressure and flow were recorded for 15 seconds. Then, the breathing circuit was switched to the tube placed in the esophagus, and signals were recorded for an additional 15-second period. During off-line analysis, individual waveforms were separated. Tracheal breaths were labeled with a score of 1 while esophageal "breaths" were labeled with -1. A neural network was defined to learn to associate waveforms to their corresponding scores. Data from 54% of the patients were used to train the neural network. Data from the remaining subjects were used for testing. Forty-six patients were studied. Neural network training was achieved with 100 tracheal and 94 esophageal waveforms from 25 patients. Neural network performance was tested on 84 tracheal and 76 esophageal waveforms from 21 subjects. The neural network assigned scores of 0.99 +/- 0.05 (mean +/- SD) to tracheal waveforms and -0.99 +/- 0.03 to esophageal waveforms. The difference between mean esophageal and tracheal scores was -1.99 with a 99.999% confidence range of -2.01 to -1.96. Any arbitrary cutoff threshold, ranging between -0.76 and 0.7, separated tracheal and esophageal score regions, yielding no false positive or negative results. A neural network differentiated consistently tracheal from esophageal intubation when the ventilation test mode was used. The ventilation mode employed is feasible in most adult patients undergoing elective procedures under general anesthesia. Further research is required to train neural networks to recognize esophageal intubation in different age groups and when different ventilation modes are applied.


Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression.
Leukocyte adhesion to the diabetic retinal vasculature results in blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Intercellular adhesion molecule-1 (ICAM-1) and the leukocyte integrin CD18 are required for these processes. Diabetes was induced in Long Evans rats, resulting in a two- to threefold increase in retinal leukocyte adhesion. Following one week of diabetes, neutrophil CD11a, CD11b, and CD18 expression was increased significantly, as were retinal ICAM-1 levels. Animals were treated with aspirin, a cyclooxygenase 2 (COX-2) inhibitor (meloxicam), or a soluble tumor necrosis factor alpha (TNF-alpha) receptor/Fc construct (TNFR-Fc, etanercept). High-dose aspirin, etanercept, and high-dose meloxicam each reduced leukocyte adhesion and suppressed blood-retinal barrier breakdown. High-dose aspirin also reduced the expression of CD11a, CD11b, and CD18, whereas meloxicam and etanercept did not. High-dose aspirin, etanercept, and high-dose meloxicam each reduced retinal ICAM-1 expression. Aspirin and meloxicam both lowered retinal TNF-alpha levels. Notably, aspirin, meloxicam, and etanercept did not change retinal vascular endothelial growth factor levels. High-dose aspirin, etanercept and high-dose meloxicam, each suppressed the retinal expression of eNOS and the DNA-binding capacity of retinal nuclear factor-kappaB. High-dose aspirin also suppressed Erk kinase activity, which is involved in CD18 up-regulation. Taken together, these data identify COX-2 and TNF-alpha as operative in the early signature pathologies of diabetic retinopathy, a newly recognized inflammatory disease.


Apelin could reduce risk of contrast-induced nephropathy in patients with congestive heart failure.
Compared to the normal population, patients with congestive heart failure are at higher risk for contrast-induced nephropathy. A variety of interventions are suggested to reduce the risk for contrast-induced nephropathy. Unfortunately results of none of current protective treatments are satisfactory. Apelin a vasodilator adipocytokine, positively inotropic agent, and free radical scavenger has been recently introduced. It has been shown that endogenous apelin levels are decreased in patients with congestive heart failure. Two major mechanisms have been suggested for pathophysiology of contrast induced nephropathy including reactive oxygen species production and impaired renal perfusion due to vasoconstriction. Pretreatment with recombinant apelin (exogenous apelin-13), could compensate decreased endogenous apelin serum levels of congestive heart failure patients. Its antioxidant and cell-protective properties, decrease nephrotoxicity of contrast agent; additionally impaired renal perfusion due to malfunction of cardiac pump will refurbish, because of positively inotropic property of apelin plus its vasodilatation effect in renal arteries. We believe that the triangle of increased contractility, decreased vascular resistance and decreased contrast agent nephrotoxicity could significantly reduce risk of contrast-induced nephropathy in patients with congestive heart failure.


A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas.
The c-myc gene comprises three exons with a single large AUG-initiated open reading frame extending from exon 2 through exon 3. Exon 1 lacks any AUG codons. Cells from a wide range of species produce two c-myc proteins that, while highly related, do not appear to arise from posttranslational interconversion. To understand the origin of the two proteins, we mapped them and analyzed the in vitro protein-coding capacity of c-myc cDNAs. Our findings show that the two proteins are derived from alternative translational initiations at the exon 2 AUG and at a non-AUG codon near the 3' end of exon 1, resulting in the production of proteins with distinct N termini. In Burkitt's lymphomas, the removal or specific mutation of exon 1 in c-myc translocations correlates with suppression of synthesis of the larger protein, and thus may contribute to the oncogenic activation of c-myc.


Properties of various Rho1 mutant alleles of Cryptococcus neoformans.
The RHO1 homologue of Cryptococcus neoformans complemented Saccharomyces cerevisiae rho1 mutations. The results of overexpression and site-specific mutagenesis of CnRHO1 in C. neoformans and S. cerevisiae indicated that although CnRHO1 could functionally substitute for the RHO1 gene of S. cerevisiae, mutants of cnrho1 manifested unique features in certain aspects.


Ethyl 2-amino-4-methyl-thio-phene-3-carboxyl-ate.
The title compound, C8H11NO2S, crystallizes with two mol-ecules, A and B, in the asymmetric unit. Each molecule features an intramolecular N-H⋯O hydrogen bond and the same H atom is also involved in an intermolecular N-H⋯S bond to generate A + B dimers. Further N-H⋯O hydrogen bonds link the dimers into a [010] chain.


