Multiscale model of the physiological control of myocardial perfusion to delineate putative metabolic feedback mechanisms.
Coronary blood flow is tightly regulated to ensure that myocardial oxygen delivery meets local metabolic demand via the concurrent action of myogenic, neural and metabolic mechanisms. Although several competing hypotheses exist, the specific nature of the local metabolic mechanism(s) remains poorly defined. To gain insights into the viability of putative metabolic feedback mechanisms and into the co-ordinated action of parallel regulatory mechanisms, we applied a multiscale modelling framework to analyse experimental data on coronary pressure, flow and myocardial oxygen delivery in the porcine heart in vivo. The modelling framework integrates a previously established lumped-parameter model of myocardial perfusion used to account for transmural haemodynamic variations and a simple vessel mechanics model used to simulate the vascular tone in each of three myocardial layers. Vascular tone in the resistance vessel mechanics model is governed by input stimuli from the myogenic, metabolic and autonomic control mechanisms. Seven competing formulations of the metabolic feedback mechanism are implemented in the modelling framework, and associated model simulations are compared with experimental data on coronary pressures and flows under a range of experimental conditions designed to interrogate the governing control mechanisms. Analysis identifies a maximally probable metabolic mechanism among the seven tested models, in which production of a metabolic signalling factor is proportional to myocardial oxygen consumption and delivery is proportional to flow. Finally, the identified model is validated based on comparisons of simulations with data on the myocardial perfusion response to conscious exercise that were not used for model identification. KEY POINTS: Although several competing hypotheses exist, we lack knowledge of specific nature of the metabolic mechanism(s) governing regional myocardial perfusion. Moreover, we lack an understanding of how parallel myogenic, adrenergic/autonomic and metabolic mechanisms work together to regulatory oxygen delivery in the beating heart. We have developed a multiscale modelling framework to test competing hypotheses against experimental data on coronary pressure, flow and myocardial oxygen delivery in the porcine heart in vivo. The analysis identifies a maximally probable metabolic mechanism among seven tested models, in which the production of a metabolic signalling factor is proportional to myocardial oxygen consumption and delivery is proportional to flow.


Bidirectional Association Between GERD and Asthma: Two Longitudinal Follow-Up Studies Using a National Sample Cohort.
A relation between gastroesophageal reflux disease (GERD) and asthma has been suggested; however, causality has not been investigated. This study aimed to delineate the causal relation between GERD and asthma. Participants of the Korean National Health Insurance Service-National Sample Cohort 2002-2013 who were ≥20 years old were selected for this study. In study I, 116,502 patients with GERD were matched in a 1:2 ratio to 233,004 control I participants, and the hazard ratio (HR) of asthma in patients with GERD was analyzed. In study II, 104,146 patients with asthma were matched in a 1:1 ratio to 104,146 control II participants, and the HR for GERD in patients with asthma was analyzed. A stratified Cox-proportional hazards model was used. Subgroup analyses were performed according to age and sex. In study I, 12.5% (14,595 of 116,502) of the GERD group and 7.8% (18,135 of 233,004) of the control I group presented asthma (P < .001). The GERD group demonstrated a 1.46-fold higher HR for asthma than the control I group (95% confidence interval [CI] = 1.42-1.49, P < .001). In study II, 16.9% (17,582 of 104,146) of the asthma group and 11.9% (12,393 of 104,146) of the control II group presented GERD (P < .001). The asthma group showed a 1.36-fold higher HR for GERD than the control II group (95% CI = 1.33-1.39, P < .001). All age and sex subgroups presented consistent results. GERD and asthma had a bidirectional relation in the study population.


Euterpe oleracea Mart. (Açai) seed extract improves physical performance in old rats by restoring vascular function and oxidative status and activating mitochondrial muscle biogenesis.
Alterations in cardiovascular and skeletal muscle function are hallmarks of ageing that lead to exercise intolerance. We aimed to examine whether the treatment with Euterpe oleracea Mart. seed extract (ASE) associated with exercise training improves aerobic exercise performance by promoting healthy ageing in the elderly. Male Wistar rats were divided into five groups: Young (3 months), Old (18 months), Old+ASE (ASE 200 mg/kg/day), Old+Training (exercise training 30 min/day; 5 days/week) and Old+Training+ASE, for 4 weeks. ASE treatment increased the exercise time and the running distance concerning the initial maximal treadmill stress test (MTST) in the Old+Training+ASE group. Exercise training or ASE treatment restored the aorta oxidative damage and antioxidant defence. It reduced the acetylcholine (ACh)-induced vasodilation in the aorta of old animals to the same values as the young and improved hypertension. Only the association of both strategies restored the ACh-induced vasodilation in mesentery arteries. Remarkably, exercise training associated with ASE increased the antioxidant defence, nitrite levels and expression of the mitochondrial SIRT-1, PGC1α in soleus muscle homogenates. ASE treatment associated with exercise training contributes to better exercise performance and tolerance in ageing by improving vascular function, oxidative stress and activating the muscle SIRT-1/PGC-1α pathway.


Somatodendritic localization and mRNA association of the splicing regulatory protein Sam68 in the hippocampus and cortex.
The RNA-binding protein Sam68 has been implicated in the signal-dependent processing of pre-mRNA and in the utilization of intron-containing retroviral mRNAs. Sam68 is predominantly nuclear but exhibits remarkable binding affinity for signalling proteins located at the membrane. We have investigated the subcellular distribution of Sam68 in adult rat cortex and hippocampus. Subcellular fractionation showed that the protein was most abundant in nuclei but also was present at a significant level in the cytosol and membrane fractions, including light and synaptic membranes derived from crude synaptosomes. Sam68 extracted from the synaptosomal fraction cosedimented with polysomes on sucrose gradients. In agreement with these findings, immunohistochemical staining indicated that Sam68 was concentrated in neuronal nuclei but was also detectable in the soma and dendrites. Sam68 immunoreactivity examined at the ultrastructural level was found to associate with dendritic microtubules, endoplasmic reticulum, and free polyribosomes, sometimes close to synapses. A combination of immunoprecipitation and RT-PCR directly confirmed that Sam68 was bound to polyadenylated mRNA in cortical lysates. The alphaCaMKII mRNA was identified as one of the coprecipitated transcripts; in contrast, the gephyrin and NR1-1 mRNAs were not coprecipitated, indicating a certain degree of sequence specificity in the association. In electrophoretic mobility shift assays, recombinant GST-Sam68 as well as brain-derived Sam68 bound with high affinity to the alphaCaMKII 3' untranslated region. These results suggest that Sam68 may accompany and, conceivably, regulate mature mRNAs during nuclear export, somatodendritic transport, and translation.


A novel method to correctly place the fasciotomy incision for decompression of the anterior and peroneal compartments of the leg.
Incorrectly placed fasciotomy incisions can lead to catastrophic complications in compartment syndrome. Two distinctly different techniques are widely practiced to decompress the anterior and peroneal compartments. In one technique the anterior compartment is decompressed directly, and then the peroneal via the inter-muscular septum, avoiding the peroneal perforators. The second technique relies on surface anatomy landmarks to place the skin incision immediately over the inter-muscular septum, and then the respective fascial envelopes are incised separately. A study in healthy active volunteers was conducted to explore the feasibility of a new technique for the placing the incision very accurately over the inter-muscular septum and so avoiding perforator vessels. Hypothesis The inter-muscular septum can be reliably identified using hand-held ultrasound, and confirmed with MRI. Fourteen healthy active volunteers underwent hand-held ultrasound to identify the antero-lateral inter-muscular septum in the left lower limb, which was then marked using cod liver oil capsules. The positions of the anterior, septal and peroneal perforators were then identified using hand-held Doppler, and marked in the same way. MRI was then used to measure the relationship between the surface land marks, the septum (compared to its US position), and the relationship of the perforators themselves. Hand held ultrasound was successful in identifying the position of the inter-muscular septum in healthy volunteers, as confirmed on MRI scanning. The position and number of peroneal and anterior perforators proved very variable. Direct decompression of the anterior compartment would result in the loss of all anterior perforators in all subjects. Decompression with the skin incision over the inter-muscular septum would not jeopardise any peroneal muscular perforators. This new technique enables decompression both the anterior and peroneal compartments through an accurately placed incision, sparing the greatest number of perforators. Two brief case histories in which the technique was used are presented.


Lateral lipid distribution and phase transition in phosphatidylethanolamine/phosphatidylserine vesicles. A cross-linking study.
To determine the nonideal mixing of two lipid components within the membrane, lipid cross-linking experiments were carried out on dipalmitoylphosphatidylethanolamine (DPPE) vesicles and on dipalmitoylphosphatidylethanolamine/dipalmitoylphosphatidylserine (DPPE/DPPS) vesicles. By comparison of the cross-linking reactions on both types of vesicle the mean neighbourhood relations within the binary lipid mixture can be obtained. To elucidate the relationship between cluster formation and phase transition, the temperature dependences of the lipid arrangement within the vesicle membrane and of the lipid order parameter describing the fluidity of the membrane were measured. Cluster size and phase transition correlate: during the phase transition of the lipid species with the lower phase-transition temperature (DPPS) the nonideality of the mixture increases by phase separation. Above the phase transition temperature of the second lipid species (DPPE) the clusters disappear and a slight alternating lipid arrangement is characteristic of the fluid phase.


[Increasing asthma mortality in Denmark 1969-1988. Not because of changed coding practices].
We have studied asthma mortality in Denmark from 1969 to 1988. Age standardized mortality rates calculated in three age groups, 10-34, 35-59, and > 60 years, disclosed similar trends. Increasing mortality from asthma in the mid-1970s to 1988 was seen in all three age groups with higher mortality in 1979-1988 as compared with 1969-1978 of 95%, 55%, and 69%, respectively. Since the eighth revision of the International Classification of Diseases (ICD-8) was used in Denmark over the entire 20-year period, changes in coding practice due to change of classification system cannot explain the findings.


Student life - How to write a patient's notes.
Writing in patients' notes is one of the most important jobs a nurse carries out. It is integral to compassionate, safe care, as it communicates the patient's condition throughout the shift, the care they received and any changes in their care plan.


