Genetic polymorphism of IgG in mink. I. Identification of 8 allotypes.
By means of intraspecific immunization of domestic mink (Mustela vison Schr.), 8, in all probability, complex IgG allotypes were detected in their sera. Based on the results of analysis of the preparations of the IgG heavy (H) and light (L) chains, as well as proteolytic IgG fragments, we assigned the allotypes detected to three groups: (1) marker of the L chain, L1; (2) allotypes of the C region of gamma-chains (H2, H3, H4, H6, and H8) and conformational allotype H7; (3) conformational allotype 5 with unknown location on the chains.


Spatio-Temporal Distribution of Bark and Ambrosia Beetles in a Brazilian Tropical Dry Forest.
Bark and the ambrosia beetles dig into host plants and live most of their lives in concealed tunnels. We assessed beetle community dynamics in tropical dry forest sites in early, intermediate, and late successional stages, evaluating the influence of resource availability and seasonal variations in guild structure. We collected a total of 763 beetles from 23 species, including 14 bark beetle species, and 9 ambrosia beetle species. Local richness of bark and ambrosia beetles was estimated at 31 species. Bark and ambrosia composition was similar over the successional stages gradient, and beta diversity among sites was primarily determined by species turnover, mainly in the bark beetle community. Bark beetle richness and abundance were higher at intermediate stages; availability of wood was the main spatial mechanism. Climate factors were effectively non-seasonal. Ambrosia beetles were not influenced by successional stages, however the increase in wood resulted in increased abundance. We found higher richness at the end of the dry and wet seasons, and abundance increased with air moisture and decreased with higher temperatures and greater rainfall. In summary, bark beetle species accumulation was higher at sites with better wood production, while the needs of fungi (host and air moisture), resulted in a favorable conditions for species accumulation of ambrosia. The overall biological pattern among guilds differed from tropical rain forests, showing patterns similar to dry forest areas.


Urine and serum biomonitoring of exposure to environmental estrogens II: Soy isoflavones and zearalenone in pregnant women.
Urine and serum biomonitoring was used to measure internal exposure to selected dietary estrogens in a cohort of 30 pregnant women. Exposure was measured over a period comprising one-half day in the field (6 h) and one day in a clinic (24 h). Biomonitoring of the dietary phytoestrogens genistein (GEN), daidzein (DDZ) and equol (EQ), as well as the mycoestrogen, zearalenone (ZEN) and its congeners, was conducted using UPLC-MS/MS. Biomonitoring revealed evidence of internal exposure to naturally occurring dietary estrogens during pregnancy. Urinary concentrations of total GEN, DDZ and EQ were similar to levels reported for general adult U.S. Measurable concentrations of total (parent and metabolites) GEN, DDZ and EQ were present in 240, 207 and 2 of 270 serum samples, respectively. Six out of 30 subjects had measurable concentrations of unconjugated GEN and/or DDZ in serum between 0.6 and 7.1 nM. Urine to serum total isoflavone ratios for GEN, DDZ and EQ were 13, 47, and 180, respectively. ZEN and its reductive metabolite, α-zearalenol (α-ZEL), were present in pregnant women (11 out of 30 subjects) as conjugates at levels near the limit of quantification. The average total urinary concentration was 0.10 μg/L for ZEN and 0.11 μg/L for α-ZEL.


Expression and clinical significance of mTOR in surgically resected non-small cell lung cancer tissues: a case control study.
Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.


Modelling of processes governing subcellular localisation of MinD in Escherichia coli.
Recent research has highlighted several examples wherein bacterial cell fate is determined by precise subcellular localisation of proteins. A prominent example is the polar localisation and oscillation of the Min proteins which is necessary for accurate cell division in Escherichia coli. Several computational models have been proposed which reproduce the oscillatory behaviour and observed phenotypes. However, these models use varying assumptions to do so leading to different mechanisms for precise polar localisation of MinD zones. To gain further insight, the authors extend a simplified model which focused on some key processes to explain the observed length scale for MinD zone formation. Using analytical approaches and numerical simulations, the authors explore cellular MinD distributions produced by these processes and propose a mechanism for precise polar localisation of MinD.


Questions Care Providers Should Ask When They Have Ethical Discretion.
AbstractSince some care providers give colleagues' interests priority over patients' and families', they are at risk of imposing their bias on patients without knowing this. In this piece I discuss how the risk increases when care providers have greater discretion and how they can best avoid this risk. I discuss identifying these situations, assessing them, and then, based on what they have concluded, intervening and use their having inadequate resources, their seeing what patients want as futile, and their making decisions regarding surrogate decision makers as paradigmatic examples. As "remedies," I suggest that care providers share with patients their rationales, validate adaptive aspects of difficult behaviors, self-disclose, and sometimes even go beyond their usual clinical practices.


Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia.
B-cell acute lymphoblastic leukemia is the most common type of pediatric leukemia. Despite improved remission rates, current treatment regimens for pediatric B-cell acute lymphoblastic leukemia are often associated with adverse effects and central nervous system relapse, necessitating more effective and safer agents. Bafilomycin A1 is an inhibitor of vacuolar H(+)-ATPase that is frequently used at high concentration to block late-phase autophagy. Here, we show that bafilomycin A1 at a low concentration (1 nM) effectively and specifically inhibited and killed pediatric B-cell acute lymphoblastic leukemia cells. It targeted both early and late stages of the autophagy pathway by activating mammalian target of rapamycin signaling and by disassociating the Beclin 1-Vps34 complex, as well as by inhibiting the formation of autolysosomes, all of which attenuated functional autophagy. Bafilomycin A1 also targeted mitochondria and induced caspase-independent apoptosis by inducing the translocation of apoptosis-inducing factor from mitochondria to the nucleus. Moreover, bafilomycin A1 induced the binding of Beclin 1 to Bcl-2, which further inhibited autophagy and promoted apoptotic cell death. In primary cells from pediatric patients with B-cell acute lymphoblastic leukemia and a xenograft model, bafilomycin A1 specifically targeted leukemia cells while sparing normal cells. An in vivo mouse toxicity assay confirmed that bafilomycin A1 is safe. Our data thus suggest that bafilomycin A1 is a promising candidate drug for the treatment of pediatric B-cell acute lymphoblastic leukemia.


The D2 dopamine receptor (DRD2) gene and family stress; interactive effects on cognitive functions in children.
TaqI A D2 dopamine receptor (DRD2) alleles, family stress, and cognitive markers, including visuospatial ability (Benton's Line Orientation) and event-related potentials (P300 amplitude and latency), were obtained in preadolescent boys of alcoholic and nonalcoholic fathers. In the presence of the DRD2 minor allele (A1+), the Family Stress score negatively correlated with the Line Orientation score and P300 amplitude. No significant correlations were found in boys lacking this allele (A1-). The interaction of the A1+ allele and the Family Stress score produced significant regression coefficients for both Line Orientation score (p = .002) and P300 amplitude (p = .04). Together, these two cognitive markers account for 37% of the variance in the Family Stress score of 47 A1 allele boys (p = .0002) but less than 1% in 71 A1- allele boys (p > .9). This provides the first evidence of a specific gene-environment interaction involving human cognitive functioning.


Antibacterial activity of cinoxacin in vitro.
Cinoxacin is a new synthetic compound similar chemically and in antimicrobial activity to oxolonic acid and nalidixic acid. It is most effective against Escherichia coli and Proteus mirabilis, but at concentrations expected in the urine it is inhibitory for all species of Enterobacteriaceae. Relative to nalidixic acid, cinoxacin has slightly greater inhibitory and bactericidal activity, less inoculum effect probably due to less heterogeneity in the susceptibility of bacterial cells, and less inhibition by high concentrations of serum protein. Both drugs are more active in an acid than an alkaline medium. Glucose can specifically antagonize the inhibitory effect against P. mirabilis. In urine the bactericidal rate and effect are decreased. Resistance to cinoxacin can be developed quickly by serial transfers in vitro. Some nonresistant organisms remained viable in bactericidal drug concentrations. The in vivo importance of the favorable features of cinoxacin must be determined by clinical trials.


Monte Carlo dosimetric study of the BEBIG Co-60 HDR source.
Although not as widespread as Ir-192, Co-60 is also available on afterloading equipment devoted to high dose rate brachytherapy, mainly addressed to the treatment of gynaecological lesions. The purpose of this study is to obtain the dosimetric parameters of the Co-60 source used by the BEBIG MultiSource remote afterloader (BEBIG GmbH, Germany) for which there are no dosimetric data available in the literature. The Monte Carlo code GEANT4 has been used to obtain the TG43 parameters and the 2D dose rate table in Cartesian coordinates of the BEBIG Co-60 HDR source. The dose rate constant, radial dose function and anisotropy function have been calculated and are presented in a tabular form as well as a detailed 2D dose rate table in Cartesian coordinates. These dosimetric datasets can be used as input data and to validate the treatment planning system calculations.


[Role of mitochondrial calcium uniporter in myocardial hypoxia/reoxygenation induced injury].
To investigate the role and mechanism of mitochondrial calcium uniporter (MCU) in myocardial hypoxia/reoxygenation injury. Isolated rat hearts were perfused with Langendorff apparatus. The hypoxia/reoxygenation injury was achieved by ligation of left anterior coronary artery for 30 min followed by release of ligation for 120 min. The left ventricular developed pressure (LVDP), the maximum rise/fall rate of left ventricular pressure (+/- dP/dt(max)), and the left ventricular end-diastolic pressure (LVEDP) were recorded. Activities of lactate dehydrogenase (LDH) in coronary effluent and reactive oxygen species (ROS) of myocardial mitochondria were spectrophotometrically assayed. Infarct size was determined by TTC staining method. Compared with the hypoxia/reoxygenation (H/R) group, ruthenium red (RR, 5 micromol/L), given at the on set of reoxygenation, significantly improved the contractile function of left ventricle, decreased the myocardial infarct size, alleviated the production of ROS in myocardial mitochondria and LDH release in coronary effluent. Spermine (20 micromol/L), given at the onset of reoxygenation, enhanced the production of ROS in the mitochondria and LDH release in coronary effluent at 5, 20 and 30 min of reoxygenation, however, there were no significant differences of ventricular contractile parameters and infarct size between groups subjected to hypoxia/reoxygenation with or without spermine treatment. Co-treatment of ROS scavenger N-2-mercaptopropionyl glycine (1 mmol/L) with spermine abolished the effect of spermine. Inhibition of mitochondrial calcium uniporter may refrain heart from hypoxia/reoxygenation injury via decreasing the production of ROS in heart mitochondria.


Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.
Hypoxia-inducible factor-1alpha (HIF-1alpha) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1alpha, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1alpha and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension. Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry. mPAP values were significantly higher than the control values after 7days of hypoxia [(18.4 +/- 0.4) mmHg, P < 0.05]. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1alpha protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1alpha protein was markedly increased by day 3 (0.20 +/- 0.02, P < 0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1alpha mRNA increased significantly after day 14 of hypoxia (0.20 +/- 0.02, P < 0.05). VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15 +/- 0.02, P < 0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1alpha mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1alpha mRNA was positively correlated with VEGF mRNA and protein (P < 0.01). HIF-1alpha and VEGF are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats.


[The impact of water level changes on the Oncomelania snail habitats in Poyang Lake regions before and after the impoundment of Three Gorges reservoir].
To explore the impact of the impoundment of Three Gorges reservoir on Oncomelania snail habitats of Poyang Lake. Four counties with schistosomiasis endemic around the Poyang Lake, naming as Xingzi, Duchang, Jinxian and Xinjian, were selected as study areas. The average daily water level of four major hydrological stations near the above 4 counties from 1997 to 2008 were collected, as well as the elevation of 215 marshlands with snails in those 4 counties, the data of schistosomiasis endemic situation and snail survey of 4 counties in the year before the impoundment of Three Gorges reservoir (2002) and the 6th year after the impoundment of Three Gorges reservoir (2008). The fluctuations of water levels of Poyang Lake, flooding day of marshland with snails as well as the changes of the indicators in snail survey and prevention and control measures before and after the impoundment of Three Gorges reservoir were compared. Before the impoundment of Three Gorges reservoir, the fluctuations of average water level of the four hydrological stations around Poyang Lake was 6.91-12.93 m; which reduced to 5.72 - 10.75 m after the impoundment. The D-value of the fluctuations of average water level was (1.06 ± 0.47) m. The date of the annual maximum water level delayed by an average of 12 d; while the date of annual minimum water level arrived an average of 12 d earlier than the impoundment of Three Gorges reservoir. The average flooding days of marshland with snails were separately (100.04 ± 42.06) d before the impoundment and (64.13 ± 22.30) d after the impoundment. The difference was statistically significant (t = 3.70, P < 0.05). The density of snails in the 4 counties around Poyang Lake was 0.8437/0.1 m(2) after the impoundment; declining by 31.04% from the snail density (1.2234/0.1 m(2)) before the impoundment. The density of infectious snails was 0.0014/0.1 m(2) after the impoundment; dropping by 67.34% from it (0.0042/0.1 m(2)) before the impoundment; the infection rate of snails was separately 0.34% after the impoundment and 0.16% before the impoundment. The difference was statistically significant (χ(2) = 53.25, P < 0.05). The coverage rate of chemotherapy increased from 4.45% (35 558/798 200) in 2002 to 9.80% (79 457/810 400) in 2008; the difference was statistically significant (χ(2) = 17 336.63, P < 0.05). The coverage rate of snail killing increased from 1.35% (389.04/28 824.66) in 2002 to 7.49% (2260.90/30 166.22) in 2008; the difference was also statistically significant (χ(2) = 28 824.66, P < 0.05). The impact of the impoundment of Three Gorges reservoir shortened the flooding days of marshland with snails and helped the prevention and control of schistosomiasis in Poyang Lake regions as the environment went against the breeding of the snails.


Changes in responses of medial pontomedullary reticular neurons during repetitive cutaneous, vestibular, cortical, and tectal stimulation.
1. In cats anesthetized with chloralose, responses of medial pontomedullary reticular neurons to stimulation of the body surface, vestibular nerves, superior colliculi, pericruciate cortices, cerebral peduncles, and spinal cord were studied at different stimulus rates. Raising the rate from 1/10 s to between 1/4 s and 2/s caused a significant decrement or increment in the response of most neurons tested. Response decrement typically began near the beginning of the higher frequency stimulus sequence and increased throughout the sequence. Response increment usually began somewhat later, rose to a peak, and then declined. Recovery from response decrement or increment usually occurred within 30-60 s at a 1/10 s stimulus rate.2. Measurements of response latency and of changes occurring in the initial and longer latency portions of responses indicated that all components of a response typically decreased or increased in parallel. Background spontaneous activity did not change during response decrements, but sometimes increased during response increment.3. Where changes could be detected, response decrement usually developed more rapidly when a sequence of repetitive stimulation was repeated.4. Response decrement was most pronounced at the highest stimulation rates and lowest stimulus intensities. Response increment was usually maximal at a stimulus rate of 1/s: at lower rates less increment occurred; at higher rates responses began to exhibit decrement.5. Response changes varied with the type of stimulus applied. Response decrements predominated when the body surface, vestibular nerves, or ipsilateral superior colliculus were stimulated. Approximately equal amounts of response increment and decrement were produced by repetitive stimulation of the cerebral peduncles and contralateral superior colliculus. Stimulation of the surface of the pericruciate cortex or of the spinal cord usually produced a long-lasting response increment.6. Generalization of response decrement and increment was observed in cases where trains of stimuli at a rate of 2/s applied to one point produced changes in the response to stimulation of another point which was tested once per 10 s and where single-shock stimulation of the first point was without effect on the test response. Generalization of response decrement occurred most often when two nearby points were stimulated. Generalization of response increment appeared to spread widely between distant cutaneous points and stimuli of different kinds.7. The response decrement and increment observed in medial pontomedullary reticular neurons displayed most of the parametric features of behavioral habituation and sensitization (8, 33) and therefore appear to represent neural analogs of these latter phenomena. The properties of response decrement suggest that it may occur to a large extent within afferent pathways leading to medial reticular neurons...


Clinical follow-up data and the rate of development of precocious and rapidly progressive puberty in patients with premature thelarche.
We aimed to evaluate the clinical follow-up data of patients with premature thelarche and determine the rate of development of precocious and early puberty in these patients. The charts of 158 girls with premature thelarche who were followed-up in our pediatric endocrinology polyclinic were reviewed. The patients were divided into three groups according to the age at onset: group 1 (0-1 month) (n=12), group 2 (1-24 months) (n=40) and group 3 (2-8 years) (n=106). At admission, the mean height standard deviation score (SDS), body weight (BW)-SDS, body mass index (BMI) and BMI-SDS were significantly higher in group 3 than in group 1 and group 2. At admission, 8.8% of the patients were obese and 24% of the patients were overweight. The majority of patients who were obese and overweight were in group 3. At the end of the follow-up, thelarche regressed in 24.7%, persisted in 32.9%, progressed in 25.9% and had a cyclic pattern in 16.5% of the patients. Precocious or rapidly progressive puberty developed in 47 of the 158 patients (29.7%). The mean age at progression to early or rapidly progressive puberty was 98.1±17.6 months. A total of 89.3% of the patients who progressed to early or rapidly progressive puberty were in group 3. Precocious or rapidly progressive puberty developed in 29.7% of subjects with premature thelarche. As patients who developed rapidly progressive puberty had a higher BW-SDS and BMI-SDS than those who did not, it is suggested that the increase in weight could stimulate rapidly progressive puberty in cases with premature thelarche.


Structural Polymorphism Kinetics Promoted by Charged Oxygen Vacancies in HfO_{2}.
Defects such as oxygen vacancy are widely considered to be critical for the performance of ferroelectric HfO_{2}-based devices, and yet atomistic mechanisms underlying various exotic effects such as wake-up and fluid imprint remain elusive. Here, guided by a lattice-mode-matching criterion, we systematically study the phase transitions between different polymorphs of hafnia under the influences of neutral and positively charged oxygen vacancies using a first-principles-based variable-cell nudged elastic band technique. We find that the positively charged oxygen vacancy can promote the transition of various nonpolar phases to the polar phase kinetically, enabled by a transient high-energy tetragonal phase and extreme charge-carrier-inert ferroelectricity of the polar Pca2_{1} phase. The intricate coupling between structural polymorphism kinetics and the charge state of the oxygen vacancy has important implications for the origin of ferroelectricity in HfO_{2}-based thin films as well as wake-up, fluid imprint, and inertial switching.


Disease severity in adult patients of Turkish ancestry with familial mediterranean fever living in Germany or Turkey. Does the country of residence affect the course of the disease?
The environment may affect the course of familial Mediterranean fever (FMF). The objective of this study was to compare disease severity between adult FMF patients in Turkey (TR) and Germany (G). Adult FMF patients of Turkish ancestry on colchicine living in Turkey (n = 40) or G (n = 35) were compared. Disease severity, C-reactive protein (CRP), and erythrocyte sedimentation rate were assessed. Groups differed significantly in the following aspects: age at onset of disease (TR: 15.6, G: 10.8 years; P = 0.02), delay between onset and initiation of colchicine treatment (TR: 6.8 years, G: 14.9 years; P < 0.001), female gender (TR: 80%, G: 57.1%; P = 0.04), and duration of disease (TR: 14.4 years, G: 23.4 years; P < 0.001). There was no significant difference in colchicine treatment concerning average dosing and duration of therapy. No significant difference could be found between the 2 groups in CRP and disease severity as assessed by the score of Pras et al. (Am J Med Genet. 1998;75:216-219) even after adjusting for potential confounding variables. Mean erythrocyte sedimentation rate was significantly higher among patients living in G (TR: 13.2 mm/first hour, G: 26.3 mm/first hour; P < 0.001). Among patients living in Germany, there was a significant difference in age at FMF onset depending on their country of birth (born in TR: 14.9 years, born in G: 6.9 years; P = 0.0001). In adult FMF patients living in Turkey or Germany, no difference in disease activity or CRP could be found. German patients were younger at onset of disease and had a longer delay between onset and initiation of colchicine treatment.


