Activation of T cell calcium influx by the second messenger ADP-ribose.
Stimulation of Jurkat T cells by high concentrations of concanavalin A (ConA) induced an elevation of the endogenous adenosine diphosphoribose (ADPR) concentration and an inward current significantly different from the Ca2+ release-activated Ca2+ current (I(CRAC)). Electrophysiological characterization and activation of a similar current by infusion of ADPR indicated that the ConA-induced current is carried by TRPM2. Expression of TRPM2 in the plasma membrane of Jurkat T cells was demonstrated by reverse transcription-PCR, Western blot, and immunofluorescence. Inhibition of ADPR formation reduced ConA-mediated, but not store-operated, Ca2+ entry and prevented ConA-induced cell death of Jurkat cells. Moreover, gene silencing of TRPM2 abolished the ADPR- and ConA-mediated inward current. Thus, ADPR is a novel second messenger significantly involved in ConA-mediated cell death in T cells.


Pathway analysis of microRNAs in mouse heart development.
MicroRNAs (miRNAs) are non-coding RNAs, which regulate gene expression by promoting degradation or repressing translation of targeted transcripts. Current researches indicate that microRNAs play essential roles in heart development, but their regulating mechanisms are still elusive. Using computational methods, we analysed microRNAs associated pathways in mouse heart development and found that 24 pathways were enriched with target genes of microRNAs. Some of these pathways are reported important in heart development, while others are associated with cancer. The computational results could be used to guide experimental design for the further understanding of the microRNAs function in heart development.


Type 2 Diabetes Increases Risk of Unfavorable Survival Outcome for Postoperative Ischemic Stroke in Patients Who Underwent Non-cardiac Surgery: A Retrospective Cohort Study.
Objective: Diabetes mellitus (DM) has been critically associated with unfavorable outcomes in the general population. We aimed to investigate the association between type 2 DM and long-term survival outcomes for postoperative ischemic stroke in patients who underwent non-cardiac surgery. Research Design and Methods: This was a retrospective cohort study of patients with non-cardiac surgery who had suffered from postoperative ischemic stroke between January 2008 and August 2019. Diabetic individuals were included in postoperative ischemic stroke patients with the DM group. The outcome of interest was long-term overall survival (OS). We conducted propensity score matching (PSM) and inverse probability treatment weighting (IPTW) to adjust for baseline characteristic differences between groups. Multivariate Cox regression analysis with stepwise selection was used to calculate the adjusted hazard ratio (HR) of OS and type 2 DM. Results: During a median follow-up of 46.2 month [interquartile range (IQR), 21.1, 84.2], 200 of 408 patients (49.0%) died. The OS rates at 3, 5, and 10 years were significantly lower for postoperative ischemic stroke patients with DM than those without DM (3 years OS: 52.2 vs. 69.5%, p < 0.001; 5 years OS: 41.6 vs. 62.4%, p < 0.001; 10 years OS: 37.2 vs. 56.6%, p < 0.001). All covariates were between-group balanced after using PSM or IPTW. The postoperative ischemic stroke patients with type 2 DM had a shortened OS in primary analysis (HR: 1.947; 95% CI: 1.397-2.713; p < 0.001), PSM analysis (HR: 2.190; 95% CI: 1.354-3.540; p = 0.001), and IPTW analysis (HR: 2.551; 95% CI: 1.769-3.679; p < 0.001). Conclusion: Type 2 DM was associated with an unfavorable survival outcome for postoperative ischemic stroke in patients who underwent non-cardiac surgery. When postoperative ischemic stroke co-occurred with type 2 DM, the potential synergies would have multiplicative mortality risk. Further research to assess the adverse effects of type 2 DM on long-term survival may be warranted.


Congenital Sebaceous Trichofolliculoma of the Upper Eyelid.
A 6-year-old male presented with a protruding hair emerging from a temporally located nodule on his left upper eyelid 5mm above the eyelid margin since birth. The lesion was excised and sent to histopathology. The features were consistent with congenital sebaceous trichofolliculoma, a rare hamartomatous skin lesion.


Bimetallic-Derived Catalytic Structures for CO2-Assisted Ethane Activation.
ConspectusIn recent years, the simultaneous upgrading of CO2 and ethane has emerged as a promising approach for generating valuable gaseous (CO, H2, and ethylene) and liquid (aromatics and C3 oxygenates) chemicals from the greenhouse gas CO2 and large-reserved shale gas. The key challenges for controlling product selectivity lie in the selective C-H and C-C bond cleavage of ethane with the assistance of CO2. Bimetallic-derived catalysts likely undergo alloying or oxygen-induced segregation under reaction conditions, thus providing diverse types of interfacial sites, e.g., metal/support (M/M'Ox) interface and metal oxide/metal (M'Ox/M) inverse interface, that are beneficial for selective CO2-assisted ethane upgrading. The alloying extent can be initially predicted by cohesive energy and atomic radius (or Wigner-Seitz radius), while the preference for segregation to form the on-top suboxide can be approximated using the work function, electronegativity, and binding strength of adsorbed oxygen. Furthermore, bimetallic-derived catalysts are typically supported on high surface area oxides. Modifying the reducibility and acidity/basicity of the oxide supports and introducing surface defects facilitate CO2 activation and oxygen supplies for ethane activation.Using in situ synchrotron characterization and density functional theory (DFT) calculations, we found that the electronic properties of oxygen species influence the selective cleavage of C-H/C-C bonds in ethane, with electron-deficient oxygen over the metal (or alloy) surface promoting nonselective bond scission to produce syngas and electron-enriched oxygen over the metal oxide/metal interface enhancing selective C-H scission to yield ethylene. We further demonstrate that the preferred structures of the catalyst surfaces, either alloy surfaces or metal oxide/metal inverse interfaces, can be controlled through the appropriate choice of metal combinations and their atomic ratios. Through a comprehensive comparison of experimental results and DFT calculations, the selectivity of C-C/C-H bond scission is correlated with the thermodynamically favorable bimetallic-derived structures (i.e., alloy surfaces or metal oxide/metal inverse interfaces) under reaction conditions over a wide range of bimetallic catalysts. These findings not only offer structural and mechanistic insights into bimetallic-derived catalysts but also provide design principles for selective catalysts for CO2-assisted activation of ethane and other light alkanes. This Account concludes by discussing challenges and opportunities in designing advanced bimetallic-derived catalysts, incorporating new reaction chemistries for other products, employing precise synthesis strategies for well-defined structures with optimized site densities, and leveraging time/spatial/energy-resolved in situ spectroscopy/scattering/microscopy techniques for comprehensive structural analysis. The research methodologies established here are helpful for the investigation of dynamic alloy and interfacial structures and should inspire more efforts toward the simultaneous upgrading of CO2 and shale gas.


Stratification of pseudoprogression and true progression of glioblastoma multiform based on longitudinal diffusion tensor imaging without segmentation.
Pseudoprogression (PsP) can mimic true tumor progression (TTP) on magnetic resonance imaging in patients with glioblastoma multiform (GBM). The phenotypical similarity between PsP and TTP makes it a challenging task for physicians to distinguish these entities. So far, no approved biomarkers or computer-aided diagnosis systems have been used clinically for this purpose. To address this challenge, the authors developed an objective classification system for PsP and TTP based on longitudinal diffusion tensor imaging. A novel spatio-temporal discriminative dictionary learning scheme was proposed to differentiate PsP and TTP, thereby avoiding segmentation of the region of interest. The authors constructed a novel discriminative sparse matrix with the classification-oriented dictionary learning approach by excluding the shared features of two categories, so that the pooled features captured the subtle difference between PsP and TTP. The most discriminating features were then identified from the pooled features by their feature scoring system. Finally, the authors stratified patients with GBM into PsP and TTP by a support vector machine approach. Tenfold cross-validation (CV) and the area under the receiver operating characteristic (AUC) were used to assess the robustness of the developed system. The average accuracy and AUC values after ten rounds of tenfold CV were 0.867 and 0.92, respectively. The authors also assessed the effects of different methods and factors (such as data types, pooling techniques, and dimensionality reduction approaches) on the performance of their classification system which obtained the best performance. The proposed objective classification system without segmentation achieved a desirable and reliable performance in differentiating PsP from TTP. Thus, the developed approach is expected to advance the clinical research and diagnosis of PsP and TTP.


Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer.
The synthetic retinoid fenretinide administered for 5 years for prevention of second breast cancer showed no difference after a median of 8 years, but a possible reduction in premenopausal women. We conducted a long-term analysis in a subgroup of women who were regularly followed up in a single center. We analyzed data after a median follow-up of 14.6 years (IQ range, 12.3-16.3 years) from 1739 women aged 30-70 (872 in the fenretinide arm and 867 in the observation arm), representing 60% of the initial cohort of 2867 women. The main efficacy endpoint was second primary breast cancer (contralateral or ipsilateral). The number of second breast cancers was 168 in the fenretinide arm and 190 in the control arm (hazard ratio = 0.83, 95% CI, 0.67-1.03). There were 83 events in the fenretinide arm and 126 in the observation arm in premenopausal women (HR = 0.62, 95% CI, 0.46-0.83), and 85 and 64 events in postmenopausal women (HR = 1.23, 95% CI, 0.63-2.40). The younger were the women, the greater was the risk reduction associated with fenretinide, which attained 50% in women aged 40 years or younger and disappeared after age 55 (P-age*treatment interaction = 0.023). There was no difference in cancers in other organs, distant metastases or survival. Fenretinide induces a significant risk reduction of second breast cancer in premenopausal women, which is remarkable at younger ages, and persists several years after treatment cessation. Since adverse events are limited, a trial in young women at high-risk is warranted.


Lattice Boltzmann model for thermal transpiration.
The conventional Navier-Stokes-Fourier equations with no-slip boundary conditions are unable to capture the phenomenon of gas thermal transpiration. While kinetic approaches such as the direct simulation Monte Carlo method and direct solution of the Boltzmann equation can predict thermal transpiration, these methods are often beyond the reach of current computer technology, especially for complex three-dimensional flows. We present a computationally efficient nonequilibrium thermal lattice Boltzmann model for simulating temperature-gradient-induced flows. The good agreement between our model and kinetic approaches demonstrates the capabilities of the proposed lattice Boltzmann method.


