Effects of Diisocyanate Structure and Disulfide Chain Extender on Hard Segmental Packing and Self-Healing Property of Polyurea Elastomers.
Four linear polyurea elastomers synthesized from two different diisocyanates, two different chain extenders and a common aliphatic amine-terminated polyether were used as models to investigate the effects of both diisocyanate structure and aromatic disulfide chain extender on hard segmental packing and self-healing ability. Both direct investigation on hard segments and indirect investigation on chain mobility and soft segmental dynamics were carried out to compare the levels of hard segmental packing, leading to agreed conclusions that correlated well with the self-healing abilities of the polyureas. Both diisocyanate structure and disulfide bonds had significant effects on hard segmental packing and self-healing property. Diisocyanate structure had more pronounced effect than disulfide bonds. Bulky alicyclic isophorone diisocyanate (IPDI) resulted in looser hard segmental packing than linear aliphatic hexamethylene diisocyanate (HDI), whereas a disulfide chain extender also promoted self-healing ability through loosening of hard segmental packing compared to its C-C counterpart. The polyurea synthesized from IPDI and the disulfide chain extender exhibited the best self-healing ability among the four polyureas because it had the highest chain mobility ascribed to the loosest hard segmental packing. Therefore, a combination of bulky alicyclic diisocyanate and disulfide chain extender is recommended for the design of self-healing polyurea elastomers.


The hemoglobin system of the serpent eel Ophisurus serpens: structural and functional characterization.
The hemoglobin system of the serpent eel Ophisurus serpens was structurally and functionally characterized with the aim of comparing it to the hemoglobin system of other fish species, as oxygen loading under the severe habitat conditions experienced by O. serpens could have necessitated specific adaptation mechanisms during evolution. The hemoglobin system of O. serpens includes one cathodic and four anodic components. The molecular mass of the α and β chains of the cathodic component as well as the 2 α and 4 β of the anodic components were determined. Analysis of the intact α and β chains from cathodic hemoglobin and their proteolytic digestion products by high-resolution MS and MS/MS experiments resulted in 92 and 95 % sequence coverage of the α and β globins, respectively. The oxygen binding properties of both hemoglobin components were analyzed with respect to their interactions with their physiological effectors. Stripped cathodic hemoglobin displayed the highest oxygen affinity among Anguilliformes with no significant effect of pH on O2-affinity. In the presence of both chloride and organic phosphates, O2-affinity was strongly reduced, and cooperativity was enhanced; moreover, cathodic hemoglobin contains two indistinguishable GTP-binding sites. Stripped anodic hemoglobins exhibited both low O2-affinity and low cooperativity and a larger Bohr effect than cathodic hemoglobin. The cathodic hemoglobin of O. serpens and the corresponding component of Conger conger share the greatest structural and functional similarity among hemoglobin systems of Anguilliformes studied to date, consistent with their phylogenetic relationship.


Paediatric Thrombosis: A Five-Year Experience From A Tertiary Care Center Of Pakistan.
Advances in imaging techniques and longer survival of chronic medical conditions contribute to the increase in paediatric thrombosis. We aim to determine the incidence, underlying risk factors, management and clinical outcome of paediatric thrombosis at a multidisciplinary facility of Pakistan. A retrospectively analysis of the medical records of patients in the paediatric age group admitted at the Aga Khan University hospital from January 2013-September 2018 was performed. Site of thrombosis, associated risks factors, management options and outcome of thrombotic event were evaluated. Of the 22,320 paediatric hospitalization, 35 paediatric patients were diagnosed with thrombosis (15 cases per 10,000 admissions). The median age of the study group was 15 years and twenty patients (57%) were male. The commonest site of thrombosis was in lower limb venous 11 (31%), followed by upper limb venous thrombosis 6 (17%), abdominal vein thrombosis 7 (20%), cerebral venous thrombosis 5 (14%), pulmonary embolism and arterial thrombosis 3(9% each). Eighty three percent had underlying clinical condition including central venous catheter [CVC] (26%), malignancy and infection (14% each), antiphospholipid antibody syndrome (9%), inherited thrombophilia (9%), congenital heart disease (6%), while thrombotic thrombocytopenic purpura and autoimmune disorder (3% each). Twelve (34%) patients were treated with heparin only, 8 (23%) received heparin followed by warfarin while warfarin as a single agent was given in 2 (5.7%) patients. One patient died of pulmonary embolism while 9 (25%) had persistence or recurrence of thrombosis. Incidence of paediatric thrombosis was 0.15%. CVC placement was the most common associated risk factor. Warfarin and heparin both were found to be safe anticoagulation option. Recurrence rate was found to be high.


Both Stat3-activation and Stat3-independent BCL2 downregulation are important for interleukin-6-induced apoptosis of 1A9-M cells.
A unique subclone of a bone marrow-derived stromal cell line, BMS2.4, produces soluble factors that inhibit proliferation of several types of hematopoietic cell lines. An understanding of these molecules may be informative about negative regulatory circuits that can potentially limit blood cell formation. We used expression cloning to identify interleukin-6 (IL-6) as one factor that suppressed growth of a pre-B-cell variant line, 1A9-M. Moreover, IL-6 induced macrophage-differentiation and apoptosis of 1A9-M cells. During this process, IL-6 downregulated expression of BCL2 in 1A9-M cells and stimulated BCL-XL expression, but had no effect on p53, Bax, or Bak gene expression. Mechanisms for transduction of IL-6-induced signals were then evaluated in IL-6-stimulated 1A9-M cells. Whereas the signal transducer and activator of transcription 3 (Stat3) was phosphorylated and activated, there was no effect on either Stat1 or Stat5. The importance of BCL2 and Stat3 on IL-6-induced macrophage-differentiation and apoptosis was studied with 1A9-M cells expressing human BCL2 or a dominant-negative form of Stat3, respectively. IL-6-induced apoptosis, but not macrophage-differentiation, was blocked by continuously expressed BCL2. A dominant-negative form of Stat3 inhibited both macrophage-differentiation and apoptosis induced by IL-6. However, diminished Stat3 activity did not prevent IL-6-induced downregulation of the BCL2 gene. Therefore, activation of Stat3 is essential for IL-6-induced macrophage-differentiation and programmed cell death in this model. Whereas overexpression of BCL2 abrogates the apoptotic response, Stat3-independent signals appear to downregulate expression of the BCL2 gene.


Do Children With Fragile X Syndrome Show Declines or Plateaus in Adaptive Behavior?
This study explores if children with fragile X syndrome (FXS) show advances, declines, or plateaus in adaptive behavior over time and the relationship of nonverbal cognitive abilities and autistic behavior on these trajectories. Parents of 55 children with FXS completed the Vineland Adaptive Behavior Scales ( Sparrow, Balla, & Cicchetti, 1984 ; Sparrow, Cicchetti, & Balla, 2005 ) between 3 and 6 times from 2 to 10 years of age. Using raw scores, results indicate that about half of the sample showed advances in adaptive behavior, whereas the other half showed declines, indicating a regression in skills. Children who were more cognitively advanced and had less autistic behaviors had higher trajectories. Understanding the developmental course of adaptive behavior in FXS has implications for educational planning and intervention, especially for those children showing declines.


Quantification of the Effect of Shuttling on Computed Tomography Perfusion Parameters by Investigation of Aortic Inputs on Different Table Positions From Shuttle-Mode Scans of Lung and Liver Tumors.
The aim of this study was to quantify the effect of shuttling on computed tomography perfusion (CTp) parameters derived from shuttle-mode body CT images using aortic inputs from different table positions. Axial shuttle-mode CT scans were acquired from 6 patients (10 phases, 2 nonoverlapping table positions 1.4 seconds apart) after contrast agent administration. Artifacts resulting from the shuttling motion were corrected with nonrigid registration before computing CTp maps from 4 aortic levels chosen from the most superior and inferior slices of each table position scan. The effect of shuttling on CTp parameters was estimated by mean differences in mappings obtained from aortic inputs in different table positions. Shuttling effect was also quantified using 95% limits of agreement of CTp parameter differences within-table and between-table aortic positions from the interaortic mean CTp values. Blood flow, permeability surface, and hepatic arterial fraction differences were insignificant (P > 0.05) for both within-table and between-table comparisons. The 95% limits of agreement for within-table blood volume (BV) value deviations obtained from lung tumor regions were less than 4.7% (P = 0.18) compared with less than 12.2% (P = 0.003) for between-table BV value deviations. The 95% limits of agreement of within-table deviations for liver tumor regions were less than 1.9% (P = 0.55) for BV and less than 3.2% (P = 0.23) for mean transit time, whereas between-table BV and mean transit time deviations were less than 11.7% (P < 0.01) and less than 14.6% (P < 0.01), respectively. Values for normal liver tissue regions were concordant. Computed tomography perfusion parameters acquired from aortic levels within-table positions generally yielded higher agreement than mappings obtained from aortic levels between-table positions indicating differences due to shuttling effect.


Promoting heart health for Southeast Asians: a database for planning interventions.
This paper is a report of baseline data that the authors collected on the prevalence of hypertension in a sample of 397 Southeast Asian immigrants residing in central Ohio and the implications of those data for the design of ethnically approved and scientifically valid interventions. The context for collection of these data over a 9-month period in 1989 is described. Baseline demographic characteristics including distributions by ethnicity, sex, age, and length of stay in the United States, as well as family heart health history, hypertension level, and heart health awareness of these subjects are presented. For example, 85 percent of the immigrants did not know what could be done to prevent heart disease. Implications for the design of ethnically approved and scientifically valid prevention strategies are discussed. Based on these data, the authors realized that multiple health education strategies tailored to what they were learning about Southeast Asians would be needed. Through Southeast Asian leaders, they were led to using wall calendars, with words specific to each Southeast Asian language, that had a monthly heart health slogan as one avenue to reach Southeast Asians. Another strategy was to develop videotapes featuring cultural content but including heart health "commercials." The authors concluded that, although scientific validity of risk reduction interventions are important, customizing these strategies to ethnically specific modes of interaction are equally important.


