Low temperatures reduce skin healing in the Jacaré do Pantanal (Caiman yacare, Daudin 1802).
Studies of skin wound healing in crocodilians are necessary given the frequent occurrence of cannibalism in intensive farming systems. Air temperature affects tissue recovery because crocodilians are ectothermic. Therefore, the kinetics of skin wound healing in Caiman yacare were examined at temperatures of 33°C and 23°C. Sixteen caiman were selected and divided into two groups of eight maintained at 23°C or 33°C. The studied individuals' scars were photographed after 1, 2, 3, 7, 15 and 30 days of the experimental conditions, and samples were collected for histological processing after 3, 7, 15 and 30 days. Macroscopically, the blood clot (heterophilic granuloma) noticeably remained in place covering the wound longer for the caiman kept at 23°C. Microscopically, the temperature of 23°C slowed epidermal migration and skin repair. Comparatively, new blood vessels, labeled using von Willebrand factor (vWF) antibody staining, were more frequently found in the scars of the 33°C group. The collagen fibers in the dermis were denser in the 33°C treatment. Considering the delayed healing at 23°C, producers are recommended to keep wounded animals at 33°C, especially when tanks are cold, to enable rapid wound closure and better repair of collagen fibers because such lesions tend to compromise the use of their skin as leather.


Impact of a clinical pharmacy program on changes in hemoglobin A1c, diabetes-related hospitalizations, and diabetes-related emergency department visits for patients with diabetes in an underserved population.
Diabetes mellitus is associated with substantial morbidity and mortality. With the rise in prevalence of diabetes, there has been an increased need for clinical pharmacy services focused on diabetes management in ambulatory clinics. However, more data IS needed to determine the overall impact that clinical pharmacists have on preventing diabetes-related inpatient admissions and emergency department (ED) visits for patients with diabetes, especially in an underserved population. To assess the impact of clinical pharmacy services on the change in hemoglobin A1c measurements, the number of diabetes-related hospitalizations, and the number of diabetes-related ED visits for patients with uncontrolled diabetes. This was a retrospective study that evaluated outcomes for patients referred to a clinical pharmacist for management of diabetes, compared with patients who were not seen by a clinical pharmacist. Adult patients aged between 18 and 89 years with a diagnosis of type 1 or type 2 diabetes mellitus were identified, using the electronic medical records from CommUnityCare outpatient clinics in central Texas during the period July 1, 2007, through July 1, 2011. Patients enrolled had poor glycemic control, defined as an A1c ≥9% at baseline (index), with at least 3 visits with a clinical pharmacist or 3 visits to usual care. Patients with at least 1 year of pre-index data, 1 year of post-index follow-up, and a post-index A1c measure were included in the study. Propensity score (PS) matching was used to create a 1:1 cohort. T-tests were used to calculate results for the main outcome variables (change in A1c, change in number of diabetes-related hospitalizations, and change in number of diabetes-related ED visits). In addition, general linear models (GLM) were used to control for baseline demographic and clinical characteristics. A total of 782 patients met inclusion criteria, 557 in the usual care (control) group and 225 in the clinical pharmacy (intervention) group. PS matching provided a 1:1 matched sample of 220 patients per cohort. When assessing the change in the number of diabetes-related hospitalizations from the pre-index year to the post-index year, patients in the control group had an increase of 8 hospitalizations (8 visits per 220 patients, mean = 0.036, SD = 0.284), while the intervention group had a decrease of 1 hospitalization (-1 visit per 220 patients, mean = -0.005, SD=0.278). Both the t-test (P = 0.06) and GLM model (P = 0.06) indicated that the difference was statistically significant. When assessing the change in the number of diabetes-related ED visits from the pre-index year to the post-index year, we found patients in the control group had an increase of 16 ED visits (16 visits per 220 patients, mean = 0.073, SD = 0.584), while the intervention group had an increase of 4 ED visits (4 visits per 220 patients, mean = -0.018, SD=0.641). Both the t-test (P = 0.18) and GLM model (P = 0.28) indicated that the difference was not statistically significant. A1c levels were reduced in the post-index period for both groups. For the control group, A1c reduction was 1.50 (from 11.17 to 9.67, SD = 2.49). For the intervention group, A1c reduction was 1.90 (from 11.09 to 9.19, SD = 2.44). Both the t-test (P = 0.04) and GLM model (P = 0.05) indicated that the A1c difference was statistically significant. Underserved patients with baseline uncontrolled diabetes who were managed by a clinical pharmacist in the outpatient setting had a higher decrease in A1c compared with usual care. The changes in diabetes-related hospitalizations and diabetes-related ED visits were in the hypothesized direction, but the comparison for ED visits was not statistically significant.


Surface-Modified Filter-Based Continuous Recovery of Microalgal Lipid-in-Solvent with High Recovery Efficiency, Long-Term Stability, and Cost Competitiveness.
Microalgal lipid-derived biofuels have been regarded as promising candidate materials to replace fossil fuels, but their production cost, especially for lipid extraction, still must be lowered substantially for field application. Although lipid extraction from concentrated wet microalgae using a nonpolar solvent is considered as a feasible method, an effective recovery method to regain the nonpolar solvent with microalgal lipid from the emulsified extraction mixture has not yet been addressed significantly. In this study, microalgal lipid is cost-efficiently recovered in continuous manner directly from the emulsified, highly concentrated extraction mixture by utilizing a surface-modified filter. The surface of a highly porous sponge filter is modified conformally by an oil-absorbing but water-repellent polymer coating via an initiated chemical vapor deposition (iCVD) process. Concentrated wet Schizochytrium sp. ABC101 microalgal cells are disrupted, and the microalgal lipid components are extracted out by adding n-hexane in the aqueous disrupted microalgae. The surface-modified filter is capable of selective permeation of the n-hexane phase with microalgal lipid while blocking the water-phase permeation simply by immersing the filter into the emulsified extraction mixture. The absorbed n-hexane phase is recovered in a continuous manner by pumping it out. The continuous filter-based recovery system shows a high recovery yield of 95% and an extremely high permeation flux of 2640 L m-2 h-1. Moreover, the recovery performance is maintained for more than 24 h without any filter-cleaning step. Techno-economic analysis of the method developed in this study with the conventional phase recovery methods shows that the rapid but highly cost-efficient filter-based recovery method will be a useful platform for scalable, continuous microalgae lipid production.


Uterine rupture in women attempting a vaginal birth following prior cesarean birth.
To determine (1) if there are any common features to fetal heart rates (FHR) and uterine activity patterns before uterine rupture, (2) if neonatal outcomes as reflected by cord blood gases are associated with the length of fetal bradycardia, and (3) if there is an increase in maternal and/or neonatal length of stay in women who experience uterine rupture during labor as compared with women following repeat cesarean section. Maternal and fetal records of 11 women identified by the ICD-9 code as having had a uterine rupture between 1990 and 1995 were retrospectively reviewed. No one common feature in FHR patterns or uterine activity existed before uterine rupture other than bradycardia, although variable and/or late decelerations commonly preceded the bradycardia. Of the neonates, 91% had cord blood pH of <7.0 and 45% had base excess greater than 15 meq/l. Of those fetuses experiencing bradycardia, 55% had placental abruption. Maternal length of stay 5 days or greater occurred in 36% of those with uterine rupture. Seventy-three percent of the neonates required admission to the Neonatal Intensive Care Unit (NICU). Despite acidemia as shown by cord pH, none of the neonates experienced seizures or multiorgan dysfunction. There is no one specific FHR or uterine activity pattern that indicates the onset of a uterine rupture, although variable and/or late decelerations occur before the onset of an FHR bradycardia. In the present study, neonatal admissions to the NICU were increased and pH values were below 7.0 in 91% when uterine rupture occurred. A decrease or cessation of uterine tone was not observed. Maternal length of stay was slightly increased following uterine rupture.


Impact of faculty and work role models on the professional socialization of dental hygienists.
The purpose of this study was to identify and assess the degree of influence dental hygiene role models in education and practice have on the professional socialization of recent dental hygiene graduates. Professional socialization was measured by two constructs: attitudes toward professionalism and interpersonal values. This study compared responses on attitudes and values scales of 1985 dental hygiene graduates who indicated they did or did not identify with a dental hygiene role model in school and at work. A comparison of responses on five other control variables also was assessed in relation to attitudes and values. Results showed that those respondents who identified with a role model in school held significantly stronger attitudes on the professional organization as major referent variable. However, graduates who did not identify with a faculty role model held stronger values on independence. Respondents who identified with a dental hygiene role model in practice held stronger values on benevolence but those who did not have a role model at work held stronger values on independence. There were no statistically significant differences between groups with or without a work role model on the attitudes scales.


Auger and Carrier Trapping Dynamics in Core/Shell Quantum Dots Having Sharp and Alloyed Interfaces.
The role of interface sharpness in controlling the excited state dynamics in CdSe/ZnSe core/shell particles is examined here. Particles composed of CdSe/ZnSe with 2.4-4.0 nm diameter cores and approximately 4 monolayer shells are synthesized at relatively low temperature, ensuring a sharp core-shell interface. Subsequent annealing results in cadmium and zinc interdiffusion, softening the interface. TEM imaging and absorption spectra reveal that annealing results in no change in the particle sizes. Annealing results in a 5-10 nm blue shift in the absorption spectrum, which is compared to calculated spectral shifts to characterize the extent of metal interdiffusion. The one- and two-photon dynamics are measured using time-resolved absorption spectroscopy. We find that biexcitons undergo biexponential decays, with fast and slow decay times differing by about an order of magnitude. The relative magnitudes of the fast and slow components depend on the sharpness of the core-shell interface, with larger fast component amplitudes associated with a sharp core-shell interface. The slow component is assigned to Auger recombination of band edge carriers and the fast decay component to Auger recombination of holes that are trapped in defects produced by lattice strain. Annealing of these particles softens the core-shell interface and thereby reduces the amount of lattice strain and diminishes the magnitude of the fast decay component. The time constant of the slow biexciton Auger recombination component changes only slightly upon softening of the core-shell interface.


Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study.
To evaluate the effect of atorvastatin in achieving stable sinus rhythm (SR) 30 days after electrical cardioversion (CV) in patients with persistent atrial fibrillation (AF). The study included 234 patients. The patients were randomized to treatment with atorvastatin 80 mg daily (n = 118) or placebo (n = 116) in a prospective, double-blinded fashion. Treatment was initiated 14 days before CV and was continued 30 days after CV. The two groups were well-balanced with respect to baseline characteristics. Mean age was 65 +/- 10 years, 76% of the patients were male and 4% had ischaemic heart disease. Study medication was well-tolerated in all patients but one. Before primary endpoint 12 patients were excluded. In the atorvastatin group 99 patients (89%) converted to SR at electrical CV compared with 95 (86%) in the placebo group (P = 0.42). An intention-to-treat analysis with the available data, by randomization group, showed that 57 (51%) in the atorvastatin group and 47 (42%) in the placebo group were in SR 30 days after CV (OR 1.44, 95%CI 0.85-2.44, P = 0.18). Atorvastatin was not statistically superior to placebo with regards to maintaining SR 30 days after CV in patients with persistent AF.


On a model of pattern regeneration based on cell memory.
We present here a new model of the cellular dynamics that enable regeneration of complex biological morphologies. Biological cell structures are considered as an ensemble of mathematical points on the plane. Each cell produces a signal which propagates in space and is received by other cells. The total signal received by each cell forms a signal distribution defined on the cell structure. This distribution characterizes the geometry of the cell structure. If a part of this structure is removed, the remaining cells have two signals. They keep the value of the signal which they had before the amputation (memory), and they receive a new signal produced after the amputation. Regeneration of the cell structure is stimulated by the difference between the old and the new signals. It is stopped when the two signals coincide. The algorithm of regeneration contains certain rules which are essential for its functioning, being the first quantitative model of cellular memory that implements regeneration of complex patterns to a specific target morphology. Correct regeneration depends on the form and the size of the cell structure, as well as on some parameters of regeneration.


Host susceptibility of citrus cultivars to Queensland fruit fly (Diptera: Tephritidae).
Citrus crops are considered to be relatively poor hosts for Queensland fruit fly, Bactrocera tryoni (Froggatt), as for other tephritid species. Australian citrus growers and crop consultants have reported observable differences in susceptibility of different citrus cultivars under commercial growing conditions. In this study we conducted laboratory tests and field surveys to determine susceptibility to B. tryoni of six citrus cultivars [(Eureka lemon (Citrus limon (L.) Osbeck); Navel and Valencia oranges (C. sinensis (L.) Osbeck); and Imperial, Ellendale, and Murcott mandarins (C. reticulata Blanco). The host susceptibility of these citrus cultivars was quantified by a Host Susceptibility Index, which is defined as the number of adult flies produced per gram of fruit infested at a calculated rate of one egg per gram of fruit. The HSI was ranked as Murcott (0.083) > Imperial (0.052) > Navel (0.026) - Ellendale (0.020) > Valencia (0.008) > Eureka (yellow) (0.002) > Eureka (green) (0). Results of the laboratory study were in agreement with the level of field infestation in the four citrus cultivars (Eureka lemon, Imperial, Ellendale, and Murcott mandarins) that were surveyed from commercial orchards under baiting treatments against fruit flies in the Central Burnett district of Queensland. Field surveys of citrus hosts from the habitats not subject to fruit fly management showed that the numbers of fruit flies produced per gram of fruit were much lower, compared with the more susceptible noncitrus hosts, such as guava (Psidium guajava L.), cherry guava (P. littorale Raddi), mulberry (Morus nigra L.), loquat (Eriobotrya japonica (Thunb.) Lindl.), and pear (Pyrus communis L.). Therefore, the major citrus crops commercially cultivated in Australia have a relatively low susceptibility to B. tryoni, with Eureka lemons being a particularly poor host for this tephritid fruit fly.


An optimized ibuprofen dosing scheme for preterm neonates with patent ductus arteriosus, based on a population pharmacokinetic and pharmacodynamic study.
Ibuprofen is a nonsteroidal anti-inflammatory agent that induces closure of the patent ductus arteriosus in neonates. Few studies of ibuprofen pharmacokinetics have been performed and were limited to small groups of preterm infants, showing a large intersubject variability and an increase in clearance with either postnatal or gestational age. A population pharmacokinetic study was performed on 66 neonates to characterize the concentration-time courses of ibuprofen. Ibuprofen clearance significantly increased from postnatal age day 1 to day 8, but not with gestational age. A relationship was shown between ibuprofen area under the curve (AUC) and patent ductus arteriosus closure rate, and an effective threshold AUC was evidenced. Dosing schemes were proposed as a function of postnatal age, to achieve this AUC and to improve the efficacy of treatment for patent ductus arteriosus in neonates. AIMS To describe ibuprofen pharmacokinetics in preterm neonates with patent ductus arteriosus (PDA) and to establish relationships between doses, plasma concentrations and ibuprofen efficacy and safety. Sixty-six neonates were treated with median daily doses of 10, 5 and 5 mg kg(-1) of ibuprofen-lysine by intravenous infusion on 3 consecutive days. A population pharmacokinetic model was developed with NONMEM. Bayesian individual pharmacokinetic estimates were used to calculate areas under the curve (AUC) and to simulate doses. A logistic regression was performed on PDA closure. Ibuprofen pharmacokinetics were described by a one-compartment model with linear elimination. Mean population pharmacokinetic estimates with corresponding intersubject variabilities (%) were: elimination clearance CL = 9.49 ml h(-1) (62%) and volume of distribution V = 375 ml (72%). Ibuprofen CL significantly increased with postnatal age (PNA): CL = 9.49*(PNA/96.3)(1.49). AUC after the first dose (AUC1D), the sum of AUC after the three doses (AUC3D) and gestational age were significantly higher in 57 neonates with closing PDA than in nine neonates without PDA closure (P = 0.02). PDA closure was observed in 50% of the neonates when AUC1D < 600 mg l(-1) h (or AUC3D < 900 mg l(-1) h) and in 91% when AUC1D > 600 mg l(-1) h (or AUC3D > 900 mg l(-1) h) (P = 0.006). No correlation between AUC and side-effects could be demonstrated. To achieve these optimal AUCs, irrespective of gestational age, three administrations at 24 h intervals are recommended of 10, 5, 5 mg kg(-1) for neonates younger than 70 h, 14, 7, 7 mg kg(-1) for neonates between 70 and 108 h and 18, 9, 9 mg kg(-1) for neonates between 108 and 180 h.


Mechanism and ion-dependence of in vitro autoactivation of yeast proteinase A: possible implications for compartmentalized activation in vivo.
Yeast proteinase A is synthesized as a zymogen which transits through the endoplasmic reticulum, the Golgi complex and the endosome to the vacuole. On arrival in the vacuole, activation takes place. It has previously been found that proteinase A can activate autocatalytically; however, the propeptide of proteinase A shows essentially no similarity to other known aspartic proteinase propeptides. To understand why proteinase A activation occurs rapidly in the vacuole but not at all in earlier compartments, we have purified the zymogen and investigated the conditions that trigger autoactivation and the mechanism of autoactivation. Autoactivation was triggered by acidic pH and its rate increased with increasing ionic strength. Kinetic evidence indicates that autoactivation mainly occurs via a bimolecular product-catalysed mechanism in which an active proteinase A molecule activates a zymogen molecule. Both the pH- and ionic-strength-dependence and the predominance of a product-catalysed mechanism are well adapted to the situation in vivo, since slow activation in the absence of active proteinase A helps to prevent activation in prevacuolar compartments, whereas, on delivery to the vacuole, lower pH, higher ionic strength and the presence of already active proteinases ensure rapid activation. Product-catalysed autoactivation may be a general mechanism by which cells ensure autoactivation of intracellular enzymes to be both rapid and compartmentalized.


Pseudomonas aeruginosa exoenzyme S is a mitogen but not a superantigen for human T lymphocytes.
Virtually all cystic fibrosis (CF) patients become infected with Pseudomonas aeruginosa, and once the infection is established, the organism is rarely cleared. One of the P. aeruginosa virulence factors, exoenzyme S, has been shown to correlate with increased morbidity and mortality both in rat models of chronic pulmonary inflammation and in human CF patients. It has previously been shown that exoenzyme S is a potent stimulus for the proliferation of T cells in greater than 95% of adults, which could contribute to the pathogenesis of CF. The goal of this study was to determine the mechanism of T-cell stimulation by exoenzyme S in an effort to shed light on the immune response and contribute to understanding its role in P. aeruginosa pathogenesis. The current studies demonstrate that exoenzyme S stimulates naive T cells, since fetal blood lymphocytes proliferated and adult lymphocytes that expressed CD45RA proliferated. The percentage of T cells activated by exoenzyme S after a 4-h culture (as measured by CD69 surface expression) was intermediate in magnitude compared to levels induced by a panel of superantigens and mitogens. To determine the mechanism of activation, the requirement for accessory cells was investigated. The proliferative response to exoenzyme S was dependent on the presence of accessory cells but was not blocked by an anti-DR antibody. Exoenzyme S activated both CD4(+) and CD8(+) T cells, but CD4(+) T cells were preferentially activated. The Vbeta repertoire of donor T cells showed no preferential activation or preferential expansion after stimulation by exoenzyme S, suggesting that it is not a superantigen. Taken together, our data suggest that exoenzyme S is a T-cell mitogen but not a superantigen. Activation of a large percentage of T lymphocytes by exoenzyme S may produce a lymphocyte-mediated inflammatory response that should be considered in the pathogenesis of CF.


Northwestern Anagram Test-Italian (Nat-I) for primary progressive aphasia.
To test the ability of the Northwestern Anagram Test-Italian (NAT-I) to distinguish between the non-fluent/agrammatic (nfv-) and phonological/logopenic (lv-) variants of primary progressive aphasia (PPA), and to determine the relationship between NAT-I variables and brain integrity in PPA patients. 13 nfvPPA and 8 lvPPA patients underwent the 44-item-version of NAT-I and brain MRI. The NAT-I was also administered to six patients with the semantic variant (sv) PPA to sample performance in cases with no grammatical deficits. Performances were recorded and compared between patient groups. Receiver Operating Characteristic curve analysis assessed the ability of NAT-I to discriminate nfvPPA and lvPPA. The correlation between anatomical changes and NAT-I variables were assessed. A shortened (22-item)-version of NAT-I was also tested for classification ability. Participants with NfvPPA performed more poorly than lvPPA patients on canonical and non-canonical sentences. NAT-I non-canonical sentence and total scores achieved the highest diagnostic accuracy in discriminating the two patient groups (area under the curve: .93 and .91, respectively). SvPPA participants showed performances similar to lvPPA. NAT-I variables correlated with the integrity of the left inferior frontal gyrus and the body of the corpus callosum. The NAT-I 22-item-version total and non-canonical sentences scores reached diagnostic accuracy comparable to the full version. The NAT-I, in particular the measure of non-canonical syntax, is an effective tool for distinguishing nfvPPA and lvPPA patients and correlated with the integrity of crucial brain regions implicated in syntactic processing. The 22-item-brief version of NAT-I is suitable for clinical practice and research.


