[Estimation of regional myocardial sympathetic neuronal function with I-123 metaiodobenzylguanidine (MIBG) myocardial images in patients with cardiomyopathy].
I-123 Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic neuronal endings. Sympathetic neuronal function in 10 patients with cardiomyopathy under stable state were studied by using MIBG and Tl-201 (Tl) SPECT images with 50% cut off level. For myocardial imaging MIBG and Tl were simultaneously injected and collected (dual injection and dual collection mode; Dd mode). Four hours delayed images were also collected. Three types of abnormal findings were noted in MIBG images in combination with Tl images. 1) Enhancement of regional MIBG washout with otherwise normal MIBG and Tl uptake in infero-lateral wall were noted in 5 patients with history of congestive heart failure (Pathophysiologically acceleration of regional sympathetic neuronal function was suspected. Mean washout ratio is 63 +/- 7% vs. 45 +/- 10% in normal region). 2) In 3 patients with dilated cardiomyopathy increase of MIBG/Tl (M/T) ratio was noted in basal septal wall (Sympathetic neuronal function is abnormally accelerated in the region with depressed coronary perfusion. Exaltation of regional sympathetic neuronal function was suspected. Mean M/T ratio is 1.6. Tentative normal range is from 0.8 to 1.20). 3) In 2 patients with dilated cardiomyopathy under severe congestive heart failure defects of MIBG uptake with normal Tl uptake were noted (Sympathetic neuronal function was depleted in spite of normal coronary perfusion. Depletion of myocardial catecolamine was suspected. M/T ratio is 0.75 and 0.7 respectively). Heterogeneous abnormality of sympathetic neuronal function was noted in MIBG images. This findings corresponded to report about heterogeneous myocardial catecholamine concentrations in hearts of recipients of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)


Interventional magnetic resonance imaging as a diagnostic and therapeutic method in treating acute pediatric atlantoaxial rotatory subluxation.
Atlantoaxial rotatory subluxation or fixation (AARF) is a rare condition, usually occurring in pediatric patients. It mimics benign torticollis but may result in permanent disability or death. The condition requires prompt diagnosis by thorough examination to avoid any treatment delays. Spiral computed tomography (CT) with three-dimensional reconstruction CT is recommended for identifying incongruence between C1 and C2 vertebrae, and magnetic resonance imaging (MRI) may be performed to exclude ligamentous injuries. In addition to static imaging, dynamic CT involves the reduction between C1 and C2 being confirmed using CT with the head turned maximally to the left and right. The present report (level of evidence, III) provides a method for treating AARF that has similar advantages as dynamic CT but avoids ionizing radiation by replacing CT with interventional MRI. The new method comprised simultaneous axial traction and manual closed reduction, performed under general anesthesia, and the use of interventional MRI to ensure that reduction was achieved and held. The head is turned maximally to the right and left during the manual reduction. A rigid cervical collar was used following reduction. Dynamic CT was not required but prior diagnostic static CT was performed in preparation. No further CT was required. There appears to be no previous studies on interventional MRI in AARF care. Being superior in its diagnostic soft-tissue visualization performance and lacking ionizing radiation, interventional MRI is a potential option for investigating and treating acute AARF in non-syndromic patients with no trauma history.


Natural course and outcomes of spontaneous isolated celiac artery dissection according to morphological findings on computed tomography angiography: STROBE compliant article.
We aimed to identify natural course and optimal management of spontaneous isolated celiac artery dissection (SICAD) according to morphologic classification determined on computed tomography angiography (CTA), and to investigate the association between symptoms and morphological classification of SICAD.This retrospective observational study included 21 consecutive patients with SICAD from January 2012 to April 2017. Demographic data, clinical features, treatment modalities, follow-up results, and CTA findings including morphologic classification, dissection length, and relative diameter of the true lumen (TLRD) were reviewed. Changes in follow-up CTA were recorded and compared to prior studies to reveal natural course of the disease.The serial changes of SICAD on follow-up CTA according to morphologic classifications were as follows; type I (5/5, no interval change), type IIa (1/1, no interval change), type IIb (1/1, partial remodeling), type IIIa (1/4, complete remodeling; 1/4, partial remodeling; 1/4, no interval change; 1/4, deterioration), type IIIb (4/6, no interval change; 2/6, partial remodeling), and type IV (2/2, no interval change). Thirteen (61.9%) symptomatic and 8 (38.1%) asymptomatic patients were all treated with conservative management with or without antiplatelet and/or anticoagulation therapies. Symptomatic group (SG) more commonly had type IIb, IIIa, IIIb, and IV than asymptomatic group (AG) (SG; 11 patients, AG; 1 patient, P = .002). TLRD in AG was larger than that in SG (SG: 40.5 ± 24.1%, AG: 61.7 ± 7.0%, P = .045).SICAD might be treated by conservative management in stable patients irrespective of the morphologic classification except for with type IV (dissecting aneurysm) and extension of celiac branch who may need an early intervention. Types IIb, IIIa, IIIb, and IV are TLRD are associated with patients' symptoms. Further studies on extended natural course of SICAD with a larger number of subjects are needed to draw a strong conclusion.


Diverse responses of species to landscape fragmentation in a simple food chain.
Habitat destruction, characterized by habitat loss and fragmentation, is a key driver of species extinction in spatial extended communities. Recently, there has been some progress in the theory of spatial food webs, however to date practically little is known about how habitat configurational fragmentation influences multi-trophic food web dynamics. To explore how habitat fragmentation affects species persistence in food webs, we introduce a modelling framework that describes the site occupancy of species in a tri-trophic system. We assume that species dispersal range increases with trophic level, exploiting pair-approximation techniques to describe the effect of habitat clustering. In accordance with the trophic rank hypothesis, both habitat loss and fragmentation generally cause species extinction, with stronger effects occurring at higher trophic levels. However, species display diverse responses (negative, neutral or positive) to habitat loss and fragmentation separately, depending on their dispersal range and trophic position. Counter-intuitively, prey species may benefit from habitat loss due to a release in top-down control. Similarly, habitat fragmentation has almost no influence on the site occupancy of the intermediate consumer in the tri-trophic system, though it decreases those of both basal species and top predator. Consequently, species' responses to habitat destruction vary as other species become extinct. Our results reiterate the importance of the interplay between bottom-up and top-down control in trophically linked communities, and highlight the complex responses occurring in even a simple food chain.


Concerted regulation of gonad differentiation by transcription factors and growth factors.
It is well known that signals from growth factors regulate gene transcription thus initiating certain steps of cellular and tissue differentiation during development. In gonad differentiation several transcription factors have been identified as the genes underlying human diseases displaying gonadal defects and as the genes necessary for gonad differentiation as demonstrated by gene disruption studies. In addition, one of the growth factors, WNT4, is known to be involved in gonadal differentiation. However, it remains unclear which gene is directly downstream of the WNT4 signal. We have recently demonstrated that Dax1 (NR0B1) gene transcription is significantly up-regulated by the presence of SF1 (NR5A1). Functional analysis showed that DAX1 acts as a repressor against SF1 through direct interaction between the repeated sequences at the N-terminus of DAX1 and a ligand-binding domain of SF1. Considering that the expressions of these factors during gonad differentiation show a sexually dimorphic pattern, it is likely that the Dax1 gene transcription is up-regulated by WNT4 signal and thereafter DAX1 suppresses the genes downstream of SF1 such as Amh and steroidogenic genes in female gonads.


Down-regulation of cellular platelet-derived growth factor receptors induced by an activated neu receptor tyrosine kinase.
The functional integration of growth factor signaling occurs at several levels in target cells. One of the most proximal mechanisms is receptor transmodulation, by which one activated receptor can regulate the expression of other receptors in the same cells. Well-established transregulatory loops involve platelet-derived growth factor (PDGF) down-regulation of epidermal growth factor (EGF) receptors and beta-type transforming growth factors modulation of PDGF receptors. We have studied the relationship between neu tyrosine kinase activation and the expression of the PDGF receptors in transfected NIH/3T3 cells. Expression of the neu oncogene, but not of the neu proto-oncogene, was associated with a decrease of PDGF alpha- and beta-receptors on the cell surface, as measured by [125-I]PDGF-AA and -BB binding. These results were corroborated by metabolic labeling and immunoprecipitation of the PDGF beta-receptors. PDGF alpha- and beta-receptor mRNAs were strongly decreased in the neu oncogene-transformed cells in comparison with control cells expressing the neu proto-oncogene. Down-regulation of the PDGF receptors and their mRNAs was also observed after EGF treatment of cells expressing a chimeric EGF receptor/neu receptor, where the neu tyrosine kinase is activated by EGF binding. These results show that the neu tyrosine kinase can down-modulate PDGF receptor expression, and the effect is mediated via decreased PDGF receptor mRNA levels.


Kinetics of lipid bilayer permeation of a series of ionisable drugs and their correlation with human transporter-independent intestinal permeability.
For low molecular weight drugs, lipid bilayer permeation is considered the major route for in vivo cell barrier passage. We recently introduced a fluorescence assay with liposomes to determine permeation kinetics of ionisable compounds across the lipid bilayer by monitoring drug-induced pH changes inside the liposomes. Here, we determined the permeability coefficients (PFLipP, FLipP for "Fluorescence Liposomal Permeability") across 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers of 35 ionisable drugs at pH6.0 and compared them to available in vivo human jejunal permeability (Peff) data. PFLipP values were furthermore compared with published Caco-2 cell permeability coefficients (PCaco-2), permeability coefficients determined with the parallel artificial membrane permeability assay (PAMPA) and with log D (pH6.0). The log PFLipP, corrected for predicted para-cellular diffusion, and log PCaco-2 correlated best with log Peff, with similar adjusted R2 (0.75 and 0.74, n=12). Our results suggest that transporter-independent intestinal drug absorption is predictable from liposomal permeability.


