Site-directed mutagenesis of cytochrome P450eryF: implications for substrate oxidation, cooperativity, and topology of the active site.
The role of five active-site residues (Phe-78, Gly-91, Ser-171, Ile-174, and Leu-175) has been investigated in P450eryF, the only bacterial P450 known to show cooperativity. The residues were selected based on two-ligand-bound P450eryF structures and previous mutagenesis studies of other cytochromes P450. To better understand the role of these residues in substrate catalysis and cooperativity, each mutant was generated in the wild-type and A245T background, a substitution that enables P450eryF to oxidize testosterone and 7-benzyloxyquinoline (7-BQ). Replacement of Phe-78 with tryptophan decreased cooperativity of 9-aminophenanthrene binding, with little effect on testosterone binding or oxidation. Interestingly, substitution of Gly-91 with alanine or phenylalanine abolished the type-I spectral change elicited by testosterone and significantly decreased testosterone hydroxylation. However, G91A/A245T showed a 4-fold higher k(cat) value with 7-BQ compared with A245T. Replacement of Ser-171 with alanine or phenylalanine did not alter cooperativity of testosterone binding but significantly decreased binding affinity and oxidation of testosterone and 7-BQ. The only mutant that exhibited an increased testosterone binding affinity and increased rates of testosterone and 7-BQ oxidation was I174F. Substitution of Ile-175 with phenylalanine decreased testosterone and 7-BQ oxidation. Reaction with phenyldiazene showed that P450eryF may be much more open above pyrrole ring B than other cytochromes P450 and indicated significant changes in active-site topology in some of the mutants. The study suggests a crucial role of residues Ser-171, Ile-174, and Leu-175, which are part of a distal ligand site, in addition to the proximal Gly-91 in determining the oxidative properties of P450eryF.


Experiences of continued presence: On the practical consequences of 'hallucinations' in bereavement.
We document the properties of experiences of continued presence (ECPs) helping to resolve controversies about their significance. We used qualitative methods in data collection and analysis. This enabled us to document the properties of ECPs. Narrative biographic interviews were carried out with 17 bereaved informants, and conversation analysis was used to identify the sources of meaning and functions of these experiences. Our informants heard voices of the deceased, saw their images, felt their touch, and sometimes felt their presence unspecified in any of the senses. Analysis revealed that ECPs were meaningfully connected to the immediate environments in which they happened but also to the personal histories of the bereaved. The narratives reveal helpful and destructive potentials of these experiences. In all cases, the functions relied on the relationship with the deceased. The authors warn against oversimplification of ECPs, as significantly contrasting practical consequences commonly occurred within as well as between cases. The findings support the use of talking therapies based on personal meanings to help those disturbed by their experiences of presence. Practitioners should not assume that ECPs are signs of pathology - often they have healing consequences. Where ECPs cause distress, the problem is likely to concern relationship difficulties with the deceased. Therapists can help clients with distressing ECPs by working on the relationship with the deceased.


Increased rate of aspiration pneumonia and poor discharge outcome among acute ischemic stroke patients following intubation for endovascular treatment.
An increased risk of aspiration pneumonia among acute ischemic stroke patients following intubation for endovascular treatment may explain the higher rates of poor outcomes among patients requiring general anesthesia compared with those performed under local sedation. Rates of aspiration pneumonia and its contribution to poor outcome at discharge (modified Rankin score ≥ 3), and in-hospital mortality were analyzed among endovascularly treated acute ischemic stroke patients at two university-affiliated comprehensive stroke centers. Logistic regression model was used to assess the contribution of intubation and aspiration pneumonia on poor outcome after adjusting for potential confounders. There were 136 acute ischemic stroke patients who received endovascular treatment: 83 patients received local sedation without intubation and 53 patients were intubated. The rates of aspiration pneumonia were 12 (14%) in endovascularly treated patients not intubated, and 12 (23%) in endovascularly treated intubated patients. Rates of poor outcomes were 46 (55%) in the non-intubated endovascularly treated patients, and 44 (83%) in intubated endovascularly treated patients. After adjusting for age, gender, National Institutes of Health Stroke Scale (NIHSS) score strata, poor outcome at discharge (OR 2.9, 95% CI 1.2-7.4) (P = 0.0243) and in-hospital mortality (OR 4.5, 95% CI 1.5-12.5) (P = 0. 0.0046) were significantly higher among intubated patients. After adjusting for pneumonia, the effect of intubation on poor outcome at discharge (OR 2.7, CI 1.1-7.1) (P = 0.0006) and in-hospital mortality (OR 4.4, CI 1.6-12.5) (P = 0.00051) remained significant in the multivariate model. Careful consideration should be exercised when emergently intubating acute ischemic stroke patients for endovascular treatment, because the rate of death and disability appears to be high. This increased rate is not explained by higher rates of subsequent aspiration pneumonia.


The Mollring Cutter remote endarterectomy: preliminary experience with a new endovascular technique for treatment of occlusive superficial femoral artery disease.
To evaluate the feasibility and efficacy of the Mollring Cutter remote endarterectomy (EA) technique in the treatment of occlusive superficial femoral artery (SFA) disease. A new device was developed to perform remote EA of occluded SFAs through a single groin incision. The technique initially uses a conventional ring stripper, which is exchanged for a double-ring cutter that transects the distal atheroma core. The entire core and cutter are removed simultaneously, and a Palmaz stent is implanted to secure the distal intimal flap. Twenty-six consecutive patients with disabling claudication or critical ischemia were treated for long segment occlusions (n = 23) and multiple stenoses (n = 3). Patients were evaluated on the intention-to-treat basis. Clinical and anatomic success was achieved in all 26 SFAs. Average length of the endarterectomized segments was 29.9 cm (range 23 to 41). Technical problems were encountered intraoperatively in four patients, including one who required a second incision at the distal SFA to retrieve a broken ring. Recovery was uneventful in all patients. At up to 6-month follow-up, one reocclusion has been seen at 5 months. Based on this early experience, remote EA with the Mollring Cutter appears to be feasible and effective method for treating occlusive SFA disease. Obviating the need for a second incision at knee level, this technique offers a less invasive approach that should facilitate postoperative recovery and earlier discharge.


Autoantibodies against AT1-receptor and alpha1-adrenergic receptor in patients with hypertension.
This study will explore the autoantibodies against AT1-receptor and alpha1-adrenergic receptor in patients with hypertension. Forty normotensives and 194 patients with hypertension were recruited for participation in this study. All patients accepted systemic combination drug treatment for antihypertension. According to the treatment results and the definition of refractory hypertension, the patients were divided into two groups: a refractory hypertension group and a non-refractory hypertension group. The epitope of the 2nd extracellular loop of type 1 angiotensin (AT1) receptor and alpha1-adrenergic receptor were synthesized and used as antigens to screen the autoantibodies against AT1-receptor and alpha1-adrenergic receptor by ELISA. The plasma renin activity and concentration of angiotensin II and catecholamine were also examined. The positive rates of the autoantibodies against AT1-receptor and alpha1-adrenergic receptor in patients with hypertension, 26.8% (52/194) and 25.3% (49/194), respectively, were higher than those in normotensives (7.5% and 5%)(p < 0.01). Further investigation showed that the frequencies of the autoantibodies against AT1-receptor and alpha1-adrenergic receptor in patients with refractory hypertension, 42.9% (42/98) and 36.7% (36/98), respectively, were higher than those in patients with non-refractory hypertension under systematic treatment (10.4% and 13.5%)(p < 0.01). The levels of circulating angiotensin II, catecholamine, proteinuria and serum creatine were also higher in the refractory hypertension group than in the non-refractory hypertension group. The findings showed that the frequencies of autoantibodies against AT1-receptor and alpha1-adrenergic receptor were higher in patients with hypertension, particularly in those with refractory hypertension, and that these autoantibodies might play a role in the pathogenesis of hypertension.


Measurement of acetabular cup anteversion with the circle theorem.
Malposition of the acetabular cup is the major risk factor of dislocation after total hip arthroplasty. Postoperatively, measuring of acetabular cup anteversion is very difficult. The new method for measuring acetabular cup anteversion on the plain radiograph of the hip with one of the circle theorems in the basic geometry was created. An all-polyethylene acetabular cup with known angle of radiographic anteversion was mouthed to the pelvic bone. Antero-posterior hip and pelvis radiographs were taken with the cup in randomly 15 different angles of anteversion. These were reviewed by 3 orthopedic residents. All data from 3 observers were collected and examined for the accuracy, inter-observers reliability and intra-observer reliability of this method. Two films (AP radiograph of the hip and the pelvis) method was used for distinguish between anteversion and retroversion. The measurements of radiographic anteversion have the accuracy of plus or minus 2 degrees. The reliability coefficients of inter-observer variation in the first and second measurements for all definitions of anteversion are high. Pair t-test showed no significant different between value of the first and the second measurements for all definitions in all observers. The intra- and inter-observer variations were 3 degrees or less for all definitions. The Acetabular cup anteversion measurement using the circle theorem iseasily to perform with high accuracy and consistency for all definitions of cup anteversion.


Development of Novel Superabsorbent Hybrid Hydrogels by E-Beam Crosslinking.
In this study, several superabsorbent hybrid hydrogel compositions prepared from xanthan gum (XG)/sodium carboxymethylcellulose (CMC)/graphene oxide (GO) were synthesized by e-beam radiation crosslinking. We studied and evaluated the effects of GO content from the chemical structure of the hydrogels according to: sol-gel analysis, swelling degree, diffusion of water, ATR-FTIR spectroscopy, network structure, and dynamic mechanical analysis. The gel fraction and swelling properties of the prepared hydrogels depended on the polymer compositions and the absorbed dose. The hybrid XGCMCGO hydrogels showed superabsorbent capacity and reached equilibrium in less than 6 h. In particular, the XGCMCGO (70:30) hydrogel reached the highest swelling degree of about 6000%, at an irradiation dose of 15 kGy. The magnitude of the elastic (G') and viscous (G″) moduli were strongly dependent on the absorbed dose. When the degree of crosslinking was higher, the G' parameter was found to exceed 1000 Pa. In the case of the XGCMCGO (80:20) hydrogel compositions, the Mc and ξ parameters decreased with the absorbed dose, while crosslinking density increased, which demonstrated that we obtained a superabsorbent hydrogel with a permanent structure.


