Acute upper airway infections.
Upper respiratory tract infections are common and important. Although rarely fatal, they are a source of significant morbidity and carry a considerable economic burden. Numerous therapies for the common cold have no effect on symptoms or outcome. Complications such as cough are not improved by over-the-counter preparations, while labelling cough alone as a symptom of asthma may result in unnecessary use of inhaled steroid treatment. Clinical presentation of sore throat does not accurately predict whether the infection is viral or bacterial, while throat culture and rapid antigen tests do not significantly change prescribing practice. Antibiotics have only a limited place in the management of recurrent sore throat due to group A beta-haemolytic streptococcal infection. Routine use of antibiotics in upper respiratory infection enhances parent belief in their effectiveness and increases the likelihood of future consultation in primary care for minor self-limiting illness. Respiratory viruses play a major role in the aetiology of acute otitis media (AOM); prevention includes the use of influenza or RSV vaccination, in addition to reducing other risk factors such as early exposure to respiratory viruses in day-care settings and to environmental tobacco smoke. The use of ventilation tubes (grommets) in secretory otitis media (SOM) remains controversial with conflicting data on developmental outcome and quality of life in young children. New conjugate pneumococcal vaccines appear safe in young children and prevent 6-7% of clinically diagnosed AOM.


Recent evolutionary radiation and host plant specialization in the Xylella fastidiosa subspecies native to the United States.
The bacterial pathogen, Xylella fastidiosa, infects many plant species in the Americas, making it a good model for investigating the genetics of host adaptation. We used multilocus sequence typing (MLST) to identify isolates of the native U.S. subsp. multiplex that were largely unaffected by intersubspecific homologous recombination (IHR) and to investigate how their evolutionary history influences plant host specialization. We identified 110 "non-IHR" isolates, 2 minimally recombinant "intermediate" ones (including the subspecific type), and 31 with extensive IHR. The non-IHR and intermediate isolates defined 23 sequence types (STs) which we used to identify 22 plant hosts (73% trees) characteristic of the subspecies. Except for almond, subsp. multiplex showed no host overlap with the introduced subspecies (subspecies fastidiosa and sandyi). MLST sequences revealed that subsp. multiplex underwent recent radiation (<25% of subspecies age) which included only limited intrasubspecific recombination (ρ/θ = 0.02); only one isolated lineage (ST50 from ash) was older. A total of 20 of the STs grouped into three loose phylogenetic clusters distinguished by nonoverlapping hosts (excepting purple leaf plum): "almond," "peach," and "oak" types. These host differences were not geographical, since all three types also occurred in California. ST designation was a good indicator of host specialization. ST09, widespread in the southeastern United States, only infected oak species, and all peach isolates were ST10 (from California, Florida, and Georgia). Only ST23 had a broad host range. Hosts of related genotypes were sometimes related, but often host groupings crossed plant family or even order, suggesting that phylogenetically plastic features of hosts affect bacterial pathogenicity.


The Missing Skull - Professor Lundborg and the mismeasure of grandma.
What is science? Or, more pertinently, what is good science? This question is central for all practitioners of science and one of the most important to convey to our students. For those of us working in interdisciplinary settings - my own department covers everything from humanities to political and natural science - the question becomes even more complicated when traditions from different disciplines collide. For me personally, whenever I think too highly of my own research and risk deviating into bad scientific practices, I think of my paternal grandmother, Elsa. Although long dead, she brings me back into the fold of good science - or so I hope - by urging me to take another turn at critically evaluating how I perform research and to keep my arrogance in check.


Transient and Steady-State Properties of Drosophila Sensory Neurons Coding Noxious Cold Temperature.
Coding noxious cold signals, such as the magnitude and rate of temperature change, play essential roles in the survival of organisms. We combined electrophysiological and computational neuroscience methods to investigate the neural dynamics of Drosophila larva cold-sensing Class III (CIII) neurons. In response to a fast temperature change (-2 to -6°C/s) from room temperature to noxious cold, the CIII neurons exhibited a pronounced peak of a spiking rate with subsequent relaxation to a steady-state spiking. The magnitude of the peak was higher for a higher rate of temperature decrease, while slow temperature decrease (-0.1°C/s) evoked no distinct peak of the spiking rate. The rate of the steady-state spiking depended on the magnitude of the final temperature and was higher at lower temperatures. For each neuron, we characterized this dependence by estimating the temperature of the half activation of the spiking rate by curve fitting neuron's spiking rate responses to a Boltzmann function. We found that neurons had a temperature of the half activation distributed over a wide temperature range. We also found that CIII neurons responded to decrease rather than increase in temperature. There was a significant difference in spiking activity between fast and slow returns from noxious cold to room temperature: The CIII neurons usually stopped activity abruptly in the case of the fast return and continued spiking for some time in the case of the slow return. We developed a biophysical model of CIII neurons using a generalized description of transient receptor potential (TRP) current kinetics with temperature-dependent activation and Ca2+-dependent inactivation. This model recapitulated the key features of the spiking rate responses found in experiments and suggested mechanisms explaining the transient and steady-state activity of the CIII neurons at different cold temperatures and rates of their decrease and increase. We conclude that CIII neurons encode at least three types of cold sensory information: the rate of temperature decrease by a peak of the firing rate, the magnitude of cold temperature by the rate of steady spiking activity, and direction of temperature change by spiking activity augmentation or suppression corresponding to temperature decrease and increase, respectively.


Associations between sex, age and spiritual well-being scores on the EORTC QLQ-SWB32 for patients receiving palliative care for cancer: A further analysis of data from an international validation study.
The EORTC QOL Group has recently completed the cross-cultural development and validation of a standalone measure of spiritual well-being (SWB) for cancer patients receiving palliative care: the EORTC QLQ-SWB32. The measure includes four scales: Relationships with Others, Relationship with Self, Relationship with Someone or Something Greater, and Existential, plus a Global-SWB item. This paper reports on further research investigating relationships between sex, age and SWB for patients receiving palliative care for cancer-adjusting for other socio-demographic, clinical and function variables, including WHO performance status and EORTC QLQ-C15-PAL emotional and physical function scores. Cross-sectional data from the validation study were used, and chi-square, independent t tests, Mann-Whitney U tests and multiple regression analyses applied. The study included 451 participants with advanced and incurable cancer, from 14 countries. Adjusted analyses found better scores for female participants than males on three of the four EORTC QLQ-SWB32 subscales; Relationship with others, Relationship with Someone or Something Greater and Existential plus Global-SWB. Older age was positively associated with better Relationship with Self. The findings from our participants suggest that it might be beneficial if healthcare providers seeking to address patients' spiritual needs pay particular attention to male patients, younger patients and those with poor emotional functioning.


Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor.
We have examined the role that the transcription factor gut-enriched Krüppel-like factor (KLF4 or GKLF) plays in activating the enterocyte differentiation marker gene intestinal alkaline phosphatase (IAP). A yeast one-hybrid screen was used to identify proteins interacting with a previously identified cis-element (IF-III) located within the human IAP gene promoter. DNA-protein interactions were determined by using EMSA. Northern blot analysis was used to study RNA expression in human colon cancer RKO cells engineered to overexpress KLF4. Transient transfections with IAP-luciferase reporter constructs were used to characterize the mechanisms by which KLF4 activates IAP transcription. The yeast one-hybrid screen and EMSA identified KLF4 as binding to IF-III. RKO cells induced to overexpress KLF4 demonstrated a corresponding dose-dependent increase in IAP expression, and EMSA with nuclear extract from these cells confirmed that KLF4 binds to the IF-III element. Transient transfections revealed that KLF4 transactivated the IAP gene largely via a critical segment in the IAP promoter that includes the IF-III cis-element. Mutant KLF4 constructs failed to fully activate IAP. We have identified the enterocyte differentiation marker IAP as a KLF4 target gene. IAP transactivation by KLF4 is likely mediated through a critical region located within the proximal IAP promoter region.


Mass-gathering Events: The Role of Advanced Nurse Practitioners in Reducing Referrals to Local Health Care Agencies.
Introduction: The introduction of advanced practitioner roles has challenged the traditional boundaries of health care. While studies have been undertaken to understand the role of physicians in respect of mass-gathering medicine, the role of advanced nurse practitioners (ANPs) has not been investigated. Problem Does the presence of an ANP reduce the referral rates of patients presenting for medical care at mass-gathering events to external health care resources? A prospective observational study was undertaken to determine whether the presence of an ANP would reduce the patient referral rate to external health care services by first aiders and paramedics working within an event medical team. Patients identified as requiring referral were reviewed by an ANP as part of the on-site medical provision for four mass-gathering events in the south of England. Additionally, information was gathered identifying which patients would have been transported to hospital by ambulance compared to those actually transported following ANP review. Statistical analysis was undertaken for three key measures (referrals to all local health resources, referrals to hospital-based acute services, and transfers to hospital by ambulance). A rounded total of 842,000 people attended four mass-gathering events held over 14 days. Of these, 652 presented for medical care, many self-referring. Using a one-tailed Fisher's Exact Test and Phi analysis, this study demonstrated statistically significant reductions in the overall referral of patients to all external health care resources (P<.001; φ=0.44), to the emergency department (ED; P<.001; φ=0.43), and a reduction in ambulance transport (P<.001; φ=0.42). Effect size analysis demonstrated a medium-sized effect evident for all of the above, which was also demonstrated in economic terms. The event medical team would have referred 105 (16.3%) of the 652 patient presentations to external health care services; 47 (7.2%) would have been transported by ambulance. In comparison, the ANP referred 23 patients (3.5%) with 11 (1.7%) being transported by ambulance. It also was noted that the first aiders and paramedics could be more selective in their referral habits that were focused primarily on the ED. Appropriately trained and experienced ANPs working within event medical teams have a positive impact on referral rates from mass-gathering events.


Position-Cortical Coherence as a Marker of Afferent Pathway Integrity Early Poststroke: A Prospective Cohort Study.
Background. Addressing the role of somatosensory impairment, that is, afferent pathway integrity, in poststroke motor recovery may require neurophysiological assessment. Objective. We investigated the longitudinal construct validity of position-cortical coherence (PCC), that is, the agreement between mechanically evoked wrist perturbations and electroencephalography (EEG), as a measure of afferent pathway integrity. Methods. PCC was measured serially in 48 patients after a first-ever ischemic stroke in addition to Fugl-Meyer motor assessment of the upper extremity (FM-UE) and Nottingham Sensory Assessment hand-finger subscores (EmNSA-HF, within 3 and at 5, 12, and 26 weeks poststroke. Changes in PCC over time, represented by percentage presence of PCC (%PCC), mean amplitude of PCC over the affected (Amp-A) and nonaffected hemisphere (Amp-N) and a lateralization index (L-index), were analyzed, as well as their association with FM-UE and EmNSA-HF. Patients were retrospectively categorized based on FM-UE score at baseline and 26 weeks poststroke into high- and low-baseline recoverers and non-recoverers. Results. %PCC increased from baseline to 12 weeks poststroke (β = 1.6%, CI = 0.32% to 2.86%, P = .01), which was no longer significant after adjusting for EmNSA-HF and FM-UE. A significant positive association was found between %PCC, Amp-A, and EmNSA-HF. Low-baseline recoverers (n = 8) showed longitudinally significantly higher %PCC than high-baseline recoverers (n = 23). Conclusions. We demonstrated the longitudinal construct validity of %PCC and Amp-A as a measure of afferent pathway integrity. A high %PCC in low-baseline recoverers suggests that this measure also contains information on cortical excitability. Use of PCC as an EEG-based measure to address the role of somatosensory integrity to motor recovery poststroke requires further attention.


Carbon dioxide fixation in Helminthosporium cynodontis.
A mycelial suspension of Helminthosporium cynodontis (ATCC24938), grown on glucose-peptone-yeast extract broth and exposed to NaH14CO3 for 5 h, fixed significant quantities of 14C into the following fractions (%): small molecular weight components, 7-4; lipid and lipoproteins, 3-9; nucleic acids, 59; the residual protein and cell wall fragments, 29-2. The labelled protein components were (%): aspartate, 39; glutamate, 18; cystine, 15; threonine, 9. Radioactive nucleic acid components were (%): adenine, 18; guanine, 18; cytidylate, 34; uridylate, 30. When the mycelium was grown in Czapek-Dox glucose medium and incubated in this medium plus NaH14CO3, the nucleic acid fraction contained 29-9% and the residual protein 49-5% of the cellular radioactivity. The removal of CO2 from the atmosphere did not reduce growth. Pyruvate carboxylase (PC) and phosphoenolypyruvate carboxykinase (PEPCK) activities were demonstrated in extracts of H. cynodontis. Synthesis of PEPCK was stimulated under conditions promoting gluconeogenesis and was reduced under conditions promoting glycolysis, while PC synthesis was similar under both conditions.


