Pathways to care: a case study of traffic injury in Vietnam.
Traffic injuries place a significant burden on mortality, morbidity and health services worldwide. Qualitative factors are important determinants of health but they are often ignored in the study of injury and corresponding development of prehospital Emergency Medical Services (EMS), especially in developing country settings. Here we report our research on sociocultural factors shaping pathways to hospital care for those injured on the roads and streets of Vietnam. Qualitative fieldwork on pathways to emergency care of traffic injury was carried out from March to August 2016 in four hospitals in Vietnam, two in Ho Chi Minh City and two in Hanoi. Forty-eight traffic injured patients and their families were interviewed at length using a semi-structured topic guide regarding their journey to the hospital, help received, personal beliefs and other matters that they thought important. Transcribed interviews were analysed thematically guided by the three-delay model of emergency care. Seeking care was the first delay and reflected concerns over money and possessions. The family was central for transporting and caring for the patient but their late arrival prolonged time spent at the scene. Reaching care was the second delay and detours to inappropriate primary care services had postponed the eventual trip to the hospital. Ambulance services were misunderstood and believed to be suboptimal, making taxis the preferred form of transport. Receiving care at the hospital was the third delay and both patients and families distrusted service quality. Request to transfer to other hospitals often created more conflict. Overall, sociocultural beliefs of groups of people were very influential. Analysis using the three-delay model for road traffic injury in Vietnam has revealed important barriers to emergency care. Hospital care needs to improve to enhance patient experiences and trust. Socioculture affects each of the three delays and needs to inform thinking of future developments of the EMS system, especially for countries with limited resources.


Fronto-Parietal Brain Responses to Visuotactile Congruence in an Anatomical Reference Frame.
Spatially and temporally congruent visuotactile stimulation of a fake hand together with one's real hand may result in an illusory self-attribution of the fake hand. Although this illusion relies on a representation of the two touched body parts in external space, there is tentative evidence that, for the illusion to occur, the seen and felt touches also need to be congruent in an anatomical reference frame. We used functional magnetic resonance imaging and a somatotopical, virtual reality-based setup to isolate the neuronal basis of such a comparison. Participants' index or little finger was synchronously touched with the index or little finger of a virtual hand, under congruent or incongruent orientations of the real and virtual hands. The left ventral premotor cortex responded significantly more strongly to visuotactile co-stimulation of the same versus different fingers of the virtual and real hand. Conversely, the left anterior intraparietal sulcus responded significantly more strongly to co-stimulation of different versus same fingers. Both responses were independent of hand orientation congruence and of spatial congruence of the visuotactile stimuli. Our results suggest that fronto-parietal areas previously associated with multisensory processing within peripersonal space and with tactile remapping evaluate the congruence of visuotactile stimulation on the body according to an anatomical reference frame.


Draft genome sequences of two novel Aeromonas species recovered in association with cyanobacterial blooms.
Aeromonas aquatica and Aeromonas lacus are two new species that have been found in association with cyanobacterial blooms from recreational Finnish lakes where adverse human health effects have been recorded. Here, we present the draft genome sequences of their type strains.


Effect of chloroquine on the bioavailability of ciprofloxacin in humans.
Chloroquine, a front-line drug in the treatment of malaria, has developed widespread resistance, especially to the Plasmodium falciparum strains. Ciprofloxacin is a second-generation quinolone used as a broad-spectrum fluoroquinolone antibacterial agent. The possibility of using ciprofloxacin as an antimalarial, especially in chloroquine-resistant strains, is very promising. They concluded from in vitro studies however that the anti-malarial effect occur at high dose level of ciprofloxacin to achieve the required serum concentrations. Studies have shown that there is little interstrain variability in the in vitro susceptibility of P. falciparum to fluoroquinolones. There is also no cross-resistance between them. Another study stated that 50% inhibition of parasite growth in vitro required 6.6 microg/mL after a high dose of ciprofloxacin was used. They thus concluded that ciprofloxacin should not be used alone. There is need for in vivo studies to ascertain the achievable serum concentration of ciprofloxacin when given alone and when given in combination with chloroquine. The serum concentration of ciprofloxacin was studied when ciprofloxacin was given alone and in combination with chloroquine in humans. Five healthy male volunteers aged (19-31) years who were not taking any of the prescribed medications and had no sensitivity to either ciprofloxacin or chloroquine, each received 500 mg ciprofloxacin orally with 250 mL of water, and after a 2-week wash-out period, 500 mg ciprofloxacin plus 600 mg of chloroquine was administered orally with 250 mL of water after informed consent. A blood sample (2.5 mL) was collected just before taking the drug at 8:00 AM representing 0 hours and continued afterward at 1, 2, 4, 8, 12, and 24 hours the following day. Serum samples were stored at -20 degrees C until analyzed. The minimal inhibitory concentrations (MIC) by diffusion through agar technique was used for the assay of serum ciprofloxacin. The following bioavailability parameters: Cmax, tmax, and AUC 0-24, AUC 0-infinity were calculated. The peak serum concentration Cmax of ciprofloxacin was 3.42 +/- 0.32 microg/mL, which dropped to 2.8 +/- 0.18 microg/mL when chloroquine was taken together with ciprofloxacin. These values were less than the in vitro 12.5 microg/mL concentrations required to inhibit P. falciparum. Though the effect of parasitemia was not ascertained, the in vivo use of ciprofloxacin alone or in combination is doubtful because increasing the dose that will reach the in vitro level will lead to toxicity in vivo.


Physiologic pharmacokinetic modeling.
Although physiologic modeling has not gained the widespread acceptance that was originally projected, it may serve as the basis for future PK/PD modeling approaches. In addition, with more effort applied to developing in vitro and animal-to-human predictions, physiologic modeling may assume a higher position in the pharmacokinetic modeling hierarchy.


Influence of three species of arbuscular mycorrhizal fungi on the persistence of aromatic hydrocarbons in contaminated substrates.
Aromatic hydrocarbons are pollutants which have mutagenic and carcinogenic properties as well as relatively high hydrosolubility. Their presence in soils makes techniques such as bioremediation an important topic for research. In this work, the effect of arbuscular mycorrhiza (AM) on the persistence of benzene, toluene, ethylbenzene and xylene (BTEX) in artificially contaminated substrates was evaluated. Leek plants were grown with three AM fungal species using a specially designed mesocosm system, in which internal air and substrate samples were analyzed by gas chromatography for BTEX content. Strong reductions in the BTEX concentration in substrates were generally observed in the presence of mycorrhizal plants. Residual BTEX content ranged between nearly total disappearance (<2%) and 40% of the original concentration, whereas there was a high persistence of hydrocarbons in the samples of substrate alone or with non-mycorrhizal plants. These results provide first evidence for an influence of AM activity in reducing pollution of substrates by aromatic hydrocarbons.


The relationship between physicians' malpractice claims history and later claims. Does the past predict the future?
To investigate whether an association exists between physicians' past and subsequent claims of medical malpractice, particularly whether a history of even unpaid claims ($0) or small claims (< $30,000) predicts subsequently higher rates of claims, especially large paid claims (> or = $30,000) (all in 1990 dollars). All medical malpractice claims closed in the state of Florida from January 1975 through August 1988 (N = 20,016, 92% involving physicians), matched with the American Medical Association's Physician Masterfile on all practicing physicians in the state of Florida during that period. Claims history was automated into physician-year claims files, then partitioned into a baseline period (1975 through 1980) and a subsequent period (1981 through 1983). Inconsequential claims were excluded, ie, cases closed without a named claimant and without expense for investigation (30.4% of raw claims). Descriptive analysis of all physician claims; odds ratio analysis of physicians in practice throughout both periods (N = 8247), comparing claims experience in baseline vs subsequent period, adjusted for specialty of practice. For all consequential physician claims, 60% were unpaid claims, 17% were small paid claims, and 23% were large paid claims. The 8247 continuously practicing physicians had a total of 6614 claims, averaging 0.9 per year, but 59.2% of physicians had no claims in 9 years, only 13.4% had any paid claims, and 7.2% had multiple paid claims. Less than 8% of physicians had any large paid claims during the baseline period, and less than 7% had any in the subsequent period. Physicians with any baseline claims (whether paid or unpaid, small or large, single or multiple) had elevated odds of subsequent claims (whether defined as any claims, any paid claims, any large claims, or multiple claims) relative to physicians with no baseline claims. With a baseline of all small claims, the adjusted odds ratio for any subsequent claim was 2.84 (95% confidence interval [CI], 2.32 to 3.49), for any subsequent paid claim was 2.97 (95% CI, 2.34 to 3.77), for all large subsequent claims was 2.42 (95% CI, 1.76 to 3.33), and for subsequent multiple claims was 2.83 (95% CI, 2.08 to 3.86). Even having a single unpaid baseline claim approximately doubled the odds. Claims history had predictive value, even with only unpaid claims. Small paid claims were better predictors than unpaid claims, large paid claims were better predictors than small paid claims, and multiple paid claims were better predictors than single paid claims. Claims history of all kinds is a reasonable statistical measure, eg, for the screening purposes of the National Practitioner Data Bank.


The anterior extrapleural approach to the thoracolumbar junction revisited.
General surgeons often provide the exposure for the anterior repair of vertebral body lesions. The standard anterior approach to the thoracolumbar junction (T11-L1) is a transpleural 9th or 10th rib thoracoabdominal incision. From October 1995 through March 1997, 22 patients underwent anterior repair of thoracolumbar junction vertebral lesions through an alternative 11th rib resection while maintaining an extrapleural approach. Exposure was excellent, as judged by the neurosurgical team completing the repairs. Chest tubes were not used routinely, and all patients healed without complications. A major limitation of the 11th rib extrapleural approach to the thoracolumbar junction has been poor exposure. This problem is eliminated with the use of an abdominal self-retaining retractor system. With many potential advantages to this 11th rib exposure (less pain, fewer pulmonary problems, and better wound healing), we consider the 11th rib incision to be the approach of choice to the thoracolumbar junction and recommend renewed interest in this incision.