Rare Presentation of Midbrain Infarction: Isolated Medial Rectus Palsy.
A 69-year-old woman presented with sudden onset of diplopia. In neurologic examination left medial rectus palsy without abduction nystagmus was detected. Brain magnetic resonance imaging revealed acute ischemic lesion in mesencephalon on diffusion-weighted images. Sponteneous resolution was observed after 1 month. Medial rectus palsy is a rare presention of acute ischemic stroke and early neuroimaging is important to establish such lesions.


Sensitivity of Botrytis cinerea to chitosan and acibenzolar-S-methyl.
The antifungal properties of chitosan and acibenzolar-S-methyl were evaluated to assess their potential for protecting grapes against Botrytis cinerea Pers.: Fr. isolated from Vitis vinifera L. The objectives were to determine the effects of these compounds on the in vitro development of B. cinerea and to assess their effectiveness at controlling grey mould on grapes stored at different temperatures. Both agents significantly inhibited the radial growth of this fungus species. The EC(50) was 1.77 mg mL(-1) for chitosan and 3.44 mg mL(-1) for acibenzolar-S-methyl. In addition, single grapes treated with aqueous solutions of chitosan (1.0 and 2.5 mg mL(-1)) and acibenzolar-S-methyl (1.0 and 3.0 mg mL(-1)) were inoculated with B. cinerea and incubated at both 4 and 24 degrees C. After 4 days at 24 degrees C, all the concentrations of chitosan and acibenzolar-S-methyl significantly reduced B. cinerea growth. However, at 4 degrees C, significant differences were only observed between chitosan at 2.5 mg mL(-1) and acibenzolar-S-methyl at both 1.0 and 3.0 mg mL(-1) and the corresponding controls. After 3 days at 24 degrees C, the greatest reduction in lesion size was obtained in grapes pretreated with acibenzolar-S-methyl at 3.0 mg mL(-1). Only the highest doses of these products significantly reduced the lesion diameters when grapes were stored for 3 days at 4 degrees C. Chitosan and acibenzolar-S-methyl could directly inhibit the growth of Botrytis cinerea in vitro and confer resistance on grapes against grey mould. Pretreatment with these compounds could be an alternative to traditional fungicides in post-harvest disease control in grapes.


Lumbar paravertebral nerve block in the management of pain after total hip and knee arthroplasty: a randomized controlled clinical trial.
The accepted mode of pain management after total hip or knee arthroplasty is patient-controlled analgesia. This study evaluates the efficacy of lumbar paravertebral nerve block in diminishing postoperative pain when used as an adjunct to patient-controlled analgesia. A total of 115 arthroplasty patients received postoperatively a lumbar paravertebral nerve block (block, n = 57) or a sham procedure (control, n = 58). The block group required approximately 10 mg less morphine for pain control than the control group during the first 4 hours postoperatively (P<.001). There were no significant differences in morphine use between the groups 4 to 24 hours postoperatively. Visual analog scale pain score measurements at 4, 8, and 24 hours did not differ significantly between the groups. Paravertebral nerve block of the lumbar plexus is an invasive procedure with some risk. Considering the added risk and minimal benefits, routine use of this procedure is not supported.


Impact of Different Oxygen Supply Methods on the Healing of Corneal Epithelial Wound and the Level of Acetylcholine.
To investigate the impact of different oxygen supply methods on corneal epithelial wound healing and acetylcholine level during wound healing. We randomly divided 75 rabbits into three groups: A, B, and C, with 25 rabbits in each group. The central corneal epithelium was removed from all eyes of the rabbits using a 5 mm trephine. Group A rabbits were given low flow oxygen (3 L/min; concentration: 33%) for 2 h per day through goggles. Group B rabbits were given low flow oxygen (3 L/min; concentration: 33%) for 2 h per day via oxygen masks for inhalation. Group C rabbits healed naturally. The area of healed corneal epithelium and acetylcholine content in corneal epithelium were determined at 12 h, 24 h, and 36 h after injury. At 12 h, 24 h, and 36 h after injury, the healing area of corneal epithelium in the three groups was in the order group A > group B > group C (P < 0.05). At all timepoints, the acetylcholine level in corneal epithelium was in the order of group A > group B > group C (P < 0.05). In all three groups, the acetylcholine content in corneal epithelium showed the order 12 h > 24 h > 36 h (P < 0.05). There was a correlation between acetylcholine expression and the area of unhealed corneal epithelium, and the correlation coefficients of groups A, B, and C were 0.80, 0.83, and 0.85 respectively. Increasing oxygen concentration through inhalation or via goggles can promote corneal epithelial wound healing, but increasing local oxygen concentration of the eye showed a better effect. Acetylcholine may play an important role in the early process of corneal epithelial wound healing.


Adjunctive virtual reality pain relief following traumatic injury: protocol for a randomised within-subjects clinical trial.
The annual mortality and national expense of the opioid crisis continue to rise in the USA (130 deaths/day, $50 billion/year). Opioid use disorder usually starts with the prescription of opioids for a medical condition. Its risk is associated with greater pain intensity and coping strategies characterised by pain catastrophising. Non-pharmacological analgesics in the hospital setting are critical to abate the opioid epidemic. One promising intervention is virtual reality (VR) therapy. It has performed well as a distraction tool and pain modifier during medical procedures; however, little is known about VR in the acute pain setting following traumatic injury. Furthermore, no studies have investigated VR in the setting of traumatic brain injury (TBI). This study aims to establish the safety and effect of VR therapy in the inpatient setting for acute traumatic injuries, including TBI. In this randomised within-subjects clinical study, immersive VR therapy will be compared with two controls in patients with traumatic injury, including TBI. Affective measures including pain catastrophising, trait anxiety and depression will be captured prior to beginning sessions. Before and after each session, we will capture pain intensity and unpleasantness, additional affective measures and physiological measures associated with pain response, such as heart rate and variability, pupillometry and respiratory rate. The primary outcome is the change in pain intensity of the VR session compared with controls. Dissemination of this protocol will allow researchers and funding bodies to stay abreast in their fields through exposure to research not otherwise widely publicised. Study protocols are compliant with federal regulation and University of Maryland Baltimore's Human Research Protections and Institutional Review Board (protocol number HP-00090603). Study results will be published on completion of enrolment and analysis, and deidentified data can be shared by request to the corresponding author. NCT04356963; Pre-results.


Effect of some chemical modifications of basic pancreatic trypsin inhibitor (BPTI) on its reaction with specific antibody.
Anti-BPTI-antibody inactivated the antitrypsin activity of basic pancreatic trypsin inhibitor. Esterification of BPTI with methanol did not affect its antitrypsin activity and precipitate formation with antibody. Acetylation, maleylation and hexa-S-carboxylation of BPTI completely inactivated the inhibitor reactivity and markedly diminished its precipitating ability. Performic acid oxidized BPTI and thermolysin digested BPTI lost its antitrypsin as well as antigenic activities. The both preparations as well as oxidized N-acetyl-L-cysteinyl-L-lysyl-L-alanylglycylglycyl-L-cysteine amide did not affect the complex formation between the inhibitor and antibody.


3D Reconstruction Aids Surgery For Complicated Hepatolithiasis.
Three-dimensional (3D) imaging may improve surgical interventions for complicated hepatolithiasis. Between July 2008 and December 2012 a total of 131 patients with complicated hepatolithiasis underwent surgical therapy in the Department of Hepatobiliary Surgery Zhujiang Hospital, Southern Medical University. 77 patients received preoperative planning using a computed tomography (CT)-based 3D reconstruction technique, and 54 received treatment based on preoperative planning with traditional imaging (CT, ultrasonography, magnetic resonance imaging/magnetic resonance cholangiography). Perioperative and long-term outcomes were analyzed. 3D reconstruction facilitated significantly more accurate diagnosis of pathological morphology than conventional imaging methods, as confirmed during surgery. Patients that received 3D reconstruction preoperative planning had significantly better clinical outcomes. The immediate stone clearance rates were 92.2% and 61.1%, respectively. Additional postoperative choledochoscopic lithotripsy raised the clearance rates to 94.8% and 81.5%, respectively. The hospital mortality rates were 0% and 1.9%, respectively, and the complication rates were 33.8% and 44.4%, respectively. With a median follow-up of 28 months (5-38 months), the long-term overall asymptomatic survival rates were 80.5% and 46.3%, respectively. 3D reconstruction preoperative planning was a significant prognostic protective factor of long-term asymptomatic survival for the patients with complicated hepatolithiasis (Cox regression analysis, RR = 0.348, 95% confidence interval 0.185-0.657, p = 0.001). Surgical therapy conducted following preoperative planning using 3D reconstruction achieved better clinical outcomes than conventional imaging techniques. Whilst conventional imaging techniques accurately identify intrahepatic stones, they are less capable of identifying bile duct stricture.


Biomineralization Induced by Cells of Sporosarcina pasteurii: Mechanisms, Applications and Challenges.
Biomineralization has emerged as a novel and eco-friendly technology for artificial mineral formation utilizing the metabolism of organisms. Due to its highly efficient urea degradation ability, Sporosarcina pasteurii(S. pasteurii) is arguably the most widely investigated organism in ureolytic biomineralization studies, with wide potential application in construction and environmental protection. In emerging, large-scale commercial engineering applications, attention was also paid to practical challenges and issues. In this review, we summarize the features of S. pasteurii cells contributing to the biomineralization reaction, aiming to reveal the mechanism of artificial mineral formation catalyzed by bacterial cells. Progress in the application of this technology in construction and environmental protection is discussed separately. Furthermore, the urgent challenges and issues in large-scale application are also discussed, along with potential solutions. We aim to offer new ideas to researchers working on the mechanisms, applications and challenges of biomineralization.


Furnham's Money Attitude Scale.
An item-analysis of responses from 186 undergraduates to the Money Attitude Scale developed by Furnham did not replicate the factor pattern which he derived.


Protein-protein interactions in the pyruvate dehydrogenase multienzyme complex: dihydrolipoamide dehydrogenase complexed with the binding domain of dihydrolipoamide acetyltransferase.
The ubiquitous pyruvate dehydrogenase multienzyme complex is built around an octahedral or icosahedral core of dihydrolipoamide acetyltransferase (E2) chains, to which multiple copies of pyruvate decarboxylase (E1) and dihydrolipoamide dehydrogenase (E3) bind tightly but non-covalently. E2 is a flexible multidomain protein that mediates interactions with E1 and E3 through a remarkably small binding domain (E2BD). In the Bacillus stearothermophilus complex, the E2 core is an icosahedral assembly of 60 E2 chains. The crystal structure of the E3 dimer (101 kDa) complexed with E2BD (4 kDa) has been solved to 2.6 A resolution. Interactions between E3 and E2BD are dominated by an electrostatic zipper formed by Arg135 and Arg139 in the N-terminal helix of E2BD and Asp344 and Glu431 of one of the monomers of E3. E2BD interacts with both E3 monomers, but the binding site is located close to the twofold axis. Thus, in agreement with earlier biochemical results, it is impossible for two molecules of E2BD to bind simultaneously to one E3 dimer. Combining this new structure for the E3-E2BD complex with previously determined structures of the E2 catalytic domain and the E2 lipoyl domain creates a model of the E2 core showing how the lipoyl domain can move between the active sites of E2 and E3 in the multienzyme complex.