Molecular Recalibration of PD-1+ Antigen-Specific T Cells from Blood and Liver.
Checkpoint inhibitors and adoptive cell therapy provide promising options for treating solid cancers such as HBV-related HCC, but they have limitations. We tested the potential to combine advantages of each approach, genetically reprogramming T cells specific for viral tumor antigens to overcome exhaustion by down-modulating the co-inhibitory receptor PD-1. We developed a novel lentiviral transduction protocol to achieve preferential targeting of endogenous or TCR-redirected, antigen-specific CD8 T cells for shRNA knockdown of PD-1 and tested functional consequences for antitumor immunity. Antigen-specific and intrahepatic CD8 T cells transduced with lentiviral (LV)-shPD-1 consistently had a marked reduction in PD-1 compared to those transduced with a control lentiviral vector. PD-1 knockdown of human T cells rescued antitumor effector function and promoted killing of hepatoma cells in a 3D microdevice recapitulating the pro-inflammatory PD-L1hi liver microenvironment. However, upon repetitive stimulation, PD-1 knockdown drove T cell senescence and induction of other co-inhibitory pathways. We provide the proof of principle that T cells with endogenous or genetically engineered specificity for HBV-associated HCC viral antigens can be targeted for functional genetic editing. We show that PD-1 knockdown enhances immediate tumor killing but is limited by compensatory engagement of alternative co-inhibitory and senescence program upon repetitive stimulation.


Application of nonpolar matrices for the analysis of low molecular weight nonpolar synthetic polymers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
The application of nonpolar matrices for the analysis of low molecular weight nonpolar synthetic polymers using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is demonstrated. Anthracene, pyrene, and acenaphthene were utilized as nonpolar matrices for the analysis of polybutadiene, polyisoprene, and polystyrene samples of various average molecular weights ranging from about 700 to 5,000. The standard MALDI-MS approach for the analysis of these types of polymers involves the use of conventional acidic matrices, such as all-trans-retinoic acid, with an additional cationization reagent. The nonpolar matrices used in this study are shown to be as equally effective as the conventional matrices. The uniform mixing of the nonpolar matrices and the nonpolar analytes enhances the MALDI-MS spectral reproducibility. Silver salts were found to be the best cationization reagents for all of the cases studied. Copper salts worked well for polystyrene, poorly for polyisoprene, and not at all for polybutadiene samples. These matrices should be useful for the characterization of hydrocarbon polymers and other analytes, such as modified polymers, which may potentially be sensitive to acidic matrices.


Results of the 2018 Japan Society for Blood Purification in Critical Care survey: current status and outcomes.
The Japan Society for Blood Purification in Critical Care (JSBPCC) has reported survey results on blood purification therapy (BPT) for critically ill patients in 2005, 2009, and 2013. To clarify the current clinical status, including details of the modes used, treated diseases, and survival rate, we conducted this cohort study using data from the nationwide JSBPCC registry in 2018. We analyzed data of 2371 patients who underwent BPT in the intensive care units of 43 facilities to investigate patient characteristics, disease severity, modes of BPTs, including the dose of continuous renal replacement therapy (CRRT) and hemofilters, treated diseases, and the survival rate for each disease. Disease severity was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores. BPT was performed 2867 times in the 2371 patients. Mean APACHE II and SOFA scores were 23.5 ± 9.4 and 10.0 ± 4.4, respectively. The most frequently used mode of BPT was CRRT (67.4%), followed by intermittent renal replacement therapy (19.1%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (7.3%). The most commonly used anticoagulant was nafamostat mesilate (78.6%). Among all patients, the 28-day survival rate was 61.7%. CRRT was the most commonly used mode for many diseases, including acute kidney injury (AKI), multiple organ failure (MOF), and sepsis. The survival rate decreased according to the severity of AKI (P = 0.001). The survival rate was significantly lower in patients with multiple organ failure (MOF) (34.6%) compared with acute lung injury (ALI) (48.0%) and sepsis (58.0%). Multivariate logistic regression analysis revealed that sepsis, ALI, acute liver failure, cardiovascular hypotension, central nervous system disorders, and higher APACHE II scores were significant predictors of higher 28-day mortality. This large-scale cohort study revealed the current status of BPT in Japan. It was found that CRRT was the most frequently used mode for critically ill patients in Japan and that 28-day survival was lower in those with MOF or sepsis. Further investigations are required to clarify the efficacy of BPT for critically ill patients.Trial Registration : UMIN000027678. The online version contains supplementary material available at 10.1186/s41100-022-00445-0.


The artificial urinary sphincter.
Urinary incontinence has many etiologies and a similarly varied and wide-ranging spectrum of therapeutic alternatives. The AMS artificial sphincter represents one of these options that has a distinct, albeit limited, place in certain patients. The authors outline the mechanical details of these devices and present their own clinical experience in a large pediatric population.


Comparative study of vascular effects of four calcium antagonists using a multi-organ functional imaging technique with thallium-201.
The vasoactive effects of calcium antagonist drugs were compared using a multi-organ functional imaging technique with thallium-201 (Tl-201). Four drugs were tested at two different doses: nifedipine (10 and 25 micrograms/kg), verapamil (100 and 250 micrograms/kg), diltiazem (100 and 250 micrograms/kg), and bepridil (2.5 and 10 mg/kg). Tl-201 was injected at three different times after drug administration to examine the time course of the effects of the drugs. The regions studied were heart, liver, kidneys, shoulder skeletal muscles, and lungs. The results showed marked changes in Tl-201 biodistribution in anesthetized dogs after administration of calcium antagonists. The major increases in count density were observed in heart and skeletal muscles, but the drug effects differed in intensity and duration. Nifedipine induced the largest variations in the doses used (136 and 153% in the heart 2 min after 10 and 25 micrograms/kg doses, respectively). Diltiazem and verapamil were most efficient at 250 micrograms/kg (134 and 115% at 2 min after injection, respectively). With bepridil the increases of cardiac and muscular uptakes of Tl-201 were transient and the 2.5 mg/kg dose induced a decrease of myocardial count density (84% at 5 min). The effects were less reproducible in the other organs studied.