Arrangement of bristles as a function of bristle number on a leg segment inDrosophila melanogaster.
The arrangement of bristles on a leg segment of the fruitflyDrosophila melanogaster was studied in various mutants that have abnormal numbers of bristles on this segment. Eighteen mutations at six different genetic loci were analyzed, plus five double or triple mutant combinations. Recessive mutations at theachaete-scute locus were found to affect distinct groups of bristles:achaete mutations remove mechanosensory bristles, whereasscute mutations remove mainly chemosensory bristles. Mechanosensory bristles remain uniformly spaced along the longitudinal axis unless their number decreases below a certain threshold, suggesting that spacing is controlled by cell interactions that cannot function when bristle cells are too far apart. Above a certain threshold, bristle spacing and alignment both become irregular, perhaps due to excessive force from these same interactions. Chemosensory bristles occupy definite positions that are virtually unaffected by removal of individual bristles from the array. Extra chemosensory bristles develop only near the six normal sites. At two of the six sites the multiple bristles tend to exhibit uniform longitudinal spacing - a property confined to mechanosensory bristles in wild-type flies. To explain the various mutant phenotypes the following scheme is proposed, with different mutations directly or indirectly affecting each step: (1) spots and stripes are demarcated within the pattern area, (2) one bristle cell normally arises within each spot, multiple bristle cells within each stripe, (3) incipient bristle cells inhibit neighboring cells from becoming bristle cells, and (4) the bristle cells within each stripe become aligned to form rows and then repel one another to generate uniform spacing.


Neural - hormonal responses to negative affective stimuli: Impact of dysphoric mood and sex.
Maladaptive responses to negative affective stimuli are pervasive, including clinically ill and healthy people, and men and women respond differently at neural and hormonal levels. Inspired by the Research Domain Criteria initiative, we used a transdiagnostic approach to investigate the impact of sex and dysphoric mood on neural-hormonal responses to negative affective stimuli. Participants included 99 individuals with major depressive disorder, psychosis and healthy controls. Functional magnetic resonance imaging (fMRI) was complemented with real-time acquisition of hypothalamo-pituitary-adrenal (HPA) and -gonadal (HPG) hormones. fMRI data were analyzed in SPM8 and task-related connectivity was assessed using generalized psychophysiological interaction. Across all participants, elevated cortisol response predicted lower brain activity in orbitofrontal cortex and hypothalamus-amygdala connectivity. In those with worse dysphoric mood, elevated cortisol response predicted lower activity in hypothalamus and hippocampus. In women, elevated cortisol response was associated with lower activity in medial prefrontal cortex and low hypothalamo-hippocampal connectivity. In women with high dysphoric mood, elevated cortisol response was associated with low hypothalamo-hippocampal connectivity. There were no interactions with diagnosis or medication. There was limited power to correct for multiple comparisons across total number of ROIs and connectivity targets; cortisol responses were relatively low. We conclude that the pathophysiology in neural-hormonal responses to negative affective stimuli is shared across healthy and clinical populations and varies as a function of sex and dysphoric mood. Our findings may contribute to the development of hormonal adjunctive therapeutics that are sex-dependent, underscoring the importance of one's sex to precision medicine.


Average Game Physical Demands and the Most Demanding Scenarios of Basketball Competition in Various Age Groups.
The purpose of this study was to compare average physical demands and the most demanding 60-s scenarios of basketball match-play between five different age groups. Sixty-four male basketball players from five different age groups were monitored across eight regular-season home games. Physical demands were examined using a local positioning system and included total distance covered, distance >18 km·h-1, the number of accelerations (≥2 m·s-2) and decelerations (≤-2 m·s-2). All four game performance variables increased significantly (58.4 - 639.2%) when calculated with rolling average techniques in comparison to average physical demand values. Furthermore, the current investigation found that while Under-12 presented the highest result in relative total distance covered (p < .001; effect size = 0.58-2.01), they also showed the lowest values in the most demanding scenarios of match play and small-to-moderate effect sizes compared with their older counterparts. Both average physical demands and the most demanding scenarios presented an increasing tendency with age when distance >18 km·h-1 in basketball players was assessed. More specifically, the Under-12 age group achieved the lowest values and showed significant differences with the other four teams in both game analysis techniques (p < .001; effect size = 0.53 - 1.32). In conclusion, average game demands are shown to remarkably underestimate the most demanding scenarios of basketball match-play, and there are multiple significant differences between particular age groups.


Ultra-Weak Metal-Metal Bonding: Is There a Beryllium-Beryllium Triple Bond?
Metal-metal triple bonds featuring s-block element have not been reported until now. Only Be-Be double bonds between have been predicted theoretically based on the intuitive electron donation from four s1 type electron-donating ligands. Herein, we theoretically predicted a novel species featuring a Be-Be triple bond in the Li6 Be2 molecule. The molecule was found to be thermodynamically stable. The presence of the triple bond was confirmed by adaptive natural density partitioning (AdNDP), electron localization function (ELF), and atoms in molecules (AIM) analyses. Moreover, the mechanical strength of the Be-Be triple bond was analyzed by using compliance matrix, pointing towards its ultra-weak nature.


SrfJ, a Salmonella type III secretion system effector regulated by PhoP, RcsB, and IolR.
Virulence-related type III secretion systems are present in many Gram-negative bacterial pathogens. These complex devices translocate proteins, called effectors, from the bacterium into the eukaryotic host cell. Here, we identify the product of srfJ, a Salmonella enterica serovar Typhimurium gene regulated by SsrB, as a new substrate of the type III secretion system encoded by Salmonella pathogenicity island 2. The N-terminal 20-amino-acid segment of SrfJ was recognized as a functional secretion and translocation signal specific for this system. Transcription of srfJ was positively regulated by the PhoP/PhoQ system in an SsrB-dependent manner and was negatively regulated by the Rcs system in an SsrB-independent manner. A screen for regulators of an srfJ-lacZ transcriptional fusion using the T-POP transposon identified IolR, the regulator of genes involved in myo-inositol utilization, as an srfJ repressor. Our results suggest that SrfJ is synthesized both inside the host, in response to intracellular conditions, and outside the host, in myo-inositol-rich environments.


Synthetic peptides in the diagnosis of neurological diseases.
For several years peptides have been used to investigate many aspects of the molecular mechanisms supporting the etiopathogenesis of neurological diseases. Even if well-established and commercially-available assays for the diagnosis of neurological diseases, based on peptides, are presently not available, much research has been focused to the comprehension of the pathogenetic mechanisms of relevant neurological diseases, such as Multiple Sclerosis, Alzheimer's disease and prion diseases. Several peptides, which strongly contributed to increase in the progress, and in the understanding of the molecular mechanisms of these important diseases, have been selected as antigens to be proposed in possible alternative diagnostic methodologies. The authors focused their attention on the possible peptides to be used as diagnostics for these three characteristic neurological diseases. In fact, Multiple Sclerosis is an autoimmune disease in which peptides have been used for the characterization of both B and T immune response, while Alzheimer's disease and prion diseases can be cumulative regarded as "protein folding disorders" in which peptides can be used to identify the misfolded protein.


Effect of acebutolol on plasma catecholamine concentrations in anesthetized dogs with ouabain-induced arrhythmias and its direct actions in vitro on the adrenal medulla.
We have performed studies on blood hormone dynamics following intravenous administration of acebutolol, a newly synthesized beta-blocker, and its direct action on the adrenal medulla in vitro. Intravenous injection of acebutolol into anesthetized dogs almost doubled the plasma adrenaline and noradrenaline concentrations within 5 to 15 minutes, while renin activity was reduced to approximately two-thirds of the pre-administration level. When arrhythmia was induced in dogs with ouabain, the plasma adrenaline and noradrenaline levels increased to 220 +/- 109 and 392 +/- 84 pg/ml, respectively, from the basal levels of 44 +/- 24 and 140 +/- 43 pg/ml. The restoration of sinus rhythm following the administration of acebutolol was accompanied by a further increase in the plasma adrenaline and noradrenaline levels to 797 +/- 364 and 1226 +/- 263 pg/ml, respectively. A perifusion experiment indicated that acebutolol directly accelerated catecholamine release from the adrenal medulla in pigs.


Thymic lineage commitment rather than selection causes genetic variations in size of CD4 and CD8 compartments.
During their development, immature CD4+ CD8+ thymocytes become committed to either the CD4 or CD8 lineage. Subsequent complete maturation of CD4+ and CD8+ cells requires a molecular match of the expressed coreceptor and the MHC specificity of the TCR. The final size of the mature CD4+ and CD8+ thymic compartments is therefore determined by a combination of lineage commitment and TCR-mediated selection. In humans and mice, the relative size of CD4+ and CD8+ peripheral T cell compartments shows marked genetic variability. We show here that genetic variations in thymic lineage commitment, rather than TCR-mediated selection processes, are responsible for the distinct CD4/CD8 ratios observed in common inbred mouse strains. Genetic variations in the regulation of lineage commitment open new ways to analyze this process and to identify the molecules involved.


Deciphering the mechanism of fungal pathogen-induced disease-suppressive soil.
One model of a disease-suppressive soil predicts that the confrontation of plant with a phytopathogen can lead to the recruitment and accumulation of beneficial microorganisms. However, more information needs to be deciphered regarding which beneficial microbes become enriched, and how the disease suppression is achieved. Here, we conditioned soil by continuously growing eight generations of cucumber inoculated with Fusarium oxysporum f.sp. cucumerinum in a split-root system. Disease incidence was found to decrease gradually upon pathogen infection accompanied with higher quantity of reactive oxygen species (ROS mainly OH• ) in roots and accumulation of Bacillus and Sphingomonas. These key microbes were proven to protect the cucumber from pathogen infection by inducing high ROS level in the roots through enrichment of pathways, including a two-component system, a bacterial secretion system, and flagellar assembly revealed by metagenomics sequencing. Untargeted metabolomics analysis combined with in vitro application assays suggested that threonic acid and lysine were pivotal to recruit Bacillus and Sphingomonas. Collectively, our study deciphered a 'cry for help' case, wherein cucumber releases particular compounds to enrich beneficial microbes that raise the ROS level of host to prevent pathogen attack. More importantly, this may be one of the fundamental mechanisms underpinning disease-suppressive soil formation.