Engineered and wild-type L. lactis promote anti-inflammatory cytokine signalling in inflammatory bowel disease patient's mucosa.
Dysbiosis of intestinal microbiota and aberrant inflammatory responses in gastrointestinal mucosa plays important roles in the development of inflammatory bowel disease (IBD). The purpose of this study was to demonstrate the probiotic activity of Lactococcus lactis and the ability of TNF-α-binding by recombinant L. lactis bearing TNF-α-binding affibodies. Various concentrations of recombinant L. lactis were exposed to TNF-α and its binding measured by ELISA. Mucosal biopsies of patients with active IBD were incubated with various L. lactis strains or E. coli DH5α strain and concentrations of TNF-α, IL-23, and IL-10 in the supernatants determined by ELISA. Recombinant L. lactis, at 1 × 109 and 1 × 108 CFU/mL, bound 22.6% and 18.4%, respectively of TNF-α (p < 0.05). When IBD-mucosa was incubated with any L. lactis strain at 1 × 109 CFU/mL, levels of TNF-α and IL-23 were significantly decreased and that of IL-10 increased relative to that for the sterile culture. Opposite trends were observed with E. coli cultures. Recombinant L. lactis at 1 × 108 CFU/mL bound as much as 62.8% (p = 0.026) of TNF-α in IBD-mucosa supernatants compared with the control strain. L. lactis strains are reported, for the first time, to induce an ex vivo anti-inflammatory cytokine profile in IBD inflamed mucosa. L. lactis could therefore constitute a promising alternative approach for treating IBD.


Recurrent caecal volvulus in an adult: Should we practice coecopexy systematically at neonatal age for incomplete common mesentery? A case report.
Malrotation is usually revealed early in infancy and or later in childhood, even more unusually in adulthood. This disorder is treated through Ladd's procedure. Literature is limited on the long-term outcomes of this approach, especially into adulthood. We present a case of a 33 years male with a history of a laparotomy as a new born for a bowel obstruction secondary to malrotation, presenting with an obstruction and colonic volvulus. Laparotomy reveals a volvulus of the coecum secondary to a failure of the coecum to attach during surgery performed at neonatal age. For a patient operated on during the neonatal period for intestinal malrotation, the examination for sub occlusive episodes should suggest a recurrence of malrotation such as coecal volvulus, and the possibility of technical malfunction during the previous procedure. This reflection leads us to consider the necessity of performing coecopexy systematically during the first surgery. Ladd's technique is the surgical treatment of the incomplete common mesentery. The fixation of the coecum could be done in a systematic way to prevent a possible coecal volvulus which can be responsible for digestive necrosis and often even a fulminant evolution.


Vocal efficiency in tracheoesophageal phonation.
Voice rehabilitation after total laryngectomy is challenging. In order to investigate and understand the function of the neoglottis sophisticated measurements need to be made. During voice production, aerodynamic energy is transformed into sound energy. In non-laryngectomized patients, the voice production efficiency is called the vocal efficiency. Vocal efficiency is an indication of how efficient the transformation of energy takes place. Vocal efficiency is calculated by dividing the output sound power by the aerodynamic power. In a group of eight laryngectomees with tracheoesophageal voice, we measured aerodynamic and acoustic quantities and calculated vocal efficiency. We used a computer setup with airflow transducers, pressure transducers, mikrotip transducers and sound intensity measurement to allow calculation of the needed parameters. The tables show the results of the power used and produced in various phonatory tasks. Relatively high levels of aerodynamic power are interpreted as increased effort to speak. The aerodynamic power is an indication of the effort needed for voice generation. The efficiency of TE-voice production is lower compared to laryngeal voice production but does show an increase when sound intensity increases, a known phenomenon in healthy laryngeal voice production.


Reversible activation of hepatic adenylate cyclase by guanyl-5'-yl-(alpha,beta-methylene)diphosphonate and guanyl-5'-yl imidodiphosphate.
Guanyl-5'-yl-(alpha,beta-methylene)di[gamma-32P]phosphonate (Gp-(CH2)pp) is not hydrolyzed by rat liver membranes under conditions in which GTP and guanyl-5'-yl imidodiphosphate (Gpp(NH)p) are hydrolyzed. Gp(CH2)pp activates adenylate cyclase in hepatic membranes with characteristics similar to those of Gpp(NH)p activation but with lower potency and effectiveness. The analogs, although with lower potency than GTP, also share the ability to change the glucagon receptor from a high to a low affinity state. Both Gp(CH2)pp and Gpp(NH)p stimulate adenylate cyclase activity following a lag period of about 1 min addition of GTP after steady state rates are achieved results in reduction in the rate following a lag period of 6 min from the time of addition of GTP. Pretreatment of the enzyme with Gpp(NH)p or Gp(CH2)pp, followed by washing the membranes, leads to a high activity state of the enzyme which slowly decays in rate unless the analogs are continuously present in the medium. These data suggest that the guanosyl nucleotide analogs act on the enzyme system by a slowly reversible process that possibly reflects slow binding and dissociation from different transition states of the enzyme system and suggest that activation of adenylate cyclase by GTP, Gpp(NH)p, and Gp(CH2)pp does not involve covalent modification of the enzyme.


Tissue-specific expression of isoaspartyl protein carboxyl methyltransferase gene in rat brain and testis.
Isoaspartyl protein carboxyl methyltransferase (PIMT) is widely distributed in mammalian tissues. Using a polymerase chain reaction-generated 124-bp DNA fragment from brain cDNA as a probe, four different sizes (approximately 4.0, 2.5, 1.7, and 1.1 kb) of transcripts were detected with northern blot analysis. They were expressed predominantly in rat brain and testis. The major transcripts were 2.5 and 1.7 kb in the brain and 2.5 and 1.1 kb in the testis. One of the major transcripts specific to the testis (1.1 kb) was determined to study the structural difference of major transcripts in the two tissues. This testicular cDNA had neither the 5' (94 nucleotides) nor the 3' (594 nucleotides) end of previously reported brain cDNA corresponding to 1.7 kb. The mRNA levels and enzyme activities of different regions and developmental changes were examined in the brain. The mRNA levels and enzyme activities were concomitantly high in cerebral cortex and hippocampus. Although they increased rapidly approximately 30 days after birth in the testis and decreased in aged rats, they increased gradually after birth and remained high during the aging of the brain. Both structural and developmental studies show that the expression of the PIMT gene in brain and testis is regulated in a tissue-specific manner.


Biochemical alterations in cotton leafworm, Spodoptera littoralis (Boisd.) related to emamectin benzoate and fipronil compared to their joint action.
Cotton leafworm, Spodoptera littoralis (Boisduval), is one of the major destructive pests of ornamental, industrial, and vegetable crops. The efficacy of technical emamectin benzoate (EMB) and fipronil (FPR) was assessed against the 4th larval instar using leaf-dip bioassay method. EMB was more efficient than FPR based on 96 h LC50 values of 0.004 and 0.023 μg/ml, respectively. Joint toxic action of the dual exposure in sequence with time interval 24 h and in mix were evaluated at LC10:LC10, LC25:LC25 and LC50:LC50 after 96 h posttreatment, as well. Their impacts on detoxification enzymes, esterases (ESTs); alkaline phosphatase (ALP); and glutathione S-transferase (GST) as well as acetylcholine esterase (AChE) were also determined. The sequential exposure of EMB after FPR (S1) produced antagonism, potentiation, and potentiation effects, respectively while sequential exposure of FPR after EMB (S2) interacted as addition, potentiation, and potentiation respectively. The rest of binary mixtures (Mix) revealed antagonistic effect regardless of concentration. Orthogonal contrast analysis showed that the highest elevations of AChE, α-EST, β- EST and ALP enzymes were obtained from Mix at LC50:LC50 (181.6%, 288.4, 229.2 and 460.9%, respectively), LC25:LC25 (131.5%, 252.8, 205.60 and 252.0, respectively) and LC10:LC10 (106.6%, 215.6%, 201.8% and 170.0%, respectively). Differently, the greatest elevation of GST activity (157.7%) resulted from S1 at LC50:LC50, while it was significantly lower at LC25:LC25 and LC10:LC10 as well as Mix and S2 at all concentrations than corresponding concentrations of FPR. These findings shed some light on the role of GST in FPR toxicity and clarified the risk of these dual exposures in elevating detoxification enzymes dangerously compared to their individual insecticides. These dual exposures should be carefully handled. Although rotational exposure at low concentrations may enhance performance and mitigate resistance risk, rotational exposure at high concentrations and Mix may indirectly contribute to the evolution of cross-resistance to other insecticides.


Chondrocyte-laden gelatin/sodium alginate hydrogel integrating 3D printed PU scaffold for auricular cartilage reconstruction.
Clinically, modified autologous rib cartilage grafts and commercial implants are commonly used for intraoperative repair of auricular cartilage defects caused by injuries. However, scaffold implantation is often accompanied by various complications including absorption and collapse, resulting in undesirable clinical outcomes. Three-dimensional printed auricular cartilage scaffolds have the advantage of individual design and biofunctionality, which attracted tremendous attention in this field. In this study, to better simulate the mechanical properties of auricular cartilage, we tested PU treated by ultrasonication and high temperature for 30 min (PU-30) or 60 min (PU-60). The results indicated that the compression modulus of PU-30 was 2.21-2.48 MPa, which similar to that of natural auricular cartilage (2.22-7.23 MPa) and was chosen for subsequent experiments. And the pores of treated PU were filled with a gelatin/sodium alginate hydrogel loaded with chondrocytes. In vivo analysis using a rabbit model confirmed that implanted PU-30 scaffold filled with chondrocytes contained hydrogel successfully integrated with normal auricular cartilage, and that new cartilage was generated at the scaffold-tissue interface by histological examination. These findings illustrate that this engineered scaffold represents a potential strategy for repair of ear cartilage damage in clinical.


35S-Atractyloside binding affinity to the inner mitochondrial membrane.
Isolated inner mitochondrial membrane contains a small number of binding sites for atractyloside (of the order of 0.1 nmole/mg of protein) with very high binding affinity (half saturation at 0.014 &mgr;M atractyloside). The high affinity binding ability of the inner mitochondrial membrane is markedly decreased upon aging, acidification of the medium or addition of ADP, but remains unchanged in the presence of uncouplers such as FCCP. Added ADP causes a two-step transition from the high affinity binding to low affinity binding (K(d) > 0.50 &mgr;M) and concomitantly a significant increase of the measured number of binding sites (about a doubling). The half maximum effect in the first step transition is given by 1 &mgr;M ADP. The use of 35S-atractyloside as a probe of the inner mitochondrial membrane conformation specifically related to the adenine nucleotide translocation is discussed.