Carvacrol-rich oregano oil and thymol-rich thyme red oil inhibit biofilm formation and the virulence of uropathogenic Escherichia coli.
Urinary tract infections are caused primarily by uropathogenic Escherichia coli (UPEC), and indwelling catheters are usually colonized by UPEC biofilms tolerant to common antibiotics. Hence, UPEC biofilms pose a substantial challenge, and there is an urgent need for effective control strategies. In this study, 79 essential oils were screened for antibiofilm ability against UPEC. Components of active oils were identified, and their antibiofilm activities were also investigated using 96-well plates with crystal violet assay, scanning electron microscopy, and confocal laser scanning microscopy. Oregano oil and thyme red oil and their major common constituents, carvacrol and thymol, significantly inhibited UPEC biofilm formation at subinhibitory concentrations (<0·01%). These findings were supported by observations that carvacrol and thymol reduced fimbriae production and the swarming motility of UPEC. Furthermore, carvacrol and thymol markedly decreased the hemagglutinating ability of UPEC, and UPEC was more easily killed by human whole blood in the presence of carvacrol and thymol. Carvacrol-rich oregano oil and thymol-rich thyme red oil have high antibiofilm and antivirulence activities against UPEC. In the wake of rising antimicrobial resistance, we envisage that carvacrol and thymol could be used to prevent biofilm formation by UPEC and to reduce its virulence.


Tracking of structural defects induced by Eu-doping in β-Ag2MoO4: their influences on electrical properties.
In this study, several methods were employed to investigate the electrical characteristics of β-Ag2MoO4 systems, both Eu-doped and undoped, synthesized using the microwave-assisted hydrothermal method. The focus extended to understanding how synthesis time influences material defects, with doping fixed at 1%. A systematic shift in the silver vacancy (VAg) concentration was observed within the doped β-Ag2MoO4 system. Specifically, this study demonstrated that the incorporation of Eu3+ into polycrystalline β-Ag2MoO4 initially increases the VAg concentration. However, as the synthesis time progresses, the VAg concentration decreases, resulting in alterations in the resulting electrical properties, arising from the intricate interplay between the number of grain boundaries and carrier density. By combining information obtained from photoluminescence, positron annihilation lifetime spectroscopy, and impedance spectroscopy, a comprehensive conduction mechanism was formulated, shedding light on both doped and undoped β-Ag2MoO4 systems.


Activation of Disulfide Redox Switch in REDD1 Promotes Oxidative Stress Under Hyperglycemic Conditions.
The stress response protein regulated in development and DNA damage response 1 (REDD1) has been implicated in visual deficits in patients with diabetes. The aim here was to investigate the mechanism responsible for the increase in retinal REDD1 protein content that is observed with diabetes. We found that REDD1 protein expression was increased in the retina of streptozotocin-induced diabetic mice in the absence of a change in REDD1 mRNA abundance or ribosome association. Oral antioxidant supplementation reduced retinal oxidative stress and suppressed REDD1 protein expression in the retina of diabetic mice. In human retinal Müller cell cultures, hyperglycemic conditions increased oxidative stress, enhanced REDD1 expression, and inhibited REDD1 degradation independently of the proteasome. Hyperglycemic conditions promoted a redox-sensitive cross-strand disulfide bond in REDD1 at C150/C157 that was required for reduced REDD1 degradation. Discrete molecular dynamics simulations of REDD1 structure revealed allosteric regulation of a degron upon formation of the disulfide bond that disrupted lysosomal proteolysis of REDD1. REDD1 acetylation at K129 was required for REDD1 recognition by the cytosolic chaperone HSC70 and degradation by chaperone-mediated autophagy. Disruption of REDD1 allostery upon C150/C157 disulfide bond formation prevented the suppressive effect of hyperglycemic conditions on REDD1 degradation and reduced oxidative stress in cells exposed to hyperglycemic conditions. The results reveal redox regulation of REDD1 and demonstrate the role of a REDD1 disulfide switch in development of oxidative stress.


Selective induction of high-ouabain-affinity isoform of Na+-K+-ATPase by thyroid hormone.
The administration of thyroid hormone is known to result in an induction of the Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) in rat skeletal muscle and other thyroid hormone-responsive tissues. Since the Na+-K+-ATPase in a variety of mammalian tissues has recently been reported to exist in at least two forms distinguishable by differing affinities for the inhibitory cardiac glycoside ouabain, we have studied the effects of 3,3',5-triiodo-L-thyronine (T3) treatment on these two forms of the enzyme in rat diaphragm. The inhibition of Na+-K+-ATPase activity in a crude membrane fraction by varying concentrations of ouabain conformed to a biphasic pattern consistent with the presence of two distinct isoforms with inhibition constants (KIs) for ouabain of approximately 10(-7) and 10(-4) M, respectively. Treatment of hypothyroid rats with T3 (50 micrograms/100 g body wt on 3 alternate days) nearly tripled that portion of the Na+-K+-ATPase activity corresponding to the high-ouabain-affinity form (increased by 178 +/- 24%), whereas the enzyme activity corresponding to the low-ouabain-affinity form was only slightly changed (increased by 20 +/- 5%). Measurement of the specific binding of [3H]ouabain to these membranes confirmed the presence of a class of high-affinity ouabain binding sites with a dissociation constant (Kd) of slightly less than 10(-7) M, whose maximal binding capacity was increased by T3 treatment by 185%. The calculated catalytic turnover associated with the high-affinity site was 70-80 molecules ATP hydrolyzed.site-1.s-1 and was unchanged by T3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Fixation-free fluorescence in situ hybridization for targeted enrichment of microbial populations.
We modified the standard ribosomal RNA-targeted fluorescence in situ hybridization (FISH) protocol by removing the fixation steps to allow recovery of unmodified nucleic acids. Using this method, hybridized cells could be visualized in two bioreactor sludges and termite hindgut samples by epifluorescence microscopy. We then targeted one bacterial and one archaeal population in the sludge samples with group-specific oligonucleotide probes using in-solution fixation-free FISH and sorted hybridized populations using fluorescence-activated cell sorting (FACS). We could show that sorted populations were highly enriched for the target organisms based on 16S rRNA gene sequencing, thus confirming probe specificity using the modified FISH protocol. This approach should facilitate subsequent genomic sequencing and analysis of targeted populations as DNA is not compromised by crosslinking during fixation.


[Idiopathic ischaemic infarction of the stomach. Case report].
Idiopathic ischaemic infarction of the stomach is an extremely rare condition since only 2 other cases have been published in the Literature so far. The Authors report a case of such entity on a 75 year old male patient, admitted from the accident and emergency department because of a upper digestive tract haemorrhage with clinical signs of hypovolemic shock. The patient subsequently underwent an upper gastro-intestinal endoscopy that suspected an ulcerated gastric neoplasm. The patient therefore underwent a total gastrectomy and was discharged home on p.o. day X. The pathology report showed an Ischaemic infarction of gastric mucosal tissue with pomphoid Oedema of submucosal layer. Ulcerative superficial necrosis with venous haemorragic swarm and focal acute pseudomembranous inflammation. Not neoplastic features. Etiopathogenetic, pathophisiologic ipoteses and clinical implication of Idiopathic ischaemic infarction of the stomach are discussed.


The Effect of Luteinizing Hormone Reducing Agent on Anxiety and Novel Object Recognition Memory in Gonadectomized Rats.
Mood disorders such as anxiety and depression are common following menopause and andropause. Lack of sex steroid hormones is suggested as the primary cause of these disturbances. The level of luteinizing hormone (LH) would also rise 3-4 times than normal in these people. The potential effects of LH on mood and cognitive symptoms following menopause and andropause are still unknown. This study aimed to investigate the effect of increased LH on novel object discrimination (NOD) memory and anxiety like behavior in gonadectomized rats. Four-month-old male and female Wistar rats were randomly assigned into 4 groups (in each sex): control rats (Cont), gonadectomized without treatment (GnX), gonadectomized treated with triptorelin, a GnRH agonist which reduces LH release eventually, (GnX+Tr), gonadectomized treated with triptorelin plus sex steroid hormone, estradiol in female and testosterone in male rats (GnX+Tr+S/T). After 4 weeks treatment, anxiety score (elevated plus maze) and NOD were measured. Data were analyzed using One-way ANOVA, and P-values less than 0.05 were considered as significant. Gonadectomy increased anxiety like behaviors (decrease of presence time in the open arms) in female rats (P=0.012), but not in male ones (P=0.662). Additionally, triptorelin alone reduced the increased anxiety score in gonadectomized female rats, compared to group treated with both triptorelin and estradiol. Furthermore, it was shown that gonadectomy and or treatment with triptorelin and sex steroids had no significant effect on novel object recognition memory in both female (P=0.472) and male rats (P=0.798). Findings of this study revealed that increased level of LH following menopause or andropause should be considered as a possible cause for increased anxiety. Also, this study showed that LH reducing agents would reduce anxiety like behavior in gonadectomized female rats. The effect of increased LH on cognitive functions such as novel object recognition memory was not evident in this study and needs further studies.


