Identification of a novel prenyl and palmitoyl modification at the CaaX motif of Cdc42 that regulates RhoGDI binding.
Membrane localization of Rho GTPases is essential for their biological functions and is dictated in part by a series of posttranslational modifications at a carboxyl-terminal CaaX motif: prenylation at cysteine, proteolysis of the aaX tripeptide, and carboxymethylation. The fidelity and variability of these CaaX processing steps are uncertain. The brain-specific splice variant of Cdc42 (bCdc42) terminates in a CCIF sequence. Here we show that brain Cdc42 undergoes two different types of posttranslational modification: classical CaaX processing or novel tandem prenylation and palmitoylation at the CCaX cysteines. In the dual lipidation pathway, bCdc42 was prenylated, but it bypassed proteolysis and carboxymethylation to undergo modification with palmitate at the second cysteine. The alternative postprenylation processing fates were conserved in the GTPases RalA and RalB and the phosphatase PRL-3, proteins terminating in a CCaX motif. The differentially modified forms of bCdc42 displayed functional differences. Prenylated and palmitoylated brain Cdc42 did not interact with RhoGDIα and was enriched in the plasma membrane relative to the classically processed form. The alternative processing of prenylated CCaX motif proteins by palmitoylation or by endoproteolysis and methylation expands the diversity of signaling GTPases and enables another level of regulation through reversible modification with palmitate.


Endocrine regulation of rat organic anion transporters.
Messenger RNA levels of rat organic anion transporter 1 (Oat1; Slc22a6) and Oat2 (Slc22a7) in kidney and Oat3 (Slc22a8) in liver are gender-predominant. Oat1 and Oat3 are male-predominant, whereas Oat2 is female-predominant. Gonadectomized and hypophysectomized (HX) rats were studied to determine whether sex steroids and/or growth hormone (GH) are responsible for these gender-divergent patterns. GH was administered to HX rats by two daily injections (simulating male secretion) or continuous infusion (simulating female secretion). Oat1 mRNA levels, normally higher in male than female kidney, were lowered by gonadectomy and HX in male rats, but not in females. Additionally, GH injections or infusion did not alter Oat1 levels in HX rats. Oat2 mRNA levels, typically much higher in female than in male kidney, were unaffected by gonadectomy. However, HX dramatically decreased Oat2 in female kidney without altering male levels. GH administered by continuous infusion increased Oat2 in kidneys of both HX male and female rats, whereas injections had no affect. Gonadectomy reduced Oat3 mRNA levels in male livers without affecting levels in female livers. In contrast, HX decreased male and elevated female Oat3 mRNA. GH injections did not significantly change Oat3 mRNA levels in HX rats, but infusion decreased Oat3 mRNA in liver. In conclusion, androgens, but not GH, are responsible for the Oat1 mRNA gender difference in kidney; the female GH secretion pattern is responsible for the Oat2 mRNA gender difference in kidney; and both androgens and the female GH secretion pattern are responsible for the Oat3 mRNA gender difference in liver.


Migraine and stroke: current perspectives.
The purpose of this article is to review the latest concepts regarding migraine and ischemic stroke. In addition, focal neurological deficits and MRI changes in migraine patients will be reviewed. A PubMed search of neurological literature pertaining to this study was conducted using specific keyword search terms pertaining to migraine and ischemic stroke. Migraine, especially with aura, is a relative risk factor for stroke. Neuroimaging demonstrates the posterior circulation as being most vulnerable, although the reason for this distribution is unclear. Factors that may contribute to stroke in migraine include changes during cortical spreading depression with hyper- or hypoperfusion of neural tissue, vasospasm and endothelial dysfunction. Estrogen affects migraine expression as well as cerebral circulation, yet most women with migraine without aura are not at increased risk. Co-morbidity with patent foramen ovale can be mechanism of both disorders via presumed lack of filtration of microemboli or toxic substances; however, closure with reversal of right to left shunt seems to be more beneficial for cryptogenic stroke than migraine. Migraine and stroke are found in specific genetic disorders such as CADASIL, HERNS and MELAS giving clues to genetic factors. Stroke associated with migraine treatments such as ergots or triptans is rare, and usually associated with special circumstances such as overuse or concomitant thrombogenic conditions. Although true migrainous infarction is rare, our understanding of the subtle associations between migraine and cerebrovascular behavior is expanding.


[Household survey of diarrhoeal disease control in P.R. china].
126,965 population, including 10,987 children less than 5 years in 20 provinces were visited, and 7,681 cases due to diarrhoea, including 1 800 cases less than 5 years were found during the survey in Aug 1988. According to the calculating methods recommended by WHO, the morbidity is 0.70 episodes/person/per year in China, 1.90 episodes/per child/per year in children less than 5 years. The highest morbidity, 2.44 episodes/per child/per year, is in the age group from 6 months to 2 years. 37.86% of all cases went to health facilities, among them 62.24% were treated in village health facilities. 63.36% of all cases received treatment. The use rate of ORT was 14.24%, including 1.98% of using ORS and 12.26% of using home fluids. The use rate of antibiotics was 55.16%. The use rate of traditional medicine was 8.07%. From Sep 1987 to Aug 1988, there were 605 deaths in 102,470 population. The death rate was 5.9 per 1,000 population. With 15 deaths due to diarrhoea, the mortality of diarrhoea was 0.002% 76.18% of 1,247 children under 7 months were breast-fed, and 19.49% of them were partially breast-fed, and 4.33% of them were bottle-fed. The result of the survey indicates that diarrhoeal disease is a major constraints to people's health and social development, and the character of high morbidity and low mortality determines that the strategy of diarrhoeal diseases Control will be prevention, and the situation of low ORT use rate and abuse of antibiotics should be improved, and it should be emphasized to train health workers of village facilities.


The impact of persisting hyperactivity on social relationships: a community-based, controlled 20-year follow-up study.
The purpose of this study was to examine whether persisting hyperactivity into adulthood was associated with impaired family, friendship, and partner relationships or poor coping skills in everyday life. A 20-year community-based follow-up of 6- to 7-year-old boys showing pervasive hyperactivity (n = 40) and unaffected controls (n = 25) was conducted. At age 27 years, participants were assessed with detailed interview techniques as well as self-report ratings. ADHD in adulthood was associated with problems in intimate relationships and negotiation skills. Antisocial behavior did not influence the association, but remitting childhood hyperactivity was not associated with social relationship difficulties in adulthood. In an untreated, community-based sample of hyperactive children, the risk for unsatisfactory social relationships is largely confined to those patients who still show ADHD in adulthood. The majority of patients who experience childhood hyperactivity have positive social relationships in adulthood.


Evidence of ritual breakage of a ground stone tool at the Late Natufian site of Hilazon Tachtit cave (12,000 years ago).
Destruction of valuables is a common behavior in human history. Ethnographic data show the polysemic, but fundamentally symbolic, nature of this act. Yet, research aimed at exploring symbolic destruction in prehistoric societies has underlined the difficulties in establishing unambiguous evidence for such behaviour. We present here the analysis of a basalt tool fragment which provides evidence for intentional breakage associated with ritual activity 12,000 years ago. The tool fragment was part of a unique assemblage of grave goods deposited in a burial pit of a woman suggested to have been a shaman (Hilazon Tachtit cave, Southern Levant). The reconstruction of the artefact's life history through morphological, 3D, use wear, residue and contextual analyses suggest that: 1) the fragment was initially part of a shallow bowl used for mixing ash or lime with water; 2) the bowl was subsequently intentionally broken through flaking along multiple axes; 3) The bowl was not used after its breakage but placed in a cache before the interment of the deceased, accompanied with other special items. The broken bowl fragment underlines the ritualistic nature of the act of breakage in the Natufian society. The research presented in this paper provides an important window into Natufian ritual behaviour during the critical period of transformation to agricultural communities. In addition, our results offer new insight into practices related to intentional destruction of valuables associated with death-related ceremonies at the end of the Palaeolithic.


Cyanide inhibits respiration yet stimulates aerobic growth of Zymomonas mobilis.
Potassium cyanide at submillimolar concentrations (20-500 microM) inhibited the high respiration rates of aerobic cultures of Zymomonas mobilis but, remarkably, stimulated culture growth. In batch culture, after an extended lag phase, exponential growth persisted longer, resulting in higher biomass densities. In aerobic chemostat cultures, elevated biomass concentration was observed in the presence of cyanide. This growth stimulation effect is attributed to decreased production of the inhibitory metabolite acetaldehyde at lowered respiration rates, when more reducing equivalents are channelled to alcohol dehydrogenase. Growth in the presence of cyanide did not alter the membrane cytochrome content. In non-growing cyanide-preincubated cells, with ethanol as the respiratory substrate, cyanide increased ATP levels; in such cells, a large part of the cyanide-sensitive respiration was inhibited within a few seconds after ethanol addition, while inhibition of the rest of respiration took several minutes. The more cyanide-sensitive respiration was apparently energy-nongenerating, and was absent in membrane preparations. Pelleting of membranes from cell-free extracts produced 'soluble' fractions in which a b-type haem was detectable by reduced minus oxidized difference spectroscopy. The function of the Z. mobilis respiratory chain in cell growth and respiratory protection, and the possible physiological role of aerobic generation of inhibitory metabolites, are discussed.


[Performance-related middle management in medical teaching. Attractiveness of incentive tools from the perspective of the teachers].
German medical schools are increasingly challenged by the competition for public funds and talented students. Therefore. many curriculum planners, deans and school administrators plan to implement a systematic and comprehensive awarding system for good teaching. The OBJECTIVE of this study was to elaborate which specific incentives would be most effective to increase the motivation and enthusiasm for teaching among basic scientists as well as residents and attendings involved in medical education. In addition, a cost-effective model should be developed, which could be used as an adjustable blue-print for an awarding system. Based on literature search, existing approaches to rewards and incentives for medical teachers were analysed by an interdisciplinary committee in coordination with the members' department heads. According to german teaching methods and available resources, a catalogue of specific incentives has been designed and ranked by a representative sample of 200 medical teachers / faculty at two universities. Thus, a variety of favourite rewarding instruments could be elaborated, which were preferred by teachers in theoretical versus clinical disciplines. The majority of the medical teachers prefer heterogeneously monetary incentives and additional protected time, followed by career-effective incentives (tenure & promotion). The discussion reflects on a transferable catalogue of different rewarding instruments, including a cost-/benefit-analysis and prerequisite students' evaluation data. A single alteration of departmental teaching budgets does not seem to be sufficient. It seems rather advisable, also to strive for a variety of different incentives on a level that predominantly affects individual teaching personnel. Even with comparatively small amounts of money, significant effects on teachers' motivation can be achieved.