Optic pit, microphthalmos and orbital cyst.
An orbital cyst was discovered by ultrasonography behind the globe of the left eye in a five-year-old boy with a left esotropia. In addition, an optic pit was present in the optic nerve head of the same eye, which was microphthalmic relative to the right eye. Although orbital cyst has been reported in the literature, this case is of interest because of the presence of two congenital anomalies in the same eye - namely, optic pit and orbital cyst. These two conditions have never been previously reported as existing together in the same eye.


Visuomotor rotations of varying size and direction compete for a single internal model in motor working memory.
When participants adapt to equal and opposite visuomotor rotations in close temporal proximity, memory of the 1st is not consolidated. The authors investigated whether this retrograde interference depends on the use of equal and opposite rotations. On Day 1, different groups of participants adapted to a -30 degrees rotation followed 5 min later by rotations of +30 degrees, +60 degrees, or -60 degrees. On Day 2, all groups were retested on the -30 degrees rotation. Either retrograde interference (in groups who adapted to rotations of opposite sign on Day 1) or retrograde facilitation (in the remaining group) was observed. In all groups, learning of the 2nd rotation resulted in unlearning of the first, indicating that all visuomotor rotations compete for common working memory resources.


Hematuria and risk for end-stage kidney disease.
Hematuria is a common clinical finding requiring medical attention and poses several clinical challenges. The main challenge is to predict the future risk for chronic kidney disease and therefore to design a long-term follow-up evaluation and treatment plan. This review focuses on the risk for subsequent end-stage kidney disease among young persons with persistent isolated microscopic hematuria. It has been recently recognized that young persons with persistent isolated microscopic hematuria have an increased risk for end-stage kidney disease, mainly secondary to primary glomerular diseases. These predominantly include IgA nephropathy, thin basement membrane disease, and Alport syndrome. Among these causes, the association with progression to chronic kidney disease is best established for IgA nephropathy and Alport syndrome. Thin basement membrane disease had been considered 'benign' by most authors, although recent findings suggest otherwise. In addition, novel diagnostic markers and therapeutic interventions for these conditions have recently been studied. Persistent isolated microscopic hematuria confers a risk for future chronic kidney disease, which is dependent on disease context, underlying genetics, environment interactions, and treatment. 'Benign (familial) hematuria' is a misnomer, which we recommend abandoning as it prompts loss to follow-up. Instead, we favor annual/biennial follow-up assessment that should include measurement of blood pressure, urinalysis, and kidney function tests.


The effects of propolis supplementation on high-sensitivity C-reactive protein, testosterone hormone, and metabolic profile in women with polycystic ovary syndrome: A randomized, triple-blinded, placebo-controlled clinical trial.
One of the most prevalent ovulation disorders is polycystic ovarian syndrome (PCOS). According to the anti-inflammatory and beneficial effects of propolis, this triple-blind controlled trial was designed to evaluate the effect of propolis on metabolic factors, high-sensitivity C-reactive protein, and testosterone in women with PCOS. Recruited patients from the gynecologist clinic were randomized based on a stratified permuted four-block randomization procedure to supplement with propolis tablets, two tablets/day (500 mg propolis/day) (n = 30) or identical placebo tablets (n = 30) for 12 weeks in 2021 until 2022. Data were collected using a demographic questionnaire, blood samples, and a checklist to record the measured parameters. A total of 57 patients completed the trial. ANCOVA test showed that hip circumference (HC)) p = 0.03), fasting insulin (p = 0.007), homeostatic model assessment for insulin resistance (p = 0.004), testosterone (p = 0.004), and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) (p = 0.02) were significantly decreased in the propolis versus the placebo group after adjustment for confounders. Although fasting blood glucose (p = 0.04) decreased significantly in the propolis group compared to the placebo, after adjusting for confounders, significance was lost (p = 0.09). Supplementation with propolis elicited positive effects on fasting insulin and insulin resistance, in addition to reducing the testosterone level, LDL/HDL, and HC, in PCOS women.


Case Report: Guillain-Barré Syndrome Associated With COVID-19.
Guillain-Barré syndrome (GBS) is a potentially fatal, immune-mediated disease of the peripheral nervous system that is usually triggered by infection. Only a small number of cases of GBS associated with COVID-19 infection have been published. We report here five patients with GBS admitted to the Neurology, Psychiatry, and Neurosurgery Hospital, Assiut University/Egypt from July 1 to November 20, 2020. Three of the five patients were positive for SARS-CoV-2 following polymerase chain reaction (PCR) of nasopharyngeal swabs on day of admission and another one had a high level of IgM and IgG; all had bilateral ground-glass opacities with consolidation on CT chest scan (GGO) and lymphopenia. All patients presented with two or more of the following: fever, cough, malaise, vomiting, and diarrhea with variable duration. However, there were some peculiarities in the clinical presentation. First, there were only 3 to 14 days between the onset of COVID-19 symptoms and the first symptoms of GBS, which developed into flaccid areflexic quadriplegia with glove and stocking hypoesthesia. The second peculiarity was that three of the cases had cranial nerve involvement, suggesting that there may be a high incidence of cranial involvement in SARS-CoV-2-associated GBS. Other peculiarities occurred. Case 2 presented with a cerebellar hemorrhage before symptoms of COVID-19 and had a cardiac attack with elevated cardiac enzymes following onset of GBS symptoms. Case 5 was also unusual in that the onset began with bilateral facial palsy, which preceded the sensory and motor manifestations of GBS (descending course). Neurophysiological studies showed evidence of sensorimotor demyelinating polyradiculoneuropathy, suggesting acute inflammatory polyneuropathy (AIDP) in all patients. Three patients received plasmapheresis. All of them had either full recovery or partial recovery. Possible pathophysiological links between GBS and COVID-19 are discussed.


MicroRNA and ovarian cancer.
Ovarian cancer remains a leading cause of morbidity and mortality, with little change in survival rates over the past 30 years. Research in the molecular biology underlying the disease demonstrates frequent mutation in the p53/Rb/p16 tumor suppressor pathways and activation of c-myc, K-ras and Akt oncogenic signaling. Recently, miRNAs have been demonstrated to play an important role in controlling proliferation, apoptosis and many other processes altered in the cancer state. In this review we discuss a number of recent publications that implicate a role for microRNAs in ovarian cancer and assess how this new field may improve our fundamental understanding of the disease and provide improved diagnostic and therapeutic approaches.


Eruption of premolars subsequent to autotransplantation. A longitudinal radiographic study.
One-hundred-and-eighteen premolars transplanted at a stage with 3/4 to 4/4 root development with an open apical foramen were followed using a standardized clinical and radiographic technique for signs of periodontal ligament healing, root development, and tooth eruption. Root growth was unimpeded in 26 per cent, impaired in 55 per cent, and arrested in 19 per cent. Eruption of transplants occurred at the time of periodontal and alveolar healing, and before any significant root growth. Furthermore, autotransplanted premolars created growth of the alveolar process along with the eruption process.


Klf8 regulates left-right asymmetric patterning through modulation of Kupffer's vesicle morphogenesis and spaw expression.
Although vertebrates are bilaterally symmetric organisms, their internal organs are distributed asymmetrically along a left-right axis. Disruption of left-right axis asymmetric patterning often occurs in human genetic disorders. In zebrafish embryos, Kupffer's vesicle, like the mouse node, breaks symmetry by inducing asymmetric expression of the Nodal-related gene, spaw, in the left lateral plate mesoderm (LPM). Spaw then stimulates transcription of itself and downstream genes, including lft1, lft2, and pitx2, specifically in the left side of the diencephalon, heart and LPM. This developmental step is essential to establish subsequent asymmetric organ positioning. In this study, we evaluated the role of krüppel-like factor 8 (klf8) in regulating left-right asymmetric patterning in zebrafish embryos. Zebrafish klf8 expression was disrupted by both morpholino antisense oligomer-mediated knockdown and a CRISPR-Cas9 system. Whole-mount in situ hybridization was conducted to evaluate gene expression patterns of Nodal signalling components and the positions of heart and visceral organs. Dorsal forerunner cell number was evaluated in Tg(sox17:gfp) embryos and the length and number of cilia in Kupffer's vesicle were analyzed by immunocytochemistry using an acetylated tubulin antibody. Heart jogging, looping and visceral organ positioning were all defective in zebrafish klf8 morphants. At the 18-22 s stages, klf8 morphants showed reduced expression of genes encoding Nodal signalling components (spaw, lft1, lft2, and pitx2) in the left LPM, diencephalon, and heart. Co-injection of klf8 mRNA with klf8 morpholino partially rescued spaw expression. Furthermore, klf8 but not klf8△zf overexpressing embryos showed dysregulated bilateral expression of Nodal signalling components at late somite stages. At the 10s stage, klf8 morphants exhibited reductions in length and number of cilia in Kupffer's vesicle, while at 75% epiboly, fewer dorsal forerunner cells were observed. Interestingly, klf8 mutant embryos, generated by a CRISPR-Cas9 system, showed bilateral spaw expression in the LPM at late somite stages. This observation may be partly attributed to compensatory upregulation of klf12b, because klf12b knockdown reduced the percentage of klf8 mutants exhibiting bilateral spaw expression. Our results demonstrate that zebrafish Klf8 regulates left-right asymmetric patterning by modulating both Kupffer's vesicle morphogenesis and spaw expression in the left LPM.


