Ceftazidime compared with gentamicin and carbenicillin in patients with cystic fibrosis, pulmonary pseudomonas infection, and an exacerbation of respiratory symptoms. British Thoracic Society Research Committee.
An open randomised comparison of a new intravenous cephalosporin, ceftazidime, with the established regimen of gentamicin and carbenicillin was carried out in patients with cystic fibrosis who had persisting pulmonary infection with Pseudomonas species and who developed acute exacerbations of respiratory symptoms. Fifty patients received ceftazidime and 32 gentamicin and carbenicillin. The ceftazidime and gentamicin were given every eight hours and the carbenicillin every six hours. The mean total daily doses were 151 mg/kg for ceftazidime, 6.3 mg/kg for gentamicin and 450 mg/kg for carbenicillin. The mean duration of treatment was 10 days in patients receiving gentamicin and carbenicillin and 12 days in those receiving ceftazidime. Of the patients with pseudomonas in the initial sputum specimen in whom sputum was cultured after treatment, six (26%) of 23 receiving gentamicin and carbenicillin and seven (18%) of 39 receiving ceftazidime had sputum free from pseudomonas at the end of treatment, but recolonisation occurred subsequently. In those receiving ceftazidime all 10 coexisting organisms were eliminated, whereas only four of seven coexisting organisms in patients receiving gentamicin and carbenicillin were eliminated. Overall clinical improvement occurred in 25 (78%) of 32 patients treated with gentamicin and carbenicillin and 48 (96%) of 50 patients treated with ceftazidime. Nineteen (59%) of the patients receiving gentamicin and carbenicillin but only 15 (30%) of those receiving ceftazidime required admission to hospital or intravenous antibiotics, or both, or died during the three months after treatment. Side effects in both groups were similar, mild, and infrequent. Thrombophlebitis occurred in four patients treated with gentamicin and carbenicillin but in no patients treated with ceftazidime.


The lipopolysaccharide O side chain of Vibrio vulnificus serogroup E is a virulence determinant for eels.
Vibrio vulnificus is a gram-negative bacterium capable of producing septicemic infections in eels and immunocompromised humans. Two biotypes are classically recognized, with the virulence for eels being specific to strains belonging to biotype 2, which constitutes a homogeneous lipopolysaccharide (LPS)-based O serogroup (which we have designated serogroup E). In the present study we demonstrated that the O side chain of this LPS determines the selective virulence of biotype 2 for eels: (i) biotype 1 strains (which do not belong to serogroup E) are destroyed by the bactericidal action of nonimmune eel serum (NIS) through activation of the alternative pathway of complement, (ii) biotype 2 strains (of serogroup E) are resistant to NIS, and (iii) rough mutants of biotype 2 lacking the O polysaccharide side chain are sensitive to NIS and avirulent for eels.


Tykes on bikes: injuries associated with bicycle-mounted child seats.
We reviewed US Consumer Product Safety Commission (CPSC) data for 1978-1988 concerning injuries related to seats used for carrying children on adult bicycles, ie, bicycle-mounted child seats. There were an estimated 4960 injuries to children during the 11-year period. The peak age of injury was two years. Fifty-five percent of victims were male. Falls accounted for 80% of the estimated injuries. Head (51%) and face (21%) injuries predominated. Twenty-one percent of estimated injuries were mild, 60% were moderate, and 19% were severe. All severe injuries involved the head or face, and all mild injuries were to extremities. Riding in a bicycle-mounted child seat exposes the child to adult-level forces, risking injury because of the bicycle's size, speed, and instability and the child's size and development. Injury prevention requires recognition of this problem, use of bicycle helmets, improvements in seat design, and educational efforts by physicians and their organizations. This report demonstrates use of CPSC national injury estimates to evaluate a product-related childhood injury and underscores the need to protect potential victims when avoidance of injury is beyond their own capabilities.


Soy isoflavone alleviates Aβ1-42-induced impairment of learning and memory ability through the regulation of RAGE/LRP-1 in neuronal and vascular tissue.
The neuroprotective properties of soy isoflavone (SIF) have been demonstrated by our previous studies and others, but its potential mechanism is not clear. Because of the key role of neurovascular dysfunction in the pathogenesis of Alzheimer's disease (AD), we hypothesized neurovascular tissue might be one neuroprotective target of SIF. In the present study, learning and memory ability, β-amyloid (Aβ) expressions both in neurovascular tissue and plasma, the receptor for advanced glycation end products (RAGE), low-density lipoprotein receptor-related protein (LRP)-1, nuclear factor-κB p65 (NF-κB p65), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expressions in neurovascular tissue were measured in Wistar rats following lateral cerebral ventricle administration of Aβ1-42 by miniosmotic pump with or without intragastric administration of SIF from 14 days before surgery to the end of experiment. The results showed that SIF could improve the impairment of learning and memory of rats induced by Aβ1-42, maintain Aβ homeostasis in brain, regulate the disordered expressions of RAGE/LRP-1 and restrain RAGE related NF-κB and inflammatory cytokines activation in neurovascular structure. These results suggested that SIF could protect Aβ-impaired learning and memory in rats, and its mechanism might be associated with the regulation of vascular Aβ transportation and vascular inflammatory reaction.


Methylated +58CpG site decreases DCN mRNA expression and enhances TGF-β/Smad signaling in NSCLC cells with high metastatic potential.
Decorin (DCN) has been suggested to display an anti-metastatic role by antagonizing bioactive TGF-β in advanced human cancers. However, the epigenetic mechanisms by which defective expression of DCN causes cancer metastasis remain unclear. We focused on non-small cell lung cancer (NSCLC) cell lines with low metastatic potential (95C) and high metastatic potential (95D), which share a similar genetic background. Quantitative PCR and clonal bisulfite sequencing indicated that the methylation levels of the +58CpG site in the DCN 5'-UTR region was significantly higher in 95D cells with low expression of DCN mRNA compared to 95C cells with high expression of DCN mRNA. In silico prediction and ChIP assay showed a correlation between +58CpG site and AhR, which was reported as a transcriptional activator. Importantly, EMSA and luciferase reporter gene assays suggested that +58CpG methylation specifically diminished the recruitment of AhR to DCN 5'-UTR sequence and caused a reduction of approximately 50% in transcriptional activity. At baseline, 95D cells exhibited higher p-Smad3 levels and lower E-cadherin expression when compared with 95C cells. The demethylating agent 5-Aza significantly led to restoration of DCN expression, reduced level of p-Smad3, increased expression of E-cadherin in 95D cells. Taken together, we identified the methylated +58CpG in DCN 5'-UTR associated with reduced expression of DCN mRNA, and revealed that +58CpG methylation may be one of the mechanisms accounting for reduced recruitment of the transcriptional activator AhR to DCN 5'-UTR, and suggest that this mechanism promotes TGF-β/Smad signaling by enhancing the phosphorylation of Smad3, thereby downregulating E-cadherin in NSCLC cells with high metastatic potential.


Newborn screening for spinal muscular atrophy - what have we learned?
Over the last decade, the treatment of spinal muscular atrophy (SMA) has become a paradigm of the importance of early and accurate diagnosis and prompt treatment. Three different therapeutic approaches that aims to increase SMN protein are approved now by Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment of SMA; their efficacies have been demonstrated in pivotal trials. The authors report on the two controlled studies and real-world evidence that have demonstrated that the treatment of patients pre-symptomatically ensures normal or only slightly sub-normal motor development in children who would otherwise develop a severe form of the disease. Furthermore, the authors highlight the several newborn screening (NBS) methods that are now available, all of which are based on real-time PCR, that reliably and robustly diagnose SMA except in subjects with disease caused by a point mutation. Pre-symptomatic treatment of SMA has been clearly demonstrated to prevent the most severe forms of the disease. NBS constitutes more than a simple test and should be considered as a global process to accelerate treatment access and provide global management of patients and parents. Even though the cost of NBS is low and health economics studies have clearly demonstrated its value, the fear of identifying more patients than the system can treat is often reported in large middle-income countries.


Role of interleukin-1beta in superovulation in rats.
In this study, the changes in interleukin-1beta (IL-1beta) mRNA expression and its localization in the ovary were studied in pregnant mares' serum gonadotropin (PMSG)-human CG (hCG) injected immature rats. Moreover, to study the in vivo role of IL-1 during ovulation, the IL-1 receptor antagonist (IL-1ra) was injected into the bilateral bursae (100 microg/15 microl/bursa) immediately or at the 3rd, 5th, 10th h after hCG injection. IL-1beta mRNA expression in the ovary had significantly (P<0.05) increased at the 6th h after hCG injection, and its level depended on the time interval between PMSG and hCG injections; the maximal IL-1beta mRNA expression was observed when hCG was injected 48 h after the PMSG injection. The signals of IL-1beta mRNA localized in the thecal layer, particularly in the large preovulatory follicles. Intrabursal IL-1ra injection at the 3rd h after hCG injection showed a trend toward lowering the number of ova shed, and the injection at the 5th h significantly (P<0.01) decreased the number of ova shed compared with the saline injected control group. At the 24th h after hCG injection, there were a few large preovulatory follicles with distinguishable theca and granulosa layers in the IL-1ra treated ovary, although these two layers were indistinguishable in the control ovary. These results indicated that IL-1beta mRNA expression was definitely induced by hCG stimulation, and, moreover, this expression was dependent on the stage of follicular maturation. IL-1 may be important for the ovulation in the superovulatory cycle by PMSG in rats.