Clinical impact of bortezomib in frontline regimens for patients with multiple myeloma.
Standard frontline therapy for multiple myeloma comprises cytoreductive therapy with or without consolidative high-dose therapy plus stem cell transplantation (HDT-SCT). Despite therapeutic advances, the disease remains incurable; most patients relapse following frontline treatment and die within 5 years of diagnosis. New options are required to enhance and prolong response, and improve survival, particularly for elderly patients and those with renal dysfunction. Preclinical studies have demonstrated the ability of bortezomib to enhance the activity of commonly used myeloma agents, an observation validated through clinical studies in both the relapsed and frontline settings. This review focuses on the growing body of clinical evidence showing the effectiveness of bortezomib and bortezomib-based combinations in newly diagnosed patients, characterized by high overall response rates and consistently high rates of complete response. A number of studies incorporating bortezomib as part of induction therapy have demonstrated no adverse impact of bortezomib on stem cell harvest and engraftment in patients proceeding to transplantation. The higher rates of complete response typically associated with bortezomib treatment may potentially improve clinical outcomes in this setting. Final results from ongoing phase III studies of bortezomib-based combinations versus standard regimens will help define the optimal use of bortezomib as a standard component of frontline therapy for multiple myeloma. Disclosure of potential conflicts of interest is found at the end of this article.


A meta-analysis of glucose-insulin-potassium therapy for treatment of acute myocardial infarction.
Glucose-insulin-potassium (GIK) therapy has been proposed to provide metabolic support to ischemic myocardium. A meta-analysis that included 1932 patients performed 10 years previously demonstrated that GIK therapy may have an important role in reducing mortality after acute myocardial infarction (AMI). Since then, many larger randomized trials investigating the role of GIK in the setting of AMI have been published; hence, the present study repeats the previous meta-analysis performed by the current authors to include these trials. A systematic MEDLINE search for all randomized, placebo-controlled studies of GIK therapy in the setting of AMI was conducted and a meta-analysis of the mortality data was performed. A total of 16 randomized trials from 1966 to 2008 were identified, with 28,374 patients included in the current meta-analysis. There was a total of 1367 deaths (9.6%) in the GIK group, with 1351 deaths (9.6%) in the control group. Meta-analysis did not reveal any benefit from GIK treatment (OR 1.0; 95% CI 0.9 to 1.1; P=0.9). Subgroup analysis of patients given high-dose GIK and in patients in whom reperfusion was not obtained did not demonstrate a benefit from GIK therapy. A meta-analysis of 16 randomized trials that spanned 40 years and involved more than 28,000 patients did not reveal any mortality benefit for ST segment elevation AMI using GIK therapy when data from the modern thrombolysis/primary percutaneous coronary intervention era were included.


Health behavior and experiences of physicians. Results of a survey of Palo Alto Medical Clinic physicians.
The results of a health practice questionnaire submitted to the 152 physician members of the Palo Alto Medical Clinic, 126 of whom responded, indicate a generally favorable profile of preventive medicine strategies. Physicians generally smoke less, drink about the same, exercise more, and use their seat belts more than the population at large. They also can expect to live longer. These results are compared with those of other physician surveys and surveys of the general public.


Selective HPLC method development for soy phosphatidylcholine Fatty acids and its mass spectrometry.
A novel, efficient and simple approach for soy phosphatidylcholine analysis according to its fatty acid composition was studied with reverse-phase high-performance liquid chromatography. The reverse-phase high-performance liquid chromatography analysis was performed isocratically using UV detector and simple mobile phase solvents consisting of isopropyl alcohol, methanol, and deionized water in the proportion of 70:8:22 v/v. The uniqueness of the proposed method was the separation of individual fatty acids of soy phosphatidylcholine. The high-performance liquid chromatography method for soy phosphatidylcholine was validated for linearity with correlation coefficient of above 0.99 for all the peaks separated according to their fatty acid composition. The intra-day and the inter-day precision studies provided the relative standard deviation of less than 2%. The limit of detection and limit of quantitation values were also calculated for all the resolved peaks of soy phosphatidylcholine. Also system performance parameters such as number of theoretical plates, capacity factor, tailing factor, separation factor, and peak resolution were studied systematically and found well within the acceptable range. The proposed high-performance liquid chromatography method was successfully applied to soy phosphatidylcholine extracted and purified from deoiled soy lecithin without any interference of impurities or solvent peaks. Individually, the collected peaks of sample soy phosphatidylcholine were subjected for mass spectroscopy. The mass spectra showed all the peaks having different saturated or unsaturated fatty acid chains attached to glyerophosphocholine moiety of soy phosphatidylcholine. The method developed is economic and well suited for estimation of soy phosphatidylcholine with its fatty acid composition.


Cemented femoral stems in patients with DDH.
Total hip arthroplasty is the procedure of choice for most adult patients with symptomatic arthrosis secondary to developmental dysplasia (DDH), but it requires complex reconstructive techniques, is usually performed in young patients, and has an increased risk of complications. THA is indicated in presence of severe pain and when osteotomy is contraindicated. The complexity of surgery is related to the degree of dysplasia. Anatomic abnormalities in the acetabulum and femur are the cause of the complexity and complications of this procedure. Acetabular bone deficiency requires reconstructive techniques before implanting the cup at the anatomic acetabular location, such as bone autograft augmentation, implanting the cup at higher level of the hip center and cup medialization. Femoral shortening and special cemented or uncemented stems are currently used to avoid intraoperative complications. While a cemented stem needs metaphyseal femoral shortening, subtrochanteric shortening requires a cementless stem. Because of these patients' age, alternative bearing surfaces, such as alumina-on-alumina couples are recommended when possible. Although the long-term results of total hip arthroplasty in DDH are inferior to those in a general population, the results show a high level of pain relief and functional improvement.


Using resonance Raman cross-section data to estimate the spin state populations of Cytochromes P450.
The cytochromes P450 (CYPs) are heme proteins responsible for the oxidation of xenobiotics and pharmaceuticals and the biosynthesis of essential steroid products. In all cases, substrate binding initiates the enzymatic cycle, converting ferric low spin (LS) to high-spin (HS), with the efficiency of the conversion varying widely for different substrates, so documentation of this conversion for a given substrate is an important objective. Resonance Raman (rR) spectroscopy can effectively yield distinctive frequencies for the ν3 "spin state marker" bands. Here, employing a reference cytochrome P450 (CYP101), the intensities of the ν3 modes (ILS) and (IHS) relative to an internal standard (sodium sulfate) yield relative populations for the two spin states; i.e., a value of 1.24 was determined for the ratio of the relative cross sections for the ν3 modes. Use of this value was then shown to permit a reliable calculation of relative populations of the two spin states from rR spectra of several other Cytochromes P450. The importance of this work is that, using this information, it is now possible to conveniently document by rR the spin state population without conducting separate experiments requiring different analytical methods, instrumentation and additional sample.


Illness-related absence among preschool children: Insights from a health intervention in Swedish preschools.
We evaluate the effect of a preschool health intervention aimed at reducing infections through improved hygiene practices and training of the staff. The large-scale design enables us to study heterogeneous effects with respect to several child and preschool characteristics that are related to the level of illness-related absence. We find no reduction, on average, in children's illness-related absence. This conclusion holds across different age groups of preschool children, and for preschools with varying levels of absence before the intervention. We find some suggestive evidence that the intervention may have induced effects operating in different directions: while improved hygiene practices may have reduced illness, stricter guidelines regarding absence during infections seems to have contributed to an increased absence level, resulting in an overall zero effect. Overall, our results suggest that reducing absence through improved hygiene practices is not easily accomplished in a child care setting.


Early electroretinography in unilateral central retinal vein occlusion as a predictor of rubeosis iridis.
Twenty-six patients with clinically nonischemic unilateral central retinal vein occlusion and four in whom clinical categorization was unclear were recruited. The scotopic electroretinogram (ERG) was recorded at presentation to a range of six different luminances. Patients were followed up for six months to assess the correlation between initial ERG response and subsequent outcome. Seven patients developed rubeosis iridis. The b-wave implicit time was the parameter most significantly associated with subsequent rubeosis, followed by b-wave/a-wave amplitude ratio and then b-wave amplitude. Neither a-wave amplitude nor implicit time was a valuable predictor. The b-wave implicit times were equally predictive of rubeosis at each of the luminances used. In individually affected eyes, a b-wave implicit time at presentation, averaged across the range of luminances used, of greater than 47.17 ms was strongly associated with later rubeosis, as was an intereye difference of greater than 7.39 ms.