The correlation between reactive oxygen species and histopathology of the liver, gut, and kidneys in animals with elevated intra-abdominal pressure.
Clinical and experimental studies have shown that the laparoscopic procedure provides a typical model of ischemia-reperfusion injury in the organs by oxygen-derived free radicals. A pneumoperitoneum produces ischemia during insufflation and reperfusion during desufflation. The aim of this study was to assess the causative role of free radical-mediated reactions in tissue damage under different intra-abdominal insufflation pressures. Thirty five mature New Zealand white rabbits were assigned to three groups of 10 animals. In groups 1, 2, and 3, the designated pressures of 10, 15, and 20 mm Hg, respectively. The remaining 5 animals underwent laparotomy, using a 10-cm midline incision taken as group 4 (control). Blood samples were collected before (0 minutes) and at the end of the procedure (60 minutes). After the collection of the last blood samples, all animals were sacrificed and the samples from the liver, kidney, and gut were obtained for histologic evaluation and also measurements of tissue malondialdehyde (MDA) levels. The nitric oxide levels were not changed in groups 1 and 2, but increased significantly in group 3. Tissue MDA levels were significantly higher in groups 1 and 2 than groups 3 and 4. Histopathologic examination of the kidney revealed some findings of reversible hypoxic cell injury, including acute cellular swelling, vascular congestion, and some early findings of irreversible injury, such as lysis of the cytoplasmic membrane in all groups and focal parancymal bleeding area in only group 3 as a consequence of increased pressure. Liver histology revealed cellular swelling and karyorhexis in hepatocytes in group 1, whereas only congestion and sinusoidal dilatation was observed in groups 2 and 3. Our experimental study showed that abdominal insufflation causes ischemia and free radical production, which seems responsible for the cell damage that occured during laparoscopic surgery.


CDC2 is down-regulated by ionizing radiation in a p53-dependent manner.
The mammalian cellular response to ionizing radiation results in delays in progression through the cell cycle at several checkpoints and includes alterations in the activity of cyclin-dependent kinases. The product of the CDC2 gene is a key kinase involved in cell cycle progression. The signaling events that regulate its expression after exposure to DNA-damaging agents are not known. We show that cdc2 mRNA and protein are down-regulated after irradiation of normal human and mouse fibroblasts with doses as low as 0.5 Gy. This down-regulation is preceded by induction of p53 and p21Waf1 proteins. In human cells in which p53 was nonfunctional and in p53-/- or p21-/- mouse embryo fibroblasts, no effect of ionizing radiation on p34cdc2 expression levels was observed. These findings indicate that CDC2 down-regulation after irradiation is p53-dependent and involves the cyclin-dependent kinase inhibitor p21Waf1 as a negative factor in the control of CDC2 expression. Correspondence between the delay in initiation of DNA synthesis in irradiated cells and the down-regulation of CDC2 is described.


Theoretical and experimental considerations of the pseudo-first-order approximation in conventional kinetic analysis of IAsys biosensor data.
The validity of the conventional interpretation of IAsys biosensor profiles in terms of pseudo-first-order kinetic behavior is subjected to closer scrutiny by its application to simulated data for low- and high-affinity interactions between ligate and immobilized ligand. As might reasonably have been expected, analysis of the simulated data for the low-affinity system (association equilibrium constant of 10(5) M-1) in such terms returned the input association and dissociation rate constants (10(3) M-1 s-1 and 10(-2) s-1, respectively)-a consequence of essential compliance with the assumed constancy of ligate concentration in the liquid phase. For the high-affinity interaction (ka = 10(5) M-1 s-1, kd = 10(-2) s-1, KAX = 10(7) M-1) the ligate concentration was depleted by up to 35%, and hence its assumed constancy was clearly an untenable approximation. Whereas no symptomatic evidence of such violation (apart from the return of incorrect estimates of ka and kd) was evident from pseudo-first-order kinetic analysis of the adsorption profiles, the corresponding analysis of desorption profiles was more informative in that the data deviated demonstrably from pseudo-first-order kinetic behavior. A second-order kinetic analysis was therefore developed and shown to be applicable to adsorption and desorption profiles, irrespective of the validity or otherwise of the pseudo-first-order kinetic approximation. Experimental results obtained for the interaction of histidine-rich glycoprotein with immobilized IgG were then used to illustrate various features of the pseudo-first-order and second-order kinetic analyses, and to determine from the second-order analysis an association equilibrium constant of 2 x 10(8) M-1, which is 20-fold greater than the value obtained by interpretation of the profiles in terms of pseudo-first-order kinetic behavior.


Gene expression profile in the endometrium on the day of oocyte retrieval after ovarian stimulation with low-dose hCG in the follicular phase.
The past decade has seen growing interest in ovarian stimulation protocols with GnRH antagonists in an effort to reduce the incidence of potential complications, such as cyst formation and ovarian hyperstimulation syndrome, and thus improve the clinical experience for patients. Current assisted reproductive technique programmes also increasingly utilize milder protocols for ovarian stimulation. In a recently published randomized controlled trial, we showed that low-dose hCG can be utilized clinically to replace recombinant FSH (rFSH) during the late follicular phase in a GnRH antagonist protocol. This regimen leads to a significant reduction in rFSH consumption, while the ICSI outcome, in terms of oocyte yield and ongoing pregnancy rate, remains comparable with the control regimen of rFSH plus a GnRH antagonist. In the present study, the influence of the administration of low-dose hCG on the endometrium was assessed. A comparison was made between two protocols for ovarian stimulation with GnRH antagonists, namely the classical protocol with rFSH and the protocol with low-dose hCG in the late follicular phase. We analysed the morphological pattern and gene expression profile of human endometrium on the day of oocyte retrieval. No morphological differences were observed and only a minimal set of 65 differentially expressed probe sets between the treatment groups were identified, enabling a similar efficacy to support implantation.


HIV/AIDS in South Africa: an overview.
This paper presents an overview of the development of HIV/AIDS in South Africa, taking into consideration the social context and analyzing the factors most likely to have influenced its spread as well as the societal response to it. The authors argue that macro factors such as social and political structures, in addition to behavioral ones, have combined to shape the course of the epidemic. Since various factors linked to social inequalities have combined to shape the pattern and growth of the HIV/AIDS epidemic in South Africa, it is inappropriate to focus on only one dimension in an attempt to combat the epidemic. Following the psycho-socio- environmental model, all potential contributing elements need to be addressed simultaneously. This calls for a true interdisciplinary and multi-sectorial approach. It also requires great commitment as well as strong political will.


Odorant Normative Data for Use in Olfactory Memory Experiments: Dimension Selection and Analysis of Individual Differences.
The present study reports normative ratings for 200 food and non-food odors. One hundred participants rated odors across measures of verbalisability, perceived descriptive ability, context availability, pleasantness, irritability, intensity, familiarity, frequency, age of acquisition, and complexity. Analysis of the agreement between raters revealed that four dimensions, those of familiarity, intensity, pleasantness, and irritability, have the strongest utility as normative data. The ratings for the remaining dimensions exhibited reduced discriminability across the odor set and should therefore be used with caution. Indeed, these dimensions showed a larger difference between individuals in the ratings of the odors. Familiarity was shown to be related to pleasantness, and a non-linear relationship between pleasantness and intensity was observed which reflects greater intensity for odors that elicit a strong hedonic response. The suitability of these data for use in future olfactory study is considered, and effective implementation of the data for controlling stimuli is discussed.


[Gene mutation pattern of Gilbert's syndrome combined with viral hepatitis and its relationship with the exploration of clinical data].
Objective: To study whether gene mutation pattern of Gilbert's syndrome (GS) is combined with viral hepatitis and its relationship with relevant clinical data. Methods: Clinical data of GS patients combined with viral hepatitis who was admitted to the Department of Infectious Diseases of Henan Provincial People's Hospital from August 2013 to December 2018 was retrospectively analyzed. The relationship between gene mutation pattern, general data (age, gender, etc.) and liver biochemical indexes was analyzed. The differences of the above data in patients with or without combined viral hepatitis were analyzed. The measurement data were compared by t-test. The categorical data was compared by the χ (2) test. The median and interquartile range of non-normally distributed data was used to indicate the central and discrete tendency. Results: A total of 107 GS eligible cases data were collected. The male to female ratio was 4.94:1 (89:18). The average age of onset was (36.36 ± 12.51) years. Alanine aminotransferase and total bilirubin levels were normal or slightly elevated, while aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase were all within the normal range. There were 49 cases in the combined viral hepatitis group (36 cases with HBV and 13 cases with HCV), and 58 cases in the GS alone group. Total bilirubin level in GS alone group was higher than the combined viral hepatitis group (z = 0.035, P < 0.05), and there were no statistically significant differences in gender, age, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyltransferase (P > 0.05). Uridine diphosphate glucuronide transferase 1A1 (UGT1A1), specifically encoded by GS was detected in all 107 cases. Mutations was mainly occurred in the upstream promoter PBREM-3263 (-3279) (86 cases) and TATA box TA insertion mutation (71 cases), and GGA-AGA Gly71Arg (57 cases) mutation in EXON1 of the coding region. All mutation forms had manifestations of homozygous and heterozygous abnormalities. The combined incidence of main mutation forms in the genetic testing data were sequenced as: A2 + B2 + C2 (17 cases, 25.23%), A1 + B1 (17 cases, 15.89%), A2 (11 cases, 10.28%), C2 (10 Cases, 9.34%), A2 + B2 (7 cases, 6.54%), A1 + B2 (7 cases, 6.54%), C1 (7 cases, 6.54%), and there was no statistically significant difference between different mutation combinations in patients with or without hepatitis (P > 0.05). The results of total data analysis showed that the total bilirubin level in the single-site mutation group was higher than the multi-site mutation group (Z=2.019, P = 0.043), and other biochemical indicators had no effect (P > 0.05) and the differences were not statistically significant. Further analysis showed that the total bilirubin level of the single-site mutation subgroup in the GS alone group was higher than the multi-site mutation subgroup (Z = 1.999, P = 0.046), and the statistical difference was similar to the combined viral hepatitis group (P > 0.05). Different mutation combinations had no effect on biochemical indexes, and had no relationship with combined viral hepatitis (P > 0.05). Conclusion: GS is common in patients with combined viral hepatitis, and there is no significant difference between the incidence of gene mutation, mutation forms, biochemical indexes, and non-hepatitis group. The increase in the number of GS mutation sites does not aggravate the deterioration of bilirubin levels due to the decrease in the content and activity of uridine diphosphate glucuronosyltransferase, and the combination of different mutation sites does not affect the changes of various biochemical indexes, and at the same time it is not related to hepatitis.


