Integrating palliative care into the modern cardiac intensive care unit: a review.
The modern cardiac intensive care unit (CICU) specializes in the care of a broad range of critically ill patients with both cardiac and non-cardiac serious illnesses. Despite advances, most conditions that necessitate CICU admission such as cardiogenic shock, continue to have a high burden of morbidity and mortality. The CICU often serves as the final destination for patients with end-stage disease, with one study reporting that one in five patients in the USA die in an intensive care unit (ICU) or shortly after an ICU admission. Palliative care is a broad subspecialty of medicine with an interdisciplinary approach that focuses on optimizing patient and family quality of life (QoL), decision-making, and experience. Palliative care has been shown to improve the QoL and symptom burden in patients at various stages of illness, however, the integration of palliative care in the CICU has not been well-studied. In this review, we outline the fundamental principles of high-quality palliative care in the ICU, focused on timeliness, goal-concordant decision-making, and family-centred care. We differentiate between primary palliative care, which is delivered by the primary CICU team, and secondary palliative care, which is provided by the consulting palliative care team, and delineate their responsibilities and domains. We propose clinical triggers that might spur serious illness communication and reappraisal of patient preferences. More research is needed to test different models that integrate palliative care in the modern CICU.


Interpretation of the shape of survival curves in terms of induction and repair/misrepair of DNA double-strand breaks.
Evidence is presented that in yeast cells one DNA double-strand break (dsb) may be considered as one potentially lethal lesion (PLL). Using a temperature conditional radiosensitive diploid yeast mutant (rad 54-3) it is demonstrated that the shoulder of survival curves, for cells plated immediately, is due to repair of dsb (PLL) within a restricted time period. Split dose experiments with the mutant rad 54-3 show that the reappearance of a shoulder is observed when two conditions are met: (1) repair of dsb (PLL) during the time interval between doses and (2) repair of mainly those dsb (PLL) which are induced by the second dose on the nutrient agar plate. Irradiation of wild type yeast cells at high dose rate followed by liquid holding treatment for 72 h (delayed plating, DP) or at low dose rate show that the bending of DP-survival curves is due to the accumulation of dsb (PLL) leading to lethal lesions probably by misrepair of dsb.


Head Start Centers Can Influence Healthy Behaviors: Evaluation of a Nutrition and Physical Activity Educational Intervention.
Because healthy habits are established early in life, it is important to teach young children about foods that contribute to a healthy diet. One of the strategies recommended by the 2015-2020 Dietary Guidelines is to implement educational programs in community settings such as child care and preschool settings. Head Start is one such educational child care setting that serves young children ages 3 to 5 years old. A community partnership was established between Jackson County Civic Action Agency and supported by the Mississippi Gulf Coast Youth Health Coalition's Childhood Obesity Initiative. A quasi-experimental nonequivalent 2-group pre/post-test study design was utilized to determine the effectiveness of a 12-week physical activity and nutrition education program delivered in a Head Start setting. There was a statistically significant improvement in fruit (F = 5.602, df = 1, p = .018) and vegetable (F = 16.061, df = 1, p < .001) recognition scores, and the number of "tried and liked" fruits (F = 5.579, df = 1, p = .019) and vegetables (F = 88.559, df = 1, p < .001) between children in the control group (n = 86) and intervention group (n = 303) when controlling for scores at baseline. Utilizing the Head Start program as a setting for health education program delivery is one available strategy to combat childhood obesity on a community level.


Intermediate Developmental Phases During Regeneration.
The initial view that regeneration can be a continuum in terms of regulatory mechanisms is gradually changing, and recent evidence points towards the presence of discrete regulatory steps and intermediate phases. Furthermore, regeneration presents an excellent example of a process generating order and pattern, i.e. a self-organization process. It is likely that the process traverses a set of intermediate phases before reaching an endpoint. Although some progress has been made in deciphering the identity of these intermediate phases, a lot more work is needed to derive a comprehensive and complete picture. Here, we discuss the intermediate developmental phases in plant regeneration and compare them with the possible intermediate developmental phases in animal regeneration.


Nonequilibrium theory of polymer stretching based on the master equation.
We present a model for fast polymer-stretching experiments. We use the master equation and argue that the end-to-end extension of a polymer molecule can be used as a stochastic variable after appropriate coarse graining. The main effect of increasing pulling speed or force loading rate is a marked hysteresis in the force-extension curve as well as an overall shift of the curve to higher forces when compared to the equilibrium curve. This can be understood in terms of the moments of the transition probability in the master equation. An analysis of the fluctuations and relaxation times is also given in the framework of our theory.


Barriers to modern contraceptive use in rural areas in DRC.
Recent research in the Democratic Republic of Congo (DRC) has shown that over a quarter of women have an unmet need for family planning and that modern contraceptive use is three times higher among urban than rural women. This study focuses on the reasons behind the choices of married men and women to use contraception or not. What are the barriers that have led to low levels of modern contraceptive use among women and men in DRC rural areas? The research team conducted 24 focus groups among women (non-users of any method, users of traditional methods and users of modern methods) and husbands (of non-users or users of traditional methods) in six health zones of three geographically dispersed provinces. The key barriers that emerged were poor spousal communication, sociocultural norms (especially the husband's role as primary decision-maker and the desire for a large family), fear of side-effects and a lack of knowledge. Despite these barriers, many women in the study indicated that they were open to adopting a modern family planning method in the future. These findings imply that programming must address mutual comprehension and decision-making among rural men and women alike in order to trigger positive changes in behaviour and perceptions relating to contraceptive use.


Atherosclerosis in psoriatic disease: latest evidence and clinical implications.
It is widely accepted that atherosclerosis is caused by chronic low-grade inflammation that results from an interaction between immune mechanisms and metabolic abnormalities within the vessel wall. Population-based studies have found an increased cardiovascular risk in patients with psoriasis and psoriatic arthritis (PsA). This risk is higher in patients with severe disease phenotypes, such as those with severe psoriasis and with musculoskeletal inflammation. Higher levels of inflammatory biomarkers also predict the development of clinical cardiovascular events in these patients. The effect of medications used for PsA on cardiovascular risk is limited to observational studies. Antitumor necrosis factor agents and methotrexate have been associated with reduced cardiovascular risk. These data highlight the importance of screening for cardiovascular risk factors in these patients.


Hydrothermal-assisted synthesis of the Na7V4(P2O7)4(PO4)/C nanorod and its fast sodium intercalation chemistry in aqueous rechargeable sodium batteries.
Both high safety and low cost give aqueous rechargeable sodium-ion batteries (ARSB) the opportunity for application in stationary energy storage, but the low operating potential of the existing cathode materials limits its energy density. Here, we introduce a hydrothermal-assisted strategy to prepare the Na7V4(P2O7)4(PO4)/C nanorod and employ it as a novel high-property cathode material for ARSB. The hierarchical structure is formed by direct in situ carbonization of the surfactants (CTAB and oxalic acid) along with the crystallization of Na7V4(P2O7)4(PO4). The prepared Na7V4(P2O7)4(PO4) with a well-defined 1D nanostructure and uniform particle size is wrapped with a thin carbon layer. For the first time, its sodium intercalation chemistry in an aqueous electrolyte was investigated. Based on the reversible phase transformation and high sodium diffusion coefficient, it is demonstrated to be reliable in an aqueous electrolyte with the rapid ion transport capability. A pair of redox plateaus is observed in the charge and discharge curves at 0.961 and 0.944 V (vs. SCE) respectively with the capacity of 51.2 mA h g(-1) at 80 mA g(-1). Favored by the open ion channel and 1D morphology, the composite exhibits superior high rate capability and 72% of the capacity remains at 1000 mA g(-1). The results not only demonstrate a high-property cathode material for ARSB, but also are helpful for design and synthesis of mixed-polyanion electrode materials with tailored architecture.


[Atherosclerosis and atheromatosis are consequtive metabolic disordes. Pathology of the biological functions of trophology and endoecology is the basis for ischemic heart disease prevention.]
Atherosclerosis and atheromatosis are different nonphysiological processes with different etiology and pathogenesis. They manifest alterations in different biological functions. According to our original phylogenetic theory of general pathology, atherosclerosis is associated with altered biological function of trophology, eating, biological reaction of exotrophy. Atherosclerosis is induced by eating of nonoptimal for phylogenetically herbivorous Homo sapiens meat diet with high content of palmitic saturated fatty acid (SFA), which leads to in vivo formation of phylogenetically early low-efficient palmitic pathway of FA metabolism instead of highly-efficient oleic pathway operating in herbivores. Accumulation of nonligand palmitic very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in the bloodstream results from nonphysiological reaction of compensation upon transport of palmitic SFA to cells. An increase in blood content of palmitic triglycerides (TG) and nonligand palmitic VLDLЛ→LDL coincides with the development of hypercholesterolemia: type IV→ type IIb → type V. Atheromatosis compensates changes in lipoproteins by activation of the biological function of endoecology (purity of the extracellular medium) in vivo, thus fulfilling the biological reaction of inflammation. This is physiological denaturation of apoВ-100 in nonligand VLDL→LDL by neutrophils via peroxidation, opsonization by the complement components, transcytosis across the endothelial monolayer and removal to the intima of elastic arteries that serves as a collection and utilization pool for phogogens from local intravascular pool of the intercellular medium. Endogenous phlogogens are utilized by phylogenetically early polyfunctional resident macrophages which are small in number and do not proliferate. Blood-borne monocytes-macrophages are also involved in this process, however, they do not express acid hydrolase of polyenic cholesteryl esters. Atheromatous masses are partially catabolized polyenic FA esterified by the alcohol cholesterol which were not internalized by cells. Atheromatosis is a process of pathological compensation in the realization of the function of endoecology. Prevention of atherosclerosis and atheromatosis should be based on elimination of the effects produced by a nonphysiological meat diet.


