Beneficial effects of prostaglandin E1 on ischemic colitis following surgery on the abdominal aorta.
To determine the effects of prostaglandin E1 (PGE1) on the intestinal circulation, an experimental dog model of ischemic colitis following abdominal aortic reconstruction was made by ligating the inferior mesenteric artery (IMA) and the internal iliac artery, with the creation of a 50% stenosis in the superior mesenteric artery (SMA). The parameters of enteric ischemia included the blood flow of the SMA, the tissue blood flow in the small intestine and left colon, the mean stump pressure of the IMA (IMAP), and the IMAP/mean systemic blood pressure ratio. With the continuous infusion of 10 ng/kg per minute of PGE1 into the descending thoracic aorta, these values increased significantly on the seventh postoperative day compared with those on the day of operation. These results thus suggest that the continuous intraarterial infusion of PGE1 may reduce ischemic changes in the colon following abdominal aortic reconstruction.


Gout and coronary heart disease: the Framingham Study.
The relationship between gout, not associated with the use of diuretics, and the development of coronary heart disease was examined in 5209 subjects originally enrolled in the Framingham Study. Based on 32 years of follow-up, the two year incidence of gout was six times greater in men (3.2/1000) as compared to women (0.5/1000). For both sexes, the incidence of gout showed no clear relationship with age. Among men who never received diuretics, those afflicted by gout, as compared to those without gout, experienced a 60% excess of coronary heart disease (95% confidence limits, 1.1-2.2), primarily attributed to a two fold excess of angina pectoris (95% confidence limits, 1.2-3.1). Although gout was usually associated with other atherogenic risk factors, control of systolic blood pressure, total cholesterol, alcohol intake, body mass index, and diabetes failed to alter the effect of gout on the preceding coronary events in men. For women, there were no significant associations between gout and coronary heart disease. We conclude that gout, unrelated to the intake of diuretics, imparts an additional risk of coronary heart disease in men, unexplained by clinically measured risk factors.


Protocol for a systematic review of treatment adherence for HIV, hepatitis C and tuberculosis among homeless populations.
Homelessness is a global issue and HIV, hepatitis C and tuberculosis are known to be prevalent in this group. Homeless populations face significant barriers to care. We aim to summarise evidence of treatment initiation and completion for homeless populations with these infections, and their associated factors, through a systematic review and meta-analysis. We will search MEDLINE, Embase and CINAHL for all study types and conference abstracts looking at either (1) treatment initiation in a cohort experiencing homelessness with at least one of HIV, hepatitis C, active tuberculosis and/or latent tuberculosis infection (LTBI); (2) treatment completion for those who initiated treatment. We will perform a meta-analysis of the proportion of those with each infection who initiate and complete treatment, as well as analysis of individual and health system factors that may affect adherence levels. We will evaluate the quality of research papers using the Newcastle-Ottawa scale. Given the political emphasis on global elimination of these diseases, and the current lack of understanding of effective and equitable treatment adherence strategies in homeless populations, this review will provide insight to policy-makers and service providers aiming to improve homeless healthcare. PROSPERO CRD42019153150.


The effects of statins on blood pressure in normotensive or hypertensive subjects--a meta-analysis of randomized controlled trials.
The aim of this meta-analysis was to investigate whether statin therapy is associated with blood pressure (BP)-lowering in patients with or without hypertension. The beneficial effects of statins on the cardiovascular system may in part be related to effects beyond lipid-lowering. It has been suggested that statins may reduce BP; however the available data are still ambiguous and often conflicting. Data from Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for the years 1966-January 2012 were searched for studies that investigated the effect of statins on BP in normotensive or in hypertensive subjects. We included all randomized controlled clinical trials that investigated this effect. Changes in systolic and diastolic BP were the key outcomes of interest. The final analysis included 18 trials and 5628 subjects (4692 normotensive and 936 hypertensive patients) randomized to receive either statins or placebo. The weighted mean difference of systolic (∆SBP) and diastolic blood pressure (∆DBP) in normotensive patients for the 11 statin trials included were 0.03 (95% CI: -0.95-1.02; p = 0.95) and -0.28 (95% CI: -0.80-0.24; p = 0.29), respectively. For hypertensive patients treated with statins (8 trials) the weighted mean difference of ∆SBP and ∆DBP were 1.45 (95% CI: -0.49-3.39; p = 0.14) and -1.32 (95% CI: -3.93-1.28; p = 0.32) respectively. Despite previous suggestions statin therapy in normotensive or hypertensive patients does not lead to significant reductions in systolic or diastolic BP.


In Vivo Testing of an Ambient Air Based, Portable, and Automated CO 2 Removal Controller for Artificial Lungs.
Portable artificial lung (AL) systems are under development, but there are few technologies available that adjust the carbon dioxide (CO 2 ) removal in response to changes in patient metabolic needs. Our work describes the second generation of a CO 2 -based portable servoregulation system that automatically adjusts CO 2 removal in ALs. Four adult sheep (68 ± 14.3 kg) were used to test the servoregulator. The servoregulator controlled air sweep flow through the lung to meet a target exhaust gas CO 2 (tEGCO 2 ) level in normocapnic and hypercapnic (arterial partial pressure of CO 2 [PaCO 2 ] >60 mm Hg) conditions at varying flow rates (0.5-1.5 L/min) and at tEGCO 2 levels of 10, 20, and 40 mm Hg. In hypercapnic sheep, average post-AL blood partial pressure of CO 2 (pCO 2 ) values were 22.4 ± 3.6 mm Hg for tEGCO 2 of 10 mm Hg, 28.0 ± 4.1 mm Hg for tEGCO 2 of 20 mm Hg and 40.6 ± 4.8 mm Hg for tEGCO 2 of 40 mm Hg. The controller successfully and automatically adjusted the sweep gas flow to rapidly (<10 minutes) meet the tEGCO 2 level when challenged with changes in inlet blood flow or target EGCO 2 levels for all animals. These in vivo data demonstrate an important step toward portable ALs that can automatically modulate CO 2 removal and allow for substantial changes in patient activity or disease status in ambulatory applications.


Mitogen-activated protein kinase is increased in the limbic structures of the rat brain during the early stages of status epilepticus.
Systemic administration of pilocarpine (PILO) in adult rat produces acute limbic seizures leading to status epilepticus. Recent studies have shown the activation of mitogen-activated protein kinase (MAPK) cascades during experimentally induced seizures. MAPK activation may be triggered by glutamatergic stimulation and may play a key role in signal transduction pathways. In the present study, immunocytochemistry was used to analyze the spatiotemporal distribution pattern of the MAPK protein and its active form (A-MAPK) following PILO-induced status epilepticus. MAPK and A-MAPK immunoreactivities exhibited different patterns of distribution in the brain of normal and epileptic rats. The saline-treated rats, as well as the animals that received PILO but did not evolve to status epilepticus, showed a weak but selective MAPK immunoreactivity, detected in the hippocampal pyramidal neurons, dentate gyrus, hilus, CA3, CA1, and entorhinal, piriform, and cingulate cortices. A-MAPK immunoreactivity was instead observed only in neurites of the CA3 and hilus and in cells of the entorhinal and piriform cortices. In PILO-treated rats, between 30 and 60 min after status epilepticus there was an increase of the immunoreactivity to both antibodies, which were differently distributed throughout several structures of the limbic system. The immunostaining showed a slight decrease after 5 h of status epilepticus. However, MAPK and A-MAPK immunopositivities decreased markedly after 12 h of status epilepticus, returning almost to the basal expression. These findings are consistent with a spatial and time-dependent MAPK expression in selected limbic structures, and its activation could represent an initial trigger for neuronal modifications that may take part in the mechanism underlying acute epileptogenesis and in long-lasting neuropathological changes of the PILO model of epilepsy.


Decreased serum ceruloplasmin concentration in aluminum welders exposed to ozone.
During an epidemiological survey on arc welders, serum copper and ceruloplasmin were determined in two groups of workers. One group consisted of aluminum welders who were divided into two groups: 13 welders working inside aluminum tanks (confined atmosphere) and 8 welders engaged in the production of vans for dump trucks (nonconfined atmosphere). The reference group consisted of 26 workers of the same plant who were not exposed to welding fumes. Ozone, the major pollutant in aluminum arc welding, was thought to be the principal factor in the significant decrease (P less than 0.01) of mean ceruloplasmin in confined welders. This decrease in the level of ceruloplasmin was still within the reference values and was not linked to age or to tobacco consumption. We found a linear relationship between ceruloplasmin concentration and the cumulated worktime along the week. This effect could be a sign in the serum of a lung reaction against oxidant activity in this type occupational exposure.


Antigenic determinants of tubular basement membranes and Bowman's capsule in rats.
Kidney sections from several inbred rat strains were studied with an indirect immunofluorescence technique using five different, selected rat antisera which contained antibodies against the tubular basement membrane (TBM). The sera came from transplanted animals, an apparently normal animal, and animals treated with spleen cells in complete Freund's adjuvant. Upon panel analysis, at least two different antigenic determinants were recognized on the proximal TBM: One was present in nine and one was present in seven of the 15 strains tested; both determinants appear to be expressed in most antigen-positive strains. Using kidneys from major histocompatibility complex (MHC)-congenic strains, it was shown that the TBM antigens are encoded outside the MHC region. Three sera produced variable staining of Bowman's capsule in association with the proximal TBM; two sera produced clearly discordant staining of Bowman's capsule and proximal TBM. The capsular antigens were also coded outside the MHC region. These observations suggested the existence of at least two different antigenic determinants on proximal TBM. Bowman's capsule appeared to have antigenic determinants in common with the proximal TBM as well as distinct determinants.


Correct axonal regeneration after target cell removal in the central nervous system of the leech.
The unique target neuron of a severed axon in the leech was selectively eliminated by intracellular injection of protease. In the absence of the target, the severed axon regenerated normally along its original pathway to the usual site of synapse, where it stopped growing without forming alternative connections.


Predictors of medication refill-seeking behavior in the ED.
Determine predictors of medication refill-seeking behavior in ED patients with chronic illness. Prospective cross-sectional ED survey conducted for 6 weeks. Public hospital ED (>140,000 visits per year). ED patients (>18 years) taking chronic medications for congestive heart failure, diabetes, and/or hypertension. Of 1168 patients surveyed, 344 (29%) presented to the ED secondary to running out of medications and requiring a medication refill. Univariate predictors included age younger than 50 years, non-Hispanic ethnicity, low income (<5000 dollars per year), self-pay payor status, and being told to call a primary care physician before medication would be refilled. Lack of knowledge about refill or pharmacy numbers on the medication bottle resulted in patients being more than twice as likely to be in the ED for a medication refill (odds ratio 2.4 [1.6, 3.6] and 2.0 [1.3, 2.9], respectively). Presenting for medication refills is common in ED patients with chronic illness.