The Natural History of Changes in Preferences for Life-Sustaining Treatments and Implications for Inpatient Mortality in Younger and Older Hospitalized Adults.
To compare changes in preferences for life-sustaining treatments (LSTs) and subsequent mortality of younger and older inpatients. Retrospective cohort study. Kaiser Permanente Northern California (KPNC). Individuals hospitalized at 21 KPNC hospitals between 2008 and 2012 (N = 227,525). Participants were divided according to age (<65, 65-84, ≥85). The effect of age on adding new and reversing prior LST limitations was evaluated. Survival to inpatient discharge was compared according to age group after adding new LST limitations. At admission, 18,254 (54.2%) of those aged 85 and older, 18,349 (20.8%) of those aged 65 to 84, and 3,258 (3.1%) of those younger than 65 had requested that the use of LST be limited. Of the 187,664 participants who initially did not request limitations on the use of LST, 15,932 (8.5%) had new LST limitations added; of the 39,861 admitted with LST limitations, 3,017 (7.6%) had these reversed. New limitations were more likely to be seen in older participants (aged 65-84, odds ratio (OR) = 2.27, 95% confidence interval (CI) = 2.16-2.39; aged ≥85, OR = 6.43, 95% CI = 6.05-6.84), and reversals of prior limitations were less likely to be seen in older individuals (aged 65-84, OR = 0.73, 95% CI = 0.65-0.83; aged ≥85, OR = 0.46, 95% CI = 0.41-0.53) than in those younger than 65. Survival rates to inpatient discharge were 71.7% of subjects aged 85 and older who added new limitations, 57.2% of those aged 65 to 84, and 43.4% of those younger than 65 (P < .001). Changes in preferences for LSTs were common in hospitalized individuals. Age was an important determinant of likelihood of adding new or reversing prior LST limitations. Of subjects who added LST limitations, those who were older were more likely than those who were younger to survive to hospital discharge.


Intrinsic Motivation Mediates the Association Between Exercise-Associated Affect and Physical Activity Among Adolescents.
American adolescents overwhelmingly engage in insufficient physical activity (PA). Attention has turned to the role of affect in shaping PA, raising questions as to whether the impact of affect on PA is direct/automatic or cognitively mediated ("Type 1" or "Type 2" in the dual-process model). This study examines whether intrinsic motivation (IM) mediates the association between affect and PA. Adolescents (N = 142, 48% Male, 20% non-Latino White, mean age = 11.04 years, mean VO2 = 37.19 ml/kg/min, mean BMI = 63.19) completed assessments of cardiorespiratory fitness, affective response to exercise on a stationary cycle, IM, preferred exercise intensity, and moderate-to-vigorous PA (MVPA; ActiGraph). Fitness, exercise intensity and MVPA assessments were repeated 5 months later. Tests for mediation showed that affect predicted PA at baseline and 5 months, and IM mediated the relationship between affect and PA both cross-sectionally (CI = 0.03, 0.17) and longitudinally (CI = 0.04, 0.18). Results suggest a cognitively mediated pathway from affect to behavior. Adolescent PA may be increased either by enhancing IM or by tailoring interventions to accommodate individuals with a predisposition to respond to exercise with negative affect. This study is registered with Clinicaltrials.gov (ID # NCT01876602).


The social construction of chronicity--a key to understanding chronic care transformations.
The purpose of this paper is to argue the importance of contemporary analysis of the modern social construction of chronicity--encapsulating the world views of the chronically ill, and the medical and health system constructions of chronic disease, through the nature of care for chronic conditions. It is argued that chronic diseases are themselves, socially constructed, despite widely accepted disease classification systems. Thus, there is a need to examine how different ideas have permeated our clinical and health system developments and their social context and vice versa. We examine historical ideas, theory and evidence about the tensions in social construction of chronic illness by those afflicted and the responses of society, the medical and health professions and increasingly the public and private institutions that shape health care. This is with the background of major differences in the two cultures that create knowledge: those based upon argument and intellectual logic--hermeneutic, and those based upon 'objectivist' empirical science, often called heuristic. Evidence-based medicine (EBM) is the flagship of disease management, increasingly narrative-based medicine and other similar genres are becoming the pragmatic face of social constructions, yet sit in juxtaposition without synthesis. A third culture has emerged of scientific intellectuals who straddle these cultures and in health care their public face is 'mixed methods'. Recent cases of modern ideas about improving chronic care were reviewed. We found that despite developments of social theory, the world view of the chronically ill exerts small influence in health system redesign, apparently dominated by chronic disease models. Confusion remains within health system reforms as to the social construction of chronicity--chronic disease, chronic condition or chronic illness and chronic care transformations. The role of Primary Care remains ambiguous straddling disease and illness. Radical redesign of health systems is taking place without an understanding and discourse about the nature of their construction. Ad hoc eclectism with unquestioning adoption of the dominant EBM paradigm is driving a new health culture based on disease-based performance incentives, which is intrusive beyond the medical model and pays little attention to narratives of illness and even less to the whole social reconstruction of illness and wellness. Health care systems cannot afford to avoid, and should actively embrace the critiques of social theory and analyses in the transformations of health systems to improve chronic care. Creative tensions between empirical and intellectual critique, and a synthetic middle ground are likely to lead to more realistic and innovative approaches spanning the nature of chronicity and the transformation of Primary Care.


Contribution of protein, starch, and fat to the apparent ileal digestible energy of corn- and wheat-based broiler diets in response to exogenous xylanase and amylase without or with protease.
The ileal energy contribution of protein, starch, and fat in response to 2 exogenous enzyme combinations was studied in 2 digestibility assays with 21- (experiment 1; 432 birds) and 42-d-old (experiment 2; 288 birds) Ross 308 broiler chickens. A 2 × 2 × 3 factorial arrangement of treatments with 2 base grains (corn or wheat), without or with high fiber ingredients (corn distillers dried grains with solubles and canola meal), and 3 enzyme treatments was implemented. Enzyme treatments, fed from 12 to 21 d or 32 to 42 d, were 1) without enzymes, 2) with xylanase from Trichoderma ressei (2,000 U/kg) and amylase from Bacillus licheniformis (200 U/kg; XA), or 3) with XA plus protease from Bacillus subtilis (4,000 U/kg; XAP). All diets contained Escherichia coli phytase (500 FTU/kg). Apparent ileal digestibility (AID) of protein, starch, and fat, as well as the apparent ileal digestible energy, were determined using titanium dioxide as inert marker. A generalized mixed model was used to test main effects and 2-way interactions at P < 0.05. An enzyme × grain interaction was detected for AID of starch at 21 and 42 d, and AID of fat at 21 d, with greater effects of enzymes in wheat-based compared with corn-based diets, but significant increments due to enzymes compared with controls in both diet types. Apparent ileal digestibility of fat at 42 d increased with enzyme supplementation compared with the control treatments. The XA and XAP treatments gradually (P < 0.05) increased AID of protein at 21 d, but only XAP increased AID of protein compared with the control at 42 d. Compared with the controls, XA increased AID energy by 52 or 87 kcal, and XAP by 104 or 152 kcal/kg of DM at 21 or 42 d, respectively. The caloric contribution of starch, fat, and protein were affected differentially by base grain and the presence of fibrous ingredients at 21 and 42 d of age.


The role of oxidative stress in COPD: current concepts and perspectives.
Worldwide, COPD is a major cause of morbidity and mortality. The clinical and functional manifestations of COPD result from lung injury occurring through various mechanisms, including oxidative stress, inflammation, protease-antiprotease imbalance and apoptosis. Oxidative stress is central to the pathogenesis of COPD, since it can directly damage lung structures and exacerbate the other mechanisms involved. The cellular and molecular events involved in such lung injury are believed to occur long before the clinical and functional expression of COPD. Although the use of bronchodilators is currently the principal treatment for COPD, bronchodilators have little or no effect on disease progression. A better understanding of the pathogenesis of COPD, together with renewed efforts in basic and clinical research, will allow the diagnosis of COPD at a pre-clinical stage and provide more appropriate monitoring of disease activity, as well as leading to the development of novel therapeutic agents that will effectively prevent the progression of the disease.


Translational systems approaches to the biology of inflammation and healing.
Inflammation is a complex, non-linear process central to many of the diseases that affect both developed and emerging nations. A systems-based understanding of inflammation, coupled to translational applications, is therefore necessary for efficient development of drugs and devices, for streamlining analyses at the level of populations, and for the implementation of personalized medicine. We have carried out an iterative and ongoing program of literature analysis, generation of prospective data, data analysis, and computational modeling in various experimental and clinical inflammatory disease settings. These simulations have been used to gain basic insights into the inflammatory response under baseline, gene-knockout, and drug-treated experimental animals for in silico studies associated with the clinical settings of sepsis, trauma, acute liver failure, and wound healing to create patient-specific simulations in polytrauma, traumatic brain injury, and vocal fold inflammation; and to gain insight into host-pathogen interactions in malaria, necrotizing enterocolitis, and sepsis. These simulations have converged with other systems biology approaches (e.g., functional genomics) to aid in the design of new drugs or devices geared towards modulating inflammation. Since they include both circulating and tissue-level inflammatory mediators, these simulations transcend typical cytokine networks by associating inflammatory processes with tissue/organ impacts via tissue damage/dysfunction. This framework has now allowed us to suggest how to modulate acute inflammation in a rational, individually optimized fashion. This plethora of computational and intertwined experimental/engineering approaches is the cornerstone of Translational Systems Biology approaches for inflammatory diseases.


Evaluation of the slope of the articular eminence and the transverse angle of the glenoid fossa in an Anatolian population.
The purpose of this study was to compare a computer-aided method specially programmed for the measurement of the posterior angle of the articular eminence with formerly used methods, to investigate the angulation differences at different depths of slices, and to evaluate correlation with the transverse angulation. Three slices (central, medial, and lateral) at various depths of the glenoid fossa belonging to 64 dry skulls and two measurement methods were used in this study. The angulation of the articular eminence were measured and the transverse angle of each fossa calculated. No statistical difference was found between the articular eminence results of the two methods. According to the results, the one factor ANOVA central slice was found to be statistically steeper than the other two slices (p < 0.05) (central = 60.33 +/- 10.19, medial = 58.26 +/- 8.6, lateral 58.28 +/- 10.1). No correlation was found between the transverse angle of the inclination of the posterior slope angulation. It was concluded that the computer-aided method is more reliable and accurate and is much easier to use when compared to the manual method. An additional important finding of this study is that the inclination of the articular eminence should be evaluated at various depths of the temporomandibular joint.