Risk of atherothrombotic events in patients after proximal deep-vein thrombosis.
Several studies have shown high incidence of atherothrombotic events (ATEs) in patients with unprovoked pulmonary embolism. This association remains understudied in patients presenting with deep-vein thrombosis (DVT). We evaluated the risk factors for and the incidence of ATEs in patients with unprovoked proximal DVT, and compared it to patients with provoked DVT and reference patients without DVT. Patients with compression ultrasonography (CUS)-proven unprovoked proximal DVT, provoked DVT, and symptomatic patients in whom DVT was excluded by CUS were followed and scored for the occurrence of ATEs. A total of 1235 patients were enrolled: 170 patients with provoked, 74 patients with unprovoked DVT, and 991 patients without DVT. During follow-up, 128 ATEs occurred (incidence 6.5/100 patient-years). Adjusted hazard ratio was not different between patients with DVT and without DVT [hazard ratio 1.4; 95% confidence interval (CI) 0.76-2.4]. In contrast, patients with unprovoked DVT suffered from ATEs more frequently than provoked DVT patients (hazard ratio 3.16; 95% CI 1.1-9.1) and reference patients (hazard ratio 2.8; 95% CI 1.3-5.7). Notably, when fully adjusted for the known ATE risk factors, the risk differences between references, provoked, and unprovoked DVT patients diminished: hazard ratio 1.1 (95% CI 0.47-2.5) and 1.7 (95% CI 0.80-3.6), respectively. Our study confirms that the risk of ATEs in patients with unprovoked DVT was higher than in those with provoked DVT or reference patients. Interestingly, our results raise the question whether the known risk factors for ATE and venous thromboembolism attribute equally in pulmonary embolism and DVT patients, and contradict a causal relation between ATE and proximal DVT.


Mouse Dfa is a repressor of TATA-box promoters and interacts with the Abt1 activator of basal transcription.
Our study of the mouse Ate1 arginyltransferase, a component of the N-end rule pathway, has shown that Ate1 pre-mRNA is produced from a bidirectional promoter that also expresses, in the opposite direction, a previously uncharacterized gene (Hu, R. G., Brower, C. S., Wang, H., Davydov, I. V., Sheng, J., Zhou, J., Kwon, Y. T., and Varshavsky, A. (2006) J. Biol. Chem. 281, 32559-32573). In this work, we began analyzing this gene, termed Dfa (divergent from Ate1). Mouse Dfa was found to be transcribed from both the bidirectional P(Ate1/Dfa) promoter and other nearby promoters. The resulting transcripts are alternatively spliced, yielding a complex set of Dfa mRNAs that are present largely, although not exclusively, in the testis. A specific Dfa mRNA encodes, via its 3'-terminal exon, a 217-residue protein termed Dfa(A). Other Dfa mRNAs also contain this exon. Dfa(A) is sequelogous (similar in sequence) to a region of the human/mouse HTEX4 protein, whose physiological function is unknown. We produced an affinity-purified antibody to recombinant mouse Dfa(A) that detected a 35-kDa protein in the mouse testis and in several cell lines. Experiments in which RNA interference was used to down-regulate Dfa indicated that the 35-kDa protein was indeed Dfa(A). Furthermore, Dfa(A) was present in the interchromatin granule clusters and was also found to bind to the Ggnbp1 gametogenetin-binding protein-1 and to the Abt1 activator of basal transcription that interacts with the TATA-binding protein. Given these results, RNA interference was used to probe the influence of Dfa levels in luciferase reporter assays. We found that Dfa(A) acts as a repressor of TATA-box transcriptional promoters.


Acute pancreatitis in childhood: research of pathogenesis and clinical implications.
Acute pancreatitis in children is more common than has previously been considered. A recent literature analysis has demonstrated significant resulting morbidity and mortality. Clinical awareness has improved dramatically, as demonstrated by the increase in the number of recent publications and etiological considerations. This review describes novel considerations in research related to the pathogenesis of acute pancreatitis and the arising clinical implications. This relationship is discussed regarding a better understanding of pathogenesis in pediatric disorders; increasing awareness; preventing damage by drugs and toxins; using novel diagnostic markers; and introducing new therapeutic tools.


Low-loss, silicon integrated, aluminum nitride photonic circuits and their use for electro-optic signal processing.
Photonic miniaturization requires seamless integration of linear and nonlinear optical components to achieve passive and active functions simultaneously. Among the available material systems, silicon photonics holds immense promise for optical signal processing and on-chip optical networks. However, silicon is limited to wavelengths above 1.1 μm and does not provide the desired lowest order optical nonlinearity for active signal processing. Here we report the integration of aluminum nitride (AlN) films on silicon substrates to bring active functionalities to chip-scale photonics. Using CMOS-compatible sputtered thin films we fabricate AlN-on-insulator waveguides that exhibit low propagation loss (0.6 dB/cm). Exploiting AlN's inherent Pockels effect we demonstrate electro-optic modulation up to 4.5 Gb/s with very low energy consumption (down to 10 fJ/bit). The ultrawide transparency window of AlN devices also enables high speed modulation at visible wavelengths. Our low cost, wideband, carrier-free photonic circuits hold promise for ultralow power and high-speed signal processing at the microprocessor chip level.


Systemic effects of H2S inhalation at human equivalent dose of pathologic halitosis on rats.
Halitosis is composed by hundreds of toxic gases. It is still not clear whether halitosis gases self-inhaled by halitosis patients cause side effects. The aim of the study was to investigate the effect of H2S inhalation at a low concentration (human equivalent dose of pathologic halitosis) on rats. The threshold level of pathologic halitosis perceived by humans at 250 ppb of H2S was converted to rat equivalent concentration (4.15 ppm). In the experimental group, 8 rats were exposed to H2S via continuous inhalation but not the control rats. After 50 days, blood parameters were measured and tissue samples were obtained from the brain, kidney and liver and examined histopathologically to determine any systemic effect. While aspartate transaminase, creatine kinase-MB and lactate dehydrogenase levels were found to be significantly elevated, carbondioxide and alkaline phosphatase were decreased in experimental rats. Other blood parameters were not changed significantly. Experimental rats lost weight and became anxious. Histopathological examination showed mononuclear inflammatory cell invasion in the portal areas, nuclear glycogen vacuoles in the parenchymal area, single-cell necrosis in a few foci, clear expansion in the central hepatic vein and sinusoids, hyperplasia in Kupffer cells and potential fibrous tissue expansion in the portal areas in the experimental rats. However, no considerable histologic damage was observed in the brain and kidney specimens. It can be concluded that H2S inhalation equivalent to pathologic halitosis producing level in humans may lead to systemic effects, particularly heart or liver damage in rats.


Three-dimensional coronary anatomy in contrast-enhanced multislice computed tomography.
A number of three-dimensional imaging modalities, such as magnetic resonance imaging, electron beam computed tomography, ultrasonography, and multislice computed tomography have been introduced in cardiovascular medicine. One of the most recently developed techniques, multislice computed tomographic coronary angiography, allows assessment of the small coronary vessels. The entire heart is scanned within a single breathhold and contrast-enhanced images are reconstructed through retrospective electrocardiographic gating. Instead of the conventional two-dimensional projection images, multislice computed tomographic data can be displayed in a three-dimensional, volume-rendered manner. This paper presents an overview of the cardiac and coronary morphology as it is imaged with contrast-enhanced multislice computed tomography. Further imaging characteristics of computed tomographic angiography are discussed.


A Recommendation System Based on AI for Storing Block Data in the Electronic Health Repository.
The proliferation of wearable sensors that record physiological signals has resulted in an exponential growth of data on digital health. To select the appropriate repository for the increasing amount of collected data, intelligent procedures are becoming increasingly necessary. However, allocating storage space is a nuanced process. Generally, patients have some input in choosing which repository to use, although they are not always responsible for this decision. Patients are likely to have idiosyncratic storage preferences based on their unique circumstances. The purpose of the current study is to develop a new predictive model of health data storage to meet the needs of patients while ensuring rapid storage decisions, even when data is streaming from wearable devices. To create the machine learning classifier, we used a training set synthesized from small samples of experts who exhibited correlations between health data and storage features. The results confirm the validity of the machine learning methodology.


Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma.
gammadelta T cells uniquely contribute to host immune defense, but how this is accomplished remains unclear. Here, we analyzed the nonclassical major histocompatibility complex class I T10 and T22-specific gammadelta T cells in mice and found that encountering antigen in the thymus was neither required nor inhibitory for their development. But when triggered through the T cell receptor, ligand-naive lymphoid-gammadelta T cells produced IL-17, whereas ligand-experienced cells made IFN-gamma. Immediately after immunization, a large fraction of IL-17(+) gammadelta T cells were found in the draining lymph nodes days before the appearance of antigen-specific IL-17(+) *beta T cells. Thus, thymic selection determines the effector fate of gammadelta T cells rather than constrains their antigen specificities. The swift IL-17 response mounted by antigen-naive gammadelta T cells suggests a critical role for these cells at the onset of an acute inflammatory response to novel antigens.


Prophylaxis with intraocular pressure lowering medication and glaucomatous progression in patients receiving intravitreal anti-VEGF therapy.
To investigate whether pretreatment with pressure-lowering medication prior to anti-vascular endothelial factor (VEGF) injections had an effect on glaucomatous progression in patients with preexisting glaucoma or ocular hypertension (OHT). A total of 66 eyes from 54 patients with a preexisting diagnosis of glaucoma or OHT, treated with six or more anti-VEGF injections were selected for chart review. Primary outcome measures were rate of visual field loss in dB/year, rate of change in retinal nerve fiber layer (RNFL) thickness in microns/year, and need for additional glaucoma intervention. The number of eyes requiring additional glaucoma medication was 5 of 20 (25.0%) and 14 of 46 (30.4%) for the pretreated and non-pretreated groups, respectively. The number of eyes requiring glaucoma laser or surgery was 4 of 20 (20.0%) and 13 of 46 (28.3%) for the pretreated and non-pretreated groups, respectively. Estimated mean rate of pattern standard deviation decline was not significant in either group (P>0.073), with no difference between groups (P=0.332). Although both groups showed significant RNFL change from baseline (P<0.011), no difference was detected between groups (P=0.467). Pretreatment has no detectable effect on structural or functional glaucomatous progression. Patients receiving repeated injections may be at risk for glaucomatous complications requiring invasive intervention.