High-fidelity simulation increases pharmacy resident perceived competence during medical emergencies.
Our objective was to assess postgraduate year one (PGY1) pharmacy resident perceived competence during medical emergencies before and after implementation of a longitudinal simulation training curriculum. At the University of California San Francisco (UCSF) Medical Center, PGY1 pharmacy residents serve as primary code team responders for code blue, code sepsis, and code stroke, among other medical emergencies. In 2015, the UCSF Residency Training Program implemented a longitudinal simulation curriculum for PGY1 pharmacy residents. Throughout the residency year, residents participated in four simulation lab sessions that addressed various medical emergencies. To assess the impact that the simulation curriculum had on resident perceived competence during medical emergencies, a 19-question survey (13 clinical questions and six control questions) was distributed to the residents at the end of the residency year. Resident responses from the 2015 to 2016 and 2016 to 2017 surveys were compared to a control residency class from 2014 to 2015 who did not undergo the simulation curriculum. Simulation-trained PGY1 pharmacy residents reported significantly greater perceived competence in five of the twelve medical emergency scenarios (acute coronary syndromes, symptomatic bradycardia, supraventricular tachycardia, ventricular tachycardia, and cardiac arrest) as compared to non-simulation-trained controls. In addition, the PGY1 pharmacy residents felt that their performance as a clinical pharmacist would significantly improve as a result of the simulation curriculum. Incorporation of a longitudinal simulation curriculum into PGY1 pharmacy resident training can positively impact resident self-reported competence when performing essential pharmacist functions during medical emergencies.


The structure of the molybdenum cofactor. Characterization of di-(carboxamidomethyl)molybdopterin from sulfite oxidase and xanthine oxidase.
A di-(carboxamidomethyl) derivative of molybdopterin, the organic component of the molybdenum cofactor, has been prepared under conditions favoring retention of all of the structural features of the molecule. The specific radioactivity of [1-14C]iodoacetamide incorporated relative to the amount of phosphate indicated two alkylation sites per pterin. Energy-dispersive x-ray analysis of the derivative showed the presence of 2 sulfurs in the derivative. An exact mass corresponding to the molecular formula C14H18N7O5S2 was obtained for the MH+ ion of the alkylated, dephosphorylated compound by fast atom bombardment mass spectroscopy. 1H NMR spectra of the phosphorylated and dephosphorylated forms of alkylated molybdopterin, in conjunction with the other data, have provided strong corroboration of the validity of the proposed structure of molybdopterin (Johnson, J. L., and Rajagopalan, K. V. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 6856-6860) as a 6-alkylpterin with a 4-carbon side chain containing an enedithiol on C-1' and C-2', a secondary alcohol on C-3', and a phosphorylated primary alcohol on C-4'. As isolated, the di-(carboxamido-methyl)molybdopterin was found to be a 5,6,7,8-tetrahydropterin.


Embryonic toxicity changes of organic nanomaterials in the presence of natural organic matter.
When elucidating the potential fate and bioavailability of nanomaterials (NMs) in an aquatic system, it is important to consider the interactions between NMs and natural organic matter (NOM). The present study compared the toxicities of carbon-based NMs, with disparate physicochemical properties, on Japanese medaka (Oryzias latipes) embryos after the addition of NOM. The measured embryonic toxicity parameters were mortality, malformation and hatching delay. Various physicochemical properties of water suspended fullerenes (nC(60)) and multi-walled carbon nanotubes (MWNTs) were modulated by organic exchange (Tol/nC(60)), stirring over time (Aqu/nC(60)) and acid treatment (f-MWNTs) followed by characterization. Tol/nC(60) produced relatively more hydrophobic surfaces and exhibited smaller closed spherical agglomerates than Aqu/nC(60). Acid-treated f-MWNTs displayed functionalized hydrophilic surfaces compared to raw MWNTs (r-MWNTs). The resultant embryonic toxicities, in the absence of NOM, were ranked in the order: f-MWNTs>Tol/nC(60)>Aqu/nC(60). As the NOM concentrations were increased, no changes in embryonic toxicities were observed on exposure of Aqu/nC(60) and r-MWNTs; whereas, the toxicities were reduced on exposure to Tol/nC(60) and f-MWNTs, due to a disappearance of hydrophobic primary spherical aggregates and partial coating, respectively. These data suggest that in the presence of NOM, the morphological differences of NMs, as well as their physicochemical properties, play a significant role in their reactions and subsequent medaka embryonic nanotoxicity.


Potentiometric flow injection system for determination of reductants using a polymeric membrane permanganate ion-selective electrode based on current-controlled reagent delivery.
A polymeric membrane permanganate-selective electrode has been developed as a current-controlled reagent release system for potentiometric detection of reductants in flow injection analysis. By applying an external current, diffusion of permanganate ions across the polymeric membrane can be controlled precisely. The permanganate ions released at the sample-membrane interface from the inner filling solution of the electrode are consumed by reaction with a reductant in the sample solution thus changing the measured membrane potential, by which the reductant can be sensed potentiometrically. Ascorbate, dopamine and norepinephrine have been employed as the model reductants. Under the optimized conditions, the potential peak heights are proportional to the reductant concentrations in the ranges of 1.0×10(-5) to 2.5×10(-7)M for ascorbate, of 1.0×10(-5) to 5.0×10(-7)M for dopamine, and of 1.0×10(-5) to 5.0×10(-7)M for norepinephrine, respectively with the corresponding detection limits of 7.8×10(-8), 1.0×10(-7) and 1.0×10(-7)M. The proposed system has been successfully applied to the determination of reductants in pharmaceutical preparations and vegetables, and the results agree well with those of iodimetric analysis.


Hormonal and cholinergic effects on amylase and lysosomal enzyme activities in pancreatic tissue and ascites of rats with acute experimental pancreatitis.
The effects of hormonal or cholinergic stimulation on survival and on activities of lysosomal enzymes and amylase in pancreatic tissue and ascites were studied in rats with induced pancreatitis. Pancreatitis per se caused an increase of the activities of cathepsin D, N-acetyl-beta-D-glucosaminidase and amylase, and a decrease of acid phosphatase in pancreatic tissue. Pancreatic protein concentration was not influenced. In pancreatitic rats administration of cerulein or carbachol markedly decreased survival rate. Cerulein increased the activities of cathepsin D and amylase in ascites and cathepsin D and acid phosphatase in pancreatic tissue. Carbachol increased the activities of cathepsin D and amylase in ascites and acid phosphatase in pancreatic tissue. Both cerulein and carbachol decreased the activity of amylase in pancreatic tissue. Administration of secretin or the anticholinergic drug Pro-Banthine did not influence survival rate or the activities of lysosomal enzymes and amylase in ascites. In pancreatic tissue the activity of acid phosphatase was slightly increased by secretin or Pro-Banthine. In conclusion, the results show a nonparallel alteration of lysosomal enzyme activities in pancreatic tissue in rats with pancreatitis. Cerulein and cholinergic stimulation decreased survival rate and brought about a marked increase of cathepsin D activity in ascites and, in the case of cerulein, also in pancreatic tissue. The implication of lysosomes and especially the catheptic proteases in the pathogenesis and outcome of acute pancreatitis deserves further attention.


Occurrence of Diplococcus pneumoniae in the upper respiratory tract of children.
The patterns of colonization of D. pneumoniae were studied over a 46-month period in a group of young children in a day-care center. Forty-four percent of nasal cultures yielded D. pneumoniae. The most frequently isolated serotypes--6, 19, and 23--accounted for 49% of the isolates; the nine most common serotypes included 80% of the isolates. Individual serotypes frequently were carried for several months. Reacquisition of a serotype previously carried occurred frequently. There was limited spread of serotypes among the children despite prolonged contact.


Did injury incidence in alpine ski racing change after equipment regulations? An evaluation based on the injury surveillance system of the Austrian Ski Federation.
To assess the effects of alpine competition equipment regulations from 2003, 2007 and 2012 on severe injury incidence. Case study METHOD: Data originated from records of the injury surveillance system of the Austrian Ski Federation. Injuries from the seasons 2001-2017 were divided in four periods between the equipment regulations. For comparison of consecutive periods, risk ratios (RR = later period / preceding period) with 95% CI were calculated. Total severe injury events, events with severe knee injuries, and events with severe ACL injuries were separately investigated. A significant increase of total severe injury incidence was found after the equipment regulation in 2003 (RR1.52, 95% CI 1.00-2.31). None of the other comparisons revealed significance (p<0.05) or statistical trends (p<0.1). Only the minority (40%) of the RR showed a reduction in the injury incidence of the Austrian Ski Team (lowest RR 0.78). 60% of the RR increased after the regulations (highest RR 1.63). Even though statistical uncertainties remain, our findings allow the conclusion, that the implemented equipment regulations did not cause a noticeable reduction of injuries. The three analysed equipment regulations were not appropriate or were counteracted by other factors.


The efficacy of supplemental magnesium in reducing atrial fibrillation after coronary artery bypass grafting.
Atrial fibrillation after coronary artery bypass is reported from 17% to 53%. Hypomagnesemia after this surgery is considered a contributing factor. Two hundred-two coronary bypass patients were randomized to magnesium (n = 105) or placebo (n = 97). The experimental group received 80-mg magnesium sulfate per kilogram ideal weight in 100 mL dextrose 5% water 30 minutes preoperatively. Postoperatively, patients received 8-mg magnesium sulfate per kilogram ideal weight intravenous per hour more than 48 hours. The control group received dextrose 5% water at these intervals. After the first bolus serum magnesium was experimental 4.75 mg/dL versus control 1.91 mg/dL, p less than 0.001, and remained different until postoperative day 4 (experimental 2.33 mg/dL vs control 2.26 mg/dL, p = 0.24). Atrial appendage and strap muscle were analyzed after the first bolus and after revascularization. There were no differences between groups in tissue magnesium or calcium. Urinary magnesium was elevated in the experimental (experimental 324.5 mg/24 hours, vs control 45.1 mg/24 hours, p = 0.01). Calcium excretion was higher (experimental 370 mg/24 hours vs control 186 mg/24 hours, p < 0.001) and was associated with lower serum calcium. Serum calcium was higher in the control through the fourth postoperative day. The incidence of atrial fibrillation was experimental 32 of 105 (30.5%) versus control 41 of 97 (42.3%) p = 0.08. Atrial fibrillation was different on the first postoperative day (experimental 3/105, 2.9% vs control 9/97, 9.3%), p = 0.05. Overall prophylactic magnesium supplementation does not significantly reduce atrial and ventricular arrhythmias. The only significant benefit of magnesium supplementation was on the first postoperative day.