Melanoma-the therapeutic considerations in the clinical practice.
The incidence of melanoma is increasing and prolonged exposure to ultraviolet (UV) radiation remains the main risk factor. Public health measures have been vital in tackling the increased incidence and prevalence of melanoma. The management of melanoma has been revolutionised with the approval of new immunotherapy treatments (anti PD-1, CTLA-4 and LAG-3 antibodies) and targeted therapies (BRAF and MEK inhibitors). With some of these therapies becoming the standard of care in the management of advanced disease, it is likely we will see their use increase in the adjuvant and neoadjuvant setting. Recently, literature has demonstrated the benefits patients could derive from the combination of immune checkpoint inhibitors (ICIs) due to the promising results on its efficacy when compared to monotherapy. However, greater clarity on its use is needed in more unique presentations such as BRAF-wild type melanoma, where the lack of driver mutations makes disease management more challenging. Surgical resection remains an integral part of the management of earlier stages of the disease with a consequent decrease in reliance on other forms of therapy such as chemotherapy and radiotherapy. Finally, we evaluated the novel emerging experimental approaches to treatment such as adoptive T cell therapy, novel oncolytic treatments and cancer vaccines. We discussed how their use could improve patients' prognosis, enhance treatment efficacy, and potentially achieve cure.


Failure to demonstrate human T cell lymphotropic virus type I in multiple sclerosis patients.
The polymerase chain reaction (PCR) technique was employed in searching for human T cell lymphotropic virus type I (HTLV-I) gag, env and pol sequences in samples of DNA prepared from two HTLV-I seropositive patients with tropical spastic paraparesis (TSP), the Swedish multiple sclerosis (MS) patients who recently have been reported to be PCR-positive for HTLV-I gag and env sequences, and eight healthy individuals. Precautions were taken in order to reduce the risk of cross-contamination in the PCR. In the two TSP patients strong signals were obtained with gag, env and pol amplification primers and detection probes. In MS patients and healthy individuals, no signals were obtained with gag and env. In occasional experiments, weak signals were seen for the pol segment for a single MS patient and/or healthy individuals, but these signals were not reproducible in subsequent experiments. Thus, the present data do not confirm the presence of HTLV-I sequences in MS patients.


[Compensation of disorders of coronary circulation by means of collaterals (according to coronarographic data].
On the basis of an analysis of about 1000 coronary angiogrammes it is established that collaterals develop in stenosis of the coronary arteries in 52.3% of the patients surviving myocardial infarction, and in 20% of those free of myocardial infarction. Coronary angiogrammes of 100 patients with coronary collaterals were examined. Twenty different ways of collateral circulation were revealed. Certain regularities were noted in the development of collaterals depending on the lesions of different coronaries or combined lesions of several arteries. Intersystemic collaterals are most typical for the occlusions of the anterior interventricular branch. In cases of occlusions of the right coronary artery either intersystemic, or intrasystemic collaterals develop, depending on the localization of the occlusion. A study of the collaterals in cases of multiple coronary lesions has demonstrated that under such conditions a complicated system of anastomoses develops, and the flow in them is multidirectional.


Comparison of impact forces, accelerations and ankle range of motion in surfing-related landing tasks.
This study aimed to describe the impact forces, accelerations and ankle range of motion in five different landing tasks that are used in training and testing for competitive surfing athletes, to assist coaches in the prescription of landing task progression and monitoring training load. Eleven competitive surfing athletes aged 24 ± 7 years participated, and inertial motion sensors were fixed to the anterior aspect of the feet, mid-tibial shafts, sacrum and eighth thoracic vertebrae on these athletes. Three tasks were performed landing on force plates and two tasks in a modified gymnastics set-up used for land-based aerial training. Peak landing force, resultant peak acceleration and front and rear side ankle dorsiflexion ranges of motion during landing were determined. The peak acceleration was approximately 50% higher when performing aerial training using a mini-trampoline and landing on a soft-density foam board, compared to a similar landing off a 50 cm box. Furthermore, the ankle ranges of motion during the gymnastic type landings were significantly lower than the other landing types (P ≤ 0.05 and P ≤ 0.001), for front and rear sides, respectively. Conclusively, increased task complexity and specificity of the sport increased the tibial peak acceleration, indicating greater training load.


Trans- and cis-stilbene isolated in cryogenic argon and xenon matrices.
Monomers of trans- (TS) and cis-stilbene (CS) were isolated in cryogenic argon and xenon matrices, and their infrared (IR) spectra were fully assigned and interpreted. The interpretation of the vibrational spectra received support from theoretical calculations undertaken at the DFT(B3LYP)/6-311++G(d,p) level of theory. In situ broadband UV irradiation of the matrix-isolated CS led to its isomerization to TS, which appeared in the photolysed matrices in both non-planar and planar configurations. The non-planar species was found to convert into the more stable planar form upon subsequent annealing of the matrices at higher temperature. TS was found to be photostable under the used experimental conditions. The structure of the non-planar TS form was assigned based on the comparison of its observed IR spectrum with those theoretically predicted for different conformations of TS. Chemometrics was used to make this assignment. Additional reasoning on the structure of the studied stilbenes is presented taking as basis results of the Natural Bond Orbital analysis.


Lymphatic vasculature in ovarian cancer.
Ovarian cancer (OVCA) is the second most common gynecological cancer and one of the leading causes of cancer related mortality among women. Recent studies suggest that among ovarian cancer patients at least 70% of the cases experience the involvement of lymph nodes and metastases through lymphatic vascular network. However, the impact of lymphatic system in the growth, spread and the evolution of ovarian cancer, its contribution towards the landscape of ovarian tissue resident immune cells and their metabolic responses is still a major knowledge gap. In this review first we present the epidemiological aspect of the OVCA, the lymphatic architecture of the ovary, we discuss the role of lymphatic circulation in regulation of ovarian tumor microenvironment, metabolic basis of the upregulation of lymphangiogenesis which is often observed during progression of ovarian metastasis and ascites development. Further we describe the implication of several mediators which influence both lymphatic vasculature as well as ovarian tumor microenvironment and conclude with several therapeutic strategies for targeting lymphatic vasculature in ovarian cancer progression in present day.


Machine vision detection of bonemeal in animal feed samples.
There is growing public concern about contaminants in food and feed products, and reflection-based machine vision systems can be used to develop automated quality control systems. An important risk factor in animal feed products is the presence of prohibited ruminant-derived bonemeal that may contain the BSE (Bovine Spongiform Encephalopathy) prion. Animal feed products are highly complex in composition and texture (i.e., vegetable products, mineral supplements, fish and chicken meal), and current contaminant detection systems rely heavily on labor-intensive microscopy. In this study, we developed a training data set comprising 3.65 million hyperspectral profiles of which 1.15 million were from bonemeal samples, 2.31 million from twelve other feed materials, and 0.19 million denoting light green background (bottom of Petri dishes holding feed materials). Hyperspectral profiles in 150 spectral bands between 419 and 892 nm were analyzed. The classification approach was based on a sequence of linear discriminant analyses (LDA) to gradually improve the classification accuracy of hyperspectral profiles (reduce level of false positives), which had been classified as bonemeal in previous LDAs. That is, all hyperspectral profiles classified as bonemeal in an initial LDA (31% of these were false positives) were used as input data in a second LDA with new discriminant functions. Hyperspectral profiles classified as bonemeal in LDA2 (false positives were equivalent to 16%) were used as input data in a third LDA. This approach was repeated twelve times, in which at each step hyperspectral profiles were eliminated if they were classified as feed material (not bonemeal). Four independent feed materials were experimentally contaminated with 0-25% (by weight) bonemeal and used for validation. The analysis presented here provides support for development of an automated machine vision to detect bonemeal contamination around the 1% (by weight) level and therefore constitutes an important initial screening tool in comprehensive, rapid, and practically feasible quality control of feed materials.


Distinguishing between longevity and buffered-deleterious genotypes for exceptional human longevity: the case of the MTP gene.
The single nucleotide polymorphism, rs2866164, in the MTP gene, has been associated with human longevity but has not been validated by subsequent longevity studies. Using our population of Ashkenazi Jews, we find that the MTP CC genotype is significantly overrepresented in centenarians and their offspring, as compared with controls (p < .05). However, when we examined MTP CC genotype frequency pattern with aging, we observed a monotonic decline between ages 55-85 years followed by a dramatic enrichment after age 90 years, forming a U-shape pattern (p < .05). Furthermore, the MTP CC genotype was buffered by three validated longevity genotypes (p < .05). This buffering effect was found to confer an enrichment of the MTP CC genotype in centenarians, whereas their absence in CC controls resulted in poorer survivorship (p < .05). Thus, we conclude that MTP CC is a buffered-deleterious genotype and that assessing genotype frequency across aging is essential for discerning longevity from buffered-deleterious genotypes.


[Calcium, cholecalciferol, and amizon: essential components in the complex therapy of chronic hepatitis].
95 patients with chronic hepatitis who presented not only with symptoms related to chronic hepatitis, but also had the signs peculiar to osteoarthropathy which sometimes clinically dominated among other symptoms were examined. Clear correlation was observed between the frequency, severity of the syndrome associated with osteoarthropathy and the decrease in mineral density of the osseous tissue. This tendency was even more seen in patients with chronic hepatitis B and C. The use of calcium medicines, preparations containing D3-vitamin and amisone as a pathogenic therapy has proved to be effective.


Distribution of saquinavir, methadone, and buprenorphine in maternal brain, placenta, and fetus during two different gestational stages of pregnancy in mice.
Efflux transporters such as P-glycoprotein (P-gp) play a critical role in the maternal-to-fetal and blood-to-brain transfer of many drugs. Using a mouse model, the effects of gestational age on P-gp and MRP expression in the placenta and brain were evaluated. P-gp protein levels in the placenta and brain were greater at mid-gestation (gd 13) than late-gestation (gd 18). Likewise, brain MRP1 levels were greater at mid-gestation, whereas, placental levels were greater at late-gestation. To evaluate these effects on drug disposition, concentrations of [(3)H]saquinavir, [(3)H]methadone, [(3)H]buprenorphine, and the paracellular marker, [(14)C]mannitol were measured in plasma, brain, placenta, and fetal samples after i.v. administrations to nonpregnant and pregnant mice. Following i.v. administration, [(3)H]saquinavir placenta-to-plasma and fetal-to-plasma ratios were significantly greater in late-gestation mice versus mid-gestation. Furthermore, late-gestation mice experienced significant increases in the [(3)H]saquinavir and [(3)H]methadone brain-to-plasma ratios 60 min after dosing relative to mid-gestation (p < 0.05). No significant differences were observed in these tissue-to-plasma ratios for buprenorphine or mannitol. Repeated dosing (three doses, once daily) decreased the differential uptake of [(3)H]saquinavir in brain but potentiated it in the fetus. These results suggest that differential expression of P-gp and possibly MRP1 contributes to the gestational-induced changes in brain and fetal uptake of saquinavir.