Merocyanine 540 as a fluorescence indicator for molecular packing stress at the onset of lamellar-hexagonal transition of phosphatidylethanolamine bilayers.
The fluorescence of Merocyanine 540 (MC 540) is sensitive to the molecular packing of membrane lipids. Therefore, the fluorescence of MC 540 is expected to be sensitive to the curvature-related packing stress at the onset of the lamellar-hexagonal phase transition. We measured the fluorescence intensity of MC 540 when the temperatures of lipid bilayers approached their lamellar-hexagonal phase transitions. The fluorescence of MC 540 in the presence of egg and dioleoylphosphatidylethanolamine bilayers increased at the respective lamellar-hexagonal phase transitions of these lipids. Furthermore, increases in fluorescence intensity were also observed at temperatures just below their phase transitions. The enhanced fluorescence was not due to the specific interaction of the dye with the ethanolamine headgroup, because no such increase was observed when the probe was exposed to phosphatidylethanolamines which do not form hexagonal phase within the range of applied temperature. In addition, when the temperature of the lamellar-hexagonal phase transition was shifted, by the addition of a small amount of phosphatidylcholine, the dependence of the fluorescence intensity on temperature was modified accordingly. We postulate that the change of MC 540 fluorescence intensity at temperatures approaching the lamellar-hexagonal phase transition reflects changes in the partition of MC 540 into the fluid lipid phase. The change in partition is influenced by the curvature stress in bilayers at temperatures just below the lamellar-hexagonal phase transition.


Microstructure, mechanical properties, and retentive forces of cobalt-chromium removable partial denture frameworks fabricated by selective laser melting followed by heat treatment.
The effect of heat treatment on the microstructure and mechanical properties of cobalt-chromium (Co-Cr) removable partial denture (RPD) frameworks fabricated by selective laser melting (SLM) is not well understood. The purpose of this in vitro study was to evaluate the suitability of SLM-fabricated Co-Cr alloys followed by heat treatment as a framework for RPDs by determining the microstructure and mechanical properties. Dumbbell specimens and RPD frameworks were fabricated by using SLM followed by heat treatment. The effects of the heat treatment on the microstructure were studied by using optical microscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD). Tensile and insertion and removal tests were performed to study the mechanical responses of selective laser melting followed by heat treatment specimens, including the ultimate tensile strength (UTS), 0.2% yield strength (0.2% YS), elongation (E), and retentive forces. Specimens fabricated by using the traditional lost-wax process were used as a control (casting) group. X-ray diffraction indicated that the γ-face-centered cubic phase dominated SLM and selective laser melting followed by heat treatment specimens. Results from optical microscopy and SEM showed microstructural changes under different fabrication and postprocessing heat treatments; it was difficult to observe the grain boundary in the SLM group, whereas submicrometer-scale grains had formed in the selective laser melting followed by heat treatment group. The selective laser melting followed by heat treatment group exhibited the highest elongation and retentive forces compared with the casting and SLM groups. SLM increased the mechanical properties of Co-Cr alloys. Postprocessing heat treatment further enhanced the tensile ductility. It is suggested that SLM followed by heat treatment is an efficient strategy for fabricating RPD frameworks.


Arresting Spliceosome Intermediates at Various Stages of the Splicing Pathway.
The spliceosome is a dynamic ribonucleoprotein particle and is assembled via sequential binding of five snRNAs and numerous protein factors. To understand the molecular mechanism of the splicing reaction, it is necessary to dissect the spliceosome pathway and isolate spliceosome intermediates in various stages of the pathway for biochemical and structural analysis. Here, we describe protocols for preparing intron-containing transcripts, cell-free splicing extracts, and in vitro splicing reactions, as well as procedures to arrest the spliceosome at different stages of the pathway for characterization of specific splicing complexes from the budding yeast Saccharomyces cerevisiae. Methods for arresting spliceosomes at specific stages include depletion with antibodies against factors required for specific steps of the pathway, use of extracts prepared from temperature-sensitive mutants, use of dominant negative mutants of DExD/H-box proteins, and use of mutant substrates.


[Ocular changes after hormone replacement therapy in postmenopausal women. A preliminary report].
Ocular function is modified with hormone therapy; however, reports in literature are highly controversial. To analyze how hormone therapy modifies intraocular pressure and the number of tears shed by Mexican women. Eighteen postmenopausal women were studied and randomly divided into two groups, according to the treatment they received: group 1, conjugated equine estrogens (CEE) 0.625 mg/day (n=9) (hysterectomized women with bilateral oophorectomy) and group 2, CEE 0.625 mg/day plus chlormadinone 1 mg/day (n=9) (women with intact uterus). Changes in intraocular pressure and Schirmer's test were analyzed at baseline and three months after the treatment. Statistical analysis was performed with Student's t test for independent and paired samples. There were no significant differences in intraocular pressure or Schirmer's test among groups, neither when comparing baseline and final results in each group independently. We could not demonstrate the effect of hormone replacement therapy on intraocular pressure and on Schirmer's test after three months of its administration.


Prevalence of Erectile Dysfunction in Patients With End-Stage Renal Disease: A Systematic Review and Meta-Analysis.
Erectile dysfunction (ED) is an under-recognized clinical entity in men with end-stage renal disease (ESRD), and studies on renal transplant recipients, patients on dialysis, and patients starting dialysis report different prevalence rates and severity of ED among these groups. To determine the prevalence and severity of ED in patients with ESRD, assessed with the International Index of Erectile Function-15 and International Index of Erectile Function-5. We performed a systematic review and meta-analysis of observational studies assessing the prevalence of ED in ESRD individuals. (PROSPERO ID: CRD42020182680). Records were identified by search in MEDLINE, Scopus, and CENTRAL databases and sources of gray literature until July 2020. We conducted a random-effects meta-analysis of proportions (double arcsine transformation). We included 94 studies with 110 patient group entries and a total of 10,320 ESRD male individuals with a mean age of 48.8 ± 14.25 years. Overall, 7,253 patients experienced ED. We estimated an overall pooled ED prevalence of 71% (95% CI: 67-74%, I2 = 92%). In the subgroup analyses, the pooled prevalence was 59% (95% CI: 53-64%, I2 = 92%) among renal transplant recipients, 79% (95% CI: 75-82%, I2 = 86%) in patients on hemodialysis, 71% (95% CI: 58-83%, I2 = 86%) in patients on peritoneal dialysis, and 82% (95% CI: 75-88%, I2 = 0%) in patients with ESRD starting dialysis. The prevalence of the severity of ED was also estimated. Further assessment of heterogeneity was conducted via sensitivity analysis, cumulative meta-analysis, and meta-regression of significant risk factors. Despite its high prevalence in patients with ESRD, ED constitutes an underestimated and taboo subject in this group. Therefore, arousing clinical concern among healthcare providers involved in ESRD management is more than necessary to screen and treat ED in patients receiving renal replacement therapy. We estimated ED solely for ESRD, included the largest number of patients compared with previous studies and estimated ED prevalence as per severity and renal replacement therapy subgroups. Contrary, because we restricted our eligibility criteria to the International Index of Erectile Function, some studies assessing ED prevalence with other validated tools were not included in this meta-analysis. Moreover, the levels of heterogeneity among studies remained high after sensitivity and meta-regression analyses, and for some moderators, the results of the meta-regression might have been underpowered. ED is highly prevalent in patients with ESRD irrespective of the type of renal replacement therapy, thereby warranting clinical attention. Pyrgidis N, Mykoniatis I, Nigdelis MP, et al. Prevalence of Erectile Dysfunction in Patients With End-Stage Renal Disease: A Systematic Review and Meta-Analysis. J Sex Med 2021;18:113-120.


Beta3-adrenergic receptor gene polymorphism is not associated with hypertension in NIDDM patients without nephropathy.
We studied the relationship between a Trp64Arg mutation of beta3-adrenergic receptor gene and hypertension in Japanese NIDDM patients without nephropathy. Eighty-three Japanese NIDDM patients (46 men, 37 women, known duration of 12 [5-31], age of 55 [40-69] years, median and [range]) with normoalbuminuria and microalbuminuria were studied. The Trp64Arg mutation in the beta3-adrenergic receptor gene was determined by the PCR-RFLP method. The frequency of the mutated allele was not greater in the hypertensive patients (18.2%, n=37) than in the normotensive (20.2%, n=46) patients. Genotypes with a mutate allele (i.e. Trp64/Arg64 + Arg64/Arg64) were observed in 23.5% in the hypertensive patients and in 35.7% in the normotensive patients, respectively. A similar finding in the allele frequency was observed when the analysis was made separately in the normoalbuminuric and microalbuminuric patients, respectively. These results suggest that a Trp64Arg mutation in the beta3-adrenergic receptor gene is not associated with hypertension in Japanese NIDDM patients without nephropathy.


Microalbuminuria and abnormal ambulatory blood pressure in adolescents with type 2 diabetes mellitus.
To determine whether risk factors for cardiovascular disease and diabetic nephropathy, as evidenced by abnormalities of ambulatory blood pressure (ABP), dyslipidemia, and microalbuminuria (MA), are present in adolescents with type 2 diabetes mellitus (T2DM). We enrolled 26 minority adolescents recently diagnosed with T2DM and 13 obese control subjects without diabetes mellitus. ABP monitoring was performed, and a 24-hour urine, a fasting lipid profile, blood urea nitrogen, creatinine, homocysteine, and hemoglobin A 1 c levels were obtained. The patients with T2DM underwent echocardiograms. Forty percent of the patients with T2DM had MA (> or = 30 mg of microalbumin/day), compared with none of the control subjects ( P < .05). There were no significant differences between patients with T2DM who had MA and patients with T2DM who didn't have MA in demographics, characteristics, casual BP, echocardiographic findings, and hemoglobin A 1 c levels. Average daytime systolic BP was greater in patients with T2DM with MA than patients without MA (129 versus 121 mm Hg, P = .03) and compared with the control subjects (113 mm Hg, P = .01). Patients with MA had an average daytime systolic BP load that was higher than patients without MA (37.1 versus 5.1%, P = .008) and compared with the control subjects (2.6%, P < .001). As in adults, adolescents with T2DM exhibit abnormalities of ABP, dyslipidemia, and microalbuminuria.


A Novel Staged Revascularization Strategy for Bilateral Severe Internal Carotid Artery Stenosis at High Risk for Hyperperfusion Syndrome.
Since bilateral severe internal carotid artery stenosis often is associated with severely decreased cerebrovascular reactivity (CVR) due to poor collateral blood flow, revascularization carries a high risk for development of hyperperfusion syndrome. In this study, we report a new staged strategy to prevent postoperative hyperperfusion syndrome in such patients. Bilateral severe cervical internal carotid artery stenosis patients with decreased CVR to 10% or less on one side were prospectively enrolled in this study. We first performed carotid artery stenting on the side with the milder CVR decrease (lower-risk side), aiming to improve hemodynamics associated with the severe CVR decrease on the greater-risk side. Then, carotid endarterectomy or carotid artery stenting was performed on the contralateral side after an interval of 4-8 weeks. In all 3 cases enrolled in this study, CVR on the greater-risk side improved to 10% or more 1 month after the first treatment. The ratio of regional cerebral blood flow on the contralateral greater-risk side was 114% 1 day after the second treatment, and HPS did not develop in any of the cases. Our treatment strategy, in which revascularization on the lower-risk side precedes that on the greater-risk side, is effective for the prevention of HPS in bilateral ICA stenosis patients.