Novel Actions of Nonsteroidal Anti-Inflammatory Drugs on Vascular Ion Channels: Accounting for Cardiovascular Side Effects and Identifying New Therapeutic Applications.
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used medications for the treatment of both acute and chronic pain. Selective cyclooxygenase-2 (COX-2) inhibitors, such as celecoxib (Celebrex(®)), rofecoxib (Vioxx(®)), and diclofenac, have been among the most widely prescribed NSAIDs because they prevent the generation of prostaglandins involved in inflammation and pain, but avoid some of the gastrointestinal complications associated with less selective COX-1/COX-2 inhibitors. In 2004, rofecoxib (Vioxx(®)) was voluntarily withdrawn from the market because of adverse cardiovascular side effects. This led to an explosion of research into the cardiovascular effects of the 'coxibs', which revealed differential cardiovascular risk profiles among the members of this drug class. The differential risk profiles may relate to the tendency of some of the drugs to elevate blood pressure (BP). An important component of BP regulation is dependent on the contractile state of vascular smooth muscle cells (VSMCs), which is controlled to a large extent by the activities of KCNQ (Kv7 family) potassium channels and L-type calcium channels. Our recently published data indicate that celecoxib, but not rofecoxib or diclofenac, at therapeutically relevant concentrations, acts as a Kv7 potassium channel activator and a calcium channel blocker, causing relaxation of VSMCs and decreasing vascular tone. These vasorelaxant ion channel effects may account for the differential cardiovascular risk profiles among the different COX-2 inhibitors. We further speculate that these properties may be exploited for therapeutic benefit in the treatment of cardiovascular diseases or other medical conditions.


Sorting at embryonic boundaries requires high heterotypic interfacial tension.
The establishment of sharp boundaries is essential for segregation of embryonic tissues during development, but the underlying mechanism of cell sorting has remained unclear. Opposing hypotheses have been proposed, either based on global tissue adhesive or contractile properties or on local signalling through cell contact cues. Here we use ectoderm-mesoderm separation in Xenopus to directly evaluate the role of these various parameters. We find that ephrin-Eph-based repulsion is very effective at inducing and maintaining separation, whereas differences in adhesion or contractility have surprisingly little impact. Computer simulations support and generalise our experimental results, showing that a high heterotypic interfacial tension between tissues is key to their segregation. We propose a unifying model, in which conditions of sorting previously considered as driven by differential adhesion/tension should be viewed as suboptimal cases of heterotypic interfacial tension.The mechanisms that cause different cells to segregate into distinct tissues are unclear. Here the authors show in Xenopus that formation of a boundary between two tissues is driven by local tension along the interface rather than by global differences in adhesion or cortical contractility.


LRIG1 and squamous epithelial uterine cervical cancer: correlation to prognosis, other tumor markers, sex steroid hormones, and smoking.
The aim is to evaluate LRIG1 as a prognosis predictor and correlations to cofactors in squamous cell cervical cancer. LRIG1 expression was studied in 128 cervical carcinomas and was compared with expression of nine other tumor markers. Smoking history was registered and pretreatment serum estradiol and progesterone levels were evaluated in 79 women. At clinical stage IB, 58% of the tumors showed LRIG1 expression, but there was a decline by increasing stage (33% in stage IV). Ninety percent of women with stage IB cancer and LRIG1 positivity survived, as compared to 64% without expression (P = 0.02). LRIG1 expression did not predict prognosis in advanced stages, but in stage IIA there was a marked relative difference, with 75% survival in tumors expressing LRIG1, as compared to 43% in those without. No correlation was found between LRIG1 and the other nine tumor markers studied. A high serum progesterone and smoking correlated to absent LRIG1 expression. We conclude that LRIG1 appears to be a significant prognosis predictor in early-stage cervical cancer, independent of the other tumor markers that were studied. Diminished expression in advanced stages and the inverse correlation to serum progesterone and smoking indicates that LRIG1 is a tumor suppressor in cervix.


Sweet's Syndrome and relapsing polychondritis signal myelodysplastic syndrome.
The emergence of certain skin conditions belonging to the group of mucocutaneous paraneoplastic syndromes may indicate the future appearance of a previously unknown malignancy. Sweet's Syndrome and relapsing polychondritis are included in this group. Sweet's Syndrome and relapsing polychondritis are very rarely found together in the same patient. This dual occurrence is more commonly found in cancer patients with associated hematological malignancies. We report the case of a 79 year-old male with Sweet's Syndrome and relapsing polychondritis, who was subsequently diagnosed with a myelodysplastic syndrome.


Local and Landscape Effects on Carrion-Associated Rove Beetle (Coleoptera: Staphylinidae) Communities in German Forests.
Intensification of anthropogenic land use is a major threat to biodiversity and thus to essential ecosystem services provided by insects. Rove beetles (Coleoptera: Staphylinidae), which react sensitively to habitat changes, are species-rich colonizers of vertebrate cadavers and contribute to the important ecosystem service of carrion decomposition. The unveiling of anthropogenic and environmental drivers that modify carrion-associated rove beetle communities should improve our understanding of the plasticity of cadaver decay. We report the presence of 80 rove beetle species on 65 decomposing piglet cadavers at forest sites characterized by a gradient of management intensity across three geographic regions in Germany. Local and landscape drivers were revealed that shape beetle abundance, diversity, and community composition. Forest management and regions affect rove beetle abundance, whereas diversity is influenced by local habitat parameters (soil pH, litter cover) and regions. The community composition of rove beetles changes with management intensification by promoting generalist species. Regarding single species, Philonthus decorus and Anotylus mutator are linked to unmanaged forests and Ontholestes tessellatus to highly used forest stands. The spatial information provided about carrion-associated rove beetle communities in German forests is not only of carrion-ecological but also of forensic entomological interest.


Broaching partially-shared identities: Critically interrogating power and intragroup dynamics in counseling practice with trans people of Color.
Background: Much of the literature on transgender and nonbinary (TGNB) experiences in counseling focuses on White experiences with few recommendations for trans people of Color (TPOC). Research suggests mental health care providers lack intersectional sensitivity with TPOC, lack knowledge of TGNB issues and engage in microaggressive behaviors, notably with Queer-identified clinicians. Aim: To explore issues of power and privilege in the counseling relationship with Queer-identified clinicians and apply the multidimensional model of broaching behavior with TGNB clients of Color. Method: A critical review of conceptual and empirical literature focusing on the interaction and impact of client and clinician race, gender, and sexual/affectional identities in the counseling relationship is presented. Informed by the authors' counseling experiences and respective positionalities as a Black Queer ciswoman and a White Queer transman, the multidimensional model of broaching behavior is applied to a composite case vignette. Results: The model provides a practical tool to facilitate critical conversations of power, privilege and identity in the counseling relationship. Conclusion: With a dearth of scholarship addressing the role of cisgender or White privilege in the counseling relationship, this article outlines strategies to broach issues partially-shared identities with TGNB clients of Color. Recommendations for culturally informed counseling practice, supervision and research are also provided.


Characterization of neuron-specific huntingtin aggregates in human huntingtin knock-in mice.
Huntington's disease (HD) is caused by a mutation causing expanded polyglutamine tracts in the N-terminal fragment of huntingtin. A pathological hallmark of HD is the formation of aggregates in the striatal neurons. Here we report that ageing human huntingtin knock-in mice expressing mutant human huntingtin contained neuronal huntingtin aggregates, as revealed by immunohistochemical analysis. In heterozygous knock-in mice with 77 CAG repeats, aggregates of N-terminal fragments of huntingtin were specifically formed in nuclei and neuropils in the striatal projection neurons, and in neuropils in their projection regions. This aggregate formation progressed depending on age, became interacted with proteolytic or chaperone proteins, and occurred most prominently in the nucleus accumbens. These mutant mice demonstrated abnormal aggressive behavior. In homozygous knock-in mice, heavy deposits of intranuclear and neuropil aggregates were detected, which extended to other regions; and characteristic large perikaryal aggregates were also found in the affected neurons. However, cell death was not observed among the striatal and affected neurons of these mutant mice. Our results indicate that the polyglutamine aggregates do not necessarily correlate with neuronal death. These human huntingtin knock-in mice should be useful to provide an effective therapeutic approach against HD.


Computed tomography manifestations of brucellosis of the sternoclavicular joint.
Computed tomography (CT) in three patients with sternoclavicular brucellosis revealed the following features: soft-tissue mass centred around the joint, sclerosis with or without lysis of the periarticular bone, and destruction and irregularity of the cortex of the sternal and clavicular articular surfaces. The CT features, in the appropriate clinical setting, should help in making the correct diagnosis and managing this serious but rare manifestation of brucellosis.


Spanning QTAIM topology phase diagrams of water isomers W4, W5 and W6.
Structural and chemical properties of the small water clusters W(4), W(5) and W(6) are investigated with the theory of atoms and molecules (QTAIM). For the W(4), W(5) and W(6) clusters, nine, fourteen and twenty-seven conformers, respectively, have been analyzed. For the W(4), W(5) and W(6) clusters one, two and three of these structures, respectively, have not been reported before. We then proceed to extend the W(4), W(5) and W(6) water cluster topology space using QTAIM; the Poincaré-Hopf topological sum rules are applied to create rules to identify the spanning set of conformer topologies, this includes finding three, ten and eight new distinct topologies that satisfy the Poincaré-Hopf relation for W(4), W(5) and W(6) respectively. The topological stability of degenerate solutions to the Poincaré-Hopf relation is compared by evaluating the proximity to rupturing of critical points of the gradient vector field of the charge density. We introduce a QTAIM topology space to replace the inconsistent use of Euclidean geometry to determine whether a cluster is 1-, 2- or 3-D. We show from the topology of the charge density that the conformers of the W(4), W(5) clusters are more energetically stable in less compact, planar forms, conversely the conformers of W(6) are more energetically stable with compact 3-D topologies. Quantifying the degree of covalent character in the hydrogen bonding for the W(4), W(5) and W(6) clusters independently verifies this finding. Differences in simple rules for the number of hydrogen bonds obeying the Bernal-Fowler ice rules between W(4), W(5) and W(6) reflect the transition from 2-D to 3-D structures being more energetically stable. In addition, we identify a new class of O-O bonding interactions that are up to 48% longer than the inter-nuclear separation and appear to be failed hydrogen bonds.