Trapped modes around freely floating bodies in a two-layer fluid channel.
Unlike the trapping of time-harmonic water waves by fixed obstacles, the oscillation of freely floating structures gives rise to a complex nonlinear spectral problem. Still, through a convenient elimination scheme the system simplifies to a linear spectral problem for a self-adjoint operator in a Hilbert space. Under symmetry assumptions on the geometry of the fluid domain, we present conditions guaranteeing the existence of trapped modes in a two-layer fluid channel. Numerous examples of floating bodies supporting trapped modes are given.


Activating Developmental Reserve Capacity Via Cognitive Training or Non-invasive Brain Stimulation: Potentials for Promoting Fronto-Parietal and Hippocampal-Striatal Network Functions in Old Age.
Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age.


Intracellular localization of calcium in the chromaffin cells of the rat adrenal medulla.
The ulstrastructural localization of calcium in the chromaffin cells of the adrenal medulla was carried out by using potassium pyroantimonate during fixation. Calcium-containing deposits were either diffuse within the cytoplasm or associated with membrane-bounded organelles. Variable amounts of precipitates were found within the nucleus and in the Golgi complex. However, the major sites of calcium antimonate deposits were the secretory granules and the mitochondria. The morphological identification of calcium-storing organelles in the adreno-medullary cells may be useful in evaluating the involvement of such intracellular compartments during the secretory process.


On deriving lumped models for blood flow and pressure in the systemic arteries.
Windkessel and similar lumped models are often used to represent blood flow and pressure in systemic arteries. The windkessel model was originally developed by Stephen Hales (1733) and Otto Frank (1899) who used it to describe blood flow in the heart. In this paper we start with the onedimensional axisymmetric Navier-Stokes equations for time-dependent blood flow in a rigid vessel to derive lumped models relating flow and pressure. This is done through Laplace transform and its inversion via residue theory. Upon keeping contributions from one, two, or more residues, we derive lumped models of successively higher order. We focus on zeroth, first and second order models and relate them to electrical circuit analogs, in which current is equivalent to flow and voltage to pressure. By incorporating effects of compliance through addition of capacitors, windkessel and related lumped models are obtained. Our results show that given the radius of a blood vessel, it is possible to determine the order of the model that would be appropriate for analyzing the flow and pressure in that vessel. For instance, in small rigid vessels ( R < 0.2 cm) it is adequate to use Poiseuille's law to express the relation between flow and pressure, whereas for large vessels it might be necessary to incorporate spatial dependence by using a one-dimensional model accounting for axial variations.


Analysis of long-term outcomes after minimally invasive spleen-preserving distal pancreatectomy under the 'Kimura-first' strategy.
Spleen-preserving distal pancreatectomy (SPDP) can be carried out by the Kimura technique (KT) or Warshaw technique (WT). This study aimed to evaluate the long-term post-operative outcomes of the two minimally invasive SPDP methods under the 'Kimura-first' strategy with a particular focus on the haemodynamic changes in the splenogastric circulation. The electronic medical records and follow-up data of patients who underwent minimally invasive SPDP in our centre from March 2016 to July 2022 were reviewed. The haemodynamic changes in splenogastric circulation were monitored by post-operative computed tomography (CT) images, and the risks they caused were assessed by long-term follow-up. A total of 112 patients (KT = 93 and WT = 19) were included in the study. The tumour size in the WT group was significantly larger than that in the KT group (P = 0.02). We also found less blood loss for patients who underwent KT (P = 0.02). The occurrence of gastric varices was significantly higher in the WT group (P = 0.022). There was no gastrointestinal bleeding in either group. There were two cases of splenic infarction in the WT group (11.1%), and the incidence was higher than that in the KT group (P = 0.026). The infarct area gradually decreased during periodic CT examinations and disappeared completely at the last review. The two groups of patients had similar results across the 15 items in three areas of the quality of life questionnaire. The 'Kimura-first' strategy, in which the WT is used as an alternative to the KT when the splenic vessels cannot be safely preserved, is feasible, and safe for minimally invasive SPDP.


A scalable, fast, and multichannel arbitrary waveform generator.
This article reports on the development of a multichannel arbitrary waveform generator that simultaneously generates arbitrary voltage waveforms on 24 independent channels with a dynamic update rate of up to 25 Msps. A real-time execution of a single waveform and/or sequence of multiple waveforms in succession, with a user programmable arbitrary sequence order is provided under the control of a stand-alone sequencer circuit implemented using a field programmable gate array. The device is operated using an internal clock and can be synced to other devices by means of transistor-transistor logic (TTL) pulses. The device can provide up to 24 independent voltages in the range of up to ± 9 V with a dynamic update-rate of up to 25 Msps and a power consumption of less than 35 W. Every channel can be programmed for 16 independent arbitrary waveforms that can be accessed during run time with a minimum switching delay of 160 ns. The device has a low-noise of 250 μV(rms) and provides a stable long-term operation with a drift rate below 10 μV/min and a maximum deviation less than ± 300 μV(pp) over a period of 2 h.


Endovascular coil embolization for ruptured kissing aneurysms associated with A1 fenestration.
Fenestration of intracranial arteries is a rare anomaly, and is frequently associated with cerebral aneurysms. In this paper, we report rare kissing aneurysms associated with A1 fenestration. A 71-year-old woman presented with subarachnoid hemorrhage. Diagnostic digital subtraction angiography revealed two saccular aneurysms at the proximal junction of a fenestration and posterior aspect of the fenestration that appeared to be 'kissing' each other. Emergent endovascular coil embolization was performed. Kissing aneurysms associated with fenestration of the horizontal segment in the anterior cerebral artery are rare, and have not been reported. During treatment of such specific types of aneurysms by endovascular treatment, three-dimensional rotational digital subtraction angiography was very useful for deciding the appropriate working angles.


[Not Available].
The theoretic concepts and social merits are dealt with of the scarcely known Bulgarian doctors--struggling philosophers-marxists (Dr. Peter Genov, 1880-1923, and dr. Stamen Iliev, 1883-1923). Their bold and never retreating struggle against the bourgeois philosophy and ideology in the field of natural history and sociology is outlined. Both are defensors and supporters of the philosophical and methodological basis of marxism-leninsm during one of the most difficult periods in the developent of Bulgarian and international labour and communist movements.


Epidemiology of Wuchereria bancrofti in Leogane, Haiti.
A survey for Wuchereria bancrofti in Leogane, Haiti, revealed that 140 of 421 individuals (33%) had a patent infection, of which 40% lived in the suburban outskirts of the city. The median microfilaria density was 19.1 per 20 mm3 of blood for suburban dwellers compared with only 8.8 for those living in the city. The vector, Culex quinquefasciatus (Say), breeds mostly in and around numerous rum distilleries, located exclusively around the periphery of the city, and this undoubtedly accounts for the higher prevalence and intensity of infection among suburban dwellers.


Familial trigonocephaly associated with short stature and developmental delay.
A family in which three male members had premature closure of the metopic suture with other suture involvement was studied. Each of the affected persons also had short stature and delayed development. The pattern of inheritance appeared to be X-linked recessive; however, the possibility of autosomal dominant inheritance with low expressivity in women could not be excluded. Findings in these patients did not fit the previously described syndromes of craniostenosis.


Completely green synthesis of colloid Adams' catalyst α-PtO2 nanocrystals and derivative Pt nanocrystals with high activity and stability for oxygen reduction.
We report a first solution strategy for controlled synthesis of Adams' catalyst (i.e., α-PtO(2)) by a facile and totally green approach using H(2)PtCl(6) and water as reactants. The prepared α-PtO(2) nanocrystals (NCs) are ultrasmall in size and have very "clean" surfaces, which can be reduced to Pt NCs easily in ethanol under ambient conditions. Such Adams' catalysts have been applied as electrocatalysts beyond the field of heterogeneous catalysis. Noticeably, the water-only synthesized α-PtO(2) NCs and their derivative Pt NCs all exhibit much higher oxygen reduction reaction (ORR) activities and stabilities than that of the state-of-art Pt/C electrocatalysts. This study provides an example on the organics-free synthesis of α-PtO(2) and Pt NCs as promising cathode catalysts for fuel cell applications and, particularly, this simple, straightforward method may open a new way for the synthesis of other "clean" functional nanomaterials.


3D Displays.
Creating realistic three-dimensional (3D) experiences has been a very active area of research and development, and this article describes progress and what remains to be solved. A very active area of technical development has been to build displays that create the correct relationship between viewing parameters and triangulation depth cues: stereo, motion, and focus. Several disciplines are involved in the design, construction, evaluation, and use of 3D displays, but an understanding of human vision is crucial to this enterprise because in the end, the goal is to provide the desired perceptual experience for the viewer. In this article, we review research and development concerning displays that create 3D experiences. And we highlight areas in which further research and development is needed.


Comparison of different treatment regimens in a case of homozygous familial hypercholesterolemia.
The laboratory results of five periods of different treatment regimens were compared in a 19-year-old girl with homozygous familial hypercholesterolemia (FH): weekly low-density lipoprotein (LDL) apheresis sessions with dextran sulfate columns (LA 15, Kaneka Corporation, Osaka, Japan) without statin administration; weekly LDL apheresis with polyacrylate columns (DALI, Fresenius Adsorber Technology, Bad Homburg, Germany) without statin; LDL apheresis as in Period 2 with 40 mg atorvastatin daily; LDL apheresis as in Period 2 with 80 mg atorvastatin daily; and fortnightly LDL apheresis sessions with polyacrilate and administration of 80 mg atorvastatin daily. The five treatments were given in the above order, and each lasted at least 2 months. To compare the effectiveness of the different methods, the blood levels of total cholesterol, LDL-cholesterol and high-density lipoprotein (HDL)-cholesterol were measured before each session, and the percentage decreases in the blood levels of total cholesterol and LDL-cholesterol were recorded during sessions in Periods 1 and 2. In Periods 1 and 2, the biological effectiveness of LDL apheresis was comparable. Atorvastatin (40 mg daily) improved the blood levels of total cholesterol and LDL-cholesterol, but lowered HDL-cholesterol values. Increasing the daily dose of atorvastatin from 40 mg to 80 mg did not significantly improve LDL-cholesterol levels. When the time between two sessions was longer (Period 5), the total cholesterol and LDL-cholesterol values worsened and were comparable to those of Period 2 during which there was no atorvastatin treatment. In this case of homozygous FH, weekly sessions of LDL apheresis in association with atorvastatin at dose of 40 mg per day gave the best results.