Outcome of lower-intensity allogeneic transplantation in non-Hodgkin lymphoma after autologous transplantation failure.
We studied the outcome of allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning regimens (reduced-intensity conditioning and nonmyeloablative) in patients with non-Hodgkin lymphoma who relapsed after autologous hematopoietic stem cell transplantation. Nonrelapse mortality, lymphoma progression/relapse, progression-free survival (PFS), and overall survival were analyzed in 263 patients with non-Hodgkin lymphoma. All 263 patients had relapsed after a previous autologous hematopoietic stem cell transplantation and then had undergone allogeneic hematopoietic stem cell transplantation from a related (n = 26) or unrelated (n = 237) donor after reduced-intensity conditioning (n = 128) or nonmyeloablative (n = 135) and were reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2006. The median follow-up of survivors was 68 months (range, 3-111 months). Three-year nonrelapse mortality was 44% (95% confidence interval [CI], 37%-50%). Lymphoma progression/relapse at 3 years was 35% (95% CI, 29%-41%). Three-year probabilities of PFS and overall survival were 21% (95% CI, 16%-27%) and 32% (95% CI, 27%-38%), respectively. Superior Karnofsky Performance Score, longer interval between transplantations, total body irradiation-based conditioning regimen, and lymphoma remission at transplantation were correlated with improved PFS. Allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning is associated with significant nonrelapse mortality but can result in long-term PFS. We describe a quantitative risk model based on pretransplantation risk factors to identify those patients likely to benefit from this approach.


L-arginine-derived nitric oxide: a major determinant of uveal blood flow.
The effect of inhibition of the L-arginine-nitric oxide pathway on regional ocular blood flow was studied in anaesthetized Beagle dogs. Under control conditions (mean arterial blood pressure 105 +/- 6 mmHg) trapping of 11 and 15-microns-diameter tracer microspheres revealed the following regional blood flows (ml min-1 g-1): retina 0.065 +/- 0.016, choroid 5.72 +/- 0.32, ciliary body 0.77 +/- 0.11, iris 0.18 +/- 0.04. After i.v. infusion of nitro-L-arginine methylester (20 mg kg-1), a potent inhibitor of nitric oxide production from L-arginine, mean arterial blood pressure increased from 105 +/- 6 mmHg by 19% to a new steady-state level of 125 +/- 7 mmHg. This increase of arterial blood pressure extended over 3 hr and was reversible after i.v. infusion of L-arginine (100 mg kg-1 over 10 min). Despite the increase in blood pressure following infusion of nitro-L-arginine methylester blood flow of choroid, ciliary body, and iris were significantly decreased by 40, 40 and 48%, respectively. Retinal blood flow did not change significantly (-12%). These results suggest that the L-arginine-nitric oxide pathway is of major importance for the adjustment of uveal blood flow under resting physiological conditions.


Application of F-18-sodium fluoride (NaF) dynamic PET-CT (dPET-CT) for defect healing: a comparison of biomaterials in an experimental osteoporotic rat model.
The aim of the current study was to measure and compare the effect of various biomaterials for the healing of osteoporotic bone defects in the rat femur using 18F-sodium fluoride dPET-CT. Osteoporosis was induced by ovariectomy and a calcium-restricted diet. After 3 months, rats were operated on to create a 4-mm wedge-shaped defect in the distal metaphyseal femur. Bone substitution materials of calcium phosphate cement (CPC), composites of collagen and silica, and iron foams with interconnecting pores were inserted. Strontium or bisphosphonate, which are well known for having positive effects in osteoporosis treatment, were added into the materials. Eighteen weeks after osteoporosis induction and 6 weeks following femoral surgery, dPET-CT studies scan were performed with 18F-Sodium Fluoride. Standardized uptake values (SUVs) and a 2-tissue compartmental learning-machine model (K1-k4, vessel density [VB], influx [ki]) were used for quantitative analysis. k3, reflecting the formation of fluoroapatite, revealed a statistically significant increase at the biomaterial-bone interface due to the Sr release from strontium-modified calcium phosphate cement (SrCPC) compared to CPC, which demonstrated enhanced new bone formation. In addition, k3 as measured in the porous scaffold silica/collagen xerogel (Sc-B30), showed a significant increase based on Wilcoxon rank-sum test (p<0.05) as compared with monolithic silica/collagen xerogel (B30) in the defect region. Furthermore, ki, reflecting the net plasma clearance of tracer to bone mineral measured in the iron foam with coating of the bisphosphonate zoledronic acid (Fe-BP), was enhanced as compared with plain iron foam (Fe) in the defect region. k3 was the most significant parameter for the characterization of healing processes and revealed the best differentiation between the 2 different biomaterials. PET scanning using 18F-sodium fluoride seems to be a sensitive and useful method for evaluation of bone healing after replacement with these biomaterials.


Cavity-Suppressing Electrode Integrated with Multi-Quantum Well Emitter: A Universal Approach Toward High-Performance Blue TADF Top Emission OLED.
A novel device structure for thermally activated delayed fluorescence (TADF) top emission organic light-emitting diodes (TEOLEDs) that improves the viewing angle characteristics and reduces the efficiency roll-off is presented. Furthermore, we describe the design and fabrication of a cavity-suppressing electrode (CSE), Ag (12 nm)/WO3 (65 nm)/Ag (12 nm) that can be used as a transparent cathode. While the TADF-TEOLED fabricated using the CSE exhibits higher external quantum efficiency (EQE) and improved angular dependency than the device fabricated using the microcavity-based Ag electrode, it suffers from low color purity and severe efficiency roll-off. These drawbacks can be reduced by using an optimized multi-quantum well emissive layer (MQW EML). The CSE-based TADF-TEOLED with an MQW EML fabricated herein exhibits a high EQE (18.05%), high color purity (full width at half maximum ~ 59 nm), reduced efficiency roll-off (~ 46% at 1000 cd m-2), and low angular dependence. These improvements can be attributed to the synergistic effect of the CSE and MQW EML. An optimized transparent CSE improves charge injection and light outcoupling with low angular dependence, and the MQW EML effectively confines charges and excitons, thereby improving the color purity and EQE significantly. The proposed approach facilitates the optimization of multiple output characteristics of TEOLEDs for future display applications.


Nuclear denotation and increased incidence of cancer: a present concern in cancer research.
The recent destruction of the nuclear electricity plant in Japan has led to nuclear leakage. The nuclear denotation has become the present issue of concern. In oncology, there is no doubt that exposure to nuclear leakage can cause cancer. In this particular brief article, the author discusses the existing evidence of nuclear denotation and the incidence of cancer.


Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries.
Metabolic enzyme variation and other patient and environmental characteristics influence smoking behaviors, treatment success, and risk of related disease. Population-specific variation in metabolic genes contributes to challenges in developing and optimizing pharmacogenetic interventions. We applied a custom genome-wide genotyping array for addiction research (Smokescreen), to three laboratory-based studies of nicotine metabolism with oral or venous administration of labeled nicotine and cotinine, to model nicotine metabolism in multiple populations. The trans-3'-hydroxycotinine/cotinine ratio, the nicotine metabolite ratio (NMR), was the nicotine metabolism measure analyzed. Three hundred twelve individuals of self-identified European, African, and Asian American ancestry were genotyped and included in ancestry-specific genome-wide association scans (GWAS) and a meta-GWAS analysis of the NMR. We modeled natural-log transformed NMR with covariates: principal components of genetic ancestry, age, sex, body mass index, and smoking status. African and Asian American NMRs were statistically significantly (P values ≤ 5E-5) lower than European American NMRs. Meta-GWAS analysis identified 36 genome-wide significant variants over a 43 kilobase pair region at CYP2A6 with minimum P = 2.46E-18 at rs12459249, proximal to CYP2A6. Additional minima were located in intron 4 (rs56113850, P = 6.61E-18) and in the CYP2A6-CYP2A7 intergenic region (rs34226463, P = 1.45E-12). Most (34/36) genome-wide significant variants suggested reduced CYP2A6 activity; functional mechanisms were identified and tested in knowledge-bases. Conditional analysis resulted in intergenic variants of possible interest (P values < 5E-5). This meta-GWAS of the NMR identifies CYP2A6 variants, replicates the top-ranked single nucleotide polymorphism from a recent Finnish meta-GWAS of the NMR, identifies functional mechanisms, and provides pan-continental population biomarkers for nicotine metabolism. This multiple ancestry meta-GWAS of the laboratory study-based NMR provides novel evidence and replication for genome-wide association of CYP2A6 single nucleotide and insertion-deletion polymorphisms. We identify three regions of genome-wide significance: proximal, intronic, and distal to CYP2A6. We replicate the top-ranking single nucleotide polymorphism from a recent GWAS of the NMR in Finnish smokers, identify a functional mechanism for this intronic variant from in silico analyses of RNA-seq data that is consistent with CYP2A6 expression measured in postmortem lung and liver, and provide additional support for the intergenic region between CYP2A6 and CYP2A7.


Did social distancing measures deployed for SARS-CoV-2/COVID-19 control have an impact on invasive meningococcal disease?
We investigated the impact of social distancing measures, used to contain or mitigate SARS-CoV-2 spread, on the transmission of invasive meningococcal disease (IMD) in Italy. To this end, the temporal correlation between the implementation of lockdown measures in 2020 and IMD incidence was evaluated. A dramatic decline of IMD incidence was observed, suggesting that the measures applied to contain SARS-CoV-2 in Italy affected other infectious diseases transmitted through direct contact and droplets, at least in the early phase of the COVID-19 pandemic.


Computer simulations of a heterogeneous membrane with enhanced sampling techniques.
Computational determination of the equilibrium state of heterogeneous phospholipid membranes is a significant challenge. We wish to explore the rich phase diagram of these multi-component systems. However, the diffusion and mixing times in membranes are long compared to typical time scales of computer simulations. Here, we evaluate the combination of the enhanced sampling techniques molecular dynamics with alchemical steps and Monte Carlo with molecular dynamics with a coarse-grained model of membranes (Martini) to reduce the number of steps and force evaluations that are needed to reach equilibrium. We illustrate a significant gain compared to straightforward molecular dynamics of the Martini model by factors between 3 and 10. The combination is a useful tool to enhance the study of phase separation and the formation of domains in biological membranes.