Exploring the Role of Adsorption and Surface State on the Hydrophobicity of Rare Earth Oxides.
Rare earth oxides (REOs) are attracting attention for use as cost-effective, high-performance dropwise condensers because of their favorable thermal properties and robust nature. However, to engineer a suitable surface for industrial applications, the mechanism governing wetting must be first fully elucidated. Recent studies exploring the water-wetting state of REOs have suggested that these oxides are intrinsically hydrophobic owing to the unique electronic structure of the lanthanide series. These claims have been countered with evidence that they are inherently hydrophilic and that adsorption of contaminants from the environment is responsible for the apparent hydrophobic nature of these surfaces. Here, using X-ray photoelectron spectroscopy and dynamic water contact angle measurements, we provide further evidence to show that REOs are intrinsically hydrophilic, with ceria demonstrating advancing water contact angles of ≈6° in a clean surface state and similar surface energies to two transition metal oxides (≳72 mJ/m2). Using two model volatile species, it is shown that an adsorption mechanism is responsible for the apparent hydrophobic property observed in REOs as well as in transition metal oxides and silica. This is correlated with the screening of the polar surface energy contribution of the underlying oxide with apparent surface energies reduced to <40 mJ/m2 for the case of nonane adsorption. Moreover, we show that the degree of surface hydroxylation plays an important role in the observed contact angle hysteresis with the receding contact angle of ceria increasing from ∼10° to 45° following thermal annealing in an inert atmosphere. Our findings suggest that high atomic number metal oxides capable of strongly adsorbing volatile species may represent a viable paradigm toward realizing robust surface coating for industrial condensers if certain challenges can be overcome.


Criterion-referenced evaluation of day one clinical competencies of veterinary students: VOLES-the VMTH (Veterinary Medicine Teaching Hospital) Online Evaluation System.
This article describes an extensive online criterion-referenced evaluation system for the assessment of veterinary students' achievement during their final year's Doctor of Veterinary Medicine (or equivalent) clinical education. Data are reported for the 2001 to 2009 University of California at Davis veterinary graduates, for a total of more than 1,100 students. These criterion-referenced evaluations extensively document the level of clinical skills attained and demonstrated during the individual clinical rotations that comprise the fourth-year curriculum. On average, in each of the 17,500 clinical rotations undertaken during this time period, student performance was assessed in at least 11 separate areas of skills, knowledge, and professional attributes. This provided more than 200,000 criterion-referenced judgments of the individual clinical attributes of graduates over nine years. The system is based on a previously detailed and validated definition of the skills, knowledge, and professional attributes that students should have demonstrated before graduation. The extensive database that this system has provided has established that this system, termed VOLES (VMTH [Veterinary Medicine Teaching Hospital] On-Line Evaluation System), is an effective tool to assess the clinical capabilities of veterinary students and their achievement of the "Day One" skills required for entering clinical practice. These expected proficiencies are balanced according to the differing expectations that each area of veterinary clinical practice demands.


Barriers to the Utilization of Low-Vision Rehabilitation Services among Over-50-Year-Old People in East and Southeast Asian Regions: A Scoping Review.
East and Southeast Asia (ESEA) are facing age-related eye health issues. Low-vision rehabilitation (LVR), which is a special rehabilitation service for individuals with vision impairment, is a promising solution for these health issues; however, poor accessibility to LVR services has been reported globally, including ESEA. Therefore, this scoping review aimed to summarize and understand the barriers to accessing LVR services in ESEA. In total, 20 articles were ultimately considered eligible for this scoping review after an electronic database search using MEDLINE (PubMed), Web of Science, Academic Search Ultimate (EBSCO), and Ichushi-Web (Japanese medical literature database), and an independent review by two reviewers. Twenty-one potential barrier factors were identified in the full-text review. Notably, age, education, economic status, "previous experience using eye care service", and "knowledge, information, and awareness" were the possible barrier factors that were examined for their association with LVR utilization, with supportive evidence in many eligible studies. We also identified research gaps relating to geographical and ethnic diversity, the scope of LVR services, and barriers among eligible articles. Therefore, by conducting further studies addressing the research gaps identified in this scoping review, these findings can be used to make LVR services more accessible to people in ESEA.


Bexarotene capsules and gel for previously treated patients with cutaneous T-cell lymphoma: results of the Australian patients treated on phase II trials.
Bexarotene (Targretin, LGD1069) is a novel synthetic retinoid analogue that binds selectively to retinoid X receptors. We describe eight previously treated patients who entered phase II international multicentre studies examining the role of bexarotene in cutaneous T-cell lymphoma. Patients received either the oral formulation (n = 7) or the topical gel (n = 1). Of the seven patients who received 300 mg/m2 per day capsules, five (71%) achieved a partial response, with mean time to onset of response of 27 days (range, 20-29) with responses persisting for a mean of 92 days (range, 57-115). The single patient receiving the topical preparation (stage IB) remains in partial response at 31 months. The major toxicity with oral administration was hypertriglyceridaemia requiring therapy. Bexarotene capsules and gel are active and generally well-tolerated agents in patients with cutaneous T-cell lymphoma and studies examining its role in previously untreated patients or as part of combination therapy are warranted.


A Randomized Comparison of Remifentanil Target-Controlled Infusion Versus Dexmedetomidine Single-Dose Administration: A Better Method for Smooth Recovery From General Sevoflurane Anesthesia.
Remifentanil target-controlled infusion and dexmedetomidine single-dose administration are known to reduce airway response and hemodynamic stimulation during anesthetic recovery. We compared the effects of 2 drugs on the prevention of cough during emergence. We enrolled 70 female patients aged 20-60 years with American Society of Anesthesiologists (ASA) I-II who underwent general anesthesia for elective thyroidectomy. The patients were randomly assigned to remifentanil (group R) or dexmedetomidine (group D). Anesthesia was maintained with sevoflurane and effect-site target-controlled infusion of remifentanil. In group D, remifentanil was discontinued, and dexmedetomidine 0.5 μg/kg was given 10 minutes before the end of surgery. In group R, remifentanil target-controlled infusion at an effective-site concentration of 2.0 ng/mL was maintained during emergence until extubation. The cough grade, hemodynamic values, respiration, and other recovery profiles were evaluated during the periextubation period. The proportion of patients with no cough or just a single cough during extubation was significantly higher in group R than in group D (96.8% vs. 55.9%). The change of mean arterial pressure and heart rate were not significantly different during extubation in both groups. Respiratory rate and the incidence of residual sedation after extubation were lower in group R. There were no desaturation events and no differences in time to extubation or duration of postanesthesia care unit stay in both groups. Remifentanil target-controlled infusion reduces emergence cough from general anesthesia more effectively than single-dose dexmedetomidine. However, a single-dose of dexmedetomidine has the effect with respect to respiratory and hemodynamic stability during emergence.


[Diurnal variation of pain perception and heart rate in the human tourniquet pain model in healthy volunteers].
The diurnal variation of pain threshold was studied in 13 healthy volunteers (age: 21 - 27 ys) using the tourniquet pain model. A tourniquet was inflated above systolic blood pressure for 1 minute and pain scores and heart rate were recorded at 0.5, 1.0, 1.5 and 2.0 minutes. The test was repeated during a study day at 6.00 h, 12.00 h, 18.00 h and 24.00 h. Significant differences of pain scores between clocktimes were found 1 minutes after inflation and after 1.5 minutes with regard to heart rate. Generally, the highest pain scores were found at 24.00 h.


34th Annual APRN Legislative Update: Trends in APRN practice authority during the COVID-19 global pandemic.
Relaxation of existing regulations in supervision, collaboration, license renewal, and portability due to the continuing COVID-19 pandemic improved practice authority for advanced practice registered nurses (APRNs) in reduced- and restricted-practice states. This 34th Annual Legislative Update covers the scope of practice changes, and legislative and regulatory decisions that most impacted APRNs across the US in 2021.


Right cardiac intracavitary metastases from a primary intracranial myxofibrosarcoma.
Primary intracranial myxofibrosarcoma is exceedingly rare, with less than 10 cases published. We present a case of a 23-year-old man with previous history of a primary low grade myxofibrosarcoma of the left parietal-occipital convexity resected in March 1999. He subsequently underwent several interventions for multiple local recurrent disease until March 2004. At that time, complete remission was documented. About 8 years later, in February 2012, the patient was admitted to the emergency room with refractory acute pulmonary oedema. On work up, sustained monomorphic ventricular tachycardia and hyperechoic myocardial mass with invasion of the right ventricular cavity were detected. Electrical cardioversion was unsuccessful and irreversible cardiac arrest followed. The autopsy confirmed multiple bilateral lung metastases, malignant pulmonary embolism and myocardial invasion by the primary tumour, with intracavitary cardiac thrombosis and absence of intracranial disease. To the best of our knowledge, this is the first report of extracranial metastases of this neoplasm.


Sex differences in mortality associated with computed tomographic angiographic measurements of obstructive and nonobstructive coronary artery disease: an exploratory analysis.
Sex differences exist in the prevalence and severity of obstructive coronary artery disease (CAD). Limited data are available to explore sex differences in prognosis with coronary computed tomographic angiographic (CCTA) measurements of CAD including novel nonobstructive plaque extent. A total of 1127 consecutive patients were clinically referred to 16-slice CCTA and followed for the occurrence of all-cause death. Time to death was calculated by univariable and multivariable Cox proportional hazard models. Four-year survival (92.1%) was similar by sex (P=0.52). Women more often had no coronary stenosis (54%) as compared with men (28%) (P<0.0001). Mortality worsened for both women (P<0.0001) and men (P=0.002) by the number of vessels with > or =50% stenosis. For women, overall mortality ranged from 3.5% for no CAD to 25.0% for women with 3-vessel plus left main obstructive CAD (P<0.0001). For men, overall mortality ranged from 2.7% for no CAD to 17.4% for males with 3-vessel plus left main obstructive CAD (P=0.002). Nonobstructive disease was prevalent in women (range, 24% to 66%) and men (range, 45% to 74%) ages 45 to > or =80 years. Nonobstructive CAD extent was a significant estimator of all-cause mortality when added to a model containing pretest CAD likelihood and obstructive CAD extent (P=0.039). For men, in a risk-adjusted model including pretest CAD likelihood and obstructive CAD, the number of nonobstructive lesions was not a significant estimator of mortality (P=0.9). For women, the relative hazard for mortality, in a multivariable model, was 1.3 per nonobstructive lesion (P=0.003), including pretest CAD likelihood and obstructive CAD as covariates. For women, risk-adjusted median mortality ranged from 2.9% to 10.9% for none to > or =4 nonobstructive lesions (P<0.0001). Based on our preliminary analyses, CCTA obstructive and nonobstructive CAD adds incremental value to clinical assessment for risk stratification. Moreover, the extent of nonobstructive CAD by CCTA predicts mortality in women but not in men and may be helpful to optimize therapeutic strategies for women.