Sexual life of males over 50 years of age with spinal-cord lesions of at least 20 years.
To assess over the past year the sexuality of male patients with spinal-cord injury (SCI) over 50 years of age with spinal lesions of at least 20 years. Subjects were stratified in two groups: 44 individuals under 60 years and 55 individuals over 60 years. A detailed sexual anamnesis was taken for all, and the SF-36 Health Survey questionnaire was completed, with questions 13 and 14 concerning overall sexual life answered through the International Index of Erectile Function. The younger group reached a median score of +50 for each domain of the SF-36; however, the differences between the two groups are not statistically relevant. The physical domain of the SF-36 showed a median score of 43.2 for the younger versus 41.1 for the older, whereas the mental domain showed 44.8 and 43.1, respectively. In the first group, 29/44 (65.9) individuals claimed erectile dysfunction versus 43/55 (78.1%) in the second, whereas 34/44 (77.2%) of the first group reported having sexual intercourse versus 13/55 (23.6%) with P<0.01 (chi2 test). In the 2nd, 29/55 (52.7%) individuals reported physical intimacy without sexual intercourse. For each group, the overall sexual satisfaction is statistically correlated to the duration of the relationship (linear progression test P<0.05). Median quality of life was high. Sexual intercourse is fundamental only for males of the first group. Most aging couples presented a different way of thinking about sex without the need for intercourse. Physicians should acquire knowledge about sexuality and aging in SCI patients. This study was not sponsored.


Transcriptomics analysis of Daheng broilers reveals that PLIN2 regulates chicken preadipocyte proliferation, differentiation and apoptosis.
Intramuscular fat content, an important meat quality trait, strongly affects flavor, juiciness, and tenderness. Sex hormones regulate lipid metabolism, and female hormones stimulate fat deposition, thereby making the female chickens always fatter than males. In this study, the effect of sex on IMF deposition was screened following transcriptomics in chickens. Results confirmed significantly higher IMF content of 150-day female chickens as compared to the male chickens. The female chickens manifested higher serum TG, LDL-C, and VLDL, and significantly lower HDL-C contents than male chickens. Moreover, differential expression of genes involved in lipid metabolism were obtained in the muscle and liver between female and male chicken, which could partly interpret the possible reasons for the sex-mediated differences of IMF content. Cellular results revealed that inhibition of PLIN2 significantly inhibited chicken preadipocyte proliferation and induces apoptosis of preadipocytes, as well as promoted adipocyte differentiation. According to our results, PLIN2 may be considered as a molecular marker for poultry meat quality and applying this gene in early breed selection.


Comparison of emergent laparoscopic and open repair of acutely incarcerated and strangulated hernias-short- and long-term results.
Incarcerated and strangulated hernias are a common clinical presentation encompassing several challenges in acute care surgery. The role of laparoscopy is still controversial and the data is scarce. Laparoscopy enables better evaluation of the incarcerated organ and its viability. The use of mesh repair in these emergent operations is also a major concern. In this series we aimed to evaluate the safety and efficacy of laparoscopic emergent repairs of acutely incarcerated and strangulated hernias, and their long-term results, in comparison to the conventional open repairs. Retrospective review of prospectively collected data of all adult patients, between the ages of 18 and 89, who underwent emergent operation due to an incarcerated and strangulated hernia between November 2017 and December 2020. During the study period, 89 patients underwent emergent operation due to incarcerated hernias-63 laparoscopic repair and 26 underwent an open repair. In the laparoscopic group (LG) 38 patients had a groin hernia and 25 had a ventral hernia, while in the open group (OG) the distribution was 12 and 14, respectively. When operated laparoscopically, all groin hernias but one were repaired in the TAPP approach and most ventral hernias were repaired using the IPOM + approach. During the peri-operative period there were 3 mortalities (1 in the LG). There were no significant differences between the groups in minor or major complications. Mean follow-up time in the LG was 27.9 months and 29.4 months in the OG. There was no significant difference in recurrence rates. Long-term results showed better outcome in the LG regarding pain at rest, difficulty doing exercise and local discomfort. Laparoscopic emergent repair of incarcerated hernias is a safe and feasible approach, with better short and long-term results compared to the open approach.


Study of the effect of current intensity on the structural performance of electrogenerated mesoporous aluminum phosphate: application for adsorption.
To keep up with the development of contaminants in the water supply, it is required to create new adsorbents or improve current ones. The adsorption capacity of AlPO4 electrocoagulated with varying current intensities was examined. AlPO4 was produced by electrolysis in a NaCl solution using aluminum electrodes and a 0.1 M phosphate buffer at varying current intensities. Current efficiency was enhanced. X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy were used to analyze the adsorbents (FTIR). The specific surface area was estimated by the quantity of methylene blue adsorbed by particles in an aqueous solution. Numerous operating factors must be addressed, including pH, starting concentration, adsorbent dose, and contact duration. The electrostatic interaction between positively charged MB molecules and negatively charged adsorbents drives adsorption at alkaline pH. When describing equilibrium adsorption, the Langmuir model is more accurate. Modeling using an adsorption isotherm may further improve the predicted specific surface area. At 0.2 amperes, the observed specific surface area was 2.86 m2/g.


