Prognostic significance of increased serum bilirubin levels coincident with cardiac decompensation in chronic heart failure.
The aim of this study was to analyze the relationship between abnormal liver function tests (LFTs) coincident with heart failure (HF) exacerbation and subsequent long-term outcome in patients with chronic HF. The study population consisted of 183 consecutive patients admitted for HF exacerbation with left ventricular ejection fraction < or =40%. Cox proportional hazard analysis revealed that serum total bilirubin (T-Bil) levels on admission (hazard ratio 1.896, p<0.001, 95% confidence interval 1.323-2.717), but not T-Bil at discharge or other LFTs, was an independent predictor of subsequent cardiac events after hospital discharge (cardiac death or readmission for HF exacerbation) The cardiac-event-free rates significantly decreased according to increasing tertiles of T-Bil stratified by the level of 0.7 and 1.2 mg/dl (p<0.001). T-Bil on admission had significant correlations with simultaneously-measured central venous pressure (CVP) (r=0.42, p<0.01) and cardiac index (CI) (r= -0.50, p<0.01). The patients demonstrating high CVP together with low CI showed significantly increased T-Bil compared with any other group. Increased T-Bil coincident with cardiac decompensation predicts a worse long-term prognosis of CHF, presumably through the potential liability to both congestion and tissue hypoperfusion simultaneously when HF deteriorates.


Patients' fear of genetic discrimination by health insurers: the impact of legal protections.
The impact of laws restricting health insurers' use of genetic information has been assessed from two main vantage points: (1) whether they reduce the extent of genetic discrimination and (2) whether they reduce the fear of discrimination and the resulting deterrence to undergo genetic testing. A previous report from this study concluded that there are almost no well-documented cases of health insurers either asking for or using presymptomatic genetic test results in their underwriting decisions, either before or after these laws, or in states with or without these laws. This report evaluates the perceptions and the resulting behavior by patients and clinicians. A comparative case study analysis was performed in seven states with different laws respecting health insurers' use of genetic information (no law, new prohibition, mature prohibition). Semistructured interviews were conducted in person with five patient advocates and with 30 experienced genetic counselors or medical geneticists, most of whom deal with adult-onset disorders. Also, multiple informed consent forms and patient information brochures were collected and analyzed using qualitative methods. Patients' and clinicians' fear of genetic discrimination greatly exceeds reality, at least for health insurance. It is uncertain how much this fear actually deters genetic testing. The greatest deterrence is to those who do not want to submit the costs of testing for reimbursement and who cannot afford to pay for testing. There appears to be little deterrence for tests that are more easily affordable or when the need for the information is much greater. Fear of discrimination plays virtually no role in testing decisions in pediatric or prenatal situations, but is significant for adult-onset genetic conditions. Existing laws have not greatly reduced the fear of discrimination. This may be due, in part, to clinicians' lack of confidence that these laws can prevent discrimination until there are test cases of actual enforcement. Ironically, there may be so little actual discrimination that it may not be possible to initiate good test cases.


Differentiation of recently infarcted myocardium from chronic myocardial scar: the value of contrast-enhanced SSFP-based cine MR imaging.
The purpose of this study is to demonstrate whether the signal intensity (SI) of myocardial infarction (MI) on contrast enhanced (CE)-cine MRI is useful for differentiating recently infarcted myocardium from chronic scar. This study included 24 patients with acute MI (36-84 years, mean age: 57) and 19 patients with chronic MI (44-80 years, mean age: 64). The diagnosis of acute MI was based on the presence of typical symptoms, i.e. elevation of the cardiac enzymes and the absence of any remote infarction history. The diagnosis of chronic MI was based on a history of MI or coronary artery disease of more than one month duration and on the absence of any recent MI within the previous six months. Retrospectively, the ECG-gated breath-hold cine imaging was performed in the short axis plane using a segmented, balanced, turbo-field, echo-pulse sequence two minutes after the administration of Gd-DTPA at a dose of 0.2 mmol/kg body weight. Delayed contrast-enhanced MRI (DCE MRI) in the same plane was performed 10 to 15 minutes after contrast administration, and this was served as the gold standard of reference. The SI of the infarcted myocardium on the CE-cine MRI was compared with that of the normal myocardium on the same image. The area of abnormal SI on the CE-cine MRI was compared with the area of hyperenhancement on the DCE MRI. The area of high SI on the CE-cine MRI was detected in 23 of 24 patients with acute MI (10 with homogenous high SI, 13 high SI with subendocardial low SI, and one with iso SI). The area of high SI on the CE-cine MRI was larger than that seen on the DCE MRI (p < 0.05). In contrast, the areas of chronic MI were seen as iso-SI with thin subendocardial low SI on the CE-cine MR in all the chronic MI patients. The presence of high SI on both the CE-cine MRI and the DCE MRI is more sensitive (95.8%) for determining the age of a MI than the presence of myocardial thinning (66.7%). This study showed the different SI patterns between recently infarcted myocardium and chronic scar on the CE-cine MRI. CE-cine MRI is thought to be quite useful for determining the age of myocardial infarction, in addition to its utility for assessing myocardial contractility.


Boron enrichment in martian clay.
We have detected a concentration of boron in martian clay far in excess of that in any previously reported extra-terrestrial object. This enrichment indicates that the chemistry necessary for the formation of ribose, a key component of RNA, could have existed on Mars since the formation of early clay deposits, contemporary to the emergence of life on Earth. Given the greater similarity of Earth and Mars early in their geological history, and the extensive disruption of Earth's earliest mineralogy by plate tectonics, we suggest that the conditions for prebiotic ribose synthesis may be better understood by further Mars exploration.


Changes in bronchial reactivity to acetylcholine with type C influenza virus infection in dogs.
To investigate the mechanisms involved in increasing bronchial reactivity, we made a model of airway reactivity increase in dogs after Type C influenza virus infection. Five beagle dogs were inoculated intranasally with the virus, and the time courses of changes in the hemagglutination inhibition (HI) antibody titer and the bronchial reactivity were determined. To assess bronchial reactivity the dogs were anesthetized, and dose-response curves of pulmonary resistance were obtained against increasing concentrations of acetylcholine aerosol. The dogs infected with the virus showed mild symptoms of rhinorrhea and cough. The HI antibody titer was significantly increased in all dogs, with peak values at 1 to 3 wk after infection. The bronchial reactivity to acetylcholine began to increase towards Day 3, reached a peak at 1 to 2 wk, and returned to a normal level at 4 wk. The airway reactivity to acetylcholine at 2 wk after infection was increased by 2.3 to 6.5 times the normal value in terms of the acetylcholine provocative concentration. The mean increase was significant at 1 wk (p less than 0.05), 2 wk (p less than 0.01), and 3 wk (p less than 0.05). Although both the HI antibody titer and the airway responsiveness increased together towards 1 to 2 wk, no close relationship between these factors was observed thereafter. The present dog model of airway hyperreactivity may be useful for further investigation of the mechanism governing increase in bronchial reactivity with respiratory viral infection in normal subjects as well as in patients with asthma.


Distinct long-term regulation of glycerol and non-esterified fatty acid release by insulin and TNF-alpha in 3T3-L1 adipocytes.
Adipose tissue lipolysis plays a central part in total body fuel metabolism. Our study was to assess the long-term regulation of glycerol and non-esterified fatty acid (NEFA) release by insulin or TNF-alpha. Fully differentiated 3T3-L1 adipocytes were exposed for up to 22 h to insulin or TNF-alpha. Long-term insulin treatment resulted in increased basal glycerol release, reaching sixfold at 22 h with 1 nmol/l insulin. Partial inhibition was observed by pharmacologically inhibiting phosphatidylinositol 3-kinase or the mitogen-activated kinase kinase--extracellular signal-regulated kinase cascades. This represented 50-60% of the response induced by 1 nmol/l TNF-alpha and approximately 40 % of the glycerol release maximally stimulated by isoproterenol (1 micromol/l, 30 min). The cellular mechanism seemed to be distinct from that of TNF-alpha: First, glycerol release in response to long-term insulin was progressive with time and did not display a lag-time characteristic of the effect of TNF-alpha. Second, pretreatment and co-treatment of the cells with troglitazone greatly inhibited TNF-alpha-induced glycerol release (128.5 +/- 10.2 to 35.4 +/- 2.1 nmol/mg protein per h) but not the effect of insulin, which was exaggerated. Third, hormone-sensitive lipase protein content was decreased (45 %) by TNF-alpha but not following long-term insulin. Finally, TNF-alpha was associated with NEFA release to the medium, whereas long-term insulin treatment was not. Moreover, glycerol release during isoproterenol-stimulated lipolysis was additive to the effect of long-term insulin, whereas NEFA release was inhibited by nearly 90 %. CONCLUSIONS INTERPRETATION: Contradictory to its short-term inhibitory effect, long-term insulin stimulates glycerol release with concomitant stimulation of NEFA re-esterification.


Influence of international emergency medicine opportunities on residency program selection.
In the last several years, there has been increasing interest in international emergency medicine (IEM) programs. A number of residency programs offer or encourage international opportunities during residency. The purpose of this study was twofold: 1) to determine whether the availability of international opportunities during residency affected the ranking of emergency medicine (EM) residency programs by graduating medical students and 2) to determine whether prior international health experience among medical students influences interviewing and ranking of residency programs with international opportunities. An eight-question survey measuring interest in IEM and its effect on ranking of programs was mailed to all 1,205 first-year EM residents from 122 accredited allopathic EM residency programs in the United States. International opportunities were defined as any program that offered an international elective during residency or had an IEM fellowship. Data were analyzed using descriptive statistics and chi-square tests. Of the 1,205 mailed surveys, 34% were returned by the first-year residents. Of all respondents, 281/408 (69%) interviewed at programs with international opportunities. Study findings revealed 62% (164/264) of the students who interviewed at programs with international opportunities considered the availability of international opportunities a positive factor in ranking residency programs. Analysis revealed that applicants with previous international health experience, 68% (104/152), were more likely to rank EM residency programs with international opportunities higher than those that did not. This study suggests that the availability of international opportunities during residency positively affected residency ranking. This relationship was stronger in medical students with prior international health experience.