Tatp-mediated intracellular delivery of pharmaceutical nanocarriers.
CPPs (cell-penetrating peptides), including Tatp (transactivator of transcription peptide), have been successfully used for intracellular delivery of a wide variety of cargoes including various nanoparticulate pharmaceutical carriers such as liposomes, micelles and nanoparticles. Here, we will consider the major results obtained in this area with emphasis on Tatp-mediated delivery of liposomes and various transfection vectors. We will also address the development of 'smart' stimuli-sensitive nanocarriers, where the cell-penetrating function can only be activated when the nanocarrier is inside the biological target, thus minimizing the interaction with non-target cells.


Stair walking transitions are an anticipation of the next stride.
According to the CDC, the majority of fall-related accidents occur during stair walking. It is likely that the required increases in range of motion and muscle activity during stair walking contribute to increased fall risk. In addition, compared to level walking, the transition strides before and after stair walking demonstrate increased fall risk. We hypothesized that the transition strides would have joint angle trajectories and muscle activity patterns that are most similar to a theoretical transition stride, calculated as the mean between the before stride and the after stride. Twelve healthy men completed the protocol of level and stair walking. We analyzed three sagittal plane joint angles and six leg muscle activity patterns of the left leg for transitions from level to stairs and from stairs to level, both up and down. We compared each time point of the transition strides to the corresponding time points of the before stride, the after stride, and a theoretical mean stride with a series of 2-sample t-tests. Contrary to our hypothesis, all transition strides exhibited the least number of significantly different time points with the after stride (34%), not the mean stride (51%). This result suggests that the mechanics of a transition stride are not simply an intermediate between a before stride and an after stride, neither are they a continuation of the before stride, but rather they are a unique anticipation of the upcoming surface.


The prevalence of asthma in general practice.
The survey reveals important data about onset of asthma and total attendances for asthma by Australian general practitioners. A comparison is made between data on asthma from the National Morbidity Survey 1962-63, and the Australian General Practitioner's Morbidity and Prescribing Survey 1969 to 1974. A slight male preponderance is demonstrated, most marked in infancy, but also in old age. The hypothesis is propounded that androgens may play a protective role in asthma, but females have a genetic advantage. It is noted that in the 'teens' and early adulthood, there is an increase in female patients. The onset of asthma occurs more often in autumn and spring than in summer and winter. The occurrence of asthma appears to becoming less relative to other disease. Although there was once relatively more asthma in the metropolitan areas compared with non-metropolitan, there is now less.


Lanthanide(II) complexes of a phosphine-borane-stabilised carbanion.
The reaction between two equivalents of the potassium salt [(Me(3)Si)(2){Me(2)P(BH(3))}C]K (4) and SmI(2)(THF)(2) in refluxing THF yields the dialkylsamarium(II) compounds [(Me(3)Si)(2){Me(2)P(BH(3))}C](2)Sm(THF) (5a) or [(Me(3)Si)(2){Me(2)P(BH(3))}C](2)Sm(THF)(3) (5b), depending on the crystallisation conditions, in good yield as air- and moisture-sensitive crystalline solids. X-ray crystallography shows that, whereas both alkyl ligands chelate the samarium(II) ion in 5a, in 5b one alkyl ligand chelates the metal centre and one binds the metal only through its borane hydrogen atoms. The reaction between YbI(2) and two equivalents of 4 in refluxing benzene yields the solvent-free dialkylytterbium(II) compound [(Me(3)Si)(2){Me(2)P(BH(3))}C](2)Yb (8). In contrast to 5a and 5b, compound 8 reacts rapidly with THF to give the free phosphine-borane (Me(3)Si)(2){Me(2)P(BH(3))}CH as the only identifiable product.


Emerging roles for semaphorins in neural regeneration.
Progressive axon outgrowth during neural development contrasts with the failure of regenerative neurite growth in the mature mammalian central nervous system (CNS). During neuroembryogenesis, spatiotemporal patterns of repellent and attractant activities in the vicinity of the growth cone favor neurite outgrowth. In the mature CNS, however, a relative balance between forces supporting and restricting axon growth has been established, only allowing subtle morphological changes in existing neuritic arbors and synapses. Following CNS injury, this balance shifts towards enhanced expression of growth-inhibiting molecules and diminished availability of their growth-promoting counterparts. Evidence is now emerging that the proteins governing developmental axon guidance critically contribute to the failure of injured central neurons to regenerate. As a first step toward elucidation of the role of chemorepulsive axon guidance signals in axonal regeneration, the effects of lesions of the central and peripheral nervous system on the expression of Semaphorin3A, the prototype and founding member of the semaphorin family of axon guidance signals, and of the Semaphorin3A receptor proteins neuropilin-1 and plexin-A1 have recently been examined. Here we review the first evidence indicating that (i) lesion-induced changes in the expression of chemorepulsive semaphorins relate to the success or failure of injured neurons to regenerate and (ii) semaphorins may represent important molecular signals controlling multiple aspects of the cellular response that follows CNS injury. In the future, genetic manipulation of the injury-induced changes in the availability of semaphorins and/or of their receptors will provide further insight into the mechanisms by which semaphorins influence neural regeneration.


Preparation of Pd-Loaded Hierarchical FAU Membranes and Testing in Acetophenone Hydrogenation.
Pd-loaded hierarchical FAU (Pd-FAU) membranes, containing an intrinsic secondary non-zeolitic (meso)porosity, were prepared and tested in the catalytic transfer hydrogenation of acetophenone (AP) to produce phenylethanol (PE), an industrially relevant product. The best operating conditions were preliminarily identified by testing different solvents and organic hydrogen donors in a batch hydrogenation process where micron-sized FAU seeds were employed as catalyst support. Water as solvent and formic acid as hydrogen source resulted to be the best choice in terms of conversion for the catalytic hydrogenation of AP, providing the basis for the design of a green and sustainable process. The best experimental conditions were selected and applied to the Pd-loaded FAU membrane finding enhanced catalytic performance such as a five-fold higher productivity than with the unsupported Pd-FAU crystals (11.0 vs. 2.2 mgproduct gcat(-1)·h(-1)). The catalytic performance of the membrane on the alumina support was also tested in a tangential flow system obtaining a productivity higher than that of the batch system (22.0 vs. 11.0 mgproduct gcat(-1)·h(-1)).