Chemical cystitis due to crystal violet dye: a case report.
Crystal violet was commonly used for the treatment of oral and vaginal candidiasis or for sterilization during operations up to the 1960s. Because crystal violet is potentially toxic to mucosal membranes, it has been replaced with other disinfectants, and crystal violet is rarely used. We report a case of chemical cystitis due to intravesical instillation of crystal violet dye. Crystal violet dye was instilled into the bladder of a 47-year-old Japanese woman to confirm the presence of a vesicovaginal fistula. Our patient developed symptoms of gross hematuria, frequent urination and lower abdominal pain. Computed tomography showed thickening of her whole bladder wall with spotted high-density lesions. Cystoscopy demonstrated desquamated epithelial cells and a hemorrhagic bladder wall. We treated our patient conservatively with nonsteroidal anti-inflammatory drugs and glucocorticoids. During follow-up, magnetic resonance images showed that the detrusor muscle of her bladder was normal. Our patient's symptoms gradually improved and she completely recovered within six months. Considering the severe side effect of crystal violet, it would be better not to use this dye to examine conditions such as a vesicovaginal fistula. Magnetic resonance imaging may help to evaluate the level of damage in the bladder wall of patients with chemical cystitis.


Control of electron transfer in DNA by peptide nucleic acids (PNA).
The one-electron oxidation of PNA-DNA hybrid containing G-triplet sequence was examined. In DNA duplex G-triplet was selectively cleaved by oxidation, whereas in PNA-DNA hybrid cleavage efficiency was extremely lowered. These result suggested that cleavage efficiency of PNA-DNA hybrid was different from that of B-form DNA duplex.


Experimental immunity against trypanosomiasis in sheep.
Three groups of male sheep were used. Group one was not inoculated; group two was inoculated with T. rhodesiense homogonate and group three with T. rhodesiense "fraction 3". Subsequently they were challenged with 1 x 10(6) T. vivax. Group inoculated with T. rhodesiense fraction 3 had high IgG levels and parasitemia was absent.


Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicenter, Randomized, Controlled Clinical Trial.
Rationale: Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS). Objectives: We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]-enriched, umbilical cord-derived MSCs) in COVID-19-related ARDS. Methods: In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT03042143), patients with moderate to severe COVID-19-related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148). The primary safety and efficacy outcomes were the incidence of serious adverse events and oxygenation index at Day 7, respectively. Secondary outcomes included respiratory compliance, driving pressure, PaO2:FiO2 ratio, and Sequential Organ Failure Assessment score. Clinical outcomes relating to duration of ventilation, lengths of ICU and hospital stays, and mortality were collected. Long-term follow-up included diagnosis of interstitial lung disease at 1 year and significant medical events and mortality at 2 years. Transcriptomic analysis was performed on whole blood at Days 0, 4, and 7. Measurements and Main Results: Sixty participants were recruited (final analysis: n = 30 received ORBCEL-C, n = 29 received placebo; 1 participant in the placebo group withdrew consent). Six serious adverse events occurred in the ORBCEL-C group and three in the placebo group (risk ratio, 2.9 [95% confidence interval, 0.6-13.2]; P = 0.25). Day 7 mean (SD) oxygenation index did not differ (ORBCEL-C, 98.3 [57.2] cm H2O/kPa; placebo, 96.6 [67.3] cm H2O/kPa). There were no differences in secondary surrogate outcomes or in mortality at Day 28, Day 90, 1 year, or 2 years. There was no difference in the prevalence of interstitial lung disease at 1 year or significant medical events up to 2 years. ORBCEL-C modulated the peripheral blood transcriptome. Conclusion: ORBCEL-C MSCs were safe in subjects with moderate to severe COVID-19-related ARDS but did not improve surrogates of pulmonary organ dysfunction.


Lutein Specific Relationships among Some Spectrophotometric and Colorimetric Parameters of Chicken Egg Yolk.
Lutein is an essential dietary carotenoid with health benefits and is inter alia responsible for the colouration of egg yolk. The relationship between lutein accumulation and egg yolk colouration was therefore studied in more detail. After feeding a low-luteine diet for 21 days, 14 birds (Lohmann brown hens aged 20 weeks) were fed a diet containing marigold (80 mg lutein/kg feed) and 14 other birds were fed a diet containing oleoresin (45 mg lutein/kg feed) for 21 days; for both groups of birds, this feeding period was followed by withdrawal for 21 days. The Roche Yolk Colour Fan (RYCF) score (0 to 15, where higher values denote greater colour intensity; R2=0.87; P<0.01) and redness (R2=0.89; P<0.01) increased with increasing lutein content of egg yolk. Total carotenoid content had a poor relationship with lightness (R2=0.13; P>0.05) and yellowness (R2=0.12; P>0.05) of the yolk. It may be concluded that increased lutein is potentially responsible for an increased RYCF score and redness (a*), but decreased yellowness (b*) and lightness (L*), of egg yolk.


Bridging Domain and Data.
Dr. Anne Carpenter addresses her career path from cell biology toward computation. Why would a researcher move outside their comfort zone into a different field, from a domain into data science? What is the best way to bridge domain and data? What is challenging about moving from domain toward data? What is amazing about bridging domain and data?


Effects of centrifugation on the degradation of short-lived proteins in exponentially growing cultured cells.
The degradation mechanisms of short-lived proteins in cultured cells are unknown, probably due to the lack of procedures which specifically affect the degradation of these proteins. We found that centrifugation of cultured cells, growing either in monolayer or in suspension, between 5000 and 25,000g for 30 min, inhibits (more than 50%) the degradation of short-lived proteins but not of long-lived proteins. Protein synthesis or cell viability is not affected. Centrifugation also disorganizes the Golgi apparatus, as checked by routine electron microscopy, and inhibits the degradation of endocytosed proteins (a lysosomal process which is controlled by the Golgi apparatus). Using different centrifugation speeds, a good correlation was found between alteration of the Golgi apparatus and inhibition of protein degradation.


Patterned distribution of immunoreactive astroglial processes in the striate (V1) cortex of New World monkeys.
The possibility of a modular organization of non-neuronal elements was analyzed in the opercular region of the striate neocortex in adult New World monkeys. For this purpose, and in order to follow possible correlations in the general organization of neuronal and astroglial elements, immunocytochemical procedures for Glial Fibrillary Acid Protein (GFAP) and Microtubule Associated Protein 2 (MAP-2), in addition to cytochrome oxidase (COX) histochemistry, were applied to tangential and coronal sections and analyzed by using computer-assisted procedures. Astroglial interlaminar processes stemming from superficial laminae did not traverse lamina IVA, and thus did not appear in deeper layers. Clearly definable interlaminar processes were predominantly concentrated in laminae II-III. A honeycomb- like lattice was observed in tangential sections, with a "cell" size distribution similar to the MAP-2-IR lattice, suggesting an intimate association with the pyramidal columns. Additionally, analysis of similar sections disclosed the periodic appearance of large patches with high density of interlaminar processes, indicating a nonhomogeneous distribution of GFAP-IR processes in the striate cortex. COX "blobs" appeared frequently to coincide with areas expressing high density of GFAP-IR elements. These findings add a new perspective to current concepts of astroglial organization in the striate cortex of primates and reveal the existence of a non-neuronal modular organization in the primate striate cerebral cortex, and suggest that possible correlations between relative distributions of neuronal and astroglial elements should be further analyzed in cortical areas with a clear modular organization such as the striate cortex.


Local structural difference between human and bovine band 3 in the anion transport inhibitor-binding region.
We have examined molecular properties of inhibitor-complexed human and bovine band 3, an anion transport protein of erythrocyte membrane, in order to demonstrate the structural characteristics of the inhibitor binding region. Band 3 modified with DIDS (4,4'-diisothiocyano-2,2'-stilbenedisulfonate), a potent anion transport inhibitor, generated a positive circular dichroic band at a wavelength of 345 nm, corresponding to a DIDS chromophore. The dichroic spectra of human band 3-DIDS complex and its bovine counterpart differed markedly in their ellipticity. Under the conditions that H2DIDS (the dihydro-derivative of DIDS) cross-linked two chymotryptic fragments of human band 3, the reagent failed to cross-link the equivalent bovine fragments. The inhibitory effect of PLP (pyridoxal 5'-phosphate), a substrate and affinity label, on phosphate influx into red blood cells was more pronounced for human band 3 than for bovine band 3. The residue Lys-562 of human band 3 was found to be modified with PLP, while the corresponding residue of bovine band 3 was devoid of reactivity with PLP.


Effect of metabolic rate on time-lag changes in otolith microchemistry: an experimental approach using Salmo trutta.
Ecologists have long been interested in relevant techniques to track the field movement patterns of fish. The elemental composition of otoliths represents a permanent record of the growing habitats experienced by a fish throughout its lifetime and is increasingly used in the literature. The lack of a predictive and mechanistic understanding of the individual kinematics underlying ion incorporation/depletion limits our fine-scale temporal interpretation of the chemical signal recorded in the otolith. In particular, the rate at which elements are incorporated into otoliths is hypothesized to depend on fish physiology. However, to date, time lags have mostly been quantified on a population scale. Here, we report results from controlled experiments (translocation and artificially enriched environment) on individual trace element incorporation/depletion rates in Salmo trutta (Salmonidae). We reported significant lags (i.e. weeks to months) between changes in water chemistry and the subsequent change in otolith composition and highlighted substantial inter-individual variations in the timing and magnitude of Sr/Ca and Ba/Ca responses. These differences are partially linked to the energetic status (i.e. metabolic rate) of the individuals. It therefore appears that individuals with the highest metabolic rate are more likely to record detailed (i.e. brief) temporal changes than individuals having lower metabolic values. The time taken for environmental changes to be reflected in the growing otolith thus can no longer be assumed to remain a constant within populations. Results from the current study are a step towards the fine reconstruction of environmental histories in dynamic environments.


The Egyptian Escalator: Gaining access to distal parent vessel in giant and large aneurysms.
Flow-diverter stents have become the mainstay of endovascular treatment for giant and large intracranial aneurysms. However, the local aneurysmal hemodynamics, the incorporation of the parent vessel and the frequent wide-neck configuration render gaining stable distal parent artery access difficult. In this technical video, we present three cases in which we employed the so called "Egyptian Escalator technique" for obtaining and maintaining stable distal access: after looping the microwire and microcatheter inside the aneurysmal sac and exiting in the distal parent artery, we deployed a stent-retriever and utilized a gentle traction on the microcatheter in order to straighten the intra-aneurysmal loop. Afterwards, a flow-diverter stent was deployed, with optimal coverage of the aneurysmal neck. The "Egyptian Escalator" technique provides a useful approach for obtaining stable distal access for flow-diverter deployment in giant and large aneurysm (supplementary mmc1 (Video 1)).