Lupus-specific autoantibodies in concomitant human immunodeficiency virus and systemic lupus erythematosus: case report and literature review.
To report a case of systemic lupus erythematosus (SLE) in a patient with human immunodeficiency virus (HIV) infection. We also reviewed the medical literature for similar cases to assess the role of "lupus-specific antibodies" in the diagnosis of SLE in the presence of HIV infection. We described the presentation, clinical course, and serologic studies of our patient and reviewed the English language medical literature from 1966 to 1999 using MEDLINE with the keywords "SLE," "HIV," "acquired immune deficiency syndrome (AIDS)," and "autoantibodies." Our patient with long-standing HIV infection presented with fever, arthralgias and arthritis, photosensitive rash, oral ulcers, alopecia, headache, pleuritic chest pain, and lymphadenopathy. Laboratory testing showed leukopenia, thrombocytopenia, antibodies against ribonucleoprotein, Smith, and ribosomal-P, as well as immunoglobulin G anticardiolipin antibodies. Review of the literature revealed only 25 cases of concomitant SLE and HIV. In these cases, rheumatologic signs and symptoms were common in HIV and overlapped significantly with SLE. Autoantibodies also occurred frequently in both diseases. There are very few reported cases of concomitant HIV and SLE. These diseases may be largely mutually exclusive, but distinguishing the two can be difficult because of the high degree of rheumatic complaints and autoantibodies in HIV-positive patients. As illustrated by the patient presented, SLE should be considered in HIV-positive patients with rheumatologic complaints.


Suicidal shotgun wound employing a shotgun barrel, a shotgun shell, and a BB.
A vast majority of firearms-related suicides involve the conventional use of a properly functioning, intact firearm. Occasionally, forensic investigators encounter a case wherein the firearm suicide victim employs some form of unconventional use of a weapon, or utilizes an unusual weapon type. In this case report, the authors present an unusual case in which a man committed suicide by using a shotgun shell, a shotgun barrel (separate from the rest of the gun), and a BB. Some confusion as to the cause and manner of death was present during the initial scene investigation. Examination at autopsy revealed the cause of death to be a shotgun wound of the chest and prompted further scene investigation. Therefore, this case serves as another example of the importance of cooperation between scene investigators and forensic pathologists when investigating a death. A review of suicidal firearm cases using unconventional means and/or firearms is presented.


One-pot construction of sterically challenging and diverse polyarylphenols via transition-metal-free benzannulation and their potent in vitro antioxidant activity.
This paper reports the novel and efficient one-pot synthesis of highly functionalized polyarylphenols from readily available 1,3-diarylpropan-2-ones and chalcones or cinnamaldehyde derivatives via benzannulation under transition-metal-free and aerobic conditions. This benzannulation proceeds through cascade Michael addition/intramolecular aldol/tautomerization/oxidation. This protocol produces various tetra- and tri-aryl substituted phenols in moderate to good yield. The synthesized compounds exhibited potent antioxidant activities compared to the standard BHT.


Relationships of leaf Fatty acids to cold hardening of citrus seedlings.
Three cultivars of citrus with different sensitivities to freezing temperatures (citron, Citrus medica L.; rough lemon, C. limon Burm. F; sour orange, C. aurantium L.) were cold hardened for 4 weeks. Lipids from leaves of hardened and control seedlings were fractionated and analyzed for fatty acids. The absolute amount of triglycerides and phospholipids increased in the leaves upon hardening. With hardening, total linoleic acid also increased 141% in citron, 210% in rough lemon, and 233% in sour orange. Specific increases in linoleic acid were found in triglycerides, in the four phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol), and in neutral lipids more polar than triglycerides. Trans-3-hexadecenoic acid was found only in phosphatidylglycerol.


[From gene to disease; dopamine-beta-hydroxylase deficiency and orthostatic hypotension].
The DBH gene encodes dopamine-beta-hydroxylase (DbetaH), the enzyme that catalyses the formation of norepinephrine from dopamine. Inactivation of this enzyme due to a mutation of the DBH gene causes a selective (nor)-adrenergic failure of the sympathetic nervous system. This manifests as a severe orthostatic syndrome in which sweating and a normal parasympathetic function are preserved. Several mutations of the DBH gene that cause this very rare syndrome have now been identified. Diagnosis is made on the basis of clinical features and the finding of increased plasma dopamine in the near-absence of norepinephrine. A sole finding of absent plasma DbetaH is insufficient, since about 4% of the population have absent DbetaH. This trait cosegregates with a polymorphism in the promoter region of the DBH gene and is not associated with sympathetic failure. The orthostatic syndrome of DbetaH deficiency can be treated with the non-natural amino acid L-dihydroxyphenylserine, which is decarboxylated to norepinephrine by the ubiquitous aromatic-L-amino acid decarboxylase.


[A Case of Severe Peripheral Polyneuropathy Occurring after Entecavir Treatment in a Hepatitis B Patient].
Entecavir (Baraclude®) is an oral antiviral drug used for the treatment of HBV. Entecavir is a reverse transcriptase inhibitor which prevents the HBV from multiplying. Most common adverse reactions caused by entecavir are headache, fatigue, dizziness, and nausea. Until now, there has been no report of peripheral neuropathy as a side effect associated with entecavir treatment. Herein, we report a case of peripheral neuropathy which probably occurred after treatment with entecavir in a hepatitis B patient. The possibility of the occurrence of this side effect should be carefully taken into consideration when a patient takes a high dose of entecavir for a long period of time or has risk factors for neuropathy at the time of initiating entecavir therapy.


Genome Sequencing of Wastewater Confirms the Arrival of the SARS-CoV-2 Omicron Variant at Frankfurt Airport but Limited Spread in the City of Frankfurt, Germany, in November 2021.
Wastewater-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance of Frankfurt Airport by genome sequencing was used to detect SARS-CoV-2 variants entering the region. In November 2021, we found all characteristic mutations of Omicron in wastewater originating from Frankfurt Airport before the first confirmed clinical report from an arriving passenger on 26 November 2021.


Significantly different immunological score in lung adenocarcinoma and squamous cell carcinoma and a proposal for a new immune staging system.
TNM stage is not enough to accurately predict the prognosis of patients with non-small cell lung cancer (NSCLC). This study aimed to establish the immunological score (IS) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), separately, and propose a new staging system in NSCLC. We used the multiplex fluorescent immunohistochemistry (mIHC) technology to detect 17 immune biomarkers of 304 patients with NSCLC. The LASSO-COX regression model was used to establish the ISNSCLC in the training cohorts. The ISNSCLC was then validated in the validation cohort. The constructed ISLUAD contained three immune features: CD4+CD73+ core of tumor (CT), PD-L1+ CT, and IDO+ invasive margin (IM). ISLUSC also contained two immune features: CD8+CD39-CD73- CT, CD8+Tim-3+ IM. In the training cohort, significant prognostic differences were found upon comparing low-ISNSCLC patients with high-ISNSCLC patients. For LUAD, the 5-y disease-free survival (DFS) rates were 54.7% vs. 8.1% and the 5-y overall survival (OS) rates were 82.4% vs. 36% (all P< .0001). For LUSC, the 5-y DFS rates were 74.0% vs. 14.7% and the 5-y OS rates were 78.2% vs. 17.6% (all P< .0001). Multivariate analyses indicated that ISNSCLC was an independent indicator for prognosis. Finally, we combined ISNSCLC with clinicopathological factors to establish a TN-I staging system and two nomogram models for clinical use. The TN-I stage had better prediction accuracy than TNM stage. The newly established ISLUAD and ISLUSC were completely different, and both were excellent indicators for the prognostic prediction. The TN-I stage could effectively improve prognostic accuracy and facilitate clinical application. Abbreviations NSCLC, non-small cell lung cancer; IS, immunological score; mIHC, multiplex fluorescent immunohistochemistry; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; CT, core of tumor; IM, invasive margin; DFS, disease-free survival; OS, overall survival; SITC, the Society for Immunotherapy of Cancer; FFPE, formalin-fixed paraffin-embedded; MWT, microwave treatment; DCA, decision curve analysis; ROC, receiver operating characteristic; AUC, area under the curve; EGFR, epidermal growth factor receptor.


Effect of GnRH injection timing in the production of pronuclear-stage zygotes used for DNA microinjection.
This study was aimed at developing a hormonal treatment protocol in order to optimize the proportion of pronuclear-stage embryos to be used for DNA microinjection in a goat transgenic founder production programme. A total of 46 adult BELE and 47 adult standard goats (1-5 years old) were used as donors and recipients, respectively. They were heat-synchronized using intravaginal sponges containing 60 mg medroxyprogesterone acetate for 10 days with an injection of 125 microg cloprostenol on the morning of the eighth day. Recipients were injected with 400 IU eCG at the time of sponge removal while donors received a total of 133 mg NIH-FSH-P1 (Folltropin-V) given twice daily in decreasing doses over 3 days starting 48 h before sponge removal. Ovulation was induced in donors by injecting 100 microg of GnRH at 24 h (GnRH24) or 36 h (GnRH36) after sponge removal. Embryo recovery was performed by oviduct flushing following a standard mid-ventral laparotomy procedure. The proportion of embryos in the pronuclear stage of development was higher in the GnRH36 group (90% vs 34%, p < 0.01). Embryos were microinjected with a DNA expression cassette followed by transfer to the oviduct of synchronized recipients. A higher, yet not statistically significant, pregnancy rate was found in the recipients transferred with pronuclear-stage embryos compared with those transferred with 2-cell-stage embryos (64% vs 37%, chi-square p = 0.06). One transgenic female founder was produced from the group of recipients transferred with pronuclear-stage microinjected embryos.


Mechanical and Water-Resistant Properties of Eco-Friendly Chitosan Membrane Reinforced with Cellulose Nanocrystals.
Environmentally benign and biodegradable chitosan (CS) membranes have disadvantages such as low mechanical strength, high brittleness, poor heat resistance and poor water resistance, which limit their applications. In this paper, home-made cellulose nanocrystals (CNC) were added to CS to prepare CNC/CS composite membranes through mechanical mixing and solution casting approaches. The effects of CNC dispersion patterns and CNC contents on the properties of composite membranes were studied. The analysis of the surface and cross-section morphology of the membranes showed that the dispersion performance of the composite membrane was better in the case that CNC was dissolved in an acetic acid solution and then mixed with chitosan by a homogenizer (Method 2). CNC had a great length-diameter ratio and CNC intensely interacted with CS. The mechanical properties of the composite membrane prepared with Method 2 were better. With a CNC content of 3%, the tensile strength of the composite membrane reached 43.0 MPa, 13.2% higher than that of the CNC-free membrane. The elongation at break was 41.6%, 56.4% higher than that of the CNC-free membrane. Thermogravimetric, contact angle and swelling analysis results showed that the addition of CNC could improve the heat and water resistance of the chitosan membrane.