Characterization of human parainfluenza viruses. I. The structural proteins of parainfluenza virus 2 and their synthesis in infected cells.
Two strains of human parainfluenza virus 2 (HPV2), P2 1972/6 and P2 1980, grow to high titre in MEK3 cells, and their structural proteins and virus-induced protein synthesis have been characterized by gel electrophoresis and immunoprecipitation. Purified viruses contain seven polypeptides, including cellular actin: L (175K mol. wt.), HN (72K to 74K), NP (66K to 67K), F1 (52K to 58K), P (49K), A (44.5K) and M (39K). Virus-induced polypeptide synthesis was first detected at 8 h post-infection with the appearance of NP; other major structural proteins were detected from 10 to 12 h after infection and onwards. The synthesis of both the structural glycoproteins was demonstrated, although proteolytic processing could not be detected. Reproducible differences in the gel migration of the HN, F1 and NP polypeptides were found in whole virus, in infected cells and cells subjected to immunoprecipitation. These differences may reflect genetic diversity within HPV2 and provide a means of probing the molecular epidemiology of these viruses.


Novel pathways in the pathobiology of human abdominal aortic aneurysms.
Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males >65 years. The pathobiological mechanisms of human AAA are poorly understood. The goal of this study was to identify novel pathways involved in the development of AAAs. A custom-designed 'AAA-chip' was used to assay 43 of the differentially expressed genes identified in a previously published microarray study between AAA (n = 15) and control (n = 15) infrarenal abdominal aorta. Protein analyses were performed on selected genes. Altogether 38 of the 43 genes on the 'AAA-chip' showed significantly different expression. Novel validated genes in AAA pathobiology included ADCY7, ARL4C, BLNK, FOSB, GATM, LYZ, MFGE8, PRUNE2, PTPRC, SMTN, TMODI and TPM2. These genes represent a wide range of biological functions, such as calcium signaling, development and differentiation, as well as cell adhesion not previously implicated in AAA pathobiology. Protein analyses for GATM, CD4, CXCR4, BLNK, PLEK, LYZ, FOSB, DUSP6, ITGA5 and PTPRC confirmed the mRNA findings. The results provide new directions for future research into AAA pathogenesis to study the role of novel genes confirmed here. New treatments and diagnostic tools for AAA could potentially be identified by studying these novel pathways.


The effect of stillbirth and late termination of pregnancy on the emergence of post-traumatic symptoms among attending medical personnel.
The purpose of this paper was to assess the impact and the post-traumatic potential of late termination of pregnancy (TOP) and stillbirth on medical staff and characterise personal attributes that modulate these possible outcomes. Fifty-one participants involved in the treatment of women undergoing late TOPs and stillbirths answered questionnaires including demographics, Neuroticism subscale of the Big Five Inventory (BFI), Life Orientation Test-Revised (LOT-R), Posttraumatic Diagnostic Scale (PDS), Brief Symptom Inventory (BSI-18) and questions regarding exposure to stillbirths and late TOPs. None of the participants met the full post-traumatic stress disorder (PTSD) criteria. A correlation with a marginal significance was found between the number of TOP's/stillbirths attended during the past year and traumatic symptoms. Neuroticism moderated the association between presence in TOP's/stillbirths and post-traumatic symptoms among those who attended this event over the past month. According to our results, medical personnel do not appear to develop long-term and lingering posttraumatic symptoms following attending TOP's/stillbirths. Impact StatementWhat is already known on this subject? There is a very little research on the ways in which medical personnel respond to Stillbirths, late miscarriages and terminations of pregnancy (TOP) of their patients and on the possible effect of their personality traits in this response.What do the results of this study add? According to our results, medical personnel do not appear to develop long-term and lingering posttraumatic symptoms following attending TOP's/stillbirths.What are the implications of these findings for clinical practice and/or further research? Further studies are warranted to better assess the impact of exposure to traumatic events in general and on the effect of late TOP and stillbirths in particular, on medical personnel and to identify interventions that may prevent posttraumatic symptoms among staff members when they happen.


Dependence of McrBC cleavage on distance between recognition elements.
DNA cleavage by the modification-dependent restriction enzyme McrBC requires the presence of two suitably modified recognition elements appropriately spaced in the substrate. To characterize the spacing requirement in more detail, we have constructed a plasmid with a single McrBC cleavage site, in which the distance between recognition elements could be systematically varied while preserving the local sequence surrounding the recognition elements. Optimal separation between elements was 55-103 basepairs, with detectable cleavage observed at spacing of 32 bp to 2 kb; no cleavage was seen with spacing of 22 bp or less or with 3 kb between elements. Changing the spacing by 4 basepairs within the optimal range had little effect on the efficiency of cleavage, suggesting that the recognition elements need not lie on the same face of the DNA helix.


Three-rods test as drivers' license vision test from the viewpoint of reproducibility, eye deviation, and functional visual acuity.
Three-rods test is required as depth perception vision test to obtain motor vehicle license to drive taxies, buses, and trucks in Japan. Functional visual acuity is measured automatically by successive visual target presentation in a fixed period of time. This study examined three-rods test from the viewpoint of reproducibility, eye deviation, and functional visual acuity to assess the feasibility for drivers' license vision test. At three-rods test, a central rod was moved at the speed of 50 mm/sec forward and backward automatically against two fixed rods on both sides inside an illuminated box. An examinee at the distance of 2.5 m observed the rods inside the box from a small window and pushed a button to stop the central rod in alignment with the fixed rods. Erred distance of the central rod from the fixed rods as a mean of 4 measurements was used. At functional visual acuity test, an examinee moved a joystick to the same direction as Landolt-C opening as a visual target which was sequentially presented every 2 seconds for 30 times in 1 minute. The mean erred distance of three-rods test was reproducible between two tests done on separate occasions (n = 44, ρ = 0.679, P < 0.0001, Spearman rank correlation). Exophoria induced by wearing 4-prism-diopter base-out prism did not significantly influence the mean erred distance while vertical diplopia induced by wearing 4-prism-diopter base-up prism disrupted the measurement (n = 9). The mean erred distance of three-rods test was better correlated with functional visual acuity tested with both eyes open than with conventional visual acuity with both eyes open (n = 17, ρ = 0.2 versus ρ = 0.179). In the context of the small sample size in the present study, the three-rods test was reproducible, and testable in the presence of phoria, but not testable in diplopia, indicating the feasibility as a depth perception vision test.