An ancient neurotrophin receptor code; a single Runx/Cbfβ complex determines somatosensory neuron fate specification in zebrafish.
In terrestrial vertebrates such as birds and mammals, neurotrophin receptor expression is considered fundamental for the specification of distinct somatosensory neuron types where TrkA, TrkB and TrkC specify nociceptors, mechanoceptors and proprioceptors/mechanoceptors, respectively. In turn, Runx transcription factors promote neuronal fate specification by regulating neurotrophin receptor and sensory receptor expression where Runx1 mediates TrkA+ nociceptor diversification while Runx3 promotes a TrkC+ proprioceptive/mechanoceptive fate. Here, we report in zebrafish larvae that orthologs of the neurotrophin receptors in contrast to terrestrial vertebrates mark overlapping and distinct subsets of nociceptors suggesting that TrkA, TrkB and TrkC do not intrinsically promote nociceptor, mechanoceptor and proprioceptor/mechanoceptor neuronal fates, respectively. While we find that zebrafish Runx3 regulates nociceptors in contrast to terrestrial vertebrates, it shares a conserved regulatory mechanism found in terrestrial vertebrate proprioceptors/mechanoceptors in which it promotes TrkC expression and suppresses TrkB expression. We find that Cbfβ, which enhances Runx protein stability and affinity for DNA, serves as an obligate cofactor for Runx in neuronal fate determination. High levels of Runx can compensate for the loss of Cbfβ, indicating that in this context Cbfβ serves solely as a signal amplifier of Runx activity. Our data suggests an alteration/expansion of the neurotrophin receptor code of sensory neurons between larval teleost fish and terrestrial vertebrates, while the essential roles of Runx/Cbfβ in sensory neuron cell fate determination while also expanded are conserved.


Cost and Clinical Outcomes Evaluation Between the Endoaortic Balloon and External Aortic Clamp in Cardiac Surgery.
Endoaortic balloon occlusion facilitates cardioplegic arrest during minimally invasive surgery (MIS). Studies have shown endoclamping to be as safe as traditional aortic clamping. We compared outcomes and hospital costs of endoclamping versus external aortic occlusion in a large administrative database. There were 52,882 adults undergoing eligible cardiac surgery (October 2015 to March 2020) identified in the Premier Healthcare Database. Endoclamp procedures (n = 419) were 1:3 propensity score matched to similar procedures using external aortic occlusion (n = 1,244). Generalized linear modeling measured differences in in-hospital complications (major adverse renal and cardiac events, including mortality, new-onset atrial fibrillation, acute kidney injury [AKI], myocardial infarction [MI], postcardiotomy syndrome, stroke/transient ischemic attack [TIA], and aortic dissection) and length of stay (LOS). The mean age was 63 years, and 53% were male (n = 882). The majority (93%, n = 1,543) were mitral valve procedures, and 17% of procedures (n = 285) were robot-assisted. Total hospitalization costs were not statistically significantly different between the 2 groups ($52,158 vs $49,839, P = 0.06). The median LOS was significantly shorter in the endoclamp group (incident rate ratio = 0.87, P < 0.001). Mortality, atrial fibrillation, AKI, and stroke/TIA were similar between the 2 groups. MI and postcardiotomy syndrome were lower in the endoclamp group (odds ratio [OR] = 0.14, P = 0.006, and OR = 0.27, P = 0.005). There were no aortic dissections in the endoclamp group. Aortic endoclamping in MIS was associated with similar costs, shorter LOS, no dissections, and comparably low mortality and stroke rates when compared with external clamping in this hospital billing dataset. These results demonstrate the clinical safety and efficacy of endoaortic balloon clamping in a real-world setting. Further studies are warranted.


Insulin resistance in pheochromocytoma improves more by surgical rather than by medical treatment.
Pheochromocytoma, a neuroendocrine tumor, is often associated with hyperglycemia. To investigate the underlying pathogenetic mechanisms, five patients (3 women and 2 men, aged 49+/-2.5, mean+/-SD) with benign adrenal pheochromocytoma were studied with an oral glucose tolerance test (OGTT) and the euglycaemic clamp technique. They were studied preoperatively without taking any medication (stage I), after taking an alpha adrenergic receptor blocking agent (stage II), after taking both an alpha and a beta adrenergic receptor blocking agent (stage III), and after surgical removal of the tumor (stage IV). Before any treatment, fasting blood glucose levels and glucose levels during the OGTT were pathologic in all patients. In all patients, mean glucose levels of the OGTTs performed at the three preoperative stages of the study were significantly higher than those of the OGTT performed postoperatively (ANOVA, alpha<0.05). Insulin levels during the OGTTs performed preoperatively peaked at 90 min while postoperatively they peaked at 60 min. No statistically significant difference was found among mean insulin levels during the OGTTs performed at all stages of the study. The clamp-based insulin sensitivity index (SI) improved progressively from stage I to IV of the study (ANOVA, alpha<0.05) (SIs of stages I, II, III, and IV were, respectively, 3.23+/-0.9 (mean+/-SE), 3.79+/-0.7, 4.67+/-0.3, 6.38+/-1 (10(-4) dl/kg x min per microU/ml)). In conclusion, the pheochromocytoma-associated metabolic alterations of glucose homeostasis improved substantially only after removal of the tumor. The administration of alpha and beta adrenergic receptor blocking agents resulted in a slight but statistically significant improvement in glucose utilization whereas it completely normalized the cardiovascular manifestations of the disease. Thus, it is possible that either the dose of the adrenergic receptor blocking agent needed to control cardiovascular manifestations of pheochromocytoma is different than that needed for glucose metabolism normalization, or that other pheochromocytoma-associated factors may influence directly and/or indirectly carbohydrate homeostasis.


Thrombolysis for patients with acute ischaemic stroke.
Stroke is the leading cause of physical disability, and thrombolysis is a promising treatment for acute ischaemic stroke. Alteplase has significant benefits for patients if it is administered within four and a half hours of stroke onset. This article uses a case study approach to explore a patient's journey through admission, triage, eligibility and administration of alteplase therapy. It emphasises the post-monitoring role of the nurse.


Frequency-domain full-waveform inversion-based musculoskeletal ultrasound computed tomography.
Recently, full-waveform inversion (FWI) has become a promising tool for ultrasound computed tomography (USCT). However, as a computationally intensive technique, FWI suffers from computational burden, especially in conventional time-domain full-waveform inversion (TDFWI). On the contrary, frequency-domain full-waveform inversion (FDFWI) provides a relatively high computational efficiency as the propagation of discrete frequencies is much cheaper than full time-domain modeling. FDFWI has already been applied in soft tissue imaging, such as breast, but for the musculoskeletal model with high impedance contrast between hard and soft tissues, there is still a lack of an effective source estimation method. In this paper, a water-referenced data calibration method is proposed to address the source estimation challenge in the presence of bones, which achieves consistency between the measured and simulated data before the FDFWI procedure. To avoid the cycle-skipping local minimum effect and facilitate the algorithm convergence, a starting frequency criterion for musculoskeletal FDFWI is further proposed. The feasibility of the proposed method is demonstrated by numerical studies on retrieving the anatomies of the leg models and different musculoskeletal lesions. The study extends the advanced FDFWI method to the musculoskeletal system and provides an alternative solution for musculoskeletal USCT imaging with high computational efficiency.


Immunological and virological characterization of HIV-1 viremia controllers in the North Region of Brazil.
A rare phenotype of clinical non-progressors to AIDS is not well understood and the new protocol for universal treatment, may block the understanding of viral control thus it is crucial to define this controversial group. A cohort of 30 persons followed a criteria for viremia control groups 1 (VC1; n = 2) and 2 (VC2; n = 7) and non-viral controllers (NC; n = 21) including number of years of diagnosis, LTCD4+, LTCD8+ counts, plasma viral load and the absence of ART; 241 uninfected control persons were matched to age and sex. Infected persons were regularly examined and submitted to two or three annual laboratory measurements. Polymorphisms and allele frequencies of CCR5Δ32 and SDF1-3'A were detected in the genomic DNA. Plasma levels of cytokines (IL-2, IL-4, IL-5, IL-9, IL-10, IL-13, IL-17 and IFN-y) were measured. The group investigated is originated from a miscigenetic population and demographic and social characteristics were not significantly relevant. LTCD4+ median values were higher among VC than NC, but significantly lower than uninfected controls. Evolution of LTCD4+ and LTCD8+ counts, showed a slight increase of LTCD4+ among VC, but a significant decrease in the NC. The percentage of annual change in LTCD4+ was also significantly different between the groups. LTCD4+/LTCD8+ ratio was inverted but not significant among the VC, thus the ratio may be a useful biomarker for the VC. A clear signature indicated a change from Th1 to Th2 cytokine profiles from VC to NC, respectively. The knowledge of viral controllers characteristics in different population groups is important to define a strict universal definition for the sake of learning about the pathogenesis of HIV-1. Data on LTCD4+ seems to be stable and repetitive from published data, but the LTCD8+ response and the significance of LTCD4+/LTCD8+ ratio values are in need to further exploration as biomarkers. The change from Th1 to Th2 cytokine profile may help to design and adjust specific treatment protocols for the group.


Biocides in hydraulic fracturing fluids: a critical review of their usage, mobility, degradation, and toxicity.
Biocides are critical components of hydraulic fracturing ("fracking") fluids used for unconventional shale gas development. Bacteria may cause bioclogging and inhibit gas extraction, produce toxic hydrogen sulfide, and induce corrosion leading to downhole equipment failure. The use of biocides such as glutaraldehyde and quaternary ammonium compounds has spurred a public concern and debate among regulators regarding the impact of inadvertent releases into the environment on ecosystem and human health. This work provides a critical review of the potential fate and toxicity of biocides used in hydraulic fracturing operations. We identified the following physicochemical and toxicological aspects as well as knowledge gaps that should be considered when selecting biocides: (1) uncharged species will dominate in the aqueous phase and be subject to degradation and transport whereas charged species will sorb to soils and be less bioavailable; (2) many biocides are short-lived or degradable through abiotic and biotic processes, but some may transform into more toxic or persistent compounds; (3) understanding of biocides' fate under downhole conditions (high pressure, temperature, and salt and organic matter concentrations) is limited; (4) several biocidal alternatives exist, but high cost, high energy demands, and/or formation of disinfection byproducts limits their use. This review may serve as a guide for environmental risk assessment and identification of microbial control strategies to help develop a sustainable path for managing hydraulic fracturing fluids.


[Free medial leg flap with fasciocutaneous branch of tibial nutrient artery].
According to the results of anatomical study in 20 fresh cadaver legs and transparent specimens of 10 medial leg flaps, it is found that the tibial nutrient artery arises from the posterior tibial artery and runs obliquely downwards close to the surface of the popliteal muscle, and at the level of 61.62 +/- 15 mm below the tibial tuberosity it sends out the fasciocutaneous branch, which becomes one of the main nutritional vessels of the medial area of the leg. Vascularized transplantation of the medial leg free flap which is supplied by the fasciocutaneous branch of the above named artery has been undertaken with satisfactory results clinically.


