[Bronchogenic cysts of the mediastinum in children. Apropos of 14 cases].
Fourteen children, aged from 2 months to 14 years, underwent surgical excision of a bronchogenic cyst in the mediastinum. Nine of these children were asymptomatic and the finding of the tumor was purely accidental. Retrotracheal and subcarinal localizations were more often symptomatic but their visualization on standard chest roentgenograms was sometimes difficult. An oesophagogram was helpful for the diagnosis in those circumstances. No postoperative complication occurred in our series.


Aldosterone renin ratio and chronic kidney disease.
As a component of the metabolic syndrome, hypertension (HTN) is increasing throughout the world with variable percentages, but mostly among developing world. Aldosterone plays a role in the relationship between aldosterone and nephropathy. We aimed to evaluate the relationship between aldosterone renin ratio (ARR) and chronic kidney disease (CKD). Variables drawn from the computerized hospital information database were all patients who had an ARR above 35 (if aldosterone reading was above 300 pmol/L). A total of 1584 patients, of whom 777 were male and 807 were female, with a mean [standard deviation (SD)] of 43.3 (16.5) years were studied. The mean ARR was 210.1 (SD: 246.4) in males and 214.3 and 210.1 in females, P = 0.51. The mean estimated glomerular filtration rate (eGFR) was 50.2 (SD 12.6); in males, it was 49.99 (0.90) and in females, it was 50.48 (0.92), P = 0.70. The regression model revealed a negative relationship between ARR and GFR with a coefficient of -2.08, 95% confidence interval: -4.6, 0.21, P = 0.07. CKD population with HTN tends to have a very high level of ARR, and those with advanced CKD have higher ARR. However, high ARR could have low eGFR and kidney dysfunction on follow-up. In view of high prevalence of noncommunicable disease and high early CKD population, there is an important need to consider comprehensive management strategies that involve the blockage of high renin-angiotensin-aldosterone and the use of mineralocorticosteroid receptor blockers.


The Role of the Lateral Intraparietal Area in (the Study of) Decision Making.
Over the past two decades, neurophysiological responses in the lateral intraparietal area (LIP) have received extensive study for insight into decision making. In a parallel manner, inferred cognitive processes have enriched interpretations of LIP activity. Because of this bidirectional interplay between physiology and cognition, LIP has served as fertile ground for developing quantitative models that link neural activity with decision making. These models stand as some of the most important frameworks for linking brain and mind, and they are now mature enough to be evaluated in finer detail and integrated with other lines of investigation of LIP function. Here, we focus on the relationship between LIP responses and known sensory and motor events in perceptual decision-making tasks, as assessed by correlative and causal methods. The resulting sensorimotor-focused approach offers an account of LIP activity as a multiplexed amalgam of sensory, cognitive, and motor-related activity, with a complex and often indirect relationship to decision processes. Our data-driven focus on multiplexing (and de-multiplexing) of various response components can complement decision-focused models and provides more detailed insight into how neural signals might relate to cognitive processes such as decision making.


Site-specific integration mediated by a hybrid adenovirus/adeno-associated virus vector.
Adenovirus (Ad) and adeno-associated virus (AAV) have attractive and complementary properties that can be exploited for gene transfer purposes. Ad vectors are probably the most efficient vehicles to deliver foreign genes both in vitro and in vivo. AAV exhibits the unique ability to establish latency by efficiently integrating at a specific locus of human chromosome 19 (AAVS1). Two viral elements are necessary for the integration at AAVS1: Rep68/78 and the inverted terminal repeats (AAV-ITRs). In this study, we report the development of two helper-dependent adenoviral (HD) vectors, one carrying the Rep78 gene, the other an AAV-ITR-flanked transgene. Although Rep proteins have been demonstrated to interfere with Ad replication, HD Rep78 vector was successfully amplified on serial passages in 293CRE4 cells with a yield of 50-100 transducing units per cell. DNA integration at the AAVS1 site also was demonstrated in hepatoma cells coinfected with the HD-expressing Rep78 and with the second HD vector carrying a transgene flanked by AAV-ITRs. The high transduction efficiency, large cloning capacity, and high titer of the HD, combined with the site-specific integration machinery provided by AAV-derived components, make the Ad/AAV hybrid viruses a promising vehicle for gene therapy.


Amplification of JC virus DNA from brain and cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy.
We have established an assay to detect JC viral DNA in brain tissue and CSF of patients with progressive multifocal leukoencephalopathy (PML) and amplified a 106-base pair segment of the gene encoding JC viral large T antigen by polymerase chain reaction (PCR) from the brains of eight patients with PML and from one of six CSF samples. Brain and CSF of patients without PML did not yield JC virus-specific DNA amplification products. Southern analysis documented that the sequences of the 106-base pair PCR product and JC viral DNA are identical. This assay can be used in the diagnosis of PML and to investigate the biology of JC virus.


Residential neighborhood greenery and children's cognitive development.
Children who grow up in neighborhoods with more green vegetation show enhanced cognitive development in specific domains over short timespans. However, it is unknown if neighborhood greenery per se is uniquely predictive of children's overall cognitive development measured across many years. The E-Risk Longitudinal Study, a nationally representative 1994-5 birth-cohort of children in Britain (n = 1658 urban and suburban-dwelling participants), was used to test whether residential neighborhood greenery uniquely predicts children's cognitive development across childhood and adolescence. Greenery exposure was assessed from ages 5 to 18 using the satellite imagery-based normalized difference vegetation index (NDVI) in 1-mile buffers around the home. Fluid and crystalized intellectual performance was assessed in the home at ages 5, 12, and 18 using the Wechsler Intelligence Scale, and executive function, working memory, and attention ability were assessed in the home at age 18 using the Cambridge Neuropsychological Test Automated Battery. Children living in residences surrounded by more neighborhood greenery scored significantly higher, on average, on IQ measures at all ages. However, the association between greenery and cognitive measures did not hold after accounting for family or neighborhood socioeconomic status. After adjustment for study covariates, child greenery exposure was not a significant predictor of longitudinal increases in IQ across childhood and adolescence or of executive function, working memory, or attention ability at age 18. Children raised in greener neighborhoods exhibit better overall cognitive ability, but the association is likely accounted for by family and neighborhood socioeconomic factors.


Lithocholic acid in human-blood serum.
Lithocholic acid was present in the serum of three patients with, jaundice and, in smaller amounts, in two healthy adults. This bile acid occurs naturally in human feces but induces cirrhosis of the liver when fed to a wide variety of experimental animals. The finding of lithocholic acid in blood is of interest because of its possible role in injuring human liver.


Intra-articular saline injection is as effective as corticosteroids, platelet-rich plasma and hyaluronic acid for hip osteoarthritis pain: a systematic review and network meta-analysis of randomised controlled trials.
Intra-articular (IA) injections represent a commonly used modality in the treatment of hip osteoarthritis (OA). Commonly used injections include corticosteroids (CCS), hyaluronic acid (HA) and platelet-rich plasma (PRP). A network meta-analysis allows for comparison among more than two treatment arms and uses both direct and indirect comparisons between interventions. The objective of this network meta-analysis is to compare the efficacy of the various IA injectable treatments in treating hip OA at up to 6 months of follow-up. This is a systematic review and network meta-analysis. Bayesian random-effects model was performed to assess the direct and indirect comparisons of all treatment options. PubMed, Embase, Cochrane Central Register of Controlled Trials, Scopus and Web of Science, from inception to October 2019. Randomised controlled trials assessing the efficacy of CCS, HA, PRP and placebo in the form of IA saline injection for patients with hip OA. Eleven randomised controlled trials comprising 1353 patients were included. For pain outcomes at both 2-4 and 6 months, no intervention significantly outperformed placebo IA injection. For functional outcomes at both 2-4 and 6 months, no intervention significantly outperformed placebo IA injection. Regarding change from baseline at 2-4 months and 6 months, pooled data demonstrated that all interventions (including placebo), with the exception of HA+PRP, led to a clinically important improvement in both pain, exceeding the minimal clinically important difference. Evidence suggests that IA hip saline injections performed as well as all other injectable options in the management of hip pain and functional outcomes.


Tellurium compound AS101 ameliorates experimental autoimmune encephalomyelitis by VLA-4 inhibition and suppression of monocyte and T cell infiltration into the CNS.
Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) involving demyelinating and neurodegenerative processes. Several of the major pathological CNS alterations and behavioral deficits of MS are recapitulated in the experimental autoimmune encephalitis (EAE) mouse model in which the disease process is induced by administration of myelin peptides. Development of EAE requires infiltration of inflammatory cytokine-generating monocytes and macrophages, and auto-reactive T cells, into the CNS. Very late antigen-4 (VLA-4, α4β1) is an integrin molecule that plays a role in inflammatory responses by facilitating the migration of leukocytes across the blood-brain barrier during inflammatory disease, and antibodies against VLA-4 exhibit therapeutic efficacy in mouse and monkey MS models. Here, we report that the tellurium compound AS101 (ammonium trichloro (dioxoethylene-o,o') tellurate) ameliorates EAE by inhibiting monocyte and T cell infiltration into the CNS. CD49d is an alpha subunit of the VLA-4 (α4β1) integrin. During the peak stage of EAE, AS101 treatment effectively ameliorated the disease process by reducing the number of CD49d(+) inflammatory monocyte/macrophage cells in the spinal cord. AS101 treatment markedly reduced the pro-inflammatory cytokine levels, while increasing anti-inflammatory cytokine levels. In contrast, AS101 treatment did not affect the peripheral populations of CD11b(+) monocytes and macrophages. AS101 treatment reduced the infiltration of CD4(+) and CD49(+)/VLA4 T cells. In addition, treatment of T cells from MS patients with AS101 resulted in apoptosis, while such treatment did not affect T cells from healthy donors. These results suggest that AS101 reduces accumulation of leukocytes in the CNS by inhibiting the activity of the VLA-4 integrin and provide a rationale for the potential use of Tellurium IV compounds for the treatment of MS.