Stress cardiovascular magnetic resonance imaging: current and future perspectives.
Vasodilator and dobutamine are the main pharmacological agents used in current stress cardiovascular magnetic resonance (CMR). Exercise stress has well-established advantages and it is commonly used in other stress imaging, but the technical considerations have limited its use in stress CMR. In this review, we will describe the diagnostic performance, prognostic value, strengths and challenges of current stress CMR techniques. We will also discuss future perspectives of exercise stress CMR. Areas covered: Despite notable mechanistic differences, vasodilator and dobutamine stress CMR offer similar diagnostic and prognostic value in coronary artery disease. Combined perfusion and wall motion assessment has been explored with dobutamine stress CMR: diagnostic sensitivity improved at the expense of reduced specificity. However, a combined assessment may provide additional prognostic value in selected patients. There is emerging interest and promising data in exercise stress CMR because of the availability of CMR-compatible stress equipment and development of novel real-time sequences that allow imaging during exercise with adequate spatiotemporal resolution. Expert commentary: Exercise stress CMR is able to assess wall motion abnormalities, perfusion defects, exercise capacity and viability in a single examination. This holds important clinical potential in a variety of cardiovascular conditions.


Standardization of lipid, lipoprotein, and apolipoprotein measurements.
Accurate laboratory measurement of serum cholesterol has become a national public health priority. National proficiency testing surveys indicate that laboratory inaccuracy in cholesterol testing is more of a problem than precision. Like precision, accuracy is a function of multiple pre-analytical and analytical sources of variation. Controlling pre-analytical sources of variation helps minimize such sources of variation as intraperson biological, behavioral, and clinical differences, and variations caused by sample collection, handling, and shipping. Standardization of analytical sources of variation helps to achieve and maintain desirable analytical performance, accurate reporting, and correct interpretation of a reported cholesterol result. The intraperson total variation in lipoproteins and their constituents is of primary interest when one is interpreting a single result or a series of results from a single person. The mean of multiple specimens from the same person is required if one is to obtain an accurate value for intraperson total cholesterol and minimize pre-analytical sources of variation. Standardizing analytical sources of variation in some instrument systems requires standardizing results by using "fresh" patients' specimens.


Characterization of beta-galactosidase--lactose-permease chimaeras of Escherichia coli.
Escherichia coli strains have been isolated in which 3, 39 or 805 5'-end codons of lacZ, the gene for the cytoplasmic enzyme beta-galactosidase are fused to codon 9 of lacY, the gene for lactose permease. Lactose-permease-deficient cells, carrying the lacZ-Y fusions on F' lac pro episomes, are phenotypically positive on eosin/methylene blue/lactose or on melibiose plates, demonstrating that the beta-galactosidase--lactose-permease chimaeras transport lactose and melibiose in vivo. The apparent affinity for beta-D-galactopypanosyl 1-thio-beta-D-galactopyranoside (GalSGal) in cells is similar to that of the wild-type gene product. The maximum velocity of active GalSGal transport is reduced in all three fusion strains. Both lactose and p-nitrophenyl alpha-D-galactopyranoside inhibit GalSGal uptake. As demonstrated by immunoblot experiments the chimaeras cross-react with polyclonal antibodies directed against native lactose permease and they are present in the cell envelope fraction of homogenates. Their apparent molecular weights upon electrophoresis in NaDodSO4/polyacrylamide gels correspond to those expected from their respective primary sequences, taking into account the migration properties of wild-type lactose permease. It is proposed that substitution of eight N-terminal lactose permease residues by N-terminal beta-galactosidase residues neither prevents membrane incorporation of permease nor completely impairs the ability to transport galactosides actively. Alternative interpretations of the experimental results are discussed.


[The modelling of productivity level and the comparability of sport evaluation depending on the athlete age.]
Throughout the life, a person's working capacity is variable. It is influenced by a wide range of factors, both external and internal, which are difficult to take into account in various studies. An approximation of the density function of the given distribution, based on the assumption of the random nature of the physical condition, depending on a number of different reasons, among competitors and the hypothesis of the asymmetric distribution of athletes' achievements, shown at different ages, is formed. Optimum parameters of a log-normal distribution describing the working capacity of a person according to his or her age are determined by using the least squares method. This is a comparative analysis of the received model and the previously known methods, which were created by Litvinov and Spiridonov. The study has showed the validity of the method for determining age coefficients and the possibility of its practical application.


Neuroleptic Malignant Syndrome Secondary to Metoclopramide Use in an Elderly Gastroenterologic Surgery Patient.
An 84-year-old African American woman was admitted to the hospital secondary to severe abdominal pain accompanied by septic shock. She underwent exploratory laparotomy, which revealed extensive small bowel necrosis likely due to small bowel torsion. A small bowel resection was performed with primary anastomoses and the patient was subsequently transferred to the intensive care unit (ICU). She recovered from shock but had a persistent gastroparesis interfering with enteral feeding, for which metoclopramide was prescribed. She was then transferred to a general medical-surgical unit in a stable condition where she received a total of four 10-mg oral doses of metoclopramide administered every 8 hours. Approximately 32 hours after receiving the first dose of metoclopramide, the patient was subsequently transferred back to the ICU because of fever and inability to maintain respirations. Neuroleptic malignant syndrome was suspected, and the patient was intubated and received supportive care. After a week in the ICU, she was discharged back to the medical-surgical unit in a stable condition and recovered completely. The patient was later discharged home.


A Novel Tool for the Assessment Oxidative Stress in Age-Related Macular Degeneration: Thiol/Disulfide Homeostasis Revisited.
To investigate thiol/disulfide status using a novel automated assay in patients with age-related macular degeneration (AMD) compared to age-matched healthy controls. A total of 64 AMD patients [51 (79%) non-exudative, 13 (21%) exudative AMD] and 21 age-matched healthy control subjects were enrolled in this study. Plasma total thiol, native thiol, disulfide levels were measured and native thiol/disulfide ratio (TDR) was calculated using a novel spectrophotometric assay. Patients with AMD had significantly lower levels of total thiol (434.8 ± 7.0 μmol/L vs. 472.2 ± 7.9 μmol/L, p < 0.001), native thiol (393.6 ± 6.5 μmol/L vs. 437.5 ± 7.1 μmol/L, p = 0.004) compared to healthy controls. However, plasma disulfide levels were higher in AMD patients (20.6 ± 0.9 μmol/L vs. 17.3 ± 1.3 μmol/L, p = 0.113) compared to healthy controls. The TDR was not statistically different between the early AMD group and healthy controls (24.2 ± 2.3 vs. 29.5 ± 3.1, p = 0.345). However, intermediate and advanced stage AMD groups had significantly lower levels of TDR compared to healthy controls (21.6 ± 2.6 vs. 29.5 ± 3.1, p = 0.023 and 20.3 ± 1.2 vs. 29.5 ± 3.1, p = 0.005, respectively). Native TDR was significantly lower in patients with exudative and non-exudative AMD (19.9 ± 2.3 vs. 29.5 ± 3.1, p = 0.024 and 21.8 ± 1.14 vs. 29.47 ± 3.1 respectively, p = 0.011). A greater extent of thiol consumption occurred in AMD patients compared to age-matched healthy controls. However, despite the similar levels of total thiol levels between several grades of AMD, the plasma native TDR value was decreased in accordance with the severity of the disease, which reflected the disease grade better.


Life Expectancy after Liver Transplantation for NASH.
Introduction: Non-Alcoholic Steatohepatitis is an increasing reason for liver transplantation in the western world. Knowledge of recipient life expectancy may assist in prudent allocation of a relatively scarce supply of donor livers. Research Questions: We calculated life expectancies for Non-alcoholic steatohepatitis (NASH) patients both at time of transplant and one year later, stratified by key risk factors, and examined whether survival has improved in recent years. Design: Data on 6635 NASH patients who underwent liver transplantation in the MELD era (2002-2018) from the United States OPTN database were analyzed using the Cox proportional hazards regression model and life table methods. Results: Factors related to survival were age, presence of diabetes or hepatic encephalopathy (HE), and whether the patient required dialysis in the week prior to transplant. Other important factors were whether the patient was working, hospitalization prior to transplant, ventilator support, and length of hospital stay (LOS). Survival improved over the study period at roughly 4.5% per calendar year during the first year posttransplant, though no improvement was observed in those who had survived one year. Conclusion: Life expectancy in NASH transplant patients was much reduced from normal, and varied according to age, medical factors, status at transplant, and post transplant course. Over the 17-year study period, patient survival improved markedly during the first year posttransplant, though not thereafter. The results given here may prove helpful in medical decision-making regarding treatment for both liver disease and other medical conditions, as they provide both clinicians and their patients with evidence-based information on prognosis.


An Introduction to the Psychopharmacology of Children and Adolescents With Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that requires a multidisciplinary approach to treatment. Psychopharmacology can play an important role within an array of services to help children and adolescents with ASD. This article reviews the current evidence supporting the use of various psychiatric medications to treat common symptoms that often compromise functioning: severe irritability, interfering repetitive behaviors, ADHD, anxiety, depression, and sleep dysregulation. Based on the accumulating research, the article also offers practice recommendations. The article primarily draws on the science generated by investigators from the Research Units on Pediatric Psychopharmacology Autism Network. This body of work consists of randomized controlled trials, meta-analyses, open trials, and review articles. There are currently no FDA-approved medications to treat the core symptoms of ASD. Consequently, all medications, besides risperidone and aripiprazole for severe irritability, are considered off-label. Additionally, due to reduced levels of effectiveness and higher rates of side effects, more typical medications such as antidepressants and stimulants should be used with caution. However, the evidence indicates that the thoughtful use of psychiatric medication in conjunction with other interventions may be beneficial in helping children and adolescents with ASD thrive at school and home.


Effects of resibufogenin in experimental hypertension.
There are two major pathophysiologic processes involved in the development of hypertension: (1) expanded extracellular fluid volume and (2) vasoconstriction. We have developed a model of preeclampsia in the rat, in which excessive volume expansion (VE) plays a role. These animals excrete increased amounts of the bufodienolide, marinobufagenin (MBG), even before their hypertension and proteinuria become established. Furthermore, their hypertension is corrected by administration of resibufogenin (RBG), a compound structurally similar to MBG. We studied two models of experimental hypertension in the nonpregnant animal, produced either by deoxycorticosterone acetate (DOCA)-salt administration or by angiotensin infusion. RBG administered to the DOCA-salt rats lowered blood pressure and reduced proteinuria in the VE animals, but had no affect on the rats infused with angiotensin. Furthermore, although the production of superoxide anion in the aortas of both groups of hypertensive rats was increased over control, RBG reduced these levels to normal in the VE (DOCA-salt) animals only. RBG had no effect in the angiotensin-infused rats. The urinary excretion of angiotensinogen did not rise in VE-mediated hypertension, but did increase in the angiotensin-infused rats. MBG plays an important role in the causation of hypertension in the VE rats, but not in the vasoconstrictive model. RBG is effective only in VE-mediated hypertension.