Intimate violence and black women's health.
After reviewing the literature on health effects of intimate violence, we report secondary analyses of responses of 439 black women who participated in the Commonwealth Fund's national survey on women's health. Lower income women were more likely to experience partner violence but not childhood abuse; and income group was related to self-esteem, depressive symptoms, and perceived health status. Childhood physical and sexual abuse and partner violence were intercorrelated; both abuse history and partner violence were related to greater risk for depressive symptoms, lower life satisfaction, and lower perceived health care quality. Partner violence was also related to lower self-esteem and perceived health status. Sexually abused women had more difficulties in interpersonal relationships, including lower perceived health care quality even with self-esteem and depressive symptoms controlled. Implications for prevention, training, and future research as well as methodological issues in research on violence against black women are discussed.


[Biologic properties of Ralstonia solanacearum].
Two methods of estimation of potato cultivars for resistance to the agent of brown bacterial rot (Ralstonia solanacearum) were used. The distribution of the most widespread agricultural zoned potato cultivars into groups depending on the degree of their resistance to bacterial quarantine agent, potentially dangerous for Ukraine, can be used in the selection of the potato varieties resistant to the agent, and in the development of integrated plant protection systems. R. solanacearum was not detected in the potato samples from Chernovtsy and Kyiv Regions. However, agricultural zoned Ukrainian Solanaceae cultivars are sensitive to the collection R. solanacearum strains. Therefore, the agent is potentially dangerous and requires continuous control over its appearance and propagation.


Differential amygdala habituation to neutral faces in young and elderly adults.
Habituation is a highly adaptive property of the nervous system, which allows for the allocation of attention and other cognitive resources to more imperative environmental events. The amygdala is an important site of habituation in humans, but no studies to date have examined the effects of aging on amygdala habituation. Given the amygdala's role in evaluating the salience of a stimulus and initiating behavioral responses, the potential importance of amygdala habituation in aging may be far-reaching. Therefore, we assessed for differences in habituation in the amygdalae of healthy young and elderly adults during repeated presentations of neutral human faces using functional magnetic resonance imaging (fMRI). In addition, we evaluated the relationship between amygdala volume and habituation, to examine the effects of atrophy. Eighteen healthy young controls and 18 healthy elderly subjects were scanned with fMRI during viewing of repeatedly presented neutral human face stimuli. Significant fMRI signal decrement was observed across all subjects for early versus late face presentations. Analysis of group, condition, and hemisphere revealed a significant three-way interaction, with right greater than left habituation in the young, but left greater than right amygdala habituation in the elderly. Volumetric and correlational analyses demonstrated that amygdala volume is associated with habituation in the right, but not left, hemisphere. We conclude that, in healthy elderly adults, the amygdala retains its adaptive habituation response, but speculate that intrinsic changes in amygdala anatomy during aging may modulate its laterality.


Analysis of conversational topic shifts: a multiple case study.
Investigation into the natural conversational discourse of patients with Dementia of the Alzheimer Type has received minimal attention, in part due to the inherent methodological problems. There are no satisfactory theoretical models of conversation; existing global checklists give minimal information on meaning relationships and analysis of conversation does not lend itself to group studies. The present study offered an initial example of how meaning relationships, expressed through topic shifting behavior, can be described in DAT and normal elderly subjects in natural conversational discourse. Categorization of topic units was done in an attempt to describe general phenomena, type of shift, reason for shift, and contextual relationship. Although very little differences were visually observed in the general categories, some convergence of data were observed in other topic shift categories. Discussion of the results in relation to a discourse processing model is presented.


Local and paravertebral block anesthesia for outpatient elective breast cancer surgery.
Most breast cancer operations in the United States are performed with the patient given general anesthesia. We retrospectively reviewed our prospective breast cancer database to determine the percentage of patients who underwent breast cancer operations with either local or paravertebral block regional anesthesia from January 1 through June 30, 2008. Fifty-two of 70 patients (74%) were able to undergo breast cancer surgery with local or paravertebral block regional anesthesia. Operations included mastectomy, full axillary dissections, and expander or implant reconstruction. There were no conversions to general anesthesia and no unplanned overnight admissions. Only 5 of 52 patients (10%) undergoing surgery with local or paravertebral block regional anesthesia developed postoperative nausea or vomiting. We conclude that most elective outpatient breast cancer surgery operations can be performed with the patients given local or regional anesthesia.


Breakage of internal maxillary distractor: considerable complication of maxillary distraction osteogenesis.
Maxillary distraction osteogenesis using intraoral distractors is now one of the standard treatments of maxillary retrusion. This report shows 2 cases of breakage of this internal maxillary distractor in patients with cleft lip and palate; one was observed during the distraction period and the other was during the retention period. The first case required a rotational movement of the distraction segment, and this movement caused the laterally dislocation of the posterior part of the distractor, where the distractor suffered some mechanical forces by mouth opening. In the latter case, breakage of distractor was observed on the radiographs taken 3 months after distraction and this complication may have been caused by mechanical force by occlusion and mastication. Both breakages were found at the joint of the anchorage plate and the extension rod, which has some flexibility for adjusting the plate to the bone surface. Therefore, surgeons should pay special attention for this mechanical weak area in this distractor not only during the advancement period, but also during the retention period and should avoid unnecessary frequent bending for adopting the bone surface, which directly weakens the joint.


Non-additive genetic effects for fertility traits in Canadian Holstein cattle.
The effects of additive, dominance, additive by dominance, additive by additive and dominance by dominance genetic effects on age at first service, non-return rates and interval from calving to first service were estimated. Practical considerations of computing additive and dominance relationships using the genomic relationship matrix are discussed. The final strategy utilized several groups of 1000 animals (heifers or cows) in which all animals had a non-zero dominance relationship with at least one other animal in the group. Direct inversion of relationship matrices was possible within the 1000 animal subsets. Estimates of variances were obtained using Bayesian methodology via Gibbs sampling. Estimated non-additive genetic variances were generally as large as or larger than the additive genetic variance in most cases, except for non-return rates and interval from calving to first service for cows. Non-additive genetic effects appear to be of sizeable magnitude for fertility traits and should be included in models intended for estimating additive genetic merit. However, computing additive and dominance relationships for all possible pairs of individuals is very time consuming in populations of more than 200 000 animals.


The impact of roasting on cocoa quality parameters.
Roasting is an essential process in cocoa industry involving high temperatures that causes several physicochemical and microstructural changes in cocoa beans that ensure their quality and further processability. The versatility in roasting temperatures (100 - 150 °C) has attracted the attention of researchers toward the exploration of the effects of different roasting conditions on the color, proximal composition, cocoa butter quality, concentration of thermolabile compounds, formation of odor-active volatile organic compounds, generation of melanoidins, production of thermal processes contaminants in cocoa nibs, among others. Some researchers have drowned in exploring new roasting parameters (e.g., the concentration of water steam in the roasting chamber), whilst others have adapted novel heat-transfer techniques to cocoa nibs (e.g., fluidized bed roasting and microwaves). A detailed investigation of the physicochemical phenomena occurring under different cocoa roasting scenarios is lacking. Therefore, this review provides a comprehensive analysis of the state of art of cocoa roasting, identifies weak and mistaken points, presents research gaps, and gives recommendations to be considered for future cocoa studies.


Contracaecum osculatum and other anisakid nematodes in grey seals and cod in the Baltic Sea: molecular and ecological links.
Populations of grey seals (Halichoerus grypus), sprats (Sprattus sprattus) and cod (Gadus morhua) in the Baltic Sea are relatively stationary. The present work, applying classical and molecular helminthological techniques, documents that seals and cod also share a common parasite, the anisakid nematode Contracaecum osculatum, which uses seals as the final host and fish as transport hosts. Sequencing mitochondrial genes (COX1 and COX2) in adult worms from seals and third-stage larvae from livers of Baltic fish (sprats and cod), showed that all gene variants occur in both seals and fish. Other anisakid nematodes Pseudoterranova decipiens and Anisakis simplex are also found in both seals and cod in the Baltic Sea, but at much lower rates. The Baltic grey seal population was left at a critically low level (comprising a few hundred individuals) during the latter part of the 20th century, but since the year 2000 a marked increase in the population has been observed, reaching more than 40,000 individuals at present. Ecological consequences of the increased seal abundance may result from increased predation on fish stocks, but recent evidence also points to the influence of elevated parasitism on fish performance. Contracaecum osculatum larvae preferentially infect the liver of Baltic cod, considered a vital organ of the host. Whereas low prevalences and intensities in cod were reported during the 1980s and 1990s, the present study documents 100% prevalence and a mean intensity of above 80 worms per fish. Recent studies have also indicated the zoonotic potential of C. osculatum larvae in fish, following the consumption of raw or under-cooked fish. Therefore the present work discusses the impact of parasitism on the cod stock and the increasing risk for consumer health, and lists possible solutions for control.


Energy landscape and dynamics of the beta-hairpin G peptide and its isomers: Topology and sequences.
We have investigated free energy landscape [MM/PBSA + normal modes entropy] of permutations in the G peptide (41-56) from the protein G B1 domain by studying six isomers corresponding to moving the hydrophobic cluster along the beta-strands (toward the turn: T1, AGEWTYDDKTFTVTET; T2, GEDTWDYATFTVTKTE; T3, GEDDWTYATFTVTKTE; toward the end: E1, WTYDDAGETKTFTVT; E2, WEYTGDDATKTETFTV; E3, WTYEGDDATKTETFTV). The free energy terms include molecular mechanics energy, Poisson-Boltzmann electrostatic solvation energy, surface area solvation energy, and conformational entropy estimated by using normal mode analysis. From the wild type to T1, then T3, and finally T2, we see a progressively changing energy landscape, toward a less stable beta-hairpin structure. Moving the hydrophobic cluster outside toward the end region causes a greater change in the energy landscape. alpha-Helical instead of a beta-hairpin structure was the most stable form for the E2 isomer. However, no matter how much the sequence changes, for all variants studied, ideal "native" beta-hairpin topologies remain as minima (regardless of whether global or local) in the energy landscape. In general, we find that the energy landscape is dependent on the hydrophobic cluster topology and on the sequence. Our present study indicates that the key is the relative conformational energies of the different conformations. Changes in the sequence strongly modulate the relative stabilities of topologically similar regions in the energy landscape, rather than redefine the topology space. This finding is consistent with a population redistribution in the process of protein folding. The limited variation of topological space, compared with the number of possible sequence changes, may relate to the observation that the number of known protein folds are far less than the sequential allowance.