Bioluminescence tomography using eigenvectors expansion and iterative solution for the optimized permissible source region.
A reconstruction algorithm for bioluminescence tomography (BLT) has been developed. The algorithm numerically calculates the Green's function at different wavelengths using the diffusion equation and finite element method. The optical properties used in calculating the Green's function are reconstructed using diffuse optical tomography (DOT) and assuming anatomical information is provided by x-ray computed tomography or other methods. A symmetric system of equations is formed using the Green's function and the measured light fluence rate and the resulting eigenvalue problem is solved to get the eigenvectors of this symmetric system of equations. A space can be formed from the eigenvectors obtained and the reconstructed source is written as an expansion of the eigenvectors corresponding to non-zero eigenvalues. The coefficients of the expansion are found to obtain the reconstructed BL source distribution. The problem is solved iteratively by using a permissible source region that is shrunk by removing nodes with low probability to contribute to the source. Throughout this process the permissible region shrinks from the entire object to just a few nodes. The best estimate of the reconstructed source is chosen that which minimizes the difference between the calculated and measured light fluence rates. 3D simulations presented here show that the reconstructed source is in good agreement with the actual source in terms of locations, magnitudes, sizes, and total powers for both localized multiple sources and large inhomogeneous source distributions.


Heat-related mortality during a 1999 heat wave in Chicago.
During the summer of 1999, Chicago's second deadliest heat wave of the decade resulted in at least 80 deaths. The high mortality, exceeded only by a 1995 heat wave, provided the opportunity to investigate the risks associated with heat-related deaths and to examine the effectiveness of targeted heat-relieving interventions. We conducted a case-control study to determine risk factors for heat-related death. We collected demographic, health, and behavior information for 63 case patients and 77 neighborhood-and-age-matched control subjects and generated odds ratios (ORs) for each potential risk factor. Fifty-three percent of the case patients were aged <65 years, and psychiatric illness was almost twice as common in the younger than the older age group. In the multivariate analysis, the strongest risk factors for heat-related death were living alone (OR=8.1; 95% confidence interval [CI], 1.4-48.1) and not leaving home daily (OR=5.8; 95% CI, 1.5-22.0). The strongest protective factor was a working air conditioner (OR=0.2; 95% CI, 0.1-0.7). Over half (53%) of the 80 decedents were seen or spoken to on the day of or day before their deaths. A working air conditioner is the strongest protective factor against heat-related death. The relatively younger age of case patients in 1999 may be due to post-1995 interventions that focused on the elderly of Chicago. However, social isolation and advanced age remain important risk factors. Individual social contacts and educational messages targeted toward at-risk populations during heat waves may decrease the number of deaths in these groups.


Cultivated strains of Agaricus bisporus and A. brasiliensis: chemical characterization and evaluation of antioxidant and antimicrobial properties for the final healthy product--natural preservatives in yoghurt.
Agaricus bisporus (J. E. Lange) Emil J. Imbach and Agaricus brasiliensis Wasser, M. Didukh, Amazonas & Stamets are edible mushrooms. We chemically characterized these mushrooms for nutritional value, hydrophilic and lipophilic compounds. The antioxidant and antimicrobial activities of methanolic and ethanolic extracts were assessed. Hepatotoxicity was also evaluated. The ethanolic extract of both species was tested for inhibition of Listeria monocytogenes growth in yoghurt. Both species proved to be a good source of bioactive compounds. A. brasiliensis was richer in polyunsaturated fatty acids and revealed the highest concentration of phenolic acids, and tocopherols. A. bisporus showed the highest monounsaturated fatty acids and ergosterol contents. A. brasiliensis revealed the highest antioxidant potential, and its ethanolic extract displayed the highest antibacterial potential; the methanolic extract of A. bisporus revealed the highest antifungal activity. A. brasiliensis possessed better preserving properties in yoghurt.


Hazardous effects of curcumin on mouse embryonic development through a mitochondria-dependent apoptotic signaling pathway.
In this study, we examined the cytotoxic effects of curcumin, the yellow pigment of Curcuma longa, on the blastocyst stage of mouse embryos, subsequent embryonic attachment, and outgrowth in vitro and in vivo implantation by embryo transfer. Mouse blastocysts were incubated in medium with or without curcumin (6, 12 or 24 μM) for 24 h. Cell proliferation and growth were investigated using dual differential staining, apoptosis was analyzed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and implantation and post-implantation development of embryos were measured by in vitro development analysis and in vivo embryo transfer, respectively. Blastocysts treated with 24 μM curcumin displayed significantly increased apoptosis and decreased total cell number. Interestingly, we observed no marked differences in the implantation success rates between curcumin-pretreated and control blastocysts during in vitro embryonic development through implantation with a fibronectin-coated culture dish. However, in vitro treatment with 24 μM curcumin was associated with decreased implantation rate and increased resorption of postimplantation embryos in mouse uterus, as well as decreased fetal weight in the embryo transfer assay. Our results collectively indicate that in vitro exposure to curcumin triggers apoptosis and retards early postimplantation development after transfer to host mice. In addition, curcumin induces apoptotic injury effects on mouse blastocysts through ROS generation, and further promotes mitochondria-dependent apoptotic signaling processes to impair sequent embryonic development.


Single use versus reusable catheters in intermittent catheterisation for treatment of urinary retention: a protocol for a multicentre, prospective, randomised controlled, non-inferiority trial (COMPaRE).
Chronic urinary retention is a common lower urinary tract disorder, mostly neurogenic or idiopathic in origin. The preferred treatment is clean intermittent urinary self-catheterisation (CISC) four to six times a day. In most European countries, virtually all patients use single use catheters, which is in contrast to several countries where the use of reusable catheters is more common. The available literature on the use of reusable catheters is conflicting and until now, no randomised controlled trial with sufficient power has been performed to investigate if reusable catheters for CISC is as safe as single use catheters. We described this protocol for a prospective, randomised controlled non-inferiority trial to investigate if the use of reusable catheters is as safe as single use catheters for CISC patients, measured by symptomatic urinary tract infections (sUTIs). Secondary objectives are adverse events due to a sUTI, urethral damage, stone formation, quality of life and patient satisfaction. A cost-effectiveness analysis will also be performed. 456 Participants will be randomised into two groups stratified for age, gender, menopausal status and (non-)neurogenic underlying disorder. The intervention group will replace the reusable catheter set every 2 weeks for a new set and replace the cleaning solution every 24 hours. The control group continues to use its own catheters. The primary outcome (amount of sUTIs from baseline to 1 year) will be tested for non-inferiority. Categorical outcome measures will be analysed using χ2 tests and quantitative outcome variables by t-tests or Mann-Whitney U tests. Two-sided p values will be calculated. This protocol was reviewed and approved by the Medical Ethics Committee of the Erasmus MC (MEC 2019-0134) and will be performed according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist for non-inferiority trials. The results of this randomised controlled non-inferiority trial will be published in a peer-reviewed journal and will be publicly available. NL8296.


Recovery in skeletal muscle contractile function after prolonged hindlimb immobilization.
Contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus (EDL), and fast-twitch superficial region of the vastus lateralis were determined in vitro (22 degrees C) in rats remobilized after prolonged (3 mo) hindlimb immobilization (IM). For all muscles the muscle-to-body weight ratio was significantly depressed by IM, and the ratios failed to completely recover even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than the slow-twitch SOL. The IM shortened the SOL isometric twitch duration due to a reduced contraction and half-relaxation time. These parameters returned to control levels by the 14th day of recovery. Peak tetanic tension (Po, g/cm2) declined with IM by 46% in the SOL but showed no significant change in the fast-twitch muscles. After IM the SOL Po (g/cm2) recovered to control values by 28 days. The recovery of Po in absolute units (g) was considerably slower and did not return to control levels until 60 (SOL) to 90 (EDL) days. The maximum shortening velocity was not altered by IM in any of the muscles studied. These results demonstrate that both fast- and slow-twitch skeletal muscles possess the ability to completely recover normal contractile function following prolonged periods of hindlimb IM.


Power as an emotional liability: Implications for perceived authenticity and trust after a transgression.
People may express a variety of emotions after committing a transgression. Through 6 empirical studies and a meta-analysis, we investigate how the perceived authenticity of such emotional displays and resulting levels of trust are shaped by the transgressor's power. Past findings suggest that individuals with power tend to be more authentic because they have more freedom to act on the basis of their own personal inclinations. Yet, our findings reveal that (a) a transgressor's display of emotion is perceived to be less authentic when that party's power is high rather than low; (b) this perception of emotional authenticity, in turn, directly influences (and mediates) the level of trust in that party; and (c) perceivers ultimately exert less effort when asked to make a case for leniency toward high rather than low-power transgressors. This tendency to discount the emotional authenticity of the powerful was found to arise from power increasing the transgressor's perceived level of emotional control and strategic motivation, rather than a host of alternative mechanisms. These results were also found across different types of emotions (sadness, anger, fear, happiness, and neutral), expressive modalities, operationalizations of the transgression, and participant populations. Altogether, our findings demonstrate that besides the wealth of benefits power can afford, it also comes with a notable downside. The findings, furthermore, extend past research on perceived emotional authenticity, which has focused on how and when specific emotions are expressed, by revealing how this perception can depend on considerations that have nothing to do with the expression itself. (PsycINFO Database Record


Disentangling detector data in XFEL studies of temporally resolved solution state chemistry.
With the arrival of X-ray Free Electron Lasers (XFELs), 2D area detectors with a large dynamic range for detection of hard X-rays with fast readout rates are required for many types of experiments. Extracting the desired information from these detectors has been challenging due to unpredicted fluctuations in the measured images. For techniques such as time-resolved X-ray Diffuse Scattering (XDS), small differences in signal intensity are the starting point for analysis. Fluctuations in the total detected signal remain in the differences under investigation, obfuscating the signal. To correct such artefacts, Singular Value Decomposition (SVD) can be used to identify and characterize the observed detector fluctuations and assist in assigning some of them to variations in physical parameters such as X-ray energy and X-ray intensity. This paper presents a methodology for robustly identifying, separating and correcting fluctuations on area detectors based on XFEL beam characteristics, to enable the study of temporally resolved solution state chemistry on the femtosecond timescale.