Multi-pad electrode for effective grasping: design.
We designed a new surface multi-pad electrode for the electrical stimulation of the forearm that is effective in controlling functional grasp in hemiplegic patients. The electrode shape and size were designed on the basis of the surface stimulation map of the forearm, determined from measurements in seven hemiplegic patients who had limited or absent voluntary movements of the fingers, thumb and wrist. The stimulation map for each patient was assessed with a conventional set of single pad Pals Platinum electrodes. Since the sites for the stimulation varied greatly between patients, the end result was a rather large multi-pad electrode. Modulating multi-pad electrode size, shape, position and individual pad stimulation parameters allows us to accommodate the diversity of the neural tissues in patients that need to be activated for functional grasp. This also allows asynchronous activation of different portions of the muscle and dynamic adaptation of the stimulation sites to appropriate underlying tissues during functional use. The validity of the determined stimulation map was tested in the same group of hemiplegic patients. The selected set of active pads resulted in fully functional and reproducible palmar and lateral grasps similar to healthy-like grasps.


Mu and kappa opioids modulate mouse embryonic stem cell-derived neural progenitor differentiation via MAP kinases.
As embryonic stem cell-derived neural progenitors (NPs) have the potential to be used in cell replacement therapy, an understanding of the signaling mechanisms that regulate their terminal differentiation is imperative. In previous studies, we discovered the presence of functional mu opioid receptors (MOR) and kappa opioid receptors (KOR) in mouse embryonic stem cells and NPs. Here, MOR and KOR immunoreactivity was detected in NP-derived oligodendrocytes during three stages of their maturation in vitro. Moreover, we examined the modulation of retinoic acid-induced NP differentiation to astrocytes and neurons by mu, [D-ala(2), mephe(4), gly-ol(5)] enkephalin, or kappa, U69, 593, opioids. Both opioid agonists inhibited NP-derived neurogenesis and astrogenesis via their corresponding receptors as determined by immunocytochemistry. By administering selective inhibitors, we found that opioid inhibition of NP-derived astrogenesis was driven via extracellular-signal regulated kinase (ERK), while the p38 mitogen-activated protein kinase pathway was implicated in opioid attenuation of neurogenesis. In addition, mu and kappa opioids stimulated oligodendrogenesis from NP-derived NG2(+) oligodendrocyte progenitors via both ERK and p38 signaling pathways. Accordingly, both opioids induced ERK phosphorylation in NG2(+) cells. These results indicate that small molecules, such as MOR and KOR agonists may play a modulatory role in NP terminal differentiation.


Enhancing concentration, mood and memory in healthy individuals: an empirical study of attitudes among general practitioners and the general population.
To study attitudes towards enhancing concentration, mood and memory in healthy individuals among the general public and general practitioners (GPs). A questionnaire consisting of vignettes including three cases dealing with enhancement of concentration, mood and memory was sent during 2006 to 1000 randomly selected people from Stockholm and 300 GPs. We asked about the use of pharmaceuticals for healthy individuals for the benefit of others and the benefit to oneself; we also asked whether or not society should pay the cost. Finally, we asked about enhancement of healthy people's concentration, mood and memory through the use of natural remedies. Fifty-two per cent of the general public and 39% of the GPs responded. While the use of natural remedies was perceived as fairly acceptable, majorities in both groups were negative with regard to the use of pharmaceuticals to enhance concentration, mood and memory in a healthy individual. The general public tended to be less negative than the GPs. There was a significant difference between the reasons for providing enhancement; altruistic reasons seem to be more acceptable than egoistic ones. For both groups, enhancing mood was more controversial than enhancing memory. Despite the large dropout rate, the study indicates that enhancement by means of natural remedies of different human capacities is acceptable to the general public, while only small minorities of both groups are inclined to allow the use of pharmaceuticals. When compared to the egoistic reason, the altruistic one for enhancing concentration, mood and memory with pharmaceuticals seems to influence the general public's inclination to support prescriptions; this was also the case among the GPs, but only as regards mood enhancement.


Marrow Stimulation Has Relatively Inferior Patient-Reported Outcomes in Cartilage Restoration Surgery of the Knee: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Multiple cartilage repair techniques are available for chondral defects in the knee. Optimal treatment is controversial. To evaluate change from baseline in the 5 Knee injury and Osteoarthritis Outcome Score (KOOS) subscales among different cartilage repair techniques of the knee. Systematic review and meta-analysis; Level of evidence, 1A. Medline and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for randomized controlled trials with minimum 1 year follow-up reporting change from baseline KOOS (delta KOOS) subscale values. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. A meta-analysis was performed on the following surgery types: microfracture (Mfx); augmented microfracture techniques (Mfx+Augment); and culture-based therapies, including autologous chondrocyte implantation (ACI) and matrix-assisted autologous chondrocyte implantation (MACI). A random-effects metaregression model was used. A total of 14 randomized trials with a total of 775 patients were included. The KOOS Sport and Recreation (Sport) and KOOS Quality of Life (QOL) were the 2 most responsive subscales after operative intervention. Outcomes from Mfx and Mfx+Augment were not different in any of the 5 KOOS subscales (minimum P > .3). The mean delta KOOS Sport after ACI/MACI was 9.9 points greater than after Mfx (P = .021) and 11.7 points greater than after Mfx+Augment (P = .027). Longer follow-up time correlated with greater delta KOOS Sport (P = .028). Larger body mass index led to greater delta KOOS QOL (P = .045). Larger cartilage defect size correlated with greater delta KOOS Pain and KOOS Activities of Daily Living scores (P = .023 and P = .002, respectively). The KOOS Sport and QOL were the most responsive subscales after cartilage restoration surgery of the knee. Culture-based therapies (ACI/MACI) led to clinically relevant improvements in the KOOS Sport score compared with marrow stimulation and may be a more appropriate treatment in younger and more active individuals. There were no benefits to Mfx+Augment over Mfx alone in any of the KOOS subscales.


Flt3 ligand therapy for recipients of allogeneic bone marrow transplants expands host CD8 alpha(+) dendritic cells and reduces experimental acute graft-versus-host disease.
Recent evidence suggests that dendritic cells (DCs) can regulate and amplify immune responses. Flt3 ligand (FL)-derived DC function was tested as a stimulator of allogeneic lymphocytes in vitro and in vivo. Treatment of mice with FL dramatically expanded DC number, but DCs isolated from FL-treated mice (FL DCs) were poor stimulators of allogeneic T-cell responses in vitro. Further activation of FL DCs did not restore their stimulatory ability, and FL DCs did not suppress the stimulation of the allogeneic T cells by normal DCs. FL treatment significantly increased the CD8 alpha(+) DC subset, which appeared to be the reason for their poor stimulatory capacity. These observations were confirmed in vivo using a mouse model of acute graft-versus-host disease (GVHD) wherein host DCs play a critical role. FL treatment of recipients before allogeneic bone marrow transplantation dramatically suppressed donor T-cell responses to host antigens, thereby reducing GVHD mortality (P <.01). These data represent a novel strategy that alters host DCs and reduces acute GVHD.


Post-weaning management of modern dairy cattle genetics for beef production: a review.
The contribution of dairy steers to the U.S. fed beef supply has increased from 6.9% to 16.3% over the last two decades; in part, due to declining beef cow numbers and the increased use of sexed dairy semen to produce genetically superior replacement heifers from the best dairy cows. Raising dairy cattle for beef production offers unique opportunities and challenges when compared with feeding cattle from beef breeds. Dairy steers offer predictable and uniform finishing cattle performance (ADG, DMI, G:F) as a group and more desirable quality grades on average compared with their beef steer counterparts. However, dairy steers have lesser dressing percentages and yield 2%-12% less red meat compared with beef steers due to a greater ratio of bone to muscle, internal fat, organ size, and gastrointestinal tract weight. In addition, carcasses from dairy steers can present problems in the beef packing industry, with Holstein carcasses being longer and Jersey carcasses being lighter weight than carcasses from beef breeds. Beef × dairy crossbreeding strategies are being implemented on some dairy farms to increase the income generated from dairy bull calves, while beef × dairy crossbreeding strategies can also improve the G:F and red meat yield of beef produced from the U.S. dairy herd. This alternative model of beef production from the dairy herd is not without its challenges and has resulted in variable results thus far. Successful adoption of beef × dairy crossbreeding in the cattle industry will depend on the proper selection of beef sires that excel in calving ease, growth, muscling, and marbling traits to complement the dairy genetics involved in beef production.


Estimating intensity of physical activity: a comparison of wearable accelerometer and gyro sensors and 3 sensor locations.
Automatic estimation of physical activity using wearable sensors can be used for promotion of a healthier lifestyle. In this study, accelerometers and gyroscopes attached to ankle, wrist and hip were used to estimate intensity of physical activity. The estimates are compared to metabolic equivalent (MET) obtained from a portable cardiopulmonary exercise testing system. Data from common everyday tasks and exercise were collected with 11 subjects. The tasks include, e.g., ironing, vacuuming, walking, running and cycling on exercise bicycle (ergometer). The strongest linear correlation with metabolic equivalent was obtained with the tri-axial accelerometer attached to the ankle (r=0.86).