Impact of Eruptive vs Noneruptive Calcified Nodule Morphology on Acute and Long-Term Outcomes After Stenting.
Whether an eruptive or noneruptive target lesion calcified nodule (CN) portends worse acute and long-term clinical outcomes after stenting has not been established. The authors sought to compare acute and long-term clinical outcomes in eruptive CN vs noneruptive CN morphology. Using optical coherence tomography, an eruptive CN was defined as an accumulation of small calcium fragments protruding and disrupting the overlying fibrous cap, typically with small amount of thrombus. A noneruptive CN was defined as an accumulation of small calcium fragments with a smooth intact fibrous cap without an overlying thrombus. The primary endpoint was target lesion failure (TLF) including cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization in patients with ≥6-month follow-up. Among 3,231 patients with evaluable pre- and postintervention OCT, 236 patients had lesions with CNs (7.3%). After eliminating 4 secondary lesions and 6 patients without ≥6-month follow-up, 126 (54.8%) lesions with eruptive CNs and 104 (45.2%) lesions with noneruptive CNs formed the current report. Compared with noneruptive CNs, eruptive CNs were independently associated with greater stent expansion (89.2% ± 18.7% vs. 81.5% ± 18.9%; P = 0.003) after adjusting for morphologic and procedural factors. At 2 years, eruptive CNs trended toward more TLF compared with noneruptive CNs (Kaplan-Meier estimates, 19.8% vs 12.5%; P = 0.11) and significantly more target lesion revascularization (18.3% vs 9.6%; P = 0.04). In the adjusted model, eruptive CNs were independently associated with 2-year TLF (HR: 2.07; 95% CI: 1.01-4.50; P = 0.048). Compared with noneruptive CN morphology, lesions with an eruptive CN appearance on optical coherence tomography had a worse poststent long-term clinical outcome despite better acute stent expansion.


Gagel's granuloma (localized Langerhans cell histiocytosis) in the pituitary stalk.
A 46-year-old man with diabetes insipidus, hypothyroidism and hypocortisolism was found to have a tumor of the pituitary stalk. After transsphenoidal resection of the tumor substitution of cortisol and thyroxin was necessary. Pathological examination of the lesion revealed an extremely rare granulomatous infiltration classified as Gagel's granuloma (Langerhans' cell histiocytosis). Pre- and postoperative magnetic resonance imaging (MRI) studies, differential diagnosis and treatment of such lesions are presented.


Metabolic but not transcriptional regulation by PKM2 is important for natural killer cell responses.
Natural Killer (NK) cells have an important role in immune responses to viruses and tumours. Integrating changes in signal transduction pathways and cellular metabolism is essential for effective NK cells responses. The glycolytic enzyme Pyruvate Kinase Muscle 2 (PKM2) has described roles in regulating glycolytic flux and signal transduction, particularly gene transcription. While PKM2 expression is robustly induced in activated NK cells, mice lacking PKM2 in NK cells showed no defect in NK cell metabolism, transcription or antiviral responses to MCMV infection. NK cell metabolism was maintained due to compensatory PKM1 expression in PKM2-null NK cells. To further investigate the role of PKM2, we used TEPP-46, which increases PKM2 catalytic activity while inhibiting any PKM2 signalling functions. NK cells activated with TEPP-46 had reduced effector function due to TEPP-46-induced increases in oxidative stress. Overall, PKM2-regulated glycolytic metabolism and redox status, not transcriptional control, facilitate optimal NK cells responses.


Aristotle and headless clones.
Cloned organisms can be genetically altered so that they do not exhibit higher brain functioning. This form of therapeutic cloning allows for genetically identical organs and tissues to be harvested from the clone for the use of the organism that is cloned. "Spare parts" cloning promises many opportunities for future medical advances. What is the ontological and ethical status of spare parts, headless clones? This paper attempts to answer this question from the perspective of Aristotle's view of the soul. Aristotle's metaphysics as applied to his view of biological essences generates an ethic that can contribute to moral reasoning regarding the use of headless spare parts clones. The task of this paper is to show the implications that Aristotle's view of the soul, if it is true, would have on the ethics of headless, spare parts cloning.


Appropriate margin thresholds for isocontour metabolic volumetry of fluorine-18 fluorodeoxyglucose PET in sarcoma: a hybrid PET/MRI study.
Metabolic volumetry and heterogeneity indexes are increasingly being used in fluorine-18 fluorodeoxyglucose (F-FDG) PET, mostly using isocontour methods. However, there is no standard method to determine optimal margin thresholds for isocontour volume of interest (VOIiso). Here, VOIiso with various margin thresholds were compared with exact anatomical tumor volumes in sarcoma using a hybrid PET/MRI scanner. F-FDG PET/MRI images were retrospectively analyzed for 36 lesions of soft tissue or bone sarcoma. VOIiso of tumors was drawn with varying margin thresholds; standardized uptake value (SUV) 1.0-4.0 with an increment of 0.5 and 30-70% of maximal SUV (SUVmax) with an increment of 10%. Exact anatomical tumor volumes (VOIMRI) were drawn manually on the basis of MRI. In each VOI, metabolic tumor volume, SUVmean, total lesion glycolysis, and SD were measured and compared between VOIiso and VOIMRI. Significant correlations were observed between the indexes from VOIiso and VOIMRI. For metabolic tumor volume, no significant difference existed between VOIiso and VOIMRI with margin thresholds of 30 and 40% of SUVmax, and SUV 1.5. For SUVmean, no significant difference existed with 30% of SUVmax, and SUV 1.5. For total lesion glycolysis, no significant difference existed with 40% of SUVmax, SUV 1.5, and 2.0. For SD, no significant difference existed with 30% of SUVmax, SUV 1.5, and 2.0. Margin thresholds of 30 or 40% of SUVmax and SUV 1.5 or 2.0 may be used for the VOIiso method in F-FDG PET images of sarcoma. VOIiso with these margin thresholds are expected to produce reliable metabolic, volumetric, and heterogeneity indexes on F-FDG PET images.


The antiglucocorticoid, cortexolone, fails to promote in vitro activation of cytoplasmic glucocorticoid receptors from the human leukemic cell line CEM-C7.
Cortexolone functions as an antiglucocorticoid in the human leukemic cell line CEM-C7, since it blocks the growth inhibition and cell lysis mediated by the potent agonist triamcinolone acetonide (TA). At high concentrations (10(-5) M) cortexolone alone is inactive. The ability of cortexolone to block the TA-mediated biological effects is reflected in its ability (1000-fold molar excess) to effectively block the binding of [3H]TA to the cytoplasmic unactivated form of the receptors eluted from DEAE-cellulose at approx. 180 mM potassium phosphate (KP). Likewise a 1000-fold molar excess of TA inhibits the specific binding of [3H]cortexolone to the unactivated receptors and to a peak which elutes at low salt concentration (35 mM KP) but does not appear to represent activated [3H]cortexolone-receptor complexes. Thermal activation/transformation (25 degrees C for 30 min +/- 10 mM ATP) of the [3H]TA-receptor complexes significantly enhances the subsequent DNA-cellulose binding capacity of these complexes and also results in their elution from DEAE-cellulose at the low salt (50 mM KP) activated position. In contrast, exposure of the cytoplasmic [3H]cortexolone-receptor complexes to identical in vitro activating (transforming) conditions fails to enhance subsequent DNA-cellulose binding capacity or to result in the appropriate shift in DEAE-cellulose elution profile. This inability of [3H]cortexolone to facilitate activation/transformation of receptors was also verified using cytosol prepared from the glucocorticoid-resistant 'activation-labile' mutant, 3R7. Taken collectively the data suggest that cortexolone, unlike an agonist such as TA, fails to promote in vitro activation/transformation, a conformational change which also occurs in vivo under physiological conditions and is a prerequisite for nuclear binding.


The epidemiology of mandibular fractures treated at the Toronto general hospital: A review of 246 cases.
Mandibular fractures constitute a substantial proportion of cases of maxillofacial trauma. This study investigated the incidence, causes and treatment of mandibular fractures at a hospital in Toronto. The medical records and radiographs for 246 patients treated for mandibular fracture at the Toronto General Hospital over a 51 2-year period (from 1995 to 2000) were reviewed. Data on the patients age, sex, smoking status, alcohol and drug use, mechanism of injury, treatment modality, and post-operative complications were recorded and assessed. Men 21 to 30 years of age sustained the most mandibular fractures. The ratio of males to females was 5:1. Most fractures were caused by violent assault (53.5%), followed by falls (21.5%) and sports activities (12.2%). Alcohol was a contributing factor at the time of injury in 20.6% of fractures for which this information was available. Nearly half of all cases were treated by open reduction (49.1%). Complications occurred in 5.3% of patients. The incidence and causes of mandibular fracture reflect trauma patterns within the community and, as such, can provide a guide to the design of programs geared toward prevention and treatment.


Supercharged End-to-Side Anterior Interosseous to Ulnar Motor Nerve Transfer for Hirayama Disease: A Case Report.
Hirayama disease is a rare condition of cervical myelopathy. Its early identification and correction can optimize functional outcomes. However, late presentation and some more severe cases may be associated with loss of hand function. Among the cases described, there are no reports of nerve transfers for this condition. We presented the first case report of a Hirayama disease of isolated ulnar nerve impairment managed with nerve transfer. Electroneuromyography showed isolated preganglionic involvement of C7, C8, and T1, with no sensory changes. The patient underwent nerve transfer with anterior interosseous nerve to ulnar nerve supercharge end-to-side, recovering hand function in 7 months.