Right heart transcatheter valve therapies - a review of prostheses for the pulmonary and tricuspid positions.
Minimally invasive, catheter-based treatment of valvular dysfunction has become an integral part of clinical routine. As left heart valvular disease is much more common and thus commercially of interest, transcatheter solutions for the treatment of aortic and mitral valvular defects were the first to become broadly clinically available, while even today options for the right heart valve are rare. This review looks at innovative attempts at developing effective transcatheter heart valve prostheses for the pulmonary and tricuspid heart valves, details their experience and highlights those that have made their way to application in humans.


Acute kidney injury in hospitalized COVID-19 patients.
Acute kidney injury (AKI) in COVID-19 patients is associated with poor prognosis. However, the incidence, risk factors and potential outcomes of AKI in hospitalized patients are not well studied. This is a retrospective cohort study conducted in two major university hospitals. Electronic health records of the patients, 18 years or older, hospitalized between 13 April and 1 June 2020 with confirmed COVID-19 were reviewed. We described the incidence and the risk factors for AKI development in COVID-19 patients. Furthermore, we investigated the effects of AKI on the length of hospital and intensive care unit (ICU) stay, the admission rates to ICU, the percentage of patients with cytokine storm and in-hospital mortality rate. Among 770 hospitalized patients included in this study, 92 (11.9%) patients developed AKI. The length of hospitalized days (16 vs 9.9, p < 0.001) and days spent in the hospital until ICU admission (3.5 vs. 2.5, p = 0.003) were higher in the AKI group compared to patients without AKI. In addition, ICU admission rates were also significantly higher in patients with AKI (63% vs. 20.7%, p < 0.001). The percentage of patients with AKI who developed cytokine storm was significantly higher than patients without AKI (25.9% vs. 14%, p = 0.009). Furthermore, the in-hospital mortality rate was significantly higher in patients with AKI (47.2% vs. 4.7%, p < 0.001). AKI is common in hospitalized COVID-19 patients. Furthermore, we show that AKI increases the admission rates to ICU and in-hospital mortality. Our findings suggest that AKI should be effectively managed to prevent the adverse outcomes in COVID-19 patients.


Ethynylbenzenoid metabolites of Antrodia camphorata: synthesis and inhibition of TNF expression.
An improved synthesis of the anti-inflammatory natural product antrocamphin A (2), involving a key Castro-Stephens reaction, is presented, along with the first total synthesis of its congener antrocamphin B (3). Approaches towards the more complex co-metabolite antrodioxolanone (4) were unsuccessful, but a samarium diiodide-mediated pinacol coupling of antrocamphin B did provide the chiral epimers (51). Antrocamphin A (2) inhibits Tumour Necrosis Factor (TNF) reporter gene expression, but its development as an anti-inflammatory agent may be limited by cytotoxicity.


[Biocompatibility testing of various biomaterials as dependent on immune status].
This study deals with the ingrowth behaviour of biomaterials (hydroxyapatite, cp-titanium, cobalt-chromium-molybdenum and PAEK) in relationship to the immunological competence in an animal model. Measured were the production of extracellular matrix (ECM) after implantation in non-immunocompetent naked mice and immunocompetent wild mice. Intention of the trial was to find out if either the immunological competence or the duration of implantation influences the quantity of produced ECM. In addition, the ingrowth behaviour was investigated under these conditions by using four different biomaterials. Biomaterials (hydroxyapatite, cp-titanium, cobalt-chromium-molybdenum and PAEK) were implanted for 14 or 60 days, respectively. CLSM, SEM and SEM-EDX were used for analysis of the ECM and for measuring the distance between ECM and the biomaterials. CLSM was also used for the detection of collagen I and III as a parameter of the quality of osteointegration. In all cases a matrix grew on the surface of the biomaterials. The CLSM detected a co-localisation of collagen I and III. In the case of hydroxyapatite collagen I and III were found at a distance of 1 micro m over the surface. The largest space between the surface of the implant and the ECM was found in the case of PAEK. The smallest space was in the case of hydroxyapatite. In all investigated biomaterials the proportion of collagen I to collagen III varied through the duration of implantation. As is known from the literature we found different ingrowth behaviours on using different biomaterials. Furthermore, we found a statistically significant influence of the immunological competence of the host with regard to ECM production. We draw the conclusion that immunological competence improves the ingrowth behaviour of biomaterials.


Effect of mastitis incidence on litter size, litter weight, and milk composition of rabbit does.
This study aimed to examine the effect of mastitis incidence on the litter size, litter birth weight, and milk composition of Hycole does on a commercial rabbit farm during their third and fourth parity. At third parity does were assigned to the "No mastitis" (n = 30) and "Mastitis" (n = 28) groups on the basis of visible abscesses in the mammary gland area. The microbiological analysis revealed the presence of different pathogenic bacteria. At third parity, "Mastitis" females had fewer kits than the "No mastitis" group, and the average birth weight was lower. On day 2 of the third lactation, "Mastitis" does produced significantly less milk daily compared with the "No mastitis" group. A significant effect on the incidence of mastitis on the litter size and litter weight during the growth of kits up to the 35th day was also observed. The effect of the incidence of mastitis on milk chemical composition was limited. At the fourth parity, the litter characteristics and daily milk yield were leveled in "Mastitis" and "No mastitis" females. To conclude, our study showed that mastitis negatively affects litter size, birth weight, and daily milk yield in the current parity. However, early detection and proper treatment allowed to obtain good reproductive results and healthy kits in the next parity.


World Transplant Congress. Boston, Massachusetts, USA, 22-27 July 2006.
The World Transplant Congress (WTC) is the first joint international transplant meeting co-organised by the Transplantation Society, the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS). It was the first meeting of this calibre that was being held by three world-renowned authorities in the field of transplantation. Under the direction of the congress president, AB Cosimi, the attendance of this meeting is a 'must' for all working in the field of transplantation. The congress had provided an important forum for the exchange of new scientific and clinical information that is relevant to solid organ and tissue transplantation. In addition, it also created an arena for the interchange of ideas regarding the care and management of transplant recipients. There were many sessions that were engineered in order to facilitate the discussion of socioeconomic, ethical and regulatory issues related transplantation. On the whole, the meeting has set a very high standard for any future transplant congresses to match-providing the delegates with updates on transplantation with the new scientific prospectives in T cell costimulation, innate immunity (dendritic cells), anatomy of immune response and regulatory T cell biology. More importantly, it has highlighted the potentials of harnessing these new findings for future biological therapies in preventing rejection and inducing tolerance.


[Pressure and metabolic effects of terazosin in essential hypertension].
To assess the efficacy and safety of different doses of the alpha-1 blocker terazosin on long-term therapy, 12 essential hypertensives (7 males, 5 females, aged 27-61) were investigated. The study was conducted according to the Latin square design and each patient underwent 4 periods of treatment with 2, 5, 10 mg/day terazosin and placebo, in a double-blind, randomized order. Each treatment lasted 4 weeks. In comparison to placebo, a fall in diastolic pressure was observed already with the 2 mg/daily dose, with a decrease > 10 mmHg in 7 patients (responders). Body weight increased in a dose dependent manner, while atrial natriuretic peptide, serum glucose and insulin during oral glucose tolerance test, total cholesterol, HDL and LDL cholesterol, triglycerides were unaffected. It is concluded that terazosin is effective and safe in essential hypertensives already at 2 mg daily dose. Further reduction in blood pressure at higher doses is likely to be counteracted by salt and water retention.


Retrograde femoral nailing in elderly patients: outcome and functional results.
Functional outcome after retrograde femoral intramedullary nailing was investigated in 35 patients older than 60 years (mean, 86 years) with 36 fractures, comprising 15 (41.7%) shaft and 21 (58.3%) distal fractures; overall, 7 (19.4%) periprosthetic fractures occured. Twenty-two (62.9%) of 35 patients were evaluated at a mean 16.5-month follow-up with the Lyshom-Gillquist score and the SF-8 questionaire. Primary union rate was 97.8%, with no significant differences in duration of surgery, bone healing, mobilization, and weight bearing among different fracture types; periprosthetic fractures revealed a significantly delayed mobilization (P=.03). Complications occured significantly more often among distal femoral fractures (P=.009), including all revision surgeries. The most frequently encountered complication was loosening of distal locking bolts (n=3). Lysholm score results were mainly influenced by age-related entities and revealed fair results in all fractures (mean in the femoral shaft fracture group, 78.1 vs mean in the distal femoral fracture group, 74.9; P=.69), except in the periprosthetic subgroup, which had good results (mean, 84.8; P=.23). This group also had increased physical parameters according to SF-8 score (P=.026). No correlation existed between SF-8 physical parameters and patient age or surgery delay, whereas a negative correlation existed between patient age and SF-8 mental parameters (P=.012). Retrograde femoral intramedullary nailing is commonly used in elderly patients due to reliable bone healing, minimal soft tissue damage, and immediate full weight bearing. It also offers a valid alternative to antegrade nailing in femoral shaft fractures.