[Cellular immunologic reactions in mice tolerant to the transplantation antigens after immunization with the cross-reacting microbial antigens].
In combined administration of cyclophosphamide and lymphocytes of mice (CC57BR XX C3H) F1 to mice CC57BR there was observed a tolerance to alloantigens of mice C3H. Immunization of the tolerant mice with the vaccines of streptococcus, group A, and Candida albicans, containing antigens similar to the transplantation ones, led, to the partial destruction of the tolerance. This was expressed in the reduction in the CC57BR mice of the survival of skin allotransplants of mice C3H and the appearance in the lymphoid organs of lymphocytes with the cytotoxic activity against the allogenic target cells. In case of the tolerance destruction the amount of the recipient's lymphocytes forming rosettes with the erythrocytes of mice C3H remained unchanged, but the stem cell count fell in the spleen and the lymph nodes. The total amount of the T- and B-lymphocytes in the lymphoid organs was unchanged in destruction of the tolerance.


Rapid, microwave-assisted synthesis of Gd2O3 and Eu:Gd2O3 nanocrystals: characterization, magnetic, optical and biological studies.
Ultra-small crystals of undoped and Eu-doped gadolinium oxide (Gd2O3) were synthesised by a simple, rapid microwave-assisted route, using benzyl alcohol as the reaction solvent. XRD, XPS and TEM analysis reveal that the as-prepared powder material consists of nearly monodisperse Gd2O3 nanocrystals with an average diameter of 5.2 nm. The nanocrystals show good magnetic behaviour and exhibit a larger reduction in relaxation time of water protons than the standard Gd-DTPA complex currently used in MRI imaging. Cytotoxicity studies (both concentration- and time-dependent) of the Gd2O3 nanocrystals show no adverse effect on cell viability, evidencing their high biological compatibility. Finally, Eu:Gd2O3 nanocrystals were prepared by a similar route and the red luminescence of Eu3+ activator ions was used to study the cell permeability of the nanocrystals. Red fluorescence from Eu3+ ions observed by fluorescence microscopy shows that the nanocrystals (Gd2O3 and Eu:Gd2O3) can permeate not only the cell membrane but can also enter the cell nucleus, rendering them candidate materials not only for MRI imaging but also for drug delivery when tagged or functionalized with specific drug molecules.


Experimentally derived sticking efficiencies of microparticles using atomic force microscopy.
The sticking efficiencies (alpha) of colloidal particles have been derived from the intersurface potential energy between 2 microm carboxylated polystyrene microspheres and a silica glass plate using the interaction force boundary layer model. The intersurface potential energies were calculated from force-distance data measured using atomic force microscopy (AFM) and from calculations based on Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. AFM forces were measured in aqueous solutions over a range of pH and ionic strength conditions, and DLVO calculations were performed on identical systems. In most conditions, sticking efficiencies that were calculated from AFM data are considerably largerthan values calculated from DLVO predictions. Sticking efficiencies vary between 0 and 1 and are strongly dependent upon solution chemistry. AFM-derived sticking efficiencies are consistent with measured microsphere and collector zeta-potentials; sticking efficiencies are lower for more negatively charged surfaces. These results provide the first alpha estimates of a microparticle-collector system that are calculated directly from physically measured interfacial nanoforces. This study clearly demonstrates that significant differences exist between DLVO- and AFM-derived sticking efficiencies.


The influence of knee position on ankle dorsiflexion - a biometric study.
Musculus gastrocnemius tightness (MGT) can be diagnosed by comparing ankle dorsiflexion (ADF) with the knee extended and flexed. Although various measurement techniques exist, the degree of knee flexion needed to eliminate the effect of the gastrocnemius on ADF is still unknown. The aim of this study was to identify the minimal degree of knee flexion required to eliminate the restricting effect of the musculus gastrocnemius on ADF. Bilateral ADF of 20 asymptomatic volunteers aged 18-40 years (50% female) was assessed prospectively at six different degrees of knee flexion (0°, 20°, 30°, 45°, 60°, 75°, Lunge). Tests were performed following a standardized protocol, non weightbearing and weightbearing, by two observers. Statistics comprised of descriptive statistics, t-tests, repeated measurement ANOVA and ICC. 20 individuals with a mean age of 27 ± 4 years were tested. No significant side to side differences were observed. The average ADF [95% confidence interval] for non weightbearing was 4° [1°-8°] with the knee extended and 20° [16°-24°] for the knee 75° flexed. Mean weightbearing ADF was 25° [22°-28°] for the knee extended and 39° [36°-42°] for the knee 75° flexed. The mean differences between 20° knee flexion and full extension were 15° [12°-18°] non weightbearing and 13° [11°-16°] weightbearing. Significant differences of ADF were only found between full extension and 20° of knee flexion. Further knee flexion did not increase ADF. Knee flexion of 20° fully eliminates the ADF restraining effect of the gastrocnemius. This knowledge is essential to design a standardized clinical examination assessing MGT.


A park-based group mobility program for older adults with difficulty walking outdoors: a quantitative process evaluation of the Getting Older Adults Outdoors (GO-OUT) randomized controlled trial.
Process evaluations of randomized controlled trials (RCTs) of community exercise programs are important to help explain the results of a trial and provide evidence of the feasibility for community implementation. The objectives of this process evaluation for a multi-centre RCT of outdoor walking interventions for older adults with difficulty walking outdoors, were to determine: 1) implementation fidelity (the extent to which elements of the intervention were delivered as specified in the original protocol) and 2) participant engagement (the receipt of intervention components by the participants) in the Getting Older Adults Outdoors (GO-OUT) trial. GO-OUT participants attended an active 1-day workshop designed to foster safe, outdoor walking skills. After the workshop, 190 people at 4 sites were randomized to an outdoor walk group (OWG) (n = 98) which met 2x/week for 10 weeks, or the weekly reminders (WR) group (n = 92) which received a phone reminder 1x/week for 10 weeks. The OWG had 5 components - warm-up, continuous distance walk, task-oriented walking activities, 2nd continuous distance walk, and cool-down. Data on implementation fidelity and participant engagement were gathered during the study through site communications, use of standardized forms, reflective notes of the OWG leaders, and accelerometry and GPS assessment of participants during 2 weeks of the OWG. All sites implemented the workshop according to the protocol. Participants were engaged in all 8 activity stations of the workshop. WR were provided to 96% of the participants in the WR intervention group. The 5 components of the OWG sessions were implemented in over 95% of the sessions, as outlined in the protocol. Average attendance in the OWG was not high - 15% of participants did not attend any sessions and 64% of participants in the OWG attended > 50% of the sessions. Evaluations with accelerometry and GPS during week 3 and 9 OWG sessions suggest that participants who attended were engaged and active during the OWG. This process evaluation helps explain the main study findings and demonstrates the flexibility required in the protocol for safe and feasible community implementation. Future research could explore the use of additional behaviour change strategies to optimize attendance for community implementation. ClinicalTrials.gov NCT03292510 Date of registration: September 25, 2017.


FAIR+E pathogen data for surveillance and research: lessons from COVID-19.
The COVID-19 pandemic has exemplified the importance of interoperable and equitable data sharing for global surveillance and to support research. While many challenges could be overcome, at least in some countries, many hurdles within the organizational, scientific, technical and cultural realms still remain to be tackled to be prepared for future threats. We propose to (i) continue supporting global efforts that have proven to be efficient and trustworthy toward addressing challenges in pathogen molecular data sharing; (ii) establish a distributed network of Pathogen Data Platforms to (a) ensure high quality data, metadata standardization and data analysis, (b) perform data brokering on behalf of data providers both for research and surveillance, (c) foster capacity building and continuous improvements, also for pandemic preparedness; (iii) establish an International One Health Pathogens Portal, connecting pathogen data isolated from various sources (human, animal, food, environment), in a truly One Health approach and following FAIR principles. To address these challenging endeavors, we have started an ELIXIR Focus Group where we invite all interested experts to join in a concerted, expert-driven effort toward sustaining and ensuring high-quality data for global surveillance and research.


Very Low-Density Lipoprotein Cholesterol May Mediate a Substantial Component of the Effect of Obesity on Myocardial Infarction Risk: The Copenhagen General Population Study.
Individuals with obesity have higher concentrations of very low-density lipoprotein (VLDL) cholesterol and increased risk of myocardial infarction. We hypothesized that VLDL cholesterol explains a fraction of the excess myocardial infarction risk in individuals with obesity. We included 29 010 individuals free of myocardial infarction at baseline, nested within 109 751 individuals from the Copenhagen General Population Study. During 10 years of follow-up, 2306 individuals developed myocardial infarction. Cholesterol content in large and small VLDLs, in intermediate-density lipoprotein (IDL), and in LDL was measured directly with nuclear magnetic resonance spectroscopy. Median concentrations of cholesterol in large and small VLDLs were 0.12 mmol/L (interquartile range [IQR], 0.07-0.20 mmol/L; 4.5 mg/dL [IQR, 2.6-6.9 mg/dL]) and 0.6 mmol/L (IQR, 0.5-0.8 mmol/L; 25 mg/dL [IQR, 20-30 mg/dL]) in individuals with obesity vs 0.06 mmol/L (IQR, 0.03-0.1 mmol/L; 2.2 mg/dL [IQR, 1.1-3.8 mg/dL]), and 0.5 mmol/L (IQR, 0.4-0.6 mmol/L; 20 mg/dL (IQR, 16-25 mg/dL]) in individuals with normal weight; in contrast, concentrations of IDL and LDL cholesterol were similar across body mass index (BMI) categories. Cholesterol in large and small VLDLs combined explained 40% (95% CI, 27%-53%) of the excess risk of myocardial infarction associated with higher BMI. In contrast, IDL and LDL cholesterol did not explain excess risk of myocardial infarction, whereas systolic blood pressure explained 17% (11%-23%) and diabetes mellitus explained 8.6% (3.2%-14%). VLDL cholesterol explains a large fraction of excess myocardial infarction risk in individuals with obesity. These novel findings support a focus on cholesterol in VLDL for prevention of myocardial infarction and atherosclerotic cardiovascular disease in individuals with obesity.