Multidrug chemotherapy (vincristine-bleomycin-methotrexate) followed by radiotherapy in inoperable carcinomas of the head and neck: a pilot study of the Radiation Therapy Oncology Group.
This is a report on the Radiation Therapy Oncology Group (RTOG) Pilot Study 77-08, of a combination of chemotherapy with vincristine-bleomycin-methotrexate, followed by curative radiotherapy for inoperable carcinomas of the head and neck. The main objectives of the study were to determine toxicity, tumor control, and survival. Included were patients with untreated advances carcinomas, with no distant metastasis. Chemotherapy started with vincristine--1.5 mg/m2 (maximum of 2 mg) by I.V. injection, followed by bleomycin drip of 48 hours (15 units per day), and then methotrexate (200 mgs/m2 divided in equal doses 6 hours apart) with folinic acid rescue. Forty patients were registered for the study. Eleven of these received 1 course of the stated chemotherapy, and 28 were given 2 courses, with a 1-week rest period between them. Radical curative radiotherapy was usually started 2 weeks after chemotherapy. Salvage surgery was considered for persistent or recurrent tumor in the primary area, neck, or both. The level of toxicity that resulted from this combined therapy was considered acceptable. The percentage of complete response in the primary tumor was 6% with chemotherapy; 46% after irradiation; and 65% when surgery was added. The complete response (C.R.) in the primary tumor ranged from 54% for T-4 to 100% for T-2, 20% of T-3, and N with this therapeutic regime was--41% initially, 24% at one year, 19% at two years, and 16% at three years. The survival at one, two and three years after beginning radiotherapy was 54%, 30%, and 16%, respectively. This is considered a very satisfactory result for these very advances inoperable patients.


An integrated anaerobic system for on-site treatment of wastewater from food waste disposer.
In this study, an integrated system of siphon-driven self-agitated anaerobic reactor (SDSAR) and anaerobic fixed bed reactor (AFBR) was conducted for the treatment of wastewater from food waste disposer (FWD), and the effect of influent total solids (TS) concentration on the process performance was evaluated. When the influent TS concentration increased from 7.04 to 15.5 g/L, the methane gas production rate increased from 0.45 to 0.92 L-CH4/L/day. However, with the influent TS concentration of food waste (FW) further increased to 23.5 g/L, a large amount of scum formed and accumulated in the SDSAR. According to the result of chemical oxygen demand (COD) recovery, the proportion of COD remained in the effluent at different TS concentrations was only around 2%. On the other hand, with an increase in TS concentration, the proportion of COD remained in the reactors increased significantly. Our results demonstrated that effluent from the integrated system can meet the water quality requirements recommended by Japan Sewage Works Association (JSWA) for wastewater from FWD. In addition, to enhance the process stability, the influent TS concentration should be maintained below 15.5 g/L.


Advances in biomedical sensor technology: a review of the 1985 patent literature.
The 1985 patent literature pertaining to biomedical sensor technology is reviewed and an assessment made of the types of devices that are most likely to reach commercialisation. Novel systems that are described comprise electrochemical, optical, thermal and other transducers for monitoring key components of clinical samples. These include blood gases and electrolytes, metabolites, enzymes, proteins, antibodies and antigens.


Preliminary study in the evaluation of anti-aging cosmetic treatment using two complementary methods for assessing skin surface.
One of the constantly developing fields in the area of cosmetology is the analysis of the efficacy of cosmetics products. Various instrumental techniques are available nowadays to evaluate changes in skin surface and measure anti-wrinkle activity. The aim of our study was to present and confront two methods of the analysis of skin surface, Primos and Visioscan, regarding their applicability in evaluating anti-wrinkle properties of cosmetic formulations and treatments. The study was performed on women, taking part in anti-wrinkle cosmetic treatments. Various skin aging parameters were analyzed, including skin surface changes. The results obtained with Visioscan and Primos were compared regarding their usefulness in anti-wrinkling properties assessment. The assessment of skin condition suggested anti-wrinkle properties of the applied cosmetic treatment. Both Visioscan and Primos analyses were consistent with each other and had similar faults as well. The results of this study show that both complementary technologies (Visioscan and Primos) are appropriate for characterizing the skin surface and could be useful in testing the efficacy of anti-aging properties. There are some measurements which are unique to just one method, none, however, seems to be significantly more useful for efficacy testing than the other.


High-Frequency Ultrasound Imaging Findings of Different Mental Injectable Soft Tissue Fillers.
In recent years, the use of mental injectable soft tissue fillers is popular. However, some fillers are difficult to distinguish from pathological tissue, and some non-absorbable fillers need to be removed in time. Therefore, identification of different fillers is important. In this study, we summarized the ultrasonic manifestations of different mental injectable soft tissue fillers to provide references for clinical practice. We screened the mental ultrasound images from November 2014 to November 2021 in the Plastic Surgery Hospital of Chinese Academy of Medical Sciences, identified different filling injection materials, and summarized and classified the ultrasonic characteristics of each filling material. A total of 244 cases were included, involving 62 cases of hyaluronic acid, 126 cases of polyacrylamide hydrogel, 19 cases of growth factor, 16 cases of calcium hydroxyapatite, 15 cases of silicone oil and 6 cases of fat. The ultrasonic manifestation of hyaluronic acid was anechoic area, which could be divided into six types according to the distribution characteristics. The ultrasonography of polyacrylamide hydrogel showed fine punctate echo, which could be divided into nine types. The ultrasonographic appearance of growth factor was similar to the echo of the surrounding tissue, and the boundary was not clear. Calcium hydroxyapatite was characterized by uneven hyperechoic area, which was spread in the tissue space, with unclear boundary with surrounding tissues. Sonographic patterns of silicone oil were hyperechoic and cloudy on high-frequency ultrasound. The deep tissue and periosteum layer were not clear. Transplanted fat showed isoechoic area or uneven low-echo area, with clear boundary and peripheral adipose tissue acoustic enhancement. High-frequency ultrasound is safe and reliable for identification and typing of chin filling injection materials, which can be applied in clinical practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Viabahn Stent Graft for the Endovascular Treatment of Occlusive Lesions in the Femoropopliteal Artery: A Retrospective Cohort Study with 4-Year Follow-Up.
The polytetrafluoroethylene-covered Viabahn stent may be effective for the endovascular treatment of patients with femoropopliteal artery occlusive lesions. However, the long-term efficacy of Viabahn stent remains unclear. The aim of the study is to evaluate the long-term patency of Viabahn stent grafts in patients with occlusive lesions in the femoropopliteal artery. Consecutive patients with occlusive lesions in the femoropopliteal artery who had been treated with Viabahn stent grafts during the period from June 2013 to December 2016 at our center were retrospectively included. Accumulative incidences of primary patency and secondary patency were estimated by Kaplan-Meier survival analysis, and the predictors of primary patency were evaluated by Cox regression analysis. A total of 66 patients underwent successful endovascular treatment and were included in the study. Endovascular treatment with a Viabahn stent was associated with a complication rate of 9.1% and a 30-day mortality rate of 1.5%. Sixty-one patients were followed for a mean duration of 29.5 months. The 1-year, 2-year, 3-year, and 4-year primary patency rates were 81.7%, 74.7%, 67.6%, and 58.9%, respectively. The secondary patency rates were 94.9%, 92.9%, 90.1%, and 90.1%, respectively. The overall major amputation rate was 5.0%. The results of multivariate Cox regression analyses showed that stent location was the only independent predictor of primary patency (P = 0.001). Implantation of a Viabahn stent above the knee, compared with implantation below the knee, was associated with a higher rate of primary patency. The Viabahn stent graft is associated with a satisfactory rate of long-term patency for the endovascular treatment of occlusive lesions in the femoropopliteal artery, especially for those located above the knee.


Formate-driven growth coupled with H(2) production.
Although a common reaction in anaerobic environments, the conversion of formate and water to bicarbonate and H(2) (with a change in Gibbs free energy of ΔG° = +1.3 kJ mol(-1)) has not been considered energetic enough to support growth of microorganisms. Recently, experimental evidence for growth on formate was reported for syntrophic communities of Moorella sp. strain AMP and a hydrogen-consuming Methanothermobacter species and of Desulfovibrio sp. strain G11 and Methanobrevibacter arboriphilus strain AZ. The basis of the sustainable growth of the formate-users is explained by H(2) consumption by the methanogens, which lowers the H(2) partial pressure, thus making the pathway exergonic. However, it has not been shown that a single strain can grow on formate by catalysing its conversion to bicarbonate and H(2). Here we report that several hyperthermophilic archaea belonging to the Thermococcus genus are capable of formate-oxidizing, H(2)-producing growth. The actual ΔG values for the formate metabolism are calculated to range between -8 and -20 kJ mol(-1) under the physiological conditions where Thermococcus onnurineus strain NA1 are grown. Furthermore, we detected ATP synthesis in the presence of formate as a sole energy source. Gene expression profiling and disruption identified the gene cluster encoding formate hydrogen lyase, cation/proton antiporter and formate transporter, which were responsible for the growth of T. onnurineus NA1 on formate. This work shows formate-driven growth by a single microorganism with protons as the electron acceptor, and reports the biochemical basis of this ability.


Inhibition of platelet [3H]-imipramine binding by human plasma protein fractions.
Inhibition of high-affinity [3H]-imipramine binding to platelet membranes by human plasma fractions and isolated plasma proteins was investigated. Several plasma proteins were found to contribute to the observed apparent inhibition and this contribution was assessed in terms of inhibitor units. Alpha 1 acid glycoprotein, high density and low density lipoprotein, IgG and alpha 1-antitrypsin were identified as effective non-specific inhibitors. Alpha-1-acid glycoprotein was confirmed to be the most potent plasma protein inhibitor. Cohn fractions were evaluated for the presence of the postulated endocoid of [3H]-imipramine binding site.


Clear view of the index sesamoid: a sign of irreducible metacarpophalangeal joint dislocation.
If the index sesamoid bone is clearly seen in the joint following significant injury to the index metacarpophalangeal joint on radiographic examination, there is the probability of incarceration of the volar plate. In almost all cases, an open reduction will be necessary to re-establish the normal relationship between the second metacarpal and the proximal phalanx. In a case of irreducible dislocation of the index metacarpophalangeal joint, attempted reduction caused the injury to appear as a subluxation.


Fundamental equation of thermodynamics for protein-ligand binding.
For the internal energy and every thermodynamic potential that can be defined by a Legendre transform, there is a fundamental equation that contains all the thermodynamic information about a system. For a system involving the binding of molecular oxygen and hydrogen ions by a protein, fundamental equations are given for the Gibbs energy G, the transformed Gibbs energy G' at specified pH, and the further transformed Gibbs energy G" at specified pH and specified concentration of molecular oxygen. The Maxwell equations for these various Gibbs energies are important because they provide the connection with experimentally determined properties and increase our understanding of these properties. Measurements of the average number of oxygen molecules bound as a function of T, pH and concentration of molecular oxygen make it possible to calculate Delta(f)G"(o) of the reactant. Maxwell equations make it possible to calculate the average number of hydrogen ions bound, Delta(f)S"(o), Delta(f)H"(o) and their partial derivatives. These relations are illustrated with numerical calculations on a simple reaction system.