Analysis of the improvement of serological indexes in patients with diabetic nephropathy and hypertension using Valsartan combined with Nifedipine controlled-release regimen.
To investigate the effect of valsartan combined with nifedipine controlled-release Tablets on diabetic nephropathy (DN) patients with hypertension. The clinical records of 80 DN patients with hypertension registered in our hospital from April 2020 to April 2021 were collected. The records showed that 38 patients were treated with oral nifedipine controlled-release tablets (control group) and 42 - with oral valsartan combined with nifedipine controlled-release tablets (observation group). The improvement of serological indexes after treatment was compared and analyzed between the two groups. After treatment, the levels of fasting blood glucose (FBG), systolic and diastolic blood pressure, bone oligomeric matrix protein (COMP), thrombin regulatory protein (TM) and Microalbumin (mALB) in the observation group were lower than those in the control group (P<0.05), while the level of angiopoietin-1 (Ang-1) was higher than those in the control group (P<0.05). After the treatment, the levels of homocysteine (Hcy), Cystatin C (CysC) and transforming growth factor β1(TGF-β1) in the observation group were lower than those in the control group (P<0.05). The levels of adiponectin (APN), aldosterone (ALD) and gastric growth promoting factor (ghrelin) in the observation group after the treatment were lower than those in the control group (P<0.05). A combination of valsartan and nifedipine controlled-release tablets in DN patients with hypertension can effectively control blood glucose and blood pressure, improve the serological indexes such as COMP, TM, mAlb, Ang-1, Hcy, CysC, TGF-β1, APN, ALD and ghrelin, and potentially reduce and delay renal function damage.


Gross anatomical variations of the insular cortex in first-episode schizophrenia.
Magnetic resonance imaging (MRI) studies have revealed gray matter reductions in the insular cortex of schizophrenia patients. Despite large inter-individual anatomical variations in the insular gyri of human brains, the gross anatomical features of the insular cortex and their relationships with clinical characteristics remain largely unknown in schizophrenia. The present MRI study investigated variations in the insular gross anatomy (i.e., the development and split patterns of each gyrus and gyrus numbers) and their relationships with clinical variables and insular gray matter volumes in 66 patients with first-episode schizophrenia (FE-Sz) and 66 age- and sex-matched healthy controls. The FE-Sz group had a significantly larger number of insular gyri bilaterally with well-developed accessory, middle short, and posterior long insular gyri than the control group, and this was associated with a younger onset age and severe positive symptoms. The split patterns of major insular gyri did not significantly differ between the groups. The FE-Sz group was also characterized by a smaller gray matter volume in the insular cortex than the control group; however, this was not associated with the insular gross anatomy or clinical characteristics. As the insular gyral organization reflects brain development during mid to late gestation, the gross anatomical features of the insular cortex in schizophrenia, which were independent of gray matter volumes, may be used as early neurodevelopmental abnormality markers for the illness.


Perception of quality and complexity in wine and their links to varietal typicality: An investigation involving Pinot noir wine and professional tasters.
Quality and complexity are abstract terms employed frequently to describe a wine's overall attributes. In the present study, we investigated: (i) attributes driving wine professionals' judgments of quality and complexity in Pinot noir wines; (ii) the relation between these two abstract concepts; and (iii) association of each concept with varietal typicality. Twenty-two wine professionals evaluated 18 New Zealand Pinot noir wines in both clear and opaque glassware via two sensory tasks, a descriptive rating task and an 8-attribute, perceived complexity questionnaire. Sensory data were associated with wine UV-spectrophotometry colour measures to aid interpretation of the influence of tasting-glass colour. Results demonstrated the key drivers of perceived quality were descriptors varietal typicality, expressiveness, overall structure, and attractive fruit aromatics, along with complexity questionnaire attributes of harmony, balance and number of identifiable flavours. Reductive notes drove low-quality judgments. Data show that quality and complexity were positively associated concepts and that both were linked positively with varietal typicality. Visual influence was not a major driver of wine professionals' judgments but being able to see a wine's colour influenced tasters' judgments to wines at each end of the price/quality spectrum. We discuss the results in terms of cognitive phenomena associated with judgments by those with domain-specific expertise.


Nuclear-relaxed elastic and piezoelectric constants of materials: Computational aspects of two quantum-mechanical approaches.
Two alternative approaches for the quantum-mechanical calculation of the nuclear-relaxation term of elastic and piezoelectric tensors of crystalline materials are illustrated and their computational aspects discussed: (i) a numerical approach based on the geometry optimization of atomic positions at strained lattice configurations and (ii) a quasi-analytical approach based on the evaluation of the force- and displacement-response internal-strain tensors as combined with the interatomic force-constant matrix. The two schemes are compared both as regards their computational accuracy and performance. The latter approach, not being affected by the many numerical parameters and procedures of a typical quasi-Newton geometry optimizer, constitutes a more reliable and robust mean to the evaluation of such properties, at a reduced computational cost for most crystalline systems. © 2016 Wiley Periodicals, Inc.


Precise determination of cadmium and lead isotopic compositions in river sediments.
A method for the accurate determination of Cd and Pb isotope compositions in sediment samples is presented. Separation of Cd and Pb was designed by using an anionic exchange chromatographic procedure. Measurements of Cd isotopic compositions were carried out by multi-collector inductively coupled plasma mass spectrometer (MC-ICPMS), by using standard-sample bracketing technology for mass bias correction and Pb isotopic ratios were determined by thermal ionization mass spectrometry (TIMS). The factors that affect the accurate and precise Cd isotope compositions analysis, such as instrumental mass fractionation and isobaric interferences, were carefully evaluated and corrected. The Cd isotopic results were reported relative to an internal Cd solution and expressed as the delta(114/110)Cd. Five Cd reference solutions and one Pb standard were repeatedly measured in order to assess the accuracy of the measurements. Uncertainties obtained were estimated to be lesser than 0.11 per thousand (2s) for the delta(114/110)Cd value. Analytical uncertainties in 2s for Pb isotopic ratios were better than 0.5 per thousand. The method has been successfully applied to the investigation of Cd and Pb isotope compositions in sediment samples collected from North River in south China.