Sleep Duration, Mortality, and Heredity-A Prospective Twin Study.
A number of studies have shown a U-shaped association between sleep duration and mortality. Since sleep duration is partly genetically determined, it seems likely that its association with mortality is also genetically influenced. The purpose of the present study was to investigate the influence on heredity on the association between sleep duration and mortality. We used a cohort of 14267 twins from the Swedish Twin Registry. A Cox proportional hazards regression analysis, adjusted for a number of covariates, confirmed a clear U shape with a hazard ratio (HR) = 1.34 and 95% confidence interval (CI) = 1.15-1.57 for a sleep duration of ≤6.5 hours and HR = 1.18 (CI = 1.07-1.30) for sleep of ≥9.5 hours. Reference value was 7.0 hours. A co-twin analysis of 1942 twins discordant on mortality showed a HR = 2.66 (CI = 1.17-6.04) for long (≥9.5 hours) sleep in monzygotic twins and an HR = 0.66 (CI = 0.20-2.14) for short (<6.5 hours) sleep. In dizygotic twins, no association was significant. The heritability for mortality was 28% for the whole group, while it was 86% for short sleepers and 42% for long sleepers. Thus, the link with mortality for long sleep appears to be more due to environmental factors than to heredity, while heritability dominates among short sleepers. We found that both long and short sleep were associated with higher total mortality, that the difference in mortality within twin pairs is associated with long sleep, and that short sleep has a higher heritability for mortality, while long sleep is associated with more environmental influences on mortality.


[Multiple activities carried out by nurses at a hospitalization unit].
The study aimed at knowing the activities performed by nurses in internment units of ageneral hospital of Rio Grande do Sul, Brazil. The data have been collected by means of free observation per time sampling, semi-structured interviews and consultation on documents. The subjects were nurses who act in the internment units who were chosen at random. The results showed that the nurse coordinates the care, executes several procedures and provides infrastructure conditions for the development of the collective work. The nurse articulation capacity has been identified both in relation to the nursing team organization and in the organization of the hospital environment.


Reaching Low-Income Mothers to Improve Family Fruit and Vegetable Intake: Food Hero Social Marketing Campaign-Research Steps, Development and Testing.
The objective of this study was to create/test a social marketing campaign to increase fruit/vegetable (FV) intake within Oregon Supplemental Nutrition Assistance Program (SNAP) eligible families. Focus groups (n = 2) and pre/post campaign phone surveys (n = 2082) were conducted in intervention counties (IC) and one control county. Participants were female (86%-100%) with 1-2 children at home. Mean FV intake/without juice was 3.1 servings/day; >50% preferred the Internet for delivery of healthy eating information. Participants reported time/financial burdens, low household FV variety and desirability of frozen/canned FV, and acceptance of positive messages. A Food Hero (FH) campaign was created/delivered daily August-October 2009 to mothers through multiple channels (e.g., grocery stores, online, educators). Results showed that the IC had better FH name recall (12%) and interpretation of intended messages (60%) vs. control (3%, 23%, respectively). Compared to controls, the IC were less likely to report healthy food preparation as time consuming or a FV rich diet expensive, and it was easier to get their family to eat fruit. Results did not vary based on county/household characteristics. The FH campaign increased FH awareness and positive FV beliefs. A longer campaign with FV assessments will increase understanding of the target audience, and allow for campaign refinement.


Informed consent in Italy-traditional versus the law: a gordian knot.
Italian law no. 86 of 5 June 2012, which establishes a set of rules on the matter of breast implants, came into effect in July 2012. The law is at the center of a widespread and animated cultural debate that in recent years has been taking place in Italy. The fundamental prohibition imposed by the law concerns the age limit. Breast implants for exclusively aesthetic purposes are allowed only if the legal age (18 years) has been reached. This prohibition does not apply in cases of severe congenital malformations certified by a physician operating within the National Health Service or by a public health care institution. The legal imposition of an age limit raises a number of perplexities: one at a bioethical level and one that is strictly juridical. In fact, it is impossible to deal with this issue unless the wider debate concerning the self-determination and autonomy of underage patients in biomedical matters is considered. It appears, then, that the issue is again exclusively related to the peculiarity of cosmetic surgery, which when aimed at correcting "only" the pathologic experiences of self-image, does not acquire the dignity of therapy. If, however, the improvement of self-image serves to achieve a better psycho-emotional balance and favors the development of social relations undermined by evident physical defects, age restrictions can be disregarded. The authors believe the real risk is that the law imposed by the Italian state is based on assumptions and preformed value judgments. Furthermore, in the understanding of needs, legislation often is biased toward objective biophysical problems without attaching due importance to subjective psychological and social problems. While acknowledging the seriousness of the issue, the authors do not agree with the legislature's rigidity. However, plastic surgeons must form a plan for addressing the concerns about breast implants and evaluating whether they are appropriate for adolescents, taking into account the unique psychological and developmental considerations of adolescent cosmetic surgery patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


The Use of the MolecuLight i:X in Managing Burns: A Pilot Study.
The MolecuLight i:X Imaging Device is a portable, noninvasive, real-time camera used to visualize the bacterial load in a wound. It uses violet light illumination and a dual bandpass optical filter to capture the fluorescence of endogenous structures in the tissue matrix and harmful bacteria. The MolecuLight i:X captures images of wounds and highlights potentially detrimental levels of bacteria. This is an initial evaluation of using the MolecuLight i:X camera in the management of burns to demonstrate the following: the ability of the device to guide clinicians in their management of the burn (ie, detect, identify, and specify swabbing locations). Burn wounds were photographed under standard light and violet light illumination to compare presentations of obvious infection signs and symptoms. Microbiology swab samples were obtained to correlate any bacterial presence to the images. The fluorescence images were used to guide swabs to where the bacteria were congregating. Twenty patients were imaged. Four patients did not have bacterial contamination based on their images and swab results. Sixteen patients showed growth of Staphylococcus aureus, Pseudomonas aeruginosa, or other bacteria. Nine of the patients, by definition, had infections. These findings were correlated with the typical signs and symptoms of infection, the fluorescence images, and the microbiology results. The efficacy of the MolecuLight i:X is evident due to the microbiology results correlating to the images. Further research is being done to test the device in terms of being an early intervention tool. With these early results and guidance of swab samples, the MolecuLight i:X may be able to detect bacterial load before an infection and subsequent graft failure, thereby shortening lengths of hospital stay and improving overall healing.


Ball-Milling-Enabled Reactivity of Manganese Metal*.
Efforts to generate organomanganese reagents under ball-milling conditions have led to the serendipitous discovery that manganese metal can mediate the reductive dimerization of arylidene malonates. The newly uncovered process has been optimized and its mechanism explored using CV measurements, radical trapping experiments, EPR spectroscopy, and solution control reactions. This unique reactivity can also be translated to solution whereupon pre-milling of the manganese is required.