From the immune system to mood disorders especially induced by Toxoplasma gondii: CD4+ T cell as a bridge.
Toxoplasma gondii (T. gondii), a ubiquitous and obligatory intracellular protozoa, not only alters peripheral immune status, but crosses the blood-brain barrier to trigger brain parenchymal injury and central neuroinflammation to establish latent cerebral infection in humans and other vertebrates. Recent findings underscore the strong correlation between alterations in the peripheral and central immune environment and mood disorders. Th17 and Th1 cells are important pro-inflammatory cells that can drive the pathology of mood disorders by promoting neuroinflammation. As opposed to Th17 and Th1, regulatory T cells have inhibitory inflammatory and neuroprotective functions that can ameliorate mood disorders. T. gondii induces neuroinflammation, which can be mediated by CD4+ T cells (such as Tregs, Th17, Th1, and Th2). Though the pathophysiology and treatment of mood disorder have been currently studied, emerging evidence points to unique role of CD4+ T cells in mood disorder, especially those caused by T. gondii infection. In this review, we explore some recent studies that extend our understanding of the relationship between mood disorders and T. gondii.


Effect of propolis extract on acute carbon tetrachloride induced hepatotoxicity.
Ethanolic extract of propolis was administered to rats intoxicated by carbon tetrachloride. Administration of bolus dose of CCl4 (1.5 ml/kg, ip) resulted in elevation of serum transaminases and serum alkaline phosphatase activities. Levels of hepatic lipid peroxidation were significantly increased. On the contrary, there was significant decrease in hepatic reduced glutathione level. The propolis extract (100 and 200 mg/kg, po) exhibited recoupment in both pre- and post-treatment (prophylactic and curative studies) of biochemical changes induced by CCl4. The post treatment of 200 mg/kg, po extract showed most significant hepatoprotective effect. Histopathological studies showed damage in hepatocytes and disturbed chord arrangement after toxicant administration. Propolis extract (200 mg/kg, po) was found to be more effective in restoring CCl4 induced histopathological alterations.


Gaisbock Syndrome: A Review of Contemporary Studies, Pathogenesis, Complications, and Possible Treatment.
Gaisbock syndrome is the term ascribed to several conditions initially observed by Felix Gaisbock, MD, (from Innsbruck, Tyrol, Austria) in 1905 when he described a group of hypertensive male patients who had high hematocrit levels, normal leukocyte counts, and no splenomegaly. These patients had an overweight, stocky habitus, a plethoric appearance with suffusion of the eyes, tense and anxious personalities, a cigarette smoking habit, vascular disease, headaches, and facial rubor. Later studies identified alcoholism, diuretic therapy, and physical or emotional stress as additional risk factors that might contribute to the onset of this syndrome. This review revisits Gaisbock syndrome based on recent literature, and will highlight contemporary studies that have established an association between erythrocytosis and hypertension and associated risk factors. Several mechanisms help explain the pathophysiology underlying Gaisbock's observations, and these include psychiatric disorders resulting in chronic stress, volume contraction secondary to diuretics and hypertension, and obstructive sleep apnea with nocturnal hypoxemia and erythropoietin production. Complications associated with this syndrome include the formation of microthrombi with cerebral infarction; treatment should focus on the management of hypertension and a reduction in risk factors, such as obesity, cigarette smoking, and alcohol use. Gaisbock syndrome involves several clinical disorders, has a complex pathogenesis, and leads to a better understanding of the causes of erythrocytosis during patient evaluation.


Reproducibility of the Glaucoma-scope in cadaver eyes.
We evaluated the intra- and inter-observer variability of depth measurements of the optic disc in cadaver eyes using the Glaucoma-scope. Intra-observer variation of 10 separately captured images became significantly greater with increasing depth of the optic cup (p < 0.001). The standard deviation of depth measurements were 9.06 mu over the neural rim, 25.00 mu along the cup wall, and 40.94 mu at the bottom of the optic cup. However, intra-observer variation of a single captured image did not increase with greater optic cup depth. Intra-observer variation, but not inter-observer variation, generally was greater when measuring the superior than inferior optic disc (p < 0.05). This study suggests that when capturing separate optic disc images with the Glaucoma-scope, increased variation in depth measurements can be expected with greater optic cup depth and in the superior portion of the optic disc.


Bringing comfort to Haiti.
On January 12, 2010, a devastating earthquake ravaged one of the poorest nations in the western hemisphere. A week later, the U.S. Naval Ship Comfort was anchored off Port-au-Prince to perform a mission of mercy for hundreds of critically injured victims of this disaster. The staff of the U.S. Naval Ship Comfort included military as well as civilian volunteer healthcare professionals, working as a team day and night under adverse conditions to save lives and optimize outcomes for the survivors.


Indian task force for celiac disease: current status.
There are limited data on celiac disease (CD) from India. The limited knowledge about CD in India might be attributed to several factors. The first meeting of the Indian Task Force for Celiac Disease was held in the Asian Institute of Gastroenterology, Hyderabad, India in December 2008. The objectives of the meeting were to focus research on prevalence of CD in the wheat-eating Northern vs the rice-eating Southern Indian population, low-budget serological assays to study the underprivileged population, to involve other medical subspecialties in CD, to suggest proper legislation regarding wheat food labeling, and to organize affordable food substitutes for patients with celiac disease.


Infection of wild-type Autographa californica multicapsid nucleopolyhedrovirus induces in vivo apoptosis of Spodoptera litura larvae.
Direct evidence of in vivo apoptosis of Spodoptera litura larvae was demonstrated by haemocoel inoculation with wild-type Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) budded virus (BV). In sharp contrast to natural infection, cadavers did not melt, liquefy and melanize. Typical morphological changes of apoptosis in insect haemocytes post-infection, including blebbing of the cell surface, chromatin margination and condensation, vacuolization of the cytoplasm and formation of apoptotic bodies, were observed by light and electron microscopy. Total DNAs extracted from virus-infected haemocytes showed DNA ladders. Cleavage of chromatin DNA by endogenous endonucleases were detected in the cells of most tissues cells, including epithelial cells and fat body cells, using terminal dUTP nick end labelling assays. Virogenic stroma and viral nucleocapsids could be seen in the nuclei of a few haemocytes. Yields of BV and OV (occluded virus) produced from the infected S. litura larvae were much lower than from the infected S. exigua larvae. These data suggest that host apoptotic responses to virus infection reduce AcMNPV spread at the level of the organism and that apoptosis could be a host-range limiting factor for baculovirus infections.


[Pathology of arteriosclerosis--an overview].
Arteriosclerosis is vascular disease characterized by thickening, hardening and remodelling of the arterial wall and classified into following three categories: atherosclerosis, Mönckeberg's medial calcific sclerosis, and arteriolosclerosis. Fibromuscular intimal thickening starts its development in the fetal age of the 6th month and continues to grow with aging. The specific topography of early atherosclerotic lesions is primarily attributed to wall shear stress, one of hemodynamic forces. The lesion will proliferate to form atherosclerosis when complicated by hyperlipidemia, hypertension, and/or other clinical risk factors. The major complications of atherosclerosis, stenosis of the arterial lumen and thrombus formation at ulcerated arterial walls, frequently cause such lethal diseases as ischemia of various pivotal organs or rupture of aneurysms.


Activation Kinetics of NAD-Dependent Malic Enzyme of Cauliflower Bud Mitochondria.
NAD-dependent malic enzyme (EC 22.214.171.124) was obtained from isolated mitochondria of cauliflower buds (Brassica oleracea L., var. botrytis). The NAD-linked activity is accompanied by a minor NADP-linked activity. Some contaminant NADP-malic enzyme from the supernatant and the plasma membrane is usually present in crude mitochondrial preparations. NAD-dependent malic enzyme has been purified 38-fold by ammonium sulfate fractionation and gel permeation chromatography, to a specific activity up to 2 micromoles per minute per milligram.The nature of the activating effect of coenzyme A and dithiothreitol has been investigated. Both compounds act by decreasing the apparent Michaelis constants for l-malate and NAD(+) (and NADP(+)), V(max) remaining approximately constant. However, enzyme fully activated by dithiothreitol can still be stimulated up to 2.4-fold by coenzyme A treatment.Velocity versus substrate responses show hyperbolic kinetics under present assay conditions (pH 7.5, 2 millimolar Mn(2+)), but biphasic kinetics have been observed with enzyme purified in the presence of 10 millimolar dithiothreitol, suggesting enzyme heterogeneity with respect to an activated state. This condition is reverted to linearity by treatment with coenzyme A. K(m) values do not vary with changing concentrations of the second substrate. Enzyme molecular weight is 400,000 in the completely activated state and 200,000 in the ;inactivated' state; intermediate forms are also found. All coenzyme A derivatives tested are effective activators, showing activation constants lower than for coenzyme A itself. The concentration dependence of the activation is sigmoidal.