Identification of the isomer of methionine sulfoximine that extends the lifespan of the SOD1 G93A mouse.
In previous studies methionine sulfoximine (MSO) significantly extended the lifespan of the SOD1 G93A mouse model for ALS. Those studies used commercially available MSO, which is a racemic mixture of the LS and LR diastereomers, leaving unanswered the question of which isomer was responsible for the therapeutic effects. In this study we tested both purified isomers and showed that the LS isomer, a well-characterized inhibitor of glutamine synthetase, extends the lifespan of these mice, but the LR isomer, which has no known activity, does not.


BC032913 as a Novel Antisense Non-coding RNA is Downregulated in Gastric Cancer.
Long non-coding RNAs (lncRNAs) are a subset of non-coding RNAs. Abnormal expression of lncRNAs is associated with the development of cancers including gastric cancer (GC). Increasing evidence in this field reveals that lncRNAs have a key role in biological actions via modulating the expression of genes at various genomic levels. BC032913, as a novel antisense lncRNA, may have a role in GC progression. The very aim of this study was to examine the clinical significance and the functional role of lncRNA BC032913 in GC. QRT-PCR technique was exerted to survey the expression level of BC032913 in GC tissues and matched adjacent non-tumorous tissues. Furthermore, the association between clinicopathological parameters and the expression level of BC032913 was evaluated. BC032913 expression was downregulated in cancerous tissues as compared with adjacent non-tumorous tissues (P = 0.0108). Downregulation of BC032913 expression did not demonstrate a significant association with clinicopathological parameters. LncRNA BC032913 may be considered as an impressive therapeutic target for GC.


Guardianship in hospitals: a collaborative pilot project.
Objectives This paper describes the development, implementation and preliminary results of a collaborative pilot project aimed at reducing the time hospital-based patients with cognitive impairments spend waiting for the allocation of legally appointed Advocate Guardian decision makers from the Office of the Public Advocate (OPA). The aim of the study was to investigate the effect of increased availability of public advocate guardians on guardian allocation waits, patient discharge outcomes and healthcare system demand. Methods A multi-institutional pilot program created a dedicated hospital guardian team within OPA, funded by the health networks, to reduce the time to guardian allocation for patients within each network. A multisite, quasi-experimental historical control group design was used, with initial data collection over 12 months, followed by study of 12-month post-implementation cohorts. Results Under the pilot program, the time from guardianship order lodgement to guardian allocation decreased significantly from 46.5 to 22.9 days, halving the average time hospital-based patients spend waiting for a guardian (difference -23.55 days, two-sample t(154) = -6.575, P < 0.0001, 95% confidence interval [-30.65, -16.48].). Mean total length of stay decreased from 163.2 to 148.5 days. The estimated value of the reduction in allocation wait time was A$15473 per patient, or A$5 of resources released per A$1 spent on increased staffing. Conclusions Direction of a small amount of resources from health services to staff within OPA appears to have created much greater savings for the health services involved. The pilot program has reduced the period of time vulnerable patients spend waiting in hospital for a guardian. What is known about the topic? Guardianship resources are under increasing stress, with demand outstripping funding and hospital-based applicants deprioritised due to assumptions of lower risk, leading to extensive wait times for guardian allocation. What does this paper add? The paper quantifies the impact of greater guardianship resourcing on access to both guardianship and healthcare resources, highlighting benefits for vulnerable patient groups, healthcare system sustainability and access to both guardianship and healthcare resources for the broader community. What are the implications for clinicians? Improving patient flow through healthcare systems may involve allocating resources to services that are managed outside the healthcare system where 'bottlenecks', such as wait times for guardian allocation, have been identified.


Microplate biochemical determination of Russian VX: influence of admixtures and avoidance of false negative results.
Two microplate spectroscopic methods for determination of organophosphates, based on inhibition of acetylcholinesterase (AChE) activity, were further improved and evaluated for determination of the chemical weapon agent Russian VX (RVX) in aqueous solutions. The linear range of the Hestrin method (74.8-1120 pM) was 3.1-fold wider than that of the Ellman method (37.4-374 pM). Limits of detection and quantification of RVX for both methods were below the maximal allowable concentration of RVX in water-soluble washouts. One of the early products of RVX hydrolysis, N,N-diethylaminoethanethiol, like reduced glutathione, caused false negative results in the Ellman method at concentrations exceeding 10 μM; individual blanks were necessary to eliminate the effect. The Hestrin method showed greater specificity (~3 orders of magnitude) for analysis of samples containing mercaptans. A major product of RVX degradation, 2,2'-dithiobis(N,N-diethylethanamine), caused significant inhibition of AChE at concentrations of ≥0.1 mM (P<0.01) and had a false positive effect at higher concentrations (≥2 mM). For environmental monitoring of RVX, the method based on Hestrin is preferred over that based on Ellman, principally because the former method was less sensitive to interference from major admixtures and did not give rise to potentially dangerous false negative results.


Crystalline lens optical dysfunction through aging.
To evaluate the optical and densitometric changes that take place in the crystalline lens with aging. Cross-sectional study. Seventy-two eyes of 72 patients of different ages (8-80 years) with a clear lens, a visual acuity of 20/25 or better, and no ocular disease. In each case, the lens thickness, optical density, modulation transfer function (MTF), and intraocular aberrations were measured. Embryonic and fetal nucleus density, lens thickness, intraocular high-order aberration (HOA), and 0.1 MTF. Embryonic, anterior, and posterior fetal nucleus densities show a positive correlation with age (P<0.0001, P<0.0001, and P<0.0001, respectively). Lens thickness also shows a positive correlation with age (P<0.0001). Total ocular and corneal HOAs for a 6-mm pupil show a positive correlation with age (P = 0.036 and P<0.0001, respectively). Ocular and corneal Zernike polynomials Z4i+Z6i and intraocular spherical aberration (Z4(0)) also show a positive correlation with age (P = 0.001, P = 0.039, and P = 0.001, respectively). Intraocular coma aberration (Z3(-1)) shows a negative linear correlation with age (P<0.0001). In addition, 0.1 MTF decreased with age from 18.557 to 10.100 cycles per degree. There is a degradation of the optical quality of the crystalline lens with aging that is associated with morphological changes (thickness and density). These results are important for the consideration of lens replacement in the absence of evident cataract.


Homoharringtonine in combination with cytarabine and aclarubicin in the treatment of refractory/relapsed acute myeloid leukemia: a single-center experience.
To assess the efficacy and toxicity of HAA regimen (Homoharringtonine 4 mg/m(2)/day, days 1-3; cytarabine 150 mg/m(2)/day, days 1-7; aclarubicin 12 mg/m(2)/day, days 1-7) as a salvage therapy in the treatment of refractory and/or relapsed acute myeloid leukemia (AML), 46 patients with refractory and/or relapsed AML, median age 37 (16-65) years, participated in this clinical study. The median follow-up was 41 (10-86) months. Eighty percent of patients achieved complete remission (CR), and the first single course of re-induction HAA regimen resulted in CR rate of 76.1 %. The study protocol allowed two courses of induction. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 90 %, 88.9 %, and 37.5 %, respectively. For all patients, the estimated 3-year overall survival (OS) rate was 42 %, and the estimated relapse free survival (RFS) at 3 years for the 36 CR cases was 49 %. The toxicities associated with HAA regimen were acceptable. HAA is a good choice in cases with refractory/relapsing AML for salvage chemotherapy, preferably with a high-efficacy and low-toxicity profile.


An investigation of 3D spinal alignment in cervicogenic headache.
There is a growing interest in the impact of body posture influences on outcome measures of cervicogenic headache (CGH). To evaluate differences in the 3D spinal alignment in cases suffering from chronic CGH compared to a group of strictly matched control participants without CGH. A single-blinded, comparative cohort design. 100 participants suffering from frequent headaches for at least 3 months who fulfilled the CHISG criteria for CGH were match by age and sex to 100 asymptomatic control group participants. A 4D Formetric device was used to assess participants' posture variables of: 1) thoracic kyphosis max (ICT-ITL in degrees); 2) trunk lateral imbalance (VP-DM in mm); 3) Trunk anterior inclination (VP-DM in mm); 4) lumbar lordotic angle (ITL-ILS max in degrees); 5) Vertebral rotation (rms) in degrees. A matched-pairs binary logistic regression was used to determine whether measurements of posture demonstrated an association with the likelihood of the presence of CGH. There were statistically significant differences between the CGH and control group for all posture variables indicating larger posture displacements in the CGH group: ICT-ITL (p < .001), Lateral VP-DM (p < .001), Sagittal VP-DM (p < .001), ITL-ILS (p < .001), RMS (p < .001). Logistic regression revealed that as posture displacement increased, a statistically significant increased likelihood of having CGH occurred: (ICT-ITL (max) (p < .001); Trunk imbalance VP-DM (p < .004); Trunk inclination VP-DM (p < .001); and vertebral rotation (RMS) (p = .007). No such relationship was found for Lumbar Lordosis ITL-ILS max. Participants with CGH exhibited increased magnitudes of thoracolumbar posture displacements which corresponded to an increased odds of suffering from CGH compared to matched control participants.


Akt stabilizes estrogen receptor alpha with the concomitant reduction in its transcriptional activity.
We have investigated the effect of Akt on estrogen receptor (ER) alpha protein level and its transcriptional activity. Transient transfection studies revealed that constitutively active Akt1 up-regulated ERalpha at the post-transcriptional level. Studies using Akt inhibitor and dominant-negative Akt1 showed that Akt1 kinase activity is required for the up-regulation of ERalpha. Cycloheximide decay assays and studies with proteasome inhibitor indicated that Akt1-mediated up-regulation of ERalpha was maintained by inhibiting proteasome-mediated degradation of ERalpha. When Akt consensus phosphorylation site mutant, ERalphaS167A was tested for Akt1-mediated up-regulation, increase of ERalphaS167A by Akt1 was significantly impaired as compared to wild type ERalpha. In addition, dominant-negative glycogen synthase kinase (GSK) 3beta and LiCl could also partially up-regulate ERalpha protein level, suggesting that concerted action of Akt1-mediated phosphorylation on S167 and kinase activity of Akt-downstream GSK3beta could affect ERalpha protein level. Paradoxically, co-expression of Akt1 could down-regulate transcriptional activity of ERalpha. The inhibitory effect of Akt1 on ERalpha transcriptional activity was not attributable to changes in subcellular distribution of ERalpha. Transfection studies using increasing amount of Akt1 and ERalpha indicated that the transcriptional activity of ERalpha was negatively regulated by ERalpha protein quantities at higher ERalpha concentrations. Chromatin immunoprecipitation assays revealed that at Akt1 concentration high enough to induce up-regulation of ERalpha, association of ERalpha to promoter region of ERalpha target pS2 gene was impaired. Taken together, these data suggest that Akt1 could increase ERalpha protein level with simultaneous reduction in its transcriptional activity, possibly by modulating association of ERalpha to the target gene promoters.


