Escalating carbon emissions from North American boreal forest wildfires and the climate mitigation potential of fire management.
Wildfires in boreal forests release large quantities of greenhouse gases to the atmosphere, exacerbating climate change. Here, we characterize the magnitude of recent and projected gross and net boreal North American wildfire carbon dioxide emissions, evaluate fire management as an emissions reduction strategy, and quantify the associated costs. Our results show that wildfires in boreal North America could, by mid-century, contribute to a cumulative net source of nearly 12 gigatonnes of carbon dioxide, about 3% of remaining global carbon dioxide emissions associated with keeping temperatures within the Paris Agreement's 1.5°C limit. With observations from Alaska, we show that current fire management practices limit the burned area. Further, the costs of avoiding carbon dioxide emissions by means of increasing investment in fire management are comparable to or lower than those of other mitigation strategies. Together, our findings highlight the climate risk that boreal wildfires pose and point to fire management as a cost-effective way to limit emissions.


Early response predicts thalidomide efficiency in patients with advanced multiple myeloma.
Sixty-five patients who were primary or secondary refractory to melphalan/prednisone or other type of chemotherapy, or relapsed within 6 months after high dose chemotherapy with stem cell support, were given thalidomide at a dose of 200 mg/d escalating to 800 mg. The patients were followed for a median of 2 years and 22 weeks. Response was evaluated according to M-protein reduction combined with improvement of haemoglobin (Hb) concentration, renal function and pain. Altogether, 14% of patients had a minor response, 14% partial response and 6% complete response. Median survival was 12 months and 29% were alive at last contact. Decline of M protein started early and a minimum 25% reduction of M protein was detected in 14 of 20 responders (70%) after 3 weeks, and in 20 of 22 responders (91%) after 5 weeks of treatment. Reduction of M protein continued for 3 months and further decline was observed in only four patients. The Hb concentration showed a different time course, with a significant increase after 3 months and further increases continued for up to 12 months. Blood concentration levels of thalidomide from 40 patients were used to evaluate the pharmacokinetics of the drug. Rate of absorption, rate of elimination, volume of distribution, clearance and elimination half-life were calculated to be 0.200/h, 0.140/h, 0.886 l/kg, 0.126 l/h/kg and 4.98 h respectively. We found no relationship between thalidomide concentration and effect after 12 weeks.


GroEL heat shock protein of Haemophilus ducreyi: association with cell surface and capacity to bind to eukaryotic cells.
The Haemophilus ducreyi homolog of GroEL, a 58.5-kDa heat shock protein (Hsp), is a dominant protein produced not only in response to heat stress but also under in vitro growth conditions. Extracellular localization of the 58.5-kDa Hsp was investigated by whole-cell enzyme-linked immunosorbent assay (ELISA) and immunoelectron microscopy and in supernatants of washed bacteria by immunoblotting with a Haemophilus ducreyi GroEL-specific mouse monoclonal antibody (BB11). To investigate binding of the Hsp to eukaryotic cells, the 58.5-kDa Hsp was purified by ion-exchange and size exclusion chromatography; incubated with HEp-2 cells, HeLa cells, and human fibroblasts; and then analyzed by immunoblotting. Direct involvement of the 58.5-kDa Hsp in the adherence of H. ducreyi to HEp-2 cells was investigated by using an inhibition assay. An epitope of the 58.5-kDa Hsp was detected by whole-cell ELISA on all of the strains tested, suggesting that it is associated with the cell surface. This was also supported by immunoelectron microscopy results. In supernatants of washed bacteria, the 58.5-kDa Hsp was detected by immunoblotting after 10 h of cultivation. The 58.5-kDa Hsp bound to the eukaryotic cells tested but exerted only limited (about 20%) inhibition of H. ducreyi adherence to HEp-2 cells. These results demonstrate that the 58.5-kDa Hsp of H. ducreyi is associated with the bacterial surface, binds to eukaryotic cells, and partially influences H. ducreyi adherence to HEp-2 cells, indicating possible involvement of the 58.5-kDa Hsp in the attachment of bacteria to host cells and to each other.


Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study.
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental syndrome that has been studied intensively in order to understand relationships between the genetic microdeletion, brain development, cognitive function, and the emergence of psychiatric symptoms. White matter microstructural abnormalities identified using diffusion tensor imaging methods have been reported to affect a variety of neuroanatomical tracts in 22q11.2DS. In the present study, we sought to combine two discovery-based approaches: (1) white matter query language was used to parcellate the brain's white matter into tracts connecting pairs of 34, bilateral cortical regions and (2) the diffusion imaging characteristics of the resulting tracts were analyzed using a machine-learning method called support vector machine in order to optimize the selection of a set of imaging features that maximally discriminated 22q11.2DS and comparison subjects. With this unique approach, we both confirmed previously-recognized 22q11.2DS-related abnormalities in the inferior longitudinal fasciculus (ILF), and identified, for the first time, 22q11.2DS-related anomalies in the middle longitudinal fascicle and the extreme capsule, which may have been overlooked in previous, hypothesis-guided studies. We further observed that, in participants with 22q11.2DS, ILF metrics were significantly associated with positive prodromal symptoms of psychosis.


Free amino acids of tronchuda cabbage (Brassica oleracea L. Var. costata DC): influence of leaf position (internal or external) and collection time.
The free amino acid profile of 18 samples of tronchuda cabbage ( Brassica oleracea L. var. costata DC) leaves, harvested at three different months, was determined by HPLC/UV-vis. The tronchuda cabbage leaves total free amino acid content varied from 3.3 to 14.4 g/kg fresh weight. Generally, arginine was the major compound, followed by proline, threonine, glutamine, cysteine, and glutamic acid. This study indicates that free amino acids are not similarly distributed: in external leaves, proline and arginine were the major free amino acids, while in internal ones, arginine was the main free amino acid, followed by threonine, glutamine, and cysteine. Significant differences were observed for valine, proline, arginine, leucine, cysteine, lysine, histidine, and tyrosine contents. The levels of some free amino acids were significantly affected by the collection period. In external leaves, this occurred with glutamic acid, serine, valine, leucine, cysteine, and ornithine contents, while in internal leaves, it occurred with aspartic acid, arginine, and total contents.


Study of Echocardiogram Parameters from PPG Signal Using Self-Organized Operational Map-based Network.
Two crucial echocardiography parameters -left ventricular ejection fraction (LVEF) and myocardial performance index (MPI) are referred by clinicians to diagnose heart health. Here, an attempt was made to study the possibility of predicting values of LVEF and MPI from Photoplethysmography (PPG) signals. The classification of patients based on the LVEF and MPI values was also evaluated. After PPG signal feature extraction, the Dual Attention-Self Organised Operational Map-LSTM-Conv Network (DASLCN) was used to find the necessary results. Self-organized operational maps (SOOM) helped map the features before sending them to BiLSTM and 1D CNN layers. The results obtained were regression=0.86 with error% of 5.32±8.9 for MPI and accuracy=0.90 & sensitivity=0.89 for LVEF. This technique might help diagnose heart conditions from PPG signals without routine echocardiography.Clinical relevance- PPG is an easy cost-effective portable technique. Whereas, clinical echocardiography is possible only in specialized hospitals. Thus, exploring PPG signals to predict LVEF and MPI values were tried here. This study has been made on whether the grouping of patients based on the range of LVEF and MPI values was possible or not. Newly designed DASLCN helped to perform regression and classification in the same network.


Intraoperative and perioperative complications during revision arthroplasty for salvage of a failed total ankle arthroplasty.
Revision of a failed total ankle arthroplasty (TAA) remains a challenge. Advances in total ankle implant design have renewed interest in revision TAA as an alternative to ankle arthrodesis or amputation in the management of a failed TAA. The purpose of our study was to review a series of failed Agility TAA revised to INBONE II TAA and identify reasons for revision as well as perioperative complications. A retrospective review of 35 cases of failed Agility TAA revised to an INBONE II TAA was performed at 1 institution. Patient demographics, indications for revision, radiographs, and complications were reviewed. The average follow-up was 9.1 months (range, 0-28 months). All revisions were performed by 1 of 2 foot and ankle surgeons familiar with both prostheses. The Agility TAA lasted a mean of 6.7 years prior to revision to an INBONE II TAA. Revision TAA was indicated due to mechanical loosening, osteolysis, periprosthetic fracture, and a dislocated prosthesis. Adjunctive procedures were performed in 31 of 35 cases. There were 6 intraoperative and 5 acute postoperative complications, leading to an overall 31.4% complication rate. There was 1 patient with continued pain postoperatively who underwent a second revision of the INBONE II 20 months postoperatively. Revision TAA was a viable treatment option for failed TAA. A high risk of perioperative complications remains, and physicians should be aware of the challenges that occur during these procedures in order to plan for them preoperatively. Level IV, retrospective case series.


Intravenous immunoglobulin preparations as immunomodulatory agents.
Certain immunopathologic conditions, such as hypersensitivity and autoimmune diseases, are characterized by quantitative and/or qualitative alterations of immune reactions. It is now believed that such immunologic disturbances generate from inadequate internal control and regulation of immunologic reactivity. Important member of the complex regulatory network that supervises an immune response are antibodies themselves. Since antibody is bifunctional molecule, its regulatory action deals with two separate molecular structures denoted as Fab and Fc portion. By Fab fragment, antibody interferes with the reaction with antigens, or participates in the regulatory idiotype/antiidiotype interactions. Fc-mediated regulation includes influence on complement activation cascade, formation and clearance of immune complexes, phagocytosis, ADCC activity, T- and B-cell function, cytokine profile, etc. In general, antibody triggers immune reactions, but also has the capacity to suppress them. Exogenous antibodies are likely to elicit similar effects on immune processes. Actually, it has been demonstrated that intravenously given immunoglobulins, particularly high-dose IgG, effectively combat harmful immune response in some chronic inflammatory and autoimmune disorders. Hence, preparations of immunoglobulins for intravenous use (IVIG) can be considered as an immunomodulatory agent. To achieve the property of modulating the immune response, IVIG products must contain intact (7S) IgG molecule and maintain sufficient concentrations in plasma.