[Prognosis after radical surgery in prostatic cancer patients with lymph nodes metastases].
We investigated prognosis of clinically localized prostatic adenocarcinoma patients who revealed to have had lymph nodes metastases by undergoing radical surgery. Eighty six patients were operated during the last 15 years under the clinical diagnosis of A2, 9 patients, B1, 15 B2, 13 and C, 49, respectively. Total prostatectomy was done to 51, total cystoprostatectomy to 33 and total pelvic excentration to 2 patients. Of these patients, 22.2% with stage A2, 20.2% with B1, 7.7% with B2 and 43.8% with C had positive nodes and the rate of positive nodes in stage C was significantly higher than that in other stages (p < 0.01). Regarding histological differentiation, 15.4% of well, 23.7% of moderate and 51.6% of poor by differentiated had positive nodes and the rate of positive nodes in poor by differentiated was significantly higher (p < 0.01). In 2 of 21 cases whose lymph nodes were dissected to the level of the aortic bifurcation, positive nodes were detected only in the external and common iliac areas. These two cases were missed, i.e., "false negative" if limited nodes dissection was performed. All patients with positive nodes were treated with hormonal therapy. The 5-year cancer specific survival rate of patients with positive (n = 27) and negative (n = 59) nodes were 66.4% and 92.4%, respectively. The prognosis of patients with positive nodes were significantly worse than that of patients with negative nodes (p < 0.001). Among 27 patients with positive nodes, significant prognostic factor was not number or extent of positive nodes, but histological differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessing the health-related management of people with differences of sex development.
Health care requirements and perception of people with differences of sex development (DSD) have changed enormously since the "Chicago Consensus Conference" in 2005. Therefore, new standards of care and evaluation of care have to be developed. We summarize the social and legal approach to care for DSD during the last two decades and report the main results of European research activities. The last two decades were accompanied by legal and societal discussion regarding how to deal with a nonbinary concept of sex. This leads to the necessity to assess health care requirements for individuals with DSD in an objective manner. We briefly review the results of the recently funded European research projects dealing with health-related issues in DSD like EU COST Action DSD, I-DSD, and dsd-LIFE, and address the compilation of quality indicators that will be needed to benchmark health care provision and health care-related outcomes. The benchmarking process has to be implemented among health care providers for individuals with DSD within the European Reference Networks for Rare Conditions.


Infection prevention and control measures for acute respiratory infections in healthcare settings: an update.
Viruses account for the majority of the acute respiratory tract infections (ARIs) globally with a mortality exceeding 4 million deaths per year. The most commonly encountered viruses, in order of frequency, include influenza, respiratory syncytial virus, parainfluenza and adenovirus. Current evidence suggests that the major mode of transmission of ARls is through large droplets, but transmission through contact (including hand contamination with subsequent self-inoculation) and infectious respiratory aerosols of various sizes and at short range (coined as "opportunistic" airborne transmission) may also occur for some pathogens. Opportunistic airborne transmission may occur when conducting highrisk aerosol generating procedures and airborne precautions will be required in this setting. General infection control measures effective for all respiratory viral infections are reviewed and followed by discussion on some of the common viruses, including severe acute respiratory syndrome (SARS) coronavirus and the recently discovered novel coronavirus.


Effects of a fish oil diet on pigs' cardiopulmonary response to bacteremia.
Since an omega 3 fatty acid (FA) diet may have beneficial effects in inflammatory processes, we tested the hypothesis that the physiologic response to sepsis could be modified by altering the eicosanoid precursor pool via an omega 3 FA diet. Two groups (n = 8) of pigs were prefed for 8 days either an omega 3 FA or an omega 6 FA diet (Weaner Pig Feed with either menhaden or corn oil to produce a eucaloric feed with 15% fat) and then injected with live Escherichia coli. The omega 3 FA diet increased the concentration of eicosapentainoic acid (EPA, 20:5 omega 3) in plasma lipids, and increased the ratio of EPA to arachidonic acid (AA, 20:4 omega 6) in platelets from 1:20 to 1:1 over the 8 days. Following the injection of bacteria, there was a fall in PaO2 and blood pressure that was attenuated (p less than 0.05) by the omega 3 FA diet. The omega 3 FA diet, compared to the omega 6 FA diet, also attenuated the rise in thromboxane B2 (3.0 +/- 1.1 vs 12.9 +/- 5.7 ng/mL) and 6 keto-PGF1 alpha (0.8 +/- 0.5 vs 1.7 +/- 1.1 ng/mL) associated with bacteremia. We conclude that dietary omega 3 FA attenuated the physiologic response to sepsis, possibly by modifying arachidonic acid metabolism.


Comparison of the efficacy and safety of two formulations of diclofenac sodium 0.1% eyedrops in controlling postoperative inflammation after cataract surgery.
To compare the efficacy and safety of diclofenac sodium 0.1% eyedrops packaged in an Abak multidose container without preservative (Dicloabak) with the reference product, sodium merthiolate-preserved diclofenac sodium 0.1% eyedrops, in controlling postoperative inflammation after cataract surgery. The multicenter, controlled, randomized, single-masked study included 194 patients (Dicloabak 96, preserved diclofenac 98) scheduled to have cataract surgery by phacoemulsification with foldable intraocular lens. All were evaluated preoperatively and postoperatively after 1, 7, and 28 days. Postoperative inflammation was measured by the total score of anterior chamber cells and flare. Ocular plin, conjunctival hyperemia and ciliary flush were also assessed. Postoperative patient assessments also included visual acuity, objective tolerance by slit-lamp, fluorescein test, and subjective evaluation of local tolerance. There was no statistically significant difference between the groups in the total score of flare and cells or the degree of conjunctival hyperemia and ciliary flush at any study visit. Dicloabak was demonstrated to be not inferior to preserved diclofenac at all assessment times. The overall assessment of local tolerance was similar for both study medications. Preservative suppression did not alter diclofenac efficacy. Results support the good safety profile of both formulations when dosed three times daily for 4 weeks in absence of concomitant use of drugs potentially toxic for cornea. Preservative-free formulations like Dicloabak should be preferred to generic diclofenac formulations including other ingredients and may improve the safety profile of this topical nonsteroid anti-inflammatory drug.


Intramuscular Injection and Complex Regional Pain Syndrome Development After "Harmless" Procedures.
Complex regional pain syndrome (CRPS) is a puzzling pain condition, typically occurring after trauma. Incidents as innocent as IV injection and vaccine administration may serve as the impetus for an as yet poorly understood cascade of neuro-inflammation and somatosensory changes. A condition with variable degrees of psychological involvement, disability, and purely clinical diagnostic criteria, the diagnosis is often significantly delayed before effective treatment is begun, decreasing the likelihood of success. A 58-year-old female initially presented with painless peripheral edema of the left arm without erythema or loss of function, with later bilateral development of multiple domains of symptoms consistent with CRPS. Plausible initiation events in this instance were an IV insertion in the left cubital fossa and vaccination into the right deltoid. Delay in diagnosis is common but utilization of the Budapest Criteria for diagnosis and prompt treatment improves outcomes.


Long-lasting handling affects behavioural reactivity in adult rats of both sexes prenatally exposed to diazepam.
Environmental stressors can substantially affect the adaptive response of rats to novelty in a sexually dimorphic manner. Gender-related differences are also observed in neurochemical and behavioural patterns of adult rats following prenatal exposure to diazepam (DZ). In the present study the behavioural reactivity to novelty is investigated in open field (OF) and in acoustic startle reflex (ASR) tests, in non handled (NH), short-lasting handled (SLH) and long-lasting handled (LLH) adult male and female rats prenatally exposed to DZ. A single daily s.c. injection of DZ (1.5 mg/kg) over gestation days 14-20 decreases GABA/BDZ receptor function in both sexes, as shown by the decreased electrographic hippocampal response to DZ and the increased response to picrotoxin, after intra-locus coeruleus injection of the two compounds. In OF NH DZ-exposed males display a lower total distance travelled (TDT), a higher rearing frequency (RF) and a greater number of transitions in the centre of the arena (CNT) compared to NH rats prenatally exposed to vehicle. Conversely, NH DZ-exposed females show slight changes in TDT and RF and a greater reduction in CNT and in the amount of time spent in the centre of the arena (CAT). These effects are associated with an increase in the peak amplitude of the ASR in both sexes. Short-lasting handling slightly influences DZ-evoked effects in animals of both sexes. In DZ-exposed males long-lasting handling attenuates the reduction in TDT and the enhancement in RF, prevents the increase in CNT and reduces the peak amplitude of ASR. In DZ-exposed females, long-lasting handling increases TDT and RF, induces a lower avoidance of the centre of the arena, and does not modify the peak amplitude of ASR, when compared to controls. These findings indicate that prenatal exposure to DZ differently affects behavioural reactivity in adult male and female rats, and suggest that a long-lasting handling is able to attenuate some behavioural deficits induced by prenatal DZ exposure.


Low-risk gestational trophoblastic neoplasia and methotrexate resistance: predictors of response to treatment with actinomycin D and need for combination chemotherapy.
To determine whether any clinical parameters predict the need for multiagent chemotherapy for treatment of low-risk gestational trophoblastic neoplasia (GTN) after the development of methotrexate (MTX) resistance. We retrospectively analyzed clinical data from the New England Trophoblastic Disease Center from women with post-molar GTN between 1973 and 2003. We analyzed data from 150 women (40 with partial mole, 110 with complete mole) who received single-agent MTX for low-risk GTN using FIGO and WHO scoring systems. Of the 45 women who developed MTX resistance, the majority (37/45) of these patients received actinomycin D, with 10 patients ultimately requiring multiagent chemotherapy. The requirement for multiagent chemotherapy following MTX resistance was associated with a beta-hCG > 600 mlU/mL 1 week following initial MTX therapy (p < 0.03). Conversely, a beta-hCG < 600 mlU/mL 1 week following initial MTX therapy was as-sociated with a 93% probability of remission with actinomycin D alone. All patients went into durable remission. The prognosis for patients with low-risk GTN following molar gestation is excellent, with 100% remission rate, though a small but significant proportion (7%) required multiagent chemotherapy. The need for multiagent chemotherapy was associated with beta-hCG levels 1 week following initial MTX therapy.


Thyroidectomy in patients at high-risk of bleeding: can it be safely performed?
This study evaluated the safety of thyroid surgery in patients where anticoagulation was unavoidable or in patients with coagulopathy. The records of all patients having high risk of bleeding at the time of thyroidectomy (July 2000 and March 2005) were retrospectively reviewed to evaluate intraoperative and postoperative bleeding. Ten patients were studied. Thyroid lobectomy with isthmusectomy (N=3) and bilateral thyroidectomy (N=7) were performed. Intraoperative surgical hemostasis was meticulous using ligasure vessel sealing system. Patients were divided in 3 groups. Group I (N=2) had small-vessel vasculitis, underwent thyroidectomy under full heparinization. Heparin therapy was continued until full anticoagulation by oral anticoagulants. Group II (N=2) had a documented congenital coagulation defect, had a pre and postoperative special protocols. Group III (N=6) underwent simultaneous thyroid and cardiac surgery (e.g.: intraoperative full heparinization and postoperative antiplatelet therapy in some cases). No extra-bleeding was noted on surgical reports. In the postoperative period, one patient developed a superficial small hematoma in the neck that resolved spontaneously. Transient unilateral laryngeal nerve palsy and transient hypocalcemia were seen in one and two patients respectively. Thyroidectomy in patients with coagulopathy is feasible with low risk of bleeding if meticulous hemostasis, particularly using ligasure vessel sealing system, is respected.