Anti-inflammatory and membrane-stabilizing stigmastane steroids from Alchornea floribunda leaves.
Alchornea floribunda (Euphorbiaceae) leaves are widely used in African ethnomedicine for the management of acute and chronic inflammatory disorders. In the present study, bioactivity-guided fractionation led to the isolation of two known (1 and 3) and one new (2) stigmastane steroids from the hexane extract of Alchornea floribunda leaves. The anti-inflammatory activities of these compounds were evaluated using IN VITRO and IN VIVO animal models. The compounds 1, 2, and 3 at 50 and 100 microg/ear significantly (p < 0.05) inhibited xylene-induced ear edema in mice in a dose-dependent manner. The topical anti-inflammatory effect of 1 and 2 are significantly (p < 0.05) higher than that of indomethacin and prednisolone. At 20 mg/kg (i. p.), all the compounds significantly (p < 0.05) inhibited acute inflammation induced by subplantar injection of egg albumen in rats. Compound 1 exhibited an anti-inflammatory effect (50.9 % edema inhibition) comparable (p < 0.05) to that of prednisolone (48.0 % edema inhibition) at 3 h. Compounds 1, 2, and 3 (50 microg/mL) significantly (p < 0.05) inhibited heat-induced haemolysis of human erythrocytes in vitro, but had no effect on hypotonicity-induced hemolysis. The compounds were elucidated as (24R)-5alpha-stigmast-3,6-dione ( 1), 5alpha-stigmast - 23-ene-3,6-dione ( 2), and 3beta-hydroxy-5alpha-stigmast-24-ene ( 3) by spectral analysis. The results of this study show that these compounds may, in part, account for the anti-inflammatory effect of Alchornea floribunda leaves. This is the first report on the isolation and structure elucidation of these anti-inflammatory steroids from Alchornea floribunda leaves.


The Kidney Protective Effects of the Sodium-Glucose Cotransporter-2 Inhibitor, Dapagliflozin, Are Present in Patients With CKD Treated With Mineralocorticoid Receptor Antagonists.
Mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce the risk of kidney failure in chronic kidney disease (CKD). We performed an analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial by baseline conventional MRA (spironolactone and eplerenone) prescription. Participants with CKD (estimated glomerular filtration rate [eGFR] 25-75 ml/min per 1.73 m2; urinary albumin-to-creatinine ratio 200-500 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or kidney or cardiovascular (CV) death. A prespecified kidney-specific secondary outcome was as the primary outcome but without CV death. Hyperkalemia (serum potassium ≥6.0 mmol/l) was an exploratory end point. Time-to-event analyses (proportional hazards [Cox] regression) assessed dapagliflozin versus placebo in patient subgroups defined by baseline conventional MRA use. A total of 229 of 4304 DAPA-CKD participants (5.3%) were receiving conventional MRAs at baseline (dapagliflozin n = 109, placebo n = 120). The effect of dapagliflozin on the primary outcome was consistent in participants prescribed (hazard ratio [HR] 0.76, 95% CI 0.40-1.47) and not prescribed (HR 0.60, 95% CI 0.50-0.72, P-interaction = 0.59) MRAs. This consistency was maintained for the kidney-specific outcome. The effect of dapagliflozin on hyperkalemia (HR 0.87, 95% CI 0.70-1.09) was consistent among those prescribed (HR 0.94, 95% CI 0.41-2.20) and not prescribed (HR 0.87, 95% CI 0.69-1.10, P-interaction = 0.96) MRAs. Adverse events (AEs) leading to discontinuation and serious AEs were similar between treatment groups, regardless of baseline MRA prescription. Dapagliflozin was similarly safe and efficacious in reducing major adverse kidney outcomes in participants with CKD who were or were not prescribed MRAs at baseline.


Mental health and working conditions among French medical students: A nationwide study.
Medical students' mental health is a public health problem that has worsened with COVID 19's pandemic. There is a lack of French data. The principal aim was to assess French medical students' mental health. An online cross-sectional survey was performed between May 27 and June 27, 2021. An anonymous questionnaire was sent via academic email addresses by medical faculties and secondly on social media. We assessed 7-day anxiety and depressive symptoms were evaluated with the Hospitalization Anxiety and Depression scale, 12-month major depressive episode (MDE) with the Composite International Diagnostic Interview- Short Form, burnout with the Maslach Burnout Inventory, 12-month suicidal ideation, humiliation, sexual harassment, and sexual aggression during their curriculum. Multivariable logistic regression was performed to identify main MDE associated factors. 11,754 participants (response rate: 15.3%) were included. Prevalence of 7-day anxiety symptoms, 7-day depressive symptoms, 12-month MDE, and 12-month suicidal thoughts were 52%, 18%, 25%, and 19% respectively. Burnout syndrome concerned 67% of clinical students and residents and 39% of preclinical students. Prevalence of humiliation, sexual harassment, and sexual abuse during their curriculum were 23%, 25%, and 4%, respectively. Having important (OR = 1.44, IC 95 [1.31-1.58], p < 0.001) or very important financial issues (OR = 2.47, IC 95 [2.15-2.85], p < 0.001), experienced humiliation (OR = 1.63, IC 95 [1.46-1.81], p < 0.001), sexual harassment (OR = 1.43, IC 95 [1.28-1.59], p < 0.001) and sexual abuse (OR = 1.52, IC 95 [1.24-1.85], p < 0.001) were associated with an increased risk of MDE. This is the largest study on French medical students' mental health. These results point to very particular conditions in French students environment that need to be addressed to improve their mental health.


[Autonomic device for continuous monitoring and correction of muscle activity: Miotonik-02].
The paper outlines a portable device with self-contained power supply, which records with electrodes applied to the skin and subsequently processes electric myosignals from human muscles. The device is designed for the therapy and rehabilitation of patients with some motor diseases via biological feedback. The paper also considers the block diagram and provides the technical data of the device.


No meaningful association of neighborhood food store availability with dietary intake, body mass index, or waist circumference in young Japanese women.
The affordability of food is considered as an important factor influencing people's diet and hence health status. The objective of this cross-sectional study was to test the hypothesis that neighborhood food store availability is associated with some aspects of dietary intake and thus possibly with body mass index (BMI) and waist circumference in young Japanese women. Subjects were 989 female Japanese dietetic students 18 to 22 years of age. Neighborhood food store availability was defined as the number of food stores within a 0.5-mile (0.8-km) radius of residence (meat stores, fish stores, fruit and vegetable stores, confectionery stores/bakeries, rice stores, convenience stores, and supermarkets/grocery stores). Dietary intake was estimated using a validated, comprehensive self-administered diet history questionnaire. No association was seen between any measure of neighborhood food store availability and dietary intake, except for a positive association between confectionery and bread availability (based on confectionery stores/bakeries, convenience stores, and supermarkets/grocery stores) and intake of these items (P for trend = .02). Further, no association was seen for BMI or waist circumference, except for an inverse relationship between availability of convenience stores and BMI and a positive relationship between store availability for meat (meat stores and supermarkets/grocery stores) and fish (fish stores and supermarkets/grocery stores) and waist circumference. In conclusion, this study of young Japanese women found no meaningful association between neighborhood food store availability and dietary intake, BMI, or waist circumference, with the exception of a positive relationship between availability and intake for confectionery and bread.


Failure of chloramphenicol and cefotaxime therapy in Klebsiella meningitis: possible role of antibiotic antagonism.
We have described a patient with Klebsiella pneumoniae meningitis who was treated with cefotaxime and chloramphenicol concomitantly, and whose slow initial resolution and subsequent relapse plus in vitro evidence of antagonism of cefotaxime appear to indicate that chloramphenicol interfered with the activity of the cephalosporin. Thus, concomitant use of chloramphenicol should probably be avoided or used advisedly in adults with gram-negative bacillary meningitis susceptible to a third generation cephalosporin.


Effect of cyclosporin A on the survival and ultrastructure of Echinococcus granulosus protoscoleces in vitro.
Surgical treatment of human hydatidsosis involves the use of various scolicidal agents to kill infective Echinococcus granulosus protoscoleces that may disseminate into the peritoneal cavity during surgery and potentially re-infect the patient. Currently, no scolicidal agent is completely effective in killing intracystic protoscoleces in humans. Cyclosporin A (CsA) has previously been found to be lethal for E. granulosus protoscoleces in vitro. In this study, we further assessed the effectiveness of CsA as a scolicidal agent by testing the toxic effect of CsA at higher doses over various time-periods. Experiments were performed on activated and unactivated protoscoleces cultured in nutrient medium or sheep hydatid cyst fluid. All activated protoscoleces were killed following culture in 100 microg/ml of CsA for 3 days and 50 or 20 microg/ml for 5 days. The lethal effect of CsA on unactivated protoscoleces varied but reached 100% over 15 days in culture with 100 or 50 microg/ml of CsA. Pulse treatment of protoscoleces with 50, 20 or 10 microg/ml of CsA for 5 min or 72 h killed all parasites by day 10 and day 5 respectively. Untreated protoscoleces remained greater than 95 % viable for the duration of experiments. Changes in protoscolex ultrastructure induced by treatment with 10 microg/ml of CsA over 10 days in in vitro culture was assessed by TEM. Protoscolex alterations observed in treated parasites included an increase in cellular vacuolization, swelling of mitochondria, rounding of cells, damage to the tegument, decrease in glycogen, a breakdown of the extracellular matrix and an increase in lipid globules. The untreated protoscoleces, by comparison, had few changes during the 10-day culture period with the exception of large amounts of extracellular glycogen observed in the protoscoleces at culture days 7 and 10. From these results, CsA is clearly an effective scolicidal agent in vitro that may have potential application as a new therapeutic agent in the treatment of human hydatid disease.


Do infants with major congenital anomalies have an excess of macrosomia?
Infants that develop congenital anomalies may also have an excess prevalence of macrosomia (birth weight > or =4,000 g). This may indicate that abnormalities of glycemic control play a role in the etiology of birth defects. This study was undertaken to determine whether all infants with congenital anomalies have an excess of macrosomia and whether it is confined to specific types of anomalies. A case-control study was conducted, comparing the birth weights of 8,226 infants with congenital anomalies ascertained by the Texas Birth Defects Monitoring Division with those of 965,965 infants without birth defects. Odds ratios were calculated to determine the association between birth weight and congenital anomalies, for 45 specific defects, and for all these defects combined. For all 45 defects combined, a significant association occurred only in the highest birth weight category. Infants with congenital anomalies were more likely than infants without birth defects to have a birth weight > or =4,500 g (OR = 1.65; 95% CI = 1.39-1.96). Infants born with ventricular septal defects, atrial septal defects, ventricular hypertrophy, or anomalies of the great vessels were 1.5-2.5 times more likely to weigh > or =4,000 g than were infants without birth defects. Based on small numbers, a stronger excess of macrosomia was observed for infants with encephalocele, holoprosencephaly, anomalies of the corpus callosum, preaxial polydactyly, and omphalocele. Our data suggest that infants with specific congenital anomalies are more likely to be macrosomic than are infants without an anomaly. If these findings are confirmed, associations between macrosomia and specific types of birth defects may help to identify birth defects that are caused by alterations in glycemic control.