Reduction of TRPV1 expression in the trigeminal system by botulinum neurotoxin type-A.
Botulinum neurotoxin type-A (BoNT-A) is clinically used for patients with pain disorders and dystonia. The precise mechanism whereby BoNT-A controls pain remains elusive. Here, we studied how BoNT-A affects the expression of the transient receptor potential vanilloid subfamily member 1 (TRPV1), a cation channel critically implicated in nociception, in the trigeminal system. Histological studies revealed that subcutaneous BoNT-A injection (0.25, 0.5, or 5 ng/kg) into the face targeted the ophthalmic division of trigeminal ganglion (TG) neurons and decreased TRPV1-immunoreactive neurons in the TG and TRPV1-immunoreactive fibers in rat trigeminal terminals. Of note, TG neurons that received projections from the dura mater, a principal site of headache generation, had reduced TRPV1 expression. BoNT-A-induced cleavage of SNAP25 (synaptosomal-associated protein of 25-kDa) in the TG became obvious 2 days after BoNT-A administration and persisted for at least 14 days. Quantitative real-time RT-PCR (reverse transcription-polymerase chain reaction) data indicated that the TRPV1-decreasing effects of BoNT-A were not mediated by transcriptional downregulation. By employing a surface protein biotin-labeling assay, we demonstrated that BoNT-A inhibited TRPV1 trafficking to the plasma membrane in primary TG neurons. Moreover, Y200F-mutated TRPV1, which is incapable of trafficking to the plasma membrane, was expressed in PC12 cells by transfection, and pharmacological studies revealed that TRPV1 in the cytoplasm was more predisposed to proteasome-mediated proteolysis than plasma membrane-located TRPV1. We conclude that the mechanism by which BoNT-A reduces TRPV1 expression involves the inhibition of TRPV1 plasma membrane trafficking and proteasome-mediated degradation in the cytoplasm. This paradigm seems to explain how BoNT-A alleviates TRPV1-mediated pain. Our data reveal a likely molecular mechanism whereby BoNT-A treatment reduces TRPV1 expression in the trigeminal system and provide important clues to novel therapeutic measures for ameliorating craniofacial pain.


Follicular lymphoma in the United States: first report of the national LymphoCare study.
Optimal therapy of follicular lymphoma (FL) is not defined. We analyzed a large prospective cohort study to identify current demographics and patterns of care of FL in the United States. The National LymphoCare Study is a multicenter, longitudinal, observational study designed to collect information on treatment regimens and outcomes for patients with newly diagnosed FL in the United States. Patients were enrolled between 2004 and 2007. There is no study-specific prescribed treatment regimen or intervention. Two thousand seven hundred twenty-eight subjects were enrolled at 265 sites, including the 80% of patients enrolled from nonacademic sites. Using the Follicular Lymphoma International Prognostic Index (FLIPI), three distinct groups independent of histologic grade could be defined. Initial therapeutic strategy was: observation, 17.7%; rituximab monotherapy, 13.9%; clinical trial 6.1%; radiation therapy, 5.6%; chemotherapy only, 3.2%; chemotherapy plus rituximab, 51.9%. Chemotherapy plus rituximab regimens were: rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone, 55.0%; rituximab plus cyclophosphamide, vincristine, and prednisone, 23.1%; rituximab plus fludarabine based, 15.5%; other, 6.4%. The choice to initiate therapy rather than observe was associated with age, FLIPI, stage, and grade (P < .01). Significant differences in treatment (P < .01) across regions of the United States were noted. Contrary to practice guidelines, treatment of stage I FL frequently omits radiation therapy. Widely disparate therapeutic approaches are utilized for FL. Initial therapy is deferred in a small subset of patients. There is no single standard of care for the treatment of de novo FL, although antibody use is ubiquitous when therapy is initiated. These disparate approaches to the initial care of patients with FL render a heterogeneous group of patients at relapse.


The oxygen consumption associated with unloaded walking and load carriage using two different backpack designs.
The purpose of this study was to assess the energy expenditure associated with load carriage using both a traditional rucksack and a new rucksack design, the AARN rucksack, which incorporates front balance pockets. Nine volunteers walked at 3 km h(-1) at various uphill and downhill gradients on a treadmill without a load and carrying a load of 25.6 kg in each of the rucksacks. The oxygen consumption associated with both of the loading conditions was significantly (P < 0.001) higher than that associated with unloaded walking at all downhill gradients tested, although there was no significant difference between the two loading conditions. During the uphill gradients the oxygen consumption associated with the AARN pack was significantly (P < 0.05) lower than that associated with the traditional pack at the 0%, 5%, 10% and 20% gradients. The mean (%) differences at these gradients, expressed in ml x kg(-1) x min(-1) were 1.18 (9%), 1.45 (8%), 1.76 (8%) and 1.88 (6%), respectively. On average for the whole protocol, the oxygen consumption associated with the AARN rucksack was 5% lower than that associated with the traditional rucksack [mean (SD) 17.28 (7.46) ml x kg(-1) x min(-1) for the AARN pack and 18.20 (7.84) ml x kg(-1) x min(-1) for the traditional pack]. The findings of the present study suggest that a load carriage system that allows the load to be distributed between the back and font of the trunk is more appropriate for carrying relatively heavy loads than a system that loads the back only.


Salmonella vaccine vectors displaying delayed antigen synthesis in vivo to enhance immunogenicity.
We have developed a regulated delayed antigen synthesis (RDAS) system for use in recombinant attenuated Salmonella vaccine (RASV) strains to enhance immune responses by reducing the adverse effects of high-level antigen synthesis. This system includes a chromosomal repressor gene, lacI, expressed from the arabinose-regulated araC PBAD promoter. LacI serves to regulate expression from a plasmid promoter, Ptrc, that directs antigen synthesis. In the presence of arabinose LacI is produced, which binds to Ptrc, blocking antigen synthesis. In vivo, an arabinose-poor environment, the concentration of LacI decreases with each cell division, allowing increased antigen synthesis. To optimize the system and for comparison, we altered the lacI ribosome-binding site, start codon, and/or codon content to construct RDAS strains chi9095, chi9959, and chi9241, synthesizing from low to high levels of LacI, respectively, and non-RDAS strain chi9555 as a control. We evaluated this system with two test antigens, the green fluorescent protein for initial in vitro assessment and the Streptococcus pneumoniae PspA protein for validation of our system in mice. All RASV strains expressing PspA generated high antilipopolysaccharide antibody titers, indicating that expression of lacI did not interfere with the capacity to induce an immune response. Strain chi9241 induced significantly higher anti-PspA IgG and IgA antibody titers than strain chi9555, which expressed PspA constitutively. Anti-PspA antibody titers were inversely correlated to the level of LacI synthesis. Strain chi9241 also induced significantly greater protective efficacy against challenge with virulent S. pneumoniae. These results suggest that regulated delayed antigen synthesis is useful for improving immunogenicity of RASV strains.


Screening of Secreted Proteins of Sporisorium reilianum f. sp. zeae for Cell Death Suppression in Nicotiana benthamiana.
Sporisorium reilianum f. sp. zeae (SRZ) is a biotrophic fungus causing head smut in maize. Maize infection with SRZ leads to very little cell death suggesting the presence of cell-death suppressinpg effectors. Several hundred effector proteins have been predicted based on genome annotation, genome comparison, and bioinformatic analysis. For only very few of these effectors, an involvement in virulence has been shown. In this work, we started to test a considerable subset of these predicted effector proteins for a possible function in suppressing cell death. We generated an expression library of 62 proteins of SRZ under the control of a strong constitutive plant promoter for delivery into plant cells via Agrobacterium tumefaciens-mediated transient transformation. Potential apoplastic effectors with high cysteine content were cloned with signal peptide while potential intracellular effectors were also cloned without signal peptide to ensure proper localization after expression in plant cells. After infiltration of Nicotiana benthamiana leaves, infiltration sites were evaluated for apparent signs of hypersensitive cell death in absence or presence of the elicitin INF1 of Phytophthora infestans. None of the tested candidates was able to induce cell death, and most were unable to suppress INF1-induced cell death. However, the screen revealed one predicted cytoplasmic effector (sr16441) of SRZ that was able to reliably suppress INF1-induced cell death when transiently expressed in N. benthamiana lacking its predicted secretion signal peptide. This way, we discovered a putative function for one new effector of SRZ.


An outbreak of shigellosis due to Shigella flexneri serotype 3a in a prison in Iran.
On June 16 and 17, 2007, the medical clinic of a prison in Isfahan, Iran received multiple reports of gastrointestinal illness among prisoners. A cross-sectional study was therefore undertaken to determine the extent, causative agent and possible source of the outbreak. A case-patient was defined and patient information was collected with a standardized questionnaire. Stool samples were collected from the patients and restaurant employees, and analyzed for the presence of enteric bacteria by routine bacteriological methods. Shigella isolates were identified and serotyped by commercially available antisera. The relationship between the strains was determined using antimicrobial drug resistance pattern analysis and enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR). Seven hundred one inmates experienced gastrointestinal illness and severe diarrhea. The attack rate was 14.02%. Rectal swabs and stool cultures recovered from patients tested positive for Shigella flexneri serotype 3a. All tested isolates had a similar antibiotic resistance and ERIC-PCR pattern. Our findings demonstrated that raw vegetables were more likely to be the causative agent of this outbreak. The results indicated that a single clone of S. flexneri was responsible for this outbreak. Although we could not trace the exact origin of the organism, the consumption of raw vegetables one day prior to the onset of illness was strongly associated with an increased risk of S. flexneri infection. This study emphasizes the need for accurate monitoring and surveillance of food and vegetables consumed in prisons.