Evaluation of the reperfusion syndrome after liver ischemia in the rat.
Hepatic surgery in man often requires a transient interruption of the blood flow to the liver. After the vascular declamping the hepatic reperfusion induces a group of phenomena commonly called "reperfusion injuries." The aim of this study was to evaluate the presence and effect of vasoactive agents that could induce the acute pulmonary arterial hypertension which contributes to reperfusion injury. Wistar rats were used. The hepatic ischemia was induced by crossclamping the whole hepatic hilus for 20, 40, and 60 min. In control experiments a sham operation was performed. Blood samples were collected from the suprahepatic inferior vena cava. Strips of the main pulmonary artery were set up in an isolated organ bath and tested for the response to noradrenaline, adrenaline, KCl, and plasma samples. Plasma levels of catecholamines were determined by high-performance liquid chromatography. Plasma concentration of noradrenaline significantly increased from 1.6 +/- 0.4 (control) to 10.8 +/- 2.9 ng.ml-1 and adrenaline concentration rose from 2.7 +/- 0.7 to 38.7 +/- 7.6 ng.ml-1 after ischemia. Noradrenaline potency, compared to control values, significantly increased after prolonged liver ischemia. The plasma samples collected after prolonged liver ischemia caused a greater contraction of the pulmonary artery than from control plasma. This contraction is partially inhibited by phentolamine. We conclude that hepatic ischemia modifies the response of the pulmonary artery to exogenous noradrenaline. At the same time it induces an increase in the plasma levels of adrenaline and noradrenaline. The resulting combined effect may cause the pulmonary hypertension which has been observed in reperfusion injury.


Timing and predictors of femoral haematoma development after manual compression of femoral access sites.
To identify the timing and predictors of haematoma development after manual compression of femoral arteriotomies. The study involved 239 consecutive patients undergoing cardiac catheterization at King Abdullah University Hospital, Irbid, Jordan. Size and timing of haematoma development were recorded. A total of 33 prespecified variables were evaluated by univariate analysis to identify predictors of haematoma development. These predictors were again analyzed using multivariate logistic regression model. Femoral haematomas developed in thirty nine patients leading to an overall frequency of 16.3%. More than two-thirds (74.4%) of the haematomas occurred later in the bed unit. Only 8 among 33 studied variables were found to be significant predictors of haematoma development upon multivariate analysis. These predictors are low haematocrit level before the procedure, advanced age, wider waist circumference, high systolic blood pressure, multiple artery puncture, longer ACT at the end of the procedure, anticoagulant treatment before procedure, and Glycoprotein IIB/IIIa inhibitors use during the procedure. Identifying predictors of haematoma development at femoral access sites and trying to correct or modify them when possible, can have a major impact on reducing the frequency of this serious complication. If an assessment indicates that a patient is at high risk, then several cautious management strategies should be implemented in this setting prior to performing cardiac catheterization.


Giant secretory multifocal adrenal myelolipoma: a diagnostic dilemma.
A 38-yearr-old man presented with erectile dysfunction and infertility. On examination, he was hypertensive and detected to have a left flank mass. Blood investigations were unremarkable except raised serum noradrenaline levels. Imaging revealed multiple well-defined fat-containing hypodense lesions in left suprarenal area with largest one measuring 14×16 cm, suggestive of left adrenal myelolipoma. Diagnostic dilemma was posed due to discordance between clinical, biochemical and imaging findings. Left adrenal mass resection was planned keeping the possibility of pheochromocytoma. However, histopathology revealed it to be adrenal myelolipoma. Hypertension was resolved in the postoperative period and serum noradrenaline levels were normalised. Final diagnosis of a secretary adrenal myelolipoma was made, which is an extremely rare entity.


[Neurorehabilitation, neurology, rehabilitation medicine].
We have read several publications of great authority on the neurological profession in the last two years in which were expressed assessments of the current situation combined with opinions about neurology and the necessity to reorganize neurological patient care. These articles took up the question of neurorehabilitation too. The authors, who on a daily basis, deal with the rehabilitation of people with disabilities as a consequence of neurological conditions, summarize some important definitions of rehabilitation medicine and the present system of neurological rehabilitation, as it is defined by the rehabilitation profession.


Latest developments in the assessment and management of chronic musculoskeletal pain syndromes in children.
As many as 25% of new patients in pediatric rheumatology clinics present with idiopathic chronic pain and recent data suggest the prevalence of these conditions is increasing. Knowledge of the latest developments in assessment and treatment is critical for providing optimal clinical care. This review summarizes advances published in the past year forwarding our understanding of chronic musculoskeletal pain syndromes in children. Research has recently focused on the impairment associated with chronic pain syndromes in children, issues impacting the diagnosis of these conditions, and the efficacy of pharmacological and psychosocial treatments. No diagnostic criteria have been developed for specific chronic pain syndromes in children; however, data from several studies substantiate the need for thorough assessment of the child and family in multiple domains. In addition, studies have expanded both pharmacologic and psychosocial treatment options for children with these syndromes. Despite a growing body of research on chronic pain syndromes in children, there are no established standards of care. Data continues to support an interdisciplinary approach for effectively assessing and managing these conditions.


A Review on the Evolving Roles of MiRNA-Based Technologies in Diagnosing and Treating Heart Failure.
MiRNA-regulated processes are pivotal in cardiovascular homeostasis and disease. These short non-coding RNAs have ideal properties that could be utilized as potential biomarkers; moreover, their functions as post-transcriptional regulators of mRNA make them interesting therapeutic targets. In this review, we summarize the current state of miRNA-based biomarkers in a variety of diseases leading to heart failure, as well as provide an outlook on developing miRNA-based therapies in the heart failure field.


Aspirin inhibits fractalkine expression in atherosclerotic plaques and reduces atherosclerosis in ApoE gene knockout mice.
To determine the fractalkine expression in the aorta of ApoE (-/-) mice and the effect of high-dose aspirin intervention on fractalkine expression and atherosclerotic lesion formation. Twenty-one male ApoE gene knockout mice were randomized into three groups to receive either placebo in addition to normal mice chow (n = 7), placebo in addition to a high-fat diet (n = 7), or aspirin (58 mg/kg/d) in addition to a high-fat diet (n = 7). After 12 weeks of study, the mice were euthanized and serum cholesterol, thromboxane B(2), and 6-keto-PGF(1alpha) were examined. Fractalkine and cyclooxygenase expression in aorta were measured and the atherosclerotic lesion analyzed. Pathology image analysis showed that the atherosclerotic plaque was the most extensive in the high-fat diet group while the addition of aspirin greatly reduced the severity of the plaque. Both RT-PCR analysis and immunohistochemical analysis showed that fractalkine expression was the strongest in the high-fat diet group and was significantly decreased by aspirin treatment. Serum thromboxane B(2) was lowered by aspirin while 6-keto-PGF(1alpha) and cholesterol remained unchanged. The results of our study indicate that high dose aspirin can improve the atherosclerotic lesion and suppress the fractalkine expression in murine aorta.


Neuromodulation by GABA converts a relay into a coincidence detector.
Modulation of synaptic strength by γ-aminobutyric acid receptors (GABARs) is a common feature in sensory pathways that contain relay cell types. However, the functional impact of these receptors on information processing is not clear. We considered this issue at bushy cells (BCs) in the cochlear nucleus, which relay auditory nerve (AN) activity to higher centers. BCs express GABA(A)Rs, and synaptic inputs to BCs express GABA(B)Rs. We tested the effects of GABAR activation on the relaying of AN activity using patch-clamp recordings in mature mouse brain slices at 34°C. GABA affected BC firing in response to trains of AN activity at concentrations as low as 10 μM. GABA(A)Rs reduced firing primarily late in high-frequency trains, whereas GABA(B)Rs reduced firing early and in low-frequency trains. BC firing was significantly restored when two converging AN inputs were activated simultaneously, with maximal effect over a window of <0.5 ms. Thus GABA could adjust the function of BCs, to suppress the relaying of individual inputs and require coincident activity of multiple inputs.


Can sickness absence be predicted at the pre-placement health assessment?
Pre-placement health assessments may be used not only to assess fitness for work but also to predict sickness absence. A risk assessment based on available evidence is proposed for making such judgements.


Fate of the facet joints after instrumented intertransverse process fusion.
A success or failure of an intertransverse process fusion has been determined by the fusion status of the intertransverse fusion mass alone, and little consideration has been given to the fusion status of the facet joint. The purpose of this study was to assess the fusion status of the facet joints at the fusion level and its impact on the overall fusion outcome. Sixteen patients (19 levels) treated with decompression and intertransverse process fusion using pedicle screw fixation without facet arthrodesis were entered into a cross sectional study in which the fusion status of the intertransverse fusion masses and facet joints at each fusion level were evaluated and combined at an average duration of followup of 35 months (range, 22-61 months). Union rate of the intertransverse process fusion (58%, 22 of 38) was lower than the spontaneous fusion rate of the facet joint (68%, 26 of 38). However, the combination of the two fusion statuses at each fusion level generated 89% of the overall fusion rate (17 of 19 levels). With surgery, all patients had a good or excellent clinical outcome, but the outcome had no relation to the overall fusion status. The results suggest that the fusion status of the facet joint should be considered in determining overall fusion status after combined decompression with instrumented intertransverse process fusion.


SOCS proteins in T helper cell differentiation: implications for allergic disorders?
Asthma, allergic rhinitis and atopic dermatitis are allergic immune disorders characterised by a predominance of T helper 2 (Th2) cells, the resulting elevation of allergen-specific IgE, and mast-cell- and basophil-associated inflammation. The cytokine environment at the site of the initial antigen stimulation determines the direction of Th-cell differentiation into Th1 or Th2 cells. The SOCS (suppressor of cytokine signalling) proteins are implicated in the control of the balance between Th1 and Th2 cells in this process. SOCS3 is predominantly expressed in Th2 cells and inhibits Th1 differentiation; conversely, SOCS5 is expressed predominantly in Th1 cells and inhibits Th2 differentiation. Here, we discuss the role of SOCS proteins in Th-cell differentiation and explore the potential of SOCS proteins as targets for therapeutic strategies in allergic disorders.


Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product.
Using an expression cDNA cloning approach, we examined human tumor cell lines for novel oncogenes that might evade detection by conventional techniques. We isolated a transforming sequence that was highly efficient in transforming NIH 3T3 mouse fibroblasts. DNA sequence analysis identified the gene as the human homolog of a recently cloned alpha subunit of mouse GTP-binding protein G alpha 12. NIH 3T3 cells transfected with G alpha 12 cDNA grew in soft agar and were tumorigenic in nude mice. There were no apparent mutations in the cloned cDNA in comparison with a G alpha 12 cDNA clone isolated from a normal human epithelial cell library, implying that overexpression alone was sufficient to cause NIH 3T3 cell transformation. The observed altered growth properties mediated by G alpha 12 showed a certain degree of dependency on serum factors, and its mitogenic potential was also potently inhibited by suramin treatment.


A new species of lizard genus Potamites from Ecuador (Squamata, Gymnophthalmidae).
Potamitesflavogularis sp. nov. is described from the Napo and Tungurahua Provinces around 1800 m elevation in eastern Ecuador. The new species is closely related, sibling, and sympatric to Potamites cochranae to which it has been previously confused. It is characterized by the absence of isolated basal flounces of spines and presence of calcareous spinules on flounces of the hemipenis, a short (1,30-1,41 times SVL) and slightly compressed tail without tubercles, tympanum slightly recessed, subimbricate ventral scales, lateral body scales lacking conspicuous enlarged tubercles, four longitudinal rows of dorsal tubercles, 6 transverse series of ventral scales, absence of intercalated scales along sides of tail, and absence of tubercles on sides of neck and gular regions. Like their congeners, the new species was found close to vegetation surrounding streams in primary and secondary forests.


Endorectal ultrasound: its role in the diagnosis and treatment of rectal cancer.
With development over the past 25 years of new surgical techniques and neoadjuvant therapy regimens for rectal cancer, physicians now have a range of treatment options that minimize morbidity and maximize the potential for cure. Accurate pretreatment staging is critical, ensuring adequate therapy and preventing overtreatment. Many options exist for staging primary rectal cancer. However, endorectal ultrasound (ERUS) remains the most attractive modality. It is an extension of the physical examination, and can be performed easily in the office. It is cost effective and is generally well tolerated by the patient, without need for general anesthesia. The authors discuss the data currently available on ERUS, including its accuracy and limitations, as well as the technical aspects of performing ERUS and interpreting the results. They also discuss new ultrasound technologies, which may improve rectal cancer staging in the future.


Abscess formation within cerebellar metastatic carcinoma--report of two cases and review of the literature.
The occurrence of an abscess in conjunction with a tumor in the brain is very rare. Only presumptions exist about their origin and manner of dissemination. Preoperative discrimination between a brain tumor with cystic degeneration and a brain abscess within a tumor may be difficult or even impossible. The purpose of this report is to demonstrate the difficulty of such discrimination using conventional CT diagnostics alone. Two patients with abscess formation in association with metastatic carcinoma in the cerebellum are presented and compared with similar cases in the literature. The etiology and the route of dissemination are discussed. In our first patient with previously diagnosed lung carcinoma and a CT showing suspected cerebellar metastasis only, an abscess caused by Propionibacterium acnes was found in the cerebellum and treated surgically. No tumor was recognised during the operation. Post-mortem examination six weeks later revealed the coexistence of remnants of a chronic abscess as well as metastatic lung carcinoma at the operation site. The second patient presented with an enhanced, ring-like cystic cerebellar lesion. During surgery, a purulent exudate with a coagulase-negative type of Staphylococcus species was found within the metastatic carcinoma of unknown origin. Both were radically excised and the patient recovered well. Neither patient had a history of previous infection and the pathway for abscess formation in both patients remained unclear. About 30 cases of abscesses associated with intracranial neoplasms were found in the literature. Including our own report, only three cases of abscesses within metastatic carcinoma have been published. Modern diagnostic tools reported to differentiate more reliably between an abscess and a tumor are diffusion-weighted MR and proton MR spectroscopy techniques. Brain imaging using CT alone may not reliably demonstrate both coexisting lesions or differentiate between them. It is important to know that a metastatic brain lesion can occur in association with a brain abscess and that tissue sampling for pathological as well as microbiological testing is of crucial importance for optimal therapy for both lesions.


Mental health and barriers to the achievement of the 'right to health'.
This paper explores issues relating to access to physical and mental health care for people with mental health problems in light of Australia's endorsement in 2008 of the Convention of the Rights of Persons with Disabilities, which established the right to health and to health care. Interviews were conducted with 10 key stakeholders with legal, policy, clinical and advocacy roles within South Australia and at a national and international level. Participants identified several barriers to the achievement of the right to health for people with mental illness, with discussion highlighting the legal definition of rights, governance of health and mental health, and structural barriers to receipt of care as the primary barriers. The data are explored in relation to social models of disability.


Metabolic evaluation of stone disease patients: a practical approach.
In the last three decades, minimally invasive techniques have progressed significantly, replacing traditional open surgery as the mainstay of stone disease surgical treatment. The challenge for the next millennium remains medical prevention of calcium urolithiasis, a field where less dramatic progress has been achieved during the same period of time. The purpose of this article is to provide the practicing urologist with current practical guidelines for the assessment and management of calcium urolithiasis patients. The recommendations are based on the latest available information regarding the pathogenesis, medical treatment options, and decision-making rationale when managing these challenging patients. Every urolithiasis patient should undergo a basic evaluation, which is considered the minimal essential diagnostic work-up, in order to rule out obvious, treatable systemic causes of urinary stone disease. All patients should be advised about conservative nonspecific preventive measures. High-risk stone patients should have a more extensive metabolic evaluation based on two 24-hour urine samples. Treatment protocols for each patient are tailored individually according to the metabolic evaluation findings.


Lambda red recombineering in Escherichia coli occurs through a fully single-stranded intermediate.
The phage lambda-derived Red recombination system is a powerful tool for making targeted genetic changes in Escherichia coli, providing a simple and versatile method for generating insertion, deletion, and point mutations on chromosomal, plasmid, or BAC targets. However, despite the common use of this system, the detailed mechanism by which lambda Red mediates double-stranded DNA recombination remains uncertain. Current mechanisms posit a recombination intermediate in which both 5' ends of double-stranded DNA are recessed by λ exonuclease, leaving behind 3' overhangs. Here, we propose an alternative in which lambda exonuclease entirely degrades one strand, while leaving the other strand intact as single-stranded DNA. This single-stranded intermediate then recombines via beta recombinase-catalyzed annealing at the replication fork. We support this by showing that single-stranded gene insertion cassettes are recombinogenic and that these cassettes preferentially target the lagging strand during DNA replication. Furthermore, a double-stranded DNA cassette containing multiple internal mismatches shows strand-specific mutations cosegregating roughly 80% of the time. These observations are more consistent with our model than with previously proposed models. Finally, by using phosphorothioate linkages to protect the lagging-targeting strand of a double-stranded DNA cassette, we illustrate how our new mechanistic knowledge can be used to enhance lambda Red recombination frequency. The mechanistic insights revealed by this work may facilitate further improvements to the versatility of lambda Red recombination.


Simultaneous Measurements of Steady State Chlorophyll a Fluorescence and CO(2) Assimilation in Leaves: The Relationship between Fluorescence and Photosynthesis in C(3) and C(4) Plants.
Rates of CO(2) assimilation and steady state chlorophyll a fluorescence were measured simultaneously at different intercellular partial pressures of CO(2) in attached cotton (Gossypium hirsutum L. cv Deltapine 16) leaves at 25 degrees C. Electron transport activity for CO(2) assimilation plus photorespiration was calculated for these experiments. Under light saturating (1750 microeinsteins per square meter per second) and light limiting (700 microeinsteins per square meter per second) conditions there was a good correlation between fluorescence and the calculated electron transport activity at 19 and 200 millibars O(2), and between fluorescence and rates of CO(2) assimilation at 19 millibars but not 200 millibars O(2). The values of fluorescence measured at about 220 microbars intercellular CO(2) were not greatly affected by increasing O(2) from 19 to 800 millibars. Fluorescence increased with light intensity at any one intercellular CO(2) partial pressure. But the values obtained for fluorescence, expressed as a ratio of the maximum fluorescence obtained in DCMU-treated tissue, over the same range of CO(2) partial pressure at 500 microeinsteins per square meter per second were similar to those obtained at 1000 and 2000 microeinsteins per square meter per second. There were two phases in the observed correlation between fluorescence and calculated electron transport activity: an initial inverse relationship at low CO(2) partial pressures which reversed to a positive correlation at higher values of CO(2) partial pressures. Similar results were observed in the C(3) species Helianthus annuus L., Phaseolus vulgaris L., and Brassica chinensis. In all C(4) species (Zea mays L., Sorghum bicolor L., Panicum maximum Jacq., Amaranthus edulis Speg., and Echinochloa frumentacea [Roxb.] Link) examined changes in fluorescence were directly correlated with changes in CO(2) assimilation rates. The nature and the extent to which Q (primary quencher) and high-energy state (q(E)) quenching function in determining the steady state fluorescence obtained during photosynthesis in leaves is discussed.


Multicenter double-blind randomized clinical trial of imidazole salicylate versus ibuprofen in patients with osteoarthrosis.
Imidazole salicylate (750 mg t.i.d.) was compared with ibuprofen (400 mg t.i.d.) in a 30-day multicenter double-blind clinical trial in patients with osteoarthrosis. Both drugs were effective in relieving joint pain and in reducing the duration of morning stiffness. A statistically significant reduction of the severity of these symptoms was observed already one week after the start of treatment, lasting until the end of the study. No significant differences in efficacy were demonstrated between the two drugs throughout the trial. The systemic tolerability, assessed by changes in tests of hematological, liver and kidney function, was excellent with both treatments. The incidence of side effects (mostly gastrointestinal complaints) was fairly low in both groups, and lower in the group treated with imidazole salicylate.


Inpatient palliative care encounter and 30-day readmission among hospitalizations for heart failure.
Aim: To determine the association between inpatient palliative care encounter (PCE) and 30-day rehospitalization. Materials & methods: The Nationwide Readmission Database was used in a cross-sectional design study. Comorbidities and a palliative care encounter (PCE; V66.7) were defined using ICD-9 codes. Results: Overall, 21.28% of 3,534,480 index hospitalizations were readmitted. PCE occurred in 1.66% of index hospitalizations and was associated with a lower odds of 30-day rehospitalization (adjusted odds ratio, 0.38; 95% CI: 0.35-0.40). This association remained significant when assessed by discharge destination. Conclusion: PCE was associated with a lower relative odds of 30-day rehospitalization. A 73% decrease in the relative odds of 30-day rehospitalization among discharges to a facility, 64% for home with home health, and 22% for discharges to home.


