Mass transfer efficiency of a commercial hollow fibre oxygenator during six-hour in vitro perfusion with steady and with pulsatile blood flow.
Detailed data about the behaviour of commercial membrane oxygenators with pulsatile blood flow are rarely available. This work deals with an experimental evaluation of the effects induced on gas transfer efficiency by pulsatile perfusion of a hollow fibre oxygenator (Monolyth Sorin Biomedica). The oxygenator was subjected to two in vitro trials both carried out with identical experimental protocols except for the flow type, steady and pulsatile. A roller pump with pulsatile module (Stöckert Instrument) was used to generate both flow types. Three different mean blood flow rates (3.2, 4.0 and 4.8 L/min) were tested. The experiments lasting six hours were carried out using bovine blood with inlet conditions according to AAMI standard requirements. Blood samples were withdrawn every hour and the calculated gas transfer obtained in the two sessions were compared. The device proved to be well-designed for steady flow and to be liable to similar gas transfer performance when used in pulsatile conditions. Furthermore, the use of pulsatile flow rather than steady flow provided more consistent conditions and resulted in a higher eventual oxygen transfer efficiency (final mean difference = 6.2%, p < 0.05), proving to be able to avoid any performance decays.


Influence of seasonality on the natural modulation of oxidative stress biomarkers in mangrove crab Ucides cordatus (Brachyura, Ucididae).
The estuaries are characterized by the formation of salinity gradients and are frequently associated with anthropic activities. Studies that show the condition of organisms against the natural environmental variations are fundamental for future evaluation of environmental change due to anthropic impacts. Biomarkers are useful tools defined as biological changes in low levels of organization induced by stressors and considered as predictive responses of more severe effects. The aim of this study was to characterize the modulation of biochemical biomarkers in Ucides cordatus against the natural variation a pristine mangrove forest in an Amazonic estuary (Japerica Bay). The samplings were carried out throughout one year at rainy-dry transitional period (June/2013), dry period (September/ 2013), dry-rainy transitional period (November/ 2013) and rainy period (February/ 2014) in the lower, middle and upper estuary. The biochemical biomarkers evaluated were glutathione-S-transferase (GST), glutamate cysteine-ligase (GCL), total antioxidant capacity (ACAP), reduced glutathione (GSH) concentration and the lipid peroxidation (LPO). There was a decrease in the activity of both enzymes, GSH concentration and lower LPO in the rainy-dry transitional period for the organisms of all sites, pointing to this period as a season of greater metabolic stability. The organisms, especially those of the middle estuary, presented physiological plasticity against the variations of the environment which they are submitted. Seasonality, more than salinity influence due to position in estuary, is the main modulator of biomarkers. Also, our results indicate that the species presents high viability for biomonitoring studies.


Oxytocin-specific RNA, oxytocin and progesterone concentrations in corpora lutea of heifers treated with oxytocin.
Sixteen virgin Holstein heifers were used to study the role of oxytocin in luteal function. Oxytocin (100 i.u.) was administered on Days 2-5 (Exp. 1) or Days 2-6 (Exp. 2), and the corpora lutea were collected and weighed on Day 6 or Day 8, respectively. Plasma progesterone values and tissue concentrations of progesterone and oxytocin were determined by radioimmunoassay. In addition, the tissue level of the oxytocin-specific transcript was measured by dot-blot hybridization. Expression of the oxytocin-specific transcript was not affected by oxytocin treatment in either experiment. In contrast, plasma progesterone values and tissue progesterone and oxytocin concentrations were all decreased after 5 days of oxytocin treatment (Exp. 2), but not after 4 days (Exp. 1). Since oxytocin concentrations were reduced while the level of its transcript remained unaffected, oxytocin injections might be influencing either peptide processing or release.


Thanatophoric dysplasia: case report of an autopsy complemented by postmortem computed tomographic study.
Thanatophoric dysplasia (TD) is one of the most common lethal skeletal dysplasias, which was first designated as thanatophoric dwarfism and described in 1967. The authors report a case of a Caucasian girl with TD, born to a 31-year-old woman without comorbidities. The newborn presented respiratory distress immediately after delivery, progressing to death in less than 2 hours. An autopsy was carried out after postmortem tomographic examination. The autopsy findings depicted extensive malformations of the skeletal system and the brain. The aim of this report is to discuss the pathogenesis and correlate the morphologic features of TD that were disclosed at the tomography and the autopsy.


Interaction of miltefosine with the lipid and protein components of the erythrocyte membrane.
Miltefosine (MT) is an alkylphospholipid that has been approved for the treatment of breast cancer metastasis and visceral leishmaniasis, although its mechanism of action remains poorly understood. Electron paramagnetic resonance spectroscopy of a spin-labeled lipid and a thiol-specific spin label showed that MT causes an increase in the molecular dynamics of erythrocyte ghost membranes and detergent-resistant membranes (DRMs) prepared from erythrocyte ghosts. In the vesicles of lipid raft constituents, it was shown that 20 mol % sphingomyelin could be replaced by 20 mol % MT with no change in the molecular dynamics. The effect of MT in DRMs was more pronounced than in erythrocyte ghosts, supporting the hypothesis that MT is a lipid raft modulator. At the reported MT-plasma concentrations found during the treatment of leishmaniasis (31-90 µg/mL), our measurements in the blood plasma indicated a hemolytic level of 2%-5%. The experiments indicated that MT acts predominantly on the protein component of the membrane. MT aggregates may wrap around the hydrophobic polypeptide chains, forming micelle-like structures that stabilize protein conformations more exposed to the solvent. Proteins with higher hydrophobicity may induce the penetration of the hydrophilic groups of MT into the membrane and cause it to rupture.


Effect of internal gradients in the nuclear magnetic resonance measurement of the surface-to-volume ratio.
We consider a system of spins diffusing in a static inhomogeneous (nonuniform-gradient) magnetic field B in a restricted geometry and in the presence of surface relaxation. We show that the short-time diffusional decay of nuclear magnetization is controlled by the field scattering kernel F(t) identical with [B(t)-B(0)](2), which is a measure of the average field inhomogeneity sampled by the spins in time t and does not depend on the particular sequence of radio-frequency pulses used. Magnetization in arbitrary sequences can be straightforwardly computed by evaluating elementary integrals of F(t). Diffusion takes place while the field is on, so that the spins precess as they diffuse, in contrast to the simpler problem of purely classical diffusion considered in [P. P. Mitra, P. N. Sen, and L. M. Schwartz, Phys. Rev. B 47, 8565 (1993)] which is applicable only to the ideal pulsed-field gradient experiment. We compute the short-time asymptotic form of F(t) and find that it depends on the surface-to-volume ratio (S/V) of the pore space as well as on the average of the gradients over the bounding surface. In a system with nonuniform gradients that vary faster near the surface than in the bulk, as for internal susceptibility fields, this gradient surface average may be much larger than the gradients in the bulk, significantly enhancing the apparent S/V. We discuss the application of our results to the widely used Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence as well as proposing a modification of it, which we term "padded" CPMG, that may be preferable in systems with significant surface relaxation. We indicate how each sequence can be used to probe the internal fields.


Performance measures for management of chronic heart failure patients with acute coronary syndrome in China: results from the Bridging the Gap on Coronary Heart Disease Secondary Prevention in China (BRIG) Project.
Chronic heart failure (CHF) is a severe clinical syndrome associated with high morbidity and mortality, and with high health care expenditures. No nationwide data are currently available regarding the quality of clinical management of CHF patients in China. The aim of this study was to assess the quality of care of CHF inpatients in China. The American College of Cardiology/American Heart Association Clinical Performance Measures for Adults with Chronic Heart Failure (Inpatient Measurement Set) with slight modifications was used to measure the performance status in 612 CHF patients with acute coronary syndrome (ACS) from 65 hospitals across all regions of China. The implementation rates of guideline recommended strategies for CHF management were low. Only 57.5% of the CHF patients received complete discharge instructions, 53.6% of the patients received evaluation of left ventricular systolic function, 62.8% received an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker at discharge, and 52.7% received a β-blocker at discharge, 56.3% of the smokers received smoking cessation counseling. The rate of warfarin utilization was only 9.7% in CHF patients with atrial fibrillation. Most patients (81.4%) did not receive all the first four treatments. There were marked differences in the quality of CHF management among patients with different characteristics. Performance measures provide a standardized method of assessing quality of care, and can thus highlight problems in disease management in clinical practice. The quality of care for CHF patients with ACS in China needs to be improved.


Ion transport across solid-state ion channels perturbed by directed strain.
We combine quantum-chemical calculations and molecular dynamics simulations to consider aqueous ion flow across non-axisymmetric nanopores in monolayer graphene and MoS2. When the pore-containing membrane is subject to uniaxial tensile strains applied in various directions, the corresponding permeability exhibits considerable directional dependence. This anisotropy is shown to arise from directed perturbations of the local electrostatics by the corresponding pore deformation, as enabled by the pore edge geometries and atomic compositions. By considering nanopores with ionic permeability that depends on the strain direction, we present model systems that may yield a detailed understanding of the structure-function relationship in solid-state and biological ion channels. Specifically, the observed anisotropic effects potentially enable the use of permeation measurements across strained membranes to obtain directional profiles of ion-pore energetics as contributed by groups of atoms or even individual atoms at the pore edge. The resulting insight may facilitate the development of subnanoscale pores with novel functionalities arising from locally asymmetric pore edge features.


Adolescent abuse of dextromethorphan.
Dextromethorphan hydrobromide (DXM), a constituent of more than 125 patent cough/cold remedies, is the most popular antitussive medication in the United States. Cough syrups or capsules also contain additional ingredients such as acetaminophen, chlorpheniramine maleate, guaifenesin, and/or pseudoephedrine, and toxicity with overdosage is additive to that of dextromethorphan alone. An unknown number of adolescents in the United States and Europe intoxicate themselves with acute megadoses of dextromethorphan. A megadose of DXM is defined as 5 to 10 times the dose recommended for control of annoying nonproductive coughs. Although a moderate overdose of pure DXM hydrobromide is free of serious adverse effects, approximately 5% of persons of European ethnicity lack the ability to metabolize the drug normally, leading to rapid acute toxic levels. Variable quantities of pure dextromethorphan powder in multiples of 1 gram are easily available from the worldwide web, including e-Bay. Recipe-like extraction procedures are quickly available on the Internet for seemingly simple and inexpensive home manufacture of concentrated dextromethorphan powder from Coricidin HBP Cough & Cold tablets (street name triple C). Adolescents intoxicate themselves at parties and even before or after school since the drug is legal, relatively inexpensive, and easily purchased or shoplifted at drug or convenient stores. Acute megadoses of the drug have profound psychological and physiological effects similar to those of phencyclidine (PCP). Megadoses of dextromethorphan used to self-intoxicate, can produce a false-positive screening test for phencyclidine in a urine specimen.