Further case of microdeletion of 8q24 with phenotype overlapping Langer-Giedion without TRPS1 deletion.
Langer-Giedion syndrome results from a microdeletion at 8q24.1 encompassing the EXT1 and the adjacent TRPS1 gene. We report on a boy with an oligo array-cgh characterized small microdeletion involving EXT1 alone but with some features of Langer-Giedion syndrome suggesting a functional disturbance of TRPS1. This boy, in addition to a mild Langer-Giedion like phenotype, also had some unusual features including prominent toe pads and fat pads on the soles of his feet similar to those described in Pierpont syndrome.


Rapid penetration of lucifer yellow into vital teeth and dye coupling between odontoblasts and neighbouring pulp cells in the cat.
The location and long process of odontoblasts appear well suited to detection of external stimuli. The odontoblasts may transmit the information not individually but as a syncytium via gap junction, which functions as a mechanism for intercellular linking cells and as the route for dye coupling. The aims of the present study were to examine dye penetration through enamel and dentin, and to confirm dye coupling between odontoblasts (OBs) or between odontoblasts and other pulpal cells beneath the odontoblastic layer (PCs). Either lucifer yellow (LY) or borate buffer (control) was applied to etched enamel surface of feline canines for 30 min at atmospheric pressure. In the decalcified sections, lucifer yellow positive cells were found not only in but also beneath the odontoblastic layer (experiment 1). In the isolated pulp cells, all OBs (27/27) and some PCs (6/9) that were immunocytochemically differentiated using two monoclonal antibodies were labelled with LY (experiment 2). These results indicate the remarkably quick movement of LYE through enamel and dentin into the superficial pulp. In experiment 3, fresh OBs and PCs were isolated from feline canines to which LY had not been applied. LY was iontophoretically injected into an OB-like cell that had an oval cell body and a long monopolar process. Some PCs and OBs identified immunocytochemically were labelled with LY, with the exception of a few LY-negative cells. These findings indicate that dye coupling exists not only between OBs but also between OBs and PCs. Thus, the coupling provides evidence for a functional link via which information is transmitted between OBs and PCs.


Electroacupuncture attenuates ketamine-induced neuronal injury in the locus coeruleus of rats through modulation of the CAMK II/CREB pathway.
Ketamine, despite its efficacy in treating depression, raises concerns regarding safety due to potential abuse, cognitive impairment, and bladder toxicity. Ketamine can affect the locus coeruleus (LC) norepinephrine and attention networks. This study explored the protective effects of electroacupuncture (EA) on the LC of rats exposed to repeated administration of ketamine while investigating the potential role of the Calcium CaM-dependent protein kinase II (CAMK II)/ cAMP response element binding protein (CREB) pathway in mediating EA's impact on ketamine-induced neuronal injury in LC. Rats were repeatedly injected intraperitoneally with ketamine hydrochloride (50 mg/kg) once daily for seven days. Subsequently, EA was performed at the acupoints "Zusanli" (ST36) and "Sanyinjiao" (SP-6) once daily following ketamine administration. The Morris water maze test was employed to assess behavioral changes in the rats. Neuronal injury was examined using Nissl staining, and the expression of CAMK II, CREB, and phospho-CREB (p-CREB) was evaluated through immunohistochemistry and western blotting. EA mitigated the cognitive and exploratory impairments and attenuated neuronal injury in the LC induced by repeated administration of ketamine. The expression of CAMK II and p-CREB proteins in the LC increased following 7 days of ketamine administration. However, EA treatment led to a downregulation of CAMK II and p-CREB expression. Repeated administration of ketamine in male rats can lead to neuronal injury and neurobehavioral dysfunction. However, EA was found to ameliorate neurodegeneration in the LC and enhance neurobehavioral symptoms. This therapeutic effect of EA may be attributed to its modulation of the CAMKII/CREB pathway, thereby mitigating the aforementioned adverse effects.


Adaptive abilities of hospitalized alcoholics and matched controls. The brain-age quotient.
Comparison of alcoholics' and controls' Brain-Age Quotients and performance on various educational and problem-solving variables indicated that the alcoholics were comparable to the controls in verbal ability but were deficient in problem-solving ability.


Evaluation of a new vaginal contraceptive.
A new chemical contraceptive in the form of a vaginal suppository was evaluated in a series of in vitro and in vivo tests and compared to a leading contraceptive foam and cream. Good in vitro spermicidal effect was observed, but problems in solubility and the position of the suppository against the external cervical os may lead to less clinical effectiveness if not properly evaluated prior to its use.


Use of smartphone apps in bipolar disorder: An international web-based survey of feature preferences and privacy concerns.
Smartphone apps have potential for delivering interventions and supporting self-management in bipolar disorder (BD), however clinical trials of mental health apps have high dropout rates and low sustained use in real-world contexts. To support the development of app-based interventions, we explored use of and attitudes towards apps amongst people with BD, specifically concerns about privacy and preferences for various app features. An international web-based survey was used to investigate concerns about privacy and the perceived importance of various app features among people with BD. Quantitative findings were summarised using descriptive statistics. Qualitative content analysis was used to investigate free-text responses. A total of 919 people completed the survey; 97.5% reported using smartphone apps in general. Concerns regarding data security were prevalent. Commonly prioritised mHealth features included content quality/accuracy, ease and flexibility of use, cost, and data security. The ability to share data with others, rewards for use, inter-app connectivity, and peer support were endorsed as important by fewer than half of respondents. Qualitative findings suggested that sustained app use could be supported by novel and positive content, customisation, meaningful use of data, interactivity, and perceived real-world benefits. The findings of the present study offer important design considerations for the development and evaluation of future app-based interventions for BD. Importantly, some features that have previously been suggested as clinically beneficial or likely to support engagement were perceived ambivalently, emphasising the need for in-depth consultation with potential end users during app development.


Eliciting Patient Insights on the Burden of Nontuberculous Mycobacterial Lung Disease (NTM-LD) and Healthcare Gaps in Germany Through Qualitative Semi-structured Interviews.
Nontuberculous mycobacterial lung disease (NTM-LD) is a rare but growing health concern, particularly affecting vulnerable patients with chronic lung conditions. Understanding the patients' perspective on their disease and treatment expectations can help to identify healthcare gaps and improve overall patient care. Therefore, the main objective of the survey study was the evaluation of patient insights on the burden of the disease and healthcare gaps. The study used an online survey as a pre-screener to facilitate recruitment followed by semi-structured qualitative interviews. The interviews were conducted by phone from April 2019 to February 2020 in German language. Only patients with a self-reported confirmed NTM-LD diagnosis, managed and insured in Germany were included in this study. In total, 20 semi-structured qualitative interviews were conducted. Most (85%) patients had at least one coexisting pulmonary condition with cystic fibrosis (CF, n = 9) being most common. Chronic cough, fatigue, and dyspnea were the most reported symptoms. Of all the symptoms reported, fatigue was perceived as the most burdensome and 85% of patients felt limited in their daily life. It took a median of 5 months for patients to receive an accurate diagnosis of NTM-LD and that time was doubled when excluding patients with CF (range 0-480 months). Ninety percent of interviewed patients (n = 18) received drug treatment for NTM-LD and most of them (n = 17) reported having experienced side effects from their treatment. Patients' expressed a particular need for more comprehensive and reliable patient-friendly information on NTM-LD and a better awareness of physicians as well. NTM-LD can considerably impair the lives of patients and their families and/or caregivers. A multidisciplinary approach and establishment of more widespread regional expert centers for NTM-LD management in Germany with well-structured referral and communication pathways accompanied by peer-to-peer support of patient advocacy groups are urgently needed.


JNJ-64794964 (AL-034/TQ-A3334), a TLR7 agonist, induces sustained anti-HBV activity in AAV/HBV mice via non-cytolytic mechanisms.
JNJ-64794964 (JNJ-4964/AL-034/TQ-A3334), an oral toll-like receptor 7 agonist, is being investigated for the treatment of chronic hepatitis B (CHB), a condition with a high unmet medical need. The anti-hepatitis B (HBV) activity of JNJ-4964 was assessed preclinically in an adeno-associated virus vector expressing HBV (AAV/HBV) mouse model. Mice were treated orally with 2, 6 or 20 mg/kg of JNJ-4964 once-per-week for 12 weeks and then followed up for 4 weeks. At 6 mg/kg, a partial decrease in plasma HBV-DNA and plasma hepatitis B surface antigen (HBsAg) was observed, and anti-HBs antibodies and HBsAg-specific T cells were observed in 1/8 animals. At 20 mg/kg, plasma HBV-DNA and HBsAg levels were undetectable for all animals 3 weeks after start of treatment, with no rebound observed 4 weeks after JNJ-4964 treatment was stopped. High anti-HBs antibody levels were observed until 4 weeks after JNJ-4964 treatment was stopped. In parallel, HBsAg-specific immunoglobulin G-producing B cells and interferon-γ-producing CD4+ T cells were detected in the spleen. In 2/4 animals, liver HBV-DNA and HBV-RNA levels and liver hepatitis B core antigen expression dropped 4 weeks after JNJ-4964 treatment-stop. In these animals, HBsAg-specific CD8+ T cells were detectable. Throughout the study, normal levels of alanine aminotransferase were observed, with no hepatocyte cell death (end of treatment and 4 weeks later) and minimal infiltrations of B and T cells into the liver, suggesting induction of cytokine-mediated, non-cytolytic mechanisms.


The lack of correlation between inhibition of aggregation and cAMP levels with canine platelets.
Arachidonic acid (AA) induced aggregation of canine platelets can be inhibited by various phosphodiesterase inhibitors (PDIs) with the order of potency IBMX greater than or equal to papaverine greater than Ro 20-1724 greater than theophylline. With aggregation induced by AA plus epinephrine (EPI), only IBMX and papaverine inhibited at 100 microM. None of these PDIs affected the basal cAMP levels but all potentiated the PGE1-stimulated cAMP production, with the order of potency being Ro 20-1724 greater than papaverine greater than IBMX greater than theophylline. PGE1 at 1 microM caused a sharp increase in cAMP and complete inhibition of platelet aggregation induced by AA plus EPI. However, when EPI was added before PGE1, there was no elevation of cAMP yet inhibition of aggregation still occurred. Our results indicated that inhibition of platelet aggregation does not require a measurable increase in cAMP.