Managing school interaction networks during the COVID-19 pandemic: Agent-based modeling for evaluating possible scenarios when students go back to classrooms.
The most unexpected and toughest phenomenon that has occurred in recent times is the global COVID-19 pandemic. One of the first measures to prevent the spread of the disease was to close educational institutions. The students were forced to start a learning process through social networks and web platforms. In some countries, a return to face-to-face classes was established. However, weeks later, some of them had to return to virtual activities due to an upswing in the COVID-19 cases. In Mexico, classes have been held virtually, with face-to-face activities only re-established in two of the 32 states. In our state, Yucatan, scholarly activities are still virtual. In this work, the dispersion of COVID-19 at different academic establishments in Yucatan was simulated. Networks of Friendship, noncordial treatment, family ties and study groups were considered. Based on these networks, we evaluated the possibility of returning to school without inducing a rebound in the COVID-19 cases in the state. Agent-based simulations were used, with each student as an agent. Interaction rules were established based on international research regarding good practices in times of COVID-19. We used seven networks from different academic institutions, ranging from primary through college level. As a result, possible contagion curves were obtained for different scenarios, which leads to a discussion about the measures that would be relevant once a return to face-to-face classes is overseen. Simulations show that isolating students and reducing the number of students in the same classroom are good strategies and substantially reduce the possible contagiousness.


Highs and lows in laparoscopic pancreaticoduodenectomy.
Laparoscopic pancreaticoduodenectomy (PD) is not widely accepted, and its use is controversial. Only correct patient selection and appropriate training of groups experienced in pancreatic surgery and laparoscopy will be able to establish its role and its hypothetical advantages. Out of 138 pancreatic surgeries performed in a two-year period (2017-2019), 23 were laparoscopic PD. We evaluate its efficacy and safety compared to 31 open PD. There were no cases of B/C pancreatic or biliary fistula, nor any cases of delayed gastric emptying in the laparoscopic group, but hemorrhage required one reoperation. The conversion rate was 21% (five cases): one due to bleeding, and the remainder for non-progression. The converted patients showed no differences compared to those completed by laparoscopy. There were no differences between laparoscopic and open PD in surgical time, postoperative complications, reintervention rate, readmissions or mortality. R0 resection in tumor cases was 85% for laparoscopy and 69% in open surgery without statistical significance. The postoperative hospital stay was shorter in the laparoscopic PD group (eight vs. 15 days). In a selected group, laparoscopic PD can be safely and effectively performed if carried out by groups who are experts in pancreatic surgery and advanced laparoscopy. The technique has the same postoperative results as open surgery and is oncologically adequate, with less hospital stay. Proper patient selection, a step-by-step program and a lax and early conversion prevents serious operating accidents.


Lipid Profiles of College Female Student-Athletes Participating at Different Competition Levels of Organized Sport.
College-aged women are not meeting weekly moderate-to-vigorous physical activity to support lipids protecting against cardiovascular disease onset. Participating in organized sport could assist in physical activity engagement and maintenance while positively impacting lipids predicting cardiovascular disease. However, women may be discouraged from participating in sports if they perceive benefits to be mostly seen at the higher competition levels, thus hindering seeking sports involvement at lesser-intensity levels. A total of N = 78 female athletes participating at the National Collegiate Athletic Association (n = 21), National Junior College Athletic Association (n = 29), and student club (n = 28) completed a personal characteristics questionnaire and provided blood samples to compare physical activity involvement and lipid health profiles. Linear regression modeling was used to assess how the independent variables (i.e., sport level, age, systolic blood pressure, race/ethnicity, sport/physical activity involvement hours per week, and years playing sports) on the dependent variables [i.e., total cholesterol, high density lipid (HDL), and total cholesterol-HDL ratio]. Total sample cholesterol 165.7 ± 34.0, HDL 62.8 ± 15.03, and total cholesterol-HDL ratio 2.8 ± 0.6 were all within a healthy recommendation range, along with per sport level. NJCAA sport level significantly predicted lower total cholesterol, p = 0.043, while identifying as Black significantly predicted higher total cholesterol, p = 0.008. Similarly, identifying as Black significantly predicted higher HDL, p = 0.021. Furthermore, increased systolic blood pressure significantly predicted higher total cholesterol-HDL ratios, p = 0.014. Organized sports participation may help meet physical activity requirements, support healthy lipid profiles, and ward off cardiovascular disease development in female college students regardless of competition level.


High-performance cellulose acetate/polysulfone blend ultrafiltration membranes for removal of heavy metals from water.
Neat cellulose acetate (CA) and CA/polysulfone (PSf) blend ultrafiltration membranes in the presence of polyvinylpyrrolidone as a pore former were prepared via a phase inversion technique. The prepared membranes were characterized by Fourier transform infrared, scanning electron microscopy, mechanical strength, water content, porosity, permeate flux and heavy metals (Pb2+, Cd2+, Zn2+ and Ni2+) rejection to comprehend the impact of polymer blend composition and additive on the properties of the modified membranes. The water flux expanded by increasing of PSf content in the polymer composition. CA/PSf (60/40) had the highest flux among prepared membranes. Prepared blend membranes were able to remove heavy metals from water in the following order: Pb2+ > Cd2+ > Zn2+ > Ni2+. The CA/PSf (80/20) blend membrane had great performance among prepared membranes due to the high heavy metals removal and permeate flux.


Determination of 5-fluorouracil (NSC-19893) plasma levels in rats and man by isotope dilution-mass fragmentography.
A highly sensitive and specific rapid assay for 5-fluorouracil (5-FU) in plasma samples at concentrations as low as 1 ng/ml was developed using mass fragmentography. Highly enriched C14-5-FU was empolyed as an internal standard. A two-compartmental open model for the disposition of free 5-FU in plasma is proposed. The beta-phase of 5-FU plasma elimination describes the pool size of anabolic metabolites, assuming this model is correct. Injections of 5-fu at 15, 40, and 90 mg/kg in rats resulted in an alpha-phase of elimination from plasma with a half-life of 10-18 minutes. The beta-phase could only be measured after the injection of 90 mg/kg of 5-FU and amounted to about 20 hours in two rats. Higher doses resulted in an unproportional increase in 5-FU plasma concentrations in the beta-phase, thus establishing nonlinear kinetics, presumably of the degradative metabolism. Plasma concentrations of 5-FU in man were measured after oral and intravenous administration of 15 mg/kg of 5-FU. Plasma elimination half-lives after intravenous doses were 12 minutes and dropped below measurable levels 2 hours after administration in three patients. After oral administration, peak plasma levels of 5-FU varied between 0.8 and 60 mug/ml of 5-FU in three patients after 10 minutes to 2 hours. Two of these patients showed rapid absorption and a measurable beta-phase of 5-FU plasma elimination possibly indicating a larger anabolic pool size of 5-FU-derived nucleosides and nucleotides when compared to patients receiving intravenous doses. This study may provide a pharmacokinetic rationale to monitor patients receiving 5-FU treatment.


Corridor disease in South Africa: a review of the current status.
The African buffalo (Syncerus caffer) is a reservoir host of Theileria parva lawrencei the causative organism of Corridor or buffalo disease of cattle. This organism can apparently transform its behaviour when tick-passaged through cattle to resemble that of Theileria parva parva, causing classic East Coast fever (ECF). These are major considerations for the strict quarantine measures imposed on buffaloes from Corridor disease endemic areas in South Africa. Results of continuing studies on diagnosis, chemotherapy, transmission and attempts to transform the behaviour of T.p. lawrencei in the laboratory, are discussed.


Robotic partial nephrectomy for management of renal mass in patients with a solitary kidney: can we expand the indication to T2 and T3 disease?
Management of complex renal masses is challenging in a solitary kidney setting. We retrospectively compared oncological and renal functional outcomes between robotic and open partial nephrectomy (PN) in patients with a pT2-pT3 renal mass and a solitary kidney. From a multi-institutional series, we identified 20 robotic partial nephrectomies (RPN) and 15 open partial nephrectomies (OPN) patients confirmed to have a pT2 or pT3 renal cancer. Surgeries were performed between January 2012 and July 2019. Patients with familial renal cell carcinoma, prior ipsilateral PN, or multiple ipsilateral synchronous tumors were excluded from the analysis. Baseline characteristics, perioperative and postoperative outcomes were compared using χ2 test, Fisher's Exact Test, Mann-Whitney U Test, and Student's t-test. Baseline characteristics were comparable. Cold ischemia was utilized more in the open group (92.9% vs. 15.8%, P<0.001). OPN group had a longer ischemia time (48.9 min vs. 27.3 min, P<0.001), a higher major complication rate (38.5% vs. 11.1%, P=0.009), and a higher length of stay was (5 vs. 3.5 days, P=0.023). Positive surgical margin rate was comparable (20% OPN vs. 15% RPN; P=1.000). At a mean follow up of 21 months local recurrence rates (1 OPN vs. 2 RPN, P=1.000) were comparable, chronic kidney disease upstaging rate (46.7% OPN vs. 45.0% RPN, P=0.922) and estimated glomerular filtration rate preservation at one year (75.2%% in OPN vs. 79.1% RPN, P=0.707) were comparable. In select cases and experienced hands, the robotic approach offers a reasonable alternative to open surgery in patients with pT2 and pT3 tumors and a solitary kidney.


The 101 most frequently cited articles in ophthalmology journals from 1850 to 1949.
We screened 32 ophthalmology journals that had published articles during the period from 1850 through 1949 to identify top-cited articles in the field of ophthalmology (hereafter referred to as citation classics) using the online database Science Citation Index Expanded (Thompson Reuters, Chicago, Illinois). The 101 most frequently cited articles were published in 16 journals. Archives of Ophthalmology had the most top-cited articles (n = 31), followed by American Journal of Ophthalmology (n = 24) and Albrecht von Graefe's Archiv für Ophthalmologie (n = 9). These articles originated from 14 countries, with the United States publishing the majority (n = 58). Most of the citation classics are clinical studies on topics such as rubella cataract, retinopathy of prematurity, keratoconjunctivitis sicca, sympathetic ophthalmia, and the first report of eponymous diseases (eg, Leber hereditary optic neuropathy, Duane retraction syndrome, and Stargardt disease). A considerable number of these articles were ignored initially and for several decades after publication, but, like the classic fairy tale Sleeping Beauty, they have been rediscovered. Our study provides a historical perspective on the classic papers in the literature that are still influential in ophthalmology.