Satellite glial cells in situ within mammalian prevertebral ganglia express K+ channels active at rest potential.
Patch-clamp experiments were performed on satellite glial cells wrapped around sympathetic neurons in the rabbit coeliac ganglion. With the cleaning method used, the glial cells could be kept in place and were directly accessible to the patch-clamp pipettes. Whole-cell recordings showed that glial cells had almost ohmic properties. Their resting potential (-79.1 +/- 1.2 mV) was found to be very nearly the same as the K+ reversal potential and approximately 20 mV more negative than that of the neurons they encapsulated. Unitary currents from ionic channels present in the glial membrane were recorded in the cell-attached configuration with pipettes filled with various amounts of K+, Na+ and gluconate. Only K(+)-selective channels with slight inwardly rectifying properties (in the presence of 150 mM [K+]o) were detected. These channels were active (Po = 0.7-0.8) at the cell resting potential. The channel conductance, but not its opening probability, was dependent on the [K+] in the pipette. Cl(-)-selective channels (outwardly rectifying and large conductance channels) were detected in excised patches. The properties of the K+ channels (increased inward current with [K+] and detectable outward current at low [K+]) are well suited for siphoning the K+ released by active neurons.


Constraints on growth and allocation patterns of Silphium integrifolium (Asteraceae) caused by a cynipid gall wasp.
Insect herbivory can have important effects on plant life histories and architecture. We quantified the impact that a cynipid gall wasp, Antistrophus silphii, had on growth, reproduction, and biomass allocation patterns of Silphium integrifolium growing in the tallgrass prairie of northeastern Kansas. Experimentally galled individual Silphium shoots (ramets) had reduced shoot growth, leaf and flower head production, and delayed flowering compared to gall-free control shoots. Gall formation completely halted normal apical growth in 65% of the shoots. Galling did not affect individual flower head weight, the numbers of achenes per flower head or achene weight. Silphium plants (genets) with a high proportion of galled shoots had lower total biomass, a lower proportion of total biomass allocated to flower heads, higher allocation to leaves, but no change in allocation to stems or rhizome. High gall densities reduced the number of flower heads per plant and shortened the time between flower head initiation and maturity. An adaptive interpretation of these results would be that the survivorship and future performance of galled Silphium may be promoted by maintaining allocation to rhizome. However, reduced shoot growth and delayed reproduction in galled Silphium may weaken its competitive ability and reduce pollination success, so that any adaptive advantage to Silphium's allocation responses to galls may be outweighed by disadvantages from its growth and flowering phenology responses. We conclude that a more parsimonious interpretation of these results is that gall-induced allocation changes are due to architectural constraints placed by galls on meristem activity, rather than to any adaptive response on the part of the plant.


A novel algorithm for analyzing drug-drug interactions from MEDLINE literature.
Drug-drug interaction (DDI) is becoming a serious clinical safety issue as the use of multiple medications becomes more common. Searching the MEDLINE database for journal articles related to DDI produces over 330,000 results. It is impossible to read and summarize these references manually. As the volume of biomedical reference in the MEDLINE database continues to expand at a rapid pace, automatic identification of DDIs from literature is becoming increasingly important. In this article, we present a random-sampling-based statistical algorithm to identify possible DDIs and the underlying mechanism from the substances field of MEDLINE records. The substances terms are essentially carriers of compound (including protein) information in a MEDLINE record. Four case studies on warfarin, ibuprofen, furosemide and sertraline implied that our method was able to rank possible DDIs with high accuracy (90.0% for warfarin, 83.3% for ibuprofen, 70.0% for furosemide and 100% for sertraline in the top 10% of a list of compounds ranked by p-value). A social network analysis of substance terms was also performed to construct networks between proteins and drug pairs to elucidate how the two drugs could interact.


Polysaccharides and lignin from oak wood used in cooperage: Composition, interest, assays: A review.
It is widely accepted that alcoholic beverage quality depends on their ageing in premium quality oak wood. From the choice of wood to beverage ageing, through the different steps in cask manufacturing, many factors should be considered. One of the biggest challenge in cooperages is to take into account all these factors. Most of the studies are interested in phenolic compounds, extracted during ageing and especially involved in wine oxidation, colour, and sensory properties such as astringency and bitterness. Oak aroma volatile compounds have also been the subject of numerous studies. These compounds of interest are part of low molecular weight compounds which represent 2%-10% of oak wood composition. However, three polymers constitute the main part of oak wood: cellulose, hemicellulose and lignin. As far as we are aware, few studies concerning the role of these major macromolecules in oak wood have been published previously. This article reviews oak wood polysaccharides and lignin, their potential interest and different assays used to determine their content.


Developmental aspects of epilepsy with special reference to age-dependent epileptic encephalopathy.
The specificity of childhood epilepsy was characterized by investigating the evolutional changes with age and prognoses of age-dependent epileptic encephalopathy from the developmental aspect through a long-term follow-up. Three types of age-dependent epileptic encephalopathy showed mutual evolutional changes at certain ages. This indicated an important role of the brain development in the clinicoelectroencephalographical manifestations of age-dependent epileptic encephalopathy. Furthermore, the evolutional changes demonstrated an association with organic brain damage and etiology in addition to the age factors. The evolutional changes occurred more frequently in the cases with overt organic brain pathology. The prognosis was poorer in cases which underwent an evolutional change.