Generation n + 1: Projected numbers of babies born to women with PKU compared to babies with PKU in the United States in 2009.
Newborn PKU screening has been available since the mid-1960s, and the first group of screened babies is now a complete reproductive cohort (age 15-44). Untreated maternal PKU (MPKU) often results in significant developmental and physical disabilities in exposed fetuses, and could potentially offset some or all of the benefits produced by newborn PKU screening and dietary treatment. Based on the age distribution of the United States population in 2009, and using different estimates of PKU frequency (1/10,000; 1/15,000; 1/20,000), the projected number of babies born to women with PKU was compared to the projected number of babies born with PKU. In 2009, there were about 62,000,000 women age 15-44, with a fertility rate of 66.7 births/1,000 women. Of these women, depending on the incidence of PKU, 3,097-6,195 were estimated to have PKU, and they would have delivered 207-413 babies. In that same year, the number of births was 4,118,055, which would have resulted in 206-412 babies with PKU. Thus, in the United States, at all estimates of PKU frequency, the number of babies exposed to MPKU is equal to the number of babies born with PKU. This ratio varies with the fertility rate but is not dependent on the incidence of PKU. The benefits of newborn PKU screening and treatment could be significantly curtailed if adequate resources, education, and funding are not available to follow and monitor women with MPKU and their babies.


Fatty acid changes in liver choline and ethanolamine glycerophospholipids in aspirin-treated rats fed linoleate, gamma-linolenate and fish oil.
The effects of dietary linoleic acid, gamma-linolenic acid and marine fatty acids on the development of aspirin-induced gastric hemorrhage and the distribution of liver glycerophospholipid fatty acids in fat-deficient growing rats were studied. Aspirin (100 mg/day)-treated and nontreated rats were fed for 7 days, a mixed diet of 2.5% safflower oil and 7.5% hydrogenated coconut oil (SFO/HCO) or 7.5% fish oil (SFO/FO), or 2.5% gamma-linolenate concentrate and 7.5% fish oil (GLA/FO). Gastric hemorrhage was induced in animals by aspirin treatment to various extents. It was not affected by FO feeding, but was significantly alleviated by GLA feeding. Aspirin treatment reduced the proportions of 20:4n-6 in liver phosphatidylcholine. FO feeding (in SFO/FO and GLA/FO rats) further reduced the 20:4n-6 level and replaced it by n-3 fatty acids. GLA feeding, on the other hand, elevated the proportion of 20:4n-6. As a result, the reduction of 20:4n-6 by fish oil feeding, was less significant in GLA/FO rats than in SFO/FO rats. The degree of gastric hemorrhage appeared to relate negatively to the levels of 20:4n-6 in liver phosphatidylcholine, and to the sum of 20:4n-6 and 20:5n-3 when FO was included in the diet. It is suggested that long-chain polyunsaturated fatty acids (20:4n-6 and 20:5n-3) per se in addition to being precursors of prostaglandins, may also affect the development of gastric hemorrhage, possibly by modulating the permeability of cell membranes in the gastric mucosa.


Erythromycin increases bactericidal activity of surface liquid in human airway epithelial cells.
Macrolide antibiotics have clinical benefits in patients with diffuse panbronchiolitis and in patients with cystic fibrosis. Although many mechanisms have been proposed, the precise mechanisms are still uncertain. We examined the effects of erythromycin on bactericidal activity of airway surface liquid secreted by cultured human tracheal epithelial cells. Airway surface liquid was collected by washing the surface of human tracheal epithelial cells with a sodium solution (40 meq/l). Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were incubated with airway surface liquid, and the number of surviving bacteria was examined. The number of bacteria in airway surface liquid from the cells cultured in medium alone was significantly lower than that in the sodium solution. Furthermore, the number of bacteria in airway surface liquid from the cells treated with erythromycin was significantly lower than that in airway surface liquid from the cells treated with solvent alone. The production of mRNA and protein of human beta-defensin-1 and human beta-defensin-2 was significantly increased by erythromycin. Bactericidal activity of airway surface liquid was observed at low concentrations (40 meq/l) of sodium but not at higher concentrations (> or =80 meq/l). Airway surface liquid did not contain significant amounts of antibiotics supplemented in the culture medium. Erythromycin at the levels in airway surface liquid and in culture medium did not inhibit bacterial growth. These results suggest that erythromycin may increase bactericidal activity of airway surface liquid in human airway epithelial cells through human beta-defensins production and reduce susceptibility of the airway to bacterial infection.


Co-culture with pig membrana granulosa cells modulates the activity of cdc2 and MAP kinase in maturing cattle oocytes.
Bovine cumulus-enclosed oocytes, initially cultured up to diakinesis (8 h of initial culture) or metaphase I (12 h of initial culture), were subsequently co-cultured for 6 h in contact with pig membrana granulosa (PMG) cells and then assayed for histone H1 and MAP kinase activities. In addition, the phosphorylation state of ERK 1,2 proteins was determined by Western blotting. The alterations in nuclear envelope breakdown, meiotic spindle formation and the patterns of chromosome condensation were analysed by immunofluorescence and transmission electron microscopy. The diakinesis-stage oocytes (initially cultured for 8 h) already possessed high histone H1 kinase and MAP kinase activities that were correlated with condensed and partially individualised chromosomes. The ERK 1 and most ERK 2 proteins were partly phosphorylated. Following the 6 h co-culture of these oocytes with PMG a rapid decrease in MAP kinase activity and a slower decrease in histone H1 kinase occurred, as well as ERK 1 and ERK 2 dephosphorylation. Both kinase activities and ERK 1,2 phosphorylation were fully restored following the release of the oocytes from co-culture and a subsequent culture in the absence of PMG. Moreover, the clumped bivalents were reindividualised and 56% of these oocytes reached metaphase II after 20 h of culture without PMG. The metaphase I oocytes, initially cultured for 12 h, displayed a fusiform meiotic spindle and a metaphase array of chromosomal bivalents, accompanied by high levels of both histone H1 and MAP kinase activity. Co-culture of MI oocytes with PMG abolished the activity of both kinases and caused the dephosphorylation of ERK 1 and ERK 2. Furthermore, the spindle microtubules were depolymerised and the chromosomal bivalents clumped into a single mass. Neither of the protein kinase activities nor the meiotic spindle were restored following subsequent culture in the absence of PMG for up to 20 h. These observations indicate that under in vitro conditions membrana granulosa cells can cause a prompt decrease in histone H1 and MAP kinase activities, and metaphase I oocytes. While these events are fully reversible in late diakinesis oocytes, metaphase I oocytes did not complete maturation after release from co-culture.


Molecular pathways: the complexity of the epigenome in cancer and recent clinical advances.
Human cancer is causally linked to genomic and epigenomic deregulations. Epigenetic abnormalities occurring within signaling pathways regulating proliferation, migration, growth, differentiation, transcription, and death signals may be critical in the progression of malignancies. Consequently, identification of epigenetic marks and their bioimplications in tumors represents a crucial step toward defining new therapeutic strategies both in cancer treatment and prevention. Alterations of writers, readers, and erasers in cancer may affect, for example, the methylation and acetylation state of huge areas of chromatin, suggesting that epi-based treatments may require "distinct" therapeutic strategies compared with "canonical" targeted treatments. Whereas anticancer treatments targeting histone deacetylase and DNA methylation have entered the clinic, additional chromatin modification enzymes have not yet been pharmacologically targeted for clinical use in patients. Thus, a greater insight into alterations occurring on chromatin modifiers and their impact in tumorigenesis represents a crucial advancement in exploiting epigenetic targeting in cancer prevention and treatment. Here, the interplay of the best known epi-mutations and how their targeting might be optimized are addressed.


Performance of flow cytometry to screen urine for bacteria and white blood cells prior to urine culture.
The gold standard test for the diagnosis of urinary tract infection is bacterial culture. However, urine cultures are labor intensive and costly. Furthermore, since results take 1-2 days many patients are treated presumptively prior to culture results being known. We evaluated the Sysmex UF-1000i for the quantification of bacteria and white blood cells (WBCs) in urine in order to determine if it could be used to predict positive culture in comparison to the use of gram stain as a screening tool. The UF-1000i demonstrated good linearity, within and between run precision for bacterial and WBC quantification. Using ROC analysis, the AUC for predicting a positive culture (>10(5)cfu/mL) was 0.95 and 0.90 for bacteria and WBCs, respectively, with optimum cutoffs of 288.9 bacteria/μL and 31.8WBCs/μL, respectively. At these cutoffs, sensitivity (SE) and specificity (SP) for culture positivity were 0.93 and 0.86, respectively, for bacterial counts and 0.89 and 0.79, respectively, for WBC counts. The use of gender specific bacterial cutoffs improved performance, especially in males. In comparison, SE and SP of urine Gram stain were 0.94 and 0.68, respectively. Quantification of bacteria in unspun urine samples by the Sysmex UF-1000i can be used to screen urine samples for those likely to grow >10(5)cfu/mL. The Sysmex UF-1000i demonstrated increased SP over urine Gram stain, and in this study population could reduce unnecessary reflex urine cultures by 55%.