Salaried general practice in Czechoslovakia: personal observations and impressions.
In 1991, a visit was undertaken, to the former Czechoslovakia, during which discussions were held with general practitioners. Some personal observations and impressions from the visit are presented. For four decades, salaried general practice was a feature of the Czechoslovakian health care system. Primary health care comprised three strands: paediatric services, an occupational health service and community general practitioner care. The main point of service delivery was the polyclinic which, although being large and impersonal, provided easy access to other primary and secondary services. General practitioners, over half of whom were women, had regular leave entitlement and predictable hours of work, out of hours work being provided through separate contracts based on primary care emergency centres. However, doctors were poorly paid compared with industrial workers. Following the 'velvet revolution' in 1989, all aspects of the health service have been subject to major review, and salaried general practice is likely to give way to a more entrepreneurial system.


Ultrashort-pulse lasers treating the crystalline lens: will they cause vision-threatening cataract? (An American Ophthalmological Society thesis).
To demonstrate that ultrashort-pulse laser treatment in the crystalline lens does not form a focal, progressive, or vision-threatening cataract. An Nd:vanadate picosecond laser (10 ps) with prototype delivery system was used. Primates: 11 rhesus monkey eyes were prospectively treated at the University of Wisconsin (energy 25-45 μJ/pulse and 2.0-11.3M pulses per lens). Analysis of lens clarity and fundus imaging was assessed postoperatively for up to 4½ years (5 eyes). Humans: 80 presbyopic patients were prospectively treated in one eye at the Asian Eye Institute in the Philippines (energy 10 μJ/pulse and 0.45-1.45M pulses per lens). Analysis of lens clarity, best-corrected visual acuity, and subjective symptoms was performed at 1 month, prior to elective lens extraction. Bubbles were immediately seen, with resolution within the first 24 to 48 hours. Afterwards, the laser pattern could be seen with faint, noncoalescing, pinpoint micro-opacities in both primate and human eyes. In primates, long-term follow-up at 4½ years showed no focal or progressive cataract, except in 2 eyes with preexisting cataract. In humans, <25% of patients with central sparing (0.75 and 1.0 mm radius) lost 2 or more lines of best spectacle-corrected visual acuity at 1 month, and >70% reported acceptable or better distance vision and no or mild symptoms. Meanwhile, >70% without sparing (0 and 0.5 mm radius) lost 2 or more lines, and most reported poor or severe vision and symptoms. Focal, progressive, and vision-threatening cataracts can be avoided by lowering the laser energy, avoiding prior cataract, and sparing the center of the lens.


TB treatment in a chronic complex emergency: treatment outcomes and experiences in Somalia.
Médecins Sans Frontières (MSF) provides TB treatment in Galkayo and Marere in Somalia. MSF international supervisory staff withdrew in 2008 owing to insecurity but maintained daily communication with Somali staff. In this paper, we aimed to assess the feasibility of treating TB in a complex emergency setting and describe the programme adaptations implemented to facilitate acceptable treatment outcomes. Routinely collected treatment data from 2005-2012 were retrospectively analysed. In multivariate analyses, factors associated with successful outcome (cure or completion versus failure, death and default) were assessed, including the presence of international supervisory staff. Informal interviews were conducted with Somali staff regarding programmatic factors affecting patient management and perceived reasons for default. In total, 6167 patients were admitted (34.8% female; median age 24.0 years [IQR 13.0-38.0 years]). Treatment success was 79% (programme range 69-87%). Presence of international staff did not improve outcomes (adjusted OR 0.85, 95% CI 0.66-1.09; p=0.27). Perceived reasons for default included being away from family, nomadic group, insecurity, travel cost, need to return to grazing land or feeling better. Despite the challenges, a high percentage of patients were successfully treated. Treatment outcomes were not adversely affected by withdrawal of international supervisory staff.


Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection.
The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection. This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was development of SARS-CoV-2 infection. 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for SARS-CoV-2 RT-PCR positivity at screening. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. There were 28 adverse events in CCP and 58 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs. 25.2 days; p=0.49) and COVID-19 (26.3 vs. 25.9 days; p=0.35) were similar for both groups. In this trial, which enrolled persons with recent exposure to a person with confirmed COVID-19, high titer CCP as post-exposure prophylaxis appeared safe, but did not prevent SARS-CoV-2 infection. Clinicaltrial.gov number NCT04323800 .


[Obesity as disease and as social problem].
This text is part of a broader line of study that aims to analyze how and why certain eating habits and bodily practices have become social problems, as is the case with fatness. We will show that the ideas that support the definition of obesity as a chronic and avoidable disease are leading experts and health authorities, and other social workers, to know and to think about its evolution in terms of "global" illness (epidemic) and to consider cultural factors as their main cause (obesogenic environment). Paradoxically, the international and national preventive measures taken are focused on changing individual behavior and, in particular, eating habits. The concepts about the regulation of excess weight and food provide interesting information about a particular understanding of lifestyles and culture and they take into account the current promotion of health patterns.


[Disease concept and definition of irritable bowel syndrome].
Irritable bowel syndrome (IBS) is a disease entity characterized by recurrent abdominal pain or discomfort associated with altered bowel movement, in which no obvious pathogenetic lesion is identified to explain the symptoms. Postulated pathogenesis for IBS are; motility disorder, visceral sensation abnormalities, complex relationship between brain and gut, relationship to personality, and post-infectious abnormalities in the colonic mucosa. Though many possibilities are presented, diagnostic criteria for IBS are entirely based on the subjective symptoms of the patients. Stress or psychological distress seem to play some roles in the pathogenesis, any of the diagnostic criteria for IBS do not include such aspects. Manning's criteria seem to be the first one to mention the diagnostic criteria. Rome consensus (1988) provoked the attention to IBS among the investigators, with followers like Rome II (1999), and BMW(2000) in Japan. Recently, Rome III criteria was published, which is more clinical oriented.


Malignant lymphoma and rheumatic symptoms.
A patient intially thought to have a connective tissue disease, later shown by biopsy to have Hodgkin's disease is described. The progress of her illness suggests that she is suffering from a connective tissue disease, too, or possibly secondary immune complex disease.


Genomic Tagging of AGO1 Using CRISPR/Cas9-Mediated Homologous Recombination.
Tagging of genes at the endogenous loci is a powerful strategy for the analysis of protein function. We have developed a homologous recombination-based approach for inserting epitope tag into Drosophila AGO1 locus by employing the CRISPR/Cas9 technology. The methodology involves co-expression of sgRNA (containing 20-nucleotide AGO1 targeting sequence) and Cas9 protein, together with a donor template that has HA-AGO1 cassette flanked by sequences homologous to the AGO1 locus. The integration is efficient and readily monitored by immunostaining of the transgenic cell line. This method facilitates rapid generation of stable cell lines and allows insertion of any tag sequence into endogenous loci, thus accelerating characterization of the tagged proteins.


Hypotension and Hypocapnia During General Anesthesia in Piglets: Study of S100b as an Acute Biomarker for Cerebral Tissue Injury.
Hypotension and/or hypocapnia might increase general anesthesia (GA)-related neuromorbidity in infants, but safe levels of perioperative blood pressure are poorly defined. Serum protein S100b has been used as screening, monitoring, and prediction tool in the management of patients with traumatic brain injury. Using an animal model, we investigated serum S100b as an acute biomarker of cerebral hypoperfusion and cerebral cell dysfunction during hypotension, hypocapnia, or combined hypotension/hypocapnia during GA. Fifty-seven sevoflurane-midazolam anesthetized piglets aged 4 to 6 weeks were randomly allocated to control (n=9), hypotension (n=18), hypocapnia (n=20), or combined hypotension and hypocapnia (n=10). Hypotension (target mean arterial blood pressure: 35 to 38 or 27 to 30 mm Hg) was induced by blood withdrawal and nitroprusside infusion, and hypocapnia by hyperventilation (target PaCO2: 28 to 30 and 23 to 25 mm Hg). Serum S100b and albumin were measured at baseline, before and 60 minutes after the interventions, and following 60-minute recovery. Serum S100b concentrations decreased over time (P=0.001), but there was no difference in S100b between control piglets and those exposed to hypotension, hypocapnea, or a combination of the both (P=0.105). Albumin decreased in all 4 groups (P=0.001). S100b did not increase following 60 minutes of systemic hypotension and/or hypocapnia during GA in piglets. In this setting, the use of S100b as a biomarker of cerebral cell tissue dysfunction cannot be supported.


Flavor preferences conditioned by postingestive effect of sucrose and porcine digestive peptides in postweaning pigs.
Pigs can learn to prefer a flavor if it has been previously associated to positive consequences. The aim of this experiment was to study flavor preferences conditioned by the postingestive effect of nutrients in pigs. In total, 240 weanling piglets were allocated in 24 pens (10 piglets/pen) and distributed to 2 groups of animals (12 pens per group). Pigs in Group 1 (G1) were trained during 8 d with one flavor [positive conditioned stimulus (CS+)] into a protein solution [4% porcine digestible peptides (PDP)] on odd days and another flavor [negative conditioned stimulus (CS-)] into 100 mM of monosodium glutamate (MSG) solution on even days (5-L bottle for 24 h). In the second group of pigs [Group 2 (G2)], CS+ was mixed into a 4% sucrose solution in odd days and CS- into 1% sucrose + 0.08% saccharine on even days. Therefore, treatments were defined as CS+, the flavor associated with PDP or sucrose, on odd days, which were assumed to have a higher postingestive effect than MSG or saccharine + sucrose, the ingredients associated to CS-. Concentration of ingredients in the solutions were chosen to ensure that hedonic attraction for PDP and MSG solutions and for sucrose and saccharine + sucrose were similar (checked in previous double-choice studies). The amount of solution offered during training period was prepared to be totally consumed each day to equalize flavors intake. Flavors (0.0375% anise or garlic) were counterbalanced across replicates to act as CS+ or CS-. Double-choice test between flavors dissolved in water (CS+ and CS-) were performed by selecting 2 pigs/pen on days 1, 6, and 8 after the training period. Solution intake was measured after 30 min. Piglets showed higher intakes for CS+ than CS- in G2 [212 vs. 76 mL and 168 vs. 86 mL (P < 0.05) and 195 vs. 78 mL (P = 0.15)] on days 1, 6, and 8, respectively. Differences between CS+ and CS- consumption were observed in G1 on day 8 (231 vs. 130 mL; P < 0.05). In conclusion, weanling pigs can acquire flavor preferences through associative learning between a flavor and postingestive effects of some nutrients.