Risk factors for indicators of opioid-related harms amongst people living with chronic non-cancer pain: Findings from a 5-year prospective cohort study.
The literature suggests patient characteristics and higher opioid doses and long-term duration are associated with problematic opioid behaviours but no one study has examined the role of all these factors simultaneously in a long-term prospective cohort study. Five-year, community-based, prospective cohort of people prescribed opioids for chronic non-cancer pain (CNCP). Logistic mixed effect models with multiple imputation were used to address missing data. Oral morphine equivalent (OME) mg per day was categorised as: 0 mg OME/day, 1-49 mg OME/day (reference), 50-89 mg OME/day, 90-199 mg OME/day and 200mg+ OME/day. Patient risk factors included: age, gender, substance use, mental health history and pain-related factors. Main outcomes included: Prescribed Opioids Difficulties Scale (PODS), Opioid-Related Behaviours In Treatment (ORBIT) scale, and ICD-10 opioid dependence. Multiple confounders for problematic opioid behaviours were assessed. Of 1,514 participants 44.4% were male (95%CI 41.9-46.9) and their mean age was 58 years (IQR 48-67). Participants had a mean duration of pain of 10 years (IQR 4.5-20.0) and had been taking strong opioids for a median of four years (IQR 1.0-10.0). At baseline, median OME/day was 73 (IQR 35-148). At 5-years, 85% were still taking strong opioids. PODS moderate-high scores reduced from 59.9% (95%CI 58.8-61.0) at baseline to 51.5% (95%CI 50.0-53.0) at 5-years. Around 9% met criteria for ICD-10 opioid dependence at each wave. In adjusted mixed effect models, the risk factors most consistently associated with problematic opioid use were: younger age, substance dependence, mental health histories and higher opioid doses. Both patient risk factors and opioid dose are associated with problematic opioid use behaviours.


Physiological, proteomic and transcriptional responses of wheat to combination of drought or waterlogging with late spring low temperature.
Spring low temperature events affect winter wheat (Triticum aestivum L.) during late vegetative or reproductive development, exposing plants to a subzero low temperature stress when winter hardening is lost. The increased climatic variability results in wheat being exposed to more frequent adverse impacts of combined low temperature and water stress, including drought and waterlogging. The responses of potted wheat plants cultivated in climatic chambers to these environmental perturbations were investigated at physiological, proteomic and transcriptional levels. At the physiological level, the depressed carbon (C) assimilation induced by the combined stresses was due mainly to stomatal closure and damage of photosynthetic electron transport. Biochemically, the adaptive effects of early moderate drought or waterlogging stress were associated with the activation of antioxidant enzyme system in chloroplasts and mitochondria of leaf under low temperature. Further proteomic analysis revealed that the oxidative stress defence, C metabolism and photosynthesis related proteins were modulated by the combined low temperature and water stress. Collectively, the results indicate that impairment of photosynthesis and C metabolism was responsible for the grain yield loss in winter wheat under low temperature in combination with severe drought or waterlogging stress. In addition, prior mild drought or waterlogging contributed to the homeostasis of oxidative metabolism and relatively better photosynthesis, and hence to less grain yield loss under later spring low temperature stress.


Next generation sequencing identifies mutations in Atonal homolog 7 (ATOH7) in families with global eye developmental defects.
The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. Most of these clinical features overlap with defects in the Norrin/β-catenin signalling pathway that is characterized by dysgenesis of the retinal and hyaloid vasculature. Our findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye. This work also provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression.


Interaction of platelet-activating factor with cultured guinea pig tracheal epithelial cells.
The present study has examined the interaction of platelet-activating factor (PAF) with cultured guinea pig tracheal epithelial cells (GTE). PAF stimulated GTE to release endogenous arachidonic acid and metabolize it to prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Prostanoid production by GTE in response to PAF was dose-dependent (0.1-100 nM) and was maximal within 5 min. PGE2 and PGF2 alpha levels increased by 3.3 +/- 0.8 and 3.2 +/- 0.6 ng/10(6) cells respectively over basal levels in response to 100 nM-PAF. The ability of GTE to synthesize and/or catabolize PAF was also examined. GTE readily incorporated [3H]acetate into a product which migrated on t.l.c. with PAF. However, further characterization of this product suggested that label had not been incorporated into PAF, but rather that it was incorporated into another lipid product with chromatographic characteristics similar to those of PAF. In contrast, GTE readily metabolized PAF to inactive products. When [3H]PAF was incubated with GTE, 50% of the total [3H]PAF added was catabolized in approx. 15 min. The major route of catabolism of PAF by GTE was the deacetylation-reacylation pathway, which yielded 1-O-[3H]alkyl-2-acyl-sn-glycerophosphocholine. Determination of the nature of the long-chain acyl group incorporated into the sn-2 position of the newly synthesized products revealed that oleic and linoleic acids were the major fatty acids present. Taken together, these results suggest that respiratory epithelial cells respond to stimulation by PAF with enhanced production of PGE2 and PGF2 alpha, and also have the capacity to modulate inflammatory reactions in the airways by their ability to degrade this potent inflammatory mediator.


Large-Scale Silicon Nanophotonic Metasurfaces with Polarization Independent Near-Perfect Absorption.
Optically thin perfect light absorbers could find many uses in science and technology. However, most physical realizations of perfect absorption for the optical range rely on plasmonic excitations in nanostructured metallic metasurfaces, for which the absorbed light energy is quickly lost as heat due to rapid plasmon decay. Here we show that a silicon metasurface excited in a total internal reflection configuration can absorb at least 97% of incident near-infrared light due to interferences between coherent electric and magnetic dipole scattering from the silicon nanopillars that build up the metasurface and the reflected wave from the supporting glass substrate. This "near-perfect" absorption phenomenon loads more than 50 times more light energy into the semiconductor than what would be the case for a uniform silicon sheet of equal surface density, irrespective of incident polarization. We envisage that the concept could be used for the development of novel light harvesting and optical sensor devices.


Structural and functional damage to neuronal nuclei caused by extracellular tau oligomers.
Neuronal nuclei are normally smoothly surfaced. In Alzheimer's disease (AD) and other tauopathies, though, they often develop invaginations. We investigated mechanisms and functional consequences of neuronal nuclear invagination in tauopathies. Nuclear invagination was assayed by immunofluorescence in the brain, and in cultured neurons before and after extracellular tau oligomer (xcTauO) exposure. Nucleocytoplasmic transport was assayed in cultured neurons. Gene expression was investigated using nanoString nCounter technology and quantitative reverse transcription polymerase chain reaction. Invaginated nuclei were twice as abundant in human AD as in cognitively normal adults, and were increased in mouse neurodegeneration models. In cultured neurons, nuclear invagination was induced by xcTauOs by an intracellular tau-dependent mechanism. xcTauOs impaired nucleocytoplasmic transport, increased histone H3 trimethylation at lysine 9, and altered gene expression, especially by increasing tau mRNA. xcTauOs may be a primary cause of nuclear invagination in vivo, and by extension, impair nucleocytoplasmic transport and induce pathogenic gene expression changes. Extracellular tau oligomers (xcTauOs) cause neuronal nuclei to invaginate. xcTauOs alter nucleocytoplasmic transport, chromatin structure, and gene expression. The most upregulated gene is MAPT, which encodes tau. xcTauOs may thus drive a positive feedback loop for production of toxic tau.


The clinical spectrum and natural history of pure akinesia with gait freezing.
Gait freezing as a presenting and relatively restricted condition is uncommon but a distinctive disorder. This entity was initially defined as "pure akinesia with gait freezing", and later a neuropathological substrate of progressive supranuclear palsy has been recognized. Limited studies have reported the clinical evolution after presentation, which is important for patient counseling. The objective of this study was to assess the demographic and clinical features, treatment-response, neuroimaging, and evolution of pure akinesia with gait freezing. A retrospective review of patients with this phenotype as previously defined was performed. Patients included had no or minimal limb rigidity and/or bradykinesia and no resting tremor, and all underwent neuroimaging of the brain after onset. Inclusion criteria were met by 30 patients, who were followed up to 21 years after symptom onset. During their course, 28 patients had falls (93 %), 12 patients had dysarthria (40 %), and 13 had handwriting changes (43 %). All patients had progression of their gait disorder over time, but with a variable interval until falls occurred. None of the patients developed vertical gaze palsy or met diagnostic criteria for an alternative parkinsonian disorder. Pure akinesia with gait freezing is a distinctive disorder that can be recognized in the clinic. Despite the previously reported progressive supranuclear palsy-like neuropathology, the clinical course is much less aggressive and disabling than classic Richardson syndrome, although fall risk eventually develops in nearly all patients. Bradykinesia, tremor, and rigidity do not develop, distinguishing pure akinesia with gait freezing from Parkinson's disease and other parkinsonian disorders.


[State of the cerebral circulation according to radiocirculographic data in patients with diabetes mellitus].
Cerebral circulation velocity was studied by the method of radiociruclography in patients (101) with various forms of diabetes mellitus. There was revealed a decrease in this velocity in the majority (2/3) of these patients. Early preclinical forms of affections of the vessels of the brain were revealed, and the degree of these changes was established. This method permitted to detect an association between a disturbed cerebral circulation and the most frequent complication occurring in patients with diabetes mellitus (atherosclerosis and microangiopathies).


Grievances against physicians: 11 years' experience of a medical society grievance committee.
To understand causes of patient dissatisfaction that result in complaints. Grievances received by the grievance committee between January 1, 1989, and January 1, 2000, were reviewed. A 2-county area of North Carolina. Of 29 patients who filed grievances, the 9 male (31%) and 20 female (69%) patients had a mean (+/-SD) age of 39 (+/-19) years. In 18 instances, the patient consulted the physician less than 3 times (64%) before the complaint and in 8 instances more than 4 times (29%). Main outcome measures Allegations of the grievance and the committee's findings. Grievances fell into 5 categories: failure to fulfill expectations for examination and treatment (38%), failure to promptly diagnose (20%), rudeness (17%), producing excessive pain or practicing beyond the area of expertise (13%), and inappropriate behavior related to billings (10%). In 45% of the grievances, the committee found no breach of practice standards. In 17% of the cases, the physician resolved the grievance by apologizing, adjusting a bill, or completing insurance forms. Most grievances were filed by younger women against newly encountered physicians and were related to inadequate communication or alleged delay in diagnosis.