Development of a second version of the Cobas AmpliPrep/Cobas TaqMan hepatitis C virus quantitative test with improved genotype inclusivity.
Hepatitis C virus (HCV) RNA measurement has been facilitated by the introduction of real-time PCR-based assays with low limits of detection and broad dynamic ranges for quantification. In the present study, the performance of two second-version prototypes of the Cobas AmpliPrep/Cobas TaqMan HCV Quantitative Test (CAP/CTM v2) with decreased sample input volume and improved genotype inclusivity was investigated. A total of 232 serum and plasma samples derived from patients with chronic hepatitis C (genotype 1 [GT1], n = 108; GT2, n = 8; GT3, n = 24; GT4, n = 87; GT5, n = 3; and GT6, n = 2) were processed in parallel with the Cobas AmpliPrep/Cobas TaqMan HCV Test (CAP/CTM), Cobas Amplicor HCV Monitor Test v2.0 (CAM), and two second-version prototype formulations of CAP/CTM, Mastermix 1 (MMx1) and MMx2. In addition, three GT4 transcripts containing rare variant sequences were tested. The mean log(10) HCV RNA differences for the best-performing CAP/CTM v2/MMx2 formulation in comparison to CAM were -0.05, 0.05, -0.12, -0.10, -0.44, and -0.29 for patients with GT1, GT2, GT3, GT4, GT5, and GT6 infections, respectively. GT1, GT2, and GT4 samples including isolates with known variants within the 5' untranslated region (G145A, A165T) that were underquantified with CAP/CTM were correctly quantified with the second-version prototype. In addition, CAP/CTM v2 was able to accurately quantify the three transcripts with rare variant sequences. In conclusion, CAP/CTM v2 accurately quantifies HCV RNA across all HCV genotypes, including specimens with rare polymorphisms previously associated with underquantification.


Networkcontrology.
An increasing number of complex systems are now modeled as networks of coupled dynamical entities. Nonlinearity and high-dimensionality are hallmarks of the dynamics of such networks but have generally been regarded as obstacles to control. Here, I discuss recent advances on mathematical and computational approaches to control high-dimensional nonlinear network dynamics under general constraints on the admissible interventions. I also discuss the potential of network control to address pressing scientific problems in various disciplines.


Perceptions of gender equality in work-life balance, salary, promotion, and harassment: results of the NASPGHAN task force survey.
Gender equality in the workplace has not been described in pediatric gastroenterology. An electronic survey that explored perceptions of career parity, work-life balance, and workplace harassment was sent to all members of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Reponses were anonymous. Of the 303 respondents (21%), there was an even distribution across geographic region, age, and gender (54% men). Gender affected perception of salary and promotion; 46% of men but only 9% of women feel that "women earn the same as men" (P < 0.001). Similarly, 48% of men but only 12% of women feel that "women rise at the same rate as men" (P < 0.001). Both genders of academic practice respondents, compared with other practice models, perceived men were promoted more quickly than women (P = 0.008). Women had higher dissatisfaction with mentoring than men (29% vs 13%, P = 0.03). Significantly more men than women reported spouses with "flexible jobs" (35% vs 14%, P < 0.001). Having a spouse with "flexible job" or having children (preschool or school age), however, did not affect satisfaction with work-life balance for either gender. Overall, women are more likely to be dissatisfied with work-life balance than men (P = 0.046). Satisfaction with work-life balance is lower among women versus men pediatric gastroenterologists, but does not correlate with flexibility of spouse's job or caring for young children. Gender-divergent perception of promotion, parity of compensation, and mentoring requires further investigation.


Synovial fluid neutrophils transcribe and express class II major histocompatibility complex molecules in rheumatoid arthritis.
To investigate a potential interaction between neutrophils and T cells in rheumatoid arthritis (RA), by defining the optimal conditions for induction of class II major histocompatibility complex (MHC) expression on peripheral blood neutrophils in vitro and investigating the capacity for neutrophils to express class II MHC molecules in RA. Surface expression of class II MHC and costimulatory molecules by peripheral blood and synovial fluid (SF) neutrophils obtained from healthy controls and patients with RA was measured by flow cytometry and fluorescence microscopy. Intracellular class II MHC protein and messenger RNA (mRNA) were detected by Western blotting and Northern blotting, respectively. Freshly isolated peripheral blood neutrophils from controls did not express surface class II MHC; expression was induced by culture with appropriate cytokines. Freshly isolated peripheral blood neutrophils from patients with RA expressed mRNA, but there was no surface expression of class II MHC. Freshly isolated SF neutrophils from patients with RA contained high levels of class II MHC mRNA, did not express surface class II MHC, but did have large intracellular amounts of this protein as detected by Western blotting. After culture for 20 hours in vitro, SF neutrophils from RA patients expressed large amounts of surface class II MHC but very low levels of costimulatory molecules CD80 and CD86. Fluorescence microscopy localized surface class II MHC to discrete areas on the neutrophil. Class II MHC-expressing neutrophils stimulated T cell proliferation. Peripheral blood neutrophils from patients with RA but not healthy controls express class II MHC mRNA. SF neutrophils in RA synthesize and express large amounts of class II MHC but not costimulatory molecules. This might underlie a novel interaction with T cells that is important in terms of disease pathology.


Norepinephrine transport inhibition for treatment of vasovagal syncope.
Norepinephrine transporter inhibitors, such as sibutramine, have been shown to prevent vasovagal syncope induced by tilt testing in healthy volunteers. As a test of concept we assessed whether sibutramine prevents fainting in highly symptomatic VVS patients. This was an open label, dose-ranging protocol of sibutramine 10, 15, and 20 mg daily for ≥4 weeks per dose, with progression dictated by response and tolerance. Responders were predefined as having >50% reduction in spell frequency, compared to baseline spell frequency. The cohort included seven subjects (6 women; 32 ± 7 years) who had a median of 593 faints over a median of 180 months. The patients had had 7 ± 4 previous treatment attempts without a satisfactory response. The mean duration of exposure to 10 mg, 15 mg, and 20 mg doses were 45 ± 33 days, 98 ± 89 days, and 137 ± 83 days. Six patients tolerated the maximum dose, and 1 patient dropped out due to adverse effects at 15 mg/day. The median frequency of spells at baseline, 10, 15, and 20 mg/day was 12, 4.4, 2.8, and 1 events/28 days (P = 0.0048). Five patients were responders and 2 were nonresponders. Among responders, the median frequency of spells at baseline, 10, 15, and 20 mg/day was 14, 4.8, 0.8, and 0.4 events per 28 days (P = 0.0089). No patients developed hypertension. In this open label series, sibutramine prevented vasovagal syncope in most highly symptomatic patients.


Mesenteric venous thrombosis.
MVT is an uncommon form of visceral ischemia. Symptoms and signs of MVT are usually nonspecific and should not be relied on for accurate diagnosis. A simple, logical diagnostic algorithm can be used to manage most of these patients (Fig. 6). CT or MRI appears to be the most sensitive diagnostic test and should be obtained early for any patient suspected of harboring MVT. Patients with peritonitis require prompt abdominal exploratory laparotomy to rule out ischemic bowel. Once the diagnosis of acute MVT is confirmed, the patient should be anticoagulated with heparin. During operation, all nonviable bowel should be resected with intent for a second-look laparotomy after 24 hours if there is any question of ongoing ischemia. We recommend using fluorescein-assisted evaluation of marginally viable bowel intraoperatively. After the operation, anticoagulation is continued with heparin and then oral warfarin sodium when the patient's bowel function returns. For those patients without peritonitis, we recommend prompt anticoagulation followed by at least a 48- to 72-hour period of close observation. All patients who have had an episode of acute MVT and do not have a contraindication to anticoagulation should be anticoagulated on a life-long basis with warfarin sodium. Despite our increased awareness of acute MVT, the 30-day mortality rate remains high. Acute MVT typically has a more insidious and unpredictable course than do other forms of visceral ischemic syndromes, with a mortality rate as high as that of its arterial counterpart. Although there has been a slight improvement in survival during the last 20 years, the recurrence rate remains high and the long-term prognosis is poor in this group of patients. Survival of patients with chronic MVT is better than that of those with acute MVT and appears to be determined by the underlying disease.


Molecular evolution of prepro-thyrotropin-releasing hormone in the chicken (Gallus gallus) and its expression in the brain.
A cDNA encoding prepro-thyrotropin-relaesing hormone (ppTRH) in chicken (Gallus gallus) was isolated and the sites of expression in the brain were determined. The chicken ppTRH cDNA encodes 260 amino acids, including four TRH progenitor sequences (-Lys/Arg-Arg-Gln-His-Pro-Gly-Lys/Arg-Arg-). It is interesting to note that chicken ppTRH harbors four TRH progenitor-like sequences. According to the hydropathy profile of chicken ppTRH, not only the TRH progenitor sequences but also the TRH progenitor-like sequences are localized in hydrophilic regions. The TRH progenitor-like sequences might be related to structural conservation in the evolution of ppTRH, although they cannot be processed into TRH due to the mutation of several amino acids. According to the alignment of the deduced amino-acid sequences of known vertebrate ppTRHs and the molecular phylogenetic tree we constructed, we speculate on the molecular evolution of ppTRH in vertebrates. In situ hybridization demonstrated experession of the ppTRH gene in the nucleus preopticus periventricularis, nucleus preopticus medialis, regio lateralis hypothalami, paraventricular nucleus, nucleus periventricularis hypothalami, and nucleus ventromedialis hypothalami in the chicken brain.


Maxillary post-traumatic outcome correction. Literature review and personal experience. Part II: loss of maxillary substance (free grafts of autologous bone).
Loss of maxillary substance following trauma varies significantly in relation to the dimensions, site and type of tissue involved. Anatomical maxillary interruptions, loss of dental elements and consequent bone re-absorption give rise to altered chewing, swallowing and speech functions. Treatment of pathological conditions over the years has seen the development of surgical protocols designed to achieve simultaneous aesthetic and functional restoration of the stomatognatic apparatus. The advent of osteointegrated implantology and continual progress in pre-prosthesis surgical techniques have undoubtedly revolutionised established approaches to prosthetic rehabilitation by introducing the concept of supported implant prostheses. The implantation protocols used are a safe and reproducible treatment method suitable for adequate anchorage of such prosthetic implants; the application of such protocols in any case is subordinated to the presence of adequate morpho-volumetric bone at the skeletal bases. Depending on the entity of maxillary loss of substance, the reconstruction methods we propose, in agreement with numerous other authors, are based on the use of free and free-revascularised autologous bone grafts or, even more recently, the application of osteogenetic distraction techniques. The purpose of this article is to evaluate treatment of loss of maxillary substance following trauma by means of non-revascularised free flaps. The use of free grafts of autologous bone is elective in patients presenting bone deficits less than 6 cm with and/or without upkeep of maxillary and mandibular cortical bone continuity but without compromise to the integrity and trophism of the soft tissues.


Direct observation of molybdenum disulfide, MoS2, domains by using a liquid crystalline texture method.
Because the properties of molybdenum disulfide (MoS2) are strongly influenced by the sizes and boundaries of its domains, the direct visualization of large-area MoS2 domains is one of the most important challenges in MoS2 research. In the current study, we developed a simple and rapid method to observe and determine the boundaries of MoS2 domains. The technique, which depends on observations of nematic liquid crystal textures on the MoS2 surface, does not damage the sample and is not limited by domain size. Thus, this approach should significantly aid not only efforts aimed at gaining an understanding of the relationships between grain boundaries and properties of MoS2 but also those focusing on how domain sizes are controlled during large-area synthesis.