Kinetics of loss of a recombinant plasmid in Bacillus subtilis.
Recombinant plasmid pCEDS is structurally unstable in Bacillus subtilis cultures. We have previously shown that stability can be independently increased by changing from a complex medium supporting high growth rates to a chemically-defined medium supporting a lower growth rate and removal of a 4.77-kb EcoRI fragment from pCED3 to give plasmid YS1. Further stabilization was achieved by combining the two approaches. In the present work, we show that the stabilization of the plasmid-encoded LacZ(+) phenotype can be explained solely by the effect on the growth rate ratio between cells containing modified and parental plasmids. By using modified stability experiments (where a single cell rather than a suspended colony was used to initiate growth), independent growth rate measurements, and a simple mathematical model, we can describe the kinetics of the loss of the LacZ(+) phenotype in terms of two variables, alpha and p (where alpha is the ratio of growth rates between modified and parental cells, and p is the probability of obtaining modified cells from parental cells). Under the conditions tested, the average values of alpha were 1.52 for cultures growing in complex medium, 1.28 for cultures growing in defined medium, and 1.18 for cultures containing the modified plasmid pYS1 growing in complex medium. The calculated p values ranged between 10(-8) and 10(-10) under all conditions. Plasmid (pYS137) was used to directly estimate plasmid deletion rates in B. subtilis and it showed a rate between 5 x 10(-8) and 1.1 x 10(-9) deletions/cell/generation. In contrast to B. subtilis, there were no detectable differences in growth rates between Escherichia coli strains harboring plasmid pCEDS and plasmid-free cells. These results explain the observed stability of pCEDS in E. coli cultures and indicate that readily detected instability in B. subtilis cultures can be the result of rare deletion events.


Prevalence of antimicrobial resistance of Streptococcus pneumoniae in Chinese children: four hospitals surveillance.
To investigate the nasal carriage of antibiotic-resistant pneumococci in children of < 5 years old in the following four cities, Beijing, Shanghai, Guangzhou and Xi'an. A total of 647 pneumococci strains were isolated and detected. Minimal inhibition concentrations (MICs) of antibiotics were determined by E-test. Disk diffusion test was used for the measurement of antimicrobial susceptibility. Prevalence of penicillin non-susceptible Streptococcus pneumoniae in the four cities was 41%, with Guangzhou (60.8%) ranking first, followed by Xi'an (45%), Shanghai (37%) and Beijing (25.9%). The majority of penicillin non-susceptibility isolates (23.9% - 53.8%) had a low level of resistance (MIC 0.64 - 1.5 microg/ml). The most sensitive antimicrobials in terms of percentage of susceptible organisms were amoxicillin-clavulanic acid (99.4%), followed by ceftriaxone (92.1%); cefurxime and cefaclor were slightly more sensitive than penicillin with susceptibility of 74.8% and 77.9%. Erythromycin, tetracycline and TMP-SMZ were highly resistant (83.6%, 82.1% and 76.2% respectively). Among erythromycin resistant isolates, 100% were resistant to azithromycin, 98.6% to clarithromycin, 97.2% to roxithromycin and spiramycin, and 96.6% to clindamycin. 97.2% (141/145) were typical of the macrolides-lincosamides-streptogramons B (MLSB) resistance phenotype, and 2.8% (4/145) were M phenotype. The group of PRSP was with significantly higher rates of non-susceptibility for ceftriaxone (18.4%), cefurxime (58.6%), cefaclor (53.4%), compared with the group of PEN-S (0.5%, 1.8% and 0.2%, respectively) and the rate of multi-drug resistance in the isolates of PRSP group (92.9%) was significantly higher than that of PEN-S group (59.2%). The rates of penicillin and multi-drug resistance among isolates of pneumococci carried nasally in are high children and the high prevalence of multi-drug resistance in the Chinese population may be becoming one of the most serious problems in this century.


Choosing a powerful lithotriptor.
Clinicians have no yardstick to help them choose the most efficient lithotriptor. Their leading priority is a system allowing complete disintegration of the stone with the minimum number of shocks and a low re-treatment rate. One of the prerequisites of this system is a powerful shock wave generator. "Power" is as yet ill defined in lithotripsy. Therefore clinicians' choice depends upon other factors. Acoustic output measurements were recorded on 3 commercial lithotriptors representing the 3 main shock wave generating systems. These were the Dornier MPL 9000 (standard and X-155 electrodes), the Siemens (Lithostar, Lithostar Plus and System C) and the Wolf Piezolith 2300. The shock wave measurements were correlated to the capability of the lithotriptors to disintegrate standard stone models in vitro. Two factors were identified. The pulse intensity integral in the focus and the size of the focal zone proved to be the most important factors to assess and compare the efficacy or "power" of different lithotriptors. Together they can help clinicians to identify and choose the most efficient shock wave generating systems.


In vivo selection of neutralization-resistant virus variants but no evidence of B cell tolerance in lymphocytic choriomeningitis virus carrier mice expressing a transgenic virus-neutralizing antibody.
B cell tolerance is maintained by active deletion and functional anergy of self-reactive B cells depending on the time, amount, and site of the self-antigen expression. To study B cell tolerance toward a transplacentally transmitted viral Ag, we crossed transgenic mice expressing the mu heavy and the kappa light chain of the lymphocytic choriomeningitis virus (LCMV)-neutralizing mAb KL25 (HL25-transgenic mice) with persistently infected LCMV carrier mice. Although HL25-transgenic LCMV carrier mice exhibited the same high virus titers as nontransgenic LCMV carrier mice, no evidence for B cell tolerance was found. In contrast, enhanced LCMV-neutralizing Ab titers were measured that, however, did not clear the virus. Instead, LCMV isolates from different tissues turned out to be neutralization resistant Ab escape variants expressing different substitutions of amino acid Asn119 of the LCMV-glycoprotein 1 that displays the neutralizing B cell epitope. Virus variants with the same mutations were also selected in vitro in the presence of the transgenic mAb KL25 confirming that substitutions of Asn119 have been selected by LCMV-neutralizing Abs. Thus, despite abundant expression of viral neo-self-antigen in HL25-transgenic LCMV carrier mice, transgenic B cells expressing LCMV-neutralizing Abs were rather stimulated than tolerized and neutralization resistant Ab escape variants were selected in vivo.


Impairment of Proteasome and Autophagy Underlying the Pathogenesis of Leukodystrophy.
Impairment of the ubiquitin-proteasome-system (UPS) and autophagy causing cytoplasmic aggregation of ubiquitin andp62 have been implicated in the pathogenesis of most neurodegenerative disorders, yet, they have not been fully elucidated in leukodystrophies. The relationship among impairment of UPS, autophagy, and globoid cell leukodystrophy (GLD), one of the most common demyelinating leukodystrophies, is clarified in this study. We examined the ubiquitin and autophagy markers in the brains of twitcher mice, a murine model of infantile GLD, and in human oligodendrocytes incubated with psychosine. Immunohistochemical examinations showed spatiotemporal accumulation of ubiquitin- and p62-aggregates mainly in the white matter of brain and spinal cord at disease progression. Western blot analysis demonstrated a significant accumulation of ubiquitin, p62, and LC3-II in insoluble fraction in parallel with progressive demyelination and neuroinflammation in twitcher brains. In vitro study validated a dose- and time-dependent cytotoxicity of psychosine upon autophagy and UPS machinery. Inhibition of autophagy and UPS exacerbated the accumulation of insoluble ubiquitin, p62, and LC3-II proteins mediated by psychosine cytotoxicity as well as increased cytoplasmic deposition of ubiquitin- and p62-aggregates, and accumulation of autophagosomes and autolysosomes. Further, the subsequent accumulation of reactive oxygen species and reduction of mitochondrial respiration led to cell death. Our studies validate the impairment of proteasome and autophagy underlying the pathogenesis of GLD. These findings provide a novel insight into pathogenesis of GLD and suggest a specific pathomechanism as an ideal target for therapeutic approaches.


SMK-1/PPH-4.1-mediated silencing of the CHK-1 response to DNA damage in early C. elegans embryos.
During early embryogenesis in Caenorhabditis elegans, the ATL-1-CHK-1 (ataxia telangiectasia mutated and Rad3 related-Chk1) checkpoint controls the timing of cell division in the future germ line, or P lineage, of the animal. Activation of the CHK-1 pathway by its canonical stimulus DNA damage is actively suppressed in early embryos so that P lineage cell divisions may occur on schedule. We recently found that the rad-2 mutation alleviates this checkpoint silent DNA damage response and, by doing so, causes damage-dependent delays in early embryonic cell cycle progression and subsequent lethality. In this study, we report that mutations in the smk-1 gene cause the rad-2 phenotype. SMK-1 is a regulatory subunit of the PPH-4.1 (protein phosphatase 4) protein phosphatase, and we show that SMK-1 recruits PPH-4.1 to replicating chromatin, where it silences the CHK-1 response to DNA damage. These results identify the SMK-1-PPH-4.1 complex as a critical regulator of the CHK-1 pathway in a developmentally relevant context.


Resistance/susceptibility to lethal Sendai virus infection genetically linked to a mucociliary transport polymorphism.
Linkage was tested between a mucociliary transport polymorphism and resistance/susceptibility to lethal Sendai virus infection in segregant hybrid mice of C57BL/6J and DBA/2J parents. The distribution of paired phenotypes for tracheal mucociliary transport rates and susceptibility to lethal Sendai virus infection in 171 F1 X DBA/2J mice showed strong interaction of the parental phenotypes.


Origin of plasmonic Fano resonance in metal-hole/split-ring-resonator metamaterials disclosed by temporal coupled-mode theory.
In plasmonic Fano resonance, the interaction between a discrete plasmonic mode and a continuum of plasmonic mode gives rise to an asymmetric line shape in the scattering or absorption spectrum, enabling a wide range of applications such as sensing, switching, and slow light devices. Here, we establish a theoretical solution in the framework of temporal coupled-mode theory (TCMT) to study the three-dimensional (3D) and two-dimensional (2D) Fano resonances induced by strong coupling between metal hole (MH) and split ring resonator (SRR) array. We first separately analyze the transmission spectra of the MH array and SRR array under different polarized light excitation. We further investigate the electromagnetic field and charge density distribution corresponding to the resonant modes at the peak or valley wavelength of the transmission spectrum and figure out the electric/magnetic dipole feature of these resonance modes. We then establish a theoretical solution by TCMT for Fano resonances arising from the coupling of these modes. The calculated transmission spectrum is closely matching with the numerically simulated transmission spectrum for these Fano resonances in the MH-SRR array, which effectively elucidates that the asymmetry of the Fano resonances is caused by the coupling between bright and dark plasmonic modes involved in the two structures. Our results can help to understand the profound physics in such coupled plasmonic systems.