Large-scale land-sea interactions extend ozone pollution duration in coastal cities along northern China.
Land-sea atmosphere interaction (LSAI) is one of the important processes affecting ozone (O3) pollution in coastal areas. The effects of small-scale LSAIs like sea-land breezes have been widely studied. However, it is not fully clear how and to what extent the large-scale LSAIs affect O3 pollution. Here we explored an O3 episode to illuminate the role of large-scale LSAIs in O3 pollution over the Bohai-Yellow Seas and adjacent areas through observations and model simulations. The results show that the northern Bohai Sea's coastal region, influenced by the Mongolian High, initially experienced a typical unimodal diurnal O3 variation for three days, when O3 precursors from Beijing-Tianjin-Hebei, Shandong, and Northeast China were transported to the Bohai-Yellow Seas. Photochemical reactions generated O3 within marine air masses, causing higher O3 levels over the seas than coastal regions. As the Mongolian High shifted eastward and expanded, southerly winds on its western edge transported O3-rich marine air masses toward the coast, prolonging pollution for an additional three days and weakening diurnal variations. Subsequently, emissions from the Korean Peninsula and marine shipping significantly affected O3 levels in the northern Bohai Sea (10.7% and 13.7%, respectively). Notably, Shandong's emissions played a substantial role in both phases (27.5% and 26.1%, respectively). These findings underscore the substantial impact of large-scale LSAIs driven by the Mongolian High on O3 formation and pollution duration in coastal cities. This insight helps understand and manage O3 pollution in northern Bohai Sea cities and broadly applies to temperate coastal cities worldwide.


Gene expression profiles and bioinformatics analysis of human umbilical vein endothelial cells exposed to PM2.5.
Cardiovascular system is demonstrated the main target of PM2.5 and the objective of this study was to explore the toxic effect and molecular mechanisms caused by PM2.5 in primary human umbilical vein endothelial cells (HUVECs) using microarray and bioinformatics analysis. The results showed that 591 genes were differentially expressed triggered by PM2.5, of which 174 genes were down-regulated, while 417 genes were up-regulated. Gene ontology analysis revealed that PM2.5 caused significant changes in gene expression patterns, including response to stimuli, immune response, and cellular processes. Pathway analysis and Signal-net analysis suggested that endocytosis, chemokine signaling pathway, RNA transport, protein processing in endoplasmic reticulum (ER) and autophagy regulation were the most critical pathways in PM2.5-induced toxicity in HUVECs. Moreover, gene expression confirmation of LIF, BCL2L1, CSF3, HMOX1, RPS6, PFKFB, CAPN1, HSPBP1, MOGS, PREB, TUBB2A, GABARAP by qRT-PCR indicated that endocytosis might be involved in the cellular uptake of PM2.5 by forming phagosomes, and subsequently inflammation, hypoxia and ER stress was occurred, which finally activated autophagy after PM2.5 exposure in HUVECs. In summary, our data can serve as fundamental research clues for further studies of PM2.5-induced toxicity in HUVECs.


A Political Case of Penetrating Cranial Trauma: The Injury of James Scott Brady.
James Brady, the White House press secretary during President Ronald Reagan's first term in office, was 1 of 4 people (including the President) wounded during an attempted assassination attempt on President Reagan's life on March 30, 1981. John Hinckley, Jr. was found not guilty of this attempt by reason of insanity. The assassination attempt was a ploy by Hinckley, Jr. to impress the actress Jodie Foster. Brady was the most seriously injured of the 4 who were wounded. He suffered a gunshot wound to the left forehead that traveled through the left frontal lobe, corpus callosum, and then into the right frontal and temporal lobes. He initially required a bifrontal craniotomy for evacuation of a right frontotemporal intraparenchymal hemorrhage and debridement of tract. His postoperative course was complicated by seizures, cerebrospinal fluid leakage (necessitating multiple reparative procedures), aspiration pneumonia, and pulmonary emboli. Despite the severity of his injury and perioperative morbidities, Mr. Brady made good recovery. Although permanently left with residual weakness on the left side of his body, making a wheelchair necessary, Brady maintained cognitive and personality traits that were very close to his preinjury baseline. As a result, James Brady and his wife, Sarah, led a call to create legislative reform subsequently known as the "Brady Bill." This bill controversially made mandatory background checks for the purchase of firearms from licensed dealers. Our work aims to describe the assassination attempt, the neurosurgical injury and management of Mr. Brady's case, and the brief historical sequel that followed.


Unlocking the in vitro anti-inflammatory and antidiabetic potential of Polygonum maritimum.
Several Polygonum species (Polygonaceae) are used in traditional medicine in Asia, Europe and Africa to treat inflammation and diabetes. Evaluate the in vitro antioxidant, anti-inflammatory and antidiabetic potential of methanol and dichloromethane extracts of leaves and roots of the halophyte Polygonum maritimum L. Antioxidant activity was determined (up to 1 mg/mL) as radical-scavenging activity (RSA) of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), copper (CCA) and iron (ICA) chelating activities and iron reducing power (FRAP). NO production was measured in lipopolysaccharide (LPS)-stimulated macrophages for 24 h at concentrations up to 100 μg/mL and antidiabetic potential was assessed by α-amylase and α-glucosidase inhibition (up to 10 mg/mL) assays. The phytochemical composition of the extracts was determined by gas chromatography-mass spectrometry (GC-MS). The methanol leaf extract had the highest activity against DPPH• (IC50 = 26 μg/mL) and ABTS+• (IC50 = 140 μg/mL), FRAP (IC50 = 48 μg/mL) and CCA (IC50 = 770 μg/mL). Only the dichloromethane leaf extract (LDCM) showed anti-inflammatory activity (IC50 = 48 μg/mL). The methanol root (IC50 = 19 μg/mL) and leaf (IC50 = 29 μg/mL) extracts strongly inhibited baker's yeast α-glucosidase, but LDCM had higher rat's α-glucosidase inhibition (IC50 = 2527 μg/mL) than acarbose (IC50 = 4638 μg/mL). GC-MS analysis identified β-sitosterol, stigmasterol, 1-octacosanol and linolenic acid as possible molecules responsible for the observed bioactivities. Our findings suggest P. maritimum as a source of high-value health promoting commodities for alleviating symptoms associated with oxidative and inflammatory diseases, including diabetes.


Vitamin D receptor signaling and pancreatic cancer cell EMT.
Pancreatic ductal adenocarcinoma (PDAC) still remains one of the most fatal human malignant tumors. Long-term survival rate is still extremely pathetic even for patients who receive surgery. Epithelial-to-mesenchymal transition (EMT), which is a physiologic process of morphological as well as genetic changes in carcinoma cells, plays a vital role in aggressiveness of PDAC. Meanwhile EMT is also the reason why pancreatic cancer cells achieve such huge metastatic potentials. Many tumor microenvironmental factors such as cytokines, growth factors, as well as chemotherapeutic agents may induce EMT. Our study provides evidence regarding effects of EMT on pancreatic cancer progression, focusing on the correlation between EMT and other pathways which are crucial to tumor progression, especially vitamin D receptor signaling pathway. Research on signal pathways resulting in EMT inactivation during these disease processes may offer innovative ideas on plasticity of cellular phenotypes as well as possible therapeutic interventions.


Debate: Should the loss of disability adjusted life years (DALY) define the focus of Global Hematology?: The case for prioritizing capacity building in anemia management and blood transfusion.
Setting priorities in healthcare is always contentious given the array of possible services at primary, secondary, and tertiary levels of care, not to mention potential public health interventions. The central goals in global policy have been reducing inequity within and between countries, protecting vulnerable groups (particularly women and children) and reducing the major communicable diseases which have historically been a major burden in lower- and middle-income countries. Here limited relative and absolute spending on healthcare have spurred a series of initiatives in Global Health over the last 50 years which have led to significant gains in measures of morbidity and mortality. Against this background there remains the continuing question of how to adapt current medical practice in higher income countries for training and planning of services in lower- and middle-income countries. Here, the historical development of Global Health is outlined, and lessons drawn from the surveys of the global burden of disease and health economic analysis to understand how we can apply these principles to define Global Hematology. It remains likely that in lower-income countries effort should be concentrated on developing laboratory services and blood transfusion, to allow safe and effective support for the assessment of treatment of anemia, sickle cell disease, maternal and child health and urgent surgery and obstetric services. However, the principles of Global Health, could also be used for hematological malignancies to develop a framework for Global Hematology for all settings.


Evaluation of the acid-cleavable isotope-coded affinity tag reagents: application to camptothecin-treated cortical neurons.
The new generation of isotope-coded affinity tag (ICAT) reagents have been evaluated by labeling an equimolar amount of bovine serum albumin (BSA) with ICAT-12C9 and ICAT-13C9, combining the mixtures, digesting them with trypsin and analyzing the digestate both by muRPLC-tandem MS and by matrix-assisted laser desorption ionization (MALDI) TOF/TOF MS. The use of 13C in place of 2H resulted in both of the labeled peptides having identical elution characteristics in a reversed-phase separation. This similarity in elution allows ICAT-labeled peptides to be effectively analyzed using a muRPLC-MALDI-MS strategy as well. All of the cysteinyl-containing tryptic peptides from BSA were identified with only a 10% variation in the relative abundance measurements between the light and heavy versions of each peptide. A facile method for the removal of contaminants that arise from the cleaved biotin moiety that otherwise interfere with downstream separations and MS analysis has also been developed. The new ICAT reagents were then applied to the analysis of a cortical neuron proteome sample to identify proteins regulated by the antitumor drug, camptothecin.