Phylogenomic analysis of Haemophilus parasuis and proposed reclassification to Glaesserella parasuis, gen. nov., comb. nov.
The Gram-negative bacterium Haemophilus parasuis is the etiologic agent of Glässer's disease in pigs, and causes significant economic losses to the swine industry. This bacterium has been classified as a member of the family Pasteurellaceae in the genus Haemophilus, but phylogenetic relatedness has not been adequately examined to support this genus classification. Phenotypically, all 38 strains of H. parasuis tested were positive for catalase activity, oxidase activity, V-factor requirement, and acid formation from maltose and d-galactose without gas. All strains were negative for X-factor requirement, formation of indole from tryptophan, urease, l-arabinose, and α-glucosidase activity. To determine whether H. parasuis belongs to one of the current Pasteurellaceae genera 40 H. parasuis genomes, plus those of representative Pasteurellaceae, were subjected to phylogenetic analysis of concatenated, multi-protein alignments. Sequence variation at 16S rRNA and rpoB loci allowed the 15 reference serovars of H. parasuis to be integrated into the whole-genome tree. The phylogenetic analysis showed H. parasuis to be a distinct and tight clade whose sister taxon is the genus Bibersteinia. Within H. parasuis two clades were identified with individual serovars distributed between the two. As a result, H. parasuis was confirmed as a member of the family Pasteurellaceae, but was distinct from other genera in this family. Therefore, we propose the name Glaesserella parasuis, gen. nov., comb. nov. for bacterial strains currently classified as H. parasuis. The reference strain of this species is ATCC 19417 (1374)T, NCTC 4557T, DSM 21448T, CCUG 3712T.


In ovo delivery of CpG DNA reduces avian infectious laryngotracheitis virus induced mortality and morbidity.
Endosomal toll-like receptor-21 and -9 sense CpG DNA activating production of pro-inflammatory mediators with antimicrobial effects. Here, we investigated the induction of antiviral response of in ovo delivered CpG DNA against infectious laryngotracheitis virus (ILTV) infection. We found that in ovo delivered CpG DNA significantly reduces ILTV infection pre-hatch correlating with the expression of IL-1β and increase of macrophages in lungs. As assessed in vitro, CpG DNA stimulated avian macrophages could be a potential source of IL-1β and other pro-inflammatory mediators. Since we also found that in ovo CpG DNA delivery maintains increased macrophages in the lungs post-hatch, we infected the chickens on the day of hatch with ILTV. We found that in ovo delivered CpG DNA significantly reduces mortality and morbidity resulting from ILTV infection encountered post-hatch. Thus, CpG DNA can be a candidate innate immune stimulant worthy of further investigation for the control of ILTV infection in chickens.


[Prospective comparison of ARTOSCAN-MRI and arthroscopy in knee injuries].
The results of magnetic resonance imaging (MRI) were compared with those of arthroscopy in a prospective series of 276 patients. A "dedicated system" for MRI of limbs and peripheral joints--the 0,2 Tesla ARTOSCAN (ESAOTE, Italy)--was used for imaging knee joint lesions. T1-weighted spin echo sagittal images, T2-weighted gradient-echo coronal images, and axial views for lesions of bone and the femoropatellar joint were acquired. If necessary paraxial sagittal and oblique coronal views were obtained for imaging of the cruciate ligaments. This protocol allowed excellent visualization of the cruciate ligaments, medial and lateral meniscus in almost all patients. Compared with arthroscopy performed within 48 hours after imaging, the sensitivity, specificity, and accuracy were respectively, 91, 92 and 91 per cent for tears of the medial meniscus; 80, 96, and 92 per cent for tears of the posterior meniscus; 100, 100, and 100 per cent for tears of the posterior cruciate ligament; 93, 98, and 99 per cent for tears of the anterior cruciate ligament; and 73, 100, and 92 per cent for full-thickness articular cartilage lesions. The examination can be performed within 30 to 45 minutes at a cost that is lower than that of diagnostic arthroscopy. ARTOSCAN imaging is a safe and valuable adjunct to the clinical examination of the knee and an aid to efficient preoperative planning.


N-acetyllactosamine-induced retraction of bundle-forming pili regulates virulence-associated gene expression in enteropathogenic Escherichia coli.
Enteropathogenic Escherichia coli (EPEC) are a major cause of infant morbidity and mortality due to diarrhoea in developing countries. The pathogenesis of EPEC is dependent on a coordinated multi-step process culminating in the intimate adherence of the organisms to the host's intestinal mucosa. During the initial stages of the EPEC colonization process, the fimbrial adhesin, bundle-forming pili (BFP), plays an integral role. We previously reported that the major BFP structural subunit, bundlin, displays lectin-like properties, which enables BFP to initially tether EPEC to N-acetyllactosamine (LacNAc) glycan receptors on host cell surfaces. We also reported that incubating EPEC with synthetic LacNAc-bearing neoglycoconjugates not only inhibits their adherence to host cells, but also induces BFP retraction and subsequent degradation of the bundlin subunits. Herein, we demonstrate that the periplasmic serine protease, DegP, is required for degrading bundlin during this process. We also show that DegP appears to act as a bundlin chaperone during BFP assembly and that LacNAc-BSA-induced BFP retraction is followed by transcriptional upregulation of the BFP operon and downregulation of the locus of enterocyte effacement operons in EPEC.


Rapid identification of Enterobacteriaceae associated with bacteremia: a preliminary report.
A preliminary report of a method to rapidly identify Enterobacteriaceae associated with bacteremia is described. When both bottles of a blood culture set revealed gram-negative rods on the Gram stain, an aliquot of the positive culture sample was repeatedly washed in sterile deionized water to remove RBCs and culture media. The concentrated suspension of organisms was used to inoculate API 20ETM identification strips which were generally read within 6-8 hr. Samples were also processed using conventional techniques. Ten episodes of bacteremia associated with Enterobacteriaceae were correctly identified using this rapid system. One Klebsiella pneumoniae with growth only in the aerobic bottle was excluded from the study, but was identified by conventional methods. Further advantages of this protocol are described.