Inhibition of 2A-mediated 'cleavage' of certain artificial polyproteins bearing N-terminal signal sequences.
Where 2A oligopeptide sequences occur within ORFs, the formation of the glycyl-prolyl peptide bond at the C-terminus of (each) 2A does not occur. This property can be used to concatenate sequences encoding several proteins into a single ORF: each component of such an artificial polyprotein is generated as a discrete translation product. 2A and '2A-like' sequences have become widely utilised in biotechnology and biomedicine. Individual proteins may also be co- and post-translationally targeted to a variety of sub-cellular sites. In the case of polyproteins bearing N-terminal signal sequences we observed, however, that the protein downstream of 2A (no signal) was translocated into the endoplasmic reticulum (ER). We interpreted these data as a form of 'slipstream' translocation: downstream proteins, without signals, were translocated through a translocon pore already formed by the signal sequence at the N-terminus of the polyprotein. Here we show this effect is, in fact, due to inhibition of the 2A reaction (formation of fusion protein) by the C-terminal region (immediately upstream of 2A) of some proteins when translocated into the ER. Solutions to this problem include the use of longer 2As (with a favourable upstream context) or modifying the order of proteins comprising polyproteins.


Influenza vaccination and reduction in risk of ischemic heart disease among chronic obstructive pulmonary elderly.
COPD estimates the third leading cause of death by 2020. To reduce its complications becomes an important issue. The purpose of this study is to investigate the influenza vaccine effect for IHD occurrence with secondary to COPD. We used 11 years Taiwan National Health Insurance cohort research database and analyzed the relationships between vaccination and incident of IHD for COPD patients stratified by age. Total 29,178 COPD patients, 703 patients got vaccination out of 1464 who have developed IHD and 6010 patients vaccinated out of 27,714 that did not developed IHD. Major findings we observed: vaccination was associated with a reduced risk of IHD (OR, 0.746; 95% CI, 0.595-0.937) in elderly COPD patients. Influenza vaccination was associated with a reduced risk for IHD only in elderly COPD patients. Moreover, COPD patients with IHD had higher vaccination rate than without IHD.


The treatment of facial palsy from the point of view of physical and rehabilitation medicine.
There are evidences to support recommending the early intake of prednisone (in its appropriate dose of 1 mg/kg body weight for up to 70 or 80 mg/day) or the combined use of prednisone and acyclovir (or valacyclovir) within 72 h following the onset of paralysis in order to improve the outcome of Bell's palsy (BP). Although there may be a controversy about the role of physiotherapy in BP or facial palsy, it seemed that local superficial heat therapy, massage, exercises, electrical stimulation and biofeedback training have a place in the treatment of lower motor facial palsy. However, each modality has its indications. Moreover, some rehabilitative surgical methods might be of benefit for some patients with traumatic facial injuries or long standing paralysis without recovery, but early surgery in BP is usually not recommended. However, few may recommend early surgery in BP when there is 90-100% facial nerve degeneration. The efficacy of acupuncture, magnetic pellets and other modalities of physiotherapy needs further investigation. The general principles and the different opinions in treating and rehabilitating facial palsy are discussed and the need for further research in this field is suggested.


Prenatal phencyclidine treatment induces behavioral deficits through impairment of GABAergic interneurons in the prefrontal cortex.
We previously reported that prenatal treatment with phencyclidine (PCP) induces glutamatergic dysfunction in the prefrontal cortex (PFC), leading to schizophrenia-like behavioral deficits in adult mice. However, little is known about the prenatal effect of PCP treatment on other types of neurons. We focused on γ-aminobutyric acid (GABA)-ergic interneurons and evaluated the effect of prenatal PCP exposure on the neurodevelopment of GABAergic interneurons in the PFC. PCP was administered at the dose of 10 mg/kg/day to pregnant dams from embryonic day 6.5 to 18.5. After the pups were reared to adult, we analyzed their GABAergic system in the PFC using immunohistological, biochemical, and behavioral analyses in adulthood. The prenatal PCP treatment decreased the density of parvalbumin-positive cells and reduced the expression level of glutamic acid decarboxylase 67 (GAD67) and GABA content of the PFC in adults. Additionally, prenatal PCP treatment induced behavioral deficits in adult mice, such as hypersensitivity to PCP and prepulse inhibition (PPI) deficits. These behavioral deficits were ameliorated by pretreatment with the GABAB receptor agonist baclofen. Furthermore, the density of c-Fos-positive cells was decreased after the PPI test in the PFC of mice treated with PCP prenatally, and this effect was ameliorated by pretreatment with baclofen. These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.


[Neuronal secretory activity of the hypothalamic large-cell nuclei in rats with spontaneous hypertension].
The study was carried out in 24 male rats with spontaneous hypertension (SHR, Kyoto Wistar) and control Wistar rats aged 8 and 12 weeks with the objective of detecting the time of activation of large cell neurosecretory nuclei of the anterior hypothalamus in rats with spontaneous hypertension. The activity of neurons of the supraoptical and paraventricular nuclei was evaluated by two quantitative methods. One of them allows the study of distribution of neurosecretory cells by phases of synthesis in these nuclei in 8- and 12-week-old animals. Along with this morphometrical method, the average diameter of neurosecretory cells and their nuclei was determined after Gomori's staining with chromium-alumen hematoxylin. Spontaneously hypertensive and control normotensive rats by 12 weeks of development were found to have an enhanced function of neurosecretory nuclei apparently associated with the age change in their functional activity. In spontaneously hypertensive rats, more pronounced activation of the supraoptic and paraventricular nuclei manifested by hypertrophy of neurons and their nuclei occurs only with the development of hypertension and is absent in the pre-hypertensive stage.


Laser induced deflection technique for absolute thin film absorption measurement: optimized concepts and experimental results.
Using experimental results and numerical simulations, two measuring concepts of the laser induced deflection (LID) technique are introduced and optimized for absolute thin film absorption measurements from deep ultraviolet to IR wavelengths. For transparent optical coatings, a particular probe beam deflection direction allows the absorption measurement with virtually no influence of the substrate absorption, yielding improved accuracy compared to the common techniques of separating bulk and coating absorption. For high-reflection coatings, where substrate absorption contributions are negligible, a different probe beam deflection is chosen to achieve a better signal-to-noise ratio. Various experimental results for the two different measurement concepts are presented.


Localization of lysosomal antigens in activated T-lymphocytes.
The lysosomal compartment has been examined in activated T-lymphocytes by immunogold electron microscopy and subcellular fractionation. Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of radiolabelled extracts of the T-cells showed that they contained three antigens which are fundamental to normal lysosomal function: a representative lysosomal enzyme beta-glucuronidase, a lysosomal associated membrane protein (LAMP-1), and the cation-independent mannose 6-phosphate lysosomal enzyme targeting receptor (MPR). Immunogold labelling showed that beta-glucuronidase was present in the rough endoplasmic reticulum, the Golgi complex and Golgi-associated vesicles. The enzyme was also found to accumulate in distinct, non-Golgi organelles in which LAMP-1 was co-localized, probably lysosomes. LAMP-1 was also found in tubular elements of the Golgi and in a complex of vesicles clustered near the nucleus where MPR was also present at high density. Fractionation of homogenates from lymphocytes on Percoll gradients revealed that beta-glucuronidase was distributed throughout the low density region containing rough endoplasmic reticulum, Golgi and plasma membrane components, and the high density region which contained only lysosomal activity. Multiple immunogold electron microscopy of the latter fraction showed the presence of homogenous vesicles which had large amounts of beta-glucuronidase within the lumen, LAMP-1 at the periphery and no MPR. These vesicles were probably mature lysosomes, arising from pre-lysosomal organelles enriched for LAMP-1 and MPR.


Dual-modal visibility metrics for interactive PET-CT visualization.
Dual-modal positron emission tomography and computed tomography (PET-CT) imaging enables the visualization of functional structures (PET) within human bodies in the spatial context of their anatomical (CT) counterparts, and is providing unprecedented capabilities in understanding diseases. However, the need to access and assimilate the two volumes simultaneously has raised new visualization challenges. In typical dual-modal visualization, the transfer functions for the two volumes are designed in isolation with the resulting volumes being fused. Unfortunately, such transfer function design fails to exploit the correlation that exists between the two volumes. In this study, we propose a dual-modal visualization method where we employ 'visibility' metrics to provide interactive visual feedback regarding the occlusion caused by the first volume on the second volume and vice versa. We further introduce a region of interest (ROI) function that allows visibility analyses to be restricted to subsection of the volume. We demonstrate the new visualization enabled by our proposed dual-modal visibility metrics using clinical whole-body PET-CT studies of various diseases.


MM1, a temperate bacteriophage of the type 23F Spanish/USA multiresistant epidemic clone of Streptococcus pneumoniae: structural analysis of the site-specific integration system.
We have characterized a temperate phage (MM1) from a clinical isolate of the multiply antibiotic-resistant Spanish/American 23F Streptococcus pneumoniae clone (Spain(23F)-1 strain). The 40-kb double-stranded genome of MM1 has been isolated as a DNA-protein complex. The use of MM1 DNA as a probe revealed that the phage genome is integrated in the host chromosome. The host and phage attachment sites, attB and attP, respectively, have been determined. Nucleotide sequencing of the attachment sites identified a 15-bp core site (5'-TTATAATTCATCCGC-3') that has not been found in any bacterial genome described so far. Sequence information revealed the presence of an integrase gene (int), which represents the first identification of an integrase in the pneumococcal system. A 1.5-kb DNA fragment embracing attP and the int gene contained all of the genetic information needed for stable integration of a nonreplicative plasmid into the attB site of a pneumococcal strain. This vector will facilitate the introduction of foreign genes into the pneumococcal chromosome. Interestingly, DNAs highly similar to that of MM1 have been detected in several clinical pneumococcal isolates of different capsular types, suggesting a widespread distribution of these phages in relevant pathogenic strains.