Eukaryotic cells are dynamically ordered or critical but not chaotic.
Two important theoretical approaches have been developed to generically characterize the relationship between the structure and function of large genetic networks: the continuous approach, based on reaction-kinetics differential equations, and the Boolean approach, based on difference equations and discrete logical rules. These two approaches do not always coincide in their predictions for the same system. Nonetheless, both of them predict that the highly nonlinear dynamics exhibited by genetic regulatory systems can be characterized into two broad regimes, to wit, an ordered regime where the system is robust against perturbations, and a chaotic regime where the system is extremely sensitive to perturbations. It has been a plausible and long-standing hypothesis that genomic regulatory networks of real cells operate in the ordered regime or at the border between order and chaos. This hypothesis is indirectly supported by the robustness and stability observed in the phenotypic traits of living organisms under genetic perturbations. However, there has been no systematic study to determine whether the gene-expression patterns of real cells are compatible with the dynamically ordered regimes predicted by theoretical models. Using the Boolean approach, here we show what we believe to be the first direct evidence that the underlying genetic network of HeLa cells appears to operate either in the ordered regime or at the border between order and chaos but does not appear to be chaotic.


Pharmacological activities of chemically characterized essential oils from Haplophyllum tuberculatum (Forssk.).
The present work aimed at characterizing the phytochemical composition of Haplophyllum tuberculatum essential oil (HTEO), assessing its antifungal activity against various fungal strains, evaluating its insecticidal and repulsive properties against Callosobruchus maculatus, and determine its antioxidant capacity. To this end, Gas chromatography-mass spectrometry analysis detected 34 compounds in HTEO, with β-Caryophyllene being the major constituent (36.94%). HTEO demonstrated predominantly modest antifungal effects, however, it sustains notable activity, particularly against Aspergillus flavus, with an inhibition rate of 76.50% ± 0.60%. Minimum inhibitory concentrations ranged from 20.53 ± 5.08 to 76.26 ± 5.08 mg/mL, effectively inhibiting fungal growth. Furthermore, the antifungal, and antioxidant activities of HTEO were evaluated in silico against the proteins Aspergillus flavus FAD glucose dehydrogenase, and beta-1,4-endoglucanase from Aspergillus niger, NAD(P)H Oxidase. Moreover, HTEO displayed strong insecticidal activity against C. maculatus, with contact and inhalation tests yielding LC50 values of 30.66 and 40.28 μL/100g, respectively, after 24 h of exposure. A dose of 5 μL/100g significantly reduced oviposition (48.85%) and inhibited emergence (45.15%) compared to the control group. Additionally, HTEO exhibited a high total antioxidant capacity of 758.34 mg AAE/g EO, highlighting its antioxidant potential. Insilico results showed that the antifungal activity of HTEO is mostly attributed to γ-Cadinene and p-Cymen-7-ol, while antioxidant is attributed to α-Terpinyl isobutyrate displayed. Overall, HTEO offers a sustainable and environmentally friendly alternative to synthetic products used to manage diseases.


Age-related changes in CD4+CD25+FOXP3+ regulatory T cells and their relationship with lung cancer.
CD4+CD25+FOXP3+ regulatory T cells (Treg) inhibit the anti-tumour immune response and reduce the effect of cancer immunotherapy. Although studies have demonstrated that the number and suppressive activity of Treg increase with age, it is not clear whether these changes correlate with a higher incidence of tumours in the elderly. This study was designed to explore the relationship between increase in CD4+CD25+FOXP3+ Treg and the higher risk of lung cancer in the elderly. Seventy lung cancer patients and 60 sex- and age-matched controls were recruited. Both groups were divided into three subgroups based on their age (young, middle-aged, or elderly). The proportion of CD4+CD25+FOXP3+ /CD4+ T cells was detected using flow cytometry, and the level of FOXP3 mRNA in the peripheral blood was examined with real-time RT-PCR. The levels of CD4+CD25+FOXP3+/CD4+ T cells and FOXP3 mRNA were significantly higher in lung cancer patients than in healthy controls (t = 7.16, P < 0.01 and t = 3.65, P < 0.01, respectively). Within the healthy groups, the elderly group had larger proportion of CD4+CD25+FOXP3+ Treg (F = 32.54, P < 0.01) and higher FOXP3 mRNA expression (F = 4.76, P < 0.01) than their younger counterparts. Among the six subgroups, the elderly lung cancer patients exhibited the highest levels of both CD4+CD25+FOXP3+ Treg (11.81 ± 2.40%) and FOXP3 mRNA (3.14 ± 1.30). The accumulation of CD4+CD25+FOXP3+ Treg with age correlates well with the increasing incidence of lung cancer in the elderly.


Design and analysis of an MR rotary brake for self-regulating braking torques.
This paper presents a novel Magneto-rheological (MR) brake system that can self-regulate the output braking torques. The proposed MR brake can generate a braking torque at a critical rotation speed without an external power source, sensors, or controllers, making it a simple and cost-effective device. The brake system consists of a rotary disk, permanent magnets, springs, and MR fluid. The permanent magnets are attached to the rotary disk via the springs, and they move outward through grooves with two different gap distances along the radial direction of the stator due to the centrifugal force. Thus, the position of the magnets is dependent on the spin speed, and it can determine the magnetic fields applied to MR fluids. Proper design of the stator geometry gives the system unique torque characteristics. To show the performance of an MR brake system, the electromagnetic characteristics of the system are analyzed, and the torques generated by the brake are calculated using the result of the electromagnetic analysis. Using a baseline model, a parametric study is conducted to investigate how the design parameters (geometric shapes and material selection) affect the performance of the brake system. After the simulation study, a prototype brake system is constructed and its performance is experimentally evaluated. The experimental results show that the prototype produced the maximum torque of 1.2 N m at the rotational speed of 100 rpm. The results demonstrate the feasibility of the proposed MR brake as a speed regulator in rotating systems.


Localized osseous cryptococcal infection. Report of 2 cases.
Cryptococcal infection in man is widely disseminated and commonly involves the central nervous system. Primary bone involvement is rare. We report on 2 cases of localized cryptococcal osseous lesions treated successfully by surgery.


TMIG-2DPAGE: a new concept of two-dimensional gel protein database for research on aging.
Cellular proteins of a normal human diploid fibroblast line (TIG-3) at various stages of replicative aging were resolved by horizontal isoelectric focusing on an immobilized pH gradient, followed by vertical sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). Spot proteins were visualized by silver staining and quantitated by image processing. All corresponding spots were matched among two-dimensional gel images, and variation profiles in relative abundance of individual proteins during in vitro aging were classified into five categories, i.e., (i) increase, (ii) decrease, (iii) increase followed by decrease, (iv) decrease followed by increase, and (v) irregular or nonsignificant variation. The new concept of the Tokyo Metropolitan Institute of Gerontology two-dimensional gel protein database (TMIG-2DPAGE) was prepared from the above data to support research on cellular aging. The database was put on our World Wide Web home page at the URL of http://www.tmig.or.jp/2D/ to allow free access through the Internet. The individual protein data entries were linked to the standard spot protein map of the two-dimensional gel image in order to be accessible by clicking the mouse on it.


Multinuclear Magnetic Resonance Investigation of Crystalline Alkali Molybdates.
A variety of crystalline alkali molybdate phases are characterized by (23)Na, (133)Cs, and (95)Mo magic-angle-spinning nuclear magnetic resonance (MAS NMR) to provide spectroscopic handles for studies of devitrification products in borosilicate nuclear waste glasses. The NMR parameters obtained from line-shape simulations are plotted as a function of various structural parameters to discern trends that may prove useful in the determination of unknown phases. These are applied to Cs3Na(MoO4)2, the most common precipitate found in cesium- and molybdenum-bearing model nuclear waste glasses, the crystal structure of which has not yet been determined, to provide structural constraints that may guide the refinement of powder X-ray diffraction data.


Hepatitis E virus infection causing isolated fetal ascites: a case report.
Maternal hepatitis infection, excepting hepatitis E, causing isolated fetal ascites with variable outcome has been reported previously. We present a case of maternal hepatitis E virus (HEV) infection causing isolated fetal ascites which resolved spontaneously during pregnancy and resulted in a term live-born baby with anti-HEV seropositivity. A 39-year-old primigravida woman was diagnosed with acute HEV infection at 15 weeks of gestation. Ultrasound at 19 weeks showed significant fetal ascites with abdominal calcifications. Fetal karyotype did not show any abnormality. Cord blood was positive for anti-HEV IgM and negative for other intrauterine infections. Ultrasound at 25 weeks showed partial resolution of fetal ascites with complete resolution at 30 weeks. She delivered a healthy baby at 38 completed weeks, with normal liver enzymes at birth and 1-month follow-up.


The hydrodynamics of jet propulsion swimming in hatchling and juvenile European common cuttlefish, Sepia officinalis.
Cuttlefish swim using jet propulsion, taking a small volume of fluid into the mantle cavity before it is expelled through the siphon to generate thrust. Jet propulsion swimming has been shown to be more metabolically expensive than undulatory swimming, which has been suggested to be due to the lower efficiency of jet propulsion. The whole-cycle propulsive efficiency of cephalopod molluscs ranges from 38 to 76%, indicating that in some instances jet propulsion can be relatively efficient. Here, we determined the hydrodynamics of hatchling and juvenile cuttlefish during jet propulsion swimming to understand the characteristics of their jets, and whether their whole-cycle propulsive efficiency changes during development. Cuttlefish were found to utilise two jet types: isolated jet vortices (termed jet mode I) and elongated jets (leading edge vortex ring followed by a trailing jet; termed jet mode II). The use of these jet modes differed between the age classes, with newly hatched animals nearly exclusively utilising mode I jets, while juveniles showed no strong preferences. Whole-cycle propulsive efficiency was found to be high, ranging from 72 to 80%, and did not differ between age classes. During development, Strouhal number decreased as Reynolds number increased, which is consistent with animals adjusting their jetting behaviour in order to maximise whole-cycle propulsive efficiency and locomotor performance. Although jet propulsion swimming can have a relatively high energetic cost, in cuttlefish and nautilus, both neutrally buoyant species, the whole-cycle propulsive efficiency is actually relatively high.