Lack of Sprouty 1 and 2 enhances survival of effector CD8+ T cells and yields more protective memory cells.
Identifying novel pathways that promote robust function and longevity of cytotoxic T cells has promising potential for immunotherapeutic strategies to combat cancer and chronic infections. We show that sprouty 1 and 2 (Spry1/2) molecules regulate the survival and function of memory CD8+ T cells. Spry1/2 double-knockout (DKO) ovalbumin (OVA)-specific CD8+ T cells (OT-I cells) mounted more vigorous autoimmune diabetes than WT OT-I cells when transferred to mice expressing OVA in their pancreatic β-islets. To determine the consequence of Spry1/2 deletion on effector and memory CD8+ T cell development and function, we used systemic infection with lymphocytic choriomeningitis virus (LCMV) Armstrong. Spry1/2 DKO LCMV gp33-specific P14 CD8+ T cells survive contraction better than WT cells and generate significantly more polyfunctional memory T cells. The larger number of Spry1/2 DKO memory T cells displayed enhanced infiltration into infected tissue, demonstrating that absence of Spry1/2 can result in increased recall capacity. Upon adoptive transfer into naive hosts, Spry1/2 DKO memory T cells controlled Listeria monocytogenes infection better than WT cells. The enhanced formation of more functional Spry1/2 DKO memory T cells was associated with significantly reduced mTORC1 activity and glucose uptake. Reduced p-AKT, p-FoxO1/3a, and T-bet expression was also consistent with enhanced survival and memory accrual. Collectively, loss of Spry1/2 enhances the survival of effector CD8+ T cells and results in the formation of more protective memory cells. Deleting Spry1/2 in antigen-specific CD8+ T cells may have therapeutic potential for enhancing the survival and functionality of effector and memory CD8+ T cells in vivo.


A-to-I pre-mRNA editing of the serotonin 2C receptor: comparisons among inbred mouse strains.
The serotonin receptor 5HT2CR pre-mRNA is subject to adenosine deamination (RNA editing) at five residues located within a 15 nucleotide stretch of the coding region. Such changes of adenosine to inosine (A-to-I) can produce 32 mRNA variants, encoding 24 different protein isoforms, some of which vary in biochemical and pharmacological properties. Because serotonin mediates diverse neurological processes relevant to behavior and because inbred mouse strains vary in their responses to tests of learning and behavior, we have examined the A-to-I editing patterns of the 5HT2CR mRNA in whole brains from eight mouse strains. By sequencing approximately 100 clones from individual mice, we generated detailed information on levels of editing at each site and patterns of editing that identify a total of 28 mRNA and 20 protein isoforms. Significant differences between individuals from different strains were found in total editing frequency, in the proportion of transcripts with 1 and 4 edited sites, in editing frequency at the A, B, E and D sites, in amino acid frequencies at positions 157 and 161, and in subsets of major protein isoforms. Primer extension assays were used to show that individuals within strains (six C3H.B-+rd1 and four 129SvImrJ) displayed no significant differences in any feature. These findings suggest that genetic background contributes to subtle variation in 5HT2CR mRNA editing patterns which may have consequences for pharmacological treatments and behavioral testing.


Structural and histological observations on the male reproductive system of adult red poplar leaf beetle Chrysomela populi Linnaeus, 1758 (Coleoptera: Chrysomelidae).
This study described the anatomy and histology of the male reproductive system in Chrysomela populi, which is an economically important species belonging to the family Chrysomelidae. Therefore, reproductive biology has been studied to combat this insect. As well as, the characters associated with the reproductive tract have been potential to discuss aspects of the system and to better understand the reproductive dynamics. The male reproductive system of C. populi has a pair of testes, a pair of vas efferentia and deferentia, a pair of seminal vesicles, a pair of accessory glands, an ejaculatory bulb, an ejaculatory duct, and an aedeagus. The testis consists of two flower-shaped lobes. Each testis has 20 sperm tubules (testicular follicles) containing cysts of germ cells at various developmental stages within the light orange peritoneal sheath. Testicular follicles are composed of three different (growth, maturation, and differentiation) zones. In the middle region of each testis joins with the vas efferens. The testis is attached to the seminal vesicle by a small stalk like vas efferens. In the lumen of the vas efferens, seminal vesicle, and vas deferens, sperms form clumps in the form of thin threads. The proximal end of the vas deferens is connected to the common ejaculatory duct. It joins with the ejaculatory bulb. Around the ejaculator bulb, there is a pair of convoluted, flat-surface tubular structure accessory glands. Posterior ejaculatory duct joins with the aedeagus.


Predictors of home discharge after scheduled surgery for degenerative cervical myelopathy.
Degenerative cervical myelopathy (DCM) is an important public health issue. Surgery is the mainstay of treatment for moderate and severe DCM. Delayed discharge of patients after DCM surgery is associated with increased healthcare costs. There is a paucity of data regarding predictive factors for discharge destination after scheduled surgery for patients with DCM. The purpose of this study was to identify factors predictive of home versus nonhome discharge after DCM surgery. Patients undergoing scheduled DCM surgery who had been enrolled in a prospective DCM substudy of the Canadian Spine Outcomes and Research Network registry between January 2015 and October 2020 were included in this retrospective analysis. Patient data were evaluated to identify potential factors predictive of home discharge after surgery. Logistic regression was used to identify independent factors predictive of home discharge. A multivariable model was then used as a final model. Overall, 639 patients were included in the initial analysis, 543 (85%) of whom were discharged home. The mean age of the entire cohort was 60 years (SD 11.8 years), with a BMI of 28.9 (SD 5.7). Overall, 61.7% of the patients were female. The mean length of stay was 2.72 days (SD 1.7 days). The final internally validated bootstrapped multivariable model revealed that younger age, higher 9-Item Patient Health Questionnaire score, lower Neck Disability Index scores, fewer operated levels, mJOA scores indicating mild disease, anterior cervical discectomy and fusion procedure, and no perioperative adverse effects were predictive of home discharge. Younger age, less neck-related disability, fewer operated levels, more significant depression, less severe myelopathy, anterior cervical discectomy and fusion procedure, and no perioperative adverse effects are predictive of home discharge after surgery for DCM. These factors can help to guide clinical decision-making and optimize postoperative care pathways.