Metabolic adaptations of three inbred strains of mice (C57BL/6, DBA/2, and 129T2) in response to a high-fat diet.
Although it is now becoming more evident that the strain of mouse used to generate genetically modified models for the study of endocrine disorders contributes to the ensuing phenotype, metabolic characterization of these common strains used to produce genetically altered mice has been limited. The aim of this study therefore was to measure various metabolic parameters in C57BL/6, DBA/2, and 129T2 mice fed a control or a high-fat diet. Mice were fed either a control (7 g/100 g) or a high-fat (60 g/100 g) diet for 6 wk. During wk 6, spontaneous and voluntary physical activity and resting energy expenditure were determined. DBA/2 mice that consumed the control diet gained more weight and had larger regional fat pad depots than either C57BL/6 or 129T2 mice (P < 0.05). Spontaneous and voluntary activity was lower in 129T2 mice compared with DBA/2 or C57BL/6 mice (P < 0.05). Resting energy expenditure (corrected for body weight) was greater in C57BL/6 mice than in DBA/2 or 129T2 mice (P < 0.05), whereas glucose and fat oxidation did not differ among the 3 strains of mice. Plasma glucose concentrations in food-deprived mice were higher and insulin concentrations lower in 129T2 compared with C57BL/6 mice (P < 0.05), but were not affected by the high-fat diet in any of the 3 strains tested. This study shows that these 3 commonly used inbred strains of mice have different inherent metabolic characteristics. It further highlights that the background strain used to produce genetically modified mice is critical to the resultant phenotype.


The impact of MRI on the clinical management of inflammatory arthritides.
In the past two decades, MRI has gained a major role in research and clinical management of patients with inflammatory arthritides, particularly in spondyloarthritis (SpA), rheumatoid arthritis (RA), and osteoarthritis (OA). MRI is regarded as the most sensitive imaging modality for detecting early SpA in young patients with inflammatory back pain and normal radiographs of the sacroiliac joints. The recently published Assessment of SpondyloArthritis International Society classification criteria for axial SpA include for the first time a positive MRI demonstrating sacroiliitis as an imaging criterion indicative of SpA together with at least one clinical feature of SpA. Recent data show that systematic assessment of sacroiliitis displayed on MRI has much greater diagnostic utility than previously reported and highlight the diagnostic relevance of structural lesions. In RA, MRI has predictive value for the development of disease in new onset undifferentiated arthritis, and MR pathology at disease onset is a highly significant predictor of radiographic erosions. Consequently MRI has been credited with an important role in the new ACR/EULAR 2010 classification criteria for RA. In OA, bone marrow edema (BME) and synovitis may serve as biomarkers in interventional trials. Treatment interventions targeting BME and synovitis observed on MRI in inflammatory arthritides may have a disease-modifying effect as these lesions are potentially reversible and have been shown to be associated with structural progression. Research should focus on the prognostic significance of MRI lesions in larger cohorts and whether adding MRI to routine care improves clinical and radiographic outcome in patients with inflammatory arthritides.


Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection.
The release of microparticles from eukaryotic cells is a well-recognized phenomenon. We demonstrate here that the chemokine receptor CCR5, the principal co-receptor for macrophage-tropic human immunodeficiency virus (HIV)-1, can be released through microparticles from the surface of CCR5+ Chinese hamster ovary cells and peripheral blood mononuclear cells. Microparticles containing CCR5 can transfer the receptor to CCR5- cells and render them CCR5+. The CCR5 transfer to CCR5-deficient peripheral blood mononuclear cells homozygous for a 32-base-pair deletion in the CCR5 gene enabled infection of these cells with macrophage-tropic HIV-1. In monocytes, the transfer of CCR5 could be inhibited by cytochalasin D, and transferred CCR5 could be downmodulated by chemokines. A transfer of CCR5 from peripheral blood mononuclear cells to endothelial cells during transendothelial migration could be demonstrated. Thus, the transfer of CCR5 may lead to infection of tissues without endogenous CCR5 expression. Moreover, the intercellular transfer of membrane proteins by microparticles might have broader consequences for intercellular communication beyond the effects seen for HIV-1.


The ataxia related G1107D mutation of the plasma membrane Ca2+ ATPase isoform 3 affects its interplay with calmodulin and the autoinhibition process.
The plasma membrane Ca2+ ATPases (PMCA pumps) have a long, cytosolic C-terminal regulatory region where a calmodulin-binding domain (CaM-BD) is located. Under basal conditions (low Ca2+), the C-terminal tail of the pump interacts with autoinhibitory sites proximal to the active center of the enzyme. In activating conditions (i.e., high Ca2+), Ca2+-bound CaM displaces the C-terminal tail from the autoinhibitory sites, restoring activity. We have recently identified a G1107D replacement within the CaM-BD of isoform 3 of the PMCA pump in a family affected by X-linked congenital cerebellar ataxia. Here, we investigate the effects of the G1107D replacement on the interplay of the mutated CaM-BD with both CaM and the pump core, by combining computational, biochemical and functional approaches. We provide evidence that the affinity of the isolated mutated CaM-BD for CaM is significantly reduced with respect to the wild type (wt) counterpart, and that the ability of CaM to activate the pump in vitro is thus decreased. Multiscale simulations support the conclusions on the detrimental effect of the mutation, indicating reduced stability of the CaM binding. We further show that the G1107D replacement impairs the autoinhibition mechanism of the PMCA3 pump as well, as the introduction of a negative charge perturbs the contacts between the CaM-BD and the pump core. Thus, the mutation affects both the ability of the pump to optimally transport Ca2+ in the activated state, and the autoinhibition mechanism in its resting state.


Perturbations of Plasmodium Puf2 expression and RNA-seq of Puf2-deficient sporozoites reveal a critical role in maintaining RNA homeostasis and parasite transmissibility.
Malaria's cycle of infection requires parasite transmission between a mosquito vector and a mammalian host. We here demonstrate that the Plasmodium yoelii Pumilio-FBF family member Puf2 allows the sporozoite to remain infectious in the mosquito salivary glands while awaiting transmission. Puf2 mediates this solely through its RNA-binding domain (RBD) likely by stabilizing or hastening the degradation of specific mRNAs. Puf2 traffics to sporozoite cytosolic granules, which are negative for several markers of stress granules and P-bodies, and disappear rapidly after infection of hepatocytes. In contrast to previously described Plasmodium berghei pbpuf2(-) parasites, pypuf2(-) sporozoites have no apparent defect in host infection when tested early in salivary gland residence, but become progressively non-infectious and prematurely transform into EEFs during prolonged salivary gland residence. The premature overexpression of Puf2 in oocysts causes striking deregulation of sporozoite maturation and infectivity while extension of Puf2 expression in liverstages causes no defect, suggesting that the presence of Puf2 alone is not sufficient for its functions. Finally, by conducting the first comparative RNA-seq analysis of Plasmodium sporozoites, we find that Puf2 may play a role in directly or indirectly maintaining the homeostasis of specific transcripts. These findings uncover requirements for maintaining a window of opportunity for the malaria parasite to accommodate the unpredictable moment of transmission from mosquito to mammalian host.


The workload of obstetric doctors working in different modes at a medical center.
The workload of obstetric and gynecologic (OB-GYN) physicians has been an unprecedented increase because of the decrease in the number of such physicians. This study aimed to demonstrate that the hospitalist mode was the best mode for the work-life balance of OB-GYN physicians. This was a retrospective study in a tertiary academic hospital. Patients were admitted to the labor ward for delivery. The number of deliveries performed by each OB-GYN physician in different working modes was measured. We reviewed the medical charts of women admitted for delivery as well as the shift schedule of OB-GYN physicians from January 1, 2018, to June 30, 2018. We classified deliveries into three modes: the traditional mode (patient designation), on-call mode, and the hospitalist mode. Traditional mode was the work mode currently. On-call mode and the hospitalist mode were simulated conditions. The number of deliveries and the total OB-GYN physician worked time for their shift were recorded. The differences between the three modes and between OB-GYN physicians were assessed using analysis of variance. In total, 237 deliveries were recorded over 6 months (3 deliveries were excluded from our data); these deliveries were performed by four OB-GYN physicians named A to D. Significant differences in workload were noted between OB-GYN physicians working in the traditional mode and those in the on-call mode, but no significant differences were noted among those working in the hospitalist mode. All OB-GYN physicians worked an average of seven shifts, and no significant differences among them were noted. The hospitalist mode might be the optimal mode for OB-GYN physicians to achieve a favorable work-life balance if their original main jobs are obstetric practice.


Mechanism of in vitro differentiation of bone marrow stromal cells into neuron-like cells.
In order to study whether marrow stromal cells (MSCs) can be induced into nerve-like cells in vitro, and the mechanism, the MSCs in Wistar rats were isolated and cultured, and then induced with DMSO and BHA in vitro. The expression of specific marking proteins in neurons, glia and neural stem cells were detected before preinduction, at 24 h of preinduction, at 6 h, 24 h, and 48 h of neuronal induction by using immunohistochemistry and Western blotting. The ultrastructural changes after the inducement were observed. The results showed that after the inducement, many MSCs turned into bipolar, multipolar and taper, and then intersected as network structure. At the same time, some MSCs had the typical neuron-like ultrastructure. Immunohistochemistry revealed that NeuN and Nestin expression was detectable after inducement, but there was no GFAP and CNP expression. Western blotting showed the expression of Nestin was strong at 6 h of neuronal induction, and decreased at 24 h, 48 h of the induction. NeuN was detectable at 6 h of neuronal induction, and increased at 24 h, 48 h of the induction. It was concluded MSCs were induced into neural stem cells, and then differentiated into neuron-like cells in vitro.


Transcatheter arterial chemoembolization for intermediate-stage hepatocellular carcinoma: clinical outcome and safety in elderly patients.
The aim of our study was to compare clinical outcomes between elderly patients aged ≥75 years (elderly group, n=66) with intermediate hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE) and younger patients aged <75 years (control group, n=84) with intermediate HCC undergoing TACE. Clinical outcomes, including overall survival (OS) and tumor response rate at initial therapy, were compared between these two groups. The median survival time and the 1- and 3-year cumulative OS rates were 2.90 years and 84.1% and 48.0%, respectively, in the elderly group and 2.44 years and 78.2% and 39.3%, respectively, in the control group (p=0.887). The objective response rate in the elderly group was 81.8% (54/66 patients), while that in the control group was 78.6% (66/84 patients) (p=0.227). Elderly patients with intermediate HCC undergoing TACE had a prognosis comparable with that of younger patients with intermediate HCC undergoing TACE.