Hepatitis B Virus Infection Is a Risk Factor for Periprosthetic Joint Infection Among Males After Total Knee Arthroplasty: A Taiwanese Nationwide Population-Based Study.
Periprosthetic joint infection (PJI) is a grave complication that can affect patients undergoing total knee arthroplasty (TKA). In this study, we aim to determine whether hepatitis B virus (HBV) infection is a risk factor for PJIs.All patients (1184 males, 3435 females) undergoing primary TKA in Taiwan from 2001 to 2010 were recruited for analysis.The incidence of PJI was 523 among the males with HBV infection and 110 among the males without HBV (per 10,000 person-years, P < 0.001). The males with HBV infection had a 4.32-fold risk of PJI compared with the males without HBV. HBV infection and diabetes were the risk factors for PJI among males. The incidence of PJI was 58.8 among the females with HBV infection and 75.2 among the females without HBV (per 10,000 person-years, P = 0.67). The risk of PJI was higher for the males with HBV infection than for the males without 0.5 to 1 year after TKA (hazard ratio [HR] = 18.7, 95% confidence interval (CI) = 1.90-184) and >1 year after TKA (HR = 4.80, 95% CI = 1.57-14.7).HBV infection is a risk factor for PJI after TKA among males.


Magnesium sulfate treatment reverses seizure susceptibility and decreases neuroinflammation in a rat model of severe preeclampsia.
Eclampsia, defined as unexplained seizure in a woman with preeclampsia, is a life-threatening complication of pregnancy with unclear etiology. Magnesium sulfate (MgSO4) is the leading eclamptic seizure prophylactic, yet its mechanism of action remains unclear. Here, we hypothesized severe preeclampsia is a state of increased seizure susceptibility due to blood-brain barrier (BBB) disruption and neuroinflammation that lowers seizure threshold. Further, MgSO4 decreases seizure susceptibility by protecting the BBB and preventing neuroinflammation. To model severe preeclampsia, placental ischemia (reduced uteroplacental perfusion pressure; RUPP) was combined with a high cholesterol diet (HC) to cause maternal endothelial dysfunction. RUPP+HC rats developed symptoms associated with severe preeclampsia, including hypertension, oxidative stress, endothelial dysfunction and fetal and placental growth restriction. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ; mg/kg) required to elicit seizure in RUPP + HC ± MgSO4 and compared to normal pregnant controls (n = 6/group; gestational day 20). RUPP+HC rats were more sensitive to PTZ with seizure threshold being ∼ 65% lower vs. control (12.4 ± 1.7 vs. 36.7 ± 3.9 mg/kg PTZ; p<0.05) that was reversed by MgSO4 (45.7 ± 8.7 mg/kg PTZ; p<0.05 vs. RUPP+HC). BBB permeability to sodium fluorescein, measured in-vivo (n = 5-7/group), was increased in RUPP+HC vs. control rats, with more tracer passing into the brain (15.9 ± 1.0 vs. 12.2 ± 0.3 counts/gram ×1000; p<0.05) and was unaffected by MgSO4 (15.6 ± 1.0 counts/gram ×1000; p<0.05 vs. controls). In addition, RUPP+HC rats were in a state of neuroinflammation, indicated by 35 ± 2% of microglia being active compared to 9 ± 2% in normal pregnancy (p<0.01; n = 3-8/group). MgSO4 treatment reversed neuroinflammation, reducing microglial activation to 6 ± 2% (p<0.01 vs. RUPP+HC). Overall, RUPP+HC rats were in a state of augmented seizure susceptibility potentially due to increased BBB permeability and neuroinflammation. MgSO4 treatment reversed this, increasing seizure threshold and decreasing neuroinflammation, without affecting BBB permeability. Thus, reducing neuroinflammation may be one mechanism by which MgSO4 prevents eclampsia during severe preeclampsia.


The influence of storage method on the transparency of pig crystalline lens.
The porcine eye is frequently used as a research model. This paper analyzes the effect of different storage methods on the transparency of pig crystalline lens. A spectral transmission curve (from 220 to 780 nm) for the crystalline lens was determined experimentally after storage in different conditions: saline solution, formalin, castor oil, and freezing at -80°C. The total transmission in the visible spectrum, which was used as an index of transparency, was calculated from these curves. For comparative purposes, fresh lenses were evaluated and used as controls. Storing the porcine crystalline lens in saline solution or castor oil resulted in a transparency loss of approximately 10% after 24 h and storage in formalin resulted in a loss of nearly 30%. Storage by freezing at -80°C for 4 weeks maintained the transparency of the crystalline lens; the spectral transmission measured immediately after defrosting at room temperature coincided exactly with that of the freshly extracted lens. The transparency of porcine crystalline lens is affected by the storage method. The visible spectrum is the most affected, evidenced by the effect on the transparency and consequently the amount of light transmitted. The results show that freezing at -80°C maintains the transpa rency of the crystalline lens for at least 4 weeks.


Tamoxifen enhancement of TNF-alpha induced MnSOD expression: modulation of NF-kappaB dimerization.
Manganese superoxide dismutase (MnSOD) has been shown to suppress the development of cancer. Tamoxifen (TAM), a nonsteroidal anti-estrogen that is widely used in chemotherapy, is known to be a modulator of antioxidant status. However, the mechanism by which TAM mediates antioxidant enzyme induction remains unclear. In this study we investigated TAM enhancement of MnSOD induction by TNF-alpha. The results show that co-treatment with TAM and TNF-alpha increases the MnSOD promoter/enhancer driven luciferase activity, MnSOD mRNA and protein levels. Interestingly, co-treatment with TAM and TNF-alpha drastically decreases the binding activity of the p50/p50 homodimer and increases that of the p50/p65 heterodimer compared to TNF-alpha alone. This change in DNA binding could not be attributed to a decrease in the level of p50, its precursor, p105, or its inhibitors. Furthermore, TAM did not enhance degradation of IkappaB-alpha. These results suggest that p50/p50 homodimer may act as an inhibitory complex of MnSOD expression. Modulation of the DNA binding activity in favor of the p50/p65 complex may enhance NF-kappaB mediated induction of MnSOD by TAM. These findings reveal a potential novel mechanism for the induction of the human MnSOD gene.


Position-specific trapping of topoisomerase II by benzo[a]pyrene diol epoxide adducts: implications for interactions with intercalating anticancer agents.
DNA topoisomerase II (Top2) is the target of some of the most effective anticancer DNA intercalators. To determine the effect of intercalating ligands at defined positions relative to a known DNA cleavage site for human Top2alpha, we synthesized oligodeoxynucleotides containing single trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide (DE) deoxyadenosine (dA) adducts of known absolute configuration, placed at specific positions in a duplex sequence containing staggered Top2 cleavage sites on both strands. Because the orientations of the intercalated hydrocarbon are known from NMR solution structures of duplex oligonucleotides containing these dA adducts, a detailed analysis of the relationship between the position of intercalation and trapping of Top2 is possible. Our findings demonstrate that (i) Top2 cleavage complexes are trapped by intercalation of the hydrocarbon at either of the staggered cleavage sites or immediately adjacent to the base pairs flanking the cleavage sites within the stagger; (ii) both concerted and nonconcerted cleavage by both subunits of a Top2 homodimer were detected depending on the position of the benzo[a]pyrene DE dA adduct; and (iii) intercalation immediately outside of the staggered Top2 cleavage site, and to a lesser extent in the middle of the stagger, prevents Top2 from cleaving DNA at this site, consistent with the effect of some intercalators as suppressors of Top2-mediated DNA cleavage. These results identify specific binding sites for intercalators that result in trapping of Top2. Such poisoning of Top2 by bulky polycyclic aromatic hydrocarbon DE adducts constitutes a potential mechanism for their carcinogenic activity.


Blood transfusion and coagulopathy in geriatric trauma patients.
Trauma resuscitation has undergone a paradigm shift with new emphasis on the early use of blood products and increased proportions of plasma and platelets. However, it is unclear how this strategy is applied or how effective it is in the elderly population. The study aim is to identify differences in transfusion practices and the coagulopathy of trauma in the elderly. Data was prospectively collected on all consecutive patients that met trauma activation criteria at a Level I trauma centre. Data fields included patient demographics, co-morbidities, injury and resuscitation data, laboratory values, thromboelastography (TEG) results, and outcome measures. Elderly patients were defined as those 55 and older. Propensity-score matched analysis was completed for patients receiving blood product transfusion. Patients were matched by gender, mechanism, injury severity score (ISS), head injury, and time from injury. Total of 628 patients were included, of which 142 (23%) were elderly. Elderly patients were more likely to be female (41% vs. 24%), suffer blunt mechanism of trauma (96% vs. 80%), have higher ISS scores (mean 25.4 vs. 21.6) and mortality (19% vs. 8%). Elderly patients were significantly more likely to receive a blood transfusion (42% vs. 30%), specifically for red cells and plasma. Propensity-matched analysis resulted in no difference in red cell transfusion or mortality. Despite the broad similarities between the matched cohorts, trauma coagulopathy as measured by TEG was less commonly observed in the elderly. Our results suggest that elderly trauma patients are more likely to receive blood products when admitted to a trauma centre, though this may be attributed to under-triage. The results also suggest an altered coagulopathic response to traumatic injury which is partially influenced by increased anticoagulant and antiplatelet medication use in the geriatric population. It is not clear whether the acute coagulopathy of trauma is equivalent in geriatric patients, and further study is therefore warranted.


Efficacy of Panax ginseng extract combined with cephalexin as a dry cow therapy.
Our objective was to evaluate the efficacy of intramammary administration, at drying-off, of a Panax ginseng extract (PGe) combined with cephalexin (Ceph) on the post-calving bacteriological cure rate of pre-existing intramammary infections (IMI) and on the occurrence of new IMI during the dry period. In addition, milk yield and somatic cell count (SCC) in the post-treatment lactation were evaluated. One hundred and eight late-lactation cows were randomly divided into two experimental groups and were treated at drying-off with Ceph alone or PGe combined with Ceph.Cure rates for IMI present at drying-off were similar for both treatments (OR = 0.95, 95% CI = 0.33-2.74). Cure rates for Staphylococcus aureus were lower (OR = 15.4, 95% CI = 1.66-142.52) in quarters treated with PGe + Ceph than in those treated with Ceph alone. Intramammary infusion of PGe + Ceph at drying-off had no effect on preventing new dry period IMI (OR = 0.75, 95% CI = 0.38-1.51), compared with infusion of Ceph alone. Milk production and SCC in the ensuing lactation were not affected by PGe + Ceph treatment. In conclusion, addition of PGe to dry cow therapy did not show any advantage over the use of dry cow therapy alone.