Common cancers in the elderly.
The proportion of elderly persons (65 years or older) has increased in most countries during the last few decades, and will increase further in the coming years. Annual age-standardised cancer incidence rates per 100,000 elderly persons (1988 to 1992) were calculated based on data from cancer registries in 51 countries in 5 continents kept by the International Agency for Research on Cancer (IARC) and International Association of Cancer Registries (IACR). The proportions of all cancers among elderly men and women were 61 and 56% respectively. All cancers combined (except nonmelanoma skin cancer) were, based on the standardised rates, almost 7-fold more frequent among elderly men (2158 per 100,000 person-years), and around 4-fold more frequent among elderly women (1192 per 100,000 person-years) than among younger persons (30 to 64 years old). However, large variations exist between different cancer sites. Contrary to the pattern in younger age groups, in which annual cancer rates are almost equally distributed among the 2 genders, elderly men have an almost double cancer incidence rate compared with elderly women. For all major specific cancer sites except testicular cancer, the incidence rate is significantly higher among the elderly than among any groups of younger and middle-aged persons. Among elderly men, cancer of the prostate (451 per 100,000), the lung (449 per 100,000) and the colon (176 per 100,000) make up around half of all diagnosed cancers. Prostate cancer is around 22 times more frequent among elderly men than among younger men. The corresponding most frequent cancers among elderly women, making up 48% of all malignant cancers, are breast (248 per 100,000), colon (133 per 100,000), lung (118 per 100,000) and stomach cancer (75 per 100,000). For most cancers, marked geographical variations in incidence rates are found among the elderly, reflecting socioeconomic differences, particularly between the developing and the developed countries. In contrast with other major causes of death among the elderly, cancer incidence and mortality have not in general declined, indicating that primary prevention (especially cessation of tobacco smoking) remains a most valuable approach to decrease mortality; for most of the major cancers (prostate, colon, breast) the causes remain almost unknown. Thus, research into potential causes is urgently needed for future prevention. Since the mortality rates for female cancer in general are declining, and since the incidence is increasing more steeply than the mortality among the men, the number of living elderly ever diagnosed with a cancer will further increase during the next years. Therefore, it is important to emphasise the increasing need for research into the prevention of cancer and the planning of treatment and care in the elderly.


Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD.
CKD, characterized by retained uremic solutes, is a strong and independent risk factor for thrombosis after vascular procedures . Urem ic solutes such as indoxyl sulfate (IS) and kynurenine (Kyn) mediate prothrombotic effect through tissue factor (TF). IS and Kyn biogenesis depends on multiple enzymes, with therapeutic implications unexplored. We examined the role of indoleamine 2,3-dioxygenase-1 (IDO-1), a rate-limiting enzyme of kynurenine biogenesis, in CKD-associated thrombosis after vascular injury. IDO-1 expression in mice and human vessels was examined. IDO-1-/- mice, IDO-1 inhibitors, an adenine-induced CKD, and carotid artery injury models were used. Both global IDO-1-/- CKD mice and IDO-1 inhibitor in wild-type CKD mice showed reduced blood Kyn levels, TF expression in their arteries, and thrombogenicity compared with respective controls. Several advanced IDO-1 inhibitors downregulated TF expression in primary human aortic vascular smooth muscle cells specifically in response to uremic serum. Further mechanistic probing of arteries from an IS-specific mouse model, and CKD mice, showed upregulation of IDO-1 protein, which was due to inhibition of its polyubiquitination and degradation by IS in vascular smooth muscle cells. In two cohorts of patients with advanced CKD, blood IDO-1 activity was significantly higher in sera of study participants who subsequently developed thrombosis after endovascular interventions or vascular surgery. Leveraging genetic and pharmacologic manipulation in experimental models and data from human studies implicate IS as an inducer of IDO-1 and a perpetuator of the thrombotic milieu and supports IDO-1 as an antithrombotic target in CKD.


Wasp venom rush immunotherapy induces transient downregulation of B cell surface molecule expression.
Little is known about the involvement of B cells in venom immunotherapy (VIT). To elucidate changes in the B cell phenotype during this process, we examined the expression of several surface molecules on peripheral B cells before and during VIT. 15 venom-allergic patients with a history of systemic reactions after a wasp sting and venom-specific skin test reactivity as well as serum IgE were investigated before VIT (day 1), 1 day after reaching a maintenance dose of 100 microg (day 6) during inpatient rush VIT, and again on day 26 during continued outpatient maintenance therapy. Changes in the serum levels of total IgE, allergen-specific IgE (sIgE) and sIgG4 were measured by ELISA. Expression of several surface molecules on double-labelled B cells was studied by flow cytometry of peripheral blood mononuclear cells. Levels of total IgE, sIgE and sIgG4 showed a significant increase after 26 days of VIT. On day 6, cell surface expression of HLA- II-DR, CD5, CD32 and CD54 was decreased in intensity and numbers of positive cells compared to day 1, while on day 26, expression of these molecules approached again baseline levels. Furthermore, a trend to decreased CD23 was noted on day 6. No changes were observed for CD40, CD86, CD95 and HLA-I-ABC. These data show that during initiation of rush VIT, B cell expression of surface molecules involved in T-B cell cooperation and antigen presentation is downmodulated. B cells may thus be additional direct or indirect targets of high-dose antigen therapy and contribute to the persistence of TH1 responses during maintenance VIT treatment.


IgA polymorphism in mice: NZB and BALB/c mice produce two forms of IgA.
There are two different forms of mouse IgA immunoglobulins, one in which light chains are disulfide-linked to each other (IgAL-L) and the second where light chains are linked to heavy chains (IgAH-L). IgA myeloma proteins from BALB/c mice are IgAL-L and those from NZB are IgAH-L. To determine whether these two forms of IgA represent allotypic or isotypic variants, we purified serum IgA and prepared IgA-secreting somatic cell hybrids from mitogen-stimulated BALB/c and NZB mice and determined the pattern of light chain linkage. It was found that each strain produces both forms of IgA and that both forms share the allotypic determinants characteristic of the mouse strain.


Pre-operative uterine artery embolization before hysterectomy or myomectomy: a single-center review of 53 patients.
To assess outcomes of planned pre-operative uterine artery embolization (UAE) in patients with uterine fibroids at high risk for bleeding prior to hysterectomy or myomectomy. A retrospective review of 53 consecutive patients who underwent planned UAE followed by surgery from 2004 to 2019 was performed in a subset of patients deemed high risk for bleeding by the referring surgeon due to bulky fibroids and/or adhesions. Characteristics of the largest fibroid, total number of fibroids, embolic agents, estimated blood loss (EBL), complications, and other factors were collected. 53 patients (mean age = 41) had an elective UAE prior to a hysterectomy 24 (45%) or myomectomy 29 (55%). Median interval between UAE & surgery was 21.6 h (range 1.75 h-57 days). Of the myomectomies, 13 (45%) were open, 15 (52%) hysteroscopic and 1 laparoscopic. Mean number of fibroids/patient was 4.1 (SD 1.3), mean fibroid volume was 328 cm3 (range 11-741), and the mean fibroid diameter in longest dimension was 7.4 cm (range 3.2-15). Mean EBL was 90 (SD 99.5 mL). Three (10%) myomectomy patients required blood transfusion. All hysterectomies were via a laparotomy. Mean fibroid volume was 1699 cm3 (range 93-9099 cm3) with a mean maximum diameter of 16.2 cm (range 6.5-29.6) and an average of 2.4 (SD 1.7) fibroids. Mean EBL was 352 (SD 220 mL). Four (17%) hysterectomy patients required an intra- or post-operative blood transfusion. At a mean 1-year follow-up (range 1 month-14 years), 70% of UAE-myomectomy patients and 74% of UAE-hysterectomy patients reported symptom resolution. Three (6%) patients were readmitted: one for osteodiscitis, one wound dehiscence, and one for an infected retained fibroid after myomectomy. Planned pre-operative UAE resulted in intraoperative blood loss similar to "all-comer" myomectomy and hysterectomy patients in the literature. Further studies may elucidate which patients would be the best candidates for this staged treatment paradigm.


The effects of HHV-8 vMIP-II on SIVmac251 infection and replication competent and incompetent SIVmac239Delta3 vectors.
Human herpesvirus type 8 vMIP-II has one of the broadest ranges of chemokine receptor binding and therefore a multiplicity of biologic effects, both immunologic and antiviral. These properties make vMIP-II an attractive effector gene to be expressed from gene therapy vectors. The present studies were concerned with both therapeutic approaches: (1) an anti-simian immunodeficiency virus (SIV) biologic, and (2) an effector gene in SIV-based vectors. Regarding its antiviral properties, vMIP-II expressed from bacteria and SIV-based vectors bound the surface of CEMx174 cells and specifically suppressed SIVmac251 infection. A CCR3 monoclonal antibody partially inhibited vMIP-II binding, suggesting that both SIVmac251 and vMIP-II utilize a similar CCR3-like receptor for CEMx174 cell binding. Replication competent SIV-based vectors containing forward and reverse vMIP-II produced neither identifiable vMIP-II nor virions for the first 21 days. Virus replication occurred after this period. Significant sequence alterations in the forward vMIP-II containing replication competent vector transcripts were responsible for the failure of vMIP-II expression. The genetic basis for the initial failure to replicate virus and its later restoration was not determined but appeared in the II-PIMv containing vectors to coincide with deletions and compensatory rearrangements in nef 3' of the polypurine tract. Cells transfected with SIVmac239Delta3DeltaLTR-vMIP-II vectors expressed biologically active vMIP-II that bound CEMx174 cells and suppressed SIVmac251 infection. These data suggest that replication defective SIV vectors expressing immunobiolgic genes such as vMIP-II may prove useful in gene therapies, particularly in augmenting immune responses in chronically infected individuals.