The first Anglo-Dutch contacts in plastic surgery: a brief historical note.
This paper outlines briefly the part played by two Dutch surgeons Jan Esser and Carel Koch and their contacts in England in the development of plastic surgery on the Continent and in Great Britain. Photographs and letters from the archives of Jan Esser throw a new light on the early days of the new specialty of plastic and reconstructive surgery.


Pass/Fail USMLE Step 1 Scoring-A Radiology Program Director Survey.
In February 2020, administrators for the US medical licensing examination (USMLE) announced that Step 1 reporting would change to pass/fail in hopes of reducing the overemphasis of USMLE performance on the residency selection system and improving medical student well-being. Our objective was to determine the perspectives of diagnostic radiology (DR), interventional radiology (IR), and nuclear medicine (NM) program directors (PDs) regarding pass/fail USMLE Step 1 scoring. A survey composed of thirteen questions on a three-point Likert scale, five demographic questions, and a free-text question was distributed to 179 DR, 84 IR, and 34 NM PDs from ACGME-accredited residency programs. In total, 140 unique responses were obtained (response rate = 47.1%). The PD respondents had a male predominance of 79.1%, average age of 46 ± 7.2 years, and average tenure of 5.9 ± 5.2 years. A majority of PDs (69.6%) disagreed that the change is a good idea, and a minority (21.6%) believe the change will improve medical student well-being. Further, 90.7% of PDs believe a pass/fail format will make it more difficult to objectively compare applicants and most will place more emphasis on USMLE Step 2 scores and medical school reputation (89.3% and 72.7%, respectively). The lasting impact of pass/fail Step 1 scoring are uncertain and many radiology PDs do not support this change. While the central motivations to reduce the overemphasis on USMLE Step 1 performance and improve medical student well-being are admirable, it remains to be seen if pass/fail scoring will accomplish these goals.


Assessing the effects of tertiary treated wastewater reuse on the presence emerging contaminants in a Mediterranean river (Llobregat, NE Spain).
The Llobregat River, which is characterized by important fluctuations of the flow rates, receives treated waters from WWTPs. During the years 2007 and 2008, the Llobregat River basin suffered from a severe drought which affected the supply of drinking water facilities (DWF) that rely on the exploitation of the river water. The Catalan Water Agency implemented a water reuse experiment with the objective of maintaining the river flow rate at sufficiently high level so as to ensure the supply of raw water to Barcelona's major DWF. A total of 103 emerging contaminants belonging to the groups of pharmaceuticals (74), illicit drugs (17) and oestrogens (12) were determined using LC-MS/MS methods in river water samples during the water reuse campaign. The effect of the reclaimed water discharge on the river water quality, in terms of contamination loads and environmental risk (based on the concentration addition mode), is discussed. Fifty-eight pharmaceuticals out of 74 monitored were detected at least in one sample. In river water upstream (site R0) majority of compounds were detected at low nanograms per litre levels, while downstream of discharge of tertiary effluent only few compounds were detected at levels higher than 100 ng L(-1) (i.e. acetaminophen, diclofenac, erythromycin, sulfamethazine), but never exceeding 500 ng L(-1). The total concentration of illicit drugs was found to be very low at both sampling sites (<50 ng L(-1)). No relevant ecotoxicity risks were identified, except for pharmaceuticals vs. algae. In general, the discharge of reclaimed water in the river influenced perceptibly in terms of concentrations, mass loads and environmental risk, especially for pharmaceuticals and in less extent for illicit drugs. Nevertheless, it was not very significant in any case.


Gastric stenosis after laparoscopic sleeve gastrectomy in morbidly obese patients.
Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric procedure. The objective of this study is to describe a series of patients who were subjected to LSG and then developed gastric stenosis, with an emphasis on their treatment and a discussion of the possible underlying mechanisms. From January 2006 to October 2012, 717 patients with morbid obesity underwent LSG in our institution. Out of 717 patients, 571 (79.6 %) were women. The mean age was 36.9 years with a BMI of 37.3 kg/m(2). Five patients (0.69 %) developed gastric stenosis. Treatment of the stenosis was endoscopic dilatations; however, one patient required a conversion to laparoscopic Roux-en-Y gastric bypass. Stenosis after LSG is rare but requires early diagnosis and treatment.


EGCG attenuate EGF triggered matrix abundance and migration in HPV positive and HPV negative cervical cancer cells.
Our previous laboratory findings suggested the beneficial effects of epigallocatechin gallate (EGCG) against cervical cancer (CC) cells survival. The present study is aimed at identifying the effects of EGCG in preventing the actions of epidermal growth factor (EGF) in human papilloma virus (HPV) 68 positive ME180 and HPV negative C33A CC cells. An elevated level of EGF in tumor micro-environment (TME) is linked to the metastasis of several cancers including CC. We hypothesized that EGCG has the ability to block the actions of EGF. To test this, survival assay was performed in cells treated with or without EGF and EGCG. The mitochondrial activity of cells was ascertained using MTT assay and mitored staining. Protein and non-protein components in the extracellular matrix such as collagen and sulphated glycosaminoglycans (GAGs) were evaluated using sirius red and alcian blue staining, respectively. Matrix metalloproteinase-2 (MMP-2) gene expression and enzymatic activity were assessed using real time-reverse transcriptase-polymerase chain reaction (RT-PCR) and gelatin zymography. Wound healing assay was performed to assess the EGF induced migratory ability and its inhibition by EGCG pre-treatment. Clonogenic assay showed that EGCG pre-treatment blocked the EGF driven colony formation. In silico analysis performed identified the efficacy of EGCG in binding with different domains of EGF receptor (EGFR). EGCG pre-treatment prevented the epithelial-mesenchymal transition (EMT) and metabolic activity induced by EGF, this is associated with concomitant reduction in the gene expression and enzyme activity of MMP-2. Further, reduced migration and ability to form colonies were observed in EGCG pre-treated cells when stimulated with EGF. HPV positive ME180 cells showed increased migratory and clonogenic ability upon EGF stimulation, whose effects were not much significant in HPV negative C33A cells. EGCG effectively blocked the actions of EGF in both HPV positive and HPV negative conditions and can be advocated as supplementary therapy for the management of EGF driven CC. However, further studies using cell line-derived xenograft (CDX)/patient-derived xenograft (PDX) model system is warranted to validate the therapeutic utility of EGCG.


Development and Validation of a Risk Score Screening Tool to Identify People at Risk for Hypertension in Shanghai, China.
This study aimed to develop a screening tool based on a risk scoring approach that could identify individuals at high risk for hypertension in Shanghai, China. A total of 3147 respondents from the 2013 Shanghai Chronic Disease and Risk Factor Surveillance were randomly divided into the derivation group and validation group. The coefficients obtained from multivariable logistic regression were used to assign a score to each variable category. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point and to evaluate the screening performance. Age, family history of hypertension, having diabetes, having dyslipidemia, body mass index, and having abdominal obesity contributed to the risk score. The area under the ROC curve was 0.817 (95% CI: 0.797-0.836). The optimal cut-off value of 20 had a sensitivity of 83.4%, and a specificity of 64.3%, demonstrating good performance. We developed a simple and valid screening tool to identify individuals at risk for hypertension. Early detection could be beneficial for high-risk groups to better manage their conditions and delay the progression of hypertension and related complications.


Flexion deformity and laxity as a function of knee position at the time of tensioning of rigid anatomic hamstring ACL grafts.
Anatomic ACL grafts routinely display the anisometric length-tension behaviour seen in the native ligament with maximum length in full knee extension. Recent improvements in hamstring graft preparation and fixation have improved graft rigidity to the point where total graft lengthening after implantation may be less than 1 mm. Despite this it remains common practice to fix these grafts in a knee flexed position. Nineteen participants underwent all-inside ACL reconstruction with optimally preconditioned 4 strand semitendinosus grafts using bi-cortical adjustable suspensory loop fixation. Using a computer navigation system, baseline measures of anisometricity, extension range, and tibial rotation were made. The graft was tensioned and provisionally fixed with the knee flexed 5° beyond its anisometric point and extension range recorded. The graft was then definitively fixed with the knee fully extended and extension range and tibial rotation recorded again. Anterior laxity measurements were made pre-operatively and postoperatively using a manual arthrometer and compared to those from the contralateral limb. Fixing the graft with the knee flexed produced a mean FD of 10.9° (p < 0.0001) and fixing in extension restored full extension (p = 0.661). Fixing in extension restored anterior laxity at 30° (p = 0.224) and at 90° (p = 0.668). There were very strong correlations between post-operative and control extension range (r = 0.931, p < 0.0001) and anterior laxity and 30° (r = 0.830, p < 0.0001) measures. Constraint of tibial internal rotation increased by 2.9° during the pivot-shift (p < 0.001) and increased with pivot shift grade (r = 0.474, p = 0.040). Fixing rigid anatomic hamstring grafts in a knee flexed position routinely produces a flexion deformity. Tensioning and fixing grafts with the knee fully extended restores full extension and anterior laxity at 30° and 90°. Rotational constraint is significantly improved and correlates with the pivot-shift grade. Rigid anatomic grafts should be tensioned and fixed with the knee fully extended.


[Outcome of patients treated with intra-peritoneal immunochemotherapy for ovarian cancer].
The aim of this study is to show that i.p. chemotherapy improves the evolution of the patients with an ovarian cancer, as the risk of a small number of complications due to this route of administration. 85 patients (11 stage Ic, 4 IIc and 70 stage III) were treated from 1980 to 1993 (median of follow up > 77 months) by a cisplatin based immunochemotherapy administered intraperitoneally, by a needle. Median overall survival exceeds, 72 months (60 months for stage III). Out of 41 relapses, 11 took place after 48 months of follow up. Delayed general complications consisted of 2 chronic nephotoxicities due to CDDP and one leukemia. Local complications are dominated by serous adherences (5 cases of plastic peritonitis). Secondary cytoreductions turned out to be beneficial in this series in spite of relapse diagnosis of them being carried out to late. Classic imagery remains disappointing for the exploration of the pelvic abdominal region. Paclitaxel by i.p. way seems very promising, which should launch once again interest in secondary debulking surgery.