Vaccination of langur monkeys (Presbytis entellus) against Leishmania donovani with autoclaved L. major plus BCG.
The protective potential of killed Leishmania major (ALM) along with BCG was evaluated against L. donovani in Indian langur monkeys in single and triple dose schedules. A delayed protection was observed in monkeys after a single dose schedule of ALM (3 mg)+BCG (3 mg) given intradermally 2 months before intravenous challenge with L. donovani. Triple dose schedule each of 1 mg ALM + 1 mg BCG was more effective. The status remained unchanged until the end of the experiment (approximately 8 months). The study indicates that a combination of ALM + BCG may be a good candidate vaccine for exploiting against human Kala-azar.


IMP, GTP, and 6-phosphoryl-IMP complexes of recombinant mouse muscle adenylosuccinate synthetase.
Prokaryotes have a single form of adenylosuccinate synthetase that controls the committed step of AMP biosynthesis, but vertebrates have two isozymes of the synthetase. The basic isozyme, which predominates in muscle, participates in the purine nucleotide cycle, has an active site conformation different from that of the Escherichia coli enzyme, and exhibits significant differences in ligand recognition. Crystalline complexes presented here of the recombinant basic isozyme from mouse show the following. GTP alone binds to the active site without inducing a conformational change. IMP in combination with an acetate anion induces major conformational changes and organizes the active site for catalysis. IMP, in the absence of GTP, binds to the GTP pocket of the synthetase. The combination of GTP and IMP results in the formation of a stable complex of 6-phosphoryl-IMP and GDP in the presence or absence of hadacidin. The response of the basic isozyme to GTP alone differs from that of synthetases from plants, and yet the conformation of the mouse basic and E. coli synthetases in their complexes with GDP, 6-phosphoryl-IMP, and hadacidin are nearly identical. Hence, reported differences in ligand recognition among synthetases probably arise from conformational variations observed in partially ligated enzymes.


Implicit Annealing in Kernel Spaces: A Strongly Consistent Clustering Approach.
Kernel k-means clustering is a powerful tool for unsupervised learning of non-linearly separable data. Its merits are thoroughly validated on a suite of simulated datasets and real data benchmarks that feature nonlinear and multi-view separation. Since the earliest attempts, researchers have noted that such algorithms often become trapped by local minima arising from the non-convexity of the underlying objective function. In this paper, we generalize recent results leveraging a general family of means to combat sub-optimal local solutions to the kernel and multi-kernel settings. Called Kernel Power k-Means, our algorithm uses majorization-minimization (MM) to better solve this non-convex problem. We show that the method implicitly performs annealing in kernel feature space while retaining efficient, closed-form updates. We rigorously characterize its convergence properties both from computational and statistical points of view. In particular, we characterize the large sample behavior of the proposed method by establishing strong consistency guarantees as well as finite-sample bounds on the excess risk of the estimates through modern tools in learning theory. The proposal's efficacy is demonstrated through an array of simulated and real data experiments.


Vitamin deficiencies and public interventions in the Federal Republic of Germany.
Vitamin supply of adults in the Federal Republic of Germany is - on the average of the population - satisfactory; i.e. the great majority of test persons who underwent biochemical tests (in each case more than 70%) has been found to show at least satisfactory values of vitamin supply with the usual diet. Measuring values of folic acid, thiamin and vitamin B6 were most frequent in the critical range. Uncertain supply with riboflavin, vitamin A and vitamin C has been found in some age and professional groups only; supply with vitamin B12, vitamin E and niacin was not certain in some exceptional cases only. Groups of above-average risk of uncertain vitamin supply so far are young women (18-24 years) and senior men (above 65 years). The pattern of supply gaps is clearly different: in young women, uncertain supply includes folic acid, riboflavin, vitamin B6 and (as the only group) vitamin E; in older men, it includes vitamin C, vitamin A and riboflavin). The educational level is another important factor of influence which has to be taken into account. This is pleasant finding because it gives reason to assume that improved capability to inform oneself leads, at least in part of the population, to a more balanced diet. In cases of lower educational levels, on the other hand, the interest in questions of health and maintenance of health is much lower. This also becomes manifest in a clearly reduced readiness to participate in nutritional inquiries.(ABSTRACT TRUNCATED AT 250 WORDS)


Pesticide contamination and phytotoxicity of sediment interstitial water to tropical benthic microalgae.
Many organic compounds including some herbicides concentrate in sediment, thus it may be expected that interstitial waters contain higher concentrations of these contaminants than the water column. To estimate benthic microalgal exposure to pesticides, sediment and interstitial water sampled in the dry season from four major rivers in north Queensland, Australia, were analysed for these contaminants. Interstitial water extracts from the sediments were tested for acute phytotoxicity to benthic microalgae using PAM fluorometry and the results were compared with chemical analyses of the same water samples. A range of pesticides were detected in both sediment and interstitial waters from all sites, notably the herbicide diuron at concentrations ranging from 0.3 to 11 μg kg(-1) dry weight sediment, and up to 68 ng L(-1) in interstitial waters. Herbicide concentrations estimated from partition coefficients and the sediment concentrations typically overestimated analytically determined concentrations present in interstitial water by an order of magnitude. The analytically determined herbicide concentrations in the interstitial water explained most of the phytotoxicity measured with the bioassay; however, photoinhibition was slightly higher than expected based on analytical results, indicating the presence of unidentified phytotoxins. These results demonstrate the presence of pesticides in interstitial waters in the Tropical dry season, sometimes at concentrations that may affect sensitive benthic organisms, and supports the use of the I-PAM bioassay as a valuable tool in exposure- and environmental risk- and impact-assessments.


Detailed characterization of polydnavirus immunoevasive proteins in an endoparasitoid wasp.
Polydnaviruses are a unique group of insect viruses in terms of their obligate and symbiotic associations with some parasitic wasps. The Cotesia kariyai polydnavirus (CkPDV) replicates only in ovarian calyx cells of C. kariyai female wasps and is injected into the wasp's host, the armyworm Pseudaletia separata, along with the eggs. A previous study indicated the possibility that one of the CkPDV surface proteins mediates immunoevasion by the wasp from the encapsulation reaction of the host insect's hemocytes. This protein was named immunoevasive protein (IEP). The present studies substantially confirmed the previous observation by showing that an anti-IEP IgG neutralizes immunoevasive activity on the wasp eggs. Further, we isolated the IEP homologue (IEP-2) cDNA and IEP (IEP-1) cDNA, sequenced them and found that both are cysteine-rich proteins, each containing epidermal growth factor (EGF)-like repeats. IEP genes were not found to reside in the CkPDV genome, but in the wasp chromosomal DNA. IEPs are synthesized in the female reproductive tract and their expression was detected from 4 days after pupation, 1 day later than expression of the virus capsid proteins. In situ hybridization and immunocytochemistry indicated that the lateral oviduct cells of the reproductive tracts produce IEP-1/IEP-2 mRNAs and secrete the proteins into the oviduct. These data suggest that the expression pattern and localization of IEPs are different from other components of CkPDV virions.


Clinical Development and Implementation of an Institutional Guideline for Prospective EEG Monitoring and Reporting of Delayed Cerebral Ischemia.
Delayed cerebral ischemia (DCI) is the most common and disabling complication among patients admitted to the hospital for subarachnoid hemorrhage (SAH). Clinical and radiographic methods often fail to detect DCI early enough to avert irreversible injury. We assessed the clinical feasibility of implementing a continuous EEG (cEEG) ischemia monitoring service for early DCI detection as part of an institutional guideline. An institutional neuromonitoring guideline was designed by an interdisciplinary team of neurocritical care, clinical neurophysiology, and neurosurgery physicians and nursing staff and cEEG technologists. The interdisciplinary team focused on (1) selection criteria of high-risk patients, (2) minimization of safety concerns related to prolonged monitoring, (3) technical selection of quantitative and qualitative neurophysiologic parameters based on expert consensus and review of the literature, (4) a structured interpretation and reporting methodology, prompting direct patient evaluation and iterative neurocritical care, and (5) a two-layered quality assurance process including structured clinician interviews assessing events of neurologic worsening and an adjudicated consensus review of neuroimaging and medical records. The resulting guideline's clinical feasibility was then prospectively evaluated. The institutional SAH monitoring guideline used transcranial Doppler ultrasound and cEEG monitoring for vasospasm and ischemia monitoring in patients with either Fisher group 3 or Hunt-Hess grade IV or V SAH. Safety criteria focused on prevention of skin breakdown and agitation. Technical components included monitoring of transcranial Doppler ultrasound velocities and cEEG features, including quantitative alpha:delta ratio and percent alpha variability, qualitative evidence of new focal slowing, late-onset epileptiform activity, or overall worsening of background. Structured cEEG reports were introduced including verbal communication for findings concerning neurologic decline. The guideline was successfully implemented over 27 months, during which neurocritical care physicians referred 71 SAH patients for combined transcranial Doppler ultrasound and cEEG monitoring. The quality assurance process determined a DCI rate of 48% among the monitored population, more than 90% of which occurred during the duration of cEEG monitoring (mean 6.9 days) beginning 2.7 days after symptom onset. An institutional guideline implementing cEEG for SAH ischemia monitoring and reporting is feasible to implement and efficiently identify patients at high baseline risk of DCI during the period of monitoring.


A national survey of ambulance paramedics on the identification of patients with end of life care needs.
Developing the proactive identification of patients with end of life care (EoLC) needs within ambulance paramedic clinical practice may improve access to care for patients not benefitting from EoLC services at present. To inform development of this role, this study aims to assess whether ambulance paramedics currently identify EoLC patients, are aware of identification guidance and believe this role is appropriate for their practice. Between 4 November 2019 and 5 January 2020, registered paramedics from nine English NHS ambulance service trusts were invited to complete an online questionnaire. The questionnaire initially explored current practice and awareness, employing multiple-choice questions. The Gold Standards Framework Proactive Identification Guidance (GSF PIG) was then presented as an example of EoLC assessment guidance and further questions, permitting free-text responses, explored attitudes towards performing this role. 1643 questionnaires were analysed. Most participants (79.9%; n = 1313) perceived that they attended a patient who was formally unrecognised as within the last year of life on at least a monthly basis. Despite 72.0% (n = 1183) of paramedics indicating that they had previously made an EoLC referral to a General Practitioner (GP), only 30.5% (n = 501) were familiar with the GSF PIG and of those only 25.9% (n = 130) had received training in its use. Participants overwhelmingly believed that they can (94.4%; n = 1551) and should (97.0%; n = 1594) perform this role, yet current barriers were identified as the inaccessibility of a patient's medical records, inadequate EoLC education and communication difficulties. Consequently, facilitators to performing this role were identified as the provision of further training in EoLC assessment guidance and establishing accessible, responsive EoLC referral pathways. Ambulance paramedics frequently encounter patients that they perceive are not receiving appropriate EoLC provision, and participants in this study overwhelmingly supported a role in highlighting this to primary care providers. Though many paramedics are already making referrals for these patients, the majority are performed without knowledge of validated EoLC assessment guidance. Provision of EoLC assessment training might therefore be expected to improve the timeliness and sensitivity of referrals, potentially addressing current inequalities in access to EoLC. The communication difficulties currently encountered when making a referral might be addressed by the provision of dedicated EoLC referral pathways. Future qualitative and quantitative evaluation of local initiatives providing both assessment training and referral pathways would be hugely beneficial for revealing the benefits and barriers associated with the development of this role in practice.