Branchial cleft cyst in the parotid gland in a human immunodeficiency virus-negative patient.
In branchial lymphoepithelial cyst (BLEC), which is also known as branchial cleft cyst, the remnants of a branchial arch develop into a cyst, causing swelling. The first case of BLEC in the parotid gland was reported by Hildebrant in 1895. Since then, BLEC in the parotid gland has continued to be reported, but in rare cases. A 45-year-old man presented to our hospital with a swelling of the left cheek of approximately 6 months' duration. The patient underwent a superficial parotidectomy and was pathologically diagnosed with BLEC. Of note, this was the first case of non-human immunodeficiency virus (HIV)-related BLEC of the parotid gland in South Korea. BLEC is a benign condition, but its treatment depends on the presence of HIV infection. In HIV-negative patients, BLEC does not require a further work-up to evaluate metastasis. Our case report describes the diagnosis and treatment of BLEC in a patient without HIV.


Hydrogen tunneling in protonolysis of platinum(II) and palladium(II) methyl complexes: mechanistic implications.
Platinum(II) and palladium(II) complexes are well-known to catalyze the partial oxidation of alkanes. Herein, we present experimental evidence that tunneling occurs in the protonolysis of M(II)-CH(3) (M = Pt, Pd) model systems. We propose that there may be a connection between the observation of tunneling and a protonolysis mechanism involving direct protonation of the M-C bond and that tunneling may also be expected for electrophilic C-H activation of methane by Pt(II) and Pd(II) that proceeds via direct proton loss from a sigma complex.


Ethnicity, age and incidence rates for renal replacement therapy (RRT) in Birmingham, UK: 1990-2004.
Birmingham is a densely populated, industrial city with a high social deprivation index and large black (B) and Indo-Asian (I) populations. End stage renal failure is known to be more common in ethnic minorities and urban communities. Workforce planning requires accurate epidemiological data but most studies of the effect of ethnicity in the UK are from the early 1990s. RRT acceptance rates for adults (>16 years) in Birmingham were calculated for the 5-year periods 1990-5 and 1999-2004 using the 1991 and 2001 UK population census datasets and local programmes data. The adult population of Birmingham Health Authority increased slightly (961,041 in 1991 v 977,099 in 2001) but the proportion of W fell (82.7% to 74.3%) while B (5.3% to 7.0%) and I (10.4% to 17.2%) both increased.Median age was lower for I (33.5 1991, 32.9 2001) than B(33.8 1991, 37.4 2001) and W (45.1 1991, 45.9 2001).Numbers of new patients increased by 29% in W, 98% in B and 109% in I. There was also a substantial increase in acceptance rates (W 92 to 129 pmp, I 175 to 243 pmp, B 191 to 278 pmp) but the proportional increase in I (26.9%) was less than in W (41.5%) or B (48.2%). This is because almost all the increase in RRT acceptance rates for all ethnic groups was seen in the over 55 age group (256 pmp 1991, 481 pmp 2001) but 85% of the population growth for I was in the under 55 age group. In all ethnic groups there was a striking increase in acceptance rates for the over 70's (W 177 to 440 pmp, I 536 to 1711 pmp, B 301 to 1858 pmp). All acceptance rates were equivalent to the highest previously described in the UK. This may be due to local factors including social deprivation, availability of care and physicians attitudes. The increase in patient numbers was due to rising ethnic minority populations and increasing acceptance rates, especially in the elderly.The take-on rate is likely to rise disproportionately for I as the population ages over the next 10 years. This indicates that the future need for RRT in UK inner city areas, especially those with a large elderly ethnic population, will be greater than previously estimated.


Effect of salinity stress on growth and carbohydrate metabolism in three rice (Oryza sativa L.) cultivars differing in salinity tolerance.
Rice seedlings cv. Khao Dawk Mali 105 (salt-sensitive), Luang Anan (moderately salt-tolerant) and Pokkali (salt-tolerant) were exposed to 0, 50, 100 and 150 mM NaCI for 9 d. Salinity stress caused reduction in leaf relative water contents in all cultivars. Shoot length of cv. Pokkali was least affected by salinity stress whereas increased root length in response to salinity stress was apparent in cvs. Khao Dawk Mali 105 and Luang Anan. Increased salinity level also caused reduction in fresh and dry weights in cvs. Khao Dawk Mali 105 and Luang Anan, but had no effect in cv. Pokkali except at 150 mM. Accumulation of total soluble sugars and sucrose in mature leaves were observed in cv. Khao Dawk Mali 105 exposed to high level of salinity whereas their concentrations in cvs. Luang Anan and Pokkali remained the same as control plants. Accumulation of sucrose in cv. Khao Dawk Mali 105 was suggested to be resulted from the alteration of photosynthate partitioning since the activities of sucrose phosphate synthase were not affected by salinity in this cultivar. On the contrary, salinity stress induced an accumulation of starch in cv. Pokkali. It is suggested that partitioning sugars into starch may involve in salinity tolerance by avoiding metabolic alterations.


The influence of a hydraulic prosthetic ankle on residual limb loading during sloped walking.
In recent years, numerous prosthetic ankle-foot devices have been developed to address the demands of sloped walking for individuals with lower-limb amputation. The goal of this study was to compare the performance of a passive, hydraulic ankle-foot prosthesis to two related, non-hydraulic ankles based on their ability to minimize the socket reaction moments of individuals with transtibial amputation during a range of sloped walking tasks. After a two-week accommodation period, kinematic data were collected on seven subjects with a transtibial amputation walking on an instrumented treadmill set at various slopes. Overall, this study was unable to find significant differences in the torque at the distal end of the prosthetic socket between an ankle-foot prosthesis with a hydraulic range-of-motion and other related ankle-foot prosthesis designs (rigid ankle, multiaxial ankle) during the single-support phase of walking. In addition, socket comfort and perceived exertion were not significantly different for any of the ankle-foot prostheses tested in this study. These results suggest the need for further work to determine if more advanced designs (e.g., those with microprocessor control of hydraulic features, powered ankle-foot designs) can provide more biomimetic function to prosthesis users.


Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk.
This study aimed to investigate the relationship in bilateral retinoblastoma survivors between the incidence of second tumors and the age when external beam radiation (EBR) was used. A retrospective analysis of patients diagnosed with retinoblastoma was performed by examining records for background information and treatment information as well as reviewing documentation of patients with second nonocular tumors. Two telephone interviews were conducted for follow-up as well as inquiries directed to tumor registries and state databases. The original study included 1729 patients treated in New York and Boston; the current study includes only the 1506 patients treated in New York. Of those, 816 patients were diagnosed with bilateral retinoblastoma, had sufficient treatment data to be useful, and survived at least 1 year from diagnosis. The subjects were observed for evidence of the development of second nonocular tumors. There was a significant decrease in tumor-free survival among patients treated with EBR before the age of 12 months, but no significant difference between the group treated with EBR after the age of 12 months and the group not treated with EBR. For tumors in the field of radiation, patients treated with early EBR showed a significant decrease in tumor-free survival when compared to patients treated with late EBR, with no significant difference between late radiation and no radiation. There were no significant differences between groups for tumors out of the field of radiation. Significant differences attributable to the use of EBR were found only for tumors of the skull and face bones and for tumors of the soft tissue of the head. The long-term effect of radiation treatment on survivors of bilateral retinoblastoma is to increase the incidence and affect the distribution of second tumors. However, no increased risk is observed for tumors out of the field of radiation among patients who underwent radiation, and the risk for tumors in the field of radiation is heavily dependent on the age at which EBR is given and may be acceptably small to the patient after the age of 12 months.


Pain after Arteriovenous Access Creation.
Dialysis access creation is a common outpatient procedure that can be completed using general, regional, or local anesthetic techniques. There are few endorsed guidelines regarding opioid-based pain control following fistula creation. The purpose of this study was to determine whether utilization of regional anesthesia (RA) is associated with the decreased use of narcotics postoperatively. We performed a prospective cohort study including all patients undergoing arteriovenous fistula creation with one vascular surgeon from August 2019 to February 2020. Patients were selected for regional versus general anesthesia. Selection for anesthesia type was determined by the primary anesthesiologist. Patients selected for RA underwent supraclavicular brachial plexus block with 30 cm3 of 0.5% ropivacaine. Patients were seen in clinic follow-up and completed a questionnaire regarding their postoperative opiate use and pain control. In the study period, 52 patients underwent arteriovenous fistula creation and completed the follow-up questionnaire. Forty patients received RA. Seventy-five percent of patients sent home with a narcotic prescription filled the prescription. There was a significant difference in postoperative opioid use between the two study groups. Patients who received regional block took on average 3.3 pills totaling 16.5 morphine milligram equivalents, whereas patients who received general anesthesia took on average 6.64 pills totaling 33.2 morphine milligram equivalents (P = 0.04). Morbidity and mortality related to opiate use continues to be a public health issue in the United States. This study demonstrates that regional anesthetic techniques in comparison to general anesthesia can result in a significant decrease in postoperative opiate consumption.


Gum arabic-curcumin conjugate micelles with enhanced loading for curcumin delivery to hepatocarcinoma cells.
Curcumin is conjugated to gum arabic, a highly water soluble polysaccharide to enhance the solubility and stability of curcumin. Conjugation of curcumin to gum arabic is confirmed by (1)H NMR, fluorescence and UV spectroscopy studies. The conjugate self assembles to spherical nano-micelles (270 ± 5 nm) spontaneously, when dispersed in aqueous medium. Spherical morphology of the self assembled conjugate is evidenced by field emission scanning electron microscopy and transmission electron microscopy. The self assembly of the amphiphilic conjugate into micelle in aqueous medium significantly enhances the solubility (900 fold of that of free curcumin) and stability of curcumin in physiological pH. The anticancer activity of the conjugate micelles is found to be higher in human hepatocellular carcinoma (HepG2) cells than in human breast carcinoma (MCF-7) cells. The conjugate exhibits enhanced accumulation and toxicity in HepG2 cells due to the targeting efficiency of the galactose groups present in gum arabic.