Ultraviolet Photodissociation of Tryptic Peptide Backbones at 213 nm.
We analyzed the backbone fragmentation behavior of tryptic peptides of a four-protein mixture and of E. coli lysate subjected to ultraviolet photodissociation (UVPD) at 213 nm on a commercially available UVPD-equipped tribrid mass spectrometer. We obtained 15 178 unique high-confidence peptide UVPD spectrum matches by recording a reference beam-type collision-induced dissociation (HCD) spectrum of each precursor, ensuring that our investigation includes a broad selection of peptides, including those that fragmented poorly by UVPD. Type a, b, and y ions were most prominent in UVPD spectra, and median sequence coverage ranged from 5.8% (at 5 ms laser excitation time) to 45.0% (at 100 ms). Overall, the sequence fragment intensity remained relatively low (median: 0.4% (5 ms) to 16.8% (100 ms) of total intensity), and the remaining precursor intensity, high. The sequence coverage and sequence fragment intensity ratio correlated with the precursor charge density, suggesting that UVPD at 213 nm may suffer from newly formed fragments sticking together due to noncovalent interactions. The UVPD fragmentation efficiency therefore might benefit from supplemental activation, as was shown for ETD. Aromatic amino acids, most prominently tryptophan, facilitated UVPD. This points to aromatic tags as possible enhancers of UVPD. Data are available via ProteomeXchange with identifier PXD018176 and on spectrumviewer.org/db/UVPD-213nm-trypPep.


Coagulating Colubrids: Evolutionary, Pathophysiological and Biodiscovery Implications of Venom Variations between Boomslang (Dispholidus typus) and Twig Snake (Thelotornis mossambicanus).
Venoms can deleteriously affect any physiological system reachable by the bloodstream, including directly interfering with the coagulation cascade. Such coagulopathic toxins may be anticoagulants or procoagulants. Snake venoms are unique in their use of procoagulant toxins for predatory purposes. The boomslang (Dispholidus typus) and the twig snakes (Thelotornis species) are iconic African snakes belonging to the family Colubridae. Both species produce strikingly similar lethal procoagulant pathologies. Despite these similarities, antivenom is only produced for treating bites by D. typus, and the mechanisms of action of both venoms have been understudied. In this study, we investigated the venom of D. typus and T. mossambicanus utilising a range of proteomic and bioactivity approaches, including determining the procoagulant properties of both venoms in relation to the human coagulation pathways. In doing so, we developed a novel procoagulant assay, utilising a Stago STA-R Max analyser, to accurately detect real time clotting in plasma at varying concentrations of venom. This approach was used to assess the clotting capabilities of the two venoms both with and without calcium and phospholipid co-factors. We found that T. mossambicanus produced a significantly stronger coagulation response compared to D. typus. Functional enzyme assays showed that T. mossambicanus also exhibited a higher metalloprotease and phospholipase activity but had a much lower serine protease activity relative to D. typus venom. The neutralising capability of the available boomslang antivenom was also investigated on both species, with it being 11.3 times more effective upon D. typus venom than T. mossambicanus. In addition to being a faster clotting venom, T. mossambicanus was revealed to be a much more complex venom composition than D. typus. This is consistent with patterns seen for other snakes with venom complexity linked to dietary complexity. Consistent with the external morphological differences in head shape between the two species, CT and MRI analyses revealed significant internal structural differences in skull architecture and venom gland anatomy. This study increases our understanding of not only the biodiscovery potential of these medically important species but also increases our knowledge of the pathological relationship between venom and the human coagulation cascade.


Inactivation of the transcription factor Elf3 in mice results in dysmorphogenesis and altered differentiation of intestinal epithelium.
The mammalian small intestine is lined by a highly specialized epithelium that functions in the digestion and absorption of nutrients. The molecular mechanisms that direct intestinal epithelial cell morphogenesis and terminal differentiation are poorly understood. We have previously identified Elf3 (E74-like factor-3) as a member of the ETS transcription factor family strongly expressed in small intestinal epithelium. The aim of this study is to investigate the biological roles of Elf3 in vivo. Mice with a null mutation of Elf3 were generated through targeted gene disruption. Characterization of intestinal development was performed by histologic and immunohistochemical techniques. Targeted disruption of Elf3 resulted in fetal lethality of about 30% at around embryonic day 11.5. Seventy percent of the Elf3-deficent progeny were born and displayed severe alterations of tissue architecture in the small intestine, manifested by poor villus formation and abnormal morphogenesis and terminal differentiation of absorptive enterocytes and mucus-secreting goblet cells. Crypt cell proliferation, however, appeared intact in Elf3-deficient mice.Elf3-deficient enterocytes express markedly reduced levels of the transforming growth factor beta type II receptor (TGF-beta RII), an inducer of intestinal epithelial differentiation. Elf3 is an important regulator of morphogenesis and terminal differentiation of epithelial cell lineages in the small intestine.


Nutrigenomics: Opportunities & challenges for public health nutrition.
The hierarchical information flow through DNA-RNA-protein-metabolite collectively referred to as 'molecular fingerprint' defines both health and disease. Environment and food (quality and quantity) are the key factors known to affect the health of an individual. The fundamental concepts are that the transition from a healthy condition to a disease phenotype must occur by concurrent alterations in the genome expression or by differences in protein synthesis, function and metabolites. In other words, the dietary components directly or indirectly modulate the molecular fingerprint and understanding of which is dealt with nutrigenomics. Although the fundamental principles of nutrigenomics remain similar to that of traditional research, a collection of comprehensive targeted/untargeted data sets in the context of nutrition offers the unique advantage of understanding complex metabolic networks to provide a mechanistic understanding of data from epidemiological and intervention studies. In this review the challenges and opportunities of nutrigenomic tools in addressing the nutritional problems of public health importance are discussed. The application of nutrigenomic tools provided numerous leads on biomarkers of nutrient intake, undernutrition, metabolic syndrome and its complications. Importantly, nutrigenomic studies also led to the discovery of the association of multiple genetic polymorphisms in relation to the variability of micronutrient absorption and metabolism, providing a potential opportunity for further research toward setting personalized dietary recommendations for individuals and population subgroups.


Thermally evaporated In2O3 nanoloquats with tunable broad-band emissions.
We describe synthesis of In2O3 nanoloquats grown by thermal evaporation under different oxygen flow rates and temperatures. Gold nanoparticles were used the catalysts and were dispersed on the silicon wafer to assist growth of In2O3 nanoloquats. The nanostructures of In2O3 nanoloquats were characterized by scanning electron microscopy, transmission electron microscopy and X-ray diffraction. The photoluminescence study reveals that In2O3 nanoloquats could emit different broadband luminescence peaks in the range of 410-620 nm by tuning different oxygen flow rates and temperatures. The wide tuning range in the emission peaks of In2O3 nanoloquats has potential in applications of white light illumination.


Indigenous land-based approaches to well-being: The Sibi (River) program in subarctic Ontario, Canada.
The Albany River system holds a special significance for the Omushkego Cree of subarctic Ontario, Canada, embodying their cultural roots, history, and the Cree way of life and worldviews. Through the Sibi program, youth learned traditional fishing practices from Elders and on-the-land experts, gaining valuable knowledge on the land and river. The program addressed barriers to being on the land, while also creating a space for the transfer of Indigenous knowledge and revitalising community social networks. The program took place in the summer, following the Omushkego Cree's seasonal cycle and employed community-based participatory research approach. Photovoice and semi-structured interviews were used to identify elements of well-being from an Indigenous perspective. Regardless of age or experience, participants expressed positive emotions while being on the land, highlighting how strengthening social and community networks, intergenerational knowledge transfer, and fostering cultural continuity contribute to improved well-being. Program outcomes emphasize the importance of collaboration with communities to gain insights into their needs, priorities, and values, ultimately creating more sustainable and effective well-being programs. By fostering engagement and recognizing the environment's significance, sustainable and long-term solutions can be pursued to address challenges faced by communities, ultimately advancing health and well-being for both present and future generations.The Albany River system holds a special significance for the Omushkego Cree of subarctic Ontario, Canada, embodying their cultural roots, history, and the Cree way of life and worldviews. Through the Sibi program, youth learned traditional fishing practices from Elders and on-the-land experts, gaining valuable knowledge on the land and river. The program addressed barriers to being on the land, while also creating a space for the transfer of Indigenous knowledge and revitalising community social networks. The program took place in the summer, following the Omushkego Cree's seasonal cycle and employed community-based participatory research approach. Photovoice and semi-structured interviews were used to identify elements of well-being from an Indigenous perspective. Regardless of age or experience, participants expressed positive emotions while being on the land, highlighting how strengthening social and community networks, intergenerational knowledge transfer, and fostering cultural continuity contribute to improved well-being. Program outcomes emphasize the importance of collaboration with communities to gain insights into their needs, priorities, and values, ultimately creating more sustainable and effective well-being programs. By fostering engagement and recognizing the environment's significance, sustainable and long-term solutions can be pursued to address challenges faced by communities, ultimately advancing health and well-being for both present and future generations.


Sex differences in the effects of pubertal development on responses to a corticotropin-releasing hormone challenge: the Pittsburgh psychobiologic studies.
We propose that sex differences in HPA regulation may emerge during puberty and help to explain sex differences in depression. In this study, we examined sex differences in cortisol responses to CRH challenge across pubertal stages in carefully screened control subjects from the Pittsburgh Psychobiologic Studies. Participants were 7-16 years of age, physically healthy, and had no personal or family history of psychiatric disorder. Physician-rated Tanner staging was conducted, followed by CRH challenge sessions including 30-40 minutes pre-infusion baseline, 1 microg/kg CRH infusion, 90-180 minutes of post-infusion measures, and 9-10 plasma cortisol samples. Girls showed increasing total cortisol responses to CRH across Tanner stages, explained by slower recovery from peak cortisol levels, while boys showed similar total responses across Tanner stages. Results show subtle sex differences in the influence of puberty on HPA regulation at the pituitary level, which may represent one factor underlying the emergence of girls' greater rates of depression during this time.