Effect of pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer: A meta-analysis .
Pertuzumab, as an adjunctive therapy to trastuzumab and docetaxel, has been reported to be potentially beneficial for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of pertuzumab supplementation in patients with HER2-positive metastatic breast cancer. Medline, SCOPUS, Google Scholar, Cochrane library databases, EMBASE, Springer, and Science Direct were systematically searched. Randomized controlled trials (RCTs) assessing the effect of pertuzumab + trastuzumab + docetaxel vs. trastuzumab + docetaxel on the treatment of HER2-positive metastatic breast cancer were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were death, overall survival, and progression-free survival. Meta-analysis was performed using fixed- or random-effect model. Five RCTs involving 3,742 patients were included in the meta-analysis. Overall, compared with placebo and trastuzumab + docetaxel treatment, combination treatment of pertuzumab + trastuzumab + docetaxel treatment was associated with the significantly reduced death (hazard ratio (HR) = 0.67; 95% confidence interval (CI) = 0.57 - 0.78; p < 0.005) as well as improved overall survival (HR = 0.66; 95% CI = 0.35 - 0.67; p = 0.98) and progression-free survival (HR = 0.64; 95% CI = 0.58 - 0.71; p < 0.005). Moreover, pertuzumab supplementation did not increase the number of patients with reductions in the left ventricular ejection fraction (LVEF) of 10% or more (risk ratio (RR) = 0.70; 95% CI = 0.47 - 1.04; p = 0.07). Pertuzumab + trastuzumab + docetaxel treatment significantly reduced death, increased overall survival, and progression-free survival in patients with HER2-positive metastatic breast cancer compared to placebo and trastuzumab + docetaxel treatment, but showed no increased adverse events. .


Jet-cooled spectroscopy of paracetamol.
We have measured the resonant 2-photon ionization spectrum of jet-cooled p-acetaminophenol (paracetamol) between 33,400 cm(-1) and 45,500 cm(-1), and analysed the results in the light of theoretical calculations of the ground-state geometry and vibrational frequencies. The experimental spectrum consists of a large number of clearly resolved vibronic transitions, and some evidence of rotational structure. It is dominated by a repeated progression with a regular spacing of 33 cm(-1) (believed to be the methyl-torsion mode) in combination with normal modes of vibration which involve the stretching of the C-C bonds in the phenyl ring and bending of the C-N-C bond in the amide group. The intensity pattern of the progressions in the methyl torsion is consistent with structural changes between the minimum-energy geometries in the ground and excited states.


Monitoring antidonor alloantibodies as a predictive assay for renal allograft tolerance/long-term observations in nonhuman primates.
In an effort to define reliable assays that might predict postimmunosuppressant-withdrawal development of chronic rejection (CR), despite conditioning for tolerance induction, we evaluated various immunological responses in nonhuman primate renal allograft recipients. Fourteen Cynomolgus monkeys received low dose total body irradiation, thymic irradiation, antithymocyte globulin, and peritransplant CD154 blockade, followed by a one-month course of cyclosporine. Recipients underwent major histocompatibility complex mismatched kidney transplantation with donor bone marrow infusion (Group A, n=8), without donor cell infusion (Group B, n=2), or with donor splenocyte infusion (Group C, n=4). All Group A recipients developed mixed chimerism and four of them survived long-term without rejection. The remaining four rejected their kidney allografts either chronically or acutely. All recipients in Groups B and C failed to develop chimerism and rejected their allografts. Among various in vitro assays, detection of anti-donor alloantibody (ADA) by flow cytometry (FCM) was the most relevant to long-term outcome. All five recipients that developed both anti-T cell and B cell IgG ADA in Groups A, B and C, developed histological evidence of CR within 200 days of the appearance of ADA. One of two recipients that developed only anti-B cell IgG ADA eventually developed CR over two years following discontinuation of immunosuppression and 1.5 years after ADA development. Another recipient with very low anti-B cell ADA has never developed CR. ADA monitoring with FCM assay appears to be useful in predicting the failure of tolerance prior to the development of functional or histologic abnormalities of the renal allograft.


Perturbation Analysis for Finite-Time Stability and Stabilization of Probabilistic Boolean Networks.
This article analyzes the function perturbation impact on the finite-time stability and stabilization of the probabilistic Boolean networks (PBNs). First, the concept of stability in the distribution of PBNs is divided into two disjoint concepts, that is, finite-time stability with probability one (FTSPO) and asymptotical stability with probability one (ASPO), and a new criterion is proposed for the verification of ASPO. Second, by constructing a parameterized set, it is shown that PBNs subject to function perturbation keep FTSPO if and only if the perturbed point does not belong to the parameterized set, while PBNs become ASPO if and only if the perturbed point belongs to the parameterized set. Third, as an application of perturbed stability analysis, the robust state-feedback stabilization is discussed for probabilistic Boolean control networks (PBCNs) with function perturbation. Finally, the obtained results are applied to a WNT5A network and lac operon in the Escherichia coli, respectively.


P037 Effect of Ozanimod Treatment and Discontinuation on Absolute Lymphocyte Count in Moderate-to-Severe Ulcerative Colitis: Results from a Phase 3 Trial.
Ozanimod is an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, which reduces migration of lymphocytes involved in adaptive immunity from lymphoid tissues to blood and inflamed tissues while preserving components of the innate immune response. Ozanimod is approved in multiple countries for the treatment of relapsing forms of multiple sclerosis and in the US for the treatment of moderately-to-severely active ulcerative colitis (UC). The reduction of circulating lymphocytes is expected based on the mechanism of action of ozanimod and thought to be an important driver of efficacy. We assessed absolute lymphocyte count (ALC) during ozanimod induction and maintenance, and after ozanimod discontinuation, per protocol, in adults with moderately-to-severely active UC to characterize the time course of ALC reduction and recovery. The analysis included patients who received ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or placebo once daily in True North, a phase 3 randomized trial (NCT02435992). During a 10-week induction period, patients were randomized 2:1 to double-blind treatment with ozanimod or placebo (Cohort 1) or received open-label ozanimod (Cohort 2). Patients from either cohort with a clinical response to ozanimod at week 10 were re-randomized 1:1 to double-blind treatment with ozanimod or placebo during maintenance through week 52. Placebo-treated patients with a clinical response at week 10 continued placebo during maintenance. ALC was assessed at baseline and at visits throughout induction and maintenance. A total of 69 patients received continuous placebo treatment, 230 received continuous ozanimod treatment, and 227 received ozanimod during induction and placebo during maintenance. In patients who received continuous placebo, mean ALC remained stable between 1.8‒2.1 x 109/L over time (normal range: 1.02‒3.36 x 109/L). In ozanimod-treated patients, mean ALC was reduced to 43%‒45% of baseline and 70%‒73% of patients had ALC shifts from normal at baseline to low (9/L) at week 10. In patients who continued ozanimod, mean ALC reductions were sustained at approximately the same level and ALC shifts from normal at baseline to low were maintained in 73%‒89% of patients during maintenance. In patients who received ozanimod induction therapy and then were re-randomized to placebo for maintenance, mean ALC recovered within 8 weeks to levels similar to baseline at induction and the proportion of patients with ALC shifts from normal at baseline to low decreased from 73% at week 10 to 6% at week 52. Fewer than 2% of ozanimod-treated patients had ALC 9/L during either induction or maintenance and ALC generally returned to ≥ 0.2 x 109/L while patients remained on ozanimod. Among those who switched from ozanimod induction to placebo maintenance, there were no occurrences of ALC 9/L at the end of maintenance. No patients with a serious/opportunistic infection had concurrent ALC 9/L. Consistent with the mechanism of action of ozanimod, ALC reductions occurred during ozanimod induction and were sustained during maintenance. Incidence of ALC 9/L was low. ALC recovered after switching to placebo and most patients did not require treatment discontinuation because of changes in ALC.


Racial and ethnic differences in knowledge and attitudes about genetic testing in the US: Systematic review.
Precision medicine has grown over the past 20 years with the availability of genetic tests and has changed the one-size-fits-all paradigm in medicine. Precision medicine innovations, such as newly available genetic tests, could potentially widen racial and ethnic disparities if access to them is unequal and if interest to use them differs across groups. The objective of this systematic review was to synthesize existing evidence on racial and ethnic differences in knowledge of and attitudes toward genetic testing among adult patients and the general public in the US, focusing on research about the use of genetic testing in general, not disease-specific tests. Twelve articles published in 1997-2017 met inclusion and exclusion criteria, with 10 including knowledge variables and seven including attitude variables. Studies found consistent patterns of lower awareness of genetic testing in general among non-Whites compared to Whites, lower factual knowledge scores among Blacks and Hispanics/Latinos, and mixed findings of differences in awareness of direct-to-consumer (DTC) genetic testing or the term precision medicine. Blacks, Hispanics/Latinos, and non-Whites generally had more concerns about genetic testing than Whites. The findings suggest that patients and the general public need access to culturally appropriate educational material about the use of genetic testing in precision medicine.


Atlantoaxial stabilization using multiaxial C-1 posterior arch screws.
The authors present a novel technique of atlantoaxial fixation using multiaxial C-1 posterior arch screws. The technique involves the insertion of bilateral multiaxial C-1 posterior arch screws, which are connected by crosslinked rods to bilateral multiaxial C-2 pars screws. The clinical results are presented in 3 patients in whom anomalies of the vertebral arteries, C-1 lateral masses, and/or posterior arch of C-1 presented difficulty using existing fixation techniques with transarticular screws, C-1 lateral mass screws, or posterior wiring. The C-1 posterior arch screws achieved solid fixation and their insertion appeared to be technically less demanding than that of transarticular or C-1 lateral mass screws. This technique may reduce the risk of complications compared with existing techniques, especially in patients with anatomical variants of the vertebral artery, C-1 lateral masses, or C-1 posterior arch. This technique may prove to be an attractive fixation option in patients with normal anatomy.