Feasibility of NOTES omental plug repair of perforated peptic ulcers: results from a clinical pilot trial.
Ulcer perforation carries up to a 30 % 1-year mortality rate. Intervention-related adverse events are among statistically significant predictors of 1-year mortality. A natural orifice transluminal endoscopic surgical (NOTES) approach may be less invasive and may decrease procedure-related adverse events by diminishing the so-called second hit, thus leading to decreased morbidity and mortality. We sought to assess the feasibility of an endoscopic transluminal omental plug technique in patients with perforated gastroduodenal ulcers under laparoscopic guidance. Patients with suspected acute gastroduodenal ulcer perforations were offered participation in this prospective pilot study. Closure of the perforation was attempted using the NOTES omental plug technique. Demographic, clinical, endoscopic, and radiographic data were abstracted, as were data for morbidity, mortality, and pilot data regarding quality of life (QOL). From February 2010 through February 2012, a total of 17 patients presented to a tertiary care center with clinically suspected perforated ulcer. Of seven patients (mean age 79 years, range 64-89 years) who consented to the study, three underwent the study procedure. All patients had multiple comorbidities. Two patients presented with 4-6 mm perforated peptic ulcers and underwent successful laparoscopic-assisted NOTES omental and falciform ligament patch closure, respectively. Postoperative radiographic contrast studies showed no leak, and patients were discharged home on postoperative days 3 and 4. The third patient had undergone enterocutaneous fistula repair with herniorrhaphy 6 weeks before. Although a transluminal endoscopic approach was feasible, the omentum was under too much tension to be secured. This procedure was converted to an open omental patch repair. For all but one patient who provided consent, obtaining QOL data was feasible. Initial results from a laparoscopic-assisted NOTES approach for closure of perforated peptic ulcers appear promising and enable swift recovery in selected patients. This is especially important in elderly and/or immunocompromised patients. Technical details and patient selection criteria continue to evolve.


Mutations affecting the Shine-Dalgarno sequences of the untranslated region of the Escherichia coli gltBDF operon.
Individual mutations which affected each of the two Shine-Dalgarno sequences at the 5' untranslated region of the gltB gene of Escherichia coli were characterized. They were isolated in plasmids carrying a gltB'-'lacZ protein fusion preceded by the regulatory region of the gltBDF operon. Subcloning and nucleotide sequencing of approximately 1,206 bp of DNA encompassing the gltBDF regulatory region showed that the mutations affected the first base at each of the two identical Shine-Dalgarno sequences, SD1 and SD2, located 40 and 8 bases, respectively, upstream from the putative gltB open reading frame. Only mutation gltB2r227, an adenine in place of a guanine, affecting the first base of SD2, lowered beta-galactosidase expression significantly, i.e., about fivefold. The results suggest that SD2 is the preferred functional site at which ribosomes initiate gltB mRNA translation.


Evaluation of properties microcrystalline chitosan as a drug carrier. Part 1. In vitro release of diclofenac from mictocrystalline chitosan hydrogel.
The influence of microcrystalline chitosan hydrogel, alone (MCCh) as well as in combination with methylcellulose (MC) or Carbopol (CP), on the release of diclofenac free acid (DA) and its salt (DS) was studied in vitro. Commercial Olfen gel (Mepha Ltd., Switzerland) was applied as a reference preparation. The influence of hydrophilizing agents (1,2-propylene glycol and glycerol) and methycellulose hydrogel on the rheological properties of the vehicle and on the release of drug from modified MCCh hydrogel was studied. The quantity of the released substance was determined by UV-spectroscopy. The results confirmed that release was dependent on the chemical character of the drug and on the type of vehicle. The process of diclofenac release from MCCh hydrogels as well as from Carbopol hydrogels runs in two phases. The first phase is characterised by rapid release whereas in the second phase the release is much slower. The most suitable basis for diclofenac is microcrystalline chitosan hydrogel with addition glycerol, 1,2-propylene glycol, and methylcellulose hydrogel.


Genetic evidence linking lung cancer and COPD: a new perspective.
Epidemiological studies indicate that tobacco smoke exposure accounts for nearly 90% of cases of chronic obstructive pulmonary disease (COPD) and lung cancer. However, genetic factors may explain why 10%-30% of smokers develop these complications. This perspective reviews the evidence suggesting that COPD is closely linked to susceptibility to lung cancer and outlines the potential relevance of this observation. Epidemiological studies show that COPD is the single most important risk factor for lung cancer among smokers and predates lung cancer in up to 80% of cases. Genome-wide association studies of lung cancer, lung function, and COPD have identified a number of overlapping "susceptibility" loci. With stringent phenotyping, it has recently been shown that several of these overlapping loci are independently associated with both COPD and lung cancer. These loci implicate genes underlying pulmonary inflammation and apoptotic processes mediated by the bronchial epithelium, and link COPD with lung cancer at a molecular genetic level. It is currently possible to derive risk models for lung cancer that incorporate lung cancer-specific genetic variants, recently identified "COPD-related" genetic variants, and clinical variables. Early studies suggest that single nucleotide polymorphism-based risk stratification of smokers might help better target novel prevention and early diagnostic strategies in lung cancer.


A necessarily complex model to explain the biogeography of the amphibians and reptiles of Madagascar.
Pattern and process are inextricably linked in biogeographic analyses, though we can observe pattern, we must infer process. Inferences of process are often based on ad hoc comparisons using a single spatial predictor. Here, we present an alternative approach that uses mixed-spatial models to measure the predictive potential of combinations of hypotheses. Biodiversity patterns are estimated from 8,362 occurrence records from 745 species of Malagasy amphibians and reptiles. By incorporating 18 spatially explicit predictions of 12 major biogeographic hypotheses, we show that mixed models greatly improve our ability to explain the observed biodiversity patterns. We conclude that patterns are influenced by a combination of diversification processes rather than by a single predominant mechanism. A 'one-size-fits-all' model does not exist. By developing a novel method for examining and synthesizing spatial parameters such as species richness, endemism and community similarity, we demonstrate the potential of these analyses for understanding the diversification history of Madagascar's biota.


The chaperone-like activity of rat HspB8/Hsp22 and dynamic molecular transition related to oligomeric architectures in vitro.
HspB8/Hsp22 is a functionally distinct small heat shock proteins (sHsp) and is preferentially expressed in brain, heart, skeletal, and smooth muscle. HspB8 is also associated with neuromuscular function and protein quality control by proteasomes in cardiac hypertrophy. However, the molecular properties in vitro and molecular oligomerization remain uncertain. In this investigation, the rat HspB8 gene was expressed in E.coli cells, and mature HspB8 protein was efficiently prepared. The chaperone-like activity of HspB8 in vitro was quantitatively analyzed by model substrates. Size exclusion chromatography revealed that HspB8 had polydisperse oligomers and underwent dynamic molecular transition in solution, existing in a dynamic equilibrium between various oligomers. In a nonphysiological solution, HspB8 was predominantly octamers. In a physiological solution (pH 7.4), HspB8 mainly formed tetramers. The dynamic interactive transition maybe was helpful to maintain its molecular complxes in solution. In a FRET assay, subunit exchange occurred frequently between the various oligomers with a rate of 0.12, 0.089, and 0.064 min(-1) at 50°C, 43°C, and 37°C, respectively. It also demonstrated the dynamic molecular properties of HspB8 in solution.


Oxygen transport in acute pulmonary oedema and in acute exacerbations of chronic bronchitis.
When breathing air, the average arterial oxygen tension in eight patients with acute pulmonary oedema was significantly higher than in eight other patients suffering from an acute exacerbation of chronic bronchitis, but the mixed venous oxygen tension was very similar in both groups. This largely arose from the smaller arteriovenous difference of oxygen content in the bronchitic cases, presumably due to their higher cardiac output, associated with raised arterial CO(2) tensions. Oxygen therapy (60-90% for pulmonary oedema, 30% for the bronchitics) raised the mixed venous oxygen tensions to a similar level in both groups. We suggest that the major need for oxygen therapy lies in patients who maintain their oxygen consumption but show a reduction in mixed venous tension when breathing air. Although partial correction of arterial hypoxaemia is adequate in chronic bronchitis-in which the cardiac output is maintained-high concentrations of oxygen are necessary in pulmonary oedema, in which the cardiac output is low.


Effect of phytohormones on seed germination and seedling growth of Coriandrum sativum L.
Coriander commonly known as Dhania or Chinese parsley is generally grown for its use in soups, salads, dressing vegetables, seasoning and chutney. Effect of two phytohormones viz. GA3 and 2,4-D on seed germination, seedling growth and various physiological and biochemical parameters were studied. The hormones were applied individually in different concentrations (10, 50 and 100 μM concentrations). Both the hormones enhanced the germination percentage, seedling growth (root and shoot length), leaf area, chlorophyll and carotenoid content. The application of these hormones also decreased the germination time. Maximum germination, shoot length, leaf area and carotenoid content was observed in 100 μm concentration of GA3. Root length, chl. a and chl. b was maximum in 50 μM of 2,4-D and 100 μm GA3, respectively. The application of two hormones exhibited a marked increase on all the parameters studied as compared to the control.


Transition from military to civilian: Identity, social connectedness, and veteran wellbeing.
Military identity and a sense of social connectedness may help explain differences in contemporary veteran wellbeing following transition from military to civilian life. However, it is unclear how these constructs interrelate. The current study quantitatively explored the role of social connectedness in the relationship between military identity and subjective wellbeing among contemporary ex-serving Australian Defence Force veterans. To facilitate analyses, data from 358 veterans were used to first explore the suitability of the factor structure of the Warrior Identity Scale. Subsequently, the potential moderating and mediating effects of social connectedness in the relationship between military identity and wellbeing were explored via path analysis. Confirmatory factor analysis of the Warrior Identity Scale revealed support for the multidimensional construct of military identity, and a revised six-factor measurement model was found suitable for further path analysis. Consistent with past research, social connectedness positively related to quality of life and negatively related to psychological distress. There was no support for a moderation effect of social connectedness. However, results indicated military identity indirectly influenced wellbeing and distress via differential relationships with social connectedness. Specifically, private and public regard for the military and not feeling like an outsider positively related to social connectedness. In contrast, interdependence with other veterans, viewing the military as family, and the centrality of military identity negatively related to social connectedness. The results suggest nurturing the protective aspects of military identity and addressing inhibitory aspects of military identity may support a sense of social connectedness and wellbeing among ex-serving veterans.


Why are angles misperceived?
Although it has long been apparent that observers tend to overestimate the magnitude of acute angles and underestimate obtuse ones, there is no consensus about why such distortions are seen. Geometrical modeling combined with psychophysical testing of human subjects indicates that these misperceptions are the result of an empirical strategy that resolves the inherent ambiguity of angular stimuli by generating percepts of the past significance of the stimulus rather than the geometry of its retinal projection.