Biosorption of copper and zinc by Cymodocea nodosa.
The adsorption of the two metal ions Cu and Zn in a single-component system by Cymodocea nodosa, a brown alga, under different pH conditions was investigated. The solution pH significantly affected the exhibited uptake, being maximum at a pH value of 4.5. Multi-component mixture biosorption in aqueous solutions is also reported. A comparison was made between the single-component saturation uptake and the multi-component uptakes. To evaluate the two-metal sorption system performance, simple isotherm curves had to be replaced by three-dimensional sorption isotherm surfaces. In order to describe the isotherm surfaces mathematically, three Langmuir-type models were evaluated. The isotherms indicate a competitive uptake with Cu being preferentially adsorbed. In addition, different tests were carried out to compare the process efficiency working continuously in small columns.


The receptor for advanced glycation end products and acute lung injury/acute respiratory distress syndrome.
The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor and evolutionary member of the immunoglobulin superfamily that is involved in the host response to infection, injury, and inflammation. It exists in two forms: membrane-bound and soluble forms (sRAGE). RAGE recognizes a variety of ligands and, via a receptor-driven signaling cascade, activates the transcription factor NF-κB, leading to the expression of proinflammatory cytokines. The soluble form, sRAGE, is a decoy receptor and competitively inhibits membrane RAGE activation. RAGE is constitutively expressed abundantly in the lung under basal conditions. This expression is enhanced during inflammatory states such as with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This review summarizes the characteristics of RAGE, RAGE isoforms, RAGE ligands, and signaling pathways in the pathogenesis of ALI and ARDS. Additionally, the review explores the potential of RAGE as an important therapeutic target in ALI/ARDS.


Determination of Ultratrace Level 135Cs and 135Cs/137Cs Ratio in Small Volume Seawater by Chemical Separation and Thermal Ionization Mass Spectrometry.
The atomic ratio of 135Cs/137Cs is a powerful fingerprint for distinguishing the source terms of radioactive contamination and tracing the circulation of water masses in the ocean. However, the determination of the 135Cs/137Cs ratio is very difficult due to the ultratrace level of 135Cs (<0.02 mBq/m3) and 137Cs (<2 Bq/m3) in the ordinary seawater samples. In this work, a sensitive method was developed for determination of 135Cs concentration and 135Cs/137Cs ratio in seawater using chemical separation combined with thermal ionization mass spectrometry (TIMS) measurement. Cesium was first preconcentrated from seawater using ammonium molybdophosphate-polyacrylonitrile column chromatography and then purified using cation exchange chromatography to remove the interferences. With this method, decontamination factors of 6.0 × 106 for barium and 1800 for rubidium and a chemical yield of more than 60% for cesium were achieved. By using glucose as an activator, the ionization efficiency of cesium was significantly improved to 50.6%, and a constant high current of Cs+ (20 V) can be maintained for more than 180 min, which ensures sensitive and reliable measurement of low level 135Cs and 137Cs. Detection limits of 4.0 × 10-17 g/L for both 135Cs and 137Cs for 200 mL seawater were achieved, which enables the accurate determination of 135Cs concentration and 135Cs/137Cs ratio in a small volume of seawater samples (<200 mL). The developed method has been validated by analysis of seawater reference material IAEA-443. Seawater samples collected from the Greenland Sea, Baltic Sea, and Danish Straits have been successfully analyzed for 135Cs concentrations and 135Cs/137Cs ratios, and the results showed that 135Cs concentrations in the seawater of the Baltic Sea is much higher than that in the Greenland Sea, which is attributed to the high deposition of Chernobyl accident derived radiocesium in the Baltic Sea region.


Actin-containing sera from patients with adult respiratory distress syndrome are toxic to sheep pulmonary endothelial cells.
Actin released from damaged cells after a variety of tissue injuries appears to be involved in multiple organ dysfunction syndrome. Under experimental conditions, when the quantity of actin present in plasma is made to exceed the protective capacity of the actin-scavenging mechanism, microembolism and pulmonary vascular angiopathy have been noted in rats. It remains to be determined whether this injury is a result of a direct toxic effect or occurs indirectly via platelet activation or fibrin interactions. We examined the effect of sera from patients with adult respiratory distress syndrome (ARDS), as well as G-actin added to normal serum, on the viability, morphology, and function of cultured sheep pulmonary artery endothelial cells (SPAEC). Both patient sera and normal sera to which actin was added were toxic in the cell culture model; this toxicity could be abrogated, at least partially, by preincubation with gelsolin, which is known to complex with actin. A significant portion of the toxicity of sera from patients with ARDS was sensitive to heat (56 degrees C), suggesting an important role of complement. Sera from patients with ARDS were shown to contain filaments of F-actin by immunoblot and rhodamine phalloidin staining after ultracentrifugation. Thus, saturation of the actin-scavenging system by addition of exogenous G-actin to plasma produces direct pulmonary endothelial cell injury. Furthermore, plasma from patients with ARDS secondary to bacterial pneumonia is toxic to SPAEC, and a small but significant contributory role of actin is apparent in these studies.


cGMP-dependent channel protein from photoreceptor membranes: single-channel activity of the purified and reconstituted protein.
The cGMP-dependent channel protein has been purified from bovine rod photoreceptor membranes and incorporated into planar lipid membranes. At low divalent cation concentrations, cGMP stimulated single-channel current fluctuations. The probability Po of the channel being open strongly depended on the cGMP concentration (EC50 = 31 microM; Hill coefficient, n = 2.3); whereas the single-channel conductance (lambda = 26 pS) was independent of the agonist concentration. The agonist-stimulated increase in the probability of an open channel was largely due to shorter closed times and, to a lesser extent, due to the channel staying open for a longer time. The current-voltage relationship of the single open channel deviated from ohmic behavior, and the open probability decreased at more negative membrane potentials. The rectification of the macroscopic cGMP-induced current in artificial bilayers that contained many channel copies can be accounted for by the voltage dependence of channel gating together with the nonlinearity of the current-voltage curve of an open channel. Current fluctuations exhibited a variety of sublevels, indicating that the channel may exist in more than one conductive state.


Traumatic subaxial cervical facet subluxation and dislocation: epidemiology, radiographic analyses, and risk factors for spinal cord injury.
Distractive flexion injuries (DFIs) of the subaxial cervical spine are major contributors to spinal cord injury (SCI). Prompt assessment and early intervention of DFIs associated with SCI are crucial to optimize patient outcome; however, neurologic examination of patients with subaxial cervical injury is often difficult, as patients commonly present with reduced levels of consciousness. Therefore, it is important to establish potential associations between injury epidemiology and radiographic features, and neurologic involvement. The aims of this study were to describe the epidemiology and radiographic features of DFIs presenting to a major Australian tertiary hospital and to identify those factors predictive of SCI. The agreement and repeatability of radiographic measures of DFI severity were also investigated. This is a combined retrospective case-control and reliability-agreement study. Two hundred twenty-six patients (median age 40 years [interquartile range = 34]; 72.1% male) who presented with a DFI of the subaxial cervical spine between 2003 and 2013 were reviewed. The epidemiology and radiographic features of DFI, and risk factors for SCI were identified. Inter- and intraobserver agreement of radiographic measurements was evaluated. Medical records, radiographs, and computed tomography and magnetic resonance imaging scans were examined, and the presence of SCI was evaluated. Radiographic images were analyzed by two consultant spinal surgeons, and the degree of vertebral translation, facet apposition, spinal canal occlusion, and spinal cord compression were documented. Multivariable logistic regression models identified epidemiology and radiographic features predictive of SCI. Intraclass correlation coefficients (ICCs) examined inter- and intraobserver agreement of radiographic measurements. The majority of patients (56.2%) sustained a unilateral (51.2%) or a bilateral facet (48.8%) dislocation. The C6-C7 vertebral level was most commonly involved (38.5%). Younger adults were over-represented among motor-vehicle accidents, whereas falls contributed to a majority of DFIs sustained by older adults. Greater vertebral translation, together with lower facet apposition, distinguished facet dislocation from subluxation. Dislocation, bilateral facet injury, reduced Glasgow Coma Scale, spinal canal occlusion, and spinal cord compression were predictive of neurologic deficit. Radiographic measurements demonstrated at least a "moderate" agreement (ICC>0.4), with most demonstrating an "almost perfect" reproducibility. This large-scale cohort investigation of DFIs in the cervical spine describes radiographic features that distinguish facet dislocation from subluxation, and associates highly reproducible anatomical and clinical indices to the occurrence of concomitant SCI.


The adaptor protein Lad associates with the G protein beta subunit and mediates chemokine-dependent T-cell migration.
Lck-interacting adaptor protein/Rlk/Itk-binding protein (Lad/RIBP) was previously identified as an adaptor protein involved in TCR-mediated T-cell activation. To elucidate the functions of Lad further, we here performed yeast 2-hybrid screening using Lad as bait and discovered that the G protein beta subunit (G beta) is a Lad-binding partner. Since the most well-known G protein-coupled receptor in T cells is the chemokine receptor, we investigated whether Lad is involved in chemokine signaling. We found that, upon chemokine treatment, Lad associated with G beta in Jurkat T cells. Furthermore, ectopic expression of dominant-negative Lad or the reduction of endogenous Lad expression by siRNA impaired the chemokine-induced migration of T cells, indicating that Lad is required for chemokine-induced T-cell migration. Subsequent investigation of the signaling pathways revealed that, in response to chemokine, Lad associated with the tyrosine kinases Lck and Zap-70 and that Lad was essential for the activation of Zap-70. Moreover, Lad was required for the chemokine-dependent tyrosine phosphorylation of focal adhesion molecules that included Pyk2 and paxillin. Taken together, these data show that, upon chemokine stimulation, Lad acts as an adaptor protein that links the G protein beta subunit to the tyrosine kinases Lck and Zap-70, thereby mediating T-cell migration.


Closing the Social Class Achievement Gap for First-Generation Students in Undergraduate Biology.
Many students start college intending to pursue a career in the biosciences, but too many abandon this goal because they struggle in introductory biology. Interventions have been developed to close achievement gaps for underrepresented minority students and women, but no prior research has attempted to close the gap for first-generation students, a population that accounts for nearly a fifth of college students. We report a values affirmation intervention conducted with 798 U.S. students (154 first-generation) in an introductory biology course for majors. For first-generation students, values affirmation significantly improved final course grades and retention in the second course in the biology sequence, as well as overall GPA for the semester. This brief intervention narrowed the achievement gap between first-generation and continuing generation students for course grades by 50% and increased retention in a critical gateway course by 20%. Our results suggest that educators can expand the pipeline for first-generation students to continue studying in the biosciences with psychological interventions.