Utility of Magnetic Resonance Imaging in Differentiating Cerebrospinal Fluid Leak from Middle Ear Effusion.
To demonstrate the clinical utility, sensitivity, and specificity of standard magnetic resonance imaging (MRI) sequences in differentiating temporal bone cerebrospinal fluid leaks from all other middle ear effusions. Retrospective imaging review. Academic medical center. Patients with cerebrospinal fluid leaks or other middle ear effusions who also underwent MRI. Patients were assigned to cerebrospinal fluid leak and other effusion cohorts based on clinical course, findings at surgery/myringotomy, and beta-2 transferrin fluid analysis. Reviewers blinded to the clinical outcome examined T1-weighted, T2-weighted, diffusion-weighted, fluid-attenuated inversion recovery (FLAIR), and 3-dimensional (3D) acquired T2-weighted MRI sequences. For each sequence, fluid imaged in the temporal bone was graded as either similar or dissimilar in signal intensity to cerebrospinal fluid in the adjacent subarachnoid space. Signal similarity was interpreted as being diagnostic of a leak. Test characteristics in predicting the presence of a leak were calculated for each series. Eighty patients met criteria (41 leaks, 39 other effusions). The 3D T2 series was 76% sensitive and 100% specific in diagnosing a leak, and FLAIR was 44% sensitive and 100% specific. The T1-weighted (73% sensitive, 69% specific), T2-weighted (98% sensitive, 5.1% specific), and diffusion-weighted (63% sensitive, 66% specific) series were less useful. MRI, with attention to 3D T2 and FLAIR series, is a noninvasive and highly specific test for diagnosing cerebrospinal fluid leak in the setting of an indeterminate middle ear effusion.


Functional genomic analysis of the 61D-61F region of the third chromosome of Drosophila melanogaster.
Assigning functional significance to completed genome sequences is one of the next challenges in biological science. Conventional genetic tools such as deficiency chromosomes help assign essential complementation groups to their corresponding genes. We describe an F2 genetic screen to identify lethal mutations within cytogenetic region 61D-61F of the third chromosome of Drosophila melanogaster. One hundred sixteen mutations were identified by their failure to complement both Df(3L)bab-PG and Df(3L)3C7. These alleles were assigned to 14 complementation groups and 9 deficiency intervals. Complementation groups were ordered using existing deficiencies, as well as new deficiencies generated in this study. With the aid of the genomic sequence, genetic and physical maps in the region were correlated by use of PCR to localize the breakpoints of deficiencies within a 268-kb genomic contig (GenBank accession No. AC005847). Six essential complementation groups were assigned to specific genes, including genes encoding a porphobilinogen deaminase and a Sac1-like protein.


Elevated levels of circulating fibroblast growth factor 23 with hypercalcemia following discontinuation of denosumab.
We report a case of a 47-year-old woman with hypercalcemia 6 months after discontinuation of denosumab. She underwent right mastectomy for breast cancer and had received aromatase inhibitor and denosumab therapy for 5 years. Thirst, appetite loss, and bilateral ankle pain began few months after cessation of denosumab. She was admitted to the hospital for hypercalcemia and hyperthyroidism 6 months after the last dose of denosumab. Laboratory investigations revealed hypercalcemia, normophosphatemia, normal renal function, and elevated levels of fibroblast growth factor 23 (FGF-23). Serum tartrate-resistant acid phosphatase 5b and urine N-terminal cross-linked telopeptide of type I collagen were both elevated, and bone scintigraphy revealed increase of whole bone uptake. Radiological examinations showed no recurrence of breast cancer or tumors that secrete intact PTH or FGF-23. Hypercalcemia, which lasted for 1 month, was refractory to discontinuation of the aromatase inhibitor, normalization of thyroid hormone levels, saline hydration, and calcitonin administration, but was effectively treated with zoledronic acid. Abnormal uptake on bone scintigraphy and ankle pain both resolved a few months after treatment, and hypercalcemia has not recurred in the ensuing 2 years. In conclusion, we found elevated levels of circulating FGF-23 with hypercalcemia following the discontinuation of denosumab. FGF-23 might be a surrogate marker for massive bone resorption triggered by discontinuation of long-term denosumab treatment.


One-year results of transcatheter aortic valve implantation as an alternative treatment for severe aortic stenosis in high-risk patients.
Aortic valve replacement (AVR) remains the gold standard treatment for symptomatic severe aortic stenosis (AS). For the past 10 years, transcatheter aortic valve implantation (TAVI) has been applied in patients with high surgical mortality and morbidity risks. The preliminary results of our TAVI patients are presented in this study. Ten high-risk patients with severe AS, for AVR, were referred and accepted for TAVI in the 6 month period from May 2010 to October 2010. The patient age, logistic EuroSCORE, femoral arterial diameter, aorta annulus size, aorta valve area (AVA), mean aortic pressure gradient (MPG), as well as coronary angiography results were all collected. Six patients were treated via the transapical approach in March 2010, whereas the other four were treated with the transfemoral approach, according to their femoral artery diameter and arterial quality. This study focuses on the immediate, 1 month, 3 month, and 1 year results of TAVI. The average age of the 10 patients receiving TAVI was 81.5 years. The mean calculated EuroSCORE was 28.3 ± 7.9%. The mean AVA was 0.61 ± 0.19 cm(2). The MPG was 48 ± 16 mmHg. The surgical technical success achieved 100%. There was no reported moderate to severe postoperative paravalvular aortic regurgitation, permanent complete atrioventricular block, major access site complication, or embolic stroke. Chronic renal failure, which necessitated permanent hemodialysis, developed in 10% of the patients. One acute myocardial infarction and one case of pneumonia developed postoperatively. The AVA was increased by 251%, whereas the MPG was decreased by 80% at the 3 month follow-up. The 30-day mortality rate was 10%. The all-cause 1-year mortality rate was 20%. This new technique and device requires greater caution and needs more practice to accumulate sufficient experience. The studied patients were very fragile, due to old age and multiple comorbidities. Our results are similar to findings of multicenter trials. With careful patient screening and selection, TAVI can be a promising treatment for high-risk severe AS patients.


Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause.
We made longitudinal measurements of bone mineral density (BMD) in 139 normal women (ages 20-88 yr) at midradius (99% cortical bone) and lumbar spine (approximately 70% trabecular bone) by single- and dual-photon absorptiometry. BMD was measured 2-6 (median, 3) times over an interval of 0.8-3.4 yr (median, 2.1 yr). For midradius, BMD did not change (+0.48%/yr, NS) before menopause but decreased (-1.01%/yr, P less than 0.001) after menopause. For lumbar spine, there was significant bone loss both before (-1.32%/yr, P less than 0.001) and after (-0.97%/yr, P = 0.006) menopause; these rates did not differ significantly from each other. Our data show that before menopause little, if any, bone is lost from the appendicular skeleton but substantial amounts are lost from the axial skeleton. Thus, factors in addition to estrogen deficiency must contribute to pathogenesis of involutional osteoporosis in women because about half of overall vertebral bone loss occurs premenopausally.


Behavior of laboratory animals under unnatural conditions.
Domestic animals are animals whose living conditions and reproduction, among other things, are controlled by man. As such, the current discussion about the welfare of domestic animals is similar for farm, companion, laboratory, and zoo animals. It concerns identification of the behavioral and physiological needs of the animals and development of living conditions that enable them to satisfy these needs. The paper describes two approaches that have been used in behavior biology to identify such needs. One approach is the measurement of stress responses that may be activated when an animal's needs are not fulfilled. The other approach is the use of operant conditioning techniques to establish demand functions by which the motivation of an animal to perform a specific behavior is measured. It is concluded that, since welfare is characterized by the absence of a number of factors, such as stress, pain, fear, disease, hunger etc., many types of measurements must be applied to ensure optimal welfare.


[The Eppendorf University Hospital, Hamburg--a cradle of German- speaking anesthesia?].
"The time will come when German medicine, too, will have to concern itself with the issue of a professional narcotiseur. Until then it will be our duty to keep the interest in narcosis, which has increased satisfactorily in the past years, alive." With this statement the editors of the journal "Der Schmerz" substantiated the publication og a German-speaking anestesiological journal in 1928. Ernst von der Porten, a professional anesthesist working in Hamburg was the chief initiator for the appearance of the new journal. Possible he was incited by his former teacher, the Eppendorf surgeon Paul Sudeck, to delve deeper into our special field. Very early Sudeck himself began to concern himself with anesthesiological questions and he found an ardent supporter of the idea of specialisation in anesthesiology (quite unheard of in Germany at that time) in Helmut Schmidt, a staff member. Schmidt habilitated on an anesthesiological theme and that again was reason enough for the editors to write an editorial about. Schmidt who one of the chief organizers of the "90. Tagung Deutscher Naturforscher und Arzte" in the late summer of 1928 was hindered by the surgeons on founding the Deutsche Narkosege-sellschaft (German Narcosis Society) with colleagues. After World War II German surgeons rethought their position, mainly influenced by Anglo-American narcosis specialists. After the foundation of the Deutsche Gesellschaft für Anaesthesiein the year 1953, the first professorate for the special field of anesthesiology was given to Karl Horatz--one of the founding members--10 years later. Not surprisingly the professorate was instituted at the university hospital in Eppendorf which could be called the cradle of German-speaking anesthesia. The following concerns itself with some of the impulses that were given by the "Neues Allgemeines Krankenhaus Eppendorf" and became important stepping stones in our special field through the decades.


Comparison of mandelate dehydrogenases from various strains of Acinetobacter calcoaceticus: similarity of natural and 'evolved' forms.
In previous work it had been shown that Acinetobacter calcoaceticus wild-type strain NCIB 8250 had only an L-mandelate deydrogenase but it could give rise to mutants that contained an evolved D-mandelate dehydrogenase; conversely, wild-type strain EBF 65/65 had only a D-mandelate dehydrogenase but gave rise to mutants that possessed an evolved L-mandelate dehydrogenase. Several other wild-type strains of A. calcoaceticus have now been shown to grow on both enantiomers of mandelate. In every case the L-mandelate dehydrogenases were found to be much more heat-stable and insensitive to inhibition by p-chloromercuribenzoate than were the D-mandelate dehydrogenases when measured in bacterial extracts. All the D-mandelate dehydrogenases in the wild-type strains were inactivated to about the same extent by an antiserum that had been raised in a rabbit against an evolved D-mandelate dehydrogenase. An evolved D-mandelate deydrogenase (from a mutant strain derived from strain NCIB 8250) and an original D-mandelate dehydrogenase (from a mutant strain derived from strain EBF 65/65) were purified to homogeneity by the same procedure and were indistinguishable as judged by immunological cross-reactivity of the native and the sodium-dodecyl-sulphate-denatured enzymes, solubility in cholate, net charge at pH 7.5, pI value, salting-out properties, Mr value, apparent K(m) value for D-mandelate, heat-stability and sensitivity to p-chloromercuribenzoate. The most likely explanation for the appearance of evolved mandelate dehydrogenases in strains of A. calcoaceticus is that cryptic genes become expressed.