Amyloid pathology but not APOE ε4 status is permissive for tau-related hippocampal dysfunction.
We investigated whether the impact of tau-pathology on memory performance and on hippocampal/medial temporal memory function in non-demented individuals depends on the presence of amyloid pathology, irrespective of diagnostic clinical stage. We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Two hundred and thirty-five participants completed task functional MRI and provided CSF (92 cognitively unimpaired, 100 experiencing subjective cognitive decline and 43 with mild cognitive impairment). Presence (A+) and absence (A-) of amyloid pathology was defined by CSF amyloid-β42 (Aβ42) levels. Free recall performance in the Free and Cued Selective Reminding Test, scene recognition memory accuracy and hippocampal/medial temporal functional MRI novelty responses to scene images were related to CSF total-tau and phospho-tau levels separately for A+ and A- individuals. We found that total-tau and phospho-tau levels were negatively associated with memory performance in both tasks and with novelty responses in the hippocampus and amygdala, in interaction with Aβ42 levels. Subgroup analyses showed that these relationships were only present in A+ and remained stable when very high levels of tau (>700 pg/ml) and phospho-tau (>100 pg/ml) were excluded. These relationships were significant with diagnosis, age, education, sex, assessment site and Aβ42 levels as covariates. They also remained significant after propensity score based matching of phospho-tau levels across A+ and A- groups. After classifying this matched sample for phospho-tau pathology (T-/T+), individuals with A+/T+ were significantly more memory-impaired than A-/T+ despite the fact that both groups had the same amount of phospho-tau pathology. ApoE status (presence of the E4 allele), a known genetic risk factor for Alzheimer's disease, did not mediate the relationship between tau pathology and hippocampal function and memory performance. Thus, our data show that the presence of amyloid pathology is associated with a linear relationship between tau pathology, hippocampal dysfunction and memory impairment, although the actual severity of amyloid pathology is uncorrelated. Our data therefore indicate that the presence of amyloid pathology provides a permissive state for tau-related hippocampal dysfunction and hippocampus-dependent recognition and recall impairment. This raises the possibility that in the predementia stage of Alzheimer's disease, removing the negative impact of amyloid pathology could improve memory and hippocampal function even if the amount of tau-pathology in CSF is not changed, whereas reducing increased CSF tau-pathology in amyloid-negative individuals may not proportionally improve memory function.


Temporomandibular joint formation and condyle growth require Indian hedgehog signaling.
The temporomandibular joint (TMJ) is essential for jaw function, but the mechanisms regulating its development remain poorly understood. Because Indian hedgehog (Ihh) regulates trunk and limb skeletogenesis, we studied its possible roles in TMJ development. In wild-type mouse embryos, Ihh expression was already strong in condylar cartilage by embryonic day (E) 15.5, and expression of Ihh receptors and effector genes (Gli1, Gli2, Gli3, and PTHrP) indicated that Ihh range of action normally reached apical condylar tissue layers, including polymorphic chondroprogenitor layer and articular disc primordia. In Ihh(-/-) embryos, TMJ development was severely compromised. Condylar cartilage growth, polymorphic cell proliferation, and PTHrP expression were all inhibited, and growth plate organization and chondrocyte gene expression patterns were abnormal. These severe defects were partially corrected in double Ihh(-/-)/Gli3(-/-) mutants, signifying that Ihh action is normally modulated and delimited by Gli3 and Gli3(R) in particular. Both single and double mutants, however, failed to form an articular disc primordium, normally appreciable as an independent condensation between condylar apex and neighboring developing temporal bone in wild-type. This failure persisted at later stages, leading to complete absence of a normal functional disc and lubricin-expressing joint cavities. In summary, Ihh is very important for TMJ development, where it appears to regulate growth and elongation events, condylar cartilage phenotype, and chondroprogenitor cell function. Absence of articular disc and joint cavities in single and double mutants points to irreplaceable Ihh roles in formation of those critical TMJ components.


The Concerning Disaggregation of Gender and Racial/Ethnicity Disparity Investigation at Recent ASCO Annual Meetings.
There has been a recent emphasis in the peer-reviewed oncology literature on examining disparities by gender. Such emphasis provides an excellent opportunity to simultaneously examine race/ethnicity disparities in the same cohort. The degree to which gender disparities research has been performed concomitantly with racial disparities research at prominent oncologic societies has yet to be investigated. ABSTRACTs presented at the American Society of Clinical Oncology (ASCO) annual meeting were reviewed. Abstracts selected for the oral abstract or clinical science symposium sessions at the 2020, 2021, and 2022 annual meetings were evaluated to determine the amount of gender disparities research presented. Such research was further assessed to determine whether racial/ethnicity disparities were examined simultaneously. From 2020 to 2022, 1219 abstracts were presented at the ASCO annual meetings, oral abstract or clinical science symposium sessions. Of these, 7 involved gender disparities examination, of which only 2 (29%) concomitantly examined race/ethnicity. No study since 2020 concomitantly examined gender and racial disparities. More than 70% of gender disparities work presented at ASCO has been disaggregated from concomitant racial disparities examination, with complete disaggregation since 2021. Gender disparities work remains a miniscule aspect of the overall research landscape. Future work in examining gender disparities may be best aggregated with racial/ethnicity disparities to optimize timely solutions in both areas; such work could potentially be incentivized from the inclusion criteria of future funding mechanisms.


Advice for acute low back pain: a comparison of what research supports and what guidelines recommend.
Advice is widely considered an effective treatment for acute low back pain (LBP); however, details on what and how to deliver this intervention is less clear. We assessed and compared clinical trials that test advice for acute LBP with practice guidelines for their completeness of reporting and concordance on the content, method of delivery, and treatment regimen of advice interventions. Systematic review. Advice randomized controlled trials were identified through a systematic search. Guidelines were taken from recent overviews of guidelines for LBP. Completeness of reporting was assessed using the Template for Intervention Description and Replication checklist. Thematic analysis was used to characterize advice interventions into topics across the aspects of content, method of delivery, and regimen. Concordance between clinical trials and guidelines was assessed by comparing the number of trials that found a statistically significant treatment effect for an intervention that included a specific advice topic with the number of guidelines recommending that topic. The median (interquartile range) completeness of reporting for clinical trials and guidelines was 8 (7-9) and 3 (2-4) out of nine items on the Template for Intervention Description and Replication checklist, respectively. Guideline recommendations were discordant with clinical trials for 50% of the advice topics identified. Completeness of reporting was less than ideal for randomized controlled trials and extremely poor for guidelines. The recommendations made in guidelines of advice for acute LBP were often not concordant with the results of clinical trials. Taken together, these findings mean that the potential clinical value of advice interventions for patients with acute LBP is probably not being realized.


Acute common femoral arterial trauma.
1) Acute common femoral arterial injuries remain relatively uncommon in both military and civilian practice. 2) The recent experience in Vietnam has provided the most complete statistics regarding this type of injury. Among 1,000 acute major arterial injuries, the incidence of common femoral arterial trauma was approximately 5%. This present study reports 109 acute common femoral arterial injuries. Nearly two thirds of the injuries were caused by fragments and slightly more than one half of the injuries were lacerations. It was possible to perform autogenous vein graft repairs in about 57%, end-to-end anastomoses in about 25%, and lateral suture repair in about 10% of the injuries. Prosthetic material was used in only three repairs. 3) The overall complication rate was 28.3%, the amputation rate was 13.2%, and the mortality rate was 2.8%. 4) In the treatment of iatrogenic injuries associated with diagnostic catheterizations of the common femoral artery at Walter Reed Army Medical Center, there were no complications and no mortalities.


Influence of radiation dose and reconstruction algorithm in MDCT assessment of airway wall thickness: A phantom study.
Wall thickness (WT) is an airway feature of great interest for the assessment of morphological changes in the lung parenchyma. Multidetector computed tomography (MDCT) has recently been used to evaluate airway WT, but the potential risk of radiation-induced carcinogenesis-particularly in younger patients-might limit a wider use of this imaging method in clinical practice. The recent commercial implementation of the statistical model-based iterative reconstruction (MBIR) algorithm, instead of the conventional filtered back projection (FBP) algorithm, has enabled considerable radiation dose reduction in many other clinical applications of MDCT. The purpose of this work was to study the impact of radiation dose and MBIR in the MDCT assessment of airway WT. An airway phantom was scanned using a clinical MDCT system (Discovery CT750 HD, GE Healthcare) at 4 kV levels and 5 mAs levels. Both FBP and a commercial implementation of MBIR (Veo(TM), GE Healthcare) were used to reconstruct CT images of the airways. For each kV-mAs combination and each reconstruction algorithm, the contrast-to-noise ratio (CNR) of the airways was measured, and the WT of each airway was measured and compared with the nominal value; the relative bias and the angular standard deviation in the measured WT were calculated. For each airway and reconstruction algorithm, the overall performance of WT quantification across all of the 20 kV-mAs combinations was quantified by the sum of squares (SSQs) of the difference between the measured and nominal WT values. Finally, the particular kV-mAs combination and reconstruction algorithm that minimized radiation dose while still achieving a reference WT quantification accuracy level was chosen as the optimal acquisition and reconstruction settings. The wall thicknesses of seven airways of different sizes were analyzed in the study. Compared with FBP, MBIR improved the CNR of the airways, particularly at low radiation dose levels. For FBP, the relative bias and the angular standard deviation of the measured WT increased steeply with decreasing radiation dose. Except for the smallest airway, MBIR enabled significant reduction in both the relative bias and angular standard deviation of the WT, particularly at low radiation dose levels; the SSQ was reduced by 50%-96% by using MBIR. The optimal reconstruction algorithm was found to be MBIR for the seven airways being assessed, and the combined use of MBIR and optimal kV-mAs selection resulted in a radiation dose reduction of 37%-83% compared with a reference scan protocol with a dose level of 1 mGy. The quantification accuracy of airway WT is strongly influenced by radiation dose and reconstruction algorithm. The MBIR algorithm potentially allows the desired WT quantification accuracy to be achieved with reduced radiation dose, which may enable a wider clinical use of MDCT for the assessment of airway WT, particularly for younger patients who may be more sensitive to exposures with ionizing radiation.


Monitoring the radiation dose to a multiprogrammable pacemaker during radical radiation therapy: a case report.
Multiprogrammable pacemakers, using complimentary metaloxide semiconductor (CMOS) circuitry, may fail during radiation therapy. We report about a patient who received 6,400 cGy for unresectable carcinoma of the left lung. In supine treatment position, arms raised above the head, the pacemaker was outside the treated area by a margin of at least 1 cm, shielded by cerrobend blocking mounted on a tray. From thermoluminescent dosimeter (TLD) measurements, we estimate that the pacemaker received 620 cGy in scatter doses. Its function was monitored before, during, and after completion of radiation therapy. The pacemaker was functioning normally until the patient's death 5 months after completion of treatment. The relevant electrocardiograms (ECGs) are presented.