L-carnitine pretreatment protects slow-twitch skeletal muscles in a rat model of ischemia-reperfusion injury.
Ischemia-reperfusion (I/R) injury negatively affects the outcome of surgical interventions for amputated or severely traumatized extremities. This study aimed to evaluate the protective role of l-carnitine on the contractile properties of fast-twitch (extensor digitorum longus [EDL]) and slow-twitch (soleus [SOL]) skeletal muscles following I/R-induced injury in a rat model. Rats were divided into 4 groups (1) saline pretreatment, (2) l-carnitine pretreatment, (3) saline pretreatment and I/R, and (4) l-carnitine pretreatment and I/R. Twitch and tetanic contractions in the EDL and SOL muscles in each group were recorded. Additionally, a fatigue protocol was performed in these muscles. Twitch and tetanic contraction amplitudes were lower in the EDL and SOL muscles in which I/R was induced (P < .01). l-Carnitine pretreatment significantly increased tetanic contraction amplitude in the SOL muscles following I/R (P < .01) but not in the EDL muscles. l-Carnitine pretreatment did not alter the fatigue response in any of the muscles.


Interleukin-2 and a T cell hybridoma (MP6) derived B cell-stimulatory factor act synergistically to induce proliferation and differentiation of human B-chronic lymphocytic leukemia cells.
In this paper we communicate that cells of a selected B-CLL clone (I83), after 2 days of Staphylococcus aureus Cowan strain 1 (SAC) activation, respond to recombinant IL-2 (rIL-2) and a B cell stimulatory factor (BSF-MP6) and act in strong synergism with induction of simultaneous high-rate proliferation and differentiation. None of the factors alone or other lymphokines (IFN-gamma, TNF-alpha, 12 kDa BCGF, IL-1, IL-4, IL-5, IL-6) induced significant DNA synthesis in SAC-activated cells. However, low levels of IgM were produced by cells stimulated by SAC + rIL-2. The SAC activation was followed by an increase in IL-2 receptor (IL-2R; CD25) expression, and the proliferation induced by BSF-MP6 + rIL-2 could be blocked in a dose-dependent manner by alpha-CD25 antibody. Furthermore, flow cytometric cell cycle studies showed that SAC and BSF-MP6 + rIL-2 stimulated cells underwent a complete transition through the cell cycle to become arrested in G1. The induced proliferation by BSF-MP6 + rIL-2 was dependent on serum but independent of the 2.8% of CD4, CD8, CD14, and CD16 positive cells contaminating the I83 cell population. Previously, we reported that I83 cells activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) were induced to differentiation only but that the addition of BSF-MP6 induced DNA synthesis concomitantly with the differentiation. This paper demonstrates that physiological stimuli can induce both high-rate proliferation and differentiation in a B-CLL clone in vitro. It also suggests that the low proliferation and the differentiation block in vivo, characteristic of most B-CLLs, may reflect a subnormal response of B-CLL cells to growth and differentiation factors, or a dysfunction in the factor production by the patients' T cells.


The challenges facing training in pediatric surgery worldwide.
Like most specialties, pediatric surgery is becoming more complex, and changes to health systems have not always been in the best interests of trainees or their surgical teachers. This paper outlines four of the current challenges faced by training boards in pediatric surgery worldwide, and documents their implications for the future training of pediatric surgeons.


Cardiac-derived extracellular matrix: A decellularization protocol for heart regeneration.
Extracellular matrix (ECM) is a fundamental component of the heart, guiding vital cellular processes during organ homeostasis. Most cardiovascular diseases lead to a remarkable remodeling of the ECM, accompanied by the formation of a fibrotic tissue that heavily compromises the heart function. Effective therapies for managing fibrosis and promoting physiological ECM repair are not yet available. The production of a decellularized extracellular matrix (d-ECM) serving as a three-dimensional and bioactive scaffold able to modulate cellular behavior and activities is considered crucial to achieve a successful regeneration. The protocol represents a step-by-step method to obtain a decellularized cardiac matrix through the combination of sodium dodecyl sulphate (SDS) and Triton X-100. Briefly, cardiac samples obtained from left ventricles of explanted, pathological human hearts were dissected and washed to remove residual body fluids. Samples were then snap-frozen and sliced by a cryostat into 350 μm thick sections. The sections obtained were decellularized using a solution containing 1% Triton X-100 and 1% SDS in combination, for 24 hours, until observing the color change from brownish-red to translucent-white. As a result, the protocol shows efficiency in preserving ECM architecture and protein composition during the whole process, suggesting that it is worthwhile, highly reproducible and produces a well- preserved decellularized extracellular matrix from cardiac samples. Notwithstanding, some limitations need to be addressed, such as the risk for microbial contamination and the unpredictable trend of the protocol when applied to decellularize samples other than myocardium, vessels, or skin. These issues require antibiotics mixture supplement during the procedure followed by UV sterilization, and appropriate adjustments for a tissue-specific utilization, respectively. The protocol is intended to produce a cardiac d-ECM for cell settlement, representing the ideal scaffold for tissue engineering purposes.


Effect of a topical anesthetic cream (EMLA) in reducing pain caused by infiltration of local anesthetic in eyelid surgery.
EMLA (eutectic mixture of local anesthetics) cream is a topical formulation of a mixture of lidocaine and prilocaine. It has been used to achieve local analgesia after application under an occlusive dressing. We carried out a double-blind randomized controlled clinical trial to assess the effect of 5% EMLA (25 mg/mL of lidocaine and of prilocaine) in reducing the pain caused by infiltration of local anesthetic in eyelid surgery. Pain was assessed by means of a modified visual analogue scale ranging from 0 (no pain) to 10 (excruciating pain) in 25 consecutive patients (average age 65 years) undergoing bilateral eyelid surgery. Clinical significance was defined as a difference in pain scores of 3 or more between EMLA and placebo. The mean pain scores for EMLA and placebo were 3.1 and 4.0 respectively, a nonsignificant difference. The EMLA preparation was found not to be clinically effective in reducing pain caused by infiltration of local anesthetic in eyelid surgery.


A Multisensing Setup for the Intelligent Tire Monitoring.
The present paper offers the chance to experimentally measure, for the first time, the internal tire strain by optical fiber sensors during the tire rolling in real operating conditions. The phenomena that take place during the tire rolling are in fact far from being completely understood. Despite several models available in the technical literature, there is not a correspondently large set of experimental observations. The paper includes the detailed description of the new multi-sensing technology for an ongoing vehicle measurement, which the research group has developed in the context of the project OPTYRE. The experimental apparatus is mainly based on the use of optical fibers with embedded Fiber Bragg Gratings sensors for the acquisition of the circumferential tire strain. Other sensors are also installed on the tire, such as a phonic wheel, a uniaxial accelerometer, and a dynamic temperature sensor. The acquired information is used as input variables in dedicated algorithms that allow the identification of key parameters, such as the dynamic contact patch, instantaneous dissipation and instantaneous grip. The OPTYRE project brings a contribution into the field of experimental grip monitoring of wheeled vehicles, with implications both on passive and active safety characteristics of cars and motorbikes.


Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models.
The genus Ocimum are used in cooking, however, their essential oils are utilized in traditional medicine as aromatherapy. The present study was carried out to investigate the chemical composition and systemic anti-inflammatory activity of the Ocimum basilicum essential oil (EOOB) and its major component estragole, as well as its possible mechanisms of action. The Ocimum basilicum essential oil was obtained by hydrodistillation and analyzed by GC-MS. The anti-inflammatory action was verified using acute and chronic in vivo tests as paw edema, peritonitis, and vascular permeability and granulomatous inflammation model. The anti-inflammatory mechanism of action was analyzed by the participation of histamine and arachidonic acid pathways. The chemical profile analysis identified fourteen components present in the essential oil, within them: estragole (60.96%). The in vivo test results show that treatment with EOOB (100 and 50 mg/kg) and estragole (60 and 30 mg/kg) significantly reduced paw edema induced by carrageenan and dextran. The smallest doses of EOOB (50 mg/kg) and estragole (30 mg/kg) showed efficacy in the reduction of paw edema induced by histamine and arachidonic acid, vascular permeability inhibition and leukocyte emigration in the peritoneal fluid. Theses doses were capable of reducing the chronic inflammatory process. The results observed between the EOOB and estragole demonstrate efficacy in anti-inflammatory activity, however, the essential oil is more efficacious in the acute and chronic anti-inflammatory action. This study confirms the therapeutic potential of this plant and reinforces the validity of its use in popular medicine.


Are mirror-symmetric objects of special importance for 3D shape perception? A reply to Sawada and Pizlo (2022).
Yu, Todd, and Petrov (2021) and Yu, Petrov, and Todd (2021) investigated failures of shape constancy that occur when objects are viewed stereoscopically at different distances. Although this result has been reported previously with simple objects such as pyramids or cylinders, we examined more complex objects with bilateral symmetry to test the claim by Li, Sawada, Shi, Kwon, and Pizlo (2011) that the perception of those objects is veridical. Sawada and Pizlo (2022) offer several criticisms of our experiments, but they seem to suggest that the concept of shape is defined by what is computable by their model. If stimuli are used that cannot be discriminated by their model, they are dismissed as degenerate, and tasks that cannot be performed by their model are assumed to be based on something other than shape. This allows them to disregard empirical evidence that is inconsistent with their model. We argue, in contrast, that all reliable aspects of shape perception are deserving of explanation. We also argue that there are many different attributes of shape and many different sources of information about shape that may be relevant in different contexts. It is unlikely that all of them can be explained by a single model.