Assessing the Flexibility of the Prochlorosin 2.8 Scaffold for Bioengineering Applications.
Cyclization is a common strategy to confer proteolytic resistance to peptide scaffolds. Thus, cyclic peptides have been the focus of extensive bioengineering efforts. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a superfamily of peptidic natural products that often contain macrocycles. In the RiPP family of lanthipeptides, macrocyclization is accomplished through formation of thioether cross-links between cysteines and dehydrated serines/threonines. The recent production of lanthipeptide libraries and development of methods to display lanthipeptides on yeast or phage highlights their potential for bioengineering and synthetic biology. In this regard, the prochlorosins are especially promising as the corresponding class II lanthipeptide synthetase ProcM matures numerous precursor peptides with diverse core peptide sequences. To facilitate future bioengineering projects, one of its native substrates, ProcA2.8, was subjected in this study to in-depth mutational analysis to test the limitations of ProcM-mediated cyclization. Alanine scan mutagenesis was performed on all residues within the two rings, and multiple prolines were introduced at various positions. Moreover, mutation, deletion, and insertion of residues in the region linking the two lanthionine rings was tested. Additional residues were also introduced or deleted from either ring, and inversion of ring forming residues was attempted to generate diastereomers. The findings were used for epitope grafting of the RGD integrin binding epitope within prochlorosin 2.8, resulting in a low nanomolar affinity binder of the αvβ3 integrin that was more stable toward proteolysis and displayed higher affinity than the linear counterpart.


Platelet-vessel wall interaction in health and disease.
Upon vessel wall injury platelets rapidly adhere to the exposed subendothelial matrix which is mediated by several cellular receptors present on platelets or endothelial cells and various adhesive proteins such as von Willebrand factor, collagen and fibrinogen. Subsequent platelet activation results in the recruitment of additional platelets and the generation of platelet aggregates forming a stable platelet plug. In addition, activated platelets form a strong link between primary and secondary haemostasis as they provide the phospholipid surface that is necessary for the assembly of activated coagulation factor complexes required for thrombin generation. Other than the physiological function acting as a first line of defence against bleeding, platelets may also contribute to pathological thrombus formation. Platelets play an important role in thromboembolic diseases and may contribute to the formation of occlusive thrombi which can lead to severe complications such as stroke or myocardial infarction. Improved understanding of the respective roles of the various cellular receptors, adhesive proteins and regulatory proteins involved in platelet-vessel wall interaction and subsequent thrombus formation, both under physiological and pathological conditions, has led to the development and investigation of a broad range of antiplatelet drugs. This review provides an overview of the current knowledge on the mechanisms involved in the interaction between platelets and vascular endothelium and discusses recent advancements in the development of drugs interfering with platelet-vessel wall interaction at various stages of thrombus formation.


Sarcopenia increases the risk for mortality in patients who undergo amputation for diabetic foot.
Although there have been reports that diabetes affects the prevalence of sarcopenia, no studies have examined the relationship between sarcopenia and mortality in patients undergoing leg amputation. The purpose of this study is to determine whether sarcopenia affects the mortality rate of patients undergoing diabetic foot amputation. From among patients who underwent limb amputation for diabetes complications, this study included 167 patients who underwent abdominal CT within 1 year of amputation. We defined sarcopenia using sex-specific cut-off points for the L3 skeletal muscle index. The 5-year survival rate was analyzed. All patients were divided into two groups and compared according to the presence of sarcopenia. The mortality rate according to sarcopenia was assessed via the Kaplan-Meier method and log-rank test. Uni- and multivariate Cox regression analyses evaluated factors associated with survival rate. Among the total of 167 patients, the overall 5-year mortality rate was 52.7%. Of the 112 patients with sarcopenia, the 5-year mortality rate was 60.7%. Of the 55 patients without sarcopenia, the 5-year mortality rate was 36.4%. Kaplan-Meier analysis showed a high mortality of the sarcopenia group in the univariate (p = 0.016) and multivariate (p = 0.047) analysis. Our study is the first to analyze the relationship between diabetic amputation and sarcopenia. Sarcopenia increases the risk of mortality in patients who undergo amputation for diabetic foot. Therefore, patients with diabetes should be careful to prevent sarcopenia with enough regular exercise as well as prevent diabetic foot disease.


[Association of the incidence of type 1 diabetes mellitus with environmental factors in Chile during the period 2000-2007].
Pollution and viral infections could be associated with the incidence of type 1 diabetes mellitus. To look for associations between the temporal patterns of Type 1 Diabetes Mellitus (T1D) in infants younger than the age of 15 years, and environmental factors, such as air pollution and viruses. Data registries from hospitals, emergency services, and the Infantile Diabetes Foundation were reviewed, corresponding to children aged less than 15 years, who received their first insulin injection between 2000 and 2007. The incidence of type 1 diabetes was computed for each epidemiological week. Environmental ozone and particulate matter rates for each week were obtained from Environmental services. Rates of influenza and respiratory syncytial virus infections were obtained from the epidemiological department of the Ministry of Health. An ecological Bayesian Poisson regression model was fitted, introducing the covariates, lagged covariates and errors, to estimate the incidence by epidemiological week. Three factors were significant by the proposed model: particulate matter PPM 2.5 (relative risk (RR): 1.003) lagged by two weeks, influenza (RR: 0.1808) and RSV (RR: 1.021). Trends and seasonality were clearly controlled by these covariates, considering the epidemiological week as a counting period. These results show that environmental factors could be related to peaks of type 1 diabetes incidence.


Microbial fuel cells for in-field water quality monitoring.
The need for water security pushes for the development of sensing technologies that allow online and real-time assessments and are capable of autonomous and stable long-term operation in the field. In this context, Microbial Fuel Cell (MFC) based biosensors have shown great potential due to cost-effectiveness, simplicity of operation, robustness and the possibility of self-powered applications. This review focuses on the progress of the technology in real scenarios and in-field applications and discusses the technological bottlenecks that must be overcome for its success. An overview of the most relevant findings and challenges of MFC sensors for practical implementation is provided. First, performance indicators for in-field applications, which may diverge from lab-based only studies, are defined. Progress on MFC designs for off-grid monitoring of water quality is then presented with a focus on solutions that enhance robustness and long-term stability. Finally, calibration methods and detection algorithms for applications in real scenarios are discussed.


A high-throughput-compatible FRET-based platform for identification and characterization of botulinum neurotoxin light chain modulators.
Botulinum neurotoxin (BoNT) is a potent and potentially lethal bacterial toxin that binds to host motor neurons, is internalized into the cell, and cleaves intracellular proteins that are essential for neurotransmitter release. BoNT is comprised of a heavy chain (HC), which mediates host cell binding and internalization, and a light chain (LC), which cleaves intracellular host proteins essential for acetylcholine release. While therapies that inhibit toxin binding/internalization have a small time window of administration, compounds that target intracellular LC activity have a much larger time window of administrations, particularly relevant given the extremely long half-life of the toxin. In recent years, small molecules have been heavily analyzed as potential LC inhibitors based on their increased cellular permeability relative to larger therapeutics (peptides, aptamers, etc.). Lead identification often involves high-throughput screening (HTS), where large libraries of small molecules are screened based on their ability to modulate therapeutic target function. Here we describe a FRET-based assay with a commercial BoNT/A LC substrate and recombinant LC that can be automated for HTS of potential BoNT inhibitors. Moreover, we describe a manual technique that can be used for follow-up secondary screening, or for comparing the potency of several candidate compounds.


Evolution of Salmonella-Host Cell Interactions through a Dynamic Bacterial Genome.
Salmonella Typhimurium has a broad arsenal of genes that are tightly regulated and coordinated to facilitate adaptation to the various host environments it colonizes. The genome of Salmonella Typhimurium has undergone multiple gene acquisition events and has accrued changes in non-coding DNA that have undergone selection by regulatory evolution. Together, at least 17 horizontally acquired pathogenicity islands (SPIs), prophage-associated genes, and changes in core genome regulation contribute to the virulence program of Salmonella. Here, we review the latest understanding of these elements and their contributions to pathogenesis, emphasizing the regulatory circuitry that controls niche-specific gene expression. In addition to an overview of the importance of SPI-1 and SPI-2 to host invasion and colonization, we describe the recently characterized contributions of other SPIs, including the antibacterial activity of SPI-6 and adhesion and invasion mediated by SPI-4. We further discuss how these fitness traits have been integrated into the regulatory circuitry of the bacterial cell through cis-regulatory evolution and by a careful balance of silencing and counter-silencing by regulatory proteins. Detailed understanding of regulatory evolution within Salmonella is uncovering novel aspects of infection biology that relate to host-pathogen interactions and evasion of host immunity.


A changing trend in eruption age and pattern of first deciduous tooth: correlation to feeding pattern.
Feeding mode during infancy and its effect on deciduous tooth appearance in oral cavity in two generations and among genders. Study aimed to compare and correlate times and patterns of deciduous tooth eruption in breastfeeding (OBF), partial breastfeeding (PBF) and spoon feeding (SF) infants and initiation of semisolid food feeding (SSF) in infants. It also aimed to address the variations in the time of eruption of first deciduous tooth and its pattern in two generations who had more than a decade of difference in ages. An open-ended questionnaire study was conducted on mothers of 265 patients from two groups, generation 1 (G1)- adults who were aged 20-35 years and second group, generation 2 (G2) - children who were below 5 years of age . A statistical significance was observed with respect to age, gender, generations, and frequency of breastfeeding, partial breastfeeding and time of initiation of semisolid food. There is a delayed eruption of teeth in present generation. For girls, it occurs at age of 7.88 months and for boys, it occurs at the age of 8.08 months.