Regulation of clones responding to dextran B1355S. II. Response of T-dependent and T-independent precursors.
The existence of precursors for TI and TD alpha 1 leads to 3 dextran antigens in BALB/c mice was demonstrated. A T-dependent dextran antigen was prepared by coupling dextran B1355S to hemocyanin and subsequent digestion with dextranase. The PFC response of BALB/c mice primed with hemocyanin to dextran-hemocyanin was found to be 8 times higher than in unprimed animals. The splenic focus assay was adapted for the analysis of precursors responding to T-dependent and T-independent dextran antigens. Pretreatment of recipients with anti-thymocyte serum abolished the response in fragment cultures to dextran-hemocyanin but did not affect the response to dextran B1355S. The frequencies of precursors in the adult BALB/c mouse responding to dextran and dextran-hemocyanin were determined by limiting dilution analysis. The frequency of T-dependent precursors was found to be almost 3 times greater than the frequency of T-independent precursors.


Functional lymphatic collectors in breast cancer-related lymphedema arm.
The pathophysiology of breast cancer-related lymphedema (BCRL) is poorly understood. The present study evaluated the lymphatic collectors in the arms of patients with BCRL. In total, 123 patients with ipsilateral BCRL who had undergone magnetic resonance lymphangiography using gadobenate dimeglumine as a contrast agent were enrolled in this study. Morphological changes and the numbers of collecting lymphatic vessels were recorded. Associations between the number of visualized lymphatic collectors and edema accumulation, subcutis thickness, and the BCRL duration and latency were analyzed. Tortuous and significantly dilated lymphatic collectors were visualized in the lymphedematous arms of 104 patients (85%). The median number of visualized lymphatic collectors was four. The duration of BCRL was weakly but significantly correlated with the number of lymphatic collectors (rs=0.2054, p=0.0226). The differences in the tissue water content and thickness of the subcutis between the bilateral arms demonstrated moderate correlations with the number of collecting lymphatics (rs=0.31 and 0.35, respectively; p<0.01). More lymphatic collectors tended to be seen in more advanced cases. There was no statistical difference in the amount of lymphatic vessels among different breast cancer treatment methods. The number of functional remaining lymphatic collectors increases with the prolongation and severity of BCRL. This may imply persistent reactions of lymphatic collectors in response to lymphostasis.


Identification and characterization of a novel splice variant of the PLCζ1 gene in bull testis tissues.
Phospholipase C zeta 1 (PLCζ1), which transcribes a key protein, has an important function in oocyte activation and embryo development because PLCζ1 can trigger a series of intracellular Ca2+ oscillations in mammals. In this study, a novel splice variant in the testis tissues of adult and fetal Chinese Holstein bulls was characterized by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing analysis. The novel splice variant PLCζ1-sv1 was derived from the PLCζ1 complete transcript (PLCζ1-complete) by alternative splicing; the alternative splicing pattern exhibited alternative 5'-splice sites. The full-length transcript, PLCζ1-complete, is the main transcript found in fetal and adult cow testis tissue. Quantitative real-time PCR (qPCR) analysis demonstrated that the expression levels of the PLCζ1-complete transcript were significantly higher than those of the PLCζ1-sv1 splice variant in bovine testis tissues. PLCζ1 protein sequencing analysis showed that the amino acids at positions 453 to 457 were deleted in PLCζ1-sv1, thereby terminating transcription prematurely. In summary, this study provided information to elucidate the structure and function of the bovine PLCζ1 gene.


Reaction kinetics and transformation of carbadox and structurally related compounds with aqueous chlorine.
The potential release of carbadox (CDX), a commonly used antibacterial agent in swine husbandry, into water systems is of a concern due to its carcinogenic and genotoxic effects. Until this study, the reactivity of carbadox (possessing quinoxaline N,N'-dioxide and hydrazone moieties) toward aqueous chlorine has yetto be investigated in depth. Chemical reactivity, reaction kinetics, and transformation pathways of carbadox and structurally related compounds with free chlorine under typical water treatment conditions were determined. This study found that only CDX and desoxycarbadox (DCDX), a main metabolite of CDX with no ring N-oxide groups, react rapidly with free chlorine while other structurally related compounds including olaquindox, quindoxin, quinoxaline N-oxide, quinoxaline, and quinoline N-oxide do not. The reaction kinetics of CDX and DCDX with chlorine are highly pH dependent (e.g., the apparent second-order rate constant, kapp, for CDX ranges from 51.8 to 3.15 x 10(4) M(-1)s(-1) at pH 4-11). The high reactivity of CDX and DCDX to chlorine involves deprotonation of their hydrazone N-H moieties where initial chlorine attack results in a reactive intermediate that is further attacked by nucleophiles in the matrix to yield non-chlorinated, hydroxylated, and larger molecular weight byproducts. All of the CDX's byproducts retain their biologically active N-oxide groups, suggesting that they may remain as active antibacterial agents.


Outpatient Intraperitoneal Catumaxomab Therapy for Malignant Ascites Related to Advanced Gynecologic Neoplasms.
Catumaxomab (CATU) is a trifunctional antibody approved for intraperitoneal (i.p.) treatment of malignant ascites (MA) related to carcinomas expressing the epithelial cell-adhesion molecule (EpCAM). CATU is mostly given to hospitalized patients, although outpatient treatment seems appropriate in selected individuals. This observational trial sought to obtain more detailed information regarding the feasibility of CATU in outpatients with MA related to various gynecologic tumors, including epithelial ovarian (EOC) and metastatic breast cancer (MBC). A total of 30 patients were included, 17 with EOC, 7 with MBC, and 6 with other malignancies. The patients had failed a median of 5 (range 1-12) previous systemic treatments. CATU was administered via an indwelling i.p. catheter at four increasing doses (i.e., 10, 20, 50, and 150 µg) given at 4-day intervals over 2 weeks. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 4.03. Puncture-free survival (PuFS) was calculated from the start of CATU until the next puncture for MA, death, or loss to follow-up. Overall survival (OS) was calculated from the start of CATU to death from any reason or loss to follow-up. We also investigated various clinical parameters to predict PuFS and OS. These included age, tumor type, performance status, intensity of pretreatment, presence of extraperitoneal metastases, relative lymphocyte count at baseline, patient adherence to therapy, and the patients' ability to undergo systemic treatment after CATU. CATU was exclusively given on an outpatient basis, and 19 patients (63.3%) received all four planned i.p. instillations. Toxicity was the reason for discontinuation in only 2 patients. Toxicity was generally manageable, with abdominal pain, nausea/vomiting, fatigue, and fever the predominant adverse effects. Secondary hospitalization was necessary for 7 patients (23.3%), with a general deteriorated condition in 5 and fever/infection or abdominal pain in 1 patient each. Subsequent systemic treatment was possible in 11 patients (36.7%). Only 5 patients (16.7%) required a second puncture after i.p. CATU. The median PuFS was 56 days, and the median OS was 79.5 days. Positive predictors of both PuFS and OS were performance status, absence of extraperitoneal tumor, the capability to receive all four CATU infusions, and the ability to undergo subsequent systemic treatment. Outpatient i.p. CATU therapy for MA related to various gynecologic carcinomas is safe and effective in producing good ascites control in most individuals, allowing for subsequent systemic therapy in a substantial proportion of patients. Intraperitoneal treatment with the trifunctional antibody catumaxomab (CATU) was possible in a selected population of 30 outpatients with malignant ascites due to epithelial female genital tract or breast carcinoma. Toxicity was largely manageable. Patients in good condition at baseline, without extraperitoneal tumor and/or liver metastases, and with the ability to complete all four planned CATU instillations and the capability of undergoing subsequent systemic therapy benefited the most in terms of both puncture-free and overall survival. Outpatient i.p. CATU is safe and effective in a selected group of patients with malignant ascites due to various gynecologic malignancies and could be cost-saving compared with an inpatient approach.


Thoracic Duct Embolization-Value Analysis Using a Time-Driven Activity-Based Costing Approach: A Single Institution Experience.
To quantify cost drivers for thoracic duct embolization based on time-driven activity-based costing methods. This was an Institutional Review Board-approved (HUM00141114) and Health Insurance Portability and Accountability Act-compliant study performed at a quaternary care institution over a 14-month period. After process maps for thoracic duct embolization were prepared, staff practical capacity rates and consumable equipment costs were analyzed via a time-driven activity-based costing methodology. Sensitivity analyses were performed to identify primary cost drivers. Mean procedure duration was 4.29 hours (range: 2.15-7.16 hours). Base case cost, per case, for thoracic duct embolization was $7466.67. Multivariate sensitivity analyses performed with all minimum and maximum values for cost input variables yielded a cost range of $1001.95 (minimum) to $89,503.50 (maximum). Using local salary information and negotiated prices for materials as cost parameters, the true cost per case of thoracic duct embolization at the study institution was $8038.94. Univariate analysis demonstrated that the primary driver of staffing costs was the length of time the attending anesthesiologist was present. The predominant modifiable cost drivers included cyanoacrylate glue volume used (minimum $4467; maximum $12,467), cost of glue utilized (minimum $5217; maximum $10,467), and cost of coils utilized (minimum $7377; maximum $10,917). Univariate analysis predicted that the use of Histoacryl glue in place of TRUFILL cyanoacrylate glue resulted in a cost savings of $2947.50 per case. The base cost per case for thoracic duct embolization was $7466.67. Costs, namely anesthesia staffing costs, cyanoacrylate glue, and coils were large, potentially modifiable drivers of overall cost for thoracic duct embolization.


History of spinal surgery: one neurosurgeon's perspective.
Spinal surgery has advanced from decompression procedures to complex spinal reconstruction and internal stabilization within the last 25 years, as a result of a broad-based technological boom that began in the 1970s with the advent of spinal computerized tomography and magnetic resonance imaging. These technological advances have coincided with, and developed as a result of, the concomitant rise of a complex, economically driven consortium of innovative surgeons and researchers, academic institutions, government agencies, and private industry, to form a Medical-Industrial Complex (MeIC). A major growth industry has formed, resulting in an overall societal benefit. Nevertheless, it has impacted graduate medical education and has significantly increased the cost of treating spinal disorders. Back pain and spinal disorders are a major societal health problem that is associated with a high demand for treatment services. There is a potential for abuse as well as a benefit in offering these services. The MeIC has contributed to the overall rise in the cost of health care insurance and in the migration of manufacturing jobs abroad as a solution for lowering production costs. The increased cost has had a negative impact on local and regional economies.