Identification of plant defence regulators through transcriptional profiling of Arabidopsis thaliana cdd1 mutant.
A sustainable balance between defence and growth is essential for optimal fitness under pathogen stress. Plants activate immune response at the cost of normal metabolic requirements. Thus, plants that constitutively activate defence are deprived of growth. Arabidopsis thaliana mutant constitutive defence without defect in growth and development1 (cdd1) is an exception. The cdd1 mutant is constitutive for salicylic acid accumulation, signalling, and defence against biotrophic and hemibiotrophic pathogens, without having much impact on growth. Thus, cdd1 offers an ideal genetic background to identify novel regulators of plant defence. Here we report the differential gene expression profile between cdd1 and wild-type plants as obtained by microarray hybridization. Expression of several defence-related genes also supports constitutive activation of defence in cdd1. We screened T-DNA insertion mutant lines of selected genes, for resistance against virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Through bacterial resistance, callose deposition and pathogenesis-associated expression analyses, we identified four novel regulators of plant defence. Resistance levels in the mutants suggest that At2g19810 and [rom] At5g05790 are positive regulators, whereas At1g61370 and At3g42790 are negative regulators of plant defence against bacterial pathogens.


A Preliminary Study of Effects of Channel Number and Location on the Repeatability of Motor Unit Number Index (MUNIX).
Motor Unit Number Index (MUNIX) is a technique that provides a susceptive biomarker for monitoring innervation conditions in patients with neurodegenerative diseases. A satisfactory repeatability is essential for the interpretation of MUNIX results. This study aims to examine the effect of channel number and location on the repeatability of MUNIX. In this study, 128 channels of high-density surface electromyography (EMG) signals were recorded from the biceps brachii muscles of eight healthy participants, at 10, 20, 30, 40, 50, 60, 70, 80, and 100% of maximal voluntary contraction. The repeatability was defined by the coefficient of variation (CV) of MUNIX estimated from three experiment trials. Single-channel MUNIX (sMUNIX) was calculated on a channel-specific basis and a multi-channel MUNIX (mMUNIX) approach as the weighted average of multiple sMUNIX results. Results have shown (1) significantly improved repeatability with the proposed mMUNIX approach; (2) a higher variability of sMUNIX when the recording channel is positioned away from the innervation zone. Our results have demonstrated that (1) increasing the number of EMG channels and (2) placing recording channels close to the innervation zone (IZ) are effective methods to improve the repeatability of MUNIX. This study investigated two potential causes of MUNIX variations and provided novel perspectives to improve the repeatability, using high-density surface EMG. The mMUNIX technique proposed can serve as a promising tool for reliable neurodegeneration evaluation.


Inhibitory effects of Woodward's reagent K on carrier-mediated anion transport in rabbit intestinal brush border membrane vesicles.
Woodward's reagent K (N-ethyl-5-phenylisoxazolium 3'-sulfonate) is a negatively charged reagent that covalently and irreversibly modifies carboxyl-containing amino acid residues. Under conditions of an outwardly directed hydroxide (OH.) gradient (pHin > pHout), folate uptake by jejunal brush border membrane (BBM) vesicles is mediated by a folate:OH. exchanger or a phenomenologically indistinguishable proton (H+):folate cotransporter. Under these pH conditions, Woodward's reagent K rapidly inhibits folate uptake in a pH-, temperature- and concentration-dependent manner. Rabbit BBM vesicles were prepared using the divalent cation precipitation method. Vesicle uptake of 3H-folate was measured by a rapid filtration technique. Radioactivity was gauged using a liquid scintillation counter. The initial rate of OH. gradient-stimulated folate uptake remained linear in the presence or absence of Woodward's reagent K, suggesting that Woodward's reagent K inhibition is not secondary to more rapid dissipation of the transmembrane pH gradient. Woodward's reagent K also inhibited other modes of transport mediated by the folate carrier, 3H-folate:folate exchanger, ileal sulfate (SO)4(2):OH. exchanger, but neither sodium (Na+):glucose, Na+:SO4(2.) nor Na(+):alanine cotransporters, were inhibited by 3 mM Woodward's reagent K. The inhibition of intestinal anion exchangers by Woodward's reagent K suggests a critical role for carboxyl group--containing amino acids in these transport processes.


Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition.
The main psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), can impair driving performance. Cannabidiol (CBD), a non-intoxicating cannabis component, is thought to mitigate certain adverse effects of THC. It is possible then that cannabis containing equivalent CBD and THC will differentially affect driving and cognition relative to THC-dominant cannabis. The present study investigated and compared the effects of THC-dominant and THC/CBD equivalent cannabis on simulated driving and cognitive performance. In a randomized, double-blind, within-subjects crossover design, healthy volunteers (n = 14) with a history of light cannabis use attended three outpatient experimental test sessions in which simulated driving and cognitive performance were assessed at two timepoints (20-60 min and 200-240 min) following vaporization of 125 mg THC-dominant (11% THC; < 1% CBD), THC/CBD equivalent (11% THC, 11% CBD), or placebo (< 1% THC/CBD) cannabis. Both active cannabis types increased lane weaving during a car-following task but had little effect on other driving performance measures. Active cannabis types impaired performance on the Digit Symbol Substitution Task (DSST), Divided Attention Task (DAT) and Paced Auditory Serial Addition Task (PASAT) with impairment on the latter two tasks worse with THC/CBD equivalent cannabis. Subjective drug effects (e.g., "stoned") and confidence in driving ability did not vary with CBD content. Peak plasma THC concentrations were higher following THC/CBD equivalent cannabis relative to THC-dominant cannabis, suggesting a possible pharmacokinetic interaction. Cannabis containing equivalent concentrations of CBD and THC appears no less impairing than THC-dominant cannabis, and in some circumstances, CBD may actually exacerbate THC-induced impairment.


Cost-effectiveness implications of increasing the efficiency of the extended-release naltrexone induction process for the treatment of opioid use disorder: a secondary analysis.
In a US randomized-effectiveness trial comparing extended-release naltrexone (XR-NTX) with buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse among participants recruited during inpatient detoxification (CTN-0051), the requirement to complete opioid detoxification prior to initiating XR-NTX resulted in lower rates of initiation of XR-NTX (72% XR-NTX versus 94% BUP-NX). This was a retrospective secondary analysis of CTN-0051 trial data, including follow-up data over 24-36 weeks. Eight community-based, inpatient-detoxification and follow-up outpatient treatment facilities in the United States. A total of 283 participants randomized to receive XR-NTX. Efficiency was estimated using a multivariable generalized structural equation model to explore simultaneous determinants of XR-NTX induction and induction duration (detoxification + residential days). Cost-effectiveness was estimated from the health-care sector perspective and included expected costs and quality-adjusted life-years (QALYs). Treatment site was the only modifiable factor that simultaneously increased the likelihood of XR-NTX induction and decreased induction duration. Incorporating the higher predicted probability of XR-NTX induction, and fewer predicted days of detoxification and subsequent residential treatment into the cost-effectiveness framework, reduced the incremental average 24-week total cost of XR-NTX treatment from $5317 more than that of BUP-NX (P = 0.01) to a non-statistically-significant difference of $1016 (P = 0.63). QALYs gained remained similar across arms. Adopting an efficient model of extended-release naltrexone initiation could result in extended-release naltrexone and buprenorphine-naloxone being of comparable economic value from the health-care sector perspective over 24-36 weeks for patients seeking treatment for opioid use disorder at an inpatient detoxification facility.


[Ventricular septal defect developed due to coronary artery injury after blunt chest trauma in childhood].
In the literature, cardiac response associated with blunt chest trauma in children has been reported generally as case reports, and interventricular septal rupture due to trauma is quite rare. Interventricular septal rupture can develop even in the absence of visible signs of a trauma because of the flexibility of the chest structure in children. In the present case, a seven-year-old boy with interventricular septal rupture at the mid-muscular region and left ventricle pseudoaneurysm developed due to injury to the left anterior descending coronary artery after a traffic accident is reported. Patients with cardiac murmur detected on physical examination after a blunt chest trauma must be considered as cardiac injury, and in those with signs of ischemia detected on electrocardiography, it should not be forgotten that the coronary artery may be affected.


Carbohydrate ingestion and single muscle fiber glycogen metabolism during prolonged running in men.
The aim of this study was to examine the effect of carbohydrate (CHO) ingestion on glycogen degradation in type I and type II muscle fibers during prolonged running by using a quantitative biochemical method. To this end, eight male subjects ran at 70% maximal oxygen uptake to exhaustion on a motorized treadmill on two occasions, 1 wk apart. On each occasion, the subjects ingested 8 ml/kg body wt of either placebo (Pl) or a 5.5% CHO-electrolyte solution (CHO-E) immediately before the start of the run and 2 ml/kg body wt every 20 min thereafter. Needle biopsy samples were obtained from the vastus lateralis muscle before and after each trial and also at the time coinciding with Pl exhaustion in the CHO-E trial. Running time to exhaustion was longer (P < 0.01) in the CHO-E trial compared with the Pl trial (132.4 +/- 12.3 and 104.3 +/- 8.6 min, respectively). A 25% reduction in glycogen utilization in type I fibers only was observed in the CHO-E trial compared with the Pl trial (215.2 +/- 27.5 vs. 285.4 +/- 30.1 mmol/kg dry wt; P < 0.01). Furthermore, in the CHO-E trial, in contrast to the Pl trial, both muscle ATP and phosphocreatine concentrations were well maintained throughout exercise. Therefore, because in both the Pl and CHO-E trials the type I fibers were glycogen depleted at the point of exhaustion (31.6 +/- 10.3 and 28.1 +/- 7.1 mmol/kg dry wt, respectively), it is proposed that CHO ingestion improved endurance capacity by contributing to oxidative ATP production specifically in type I fibers and by doing so delayed the development of glycogen depletion in this fiber type.


Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation.
Regulated mRNA turnover is a highly important process, but its mechanism is poorly understood. Using interleukin-2 (IL-2) mRNA as a model, we described a role for the JNK-signaling pathway in stabilization of IL-2 mRNA during T-cell activation, acting via a JNK response element (JRE) in the 5' untranslated region (UTR). We have now identified two major RNA-binding proteins, nucleolin and YB-1, that specifically bind to the JRE. Binding of both proteins is required for IL-2 mRNA stabilization induced by T-cell activation signals and for JNK-induced stabilization in a cell-free system that duplicates essential features of regulated mRNA decay. Nucleolin and YB-1 are required for formation of an IL-2 mRNP complex that responds to specific mRNA stabilizing signals.


Relationship between depression in patients with COPD and the percent of predicted FEV(1), BODE index, and health-related quality of life.
We investigated the prevalence of depression among patients with COPD treated in long-term in-patient rehabilitation facilities, using the Center for Epidemiologic Studies Depression scale (CES-D). Furthermore, the relationship between the severity of air-flow obstruction (the percent of predicted FEV(1)), BODE (body mass index, degree of air-flow obstruction, dyspnea, exercise capacity) index, health-related quality of life (St George's Respiratory Questionnaire [SGRQ]), and depression were investigated. We recruited 74 in-patients (64 males, 10 females) with COPD. The mean age of the subjects was 72.7 years (range 52-85 y). Subjects completed the CES-D, and measurements were made of pulmonary function, body mass index, Modified Medical Research Council dyspnea scale, 6-min walk test (6MWT), and SGRQ. Depression was evident in 48.6% (n = 36) of the subjects. A weak correlation was found between the CES-D scores and the percent of predicted FEV(1). The prevalence of depression showed a significant association with BODE stage. Scores for the SGRQ activity and impacts domains, and total SGRQ score were significantly worse in the subjects who were depressed. We found a high prevalence of depression among patients with stable COPD treated in long-term in-patient rehabilitation facilities. Depression among these patients, as measured by the CES-D, was associated with greater impairment in respiratory function and with poorer Modified Medical Research Council dyspnea scale and SGRQ scores. The prevalence of depression increased with BODE stage.


An evaluation of the ability of a series of full alpha-1 adrenoceptor agonists to release internal calcium in venous smooth muscle.
Our previous studies have shown that activation of postsynaptic alpha-2 adrenoceptors mainly utilizes extracellular calcium whereas activation of postsynaptic alpha-1 adrenoceptors mobilizes both extracellular and intracellular calcium to produce contractions in the canine saphenous vein. In the present study, the abilities of several full alpha-1 adrenoceptor agonists to release internal calcium for contractions in the canine saphenous vein were evaluated. Contractions to these alpha-1 agonists at two different equieffective concentrations (concentrations that produced 50 and 80% of the maximum phenylephrine response, PE50 and PE80, respectively) were determined in both zero external calcium medium and in normal calcium medium containing 5 mM La . If a correlation exists between the efficacy of an agonist and its ability to release internal Ca++, the contractile response to each agonist should be similar under these conditions. The results indicated marked variations in mechanical responses elicited by these alpha-1 agonists at both PE50 and PE80 concentrations. The data suggest a lack of correlation between efficacy and the ability to release internal calcium to induce contractions for a series of full alpha-1 adrenoceptor agonists in venous smooth muscle.


Prevalence and predictors of anxiety and depression among cervical cancer survivors in Korea.
With increasing survival rates of women with cervical cancer, quality of life of the survivors becomes a more important issue. However, little is known about the mental health of cervical cancer survivors (CCSs). This study investigated the prevalence of anxiety and depression in CCSs compared with healthy controls and identified factors associated with multidimensional model including sociodemographic, clinical, functioning and well-being, and symptom variables. The participants included 828 CCSs (mean time since treatment, 6.9 years) enrolled at 6 tertiary hospitals from 1983 to 2004 and 500 control subjects selected randomly from a representative sample of Korean women. Subjects completed the following questionnaires: the Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30, its Cervical Cancer module, and the McGill Quality of Life Questionnaire. Hospital Anxiety and Depression Scale-defined anxiety in CCSs did not differ from that in healthy controls (39.5% and 32.2%, respectively; P = 0.218). Anxiety was significantly more prevalent in younger CCSs (< or = 50 years) than in controls (40% vs 26.4%, respectively; P < 0.001). Hospital Anxiety and Depression Scale-defined depression was even lower in CCSs than in controls (34.6% vs 48.0%, respectively; P < 0.001). In multivariate analyses, the Hospital Anxiety and Depression Scale-defined anxiety and depression in CCSs were commonly associated with financial difficulty, poor body image, sexual inactivity, and low existential well-being. Low support and insomnia were uniquely related to anxiety, with older age and decrement role function uniquely related to depression. However, disease-related clinical factors were not related to either anxiety or depression. Cervical cancer survivors showed relatively good mental health compared with healthy controls; however, women who have low functioning and well-being could be at high risk of anxiety or depression or both.


Failed angioembolization of a ruptured liver hemangioma complicated by iatrogenic injury of subclavian vein during catheter insertion.
In this study, we report a case of failed angioembolization of a ruptured liver hemangioma complicated by iatrogenic injury of the subclavian vein during catheter insertion. A 30-year-old woman experienced blunt trauma upon falling from her bed. Laceration of a seemingly preexisting hepatic hemangioma was diagnosed. No other injury was detected during a preoperative diagnostic workup. Subclavian vein catheterization was performed, followed by angioembolization to control bleeding due to the ruptured hemangioma. After angioembolization, the patient's systolic blood pressure and hemoglobin levels were 70 mmHg and 5.3 g/dL, respectively. She underwent emergency laparotomy. During the surgery, a large volume of blood in the abdominal cavity due to profuse bleeding from the ruptured hemangioma was observed. Because of a hemothorax found on chest radiography, we performed thoracoscopy, which revealed a large volume of blood in the right thoracic cavity and perforation of the subclavian vein by the catheter. After the damage-control surgery, the patient recovered safely. In this case, ruptured liver hemangioma complicated by subclavian vein catheter-related injury was treated safely using damage-control surgery. The catheter-related injury could be identified and treated using thoracoscopy.


Soil-transmitted helminth infections among malaria patients determined by microscopy and real-time PCR methods at two district hospitals in Sarawak, Malaysia.
Malaria is still endemic in Sarawak and Sabah. Numerous studies have indicated that patients with malaria are commonly co-infected with helminthes particularly in endemic regions. The aim of this study was to investigate the incidence of soil-transmitted helminth (STH) infection among malaria patients using microscopy and multiplex real-time PCR at two district hospitals in Sarawak. A total of 94 patients who were clinically-suspected to have malaria were confirmed to be infected by both microscopy and multiplex real-time PCR. By the molecular method, 23.4%, 74.5% and 2.1% of the samples were positive for Plasmodium falciparum, P. vivax and mixed P. falciparum and P. vivax, respectively. Among the malaria patients, 48.9% were found to be co-infected with STHs. In comparison, microscopic examinations showed that 6.4% of the malaria patients were infected with STHs. From the real-time PCR positive samples, 31.9% had single helminth infections while 17% had mixed infections. In conclusion, this study showed that almost half of the malaria patients at the two Sarawak hospitals were co-infected with helminth. Future studies should be specifically designed to determine if there is any correlation between the two infections in terms of incidence and intensity.


Is it safe to use long-acting beta-agonists in asthma and chronic obstructive pulmonary disease? Implications of recent trials and meta-analyses.
The safety of long-acting beta-agonists (LABAs) has been hotly debated for several years, with surveillance studies suggesting increased risk of mortality, especially with use of LABA without inhaled corticosteroid (ICS). Meta-analyses of selected trials, especially those dominated by one large study, report significantly increased risks for mortality and Serious Adverse Events (SAEs). Review of all of the available evidence from clinical trials, and meta-analyses using different selection criteria, suggests that LABA with ICS in fact significantly reduces SAEs. The risk of mortality is more difficult to assess, but post-hoc analyses suggest the risk is increased with LABA monotherapy and not with concomitant use of ICS. In both asthma and chronic obstructive pulmonary disease, concomitant use of ICS should be considered best practice whenever LABAs are used.


[Roentgeno-bronchological observations in experimental autotransplantation of the lung and its lobe].
Roentgenological studies were conducted after 260 autotransplantations of the lung and its lobe, performed experimentally and observed in dynamics during the period up to 4.5 years. Following autotransplantation of the lung in an uncomplicated postoperative period within the terms up to 15 days an intensified and indistinct pulmonary pattern with the presence of small-foci shadows is observed. Further observations for a period up to 4.5 years revealed neither changes on the part of pulmonary tissues nor anatomical or functional changes in the bronchial tree and vessels. In later terms after ortho- and heterotopic autotransplantation of the lower pulmonary lobe changes due to resection of the upper and cardiac lobe were observed, being manifested in displacement of a portion of the intact lung upper lobe into the upper portion of the left pleural cavity. Following heterotopic autotransplantation of the lower pulmonary lobe in the site of the removed lung no changes in the autotransplanted pulmonary lobe were noted in later periods. The signs of mediastinal hernia were less pronounced than after orthotopic autotransplantation of the pulmonary lobe.