Intestinal Preservation Injury: A Comparison Between Rat, Porcine and Human Intestines.
Advanced preservation injury (PI) after intestinal transplantation has deleterious short- and long-term effects and constitutes a major research topic. Logistics and costs favor rodent studies, whereas clinical translation mandates studies in larger animals or using human material. Despite diverging reports, no direct comparison between the development of intestinal PI in rats, pigs, and humans is available. We compared the development of PI in rat, porcine, and human intestines. Intestinal procurement and cold storage (CS) using histidine-tryptophan-ketoglutarate solution was performed in rats, pigs, and humans. Tissue samples were obtained after 8, 14, and 24 h of CS), and PI was assessed morphologically and at the molecular level (cleaved caspase-3, zonula occludens, claudin-3 and 4, tricellulin, occludin, cytokeratin-8) using immunohistochemistry and Western blot. Intestinal PI developed slower in pigs compared to rats and humans. Tissue injury and apoptosis were significantly higher in rats. Tight junction proteins showed quantitative and qualitative changes differing between species. Significant interspecies differences exist between rats, pigs, and humans regarding intestinal PI progression at tissue and molecular levels. These differences should be taken into account both with regards to study design and the interpretation of findings when relating them to the clinical setting.


Bioactive compounds and antioxidant capacity of Chuquiraga jussieui J.F.Gmel from the highlands of Ecuador.
Chuquiraga jussieui J.F.Gmel is grown between 3000 and 5000 meters above sea level throughout the Andean region of Ecuador and used by the indigenous populations of the Andes for medicinal purposes. Here, we determined the total phenolic, flavonoids, vitamin C and carotenoids content of the leaves and flowers of Ch. jussieui J.F.Gmel from different highlands of Ecuador as well as the capacity of a crude methanolic extract from the both parts of the plant to scavenge free radicals and protect red blood cell membranes from lipid oxidation. The leaves showed a high bioactive compound content in comparison to the flowers. The crude extract from the leaves proved to be more effective than the flowers in reducing iron and scavenging the DPPH, O2- and H2O2 radicals, as well as in protecting cellular membrane against lipid oxidation, demonstrating that Ch. jussieui J.F.Gmel represents an important source of bioactive compounds with relevant healthy properties.


DNAxs/DNAStatistX: Development and validation of a software suite for the data management and probabilistic interpretation of DNA profiles.
The data management, interpretation and comparison of sets of DNA profiles can be complex, time-consuming and error-prone when performed manually. This, combined with the growing numbers of genetic markers in forensic identification systems calls for expert systems that can automatically compare genotyping results within (large) sets of DNA profiles and assist in profile interpretation. To that aim, we developed a user-friendly software program or DNA eXpert System that is denoted DNAxs. This software includes features to view, infer and match autosomal short tandem repeat profiles with connectivity to up and downstream software programs. Furthermore, DNAxs has imbedded the 'DNAStatistX' module, a statistical library that contains a probabilistic algorithm to calculate likelihood ratios (LRs). This algorithm is largely based on the source code of the quantitative probabilistic genotyping system EuroForMix [1]. The statistical library, DNAStatistX, supports parallel computing which can be delegated to a computer cluster and enables automated queuing of requested LR calculations. DNAStatistX is written in Java and is accessible separately or via DNAxs. Using true and non-contributors to DNA profiles with up to four contributors, the DNAStatistX accuracy and precision were assessed by comparing the DNAStatistX results to those of EuroForMix. Results were the same up to rare differences that could be attributed to the different optimizers used in both software programs. Implementation of dye specific detection thresholds resulted in larger likelihood values and thus a better explanation of the data used in this study. Furthermore, processing time, robustness of DNAStatistX results and the circumstances under which model validations failed were examined. Finally, guidelines for application of the software are shared as an example. The DNAxs software is future-proof as it applies a modular approach by which novel functionalities can be incorporated.


Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development.
There are 8 different human syndromes caused by mutations in the cholesterol synthesis pathway. A subset of these disorders such as Smith-Lemli-Opitz disorder, are associated with facial dysmorphia. However, the molecular and cellular mechanisms underlying such facial deficits are not fully understood, primarily because of the diverse functions associated with the cholesterol synthesis pathway. Recent evidence has demonstrated that mutation of the zebrafish ortholog of HMGCR results in orofacial clefts. Here we sought to expand upon these data, by deciphering the cholesterol dependent functions of the cholesterol synthesis pathway from the cholesterol independent functions. Moreover, we utilized loss of function analysis and pharmacological inhibition to determine the extent of sonic hedgehog (Shh) signaling in animals with aberrant cholesterol and/or isoprenoid synthesis. Our analysis confirmed that mutation of hmgcs1, which encodes the first enzyme in the cholesterol synthesis pathway, results in craniofacial abnormalities via defects in cranial neural crest cell differentiation. Furthermore targeted pharmacological inhibition of the cholesterol synthesis pathway revealed a novel function for isoprenoid synthesis during vertebrate craniofacial development. Mutation of hmgcs1 had no effect on Shh signaling at 2 and 3 days post fertilization (dpf), but did result in a decrease in the expression of gli1, a known Shh target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 mutants. These data raise the possibility that deficiencies in cholesterol modulate chondrocyte differentiation by a combination of Shh independent and Shh dependent mechanisms. Moreover, our results describe a novel function for isoprenoids in facial development and collectively suggest that cholesterol regulates craniofacial development through versatile mechanisms.


[Is there a gestosis weather? Correlation of EPH gestosis with meteorologic conditions].
A historical survey on the subject of weather and eclampsy is given in the introduction, at the beginning of which the names Smellie (1752), Boutteilloux (1816), Lachapelle (1925) and Zangemeister (1900) are mentioned. In the ten-year report the gestosis indices according to Goecke (n = 56,461) in the grouping 0/I-III/ = greater than IV are correlated with six general weather situations in each of the four seasons. From the chi 2 component test according to Krauth a relevant chi 2 limit of 8,95 is established. Only the following four out of altogether (6 x 4 =) 24 weather situations prove to be associated with lower (I-III) and higher (= greater than 4) indices of gestosis. 1. Anticyclonic situations with central high in winter with indices of gestosis I-III; 2. cyclonic flow-patterns in autumn with indices of gestosis I-III; 3. situations with central low in summer with indices of gestosis = greater than IV; 4. low gradient cyclonic situations in summer with fewer indices of gestosis. In spring the indices groups do not reach or exceed the limit of significance in any of the six weather situations. The four weather situations connected with gestosis are demonstrated by means of typical examples of infrared and visual satellite photos. Summing up, the different valence of scientific evidence and clinic relevance of the results is indicated.


Maternal experiences with and sources of information on galactagogues to support lactation: a cross-sectional study.
An increase in the marketing and use of herbal galactagogues among breastfeeding mothers in the US has raised the issue of how best to provide support and information on the use of these products, particularly in light of limited availability of certified lactation counselors and continued suboptimal rates of breastfeeding globally. Currently, no cross-sectional data are available on the experiences and attitudes of mothers regarding the use of herbal and pharmaceutical galactagogues for lactation in the US. The findings of an online survey of 188 breastfeeding mothers on experiences with and sources of information on galactagogues are presented. Most mothers (76%) reported that while breastfeeding, they felt as though they were not making enough milk to meet the needs of their child, and yet 54% also indicated that they had not supplemented with formula. A large proportion of respondents reported utilizing galactagogues to increase lactation and finding them useful. The results indicated that most women learned about galactagogues from the Internet or by word of mouth through friends. Lactation consultants were the third-most reported sources of information on these products. While many respondents reported perceiving galactagogues as innocuous, more evidence on safety and efficacy is needed to support women properly who seek out and use them. Large-scale studies of the prevalence of galactagogue use in the US and rigorous evaluation of use globally are needed to ensure that mothers who choose to breastfeed may safely avail themselves of all options when counseling support is insufficient.


Genetic and immunohistochemical detection of mutations inactivating the keratinocyte transglutaminase in patients with lamellar ichthyosis.
Autosomal recessive lamellar ichthyosis is a clinically heterogeneous group of severe congenital keratinization disorders that is characterized by generalized hyperkeratosis and variable erythema. About half of the patients have mutations in the TGM1 gene, which encodes the keratinocyte transglutaminase. Linkage studies have shown that at least two further loci for autosomal recessive lamellar ichthyosis must exist. We present here two patients with lamellar ichthyosis caused by mutations in the TGM1 gene. The first patient is compound heterozygous for the novel missense mutation C53S and the splice mutation A3447G. The second patient, a child of consanguineous parents from Tunisia, is homozygous for the unknown nonsense mutation W263X. This is the first report of a mutation, C53S, that affects the region of the keratinocyte transglutaminase that is essential for anchorage of the enzyme to the plasma membrane. A novel, rapid in situ transglutaminase activity assay revealed the absence of keratinocyte transglutaminase activity in both patients. The mutations described are hence causative for the ichthyosis phenotype.


Adherence, Attitudes and Beliefs of Growth Hormone Deficient Patients - A Questionnaire-based Cohort Study.
GHD is a chronic and systemic disease requiring daily replacement of growth hormone (GHRT). Adherence and attitudes of adult GHD patients are not well known. We sought to assess patients' knowledge of growth hormone deficiency (GHD) in association with treatment adherence and attitudes regarding available and upcoming treatment options. We performed a cross-sectional survey with a custom-made questionnaire at a single centre assessing data on demographics, knowledge of GHD, adherence and attitudes towards GHRT. Of 106 eligible patients actively followed for GHD 70 returned the completed survey (return-rate 66%, 34 m/36 f; age 56±14 years). 46 patients were actively treated, but almost one third (n=24) refused GHRT. 12 patients had participated in clinical trials with LAGH (long-acting growth hormone). Overall, patients with GHRT showed good adherence. Patients refusing GHRT mostly feared side effects and/or had a lack of information/perceived effect. Disease knowledge and level of education were higher in treated than untreated patients (p=0.023/0.017). Only 36% of respondents would initiate treatment with LAGH. Patients with prior LAGH experience and patients with childhood-onset GHD were more likely to adopt LAGH (p=0.048/0.031). Most often, misinformation causes patients to refuse GHRT. Possibly the understanding of their condition and consequences of non-treatment is limited. To improve adherence more focused educational and behavioural strategies may be needed. Willingness to begin a therapy with LAGH was lower than expected (36%). The reasons for reluctance against LAGH need to be elucidated.