The effect of endogenously released glucose, insulin, glucagon-like peptide 1, ghrelin on cardiac output, heart rate, stroke volume, and blood pressure.
Ingestion of a meal increases the blood flow to the gastrointestinal organs and affects the heart rate (HR), blood pressure and cardiac output (CO), although the mechanisms are not known. The aim of this study was to evaluate the effect of endogenously released glucose, insulin, glucagon-like peptide 1 (GLP-1), ghrelin on CO, HR, stroke volume (SV), and blood pressure. Eleven healthy men and twelve healthy women ((mean ± SEM) aged: 26 ± 0.2 y; body mass index: 21.8 ± 0.1 kg/m(2))) were included in this study. The CO, HR, SV, systolic and diastolic blood pressure, antral area, gastric emptying rate, and glucose, insulin, GLP-1 and ghrelin levels were measured. The CO and SV at 30 min were significantly higher, and the diastolic blood pressure was significantly lower, than the fasting in both men and women (P < 0.05). In men, significant correlations were found between GLP-1 level at 30 min and SV at 30 min (P = 0.015, r = 0.946), and between ghrelin levels and HR (P = 0.013, r = 0.951) at 110 min. Significant correlations were also found between the change in glucose level at 30 min and the change in systolic blood pressure (P = 0.021, r = -0.681), and the change in SV (P = 0.008, r = -0.748) relative to the fasting in men. The insulin 0-30 min AUC was significantly correlated to the CO 0-30 min AUC (P = 0.002, r = 0.814) in men. Significant correlations were also found between the 0-120 min ghrelin and HR AUCs (P = 0.007, r = 0.966) in men. No statistically significant correlations were seen in women. Physiological changes in the levels of glucose, insulin, GLP-1 and ghrelin may influence the activity of the heart and the blood pressure. There may also be gender-related differences in the haemodynamic responses to postprandial changes in hormone levels. The results of this study show that subjects should not eat immediately prior to, or during, the evaluation of cardiovascular interventions as postprandial affects may affect the results, leading to erroneous interpretation of the cardiovascular effects of the primary intervention. NCT01027507.


An efficient, mild and solvent-free synthesis of benzene ring acylated harmalines.
A facile synthesis of a series of benzene ring acylated analogues of harmaline has been achieved by Friedel-Crafts acylation under solvent-free conditions at room temperature using acyl halides/acid anhydrides and AlCl3. The reaction afforded 10- and 12-acyl analogues of harmaline in good yield, along with minor quantities of N-acyl-tryptamines and 8-acyl analogues of N-acyltryptamines.


Optical fiber Fabry-Perot interferometer coupled to a 3-D integrated waveguide for 3-D position sensing.
Optical fiber extrinsic Fabry-Perot interferometers (EFPIs) have been extensively demonstrated for the measurement of displacement and displacement-related physical quantities, e.g., acceleration, pressure, with high sensitivity and resolution. Despite its wide and successful applications, a conventional EFPI is limited to measuring only one-dimensional (out-of-plane) movement of its external reflector. In this Letter, a new strategy for optical fiber sensing, particularly for EFPI sensing, is proposed and demonstrated, allowing for three-dimensional (3-D) measurements based on a hybrid and compact EFPI device. A 3-D integrated optical waveguide array is aligned against a lead-in optical fiber with an air gap, where an EFPI is formed by the end facet of the optical fiber and the end facet of the waveguide array. As a proof of concept, we experimentally demonstrate that 3-D positioning can be achieved from the EFPI with sub-micron resolution by simultaneously measuring the reflection and transmission of the device. The proposed strategy of using an optical waveguide as an external reflector for an optical fiber EFPI, combined with machine learning-based analysis, opens new avenues in the development of compact yet multi-dimensional sensors.


Factors influencing within-group conflict over defence against conspecific outsiders seeking breeding positions.
In social species, groups face a variety of threats from conspecific outsiders. Defensive actions are therefore common, but there is considerable variation in which individuals contribute and to what extent. There has been some theoretical exploration of this variation when the defence is of shared resources, but the relative contributions when a single intruder threatens a particular breeding position have received less attention. Defensive actions are costly, both for the individual and dependent young, and contributions are likely to differ depending on individual sex, rank and size, current breeding stage, infanticide risk and relatedness levels. Here, we model analytically the relative fitness benefits of different group members to engaging in defence against individual intruders and determine when within-group conflicts of interest might arise over these defensive contributions. Conflicts of interest between the challenged breeder and other group members depend on relatedness to the brood and the potential relatedness reduction if an intruder acquires breeding status. Conflicts are more likely to occur when there is a low chance of winning the contest, low infanticide rates, inefficient defence from helpers, a long remaining brood-dependency period and high external (non-contest-related) mortality. Our work can help explain variation in defensive actions against out-group threats.


TongueToSpeech (TTS): Wearable wireless assistive device for augmented speech.
Speech is an important aspect of human communication; individuals with speech impairment are unable to communicate vocally in real time. Our team has developed the TongueToSpeech (TTS) device with the goal of augmenting speech communication for the vocally impaired. The proposed device is a wearable wireless assistive device that incorporates a capacitive touch keyboard interface embedded inside a discrete retainer. This device connects to a computer, tablet or a smartphone via Bluetooth connection. The developed TTS application converts text typed by the tongue into audible speech. Our studies have concluded that an 8-contact point configuration between the tongue and the TTS device would yield the best user precision and speed performance. On average using the TTS device inside the oral cavity takes 2.5 times longer than the pointer finger using a T9 (Text on 9 keys) keyboard configuration to type the same phrase. In conclusion, we have developed a discrete noninvasive wearable device that allows the vocally impaired individuals to communicate in real time.


Open distal gastrectomy versus laparoscopic distal gastrectomy for early gastric cancer: a retrospective study.
Laparoscopic distal gastrectomy (LDG) is gaining popularity because its early postoperative effect has been shown to be better than open distal gastrectomy (ODG). However, to our knowledge, there are no studies demonstrating ODG is oncologically equivalent to LDG. This is a retrospective study based on the prospectively maintained database of the People's Hospital of Jinan City. Patients with operable, pathologically confirmed early-stage gastric cancer were included, while those with advanced disease or carcinoma in situ were excluded. Extracted data included age, body mass index (BMI), sex, clinical TNM stage, and pathologic stage. The primary outcome was 5-year overall survival, and the secondary outcomes included cancer-specific survival, cost-effectiveness, and quality of life. A total of 126 patients were finally enrolled and included 61 in the ODG group and 65 in the LDG group. Baseline clinical and pathological characteristics were generally balanced between the two groups. After a median follow-up of 8.31 years, the 5-year overall survival rate was estimated to be 82.8% (95% CI: 69.4-90.7%) for the ODG group and 86.7% (95% CI: 73.9-93.5%) for the LDG group and the recurrence patterns were similar between the two groups. Our data showed that the surgical results of both approaches are satisfactory, and LDG offers a reasonable option to ODG in patients with early gastric cancer.


Percutaneous mitral balloon valvotomy in pregnancy using the Inoue balloon technique.
We describe a 40-year-old female who was 27 weeks pregnant and had severe rheumatic mitral valve stenosis. The patient presented with severe biventricular heart failure and fast atrial fibrillation. Soon after admission the patient sustained a cardiac arrest and was successfully resuscitated. Despite maximal medical therapy the patient was still in pulmonary edema. Beta blockers were contraindicated as the patient had bronchial asthma. Balloon mitral valvotomy using an Inoue 26 mm balloon catheter was done. The procedure was done with pelvic and abdominal shielding. To minimize radiation exposure no angiography was done and the procedure was done with echo-Doppler guided stepwise mitral valve dilatation. The mitral valve area after balloon valvotomy increased from 0.9 to 2 cm2. The total fluoroscopy time was 14 minutes. At 6-week follow-up the patient was virtually asymptomatic. Vaginal delivery was uneventful. Balloon mitral valvotomy using the Inoue technique in pregnancy with echo guided stepwise dilatation is accomplished with minimal radiation exposure, provided abdominal shielding is implemented throughout the procedure.


Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats.
Docosahexaenoic acid (C22:6, n-3), a major n-3 fatty acid of the brain, has been implicated in restoration and enhancement of memory-related functions. Because Alzheimer's disease impairs memory, and infusion of amyloid-beta (Abeta) peptide (1-40) into the rat cerebral ventricle reduces learning ability, we investigated the effect of dietary pre-administration of docosahexaenoic acid on avoidance learning ability in Abeta peptide-produced Alzheimer's disease model rats. After a mini-osmotic pump filled with Abeta peptide or vehicle was implanted in docosahexaenoic acid-fed and control rats, they were subjected to an active avoidance task in a shuttle avoidance system apparatus. Pre-administration of docosahexaenoic acid had a profoundly beneficial effect on the decline in avoidance learning ability in the Alzheimer's disease model rats, associated with an increase in the cortico-hippocampal docosahexaenoic acid/arachidonic acid molar ratio, and a decrease in neuronal apoptotic products. Docosahexaenoic acid pre-administration furthermore increased cortico-hippocampal reduced glutathione levels and glutathione reductase activity, and suppressed the increase in lipid peroxide and reactive oxygen species levels in the cerebral cortex and hippocampus of the Alzheimer's disease model rats, suggesting an increase in antioxidative defence. Docosahexaenoic acid is thus a possible prophylactic means for preventing the learning deficiencies of Alzheimer's disease.


Using an interactive journal club to enhance nursing research knowledge acquisition, appraisal, and application.
Nursing practice is intricate and multifaceted. It requires the application of current, health-related research. Nurses are expected to employ evidence-informed practice in making decisions about the clinical care of their clients. A journal club is one method that can help promote an increased awareness of research, educating students to critique and use research findings. In this descriptive pilot study, the use of a journal club was evaluated. University undergraduate nursing students (N=35) across three sites in eastern Canada participated. Although the results are limited, participants found the journal club sessions enjoyable and beneficial for helping them interpret research findings and apply research to clinical practice. More research directed at helping nursing students critique and apply research to nursing practice is warranted.