Seascape genomics provides evidence for thermal adaptation and current-mediated population structure in American lobster (Homarus americanus).
Investigating how environmental features shape the genetic structure of populations is crucial for understanding how they are potentially adapted to their habitats, as well as for sound management. In this study, we assessed the relative importance of spatial distribution, ocean currents and sea surface temperature (SST) on patterns of putatively neutral and adaptive genetic variation among American lobster from 19 locations using population differentiation (PD) approaches combined with environmental association (EA) analyses. First, PD approaches (using bayescan, arlequin and outflank) found 28 outlier SNPs putatively under divergent selection and 9770 neutral SNPs in common. Redundancy analysis revealed that spatial distribution, ocean current-mediated larval connectivity and SST explained 31.7% of the neutral genetic differentiation, with ocean currents driving the majority of this relationship (21.0%). After removing the influence of spatial distribution, no SST were significant for putatively neutral genetic variation whereas minimum annual SST still had a significant impact and explained 8.1% of the putatively adaptive genetic variation. Second, EA analyses (using Pearson correlation tests, bayescenv and lfmm) jointly identified seven SNPs as candidates for thermal adaptation. Covariation at these SNPs was assessed with a spatial multivariate analysis that highlighted a significant temperature association, after accounting for the influence of spatial distribution. Among the 505 candidate SNPs detected by at least one of the three approaches, we discovered three polymorphisms located in genes previously shown to play a role in thermal adaptation. Our results have implications for the management of the American lobster and provide a foundation on which to predict how this species will cope with climate change.


Biosynthesis of wall teichoic acids in Staphylococcus aureus H, Micrococcus varians and Bacillus subtilis W23. Involvement of lipid intermediates containing the disaccharide N-acetylmannosaminyl N-acetylglucosamine.
The precursors for linkage unit (LU) synthesis in Staphylococcus aureus H were UDP-GlcNAc, UDP-N-acetylmannosamine (ManNAc) and CDP-glycerol and synthesis was stimulated by ATP. Moraprenol-PP-GlcNAc-ManNAc-(glycerol phosphate)1-3 was formed from chemically synthesised moraprenol-PP-GlcNAc, UDP-ManNAc and CDP-glycerol in the presence of Triton X-100. LU intermediates formed under both conditions served as acceptors for ribitol phosphate residues, from CDP-ribitol, which comprise the main chain. The initial transfer of GlcNAc-1-phosphate from UDP-GlcNAc was very sensitive to tunicamycin whereas the subsequent transfer of ManNAc from UDP-ManNAc was not. Poly(GlcNAc-1-phosphate) and LU synthesis in Micrococcus varians, with endogenous lipid acceptor, UDP-GlcNAc and CDP-glycerol, was stimulated by UDP-ManNAc. Synthesis of LU on exogenous moraprenol-PP-GlcNAc, with Triton X-100, was dependent on UDP-ManNAc and CDP-glycerol and the intermediates formed served as substrates for polymer synthesis. Membranes from Bacillus subtilis W23 had much lower levels of LU synthesis, but UDP-ManNAc was again required for optimal synthesis in the presence of UDP-GlcNAc and CDP-glycerol. Conditions for LU synthesis on exogenous moraprenol-PP-GlcNAc were not found in this organism. LU synthesis on endogenous acceptor in the absence of UDP-ManNAc was explained by contamination of membranes with UDP-GlcNAc 2-epimerase. Under appropriate conditions, low levels of this enzyme were sufficient to convert UDP-GlcNAc into a mixture of UDP-Glc-NAc and UDP-ManNAc and account for LU synthesis. The results indicate the formation of prenol-PP-GlcNAc-ManNAc-(glycerol phosphate)1-3 which is involved in the synthesis of wall teichoic acids in S. aureus H, M. varians and B. subtilis W23 and their attachment to peptidoglycan.


"Abortion--it is my own body": women's narratives about influences on their abortion decisions in Ghana.
Globally, abortion has emerged as a critical determinant of maternal morbidity and mortality. The Ghana government amended the country's abortion law in 1985 to promote safe abortion. This article discusses the findings of a qualitative study that explored the decision-making experiences of 28 female abortion seekers aged between 15 and 30 years in Ghana. Key findings from the study are that individuals claimed autonomy in their abortion decisions; underlying the abortion decisions were pragmatic concerns such as economic difficulties, child spacing, and fear of parental reaction. In conclusion, we examine the health implications of Ghanaian women's abortion decisions.


[Prenatal diagnosis of bronchopulmonary sequestration at the 26th week of gestation: report of a case].
A case report of a 18 years-old women on her first pregnancy, (26 weeks). US detected a live fetus with pulmonary sequestration diagnosis. On week 39 vaginal delivery occurred. A live newborn, Apgar 7-8 and Silverman 4-4 (one minute and five minutes respectively) was obtained. When diagnoses was confirmed, a surgical resection was performed (five days) and the child died at day-15 due to nosocomial sepsis. This case shows the convenience of prenatal diagnosis for management decisions.


Take action to prevent diabetes--the IMAGE toolkit for the prevention of type 2 diabetes in Europe.
When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: prevention is better than cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe. The good news is that diabetes is preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small changes in lifestyle will bring big changes in health. Through joint efforts, more people will be reached. The time to act is now.


Comparison of in vivo anti-melanoma effect of enantiomeric alpha-methyl- and alpha-ethyl-4-S-cysteaminylphenol.
Melanogenesis appears to be a unique target to develop anti-tumour agents specific for malignant melanoma. Among the anti-melanoma compounds that we have examined, 4-S-cysteaminylphenol (4-S-CAP), a phenolic amine, was found to have the most promising anti-melanoma effects. To further improve the efficacy as anti-melanoma agents, we have recently synthesized enantiomers of alpha-Me-4-S-CAP and alpha-Et-4-S-CAP. The enantiomers were found to be good substrates for tyrosinase. In vitro experiments showed that the enantiomers were highly cytotoxic to B16-F1 melanoma cells, and the cytotoxic effect was proved to be tyrosinase-dependent. In the present study, in vivo cytotoxicity experiments showed that i.p. administration of R-alpha-Me-4-S-CAP and S-alpha-Et-4-S-CAP (and 4-S-CAP) strongly inhibited the subcutaneous growth of B16 melanoma in mice, while the corresponding enantiomers were much less effective. Similarly, i.p. treatment with R-alpha-Me-4-S-CAP or S-alpha-Et-4-S-CAP, but not with 4-S-CAP, caused strong depigmentation of follicular melanocytes in C57BL black mice. Among 4-S-CAP and the enantiomers, only R-alpha-Et-4-S-CAP caused a moderate decrease in blood pressure in spontaneously hypertensive rats. These results confirm that the use of enantiomers increases the efficacy of tyrosinase-dependent cytotoxic phenolic amines.


Molecular cloning of the ferrichrome-iron receptor of Escherichia coli K-12.
A receptor protein in the outer membrane of Escherichia coli K-12 is required for the binding of ferrichrome-iron at the cell surface and for the transport of iron from this complex into the cell. This protein of Mr 78,000 is the product of the fhuA (previously called tonA) gene, located at 3.5 min on the E. coli chromosome. We cloned the fhuA gene into plasmid p343, a high-copy-number cosmid derived from pBR322. An 8.5-kilobase pair fragment of E. coli chromosomal DNA, generated by hydrolysis with the restriction endonuclease HindIII, was found to have conferred the FhuA+ phenotype to E. coli P8, which lacks the ferrichrome-iron receptor. A partial physical map of this recombinant plasmid pPM18 was established by determining the restriction endonuclease sites for BglII, EcoRI, PstI, PvuII, SmaI, and XhoI. The fhuA gene was localized to a 3.5-kilobase pair fragment of DNA whose extremities were defined by the restriction sites PstI-PvuII. A 7.5-fold enhancement of the rate of transport of iron from the ferrichrome complex was measured for cells which contained pPM18 as compared to wild-type E. coli K-12. Overproduction of the FhuA protein was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane proteins of the recombinant plasmid-containing strain. Proteins encoded by the subcloned DNA fragments were identified by [35S]methionine labeling of maxicells of E. coli CSR603, which contained recombinant plasmids; only one polypeptide chain, the presumptive fhuA gene product, was detected.


Single-shot channel activation accounts for duration of inhibitory postsynaptic potentials in a central neuron.
In the goldfish Mauthner cell, inhibitory postsynaptic currents evoked by intracellular stimulation of presynaptic neurons decay exponentially, with a mean time constant of 6.65 milliseconds. Analysis of membrane conductance fluctuations induced by iontophoresis of glycine and gamma-aminobutyric acid indicates a mean inhibitory channel lifetime of 7.15 milliseconds. The results thus suggest that the relaxation kinetics of activated inhibitory channels are rate-limiting during decay of the inhibitory postsynaptic current.


The human host response to monkeypox infection: a proteomic case series study.
The rapid rise of monkeypox (MPX) cases outside previously endemic areas prompts for a better understanding of the disease. We studied the plasma proteome of a group of MPX patients with a similar infection history and clinical manifestation typical for the current outbreak. We report that MPX in this case series is associated with a strong plasma proteomic response among nutritional and acute phase response proteins. Moreover, we report a correlation between plasma proteins and disease severity. Contrasting the MPX host response with that of COVID-19, we find a range of similarities, but also important differences. For instance, CFHR1 is induced in COVID-19, but suppressed in MPX, reflecting the different roles of the complement system in the two infectious diseases. Of note, the spatial overlap in response proteins suggested that a COVID-19 biomarker panel assay could be repurposed for MPX. Applying a targeted protein panel assay provided encouraging results and distinguished MPX cases from healthy controls. Hence, our results provide a first proteomic characterization of the MPX human host response and encourage further research on protein-panel assays in emerging infectious diseases.