Differential ATAC-seq and ChIP-seq peak detection using ROTS.
Changes in cellular chromatin states fine-tune transcriptional output and ultimately lead to phenotypic changes. Here we propose a novel application of our reproducibility-optimized test statistics (ROTS) to detect differential chromatin states (ATAC-seq) or differential chromatin modification states (ChIP-seq) between conditions. We compare the performance of ROTS to existing and widely used methods for ATAC-seq and ChIP-seq data using both synthetic and real datasets. Our results show that ROTS outperformed other commonly used methods when analyzing ATAC-seq data. ROTS also displayed the most accurate detection of small differences when modeling with synthetic data. We observed that two-step methods that require the use of a separate peak caller often more accurately called enrichment borders, whereas one-step methods without a separate peak calling step were more versatile in calling sub-peaks. The top ranked differential regions detected by the methods had marked correlation with transcriptional differences of the closest genes. Overall, our study provides evidence that ROTS is a useful addition to the available differential peak detection methods to study chromatin and performs especially well when applied to study differential chromatin states in ATAC-seq data.


Role of monokine induced by interferon-γ in liver injury induced by hepatitis B virus in mice.
The chemokine monokine induced by interferon-γ (Mig) is involved in the recruitment of inflammatory cells and liver injury during hepatitis B virus (HBV) infection. HBV protein X contributes to Mig expression in vitro by activation of nuclear factor (NF)-κB; however, the molecular mechanisms by which HBV induces Mig expression in vivo are unknown. In this paper, we established a mouse model for HBV study by tail vein injection of HBV genome-containing adenovirus vectors. Host immune response to the secreted hepatitis B surface antigen and e antigen was detected and serum alanine aminotransferase (ALT) was elevated at different time points. We also demonstrated that peripheral and intrahepatic Mig expression was increased after Ad-HBV infection. This was followed by inflammatory cell migration and formation of inflammatory foci in the liver. In addition, NF-κB p65 subunit translocated from the cytoplasm to the nucleus, and phosphoinositide 3-kinase/Akt, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were to some extent phosphorylated after HBV injection. Following tail vein injection of Mig siRNA/in vivo-jetPEI-Gal complex, Mig expression was partially suppressed, inflammatory cell migration was inhibited, serum level of ALT were reduced. In conclusion, through NF-κB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3-kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo.


Recyclable and superior selective CO2 adsorption of C4B32 and Ca@C4B32: a new category of perfect cubic heteroborospherenes.
The capture and separation of CO2 have attracted significant interest as a strategy to control the global emission of greenhouse gases. From the perspective of environmental protection, it is crucial to explore high-performance adsorbents that can efficiently capture CO2. Herein, we report a density functional theory study on the viability of the heteroborospherene C4B32 for the first time. C2v C4B32 was revealed to be a perfect cubic heteroborospherene with the HOMO-LUMO gap of 3.47 eV at the PBE0 level. Then, we evaluated the potential application of C4B32 in the capture and separation of CO2. Our results indicate that the cubic-like C4B32 can efficiently capture CO2 with a -1.34 eV adsorption energy via chemisorption at the most acidic and basic sites of the cage. The strong interaction between CO2 and C4B32 could be supported by an effective charge transfer and orbital overlap. C4B32 also displayed high selectivity for the separation of CO2 from NH3, N2, CH4, CO, and H2 mixtures. Furthermore, it was feasible to tune the CO2-capture ability of C4B32 by metal-doping, which regulated the Lewis acidity/basicity of the C4B32 surface. In particular, Ca-doping could significantly enhance the CO2-capture ability of C4B32. Our results show that as a highly symmetrical and stable heteroborospherene, C4B32 can be used as a building block for the design and synthesis of novel nanomaterials for the capture and separation of CO2.


Distribution of health facilities in Nigeria: Implications and options for Universal Health Coverage.
Nigeria is considering adopting Universal Health Coverage (UHC) as an official policy target to ensure access to quality health care services for her population without financial hardship. To facilitate discussion on the topic, the President of Nigeria convened a UHC summit in March 2014 to discuss Nigeria's options and strategies to achieve UHC. A strategy for achieving UHC requires analysis of the available infrastructure to deliver the services. We review the geographic and sectoral distribution of health facilities in Nigeria and discuss implications on the UHC strategy selected. Secondary analysis of data from the Federal Ministry of Health's facility register was performed to assess the geographic and sectoral distribution of health facilities in Nigeria. Additionally, an extensive literature review was conducted to understand UHC strategies used by various countries and the associated health facility requirements. Primary health facilities make up 88% of health facilities in Nigeria while secondary and tertiary health facilities make up 12% and 0.25%, respectively. There are more government-owned health facilities than privately owned health facilities (67% vs 33%). Secondary health facilities are predominantly privately owned. The ratio of public to private health facilities is much higher in the northern part of the country than in the southern part. The distribution of health facilities across Nigeria is nonuniform. As such, a UHC strategy must be responsive to the variation in health facility distribution across the country. Additional investments are needed in some parts of the country to improve access to tertiary health facilities and leverage private sector capacity.


Disregarded Free Chains Affect Bacterial Adhesion on Cross-Linked Polydimethylsiloxane Surfaces.
The surface properties exhibited by chemically cross-linked polydimethylsiloxanes (CPDMS) such as morphology, stiffness, and wettability have garnered great interest in the study of bacteria-material interactions. Nevertheless, the hidden factor of uncross-linked free PDMS chains that dissociate in CPDMS has often been overlooked when studying the biofilm formation on these polymeric elastomer surfaces. Here, we undertake a comparative characterization of the effects of free chains in CPDMS on bacterial adhesion to both flat and textured Sharklet CPDMS surfaces. Surprisingly, compared to unextracted surfaces, removing free chains from flat and textured CPDMS through solvent extraction results in a tremendous increase in bacterial colony-forming units for both Gram-negative and Gram-positive bacteria up to 2-3 orders in the initial adhesion stage of 2 h. These findings demonstrate that the solvent extraction of free chains from CPDMS is essential in studying the interactions between bacteria and silicone elastomer materials when focusing on a single variable.


Effect of organic production and fertilizer variables on the sensory properties of pac choi (Brassica rapa var. Mei Qing Choi) and tomato (Solanum lycopersicum var. Bush Celebrity).
The increased popularity of organic production has amplified the need for research that will help in understanding how this production system affects the final quality of vegetables. The effects of organic and conventional production on the sensory characteristics of pac choi (often called bok choy) and tomato were studied. Samples were grown in high tunnel and field environments at the Kansas State University Horticulture Research Center located in Olathe, Kansas. Highly trained descriptive panelists from the Sensory Analysis Center at Kansas State University used previously developed flavor lexicons for tomatoes and leafy greens to evaluate the samples. ANOVA at a 95% confidence level was used to detect significant differences between treatments for individual attributes. Crispness, green-grassy/leafy, piney, and pungent attributes were normally higher in conventional pac choi only for the field samples. Pac choi grown in high tunnels showed slight differences only at individual amounts of fertilizer. Organic tomatoes grown in the field were generally juicier and less mealy compared to conventionally grown tomatoes. In the high tunnel, organic tomatoes were generally stronger in the characteristic tomato aroma. However, all differences generally were very small. It can be concluded that organic and conventional production systems do not create major sensory differences in the vegetables evaluated. The few differences that do exist are so small they may not be of practical importance.


Towards worldwide standardisation of HbA1c determination.
Haemoglobin A(1)c (HbA(1)c) or glycohaemoglobin is one of the most important parameters in the management of patients with diabetes mellitus, but to date there is no international standard for determining HbA(1)c. Most of the routine HbA(1)c assays are standardised against one of the local standardisation schemes like the NGSP (USA) and other schemes (Japan, Sweden). Still, results of HbA(1)c tests diverge considerably, as do the accompanying clinical decision limits. The IFCC Working Group on HbA(1)c Standardisation has developed a reference method and also set up a reference system for HbA(1)c, in which the analyte is defined as beta-N-glycated haemoglobin. This reference system consists of a network of reference laboratories that uses the reference methods and certified reference materials for optimal measurement of HbA(1)c in human blood. The main task of the network is to assign values to secondary reference materials, to be used by manufacturers of routine HbA(1)c assays to calibrate their assays. The high specificity of the reference method results in lower HbA(1)c values in blood samples, since the unspecific components falsely identified as HbA(1)c in routine methods are not measured by the reference method. The reference range for the new reference method was determined as 3 to 4% and the clinical decision limits were translated from existing guidelines: goal of treatment 5% HbA(1)c, change of therapy advised at HbA(1)c greater than 6%. Despite these lower values, worldwide implementation of the IFCC reference system for HbA(1)c is recommended, in order to end the great divergence in HbA(1)c results, with which physicians and patients are confronted today.


Young children's understanding of the cognitive verb forget.
Investigation of children's understanding of the cognitive verb forget has shown that young children do not consider the role of prior knowledge when using this verb. Thus, someone may be said to have forgotten a fact despite not ever having previously known it. However, forget can also be used to refer to a failure to recall a prior intention. Three experiments examined the role of prior intention as well as prior knowledge in the comprehension of forget by 160 young children aged four to eight years. The results showed that children initially have two interpretations of forget: as an unfulfilled desire rather than a failure to recall a prior intention, and as a state of not knowing rather than a failure to recall prior knowledge. Explanations for the late comprehension of forget are discussed in terms of representation of knowledge and intention, processing capacity and exposure to pragmatic usages.