Assay of vitamin B in urine by capillary electrochromatography with methacrylate-based monolithic column.
A novel and simple method for the separation of major vitamin B analytes, such as thiamine, riboflavin, nicotinamide, vitamin B4, pyridoxine, has been developed by CEC using the monolithic column. It has been found that the baseline separation of the five analytes could be achieved with 5.0 mM phosphate buffer at pH 4.0. Compared with the open-tubular capillary and the bared capillary columns, the poly(butylmethacrylate-co-ethylene glycol dimethacrylate) monolithic capillary could exhibit the best resolution in the analysis. Then the method was validated and the linear calibration ranges were obtained with correlation coefficients more than 0.997. The precision and the recovery were also investigated and showed a good result. Furthermore, the proposed method was successfully applied to assay the concentration of vitamin B analytes and the metabolic situation in human urine samples.


An efficient method of agrobacterium-mediated genetic transformation and regeneration in local Indian cultivar of groundnut (Arachis hypogaea) using grafting.
Groundnut (Arachis hypogaea L.) is an industrial crop used as a source of edible oil and nutrients. In this study, an efficient method of regeneration and Agrobacterium-mediated genetic transformation is reported for a local cultivar GG-20 using de-embryonated cotyledon explant. A high regeneration 52.69 ± 2.32 % was achieved by this method with 66.6 μM 6-benzylaminopurine (BAP), while the highest number of shoot buds per explant, 17.67 ± 3.51, was found with 20 μM BAP and 10 μM 2,4-dichlorophenoxyacetic acid (2,4-D). The bacterial culture OD, acetosyringone and L-cysteine concentration were optimized as 1.8, 200 μM and 50 mg L(-1), respectively, in co-cultivation media. It was observed that the addition of 2,4-D in co-cultivation media induced accumulation of endogenous indole-3-acetic acid (IAA). The optimized protocol exhibited 85 % transformation efficiency followed by 14.65 ± 1.06 % regeneration, of which 3.82 ± 0.6 % explants were survived on hygromycin after selection. Finally, 14.58 ± 2.95 % shoots (regenerated on survived explants) were rooted on rooting media (RM3). In grafting method, regenerated shoots (after hygromycin selection) were grafted on the non-transformed stocks with 100 % survival and new leaves emerged in 3 weeks. The putative transgenic plants were then confirmed by PCR, Southern hybridization, reverse transcriptase PCR (RT-PCR) and β-glucuronidase (GUS) histochemical assay. The reported method is efficient and rapid and can also be applied to other crops which are recalcitrant and difficult in rooting.


Single-nucleotide polymorphisms in adiponectin, AdipoR1, and AdipoR2 genes: insulin resistance and type 2 diabetes mellitus candidate genes.
It has already been a decade and a half since the discovery of adiponectin and its role as an insulin sensitizer and only 7 years since its receptors, AdipoR1 and AdipoR2, were described. A single-nucleotide polymorphism (SNP) is a DNA sequence variation that affects only one nucleotide; it may vary from one population to another with different predisposing factors to diseases and other ailments. Once some of the effects of adiponectin and its receptors were known, it was not long until an effort was made to find the associations between specific SNPs of the genes of this hormone and its receptors as genetic risk factors for insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, although these genes were investigated as possible candidates related to the development of these metabolic disorders. All of these possible associations were studied in different populations from France, Finland, the United Kingdom, North America, and Japan, showing hardly concluding results, and because of that it is highly controversial to directly associate one of the genes mentioned above to insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. All of these inconsistencies lead to a review that summarizes the SNPs of the genes of adiponectin, AdipoR1, and AdipoR2 that are mostly related to insulin resistance syndrome, type 2 diabetes mellitus, and metabolic syndrome, although presenting the possible factors that should be taken into account to homogenize the results obtained until now.


Regulation of protein phosphatase activity by the deinhibitor protein.
In liver and muscle the major active phosphorylase and synthase phosphatase activity is associated with the glycogen particle. When we examined the effect of the inhibitor-1 and modulator protein on the enzyme present in crude glycogen fractions from dog liver, the phosphorylase phosphatase was not or only slightly affected. Since the enzyme isolated from the glycogen complex by DEAE-cellulose chromatography could be inhibited by inhibitor-1 as well as the modulator protein, it was assumed that an unknown mechanism or factor present in the glycogen fraction was responsible for this reduced sensitivity of the protein phosphatase. This led to the discovery (7) of the deinhibitor protein which has now been extensively purified from dog liver. The deinhibitor protein was shown to be thermostable, ethanol- and trichloroacetic acid-resistant, but non-dialyzable and it was destroyed by pronase or trypsin. The apparent molecular weight was estimated at about 17,500 in gel filtration, 8,300 in sodium dodecyl sulfate polyacrylamide gel electrophoresis and 5,500 in sucrose density gradient centrifugation, behavior which is consistent with the assumption that the deinhibitor protein may have little ordered structure. Glycogen synthesis requires both phosphorylase and glycogen synthase as dephosphorylated enzymes. The interaction of the deinhibitor protein with the protein phosphatase brings about several effects which, when considered together, could all facilitate the dephosphorylation of glycogen synthase and phosphorylase. The protein phosphatase present in a resuspended glycogen pellet dephosphorylates inhibitor-1 in the absence of Mn2+. This ability of the phosphatase, which is lost during purification of the enzyme, can be restored upon addition of the deinhibitor protein. Owing to the association of the deinhibitor protein with the active phosphatase the enzyme becomes insensitive to inhibition by inhibitor-1 and the modulator protein, and more resistant to the conversion into the FA-ATP,Mg-dependent form, brought about by the modulator protein. During the activation of the ATP,Mg-dependent phosphatase under conditions where kinase FA is rate limiting, the deinhibitor protein increases the level without affecting the rate of activation.


How Do Aromatic Nitro Compounds React with Nucleophiles? Theoretical Description Using Aromaticity, Nucleophilicity and Electrophilicity Indices.
In this study, we present a complete description of the addition of a model nucleophile to the nitroaromatic ring in positions occupied either by hydrogen (the first step of the SNAr-H reaction) or a leaving group (SNAr-X reaction) using theoretical parameters including aromaticity (HOMA), electrophilicity and nucleophilicity indices. It was shown both experimentally and by our calculations, including kinetic isotope effect modeling, that the addition of a nucleophile to the electron-deficient aromatic ring is the rate limiting step of both SNAr-X and SNAr-H reactions when the fast transformation of σH-adduct into the products is possible due to the specific reaction conditions, so this is the most important step of the entire reaction. The results described in this paper are helpful for better understanding of the subtle factors controlling the reaction direction and rate.


Changes in hemoglobin-oxygen affinity with shape variations of red blood cells.
Shape variations of red blood cells (RBCs) are known to occur upon exposure to various drugs or under diseased conditions. The commonly observed discocytic RBCs can be transformed to echinocytic or stomatocytic shape under such conditions. Raman spectra of the three major shape variations, namely discocyte, echinocyte, and stomatocyte, of RBCs were studied while subjecting the cells to oxygenated and deoxygenated conditions. Analysis of the recorded spectra suggests an increased level of hemoglobin (Hb)-oxygen affinity for the echinocytes. Also, some level of Hb degradation could be noticed for the deoxygenated echinocytes. The effects may arise from a reduced level of intracellular adenosine triphosphate in echinocytic cells and an increased fraction of submembrane Hb.


A combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau but minimal levels of other key modifications.
Abnormal changes of neuronal Tau protein, such as phosphorylation and aggregation, are considered hallmarks of cognitive deficits in Alzheimer's disease. Abnormal phosphorylation is thought to precede aggregation and therefore to promote aggregation, but the nature and extent of phosphorylation remain ill-defined. Tau contains ∼85 potential phosphorylation sites, which can be phosphorylated by various kinases because the unfolded structure of Tau makes them accessible. However, methodological limitations (e.g. in MS of phosphopeptides, or antibodies against phosphoepitopes) led to conflicting results regarding the extent of Tau phosphorylation in cells. Here we present results from a new approach based on native MS of intact Tau expressed in eukaryotic cells (Sf9). The extent of phosphorylation is heterogeneous, up to ∼20 phosphates per molecule distributed over 51 sites. The medium phosphorylated fraction Pm showed overall occupancies of ∼8 Pi (± 5) with a bell-shaped distribution; the highly phosphorylated fraction Ph had 14 Pi (± 6). The distribution of sites was highly asymmetric (with 71% of all P-sites in the C-terminal half of Tau). All sites were on Ser or Thr residues, but none were on Tyr. Other known posttranslational modifications were near or below our detection limit (e.g. acetylation, ubiquitination). These findings suggest that normal cellular Tau shows a remarkably high extent of phosphorylation, whereas other modifications are nearly absent. This implies that abnormal phosphorylations at certain sites may not affect the extent of phosphorylation significantly and do not represent hyperphosphorylation. By implication, the pathological aggregation of Tau is not likely a consequence of high phosphorylation.


The changing epidemiology of dog bite injuries in the United States, 2005-2018.
In 2018, the most recent year for which data are available, dog bites ranked as the 13th leading cause of nonfatal emergency department visits in the United States. As dog ownership spirals upwards in the United States, it is important to continue to monitor the epidemiology of dog bite injuries. This study provides contemporary data on the incidence of dog bites injuries in the United States and in New York and profiles individuals who have been treated for dog bites in emergency departments. The study also examines the demographic correlates of the rate of injuries at the neighborhood level in New York City and maps the rate in each neighborhood. At the national level, the study examines longitudinal data on dog bite injuries from 2005 to 2018 gathered by the Centers for Disease Control and Prevention. For New York, the study analyzes data for 2005-2018 collected by the New York State Department of Health. A negative binomial regression analysis was performed on the state data to measure the simultaneous effects of demographic variables on the incidence of dog-related injuries. A thematically shaded map of the rate of dog bite injuries in New York City's neighborhoods was created to identify neighborhoods with higher-than-average concentration of injuries. In both the United States and New York the rate of dog-bite injuries increased from 2005 to 2011 and then underwent a significant decline. Injuries due to dog bites, however, still remain a sizable public health problem. Injuries are more prevalent among school-age children, inhabitants of less-densely populated areas, and residents of poorer neighborhoods. In New York City, poorer neighborhoods are also associated with fewer dogs being spayed or neutered. To reduce the rate of dog bite injuries, prevention programs - particularly those which center on teaching the dangers of canine interactions with humans - should be targeted at children. Dog bite injuries tend to be clustered in identifiable neighborhoods. Dog bite prevention programs and stricter enforcement of dog laws can target these neighborhoods.