Rapamycin inhibits anal carcinogenesis in two preclinical animal models.
The incidence of anal cancer is increasing especially among HIV-infected persons in the HAART era. Treatment of this cancer is based upon traditional chemoradiotherapeutic approaches, which are associated with high morbidity and of limited effectiveness for patients with high-grade disease. The mammalian target of rapamycin (mTOR) pathway has been implicated in several human cancers, and is being investigated as a potential therapeutic target. In archival human anal cancers, we observed mTOR pathway activation. To assess response of anal cancer to mTOR inhibition, we utilized two newly developed mouse models, one in which anal cancers are induced to arise in HPV16 transgenic mice and the second a human anal cancer xenograft model. Using the transgenic mouse model, we assessed the preventative effect of rapamycin on neoplastic disease. We saw significant changes in the overall incidence of tumors, and tumor growth rate was also reduced. Using both the transgenic mouse and human anal xenograft mouse models, we studied the therapeutic effect of rapamycin on preexisting anal cancer. Rapamycin was found to significantly slow, if not stop, the growth of both mouse and human anal cancers. As has been seen in other cancers, rapamycin treatment led to an activation of the MAPK pathway. These results provide us cause to pursue further the evaluation of rapamycin as a therapeutic agent in the control of anal cancer.


Beta 1 integrin activation mediates adhesive differences between trisomy 21 and non-trisomic fibroblasts on type VI collagen.
Trisomy 21 (Down syndrome) is a common genetic condition with a high incidence of congenital heart defects (CHD), particularly those involving abnormal development of the embryonic atrioventricular (AV) canal. Type VI collagen (Col VI) is expressed in the developing AV canal extracellular matrix, and has been associated with trisomy 21 AV canal defects in human genetic studies. Although the molecular mechanisms linking Col VI and trisomy 21 AV canal defects are not well understood, a computer model predicts increased cell adhesiveness is responsible for these CHD. We compared integrin-mediated cell adhesive properties for skin fibroblasts isolated from trisomy 21 and non-trisomic individuals on Col VI, fibronectin (FN) and type I collagen (Col I). Cell lines demonstrate similar adhesion profiles to FN and Col I, but all trisomy 21 cells display increased adhesive capacity for Col VI compared to non-trisomic fibroblasts. Cell adhesion to type VI collagen was shown to be GRGDS independent, but beta(1) integrin family dependent. Function-blocking antibodies identified alpha(3)beta(1) as the predominant integrin mediating trisomy 21 and non-trisomic skin fibroblast adhesion on Col VI. Trisomy 21 and non-trisomic fibroblasts display similar expression levels for each of the integrin receptors examined. A beta(1) integrin-activating antibody augments non-trisomic cell adhesion on Col VI, but has no effect upon trisomy 21 fibroblasts. These results demonstrate that beta(1) integrin family members mediate trisomy 21 and non-trisomic skin fibroblast adhesion for Col VI. Altered activation state of the beta(1) integrin is a mechanism responsible for increased trisomy 21 cell adhesion on Col VI.


The effects of in vitro antigen exposure upon suppressor cell function in atopic disease.
Suppressor cell dysfunction has been suggested as a cause of the heightened IgE responses seen in human atopic disease and allergy immunotherapy has been shown to be associated with the generation of antigen-specific suppressor cells. In an attempt to simulate immunotherapy, the in vitro effects of grass antigen exposure upon non-control subjects were treated with preincubation, concanavalin A or varying concentrations of a crude grass antigen preparation. The effects of the generated suppressor activities upon phytohemagglutinin-induced proliferation of fresh, autologous lymphocytes were measured. All three treatments resulted in significant suppression. There was no over-all difference in suppression between atopic and control groups. However, grass antigen exposure enhanced suppression by cells from atopic subjects (p. 05) but only to levels seen in concanavalin A treated cells from the same individuals. Further, the grass antigen preparation appeared to act in a non-specific fashion, resulting in similar mitogenic responses in cells from atopic and control groups. These findings bring into question the role of non-specific suppressor cells, as currently measured, in the pathogenesis of atopic disease. Allergy immunotherapy with crude antigen preparations likely results in non-specific immunologic perturbations which may enhance or depress its clinically valuable, antigen-specific, effects.


In-Depth Characterization of EpiIntestinal Microtissue as a Model for Intestinal Drug Absorption and Metabolism in Human.
The Caco-2 model is a well-accepted in vitro model for the estimation of fraction absorbed in human intestine. Due to the lack of cytochrome P450 3A4 (CYP3A4) activities, Caco-2 model is not suitable for the investigation of intestinal first-pass metabolism. The purpose of this study is to evaluate a new human intestine model, EpiIntestinal microtissues, as a tool for the prediction of oral absorption and metabolism of drugs in human intestine. The activities of relevant drug transporters and drug metabolizing enzymes, including MDR1 P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), CYP3A4, CYP2J2, UDP-glucuronosyltransferases (UGT), carboxylesterases (CES), etc., were detected in functional assays with selective substrates and inhibitors. Compared to Caco-2, EpiIntestinal microtissues proved to be a more holistic model for the investigation of drug absorption and metabolism in human gastrointestinal tract.


Ethnicity-based name partitioning for author name disambiguation using supervised machine learning.
In several author name disambiguation studies, some ethnic name groups such as East Asian names are reported to be more difficult to disambiguate than others. This implies that disambiguation approaches might be improved if ethnic name groups are distinguished before disambiguation. We explore the potential of ethnic name partitioning by comparing performance of four machine learning algorithms trained and tested on the entire data or specifically on individual name groups. Results show that ethnicity-based name partitioning can substantially improve disambiguation performance because the individual models are better suited for their respective name group. The improvements occur across all ethnic name groups with different magnitudes. Performance gains in predicting matched name pairs outweigh losses in predicting nonmatched pairs. Feature (e.g., coauthor name) similarities of name pairs vary across ethnic name groups. Such differences may enable the development of ethnicity-specific feature weights to improve prediction for specific ethic name categories. These findings are observed for three labeled data with a natural distribution of problem sizes as well as one in which all ethnic name groups are controlled for the same sizes of ambiguous names. This study is expected to motive scholars to group author names based on ethnicity prior to disambiguation.


[Chemical restraint and nursing care in the intensive care unit].
The intensive care unit (ICU) presents patients with an environment that is unfamiliar and isolating. In addition to the relative severity of diseases treated, ICUs frequently employ tube therapy, complex medical treatments and diverse nursing routines. Such elevates the chances that patients will experience pain and anxiety, which, in turn, raise the likelihood of patient agitation and reduce ultimate treatment effectiveness. Research has shown that 71& of ICU patients experience agitation. Nurses have main caring responsibilities in such circumstances because they provide the greatest percentage of bedside care. The role of nurses is not only to assess patient needs in a timely fashion, but also to discuss with ICU physicians the level of chemical restraint needed in order to relieve patient pain and anxiety. As chemical restraints involve side effects, a study of patient airway status and breathing and circulation needs must be done prior to application. In terms of breathing, patient breathing sounds, patterns and saturation levels must be monitored regularly in order to identify airway distress preemptively. In terms of blood circulation, patients should have their blood pressure and body fluid status monitored concurrently at regular intervals. With such data, should a patient become hypovolemic, appropriate intravenous fluid support may be administered prior to chemical restraint use in order to help prevent advanced hypotension. Based on such, it is clear that ICU team members must work closely together in order to monitor and assess patients prior to administering chemical restraints and to put into place a patient-tailored safety care plan.


Cardioversion of Atrial Fibrillation with Acupuncture.
Background: Atrial fibrillation, the most commonly treated arrhythmia, results in significant symptom burden, increased stroke risk, and costs 26 billion dollars annually in the United States alone. Maintaining sinus rhythm is often preferred, but current interventions have limitations and are associated with adverse effects. There are data suggesting that acupuncture can have a beneficial effect on maintaining sinus rhythm as well as limited data suggesting it can help convert atrial fibrillation to sinus rhythm in the acute setting. Case: An 82-year-old woman with history of heart failure with preserved ejection fraction as well as paroxysmal atrial fibrillation developed atrial fibrillation with rapid ventricular response during a hospitalization for acute exacerbation of heart failure and gastrointestinal bleeding. Given success in converting supraventricular tachycardia using ear Shen Men in a prior case as well as limited data suggesting a benefit of acupuncture in acute atrial fibrillation, acupuncture was utilized in the management of the acute atrial fibrillation. Acupuncture was initiated 4 hours after the arrhythmia began and a total of 8 ear points (4 each side) as well as bilateral pericardium 6 points were utilized. Results: Atrial fibrillation converted to sinus rhythm before the last needle was placed and the patient had no recurrence of atrial fibrillation throughout the remainder of her stay. Conclusions: Acupuncture appears to be solely responsible for the conversion of atrial fibrillation to sinus rhythm in this case, as no β-blockers, calcium channel blockers, or antiarrhythmic medicines were administered before the return to sinus rhythm. The antiarrhythmic effect noted may be from centrally mediated autonomic effects or additional mechanisms. Further study will help to define the role of acupuncture in the management of acute arrhythmias.


The thiol proteinases from the latex of Carica papaya L. II. The primary structure of proteinase omega.
The complete primary structure of the proteinase omega isolated from the latex of the Carica papaya fruits is given. The polypeptide chain contains 216 amino-acid residues, the alignment of which was deduced from sequence analyses of the native enzyme, the tryptic, chymotryptic, peptic and thermolysinolytic peptides and facilitated due to the considerable degree of homology with papain and actinidin. The location of the three disulfide bridges could be established with the help of peptic and thermolysinolytic fragments. Proteinase omega shares 148 identical amino-acid residues (68.5%) with papain and 108 ones (50%) with actinidin, including the three disulfide bridges and the free cysteine residue required for activity, as well as most of the other amino-acid residues involved in the catalytic mechanism and two thirds of the glycine residues which are of structural significance. The homology with other cysteine proteinases of different origin is discussed.


Plastin 3 Promotes Motor Neuron Axonal Growth and Extends Survival in a Mouse Model of Spinal Muscular Atrophy.
Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease. SMA is caused by mutations in the survival motor neuron gene (SMN1), leading to reduced levels of SMN protein in the CNS. The actin-binding protein plastin 3 (PLS3) has been reported as a modifier for SMA, making it a potential therapeutic target. Here, we show reduced levels of PLS3 protein in the brain and spinal cord of a mouse model of SMA. Our study also revealed that lentiviral-mediated PLS3 expression restored axonal length in cultured Smn-deficient motor neurons. Delivery of adeno-associated virus serotype 9 (AAV9) harboring Pls3 cDNA via cisterna magna in SMNΔ7 mice, a widely used animal model of SMA, led to high neuronal transduction efficiency. PLS3 treatment allowed a small but significant increase of lifespan by 42%. Although there was no improvement of phenotype, this study has demonstrated the potential use of Pls3 as a target for gene therapy, possibly in combination with other disease modifiers.