Numeral Incorporation in Russian Sign Language: Phonological Constraints on Simultaneous Morphology.
This paper looks at numeral incorporation in Russian Sign Language (RSL). Numeral incorporation is the simultaneous combination of a numeral and a base sign into one sign. Incorporating forms typically use the numerical handshape combined simultaneously with the movement, location, and orientation of the base lexical sign; for example, "three months" will be expressed through an incorporating form 3_month. RSL is a language with a two-handed numeral system. Investigating two-handed numeral incorporation in RSL provides important insights into the constraints on numeral incorporation across languages as well as into the phonological structure of RSL. Numeral incorporation is a general preference in RSL that is highly constrained: not all calendric terms can incorporate, and not all numbers can be incorporated. For example, the sign month incorporates numbers one through nine (one through five are one-handed, and six through nine are two-handed). The incorporating one-handed form 5_minute exists, while the two-handed *6_minute form does not occur (that is, its meaning is expressed sequentially), and the sign day does not incorporate numbers at all. These limits are conditioned for semantic (lexical frequency, pragmatics) and phonological reasons. Because the numeral system of RSL is two-handed, the results show, first, that numeral incorporation is not limited to one-handed numerals. In addition, the results indicate that limits on numeral incorporation are not universal across sign languages. In RSL, each paradigm shows specific numeral incorporation limits that are phonologically conditioned. These limits are explained by the interaction of phonological rules at all levels of sign sublexical features for both the numeral and lexical sign: location, orientation, handshape, and movement. The location and orientation parameters of sign, however, have not been previously noted as being factors that limit numeral incorporation and sign complexity in a sign language. Our analyses, from both the numeral incorporation data and from elicitation and RSL corpus data, show that location and orientation function as phonological constraints in the composition of two-handed signs. Specifically, location and orientation operate in handshape symmetry restrictions. Our analyses also show that signs located on the head do not allow two-handed numeral incorporation. The corpus analyses corroborated this finding: all two-handed signs on the head that we found in our RSL corpus were symmetrical and frequently included weak drop, such that we found no asymmetrical two-handed signs on the head. Another symmetry restriction relates to orientation. Analyses of the RSL numeral incorporation data and the RSL corpus data and dictionaries show that RSL disprefers asymmetrical handshapes in two-handed signs having lateral orientation (palm facing the central line) (Fenlon et al. 2013).


Physical activity and Alzheimer disease course.
To examine the association between physical activity (PA) and Alzheimer disease (AD) course. PA has been related to lower risk for AD. Whether PA is associated with subsequent AD course has not been investigated. In a population-based study of individuals aged 65 years and older in New York who were prospectively followed up with standard neurologic and neuropsychological evaluations (every ~1.5 years), 357 participants i) were nondemented at baseline and ii) were diagnosed with AD during follow-up (incident AD). PA (sum of participation in a variety of physical activities, weighted by the type of activity [light, moderate, and severe]) obtained 2.4 (standard deviation [SD], 1.9) years before incidence was the main predictor of mortality in Cox models and of cognitive decline in generalized estimating equation models that were adjusted for age, gender, ethnicity, education, comorbidities, and duration between PA evaluation and dementia onset. One hundred fifty incident AD cases (54%) died during the course of 5.2 (SD, 4.4) years of follow-up. When compared with incident AD cases who were physically inactive, those with some PA had lower mortality risk, whereas incident AD participants with much PA had an even lower risk. Additional adjustments for apolipoprotein genotype, smoking, comorbidity index, and cognitive performance did not change the associations. PA did not affect rates of cognitive or functional decline. Exercise may affect not only risk for AD but also subsequent disease duration: more PA is associated with prolonged survival in AD.


Evidence for the involvement of zinc in the association of CRISP1 with rat sperm during epididymal maturation.
Rat epididymal protein CRISP1 (cysteine-rich secretory protein 1) associates with sperm during maturation and participates in fertilization. Evidence indicates the existence of two populations of CRISP1 in sperm: one loosely bound and released during capacitation, and one strongly bound that remains after this process. However, the mechanisms underlying CRISP1 binding to sperm remain mostly unknown. Considering the high concentrations of Zn(2+) present in the epididymis, we investigated the potential involvement of this cation in the association of CRISP1 with sperm. Caput sperm were coincubated with epididymal fluid in the presence or absence of Zn(2+), and binding of CRISP1 to sperm was examined by Western blot analysis. An increase in CRISP1 was detected in sperm exposed to Zn(2+), but not if the cation was added with ethylenediaminetetra-acetic acid (EDTA). The same results were obtained using purified CRISP1. Association of CRISP1 with sperm was dependent on epididymal fluid and Zn(2+) concentrations and incubation time. Treatment with NaCl (0.6 M) removed the in vitro-bound CRISP1, indicating that it corresponds to the loosely bound population. Flow cytometry of caput sperm exposed to biotinylated CRISP1/avidin-fluorescein isothiocyanate revealed that only the cells incubated with Zn(2+) exhibited an increase in fluorescence. When these sperm were examined by epifluorescence microscopy, a clear staining in the tail, accompanied by a weaker labeling in the head, was observed. Detection of changes in the tryptophan fluorescence emission spectra of CRISP1 when exposed to Zn(2+) supported a direct interaction between CRISP1 and Zn(2+). Incubation of either cauda epididymal fluid or purified CRISP1 with Zn(2+), followed by native-PAGE and Western blot analysis, revealed the presence of high-molecular-weight CRISP1 complexes not detected in fluids treated with EDTA. Altogether, these results support the involvement of CRISP1-Zn(2+) complexes in the association of the loosely bound population of CRISP1 with sperm during epididymal maturation.


Differential phosphorylation, desensitization, and internalization of α1A-adrenoceptors activated by norepinephrine and oxymetazoline.
Loss of response on repetitive drug exposure (i.e., tachyphylaxis) is a particular problem for the vasoconstrictor effects of medications containing oxymetazoline (OXY), an α1-adrenoceptor (AR) agonist of the imidazoline class. One cause of tachyphylaxis is receptor desensitization, usually accompanied by phosphorylation and internalization. It is well established that α1A-ARs are less phosphorylated, desensitized, and internalized on exposure to the phenethylamines norepinephrine (NE), epinephrine, or phenylephrine (PE) than are the α1B and α1D subtypes. However, here we show in human embryonic kidney-293 cells that the low-efficacy agonist OXY induces G protein-coupled receptor kinase 2-dependent α1A-AR phosphorylation, followed by rapid desensitization and internalization (∼40% internalization after 5 minutes of stimulation), whereas phosphorylation of α1A-ARs exposed to NE depends to a large extent on protein kinase C activity and is not followed by desensitization, and the receptors undergo delayed internalization (∼35% after 60 minutes of stimulation). Native α1A-ARs from rat tail artery and vas deferens are also desensitized by OXY, but not by NE or PE, indicating that this property of OXY is not limited to recombinant receptors expressed in cell systems. The results of the present study are clearly indicative of agonist-directed α1A-AR regulation. OXY shows functional selectivity relative to NE and PE at α1A-ARs, leading to significant receptor desensitization and internalization, which is important in view of the therapeutic vasoconstrictor effects of this drug and the varied biologic process regulated by α1A-ARs.


Developmental and plasticity-related differential expression of two SNAP-25 isoforms in the rat brain.
In this article we study the relationship between the expression pattern of two recently identified isoforms of the 25-kD synaptosomal-associated protein (SNAP-25a and SNAP-25b) and the morphological changes inherent to neuronal plasticity during development and kainic acid treatment. SNAP-25 has been involved in vescicle fusion in the nerve terminal, and most likely participates in different membrane fusion-related processes, such as those involved in neurotransmitter release and axonal growth. In the adult brain, SNAP-25b expression exceeded SNAP-25a in distribution and intensity, being present in most brain structures . Moderate or high levels of SNAP-25a hybridization signal were found in neurons of the olfactory bulb, the layer Va of the frontal and parietal cortices, the piriform cortex, the subiculum and the hippocampal CA4 field, the substantia nigra/pars compacta, and the pineal gland, partially overlapping SNAP-25b mRNA distribution. In restricted regions of cerebral cortex, thalamus, mammillary bodies, substantia nigra, and pineal glands the two isoforms were distributed in reciprocal fashion. During development SNAP-25a mRNA was the predominant isoform, whereas SNAP-25b expression increased postnatally. The early expression of SNAP-25a in the embryo and the decrease after P21 is suggestive of a potential involvement of this isoform in axonal growth and/or synaptogenesis. This conclusion is indirectly supported by the observation that SNAP-25a mRNA, but not SNAP-25b mRNA, was upregulated in the granule cells of the adult dentate gyrus 48 hours after kainate-induced neurotoxic damage of the hippocampal CA3-CA4 regions. Increase of SNAP-25 immunoreactivity was observed as early as 4 days after kainate injection within the mossy fiber terminals of the CA3 region, and in the newly formed mossy fiber aberrant terminals of the supragranular layer. These data suggest an isoform-specific role of SNAP-25 in neural plasticity.


ABUS tumor segmentation via decouple contrastive knowledge distillation.
In recent years, deep learning-based methods have become the mainstream for medical image segmentation. Accurate segmentation of automated breast ultrasound (ABUS) tumor plays an essential role in computer-aided diagnosis. Existing deep learning models typically require a large number of computations and parameters. Aiming at this problem, we propose a novel knowledge distillation method for ABUS tumor segmentation. The tumor or non-tumor regions from different cases tend to have similar representations in the feature space. Based on this, we propose to decouple features into positive (tumor) and negative (non-tumor) pairs and design a decoupled contrastive learning method. The contrastive loss is utilized to force the student network to mimic the tumor or non-tumor features of the teacher network. In addition, we designed a ranking loss function based on ranking the distance metric in the feature space to address the problem of hard-negative mining in medical image segmentation. The effectiveness of our knowledge distillation method is evaluated on the private ABUS dataset and a public hippocampus dataset. The experimental results demonstrate that our proposed method achieves state-of-the-art performance in ABUS tumor segmentation. Notably, after distilling knowledge from the teacher network (3D U-Net), the Dice Similarity Coefficient (DSC) of the student network (small 3D U-Net) is improved by 7%. Moreover, the DSC of the student network (3D HR-Net) reaches 0.780, which is very close to that of the teacher network, while their parameters are only 6.8% and 12.1% of 3D U-Net, respectively. This research introduces a novel knowledge distillation method for automated breast ultrasound (ABUS) tumor segmentation, significantly reducing computational demands while achieving state-of-the-art performance. The method promises enhanced accuracy and feasibility for computer-aided diagnosis in diverse imaging scenarios.