Selective degradation of accumulated secretory proteins in the endoplasmic reticulum. A possible clearance pathway for abnormal tropoelastin.
The specific pathway of tropoelastin secretion was investigated in fetal calf ligamentum nuchae (FCL) cells using brefeldin A (BFA) to disrupt the secretory pathway. Electron microscopic studies of BFA-treated FCL cells showed ultrastructural changes consistent with the reported effects of BFA on intracellular organelles. When FCL cells were labeled with [3H]leucine in the presence of BFA, radiolabeled tropoelastin was not secreted, nor was there an intracellular accumulation of the protein. In contrast, fibronectin accumulated within the cells in the presence of BFA. Northern analysis of mRNA levels in FCL cells showed that the message for tropoelastin was unaffected by BFA treatment. Pulse chase experiments conducted in the presence of BFA demonstrated that the tropoelastin retained within the cells was rapidly degraded. Ammonium chloride, nocodazole, and cycloheximide had no effect on the degradation of tropoelastin, indicating that the degradation did not involve the endosome/lysosome pathway, movement via microtubules, or a short-lived protein, respectively. Incubation of FCL cells with BFA in the presence of N-acetyl-Leu-Leu-norleucinal, however, allowed tropoelastin to steadily accumulate in the cells. Cells pulsed in the presence of BFA alone showed that tropoelastin initially accumulates within the cells for approximately 1 h prior to being degraded, thus indicating that a critical threshold of tropoelastin must be reached before degradation can occur. Results from this study provide evidence for selective degradation of a soluble secreted protein by a cysteine protease following retention of the protein in the endoplasmic reticulum.


A comparison of three health status measures in primary care outpatients.
Our objective was to compare a brief, relatively new global health status measure, the Health Utilities Index Mark II (HUI), to two commonly applied health status measures (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36] and the Sickness Jgipact Profile [SIP] in a general medical outpatient population. Using a cross-sectional survey, we surveyed 160 patients in the General Medical Clinic of the Durham Veterans Affairs Medical Center. Each subject answered demographic questions and then completed the three health status measures. The mean tJgie taken to complete the measures was 3, 10, and 20 minutes for the HUI, SF-36, and SIP, respectively (p <.0001). The HUI exhibited a modest "floor" effect; that is, scores were concentrated near the sicker of the scale. In contrast, responses to the SIP were heavily concentrated near the healthier end of the scale. Spearman correlation coefficients between the HUI and scales within the other two measures ranged from. 54 (SF-36 mental health) to 0.69 (SF-36 physical functioning). Subjects accepted all measures well. These three health service measures varied in their distribution of responses and ttime required to complete. Users should consider the degree of sickness of the population to be assessed when choosing a measure.


Toward the development of prochelators as fluorescent probes of copper-mediated oxidative stress.
A fluorescent sensor prochelator, FlamB (fluorescein hydrizido 2-imidophenylboronic ester), has been developed that selectively probes for copper under conditions of oxidative stress. High levels of hydrogen peroxide trigger the release of a boronic ester masking group from the prochelator to unveil a metal chelator, FlamS (fluorescein hydrizido 2-imidophenol), that provides a modest fluorescence increase in response to Cu(2+) but not other metal ions. X-Ray crystal structures of FlamB, FlamS, and Cu-bound FlamS are all reported. The fluorescence turn-on results from opening of a fluorescein spirolactam ring upon Cu(2+) binding to FlamS in aqueous solution. Oxidation of the aryl boronic ester of FlamB to the metal-binding phenol of FlamS proceeds in organic solvents. However, in aqueous solution a competing mechanism occurs due to hydrolytic instability of the masked prochelator. Hydrolysis of FlamB leads to formation of fluorescein hydrazide, which interacts with copper or H(2)O(2) to produce fluorescein and a significant fluorescence increase.


[Intraoperative endoscopy in laparoscopic fundoplications].
Laparoscopic fundoplications are the standard surgical treatment of patients with gastroesophageal reflux disorder. Adequate technique is the most important outcome factor. There is no standardized method to evaluate the procedure itself. Intraoperative endoscopy is a method to evaluate laparoscopic fundoplications. This was a retrospective observational study of patients undergoing laparoscopic fundoplications from July 1999 to June 2004, excluding open procedures and reoperations of previous failed laparoscopic fundoplications. Intraoperative endoscopy was performed during the dissection and suturing of the procedure to determine if correction of the technique is necessary. Number of changes were recorded and analyzed with Student's t-test. Three hundred patients were operated on, 23 were excluded (14 reoperations and nine conventional laparotomies). Of the 277 patients included, 178 were males and 99 females. Average age was 43.4 +/- 14 years (range: 12-85). There were 71 Toupet and 206 Nissen fundoplications. Intraoperative endoscopy determined correction of the technique in 77 patients with 1.69 +/- 0.96 changes; 68 rotated and/or angled fundoplications, one rotation with distended stomach, one redundant gastric fundus, and seven change in the type of fundoplication from Nissen to Toupet because of tightness (3.7 +/- 1.1 changes, p = 0.0001) to achieve adequate fundoplication. Intraoperative endoscopy confirms adequate technique and prevents inadequate laparoscopic fundoplications. Further studies will determine if routine use is justified to prevent postoperative complications and to improve outcome.


Spinal cord decompression and stabilization in malignant lesions of the spine.
20 patients with neurologic deficit and pain from malignant spinal tumors (7 primary) underwent 28 decompression and stabilization procedures. Their mean age was 57 (30-74) years and 11 were women. Indications for stabilization were pathological spine fractures or a previous spinal decompression procedure. An anterior procedure was used in 2 patients with disease limited to 1 or 2 levels. A posterior procedure was used in 10 patients with widespread disease and unsatisfactory condition. Anteroposterior procedures in 1 or 2 stages were performed on 8 patients in satisfactory general condition with a malignant lesion at 1 or 2 levels and an unstable spine. Patients were submitted to radio- and/or chemotherapy postoperatively. Survival of patients treated for primary malignant tumors averaged 30 months and was 11 months for metastatic disease. 16 of the patients, especially those with nonmetastatic disease, had substantial relief of pain. Neurologic recovery was achieved in all of the anterior and combined anterior-posterior procedures and in 60% of the posterior decompressions. Complications included failure of the instrumentation in 2 cases, skin breakdown in another 2 and dislodgment of the autograft in 1.


Suicidality in hospitalized adolescents: relationship to prior abuse.
The effects of admission status, prior abuse, and the frequency and duration of both physical and sexual abuse on measures of suicidality for a sample of 117 hospitalized adolescents were investigated. Having been abused was found to have a significant association with the number of previous suicide attempts and to interact with the variable of admission status in measures of suicide ideation.


[Correlation of lumbar disc degeneration and spinal-pelvic sagittal balance].
To elucidate the relationship between spino-pelvic sagittal balance parameters and lumbar intervertebral disc degeneration of each segment through retrospective analysis in lumbar degeneration patients. Retrospective analysis was conducted for the follow-up data in 126 patients with lumbar degenerative disease from July 2009 to June 2012. There were 38 cases with whole spine plates and 88 cases with lumbar plates. All of them received magnetic resonance imaging (MRI) scans. Through software Image J, the following spino-pelvic sagittal balance parameters were measured: sagittal vertical axis (SVA, distance between C7 plumb line and posterior upper corner of S1 endplate), thoracic kyphosis (TK, T5-T12 Cobb angle), thoracolumbar kyphosis (TLK, T10-L2 Cobb angle), lumbar lordosis (LL, L1-L5 Cobb angle), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), T1 spino-pelvic inclination (T1-SPI), T9 spino-pelvic inclination (T9-SPI), spino-sacral angle (SSA), spino-pelvic angle (SPA) and C7 tilt (C7T). Based on the grading system of Pfirrmann et al, the intervertebral disc degeneration grades were acquired for each lumbar segment. According to the normal range of previous studies, each spino-pelvic sagittal balance parameter was classified into 3 groups, i.e. Group A (less than normal), Group B (normal) and Group C (more than normal). All statistical analyses were performed to compare the differences of each lumbar segment/intervertebral disc degeneration among groups by one-way ANOVA test via SPSS 18.0. And P-value < 0.05 was deemed significant. PI had a significant impact on the L5/S1 disc degeneration. And L5/S1 disc degeneration had a significant impact on sagittal balance. Among 57 cases of large PI, LL, PT, SS, SVA, C7T, SPA in L5/S1 of mild-to-moderate and severe degeneration groups was 36.91 ± 14.93 and 29.71 ± 11.30 (P = 0.045), 18.82 ± 8.27 and 25.18 ± 10.19 (P = 0.012), 39.45 ± 8.82 and 34.57 ± 8.88 (P = 0.042), 23.04 ± 26.63 and 62.15 ± 33.82 (P = 0.002), 88.85 ± 3.13 and 83.98 ± 4.62 (P = 0.003), 157.88 ± 11.20 and 147.75 ± 13.98 (P = 0.043) respectively. TLK in L1/L2 with mild-to-moderate and severe degeneration groups was 4.59 ± 7.81 and 14.91 ± 14.75 (P = 0.026). All of L1/L2, L2/L3 and L3/L4 disc degeneration had a significant impact on SPA. SPA in L1/L2, L2/L3, and L3/L4 with mild-to-moderate and severe degeneration groups was 158.47 ± 11.97 and 147.84 ± 12.72 (P = 0.031), 159.91 ± 10.78 and 148.75 ± 13.17 (P = 0.024), 158.46 ± 10.86 and 148.61 ± 13.93 (P = 0.047) respectively. With an important impact on lumbar disc degeneration, PI, either too big or too small, may predispose to the occurrences of lumbar disc degeneration. L5/S1 disc degeneration has a significant impact on pelvis postural parameters (PT, SS). L5/S1 degeneration is a key causative factor of pelvic posterior rotation and compensatory process. L5/S1 disc degeneration has an important impact on pelvis overall parameters (SVA, SPA, C7T). And the degeneration of L5/S1 is a key cause of trunk imbalance.