Past, present, and future of cervical arthroplasty.
Cervical arthroplasty was developed in an attempt to maintain cervical motion and potentially to avoid or minimize adjacent-segment degeneration. If cervical arthroplasty is successful, the long-term results of surgery for cervical disc disease should improve. However, problems associated with cervical arthroplasty have been reported: these include kyphosis, heterotopic ossification-induced motion limitation, no motion preservation even at the index level, and a higher revision rate in a limited number of cases compared with anterior cervical discectomy and fusion (ACDF). In addition, for degenerative cervical disc disorders, the risk of developing adjacent segment degeneration more than 2 years after surgery is reportedly similar for ACDF and cervical arthroplasty. Cervical disc arthroplasty is an emerging motion-sparing technology and is currently undergoing evaluation in many countries as an alternative to arthrodesis for the treatment of cervical radiculopathy and myelopathy. The decision whether to use arthrodesis or arthroplasty is a difficult one. The achievement of good prosthetic performance demands exacting implantation techniques to ensure correct placement. This fact underlines the increasing importance of special instrumentation and surgical skills that involve an understanding of prosthetic lubrication, wear, and biologic effects and familiarity with currently available information regarding kinematics, basic science, testing, and early clinical results. Fortunately, a number of devices are at the late preclinical study stage or at the early clinical trial stage, and results in many cases are promising. In the near future, it is likely that new designs will be produced to replace spinal discs totally or partially in a pathologic entity-specific manner.


The role of public exposure in moral and nonmoral shame and guilt.
Although scholarly traditions assume that shame results more from the public exposure of a transgression or incompetence than guilt does, this distinction has little empirical support. Four studies, using either undergraduate participants' responses to hypothetical scenarios, their remembered experiences, or the coding of literary passages, reexamined this issue. Supporting traditional claims, public exposure of both moral (transgressions) and nonmoral (incompetence) experiences was associated more with shame than with guilt. Shame was also more strongly linked with nonmoral experiences of inferiority, suggesting 2 core features of shame: its links with public exposure and with negative self-evaluation. The distinctive features of guilt included remorse, self-blame, and the private feelings associated with a troubled conscience.


Developments in toxicogenomics: understanding and predicting compound-induced toxicity from gene expression data.
The toxicogenomics field aims to understand and predict toxicity by using 'omics' data in order to study systems-level responses to compound treatments. In recent years there has been a rapid increase in publicly available toxicological and 'omics' data, particularly gene expression data, and a corresponding development of methods for its analysis. In this review, we summarize recent progress relating to the analysis of RNA-Seq and microarray data, review relevant databases, and highlight recent applications of toxicogenomics data for understanding and predicting compound toxicity. These include the analysis of differentially expressed genes and their enrichment, signature matching, methods based on interaction networks, and the analysis of co-expression networks. In the future, these state-of-the-art methods will likely be combined with new technologies, such as whole human body models, to produce a comprehensive systems-level understanding of toxicity that reduces the necessity of in vivo toxicity assessment in animal models.


Long-term survival advantage of MACOP-B over CHOP in intermediate-grade non-Hodgkin's lymphoma. The Australian and New Zealand Lymphoma Group.
The initial publication of the results of the Australian and New Zealand Lymphoma Group (ANZLG) randomized controlled trial comparing MACOP-B and CHOP in patients with intermediate-grade non-Hodgkin's lymphoma (NHL) showed equivalent complete response rates, time to treatment failure, and survival. Here we report the long-term follow-up of the 236 patients entered on that study to determine if there were any long-term advantages or disadvantages associated with MACOP-B. Two hundred thirty-six eligible patients were randomized between October 1986 and June 1991. The median duration of follow-up has been extended from 3.2 years in our previous publication to 6.5 years. As previously reported, the complete response (CR) rate for MACOP-B and CHOP chemotherapy was 51% and 59%, respectively. The estimated failure-free survival rate for MACOP-B and CHOP patients was 42% and 30%, respectively, at 5 years (P = 0.045) and 37% and 25%, respectively, at 8 year (P = 0.057). The estimated overall survival rate at 5 years was 54% for MACOP-B and 41% for CHOP patients (P = 0.035) and at 8 years was 45% and 36%, respectively (P = 0.16). With this extended follow-up, we have shown a long-term survival advantage for MACOP-B chemotherapy over standard CHOP in patients with intermediate-grade non-Hodgkin's lymphoma.


High expression of DNA methyltransferases in primary human medulloblastoma.
Epigenetic alterations have been implicated in cancer development. DNA methylation modulates gene expression, which is catalyzed by DNA methyltransferases (DNMTs). The objective of our study was to evaluate expression of DNMTs in medulloblastoma and analyze its correlation with clinical features. Nuclear expression of DNMT1, DNMT3A and DNMT3B was analyzed in human primary medulloblastoma of 44 patients using immunohistochemistry. Correlation of expression of DNMT levels with classical histological subtypes, novel molecular subgroups and survival of patients was analyzed. Elevated expression of DNMT1, DNMT3A and DNMT3B was observed in 63.64%, 68.18% and 72.73% of all cases, respectively. None of them showed a correlation with classical histology or survival. Concerning molecular subtypes, significantly higher expression of DNMT1 was observed in the SHH group compared to non-SHH samples (p = 0.02), but without significant difference in DNMT3A or DNMT3B levels between any subtypes. In conclusion, DNMT1, DNMT3A and DNMT3B are highly expressed in human medulloblastoma samples, suggesting that promoter hypermethylation may play a role in medulloblastoma development. Demethylation of tumor suppressor gene promoters may be considered as a possible future target in therapy of medulloblastoma.


Providers and types of spiritual care during serious illness.
Patients and palliative care experts endorse the importance of spiritual care for seriously ill patients and their families. However, little is known about spiritual care during serious illness, and whether it satisfies patients' and families' needs. The objective of this study was to describe spiritual care received by patients and families during serious illness, and test whether the provider and the type of care is associated with satisfaction with care. Cross-sectional interview with 38 seriously ill patients and 65 family caregivers about spiritual care experiences. The 103 spiritual care recipients identified 237 spiritual care providers; 95 (41%) were family or friends, 38 (17%) were clergy, and 66 (29%) were health care providers. Two-thirds of spiritual care providers shared the recipient's faith tradition. Recipients identified 21 different types of spiritual care activities. The most common activity was help coping with illness (87%) and the least common intercessory prayer (4%). Half of recipients were very or somewhat satisfied with spiritual care, and half found it very helpful for facilitating inner peace and meaning making. Satisfaction with spiritual care did not differ by provider age, race, gender, role, or frequency of visits. Types of care that helped with understanding or illness coping were associated with greater satisfaction with care. Seriously ill patients and family caregivers experience spiritual care from multiple sources, including health care providers. Satisfaction with this care domain is modest, but approaches that help with understanding and with coping are associated with greater satisfaction.


Steady oscillations in aggregation-fragmentation processes.
We report surprising steady oscillations in aggregation-fragmentation processes. Oscillating solutions are observed for the class of aggregation kernels K_{i,j}=i^{ν}j^{μ}+j^{ν}i^{μ} homogeneous in masses i and j of merging clusters and fragmentation kernels, F_{ij}=λK_{ij}, with parameter λ quantifying the intensity of the disruptive impacts. We assume a complete decomposition (shattering) of colliding partners into monomers. We show that an assumption of a steady-state distribution of cluster sizes, compatible with governing equations, yields a power law with an exponential cutoff. This prediction agrees with simulation results when θ≡ν-μ<1. For θ=ν-μ>1, however, the densities exhibit an oscillatory behavior. While these oscillations decay for not very small λ, they become steady if θ is close to 2 and λ is very small. Simulation results lead to a conjecture that for θ<1 the system has a stable fixed point, corresponding to the steady-state density distribution, while for any θ>1 there exists a critical value λ_{c}, such that for λ<λ_{c}, the system has an attracting limit cycle. This is rather striking for a closed system of Smoluchowski-like equations, lacking any sinks and sources of mass.


Attention: reaction time and accuracy reveal different mechanisms.
The authors propose that there are 2 different mechanisms whereby spatial cues capture attention. The voluntary mechanism is the strategic allocation of perceptual resources to the location most likely to contain the target. The involuntary mechanism is a reflexive orienting response that occurs even when the spatial cue does not indicate the probable target location. Voluntary attention enhances the perceptual representation of the stimulus in the cued location relative to other locations. Hence, voluntary attention affects performance in experiments designed around both accuracy and reaction time. Involuntary attention affects a decision as to which location should be responded to. Because involuntary attention does not change the perceptual representation, it affects performance in reaction time experiments but not accuracy experiments. The authors obtained this pattern of results in 4 different versions of the spatial cuing paradigm.


Factors that influence morbidity and mortality in severe preeclampsia, eclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome.
To evaluate the prognostic factors affecting morbidity and mortality in severe preeclampsia, eclampsia and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome cases. We retrospectively evaluated, 2245 cases who delivered in the Department of Obstetrics and Gynecology, Faculty of Medicine, Cukurova University, Turkey between January and December 2002. Ninety-three cases had severe preeclampsia, 26 cases eclampsia, 19 cases HELLP syndrome, and 6 cases with eclampsia and HELLP syndrome were included in this study. The pregnancy induced hypertension cases were evaluated retrospectively for socioeconomic status, obstetrical history, biochemical parameters, and maternal complications. The incidence of preeclampsia was 20.1% (453/2245), the incidence of severe preeclampsia, eclampsia, and HELLP syndrome was 6.4% (144/2245). These ratios are higher than that reported in the English literature. The complication rate was 38% in severe preeclampsia cases. Among the severe preeclampsia cases, 32 had eclampsia (22.1%), and 25 had HELLP syndrome (17.3%). The most important biochemical marker for maternal mortality is bilirubin levels. Maternal mortality was statistically higher in cases with jaundice. Also, there was a statistically significant relation between maternal complications and liver function tests, lactate dehydrogenase levels, and low platelet levels.