One-and-a-half syndrome in a patient with metastatic breast disease.
This report reviews the clinical course of a patient with breast carcinoma presenting with the classic one-and-a-half syndrome. She had no saccades to the left and no leftward eye deviation on oculocephalic movement. Her clinical examination suggested involvement in the medial longitudinal fasciculus, paramedian pontine reticular formation, and abducens nucleus. There has only been one previous case reported of a metastasis producing this syndrome. A computed tomography scan confirmed the pontine location of the lesion.


Data independent acquisition for gas chromatographic MS/MS analysis of volatile compounds.
This study presents a novel tandem mass spectrometry (MS/MS) approach utilizing a data independent acquisition (DIA) concept specifically designed with gas chromatography-electron ionization-triple quadrupole mass spectrometry (GC-EI-QqQMS). This allows compound identification based on comparison between all the experimental MS/MS product ion spectra and the simulated library data of >1,000 MS/MS transitions of 71 compounds. The simulation data were generated by using the Competitive Fragmentation Modeling (CFM-ID) 3.0 program. The approach for calculation of the DIA MS/MS library match scores was then established and applied for identification of a range of terpenoids and oxygenated compounds in perfume. The identity of each peak was confirmed using 4-241 MS/MS transitions. The established data collection and analysis methods are expected to be useful for increased confidence in volatile compound analysis.


Artificial muscle: facts and fiction.
Mechanical devices are sought to support insufficient or paralysed striated muscles including the failing heart. Nickel-titanium alloys (nitinol) present the following two properties: (i) super-elasticity, and (ii) the potential to assume different crystal structures depending on temperature and/or stress. Starting from the martensite state nitinol is able to resume the austenite form (state of low potential energy and high entropy) even against an external resistance. This one-way shape change is deployed in self-expanding vascular stents. Heating induces the force generating transformation from martensite to the austenite state while cooling induces relaxation back to the martensite state. This two-way shape change oscillating between the two states may be used in cyclically contracting support devices of silicon-coated nitinol wires. Such a contractile device sutured to the right atrium has been tested in vitro in a bench model and in vivo in sheep. The contraction properties of natural muscles, specifically of the myocardium, and the tight correlation with ATP production by oxidative phosphorylation in the mitochondria is briefly outlined. Force development by the nitinol device cannot be smoothly regulated as in natural muscle. Its mechanical impact is forced onto the natural muscle regardless of the actual condition with regard to metabolism and Ca2+-homeostasis. The development of artificial muscle on the basis of nitinol wires is still in its infancy. The nitinol artificial muscle will have to prove its viability in the various clinical settings.


Development and validation of a TaqMan PCR assay for the Australian abalone herpes-like virus.
The recent emergence of a herpes-like virus in both farmed and wild populations of abalone in Victoria, Australia, has been associated with high mortality rates in animals of all ages. Based on viral genome sequence information, a virus-specific real-time TaqMan assay was developed for detection and identification of the abalone herpes-like virus (AbHV). The assay was shown to be specific as it did not detect other viruses from either the Herpesvirales or the Iridovirales orders which have genome sequence similarities. However, the TaqMan assay was able to detect DNA from the Taiwanese abalone herpes-like virus, suggesting a relationship between the Taiwanese and Australian viruses. In addition, the assay detected < 300 copies of recombinant plasmid DNA per reaction. Performance characteristics for the AbHV TaqMan assay were established using 1673 samples from different abalone populations in Victoria and Tasmania. The highest diagnostic sensitivity and specificity were 96.7 (95% CI: 82.7 to 99.4) and 99.7 (95% CI: 99.3 to 99.9), respectively, at a threshold cycle (C(T)) value of 35.8. The results from 2 separate laboratories indicated good repeatability and reproducibility. This molecular assay has already proven useful in confirming presumptive diagnosis (based on the presence of ganglioneuritis) of diseased abalone in Victorian waters as well as being a tool for surveillance of wild abalone stocks in other parts of Australia.


The prevalence and risk factors of school absenteeism due to premenstrual disorders in Japanese high school students-a school-based cross-sectional study.
Premenstrual disorders such as premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) interfere with the daily lives of adolescents. The causes of PMS and PMDD are unknown, but lifestyle habits, such as regular exercise and taste preference are known to be associated. This study was conducted to investigate how premenstrual symptoms affect the school life in Japanese high school students and whether there was a risk factor for school absenteeism that is dependent on the types of premenstrual symptoms or lifestyle habits. A school-based survey was conducted in Sendai, an industrial city in Japan. A total of 901 girls aged 15-19 with regular menstrual cycles were assessed using the self-reporting premenstrual symptoms questionnaire (PSQ) and questions regarding school absence, taste preference, and exercise. We classified the girls into 'no/mild PMS', 'moderate-to-severe PMS' and 'PMDD' according to the PSQ. The girls were classified into the 'absent' group if they were absent for more than 1 day per month. We used multivariate logistic analysis to examine the risk factors for school absenteeism. The rates of 'moderate-to-severe PMS' and 'PMDD' were 9.9 and 3.1 %, respectively. A total of 107 girls (11.9 %) were classified into the 'absent' group. Significant differences were observed in the prevalence of all premenstrual symptoms (p < 0.001), 'age' (p < 0.001), 'a preference for salty food' (p = 0.001), and 'lack of regular exercise' (p = 0.03) between the 'absent' and 'non-absent' groups. Multivariate analysis revealed that premenstrual symptoms such as 'insomnia or hypersomnia' (odds ratio [OR] 2.27, 95 % confidence interval [CI]: 1.46-4.17) and 'physical symptoms' (OR 2.24, 95 % CI: 1.37-3.66), 'reduced social life activities' (OR 2.71, 95 % CI 1.31-5.59), and 'a preference for salty food' (OR 1.89, 95 % CI: 1.20-2.98) were risk factors for school absenteeism. One in nine Japanese female high school students were absent from school due to premenstrual symptoms. Physical premenstrual symptoms and lifestyles, such as a preference for salty food and a lack of regular exercise, were identified as risk factors for school absenteeism.


Clinical Efficacy of Polyethylene Glycol Loxenatide in the Treatment of Obese or Overweight Patients with Type 2 Diabetes Mellitus.
To determine the clinical efficacy of Polyethylene Glycol Loxenatide in the treatment of obese or overweight Type 2 Diabetes mellitus (T2DM) patients. A randomised-controlled trial. Place and Duration of the Study: Department of Endocrinology, Baoding No. 1 Central Hospital, Hebei, China, from January 2020 to January 2022. One hundred overweight and obese patients who were diagnosed with T2DM were prospectively included. They were randomly divided into two groups, with 50 cases in each group. The control group was given oral metformin + subcutaneous insulin injection. The combined treatment group was also given Polyethylene Glycol Loxenatide in addition to the control treatment. The duration of treatment was 6 months for both groups. The clinical efficacy of the two group treatments was compared. The height, body mass, weight index (body mass index (BMI)), total cholesterol (TC), 2-h postprandial blood glucose (2hPBG), high-density lipoprotein cholesterol, fasting insulin (FINS), lipids (triglycerides (TG), low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance (HOMA-IR) levels, fasting blood glucose (FPG), and glycosylated haemoglobin (HbAlc) were evaluated before and 6 months after the treatment. In addition, any adverse reactions in the two groups were observed. The overall effective rate of clinical therapy was 92% (46/50) in the combined treatment group, which was higher than that of the control group (76%, 38/50, p = 0.029). The weight and BMI levels of the combined treatment group became considerably lower than those of the control group (weight p = 0.004; BMI p <0.001), and the levels of FPG, 2hPBG, FINS, HbAlc and HOMA-IR (all p = <0.001), and the TG and TC values decreased in both groups (TG p = 0.001; TC p = 0.016). PEG Loxenatide considerably affects obese and overweight T2DM patients. With no noticeable adverse reactions, this drug is highly recommended for application and clinical promotion. Polyethylene Glycol Loxenatide, Type 2 Diabetes mellitus, Obesity, Overweight, Clinical efficacy.


Polyethylene glycol (PEG) and other bioactive solutions with neurorrhaphy for rapid and dramatic repair of peripheral nerve lesions by PEG-fusion.
Nervous system injuries in mammals often involve transection or segmental loss of peripheral nerves. Such injuries result in functional (behavioral) deficits poorly restored by naturally occurring 1-2 mm/d axonal outgrowths aided by primary repair or reconstruction. "Neurorrhaphy" or nerve repair joins severed connective tissues, but not severed cytoplasmic/plasmalemmal extensions (axons) within the tissue. PEG-fusion consists of neurorrhaphy combined with a well-defined sequence of four pharmaceutical agents in solution, one containing polyethylene glycol (PEG), applied directly to closely apposed viable ends of severed axons. PEG-fusion of rat sciatic nerves: (1) restores axonal continuity across coaptation site(s) within minutes, (2) prevents Wallerian degeneration of many distal severed axons, (3) preserves neuromuscular junctions, (4) prevents target muscle atrophy, (5) produces rapid and improved recovery of voluntary behaviors compared with neurorrhaphy alone, and (6) PEG-fused allografts are not rejected, despite no tissue-matching nor immunosuppression. If PEG-fusion protocols are not correctly executed, the results are similar to that of neurorrhaphy alone: (1) axonal continuity across coaptation site(s) is not re-established, (2) Wallerian degeneration of all distal severed axons rapidly occurs, (3) neuromuscular junctions are non-functional, (4) target muscle atrophy begins within weeks, (5) recovery of voluntary behavior occurs, if ever, after months to levels well-below that observed in unoperated animals, and (6) allografts are either rejected or not well-accepted. PEG-fusion produces rapid and dramatic recovery of function following rat peripheral nerve injuries.