Metastatic testicular rhabdomyosarcoma--a report of two cases.
Rhabdomyosarcoma is the most common type of soft tissue sarcoma in children. The tumor spreads by local extension, to regional lymph nodes, or by distant metastases. Metastatic spread to the testicle has been rarely described. The authors describe 2 boys who were found to have intratesticular metastases after presenting with primary tumors in their extremities. The first patient, an 11-year-old boy presented with primary disease in his left foot and an enlarged testicle. Rhabdomyosarcoma was found histologically in both the foot and the testicle. A second boy 17 years of age had a primary tumor involving the left upper extremity treated with amputation, chemotherapy, and radiotherapy. A relapse was noted 2 years later in the left testicle and was treated with orchiectomy. The authors discuss the implications and the management of this rare presentation of metastatic rhabdomyosarcoma.


Primary plasmablastic lymphoma of the gastrointestinal tract: A series of 13 HIV-negative cases and a review of literature.
Primary gastrointestinal plasmablastic lymphoma (GI-PBL) is a rare variant of diffuse B-cell lymphoma with an aggressive clinical course. PBL was initially reported among HIV-positive patients; however, subsequent studies have shown that it also occurs among HIV-negative patients. Its clinical characteristics remain poorly understood. This study aims to retrospectively analyze the clinicopathological findings of primary GI-PBLs in HIV-negative patients. Primary HIV-negative GI-PBL cases from 2008 to 2022 were reviewed. Clinicopathologic features and outcomes were analyzed. The cohort of 13 patients had a male-to-female ratio of 9:1 (3 patients' genders not available), with an average age of 61 (range, 30-92) years. The most involved location was the colon (n = 7 [53.8 %]), followed by the small bowel (n = 3 [23.1 %]), stomach (n = 2 [15.4 %]), rectum (n = 1 [7.7 %]), and anus (n = 1 [7.7 %]). Most patients (n = 10 [77 %]) showed isolated GI tract involvement. Eight patients had chronic inflammatory and/or immunocompromised status, including 4 with inflammatory bowel disease (all of whom underwent treatment), 3 with post-organ transplant status, and 1 with irritable bowel syndrome. All cases exhibited cytokeratin-/CD20-/PAX-5-/CD138+ and/or MUM1+ immunophenotype. Based on available data, 8 of 11 (72.7 %) patients had Epstein-Barr virus reactivation. Among 11 patients with follow-up data, the mean follow-up duration was 13.5 (range, 3-40) months; at the end of follow-up, 45.5 % of patients (5 of 11 patients) showed complete remission after chemotherapy. Primary HIV-negative GI-PBL occurs predominantly in the colon of relatively elderly males with immunosuppression. Its clinical course can be heterogenous, presenting a comorbidity with inflammatory bowel disease or post-organ transplantation status.


Extraction of Metabolites from Cancer Cells.
Cancer cells possess an elevated demand for nutrients and metabolites due to their uncontrolled proliferation and need to survive in unfavorable conditions. Autophagy is a conservative degradation pathway that counters lack of nutrients and provides organelle and protein quality control, beyond maintenance of cellular metabolism.Mass spectrometry-based metabolomics is a powerful tool to study the metabolome of a cell. Such analysis requires proper sample preparation including the extraction of metabolites. Here, we provide a protocol for the extraction of metabolites from adherent cancer cells suitable for global metabolome profiling by mass spectrometry.


Isolation, characterization, and efficacy of bacteriophages isolated against Citrobacter spp. an in vivo approach in a zebrafish model (Danio rerio).
Citrobacter infections are becoming an increasingly significant health problem in aquaculture in South-Eastern countries. The objective of this study was to isolate and evaluate the potential of lytic bacteriophages against Citrobacter infections. TEM analysis revealed that the isolated phages Citrophage MRM19 and Citrophage MRM57 were identified to be Siphovirus and Podovirus family of the order Caudovirales. The phage life-cycle studies showed that Citrophage MRM19 had an adsorption time of 18 ± 1 min and a latency period of 25 ± 3 min with burst size of 110 ± 20 phages/infected cell and Citrophage MRM57 had an adsorption time of 15 ± 1 min and a latency period of 25 ± 2 min with burst size of 50 ± 5 phages/infected cell. In vitro studies indicated that the bacterial load was reduced by 5 and 7 log units within 12 h by Citrophage MRM19 and Citrophage MRM57. The in vivo efficacy of the phages was studied using zebrafish (Danio rerio) as a model organism in low-scale tanks. The study unveiled that the use of phages increased the survival up to 17%, 23%, and 26% in the case of Citrophage MRM19, Citrophage MRM57, and phage cocktail treatment, respectively. Our study indicated that bacteriophages are suitable biocontrol agents against Citrobacter spp. especially in aquaculture industry.


Cold-inducible expression of the cell division cycle gene CDC48 and its promotion of cell proliferation during cold acclimation in zebrafish cells.
A member of the ATPases associated with diverse cellular activities (AAA) family, the cell division cycle gene CDC48/VCP (valosin-containing protein)/p97, was cloned from zebrafish and found to be a major cold-inducible protein in fish cells. CDC48 mRNA levels increased significantly after reducing the temperature from 30 to 15 degrees C for 25 days. CDC48 protein levels also increased 2.5-fold after 30 days at cold temperatures. When fish cells overexpressing CDC48 were exposed to a temperature of 15 degrees C, cell proliferation was markedly enhanced in comparison with control cells. By contrast, expression of a mutant molecule with a tyrosine-805 to alanine substitution at the C-terminal phosphorylation site inhibited cell proliferation and induced apoptosis at low temperatures. Therefore, CDC48 may promote cell cycling and cell proliferation via C-terminal tyrosine phosphorylation during cold acclimation in fish cells.