Prognostic value of diffuse versus intestinal histotype in patients with gastric cancer: a systematic review and meta-analysis.
There are two distinct types of gastric carcinoma (GC), intestinal, more frequently sporadic and linked to environmental factors, and diffuse (undifferentiated) that is highly metastatic and characterized by rapid disease progression and a poor prognosis. However, there are many conflicting data in the literature concerning the association between histology and prognosis in GC. This meta-analysis was performed to provide demonstration if histology according to Lauren classification is associated with different prognosis in patients with GC. We searched PubMed, the Cochrane Library, SCOPUS, Web of Science, CINAHL, and EMBASE for all eligible studies. The combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) in terms of overall survival (OS) were evaluated. A total of 73 published studies including 61,468 patients with GC were included in this meta-analysis. Our analysis indicates that GC patients with diffuse-type histology have a worst prognosis than those with intestinal subgroup in all studies (HR 1.23; 95% CI, 1.17-1.29; P<0.0001), in both loco-regional confined (HR 1.21; 95% CI, 1.12-1.30; P<0.0001) and advanced disease (HR 1.25; 95% CI, 1.046-1.50; P=0.014), in Asiatic (HR 1.2; 95% CI, 1.14-1.27; P<0.0001) and Western patients (HR 1.3; 95% CI, 1.19-1.41; P<0.0001), and in those not exposed (HR 1.15; 95% CI, 1.07-1.24; P<0.0001) or exposed (HR 1.27; 95% CI, 1.17-1.37; P<0.0001) to (neo)adjuvant therapy. Our results indicated that histology might be a useful prognostic marker for both early and advanced GC patients, with intestinal-type associated with a better outcome. This information could be used for stratification purpose in future clinical trials.


Mass spectrometric characterization of photooxidative protein modifications in Arabidopsis thaliana thylakoid membranes.
Oxidative and nitrosative stress leaves footprints in the plant chloroplast in the form of oxidatively modified proteins. Using a mass spectrometric approach, we identified 126 tyrosine and 12 tryptophan nitration sites in 164 nitrated proteolytic peptides, mainly from photosystem I (PSI), photosystem II (PSII), cytochrome b(6) /f and ATP-synthase complexes and 140 oxidation products of tyrosine, tryptophan, proline, phenylalanine and histidine residues. While a high number of nitration sites were found in proteins from four photosynthetic complexes indicating that the nitration belongs to one of the prominent posttranslational protein modifications in photosynthetic apparatus, amino acid oxidation products were determined mostly in PSII and to a lower extent in PSI. Exposure of plants to light stress resulted in an increased level of tyrosine and tryptophan nitration and tryptophan oxidation in proteins of PSII reaction center and the oxygen-evolving complex, as compared to low light conditions. In contrast, the level of nitration and oxidation of these amino acid residues strongly decreased for all light-harvesting proteins of PSII under the same conditions. Based on these data, we propose that oxidative modifications of proteins by reactive oxygen and nitrogen species might represent an important regulatory mechanism of protein turnover under light stress conditions, especially for PSII and its antenna proteins.


Effect of cellular level of FliK on flagellar hook and filament assembly in Salmonella typhimurium.
Frameshift mutations in the fliK gene of Salmonella result in abnormal elongation of the hook and the failure to assemble filament (polyhook phenotype). Second-site suppressor mutations restore filament assembly, but the cells often remain defective in hook-length control (polyhook-filament phenotype). Where the suppressor mutations are intragenic, the second mutation restores the original frame, generating a region of frameshifted sequence, but restoring the natural C terminus. Some of these frameshifted sequences contain a UGA (opal) termination codon. These cells have few flagella and swarm poorly. We suspected that readthrough of UGA by tRNATrp might be the reason for the partial function. When the UGA codon was changed to the Trp codon UGG, flagellar assembly and function were restored to wild-type levels. Conversely, underexpression of the wild-type fliK gene, achieved by changing the sole Trp codon in the sequence (Trp271) to UGA, decreased both the number of flagella and the ability to swarm. These results validate the readthrough hypothesis and indicate that low levels of FliK sustain some degree of flagellation and motility. At low levels of FliK, most flagella had polyhooks. With increasing amounts, the morphology progressively changed to polyhook-filament, and eventually to wild-type hook-filament. When FliK was overproduced, the hook length was slightly shorter (46(+/-7) nm) than that of the wild-type strain (55(+/-9) nm). FliK levels were measured by immunoblotting. Wild-type levels were about 40 to 80 molecules/cell. FliK synthesized by UGA readthrough could be detected when overproduced from plasmid fliK-W271opal, and the levels indicated a probability of readthrough of 0.002 to 0.01. This value was used to estimate the cellular level of underexpressed FliK, which could partly restore function to a fliK mutant, at about 0.07 to 0.8 molecule/cell. These results suggest that FliK does not form a large structure in the cytoplasm and may function as a regulatory protein for protein export. A model for hook-length control is presented that involves feedback from the assembly point to the export apparatus.


Biological substitutes/extenders for spinal arthrodesis: which agents are cost-effective?
Systematic review. To evaluate the cost-effectiveness of lumbar or cervical spinal arthrodesis using biological substitutes and extenders compared with iliac crest autograft for the treatment of degenerative spinal conditions. The cost-effectiveness of using bone graft substitutes and extenders for spinal fusion compared with using iliac crest autograft is not yet well established. A systematic search of PubMed/MEDLINE, the Cochrane Collaboration Library, EMBASE, the CRD (Centre for Reviews and Dissemination) database, and Tuft's CEA registry for literature published through December 2013 was performed to identify full formal economic analyses comparing the use of biological grafts with iliac crest bone graft in spinal fusion for thoracolumbar or cervical degenerative, deformity, and traumatic spinal conditions. Economic outcomes such as cost per improved outcome or cost per quality-adjusted life year were reported in the context of the model type, analytic perspective clinical comparisons, and sensitivity analyses employed. The search strategy yielded 88 citations, and 6 full economic analyses ultimately met our inclusion criteria. For the comparison of recombinant human bone morphogenetic protein-2 to iliac crest bone graft in the lumbar spine, data from 4 cost-effectiveness studies and 1 cost-utility study provided discordant conclusions that varied with type of data used, cost-measurement methods, and study design. In the cervical spine, one study suggested that from a societal perspective, anterior cervical discectomy and fusion (ACDF) with allograft is similarly cost-effective as ACDF with autograft. The results suggest that compared with use of iliac crest bone graft in lumbar spinal fusion, use of recombinant human bone morphogenetic protein is not cost-effective from a payer perspective with higher upfront costs, but it may be cost-effective from a societal perspective due to a decrease in lost productivity. The data in this study also suggest that from a societal perspective, ACDF with allograft is similarly cost-effective to ACDF with autograft. 3.


Evaluation of safety and efficacy of silicone rod in tarsofrontalis sling surgery for severe congenital ptosis.
To evaluate the efficacy and safety of silicone rod in tarsofrontalis sling surgery for severe congenital ptosis. A prospective, case series study was performed in 46 patients (56 eyelids) who underwent tarsofrontalis sling surgery using silicone rod for severe congenital ptosis. The efficacy of the silicone rod in tarsofrontalis sling surgery was evaluated by marginal reflex distance1 (MRD1), postoperative eyelid symmetry, and recurrence of ptosis. Safety of silicone rod was assessed by noting postoperative complications. The postoperative results were considered as good if MRD1 was 4.0 ± 0.5 mm (3.5-4.5 mm) and symmetry ≤1 mm; fair if MRD1 was 2.5 ± 0.5 mm (2-3 mm) and symmetry 1.5 to 2.0 mm; and poor if MRD1 was <2.0 mm and symmetry <2.0 mm. In cases of unilateral congenital ptosis, good results were seen in 83.3% cases, fair results in 11.1% cases, and poor results in 5.5% cases. In cases of bilateral congenital ptosis, good results were seen in 80.0% cases, fair in 15.0% cases, and poor result in 5.0% cases. Satisfactory postoperative eyelid elevation of ≥2 mm was seen in 93% cases. Complications in the form of granuloma formation, subsequent silicone rod extrusion, and recurrence occurred in 4% cases. The use of silicone rod in tarsofrontalis sling surgery for severe congenital ptosis repair is a safe and effective surgery, with few complications and easy removal and adjustment.


INVESTIGATION OF ANTIHEMOLYTIC, XANTHINE OXIDASE INHIBITION, ANTIOXIDANT AND ANTIMICROBIAL PROPERTIES OF SALVIA VERBENACA L. AERIAL PART EXTRACTS.
In this study, Salvia verbenaca L. aerial part extracts (SVEs): were screened for their antihemolytic, xanthine oxidase (XO) inhibition, antioxidant and antimicrobial activities. To investigate SVEs antihemolytic activity, the 2,2,-azobis (2-amidinopropane) dihydrochloride (AAPH) was used to induce erythrocyte oxidative hemolysis. In XO inhibition test, xanthine was used as substrate and cytochrome c for generating superoxide anions. The antioxidant activity of SVEs was examined by means of reducing power, DPPH free radical scavenging and iron chelating assays. In addition, SVEs were tested for their antimicrobial effects by evaluating antibacterial and antifungal activities. Ethyl acetate extract (EAE) contains the highest amount of total polyphenols and flavonoids (661.78 ± 4.00 mg GAE / g E) and (28.81 ± 0.38 mg QE / g E) respectively. In antihemolytic test EAE was the most active extract with an HT50 value of 165 min. SVEs gave significant inhibitory effects on XO, especially the chloroform extract (ChE) with IC50 value of 0.0088 ± 0.000 mg/ml. EAE was the most active extract in reducing power essay (EC50: 0.0047 ± 0.000 mg/ml) and in DPPH radical scavenging essay (IC50: 0.0086 ± 0.000 mg/ml). Finally, the EAE has inhibited the growth of nine bacterial strains with inhibition zone diameters of (12 to 16 mm), but no activities have found against fungal strains. S. verbenaca could be considered as a potential source of natural antihemolytic, enzyme modulator, antioxidant and antibacterial agents.


Development of improved vaccine cell lines against rotavirus.
Rotavirus is a major cause of severe gastroenteritis among very young children. In developing countries, rotavirus is the major cause of mortality in children under five years old, causing up to 20% of all childhood deaths in countries with high diarrheal disease burden, with more than 90% of these deaths occurring in Africa and Asia. Rotavirus vaccination mimics the first infection without causing illness, thus inducing strong and broad heterotypic immunity against prospective rotavirus infections. Two live vaccines are available, Rotarix and RotaTeq, but vaccination efforts are hampered by high production costs. Here, we present a dataset containing a genome-wide RNA interference (RNAi) screen that identified silencing events that enhanced rotavirus replication. Evaluated against several rotavirus vaccine strains, hits were validated in a Vero vaccine cell line as well as CRISPR/Cas9 generated cells permanently and stably lacking the genes that affect RV replication. Knockout cells were dramatically more permissive to RV replication and permitted an increase in rotavirus replication. These data show a means to improve manufacturing of rotavirus vaccine.