Naturally derived biofunctional nanofibrous scaffold for skin tissue regeneration.
Significant wound healing activity of Aloe vera (AV) and higher elastic strength of Silk fibroin (SF) along with mammalian cell compatibility makes AV and SF an attractive material for tissue engineering. The purpose of the present work was to combine their unique properties, with the advantage of electrospinning to prepare a hybrid transdermal biomaterial for dermal substitutes. The physico-chemical characterization of the developed scaffold showed finer morphology expressing amino and esteric groups with improved hydrophilic properties and favorable tensile strain of 116% desirable for skin tissue engineering. Their biological response showed favorable fibroblast proliferation compared to control which almost increased linearly by (p<0.01) 34.68% on day 3, (p<0.01) 19.13% on day 6, and (p<0.001) 97.86% on day 9 with higher expression of CMFDA, collagen and F-actin proteins. The obtained results prove that the nanofibrous scaffold with synergistic property of AV and SF would be a potential biomaterial for skin tissue regeneration.


Pathology of abortion: chromosomal and genetic correlations.
The examination of spontaneous abortion specimens is as important as doing perinatal autopsies or surgicals in today's practice of medicine. The results of the pathologist's examination assist obstetricians in specific follow-up of future pregnancies and geneticists in predicting the chances of specific developmental defects or repeat pregnancy loss. Without the information provided by the pathologist, the other specialists can offer no real assistance. More extensive use of cytogenetic analysis of placentas may help explain intrauterine fetal death in pregnancies with confined placental mosaicism, which complicates one to two percent of pregnancies. A brief review of morphologic and genetic differences between partial and complete moles emphasizes the disparate origins of these distantly related conditions.


Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer.
An acidic extracellular pH is a fundamental property of the malignant phenotype. In von Hippel-Lindau (VHL)-defective tumors the cell surface transmembrane carbonic anhydrase (CA) CA9 and CA12 genes are overexpressed because of the absence of pVHL. We hypothesized that these enzymes might be involved in maintaining the extracellular acidic pH in tumors, thereby providing a conducive environment for tumor growth and spread. Using Northern blot analysis and immunostaining with specific antibodies we analyzed the expression of CA9 and CA12 genes and their products in a large sample of cancer cell lines, fresh and archival tumor specimens, and normal human tissues. Expression was also analyzed in cultured cells under hypoxic conditions. Expression of CA IX and CA XII in normal adult tissues was detected only in highly specialized cells and for most tissues their expression did not overlap. Analysis of RNA samples isolated from 87 cancer cell lines and 18 tumors revealed high-to-moderate levels of expression of CA9 and CA12 in multiple cancers. Immunohistochemistry revealed high-to-moderate expression of these enzymes in various normal tissues and multiple common epithelial tumor types. The immunostaining was seen predominantly on the cell surface membrane. The expression of both genes was markedly induced under hypoxic conditions in tumors and cultured tumor cells. We conclude that the cell surface trans-membrane carbonic anhydrases CA IX and CA XII are overexpressed in many tumors suggesting that this is a common feature of cancer cells that may be required for tumor progression. These enzymes may contribute to the tumor microenvironment by maintaining extracellular acidic pH and helping cancer cells grow and metastasize. Our studies show an important causal link between hypoxia, extracellular acidification, and induction or enhanced expression of these enzymes in human tumors.


Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma.
Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets.


Cyclic uridine-3',5'-phosphate: molecular structure.
The crystal structure of the triethylammonium salt of cyclic uridine-3',5'-phosphate was solved by use of the tangent formula to refine phase angles based upon the positions of six of the atoms. The two independent uracil rings are planar and in the keto form. The base-sugar torsion angles are in the anti range. The sugar puckering is C3'-endo, and the ribose conformation about the C5'-C4' bond is transgauche.


Deformable boundary detection of stents in angiographic images.
In this paper, a procedure is described for deformable boundary detection of medical tools, called stents, in angiographic images. A stent is a surgical stainless steel coil that is placed in the artery in order to improve blood circulation in regions where a stenosis has appeared. Assuming initially a set of three-dimensional (3-D) models of stents and using perspective projection of various deformations of the 3-D model of the stent, a large set of synthetic two-dimensional (2-D) images of stents is constructed. These synthetic images are then used as a training set for deriving a multivariate Gaussian density estimate based on eigenspace decomposition and formulating a maximum-likelihood estimation framework in order to reach an initial rough estimate for automatic object recognition. The silhouette of the detected stent is then refined by using a 2-D active contour (snake) algorithm integrated with a novel iterative initialization technique, which takes into consideration the geometry of the stent. The algorithm is experimentally evaluated using real angiographic images containing stents.


Homocysteine and related B-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery.
Hyperhomocysteinaemia is considered to be a risk factor for cardiovascular disease (particularly stroke) and has been implicated in recurrent miscarriage and osteoporotic fracture, recognized manifestations of coeliac disease (CD). The objective of this study was to compare plasma homocysteine levels and biomarker status of metabolically related B vitamins (folate, vitamin B(12), B(6) and riboflavin) in treated and untreated CD patients and healthy controls. CD patients attending a clinic for either initial or follow-up biopsy (at least 12 months after commencing a gluten-free diet) were categorized into three groups: 1) newly diagnosed (untreated; n=35); 2) persistent villous atrophy (VA) at follow-up (n=24) or 3) recovered VA at follow-up (n=41). Blood samples were analysed for plasma homocysteine, serum and red cell folate and serum vitamin B(12) levels, and for plasma pyridoxal 5-phosphate (PLP, vitamin B(6)) and riboflavin (vitamin B(2)) status. Homocysteine concentrations were significantly higher (p=0.05) and red cell and serum folate significantly lower (p<0.001) in untreated patients compared with controls, while all three reached normal levels in recovered VA patients. Although untreated and persistent VA patients tended to have lower B(12) levels, these did not reach significance. There was no evidence of compromised B(6) or riboflavin status, even in untreated CD patients. Homocysteine concentrations were inversely associated with both serum (r=-0.421; p<0.001) and red cell (r=-0.459; p<0.001) folate and with serum vitamin B(12) (r=-0.353; p=0.001). Gluten exclusion in CD improves folate status and normalizes homocysteine concentrations. Reducing the risk of homocysteine-related disease may be another reason for aggressive diagnosis and treatment of CD.


Dietary addition of zinc-methionine influenced eggshell quality by affecting calcium deposition in eggshell formation of laying hens.
The present study explored the mechanism of Zn-methionine (Zn-Met) influencing eggshell quality of laying hens and investigated whether the mechanism was related to Ca deposition. Hyline grey layers (n 384, 38 weeks old) were divided into four groups: 0 mg Zn/kg, 40, 80 mg Zn/kg as Zn-Met, and 80 mg Zn/kg as zinc sulphate (ZnSO4). Eggshell quality, Zn contents, Zn-containing enzyme activities and expressions of shell matrix proteins in eggshell gland (ESG) were analysed. Zn-Met treatment at 80 mg/kg increased (P < 0·05) egg weight and eggshell strength throughout the experiments. The 80 mg/kg Zn-Met group (P < 0·05) had decreased mammillary knob width and larger relative atomic weight percentage of Ca, stronger signal intensity of Ca in linear distribution and the Ca was more evenly distributed in the transversal surface of eggshell. Zn contents (P < 0·001) in yolk and serum, Ca, albumin (Alb) levels in ESG as well as carbonic anhydrase (CA) activity in serum (P < 0·05) and mRNA levels of CA and Ca-binding protein-d28k (CaBP-D28k) (P < 0·001) in the 80 mg/kg Zn-Met group were the highest among all treatments. In conclusion, shell strength as one of eggshell qualities was mostly related to mammillary cone width in ultrastructure caused by the pattern of Ca deposition in eggshell formation. Also, the increase in Zn-Met-induced Ca deposition may be due to the increased Zn contents in serum and tissues, which were attributable to the increased CA concentrations in serum, Ca, Alb levels and up-regulated CA and CaBP-D28k mRNA levels in ESG.


Metabolic flux analysis of Escherichia coli in glucose-limited continuous culture. II. Dynamic response to famine and feast, activation of the methylglyoxal pathway and oscillatory behaviour.
The metabolic dynamics of the Escherichia coli K-12 strain TG1 to feast and famine were studied in glucose-limited steady-state cultures by up- and downshifts of the dilution rate, respectively. An uncoupling of anabolic and catabolic rates was observed upon dilution rate upshifts, apparent through immediately increased glucose uptake rates which were not accompanied by an immediate increase of the growth rate but instead resulted in the temporary excretion of methylglyoxal, D- and L-lactate, pyruvate and, after a delay, acetate. The energetic state of the cell during the transient was followed by measuring the adenylate energy charge, which increased within 2 min after the upshift and declined thereafter until a new steady-state level was reached. In the downshift experiment, the adenylate energy charge behaved inversely; no by-products were formed, indicating a tight coupling of anabolism and catabolism. Both dilution rate shifts were accompanied by an instantaneous increase of cAMP, presaging the subsequent changes in metabolic pathway utilization. Intracellular key metabolites of the Embden-Meyerhof-Parnas (EMP) pathway were measured to evaluate the metabolic perturbation during the upshift. Fructose 1,6-diphosphate (FDP) and dihydroxyacetone phosphate (DHAP) increased rapidly after the upshift, while glyceraldehyde 3-phosphate decreased. It is concluded that this imbalance at the branch-point of FDP induces the methylglyoxal (MG) pathway, a low-energy-yielding bypass of the lower EMP pathway, through the increasing level of DHAP. MG pathway activation after the upshift was simulated by restricting anabolic rates using a stoichiometry-based metabolic model. The metabolic model predicted that low-energy-yielding catabolic pathways are utilized preferentially in the transient after the upshift. Upon severe dilution rate upshifts, an oscillatory behaviour occurred, apparent through long-term oscillations of respiratory activity, which started when the cytotoxic compound MG reached a threshold concentration of 1.5 mg l(-1) in the medium.