Glutathione modulation and oxidative stress in human liver slices.
Glutathione (GSH) levels are modulated in human liver slices to evaluate if drug induced liver injury is enhanced by a poor liver GSH status. Liver slice GSH levels were decreased by: 1) BSO (L-buthionine-S-sulfoximine) to inhibit GSH synthesis, and by 2) APAP (acetaminophen) which consumes GSH via conjugation to a metabolite. In this study, methimazole (MMI) liver injury was evaluated in the presence of a poor GSH status. MMI was selected because its structural thione moiety is linked with hepatotoxicity and during metabolism GSH is co-oxidized. MMI (500-1000 µM) affected oxidative stress pathways and mitochondrial function, resulting in lower liver slice GSH and ATP levels. Co-incubation of MMI with BSO or APAP led to further decreases of GSH and ATP levels in some human livers, at time points and concentrations not detected with MMI alone. Variation in human response was evident and demonstrated that some subjects with a poor liver GSH status could be further compromised with high MMI concentrations. MMI induced an up-regulation of gene expression linked with the GSH pathway, mitochondrial GSH and inflammation. Co-treatment of MMI with BSO induced a mixed response of oxidative stress related genes and an up-regulation of heat shock genes. The combination of MMI with APAP increased the expression of genes involved with oxidative stress and anti-oxidant defense, likely to protect the cells from mitochondrial injury. In summary, MMI induces oxidative stress at high concentrations, which can be augmented when liver GSH levels are decreased by the co-administration of some drugs or health status.


Effect of hyperoxia on adhesion molecule expression in human endothelial cells and neutrophils.
To investigate the pathogenesis of pulmonary oxygen toxicity, we examined the effect of hyperoxia on adhesion molecule expression in cultured human pulmonary artery endothelial cells (HPAEC) and human umbilical vein endothelial cells (HUVEC). Endothelial cell monolayers were exposed to either hyperoxic (90% O(2)-5% CO(2)) or normoxic (21% O(2)-5% CO(2)) conditions for various periods. The level of intercellular adhesion molecule (ICAM)-1 expression had increased in hyperoxia-exposed HPAEC and HUVEC at 48 h (194 +/- 38 and 233 +/- 56%, respectively; P < 0.001) and at 72 h (200 +/- 43 and 223 +/- 52%, respectively; P < 0.001) compared with normoxic conditions. These hyperoxia-induced ICAM-1 expressions were dose dependently attenuated by a protein kinase C inhibitor (H-7). In contrast, the levels of P-selectin and E-selectin expression in HPAEC and HUVEC were unchanged. The levels of ICAM-1 mRNA and the numbers of adherent neutrophils were increased in HPAEC and HUVEC at 48 and 72 h of hyperoxia. On the other hand, hyperoxia caused neutrophil H(2)O(2) production without affecting the level of CD11/CD18 expression. These results suggest that increased ICAM-1 expression in endothelial cells plays an important role in neutrophil accumulation during hyperoxia.


Integrated Assembly and Flexible Movement of Microparts Using Multifunctional Bubble Microrobots.
Industrial robots have been widely used for manufacturing and assembly in factories. However, at the microscale, most assembly technologies can only pattern the micromodules together loosely and can hardly combine the micromodules to directly form an entity that cannot be easily dispersed. In this study, surface bubbles are made to function as microrobots on a chip. These microrobots can move, fix, lift, and drop microparts and integratively assemble them into a tightly connected entity. As an example, the assembly of a pair of microparts with dovetails is considered. A jacklike bubble robot is used to lift and drop a micropart with a tail, whereas a mobile microrobot is used to push the other micropart with the corresponding socket to the proper position so that the tail can be inserted into the socket. The assembled microparts with the tail-socket joint can move as an entity without separation. Similarly, different types of parts are integratively assembled to form various structures such as gears, snake-shaped chains, and vehicles, which are then driven by bubble microrobots to perform different forms of movement. This assembly technology is simple and efficient and is expected to play an important role in micro-operation, modular assembly, and tissue engineering.


A stable live bacterial vaccine.
Formulating vaccines into a dry form enhances its thermal stability. This is critical to prevent administering damaged and ineffective vaccines, and to reduce its final cost. A number of vaccines in the market as well as those being evaluated in the clinical setting are in a dry solid state; yet none of these vaccines have achieved long-term stability at high temperatures. We used spray-drying to formulate a recombinant live attenuated Listeria monocytogenes (Lm; expressing Francisella tularensis immune protective antigen pathogenicity island protein IglC) bacterial vaccine into a thermostable dry powder using various sugars and an amino acid. Lm powder vaccine showed minimal loss in viability when stored for more than a year at ambient room temperature (∼23°C) or for 180days at 40°C. High temperature viability was achieved by maintaining an inert atmosphere in the storage container and removing oxygen free radicals that damage bacterial membranes. Further, in vitro antigenicity was confirmed by infecting a dendritic cell line with cultures derived from spray dried Lm and detection of an intracellularly expressed protective antigen. A combination of stabilizing excipients, a cost effective one-step drying process, and appropriate storage conditions could provide a viable option for producing, storing and transporting heat-sensitive vaccines, especially in regions of the world that require them the most.


Catalyst characterization in the presence of solvent: development of liquid phase structure-activity relationships.
Due to the low volatility and highly oxygenated nature of biomass derived feedstocks, biomass upgrade reactions are frequently conducted in the presence of solvent to improve substrate mass transfer to the catalyst surface. However, relevant catalyst characterization techniques are most often performed in vacuum or inert gas environments, where the effect of solvent on the catalytic sites is ignored. Comparatively, characterization techniques in the presence of solvent are relatively rare, which poses challenges in developing structure-activity relationships for liquid phase reactions. In this perspective, commonly utilized techniques for probing the solid-liquid interface are briefly covered, with a focus on the role of solvent on zeolite and solid acid catalysis. New applications of techniques are proposed, most notably with ATR-FTIR, in the context of extracting thermodynamic information for the further understanding of the role of solvent on broadly applicable catalyst properties, such as acidity, and to develop structure-activity relationships for solid catalysts in solvent.


Effect of Radix Isatidis on the expression of moesin mRNA induced by LPS in the tissues of mice.
To investigate the effect of the anti-endotoxic part of Radix Isatidis on the expression of moesin mRNA in murine tissues induced by lipopolysaccharide (LPS), the sample solution of F(022) part from Radix Isatidis was intraperitoneally administered to experimental mice, and the lipopoly-saccharide (LPS) were injected into the tail vein, and then the tissues of liver, kidney and spleen were colleted and cut into slices. The mRNA was detected by moesin mRNA hybridization in situ. The staining results were observed under microscope. It was found that moesin mRNA expression was increased in the tissues of liver, kidndy and spleen in mice treated with LPS, while in the mice pre-treated with F(022) part from Radix Isatidis, the LPS-induced moesin mRNA expressions in these tissues were inhibited in a dose-dependant manner. Our study showed that F(022) part from Radix Isatidis can inhibit the LPS-induced expression of moesin mRNA in the tissues of liver, kidney and spleen in mice.


Influence of maternal smoking on placental abruption in successive pregnancies: a population-based prospective cohort study in Sweden.
The authors examined associations between cumulative smoking during a woman's first and second pregnancies and risk of placental abruption in the second pregnancy. They performed a population-based prospective cohort study of 526,690 women who delivered their first two consecutive singletons in Sweden in 1983-2001. Using logistic regression models, the authors found that, among women without placental abruption in the first pregnancy, smoking was associated with increased risk of abruption in the second pregnancy; however, this effect was confined to exposure occurring during the second pregnancy (adjusted odds ratio (OR)=1.8, 95% confidence interval (CI): 1.4, 2.3) but not the first (adjusted OR=1.1, 95% CI: 0.9, 1.3). Among women with a prior abruption, the risk of repeating abruption was increased irrespective of smoking habits. When women smoked during both pregnancies, there was an almost 11-fold increase in risk (adjusted OR=10.9, 95% CI: 7.3, 16.3). These findings suggest that women who quit smoking before pregnancy may benefit from reduced risk of abruption. The observation that the recurrence of abruption is substantially increased regardless of changes in smoking habits suggests that factors other than smoking may influence the recurrence of placental abruption.


Key within-membrane residues and precursor dosage impact the allotopic expression of yeast subunit II of cytochrome c oxidase.
Experimentally relocating mitochondrial genes to the nucleus for functional expression (allotopic expression) is a challenging process. The high hydrophobicity of mitochondria-encoded proteins seems to be one of the main factors preventing this allotopic expression. We focused on subunit II of cytochrome c oxidase (Cox2) to study which modifications may enable or improve its allotopic expression in yeast. Cox2 can be imported from the cytosol into mitochondria in the presence of the W56R substitution, which decreases the protein hydrophobicity and allows partial respiratory rescue of a cox2-null strain. We show that the inclusion of a positive charge is more favorable than substitutions that only decrease the hydrophobicity. We also searched for other determinants enabling allotopic expression in yeast by examining the COX2 gene in organisms where it was transferred to the nucleus during evolution. We found that naturally occurring variations at within-membrane residues in the legume Glycine max Cox2 could enable yeast COX2 allotopic expression. We also evidence that directing high doses of allotopically synthesized Cox2 to mitochondria seems to be counterproductive because the subunit aggregates at the mitochondrial surface. Our findings are relevant to the design of allotopic expression strategies and contribute to the understanding of gene retention in organellar genomes.


Recycling antibiotics into GUMBOS: a new combination strategy to combat multi-drug-resistant bacteria.
The emergence of multi-drug-resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded β-lactam antibiotics (ampicillin, carbenicillin, cephalothin and oxacillin) and a well-known antiseptic (chlorhexidine di-acetate) were fashioned into a group of uniform materials based on organic salts (GUMBOS) as an alternative to conventional combination drug dosing strategies. The antibacterial activity of precursor ions (e.g., chlorhexidine diacetate and β-lactam antibiotics), GUMBOS and their unreacted mixtures were studied with 25 clinical isolates with varying antibiotic resistance using a micro-broth dilution method. Acute cytotoxicity and therapeutic indices were determined using fibroblasts, endothelial and cervical cell lines. Intestinal permeability was predicted using a parallel artificial membrane permeability assay. GUMBOS formed from ineffective β-lactam antibiotics and cytotoxic chlorhexidine diacetate exhibited unique pharmacological properties and profound antibacterial activity at lower concentrations than the unreacted mixture of precursor ions at equivalent stoichiometry. Reduced cytotoxicity to invasive cell types commonly found in superficial and chronic wounds was also observed using GUMBOS. GUMBOS show promise as an alternative combination drug strategy for treating wound infections caused by drug-resistant bacteria.