Influence of defect size and localization on the engagement of reverse Hill-Sachs lesions.
Reverse Hill-Sachs (RHS) lesions can cause recurrent posterior shoulder instability because of engagement with the posterior glenoid rim; however, the effect of defect size and localization have yet to be determined. Both size and localization are critical for the engagement of an RHS defect with the posterior glenoid rim. Controlled laboratory study. Ten RHS defects with predefined extent and localization were created through an anterolateral rotator cuff sparing approach in 10 fresh-frozen cadaveric shoulder specimens using a custom-made saw guide. Computed tomography scans of all specimens were completed, and standardized measurements were performed to determine the size (alpha angle) and localization (beta angle) of the defect as well as a combination of both parameters (gamma angle). Internal rotation motions were imposed on the shoulder joint in different arm positions and with varying amount of posterior translation by means of a robot-assisted shoulder simulator. The association between engagement of the defects and the defined parameters (alpha, beta, and gamma angles) was analyzed. In 0° of abduction, a cutoff value between engaging and nonengaging defects of 37.5° for the alpha angle (100% sensitivity; 75% specificity; area under the curve [AUC], 0.875; P = .055) and 36.5° for the beta angle (100% sensitivity; 25% specificity; AUC, 0.708; P = .286) was determined. The gamma angle showed the highest discriminatory power (AUC, 0.938; P = .025) with a cutoff value of 85.5° rendering 100% sensitivity and 75% specificity in the prediction of engagement. An increase in the applied posterior translation force decreased the degrees of internal rotation necessary before engagement occurred. No engagement occurred during internal rotation with the arm in 60° of abduction or 60° of flexion. The size and localization of RHS defects are both critical factors for engagement. The combination of both parameters in terms of the gamma angle measurement might be a helpful tool to identify defects prone to engagement. Not only the size but also the localization is decisive for engagement of RHS defects. The standardized measurement of the gamma angle combines both factors and might be a helpful tool to identify defects prone to engagement warranting surgical treatment.


The rise to dominance of genetic model organisms and the decline of curiosity-driven organismal research.
Curiosity-driven, basic biological research "…performed without thought of practical ends…" establishes fundamental conceptual frameworks for future technological and medical breakthroughs. Traditionally, curiosity-driven research in biological sciences has utilized experimental organisms chosen for their tractability and suitability for studying the question of interest. This approach leverages the diversity of life to uncover working solutions (adaptations) to problems encountered by living things, and evolutionary context as to the extent to which these solutions may be generalized to other species. Despite the well-documented success of this approach, funding portfolios of United States granting agencies are increasingly filled with studies on a few species for which cutting-edge molecular tools are available (genetic model organisms). While this narrow focus may be justified for biomedically-focused funding bodies such as the National Institutes of Health, it is critical that robust federal support for curiosity-driven research using diverse experimental organisms be maintained by agencies such as the National Science Foundation. Using the disciplines of neurobiology and behavioral research as an example, this study finds that NSF grant awards have declined in association with a decrease in the proportion of grants funded for experimental, rather than genetic model organism research. The decline in use of experimental organisms in the literature mirrors but predates the shift grant funding. Today's dominance of genetic model organisms was thus initiated by researchers themselves and/or by publication peer review and editorial preferences, and was further reinforced by pressure from granting agencies, academic employers, and the scientific community.


Immune Escape of Relapsed AML Cells after Allogeneic Transplantation.
As consolidation therapy for acute myeloid leukemia (AML), allogeneic hematopoietic stem-cell transplantation provides a benefit in part by means of an immune-mediated graft-versus-leukemia effect. We hypothesized that the immune-mediated selective pressure imposed by allogeneic transplantation may cause distinct patterns of tumor evolution in relapsed disease. We performed enhanced exome sequencing on paired samples obtained at initial presentation with AML and at relapse from 15 patients who had a relapse after hematopoietic stem-cell transplantation (with transplants from an HLA-matched sibling, HLA-matched unrelated donor, or HLA-mismatched unrelated donor) and from 20 patients who had a relapse after chemotherapy. We performed RNA sequencing and flow cytometry on a subgroup of these samples and on additional samples for validation. On exome sequencing, the spectrum of gained and lost mutations observed with relapse after transplantation was similar to the spectrum observed with relapse after chemotherapy. Specifically, relapse after transplantation was not associated with the acquisition of previously unknown AML-specific mutations or structural variations in immune-related genes. In contrast, RNA sequencing of samples obtained at relapse after transplantation revealed dysregulation of pathways involved in adaptive and innate immunity, including down-regulation of major histocompatibility complex (MHC) class II genes ( HLA-DPA1, HLA-DPB1, HLA-DQB1, and HLA-DRB1) to levels that were 3 to 12 times lower than the levels seen in paired samples obtained at presentation. Flow cytometry and immunohistochemical analysis confirmed decreased expression of MHC class II at relapse in 17 of 34 patients who had a relapse after transplantation. Evidence suggested that interferon-γ treatment could rapidly reverse this phenotype in AML blasts in vitro. AML relapse after transplantation was not associated with the acquisition of relapse-specific mutations in immune-related genes. However, it was associated with dysregulation of pathways that may influence immune function, including down-regulation of MHC class II genes, which are involved in antigen presentation. These epigenetic changes may be reversible with appropriate therapy. (Funded by the National Cancer Institute and others.).


A giant frog with South American affinities from the Late Cretaceous of Madagascar.
Madagascar has a diverse but mainly endemic frog fauna, the biogeographic history of which has generated intense debate, fueled by recent molecular phylogenetic analyses and the near absence of a fossil record. Here, we describe a recently discovered Late Cretaceous anuran that differs strikingly in size and morphology from extant Malagasy taxa and is unrelated either to them or to the predicted occupants of the Madagascar-Seychelles-India landmass when it separated from Africa 160 million years ago (Mya). Instead, the previously undescribed anuran is attributed to the Ceratophryinae, a clade previously considered endemic to South America. The discovery offers a rare glimpse of the anuran assemblage that occupied Madagascar before the Tertiary radiation of mantellids and microhylids that now dominate the anuran fauna. In addition, the presence of a ceratophryine provides support for a controversial paleobiogeographical model that posits physical and biotic links among Madagascar, the Indian subcontinent, and South America that persisted well into the Late Cretaceous. It also suggests that the initial radiation of hyloid anurans began earlier than proposed by some recent estimates.


The mapping of an antibody-binding region on the Mycobacterium tuberculosis 19 kilodalton antigen.
To localize the epitopes of four independently derived murine mAb IT-10, IT-12, IT-16, and IT-19 on the 19-kDa Ag protein of Mycobacterium tuberculosis, expression plasmids were constructed containing deletions of the gene encoding the 19-kDa protein. Reaction of the 4 mAb with Western blots of the truncated recombinant proteins revealed two epitope specificities in the recognition of the 19-kDa protein. IT-10 was found to be dependent only on the presence of amino acids surrounding the first cysteine residue, whereas IT-12, IT-16, and IT-19 all required the presence of both the first and third cysteine residues. These two cysteine residues are separated by 135 amino acids, and are considered to be brought together by tertiary folding of the protein to form an assembled epitope for IT-12, IT-16, and IT-19. These three mAb demonstrated differing sensitivities to the modification of reduced 19-kDa protein using iodoacetamide: a treatment that should have prevented the reformation of disulfide bonds within the protein. This result suggests that, although IT-12, IT-16, and IT-19 appear to be specific for the same epitope, there are probably fine-specificity differences in this recognition. IT-10 was not sensitive to the absence of disulfide bonds within the 19-kDa protein, suggesting that the epitope is not conformationally sensitive, and is likely to be linear in nature.


Are there critical periods for musical development?
A critical period can be defined as a developmental window during which specific experience has a greater effect than at other times. Musical behavior involves many skills, including the basic encoding of pitch and time information, understanding scale and harmonic structure, performance, interpretation, and composition. We review studies of genetics, behavior, and brain structure and function in conjunction with the experiences of auditory deprivation and musical enrichment, and conclude that there is more supporting evidence for critical periods for basic than for more complex aspects of musical pitch acquisition. Much remains unknown about the mechanisms of interaction between genetic and experiential factors that create critical periods, but it is clear that there are multiple pathways for achieving musical expertise.


Development and Validation of the Microbiology for Health Sciences Concept Inventory.
Identifying misconceptions in student learning is a valuable practice for evaluating student learning gains and directing educational interventions. By accurately identifying students' knowledge and misconceptions about microbiology concepts, instructors can design effective classroom practices centered on student understanding. Following the development of ASM's Curriculum Guidelines in 2012, we developed a concept inventory, the Microbiology for Health Sciences Concept Inventory (MHSCI), that measures learning gains and identifies student misconceptions in health sciences microbiology classrooms. The 23-question MHSCI was delivered to a wide variety of students at multiple institution types. Psychometric analysis identified that the MHSCI instrument is both discriminatory and reliable in measuring student learning gains. The MHSCI results correlated with course outcomes, showing the value of using the instrument alongside course level assessments to measure student learning. The MHSCI is a reliable and efficient way to measure student learning in microbiology and can be used both as a faculty development tool and an effective student assessment tool.


Relationship of large and small invertases in Saccharomyces: mutant selectively deficient in small invertase.
A mutant strain of Saccharomyces cerevisiae (D10-ER1) has been isolated after a two-step mutagenesis of strain 4059-358D (SUC 1) using ethyl methane sulfonate. Cells of this new strain produced a level of total invertase equaling that of 4059 but contained only trace amounts of the small, internal, aglycan form of the enzyme (less than 0.1% of total in D10-ER1 compared with 6% in 4059). When D10.ER1 was crossed with an invertase-hyperproducing strain dgr3 (SUC3), progeny were isolated (HZ400-5A and HZ400-2C) in which levels of total invertase had at least quadrupled. The percentage of small invertase, however, remained insignificant. Levels of small invertase in strain HZ400-5A were determined by affinity chromatography on conconavalin A-Sepharose, gel permeation chromatography, and isopycnic centrifugation in CsCl. The large invertase of the SUC1 yeasts described here was found to contain a form apparently greater in size than the large invertase of the SUC2 strain FH4C; this probably reflects a higher content of carbohydrate. The overall results of this study do not support a direct structural relationship between large and small invertases. The implications on invertase biosynthesis and structure are discussed.