Androgen-responsive functions of male rat liver. Effect of chronic alcohol ingestion.
Many liver processes are sexually dimorphic, and in rats, testosterone is the major steroid hormone determinant of the differing patterns of hepatic function. The microsomal content of specific enzymes and the syntheses of specific proteins are dependent on serum testosterone to maintain this dimorphism. Because the liver of male rats is strikingly androgen responsive, and because chronic alcohol ingestion decreases serum testosterone, we sought to determine whether chronic alcohol feeding would alter the masculine pattern of hepatic liver function in male rats. We quantitated both the cytosolic and nuclear forms of the hepatic androgen receptor. Alcohol feeding of male rats results in a significant loss of both types of androgen receptor sites; the specific binding capacity of both cytosolic and nuclear receptor in alcohol-fed rats is reduced to about 30% of that in either isocalorically fed rats or rats fed ad libitum. This reduction in hepatic androgen receptor activity is concomitant with a 50% reduction in serum testosterone content in the alcohol-fed animals. In addition, the activities of two hepatic androgen-responsive proteins, namely a cytosolic estrogen binder and a microsomal enzyme, estrogen 2-hydroxylase, demonstrate a decrease in activity that parallels the decreases in both forms of the androgen receptor. Administration of testosterone to the alcohol-fed animals normalized both the hepatic androgen receptor and the androgen-responsive protein activities. From these results, we conclude that chronic alcohol feeding results in a decreased androgen responsiveness of the liver, a condition that most likely results from the decreased serum testosterone levels in the alcohol-fed animals.


In vivo findings associated with heat generation during thermomechanical compaction of gutta-percha. 2. Histological response to temperature elevation on the external surface of the root.
An in vivo investigation is described and a histological evaluation made of the effect of canal obturation by thermomechanical compaction of gutta-percha and sealer on the cementum on the lateral surface of the root and adjacent periodontal membrane and alveolar bone of the ferret canine after time intervals of 24 hours, 20 days and 40 days. These tissue reactions were compared with those in the roots of control teeth filled by lateral condensation of cold gutta-percha and sealer. Iatrogenic damage was apparent in a minority of the experimental specimens 20 and 40 days after obturation.


Whole-genome characterisation of TEM-1 and CMY-2 β-lactamase-producing Salmonella Kentucky ST198 in Lebanese broiler chain.
Salmonella enterica subsp. enterica serovar Kentucky has been associated with the worldwide ciprofloxacin-resistant (CIPR) Salmonella Kentucky sequence type 198 (ST198) epidemic clone, mostly recovered from poultry farms and products. The aim of this study was to examine whether this expanding clone exists in the Lebanese broiler chain. Eight CIPR and extended-spectrum cephalosporin-resistant Salmonella Kentucky isolates previously recovered from Lebanese broilers were genetically characterised by whole-genome sequencing. Seven of the eight isolates belonged to ST198 and were phylogenetically closely related. They all harboured mutations in the chromosomal quinolone resistance genesgyrA and parC with double and single substitutions, respectively. The blaTEM-1B and blaCMY-2 genes were both detected in six isolates. Insertion sequence ISEcp1 was located upstream of blaCMY-2, harboured by IncI1 plasmids in four strains. An IS10 transposition coupled to homologous recombination at transposition sites mediated CMY-2 plasmid integration into the chromosome of one strain. Resistance genes to aminoglycosides [aadA7 and aac(3)-Id], tetracyclines [tet(A)] and sulfonamides (sul1) were detected in five strains, among which four were positive for the presence of Salmonella genomic island 1 (SGI1) variant SGI1-K. All studied isolates harboured a variety of Salmonella pathogenicity islands (SPIs) as well as common regulatory and virulence genes. Here we report for the first time in Lebanon the detection and dissemination of the emerging highly drug-resistantSalmonella Kentucky ST198. Our findings shed new light on this clone as a potential public-health threat.


Ellagic acid attenuates beryllium sulphate-induced oxidative stress and histopathological alterations of spleen in rats.
Ellagic acid (EA) is a phenolic constituent in certain fruits and has largely been recognized for its role as an antioxidant compound. To evaluate the effect of EA on beryllium sulphate-induced splenic toxicity in rats. Male Sprague-Dawley rats were divided into four groups. The first group was used as control. Group 2 was exposed to BeSO4 (12 mg/kg, b.w.). Groups 3 and 4 were treated with EA (100 and 300 mg/kg, b.w.) daily for 6 weeks after exposing to BeSO4 (12 mg/kg, b.w.). Various biochemical and molecular biomarkers were assessed in blood and spleen. BeSO4-intoxicated rats showed significant higher WBC (6.74 ± 0.20 × 109/L vs. 11.02 ± 1.31 × 109/L, p < 0.05), Neu (1.14 ± 0.11 × 109/L vs. 2.45 ± 0.42 × 109/L, p < 0.05), Lym (3.80 ± 0.83 × 109/L vs. 9.64 ± 1.99 × 109/L, p < 0.05), and PLT (868.4 ± 43.2 × 109/L vs. 1408 ± 77.57 × 109/L, p < 0.05) than normal control animals. Moreover, an increase in MDA with depletion of GSH and SOD activity (all p < 0.05) occurred in the spleen of rats treated with BeSO4. Furthermore, BeSO4-treated rats displayed significantly higher levels of apoptotic markers (Bax, Caspase-3, PARP) (all p < 0.05). EA administration resulted in a significant reversal of hematological and apoptotic markers in beryllium sulphate-intoxicated rats. Our results suggest EA treatment exerts a significant protective effect on BeSO4-induced splenic toxicity in rats.