Presence of Dendroaspis natriuretic peptide-like immunoreactivity in human plasma and its increase during human heart failure.
To determine whether Dendroaspis natriuretic peptide (DNP), a novel peptide isolated from the venom of the Dendroaspis angusticeps snake that contains a 17-amino acid disulfide ring structure similar to that in atrial, brain, and C-type natriuretic peptides, is present in normal human plasma and myocardium and whether, like the other natriuretic peptides, DNP-like immunoreactivity (DNP-LI) is activated in human congestive heart failure (CHF). Circulating DNP-LI was assessed in 19 normal human subjects and 19 patients with CHF (New York Heart Association class III or IV) with a specific and sensitive radioimmunoassay for DNP with no cross-reactivity with the other natriuretic peptides. Immunohistochemical studies that used polyclonal rabbit anti-DNP antiserum were performed on human atrial myocardial tissue obtained from four patients with end-stage CHF who were undergoing cardiac transplantation and from three donor hearts at the time of transplantation. We report that DNP-LI circulates in normal human plasma and is present in the normal atrial myocardium. In addition, DNP-LI is increased in the plasma of patients with CHF. This study demonstrates, for the first time, the presence of a DNP-like peptide in normal human plasma and in the atrial myocardium. Additionally, these studies demonstrate increased plasma DNP-LI in human CHF. These results support the possible existence of an additional new natriuretic peptide in humans, which may have a role in the neurohumoral activation that characterizes human CHF.


A computer-based AIDS education program for nursing students.
A multidisciplinary team has developed a computer-based software program for educating nursing students and other college students about six sexually transmitted diseases (STDs). The program for educating about Acquired Immune Deficiency Syndrome (AIDS) is the first of the six "Smartbooks" to be completed, using the Hypercard Expert System shell on the Macintosh computer. Information is organized within a framework known as a concept map, and the student user progresses through the program in a self-directed way by "clicking" on the portion of the concept map that is of interest. Thus, the knowledge base can be accessed in many different ways, and is not restricted to a linear format. Comparative quantitative analysis using a control program shows consistently better student retention of information presented within the program that features concept maps. Qualitative results indicate that students find the conceptually-arranged knowledge base implicitly easy to understand, "fun" to use, and interesting to explore. Educational theory suggests that the success of such a format may be related to the schematic nature of memory.


External Quality Assessment on CD4+ T-Cell Count Using in-House Proficiency Testing Panels for CD4 Count Laboratories in Addis Ababa, Ethiopia.
CD4+ T-cell count External Quality Assessment program is important for the evaluation of performance of CD4 count laboratories. The aim of this study was to assess the quality of CD4count laboratory performance using in-house Proficiency testing panels that perform routine CD4 counts in Addis Ababa, Ethiopia, 2013/14. Participating laboratories were 20, 23 and 25 in trials 1, 2 and 3, respectively. In-house prepared fresh whole blood samples both with "normal" and "low" CD4 values were sent to participating laboratories. Percentage and absolute counts of CD4+ T-lymphocytes were done using their routine procedures. Data were analyzed for each trial including trimmed mean, standard deviation (SD), percent coefficient of variation (%CV), residual, and standard deviation index (SDI) values for both absolute counts and percentages of CD4+ lymphocytes (%CD4). Most participating laboratories produced results that were within 2SD of the mean. Average inter-laboratory precision (trimmed %CV) was 10.87% and 5.14% for CD4 absolute counts and %CD4, respectively. For normal material, the trimmed mean %CV was 9.59% and3.23% for CD4 absolute counts and %CD4, respectively. For low material, the trimmed mean % CV was 12.15% and 7.05% for CD4 absolute counts and %CD4 respectively. BDFACSCount™ users showed the best accuracy and precision as evidenced by longitudinal analysis. This study was found to help facilities in early identifying their gaps with regard to their CD4 count performance and in avoiding the challenges encountered during participation in external EQA providers like the high cost, transportation problem, feedback delay and CD4laboratory coverage.


FDG-PET/CT as a New Method for Diagnosis and Whole-Body Evaluation of Lemierre Syndrome.
Lemierre syndrome is a rare disease that is defined by a pharyngeal infection, complicated by septicemia and internal jugular vein thrombosis followed by septic emboli. Because of its rarity, a delay in diagnosis is not uncommon. However, given the mortality rate of approximately 2%, prompt diagnosis and detection of septic emboli are essential to initiate prompt treatment, preventing organ damage and ongoing sepsis. We present 3 cases that demonstrate the value of FDG-PET/CT as a possible alternative or adjunct to conventional imaging methods for diagnosis and whole-body evaluation of Lemierre syndrome.


Predicting outcomes of mesenteric ischemia postcardiac surgery: A systematic review.
This systematic review aims to identify predictors of outcomes of mesenteric ischemia in patients following cardiac surgery. A comprehensive literature search was done on EMBASE, PubMed, Ovid MEDLINE, and SCOPUS using keywords relating to bowel ischemia and cardiac surgery. Database search results were screened by at least two authors and 32 articles were selected for inclusion in this review. Data on 1907 patients were analyzed. The mean age was 70.0 ± 2.99 years and the prevalence of bowel ischemia was 1.74%. Advanced age was a significant risk factor. 63.16% of patients reported were men, and 58.4% of patients died in hospital. There was heterogeneity in the reported significance of the following preoperative risk factors: hypertension, smoking status, type 2 diabetes mellitus, end-stage renal disease, preoperative left ventricular ejection fraction <35%. Cardiopulmonary bypass (CPB) time, preoperative/operative intra-aortic balloon pump (IABP) support, and inotrope usage were significantly associated with the development of mesenteric ischemia; however, other intraoperative factors including the type of cardiac surgery and duration of aortic cross-clamping had varying levels of reported significance. There were discrepancies in the reported significance of leukocytosis and metabolic acidosis (pH <7.3) as postoperative markers. Postoperative vasopressor use, prolonged ventilation time, and elevation in lactate, transaminases, creatinine, and intestinal fatty acid-binding protein (IFABP) levels were found to be strongly associated with bowel ischemia. This systematic review found the strongest associations of mesenteric ischemia postcardiac surgery to be advanced age, CPB time, rise in lactate, transaminases, creatinine, and IFABP. IABP support, vasopressor, and inotrope use as well as prolonged ventilation were strongly linked too.


Serum gonadotropins and alpha-subunit decline in aging normal postmenopausal women.
In a group of 680 postmenopausal women participating in a population survey we investigated the relationships between serum gonadotropin, alpha-subunit and PRL concentrations and age, body mass index (BMI), and levels of sex hormone-binding globulin, estrogens, and androstenedione. Gonadotropin and alpha-subunit levels were negatively correlated with age, while PRL levels did not decrease with age. Regression means of serum concentrations in women aged 55 to 75 yr, respectively, decreased for LH from 47.1 to 32.4 IU/L, for FSH from 72.1 to 61.6 IU/L, and for alpha-subunit from 2.6 to 1.9 micrograms/L. The ratio of alpha-subunit to LH and FSH decreased with age. These changes may be caused by either a direct effect of aging on pituitary gonadotroph cells or an effect of aging on the hypothalamic regulation of these cells. Serum gonadotropin and alpha-subunit concentrations were negatively correlated with the BMI, but not with circulating estradiol levels. In addition, we found that estrone and estradiol levels were positively correlated with the BMI, while circulating levels of androstenedione and estrone were more important factors, determining estrone and estradiol levels, respectively. In conclusion, in contrast to what has been reported in normal aging men, serum LH, FSH, and alpha-subunit concentrations decrease with age in normal postmenopausal women.


A discrete-time recurrent neurofuzzy network for black-box modeling of insulin dynamics in diabetic type-1 patients.
In this work we present a data-driven modeling of the insulin dynamics in different in silico patients using a recurrent neural network with output feedback. The inputs for the identification is the rate of insulin (microU/dl/min) applied to the patient, and blood glucose concentration. The output is insulin concentration (microU/ml) present in the blood stream. Once completed the off-line modeling, this model could be used for on-line monitoring of the insulin concentration for a better treatment. The learning law of the recurrent neural network is inspired by adaptive observer theory, and proven to be convergent in the parameters and stable in the Lyapunov sense, even with only 13 samples available. Simulation results are shown to validate the presented modeling.


A Report of Two Cases of "Giant Bartholin Gland Cysts" Successfully Treated by Excision with Review of Literature.
Bartholin's gland cysts are one of the common vulval masses that may start as asymptomatic cysts but if left untreated, may become large and infected requiring medical attention. We are presenting two interesting and rare cases of giant Bartholin cyst and their treatment in this case report. Two female patients of perimenopausal age presented with giant vulval cysts to the outpatient department of Obstetrics and Gynaecology. They reached a size of 10 cm and 20 cm diameter respectively, presenting with some diagnostic and later reconstruction of the labia majus. MRI pelvis provided good information regarding the size, shape and extent of the cyst, which was very useful during surgery. Both these cases were successfully treated by excision of the cyst and histopathological examination after complete excision. One of the cases presented as dumb-bell shaped swelling with large cyst superiorly and smaller cyst extending into the buttock connected by narrow neck and showed cross fluctuation. This type of dumb-bell shaped presentation of Bartholin's cyst is rather unusual and has not been reported in the available literature.


COVID-19 pandemic impact on childhood vaccination coverage in Quebec, Canada.
Response measures to mitigate the coronavirus disease 2019 pandemic impacted access to routine vaccination services. We evaluate the impact of the pandemic on routine infant vaccination uptake by comparing vaccination coverage, vaccine delays and doses administered in 2019 and 2020, in Quebec, Canada. Using a population-based vaccination registry, we compared vaccination coverage at 3, 5, 13 and 19 months of age between 2019 and 2020 cohorts each month from January to November. For vaccine delays, we measured the cumulative proportion vaccinated in each targeted cohort monthly. We also compared the measles-containing vaccines administered before 24 months of age between the same period in 2019 and 2020. A decline in vaccination coverage and children vaccinated on time was observed in all cohorts during the first months of the pandemic. The greatest impact was observed for the 18-month vaccination visit with a difference in vaccination coverage between both cohorts of 30.9% in May. Measles-containing doses administered during the first months of the pandemic were lower in 2020 compared with 2019: -21.1% in March (95%CI-21.6;-20.4), and -39.2% in April (95%CI-40.0;-38.2). After May, the coverage increased for all cohorts to reach pre-pandemic levels after a few months for most target ages. Routine childhood vaccinations were affected during the first months of the pandemic, but catch-up occurred thereafter and vaccination coverage in affected cohorts were very close to levels of 2019 after a few months of follow-up. Real-time monitoring of childhood vaccination is essential but also for other vaccination programs, severely affected by the pandemic.