Coordinated surface activities in Variovorax paradoxus EPS.
Variovorax paradoxus is an aerobic soil bacterium frequently associated with important biodegradative processes in nature. Our group has cultivated a mucoid strain of Variovorax paradoxus for study as a model of bacterial development and response to environmental conditions. Colonies of this organism vary widely in appearance depending on agar plate type. Surface motility was observed on minimal defined agar plates with 0.5% agarose, similar in nature to swarming motility identified in Pseudomonas aeruginosa PAO1. We examined this motility under several culture conditions, including inhibition of flagellar motility using Congo Red. We demonstrated that the presence of a wetting agent, mineral, and nutrient content of the media altered the swarming phenotype. We also demonstrated that the wetting agent reduces the surface tension of the agar. We were able to directly observe the presence of the wetting agent in the presence and absence of Congo Red, and found that incubation in a humidified chamber inhibited the production of wetting agent, and also slowed the progression of the swarming colony. We observed that swarming was related to both carbon and nitrogen sources, as well as mineral salts base. The phosphate concentration of the mineral base was critical for growth and swarming on glucose, but not succinate. Swarming on other carbon sources was generally only observed using M9 salts mineral base. Rapid swarming was observed on malic acid, d-sorbitol, casamino acids, and succinate. Swarming at a lower but still detectable rate was observed on glucose and sucrose, with weak swarming on maltose. Nitrogen source tests using succinate as carbon source demonstrated two distinct forms of swarming, with very different macroscopic swarm characteristics. Rapid swarming was observed when ammonium ion was provided as nitrogen source, as well as when histidine, tryptophan, or glycine was provided. Slower swarming was observed with methionine, arginine, or tyrosine. Large effects of mineral content on swarming were seen with tyrosine and methionine as nitrogen sources. Biofilms form readily under various culture circumstances, and show wide variance in structure under different conditions. The amount of biofilm as measured by crystal violet retention was dependent on carbon source, but not nitrogen source. Filamentous growth in the biofilm depends on shear stress, and is enhanced by continuous input of nutrients in chemostat culture. Our studies have established that the beta-proteobacterium Variovorax paradoxus displays a number of distinct physiologies when grown on surfaces, indicative of a complex response to several growth parameters. We have identified a number of factors that drive sessile and motile surface phenotypes. This work forms a basis for future studies using this genetically tractable soil bacterium to study the regulation of microbial development on surfaces.


The biochemistry of nitrogen mobilization: purine ring catabolism.
The enzymatic route of purine ring catabolism has recently been completed by the discovery of several novel enzymes identified through comparative genome analyses. Here, we review these recent discoveries and present an overview of purine ring catabolism in plants. Xanthine is oxidized to urate in the cytosol, followed by three enzymatic steps taking place in the peroxisome and four reactions in the endoplasmic reticulum releasing the four ring nitrogen as ammonia. Although the main physiological function of purine degradation might lie in the remobilization of nitrogen resources, it has also emerged that catabolic intermediates, the ureides allantoin and allantoate, are likely to be involved in protecting plants against abiotic stress. Conserved alternative splicing mediating the peroxisomal as well as cytosolic localization of allantoin synthase potentially links purine ring catabolism to brassinosteroid signaling.


Insanity, belonging and citizenship: mentally ill people who went to and/or returned from Europe in the Late Ottoman Era.
The Ottoman Empire, which encompassed a vast territory, had several facilities for the protection and treatment of the mentally ill. By the late nineteenth century, some wealthy families had begun to send their patients to mental hospitals in Europe for better treatment. During the same period, the process of repatriation of mental patients who were Ottoman subjects also began. These processes, which resulted in complex bureaucratic measures, later found a place in regulations and laws. The Ottoman Empire had an additional incentive to protect mentally-ill patients during the Second Constitutional Era, when discussions about 'citizenship' reappeared. This article examines the practices of sending mentally-ill people to Europe and the repatriation of mentally-ill Ottoman subjects from European countries.


A comparison of maprotiline (Ludiomil) and amitriptyline (1).
The study described here was designed to see if it was possible to show an earlier onset of action for maprotiline (Ludiomil) compared with amitriptyline while at the same time demonstrating equal long-term effectiveness and certainly no greater side-effects. A between-patient double-blind trial with 40 patients supported these aims and was statistically significant (p less than 0.001) with regard to early onset of antidepressant effect.


Demonstration of beta-2 adrenergic receptors of high coupling efficiency in human neutrophil sonicates.
Using highly purified (greater than 95%) neutrophil (PMN) sonicates, we have studied the beta adrenergic (beta 1/beta 2) pattern of adenylate cyclase activation following agonist stimulation and have assessed the coupling characteristics of the beta adrenergic receptor to the adenylate cyclase enzyme. Adenylate cyclase was highly responsive to agonist activation, with peak isoproterenol (100 microM) stimulation resulting in the generation of 119 +/- 9.5 (mean +/- S.E.M.) pmol/mg/min cyclic AMP (224% above basal levels) compared to 171.7 +/- 8.6 following NaF (10 mM) stimulation. The agonist pattern of adenylate cyclase activation suggested the presence of beta-2 adrenergic receptors, since isoproterenol with a Kact of 0.7 microM was more potent than epinephrine (Kact = 8.5 microM) or norepinephrine (Kact = 90 microM). Butoxamine (beta-2 antagonist) was approximately 25 times more potent than practolol (beta-1 antagonist), with KDs of 0.75 microM and 17.5 microM, respectively. Receptor coupling efficiency was determined by measuring isoproterenol binding and adenylate cyclase activation with the same PMN sonicates and incubation conditions for each assay. The apparent KD for isoproterenol binding was 2.82 +/- 0.53 muM, the Kact was 0.47 +/- 0.05 muM, and the mean KD/Kact ratio was 6.5. Highly coupled receptor-enzyme systems have ratios greater than or equal to 1. Using sucrose gradient-purified PMN sonicates, we found that isoproterenol required the guanine nucleotides GTP or Gpp(NH)p to activate adenylate cyclase. The GTP effect on adenylate cyclase responsivenss to isoproterenol was associated with a 10-fold decrease in the isoproterenol binding affinity. These studies suggest that the human PMN has beta-2 adrenergic receptors which are highly coupled to the adenylate cyclase enzyme. We believe that this tissue offers a suitable model for the study of beta-2 adrenergic receptors and the mechanism of hormone-induced adenylate cyclase activation in man.


Medina embolization device for the treatment of intracranial aneurysms: 18 months' angiographic results.
The Medina embolization device (MED) is a new flow disruption device combining the design of a detachable coil with an intrasaccular flow disrupter. Safety and short-term angiographic effectiveness of this device have recently been reported. However, long-term angiographic results are lacking. We report herein the 18 months' angiographic outcome in patients treated for a wide-neck intracranial aneurysm with the MED. Nineteen patients (17 female, mean age 50 years) with 20 wide-neck intracranial aneurysms (six ruptured; 14 unruptured) were treated by the MED between January 2015 and June 2016. Procedure-related complications were systematically recorded; discharge and 6-9 months' follow-up modified Rankin Scale scores were assessed. Angiographic mid-term and long-term follow-up were performed with a mean delay of 6.4±1.5 months (n=16 aneurysms) and 17.7±4.2 months (n=15 aneurysms), respectively. Occlusion rates were evaluated after the procedure and at the mid-term and long-term follow-up using the Roy-Raymond scale. Embolization with the MED was feasible in all except two cases (2/20, 10%). One per-procedural perforation was recorded (1/20, 5%) and one MED deployment failed because of the aneurysm's shape (1/20, 5%). Three cases of thromboembolic complications were observed (3/20, 15%). Only one thromboembolic complication was responsible for clinical sequelae. Grade A occlusion rate was 61% (11/18) after the procedure, 75% at 6 months' follow-up (12/16), and 80% (12/15) at long-term follow-up. Two cases (2/18, 11%) of recanalization at mid-term were documented angiographically. No recanalization occurred between the mid-term and long-term follow-up. MED is a hybrid embolization device, combining properties of a conventional coil with those of an intrasaccular flow disrupter. Our series focusing on long-term angiographic follow-up shows a satisfactory long-term occlusion rate. Larger series with longer angiographic follow-up times are warranted to confirm these preliminary results.


Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia.
Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARalpha, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and PanIN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early PanIN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.


Characterization of the major antigenic protein 2 of Ehrlichia canis and Ehrlichia chaffeensis and its application for serodiagnosis of ehrlichiosis.
Canine monocytic ehrlichiosis, caused by Ehrlichia canis or Ehrlichia chaffeensis, can result in clinical disease in naturally infected animals. Coinfections with these agents may be common in certain areas of endemicity. Currently, a species-specific method for serological diagnosis of monocytic ehrlichiosis is not available. Previously, we developed two indirect enzyme-linked immunosorbent assays (ELISAs) using the major antigenic protein 2 (MAP2) of E. chaffeensis and E. canis. In this study, we further characterized the conservation of MAP2 among various geographic isolates of each organism and determined if the recombinant MAP2 (rMAP2) of E. chaffeensis would cross-react with E. canis-infected dog sera. Genomic Southern blot analysis using digoxigenin-labeled species-specific probes suggested that map2 is a single-copy gene in both Ehrlichia species. Sequences of the single map2 genes of seven geographically different isolates of E. chaffeensis and five isolates of E. canis are highly conserved among the various isolates of each respective ehrlichial species. ELISA and Western blot analysis confirmed that the E. chaffeensis rMAP2 failed to serologically differentiate between E. canis and E. chaffeensis infections.