Purification of N-acetyl-L-glutamate synthetase from rat liver mitochondria and substrate and activator specificity of the enzyme.
N-Acetylglutamate synthetase was purified 33,000-fold to apparent homogeneity from the matrix fraction of rat liver mitochondria. The purification procedure involved treatment of mitochondria with digitonin, ammonium sulfate fractionation, ion exchange chromatography, hydrophobic chromatography, Affi-Gel blue chromatography, acetylglutaminyl Bio-Gel chromatography, sucrose density gradient centrifugation, and isoelectric focusing. As the enzyme lost activity in contact with a glass surface, glassware coated with silicone was used throughout the purification. Triton X-100 stabilized the enzyme and was included in most buffers at a concentration of 0.1% (w/v). The purified acetylglutamate synthetase has a specific activity of 92.4 mumol min-1 (mg of protein)-1, in the presence of 1 mM L-arginine. The enzyme had a sedimentation coefficient (S20,w) of 8.1 S and its molecular weight was estimated to be about 160,000. On polyacrylamide gel electrophoresis in sodium dodecyl sulfate, the enzyme migrated as a single protein band with Mr = 57,000, indicating a composition of three subunits of similar size. The purified acetylglutamate synthetase showed a high substrate specificity for L-glutamate and acetyl-CoA, confirming the previous results with a less purified preparation (Shigesada, K., and Tatibana, M. (1978) Eur. J. Biochem. 84, 285-291). Among other 14 acyl-CoAs tested, only propionyl-CoA could substitute for acetyl-CoA, as an acyl donor, with a reaction rate 4.3% of that with acetyl-CoA at 0.5 mM. Among amino acids other than L-glutamate and derivatives or analogues of glutamate tested, the following served as an acyl acceptor: glycine at a rate 2.7% of that with L-glutamate at 1.0 mM, L-glutamine (5.0%), L-glutamate gamma-hydroxamate (15.5%), DL-alpha-aminoadipate (5.2%), and DL-alpha-aminopimelate (4.0%). The purified enzyme is markedly stimulated by L-arginine. The specificity of L-arginine as a low molecular weight activator was strict; only L-argininic acid could activate the enzyme to a lesser extent. Cationic polypeptides, such as protamine, polyarginine and polylysine, also activated the synthetase. The effect was additive to that of arginine.


Extent of Segmentectomy That Achieves Greater Lung Preservation Than Lobectomy.
This study sought to clarify the extent of segmentectomy that achieves greater lung preservation than lobectomy. This was a single-center retrospective cohort study involving 374 patients with lung cancer who were treated with either lobectomy or segmentectomy between 2013 and 2018. The percentage of preserved pulmonary function (%PPF) after surgery was compared among patients who underwent lobectomy (n = 164), segmentectomy of 2 or more segments (Seg ≥2S; n = 42), and segmentectomy of less than 2 segments (Seg <2S; n = 168). Using perfusion scintigraphy, forced expiratory volume in 1 second of the preserved target lobe was measured to examine its effect on the %PPF. The number of resected subsegments (SSs) in segmentectomy that made the %PPF higher than that observed with lobectomy was also examined. Mean %PPF was lowest in those patients who underwent lobectomy (86%), followed by Seg ≥2S (89%) and Seg <2S (95%) (P < .001), but the difference between the lobectomy and Seg ≥2S was not significant (P = .21). The forced expiratory volume in 1 second of the preserved target lobe was significantly lower in the Seg ≥2S group than in the Seg <2S group (P < .001). The number of resected SSs was 6 to 12 in lobectomy, 4 to 7 in Seg ≥2S, and 1 to 4 in Seg <2S. Although the %PPF after segmentectomy of less than 5 SSs (Seg <5SS) was significantly higher than that after lobectomy (P < .001), the %PPF after segmentectomy of 5 or more SSs (Seg ≥5SS) was not significantly different from that after lobectomy (P = .68). Both the Seg ≥2S and Seg ≥5SS groups did not differ from lobectomy in %PPF because of the low function of preserved target lobe.


Patients' Perspectives on What Makes a Better Care Experience While Undergoing Treatment for Oropharyngeal Dysphagia Secondary to Head and Neck Cancer.
Patients' perceptions on what makes a better care experience for head and neck cancer (HNca) have not been widely sought. Patients' perceptions can play a crucial role in shaping quality care and client involvement. To investigate patients' perspectives on what makes a better care experience while undergoing rehabilitation for oropharyngeal dysphagia secondary to HNca. Qualitative data were collected in the form of semi-structured interviews from eight patients after they had undergone rehabilitation for HNca. The data were thematically analysed by two researchers independently. Six themes, plus subthemes, were identified. These themes were Supportive network is essential; Reassurance from staff professionalism; Access to service; Using own motivation and resilience; Receiving the right information and Ongoing shock and adjustment. Results are discussed in context of the literature and clinical implications and future research are recommended. Collation of patients' perspectives is valuable to increase insight into what makes a better rehabilitative journey for patients with HNca. Rehabilitation that is holistic, specialised and patient-specific is highly valued by patients with HNca.


C. elegans AWA Olfactory Neurons Fire Calcium-Mediated All-or-None Action Potentials.
Neurons in Caenorhabditis elegans and other nematodes have been thought to lack classical action potentials. Unexpectedly, we observe membrane potential spikes with defining characteristics of action potentials in C. elegans AWA olfactory neurons recorded under current-clamp conditions. Ion substitution experiments, mutant analysis, pharmacology, and modeling indicate that AWA fires calcium spikes, which are initiated by EGL-19 voltage-gated CaV1 calcium channels and terminated by SHK-1 Shaker-type potassium channels. AWA action potentials result in characteristic signals in calcium imaging experiments. These calcium signals are also observed when intact animals are exposed to odors, suggesting that natural odor stimuli induce AWA spiking. The stimuli that elicit action potentials match AWA's specialized function in climbing odor gradients. Our results provide evidence that C. elegans neurons can encode information through regenerative all-or-none action potentials, expand the computational repertoire of its nervous system, and inform future modeling of its neural coding and network dynamics.


The development of a sustainable, community-supported children's bereavement camp.
This article describes the creation and development of a sustainable, community-supported children's bereavement camp. Numerous grief camps were examined prior to the project development. The project development was guided by the S.M.A.R.T. (S--Strategic/specific; M--Measurable; A--Achievable/attainable; R--Realistic; and T--Time-framed) stratagem to direct steps toward the development of the bereavement camp. Outcome measures included program participation, as well as evaluations completed by campers, family members, and volunteers. Camp attendance continues to grow, with 48 children the first year and an average of 65 the following 3 years. According to post-evaluation surveys, campers were able to integrate back into school with a decrease in stress and an increase in their ability to verbalize their grief, share feelings and begin to trust others. One child "got her sparkle back" according to her grandmother. Several campers commented that camp allowed them to see themselves as normal children. The goal of Camp Healing Hearts was that campers would laugh again, and they are.


One size does not fit all: Differential benefits of simultaneous liver-kidney transplantation by eligibility criteria.
Standard eligibility criteria for simultaneous liver-kidney transplantation (SLK) are in place in the United States. We hypothesize that the benefit associated with SLK over liver transplant alone differs by patient, depending on the specific SLK criteria met. We analyzed a retrospective US cohort of 5446 adult liver transplant or SLK recipients between January 1, 2015, and December 31, 2018, who are potentially qualified for SLK. Exposure was a receipt of SLK. We tested effect modification by the specific SLK eligibility criteria met (end-stage kidney disease, acute kidney injury, chronic kidney disease, or unknown). The primary outcome was death within 1 year of a liver transplant. We used a modified Cox regression analysis containing an interaction term of SLK * time from transplant. Two hundred ten (9%) SLK recipients and 351 (11%) liver-alone recipients died in 1 year. In the overall population, SLK was associated with a mortality benefit over liver transplant on the day of the transplant, without adjustment [HR: 0.59 (95% CI, 0.46-0.76)] and with adjustment [aHR: 0.50 (95% CI, 0.35-0.71)]. However, when SLK eligibility criteria were included, only in patients with end-stage kidney disease was SLK associated with a sustained survival benefit at day 0 [HR: 0.17 (0.08-0.35)] up to 288 (95% CI, 120-649) days post-transplant. Benefit within the first year post-transplant associated with SLK over liver-alone transplantation was only pronounced in patients with end-stage kidney disease but not present in patients meeting other criteria for SLK. A "strict SLK liberal Safety Net" strategy may warrant consideration at the national policy level.


Value of frozen sections of lymph nodes in pelvic lymphadenectomy in patients with invasive bladder tumor.
We examined the reliability of classical lymph node evaluation methods. We compared the results of preoperative computed tomography (CT) and perioperative frozen section examination of lymph nodes in patients on whom radical cystectomy was performed because of invasive bladder tumors. A total of 142 patients, in whom radical cystectomy was performed because of invasive bladder tumors between the years 1994 and 2005 in our clinic, and 284 pelvic lymph node regions were evaluated retrospectively. For each of the pelvic lymph node region, the conditions of the lymph nodes according to CT and in frozen sections were compared with the final pathology reports of the surgical specimens. Lymph node involvement was found in 36 pelvic regions out of 284 in the final pathology. It had been possible to show only two of the 36 positive lymph nodes in preoperative CT. Frozen section results of the 29 pelvic lymph node regions out of 36 that were involved according to the final pathology were positive also according to frozen section results. On the other hand, in all the 29 lymph node regions those that were positive according to frozen section had lymph node involvement in the final pathology. We recommend the performance of frozen section examination on obturator plus internal iliac lymph nodes when deciding extended lymph node dissection, and the performance of extended lymph node dissection only if the result is positive.


Prognosis of Patients with Chronic Hepatitis C Genotype 1b Infection Treated Using Daclatasvir/Asunaprevir after Sustained Virologic Response: A 6-Year Multicenter Prospective Observational Study.
Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5-60.0] months; median age: 58 [49-67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child-Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.


High frequency of HLA-A*0207 subtype in Chinese population.
HLA-A2 is the most polymorphic and most common HLA phenotype found in various ethnic populations. Seventeen HLA-A2 subtypes have been reported and characterized by molecular techniques. Differences among these subtypes are limited to a few amino acids. Among them, HLA-A*0201 is the predominant subtype among whites. The results of a recent study, however, suggest that the HLA-A*0207 subtype may be present at a high frequency in the Chinese population. To determine the exact frequency of the HLA-A*0207 subtype in the Chinese population, genomic DNA samples obtained from 54 HLA-A2-positive Chinese in Taiwan were studied by using sequence-specific primers and polymerase chain reaction. HLA-A*0207 was present in 56 percent of the studied subjects. The estimated gene frequency for HLA-A*0207 is 17.8 percent in the Chinese population. HLA-A*0207 is the most common HLA-A2 subtype among Chinese. The high frequency of the HLA-A*0207 allele in this population offers a unique opportunity to study the ways in which different HLA-A2 subtypes may influence the clinical outcome of allograft transplantation and the disease susceptibility of recipients.