Escherichia coli-induced epithelial hyporesponsiveness to secretagogues is associated with altered CFTR localization.
Both pathogenic and commensal strains of Escherichia coli colonize the human intestinal tract. Pathogenic strains differ only in the expression of virulence factors, many of which comprise a type III secretion system (TTSS). Little is known regarding the effect of E. coli on the intestinal epithelial response to the secretagogues that drive ion secretion, despite its importance in causing clinically significant diarrhoea. Using Ussing chambers to measure electrogenic ion transport of T84 intestinal epithelial cell monolayers, we found that all strains of E. coli tested (pathogenic, commensal, probiotic and lab strain) significantly reduced cAMP-dependent ion secretion after 4-8 h exposure. Enteropathogenic E. coli mutants lacking a functional TTSS caused similar hyposecretion while not causing significant apoptosis (as shown by caspase-3 cleavage) or necrosis (lactate dehydrogenase release), as did the commensal strain F18, indicating that epithelial cell death was not the cause of hyposecretion. Enteropathogenic E. coli and the TTSS mutant significantly reduced cell surface expression of the apical anion channel, cystic fibrosis transmembrane conductance regulator, which is likely the mechanism behind the pathogen-induced hyposecretion. However, F18 did not cause cystic fibrosis transmembrane conductance regulator mislocalization and the commensal-induced mechanism remains unclear.


Unusual H-type aggregation of coumarin-481 dye in polar organic solvents.
Coumarin-481 (C481) dye shows intriguing time-resolved (TR) fluorescence behavior in polar organic solvents of both protic and aprotic nature, namely, ethanol (EtOH) and acetonitrile (ACN), demonstrating the presence of multiple emitting species in the solution. Following concentration-dependent and wavelength-dependent TR fluorescence measurements and the time-resolved emission spectra (TRES) and time-resolved area-normalized emission spectra (TRANES) subsequently constructed using wavelength dependent decay parameters, we convincingly conclude that in the studied solvents a part of the dissolved dye undergoes H-type of aggregation, even at a very low dye concentration. This is quite an unusual finding because the dye C481 apparently shows reasonably good solubility in these organic solvents. As the TR measurements indicate, major contribution in the fluorescence decays is due to monomeric dye, having reasonably short lifetime (∼0.64-0.68 ns), which is in accordance with the conversion of fluorescent intramolecular charge transfer (ICT) state to nonfluorescent twisted intramolecular charge transfer (TICT) state suggested for the dye in high polarity solvents, causing an efficient nonradiative deexcitation. The minor contributions arising from the aggregated dyes show its clear presence in the decays at the blue edge of the emission spectra and have relatively longer lifetimes (∼1.2-5.2 ns) because the steric hindrance caused by the stacked dyes resists the ICT to TICT conversion. Aggregation of C481 dye as observed in the present study in polar organic solvents is an intriguing finding, as the dye is a widely used fluorescent probe for various photochemical studies, where overlooking such aggregation can mislead the observed results.


Retrospective Analysis of Dento-alveolar Injuries at a Swiss University Clinic (2011-2015).
The aim of this study was to evaluate all dento-alveolar injuries occurring within a period of 5 years that were examined at the Department of Oral Surgery and Stomatology at the University of Bern. The case histories of 852 patients (522 males and 330 females) were assessed retrospectively. The mean age was 17 years and 9 months. The youngest patient was 10 months old, the oldest was 91 years old. Most accidents were recorded in the months of March and July. Friday was observed as the weekday when accidents were at their peak. 54% of trauma patients were first examined on the day of the accident. The most frequent causes of accident were falls, cycling or sports accidents. Injury types included concussion (72.4%), subluxation (14%) and luxation (7.7%). Crown fractures without pulp exposure were recorded in 522 teeth (10.7%). Rare types of trauma were crown fractures with pulp exposure (3.7%), and avulsion injuries (3.2%). The most frequently affected teeth were central incisors (40%), followed by lateral incisors (35.6%) and canines (19.5%). 71.5% of the patients with dento-alveolar trauma also had soft-tissue injuries (from abrasions to lacerations), mostly lip (51.6%), gingival (19%), and chin injuries (10.9%). The multivariate analysis showed that age had a significant impact on concussions, subluxations, intrusions, crown fractures, root fractures and non-oral injuries. For concussions and subluxations, the probability of an injury was the highest for the mixed dentition group. For intrusions, the probability of an injury decreased with age, but it was vice versa for crown fractures, root fractures and non-oral injuries. It was found that bicycle injuries had the highest injury probability for avulsions, luxations, subluxations, soft tissue - and non-oral injuries.


[Revascularization of the deep femoral artery and its inflow vessels to treat critical limb ischemia in patients with thromboangiitis obliterans:a report of 9 cases].
Objective: To examine the effectiveness of revascularization of the deep femoral artery and its inflow vessels to treat critical limb ischemia in patients with thromboangiitis obliterans (TAO). Methods: The clinical data of 9 TAO patients with critical limb ischemia who underwent deep femoral artery and its inflow revascularization from January 2018 to October 2020 at Department of Vascular Surgery, the First Medical Center, People's Liberation Army General Hospital were retrospectively analyzed.There were all males, aged from 26 to 50 years with onset time from 1 to 7 years.All patients had severe rest pain, and 4 had ischemic ulcers or gangrene.All patients had occlusion of the deep femoral artery origins and(or) its inflow tracts, including 2 ipsilateral common iliac artery occlusion, 4 ipsilateral external iliac artery occlusion, 7 common femoral artery occlusion, and 8 deep femoral artery origins, without the involvement of the contralateral common femoral artery or its inflow tracts.Surgical procedures included femoral endarterectomy with thrombectomy, merge suture, and bypass.Technical success rate, rest pain relief, ulcer healing, patency, amputation rate, and long-term prognosis were recorded. Results: The overall technical success rate was 9/9, including 8 femoral endarterectomies with thrombectomy (with 4 patch-angioplasty with the great saphenous vein, 1 merge suture, and 3 simple sutures), 4 femoral-femoral bypasses with artificial vessels, and 1 superficial femoral artery bypass with the great saphenous vein.Rest pain disappeared after the operation immediately.The follow-up time was 10 to 44 months.All patients survived.The semi-annual patency rate was 9/9, and the one-year patency rate was 6/8.Except for one patient with significantly reduced but unhealed dorsalis ulcer up to now due to continuous heavy tobacco exposure after surgery, all others had no rest pain occurred or recurrence of foot ulcers during the follow-up.Among the 8 patients, 3 cases with recent claudication had continuous moderate tobacco exposure (10 to 20 cigarettes per day or severe passive smoking). Conclusions: For patients with thromboangiitis obliterans involved in the deep femoral artery or its inflow vessels, revascularization should be the primary choice and a good long-term prognosis is promising.Postoperative tobacco exposure (including passive smoking) is of great impact on the prognosis of TAO patients, and smoking cessation education must be reemphasized and reinforced.


High-throughput first principles search for new ferroelectrics.
We use a combination of symmetry analysis and high-throughput density functional theory calculations to search for new ferroelectric materials. We use two search strategies to identify candidate materials. In the first strategy, we start with non-polar materials and look for unrecognized energy-lowering polar distortions. In the second strategy, we consider polar materials and look for related higher symmetry structures. In both cases, if we find new structures with the correct symmetries that are also close in energy to experimentally known structures, then the material is likely to be switchable in an external electric field, making it a candidate ferroelectric. We find sixteen candidate materials, with variety of properties that are rare in typical ferroelectrics, including large polarization, hyperferroelectricity, antiferroelectricity, and multiferroism.


Serine-derivatized gadonanotubes as magnetic nanoprobes for intracellular labeling.
Gadonanotubes (GNTs), which are powerful new T(1)-weighted MRI contrast agents, were derivatized with serine amino acid substituents to produce water-soluble (2 mg ml(-1)) ser-gadonanotubes (ser-GNs) as magnetic nanoprobes for intracellular labeling. The ser-GNTs were used to efficiently label MCF-7 human breast cancer cells (1.5 x 10(9) Gd(3+) ions/cell) with no observable cytotoxicity. Cell pellets derived from the ser-GNT labeled cells give bright T(1)-weighted MR images, confirming that the ser-GNTs are a promising new nanoprobe technology for magnetic cell labeling and possibly for in vivo cellular trafficking.


Structural Features and the Anti-Inflammatory Effect of Green Tea Extract-Loaded Liquid Crystalline Systems Intended for Skin Delivery.
Camellia sinensis, which is obtained from green tea extract (GTE), has been widely used in therapy owing to the antioxidant, chemoprotective, and anti-inflammatory activities of its chemical components. However, GTE is an unstable compound, and may undergo reactions that lead to a reduction or loss of its effectiveness and even its degradation. Hence, an attractive approach to overcome this problem to protect the GTE is its incorporation into liquid crystalline systems (LCS) that are drug delivery nanostructured systems with different rheological properties, since LCS have both fluid liquid and crystalline solid properties. Therefore, the aim of this study was to develop and characterize GTE-loaded LCS composed of polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol, avocado oil, and water (F25E, F29E, and F32E) with different rheological properties and to determine their anti-inflammatory efficacy. Polarized light microscopy revealed that the formulations F25, F29, and F32 showed hexagonal, cubic, and lamellar liquid crystalline mesophases, respectively. Rheological studies showed that F32 is a viscous Newtonian liquid, while F25 and F29 are dilatant and pseudoplastic non-Newtonian fluids, respectively. All GTE-loaded LCS behaved as pseudoplastic with thixotropy; furthermore, the presence of GTE increased the S values and decreased the n values, especially in F29, indicating that this LCS has the most organized structure. Mechanical and bioadhesive properties of GTE-unloaded and -loaded LCS corroborated the rheological data, showing that F29 had the highest mechanical and bioadhesive values. Finally, in vivo inflammation assay revealed that the less elastic and consistent LCS, F25E and F32E presented statistically the same anti-inflammatory activity compared to the positive control, decreasing significantly the paw edema after 4 h; whereas, the most structured and elastic LCS, F29E, strongly limited the potential effects of GTE. Thereby, the development of drug delivery systems with suitable rheological properties may enhance GTE bioavailability, enabling its administration via the skin for the treatment of inflammation.