Endoscopic treatment of bilateral pheochromocytoma in MEN 2A syndrome: case report and review of the literature.
The benefits of laparoscopic adrenalectomy for single adrenal lesion have been well documented in literature; less experience though has been reported with simultaneous bilateral laparoscopic adrenalectomy. This operation is indicated in case of primary hypercortisolism caused by bilateral adrenocortical hyperfunction, Cushing's disease after failure of pituitary surgery, ectopic adrenocorticotropic hormone (ACTH) production by a tumour inaccessible for surgical intervention, and pheochromocytoma when it occurs bilaterally in case of multiple endocrine neoplasia type 2A and 2B. Different laparoscopic approaches have been described to perform this operation, such as the "anterior" approach (transperitoneal), the "lateral" approach (transperitoneal and retroperitoneal), and the "posterior" approach (retroperitoneal). We report a case of bilateral laparoscopic adrenalectomy in a 33 years old female affected with bilateral pheochromocytoma due to multiple endocrine neoplasia type 2A treated with a bilateral transperitoneal laparoscopic adrenalectomy and disease free after 18 months follow-up.


CIRBP is a novel oncogene in human bladder cancer inducing expression of HIF-1α.
Cold-inducible RNA binding protein (CIRBP) has been reported to be associated with distinct tumorigenesis. In this study, we investigated the role of CIRBP in human bladder cancer (BCa), indicating that CIRBP is overexpressed in BCa tissues and cell lines to promote proliferation and migration. Moreover, CIRBP could induce expression of HIF-1α via binding to the 3'-UTR of its mRNA to increase the mRNA stability in BCa cells. Furthermore, we demonstrated that PTGIS is a HIF-1α targeted gene, a major regulator in hypoxic cancer progression by activating transcription of various oncogenes. Our results also suggested that overexpression of HIF-1α may suppress the expression of PTGIS in BCa cells, by binding to HRE sequence at the promoter region of PTGIS. In addition, we found a strongly downregulation of PTGIS in BCa tissue and transcriptionally inhibited by HIF-1α in BCa cells, which could be triggered by its DNA methylation. Further result suggested that knockdown of CIRBP could promote the expression of PTGIS, meanwhile knockdown of PTGIS could partially rescue CIRBP-deficiency induced inhibition of migration and proliferation in BCa cells. Taken together, our study indicated that CIRBP could be a novel oncogene in human bladder cancer inducing transcription of HIF-1α, which could inhibit expression of methylated PTGIS.


Non-competition agreements: how to make them work for you.
In a time of staffing shortages and increased competition for shrinking reimbursement dollars, home care agencies need to protect themselves from unprincipled or unknowing employees that leave the agency to work for a competitor or for a patient, bringing with them other agency employees, patient lists, and other proprietary information. Well-drafted, attorney-reviewed, enforceable non-competition agreements can help mitigate some of these problems.


Lack of effect of 24,25-dihydroxyvitamin D3 administration on parameters of calcium metabolism.
Seven patients with disordered calcium metabolism and high normal or elevated serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] were studied before and after the administration of 24,25-(OH)2D3 to determine its effects on calcium metabolism. Despite a significant increase in the mean serum 24,25-(OH)2D level [2.1 +/- 0.6 (+/- SE) to 16.7 +/- 6.2 nmol/L; P less than 0.05] after a daily dose of 20 micrograms for 1 month, there were no consistent changes in serum calcium, immunoreactive PTH, or 1,25-(OH)2D concentrations. Intestinal calcium absorption and urinary calcium excretion rose slightly during 24,25-(OH)2D administration in the majority of the patients. In the three patients in whom it was measured, serum 1,24,25-trihydroxyvitamin D levels did not change (19 +/- 5 vs. 20 +/- 5 pmol/L). We conclude that exogenous 24,25-(OH)2D3 at this dose has no significant antagonistic action on 1,25-(OH)2D and may have weak agonistic action.


Influence of highly porous electrospun PLGA/PCL/nHA fibrous scaffolds on the differentiation of tooth bud cells in vitro.
In this study, we investigated the use of three-dimensional electrospun poly(lactic-co-glycolic acid)/poly(ε-caprolactone) (PLGA/PCL) scaffolds seeded and cultured with postnatal dental cells, for improved dental tissue regeneration. Wet-electrospinning combined with ultrasonic treatment was studied as a method to enhance scaffold porosity and to promote cell-cell interactions. We also investigated whether nano-hydroxyapatite (nHA) incorporation could enhance dental cell differentiation. All scaffolds were seeded with human tooth pulp-derived dental mesenchymal (hDM) cells, or a combination of hDM and pig dental epithelial (pDE) cells, cultured for up to 28 days. Developmentally staged samples were assessed using scanning electron microscopy, histological, immunohistochemical, DNA and alkaline phosphatase activity assays, and quantitative-PCR for ameloblastic, odontoblastic, and osteogenic related gene expression. Results showed that electrospun scaffolds exhibited sufficient porosity to support robust cell ingrowth. Additional ultrasonic treatment led to a less homogeneous scaffold porosity, resulting in evident cell clustering and enhanced hDM-pDE cell-cell interactions. Finally, nHA incorporation was found to enhance dental cell differentiation. However, it also resulted in smaller fiber diameter and reduced scaffold porosity, and inhibited cell ingrowth and proliferation. In conclusion, ultrasonically treated wet-electrospun PLGA/PCL scaffolds are a suitable material for dental tissue engineering, and support future in vivo evaluations of this model. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2597-2607, 2017.


[Gastric leiomyoblastoma. Its preoperative diagnosis by echo-guided needle aspiration. A report of 2 clinical cases].
The authors report two cases of gastric leiomyoblastoma, one benign and one malignant, come to clinical observation for digestive hemorrhage; in both cases a preoperating diagnosis of benignity or malignity was made and in one case even of histotype, thanks to fine needle biopsy. After a short introduction regarding some historical notes, the predictive parameters of malignity, the classification of this rare myoid tumor, the authors discuss the distribution of the pathology in the population, the symptomatology, the diagnostic "iter" with particular regard to the needle biopsy, the surgical treatment, and the indispensable parameters for formulating a correct prognosis.


Associations between dietary patterns and psychological factors: a cross-sectional study among Chinese postmenopausal women.
The aim of this study is to explore the association of dietary patterns with depression, perceived stress, and self-esteem among postmenopausal Chinese women. A cross-sectional study was conducted among 906 participants who attended the screening visits for two soy trials. Dietary data were collected using a validated food frequency questionnaire containing 85 food items. Principal component factor analysis was used to derive dietary patterns based on 11 food groups. Psychological factors were assessed by the Center for Epidemiologic Studies Depression Scale, Perceived Stress Scale, and Rosenberg Self-esteem Scale. We identified three dietary patterns as follows: processed foods (refined grains, preserved foods, fat meat, fried foods, and sweets), whole plant foods (whole grains, vegetables, and fruits), and animal foods (fish, lean meat, and milk products). Multivariable linear regression analyses indicated that whole plant food intake was negatively associated with depression score (P = 0.030). Processed food intake was positively associated with perceived stress (P = 0.025) and depression (P = 0.073), and negatively associated with scores of self-esteem (P = 0.046). The highest tertile of processed foods score was associated with 79.3% increased risk of depression (P for trend = 0.006), whereas the highest tertile of whole plant food score was associated with 26% reduction of depression (P for trend = 0.023) relative to the lowest tertile. Dietary patterns featuring a low intake of processed foods and/or a high intake of whole plant foods were associated with a reduced risk of depression and perceived stress.


Chromosome studies in acute leukemias developing in patients with multiple myeloma.
Chromosomal findings are reported in three patients with acute myelomonocytic leukemia and in one with reticulosarcoma leukemia who had been treated for multiple myeloma with melphalan and X-ray. All four patients had striking chromosomal anomalies. An iatrogenic causation of aneuploidy is suggested. This is supported by chromosomal findings in patients with acute leukemia following polycythemia vera and Hodgkin's disease; practically all of the leukemias have been aneuploid. A comparison is made of such "secondary" acute leukemias with "primary" acute leukemias that are aneuploid in only 40% of the cases. Chromosomal changes are not considered to be the initial event in leukemogenesis.


Cyclic cholecystokinin analogues that are highly selective for rat and guinea pig central cholecystokinin receptors.
Cholecystokinin (CCK) analogues (JMV310, JMV320, JMV328, and JMV332), obtained by side chain to side chain cyclization of a lysine residue in position 28 with a lysine residue in position 31, were found to be highly selective for the brain CCK receptor (CCK-B receptor), both in guinea pig and rat. In these analogues, the C-terminal tetrapeptide region of the molecule, which is the crucial determinant for binding to CCK-B receptors, has been constrained by cyclization. These analogues were highly potent in inhibiting binding of labeled CCK-8 to rat and guinea pig brain membranes (apparent affinity in the nanomolar range) but were poorly efficacious in inhibiting binding of labeled CCK-8 to rat or guinea pig pancreatic acini. In agreement with their low affinity for the pancreatic receptor, these CCK analogues were not very potent in stimulating amylase secretion. These cyclic CCK analogues were demonstrated to be highly selective for the brain CCK receptors.


Impaired gas mixing and low lung volume in preterm infants with mild chronic lung disease.
The aim of this study was to assess the possible role of gas mixing inefficiency in spontaneously breathing infants with mild chronic lung disease (CLD) of prematurity in relation to changes in other functional parameters. A simple bedside technique for recording and analysis of multiple breath nitrogen washout curves was applied together with occlusion mechanics. Fifteen preterm infants with mild or moderately severe CLD were studied at a mean postconceptional age of 35 wk, together with 15 healthy preterm infants at the same maturity. All infants breathed spontaneously, and the test was performed by a continuous bypass flow system, connected to a face mask, a pneumotachograph, and a nitrogen meter. The results showed impaired gas mixing with moment ratios above the 95th percentile of the normal group in 11/15 infants with CLD. Functional residual capacity (FRC) was low in 13/15 infants, but specific compliance and resistance of the respiratory system did not differ between the groups. As FRC and moment ratios were not correlated, it is suggested that they may reflect different aspects of the pathophysiology in CLD. It is concluded that low FRC and disturbed gas mixing are characteristic disturbances in CLD at different degrees of severity. The multiple breath nitrogen washout test, followed by moment analysis of end-tidal nitrogen concentrations, is a simple and sensitive method for detection of these disturbances and for monitoring purposes.