[The effect of monensin on the fermentation of feed with different proportions of hay and concentrate in an artificial rumen (rumen simulation technic)].
An experiment was conducted with rumen pouch (RUSITEC--Rumen Simulation Technique). In four fermentation vessels (V), percent proportions of hay and barley were as follows: V1--40:60, V2 - 60:40, V3--80:20 and V4--100:0. Every day 5 mg of monensin dissolved in 1 ml 96% ethanol were added to each fermentation vessel. All diets were isonitrogenous, and after an addition of urea the crude protein (CP) content made 13% in each diet. The experiment lasted 12 days: so called steady state period took the first six days when the fermentation conditions were stabilized. Monensin reduced dry matter digestibility, production of total volatile fatty acids, acetic acid, n-butyric and isovaleric acids and acetate: propionate proportion, and it increased the production of propionic and n-valeric acids. The production of methane and CO2 decreased. The higher proportion of hay in diets decreased dry matter digestibility, digestibility of detergent fibre, total and individual volatile fatty acids, CO2, methane energy yield of volatile fatty acids (E), glucose utilization, production of adenosine triphosphate and production of fermented hexoses. The production, utilization and recovery of metabolic hydrogen also decreased. The effectiveness of microbial matter synthesis (YATP = 11.3) was highest during the fermentation of feed containing 60% hay and 40% barley.


The role of ascorbic acid in the regulation of cholesterol metabolism and in the pathogenesis of artherosclerosis.
Strong clinical and experimental evidence suggests that chronic latent vitamin C deficiency leads to hypercholesterolaemia and the accumulation of cholesterol in certain tissues. Ascorbic acid supplementation of the diet of hypercholesterolaemic humans and animals generally results in a significant reduction in plasma cholesterol concentration. While most studies relating ascorbic acid to atherosclerosis have used the rabbit as a model, those concerned with elucidating the role of ascorbic acid in the regulation of cholesterol metabolism have generally used the guinea pig. Comparatively little use has been made of the non-human primates. A significant advance in recent years has been the development of a model of chronic latent scurvy in the guinea pig. Chronic dietary inadequacy of vitamin C may influence the pathogenesis of atherosclerosis as it affects not only plasma cholesterol and triglyceride concentrations but also the integrity of the vascular wall. Ascorbic acid is involved in the regulation of cholesterol metabolism in several ways. Dietary inadequacy of vitamin C is associated indirectly with a lowering of cholesterol absorption, this effect resulting from a reduction in the availability of bile acids, monoglycerides and fatty acids. The excretion of cholesterol as neutral steroids, however, appears not to be affected by ascorbic acid. Although much of the evidence for the involvement of ascorbic acid in cholesterol synthesis is equivocal, it seems likely that cholesterol synthesis is decreased in vitamin C deficiency. A series of studies using guinea pigs with chronic latent vitamin C deficiency has provided clear evidence that bile acid synthesis is reduced in this condition. Indirect evidence strongly suggests that this results from a decrease in the activity of the microsomal enzyme cholesterol 7 alpha-hydroxylase. However, some evidence suggests that the mitochondrial reactions of bile acid synthesis require ascorbic acid. The role of ascorbic acid in the regulation of steroidogenesis appears to involve selective inhibitory and stimulatory effects on the desmolase, hydroxylase and dehydrogenase reactions which lead to the formation of pregnenolone and its subsequent conversion to steroid hormones.


Comparison between anterior cervical discectomy fusion and cervical corpectomy fusion using titanium cages for reconstruction: analysis of outcome and long-term follow-up.
Retrospective comparative study of 80 consecutive patients treated with either anterior cervical discectomy fusion (ACDF) or anterior cervical corpectomy fusion (ACCF) for multi-level cervical spondylosis. To compare clinical outcome, fusion rates, and complications of anterior cervical reconstruction of multi-level ACDF and single-/multi-level ACCF performed using titanium mesh cages (TMCs) filled with autograft and anterior cervical plates (ACPs). Reconstruction of the cervical spine after discectomy or corpectomy with titanium cages filled with autograft has become an acceptable alternative to both allograft and autograft; however, there is no data comparing the outcome of multi-level ACDF and single-/multi-level ACCF using this reconstruction. We evaluated 80 consecutive patients who underwent surgery for the treatment of multi-level cervical spondylosis at our institution from 1998 to 2001. In this series, 42 patients underwent multi-level ACDF (Group 1) and 38 patients underwent ACCF (Group 2). Interbody TMCs and local autograft bone with ACPs were used in both procedures. Medical records were reviewed to assess outcome. Clinical outcome was measured by Odom's criteria. Operative time and blood loss were noted. Radiographs were obtained at 6 and 12 weeks, 6 months, 1 year, and 2 years (if necessary). Early hardware failures and pseudarthroses were noted. Cervical sagittal curvature was measured by Ishihara's index at 1 year. Group 1 had a mean age 46.2 years (range 35-60 years). Group 2 had a mean age 50.1 years (range 35-70 years).The operative time was significantly lower (P < 0.001) and blood loss significantly higher (P < 0.001) in Group 2 than in Group 1. At a minimum of 1 year follow up, patients in both groups had equivalent improvement in their clinical symptoms. The fusion rates for Group 1 were 97.6 and 92.1% for Group 2. The rates of early hardware failure were higher in Group 2 (2.6%) than in Group 1 (0%). The fusion rates for Group 1 were not significantly higher than Group 2 (P > 0.28). There was one patient in Group 1 and 2 patients in Group 2 with pseudarthroses. Complication rates in Group 2 were not significantly higher (P > 0.341). Cervical lordosis was well-maintained (80%) in both groups. Both multi-level ACDF and ACCF with anterior cervical reconstruction using TMC filled with autograft and ACP for treatment of multi-level cervical spondylosis have high fusion rates and good clinical outcome. However, there is a higher rate of early hardware failure and pseudarthroses after ACCF than ACDF. Hence, in the absence of specific pathology requiring removal of vertebral body, multi-level ACDF using interbody cages and autologous bone graft could result in lower morbidity.


Alteration of endoplasmic reticulum lipid rafts contributes to lipotoxicity in pancreatic β-cells.
Chronic saturated fatty acid exposure causes β-cell apoptosis and, thus, contributes to type 2 diabetes. Although endoplasmic reticulum (ER) stress and reduced ER-to-Golgi protein trafficking have been implicated, the exact mechanisms whereby saturated fatty acids trigger β-cell death remain elusive. Using mass spectroscopic lipidomics and subcellular fractionation, we demonstrate that palmitate pretreatment of MIN6 β-cells promoted ER remodeling of both phospholipids and sphingolipids, but only the latter was causally linked to lipotoxic ER stress. Thus, overexpression of glucosylceramide synthase, previously shown to protect against defective protein trafficking and ER stress, partially reversed lipotoxic reductions in ER sphingomyelin (SM) content and aggregation of ER lipid rafts, as visualized using Erlin1-GFP. Using both lipidomics and a sterol response element reporter assay, we confirmed that free cholesterol in the ER was also reciprocally modulated by chronic palmitate and glucosylceramide synthase overexpression. This is consistent with the known coregulation and association of SM and free cholesterol in lipid rafts. Inhibition of SM hydrolysis partially protected against ATF4/C/EBP homology protein induction because of palmitate. Our results suggest that loss of SM in the ER is a key event for initiating β-cell lipotoxicity, which leads to disruption of ER lipid rafts, perturbation of protein trafficking, and initiation of ER stress.


Epidermal growth factor activates phospholipase C-gamma 1 via G(i)1-2 proteins in isolated pancreatic acinar membranes.
In the present study, isolated pancreatic acinar membranes were used to investigate the mechanism of epidermal growth factor (EGF)-induced activation of phospholipase C (PLC). The data show that EGF caused a rapid and strong increase in tyrosine phosphorylation of the EGF receptor, with a maximum 5-15 s after the beginning of the incubation followed by a decline. With use of [3H]phosphatidylinositol 4,5-bisphosphate as an exogenous substrate, PLC activity increased fourfold on exposure of the membranes to EGF (85 nM). In contrast, EGF-induced tyrosine phosphorylation of PLC-gamma 1 was rather small, indicating that tyrosine phosphorylation of PLC-gamma 1 is not proportional to changes in PLC activity. EGF-induced activation of PLC was strongly inhibited by pretreatment of the membranes with pertussis toxin, by an antibody raised against a COOH-terminal sequence shared by alpha-subunits of the inhibitory G proteins G(i)1 and G(i)2, and by an anti-PLC-gamma 1 antibody, whereas anti-G(i) alpha 3, anti-Gq/11 alpha, and anti-PLC-beta 1 antibodies had no effect. In contrast, pertussis toxin or the anti-G(i) alpha 1-2 antibody had no effect on EGF-induced tyrosine phosphorylation of PLC-gamma 1. EGF promoted association of G(i) proteins with both the EGF receptor and PLC-gamma 1 with similar kinetics as EGF-receptor autophosphorylation. All EGF-induced responses were abolished by the specific tyrosine kinase inhibitor pp60v-arc (137-157), suggesting that EGF-receptor tyrosine kinase activity is essential for G(i)1-2-mediated activation of PLC-gamma 1. However, there was no evidence of tyrosine phosphorylation of G(i) alpha 1-2. Taken together, these data show that EGF causes activation of PLC-gamma 1 by a mechanism requiring activation of G(i)1-2 and only a small increase in tyrosine phosphorylation of PLC-gamma 1.


Purification of mycobacterial deoxyribonucleic acid.
Impurities believed to be polysaccharides have been found in mycobacterial deoxyribonucleic acid (DNA) preparations. Agar-gel diffusion of the DNA preparations against concanavalin A indicated the presence of three polysaccharides and was used to follow the purification procedures. The polysaccharides appeared to be the same for all strains studied. Precipitation of DNA with cetyltrimethylammonium bromide was used to separate impurities from some DNA preparations. The presence of the contaminants was found to affect markedly the determination of the guanine plus cytosine content according to a method dependent on the ratio of absorbancies at 260 and 280 nm; the impurities did not affect the determination by the method of thermal denaturation. The presence of a DNA-polysaccharide complex is suggested.


Epibulbar Mass With Upper Eyelid Cleft and Focal Scalp Alopecia in a Neonate: A New Case of Oculoectodermal Syndrome.
A female neonate presented with a pedunculated left lateral epibulbar mass protruding through the eyelids that originated from the temporal cornea and superolateral bulbar and palpebral conjunctiva. She had a cleft in the ipsilateral central upper eyelid with horizontal kink of the tarsus lateral to the cleft and focal patches of alopecia on the scalp. Histopathology of the epibulbar mass revealed conjunctival epithelium with underlying connective tissue, cartilage, bone, adipose, and lacrimal gland consistent with epibulbar dermoid. Genetic testing of the surgical specimen was positive for a KRAS mutation at position 146. MRI showed subarachnoid asymmetry around the left temporal lobe and a C1-C2 enhancing lesion. These clinical and molecular findings suggest that this patient has a new clinical variant of oculoectodermal syndrome, a rare disorder associated with somatic KRAS gene mutations and characterized clinically by epibulbar dermoids, alopecia, aplasia cutis, brain anomalies, umbilical hernias, and congenital heart defects.