Differential chemical derivatization integrated with chromatographic separation for analysis of isomeric sialylated N-glycans: a nano-hydrophilic interaction liquid chromatography-MS platform.
MS analysis of sialylated glycans is challenging due to their low ionization efficiency in positive ion mode as well as the possibility of in-source fragmentation. Chemical derivatization strategies have been developed to address this issue focused on removal of the labile acidic proton prior to MS analysis. Highly sialylated negatively charged glycans also exhibit high retention and unsatisfactory separation efficiency when analyzed by hydrophilic interaction liquid chromatography (HILIC) due to their high polarity. Here, we combined linkage specific derivatization of sialic acids by reaction with the condensation reagent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) in methanol with nanoscale liquid chromatographic separation prior to accurate mass Orbitrap MS analysis. Coupling DMT-MM charge neutralization of sialic acids with nano-HILIC-Orbitrap-MS not only allows for linkage specific characterization of sialylated glycans directly from the precursor mass but also improves the preceding HILIC separation by increasing the hydrophobicity and altering the selectivity of the oligosaccharide analytes. We focused on the trisialylated N-glycan fraction from haptoglobin and human plasma, enriched using weak anion exchange chromatography, as this trisialylated fraction has been linked with cancer associated changes in the serum N-glycome. The developed methodology was applied to investigate whether structural alterations in this oligosaccharide pool, enriched from the sera of pathological stage and sex matched patients bearing lung, breast, ovarian, pancreatic, or gastric cancer, demonstrate any degree of cancer specificity or whether changes in expression levels are purely cancer associated. The results of this pilot study indicate limited degrees of cancer specificity, particularly for pancreatic cancer, based on alterations in the relative abundance of specific trisialylated isomers.


Quantification of lamotrigine in patient plasma using a fast liquid chromatography-tandem mass spectrometry method with backflush technology.
Recent concerns have been raised by neurologists and patients with epilepsy regarding the bioequivalence of generic lamotrigine to the brand Lamictal. Bioequivalence studies require the quantification of lamotrigine in human plasma, including in the presence of other drugs, for studies that will use patients with epilepsy rather than healthy volunteers. Lamotrigine was extracted from plasma through a simple protein precipitation and analyzed by fast liquid chromatography coupled to heated electrospray ionization with tandem mass spectrometric detection. A backflush step to remove interferent accumulation on column was included, and a stable isotope-labeled lamotrigine was used as an internal standard. The method was validated for accuracy, precision, interday and intraday coefficient of variation, specificity, lower limit of detection, lower limit of quantification, linearity, range, instrument precision, freeze-thaw, dilution integrity, and sample stability. Specificity evaluation included consideration of the impact of other antiepileptic drugs. The described method has a linear range of 8-10,000 ng/mL of lamotrigine (r = 0.9999) and a lower limit of detection of 1 ng/mL and a lower limit of quantification of 8 ng/mL. Intraday and interday reproducibility were less than 10.0% relative SD and 10.4% relative SD, respectively, and the percent recovery varied from 96.6% to 109.3% at various lamotrigine concentrations. A backflush step reduced matrix effects and no interference peak from plasma or other antiepileptic drugs were observed. A liquid chromatography-heated electrospray ionization-tandem mass spectrometry method including a backflush step was developed and validated to measure lamotrigine concentration in patient plasma. The method will be applied to bioequivalence studies that compare brand versus generic lamotrigine.


[Development of the locomotive and neurologic symptoms in the offspring of schizophrenics during the first few years of life].
The author provides the neurological characteristics and the follow-up data on the development of locomotion in 36 children aged 3 months to 3 years born to schizophrenic patients. Three variants of motor development were distinguished: the first one--early and proper development; the second one--short-term retardation at some stages, namely before the age of 1 year and 4 months, with intermittent episodes in the development and a proper or little changed formula of the postural and motor development; the third one--appreciable retardation and perversion of the motor developmental formula, insufficiency of the extrapyramidal and cortical components of the motor act, preserved even after 3 years of age. Among the discovered neurological symptoms, disorders in the system of gaze innervation, vocal and motor disorders, motor stereotypies, disturbances of the extrapyramidal and cortical component of the motor act, the hydrocephalic syndrome can be attributed to more specific ones as regards the schizotypic dysontogenesis. They were distinguished for using in further follow-up of the children.


[Informed consent and the approval of evaluation committees in Mexican medical research].
To establish the frequency of informed consent and review by institutional review boards in Mexican medical journals. Retrospective review of prospective medical research published in seven Mexican medical journals between 1990-1993. 391 prospective studies were analyzed: 259 (66%) were cross-sectional and 132 (34%) longitudinal; 197 (51%) descriptive and 194 (49%) comparative; 277 (71%) observational and 114 (29%) experimental. In general, the informed consent was reported in 123 studies (31%), and its institutional review board approval in 41 (10%). In the 114 experimental articles the informed consent was reported in 53 (46%) and the review board approval in 28 (25%). Most Mexican researchers do not report or do not obtain informed consent nor review board approval in the articles we reviewed. This suggests the presence of legal and ethical flaws which should be overcome.


Noise distribution of an incubator with nebulizer at a neonatal intensive care unit in southern Taiwan.
The purpose of this study was to investigate the noise distribution and sources of peak noise inside an incubator with a nebulizer at a neonatal intensive care unit of a medical center in Southern Taiwan. Sound levels were monitored continuously with an electronic sound-meter for 24 hours daily over a one-week period. Three working hours (day, evening, and night hours) in the weekday and weekend (total 48 hours) were selected randomly from the one-week period of noise survey to observe peak noise at levels > or = 65 dBA. Results revealed that 24.8% of the total monitoring period had sound levels at < or = 59 dBA, 58.9% at 60-64 dBA, 10.7% at 65-69 dBA, and 5.6% at > or = 70 dBA. Furthermore, a total of 947 peak noises > or = 65 dBA were found within the 48 hours, of which 61.5% were in a range of 65-69 dBA, 24% of 70-74 dBA, 9.8% of 75-79 dBA, and 4.8% > or = 80 dBA. Human-related sources, equaling 79%, were the dominant peak noises. These noises included opening and closing doors, banging the incubator hood, conversation among staff, nursing activity inside the incubator, tearing and opening paper or bags, opening and closing trash can lids, and bumping metal carts or other apparatus. Nonhuman-related sources were 21% including alarms of monitors and running of the incubator motor. Results of this study showed that the noise distribution in the incubator with nebulizer was far above a protective limitation of 58 dBA, suggested by the American Academy of Pediatrics in 1974. However, most peak noises could be reduced by modification of staff behavior. Therefore, determinations of noise distribution and sources of peak noise in this study are useful for further noise reduction programs.


Ethical issues in mental health research: the case for community engagement.
To describe community-engaged research (CEnR) and how it may improve the quality of a research study while addressing ethical concerns that communities may have with mental health and substance abuse research. This article includes a review of the literature as well as recommendations from an expert panel convened with funding from the US National Institute of Mental Health. CEnR represents a broad spectrum of practices, including representation on institutional ethics committees, attitude research with individuals from the study population, engaging community advisory boards, forming research partnerships with community organizations, and including community members as co-investigators. CEnR poses some challenges; for example, it requires funding and training for researchers and community members. However, it offers many benefits to researchers and communities, and some form of CEnR is appropriate and feasible in nearly every study involving human participants.


IQ and the genetics of autism.
While there seems to be general agreement that genetic factors play some role in the etiology of autism, many important questions remain unresolved. The purpose of this paper is to review five issues with respect to the association between low IQ and autism from a familial-genetic viewpoint: (1) does IQ estimate the severity of the autistic genotype?; (2) what is the relationship between probands' and sibs' IQs?; (3) what is the relationship between parents' and probands' IQs?; (4) why do females with autism have lower IQs than males with the disorder?; and (5) does IQ vary with the cause of autism? With respect to each issue, possible resolutions are outlined, as are the implications for understanding the genetic mode of transmission. The review concludes with a possible model for the genetic etiology of autism.


Estimation of the impact of three different bioinformatic pipelines on sheep nemabiome analysis.
Next-generation sequencing (NGS) has provided an alternative strategy to study the composition of nematode communities with increased resolution and sensitivity. However, the handling and processing of gigabytes worth of amplicon sequence data produced by an NGS platform is still a major hurdle, limiting the use and adoption of faster and more convenient analysis software. In total 32 paired, fecal samples from Swedish sheep flocks were cultured and the larvae subsequently harvested subjected to internal transcribed spacer 2 (ITS2) amplicon sequencing using the PacBio platform. Samples were analyzed with three different bioinformatic pipelines, i.e. the DADA2, Mothur and SCATA pipelines, to determine species composition and richness. For the the major species tested in this study (Haemonchus contortus, Teladorsagia circumcinta and Trichostrongylus colubriformis) neither relative abundances nor species diversity differed significantly between the three pipelines, effectively showing that all three analysis pipelines, although different in their approaches, yield nearly identical outcomes. In addition, the samples analyzed here had especially high frequencies of H. contortus (90-95% across the three pipelines) both before and after sample treatment, followed by T. circumcinta (3.5-4%). This shows that H. contortus is the parasite of primary importance in contemporary Swedish sheep farms struggling with anthelmintic resistance. Finally, although on average a significant reduction in egg counts was achieved post-treatment, no significant shifts in major species relative frequencies occurred, indicating highly rigid community structures at sheep farms where anthelmintic resistance has been reported. The findings presented here further contribute to the development and application of NGS technology to study nemabiome compositions in sheep, in addition to expanding our understanding about the most recent changes in parasite species abundances from Swedish sheep farms struggling with anthelmintic resistance.