Geologically controlled sandy beaches: Their geomorphology, morphodynamics and classification.
Beaches that are geologically controlled by rock and coral formations are the rule, not the exception. This paper reviews the current understanding of geologically controlled beaches, bringing together a range of terminologies (including embayed beaches, shore platform beaches, relict beaches, and perched beaches, among others) and processes, with the aim of exploring the multiple ways in which geology influences beach morphology and morphodynamics. We show how in addition to sediment supply, the basement geology influences where beaches will form by providing accommodation, and in the cross-shore, aspects of rock platform morphology such as elevation and slope are also important. Geologically controlled beaches can have significant variations in sediment coverage with seasons and storms, and geological controls have fundamental influences on their contemporary morphodynamics. This includes wave shadowing by headlands and rock/coral formations inducing strong alongshore gradients in wave energy, resulting in corresponding variations in morphodynamic beach state and storm response. Geologically-induced rip currents including shadow rips, deflection rips and mega-rips that can develop on embayed beaches during storms, are an integral feature of the nearshore circulation and morphodynamics of geologically controlled beaches. We bring these processes together by presenting a conceptual model of alongshore and cross-shore levels of geological control. In the longshore dimension, this ranges from beaches that are slightly embayed, through to highly embayed beaches where headlands dominate the entire beach morphodynamic response. In the cross-shore dimension, this ranges from beaches without discernible geological controls, through to relict beaches above the influence of the contemporary littoral zone. Given the prevalence of geologically controlled beaches along the world's coasts, it is paramount for coastal management to consider how these beaches differ from unconstrained beaches and avoid applying inappropriate models and tools, especially with our uncertain future climate.


Promoting Excellence in End-of-Life Care: lessons learned from a cohort of nursing home residents with advanced Huntington disease.
Huntington disease (HD) is a genetic neurodegenerative disorder that progresses over decades and is ultimately terminal. As HD advances, patients are frequently placed in institutional care settings, including nursing homes and hospices where family, nursing staff, and interdisciplinary team members are challenged to help patients live to their highest potential and die with dignity. Edgemoor, a distinct part of the San Diego County Psychiatric Hospital, is a regional referral facility for patients with HD. Over the past 8 years, we have cared for 53 patients with advanced HD and describe our experiences by presenting their demographic characteristics and the lessons we have learned in caring for them. Ultimately, we found that the Robert Wood Johnson Foundation's Promoting Excellence in End-of-Life Care Initiative provided a meaningful framework for setting clinical priorities. This framework is used to summarize the clinical lessons that nursing staff and interdisciplinary team members learned about caring well for institutionalized individuals with advanced HD.


Specific irritability of acupuncture points as an early symptom of multiple sclerosis.
28 patients suffering from multiple sclerosis were treated by acupuncture. The age of the patients ranged from 24 to 60 yr. Results of the treatment were satisfactory, but remarkable spontaneous remissions, characteristic for this illness, make any treatment difficult to evaluate. In this article the peculiar behaviour of all treated patients is described: increased sensibility of the skin over the acupuncture loci, while insertion of the acupuncture needles provoke spasms, clonus and even tonic-clonic contractions of the muscles of the extremities. This phenomenon is very specific and can be used as an early sign of this ill-fated illness.


[Hormonal regulation of lipoate-35S transport into rat liver mitochondria].
The effect of adrenalectomy, and also of adrenaline, hydrocortisone and ACTH on the rate of lipoate-35S penetration into the mitochondria of the liver was studied in rats. Bilateral adrenalectomy proved to decrease the rate of the lipoate penetration into the organellae significantly; this was more pronounced in female than in the male rats. The capacity of hepatic mitochondria to absorp the lipoic acid was restored under the effect of single adrenaline, hydrocortisone and ACTH injections. Actinomycin D administered to the animals for a period of 3 days in combination with hydrocortisone eliminated the stimulating effect of the hormone on the lipoate transport into the mitochondria of the liver of the intact and adrenalectomized rats completely. The data obtained pointed to the regulating effect of some hormones on the intensity of penetration of lipoate into the biological structures.


Preliminary spectroscopic studies on the neuromelanic pigment of human substantia nigra nucleus.
The neuromelanic pigment obtained from human mid-brain Substantia Nigra Nucleus was studied by I.R. spectroscopy and compared with synthetic dopamine melanin. Natural neuromelanin and synthetic dopamine melanin show very similar features in two characteristic I.R. absorption regions: 1400 cm-1, typical of phenolic OH groups, and 3200 cm-1 band, typical of aminic groups. Natural mid-brain neuromelanin shows a different absorption in the I.R. region at 3000 cm-1 and in the 1300-900 cm-1 range probably due to the presence of lipidic residues bound to the molecule. The results of the U.V. spectroscopic analysis suggest a correlation between the optical density of human neuromelanic pigment and the different ages of the subjects providing the specimens.


The psychosocial and health effects of workplace reorganisation. 1. A systematic review of organisational-level interventions that aim to increase employee control.
Systematic review of the health and psychosocial effects of increasing employee participation and control through workplace reorganisation, with reference to the "demand-control-support" model of workplace health. Systematic review (QUORUM) of experimental and quasi-experimental studies (any language) reporting health and psychosocial effects of such interventions. Electronic databases (medical, social science and economic), bibliographies and expert contacts. We identified 18 studies, 12 with control/comparison groups (no randomised controlled trials). Eight controlled and three uncontrolled studies found some evidence of health benefits (especially beneficial effects on mental health, including reduction in anxiety and depression) when employee control improved or (less consistently) demands decreased or support increased. Some effects may have been short term or influenced by concurrent interventions. Two studies of participatory interventions occurring alongside redundancies reported worsening employee health. This systematic review identified evidence suggesting that some organisational-level participation interventions may benefit employee health, as predicted by the demand-control-support model, but may not protect employees from generally poor working conditions. More investigation of the relative impacts of different interventions, implementation and the distribution of effects across the socioeconomic spectrum is required.


Prediction and prevention of IDDM--1991.
Although we can now identify some nondiabetic individuals who will subsequently develop clinical insulin-dependent diabetes mellitus (IDDM), our ability to predict subsequent clinical IDDM is far from perfect. In this article, we discuss the status of knowledge regarding the natural history of preclinical IDDM and discuss, especially in relation to predicting IDDM, the genetic, immunologic, and metabolic components of the IDDM disease process.


Surgical and prosthetic concepts for optimal aesthetics: a case report.
This case report reviews the current aspects of implant surgery and implant-supported prostheses. The importance of evaluating patient expectations of the final prosthetic result prior to the commencement of any procedure is emphasized. The clinical procedure is outlined, focusing on surgical and prosthetic planning according to the desired prosthesis. The availability of various implant lengths, diameters, angulations, and coatings is reviewed with suggestions for selections to suit either the anterior or the posterior region and the available quality and quantity of the bone.


Emergency medicine research: 2030 strategic goals.
All academic medical specialties have the obligation to continuously create new knowledge that will improve patient care and outcomes. Emergency medicine (EM) is no exception. Since its origins over 50 years ago, EM has struggled to fulfill its research mission. EM ranks last among clinical specialties in the percentage of medical school faculty who are National Institutes of Health (NIH)-funded principal investigators (PIs; 1.7%) and the percentage of medical school departments with NIH-funded PIs (33%). Although there has been a steady increase in the number of NIH-funded projects and total NIH dollars, the slowing growth in the number of NIH-funded PIs and lack of growth in the number of EM departments with NIH-funded PIs is cause for concern. In response, the Association of Academic Chairs of Emergency Medicine (AACEM) Research Task Force proposes a set of 2030 strategic goals for the EM research enterprise that are based on sustaining historic growth rates in NIH funding. These goals have been endorsed by the AACEM Executive Committee and the boards of Society for Academic Emergency Medicine (SAEM), American College of Emergency Physicians (ACEP), and American Academy of Emergency Medicine (AAEM). The 2030 strategic goals include 200 NIH-funded projects led by 150 EM PIs in at least 50 EM departments with over $100M in annual funding resulting in over 3% of EM faculty being NIH-funded PIs. Achieving these goals will require a targeted series of focused strategies to increase the number of EM faculty who are competitive for NIH funding. This requires a coordinated, intentional effort with investments at the national, departmental, and individual levels. These efforts are ideally led by medical school department chairs, who can create the culture and provide the resources needed to be successful. The specialty of EM has the obligation to improve the health of the public and to fulfill its research mission.


"If I knew then what I know now": parents' reflections on raising a child with cerebral palsy.
In this study we investigated experiences of parents of children with cerebral palsy (CP) to identify areas in which health care providers and educators could improve practice. A second objective was to create educational material for parents of young children newly diagnosed with CP. A purposive sample of nine parents, who previously participated in the Adolescent Study of Quality of Life, Mobility, and Exercise, was recruited through phone. During an interview, parents reflected on the experience of raising a child with CP from birth to young adulthood. These interviews were audiotaped, transcribed, and coded using the International Classification of Functioning, Disability and Health-informed model and analyzed to identify major themes. Parents elaborated upon what was helpful and what could be changed to improve their children's and families' experiences through supports, advocacy, and education at different levels. The results informed the development of tips for parents and children with CP to enhance their families' experiences and interactions with health care providers, educators, and others.


Technique and results of linear ablation at the mitral isthmus.
This prospective clinical study evaluates the feasibility and efficacy of combined linear mitral isthmus ablation and pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). One hundred consecutive patients (13 women; age 55+/-10 years) with drug-refractory, symptomatic paroxysmal AF underwent PV isolation and linear ablation of the cavotricuspid isthmus and the mitral isthmus (lateral mitral annulus to the left inferior PV). They were compared with 100 consecutive patients (14 women; age, 52+/-10 years) undergoing PV isolation and cavotricuspid ablation without mitral isthmus ablation. Bidirectional mitral isthmus block was confirmed by demonstrating (1) a parallel corridor of double potentials during coronary sinus (CS) pacing, (2) an activation detour by pacing either side of the line, and (3) differential pacing techniques. Isolation of all PVs and cavotricuspid isthmus ablation were performed successfully in all. Mitral isthmus block was achieved in 92 patients after 20+/-10 minutes of endocardial radiofrequency application and an additional 5+/-4 minutes of epicardial radiofrequency application from within the CS in 68, resulting in a conduction delay of 151+/-26 ms during CS pacing. Thirty-two patients with mitral isthmus ablation compared with 49 without had recurrent atrial arrhythmia (P=0.02) requiring further ablation. At 1 year after the last procedure, 87 patients with mitral isthmus ablation and 69 without (P=0.002) were arrhythmia free without antiarrhythmic drugs, mitral isthmus ablation being the only factor associated with long-term success (RR for AF recurrence, 0.2; CI, 0.1 to 0.4; P<0.001). Catheter ablation of the mitral isthmus results consistently in demonstrable conduction block and is associated with a high cure rate for paroxysmal AF.