Medication Harmony: A Framework to Save Time, Improve Accuracy and Increase Patient Activation.
Incompletely reconciled medication lists contribute to prescribing errors and adverse drug events. Providers expend time and effort at every point of patient contact attempting to curate a best possible medication list, and yet often the list is incomplete or inaccurate. We propose a framework that builds upon the existing infrastructure of a health information exchange (HIE), centralizes data and encourages patient activation. The solution is a constantly accessible, singular, patient-adjudicated medication list that incorporates useful information and features into the list itself. We aim to decrease medication errors across transitions of care, increase awareness of potential drug-drug interactions, improve patient knowledge and self-efficacy regarding medications, decrease polypharmacy, improve prescribing safety and ultimately decrease cost to the health-care system.


Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).
The role of extracellular amines such as noradrenaline and serotonin and their interaction with cyclic nucleotides and intracellular polyamines in the regulation of intestinal epithelial cell proliferation is reviewed with particular reference to the differences between normal and neoplastic cells. In respect to the normal epithelium of the small intestine there is a strong case to support the notion that cell proliferation is controlled by, amongst other things, sympathetic nerves. In colonic carcinomas, antagonists for certain serotonin receptors, for histamine H2 receptors and for dopamine D2 receptors inhibit both cell division and tumour growth. Because of the reproducible variations between tumour lines in the response to these antagonists, this inhibition appears to be due to a direct effect on the tumour cells rather than an indirect effect via the tumour host or stroma. This conclusion is supported by the cytocidal effects of toxic congeners of serotonin on the tumour cells. The most salient difference between the amine responses of normal and neoplastic cells relates to the issue of amine uptake. Proliferation of crypt cells is promoted by amine uptake inhibitors, presumably because they block amine re-uptake by the amine secreting cells--sympathetic neurones and enteroendocrine cells. However, tumour cell proliferation is strongly inhibited by amine uptake inhibitors, suggesting that neoplastic cells can, and need to take up the amine before being stimulated by it. Recent revelations in the field of oncogenes also support an important association between amines, cyclic nucleotides and cell division. The ras oncogenes code for a protein that is a member of a family of molecules which relay information from extracellular regulators, such as biogenic amines, to the intracellular regulators, including cyclic nucleotides. Evidence is presented suggesting that enteroendocrine cells, enterocytes, carcinoid tumour cells and adenocarcinoma cells all have the same embryonic origin and that cells exhibiting an admixture of endocrine and proliferative properties exist in colonic tumours, but not in the normal intestinal epithelium. Thus, it appears that in the normal intestine a clear structural and functional distinction exists between the regulating cells (i.e. the sympathetic neurones and enteroendocrine cells) and the regulated cells (i.e. the undifferentiated crypt cells): cells that have acquired a regulating role are no longer able to divide and cells which are able to divide do not take up or store amines.(ABSTRACT TRUNCATED AT 400 WORDS)


A new approach for ratiometric in vivo calcium imaging of microglia.
Microglia, resident immune cells of the brain, react to the presence of pathogens/danger signals with a large repertoire of functional responses including morphological changes, proliferation, chemotaxis, production/release of cytokines, and phagocytosis. In vitro studies suggest that many of these effector functions are Ca2+-dependent, but our knowledge about in vivo Ca2+ signalling in microglia is rudimentary. This is mostly due to technical reasons, as microglia largely resisted all attempts of in vivo labelling with Ca2+ indicators. Here, we introduce a novel approach, utilizing a microglia-specific microRNA-9-regulated viral vector, enabling the expression of a genetically-encoded ratiometric Ca2+ sensor Twitch-2B in microglia. The Twitch-2B-assisted in vivo imaging enables recording of spontaneous and evoked microglial Ca2+ signals and allows for the first time to monitor the steady state intracellular Ca2+ levels in microglia. Intact in vivo microglia show very homogenous and low steady state intracellular Ca2+ levels. However, the levels increase significantly after acute slice preparation and cell culturing along with an increase in the expression of activation markers CD68 and IL-1β. These data identify the steady state intracellular Ca2+ level as a versatile microglial activation marker, which is highly sensitive to the cell's environment.


Catalytic effect of sulfoxides on the fluxional motion of 2,9-dimethyl-1,10-phenanthroline in a platinum(II) complex: evaluation of steric and electronic contributions.
Addition of external weak nucleophiles to a chloroform solution of the cationic complex ion [Pt(Me)(dmphen)(PPh(3))](+) (1) accelerates the fluxional motion of the symmetric chelating ligand 2,9-dimethyl-1,10-phenanthroline (dmphen) between nonequivalent exchanging sites. The rates of the dynamic process can be measured by line-shape analysis of the (1)H NMR spectra. Concentration-dependent measurements were carried out with the ligands SOMe(2), SO(CH(2))(4), SO(n-Bu)(2), SO(sec-Bu)(2), SO(i-Pr)(2), SOEt(Ph), SOPr(Ph), SO(Bz)(2), SO(p-MeC(6)H(4))(2), SOPh(2), SO(p-ClC(6)H(4))(2), SOMe(p-MeOC(6)H(4)), SOMe(p-MeC(6)H(4)), SOMe(Ph), SOMe(p-BrC(6)H(4)), and SOMe(p-ClC(6)H(4)). The rate constants k(obsd), when plotted against the concentration of the added ligands SOR(R'), give a family of straight lines with a common intercept, indicating that the two-term rate law k(obsd) = k(1) + k(2)[SOR(R')] is obeyed. The same rate law applies to the displacement of SOMe(2) from [Pt(Me)(phen)(SOMe(2))](+) (2) (phen = 1,10-phenanthroline) by sulfoxides (SOMe(2), SO(i-Pr)(2), SOMe(p-MeOC(6)H(4)), SO(p-MeC(6)H(4))(2), SOPh(2), SO(p-ClC(6)H(4))(2), and SO(sec-Bu)(2)). The fluxional rates in 1 are 6-7 orders of magnitude higher than the substitution rates in 2. The values of the rate constants for the two processes were resolved quantitatively into steric and electronic contributions by use of quantitative analysis of ligand effects (QALE). Inhibitory steric effects are linearly operative for the entire set of ligands, the rates of the reactions are enhanced with increasing electron donor capacity of the sulfoxides, and there is a small but significant E(ar) effect that enhances the reactivity of the aryl sulfoxides. The strict similarity of the patterns of the two processes and of their dependence upon the stereoelectronic properties of the ligands, combined with the intrinsic lability of the platinum-nitrogen bonds, would suggest the operation of stereospecific consecutive ring-opening and ring-closure steps for the fluxional motion of dmphen in 1. However, the available evidence does not allow alternative mechanisms involving intramolecular rearrangements of the five-coordinate intermediate to be ruled out.


The Association Between Olfactory Function and Cognition in Aging African American and Caucasian Men With HIV: A Pilot Study.
Older adults and people living with HIV have been shown to experience disproportionately more olfactory dysfunction. Some neurological studies suggest that olfactory dysfunction may be a precursor to cognitive dysfunction. The purpose of our study was to determine whether olfactory dysfunction was predictive of cognition. In our cross-sectional study, 51 African American and Caucasian men living with HIV (ages ≥ 40 years) were administered a cognitive performance battery and two objective olfactory measures (the University of Pennsylvania Smell Identification Test and the Smell Threshold Test). The strongest cognitive associations to the University of Pennsylvania Smell Identification Test performance were found in the Hopkins Verbal Learning Test, a measure of verbal learning and verbal memory. These findings were consistent with previous research, demonstrating a relationship between decreased olfactory function and poorer cognitive performance. An important clinical implication from these results is the potential use of olfactory dysfunction as a prodromal biomarker for HIV-associated neurocognitive disorder.


L-Sulforaphane Confers Protection Against Oxidative Stress in an In Vitro Model of Age-Related Macular Degeneration.
In age-related macular degeneration, oxidative damage and abnormal neovascularization in the retina are caused by the upregulation of vascular endothelium growth factor and reduced expression of Glutathione-S-transferase genes. Current treatments are only palliative. Compounds from cruciferous vegetables (e.g. L-Sulforaphane) have been found to restore normal gene expression levels in diseases including cancer via the activity of histone deacetylases and DNA methyltransferases, thus retarding disease progression. To examine L-Sulforaphane as a potential treatment to ameliorate aberrant levels of gene expression and metabolites observed in age-related macular degeneration. The in vitro oxidative stress model of AMD was based on the exposure of Adult Retinal Pigment Epithelium-19 cell line to 200μM hydrogen peroxide. The effects of L-Sulforaphane on cell proliferation were determined by MTS assay. The role of GSTM1, VEGFA, DNMT1 and HDAC6 genes in modulating these effects was investigated using quantitative real-time polymerase chain reaction. The metabolic profiling of L-Sulforaphane-treated cells via gas-chromatography massspectrometry was established. Significant differences between control and treatment groups were validated using one-way ANOVA, student t-test and post-hoc Bonferroni statistical tests (p<0.05). L-Sulforaphane induced a dose-dependent increase in cell proliferation in the presence of hydrogen peroxide by upregulating Glutathione-S-Transferase μ1 gene expression. Metabolic profiling revealed that L-Sulforaphane increased levels of 2-monopalmitoglycerol, 9, 12, 15,-(Z-Z-Z)- Octadecatrienoic acid, 2-[Bis(trimethylsilyl)amino]ethyl bis(trimethylsilyl)-phosphate and nonanoic acid but decreased β-alanine levels in the absence or presence of hydrogen peroxide, respectively. This study supports the use of L-Sulforaphane to promote regeneration of retinal cells under oxidative stress conditions.