Milk-based phospholipids increase morning cortisol availability and improve memory in chronically stressed men.
Phospholipids (PLs) have been shown to dampen the activity and reactivity of the hypothalamic-pituitary-adrenal axis (HPAA). To further investigate stress protective effects of PL, 75 chronically stressed men aged 30 to 51 years were enrolled in a randomized and placebo-controlled trial. The subjects received a bovine milk drink with either 0.5% PL, 1% PL, or a placebo for 42 days to test the hypothesis that supplementation with specific phospholipids would normalize the cortisol response of the HPAA. For determining HPAA activity, the cortisol awakening response was studied before and after treatment. In addition, participants were exposed to an acute stressor, the Trier Social Stress Test, to assess treatment effects on stress reactivity and stress-related memory impairment. After receiving PL-enriched milk, both PL groups showed a delayed decline from peak levels in morning salivary cortisol, suggesting a prolonged availability of free cortisol. Treatment with 0.5% PL additionally resulted in a stronger increase of cortisol after awakening, whereas no such differences could be observed in the 1% PL group and the placebo group, respectively. The acute stress response did not significantly differ among placebo and PL groups. An exploratory data analysis further revealed that elderly participants receiving the higher PL dosage had a significant better memory performance after the Trier Social Stress Test as compared with elderly participants from the placebo and low-PL dosage group; no such difference was observed at baseline. Our results suggest that PL may increase the availability of cortisol in chronically stressed men and may attenuate stress-induced memory impairments. Results of the present study are discussed within the context of previous research and current state of knowledge.


Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer.
Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile.


Cytokines and Langerhans cell mobilisation in mouse and man.
A critical event during the development of cutaneous immune responses, including those provoked by contact allergens, is the mobilisation of epidermal Langerhans cells (LC). These cells act as sentinels of the immune system in the skin, responding to a variety of local insults with migration and delivery of potentially foreign signals to draining lymph nodes. Experimental studies have revealed that the regulation of mobilisation and migration of LC display striking similarities in man and mouse. In both species it has been found that the successful induction of migration requires that LC receive (at least) 2 independent cytokine signals; provided by tumour necrosis factor-alpha (TNF-alpha) and interleukin 1beta. In addition, a similar heterogeneity in man and mouse is apparent with regard to the fraction of LC responding rapidly to mobilisation signals, with the same proportion of cells (20%-30%) being stimulated to migrate in each case. Other similarities exist between mice and humans with respect to LC function, including an age-related decrement in both LC frequency and responsiveness to TNF-alpha. Collectively these studies demonstrate that the mouse provides a valuable experimental surrogate for the human skin immune system, particularly with respect to LC biology, and suggest that it is possible to perform extrapolations between species with some confidence.


Clinical and morphological aspects of Buerger's disease.
Thirty-five patients with TAO and 35 with ASO have been studied. To determine differences between these two arterial diseases, we used clinical criteria, arteriographic and morphological methods. The peripheral (below the bifurcation of the popliteal artery) angiographic changes were found in TAO with 94% sensitivity, 94% specificity and with 96% of positive predictive value. Other clinical diagnostic criteria for differential diagnosis had a lower value (they had high sensitivity and low specificity or low sensitivity and high specificity). The histologic studies confirmed the clinical diagnoses of Buerger's disease in 92,9% cases. The pathologic findings in TAO and ASO were different. Our investigations proved that the characteristics of Buerger's disease include the development of changes not only in small and medium size arteries or veins, but also in microcirculation.


Reference genes for qRT-PCR normalisation in different tissues, developmental stages, and stress conditions of Hypericum perforatum.
Hypericum perforatum L. is a widely known medicinal herb used mostly as a remedy for depression because it contains high levels of naphthodianthrones, phloroglucinols, alkaloids, and some other secondary metabolites. Quantitative real-time PCR (qRT-PCR) is an optimized method for the efficient and reliable quantification of gene expression studies. In general, reference genes are used in qRT-PCR analysis because of their known or suspected housekeeping roles. However, their expression level cannot be assumed to remain stable under all possible experimental conditions. Thus, the identification of high quality reference genes is essential for the interpretation of qRT-PCR data. In this study, we investigated the expression of 14 candidate genes, including nine housekeeping genes (HKGs) (ACT2, ACT3, ACT7, CYP1, EF1-α, GAPDH, TUB-α, TUB-β, and UBC2) and five potential candidate genes (GSA, PKS1, PP2A, RPL13, and SAND). Three programs-GeNorm, NormFinder, and BestKeeper-were applied to evaluate the gene expression stability across four different plant tissues, four developmental stages and a set of abiotic stress and hormonal treatments. Integrating all of the algorithms and evaluations revealed that ACT2 and TUB-β were the most stable combination in different developmental stages samples and all of the experimental samples. ACT2, TUB-β, and EF1-α were identified as the three most applicable reference genes in different tissues and stress-treated samples. The majority of the conventional HKGs performed better than the potential reference genes. The obtained results will aid in improving the credibility of the standardization and quantification of transcription levels in future expression studies on H. perforatum.


Regulation of binding proteins for insulin-like growth factors (IGF) in humans. Increased expression of IGF binding protein 2 during IGF I treatment of healthy adults and in patients with extrapancreatic tumor hypoglycemia.
Insulin-like growth factors (IGFs) in blood form two complexes with specific binding proteins (BPs): a large, growth hormone (GH)-dependent complex with restricted capillary permeability, and a smaller complex, inversely related to GH, with high turnover of its IGF pool and free capillary permeability. The distribution of BPs and of IGFs I and II between these complexes was studied in sera from healthy adults treated with IGF I or/and GH and from patients with extrapancreatic tumor hypoglycemia. Like GH, IGF I administration raises IGF I and two glycosylation variants of IGFBP-3 in the large complex, but unlike GH drastically reduces IGF II. During IGF I infusion, IGFBP-3 appears in the small complex whose IGFBP-2 and IGF I increase three- to fivefold and fivefold, respectively. GH treatment, associated with elevated insulin levels, suppresses IGFBP-2 and inhibits its increase owing to infused IGF I. The small complex of tumor sera contains increased amounts of IGFBP-2 and -3, and two- to threefold elevated IGF II. low GH and/or insulin during IGF I infusion and in extrapancreatic tumor hypoglycemia enhance expression of IGFBP-2 and favor partition of IGFBP-3 into the small complex. Free capillary passage and high turnover of its increased IGF I or II pools may contribute to compensate for suppressed insulin secretion during IGF I infusion or to development of tumor hypoglycemia.


A New Tool for Assessing Mobile Device Proficiency in Older Adults: The Mobile Device Proficiency Questionnaire.
Mobile device proficiency is increasingly required to participate in society. Unfortunately, there still exists a digital divide between younger and older adults, especially with respect to mobile devices (i.e., tablet computers and smartphones). Training is an important goal to ensure that older adults can reap the benefits of these devices. However, efficient/effective training depends on the ability to gauge current proficiency levels. We developed a new scale to accurately assess the mobile device proficiency of older adults: the Mobile Device Proficiency Questionnaire (MDPQ). We present and validate the MDPQ and a short 16-question version of the MDPQ (MDPQ-16). The MDPQ, its subscales, and the MDPQ-16 were found to be highly reliable and valid measures of mobile device proficiency in a large sample. We conclude that the MDPQ and MDPQ-16 may serve as useful tools for facilitating mobile device training of older adults and measuring mobile device proficiency for research purposes.


Preparation and in vitro and in vivo evaluation of HupA PLGA microsphere.
Acetylcholinesterase inhibitors (AChEIs), including Huperzine A (HupA), have been the mainstay of treatment for Alzheimer's disease (AD). However, AChEIs can cause gastrointestinal side effects, which has been related to the high Cmax and short tmax after oral administration. Clinical trials have verified that extended-release formulation with lower Cmax and prolonged tmax, such as rivastigmine patch, could perform a similar efficacy with significantly improved tolerability compared with the oral formulations. In this study, we developed an extended-release microspheres formulation of HupA (called as HAM) with poly(lactide-co-glycolide) (PLGA) as drug carrier. HAM has showed the loading rate as 1.35% (w/w) and yielded 42% with mean particle size at 72.6 μm. In vitro and in vivo pharmacokinetics studies have showed that HAM produced a relatively smooth and continuous drug concentration in 14 days. Furthermore, in vivo pharmacokinetics data have demonstrated that the Cmax was lower and the tmax was considerably later in single intramuscular administration of HAM (1,000 μg/kg) than the counterparts in single intragastric administration of HAT (75 μg/kg/d). Meanwhile, HAM has performed a continuous inhibition to brain AChE activity in normal rats and improvement of memory deficit in Aβ1-40 i.c.v. infused AD rat model for 14 days. The results have suggested that HAM has performed good extended-release properties and good prolonged pharmacological efficacy in vivo in the 2-week period, and could exert a similar efficacy with significantly lowered gastrointestinal side effects as compared with oral formulation.


Attention genes.
A major problem for developmental science is understanding how the cognitive and emotional networks important in carrying out mental processes can be related to individual differences. The last five years have seen major advances in establishing links between alleles of specific genes and the neural networks underlying aspects of attention. These findings have the potential of illuminating important aspects of normal development and its pathologies. We need to learn how genes and experience combine to influence the structure of neural networks and the efficiency with which they are exercised. Methods for addressing these issues are central to progress in the decade ahead.