Analysis of histidine phosphorylation using tandem MS and ion-electron reactions.
Phosphorylation of proteins is essential in intracellular signal transduction pathways in eukaryotic and prokaryotic cells. Histidine phosphorylation plays an important role in two-component signal transduction in bacteria. In this study, we describe the characterization of a synthetic histidine-phosphorylated peptide with four different mass spectrometric (MS) fragmentation techniques: Collision-induced dissociation (CID), electron capture dissociation, electron-transfer dissociation, and electron detachment dissociation. Furthermore, LC-MS methods were developed to detect histidine-phosphorylated peptides, which are acid-labile, in more complex samples. From these results, we concluded that nonacidic solvent systems or fast LC methods provide the best conditions for separation of histidine-phosphorylated peptides prior to electrospray ionization mass spectrometry analysis. Electron-based fragmentation methods should be used for determination of histidine phosphorylation sites, since CID results in very facile phosphate-related neutral losses. The developed LC-MS/MS methods were successfully applied to a tryptic digest of the cytoplasmic part of the histidine kinase EnvZ, which was in vitro autophosphorylated. Finally, a new method is described for nonretentive solid-phase extraction of histidine-phosphorylated peptides using polymeric Strata-X microcolumns.


Low-energy coexisting band in 154Gd.
A low-energy coexisting band Jpi (Ex keV) 0(+) (1182), 2(+) (1418), 4(+) (1701) is identified in the deformed nucleus, 154Gd. Detailed gamma-ray spectroscopy following the beta decays of 154Eu (J=3), (g,m(1),m(2))154Tb (J=0,3,7) is used to establish this structure. The structure is explained in terms of the pairing and deformation degrees of freedom, a "pairing isomer," which results from the nu[505] upward arrow Nilsson intruder orbital.


Comprehensive Analysis of Prevalence, Epidemiologic Characteristics, and Clinical Characteristics of Monoinfection and Coinfection in Diarrheal Diseases in Children in Tanzania.
The role of interactions between intestinal pathogens in diarrheal disease is uncertain. From August 2010 to July 2011, we collected stool samples from 723 children admitted with diarrhea (cases) to 3 major hospitals in Dar es Salaam, Tanzania, and from 564 nondiarrheic children (controls). We analyzed the samples for 17 pathogens and assessed interactions between coinfections in additive and multiplicative models. At least one pathogen was detected in 86.9% of the cases and 62.8%, of the controls. Prevalence of coinfections was 58.1% in cases and 40.4% in controls. Rotavirus, norovirus genogroup II, Cryptosporidium, and Shigella species/enteroinvasive Escherichia coli were significantly associated with diarrhea both as monoinfections and as coinfections. In the multiplicative interaction model, we found 2 significant positive interactions: rotavirus + Giardia (odds ratio (OR) = 23.91, 95% confidence interval (CI): 1.21, 470.14) and norovirus GII + enteroaggregative E. coli (OR = 3.06, 95% CI: 1.17, 7.98). One significant negative interaction was found between norovirus GII + typical enteropathogenic E. coli (OR = 0.09, 95% CI: 0.01, 0.95). In multivariate analysis, risk factors for death were presence of blood in stool and severe dehydration. In conclusion, coinfections are frequent, and the pathogenicity of each organism appears to be enhanced by some coinfections and weakened by others. Severity of diarrhea was not affected by coinfections.


Multiple novel signals mediate thyroid hormone receptor nuclear import and export.
Thyroid hormone receptor (TR) is a member of the nuclear receptor superfamily that shuttles between the cytosol and nucleus. The fine balance between nuclear import and export of TR has emerged as a critical control point for modulating thyroid hormone-responsive gene expression; however, sequence motifs of TR that mediate shuttling are not fully defined. Here, we characterized multiple signals that direct TR shuttling. Along with the known nuclear localization signal in the hinge domain, we identified a novel nuclear localization signal in the A/B domain of thyroid hormone receptor α1 that is absent in thyroid hormone receptor β1 and inactive in the oncoprotein v-ErbA. Our prior studies showed that thyroid hormone receptor α1 exits the nucleus through two pathways, one dependent on the export factor CRM1 and the other CRM1-independent. Here, we identified three novel CRM1-independent nuclear export signal (NES) motifs in the ligand-binding domain as follows: a highly conserved NES in helix 12 (NES-H12) and two additional NES sequences spanning helix 3 and helix 6, respectively. Mutations predicted to disrupt the α-helical structure resulted in a significant decrease in NES-H12 activity. The high degree of conservation of helix 12 suggests that this region may function as a key NES in other nuclear receptors. Furthermore, our mutagenesis studies on NES-H12 suggest that altered shuttling of thyroid hormone receptor β1 may be a contributing factor in resistance to thyroid hormone syndrome. Taken together, our findings provide a detailed mechanistic understanding of the multiple signals that work together to regulate TR shuttling and transcriptional activity, and they provide important insights into nuclear receptor function in general.


Nup84, a novel nucleoporin that is associated with CAN/Nup214 on the cytoplasmic face of the nuclear pore complex.
The short filaments extending from the cytoplasmic face of nuclear pore complexes are thought to contain docking sites for nuclear import substrates. One component of these filaments is the large O-linked glycoprotein CAN/Nup214. Immunoprecipitation studies carried out under nondenaturing conditions, and using a variety of antibodies, reveal a novel nonglycosylated nucleoporin, Nup84, that is tightly associated with CAN/Nup214. Consistent with such an association, Nup84 is found to be exposed on the cytoplasmic face of the nuclear pore complex. cDNA sequence analyses indicate that Nup84 contains neither the GLFG nor the XFXFG repeats that are a characteristic of a number of other nuclear pore complex proteins. Secondary structure predictions, however, suggest that Nup84 contains a coiled-coil COOH-terminal domain, a conclusion supported by the observation of significant sequence similarity between this region of the molecule and various members of the tropomyosin family. Mutagenesis and expression studies indicate that the putative coiled-coil domain is required for association with the cytoplasmic face of the nuclear pore complex, whereas it is the NH2-terminal region of Nup84 that contains the site of interaction with CAN/Nup214. These findings suggest a model in which Nup84 may function in the attachment of CAN/Nup214 to the central framework of the nuclear pore complex. In this way, Nup84 could play a central role in the organization of the interface between the pore complex and the cytoplasm.


Cardiopulmonary exercise testing in interstitial lung disease.
Interstitial lung disease (ILD) can determine severe lung function impairment both at rest and during exercise. Usually, resting measurements of lung and cardiac function give enough information on the degree of the disease. Thus, exercise testing should be reserved only for particular situations such as presence at the same time of cardiac and respiratory involvement, symptomatic patients with normal spirometry, and to check the response to therapy. A better understanding of the pathophysiology and cardiorespiratory consequences of ILD can give an important contribution in improving methods of exercise testing to assess disability. In this perspective, we analyze the factors limiting exercise performance: the progressive hypoxemia that appears or is worsened by exertion; the ventilatory abnormalities that lead to a rapid shallow breathing pattern with a VE that reach the MVV; and the cardiovascular limitation with low maximum heart rate, low cardiac output and high PVR and PAP.


Performance test of the integrator system for magnetic diagnostics in KSTAR.
Ten modules of the integrator system of the initial magnetic diagnostics for the first plasma operation have been simultaneously tested in the Korea superconducting tokamak advanced research device by measuring the magnetic flux density from various magnetic diagnostics sensors when a small current was applied to the superconducting poloidal field coils. The measured drifts from the integrators show between 1x10(-6) and 1x10(-5) Wb/s. The results from the field tests before the first plasma generation are described.


The great subluxation debate: a centrist's perspective.
This commentary describes the debate and some of the associated issues involving the subluxation construct. The long-standing debate regarding the chiropractic subluxation has created substantial controversy within the profession. Currently, this phenomenon can be compared with a country with a 2-party system that has a large silent majority sitting between the 2 factions. It is argued that the position held by those in the middle (the centrists) may be the most rational view when considering all of the available evidence. It is also suggested that the subluxation construct is similar to the Santa Claus construct in that both have a factual basis as well as social utility. Ultimately, the centrists must become proactive if they want to protect the profession and further advance the evidence in regard to the subluxation. They must not only engage in the debate, but fund the research that will investigate various aspects of the subluxation and then help disseminate this evidence to fellow doctors of chiropractic, other practitioners, health care policy makers, and society at large. The role of subluxation in chiropractic practice, the progression of this debate, and the future of the profession will be directly determined by the role that centrists choose to play.


[Chemical constituents from Bidens bipinnata].
To investigate the chemical constituents of the whole plants of Bidens bipinnata, the separation and purification of constituents were performed by chromatography on macroporous resin, silica gel, MCI and Sephadex LH-20. Their structures were elucidated by spectroscopic data as quercetin (1), quercetin-3-0-alpha-L-rhamnoside (2), keampferol-3-O-beta-D-glucopyranoside (3), keampferol-3-O-alpha-L-rhamnoside (4), 3', 5-dyhydroxy-3, 6, 4'-trimethoxyl -7-O-beta-D-glucopyranoside flavonoid (5), 7, 8, 3', 4'-tetraflavanone(6), (2S)- and (2R)-isookanin-7-O-beta-D- glucopyranoside (7a/7b), (2S)- and (2R)-3'-methoxy-isookanin-8-O-beta-D-glucopyranoside (8a/8b), 6, 7, 3', 4'-tetrahydroxyaurone(9), maritimetin (10), esculetin (11), 3-O-caffeoyl-2-methyl-d-erythrono-1, 4-lactone (12), (7S, 8R) balanophonin-4-O-beta-D-glucopyranoside (13), eugenyl-O-beta-apiofuranosyl-( 1"-6') -O-beta-glucopyranoside (14), and (+)-syringaresinol-4'-O-beta-D-glucopyranoside (15). Compounds 8, 13, 14, and 15 were isolated from this genus for the first time. Compounds 1 and 6 were potent inhibitors against HSC-T6 cells in vitro and compounds 1, 2, 6, and 7 were capable of decreasing the inflammatory cytokine production of macrophage cells in vitro.