Identification of Novel Chemical Scaffolds Inhibiting Trypanothione Synthetase from Pathogenic Trypanosomatids.
The search for novel chemical entities targeting essential and parasite-specific pathways is considered a priority for neglected diseases such as trypanosomiasis and leishmaniasis. The thiol-dependent redox metabolism of trypanosomatids relies on bis-glutathionylspermidine [trypanothione, T(SH)2], a low molecular mass cosubstrate absent in the host. In pathogenic trypanosomatids, a single enzyme, trypanothione synthetase (TryS), catalyzes trypanothione biosynthesis, which is indispensable for parasite survival. Thus, TryS qualifies as an attractive drug target candidate. A library composed of 144 compounds from 7 different families and several singletons was screened against TryS from three major pathogen species (Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum). The screening conditions were adjusted to the TryS´ kinetic parameters and intracellular concentration of substrates corresponding to each trypanosomatid species, and/or to avoid assay interference. The screening assay yielded suitable Z' and signal to noise values (≥0.85 and ~3.5, respectively), and high intra-assay reproducibility. Several novel chemical scaffolds were identified as low μM and selective tri-tryp TryS inhibitors. Compounds displaying multi-TryS inhibition (N,N'-bis(3,4-substituted-benzyl) diamine derivatives) and an N5-substituted paullone (MOL2008) halted the proliferation of infective Trypanosoma brucei (EC50 in the nM range) and Leishmania infantum promastigotes (EC50 = 12 μM), respectively. A bis-benzyl diamine derivative and MOL2008 depleted intracellular trypanothione in treated parasites, which confirmed the on-target activity of these compounds. Novel molecular scaffolds with on-target mode of action were identified as hit candidates for TryS inhibition. Due to the remarkable species-specificity exhibited by tri-tryp TryS towards the compounds, future optimization and screening campaigns should aim at designing and detecting, respectively, more potent and broad-range TryS inhibitors.


Importance of radiation time and dose factors on outcome for childhood medulloblastoma.
The purpose of this study was to investigate the relationship of posterior fossa radiation therapy duration (PFRTD) and relapse-free survival (RFS) following adjuvant craniospinal RT for childhood medulloblastoma. A retrospective audit was performed assessing all children aged <18 years managed with adjuvant craniospinal RT for medulloblastoma in Australia and New Zealand in 1980-1993. Children receiving prolonged (>180 days) pre-RT chemotherapy were excluded. Data were obtained for potential prognostic factors in domains of patient, tumour and treatment factors. Radiation therapy time factors assessed were PFRTD and time interval from surgery to commencement of RT (SRTD). The end-point assessed was RFS and analysis was performed using Cox regression and Kaplan-Meier survival. One hundred and eighty-nine children were identified from 10 oncology units, with data available from 182 children for analysis. Median follow up was 5.3 years. Seventy-three per cent of children presented with disease confined to the cerebellum; 13% had initial neuraxis disease. Macroscopic resection was described in 54%; 42% received adjuvant chemotherapy. Median RT dose and RT duration to PF was 55 Gy and 45 days, respectively. Seventy-eight relapses occurred with a 10-year actuarial RFS of 58.2% (standard error +/- 4%). On univariate analysis, increasing PF dose (P = 0.002), age >5 years (P = 0.006), and more thorough extent of surgical resection (P = 0.043) were associated with improved RFS; PFRTD (P = 0.20) and SRTD (P = 0.51) were not associated with RFS. On multivariate analysis, although both PF dose (P = 0.004) and extent of surgery (P = 0.045) remained strongly significant, RT duration was now associated with RFS (P = 0.049). Other factors assessed that did not reach significance were patient age, local tumour extent, presence of internal shunt and use of chemotherapy. The importance of local treatment factors was confirmed in this audit with established prognostic factors such as primary tumour macroscopic resection and adequate PF RT dose being associated with RFS. A treatment time effect is weakly suggested, although less significant than RT dose delivered.


Myo-inositol: a potential prophylaxis against premature onset of labour and preterm birth.
The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production and secretion of pro-inflammatory chemocytokines that overall dampen the pro-labour uteroplacental environment responsible for labour onset and progress, thus reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB.


Spatiotemporal organization of neuronal activity in the cervical cord of behaving primates.
Spinal neurons operate as a processing link that integrates descending and peripheral information and in turn, generates a specific yet complex muscle command. The functional organization of spinal circuitry during normal motor behavior dictates the way in which this translation process is achieved. Nonetheless, little is known about this organization during normal motor behavior. We examined the spatial organization of neural activity in the cervical spinal cord of behaving primates performing an isometric wrist task by estimating the averaged intraspinal activity of neuronal populations. We measured population response profiles and frequency content around torque onset and tested the tendency of these profiles to exhibit a specific organization within the spinal volume. We found that the spatial distribution of characteristic response profiles was non-uniform; namely, sites with a specific response profile tended to have a preferred spatial localization. Physiologically, this finding suggests that specific spinal circuitry that controls a unique feature of motor actions (with a particular task-related response pattern) may have a segregated spinal organization. Second, attempts to restore motor function via intraspinal stimulation may be more successful when the spatial distribution of these task-related profiles is taken into account.


[Mechanism of the occurrence of ventricular bigeminy].
Twenty-seven patients, aged 15 to 77, with a variety of cardiovascular diseases and bigeminy, and 3 normal subjects were investigated, using exercise and atropin tests. Electrocardiograms were recorded at pre-ectopic intervals of no more than 0.55 sec in bigeminy and polygeminy. The common divisor for interectopic intervals, ectopic complex interpolation, P-Q and Q-T intervals of the main complex and the presence of a wave on the ascending or descending slope of the R wave in sinus QRS complex were determined. Three mechanisms were identified to explain ventricular bigeminy developing during the third phase of action potential and the supernormal myocardial excitation period. A risk group was identified with respect to persistent bigeminy, incorporating patients with the short P-Q syndrome and signs of the typical or atypical Wolff-Parkinson-White syndrome.


Localized solutions in parametrically driven pattern formation.
The Mathieu partial differential equation (PDE) is analyzed as a prototypical model for pattern formation due to parametric resonance. After averaging and scaling, it is shown to be a perturbed nonlinear Schrödinger equation (NLS). Adiabatic perturbation theory for solitons is applied to determine which solitons of the NLS survive the perturbation due to damping and parametric forcing. Numerical simulations compare the perturbation results to the dynamics of the Mathieu PDE. Stable and weakly unstable soliton solutions are identified. They are shown to be closely related to oscillons found in parametrically driven sand experiments.


Quality of life and associated factors among adults in a community in South west Nigeria.
Quality of life (QoL) is an important measure in the assessment of population well being and health status. However despite locally validated measuring tools, little is known about the quality of life and associated factors in Nigerian adults. This study therefore aimed to assess QoL and contributory factors among adults residing in a sub urban Nigerian community. A descriptive cross-sectional study of 527 adults, in Oru community was conducted. An interviewer-administered questionnaire adapted from the WHO quality of life (WHOQOL-BREF) questionnaire was used to obtain information from respondents. Associations were explored with the chi square test; multivariate analysis was done with logistic regression at 5% level of significance. Respondents mean age was 33.3 ±8.1 years. In all, 46.5 % were currently married or cohabiting. Christianity was the dominant religion, 72.7%. In all, 81.6% had good QoL. Predictors of good QoL were respondents less than 25 years [OR: 3.5 (1.264-9.508)], having educational level that is secondary and above [OR: 4.2 (1.810-9.762)]. Being Unemployed [OR: 1.9 (1.099- 3.351)], living in flats and other bigger apartments [OR: 1.8 (1.121- 3.04)], currently ill [OR: 3.7 (2.096- 6.509)], and lack of involvement in religious activities [OR: 3.1 (1.166- 8.045)] were also shown to be predictors of good QoL. The majority of those evaluated had good QoL. Further surveys involving larger samples sizes are required to explore the QoL in distinct sub-populations and in currently ill patients to strengthen the results of this study.


Cloning and sequence of the cDNA corresponding to the variable region of immunoglobulin heavy chain MPC11.
Poly(A)-containing mRNA from mouse myeloma MPC11 was transcribed into cDNA which was cloned in the PstI site of the plasmid pBR322. The transformants were screened by hybridization with a cDNA fragment, derived from plasmid p gamma(11)7, corresponding to the 5' portion of the constant region of MPC11 heavy chain. Several positive transformants were found to contain various lengths of the variable region of the heavy chain. We describe the structure and sequence of one of these clones, pV(11)2, which contains cDNA corresponding to the entire variable region of MPC11 heavy chain and extends to codon 248 in the constant region. The protein sequence deduced from the DNA sequence indicates that the variable region of MPC11 heavy chain contains 121 amino acids and belongs to subgroup II of mouse heavy chains. Comparison of this sequence with other heavy chain sequences suggests a J (joining) segment of 16 residues which overlaps five residues of the third hypervariable region. The cDNA sequence shows that there is no discontinuity between the end of the variable region and the beginning of the constant region.


The TNF Superfamily Molecule LIGHT Promotes the Generation of Circulating and Lung-Resident Memory CD8 T Cells following an Acute Respiratory Virus Infection.
The transition of effector T cells or memory precursors into distinct long-lived memory T cell subsets is not well understood. Although many molecules made by APCs can contribute to clonal expansion and effector cell differentiation, it is not clear if clonal contraction and memory development is passive or active. Using respiratory virus infection, we found that CD8 T cells that cannot express the TNF family molecule lymphotoxin-like, exhibits inducible expression, competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes (LIGHT) are unimpaired in their initial response and clonally expand to form effector cell pools. Thereafter, LIGHT-deficient CD8 T cells undergo strikingly enhanced clonal contraction with resultant compromised accumulation of both circulating and tissue-resident memory cells. LIGHT expression at the peak of the effector response regulates the balance of several pro- and antiapoptotic genes, including Akt, and has a preferential impact on the development of the peripheral memory population. These results underscore the importance of LIGHT activity in programming memory CD8 T cell development, and suggest that CD8 effector T cells can dictate their own fate into becoming memory cells by expressing LIGHT.