Rho-kinase inhibition reverses impaired Ca2+ handling and associated left ventricular dysfunction in pressure overload-induced cardiac hypertrophy.
Recent studies have implicated a relationship between RhoA/ROCK activity and defective Ca2+ homeostasis in hypertrophic hearts. This study investigated molecular mechanism underlying ROCK inhibition-mediated cardioprotection against pressure overload-induced cardiac hypertrophy, with a focus on Ca2+ homeostasis. Cardiac hypertrophy model was established by performing transverse aortic constriction (TAC) in 8-week-old male rats. Groups were assigned as SHAM, TAC and TAC+Fas (rats undergoing TAC and treated with fasudil). Rats in the TAC+Fas group were administered fasudil (5mg/kg/day), and rats in the SHAM and TAC groups were treated with vehicle for 10 weeks. Electrophysiological recordings were obtained from isolated left ventricular myocytes and expression levels of proteins were determined using western blotting. Rats in the TAC group showed remarkable cardiac hypertrophy, and fasudil treatment significantly reversed this alteration. TAC+Fas myocytes showed significant improvement in reduced contractility and Ca2+ transients. Moreover, these myocytes showed restoration of slow relaxation rate and Ca2+ reuptake. Although L-type Ca2+ currents did not change in TAC group, there was a significant reduction in the triggered Ca2+ transients which was reversed either by long-term fasudil treatment or incubation of TAC myocytes with fasudil. The hearts of rats in the TAC group showed a significant decrease in ROCK1, ROCK2, RyR2 protein levels and p-PLBS16/T17/SERCA2 ratio and increase in RhoA expression and MLC phosphorylation. However, fasudil treatment largely reversed TAC-induced alterations in protein expression. Thus, our findings indicate that upregulation of the RhoA/ROCK pathway is significantly associated with cardiac hypertrophy-related Ca2+ dysregulation and suggest that ROCK inhibition prevents hypertrophic heart failure.


Expression of Heat Shock Protein 70 Is Insufficient To Extend Drosophila melanogaster Longevity.
It has been known for over 20 years that Drosophila melanogaster flies with twelve additional copies of the hsp70 gene encoding the 70 kD heat shock protein lives longer after a non-lethal heat treatment. Since the heat treatment also induces the expression of additional heat shock proteins, the biological effect can be due either to HSP70 acting alone or in combination. This study used the UAS/GAL4 system to determine whether hsp70 is sufficient to affect the longevity and the resistance to thermal, oxidative or desiccation stresses of the whole organism. We observed that HSP70 expression in the nervous system or muscles has no effect on longevity or stress resistance but ubiquitous expression reduces the life span of males. We also observed that the down-regulation of hsp70 using RNAi did not affect longevity.


Uncovering Aberrant Mutant PKA Function with Flow Cytometric FRET.
Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPIs). Förster resonance energy transfer (FRET)-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live-cell FRET-based binding curves using a commercially available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validating our binding assay against the gold standard isothermal calorimetry (ITC), and using flow cytometric FRET to uncover the structural and functional effects of the Cushing-syndrome-causing mutation (L206R) on PKA's catalytic subunit. We discover that this mutation not only differentially affects PKAcat's binding to its multiple partners but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability, and power of flow cytometric FRET.


Induction of heat shock protein in cardiac allograft rejection--a cyclosporine-suppressible response.
The cellular response to a wide variety of stresses results in the synthesis of a family of proteins termed heat shock proteins (HSPs). To determine if acute allograft rejection could induce these proteins in a transplanted graft, we examined the HSP response to acute cardiac allograft rejection and analyzed the effect of immunosuppression upon this response. Donor hearts obtained from either Lewis (LEW) or ACI rats were heterotopically transplanted in recipient LEW rats. There were 4 experimental groups: untreated isografted (LEW to LEW) animals (n = 14), untreated allografted (ACI to LEW) animals (n = 14), cyclosporine-treated (10 mg/kg SQ/day) isografted animals (n = 12), and cyclosporine-treated allografted animals (n = 12). Animals were sacrificed on posttransplantation day 2, 4, or 6 (time of rejection for untreated allografts); n = 4-5 for each time point per group. At these times tissue obtained from the transplanted heart was examined histologically and analyzed for HSP72 by quantitative Northern and Western blots. The level of HSP72 in the untreated allografts progressively increased between 2, 4, and 6 days posttransplantation and was significantly greater than that of the untreated isografts at all time points. The HSP72 response in cyclosporine-treated allografts was significantly reduced at 4 and 6 days posttransplantation compared with the untreated allografts. In contrast, there was no difference in the HSP response in treated versus untreated isografts. Additionally, there was no difference in HSP levels in cyclosporine-treated isografts and allografts. These findings demonstrate that HSP expression in the transplanted heart correlates directly with the evolution of acute allograft rejection, and that immunosuppressive therapy inhibits the HSP response. These studies also raise the possibility of a functional role for HSPs in the allogeneic immune response.


[Effect of the pH of the medium on DNA conformation].
The hydrodynamical and optical properties of DNA were investigated in the wide-range of pH by the methods of streaming birefringence, viscometry and spectrophotometry for the different ionic strengths of environment. The measurements of the intrinsic viscosity as a function of pH allow us to determine the compactization of protonated DNA without the destruction of double-helical conformation. This transition is accompanied by a decrease in the optical anisotropy of DNA and the coefficient of molar extinction E260 (P). The increase of volume and persistence length of DNA was observed in the alkaline range of pH. Analyses of experimental data lead to an assumption that the predominant cause of these effects is the change of flexibility of DNA as a result of ionization of its bases. The data obtained were compared with those for polycationic molecules.


[Effects of Xinfeng Capsule on behaviors and myocardial ultrastructure in adjuvant arthritis rats].
To observe the effects of Xinfeng Capsule (XFC), a compound Chinese herbal medicine, on behaviors and myocardial ultrastructure in adjuvant arthritis (AA) rats. Fifty-five rats were randomly divided into normal control group, untreated group, methotrexate (MTX) group, Tripterygium wilfordii glycosides tablet (TGT) group and XFC group. There were 11 rats in each group. Except for those in the normal control group, the rats in the other groups were all intracutaneously given 0.1 ml Freund's complete adjuvant in the right hind limb. Changes of behaviors and myocardial ultrastructure of the rats in different groups were observed. Voix pedis' swelling and arthritis index in XFC, MTX and TPT groups were all obviously improved as compared with the untreated group. After XFC treatment, the autonomic activities were obviously increased, number of errors in exercise period and test period were obviously decreased, step-down latency (SDL) was lengthened and escape latency (EL) was shortened. Overall structure of myocardial myofibril and the majority of cristae was intact in XFC group. The effects of XFC in improving the behaviors and myocardial ultrastructure were better than those of MTX and TPT. Changes of behaviour and myocardial ultrastructure of AA rats can be observed. XFC can improve the myocardial ultrastructure of AA rats as well as their behaviors.


Streptomyces albus: A New Cell Factory for Non-Canonical Amino Acids Incorporation into Ribosomally Synthesized Natural Products.
The incorporation of noncanonical amino acids (ncAAs) with different side chains into a peptide is a promising technique for changing the functional properties of that peptide. Of particular interest is the incorporation of ncAAs into peptide-derived natural products to optimize their biophysical properties for medical and industrial applications. Here, we present the first instance of ncAA incorporation into the natural product cinnamycin in streptomycetes using the orthogonal pyrrolysyl-tRNA synthetase/tRNAPyl pair from Methanosarcina barkeri. This approach allows site-specific incorporation of ncAAs via the read-through of a stop codon by the suppressor tRNAPyl, which can carry different pyrrolysine analogues. Five new deoxycinnamycin derivatives were obtained with three distinct pyrrolysine analogues incorporated into diverse positions of the antibiotic. The combination of partial hydrolysis and MS/MS fragmentation analysis was used to verify the exact position of the incorporation events. The introduction of ncAAs into different positions of the peptide had opposite effects on the peptide's biological activity.


Electrocortical measures of information processing biases in social anxiety disorder: A review.
Social anxiety disorder (SAD) is characterized by information processing biases, however, their underlying neural mechanisms remain poorly understood. The goal of this review was to give a comprehensive overview of the most frequently studied EEG spectral and event-related potential (ERP) measures in social anxiety during rest, anticipation, stimulus processing, and recovery. A Web of Science search yielded 35 studies reporting on electrocortical measures in individuals with social anxiety or related constructs. Social anxiety was related to increased delta-beta cross-frequency correlation during anticipation and recovery, and information processing biases during early processing of faces (P1) and errors (error-related negativity). These electrocortical measures are discussed in relation to the persistent cycle of information processing biases maintaining SAD. Future research should further investigate the mechanisms of this persistent cycle and study the utility of electrocortical measures in early detection, prevention, treatment and endophenotype research.


Perfusion of the human finger during cold-induced vasodilatation.
We have investigated the effect of severe local cooling on the vasomotor activity of the arteriovenous anastomoses (AVAs) and other finger vessels. The right third finger was subjected to local cooling (3 degrees C) for 30-45 min in 21 healthy, thermoneutral subjects. Blood velocity in the third finger arteries of both hands was simultaneously recorded using ultrasound Doppler, and skin temperature and laser-Doppler flux from the pulp of the cooled finger were also recorded. The results demonstrate that the initial cold-induced vasoconstriction during severe local cooling involves constriction of the AVAs as well as the two main arteries supplying this finger. During cold-induced vasodilatation (CIVD), the maximum velocity values were not significantly different from those before cooling. Furthermore, the velocity fluctuations in the cooled finger were in most subjects found to be synchronous with the velocity fluctuations in the control finger. This indicates that the large blood flow to the finger and the high skin temperature during CIVD are caused by relaxation of the smooth muscle cells of the AVAs.