Ultratrace-level determination of glyphosate, aminomethylphosphonic acid and glufosinate in natural waters by solid-phase extraction followed by liquid chromatography-tandem mass spectrometry: performance tuning of derivatization, enrichment and detection.
A sensitive and robust analytical method for the quantification of glyphosate, aminomethylphosphonic acid (AMPA) and glufosinate in natural water has been developed on the basis of a derivatization with 9-fluorenylmethylchloroformate (FMOC-Cl), solid-phase extraction (SPE) and liquid chromatography followed by electrospray tandem mass spectrometry (LC-ESI-MS/MS). In order to maximize sensitivity, the derivatization was optimized regarding organic solvent content, amount of FMOC-Cl and reaction time. At an acetonitrile content of 10% a derivatization yield of 100% was reached within two hours in groundwater and surface water samples. After a twofold dilution the low acetonitrile content allowed solid-phase extraction of a sample of originally 80 mL over 200 mg Strata-X cartridges. In order to decrease the load of the LC column and mass spectrometer with derivatization by-products (e.g., 9-fluorenylmethanol FMOC-OH), a rinsing step was performed for the SPE cartridge with dichloromethane. Acidification of the sample and addition of EDTA was used to minimize complexation of the target compounds with metal ions in environmental samples. Due to the large sample volume and the complete FMOC-OH removal, limits of quantification of 0.7 ng/L, 0.8 ng/L and 2.3 ng/L were achieved in surface water for glyphosate, AMPA and glufosinate, respectively. The limits of detection were as low as 0.2 ng/L, 0.2 ng/L and 0.6 ng/L for glyphosate, AMPA and glufosinate, respectively. Surface water and ground water samples spiked at 2 ng/L showed recoveries of 91-107%.


Mutation of the chloroplast-localized phosphate transporter OsPHT2;1 reduces flavonoid accumulation and UV tolerance in rice.
Phosphorus (P) is an essential macronutrient required for plant development and production. The mechanisms regulating phosphate (Pi) uptake are well established, but the function of chloroplast Pi homeostasis is poorly understood in Oryza sativa (rice). PHT2;1 is one of the transporters/translocators mediating Pi import into chloroplasts. In this study, to gain insight into the role of OsPHT2;1-mediated stroma Pi, we analyzed OsPHT2;1 function in Pi utilization and photoprotection. Our results showed that OsPHT2;1 was induced by Pi starvation and light exposure. Cell-based assays showed that OsPHT2;1 localized to the chloroplast envelope and functioned as a low-affinity Pi transporter. The ospht2;1 had reduced Pi accumulation, plant growth and photosynthetic rates. Metabolite profiling revealed that 52.6% of the decreased metabolites in ospht2;1 plants were flavonoids, which was further confirmed by 40% lower content of total flavonoids compared with the wild type. As a consequence, ospht2;1 plants were more sensitive to UV-B irradiation. Moreover, the content of phenylalanine, the precursor of flavonoids, was also reduced, and was largely associated with the repressed expression of ADT1/MTR1. Furthermore, the ospht2;1 plants showed decreased grain yields at relatively high levels of UV-B irradiance. In summary, OsPHT2;1 functions as a chloroplast-localized low-affinity Pi transporter that mediates UV tolerance and rice yields at different latitudes.


Potent antitumor effect of TRAIL mediated by a novel adeno-associated viral vector targeting to telomerase activity for human hepatocellular carcinoma.
Adeno-associated virus (AAV) has rapidly become a promising gene delivery vehicle for its excellent advantages of low pathogenicity and long-term gene expression. However, lack of tissue specificity caused low efficiency of AAV transfer to target cells. The promoter of human telomerase reverse transcriptase (hTERT) has been implicated in mediating gene expression in cancer cells as hTERT is transcriptionally upregulated in most cancer cells. Thereby, the hTERT promoter becomes a good candidate to enhance the targeting efficiency of AAV in cancer cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a soluble cytokine to selectively kill various cancer cells without toxicity to most normal cells. It remains to be determined whether the hTERT promoter can efficiently mediate TRAIL gene therapy in cancer cells using AAV vector. A novel AAV vector containing the TRAIL gene under the control of the hTERT promoter (AAV-hTERT-TRAIL) was generated. The specific expression of hTERT-controlled genes was evaluated in cell lines. The antitumor efficacy of AAV-hTERT-TRAIL was assessed in tumor cell lines and human hepatocellular carcinoma xenograft mouse model. TRAIL expression was observed in tumor cells infected with AAV-hTERT-TRAIL at both the protein and mRNA level. AAV-hTERT-TRAIL displayed cancer-specific cytotoxicity and induced tumor cell apoptosis. Moreover, in animal experiments, intratumoral administration of AAV-hTERT-TRAIL significantly suppressed the growth of xenograft tumors and resulted in tumor cell death. AAVs in combination with hTERT-mediated therapeutic gene expression provide a promising targeting approach for developing effective therapy for human cancers. These data suggest that AAV-hTERT-TRAIL is a potent therapeutic agent for cancer therapy.


Impermeability of hagfish cerebral capillaries to horseradish peroxidase. An ultrastructural study.
Brain capillaires and their permeability to intravenously injected horseradish peroxidase, HRP, (MW: 40,000) were examined electron-microscopically in an attempt to find a structural explanation for the poorly developed blood-brain barrier in the hagfish, Myxine glutinosa. In particular, it was the aim of this study to examine the role of the numerous endothelial vesicles and tubules in the transport of this tracer between blood and brain. Many of the vesicles and tubules were found to be in continuity with the luminal or abluminal surfaces, but tubules generating channels through the endothelial cells were never observed. The cleft between adjacent endothelial cells was obliterated by punctate junctions. HRP, which was aloowed to circulate for up to 35 min, was not found in the basal lamina or in the surrounding brain parenchyma. Few of the luminal vesicles and tubules were marked by the tracer. In the intercellular cleft HRP was stopped by the junctions. It is concluded that the hagfish like other vertebrates has a blood-brain barrier to HRP, and the numerous vesicles and tubules occurring in hagfish brain endothelium are not involved in the transendothelial transport of this macromolecule.


Administration of the optimized β-Lapachone-poloxamer-cyclodextrin ternary system induces apoptosis, DNA damage and reduces tumor growth in a human breast adenocarcinoma xenograft mouse model.
β-Lapachone (β-Lap) is a 1,2-orthonaphthoquinone that selectively induces cell death in human cancer cells through NAD(P)H:quinone oxidoreductase-1 (NQO1). NQO1 is overexpressed in a variety of tumors, as compared to normal adjacent tissue. However, the low solubility and non-specific distribution of β-Lap limit its suitability for clinical assays. We formulated β-Lap in an optimal random methylated-β-cyclodextrin/poloxamer 407 mixture (i.e., β-Lap ternary system) and, using human breast adenocarcinoma MCF-7 cells and immunodeficient mice, performed in vitro and in vivo evaluation of its anti-tumor effects on proliferation, cell cycle, apoptosis, DNA damage, and tumor growth. This ternary system is fluid at room temperature, gels over 29 °C, and provides a significant amount of drug, thus facilitating intratumoral delivery, in situ gelation, and the formation of a depot for time-release. Administration of β-Lap ternary system to MCF-7 cells induces an increase in apoptosis and DNA damage, while producing no changes in cell cycle. Moreover, in a mouse xenograft tumor model, intratumoral injection of the system significantly reduces tumor volume, while increasing apoptosis and DNA damage without visible toxicity to liver or kidney. These anti-tumoral effects and lack of visible toxicity make this system a promising new therapeutic agent for breast cancer treatment.


Biophysical regulation of carbon fluxes over an alpine meadow ecosystem in the eastern Tibetan Plateau.
The eddy covariance method was used to measure net ecosystem CO2 exchange (NEE) between atmosphere and an alpine meadow ecosystem in the eastern Tibetan Plateau of China in 2010. Our results show that photosynthesis was reduced under low air temperature (T a), high vapor pressure deficit (VPD), and medium soil water content (SWC) conditions, when compared to that under other T a (i.e., medium and high), VPD (i.e., low and medium), and SWC (i.e., low and high) conditions. The apparent temperature sensitivity of ecosystem respiration (Q 10) declined with progressing phenology during the growing season and decreased with an increase of soil temperature (T s) during the non-growing season. Increased ecosystem respiration (R eco) was measured during spring soil thawing. By the path analysis, T a, T s, and VPD were the main control factors of CO2 exchange at 30-min scale in this alpine meadow. Integrated NEE, gross primary production (GPP), and R eco over the measured year were -156.4, 1164.3, and 1007.9 g C m(-2), respectively. Zoige alpine meadow was a medium carbon sink based on published data for grassland ecosystems.


Estimation of the number of amino acid substitutions per site when the substitution rate varies among sites.
A general model for estimating the number of amino acid substitutions per site (d) from the fraction of identical residues between two sequences (q) is proposed. The well-known Poisson-correction formula q = e (-d) corresponds to a site-independent and amino-acid-independent substitution rate. Equation q = (1 - e(-2d)/2d, derived for the case of substitution rates that are site-independent, but vary among amino acids, approximates closely the empirical method, suggested by Dayhoff et al. (1978). Equation q = 1/(1 + d) describes the case of substitution rates that are amino acid-independent but vary among sites. Lastly, equation q = [ln(1 + 2d)]/2d accounts for the general case where substitution rates can differ for both amino acids and sites.


Efficacy of the combination of amlodipine and valsartan in patients with hypertension uncontrolled with previous monotherapy: the Exforge in Failure after Single Therapy (EX-FAST) study.
In this randomized, double-blind, multicenter study, patients whose blood pressure (BP) was uncontrolled by monotherapy were switched directly to amlodipine/valsartan 5/160 mg (n=443) or 10/160 mg (n=451). After 16 weeks, BP control (levels <140/90 mm Hg or <130/80 mm Hg for diabetics) was achieved in 72.7% (95% confidence interval [CI], 68.6-76.9) of patients receiving amlodipine/valsartan 5/160 mg and in 74.8% (95% CI, 70.8-78.9) receiving amlodipine/valsartan 10/160 mg. Incremental reductions from baseline in mean sitting systolic and diastolic BP were significantly greater with the higher dose (20.0+/-0.7 vs 17.5+/-0.7 mm Hg; P=.0003 and 11.6+/-0.4 vs 10.4+/-0.4 mm Hg; P=.0046). Incremental BP reductions were also achieved with both regimens irrespective of previous monotherapy, hypertension severity, diabetic status, body mass index, and age. Peripheral edema was the most frequent adverse event. These results provide support for the BP-lowering benefits of complementary antihypertensive therapy with amlodipine and valsartan in patients with hypertension uncontrolled by previous monotherapy.


Differences in growth factor sensitivity between individual 3T3 cells arise at high frequency: possible relevance to cell senescence.
At low serum concentrations (3% or less), individual Swiss 3T3 cells display marked heterogeneity in proliferative capacity. Here we show that this heterogeneity arises at extremely high frequency within a clone, often with sister cells showing considerable differences in capacity for further proliferation. The heterogeneity is unlikely to be due to genetic instability or mutation. Instead, it appears to reflect physiological differences between cells in their requirement for serum growth factors. It is suggested that these differences arise because cells are unable to sustain production, at low growth factor concentrations, of some rare component which is itself required for growth factor action. We believe that the generation of heterogeneity in 3T3 cells has much in common with the phenomenon of senescence in diploid cells.