The summer school students' viewpoints about important factors in learning, Shiraz University of Medical Sciences.
The main goal of education is learning and change in behavior which has been revolutionized in the 21st century due to the rapid and widespread changes in science. The traditional approach to education does no longer meet the learners' needs, necessitating new changes in educational curricula. This study was designed to determine the factors influencing learning in the 21st century and find out the students' viewpoints on this issue. This is a descriptive study aiming at determining the students' views on new approaches to learning in the 21st century. To do so, a researcher-made questionnaire was designed. It contained 30 questions in 3 sections including demographic data, background questions and two open questions about their suggestions and criticisms. The reliability and validity of the questionnaire was pilot-tested and measured, which proved to be describable. 150 students participating in university summer schools in Shiraz University of Medical Sciences were enrolled. The questionnaires were sent to the students in person and through electronic mails. The students were asked to return the completed questionnaires to the given email address. The data were analyzed in SPSS, version 14, using descriptive statistics of frequency, mean, percentage and standard deviation and t-test. P<0.05 was considered as statistically significant. 150 questionnaires were appropriately filled out and given to the researchers. The results indicated that, according to the students, 6 factors including the use of computer in teaching, enhancement of virtual learning, the use of mobile in relations, enjoyment of electronic learning contexts, the learning focus on attitudes and the facilitating role of the lectures were the most influential factors in learning. On the other hand, the government's responsibility and responsiveness, creativity and risk taking, increase in the social relationship among the learners, focus on practical skills, and management were considered as the least influential factors in learning in the 21(st) century. It seems that the students philosophically tend to approve constructivism and cooperative learning which is learner-centered as compared to conventional education which is teacher-contended. According to experts, this type of viewpoint is in the same line with new approaches to teaching and education in the present era. Moreover, it impacts the reforms, complementation and expansion of methodology greatly.


Comparison of push-out bond strength of mineral trioxide aggregate and calcium enriched mixture cement as root end filling materials.
The purpose of this study was to compare the push-out bond strength of mineral trioxide aggregate (MTA) and calcium enriched mixture (CEM) as root end filling materials. A total of 40 root dentin slices (1 ± 0.2 mm) were prepared from freshly extracted human maxillary central teeth and their lumens were enlarged to 1.3 mm. The slices were randomly divided into two groups (n = 20). MTA and CEM cement were mixed according to manufacturer's instruction and introduced into the lumens. The specimens were wrapped in pieces of wet gauze soaked in distilled water and incubated at 37°C for 3 days. The push-out bond strength was measured using a universal testing machine. The slices were then examined under a light microscope at ×10 magnification to determine the nature of bond failure. The data were analyzed using Mann-Whitney test (P < 0.001). The mean push-out bond strength for CEM cement and MTA were 1.68 ± 0.9 and 5.94 ± 3.99 respectively. The difference was statistically significant (P < 0.001). The bond failure was predominantly of adhesive type in MTA group and cohesive type in CEM group. CEM cement showed significantly lower bond strength to the dentinal wall compared to MTA.


A multigenerational study on the correlation of values and advance directives.
The development of the Values History instrument for use in advance directive decision making has raised the question of the importance of values in eliciting advance directives. This pilot study examines the relationship between the domains of values and advance directives drawn from the Values History in three generation intrafamily triads. Significant correlations between values and advance directives were found primarily within the youngest generation. Results reveal a relatively high familiarity by the participants of the various established forms of advance directives. Also, a significant percentage of parents and grandparents was found to have signed some form of advance directive.


Oscillatory brain activity associates with neuroligin-3 expression and predicts progression free survival in patients with diffuse glioma.
Diffuse gliomas have local and global effects on neurophysiological brain functioning, which are often seen as 'passive' consequences of the tumor. However, seminal preclinical work has shown a prominent role for neuronal activity in glioma growth: mediated by neuroligin-3 (NLGN3), increased neuronal activity causes faster glioma growth. It is unclear whether the same holds true in patients. Here, we investigate whether lower levels of oscillatory brain activity relate to lower NLGN3 expression and predict longer progression free survival (PFS) in diffuse glioma patients. Twenty-four newly diagnosed patients with diffuse glioma underwent magnetoencephalography and subsequent tumor resection. Oscillatory brain activity was approximated by calculating broadband power (0.5-48 Hz) of the magnetoencephalography. NLGN3 expression in glioma tissue was semi-quantitatively assessed by immunohistochemistry. Peritumor and global oscillatory brain activity was then compared between different levels of NLGN3 expression with Kruskal-Wallis tests. Cox proportional hazards analyses were performed to estimate the predictive value of oscillatory brain activity for PFS. Patients with low expression of NLGN3 had lower levels of global oscillatory brain activity than patients with higher NLGN3 expression (P < 0.001). Moreover, lower peritumor (hazard ratio 2.17, P = 0.008) and global oscillatory brain activity (hazard ratio 2.10, P = 0.008) predicted longer PFS. Lower levels of peritumor and global oscillatory brain activity are related to lower NLGN3 expression and longer PFS, corroborating preclinical research. This study highlights the important interplay between macroscopically measured brain activity and glioma progression, and may lead to new therapeutic interventions in diffuse glioma patients.


Structural basis of Escherichia coli single-stranded DNA-binding protein stimulation of exonuclease I.
Bacterial single-stranded DNA (ssDNA)-binding proteins (SSBs) play essential protective roles in genome biology by shielding ssDNA from damage and preventing spurious DNA annealing. Far from being inert, ssDNA/SSB complexes are dynamic DNA processing centers where many different enzymes gain access to genomic substrates by exploiting direct interactions with SSB. In all cases examined to date, the C terminus of SSB (SSB-Ct) forms the docking site for heterologous proteins. We describe the 2.7-A-resolution crystal structure of a complex formed between a peptide comprising the SSB-Ct element and exonuclease I (ExoI) from Escherichia coli. Two SSB-Ct peptides bind to adjacent sites on ExoI. Mutagenesis studies indicate that one of these sites is important for association with the SSB-Ct peptide in solution and for SSB stimulation of ExoI activity, whereas the second has no discernable function. These studies identify a correlation between the stability of the ExoI/SSB-Ct complex and SSB-stimulation of ExoI activity. Furthermore, mutations within SSB's C terminus produce variants that fail to stimulate ExoI activity, whereas the SSB-Ct peptide alone has no effect. Together, our findings indicate that SSB stimulates ExoI by recruiting the enzyme to its substrate and provide a structural paradigm for understanding SSB's organizational role in genome maintenance.


Time course of tumor SUV in 18F-FDG PET of breast cancer: presentation of a simple model using a single reference point for time corrections of tumor SUVs.
Tumor standardized uptake values (SUVs) vary with the interval between 18F-FDG injection and image acquisition. This paper presents a simple method using a single reference point to make appropriate time corrections for tumor SUVs. The reference point method was algebraically deduced from observations made by Beaulieu et al., who found that tumor SUVs behaved linearly over time (∼30 to 75 min after 18F-FDG injection). Eighteen patients with breast cancer were dynamically examined with PET/CT (∼60 and 80 min after 18F-FDG injection). Maximum SUV was calculated by applying 2 different iterative reconstruction methods (high-definition reconstruction and attenuation-weighted ordered-subsets expectation maximization). Reference points for time corrections were given, and errors for corrections obtained with the reference point method were calculated. Variations in the reconstruction algorithm strongly influenced the coordinates of the reference point. Time corrections using the reference point method were more accurate at higher tumor SUVs (>8 at high-definition reconstruction and>6 at attenuation-weighted ordered-subsets expectation maximization) than at lower ones. A common origin of tumor SUVs over time exists in breast cancer. In combination with the linear behavior of tumor SUVs between approximately 30 and 80 min, such a reference point allows for straightforward time corrections of tumor SUVs. Parameters for image reconstruction must be considered because they influence the coordinates of the reference point.


Chiral Phosphoric Acid-Catalyzed Enantioselective Aza-Friedel-Crafts Addition of Naphthols with Isatin-Derived Ketimines.
The enantioselective Friedel-Crafts addition of naphthols with isatin-derived ketimines was developed with H8-BINOL-derived chiral biaryl phosphoric acid. A wide range of isatin-derived ketimines and naphthols were successfully applied and gave a series of chiral 3-amino-2-oxindoles in excellent yields with high optical purities.


The Problem and Goals Are Global, the Solutions Are Local: Revisiting Quality Measurements and the Role of the Private Sector in Global Health Professions Education.
The shortage of a competent health workforce is a global challenge. However, its manifestations and proposed solutions are very much context related (i.e., local). In addition to the shortage of health professionals, the quality of health professions education programs, institutions, and graduates, and how to measure quality, are also problematic. Commonly used metrics like the Credit Hours System and the European Credit Transfer and Accumulation System have limitations (e.g., being more focused on quantity than quality).In this Invited Commentary, the author discusses the need to revisit quality measurements in health professions education and the issue of whether the private sector has a role to play in narrowing the ever-increasing gap between the demand for health care professionals and the health care workforce shortage.


Autophosphorylation of the mammalian multifunctional protein that initiates de novo pyrimidine biosynthesis.
CAD, a large multifunctional protein that carries carbamoyl phosphate synthetase (CPSase), aspartate transcarbamoylase, and dihydroorotase activities, catalyzes the first three steps of de novo pyrimidine biosynthesis in mammalian cells. The CPSase component, which catalyzes the initial, rate-limiting step, exhibits complex regulatory mechanisms involving allosteric effectors and phosphorylation that control the flux of metabolites through the pathway. Incubation of CAD with ATP in the absence of exogenous kinases resulted in the incorporation of 1 mol of P(i)/mol of CAD monomer. Mass spectrometry analysis of tryptic digests showed that Thr(1037) located within the CAD CPS.B subdomain was specifically modified. The reaction is specific for MgATP, ADP was a competitive inhibitor, and the native tertiary structure of the protein was required. Phosphorylation occurred after denaturation, further purification of CAD by SDS gel electrophoresis, and renaturation on a nitrocellulose membrane, strongly suggesting that phosphate incorporation resulted from an intrinsic kinase activity and was not the result of contaminating kinases. Chemical modification with the ATP analog, 5'-p-fluorosulfonylbenzoyladenosine, showed that one or both of the active sites that catalyze the ATP-dependent partial reactions are also involved in autophosphorylation. The rate of phosphorylation was dependent on the concentration of CAD, indicating that the reaction was, at least in part, intermolecular. Autophosphorylation resulted in a 2-fold increase in CPSase activity, an increased sensitivity to the feedback inhibitor UTP, and decreased allosteric activation by 5-phosphoribosyl-1-pyrophosphate, functional changes that were distinctly different from those resulting from phosphorylation by either the protein kinase A or mitogen-activated protein kinase cascades.