Evaluating local benefits from conservation in Nepal's Annapurna Conservation Area.
Protected areas are integral to the global effort to conserve biodiversity, and, over the past two decades, protected area managers have begun to recognize that conservation objectives are next to impossible to achieve without considering the needs and concerns of local communities. Incentive-based programs (IBPs) have become a favored approach to protected area management, geared at fostering local stewardship by delivering benefits tied to conservation to local people. Effective IBPs require benefits to accrue to and be recognized by those experiencing the greatest consequences as a result of the protected area, and those likely to continue extractive activities if their livelihood needs are compromised. This research examines dispersal of IBP benefits, as perceived by local residents in Nepal's Annapurna Conservation Area. Results reported here are based on questionnaire interviews with 188 households conducted between September and December 2004. Results indicate that local residents primarily identify benefits from social development activities, provisions for resource extraction, and economic opportunities. Overall, benefits have been dispersed equally to households in villages on and off the main tourist route, and regardless of a household's participation in tourism. However, benefits are not effectively targeted to poorer residents, those highly dependent on natural resources, and those experiencing the most crop damage and livestock loss from protected wildlife. This article provides several suggestions for improving the delivery of conservation incentives.


Sensitizing the Tumor Microenvironment to Immune Checkpoint Therapy.
Immune checkpoint blockade (ICB) has revolutionized cancer treatment, providing remarkable clinical responses in some patients. However, the majority of patients do not respond. It is therefore crucial both to identify predictive biomarkers of response and to increase the response rates to immune checkpoint therapy. In this review we explore the current literature about the predictive characteristics of the tumor microenvironment and discuss therapeutic approaches that aim to change this toward a milieu that is conducive to response. We propose a personalized biomarker-based adaptive approach to immunotherapy, whereby a sensitizing therapy is tailored to the patient's specific tumor microenvironment, followed by on-treatment verification of a change in the targeted biomarker, followed by immune checkpoint therapy. By incorporating detailed knowledge of the immunological tumor microenvironment, we may be able to sensitize currently non-responsive tumors to respond to immune checkpoint therapy.


N-terminal pro-brain natriuretic peptide levels and short term prognosis in acute ischemic stroke.
Sparse published data are available regarding the prognostic importance of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with acute ischemic stroke. We prospectively studied 74 consecutive patients presenting with acute ischemic stroke within 24 hours of onset. All of them underwent laboratory and imaging evaluation and were treated as per guidelines. In all subjects, plasma NT-proBNP levels were measured at initial admission and again on day 7. Their mean age was 54 ± 13.5years; there were 49 males; 18 (24%) patients died during the hospital stay. A statistically significant negative correlation between log NT-proBNP and Glasgow coma scale (GCS) score (P < 0.001); and a significant positive correlation between log NT-proBNP and National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001) were observed. Baseline log NT-proBNP levels were higher among non-survivors compared with survivors (6.7 ± 0.47 vs. 5.37 ± 0.62; P = 0.06); day 7 log NT-proBNP levels were significantly higher in non-survivors compared with survivors (7.3 ± 0.26 vs. 4.5 ± 0.4; P = 0.000). In survivors, there was a statistically significant decline in log NT-proBNP levels from baseline to day 7 (5.3710 ± 0.620 vs. 4.5320 ± 0.451; P < 0.001). In contrast, among non-survivors, log NT-proBNP levels showed a statistically significant increase from baseline to day 7 (4.5322 ± 0.451 vs. 7.2992 ± 0.263; P < 0.001). On receiver operator characteristic curve (ROC) analysis, at a cut-off value of ≥ 6.0661, log NT-proBNP had a sensitivity and specificity of 98.2 and 88.9, respectively, in predicting death. Plasma log NT-pro-BNP level appears to be a useful biological marker for predicting in-hospital mortality inpatients presenting with acute ischemic stroke.


Spinal cord astrocytomas: progresses in experimental and clinical investigations for developing recovery neurobiology-based novel therapies.
Spinal cord astrocytomas (SCAs) have discernibly unique signatures in regards to epidemiology, clinical oncological features, genetic markers, pathophysiology, and research and therapeutic challenges. Overall, there are presently very limited clinical management options for high grade SCAs despite progresses made in validating key molecular markers and standardizing tumor classification. The endeavors were aimed to improve diagnosis, therapy design and prognosis assessment, as well as to define more effective oncolytic targets. Efficacious treatment for high grade SCAs still remains an unmet medical demand. This review is therefore focused on research state updates that have been made upon analyzing clinical characteristics, diagnostic classification, genetic and molecular features, tumor initiation cell biology, and current management options for SCAs. Particular emphasis was given to basic and translational research endeavors targeting SCAs, including establishment of experimental models, exploration of unique profiles of SCA stem cell-like tumor survival cells, characterization of special requirements for effective therapeutic delivery into the spinal cord, and development of donor stem cell-based gene-directed enzyme prodrug therapy. We concluded that precise understanding of molecular oncology, tumor survival mechanisms (e.g., drug resistance, metastasis, and cancer stem cells/tumor survival cells), and principles of Recovery Neurobiology can help to create clinically meaningful experimental models of SCAs. Establishment of such systems will expedite the discovery of efficacious therapies that not only kill tumor cells but simultaneously preserve and improve residual neural function.


Probabilistic projections of granular energy technology diffusion at subnational level.
Projections of granular energy technology diffusion can support decision-making on climate mitigation policies and infrastructure investments. However, such projections often do not account for uncertainties and have low spatial resolution. S-curve models of technology diffusion are widely used to project future installations, but the results of the different models can vary significantly. We propose a method to create probabilistic projections of granular energy technology diffusion at subnational level based on historical time series data and testing how various projection models perform in terms of accuracy and uncertainty to inform the choice of models. As a case study, we investigate the growth of solar photovoltaics, heat pumps, and battery electric vehicles at municipality level throughout Switzerland in 2000-2021 (testing) and until 2050 (projections). Consistently for all S-curve models and technologies, we find that the medians of the probabilistic projections anticipate the diffusion of the technologies more accurately than the respective deterministic projections. While accuracy and probabilistic density intervals of the models vary across technologies, municipalities, and years, Bertalanffy and two versions of the generalized Richards model estimate the future diffusion with higher accuracy and sharpness than logistic, Gompertz, and Bass models. The results also highlight that all models come with trade-offs and eventually a combination of models with weights is needed. Based on these weighted probabilistic projections, we show that, given the current dynamics of diffusion in solar photovoltaics, heat pumps, and battery electric vehicles in Switzerland, the net-zero emissions target would be missed by 2050 with high certainty.


A unique case of merkel cell carcinoma with ovarian metastasis.
Merkel cell carcinoma (MCC) is a rare cutaneous/mucosal malignancy with very aggressive biology and increasing incidence. Ovarian metastasis is an exceptionally rare site for MCC, and only two cases have been reported in the literature. We report MCC with ovarian metastasis. A 34 year-old female with previously excised MCC from preauricular skin presented with a pelvic mass 15 months after first diagnosis. Anti-cytokeratin (CK) 20 positivity, LCA (leucocyte common antigen), and TTF-1 (Thyroid transcription factor-1) negativity confirmed metastatic ovarian MCC. There was no evidence of recurrence or metastasis at 12 months after salpingooopherectomy. MCC should be considered in the differential diagnosis of primary and metastatic undifferentiated small round cell tumors of the ovary.


Anxiety and depression amongst patients enrolled in a public sector antiretroviral treatment programme in South Africa: a cross-sectional study.
HIV/AIDS and depression are projected to be the two leading causes of disability by 2030. HIV/AIDS and anxiety/depression are interlinked. People suffering from depression may be more likely to engage in risky sexual behaviour, and therefore at greater risk of contracting HIV. An HIV + diagnosis may trigger symptoms of anxiety and depression, which may in turn result in risky sexual behaviour and the spread of HIV. This study explores correlates of anxiety and depression in patients enrolled in a public sector ART programme in South Africa. Interviews were conducted with 716 patients initiating ART at twelve public health care facilities in the Free State. Symptoms of anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). An 8+ cut-off was used to identify possible cases of anxiety and depression. Multivariate logistic regression analysis, using STATA Version 11, was performed to identify correlates of anxiety and depression. The prevalence of symptoms of respectively anxiety and depression amongst this study population in the Free State was 30.6% and 25.4%. The multivariate logistic regression analyses identified five correlates of symptoms of anxiety and depression. Disruptive side effects (OR = 3.62, CI 1.95-6.74) and avoidant coping (OR = 1.42, CI 1.22-1.65) were associated with a greater number of symptoms of anxiety. Stigma was associated with an increase in symptoms of anxiety (OR = 1.14, CI 1.07-1.21) and of depression (OR = 1.13, CI 1.06-1.20), while being a widow (OR = 0.30, CI 0.13-0.69) and participating in a support group (OR = 0.21, CI 0.05-0.99) were associated with decreased symptoms of depression. The findings from the study provide valuable insights into the psychosocial aspects of the Free State public-sector ART programme. Combined with the literature on the intricate link between mental health problems and treatment outcomes our results emphasise firstly, the necessity that resources be allocated for both screening and treating mental health problems and, secondly, the need for interventions that will encourage support-group participation, address ART side effects, reduce maladaptive coping styles, and minimise the stigma associated with symptoms of anxiety and/or depression.


Amplitude modulation of the soleus H-reflex in the human during walking and standing.
Experiments were done to determine the amplitude of the monosynaptically mediated H-reflex of the soleus muscle at various phases of the step cycle, using a computer-based analysis procedure. In all subjects tested the amplitude of the H-reflex was strongly modulated in amplitude during the walking cycle and was highest during the stance phase. In many subjects the peak reflex amplitude occurred at about the same time as the peak soleus electromyographic (EMG) activity, but in others it occurred earlier. The form of the reflex variation (i.e., envelope of H-reflex amplitude versus phase in cycle) during the step cycle could also be quite different from that of the EMG produced during stepping. At an equal stimulus strength and EMG level, the H-reflex was always much larger, up to 3.5 X, during steadily maintained contractions while standing than during walking. The large reflexes when subjects were standing are consistent with the control of position required to maintain a stable posture in this task. Similarly, the reflexes during walking are greatest during the stance phase, when they will assist in maintaining the upright position of the body against gravity. The reflexes are smallest during the swing phase when they would oppose ankle flexion. However, since the reflex amplitude is task-dependent (i.e., greater during standing than during walking at the same EMG and stimulus levels) and is not always closely related to the EMG produced during a given task such as walking, the strong modulation of H-reflex during walking is not simply a passive consequence of the alpha-motoneuron excitation level.(ABSTRACT TRUNCATED AT 250 WORDS)