Momordica balsamina improves glucose handling in a diet-induced prediabetic rat model.
Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological treatment and dietary interventions are recommended to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Momordica balsamina (MB) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this medicinal plant in conjunction with dietary intervention on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects of MB on glucose homeostasis in a diet-induced pre-diabetes rat model in the presence and absence of dietary intervention. Pre-diabetes was induced on male Sprague Dawley rats by a high fat high carbohydrate (HFHC) diet for a period of 20 weeks. Pre-diabetic male Sprague Dawley rats were treated with MB (250 mg/kg p.o.) in both the presence and absence of dietary intervention once a day every third day for a period of 12 weeks. The administration of MB with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, with reduced plasma ghrelin concentration and glycated hemoglobin by comparison to the pre-diabetic control. MB administration also improved insulin sensitivity as evidenced by the expression of glucose transporter 4 (GLUT 4) and glycogen synthase on the prediabetic treated animals. These results suggest that MB has the potential to be used to manage pre-diabetes and prevent the progression to overt type 2 diabetes as it demonstrated the ability to restore glucose homeostasis even in the absence of dietary and lifestyle intervention.


Detailed TIMS study of Ar/C(2)H(2) expanding thermal plasma: identification of a-C:H film growth precursors.
Acetylene chemistry is studied by means of threshold ionization mass spectrometry (TIMS) in remote Ar/C(2)H(2) expanding thermal plasma to identify the growth precursors of hydrogenated amorphous carbon (a-C:H) films. More than 20 hydrocarbon species are measured, enabling a comprehensive study of acetylene chemistry in the plasma environment. It is shown that the plasma composition is controlled by the initial ratio between the acetylene flow into the reactor and argon ion and electron fluence emanating from the remote plasma source. Complete decomposition of acetylene to C, CH, CH(2), C(2), and C(2)H radicals is achieved in subsequent charge transfer and dissociative recombination reactions under low acetylene flow conditions. The formation of soft polymer-like a-C:H films can be attributed to C, C(2), and also partially to CH and C(2)H deposition. At acetylene flows higher than argon ion and electron fluence, reactions of C, CH, C(2), and C(2)H radicals with acetylene lead to the formation of various hydrocarbon species, whose behavior is dependent on whether the number of carbon atoms is even or odd. The detected resonantly stabilized C(3), C(3)H, and probably also C(5) and C(5)H radicals are unreactive with acetylene in the gas phase and are, therefore, abundantly present close to the substrate. The C(3) radical has among them the highest density, and it is identified as the significant growth precursor of Ar/C(2)H(2) expanding thermal plasma deposited hard a-C:H films.


[Effect of an abrupt rise in 2,4-dinitrophenol concentration on the growth of a turbidostat Saccharomyces cerevisiae culture].
The purpose of the work was to study the effect of an abrupt rise in 2,4-dinitrophenol concentration on the growth of a turbidostat Saccharomyces cerevisiae 14 culture. The action of DNP caused three types of response. The growth of S. cerevisiae 14 ceased when DNP concentration was raised once to 10 mg per litre at 30 degrees C and pH 4, but did not stop if that was done in a gradual manner. It took at least 0.25 to 0.5 h for the culture to develop a protection against the action of DNP at a concentration of 10 mg per litre, and a minimal DNP concentration inducing the protection was from 0.6 to 0.9 mg per litre. The pH factor could also induce DNP protection. The dynamics of changes in DNP concentration was followed up in the cells in the course of transient processes. Apparently, the ability of yeast cells to grow in media with DNP is determined by the inhibitor concentration within the first 1.5 h. Apparently, adaptation of the culture to DNP is realised due to changes in the properties of the cell membrane complex.


Gender differences in depression in representative national samples: Meta-analyses of diagnoses and symptoms.
In 2 meta-analyses on gender differences in depression in nationally representative samples, we advance previous work by including studies of depression diagnoses and symptoms to (a) estimate the magnitude of the gender difference in depression across a wide array of nations and ages; (b) use a developmental perspective to elucidate patterns of gender differences across the life span; and (c) incorporate additional theory-driven moderators (e.g., gender equity). For major depression diagnoses and depression symptoms, respectively, we meta-analyzed data from 65 and 95 articles and their corresponding national data sets, representing data from 1,716,195 and 1,922,064 people in over 90 different nations. Overall, odds ratio (OR) = 1.95, 95% confidence interval (CI) [1.88, 2.03], and d = 0.27 [0.26, 0.29]. Age was the strongest predictor of effect size. The gender difference for diagnoses emerged earlier than previously thought, with OR = 2.37 at age 12. For both meta-analyses, the gender difference peaked in adolescence (OR = 3.02 for ages 13-15, and d = 0.47 for age 16) but then declined and remained stable in adulthood. Cross-national analyses indicated that larger gender differences were found in nations with greater gender equity, for major depression, but not depression symptoms. The gender difference in depression represents a health disparity, especially in adolescence, yet the magnitude of the difference indicates that depression in men should not be overlooked. (PsycINFO Database Record


Using arts-based research to access sense of coherence in marginalised indigenous Bedouin youth.
The literature describes a mismatch between the core concepts of salutogenesis, or sense of coherence (SOC), meaning manageability and comprehensibility, as these concepts are manifested in research with Western populations, as compared to non-Western populations. The overall objective of this study is to explore this mismatch and to understand how the core concept of salutogenesis is manifested in youth ages 14-16 from the indigenous Bedouin ethnic minority culture of the Negev, Israel, in their own terms through arts-based qualitative methods. The research methods revolved 80 drawings and texts by youth who drew "a good day that went bad - and how [I] fixed it" as well as focus groups. All data, both verbal and visual, were analysed by dividing into themes and then socially contextualising the themes with a peer group. The findings reveal and concretize a mismatch in SOC between these youth and the predominant Western understandings of coping in terms of meanings, manageability and comprehensibility of coping methods. This study's theoretical recommendations are the need to take steps in the direction of closing the gap or mismatch between a universal versus culturally specific body of literature about culture and SOC. Its practical recommendations are to suggest such a methodology.


Structural and vibrational properties of corundum-type In2O3 nanocrystals under compression.
This work reports the structural and vibrational properties of nanocrystals of corundum-type In2O3 (rh-In2O3) at high pressures by using angle-dispersive x-ray diffraction and Raman scattering measurements up to 30 GPa. The equation of state and the pressure dependence of the Raman-active modes of the corundum phase in nanocrystals are in good agreement with previous studies on bulk material and theoretical simulations on bulk rh-In2O3. Nanocrystalline rh-In2O3 showed stability under compression at least up to 20 GPa, unlike bulk rh-In2O3 which gradually transforms to the orthorhombic Pbca (Rh2O3-III-type) structure above 12-14 GPa. The different stability range found in nanocrystalline and bulk corundum-type In2O3 is discussed.


MADS-box genes of maize: frequent targets of selection during domestication.
MADS-box genes encode transcription factors that are key regulators of plant inflorescence and flower development. We examined DNA sequence variation in 32 maize MADS-box genes and 32 randomly chosen maize loci and investigated their involvement in maize domestication and improvement. Using neutrality tests and a test based on coalescent simulation of a bottleneck model, we identified eight MADS-box genes as putative targets of the artificial selection associated with domestication. According to neutrality tests, one additional MADS-box gene appears to have been under selection during modern agricultural improvement of maize. For random loci, two genes were indicated as targets of selection during domestication and four additional genes were indicated to be candidate-selected loci for maize improvement. These results suggest that MADS-box genes were more frequent targets of selection during domestication than genes chosen at random from the genome.


Anterior cruciate ligament reconstruction using cryopreserved allografts.
Primary ACL reconstruction historically has been done using autograft tissues whereas allografts have been limited to revision cases and patients who are older or with lower physical demands because some animal studies suggested a slower biologic incorporation rate. The purpose of the current study was to evaluate the effectiveness of the cryopreserved Achilles tendon allograft in primary ACL reconstruction in a consecutive series of athletes. Fifty consecutive patients with a strenuous or moderate preinjury activity level, as defined by the International Knee Documentation Committee (IKDC), had ACL reconstruction using cryopreserved Achilles tendon allografts secured with bioabsorbable interference screws. Five patients were professional athletes. The average age of the patients was 36 years (range, 17-50 years). A 3- to 5-year followup study was done in all of the patients using the IKDC form. Tunnel widening was measured in the lateral radiographs at the widest level. The overall outcome was normal or nearly normal in 94% of the patients. No failures were reported in this series. Forty-six patients (92%) returned to their same preinjury sport activity level. The average KT-1000 side-to-side difference was 2.3 mm. Average tibial tunnel widening was 2.7 mm (range, 0-6 mm); no significant correlation was observed between increased tunnel size and a fair or poor clinical outcome. This experience shows that favorable results can be obtained with cryopreserved Achilles tendon allografts in athletes in whom avoiding donor site morbidity may be an issue in terms of a prompt return to sport.


The impact of AI-based modeling on the accuracy of protein assembly prediction: Insights from CASP15.
In CASP15, 87 predictors submitted around 11 000 models on 41 assembly targets. The community demonstrated exceptional performance in overall fold and interface contact predictions, achieving an impressive success rate of 90% (compared to 31% in CASP14). This remarkable accomplishment is largely due to the incorporation of DeepMind's AF2-Multimer approach into custom-built prediction pipelines. To evaluate the added value of participating methods, we compared the community models to the baseline AF2-Multimer predictor. In over 1/3 of cases, the community models were superior to the baseline predictor. The main reasons for this improved performance were the use of custom-built multiple sequence alignments, optimized AF2-Multimer sampling, and the manual assembly of AF2-Multimer-built subcomplexes. The best three groups, in order, are Zheng, Venclovas, and Wallner. Zheng and Venclovas reached a 73.2% success rate over all (41) cases, while Wallner attained 69.4% success rate over 36 cases. Nonetheless, challenges remain in predicting structures with weak evolutionary signals, such as nanobody-antigen, antibody-antigen, and viral complexes. Expectedly, modeling large complexes also remains challenging due to their high memory compute demands. In addition to the assembly category, we assessed the accuracy of modeling interdomain interfaces in the tertiary structure prediction targets. Models on seven targets featuring 17 unique interfaces were analyzed. Best predictors achieved a 76.5% success rate, with the UM-TBM group being the leader. In the interdomain category, we observed that the predictors faced challenges, as in the case of the assembly category, when the evolutionary signal for a given domain pair was weak or the structure was large. Overall, CASP15 witnessed unprecedented improvement in interface modeling, reflecting the AI revolution seen in CASP14.