[Antitumor activity of cisplatin against malignant brain tumors].
Antitumor activity of Cisplatin (cis-diamminedichloroplatinum) against malignant brain tumors was investigated from both experimental and clinical points of view. With glioma and neuroblastoma cell lines we studied inhibition of cell growth was studied and DNA histogram analyzed with flow cytometry to determine its antitumor activity in vitro. At the concentration of 1.25 micrograms/ml, DNA accumulation is S or G1-S phase and mild inhibition of cell growth were demonstrated; at the concentration of 12.5 micrograms/ml, cessation of cell cycle was observed. In the clinical study, four glioma patients were treated by intravenous administration of Cisplatin 10 mg/sqm for 5 days q 4 weekly. There were one complete response, one minor and two stable responses. Three patient with intracranial embryonal carcinoma were treated by cisplatin. One patient showed partial response and the others were stable.


Janus 2D titanium nitride halide TiNX0.5Y0.5 (X, Y = F, Cl, or Br, and X ≠ Y) monolayers with giant out-of-plane piezoelectricity and high carrier mobility.
Due to their broken out-of-plane inversion symmetry, Janus two-dimensional (2D) materials exhibit some exceptional and interesting physical properties and have recently attracted increasing attention. Herein, based on first-principles calculations, we propose a series of Janus 2D titanium nitride halide TiNX0.5Y0.5 (X, Y = F, Cl, or Br, and X ≠ Y) monolayers constructed from 2D ternary compounds TiNX (X = F, Cl, or Br), where the halogen atoms X or Y are located on each side of the monolayer, respectively. Our calculations confirm that the Janus monolayers are both dynamically and thermally stable. As compared with those of perfect TiNX monolayers, the band-structure changes of Janus TiNX0.5Y0.5 monolayers are very limited and the corresponding bandgaps only increase by about 0.1-0.2 eV. Meanwhile, the Janus TiNX0.5Y0.5 monolayers show remarkable out-of-plane piezoelectricity by virtue of their broken centrosymmetry. The calculated out-of-plane piezoelectric coefficient d31 is as high as 0.34 pm V-1, which is larger than those of most 2D piezoelectric materials reported previously. In addition, it is found that the formation of Janus structures could effectively improve the carrier mobility. The hole mobilities along the x-direction (y-direction) of Janus TiNF0.5Cl0.5 and TiNF0.5Br0.5 monolayers reach as high as 5402 (5118) and 5538 (4135) cm2 V-1 s-1 at 300 K, respectively, which is almost twice as large as those of perfect TiNX monolayers. The giant out-of-plane piezoelectricity and high carrier mobility of Janus TiNX0.5Y0.5 monolayers suggest that these novel 2D materials could be promising for applications in electronic and piezoelectric devices.


Lower limb moments differ when towing a weighted sled with different attachment points.
Sprinting while towing a sled improves sprinting parameters, however, only kinematic and temporal-spatial variables have been reported. The purpose of this study was to determine how lower extremity joint moment impulses alter when towing a sled compared to normal walking. Twelve participants walked normally, walked while towing a sled with a 50% body weight load attached at the waist, and with a 50% body weight load attached at the shoulders. Joint moment impulses were calculated for the hip, knee, and ankle. A mixed-model ANOVA with a between-subject factor of limb and repeated measures of condition was used to compare differences between limbs and towing conditions for each joint. Towing a sled increased joint moment impulses at the hip, knee, and non-dominant ankle. When compared with normal walking waist attachment increased hip extension moment impulse by 214.5% (-3.31 vs. -10.41Nms/kg), and shoulder attachment increased knee extension moment impulse by 166.9% (4.62 vs. 12.33Nms/kg). The dominant limb produced greater knee extension moment impulse (p < 0.001), while the non-dominant limb produced greater hip extension (p < 0.001) and ankle plantarflexion moment impulse (p < 0.001) across all conditions. Results suggest that walking while towing may increase hip and knee extension strength.


Precise quantification of pulsatility is a necessity for direct comparisons of six different pediatric heart-lung machines in a neonatal CPB model.
Generation of pulsatile flow depends on an energy gradient. Surplus hemodynamic energy (SHE) is the extra hemodynamic energy generated by a pulsatile device when the adequate pulsatility is achieved. The objective of this study was to precisely quantify and compare pressure-flow waveforms in terms of surplus hemodynamic energy levels of six different pediatric heart-lung machines in a neonatal piglet model during cardiopulmonary bypass (CPB) procedures with deep hypothermic circulatory arrest (DHCA). Thirty-nine piglets (average weight, 3 kg) were subjected to CPB with a hydraulically driven physiologic pulsatile pump (PPP; n=7), Jostra-HL 20 pulsatile roller pump (Jostra-PR; n=6), Stockert Sill pulsatile roller pump (SIII-PR; n=6), Stockert Sill mast-mounted pulsatile roller pump with a miniature roller head (Mast-PR; n=7), Stockert Sill mast-mounted nonpulsatile roller pump (Mast-NP; n=7), or Stockert CAPS nonpulsatile roller pump (CAPS-NP, n=7). Once CPB was begun, each animal underwent 20 minutes of hypothermia, 60 minutes of DHCA, 10 minutes of cold reperfusion, and 40 minutes of rewarming. The pump flow rate was maintained at 150 ml x kg(-1) x min(-1) and the mean arterial pressure (MAP) at 45 mm Hg. In the pulsatile experiments, the pump rate was kept at 150 bpm and the stroke volume at 1 ml/kg. The SHE (ergs/cm3) = 1,332 ([(integral fpdt) / (integral fdt)] - MAP) was calculated at each experimental stage. During normothermic CPB (15 minutes on pump), the physiologic pulsatile pump generated the highest surplus hemodynamic energy (8563 +/- 1918 ergs/cm3, p < 0.001) compared with all other pumps. The Jostra HL-20 and Stockert Sill pulsatile roller pumps also produced adequate surplus hemodynamic energy. Nonpulsatile roller pumps and the Stockert Sill mast-mounted pulsatile roller pump did not generate any extra hemodynamic energy. During hypothermic CPB and after DHCA and rewarming, the results were extremely similar to those seen during normothermic CPB. The surplus hemodynamic energy formula is a novel method to precisely quantify different levels of pulsatility and nonpulsatility for direct and meaningful comparisons. The PPP produced the greatest surplus hemodynamic energy. Most of the pediatric pulsatile pumps (except Mast-PR) generated significant surplus hemodynamic energy. None of the nonpulsatile roller pumps generated adequate surplus hemodynamic energy.


Influence of atrial natriuretic factor on uptake, intracellular distribution, and release of norepinephrine in rat adrenal medulla.
Several studies have demonstrated that atrial natriuretic factor can bind to adrenal medulla cells. Furthermore, atrial natriuretic factor immunoreactivity has been identified in chromaffin cells. The aim of the present work was to investigate atrial natriuretic factor effects on the uptake, intracellular distribution, and release of norepinephrine in the rat adrenal medulla. Results showed that 100 nM atrial natriuretic factor induced a rapid increase of norepinephrine uptake during the first minute of the incubation period. This increase was maintained for up to 60 min. In addition, only neuronal norepinephrine uptake was increased by the natriuretic factor; non-neuronal norepinephrine uptake was unaltered. Atrial natriuretic factor modified the intracellular distribution of the amine store: the granular fraction of norepinephrine increased, while the cytosolic fraction decreased. On the other hand, different concentrations (10, 50, and 100 nM) of the atrial factor decreased spontaneous [3H]norepinephrine output in a concentration-dependent manner. Furthermore, atrial natriuretic factor (10 nM) also reduced high potassium solution evoked secretion of norepinephrine. These results suggest that atrial natriuretic factor modulates sympathetic activity in the rat adrenal medulla. These effects of atrial natriuretic factor may be related to the catecholamine peripheral mechanism involved in the regulation of arterial blood pressure, smooth muscle tone, metabolic activity, etc.


Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate in Alzheimer's Disease: A Systematic Review and Meta-Analysis.
Background and Purpose: Previous studies found inconsistent results for the relationship between Alzheimer's disease and the levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate. This study performed a systematic review and meta-analysis to evaluate previous studies' results on this relationship. Method: Studies related to this outcome were obtained using a systematic search from the electronic databases of PubMed, Embase, Web of Science, and Psyc-ARTICLES in March 2018. The random-effects model was used to measure the strength of the association between Alzheimer's disease and the levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate, using the standardized mean difference. Results: Thirty-one eligible studies were included in the final analysis. There was no statistically significant association between the level of dehydroepiandrosterone and Alzheimer's disease (standardized mean difference: 0.51, 95% confidence interval: -0.44 to 1.45, Z = 1.06, p = 0.29). On the other hand, lower level dehydroepiandrosterone sulfate was observed in patients with Alzheimer's disease than in controls (standardized mean difference: -0.69, 95% confidence interval: -1.17 to -0.22, Z = -2.84, p < 0.01). Conclusion: Decreased dehydroepiandrosterone sulfate concentrations may be an important indicator for Alzheimer's disease, although whether dehydroepiandrosterone sulfate could be used as a diagnostic tool requires further research.


Birthweight and feeding practices are associated with child growth outcomes in South Asia.
Although there has been a focus on preventing stunting over the past decade, wasting has received less policy and programmatic attention. Recent national surveys from six South Asian countries were pooled to generate a dataset of 62,509 children aged 0 to 59 months to explore associations between low birthweight (LBW) and suboptimal infant and young child feeding (IYCF) practices with child wasting, severe wasting, and the co-occurrence of wasting and stunting. Logistic regression models accounted for the surveys' clustered designs and adjusted for a potential confounding factors. Children with reported LBW had significantly higher odds of being wasted (adjusted odds ratio [95% CI]: 1.60 [1.45, 1.76]) or severely wasted (1.57 [1.34, 1.83]), compared with non-LBW children. Similarly, children aged 0 to 23 months who were not breastfed within the first hour post-partum, those who were provided prelacteal feeds, and those aged 0 to 5 months who were not exclusively breastfed, were more likely to be wasted (P < 0.05 for all three feeding practices). In India, not achieving minimum diet diversity and minimum adequate diet were significantly associated with the co-occurrence of stunting and wasting. In other words, many key domains of concern to development agents who seek to address stunting are also of direct concern to those focused on wasting. The co-occurrence of wasting and stunting requires more integrated interventions. That is, programmes aimed at preventing LBW and poor IYCF to avert stunting should be linked more effectively with actions aimed at the management of wasting.