Divergent effects of GM-CSF and TGFbeta1 on bone marrow-derived macrophage arginase-1 activity, MCP-1 expression, and matrix metalloproteinase-12: a potential role during arteriogenesis.
Granulocyte/macrophage-colony stimulating factor (GM-CSF) and transforming growth factor (TGF)beta1 induce arteriogenesis in a nonischemic model of femoral artery ligation. Moreover, clinical trials demonstrated an improved collateralization after injection of bone marrow cells. In the present study, the expression of arteriogenic factors in bone marrow-derived macrophages (BMDM) was measured to verify the potential of these cells to influence collateral artery growth. GM-CSF induced in BMDM the expression of monocyte chemoattractive protein (MCP)-1, matrix-metalloproteinase (MMP)-12, and arginase-1-the latter also showing a remarkable increase in activity. During in vivo induced arteriogenesis, the accumulation rate of macrophages around proliferating collaterals was significantly increased. We also show that MCP-1 is found to be mainly expressed in the media of the vessel wall, MMP-12 in macrophages of the adventitia, and arginase at both locations. This study provides for the first time a comprehensive analysis of GM-CSF/TGFbeta1-regulated arteriogenic factors in BMDM and supports the hypothesis that arteriogenesis is a multistage mechanism, including monocyte/macrophage adhesion and transmigration, pro-arteriogenic cytokine expression, degradation of connective tissue, and collagen synthesis regulation. Selective modulation of these mechanisms as well as cell-based therapies supplying arteriogenic factors in vivo point toward new strategies to influence collateral artery growth.


Standardized spider (Arachnida, Araneae) inventory of Hankoniemi, Finland.
During a field course on spider taxonomy and ecology at the University of Helsinki, the authors had the opportunity to sample four plots with a dual objective of both teaching on field methods, spider identification and behaviour and uncovering the spider diversity patterns found in the southern coastal forests of Hankoniemi, Finland. As an ultimate goal, this field course intended to contribute to a global project that intends to uncover spider diversity patterns worldwide. With that purpose, a set of standardised methods and procedures was followed that allow the comparability of obtained data with numerous other projects being conducted across all continents. A total of 104 species and 1997 adults was collected. Of these, 41 species (39%) were Linyphiidae and 13 (12%) Theridiidae. All other families had 6 or less species represented. Linyphiidae were also dominant in terms of adult individuals captured, with 1015 (51%), followed by 428 (21%) Lycosidae, 158 (8%) Tetragnathidae and 145 (7%) Theridiidae. All other families had less than 100 individuals. The most abundant species were Neriene peltata, Alopecosa taeniata, Piratula hygrophila and Dismodicus elevatus, all with more than 100 individuals. All sites had between 56 and 62 species and between 445 and 569 individuals.


Abnormal etioplast development in barley seedlings infected with BSMV by seed transmission.
The effect of barley stripe mosaic hordeivirus (BSMV) was studied on the ultrastructure of etioplasts, protochlorophyllide forms and the greening process of barley (Hordeum vulgare cv. Pannónia) plants infected by seed transmission. The leaves of 7- to 11-day-old etiolated seedlings were examined by transmission electron microscopy, fluorescence and absorption spectroscopy. The etioplasts of infected seedlings contained smaller prolamellar bodies with less regular membrane structure, while prothylakoid content was higher than in the control. The protochlorophyllide content of virus-infected seedlings was reduced to 74% of the control. In the 77 K fluorescence spectra the relative amount of 655 nm emitting photoactive protochlorophyllide form decreased, and the amount of the 645 and 633 nm emitting forms increased in the infected leaves. A characteristic effect was observed in the process of the Shibata-shift: 40 min delay was observed in the infected leaves. The results of this work proved that BSMV infection delays or inhibits plastid development and the formation of photosynthetic apparatus.


A conserved glycine residue of trimeric autotransporter domains plays a key role in Yersinia adhesin A autotransport.
The Yersinia adhesin A (YadA) is a trimeric autotransporter adhesin of enteric yersiniae. It consists of three major domains: a head mediating adherence to host cells, a stalk involved in serum resistance, and an anchor that forms a membrane pore and is responsible for the autotransport function. The anchor contains a glycine residue, nearly invariant throughout trimeric autotransporter adhesins, that faces the pore lumen. To address the role of this glycine, we replaced it with polar amino acids of increasing side chain size and expressed wild-type and mutant YadA in Escherichia coli. The mutations did not impair the YadA-mediated adhesion to collagen and to host cells or the host cell cytokine production, but they decreased the expression levels and stability of YadA trimers with increasing side chain size. Likewise, autoagglutination and resistance to serum were decreased in these mutants. We found that the periplasmic protease DegP is involved in the degradation of YadA and that in an E. coli degP deletion strain, mutant versions of YadA were expressed almost to wild-type levels. We conclude that the conserved glycine residue affects both the export and the stability of YadA and consequently some of its putative functions in pathogenesis.


Direct cost analysis of the second year post-allogeneic hematopoietic stem cell transplantation in the Bone Marrow Transplant Centre of Tunisia.
Background: Hematopoietic stem cell transplantation (HSCT) is a medically complicated therapy with a long recovery time. In Tunisia, the National Health Insurance Fund (CNAM) covers only the first year post-transplantation, after which the costs are borne by the hospital. Objective: Describe complications that can occur during the second year post-allogeneic HSCT and calculate direct costs in different groups of patients. Methods: In this pharmacoeconomic study, medical records of the second year post-allogeneic HSCT were collected. Studied variables included frequent observed complications and medical and non-medical direct costs. Results: The average total direct cost in the population during the second year post-transplantation was $11,571, 97% of which represents direct medical costs Drugs accounted for the largest share (80%) of total direct costs, dominated by the cost of antifungals (52%) and antivirals (26%) drug . Cytomegalovirus status was seen in 9.3% of patients and was associated with a seven-fold increase in direct costs (p < 0.001).In patients who developed chronic GVHD, the average direct cost was three times higher than for those who did not (p = 0.032). Conclusion: Given the importance of direct costs in the post-transplantation period a review of the hospital financing mechanism and a new convention with the CNAM is crucial..


Volume homeostasis in normal pregnancy and pre-eclampsia: physiology and clinical implications.
The pieces of the jigsaw puzzle of volume homeostasis in human pregnancy are being put together gradually. This chapter has focused on recent advances in our understanding of factors controlling extracellular fluid volume in normal pregnancy and their disturbance in women who develop pre-eclampsia. We have explored the clinical implications of these guidelines for management of patients with pre-eclampsia. Clearly there is still much to be learned. Studies of the cellular and subcellular handling of sodium are still in their infancy and will add much to our understanding of the physiology of volume homeostasis in normal pregnancy and its disturbance in pre-eclampsia and other causes of hypertension in pregnancy.


Development and validation of the self-reported disability status scale (SRDSS) to estimate EDSS-categories.
Clinician-assessed Expanded Disease Status Scale (EDSS) is gold standard in clinical investigations but normally unavailable in population-based, patient-centred MS-studies. Our objective was to develop a self-reported gait measure reflecting EDSS-categories. We developed the self-reported disability status scale (SRDSS) with three categories (≤3.5, 4-6.5, ≥7) based on three mobility-related questions. The SRDSS was determined for 173 persons with MS and validated against clinical EDSS to calculate sensitivity and specificity. Accuracy was 88.4% (153 correctly classified) and weighted kappa 0.73 (0.62-0.84). Sensitivity/specificity-pairs were 94.5%/77.8%, 69.0%/94.7% and 100%/98.2% for SRDSS ≤3.5, 4-6.5 and ≥7, respectively. Self-reported SRDSS approximates EDSS-categories well and fosters comparability between clinical and population-based studies.


Patients with auditory neuropathy/dys-synchrony lack efferent suppression of transient evoked otoacoustic emissions.
Function of the olivocochlear reflex, measured by suppression of transient evoked otoacoustic emissions, is assessed in nine patients with bilateral auditory neuropathy/dys-synchrony and compared to matched control subjects with normal auditory function. TEOAEs were acquired using 65 dB peak sound pressure linear clicks with and without the presence of broad-band noise presented binaurally, ipsilaterally, or contralaterally in a forward masking paradigm. Efferent suppression differed significantly between subject groups (p < .0001). Mean suppression was less than 0.22 dB across all suppressor noise conditions for the auditory neuropathy/dys-synchrony subjects. TEOAE suppression averaged 4.47 (binaural), 2.41 (ipsilateral), and 1.52 (contralateral) dB in the control subjects. Suppression characteristics across the three suppressor conditions were also assessed in one patient with unilateral auditory neuropathy/dys-synchrony. The results suggest that poor efferent responses are related to compromised afferent input to the OCR pathway and support the use of efferent suppression of otoacoustic emissions as a differential measure of auditory function in patients with auditory neuropathy/dys-synchrony.


Replacement behaviors for identified functions of challenging behaviors.
Functional assessment has become a major feature of learning-based research. A critical element of the majority of these studies includes not only methods and procedures to identify the cause of the challenging behavior, but to establish replacement treatment methods. By far the most common intervention in the 176 studies we reviewed was reinforcement. Noncontingent reinforcement (NCR) was the most common reinforcement method, followed by differential reinforcement of other behavior (DRO). Reinforcement plus extinction was the second most commonly employed treatment followed by functional communication training with or without reinforcement. Researchers proved to be very creative. Forty different treatment methods were employed. The implications of these data are discussed.


A total wrist arthroplasty in rheumatoid arthritis: a case followed for 24 years.
Abstract We report a case of rheumatoid arthritis treated with a total wrist arthroplasty. A Meuli-type total wrist arthroplasty was performed on the left wrist in 1979. We have treated the patient's rheumatoid arthritis with disease-modifying antirheumatic drugs (DMARDs) (Actarit 100 mg and Mijoribine 50 mg) and nonsteroidal anti-inflammatory drugs (NSAIDs) for a total of 26 years before and after the total wrist arthroplasty. The activity of the rheumatoid arthritis has been kept at a low level. The operated wrist was followed up for 24 years postoperatively. It is thought that the antirheumatic treatments over a long period have been very successful in preventing the destruction of the operated wrist.