Cell Viability Assays for 3D Cellular Constructs.
In vitro models fall short of replicating the complex in vivo processes including cell growth and differentiation. For many years, molecular biology research and drug development have relied on the use of cells grown within tissue culture dishes. These traditional in vitro two-dimensional (2D) cultures fail to recapitulate the 3D microenvironment of in vivo tissues. Due to inadequate surface topography, surface stiffness, cell-to-cell, and cell-to-ECM matrices, 2D cell culture systems are incapable of mimicking cell physiology seen in living healthy tissues. These factors can also place selective pressure on cells that substantially alter their molecular and phenotypic properties. With these disadvantages in mind, new and adaptive cell culture systems are necessary to recapitulate the cellular microenvironment in a more accurate manner for drug development, toxicity studies, drug delivery, and much more. Newly developed biofabrication technologies capable of creating 3D tissue constructs can open new opportunities for cell growth and developmental modeling. These constructs show great promise in representing an environment that allows cells to interact with other cells and their microenvironment in a much more physiologically accurate manner. When transitioning from 2D to 3D systems, there is the need to translate common cell viability analysis techniques from that of 2D cell culture to these 3D tissue constructs. Cell viability assays are critical in evaluating the health of cells in response to drug treatment or other stimuli to better understand how these factors effect the tissue constructs. As 3D cellular systems become the new standard in biomedical engineering, this chapter provides different assays used to assess cell viability qualitatively and quantitatively in 3D environments.


Tumour angiogenesis as a chemo-mechanical surface instability.
The hypoxic conditions within avascular solid tumours may trigger the secretion of chemical factors, which diffuse to the nearby vasculature and promote the formation of new vessels eventually joining the tumour. Mathematical models of this process, known as tumour angiogenesis, have mainly investigated the formation of the new capillary networks using reaction-diffusion equations. Since angiogenesis involves the growth dynamics of the endothelial cells sprouting, we propose in this work an alternative mechanistic approach, developing a surface growth model for studying capillary formation and network dynamics. The model takes into account the proliferation of endothelial cells on the pre-existing capillary surface, coupled with the bulk diffusion of the vascular endothelial growth factor (VEGF). The thermo-dynamical consistency is imposed by means of interfacial and bulk balance laws. Finite element simulations show that both the morphology and the dynamics of the sprouting vessels are controlled by the bulk diffusion of VEGF and the chemo-mechanical and geometric properties at the capillary interface. Similarly to dendritic growth processes, we suggest that the emergence of tree-like vessel structures during tumour angiogenesis may result from the free boundary instability driven by competition between chemical and mechanical phenomena occurring at different length-scales.


Stability of plasma treated superhydrophobic surfaces under different ambient conditions.
Plasma hydrophilizing of superhydrophobic substrates has become an important area of research, for example, superhydrophobic-(super)hydrophilic patterned surfaces have significant practical applications such as lab-on-chip systems, cell adhesion, and control of liquid transport. However, the stability of plasma-induced hydrophilicity is always considered as a key issue since the wettability tends to revert back to the untreated state (i.e. aging behavior). This paper focuses on the stability of plasma treated superhydrophobic surface under different ambient conditions (e.g. temperature and relative humidity). Water contact angle measurement and X-ray photoelectron spectroscopy are used to monitor the aging process. Results show that low temperature and low relative humidity are favorable to retard the aging process and that pre-storage at low temperature (-10°C) disables the treated surface to recover superhydrophobicity. When the aging is performed in water, a long-lasting hydropholicity is obtained. As the stability of plasma-induced hydrophilcity over a desired period of time is a very important issue, this work will contribute to the optimization of storage conditions of plasma treated superhydrophobic surfaces.


A potential radioimmunoassay system for detection of Hanganutziu-Deicher type heterophile antigen(s) and antibodies in tissues and fluids.
A relatively simple, specific and sensitive radioimmunoassay system has been developed for the detection of heterophile Hanganutziu-Deicher (H-D) antigen(s) and antibodies. The 125I-labeled H-D antigen-active molecule used for the assay is a bovine erythrocyte major glycoprotein previously found to have a strong H-D antigen potency. The antigen-antibody complex was precipitated with normal human serum as the carrier protein, followed by the addition of rabbit anti-human IgG F(ab')2 serum. With this method, different H-D antigen-active molecules were compared for heterophile H-D antigen potency with reasonable sensitivity detecting about 0.3 ng of cold glycoprotein. 8 different lung cancer tissues were assayed for H-D antigen. The sera from the 8 lung cancer patients were also screened by ELISA and RIA in an attempt to correlate expression of H-D antigen on tissues with elevation of H-D antibodies. The results showed that all patients' tissues expressed the antigen(s) but only 3 of them had abnormal levels of H-D antibodies. This could have been due to excess antigens in circulation or immune complexes.


The potential of biochar as a microbial carrier for agricultural and environmental applications.
Biochar can be an effective carrier for microbial inoculants because of its favourable properties promoting microbial life. In this review, we assess the effectiveness of biochar as a microbial carrier for agricultural and environmental applications. Biochar is enriched with organic carbon, contains nitrogen, phosphorus, and potassium as nutrients, and has a high porosity and moisture-holding capacity. The large number of active hydroxyl, carboxyl, sulfonic acid group, amino, imino, and acylamino hydroxyl and carboxyl functional groups are effective for microbial cell adhesion and proliferation. The use of biochar as a carrier of microbial inoculum has been shown to enhance the persistence, survival and colonization of inoculated microbes in soil and plant roots, which play a crucial role in soil biochemical processes, nutrient and carbon cycling, and soil contamination remediation. Moreover, biochar-based microbial inoculants including probiotics effectively promote plant growth and remediate soil contaminated with organic pollutants. These findings suggest that biochar can serve as a promising substitute for non-renewable substrates, such as peat, to formulate and deliver microbial inoculants. The future research directions in relation to improving the carrier material performance and expanding the potential applications of this emerging biochar-based microbial immobilization technology have been proposed.


An adaptive switching filter based on approximated variance for detection of impulse noise from color images.
A new adaptive switching algorithm is presented where two adaptive filters are switched correspondingly for lower and higher noise ratio of the image. An adaptive center weighted vector median filter is used for the lower noise ratio whereas for higher noise ratio the noisy pixels are detected based on the comparison of the difference between the mean of the vector pixels in the window and the approximated variance of the vector pixels in the window. Then the window comprising the detected noisy pixel is further considered where the pixels are given exponential weights according to their similarity to the other neighboring pixels, spatially and radio metrically. The noisy pixels are then replaced by the weighted average of the pixels within the window. The filter is able to preserve higher signal content in the higher noise ratio as compared to other robust filters in comparison. With a little high in computational complexity, this technique performs well both in lower and higher noise ratios. Simulation results on various RGB images show that the proposed algorithm outperforms many other existing nonlinear filters in terms of preservation of edges and fine details.


Trigeminal nerve schwannoma with ancient change. Case report and review of the literature.
Ancient change in a schwannoma is a histological variant typically found in longstanding tumors. Histologically, the tumor has biphasic features typical of a schwannoma with evidence of degenerative changes that may complicate diagnosis. The authors report on a 23-year-old man with no features of neurofibromatosis who presented with headaches, blurred vision, and ataxic gait. Magnetic resonance imaging demonstrated a rim-enhancing lesion in the cerebellopontine angle with displacement of brainstem structures and no supratentorial hydrocephalus. Using a lateral suboccipital approach together with image guidance and intraoperative neurophysiological monitoring, a gross-total macroscopic excision was performed. At surgery, the tumor was found to arise from the inferior division of the trigeminal nerve. The final histological diagnosis was schwannoma with ancient change. Note that ancient change in schwannomas is a histological variant thought to result from degenerative changes in longstanding tumors. To the authors' knowledge, this is the first independent report of this histological variant in an intracranial schwannoma.


Role of adrenergic structures in functional control over the cerebral circulation.
An investigation of the cerebral circulation by the thermoelectric method showed that stimulation of the cervical sympathetic nerve leads to considerable changes in the blood supply to the brain. The changes in blood flow are biphasic in character: An initial small increase is followed by a decrease below the original level. Pharmacological analysis with alpha and beta adreno-blockers showed that the constrictor response of the cerebral vessels is due to excitation of alpha-adrenergic structures and the dilator response to excitation of beta-adrenergic structures. A possible mechanism of these changes is postulated.


Relationship of Nutritional Status, Inflammation, and Serum Albumin Levels During Acute Illness: A Prospective Study.
Low serum albumin levels resulting from inflammation-induced capillary leakage or disease-related anorexia during acute illness are associated with poor outcomes. We investigated the relationship of nutritional status and inflammation with low serum albumin levels and 30-day mortality in a large cohort. We prospectively enrolled adult patients in the medical emergency department of a Swiss tertiary care center and investigated associations of C-reactive protein (CRP) and Nutritional Risk Screening 2002 as markers of inflammation and poor nutritional status, respectively, with low serum albumin levels and mortality using multivariate regression analyses. Among the 2465 patients, 1019 (41%) had low serum albumin levels (<34 g/L), 619 (25.1%) had increased nutritional risk (Nutritional Risk Screening 2002 ≥3), and 1086 (44.1%) had CRP values >20 mg/L. Multivariate analyses adjusted for age, gender, diagnosis, and comorbidities revealed elevated CRP values (adjusted odds ratio [OR] 10.51, 95% confidence interval, 7.51-14.72, P <.001) and increased malnutrition risk (adjusted OR 2.87, 95% confidence interval, 1.98-4.15, P <.001) to be associated with low serum albumin levels, even adjusting for both parameters. Low serum albumin levels, elevated CRP values, and increased nutritional risk independently predicted 30-day mortality, with areas under the curve of 0.77, 0.70, and 0.75, respectively. Combination of these 3 parameters showed an area under the curve of 0.82 to predict mortality. Elevated parameters of inflammation and high nutritional risk were independently associated with hypoalbuminemia. All 3 parameters independently predicted mortality. Combining them during initial evaluation of patients in emergency departments facilitates mortality risk stratification.