Assessment of the implementation of the primary health care package at selected sites in South Africa.
A major objective of public health policy in South Africa is to develop a district-based health service focused on the delivery of primary health care. The primary health care package has been developed to promote the delivery of a number of services at the primary level. This paper assesses the implementation of the package in eight historically disadvantaged urban renewal nodes singled out for accelerated development through the government's urban renewal strategy. Data were gathered by way of interviews with primary health care facility managers and programme co-ordinators and through physical observations at facilities. The findings show that while some facilities were able to offer clients most of the services specified by the package, many others were unable do so. The urban renewal nodes differed noticeably in this respect.


Neoplasms in Struma Ovarii: A Review.
Struma ovarii is a well-known ovarian teratoma made up of benign thyroid tissue. These lesions demonstrate variable, normal architecture and normal thyroid immunohistochemical staining with positivity for TTF1, PAX8, and thyroglobulin. Though most are benign, some of these lesions can also present with a malignant component. Within this article, we review the most common diagnostic malignancies including papillary thyroid carcinoma, strumal carcinoid, highly differentiated follicular thyroid carcinoma, and other thyroid carcinomas. We additionally review the use of TTF1 staining to assist in differentiating these lesions from surrounding gynecologic epithelium, which is imperative in making such diagnoses. In highlighting these entities, we hope to provide practicing pathologists with an effective and concise review of these lesions to assist in more challenging cases of struma ovarii.


Moderate/severe erectile dysfunction in patients with antiphospholipid syndrome.
To evaluate sexual function of antiphospholipid syndrome (APS) patients using the Brazilian version of the validated International Index of Erectile Function (IIEF). Eleven APS male patients (Sapporo criteria) were age and race-matched with 22 healthy controls. Demographic and clinical data, drug use and antiphospholipid antibodies were evaluated. The IIEF was also self-applied. Mean age (p = 0.114), frequency of Caucasian race (p = 1.00) and married status (p = 0.438) were similar in APS and controls. Mean disease duration was 8.8 ± 4.6 years. Erectile dysfunction (ED) was frequently observed in APS versus controls (45.5 vs. 4.5%, p = 0.0096), especially moderate/severe ED (p = 0.0081). The total IIEF score (49.6 vs. 67.1, p = 0.019), erectile function (19.6 vs. 28.1, p = 0.005) and intercourse satisfaction (7.8 vs. 11.9, p = 0.009) were lower in patients than in controls. No differences were seen in orgasmic function (p = 0.114), sexual desire (p = 0.123) or overall satisfaction (p = 0.097) between the groups. The comparison between APS patients with ED (n = 5) and without ED (n = 6) revealed more arterial events in APS with ED (100 vs. 16.7%, p = 0.0152), and also longer disease duration (12 [7-16] vs. 5.5 [2-13] years, p = 0.031). A trend towards lower venous events (20 vs. 83.3%, p = 0.0801) and higher renal thrombotic microangiopathy (60% vs. 0, p = 0.0606) was observed in APS patients with ED. Demographics, clinical manifestations, smoking and antiphospholipid antibodies positivity were similar in both groups. To our knowledge, this was the first study that demonstrated moderate/severe ED in almost 50% of cases of a rare autoimmune disease. This alteration was linked to arterial events and longer disease duration.


Role for tumour necrosis factor-alpha receptors in ultraviolet-induced skin tumours.
The biological effects of tumour necrosis factor (TNF)-alpha are mediated through either the TNFR1 or the TNFR2 receptor. In the present study, the effects of ultraviolet (UV) irradiation on skin pathology and tumour promotion were studied in hairless mice deficient in either the TNFR1 or the TNFR2 receptor. SKH-1 hairless mice were crossed with either TNFR1 knockout (KO) mice or TNFR2 KO mice to develop a strain of hairless mice deficient in either of these receptors. Elastosis and other pathological indications of UVB irradiation were not affected by the loss of either receptor. The absence of either receptor, however, resulted in a highly significant reduction in skin tumours in response to UVB irradiation. Inflammatory cell influx following chronic UV irradiation was virtually eliminated in the TNFR1 KO mice, while the TNFR2 KO mice responded to UV irradiation with the normal increase in inflammatory cells throughout the lower and upper dermis. Contact hypersensitivity responses were eliminated in the TNFR2 KO mice, whereas the TNFR1 KO mice retained normal contact hypersensitivity reactions. These studies suggest that TNF-alpha plays no part in the accumulation of excessive elastin in the skin during chronic UVB exposure. However, there appears to be an important role for TNF-alpha in mediating tumorigenesis, distinct from its role in initiating cutaneous immune responses.


Atypical antipsychotic weight gain: a major clinical challenge.
The major aim of this paper is to review findings from weight management intervention studies to consider clozapine and/or olanzapine induced weight gain. A parallel aim is to summarize the challenges facing future research and provide an overview of best practice in the management of weight in mental health patients. A systematic literature search was conducted using Medline, Cinahl and PsychINFO data bases and reference lists from relevant published articles. Five studies which reported weight control practices in patients taking atypical antipsychotic medications were located and reviewed. The studies reviewed provide some important descriptive clinical insights; however, common shortcomings include small subject numbers and methodological drawbacks such as lack of a control group. There is some evidence that weight gain associated with atypical antipsychotic medication can be ameliorated by lifestyle changes such as improved nutritional practices and increased physical activity. Lifestyle interventions for individuals with psychotic disorders may need to be adapted to be most effective; for example, using strategies to counter increased appetite and to enhance physical activity. Clinicians need to be vigilant and persistent in monitoring and intervening if weight gain occurs. A standardized screening tool and clinical pathway would help clinicians to target appropriate interventions for each person prescribed atypical antipsychotic medication.


Fabrication of porous nanoflake BiMO x (M = W, V, and Mo) photoanodes via hydrothermal anion exchange.
Most Bi-based photoelectrodes have suitable band gaps and can effectively promote the water oxidation reaction. However, simple preparation methods for Bi-based binary metal oxides as photoanodes are scarce. This paper describes a simple hydrothermal anion exchange method to synthesize Bi-based binary metal oxides with controlled morphologies. This synthesis process uses BiOI as the template and Bi source, which is eventually converted to Bi-based porous nanoflake photoanodes upon reaction with MO x (M = W, V, and Mo)-containing precursors. The photoanodes show well-shaped porous nanoflake morphologies and exhibit impressive photoelectrochemical properties compared to Bi-based photoanodes synthesized by conventional methods. These three samples possess long-term stability under solar irradiation and show considerable photocurrent for sulfite oxidation.


Enhancing research publications and advancing scientific writing in health research collaborations: sharing lessons learnt from the trenches.
Disseminating research protocols, processes, methods or findings via peer-reviewed publications has substantive merits and benefits to various stakeholders. In this article, we share strategies to enhance research publication contents (ie, what to write about) and to facilitate scientific writing (ie, how to write) in health research collaborations. Empirical experience sharing. To enhance research publication contents, we encourage identifying appropriate opportunities for publications, publishing protocols ahead of results papers, seeking publications related to methodological issues, considering justified secondary analyses, and sharing academic process or experience. To advance writing, we suggest setting up scientific writing as a goal, seeking an appropriate mentorship, making full use of scientific meetings and presentations, taking some necessary formal training in areas such as effective communication and time and stress management, and embracing the iterative process of writing. All the strategies we share are dependent upon each other; and they advocate gradual academic accomplishments through study and training in a "success-breeds-success" way. It is expected that the foregoing shared strategies in this paper, together with other previous guidance articles, can assist one with enhancing research publications, and eventually one's academic success in health research collaborations.


The validity of the geometric mean method for estimating internal activities in nuclear medicine.
The activity of an internal radioactive source may be calculated by comparing the geometric mean of the regional counts in a pair of conjugate gamma camera images with the geometric mean of the counts from a small surface reference source of known activity. Allowance must be made for the effects of differential forward scatter in the detector count rates from the internal and reference sources. The magnitude of these can be predicted, and a suitable correction factor for a given collimator and energy acquisition window calculated by applying a simple count rate build-up model to the observed count rate-depth data for a point and plate source in a water tank. Using a high resolution collimator with 99mTc sources in three sets of phantom trials, the model shows that a scatter build-up correction factor of 1.20-1.22 is suitable for an internal 99mTc source in a typical adult chest or abdomen.


Genetic distance analysis using DNA polymorphisms in the alpha-globin gene cluster.
Published frequencies for alleles at the alpha- and zeta-globin gene loci within the alpha-globin gene cluster were used to calculate genetic distances between populations of South East Asia and the Pacific region. When analyses using the alpha-globin alleles, populations are grouped according to the endemicity of malaria while the groupings derived from the embryonic zeta-globin allele frequencies appear to be far less influenced by the incidence of malaria and probably reflect ancestral or chance relationships due to founder effects, migration and small population sizes.


Impaired neuroendocrine response mediates refractoriness to cardiopulmonary resuscitation in spinal anesthesia.
To determine the extent of neurogenic control on adrenal secretion in a canine model of high spinal anesthesia and cardiac arrest. Randomized, controlled, acute intensive study. University intensive care laboratory. Nineteen healthy, anesthetized, mongrel dogs. Cardiac arrest was induced in 11 spinally anesthetized dogs and 8 sham-control animals; cardiopulmonary resuscitation (CPR) was started 60 secs later. Epinephrine was injected at 4 mins and every 2 mins thereafter. Arterial blood samples were obtained before anesthesia, before arrest, and after 1, 3, 5, 7, 9, and 11 mins of CPR. At 1 and 3 mins after cardiac arrest, the control group exhibited significant increases of epinephrine and norepinephrine concentrations (p < .05) that were absent in the spinal anesthesia group. Plasma renin increased in both groups whereas aldosterone and cortisol remained unchanged. Spinal anesthesia abolishes the catecholamine release that follows cardiac arrest, while a previously postulated direct adrenal effect of hypoxia stimulating catecholamine release was not confirmed in these experiments. Since epinephrine treatment restores coronary perfusion pressure (CPP) during CPR, we conclude that catecholamine deficiency is the most likely mechanism for inadequate CPP during CPR conducted in the presence of spinal anesthesia.