Comparative yolk cholesterol content in four Spanish breeds of hens, an F2 cross, and a White Leghorn population.
Yolk cholesterol content (milligrams per gram of yolk and milligrams per egg) was studied in eggs of four Spanish breeds of hens (Castellana, Buff Prat, Vasca, and Villafranquina), an F2 from a cross between Castellana and Buff Prat (C x BP-F2), and a White Leghorn population. Birds were tested at 30 wk of age. There were differences among breeds (P < .001), cholesterol concentration being significantly lower in the C x BP-F2 (13.14 +/- .26 mg/g yolk) than in the other breeds. Villafranquina and Buff Prat showed significantly lower cholesterol (14.54 +/- .26 and 14.56 +/- .26 mg/g yolk, respectively) than the White Leghorn (16.30 +/- .26 mg/g yolk). Eggs from the Vasca breed contained significantly more cholesterol (19.09 +/- .26 mg/g yolk) than did eggs laid by the other breeds, whereas no differences were found between Leghorn and Castellana. A negative heterosis percentage of -13% was found in the C x BP-F2 when compared with the parental breed means. The reduction in cholesterol concentration per egg observed in the C x BP-F2 (220.49 mg per egg) was not related to breed differences in egg weight or to the proportion of yolk per egg. Eggs from the Vasca breed, with the lightest yolk and smallest yolk: albumen ratio (P < .05), contained the highest amount of cholesterol (304.29 mg per egg). Eggs from the White Leghorn containing the second highest amount of cholesterol (275.63 mg per egg). Thus, the variation in cholesterol content per egg was not attributable to differences in the proportion of yolk.


Chromosome integration of BAC (bacterial artificial chromosome): evidence of multiple rearrangements.
This paper reports our attempts to characterize transgene integration sites in transgenic mouse lines generated by the microinjection of large (from 30 to 145 kb) pig DNA fragments encompassing a mammary specific gene, the whey acidic protein gene (WAP). Among the various methods used, the thermal asymmetric interlaced (TAIL-) PCR method allowed us (1) to analyze transgene/genomic borders and internal concatamer junctions for eleven transgenic lines, (2) to obtain sequence information for seven borders, (3) to place three transgenes in the mouse genome, and (4) to obtain sequence data for seven transgene junctions in concatamers. Finally, we characterized various rearrangements in the borders and the inner parts of the transgene. The possibility of such complex rearrangements should be carefully considered when transgenic animals are produced with large genomic DNA fragments.


Plasma levels of monocyte chemotactic protein 3 and beta-nerve growth factor increase with amnestic mild cognitive impairment.
A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (beta-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and beta-NGF may be useful in differentiating subtypes of MCI.


[Atherothrombosis: the same process for different arterial territories?].
Atherothrombosis is a diffuse disease. Is it the same process whatever the territory? or are there specific features depending upon the location of the lesions? At the level of the plaque, from a pathophysiological standpoint, the available literature suggests a similar process whatever the territory (slow growth of the plaque, inflammation, rupture and erosion, thrombosis, embolization). The consequences of atherothrombosis may however vary from one territory to another; this may be related to differences in arterial circulations or in cell tolerance to ischemia or in adaptative mechanisms such as collateral growth.


Asbestos-related pleural plaques and lung cancer.
The English-language literature was reviewed to evaluate a possible relationship between asbestos-related pleural plaques and lung cancer in the absence of parenchymal asbestosis. There were six cohort studies in which the comparison group was limited to unexposed persons or the general population, four lung cancer case-control studies, and three autopsy studies. Of the 13 investigations, only 3 supported the hypothesis that lung cancer risk is elevated among persons with pleural plaques over the risk in unexposed people: 2 cohort studies from the same city in England with much the same data and 1 case-control study. These three studies had the most defects in design. The other ten studies failed to confirm the hypothesis. Thus, the weight of the evidence favors the conclusion that persons with asbestos-related pleural plaques do not have an increased risk of lung cancer in the absence of parenchymal asbestosis.


A regional registration technique for automated interval change analysis of breast lesions on mammograms.
Analysis of interval change is a useful technique for detection of abnormalities in mammographic interpretation. Interval change analysis is routinely used by radiologists and its importance is well-established in clinical practice. As a first step to develop a computerized method for interval change analysis on mammograms, we are developing an automated regional registration technique to identify corresponding lesions on temporal pairs of mammograms. In this technique, the breast is first segmented from the background on the current and previous mammograms. The breast edges are then aligned using a global alignment procedure based on the mutual information between the breast regions in the two images. Using the nipple location and the breast centroid estimated independently on both mammograms, a polar coordinate system is defined for each image. The polar coordinate of the centroid of a lesion detected on the most recent mammogram is used to obtain an initial estimate of its location on the previous mammogram and to define a fan-shaped search region. A search for a matching structure to the lesion is then performed in the fan-shaped region on the previous mammogram to obtain a final estimate of its location. In this study, a quantitative evaluation of registration accuracy has been performed with a data set of 74 temporal pairs of mammograms and ground-truth correspondence information provided by an experienced radiologist. The most recent mammogram of each temporal pair exhibited a biopsy-proven mass. We have investigated the usefulness of correlation and mutual information as search criteria for determining corresponding regions on mammograms for the biopsy-proven masses. In 85% of the cases (63/74 temporal pairs) the region on the previous mammogram that corresponded to the mass on the current mammogram was correctly identified. The region centroid identified by the registration technique had an average distance of 2.8+/-1.9 mm from the centroid of the radiologist-identified region. These results indicate that our new registration technique may be useful for establishing correspondence between structures on current and previous mammograms. Once such a correspondence is established an interval change analysis could be performed to aid in both detection as well as classification of abnormal breast densities.


[Initial results with the Munich knee simulator].
In orthopaedics more than 50 different clinical knee joint evaluation tests exist that have to be trained in orthopaedic education. Often it is not possible to obtain sufficient practical training in a clinical environment. The training can be improved by Virtual Reality technology. In the frame of the Munich Knee Joint Simulation project an artificial leg with anatomical properties is attached by a force-torque sensor to an industrial robot. The recorded forces and torques are the input for a simple biomechanical model of the human knee joint. The robot is controlled in such way that the user gets the feeling he moves a real leg. The leg is embedded in a realistic environment with a couch and a patient on it.


[A developmental anomaly of Meckel's cartilage].
An atypical evolution of the mandibular cartilage was recorded in systematic dissections of the neck in the Anatomy Laboratory. This anomaly led to the formation of a supernumerary bony fragment in the concavity of the lower edge of the mandibular arch, with a slight adhesion thereto. This observation is reported by the authors after a recapitulation of the embryology.


A Faculty-Led, Community-Building Program That Enhances Student-Faculty Connections within Biology.
Connections between students and faculty on campus may influence students' sense of belonging, and a greater sense of belonging has a positive effect on student success. We developed a low-cost, faculty-led program of community-building events and implemented the program in the biology department at a small liberal-arts institution with the goal of improving students' sense of community. Student responses to surveys indicated that the majority of students felt connected to faculty and students in the department; however, Black or African American students initially felt a lower level of connection to faculty than did white students. After implementing our series of community-building events, students surveyed reported high levels of satisfaction with the events. Furthermore, there was a trend toward a higher percentage of Black or African American students than white students reporting that they were more likely to reach out to faculty after participating in the community-building events. Thus, our low-cost program improved connections between students and faculty in the biology department. Collectively, our results suggest that academic departments can implement community-building programs to improve students' sense of belonging.


Trophic dynamics of hexabromocyclododecane diastereomers and enantiomers in fish in a laboratory feeding study.
The laboratory trophic transfer of hexabromocyclododecanes (HBCDs) was studied using predatory (oscar) fish and a prey species (tiger barb) exposed to a technical HBCD. Gut absorption, dynamic changes of diastereomer pattern and enantiomer fractions, and potential metabolism of HBCDs were examined. Compared with β- or γ-HBCD, α-HBCD showed lower absorption efficiency in the gut of oscar fish. A predominance of γ-HBCD was observed in the tiger barb after 5 d HBCD-exposed and oscar feeding on the tiger barb for 16 d. After 20 d of depuration, 41.1% γ-HBCD and 42.7% β-HBCD disappeared, and α-HBCD exceeded the initial amount. The transformation from γ-HBCD predominance in the food to α-HBCD predominance in the oscar was attributed mainly to the isomerization of γ-HBCD (at least 3% and up to 22.7%) to α-HBCD. Selective enrichment of the (+) α- and (-) β-enantiomers and no enantioselective enrichment of γ-HBCD were observed in the tiger barbs. No enantioselective uptake of the 3 diasteromers was found in the oscar gut. The enantiomer fractions of α- and γ-diastereomers were significantly higher, but that of β-diastereomer were significantly lower in the oscars than in the tiger barbs, indicating enantioselective metabolism of the 3 diastereomers. Two HBCD monohydroxylated metabolites were detected in the 2 fish species, but their composition patterns differed, indicating a species-specific metabolism of HBCD in the studied fish species.


Partial trisomy 9q due to maternal 9q 17q translocation.
Partial Trisomy 9q is a unique chromosomal anomaly with a distinctive phenotype. Only 5 cases have been reported in the literature till now. A large family with four affected children was studied in detail and was compared with the five previously reported cases. Determination of this novel balanced translocation in their family had helped us to offer prenatal diagnosis. This presentation is unique as even though partial trisomy 9q has been reported earlier with 9/17 translocations, our family is the first to have a translocation between q arms of chromosomes 9 and 17.


A fossil snake with limbs.
A 95-million-year-old fossil snake from the Middle East documents the most extreme hindlimb development of any known member of that group, as it preserves the tibia, fibula, tarsals, metatarsals, and phalanges. It is more complete than Pachyrhachis, a second fossil snake with hindlimbs that was recently portrayed to be basal to all other snakes. Phylogenetic analysis of the relationships of the new taxon, as well as reanalysis of Pachyrhachis, shows both to be related to macrostomatans, a group that includes relatively advanced snakes such as pythons, boas, and colubroids to the exclusion of more primitive snakes such as blindsnakes and pipesnakes.


Elucidation of the natural artemisinin decomposition route upon iron interaction: a fine electronic redistribution promotes reactivity.
The conformational analysis of artemisinin by molecular dynamics and quantum chemistry calculations revealed the existence of seven energy minima with specific interconversion pathways. Among the seven conformers, only , and were able to undergo bond rearrangements upon Fe(2+) interaction. These rearrangements were due to a peculiar puckering of the trioxane ring that brings its three oxygen atoms in an ideal geometrical position for interacting with Fe(2+) ions, promoting an electronic redistribution in the molecule. A rapid molecule rearrangement led to a stable energy minimum structure with an additional ring that is similar to a plant metabolite. Our results suggest an alternative pathway for generating toxic radical chemical species for the malaria parasite, where artemisinin is not toxic by itself but rather is an intermediate for molecular partners that generate radical structures deleterious for the parasite proteins, after electron transfers from the Fe(2+)/artemisinin complex.