Survey on reference dosimetry practice in Hokuriku region, Japan.
This study aimed to obtain reference dosimetry practices for flattened photon and electron beams. A questionnaire survey on these practices was sent to 37 facilities that performed radiotherapy using these beams in Fukui, Ishikawa, Niigata and Toyama, Japan. The survey comprised equipment (dosemeters, water phantoms, thermometers, barometers and hygrometers) and procedures for reference dosimetry (water used as the phantoms, verification of chamber placement, periodic checks of ion recombination- and polarity-corrections, pre-irradiation and relative humidity monitoring). Responses were received from 19 institutions. In the 19 institutions, a reference-class dosemeter was used for the reference dosimetry. In 6 of the 19 institutions, a 10-year-old or older dosemeter was used. Any barometers, thermometers and hygrometers were not recalibrated. Dosimetry equipment necessitates regular maintenance. Moreover, it is necessary to have a backup dosimetry system in clinics to account for potential malfunctions or instances when the primary system is sent for calibration.


Survey of Brucella spp. and Leptospira spp. antibodies in cetaceans and manatees of the Amazon basin and Atlantic Ocean, Brazil.
Aquatic mammals can act as sentinels of emerging and resurging pathogens in the environment. Brucella spp. and Leptospira spp. are 2 zoonotic pathogens relevant to aquatic mammals, and their detection can be used to assess pathogen exposure. In this study, serum from 84 individuals-63 cetaceans (families Iniidae, n = 37; Delphinidae, n = 22; and Kogiidae, n = 4) and 21 West Indian manatees Trichechus manatus-was tested by the Rose Bengal Test (RBT) and a commercial competitive enzyme-linked immunosorbent assay (c-ELISA) for detecting Brucella spp. antibodies, and the microscopic agglutination test (MAT) for screening Leptospira spp. exposure. Overall, 4.8% (3/63) of cetaceans were positive by RBT and 15.9% (10/63) by c-ELISA for Brucella spp. Serum from 8 c-ELISA positive cetaceans (with available serum) was further tested via serum agglutination test (SAT) and 1 individual was positive. c-ELISA was more sensitive than RBT. Exposure to Brucella spp. was found in 5 cetacean species: Clymene dolphin Stenella clymene, short-finned pilot whale Globicephala macrorhynchus, pygmy killer whale Feresa attenuata, melon-headed whale Peponocephala electra and Atlantic bottlenose dolphin Tursiops truncatus in the Atlantic Ocean, Brazil, expanding the range of known Brucella seropositive aquatic hosts. No evidence of Brucella spp. exposure was found in Iniidae and Kogiidae odontocetes and manatees. Antibodies against Leptospira spp. were not detected in cetaceans and sirenians by MAT. These results contribute to the evaluation of different Brucella spp. serological methods in cetaceans and manatees and highlight the epidemiology of zoonotic pathogens in aquatic mammals of the southwestern Atlantic Ocean and the Amazon basin.


Observation of weak-limit quasiparticle scattering via broadband microwave spectroscopy of a d-wave superconductor.
There has long been a discrepancy between microwave conductivity measurements in high temperature superconductors and the conductivity spectrum expected in the simplest models for impurity scattering in a d-wave superconductor. Here we present a new type of broadband measurement of microwave surface resistance that finally shows some of the spectral features expected for a d(x2-y2) pairing state. Cusp-shaped conductivity spectra, consistent with weak impurity scattering of nodal quasiparticles, were obtained in the 0.6-21 GHz frequency range in highly ordered crystals of YBa2Cu3O6.50 and YBa2Cu3O6.99.


[Activation of Na, K-ATPase from nerve cell microsomes by acetylcholine in a model system].
Microsomal Na, K-ATPase is activated by acetylcholine (5 x 10(-6)--10(-5) M) in a cell-free system including neuronal nuclei and the microsomal--cytoplasmic fraction. No enzyme activation by acetylcholine occurs in the presence of puromycin, actinomycin D and ribonuclease or upon removal of the nuclear or microsomal--cytoplasmic fraction from the system. After preincubation with acetylcholine the membranes reveal a better capacity for phosphorylation by [gamma-32P]ATP and dephosphorylation in the presence of ADP and Na+. The ATP binding by the membranes preincubated in a system with acetylcholine is also increased thereby. It was assumed that acetylcholine induces the synthesis of Na, K-ATPase or its protein activator.


Characteristics of Health Care Personnel with COVID-19 - United States, February 12-April 9, 2020.
As of April 9, 2020, the coronavirus disease 2019 (COVID-19) pandemic had resulted in 1,521,252 cases and 92,798 deaths worldwide, including 459,165 cases and 16,570 deaths in the United States (1,2). Health care personnel (HCP) are essential workers defined as paid and unpaid persons serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials (3). During February 12-April 9, among 315,531 COVID-19 cases reported to CDC using a standardized form, 49,370 (16%) included data on whether the patient was a health care worker in the United States; including 9,282 (19%) who were identified as HCP. Among HCP patients with data available, the median age was 42 years (interquartile range [IQR] = 32-54 years), 6,603 (73%) were female, and 1,779 (38%) reported at least one underlying health condition. Among HCP patients with data on health care, household, and community exposures, 780 (55%) reported contact with a COVID-19 patient only in health care settings. Although 4,336 (92%) HCP patients reported having at least one symptom among fever, cough, or shortness of breath, the remaining 8% did not report any of these symptoms. Most HCP with COVID-19 (6,760, 90%) were not hospitalized; however, severe outcomes, including 27 deaths, occurred across all age groups; deaths most frequently occurred in HCP aged ≥65 years. These preliminary findings highlight that whether HCP acquire infection at work or in the community, it is necessary to protect the health and safety of this essential national workforce.


DNA replication precedes neuronal cell death in Alzheimer's disease.
Alzheimer's disease (AD) is a devastating dementia of late life that is correlated with a region-specific neuronal cell loss. Despite progress in uncovering many of the factors that contribute to the etiology of the disease, the cause of the nerve cell death remains unknown. One promising theory is that the neurons degenerate because they reenter a lethal cell cycle. This theory receives support from immunocytochemical evidence for the reexpression of several cell cycle-related proteins. Direct proof for DNA replication, however, has been lacking. We report here the use of fluorescent in situ hybridization to examine the chromosomal complement of interphase neuronal nuclei in the adult human brain. We demonstrate that a significant fraction of the hippocampal pyramidal and basal forebrain neurons in AD have fully or partially replicated four separate genetic loci on three different chromosomes. Cells in unaffected regions of the AD brain or in the hippocampus of nondemented age-matched controls show no such anomalies. We conclude that the AD neurons complete a nearly full S phase, but because mitosis is not initiated, the cells remain tetraploid. Quantitative analysis indicates that the genetic imbalance persists for many months before the cells die, and we propose that this imbalance is the direct cause of the neuronal loss in Alzheimer's disease.


Tissue tropism related to vector competence of Frankliniella occidentalis for tomato spotted wilt tospovirus.
The development of tomato spotted wilt tospovirus (TSWV) infection in the midgut and salivary glands of transmitting and non-transmitting thrips, Frankliniella occidentalis, was studied to elucidate tissue tropism and the virus pathway within the body of this vector. Immunohistological techniques used in this study showed that the midgut, foregut and salivary glands were the only organs in which virus accumulated. The first signals of infection, observed as randomly distributed fluorescent granular spots, were found in the epithelial cells of the midgut, mainly restricted to the anterior region. The virus subsequently spread to the circular and longitudinal midgut muscle tissues, a process which occurred late in the larval stage. In the adult stage, the infection occurred in the visceral muscle tissues, covering the whole midgut and foregut, and was abolished in the midgut epithelium. The infection of the salivary glands was first observed 72 h post-acquisition, and simultaneously in the ligaments connecting the midgut with these glands. The salivary glands of transmitting individuals appeared heavily or completely infected, while no or only a low level of infection was found in the glands of non-transmitting individuals. Moreover, the development of an age-dependent midgut barrier against virus infection was observed in second instar larvae and adults. The results show that the establishment of TSWV infection in the various tissues and the potential of transmission seems to be regulated by different barriers and processes related to the metamorphosis of thrips.


Expression of a new cell surface antigen on activated murine macrophages.
A macrophage cell-surface antigen associated with pyran and Corynebacterium parvum-activated macrophages and P388D1 cells but not detectable on normal or glycogen and thioglycollate-elicited murine macrophages has been described. The antigen was demonstrated both by complement-mediated cytotoxicity and immunofluorescence, using an appropriately absorbed rabbit antiserum to P388D1. This antiserum should enable the characterization of activated macrophage cell populations on an individual cell basis and should be a useful probe to study the interactions of macrophages with tumor cells and the relationship of activation to cell-surface changes.


Large-scale meta-analysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis.
To clarify the role of common genetic variation in the Interleukin-1β (IL1B) and Interleukin-1R antagonist (IL1RN) genes on risk of knee and hip osteoarthritis (OA) and severity of knee OA by means of large-scale meta-analyses. We searched PubMed for articles assessing the role of IL1B and IL1RN polymorphisms/haplotypes on the risk of hip and/or knee OA. Novel data were included from eight unpublished studies. Meta-analyses were performed using fixed- and random-effects models with a total of 3595 hip OA and 5013 knee OA cases, and 6559 and 9132 controls respectively. The role of ILRN haplotypes on radiographic severity of knee OA was tested in 1918 cases with Kellgren-Lawrence (K/L) 1 or 2 compared to 199 cases with K/L 3 or 4. The meta-analysis of six published studies retrieved from the literature search and eight unpublished studies showed no evidence of association between common genetic variation in the IL1B or IL1RN genes and risk of hip OA or knee OA (P>0.05 for rs16944, rs1143634, rs419598 and haplotype C-G-C (rs1143634, rs16944 and rs419598) previously implicated in risk of hip OA). The C-T-A haplotype formed by rs419598, rs315952 and rs9005, previously implicated in radiographic severity of knee OA, was associated with reduced severity of knee OA (odds ratio (OR)=0.71 95%CI 0.56-0.91; P=0.006, I(2)=74%), and achieved borderline statistical significance in a random-effects model (OR=0.61 95%CI 0.35-1.06 P=0.08). Common genetic variation in the Interleukin-1 region is not associated with prevalence of hip or knee OA but our data suggest that IL1RN might have a role in severity of knee OA.


[Endoscopic naso-sinus surgery. Technical aspects].
Perioperative, anaesthetic and special technical aspects of endoscopic surgery of the paranasal sinuses are presented, which helped to reduce intraoperative bleeding and consequently shortened the time of surgery. The realization of certain operative steps has helped to ease the postoperative care accelerating the healing process in more than 400 cases.