Virtual anatomy: an anatomist's playground.
Virtual anatomy presents significant advantages over the reality of a cadaver as it can provide different views and perspectives, portability, longevity, standardization, diversity and most importantly the opportunity to learn the anatomy of the living human body instead of the corpse. Virtual anatomy is the life-like appearance of visible anatomy, a good example of which is the evolution of the Visible Human. Racial and statistical diversity is already developing as the population of photographic "Visible Humans" is now at least 10. Virtual anatomy should include additional diversity and therefore, consideration should be given to the preparation of more visible anatomy that will better support the virtual integration of all areas of physiology, kinematics, pathology and pathophysiology, development and evolution. Integration of anatomists with mathematicians, computer scientists, information scientists, physiologists, pathologists and clinicians (and LIST other basic scientist) is needed in order to facilitate this development. As this unfolds it is proposed, or challenged, that anatomists should maintain their position of responsibility for building anatomy as the foundation for all medical and healthcare education. In order to maintain that position they must understand and participate in this development and enjoy the rewards of teaching more visually empowering, functional, and clinical anatomy. The trip is a long one and is only about to begin but the train is leaving. Are you on board?


Preliminary experience with robot-assisted laparoscopic myomectomy.
The following retrospective case series evaluated the technique and feasibility of integrating robot-assisted technology in the performance of a laparoscopic myomectomy in order to overcome the limitations of conventional laparoscopy. We attempted 35 robot-assisted laparoscopic myomectomies in a university hospital setting with a conversion rate of 8.6%. There were a total of 48 myomas removed in 31 patients with completed robot-assisted laparoscopy. The mean number of myomas removed/patient was 1.6 (range 1-5). The mean diameter of myomas removed was 7.9 +/- 3.5 cm (95% CI 6.63-9.13), with the majority greater than 5 cm. The mean myoma weight was 223.2 +/- 244.1 g (95% CI 135.8-310.6). Mean operating time was 230.8 +/- 83 minutes (95% CI 201.6-260). The average estimated blood loss was 169 +/- 198.7 mL (95% CI 99.1-238.4). One patient experienced cardiogenic shock from vasopressin, two developed postoperative infections, and one was found to have adenomatous adenomyosis instead of a leiomyoma. The median length of hospital stay was 1 day. Overall, robot-assisted laparoscopic myomectomy is a promising new technique that may overcome many of the surgical limitations of conventional laparoscopy.


An automated controlled-rearing method for studying the origins of movement recognition in newly hatched chicks.
Movement recognition is central to visual perception and cognition, yet its origins are poorly understood. Can newborn animals encode and recognize movements at the onset of vision, or does this ability have a protracted developmental trajectory? To address this question, we used an automated controlled-rearing method with a newborn animal model: the domestic chick (Gallus gallus). This automated method made it possible to collect over 150 test trials from each subject. In their first week of life, chicks were raised in controlled-rearing chambers that contained a single virtual agent who repeatedly performed three movements. In their second week of life, we tested whether chicks could recognize the agent's movements. Chicks successfully recognized both individual movements and sequences of movements. Further, chicks successfully encoded the order that movements occurred within a sequence. These results indicate that newborn visual systems can encode and recognize movements at the onset of vision and argue for an increased focus on automated controlled-rearing methods for studying the emergence of perceptual and cognitive abilities.


Metastatic basal cell carcinoma.
Metastatic basal cell carcinomas of the skin are rare tumors. Early excision of the primary lesion remains the best method of treatment, although unresectable tumors can be controlled by radiation therapy. Patients with regional lymph node metastases can be managed by radical lymph node dissection, while those with systemic metastases can be palliated by a combination of chemotherapy, radiation therapy, and surgery.


Virtual Reality Applications for Neurological Disease: A Review.
Recent advancements in Virtual Reality (VR) immersive technologies provide new tools for the development of novel and promising applications for neurological rehabilitation. The purpose of this paper is to review the emerging VR applications developed for the evaluation and treatment of patients with neurological diseases. We start by discussing the impact of novel VR tasks that encourage and facilitate the patient's empowerment and involvement in the rehabilitation process. Then, a systematic review was carried out on six well-known electronic libraries using the terms: "Virtual Reality AND Neurorehabilitation," or "Head Mounted Display AND Neurorehabilitation." This review focused on fully-immersive VR systems for which 12 relevant studies published in the time span of the last five years (from 2014 to 2019) were identified. Overall, this review paper examined the use of VR in certain neurological conditions such as dementia, stroke, spinal cord injury, Parkinson's, and multiple sclerosis. Most of the studies reveal positive results suggesting that VR is a feasible and effective tool in the treatment of neurological disorders. In addition, the finding of this systematic literature review suggested that low-cost, immersive VR technologies can prove to be effective for clinical rehabilitation in healthcare, and home-based setting with practical implications and uses. The development of VR technologies in recent years has resulted in more accessible and affordable solutions that can still provide promising results. Concluding, VR and interactive devices resulted in the development of holistic, portable, accessible, and usable systems for certain neurological disease interventions. It is expected that emerging VR technologies and tools will further facilitate the development of state of the art applications in the future, exerting a significant impact on the wellbeing of the patient.


Anatomy of the ward round.
The ward round has been a central activity of hospital life for hundreds of years. It is hardly mentioned in textbooks. The ward round is a parade through the hospital of professionals where most decision making concerning patient care is made. However the traditional format may be intimidating for patients and inadequate for communication. The round provides an opportunity for the multi-disciplinary team to listen to the patient's narrative and jointly interpret his concerns. From this unfolds diagnosis, management plans, prognosis formation and the opportunity to explore social, psychological, rehabilitation and placement issues. Physical examination of the patient at the bedside still remains important. It has been a tradition to discuss the patient at the bedside but sensitive matters especially of uncertainty may better be discussed elsewhere. The senior doctor as round leader must seek the input of nursing whose observations may be under-appreciated due to traditional professional hierarchy. Reductions in the working hours of junior doctors and shortened length of stay have reduced continuity of patient care. This increases the importance of senior staff in ensuring continuity of care and the need for the joint round as the focus of optimal decision making. The traditional round incorporates teaching but patient's right to privacy and their preferences must be respected. The quality and form of the clinical note is underreported but the electronic record is slow to being accepted. The traditional multi-disciplinary round is disappearing in some centres. This may be regrettable. The anatomy and optimal functioning of the ward round deserves scientific scrutiny and experimentation.


Management of complex breast cysts.
This study was undertaken to evaluate the various strategies currently in use to manage complex cysts and specifically address the need for intervention. A review of 4562 breast sonograms obtained during an 18-month period revealed 308 complex cysts in 252 women. Data collected from review of patient records included the patient's age and risk factors for breast cancer, aspiration or biopsy results (or both), follow-up imaging studies, and management recommendations. Management recommendations for complex cysts were 1-year follow-up in 13 patients, 6-month follow-up in 148, sonographically guided aspiration in 82, aspiration with possible core biopsy in 62, and excisional biopsy in three. No malignancies were diagnosed in the group treated with follow-up imaging, sonographically guided aspiration, or excisional biopsy. One malignancy, a papilloma with a 3-mm focus of ductal carcinoma in situ, was diagnosed in one of the patients who underwent core biopsy. Of the lesions classified as complex cysts, the malignancy rate was 0.3% (1/308). This malignancy rate is lower than that for lesions classified as probably benign using mammographic criteria (i.e., for lesions classified as category 3 lesions using the Breast Imaging Reporting and Data System). Because the accepted standard practice for management of probably benign lesions is follow-up studies, the low yield of malignancy in this series suggests that complex cysts can be managed with follow-up imaging studies instead of intervention.


Pharmacological inhibition of protein tyrosine kinases axl and fyn reduces TNF-α-induced endothelial inflammatory activation in vitro.
Major surgery induces systemic inflammation leading to pro-inflammatory activation of endothelial cells. Endothelial inflammation is one of the drivers of postoperative organ damage, including acute kidney injury Tumour Necrosis Factor alpha (TNF-α) is an important component of surgery-induced pro-inflammatory activation of endothelial cells. Kinases, the backbone of signalling cascades, can be targeted by pharmacological inhibition. This is a promising treatment option to interfere with excessive endothelial inflammation. In this study, we identified activated kinases as potential therapeutic targets. These targets were pharmacologically inhibited to reduce TNF-α-induced pro-inflammatory signalling in endothelial cells. Kinome profiling using PamChip arrays identified 64 protein tyrosine kinases and 88 serine-threonine kinases, the activity of which was determined at various timepoints (5-240 min) following stimulation with 10 ng/ml TNF-α in Human umbilical vein endothelial cells in vitro. The PTKs Axl and Fyn were selected based on high kinase activity profiles. Co-localisation experiments with the endothelial-specific protein CD31 showed Axl expression in endothelial cells of glomeruli and Fyn in arterioles and glomeruli of both control and TNF-α-exposed mice. Pharmacological inhibition with Axl inhibitor BMS-777607 and Fyn inhibitor PP2 significantly reduced TNF-α-induced pro-inflammatory activation of E-selectin, VCAM-1, ICAM-1, IL-6 and IL-8 at mRNA and VCAM-1, ICAM-1, and IL-6 at protein level in HUVEC in vitro. Upon pharmacological inhibition with each inhibitor, leukocyte adhesion to HUVEC was also significantly reduced, however to a minor extent. In conclusion, pre-treatment of endothelial cells with kinase inhibitors BMS-777607 and PP2 reduces TNF-α-induced endothelial inflammation in vitro.


Functional neuroimaging in psychiatry.
Functional neuroimaging is one of the most powerful means available for investigating the pathophysiology of psychiatric disorders. In this review, we shall focus on the different ways that it can be employed to this end, describing the major findings in the field in the context of different methodological approaches. We will also discuss practical issues that are particular to studying psychiatric disorders and the potential contribution of functional neuroimaging to future psychiatric research.