Repeated bouts of exercise in patients with anterior cruciate ligament reconstruction.
Reduced quadriceps activation after anterior cruciate ligament reconstructions (ACL-R) has been reported. Patients often return to daily exercise or sport after ACL-R; however, there is little information regarding quadriceps function after exercise in this population. Therefore, the purpose of this study was to compare quadriceps strength and central activation after repeated bouts of exercise between individuals with and without a history of ACL-R. Eighteen recreationally active subjects participated in this study: 8 with unilateral ACL-R at least 6 months earlier and 10 healthy controls. All subjects performed 30 min of continuous exercise on two consecutive days. Exercise included repeated bouts of inclined treadmill walking and jumping exercises. We measured maximal isometric knee extension torque and quadriceps central activation ratio (CAR) using the superimposed burst technique before and after exercise on day 1. Subjects returned 24 h later (day 2) for a repeat testing session. There was a significant group-time interaction for knee extension torque. ACL-R subjects were weaker at baseline on day 1 of testing (P = 0.01) but exhibited no significant reduction in knee extension torque after exercise (P = 0.13), whereas the healthy control subjects did (P = 0.01). Knee extension torque on day 2 remained significantly lower than baseline for the controls (P = 0.03), but not the ACL-R (P = 0.73). On day 2, both groups experienced significantly reduced knee extension torque after exercise. There was no group-time interaction for CAR, but a group main effect indicated that, on average, ACL-R had significantly lower CAR bilaterally compared with healthy controls. The quadriceps in ACL-R knees were weaker and showed less reduction of isometric knee extension torque compared with healthy group in day 1. However, there were no group differences of quadriceps strength on day 2.


Presence of heat shock protein 47-positive fibroblasts in cancer stroma is associated with increased risk of postoperative recurrence in patients with lung cancer.
Heat shock protein 47 (HSP47), a collagen-binding protein, has a specific role in the intracellular processing of procollagen production. HSP47 expression is associated with cancer growth and metastasis in several types of cancers. However, none of the studies have assessed whether HSP47 expression is associated with the risk of postoperative recurrence of lung cancer until now. Therefore, we aimed to assess this association. The study population consisted of a cohort of consecutive patients who underwent surgery for lung cancer at Nagasaki University Hospital, Nagasaki, Japan, from January 2009 to December 2010. Patient characteristics, survival and disease-free survival (DFS), and laboratory findings were compared between patients who tested positive and negative for HSP47 expression in lung cancer cells and between those who showed high and low numbers of HSP47-positive fibroblasts in cancer stroma. A total of 133 patients underwent surgery for lung cancer. Sixty-seven patients (50.4%) had HSP47-positive cancer cells, and 91 patients (68.4%) had a higher number of HSP47-positive fibroblasts. The patients with a high number of HSP47-positive fibroblasts had a shorter DFS than those with a low number of HSP47-positive fibroblasts. Multivariate analysis identified only the presence of a high number of HSP47-positive fibroblasts as an independent risk factor for recurrence of lung cancer after surgery (odds ratio, 4.371; 95% confidence interval, 1.054-29.83; P = 0.042). The present study demonstrated that the presence of a high number of HSP47-positive fibroblasts in the cancer stroma was a risk factor for recurrence of lung cancer after surgery.


Effects of meat cooking, and of ingested amount, on protein digestion speed and entry of residual proteins into the colon: a study in minipigs.
The speed of protein digestion impacts on postprandial protein anabolism. After exercise or in the elderly, fast proteins stimulate protein synthesis more efficiently than slow proteins. It has been shown that meat might be a source of fast proteins. However, cooking temperature, acting on the macrostructure and microstructure of the meat could affect both the speed, and efficiency, of protein digestion. This study aims to evaluate, in vivo, the effect of meat cooking on digestion parameters, in the context of a complete meal. Six minipigs fitted with an ileal cannula and an arterial catheter were used. In order to measure the true ileal digestibility, tested meat was obtained from a calf, the muscle proteins of which were intrinsically labelled with (15)N-amino acids. Three cooking temperatures (60, 75 and 95°C; core temperature for 30 min), and three levels of intake (1, 1.45, and 1.90 g protein/kg body weight) were tested. Following meat ingestion, ileal digesta and arterial blood were collected over a 9-h period. The speed of digestion, evaluated from the kinetics of amino acid appearance in blood within the first 3 h, was greater for the cooking temperature of 75°C, than for 60 or 95°C. The true ileal digestibility, which averaged 95%, was not affected by cooking temperature or by the level of meat intake. The amino acid composition of the digesta flowing at the ileum was not affected by cooking temperature. These results show that cooking temperature can modulate the speed of meat protein digestion, without affecting the efficiency of the small intestinal digestion, and consequently the entry of meat protein residues into the colon.


Protein labeling and crosslinking by covalent aptamers.
In this chapter, a new approach to the selective modification of native proteins is discussed, using electrophilic covalent aptamers. These biochemical tools are generated through the site-specific incorporation of a label-transferring or crosslinking electrophile into a DNA aptamer. Covalent aptamers provide the ability to transfer a variety of functional handles to a protein of interest or to irreversibly crosslink to the target. Methods for the aptamer-mediated labeling and crosslinking of thrombin are described. Thrombin labeling is fast and selective, in both simple buffer and in human plasma and outcompetes nuclease-mediated degradation. This approach provides facile, sensitive detection of labeled protein by western blot, SDS-PAGE, and mass spectrometry.


Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide.
Human saliva contains hundreds of small proline-rich peptides originated by the proteolytic cleavage of the salivary basic Proline-Rich Proteins. Nevertheless only for few of them a specific biological activity has been assigned to date. Among them, the 1932 Da peptide (p1932) has been patented as an anti-HIV agent. In order to shed light on the possible mechanism of action of this peptide, we assessed in this study, by means of molecular dynamics calculations, circular dichroism and FTIR spectroscopic techniques, that p1932 has an intrinsic propensity to adopt a polyproline-II helix arrangement. This structural feature combined with the presence of PxxP motifs in its primary structure, represents an essential property for the exploitation of several biological activities. Next to these findings, we recently demonstrated the ability of this peptide to be internalized within cells of the oral mucosa, thus we focused onto a possible intracellular target, represented by the SH3 domains family. Its ability to interact with selected SH3 domains was finally assayed by Surface Plasmon Resonance spectroscopy. As a result, only Fyn, Hck, and c-Src SH3 domains gave positive results in terms of interaction, showing dissociation constants ranging from nanomolar to micromolar values having the best performer a KD of 148 nM. It is noteworthy that all the interacting domains belong to the Src kinases family, suggesting a role for p1932 as a modulator of the signal transduction pathways mediated by these kinases. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 714-725, 2016.


Failed intubation. A case report.
A case report illustrates one of the dangers of intubation with use of a long-acting muscle relaxant where the clinical situation was misjudged. There is still a good case to be made out for the use of suxamethonium for intubation in a routine operating list to provide additional cover in the event of 'failed intubation'.


ST Elevation Myocardial Infarction Due to Carbon Monoxide Poisoning.
Carbon monoxide is formed as a result of combustion of any carbon compound and can lead to hypoxia in many organs including the brain and the heart. Carbon monoxide poisoning in the United States is the leading cause of the fatal poisonings. In this study we present a case with no-known accompanying disease in the light of literature where myocardial infarction was developed as a result of carbon monoxide poisoning.


Ressurrection of Curimatus albula Lütken (Characiformes: Curimatidae), a senior synonym of Cyphocharax lundi Dutra, Penido, Mello & Pessali.
Curimatus albula Lütken 1874 was described from the Ribeirão da Mata at Lagoa Santa, a tributary of Rio das Velhas, Rio São Francisco basin. The species validity was questioned by Lütken (1875) himself, who suggested that the species could be a synonym of Curimatus gilbert Quoy & Gaimard, a species described from the Rio Macacu, a coastal river tributary of Guanabara bay, Rio de Janeiro. That synonymy was only formally proposed by Eigenmann (1910), and followed by most subsequent authors (e. g. Nielsen, 1974; Vari, 1992), except for Fowler (1975), who erroneously listed C. albula as the senior synonym of C. gilbert. Vari (1989) posteriorly removed both nominal species from Curimatus Oken (= Curimata Bosch) reallocating them in Cyphocharax Fowler, based on the lack of synapomorphic conditions present in other valid curimatid genera. Vari (1989) considered that those nominal species belonged to a major group within Cyphocharax also including C. grandocule Fernández-Yépez, C. modestus Fernández-Yépez, C. santacatarinae Fernández-Yépez, and C. voga Hensel, based on the presence of a rhomboidal caudal pigmentation and "random body spotting". Later, Vari (1992) included C. grandocule along with C. albula in the synonymy of C. gilbert, and listed several characters allowing further distinction of that species from the remaining species of the group (i.e., number of vertebrae, scales in transverse series, and pigmentation characters). Among the characters involving the pigmentation pattern, Vari (1992) stressed the lack of randomly arranged dark spots on the lateral and dorsolateral surfaces of the body in C. gilbert (versus present in C. voga).


Not all cultural values are created equal: Cultural change in China reexamined through Google books.
Given its major transformations in recent decades, China has figured prominently in research on cultural change. Previous research converges in showing a general trend towards individualism in contemporary China while noting that rising individualism tends to coexist with enduring collectivism. To further understand this, we tested whether perceived traditional importance of cultural values would modulate the trajectory of cultural change reflected in word usage frequencies in published books. We re-analysed Google's Chinese corpus since 1980 based on a broad sample of words associated with individualism-collectivism. We replicated the pattern of rising individualism and declining collectivism among words of modest and low perceived traditional importance. Most important, however, collectivistic words of high perceived traditional importance increased in usage frequencies with time, thus departing from the general trend towards individualism. Overall, our research underscores the role of core culture in cultural maintenance during times of rapid cultural change.