The role of collagen synthesis in ventricular and vascular adaptation to hypoxic pulmonary hypertension.
Pulmonary arterial hypertension (PAH) is a rapidly fatal disease in which mortality is typically due to right ventricular (RV) failure. An excellent predictor of mortality in PAH is proximal pulmonary artery stiffening, which is mediated by collagen accumulation in hypoxia-induced pulmonary hypertension (HPH) in mice. We sought to investigate the impact of limiting vascular and ventricular collagen accumulation on RV function and the hemodynamic coupling efficiency between the RV and pulmonary vasculature. Inbred mice were exposed to chronic hypoxia for 10 days with either no treatment (HPH) or with treatment with a proline analog that impairs collagen synthesis (CHOP-PEG; HPH + CP). Both groups were compared to control mice (CTL) exposed only to normoxia (no treatment). An admittance catheter was used to measure pressure-volume loops at baseline and during vena cava occlusion, with mice ventilated with either room air or 8% oxygen, from which pulmonary hemodynamics, RV function, and ventricular-vascular coupling efficiency (ηvvc) were calculated. Proline analog treatment limited increases in RV afterload (neither effective arterial elastance Ea nor total pulmonary vascular resistance significantly increased compared to CTL with CHOP-PEG), limited the development of pulmonary hypertension (CHOP-PEG reduced right ventricular systolic pressure by 10% compared to HPH, p < 0.05), and limited RV hypertrophy (CHOP-PEG reduced RV mass by 18% compared to HPH, p < 0.005). In an acutely hypoxic state, treatment improved RV function (CHOP-PEG increased end-systolic elastance Ees by 43%, p < 0.05) and maintained ηvvc at control, room air levels. CHOP-PEG also decreased lung collagen content by 12% measured biochemically compared to HPH (p < 0.01), with differences evident in large and small pulmonary arteries by histology. Our results demonstrate that preventing new collagen synthesis limits pulmonary hypertension development by reducing collagen accumulation in the pulmonary arteries that affect RV afterload. In particular, the proline analog limited structural and functional changes in distal pulmonary arteries in this model of early and somewhat mild pulmonary hypertension. We conclude that collagen plays an important role in small pulmonary artery remodeling and, thereby, affects RV structure and function changes induced by chronic hypoxia.


Autophagy-Dependent Beneficial Effects of Exercise.
Exercise has long been recognized as a powerful physiological stimulus for a wide variety of metabolic adaptations with implications for health and performance. The metabolic effects of exercise occur during and after each exercise bout and manifest as cumulative adaptive responses to successive exercise bouts. Studies on the beneficial effects of exercise have traditionally focused on the biosynthesis of metabolic proteins and organelles. However, the recycling of cellular components by autophagy has recently emerged as an important process involved in the adaptive responses to exercise. This review covers the regulation of autophagy by exercise, with emphasis on the potential autophagy-dependent beneficial effects of exercise.


The correlates of physical activity among adult Métis.
Métis, with a population of close to 390,000 people, are a culturally distinct and constitutionally recognized Aboriginal group in Canada that suffers from poorer overall health than non-Aboriginal Canadians. One important predictor of good health is physical activity. Guided by frameworks based on social and Aboriginal-specific determinants, we investigated the correlates of leisure-time physical activity (LTPA) and active transportation (walking) among adult Métis, with a particular focus on how culturally specific variables were associated with these two types of activity. We also examined how demographic, geographic, socioeconomic and health-related factors were associated with physical activity. We used data from Statistics Canada's 2006 Aboriginal Peoples Survey and Métis Supplement to analyze the correlates of physical activity among Métis aged 20-64, using a series of logistic regression models. Having attended a Métis cultural event in the past year was positively associated with LTPA, as was a high level of spirituality. Similarly, those who had attended a cultural event in the last year were more likely to report a high level of active transportation. Speaking an Aboriginal language and being a member of a Métis organization were not independently associated with the two types of physical activity. Self-perceived health, being male and household income were other correlates positively associated with LTPA, whereas age, body mass index and smoking were negatively associated with this type of activity. Active transportation was positively associated with self-perceived health and being female, while negatively associated with age and body mass index. The results of this study suggest that interventions aimed at increasing physical activity among adult Métis might be more successful if they are connected to cultural activities and spirituality. This research also suggests that demographic, socioeconomic and health-related factors are important considerations when designing initiatives to increase physical activity among adult Métis.


Development of a Mycobacterium bovis intranasal challenge model in mice.
Tuberculosis caused by infection with Mycobacterium tuberculosis or Mycobacterium bovis remains one of the most important infectious diseases of man and animals. The current vaccine, M. bovis bacille Calmette-Guérin (BCG) demonstrates variable efficacy in humans and cattle, and so an urgent need exists for a new vaccine to replace or supplement BCG. Novel vaccine development requires the availability of a suitable animal model in which to test potential vaccine candidates. Models for tuberculosis vaccine development include mice, guinea pigs, cattle and non-human primates. Murine models provide an economical and easily manipulated tool, but the natural aerosol infection route requires extensive facilities, equipment and validation. We sought to develop a logistically simpler intranasal M. bovis infection model for use in vaccine development for bovine tuberculosis. Intranasal M. bovis infection model in mice demonstrated distinct airway associated, dose related pathology, and was strikingly more virulent than previously employed intravenous infection with M. bovis. BCG vaccination of intranasal challenged mice induced 2 logs of protection with similar kinetics as those displayed in M. tuberculosis aerosol infection models. In conclusion, we report the development of a virulent, robust, stringent, physiological and inexpensive M. bovis intranasal infection model for the screening of potential vaccine candidates against bovine tuberculosis.


Loss of function Cbl-c mutations in solid tumors.
Receptor Tyrosine Kinase (RTK) signaling is essential for normal biological processes and disruption of this regulation can lead to tumor initiation and progression. Cbl proteins (Cbl, Cbl-b and Cbl-c) are a family of RING finger (RF) ubiquitin ligases that negatively regulate a variety of RTKs, including EGFR, MET, and RET. Recent studies have identified Cbl mutations associated with human myeloid neoplasias in approximately 5% of the cases. Cbl-c is the most recently identified human Cbl protein and is expressed exclusively in epithelial cells. We identified a novel cDNA that was isolated from a mouse mammary cancer from the C3(1) Large T Antigen transgenic model. This mutant cDNA encodes a protein that has a deletion in the RF domain of Cbl-c, thereby resembling known Cbl family mutations associated with myeoloid neoplasias. Genomic analysis of both parental and transgenic lines shows no evidence of germline mutation indicating that this mutation is likely a somatic mutation. The mutant protein enhances transformation of NIH 3T3 cells when expressed in combination with SV40 Large T antigen. Together these data are consistent with a second hit mutation. In overexpression studies, this mutant Cbl-c protein fails to mediate ubiquitination of activated EGFR and acts in a dominant negative fashion to prevent ubiquitination and downregulation of the activated EGFR by wild type Cbl proteins. Mechanistically, the mutant Cbl-c binds to the EGFR and prevents recruitment of the wild type Cbl protein. Furthermore, data mining reveals Cbl-c mutations associated with solid tumors in humans. Subsequent cell-based analysis demonstrates a similar loss of E3 function and dominant negative effects for one of these human mutations. These data suggest that like Cbl mutations in myeloid neoplasms, loss of Cbl-c function may contribute to the pathogenesis of solid tumors in murine models and in humans.


Serological response to trivalent inactivated influenza vaccine in HIV-infected adults in Singapore.
A cohort of 81 HIV-infected participants received seasonal trivalent inactivated influenza vaccine (TIV) and their humoral responses were monitored using hemagglutination inhibition (HAI) assay and enzyme-linked immunosorbent assay (ELISA). Three weeks after the vaccination, the percentage of the cohort that had an HAI titer of >1:40 was 35% (for H1N1), 43% (for H3N2) and 19% (for influenza B). An increase in HAI titer can be achieved by an increase in magnitude of the antibody responses, which can be measured by an increase in ELISA titer; as well as a quality improvement of the antibody responses through increased avidity to the virus. For some individuals, an increase in avidity alone is sufficient to reach the sero-protective titer. Notably, a number of volunteers showed an increase in ELISA titer without a rise in HAI titer. A total of 24 participants (30%) did not show any significant increase in both HAI and ELISA tests after vaccination. Apart from a lower peripheral CD4+ T cell count, the non responders' peripheral blood mononuclear cells (PBMC) also had a higher IL-10 mRNA expression after TIV vaccination ex vivo. Cytokine profiling demonstrated that, apart from a weaker MCP-1 expression in the non-responder group, PBMC from both groups responded comparably to lipopolysaccharide (LPS) stimulation in vitro. Since only 3 participants developed sero-protective titers against all 3 subtypes after vaccination, our study highlights a need to enhance the immunogenicity of the subunit vaccine for this population, potentially through harnessing the innate immunity with an external adjuvant.


Multisite-Occupancy-Driven Efficient Multiple Energy Transfer: A Straightforward Strategy to Achieve Single-Composition White-Light Emission in Ce3+-, Tb3+-, and Mn2+-Doped Silicate Phosphors.
It is unquestionably true that site occupation and energy transfer play important roles in the luminescent properties of optical materials from both practical applications and theoretical research. In this paper, multisite-occupancy-driven multiple energy transfers were used as a straightforward strategy to achieve single-composition white-light emission in Ce3+-, Tb3+-, and Mn2+-doped Ba1.2Ca0.8SiO4 (BCS) phosphors. The Ce3+-, Tb3+-, and Mn2+-doped T-phase orthosilicate BCS samples were synthesized by traditional solid-state reactions. The phase composition was checked via X-ray diffraction (XRD), and the luminescent properties were systematically studied by photoluminescence spectroscopy and fluorescence decay curves. A detailed study on the efficient and multiple energy transfers of Ce I → Mn2+, Ce II → Tb3+, and Ce II → Tb3+ → Mn2+ was carried out. Satisfactorily, the selected phosphor exhibits a high internal quantum efficiency (QE) of 81% and good thermal stability. In addition, an evident negative thermal quenching phenomenon, i.e., the emission intensity increases with increasing temperature, is provided. Moreover, the mechanism of negative thermal quenching was proposed. On the basis of these excellent luminescence properties, a white LED with color-rendering index (Ra = 89) was fabricated by integrating the phosphor on an n-UV 365 nm chip. These results show that the materials present potential application in the field of phosphor-converted white LEDs.