Physiological and pathological roles of the Hippo-YAP/TAZ signaling pathway in liver formation, homeostasis, and tumorigenesis.
The liver plays central homeostatic roles in metabolism and detoxification, and has a remarkable capacity to fully recover from injuries caused by the various insults to which it is constantly exposed. To fulfill these functions, the liver must maintain a specific size and so must regulate its cell numbers. It must also remove senescent, transformed, and/or injured cells that impair liver function and can lead to diseases such as cirrhosis and liver cancer. Despite their importance, however, the mechanisms governing liver size control and homeostasis have resisted delineation. The discovery of the Hippo intracellular signaling pathway and its downstream effectors, the transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), has provided partial elucidation of these mechanisms. The Hippo-YAP/TAZ pathway is considered to be a cell's sensor of its immediate microenvironment and the cells that surround it, in that this pathway responds to changes in elements such as the ECM, cell-cell tension, and cell adhesion. Once triggered, Hippo signaling negatively regulates the binding of YAP/TAZ to transcription factors such as TEAD and Smad, controlling their ability to drive gene expression needed for cellular responses such as proliferation, survival, and stemness. Numerous KO mouse strains lacking YAP/TAZ, as well as transgenic mice showing YAP/TAZ hyperactivation, have been generated, and the effects of these mutations on liver development, size, regeneration, homeostasis, and tumorigenesis have been reported. In this review, I summarize the components and regulation of Hippo-YAP/TAZ signaling, and discuss this pathway in the context of liver physiology and pathology.


Structure of a baculovirus sulfhydryl oxidase, a highly divergent member of the erv flavoenzyme family.
Genomes of nucleocytoplasmic large DNA viruses (NCLDVs) encode enzymes that catalyze the formation of disulfide bonds between cysteine amino acid residues in proteins, a function essential for the proper assembly and propagation of NCLDV virions. Recently, a catalyst of disulfide formation was identified in baculoviruses, a group of large double-stranded DNA viruses considered phylogenetically distinct from NCLDVs. The NCLDV and baculovirus disulfide catalysts are flavin adenine dinucleotide (FAD)-binding sulfhydryl oxidases related to the cellular Erv enzyme family, but the baculovirus enzyme, the product of the Ac92 gene in Autographa californica multiple nucleopolyhedrovirus (AcMNPV), is highly divergent at the amino acid sequence level. The crystal structure of the Ac92 protein presented here shows a configuration of the active-site cysteine residues and bound cofactor similar to that observed in other Erv sulfhydryl oxidases. However, Ac92 has a complex quaternary structural arrangement not previously seen in cellular or viral enzymes of this family. This novel assembly comprises a dimer of pseudodimers with a striking 40-degree kink in the interface helix between subunits. The diversification of the Erv sulfhydryl oxidase enzymes in large double-stranded DNA viruses exemplifies the extreme degree to which these viruses can push the boundaries of protein family folds.


Features and impact of missing values in the association of self-rated health with mortality in care homes: a longitudinal study.
Self-rated health (SRH) is a health measure used in studies of older adults. The objective of this study is to analyze SRH as a predictor of mortality in the institutionalized older population and the characteristics of those who do not provide information about their SRH on health questionnaires. This is a 15-year follow-up study of older adult residents in nursing or care homes in of Madrid, Spain. SRH was measured on a 5-point Likert type scale. The association between answering the SRH question and socio-demographic and health characteristics was evaluated through prevalence ratio (PR), estimated by Poisson regression models. Survival rates associated with SRH were studied through a multivariate Cox regression. The sample has a mean age of 83.4 (standard deviation, SD = 7.3), with 75.7% women. Twelve percent did not answer the SRH item. Those who did not answer showed a higher probability of disability (Barthel index, PR = 0.76, 95% confidence interval = 0.67-0.86) and/or dementia (PR = 8.03, 3.38-19.03). A trend for higher mortality was observed in those persons who did not respond (adjusted hazard ratio HR = 1.26, 0.75-2.11). The mortality rate was 32% higher for those who declared poor SRH in comparison with those who reported good SRH (adjusted HR = 1.32, 1.08-1.6). There is an elevated number of people who do not respond to the SRH item, mainly those with disabilities and cognitive deterioration. Lack of response to SRH is a good indicator of 15-year mortality for persons institutionalized in care or nursing homes.


Palatal lymphangioma: a case report.
Lymphangioma is a rare, congenital benign tumor involving vascular malformation, with a great potential for recurrence. It appears during the early years of life and therefore is highly common among children. We report here a five-year-old patient with a simple lymphngioma. The mother of the child reported she had noted the lesion in the palate after an injury in the area with a pen. The recommended treatment was surgical excision since this was a small and well-delimited lesion. Periodic clinical controls for 18 months showed that mucosa presented normal characteristics, with no signs of recurrence.


Could parenting stress and lack of support/confidence function as mediating mechanisms between certain environmental factors and the development of autoimmunity in children?: a study within ABIS.
Despite extensive research, the etiology of type 1 diabetes is still to a large extent unknown. We would like to propose psychoimmunology as one possible pathway. Psychological mechanisms are directly linked to hormonal and nervous signals, which increase the need for insulin and affect the immune system. Disparate factors of social, environmental, and medical character have been associated with the onset of type 1 diabetes or with the autoimmune process leading to the disease-for instance, parental age, maternal infections, delivery mood, need for neonatal intensive care, and low socioeconomic status. Our results, based on the analyses of 4337 nonselected newborn children and their mothers, show that all these risk factors were also associated with psychological mechanisms (defined as lack of social support/confidence and high parenting stress). These results support the hypothesis of psychological mechanisms as mediating variables between a number of disparate risk factors and the development of type 1 diabetes.


Stretchable Coplanar Self-Charging Power Textile with Resist-Dyeing Triboelectric Nanogenerators and Microsupercapacitors.
The integration between energy-harvesting and energy-storage devices into a self-charging power unit is an effective approach to address the energy bottleneck of wearable/portable/wireless smart devices. Herein, we demonstrate a stretchable coplanar self-charging power textile (SCPT) with triboelectric nanogenerators (TENGs) and microsupercapacitors (MSCs) both fabricated through a resist-dyeing-analogous method. The textile electrodes maintain excellent conductivity at 600% and 200% tensile strain along course and wale directions, respectively. The fabric in-plane MSC with reduced graphene oxides as active materials reaches a maximum areal capacitance of 50.6 mF cm-2 at 0.01 V s-1 and shows no significant degradation at 50% of tensile strain. The stretchable fabric-based TENG can output 49 V open-circuit voltage and 94.5 mW m-2 peak power density. Finally, a stretchable coplanar SCPT with one-batch resist-dyeing fabrication is demonstrated for powering small electronics intermittently without extra recharging. Our approach is also compatible with conventional textile processing and suggests great potential in electronic textiles and wearable electronics.


[Improved diagnosis of extrauterine pregnancy by endosonography].
Between July 1987 and January 1988, 44 patients with a tentative diagnosis of ectopic pregnancy underwent sonographic examination by means of vaginal probe at the Department of Gynecology and Obstetrics of the RWTH Aachen. The sonographic findings, all of which were confirmed by subsequent clinical and or surgical clarification, were as follows: an ectopic pregnancy was diganosed in 16 cases, an early intrauterine pregnancy in seven, an intrauterine abortion in seven, and in one case a uterine malformation-a dermoid cyst and a functional cyst. In 11 cases sonographic examination showed the interior genital region to be normal, with no sign of pregnancy. In the 16 ectopic pregnancies diagnosed, it was possible in 13 cases to visualize the pregnancy directly by sonography, including the amniotic sac, and to make measurements. In one case a normally developed ectopic pregnancy with living embryo was seen at the end of the seventh week of gestation post menstruationem. In the remaining three cases the diagnosis was established on the basis of an empty cavum uteri associated with a slightly enlarged uterus and demonstration of fluid in the pouch of Douglas. In two cases the ectopic pregnancy was correctly localized by "feeling" with the intravaginal probe to establish the cause of circumscribed pain. In three case the tentative diagnosis of an ectopic pregnancy made on the basis of sonographic findings was not confirmed by subsequent clarification procedures. The results described show that in most cases ectopic pregnancies can be demonstrated directly by sonography using an intravaginal probe.(ABSTRACT TRUNCATED AT 250 WORDS)


Impact of soil field water capacity on secondary metabolites, phenylalanine ammonia-lyase (PAL), maliondialdehyde (MDA) and photosynthetic responses of Malaysian kacip fatimah (Labisia pumila Benth).
A randomized complete block design 2 × 4 experiment was designed and conducted for 15 weeks to characterize the relationships between production of total phenolics, flavonoid, anthocyanin, leaf gas exchange, total chlorophyll, phenylalanine ammonia-lyase (PAL) and malondialdehyde (MDA) activity in two varieties of Labisia pumila Benth, namely the var. alata and pumila, under four levels of evapotranspiration replacement (ER) (100%; well watered), (75%, moderate water stress), (50%; high water stress) and (25%; severe water stress). The production of total phenolics, flavonoids, anthocyanin, soluble sugar and relative leaf water content was affected by the interaction between varieties and SWC. As the ER levels decreased from 100% to 25%, the production of PAL and MDA activity increased steadily. At the highest (100%) ER L. pumila exhibited significantly higher net photosynthesis, apparent quantum yield, maximum efficiency of photosystem II (f(v)/f(m)) and lower dark respiration rates compared to the other treatment. The production of total phenolics, flavonoids and anthocyanin was also found to be higher under high water stress (50% ER replacement) compared to severe water stress (25% ER). From this study, it was observed that as net photosynthesis, apparent quantum yield and chlorophyll content were downregulated under high water stress the production of total phenolics, flavonoids and anthocyanin were upregulated implying that the imposition of high water stress can enhance the medicinal properties of L. pumila Benth.