Estimating uncomfortable loudness levels using evoked potentials to auditory stimuli for hearing aid fitting.
Determining the loudest sound level that a person can comfortably tolerate (uncomfortable loudness level: UCL) imposes a strain on people suffering from hearing loss. In the present study, we propose a method of estimating UCL based on auditory evoked potentials (AEPs). Adults with normal hearing (18 men aged 25-56 years) participated in the study. Three tone bursts (S1, S2 and S3; a triplet) of the same frequency (either 1k, 2k or 4k Hz) were presented to the right or left ear with an interstimulus interval of 300 ms. The sound intensity decreased gradually by 5 dB HL from 80 dB (S1) to 70 dB HL (S3). The interval between triplets was 450 ± 50 ms. The frequency of a given triplet differed from the frequency of the preceding triplet. An electroencephalogram was recorded from three scalp electrode sites (Cz, C3, and C4) with the right mastoid reference. The 900-ms period after the onset of the triplet was transformed to a wavelet coefficient and averaged separately by stimulated ear and tone frequency. The UCLs were estimated by linear discriminant analysis on the basis of trained data of the other participants' subjective UCLs and the wavelet coefficients. The mean estimation error was 4.9 ± 5.0 dB. This result suggests that the UCLs could be estimated successfully on the basis of AEPs to triplets of auditory tones.


Computational simulation of trabecular adaptation progress in human proximal femur during growth.
There are a large number of clinical and experimental studies that analyzed trabecular architecture as a result of bone adaptation. However, only a limited amount of quantitative data is currently available on the progress of trabecular adaptation during growth. In this paper, we proposed a two-step numerical simulation method that predicts trabecular adaptation progress during growth using a recently developed topology optimization algorithm, design space optimization (DSO), under the hypothesis that the mechanisms of DSO are functionally equivalent to those of bone adaptation. We applied the proposed scheme to trabecular adaptation simulation in human proximal femur. For the simulation, the full trabecular architecture in human proximal femur was represented by a two-dimensional microFE model with 50 microm resolution. In Step 1, we determined a reference value that regulates trabecular adaptation in human proximal femur. In Step 2, we simulated trabecular adaptation in human proximal femur during growth with the reference value derived in Step 1. We analyzed the architectural and mechanical properties of trabecular patterns through iterations. From the comparison with experimental data in the literature, we showed that in the early growth stage trabecular adaptation was achieved mainly by increasing bone volume fraction (or trabecular thickness), while in the later stage of the development the trabecular architecture gained higher structural efficiency by increasing structural anisotropy with a relatively low level of bone volume fraction (or trabecular thickness). We demonstrated that the proposed numerical framework predicted the growing progress of trabecular bone that has a close correlation with experimental data.


Rapid variability of seawater chemistry over the past 130 million years.
Fluid inclusion data suggest that the composition of major elements in seawater changes slowly over geological time scales. This view contrasts with high-resolution isotope data that imply more rapid fluctuations of seawater chemistry. We used a non-steady-state box model of the global sulfur cycle to show that the global δ(34)S record can be explained by variable marine sulfate concentrations triggered by basin-scale evaporite precipitation and dissolution. The record is characterized by long phases of stasis, punctuated by short intervals of rapid change. Sulfate concentrations affect several important biological processes, including carbonate mineralogy, microbially mediated organic matter remineralization, sedimentary phosphorous regeneration, nitrogen fixation, and sulfate aerosol formation. These changes are likely to affect ocean productivity, the global carbon cycle, and climate.


Evaluating outcomes of computer-based classroom testing: Student acceptance and impact on learning and exam performance.
Computer-based testing (CBT) has made progress in health sciences education. In 2015, the authors led implementation of a CBT system (ExamSoft) at a dental school in the U.S. Guided by the Technology Acceptance Model (TAM), the purposes of this study were to (a) examine dental students' acceptance of ExamSoft; (b) understand factors impacting acceptance; and (c) evaluate the impact of ExamSoft on students' learning and exam performance. Survey and focus group data revealed that ExamSoft was well accepted by students as a testing tool and acknowledged by most for its potential to support learning. Regression analyses showed that perceived ease of use and perceived usefulness of ExamSoft significantly predicted student acceptance. Prior CBT experience and computer skills did not significantly predict acceptance of ExamSoft. Students reported that ExamSoft promoted learning in the first program year, primarily through timely and rich feedback on examination performance. t-Tests yielded mixed results on whether students performed better on computerized or paper examinations. The study contributes to the literature on CBT and the application of the TAM model in health sciences education. Findings also suggest ways in which health sciences institutions can implement CBT to maximize its potential as an assessment and learning tool.


The cervix cancer research network: increasing access to cancer clinical trials in low- and middle-income countries.
The burden of cervical cancer is large and growing in developing countries, due in large part to limited access to screening services and lack of human papillomavirus (HPV) vaccination. In spite of modern advances in diagnostic and therapeutic modalities, outcomes from cervical cancer have not markedly improved in recent years. Novel clinical trials are urgently needed to improve outcomes from cervical cancer worldwide. The Cervix Cancer Research Network (CCRN), a subsidiary of the Gynecologic Cancer InterGroup, is a multi-national, multi-institutional consortium of physicians and scientists focused on improving cervical cancer outcomes worldwide by making cancer clinical trials available in low-, middle-, and high-income countries. Standard operating procedures for participation in CCRN include a pre-qualifying questionnaire to evaluate clinical activities and research infrastructure, followed by a site visit. Once a site is approved, they may choose to participate in one of four currently accruing clinical trials. To date, 13 different CCRN site visits have been performed. Of these 13 sites visited, 10 have been approved as CCRN sites including Tata Memorial Hospital, India; Bangalore, India; Trivandrum, India; Ramathibodi, Thailand; Siriaj, Thailand; Pramongkutklao, Thailand; Ho Chi Minh, Vietnam; Blokhin Russian Cancer Research Center; the Hertzen Moscow Cancer Research Institute; and the Russian Scientific Center of Roentgenoradiology. The four currently accruing clinical trials are TACO, OUTBACK, INTERLACE, and SHAPE. The CCRN has successfully enrolled eight sites in developing countries to participate in four randomized clinical trials. The primary objectives are to provide novel therapeutics to regions with the greatest need and to improve the validity and generalizability of clinical trial results by enrolling a diverse sample of patients.


Pyrrolidino-4-iodotamoxifen and 4-iodotamoxifen, new analogues of the antiestrogen tamoxifen for the treatment of breast cancer.
New tamoxifen analogues were tested for their antiproliferative activity both in vitro and in vivo. Binding studies showed that both 4-iodotamoxifen and pyrrolidino-4-iodotamoxifen and 2.5-fold higher affinities for the estrogen receptor compared with tamoxifen. Pyrrolidino-4-iodotamoxifen was also 1.5-fold more effective in causing inhibition of estrogen-induced growth of MCF-7 cells compared with tamoxifen at 10(-6) M. The 4-iodotamoxifen analogue was similar to tamoxifen in its inhibitory action at 10(-6) M. Antiproliferative activities of these drugs were tested using the nitrosomethylurea-induced rat mammary tumor model. Pyrrolidino-4-iodotamoxifen caused regression in 92% of rats, whereas tamoxifen caused regression in 75% of rats. The agonist activity of the analogues was determined using the immature rat and mouse uterotrophic assays. Both tamoxifen and 4-iodotamoxifen had similar partial agonist activity, and this was greater than that seen with pyrrolidino-4-iodotamoxifen. Furthermore, pyrrolidino-4-iodotamoxifen caused a dose-dependent inhibition of estrogen-induced vaginal cornification, whereas tamoxifen and 4-iodotamoxifen did not. These studies demonstrate that pyrrolidino-4-iodotamoxifen is more effective than tamoxifen in inhibiting tumor regression and that its reduced uterotrophic activity and increased estrogen receptor binding may give it significant clinical advantages over the parent compound.


Cholesterol-crystalized coronary atheroma as a potential precursor lesion causing acute coronary syndrome: a case report.
Histopathological studies have reported the presence of cholesterol crystals in the culprit lesion in patients with sudden cardiac death. Given that cholesterol crystals themselves promote pro-inflammatory cascades, they may destabilize atherosclerotic plaques, leading to the occurrence of acute coronary events. A 60-year-old man presented with ST-segment elevation myocardial infarction. Emergent coronary angiography revealed a severely stenotic lesion (=culprit lesion) and another non-obstructive lesion in the proximal and middle segments of the left anterior descending artery (LAD), respectively. Optical coherence tomography (OCT) imaging showed that both lesions exhibited lipid-rich plaque with cholesterol crystals, and the non-obstructive lesion in the mid-LAD did not have a thin fibrous cap (its thickness = 230 μm). A drug-eluting stent was successfully implanted at the culprit lesion in the proximal LAD. On non-contrast T1-weighted magnetic resonance imaging performed 10 days after percutaneous coronary intervention (PCI), a high-intensity signal was identified at the non-obstructive mid-LAD lesion. This lesion was medically managed with aspirin, clopidogrel, and rosuvastatin due to the absence of myocardial ischaemia. However, 12 months after PCI, the patient was hospitalized again due to unstable angina pectoris. Coronary angiography revealed substantial progression of the mid-LAD lesion. Optical coherence tomography imaging prior to the second PCI showed a severely narrowed lesion containing cholesterol crystals and covered by organized thrombus. This lesion harbored an extensive amount of lipidic materials on near-infrared spectroscopy (maximum 4-mm lipid core burden index = 809). In our case, atherosclerotic plaques containing cholesterol crystals was associated with the occurrence of acute coronary syndrome. Our findings suggest that plaque with cholesterol crystals is a potential precursor to future acute coronary events.