GENE GENEALOGY AND DIFFERENTIATION AMONG ARBOREAL SPINY RATS (RODENTIA: ECHIMYIDAE) OF THE AMAZON BASIN: A TEST OF THE RIVERINE BARRIER HYPOTHESIS.
Sequence variation in the mitochondrial cytochrome b gene was examined in the arboreal spiny rat, Mesomys hispidus, collected at 15 sites along the Rio Juruá in western Amazonia, Brazil, to determine the importance of riverine barriers in the diversification of this taxon. Twenty individual haplotypes were uncovered, most of which were unique to single localities but some of which were shared among adjacent sites either along or across the river. Genealogical analyses suggest that gene flow is limited and, in combination with the unique distribution of most haplotypes, suggest that populations of this species are strongly substructured along the river. Thus, most sharing of haplotypes between adjacent localities is probably caused by historical association rather than to ongoing gene flow. Two haplotype clades were uncovered, but these correspond to headwaters versus mouth areas, not to opposite sides of the river, as would be expected by the Riverine Barrier Hypothesis. Moreover, haplotype sharing across the river was greater at its mouth than in the headwaters, a pattern opposite that expected if the river were a substantive barrier. Broader scale phylogeographic patterns of this species show that both clades have relationships to areas well outside the Rio Juruá basin. This suggests that the basin represents a relatively recent point of invasion between two more broadly distributed and differentiated geographic units of the species.


Twins with academic learning problems: antecedent characteristics.
Developmental histories of 46 children experiencing academic difficulties, all of whom had participated since birth in a longitudinal study of twins, were compared with a matched control group of twins. Genetic influences on the liability for academic difficulties are suggested, since identical pairs were more likely than fraternal pairs to be concordant both for academic difficulties and for preschool behavioral characteristics specific to the index group.


Clinical outcomes after intrastromal corneal ring segments reoperation in keratoconus patients.
To evaluate the clinical outcomes after Ferrara intrastromal corneal ring segments (ICRS) reoperation in patients with keratoconus. A total of 37 keratoconus eyes implanted with intrastromal corneal ring segments, which had an ICRS exchange, addition, reposition or removal were evaluated. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), keratometry (K), asphericity (Q) and pachymetry at the thinnest point (PTP) of the cornea were evaluated using a corneal tomography (Oculus Pentacam, USA). The mean follow-up time after the reoperation was 30.5±9.7 months. The mean UCVA improved from 20/300 to 20/80 (P=0.005); the mean BCVA improved from 20/160 to 20/50 (P=0.0002), the mean keratometry reduced from 49.33±4.19D to 46.16±3.90D (P=0.0001), the mean pachymetry at the thinnest point increased from 450±42.9μm to 469±40.8μm (P=0.0001). The asphericity increased from -0.84±0.74 to -0.35±0.81 (P=0.15) and the spherical equivalent reduced from -4.64±4.87D to -3.04±3.45D (P=0.137). The changes in the asphericity and spherical equivalent were not statistically significant. Ferrara ICRS implantation showed to be a reversible and readjustable surgical procedure for keratoconus treatment. Good outcomes can be obtained even after removal, addition, reposition or exchange of ICRS.


Tissue norepinephrine concentration in spontaneously diabetic Chinese hamsters.
There is some controversy concerning a possible effect of diabetes mellitus on the sympathetic nervous system in humans with spontaneous diabetes mellitus and in animals with experimental diabetes mellitus. In this study we compared the tissue norepinephrine (NE) concentration of normal and diabetic Chinese hamsters in the untreated state and after treatment with insulin. Diabetes resulted in a 128% increase in the NE concentration of the kidney in female but not male hamsters. The NE concentration was increased in the liver (133%) and in the cerebral cortex (118%) of both male and female hamsters. There was no significant increase in the NE concentration of hypothalamus, acinar pancreas, pancreatic islets, or heart of diabetic hamsters. Three days of insulin therapy reduced the elevated NE concentration in kidney, liver and cerebral cortex of diabetic hamsters to the levels found in normal hamsters. However, insulin therapy of normal hamsters did not reduce the tissue NE concentration of the kidney, liver, and cerebral cortex below the normal levels found in these animals. Insulin therapy reduced the hypothalamic concentration of NE in both diabetic and normal hamsters. The increase in kidney NE concentration in female diabetic hamsters was not due to a reduction in renal size, for the kidneys of both female and male diabetic hamsters were larger than those of normal hamsters. When synthesis of NE was inhibited with alpha-methyltyrosine, there was a comparable rate of fall in the tissue NE concentration in the four experimental groups, suggesting that the increased tissue NE concentration in the tissues of diabetic hamsters was not due to a decreased rate of disappearance of this compound.(ABSTRACT TRUNCATED AT 250 WORDS)


Highly enantioselective separation using a supported liquid membrane encapsulating surfactant-enzyme complex.
We developed a highly enantioselective separation system for the optically active compounds, (S)-ibuprofen and l-phenylalanine, from their racemic mixtures by employing a supported liquid membrane (SLM) encapsulating a surfactant-lipase complex (or a surfactant-alpha-chymotrypsin complex). In the present system, enzymes encapsulated in the liquid-membrane phase effectively drove the enantioselective transport of optically active compounds through the SLM. This novel SLM allowed high enantioselectivity (ee over 91%) in the optical resolution of racemic ibuprofen and phenylalanine.


Use of fibrin sealant in hypospadias surgical repair reduces the frequency of postoperative complications.
Urethrocutaneous fistulas (UCF) and flap dehiscence (FD) are the most common postoperative complications after hypospadias (HS) surgical repair. The aim of this study was to evaluate whether the application of fibrin sealant over the site of surgery and suture lines reduces these complications. A prospective cohort of consecutive patients was treated over a 3-year period. 30 patients were submitted to HS surgical repair plus application of fibrin glue over the suture line and surgical site; for comparison, another 56 subjects made up the control group which was submitted to surgical repair only. Variables assessed included: age, type of HS, fibrin sealant used, complications and number of surgical procedures required to treat recurrences. In general, the frequency of complications was 10 vs. 41% for UCF (p = 0.002), 13 vs. 50% for FD (p = 0.001), and for flap necrosis (FN) 6.7 vs. 28.6% (p = 0.01) for the treatment and control groups respectively. The number of surgical reinterventions to treat recurrences was higher in the control group than in the study group (p = 0.04). The incidence of UCF after HS surgical repair can be reduced by applying fibrin sealant over the site of surgery and the suture lines.


Identification of the Predictive Models for the Treatment Response of Refractory/Relapsed B-Cell ALL Patients Receiving CAR-T Therapy.
Chimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B-cell acute lymphoblastic leukemia (ALL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here aimed to identify the independent factors of CAR-T treatment response and construct the models for predicting the complete remission (CR) and minimal residual disease (MRD)-negative CR in r/r B-ALL patients after CAR-T cell infusion. Univariate and multivariate logistic regression analyses were conducted to identify the independent factors of CR and MRD-negative CR. The predictive models for the probability of remission were constructed based on the identified independent factors. Discrimination and calibration of the established models were assessed by receiver operating characteristic (ROC) curves and calibration plots, respectively. The predictive models were further integrated and validated in the internal series. Moreover, the prognostic value of the integration risk model was also confirmed. The predictive model for CR was formulated by the number of white blood cells (WBC), central neural system (CNS) leukemia, TP53 mutation, bone marrow blasts, and CAR-T cell generation while the model for MRD-negative CR was formulated by disease status, bone marrow blasts, and infusion strategy. The ROC curves and calibration plots of the two models displayed great discrimination and calibration ability. Patients and infusions were divided into different risk groups according to the integration model. High-risk groups showed significant lower CR and MRD-negative CR rates in both the training and validation sets (p < 0.01). Furthermore, low-risk patients exhibited improved overall survival (OS) (log-rank p < 0.01), higher 6-month event-free survival (EFS) rate (p < 0.01), and lower relapse rate after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T cell infusion (p = 0.06). We have established predictive models for treatment response estimation of CAR-T therapy. Our models also provided new clinical insights for the accurate diagnosis and targeted treatment of r/r B-ALL.


[Etiologic implication of foods in atopic dermatitis: evidence in favor].
Some of the immunopathologic mechanisms involved in IgE responses are currently being identified; Th2 lymphocytes are known to be activated in patients with atopic dermatitis with subsequent production of the cytokines interleukin (IL)-4 and IL-5, which are responsible for IgE production and eosinophil recruitment. Nevertheless, T cell activation in this disease takes place in two phases. In the first phase, Th2 cells are activated and IL-4, IL-5 and IL-13 are produced; this first stage is produced with the initial activation induced by the antigen. In the second phase there are chronic lesions, Th1 lymphocytes are activated and IFg is produced. This chronic phase is associated with the presence of eosinophils and macrophages that produce IL-12.Numerous articles have demonstrated food sensitization to be an etiopathogenic factor in atopic dermatitis. The prevalence of sensitization varies, depending on the patient's age and the severity of the disease. Children with moderate-to-severe atopic dermatitis have been observed to have a positive skin test and high IgE concentrations to various foods. Nevertheless, a positive skin test to foods in such children does not always implicate these foods as the cause of the clinical manifestations; moreover, in children showing subsequent tolerance to these foods, skin tests can sometimes remain positive and high levels of specific IgE can persist. It is now known that IgE not only participate in the degranulation of mastocyte cells but also in reactions mediated by T cells and other antigen-presenting cells (dendritic cells) which have high-affinity receptors for IgE.The immediate IgE response is well known but it is also known that in addition to the immediate response, a delayed response is also involved, evidenced by the presence of antigen-specific T cells to foods or other allergens such as inhalant allergens. After a strict exclusion diet, children with atopic dermatitis and sensitivity to foods such as milk, egg, flour and soya can develop tolerance; for this reason provocation tests with the food in question should be repeated every 2-3 years. In children with sensitivity to other foods such as dried fruits, fish, and shellfish, sensitivity can sometimes persist into adulthood without tolerance being achieved. In conclusion, there are two groups of children with atopic dermatitis. One group consists of those with atopic dermatitis (allergic disease), which is characterized by early development, high IgE titers, the presence of antigen-specific IgE to allergens and a family history of atopy and which is clinically moderate or severe. Early diagnosis and treatment are important in these children, as is the prevention of progression of the disease to bronchial asthma. The other group consists of children whose dermatitis is clinically atopic in terms of its localization and morphology, who have no demonstrable allergic disease and whose management differs from that in children presenting allergic disease.


A new approach to the morphological and cytochemical evaluation of human bone marrow CFUC in agar cultures.
A simple procedure is described for the routine morphological examination of different types of colonies and clusters in agar cultures. The following cytochemical methods are used for the identification of cells: naphthol-ASD-chloroacetate esterase, naphthol-ASD-acetate esterase with and without addition of sodium fluoride, Biebrich scarlet and acid phosphatase. Based on their cytochemical staining properties neutrophils, eosinophils, monocytes and macrophages can be readily identified in their different stages of maturation and an assessment made of the cellular composition of colonies and clusters.