Hypothalamic gene transfer of BDNF promotes healthy aging in mice.
The aging process and age-related diseases all involve perturbed energy adaption and impaired ability to cope with adversity. Brain-derived neurotrophic factor (BDNF) in the hypothalamus plays important role in regulation of energy balance. Our previous studies show that recombinant adeno-associated virus (AAV)-mediated hypothalamic BDNF gene transfer alleviates obesity, diabetes, and metabolic syndromes in both diet-induced and genetic models. Here we examined the efficacy and safety of a built-in autoregulatory system to control transgene BDNF expression mimicking the body's natural feedback systems in middle-aged mice. Twelve-month-old mice were treated with either autoregulatory BDNF vector or yellow fluorescence protein (YFP) control, maintained on normal diet, and monitored for 28 weeks. BDNF gene transfer prevented the development of aging-associated metabolic declines characterized by: preventing aging-associated weight gain, reducing adiposity, reversing the decline of brown fat activity, increasing adiponectin while reducing leptin and insulin in circulation, improving glucose tolerance, increasing energy expenditure, alleviating hepatic steatosis, and suppressing inflammatory genes in the hypothalamus and adipose tissues. Moreover, BDNF treatment reduced anxiety-like and depression-like behaviors. These safety and efficacy data provide evidence that hypothalamic BDNF is a target for promoting healthy aging.


Tool making, hand morphology and fossil hominins.
Was stone tool making a factor in the evolution of human hand morphology? Is it possible to find evidence in fossil hominin hands for this capability? These questions are being addressed with increasingly sophisticated studies that are testing two hypotheses; (i) that humans have unique patterns of grip and hand movement capabilities compatible with effective stone tool making and use of the tools and, if this is the case, (ii) that there exist unique patterns of morphology in human hands that are consistent with these capabilities. Comparative analyses of human stone tool behaviours and chimpanzee feeding behaviours have revealed a distinctive set of forceful pinch grips by humans that are effective in the control of stones by one hand during manufacture and use of the tools. Comparative dissections, kinematic analyses and biomechanical studies indicate that humans do have a unique pattern of muscle architecture and joint surface form and functions consistent with the derived capabilities. A major remaining challenge is to identify skeletal features that reflect the full morphological pattern, and therefore may serve as clues to fossil hominin manipulative capabilities. Hominin fossils are evaluated for evidence of patterns of derived human grip and stress-accommodation features.


Heterogeneously initiated transcription from the pre-B- and B-cell-specific mb-1 promoter: analysis of the requirement for upstream factor-binding sites and initiation site sequences.
The mb-1 gene, encoding a membrane immunoglobulin-associated protein, is developmentally regulated and expressed specifically in pre-B and mature B lymphocytes. Analysis of the TATA-less mb-1 promoter indicated that it directs initiation of transcription from multiple sites. Promoter sequences between -68 and +70 conferred the correct pattern of cell type-specific transcription upon a heterologous gene. Two nuclear factor-binding sites that are important for promoter function were identified between -59 and -38. Both sites interacted with ubiquitous nuclear factors in vitro. One of these factors was identified as Sp1. Multimerized copies of both factor-binding sites augmented expression from a heterologous minimal promoter in both lymphoid and nonlymphoid cells, suggesting that additional mb-1 promoter sequences are involved in determining the correct cell type specificity. Analysis of the heterogeneity of transcription initiation indicated that a mutation which increased the distance between upstream sequences and the region of initiation resulted in the utilization of a novel set of initiation sites. Moreover, an insertion of a TATA element into the mb-1 promoter at -30 biased initiation of transcription to +1 but did not abolish the use of the other sites. Mutation of an initiator sequence homology encompassing one of the major initiation sites had only a minor effect on its utilization. From these data, we conclude that upstream factor-binding sites in the TATA-less mb-1 promoter define a region in which initiation of transcription occurs at multiple sites.


Prevalence of Bartonella infection in domestic cats in Denmark.
Whole blood and serum from 93 cats (44 pets and 49 shelter/stray cats) from Denmark were tested for the presence of feline Bartonella species by culture and for the presence of Bartonella antibodies by serology. Bartonella henselae was isolated from 21 (22.6%) cats. Bacteremia prevalence was not statistically different between shelter/stray cats (13/49, 26.5%) and pet cats (8/44, 18.2%), but varied widely by geographical origin of the cats, even after stratification for cat origin or age (p < 0.001). All isolates but one were B. henselae type II. The only cat bacteremic with B. henselae type I was not co-infected with B. henselae type II. None of the cats was harboring either B. clarridgeiae or B. koehlerae. Almost half (42/92, 45.6%) of the cats were seropositive for B. henselae and antibody prevalence was similar in shelter/stray cats (23/49, 46.9%) and pet cats (19/43, 44.2%). This is the first report of isolation of B. henselae from domestic cats in Denmark. This study also indicates that domestic cats, including pet cats, constitute a large Bartonella reservoir in Denmark.


Comprehensive microRNA Profiling of Prostate Cancer.
MicroRNAs are small non-coding RNA molecules that have been shown to regulate the expression of genes linked to cancer. The relevance of microRNAs in the development, progression and prognosis of prostate cancer is not fully understood. It is also possible that these specific molecules may assist in the recognition of aggressive tumors and the development of new molecular targets. Our study investigated the importance of several microRNAs in cases of prostate cancer from 37 patients that were manually microdissected to obtain pure populations of tumor cells, normal epithelium and adjacent stroma. MicroRNA was extracted for PCR array profiling. Differentially expressed miRNAs for each case were used to compare tumor vs. normal epithelium and tumor-adjacent stroma samples. Loss of 18 miRNAs (e.g.miR-34c, miR-29b, miR-212 and miR-10b) and upregulation of miR-143 and miR-146b were significantly found in all the tumors in comparison with normal epithelium and/or stroma (p≤ 0.001). A different signature was found in the high grade tumors (Gleason score ≥ 8) when compared with tumors Gleason score 6. Upregulation of miR-122, miR-335, miR-184, miR-193, miR-34, miR-138, miR-373, miR-9, miR-198, miR-144 and miR-215 and downregulation of miR-96, miR-222, miR-148, miR-92, miR-27, miR-125, miR-126, miR-27 were found in the high grade tumors. MicroRNA profiling in prostate cancer appears to have unique expression patterns in comparison with normal tissue. These differential expressed miRNAs may provide novel diagnostic and prognostic tools that will assist in the recognition of prostate cancers with aggressive behavior.


Dynamic profiling of double-stranded RNA binding proteins.
Double-stranded (ds) RNA is a key player in numerous biological activities in cells, including RNA interference, anti-viral immunity and mRNA transport. The class of proteins responsible for recognizing dsRNA is termed double-stranded RNA binding proteins (dsRBP). However, little is known about the molecular mechanisms underlying the interaction between dsRBPs and dsRNA. Here we examined four human dsRBPs, ADAD2, TRBP, Staufen 1 and ADAR1 on six dsRNA substrates that vary in length and secondary structure. We combined single molecule pull-down (SiMPull), single molecule protein-induced fluorescence enhancement (smPIFE) and molecular dynamics (MD) simulations to investigate the dsRNA-dsRBP interactions. Our results demonstrate that despite the highly conserved dsRNA binding domains, the dsRBPs exhibit diverse substrate specificities and dynamic properties when in contact with different RNA substrates. While TRBP and ADAR1 have a preference for binding simple duplex RNA, ADAD2 and Staufen1 display higher affinity to highly structured RNA substrates. Upon interaction with RNA substrates, TRBP and Staufen1 exhibit dynamic sliding whereas two deaminases ADAR1 and ADAD2 mostly remain immobile when bound. MD simulations provide a detailed atomic interaction map that is largely consistent with the affinity differences observed experimentally. Collectively, our study highlights the diverse nature of substrate specificity and mobility exhibited by dsRBPs that may be critical for their cellular function.


Povidone-iodine intra-abdominal irrigation versus no irrigation in pediatric perforated appendicitis: A secondary economic analysis of a Bayesian randomized controlled trial.
A pilot randomized controlled trial (RCT) conducted in children (2-17 y) with perforated appendicitis demonstrated an 89% probability of reduced intra-abdominal abscess (IAA) rate with povidone-iodine (PVI) irrigation, compared with no irrigation (NI). We hypothesized that PVI also reduced 30-day hospital costs. We conducted a retrospective economic analysis of a pilot RCT. Hospital costs, inflated to 2019 U.S. dollars, were obtained for index admissions and 30-day emergency visits and readmissions. Cost differences between groups were assessed using frequentist and Bayesian generalized linear models. We observed a 95% Bayesian probability that PVI reduced 30-day mean total hospital costs ($16,555 [PVI] versus $18,509 [NI]; Bayesian cost ratio: 0.90, 95% CrI, 0.78-1.03). The mean absolute difference per patient was $1,954 less with PVI (95% CI, -$4,288 to $379). PVI likely reduced the IAA rate and 30-day hospital costs, suggesting the intervention is both clinically superior and cost saving.


Psychometric properties of a Chinese version of the Duke University Religion Index in college students and community residents in China.
A Chinese version of the Duke University Religion Index (DUREL) was developed and the psychometric properties were assessed. The study was conducted in two separate samples of 1,285 college students and 2,564 community residents. To assess test-retest reliability, the DUREL was re-administered after 1 wk. to 105 college students and 199 community residents. In both samples, three factors were extracted using principal components factor analysis with Promax rotation, which is consistent with the scale content. Internal consistency reliability was acceptable. Test-retest ICCs ranged from .45 to .89 in college students and .75 to .93 in community residents. The Chinese version of the DUREL is a useful measure of religiosity in Mandarin-speaking populations.


Radiation of benign disease--a South African perspective.
Radiation of benign disease is controversial. The approach of 55 South African radiation oncologists to 14 benign conditions was obtained and compared to available American data. In general, the approach was conservative except in cases of keloids. The South African and American approaches are remarkably similar (except with regard to ankylosing spondylitis). Private radiation oncologists are less conservative than their hospital counterparts. Randomised trials are needed firmly to establish efficacy and long-term side-effects.