Canine Cognitive Dysfunction (CCD) scores correlate with amyloid beta 42 levels in dog brain tissue.
Alzheimer's disease (AD) is a significant burden for human health that is increasing in prevalence as the global population ages. There is growing recognition that current preclinical models of AD are insufficient to recapitulate key aspects of the disease. Laboratory models for AD include mice, which do not naturally develop AD-like pathology during aging, and laboratory Beagle dogs, which do not share the human environment. In contrast, the companion dog shares the human environment and presents a genetically heterogeneous population of animals that might spontaneously develop age-associated AD-like pathology and cognitive dysfunction. Here, we quantitatively measured amyloid beta (Aβ42 or Abeta-42) levels in three areas of the companion dog brain (prefrontal cortex, temporal cortex, hippocampus/entorhinal cortex) and cerebrospinal fluid (CSF) using a newly developed Luminex assay. We found significant positive correlations between Aβ42 and age in all three brain regions. Brain Aβ42 abundance in all three brain regions was also correlated with Canine Cognitive Dysfunction Scale score in a multivariate analysis. This latter effect remained significant when correcting for age, except in the temporal cortex. There was no correlation between Aβ42 in CSF and cognitive scores; however, we found a significant positive correlation between Aβ42 in CSF and body weight, as well as a significant negative correlation between Aβ42 in CSF and age. Our results support the suitability of the companion dog as a model for AD and illustrate the utility of veterinary biobanking to make biospecimens available to researchers for analysis.


Embedding the Mental Capacity Act 2005 in clinical practice: an audit review.
Aims and method An audit cycle assessed compliance of healthcare professionals within Oxleas NHS Foundation Trust with the statutory requirements of the Mental Capacity Act 2005 in patient care. Each stage involved a retrospective review of relevant patient electronic records. The additional purpose of the audit was to make recommendations to improve compliance with the requirement of the Act by healthcare professionals and improve patient understanding of its provisions. Results The audit cycle demonstrated some improvement in clinical practice as well as the need for further efforts at raising the understanding and compliance of clinicians and the public with provisions of the Act. Clinical Implications Healthcare professionals need further understanding of the provisions of the Act and their responsibilities. There is also the need to enhance public awareness to provisions of the Act in relation to their decision-making autonomy. Stakeholders need to put strategies in place for these to be achieved.


Venous architecture of cerebral hemispheric white matter and comments on pathogenesis of medullary venous and other cerebral vascular malformations.
The parenchymal veins, especially the deep medullary veins, of the cerebral hemispheres were studied in detail by analyzing the stereoroentgenograms of multiple brain slices of postmortem injected brain specimens (injected into the internal carotid arteries in 17 cases and into the jugular veins in 12 cases). The presence of four zones--the first (or outer), the second (or candelabra), the third (or palmate) and the fourth (or subependymal) zone--of venous convergence was confirmed within the centrum semiovale, particularly in the frontoparietal area. Other venous convergences such as those related to the optic radiation in the para-atrial area were also found. Arterial branching zones were also observed in the areas similar to those of the medullary veins. It appears that these converging zones are created by rapidly growing crossing nerve fiber tracts, i.e., projection, commissural, and association fibers which grow rapidly during intrauterine and postnatal life. Pathogenesis of medullary venous malformation is also discussed from anatomical viewpoint, venoarchitecture of the pial, parenchymal, and subependymal veins and of the dural venous sinuses. The possibility of a similar mechanism (partial, mild, repetitive venoocclusive disease developing over a long period with fluctuating venous pressure) leading to formation of most (if not all) cases of medullary venous malformation and in some, if not many, cases of cerebral vascular malformations [aside from gene abnormality (chromosome 7) in familial cavernous angiomatosis, particularly in Hispanic American or other familial hereditary conditions] has been postulated.


Protein fibrillation and nanoparticle interactions: opportunities and challenges.
Due to their ultra-small size, nanoparticles (NPs) have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. NPs are recognized as promising and powerful tools to fight against the human brain diseases such as multiple sclerosis or Alzheimer's disease. In this review, after an introductory part on the nature of protein fibrillation and the existing approaches for its investigations, the effects of NPs on the fibrillation process have been considered. More specifically, the role of biophysicochemical properties of NPs, which define their affinity for protein monomers, unfolded monomers, oligomers, critical nuclei, and other prefibrillar states, together with their influence on protein fibrillation kinetics has been described in detail. In addition, current and possible-future strategies for controlling the desired effect of NPs and their corresponding effects on the conformational changes of the proteins, which have significant roles in the fibrillation process, have been presented.


[A novel bifunctional in vivo mutation detection system].
A shuttle plasmid pMCLacI/neo with two copies of LacI was integrated into mouse genome and a novel system which could detect in vivo mutation of both expression and silence genes was constructed, enabling the comparative analysis of their mutation spectra and mutant frequencies. 486 fertilized eggs from C57BL/6 mice with microinjected pMCLacI/neo plasmid were transferred into oviducts of 18 pseudo-pregnant mice, and 32 alive offsprings were screened and identified by using PCR and Southern blotting. Genomes of 5 mice had pMCLacI/neo plasmid integrated, as verified by Southern blot after the PCR screening. Only one of the two LacI in pMCLacI/neo was in expression state; and this established a model, that the status in vivo of both gene expression and silencing could be simulated. This kind of mice might be used as a novel bifunctional mutation detection system in vivo.


Accuracy of urinary dipstick testing for pH manipulation therapy.
To determine the accuracy of urinary dipstick testing for pH manipulation therapy. Three commercial brands of dipstick paper were used to measure the pH of 100 fresh urine specimens from patients with urologic diseases. These were all read by an experienced medical technician. The pH of these specimens was also measured with an electrochemical pH meter ("gold standard") performed by another experienced technician. Both were blinded to each other's results. The influence of urinary microscopic findings was also assessed. Student t test and analysis of variance were used to analyze the data. The accuracies of the dipsticks for determining pH were as follows: 54.8% to 92.8% for less than 6, 45% to 97.5% for 6 to 7, 72.2% to 83.3% for greater than 7. One of the dipsticks assessed had the lowest accuracy for all three ranges. There was a statistically significant difference between the performances of the other two as compared with the least accurate one. There were no statistically significant differences between the two more accurate dipsticks. Urinary microscopic findings and other dipstick results did not influence results. The targeted pH range for urinary pH manipulation therapy is 6 to 7. These results indicate that dipstick testing may be applicable to monitor patients on pH manipulation therapy and modify treatment when necessary. The accuracy of the device used for this purpose, however, must be determined before use.


Environmental impacts of industrial activities on floral coverage with special emphasis on detoxification enzyme activities in Cataglyphis savignyi as pollution biomarker.
The present study investigates the environmental impact of industrial activities on floral coverage within the major industrial district of Borg El-Arab City, Egypt. Additionally, it aims to evaluate the detoxification enzymatic activity of Cataglyphis savignyi as a pollution biomarker. To achieve this objective, seasonal soil samples were collected from the studied sites to determine soil properties and heavy metal concentrations. Furthermore, a seasonal specimen of C. savignyi was collected to study the enzymatic activity of acetylcholinesterase (AChE) and glutathione-S-transferase (GST). Heavy metal contamination pollution indices were calculated, and fourteen plant species were identified at the investigated sites for four successive seasons from 2020 to 2021. The soil physicochemical parameters significantly varied in the industrial sites compared to the control site. The accumulation of heavy metal contamination in soil for investigated sites followed the order Ni > As > Pb > Hg. Calculated Cdeg and PLI for industrial 3 revealed a very high degree of contamination, attributed to increased industrial activity from the chemical and silicate factories that characterize this region. The current results highlight the inhibition of GST levels in C. savignyi at the industrial site compared to the control site. In contrast, AChE increases, which might be due to heavy metals enhancing acetylcholine activity at synapses. Consequently, the antioxidant enzymatic activities are useful as biomarkers for assessing and monitoring environmental contamination. In conclusion, this study underscores insects as potent biomarkers for heavy metal contamination, marking a significant advancement in environmental monitoring. These bioindicators offer crucial insights into the impacts of climate change and industrial pollution. The research reveals distinct plant diversity variations and higher heavy metal content in industrial sites, indicating pronounced contamination. Additionally, the study highlights altered enzyme activities in insects, emphasizing their utility as biomarkers for assessing environmental contamination. This work represents a substantial leap forward in comprehending the complex dynamics between contamination and ecological balance.


A new toolbox for combining magnetoencephalographic source analysis and cytoarchitectonic probabilistic data for anatomical classification of dynamic brain activity.
Size and location of activated cortical areas are often identified in relation to their surrounding macro-anatomical landmarks such as gyri and sulci. The sulcal pattern, however, is highly variable. In addition, many cortical areas are not linked to well defined landmarks, which in turn do not have a fixed relationship to functional and cytoarchitectonic boundaries. Therefore, it is difficult to unambiguously attribute localized neuronal activity to the corresponding cortical areas in the living human brain. Here we present new methods that are implemented in a toolbox for the objective anatomical identification of neuromagnetic activity with respect to cortical areas. The toolbox enables the platform independent integration of many types of source analysis obtained from magnetoencephalography (MEG) together with probabilistic cytoarchitectonic maps obtained in postmortem brains. The probability maps provide information about the relative frequency of a given cortical area being located at a given position in the brain. In the new software, the neuromagnetic data are analyzed with respect to cytoarchitectonic maps that have been transformed to the individual subject brain space. A number of measures define the degree of overlap between and distance from the activated areas and the corresponding cytoarchitectonic maps. The implemented algorithms enable the investigator to quantify how much of the reconstructed current density can be attributed to distinct cortical areas. Dynamic correspondence patterns between the millisecond-resolved MEG data and the static cytoarchitectonic maps are obtained. We show examples for auditory and visual activation patterns. However, size and location of the postmortem brain areas as well as the inverse method applied to the neuromagnetic data bias the anatomical classification. Therefore, the adaptation to the respective application and a combination of the objective quantities are discussed.


Ultrasonic diagnosis of duplication cysts in children.
Real time ultrasound is an excellent method of detecting cystic lesions in the child's abdomen. Its accuracy in the diagnosis of intestinal duplication cysts is enhanced when it is followed by a barium study. These cysts may present a variety of ultrasonic appearances and the spectrum of findings is well represented by three consecutive cases diagnosed in 1983.