Percutaneous transradial coronary angiography and angioplasty in patients with occlusive atherosclerotic iliofemoral disease.
Not all coronary angiograms can be acquired through the femoral route. The transradial catheterisation procedure in patients with occlusive atherosclerotic iliofemoral disease is described. Transfemoral left-sided cardiac catheterisation was performed in approximately 99.5% of patients referred for coronary angiography, while out of 48 patients in whom transfemoral access was impossible, transradial coronary angiography was successful in 37. With the exception of one, all patients with coronary artery disease had lesions of the right coronary artery, more than 70% had multivessel disease and 14% had stenosis of the left main coronary artery. Ten patients had angioplasty performed during the same procedure. Complications occurred in 5 out of 39 cases, 2 (5%) of these were severe. Although the femoral route was used in more than 99% of an unselected population referred for coronary angiography, it was found that transradial angiography and angioplasty can be performed in patients with occlusive atherosclerotic iliofemoral disease with considerable success and an acceptable complication rate.


Hepatitis G virus infection in chronic liver disease.
The hepatitis G virus (HGV), a recently identified member of the Flaviviridae family, can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. To evaluate the prevalence and meaning of HGV infection in a large series of patients with chronic liver disease. Two hundred volunteer blood donors, 179 patients with chronic hepatitis C, 111 with chronic hepatitis B, 104 with alcoholic liver disease, 136 with hepatocellular carcinoma, and 24 with cryptogenic chronic liver disease were studied. HGV RNA was investigated in serum samples by reverse transcription and polymerase chain reaction amplification of the 5' non-coding region of HCV and hybridisation to a specific probe. The main features of HGV RNA seropositive and seronegative patients were compared. The prevalence of HGV infection was 3% in blood donors, 7% in chronic hepatitis C, 8% in chronic hepatitis B, 2% in alcoholic liver disease, 4% in hepatocellular carcinoma, and 8% in cryptogenic chronic liver disease. HGV infected patients tended to be younger than non-infected patients but no differences concerning sex, possible source of infection, clinical manifestations, biochemical and virological parameters, or severity of liver lesions were found. The prevalence of HGV infection in chronic liver disease seems to be relatively low in our area. Infection with HGV does not seem to play a significant pathogenic role in patients with chronic liver disease related to chronic HBV or HCV infection or to increased alcohol consumption, or in those with cryptogenic chronic liver disease.


Patient education self-management during surgical recovery: combining mobile (iPad) and a content management system.
The objective of this investigation was to assess whether a new electronic health (e-health) platform, combining mobile computing and a content management system, could effectively deliver modular and "just-in-time" education to older patients following cardiac surgery. Patients were provided with iPad(®) (Apple(®), Cupertino, CA) tablets that delivered educational modules as part of a daily "to do" list in a plan of care. The tablet communicated wirelessly to a dashboard where data were aggregated and displayed for providers. A surgical population of 149 patients with a mean age of 68 years utilized 5,267 of 6,295 (84%) of education modules delivered over a 5.3-day hospitalization. Increased age was not associated with decreased use. We demonstrate that age, hospitalization, and major surgery are not significant barriers to effective patient education if content is highly consumable and relevant to patients' daily care experience. We also show that mobile technology, even if unfamiliar to many older patients, makes this possible. The combination of mobile computing with a content management system allows for dynamic, modular, personalized, and "just-in-time" education in a highly consumable format. This approach presents a means by which patients may become informed participants in new healthcare models.


Linking genetics to structural biology: complex heterozygosity screening with actin alanine scan alleles identifies functionally related surfaces on yeast actin.
Previous genome-level genetic interaction screens with the single essential actin gene of yeast identified 238 nonessential genes that upon deletion result in deleterious, digenic complex haploinsufficiences with an actin null allele. Deletion alleles of these 238 genes were tested for complex heterozygous interactions with 32 actin alanine scan alleles, which target clusters of residues on the surface of actin. A total of 891 deleterious digenic combinations were identified with 203 of the 238 genes. Two-dimensional hierarchical cluster analysis of the interactions identified nine distinct groups, and the alleles within clusters tended to affect localized regions on the surface of actin. The mutants in one cluster all affect electrostatic interactions between stacked subunits in the long pitch helix of the actin filament. A second cluster that contains the most highly interactive alleles may disrupt the tropomyosin/myosin system, as one of the mutants in that cluster cannot support Type V myosin-dependent movement of secretory vesicles in haploids and causes processivity defects in heterozygous diploids. These examples suggest the clusters represent mutations with shared protein-protein interaction defects. These results show that complex heterozygous interaction screens have benefit for detecting actin-related genes and suggest that having actin filaments of mixed composition, containing both mutant and wild-type subunits, presents unique challenges to the cell.


Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome.
Recognition of individual faces is an integral part of both interpersonal interactions and successful functioning within a social group. Therefore, it is of considerable interest that individuals with autism and related conditions have selective deficits in face recognition (sparing nonface object recognition). We used functional magnetic resonance imaging (fMRI) to study face and subordinate-level object perception in 14 high-functioning individuals with autism or Asperger syndrome (the autism group), in comparison with 2 groups of matched normal controls (normal control group ] [NC1] and normal control group 2 [NC2]) (n = 14 for each). Regions of interest (ROIs) were defined in NC1 and then applied in comparisons between NC2 and the autism group. Regions of interest were also defined in NC2 and then applied to comparisons between NC1 and the autism group as a replication study. In the first set of comparisons, we found significant task x group interactions for the size of activation in the right fusiform gyrus (FG) and right inferior temporal gyri (ITG). Post hoc analyses showed that during face (but not object) discrimination, the autism group had significantly greater activation than controls in the right ITG and less activation of the right FG. The replication study showed again that the autism group used the ITG significantly more for processing faces than the control groups, but for these analyses, the effect was now on the left side. Greater ITG activation was the pattern found in both control groups during object processing. Individuals with autism spectrum disorders demonstrate a pattern of brain activity during face discrimination that is consistent with feature-based strategies that are more typical of nonface object perception.


It May Be Simple, But It's Not Easy: Conscious Case Management.
As in everything, case management has an evolutionary trajectory. Perhaps, the latest in case management is Conscious Case Management. In today's harried health care environment and with multiple "productivity" criteria to measure usefulness, case managers should not move to just finishing your daily responsibilities or trying to close the most cases; rather, a mindful approach, whether in listening or doing, will yield the best outcome. Instead of mindlessly completing tasks and checking off boxes, practice in-the-moment-and do so consciously.


Surgically-treated early cervical cancer: Prognostic factors and the significance of depth of tumor invasion.
The objectives of this study were to scrutinize surgical features and analyze local tumor parameters of early cervical cancer to identify patients at-risk for recurrent disease. Three hundred eight patients who underwent radical hysterectomy and pelvic lymphadenectomy between 1984 and 1997 were studied retrospectively. All radical hysterectomies were performed in a referral oncology center, and treatment policies and operating staff were the same during the study period. Operating time gradually decreased significantly during the study period from an average of 270 min to an average of 187 min (P < 0.0001), and blood loss during surgery also decreased continually from 1515 ml to 1071 ml (P < 0.0001). Postoperative radiation treatment was given to 119 patients (40%). The overall five-year survival rate was 83%, 91% for those with negative, and 53% for those with positive pelvic nodes. Univariate analysis showed that lymph node status, parametrial involvement, status of the surgical margins, capillary lymphatic space involvement, tumor size and depth of invasion were all significantly related to the occurrence of recurrent disease. Multivariate analysis revealed that lymph node involvement (hazard ratio 4.4), parametrial involvement, tumor size and depth of invasion were independent factors of prognostic significance for disease-free survival. It was concluded that the local control of cervical tumors infiltrating > 10 mm (hazard ratio 5.1) might be improved by adjuvant radiotherapy, even in the absence of lymph node metastasis, parametrial involvement or affected surgical margins.


miR-21 regulates the proliferation and apoptosis of ovarian cancer cells through PTEN/PI3K/AKT.
Phosphatase and tensin homologue deleted on chromosome ten (PTEN) regulates cell proliferation and apoptosis by inhibiting phosphatidylinositol-3 kinase (PI3K) and protein kinase (AKT) signaling. High expression of miR-21 was associated with ovarian cancer. This study aims to investigate whether miR-21 regulates PTEN/PI3K/AKT signaling as well as its role in the proliferation and apoptosis of ovarian cancer cells. Bioinformatics analysis was used to identify the binding site between miR-21 and the 3'-UTR of PTEN mRNA. A dual-luciferase reporter gene assay was performed to confirm the relationship between miR-21 and PTEN. The expression of miR-21, PTEN, and p-AKT was measured in normal ovarian cell IOSE80, ovarian cancer cell lines A2780, and SKOV3. miR-NC or miR-21 inhibitor was transfected into A2780 or SKOV3 cells followed by the analysis of the expression of miR-21, PTEN, p-AKT, cell apoptosis by flow cytometry, and proliferation by EdU assay. There was a targeted relationship between miR-21 and PTEN. Compared with IOSE80 cell, levels of miR-21 and p-AKT were significantly elevated in A2780 and SKOV3 cells, with the statistical reduction of PTEN expression (p<0.05). The inhibition of miR-21 significantly reduced the expressions of miR-21 and p-AKT and induced PTEN level in A2780 and SKOV3 cells, which also restricted cell proliferation and promoted cell apoptosis. The miR-21 expression is found elevated in ovarian cancer cells. The suppression of miR-21 increases PTEN expression, inhibits PI3K/AKT activity, promotes cell apoptosis, and reduces cell proliferation. This finding provides new leads to the future treatment of ovarian cancer.