The Mystery of Antibodies Against Polyethylene Glycol (PEG) - What do we Know?
Recent findings demonstrated anti-PEG antibody formation in some healthy individuals and patients who have not received PEGylated biotherapeutics. Some of these findings evoked criticism because of shortcomings in the antibody assays used. To better understand this topic, we established robust antibody analytics and screened two cohorts of healthy individuals and one cohort of hemophilia patients for the expression of anti-PEG antibodies. A flow cytometry approach and a fully validated ELISA platform were established to detect specific anti-PEG antibodies. Immunohistochemistry was used to test for potential binding of anti-PEG antibodies to human tissues. IgM and/or IgG anti-PEG antibodies are expressed by some healthy individuals and by some patients with hemophilia who have not received PEGylated biotherapeutics. These antibodies can be either transient or persistent and recognize PEGs of different sizes with or without terminal methoxy groups. Age and location of healthy individuals influence the prevalence of IgG but not of IgM antibodies. Anti-PEG antibodies do not cross-react with human tissues supporting the safety of the antibodies. We confirm that some healthy individuals and some patients with hemophilia express specific antibodies against PEG which are not associated with any pathology and do not bind to human tissues.


The effect of prediction accuracy on choice reaction time.
In this study, we examined the effect of prediction accuracy on reaction time (RT). Subjects performed on three blocks of choice RT trials, all of which involved the mapping of four stimuli (red, green, 1, or 0) onto two response keys. The subjects were told that the four stimuli were equally probable and that their task was to respond to each stimulus onset by pressing the correct key. In one block (stimulus-prediction), the subjects predicted, prior to each trial, the precise stimulus that would appear. In a second block (category-prediction), the subjects predicted the category of the stimulus (i.e., color or digit) that would appear. In a third block (no-prediction), the subjects simply responded to each stimulus without making a prior prediction. In the stimulus-prediction block, RT was faster for correct predictions than for incorrect predictions. In addition, RT was faster on trials in which an incorrect prediction involved the correct category than on trials in which it involved the incorrect category: that is, a "half-wrong" prediction was better than an "all-wrong" prediction. In the category-prediction block, RT was faster when the stimulus category was predicted correctly than when it was not. There was little evidence of a response-facilitation contribution to the correct-prediction effect. These results permit inferences concerning the encoding and organization of information in memory.


Learning Experience and Clinical Outcomes with Standardized Patient Simulation: A Mixed Qualitative and Quantitative Study.
To evaluate learning experience and clinical outcomes after intervention. A mixed study. A multiple cohort sample (n=75) of community nurses underwent an SP simulation. A survey and 12- and 24-month incident data were used to evaluate the learning experience and clinical outcomes. The nurses were highly satisfied with their learning. In addition, their ability to identify near-misses and the presence of incidents showed a statistically significant improvement (p < .05). SP simulation effectively improved learning experience and clinical outcomes regardless of nurses' experience. Simulation learning can have a positive impact on clinical outcomes.


Home management of cats and dogs with diabetes mellitus. Common questions asked by veterinarians and clients.
Home management of the insulin-dependent diabetic pet can be confusing and frustrating for many pet owners. This article addresses many of the common concerns of pet owners, as well as issues of interest for the veterinarian regarding insulin therapy and client communication.


Changes in blood catecholamines, insulin, corticosterone and glucose during the course of the Sephadex inflammation.
During an acute inflammation, the blood levels of noradrenaline, dopamine and insulin increase uniformly until the fourth day, then reach a climax which for dopamine is above the norm, while the suppressed levels of noradrenaline and insulin approach the norm. All values decrease on the fifth day (end of the experiment). Glucose behaves inversely, showing a minimum on the fourth day. Corticosterone displays two peaks, on the first and fourth days. The adrenaline level differs distinctly from these patterns: it is elevated on the second, fourth and fifth days. By releasing each catecholamine independently, the organism can possibly influence the course of the inflammation.


Methyl psilalate: a new antimicrobial metabolite from Psila boliviensis.
Psila boliviensis (Wedd.) Cabr. yielded a new phenylpropanoid, named methyl psilalate. The structure was established by means of standard spectroscopic techniques. The microbiological evaluation of the compound revealed antibacterial activity against Gram-positive and Gram-negative bacteria.


Acute psychosis and serotonin syndrome in the setting of "Triple-C" overdose: a case report.
Over-the-counter medication overdose is a difficult diagnostic challenge for many physicians as common drug screening assays cannot detect these substances. We present a case of acute psychosis, serotonin syndrome, and anticholinergic overdose-like properties in the setting of Coricidin HBP Cough & Cold tablets, known by their street name Triple-C. This is the first case report we are aware of involving a patient presenting with these symptoms and requiring critical-care-level support. A 31-year-old African American female with a past medical history of anxiety, childhood asthma, previous methamphetamine abuse, and coronavirus disease 2019 infection in August 2020 was brought to the emergency department by the local police department with altered mental status. Initial blood work, including extended drug screens, were unremarkable for a definitive diagnosis. This patient required critical-care-level support and high sedation because of her symptoms. Collateral history revealed the patient regularly consumed Triple-C daily for the 6 weeks prior to admission. A trial off sedation was attempted after 24 hours with no complications. The patient admitted to regular Triple-C consumption and auditory hallucinations since adolescence. She was discharged safely after 48 hours back into the community. She was lost to follow-up with psychiatry and internal medicine; however, she was evaluated in the emergency room 1 month later with a similar psychiatric presentation. Overdose of Triple-C should be kept in the differential diagnosis of patients presenting with a triad of psychosis, serotonin syndrome, and anticholinergic overdose, in the setting of unknown substance ingestion.