Can consumers self-select for appropriate use of an over-the-counter statin? The Self Evaluation of Lovastatin to Enhance Cholesterol Treatment Study.
Access to over-the-counter (OTC) statins has the potential to improve public health by reducing cardiovascular events. The Self Evaluation of Lovastatin to Enhance Cholesterol Treatment (SELECT) Study was designed to assess consumers' ability to self-select for treatment with lovastatin in an unsupervised setting. Subjects examined proposed OTC lovastatin cartons with labels that detailed an algorithm for self-selection based on age, lipid profile, and cardiovascular risk factors. Subjects viewed a carton with either a low-density lipoprotein cholesterol-based self-selection algorithm or one based on total cholesterol. Labels also contained warnings against use based on health conditions that might increase the risk of adverse events. Subjects were asked if the drug was appropriate for their use (self-assessment) and whether they would like to purchase the drug (purchase decision). A total of 1,326 consumers provided self-assessment decisions. After viewing the low-density lipoprotein cholesterol-based label, 82%, 36%, and 82% of those who self-assessed that the drug was appropriate for their use were correct with respect to the age, lipid, and risk-factor criteria, respectively. Corresponding numbers for the total cholesterol algorithm were 85%, 50% and 75%. Almost 90% of women aged <55 years who evaluated the drug indicated the drug was not right for them, and women in this age group made up only 9% of the total group of subjects who believed the drug was appropriate for their use. The label was also effective in discouraging use by women who were or may become pregnant, consumers with liver disease, and those with potential drug interactions. In conclusion, SELECT showed that consumers could use an OTC drug label in an unsupervised setting to appropriately self-select for self-management of their cholesterol with lovastatin.


Pi35(t), a new gene conferring partial resistance to leaf blast in the rice cultivar Hokkai 188.
The japonica rice cultivar Hokkai 188 shows a high level of partial resistance to leaf blast. For mapping genes conferring the resistance, a set of 190 F2 progeny/F3 families was developed from the cross between the indica rice cultivar Danghang-Shali, with a low level of partial resistance, and Hokkai 188. Partial resistance to leaf blast in the F3 families was assessed in upland nurseries. From a primary microsatellite (SSR) linkage map and QTL analysis using a subset of 126 F2 progeny/F3 families randomly selected from the above set, one major QTL located on chromosome 1 was detected in the vicinity of SSR marker RM1216. This QTL was responsible for 69.4% of the phenotypic variation, and Hokkai 188 contributed the resistance allele. Segregation analysis in the F3 families for partial resistance to leaf blast was in agreement with the existence of a major gene, and the gene was designated as Pi35(t). Another QTL detected on chromosome 8 was minor, explained 13.4% of the phenotypic variation, and an allele of Danghang-Shali increased the level of resistance in this QTL. Additional SSR markers of the targeted Pi35(t) region were further surveyed in the 190 F2 plants, and Pi35(t) was placed in a 3.5-cM interval flanked by markers RM1216 and RM1003.


[The detection of the genotoxic and mutagenic activities of disperse azo dyes for their hygienic standardization].
Evaluating level and synthesis of DNA in liver cells, counting occurrence of dominant lethal mutations, the authors studied molecular and genetic effects of dispersed polyaether mononitrodyes Orange 2K and Red-Brown G after the peroral administration and the chronic inhalation (2.5 and 4 months). Red-Brown G examined in acute and chronic exposures appeared to be powerful mutagen. Orange 2K induced minor changes of nuclear DNA functioning in liver cells, if compared to Red-Brown G. In Dominant Lethal Mutations Test both dyes were assigned to mild mutagens. The diagnosed effects are used for setting hygienic standards in the air of workplace.


[Short-time storage of human corneas in medium NCTC 135 (author's transl)].
20 human donor corneas were placed in a tissue culture medium (NCTC 135 with an additional content of 5% Actovegin resp. Solcoseryl) at +4 degrees C for 5 and 7 days. After that the temperature reversal effect was measured and the corneal endothelial cells were stained. The living cells were counted every 24 hours until no more cells could be seen. It could be shown, that compared with the MK-Medium 24% more living cells could be counted after 5 and 7 days storage in the medium. Possible causes of this improvement, practical consequences with including antibiotic prophylaxis are discussed.


Clinical validity of delayed recall tests as a gateway biomarker for Alzheimer's disease in the context of a structured 5-phase development framework.
Although Alzheimer's disease criteria promote the use of biomarkers, their maturity in clinical routine still needs to be assessed. In the light of the oncology framework, we conducted a literature review on measures used to assess delayed recall impairment due to medial temporal lobe dysfunction (i.e., free and cued word list recall tests). Ample evidence is available for phases 1 (rationale for use), 2 (discriminative ability), and 3 (early detection ability) for many of the tests in routine use. Evidence about phase 4 (performance in real world) and phase 5 (quantify impact and costs) is yet to come. Administration procedures have been standardized and cutoff scores are well validated in large Alzheimer's disease and mild cognitive impaired series. Some aspects (e.g., different task formats), however, hamper the comparability of results among different populations and the reproducibility between laboratories. No definite guideline for their use can thus be proposed at the moment. Accordingly, the maturity of such markers is not yet sufficient and requires future investigation to promote the proper use of memory measures in clinical settings.


Photosystem I-LHCII megacomplexes respond to high light and aging in plants.
Photosystem II is known to be a highly dynamic multi-protein complex that participates in a variety of regulatory and repair processes. In contrast, photosystem I (PSI) has, until quite recently, been thought of as relatively static. We report the discovery of plant PSI-LHCII megacomplexes containing multiple LHCII trimers per PSI reaction center. These PSI-LHCII megacomplexes respond rapidly to changes in light intensity, as visualized by native gel electrophoresis. PSI-LHCII megacomplex formation was found to require thylakoid stacking, and to depend upon growth light intensity and leaf age. These factors were, in turn, correlated with changes in PSI/PSII ratios and, intriguingly, PSI-LHCII megacomplex dynamics appeared to depend upon PSII core phosphorylation. These findings suggest new functions for PSI and a new level of regulation involving specialized subpopulations of photosystem I which have profound implications for current models of thylakoid dynamics.


3-Carbamoylquinoxalin-1-ium chloride.
The title compound, C(9)H(8)N(3)O(+)·Cl(-), was isolated from a liquid culture of streptomyces sp. In the cation, the ring system makes a dihedral angle of 0.2 (2)° with the amide group. The protonation creating the cation occurs at ome of the N atoms in the quinoxaline ring system. In the crystal, the ions are linked through N-H⋯O and N-H⋯Cl hydrogen bonds, forming a two-dimensional network parallel to (10[Formula: see text]).


Advances in acid anhydride induced occupational asthma.
The acid anhydrides have been signal occupational agents for study because of their inherent and complex biological activity and the wide range of associated occupational airway disease that is manifest in exposed workers in a variety of occupational settings. This year in review has shed light on many of the complexities of anhydride exposure, biologic reactivity and airway disease.


Memory for objects in canonical and noncanonical viewpoints.
This article investigates how the perspective from which we see an object affects memory. Object identification can be affected by the orientation of the object. Palmer, Rosch, and Chase (1981) coined the term canonical to describe perspectives in which identification performance is best. We present two experiments that tested the effects of object perspective on memory. Our results revealed a double dissociation between task (recognition and recall) and type of object perspective. In recognition, items studied in the noncanonical viewpoint produced higher proportions of "old" responses than did items studied in the canonical viewpoint, whereas new objects presented from a noncanonical viewpoint produced fewer "old" responses than did new objects presented from the canonical viewpoint. In free recall, conversely, objects studied from the noncanonical viewpoint produced lower recall rates than did objects studied from the canonical viewpoint. These results, which reveal a pattern similar to word frequency effects, support the psychological reality of canonical viewpoints and the frequency-of-exposure-based accounts of canonical viewpoint effects.


Plesiomonas shigelloides sipD mutant, generated by an efficient gene transfer system, is less invasive.
Plesiomonas shigelloides is widely associated with human diarrheal disease. Research on this pathogen has been hampered by the absence of an effective genetic manipulation system. In the present study, an efficient and precise conjugation transfer procedure, mediated by suicide vector pRE112 was used to overcome this limitation. The efficiency of generating double recombinants was average 74.3%, and the conjugation protocol may be applied to other P. shigelloides strains. We also identified that the SipD protein of P. shigelloides G5884 (serotype O45) is 65% similar to the SipD in Salmonella pathogenicity island 1 (SPI-1), which is a key element of the type III secretion system related to Salmonella invasion. A P. shigelloides sipD null mutant was generated via the conjugation system, using the suicide vector pRE112. The isogenic mutant strain lacking sipD showed a 50% reduction in its capacity to invade Caco-2 cells.


Feasibility of hydrogen production from ripened fruits by a combined two-stage (dark/dark) fermentation system.
Anaerobic fermentation for hydrogen (H2) production was studied in a two-stage fermentation system fed with different ripened fruit feedstocks (apple, pear, and grape). Among the feedstocks, ripened apple was the most efficient substrate for cumulative H2 production (4463.7 mL-H2 L(-1)-culture) with a maximum H2 yield (2.2 mol H2 mol(-1) glucose) in the first stage at a hydraulic retention time (HRT) of 18 h. The additional cumulative biohydrogen (3337.4 mL-H2 L(-1)-culture) was produced in the second stage with the reused residual substrate from the first stage. The major byproducts in this study were butyrate, acetate, and ethanol, and butyrate was dominant among them in all test runs. During the two-stage system, the energy efficiency (H(2) conversion) obtained from mixed ripened fruits (RF) increased from 4.6% (in the first stage) to 15.5% (in the second stage), which indicated the energy efficiency can be improved by combined hydrogen production process. The RF could be used as substrates for biohydrogen fermentation in a two-stage (dark/dark) fermentation system.


Altered generation of interleukin 1 in chronic human schistosomiasis mansoni.
Chronic schistosomiasis mansoni is associated with impaired cell-mediated immune responsiveness (CMI). To assess co-stimulatory factors essential in the induction phase of CMI, interleukin 1 (IL-1) concentration was determined in the sera and cell culture supernatants of Schistosoma mansoni-infected patients, and circulating monocytes were phenotyped, labelling membrane IL-1 and HLA-DP. In addition, adherent cell oxidative-burst capacity was investigated. Since involvement of IL-1 beta in the pathogenesis of severe granulomatous lesions could not be ruled out, 17 patients with intestinal schistosomiasis and 17 patients with hepatosplenic schistosomiasis were matched for intensity of infection and monitored 3-6 months after praziquantel therapy. Seventeen age- and sex-matched uninfected residents of the study area in Alagoas, Brazil, acted as controls. Whereas schistosomiasis patients and controls did not differ in the expression of monocyte surface antigens and the capacity of adherent cells to generate H2O2, IL-1 beta release by monocytes in vitro was significantly reduced in both intestinal and hepatosplenic patients. Low concentrations of circulating IL-1 beta were detected in comparable frequencies in untreated patients and controls. Three months after therapy, IL-1 beta was detectable in serum in an increased proportion of intestinal schistosomiasis patients. IL-1 release in vitro gradually increased in all patients and reached control values 6 months after therapy.