Socialization Alleviates Burden of Oxidative-Stress in Hippocampus and Prefrontal Cortex in Morphine Addiction Period in Male Rats.
Addiction is a compulsive drug-seeking and drug-taking behavior. Reduction of high-risk behaviors can reduce the burden of addiction in society and can improve the overall prognosis of drug addiction. The aim of this study is to show that reduction of oxidative stress with socialization will reduce occurrence of high-risk behavior during addiction period. Fifty-four male Sprague-Dawley rats were randomly divided into four groups: socialized, isolated, addicted socialized and addicted isolated. For inducing morphine dependence, rats received morphine (5 mg/rat/kg/day) for 14 days. Socialization was induced by putting two rats in a large cage for 14 days. On the other hand, isolation was induced by putting rats in separate small cages covered with black plastic for the same period. At the end of the study, rats were experimented with shuttle box for assessing avoidance memory and also tested with social interaction test to measure noveltyseeking behavior and anxiety level. Then, animals were sacrificed for neurochemical analysis. Brain was isolated to assess oxidative-stress (OS) indices such as malondialdehyde (MDA), glutathione and nitrite/nitrate in prefrontal cortex and hippocampus. After 14 days of morphine injection, rats in socialized group had improved avoidance memory, increased anxiety levels and reduced novelty-seeking behavior. Furthermore, isolated rats had reduced glutathione and nitrite/nitrate, and higher MDA levels in prefrontal cortex and hippocampus as compared to socialized rats. Pair state had positive effect on OS indices in prefrontal cortex and hippocampus and results in the reduction of relapse and poor prognosis. Thus, OS plays an important role in alleviation of severity of addiction period.


[Development of rapid methods for quantitative analysis of proteolytic reactions].
The approaches for development of express methods for quantitative control of proteolytic reactions are discussed. Recently, these reactions have taken on special significance for revealing many important problems of theoretical and practical medicine and biology as well as for technological, pharmacological and ecological monitoring. Traditional methods can be improved both by use of immobilized enzymes and substrates, and on the basis of combination of various classic biochemical and immunological approaches. The synthesis of substrates with specified properties allows new methods to be realized for the study of the proteinase activity and kinetic characteristics of the corresponding reactions both in vitro and in vivo. An application of biosensor technology is promising trend since it allows the analysis time and cost to be saved, the direct interaction between enzymes and their inhibitors and activators to be studied in a real time scale, the quantitative measurements to be performed both in liquids and in the air. Besides, biosensor technique is well compatible with computer data processing.


Molecular characterization of a novel Na⁺/H⁺ antiporter cDNA from Eucalyptus globulus.
Environmental stress factors such as salt, drought and heat are known to affect plant productivity. However, high salinity is spreading throughout the world, currently affecting more than 45 millionha. One of the mechanisms that allow plants to withstand salt stress consists on vacuolar sequestration of Na(+), through a Na(+)/H(+) antiporter. We isolated a new vacuolar Na(+)/H(+) antiporter from Eucalyptus globulus from a cDNA library. The cDNA had a 1626 bp open reading frame encoding a predicted protein of 542 amino acids with a deduced molecular weight of 59.1 KDa. Phylogenetic and bioinformatic analyses indicated that EgNHX1 localized in the vacuole. To assess its role in Na(+) exchange, we performed complementation studies using the Na(+) sensitive yeast mutant strain Δnhx1. The results showed that EgNHX1 partially restored the salt sensitive phenotype of the yeast Δnhx1 strain. However, its overexpression in transgenic Arabidopsis confers tolerance in the presence of increasing NaCl concentrations while the wild type plants exhibited growth retardation. Expression profiles of Eucalyptus seedlings subjected to salt, drought, heat and ABA treatment were established. The results revealed that Egnhx1 was induced significantly only by drought. Together, these results suggest that the product of Egnhx1 from E. globulus is a functional vacuolar Na(+)/H(+) antiporter.


Optical nanofiber as an efficient tool for manipulating and probing atomic Fluorescence.
We experimentally demonstrate efficient coupling of atomic fluorescence to the guided mode of a subwavelength-diameter silica fiber, an optical nanofiber. We show that fluorescence of a very small number of atoms, around the nanofiber can be readily observed through a single-mode optical fiber. We also show that such a technique enables us to probe the van der Waals interaction between atoms and surface with high precision by observing the fluorescence excitation spectrum through the nanofiber.


ARE PULP SENSIBILITY TESTS STILL SENSIBLE?
Electric and thermal tests are the most commonly employed methods for the diagnosis of pulp health status. The objectives of our study are to assess the validity, yield and accuracy of cold and electric pulp tests in determining the vitality of teeth requiring endodontic treatment. A cross sectional study was carried out at the Dental Clinic of Aga Khan University Hospital on 75 patients requiring endodontic treatment. Before commencement of endodontic treatment, a provisional diagnosis of pulp status was made using an electric pulp tester and cold test. The tooth was then labelled as either vital or necrotic. Then an access openings was made and tooth's actual pulp status (vital/necrotic) was determined by observing bleeding in the pulp chamber. The validity, yield and accuracy were calculated on the basis of these findings. The sensitivity, specificity, positive predictive value and negative predictive value of cold test were 84%, 88%, 93% and 73% respectively. The sensitivity & specificity of electric test were 82% and 88% respectively whereas the positive predictive value negative predictive value of electric test were 93% and 71% respectively. The accuracy of cold and electric pulp test was 85% and 84% respectively. Both cold test and EPT have similar sensitivity, specificity and accuracy values. Although vitality tests have a promising future in the diagnosis of pulp health status but within limitation of this study we found that sensibility tests have satisfactory validity and accuracy values to be used routinely prior to endodontic and restorative treatments especially when used in conjunction with one each other.


Prevention and Management of Severe Hypoglycemia and Hypoglycemia Unawareness: Incorporating Sensor Technology.
In addition to assisting in achieving improved glucose control, continuous glucose monitoring (CGM) sensor technology may also aid in detection and prevention of hypoglycemia. In this paper, we report on the current scientific evidence on the effectiveness of this technology in the prevention of severe hypoglycemia and hypoglycemia unawareness. Recent studies have found that the integration of CGM with continuous subcutaneous insulin infusion (CSII) therapy, a system known as sensor-augmented pump (SAP) therapy, very significantly reduces the occurrence of these conditions by providing real-time glucose readings/trends and automatically suspending insulin infusion when glucose is low (LGS) or, even, before glucose is low but is predicted to soon be low (PLGS). Initial data indicate that even for patients with type 1 diabetes treated with multiple daily injections, real-time CGM alone has been found to reduce both severe hypoglycemia and hypoglycemia unawareness. Closed loop systems (artificial pancreas) comprised of CGM and CSII without patient intervention to adjust basal insulin, which automatically reduce, increase, and suspend insulin delivery, represent a potential new option that is moving toward becoming a reality in the near future. Sensor technology promises to continue to improve patients' lives not only by attaining glycemic control but also by reducing hypoglycemia, a goal best achieved in conjunction with structured individualized patient education.


[Increasing prevalence of G6PD deficiency in the Netherlands].
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzyme deficiency with a high prevalence in Sub-Saharan countries and countries in the Middle East. Due to increased migration in the past decennium, the prevalence of this disorder has increased in the Netherlands. Here we present three patients with acute haemolysis due to G6PD deficiency: a male neonate with severe hyperbilirubinaemia leading to kernicterus; a 3-year-old girl with a severe acute haemolysis due to an infection; and a 5-year-old boy with acute haemolysis with no clear cause. These cases serve to trigger the awareness of all caregivers of the increased prevalence of this disorder, and of the limited health literacy of many immigrants.


Cerebro-oculo-facio-skeletal syndrome.
Cerebro-oculo-facio-skeletal (COFS) syndrome is an autosomal recessive inherited disorder characterized by congenital microcephaly, congenital cataracts and/or microphthalmia, arthrogryposis, severe developmental delay, severe postnatal growth failure and facial dysmorphism with prominent nasal root and/or overhanging upper lip. This syndrome is now recognized as a disorder belonging to the spectrum of inherited defects in Nucleotide Excision Repair (NER) resulting in profound photosensitivity. In COFS syndrome, as in Cockayne syndrome, DNA repair is impaired in the transcription-coupled NER pathway, but not in the global genome NER pathway. Fourteen cases so far described as COFS syndrome have been studied at the molecular levels. All mutations have been found in Cockayne syndrome gene, CSB, xeroderma pigmentosum genes, XPD and XPG and ERCC1 gene involved in the transcription-coupled NER pathway.


[Kawasaki disease. A report of 50 cases].
We present 50 cases of Kawasaki's disease (KD), diagnosed and controlled in our hospital between January 1984 and December 1997. Fifty patients were reviewed. In forty-six of these cases the onset was complete, according to the Research Committee of MLNS diagnosis criteria and four cases had incomplete onset. The ration male/female was 1.9/1. Both fever and oral cavity lesions were present in all cases. In 93.4% desquamation of fingers was observed. The most frequent skin lesion was maculopapular rash. Fourteen patients had atypical onset: adenophlegmon, aseptic meningitis, symptomatic hepatitis, parotiditis, queratopathia punctata and arthritis. Blood analysis showed alterations of high ESR (88% of cases), C-reactive protein (62%), leukocytosis (82%) and thrombocytosis (96%). Fifteen patients were treated with gamma globulin (IGIV), five received a single 2 g/Kg dose and ten received 400 mg/Kg per day during four days. Eight percent of our cases produced cardiovascular complications, none that included coronary aneurysms. After IGIV treatment we observed a shortening of the febrile period and amelioration of clinical symptoms. No deaths were reported.


I Still Haven't Found What I'm Looking For... Bono, Google and Glaucoma Awareness.
The effect of celebrity diagnosis on public awareness of health conditions has already been well documented. In October 2014, Bono, the lead singer with U2, revealed publicly for the first time that he has glaucoma. This study aimed to analyze the impact of Bono's announcement on public awareness of glaucoma using Google Search trends as an indicator of public interest in the disease. Google Trends was used to examine Google Search activity for the term 'Glaucoma' between 2009 and 2015 in both Ireland and the United Kingdom. Trend analyses were performed using Microsoft Excel Version 14.3.5. Increased Google Search activity for 'Glaucoma' in October 2014 was found in both Ireland and the United Kingdom. A five-fold increase from the mean Google Search activity for this term was found in Ireland and a two-fold increase from the mean Google Search activity for this term was found in the United Kingdom. No such increase in Google Search activity occurred during each country's 2014 Glaucoma Awareness week. Google Trends is useful in medical research as a means of assessing public awareness of, and/or interest in, health related topics. Current approaches to glaucoma related health promotion in both Ireland and the United Kingdom have failed to yield an increase in on-line Google Search activity. While there was an increase in interest in glaucoma it is unclear whether this led to an increase in health seeking behaviour.