[Effectiveness and tolerance of metipranolol--results of a multi-center long-term study in Switzerland].
The results of this continuing multicenter study revealed a good efficacy and tolerance of Metipranolol used in patients with ocular hypertension and chronic open-angle glaucoma. After 4 weeks' treatment a reduction in average intraocular pressure of 5.6 mmHg could be observed. This favorable effect on pressure values could be confirmed during long-term treatment up to 16 weeks (average reduction in intraocular pressure of 5.9 mmHg equal to 25%). More than 90% of patients treated with 0.1% Metipranolol showed very good or good tolerance. In conclusion, it can be established that 0.1% Metipranolol has also confirmed its value in daily practice and offers an interesting possibility for low-dosage beta-blocker therapy.


Occupational chemical exposures in an academic medical center.
Although the risks of certain chemical agents in the hospital environment are well known, problems associated with the entire spectrum of chemicals are not. To address this issue, we analyzed incident reports generated in response to chemical exposures in an academic medical center. We also reviewed workers' compensation clinic logs and the OSHA 200 log to obtain information on medical follow-up and severity. A total of 253 exposures occurred during the 3 years from 1988 to 1990. The overall incidence rate was 8.0 per 1000 person-years. Exposure rates by job title were highest for housekeepers (60.1 per 1000 person-years), followed by maintenance workers (18.6), and laboratory technicians (13.1). The most frequently involved chemical groups were disinfectants (25.9%), solvents (16.8%), and cleaning compounds (12.1%). Exposure by the dermal route was most common (37.9%). Thirteen percent of the exposures resulted in lost time and a similar percentage was reported on the OSHA log. Medical treatment was obtained by 53%. Implications for hazard communication, recordkeeping, and prevention are discussed.


Mortality following hip fracture in men with prostate cancer.
Hip fractures are associated with increased mortality and are a known adverse effect of androgen deprivation therapy (ADT) for prostate cancer (PCa). It was our aim to evaluate how mortality after hip fracture is modified by PCa and ADT. PCa dataBase Sweden (PCBaSe 2.0) is based on the National PCa Register and also contains age and county-matched PCa-free men. We selected all men (n = 14,205) who had been hospitalized with a hip fracture between 2006 and 2010; 2,300 men had a prior PCa diagnosis of whom 1,518 (66%) were on ADT prior to date of fracture. Risk of death was estimated with cumulative incidence and standardized mortality ratios (SMRs) to make comparisons with the entire PCa population and the general population. Cumulative incidences indicated that there was a higher risk of death following a hip fracture for PCa men on ADT than for PCa men not on ADT or PCa-free men, particularly in the first year. The SMRs showed that PCa men on ADT with a hip fracture were 2.44 times more likely to die than the comparison cohort of all PCa men (95%CI: 2.29-2.60). This risk was especially increased during the first month (5.64 (95%CI: 4.16-7.48)). In absolute terms, hip fractures were associated with 20 additional deaths per 1,000 person-years in PCa men not on ADT, but 30 additional deaths per 1,000 person-years for PCa men on ADT, compared to all PCa men. Hip fractures are associated with higher all-cause mortality in PCa men on ADT than in PCa men not on ADT or PCa-free men, especially within the first three months.


Angiosarcoma of the scalp with complete response to a biweekly gemcitabine and docetaxel (GEMDOC) chemotherapy regimen.
Angiosarcoma is a rare, aggressive soft-tissue sarcoma with a high rate of recurrence and distant metastasis. Only a few cases of angiosarcoma involving the scalp have been reported in the literature. We describe a case involving a 75-year-old woman who presented to the emergency department at the Detroit Medical Center with multiple painful scalp lesions. She had had similar lesions intermittently for several years that apparently had responded to treatment with antifungal creams, but those occurring in the 6 months before her presentation had not responded to that therapy. The final diagnosis was a metastatic angiosarcoma. The patient achieved complete remission following treatment with a combination chemotherapy regimen consisting of gemcitabine (1,500 mg/m²) and docetaxel (50 mg/m²) administered biweekly. The patient was free of disease at the 15-month follow-up. This regimen is well tolerated and should be considered, especially in elderly patients and patients with comorbid conditions who may not tolerate other chemotherapeutic regimens.


A newly identified role for Tomato bushy stunt virus P19 in short distance spread.
SUMMARY This study identified a role for the Tomato bushy stunt virus (TBSV) p19 protein (P19) in local lesion expansion on cowpea (Vigna unguiculata), and cell-to-cell movement in pepper (Capsicum annuum). The contribution to short distance spread in both hosts was strongly influenced by a cluster of charged amino acids between positions 72 and 78 on the 172 amino acid P19. Charged amino acids near this region between positions 43 and 85 were required for long distance spread in pepper. These results indicate that the central domain of P19 plays a key role for its activities in TBSV movement and that additional regions on this protein contribute to virus spread in a host-specific manner.


Quantitative real-time reverse transcription-polymerase chain reaction analysis of drug metabolizing and cytoprotective genes in psoriasis and regulation by ultraviolet radiation.
There are unpredictable inter-individual differences in response to ultraviolet radiation, used in the treatment of psoriasis and other common skin diseases. It is therefore essential that we attempt to identify phenotypic markers that correlate with individual treatment outcomes. Exposure of human skin to ultraviolet radiation results in the generation of reactive intermediates and oxidative stress. Hepatic drug metabolizing and cytoprotective genes are induced as an adaptive response to xenobiotics and reactive intermediates; as several of these genes are present in skin, we hypothesized that their cutaneous expression and regulation may be implicated in responses to ultraviolet radiation. We used quantitative real-time reverse transcription-polymerase chain reaction to investigate interindividual differences in the cutaneous expression of a variety of drug metabolizing and cytoprotective genes, including cytochrome P450s, glutathione S-transferases and drug transporters, and investigated the regulation of gene expression by ultraviolet radiation and in lesional psoriatic skin. We confirmed significant induction of cyclooxygenase 2 (mean 3.63-fold, range 0.14-22.6, p<0.0001) by ultraviolet radiation and showed more modest (approximately 2-fold) inductions of glutathione peroxidase, and novel inductions of glutathione S-transferase P1 and the drug transporter multidrug resistance associated protein-1. Glutathione S-transferase P1 (3.74-fold, 1.3-33.1, p<0.0001) and multidrug resistance associated protein-1 (4.06-fold, 1.3-24.8, p<0.0001) were also significantly increased in psoriatic plaque, as were P450 CYP2E1 (3.64-fold, 1-28.9 p<0.0001) and heme oxygenase-1 (10.19-fold, 2.9-49.7, p<0.0001), implying a differential adaptive response to oxidant exposure in lesional psoriatic skin. We found considerable interindividual variation in constitutive gene expression and inducibility, indicating that these genes may be associated with individuality in response to ultraviolet radiation.


Effects of breed-production system on collagen, textural, and sensory traits of 10 European beef cattle breeds.
In the current study the collagen, texture, and sensory characteristics of meat from 712 yearling males of 10 local Spanish and French beef breeds raised in their typical production systems were described. The breed-production system affected collagen and texture variables but affected sensory variables only slightly. There was a large amount of intra breed-production system variation for all the variables. French breeds had lower values for collagen solubility (~12%) than Spanish breeds (~40%). Stress (WB) varied from 36 N/cm2 in Casina to 44 N/cm2 in Salers, whereas compression stress at 80% ranged from 35 N/cm2 in Asturiana de los Valles to 40 N/cm2 in Salers. Oven cooking resulted in higher cooking losses (24%) than cooking on a grill (12%). Cooking losses increased as the grill temperature increased. Numerous significant correlations were found among variables. Carcass weight is associated with all the collagen and texture variables. Correlation coefficients among texture and collagen variables were statistically significant and these correlation coefficients were in general higher for solubility percentage than for total collagen content, highlighting the importance of the solubility of collagen rather than total collagen in determining meat textural properties. To differentiate a product in the market, it is necessary to define its characteristics. Differentiation allows increasing the added value of products and, therefore, income of the farmers. In addition, it guarantees to the consumers that the product they purchase has the intrinsic and extrinsic quality features that they seek. For consumers, beef texture is one of the most important quality attributes sought, therefore, studying factors that can affect beef texture is a major interest for the industry.


Finding the signal in the noise: Could social media be utilized for early hospital notification of multiple casualty events?
Delayed notification and lack of early information hinder timely hospital based activations in large scale multiple casualty events. We hypothesized that Twitter real-time data would produce a unique and reproducible signal within minutes of multiple casualty events and we investigated the timing of the signal compared with other hospital disaster notification mechanisms. Using disaster specific search terms, all relevant tweets from the event to 7 days post-event were analyzed for 5 recent US based multiple casualty events (Boston Bombing [BB], SF Plane Crash [SF], Napa Earthquake [NE], Sandy Hook [SH], and Marysville Shooting [MV]). Quantitative and qualitative analysis of tweet utilization were compared across events. Over 3.8 million tweets were analyzed (SH 1.8 m, BB 1.1m, SF 430k, MV 250k, NE 205k). Peak tweets per min ranged from 209-3326. The mean followers per tweeter ranged from 3382-9992 across events. Retweets were tweeted a mean of 82-564 times per event. Tweets occurred very rapidly for all events (<2 mins) and represented 1% of the total event specific tweets in a median of 13 minutes of the first 911 calls. A 200 tweets/min threshold was reached fastest with NE (2 min), BB (7 min), and SF (18 mins). If this threshold was utilized as a signaling mechanism to place local hospitals on standby for possible large scale events, in all case studies, this signal would have preceded patient arrival. Importantly, this threshold for signaling would also have preceded traditional disaster notification mechanisms in SF, NE, and simultaneous with BB and MV. Social media data has demonstrated that this mechanism is a powerful, predictable, and potentially important resource for optimizing disaster response. Further investigated is warranted to assess the utility of prospective signally thresholds for hospital based activation.