[Electrocardiographic changes and echocardiography variations in ventricular morphology in left ventricular overload].
In order to compare the ECG patterns to several echocardiographic morphological indexes in different left ventricular overloadings, 15 cases of systolic left ventricular overloading (SLVO) and 17 cases of diastolic left ventricular overloading (DLVO) were analyzed. The current ECG changes of left ventricular hypertrophy and some original parameters of ventricular repolarization have been correlated with volumes, ejection fraction and mass of the left ventricle (calculated by Reichek's formula) and with left ventricular diastolic and systolic eccentricity indexes, derived by the application of Fishl's formula to the 2D echocardiographic four or two chamber apical view. In both SLVO and DLVO we found a correlation between the left ventricular mass and Romhilt-Estes point score system (p = 0.02) as well as the degree of ventricular repolarization abnormalities (p = 0.01). In SLVO we found a direct correlation between negative P wave deflection on lead V1 and diastolic as well as systolic eccentricity index: that is, the more negative P wave the more elongated left ventricular geometry. Moreover, in SLVO we found an interesting apposite correlation, compared with DLVO, between the systolic eccentricity index and the degree of ventricular repolarization abnormalities: in SLVO ST depression or T wave inversion on left limb or left precordial leads was associated with the maintenance of an elongated shape of left ventricle, while in DLVO the same ventricular repolarization abnormalities were associated with the loss of the elongated geometry of left ventricle which became spheric. Thus ECG correlates with echocardiographic left ventricular mass if poliparametric voltage indexes are considered.(ABSTRACT TRUNCATED AT 250 WORDS)


The radiographic quantification of scapular malalignment after malunion of displaced clavicular shaft fractures.
Malunion after displaced fractures of the clavicle can result in varying degrees of scapular malalignment and potentially scapular winging. The purpose of our study was to quantify the scapular malalignment in patients with midshaft clavicle malunions showing scapular winging. Eighteen patients with symptomatic midshaft clavicle malunions showing scapular winging were identified and underwent standardized computed tomography scanning of the thorax. Specific bony landmarks on the clavicle and scapula were digitized, allowing generation of 3-dimensional points. These points were acquired bilaterally so that relative translations comparing the malunited side with the contralateral side could be obtained. Statistical analysis using a paired t test was performed. The mean time from fracture to examination was 42.9 months. There were 15 men and 3 women with a mean age of 41.6 years. The mean clavicular shortening was 21.1 mm (P = .0000004). The acromion of the affected scapula on average translated 24.3 mm. The components of this translation were medial, 11.9 mm (P = .00008); inferior, 20.7 mm (P = .0009); and anterior, 4.6 mm (P = .02). Posterior bony landmarks on the scapula including the superior and inferior angles of the scapula translated a total of 9.9 mm and 5.9 mm, respectively. This is the first study to document the degree of scapular malalignment in patients with symptomatic clavicle malunions showing scapular winging. The acromion closely follows the distal clavicular fragment and translates medially, inferiorly, and anteriorly. The translations of the superior and inferior angles of the scapula are quite variable in magnitude and direction, and on average, these angles translate substantially less than the acromion.


Mosquito control with green nanopesticides: towards the One Health approach? A review of non-target effects.
The rapid spread of highly aggressive arboviruses, parasites, and bacteria along with the development of resistance in the pathogens and parasites, as well as in their arthropod vectors, represents a huge challenge in modern parasitology and tropical medicine. Eco-friendly vector control programs are crucial to fight, besides malaria, the spread of dengue, West Nile, chikungunya, and Zika virus, as well as other arboviruses such as St. Louis encephalitis and Japanese encephalitis. However, research efforts on the control of mosquito vectors are experiencing a serious lack of eco-friendly and highly effective pesticides, as well as the limited success of most biocontrol tools currently applied. Most importantly, a cooperative interface between the two disciplines is still lacking. To face this challenge, we have reviewed a wide number of promising results in the field of green-fabricated pesticides tested against mosquito vectors, outlining several examples of synergy with classic biological control tools. The non-target effects of green-fabricated nanopesticides, including acute toxicity, genotoxicity, and impact on behavioral traits of mosquito predators, have been critically discussed. In the final section, we have identified several key challenges at the interface between "green" nanotechnology and classic biological control, which deserve further research attention.


Wu-Ling-San formula prophylaxis against recurrent calcium oxalate nephrolithiasis - a prospective randomized controlled trial.
Wu-Ling-San (WLS) formula has been proved to prevent calcium oxalate nephrolithiasis both in vitro and in vivo. This is the first prospective, randomized and placebo-controlled clinical trial of WLS in calcium oxalate nephrolithiasis prevention. All patients who enrolled were asked to drink enough fluid to urinate at least 2 L daily during the study period. A 24-hour urine collection was performed to establish the baseline levels of multiple urinary parameters before taking the medicine. The patients were randomized and divided into two groups. The medication group took 2 gm WLS formula three times daily for 1 month. The control group took 2 gm placebo three times daily for 1 month. A 24-hour urine collection was performed to evaluate multiple urinary and serum parameters from all patients during the study period. A total of 39 patients were enrolled and 28 patients completed the study. Fourteen patients were allocated to WLS group and 14 patients to placebo group. After treatment, the mean urine output level increased to 2796.4 ± 525.7 ml/day (percentage of change, 13.9 %) in the WLS formula group. With placebo therapy, the mean decreased slightly to 2521.4 ± 762.7ml/day (percentage of change, -5.7 %). The percentage of change was significantly different between the two groups (independent t-test, P=0.02). No patient complained of side effects, such as fatigue, dizziness, musculoskeletal symptoms, or gastrointestinal disturbance. WLS formula is a promising adjunct to surgical and medical management of kidney stones. Active therapy with WLS formula has a positive effect on diuresis without leading to electrolyte imbalance.


Effects of recombinant alpha-2b-interferon therapy in patients with progressive MS.
The effects of systemic recombinant interferon-alpha-2b were studied in 6 carefully selected patients with progressive multiple sclerosis. 3.0 million IU were given as daily subcutaneous injections for 6 months, 5 patients showed worsening disability, and in 4 of them new or enlarged lesions were detected in MRI. In one patient no change in disability was found; his MRI showed regressed changes. The mean progression index during the treatment was significantly higher (p < 0.02) than during the previous 2 to 3 years' period of continuous progression. The frequency of peripheral blood natural killer (CD16+) cells declined significantly 3 months during the treatment, but returned to the pretreatment values after termination the treatment. An increase of intrathecal IgG synthesis and oligoclonal bands was demonstrated in 4 and 3 patients, respectively. Our experience suggests that long-term recombinant IFN-alpha-2b treatment may activate the immunological process of MS.


Unmet Needs in Appendiceal Neuroendocrine Neoplasms.
Appendiceal neuroendocrine neoplasms (ANEN) are mostly discovered coincidentally during appendicectomy and usually have a benign clinical course; thus, appendicectomy alone is considered curative. However, in some cases, a malignant potential is suspected, and therefore additional operations such as completion right hemicolectomy are considered. The existing European Neuroendocrine Tumour Society (ENETS) guidelines provide useful data about epidemiology and prognosis, as well as practical recommendations with regards to the risk factors for a more aggressive disease course and the indications for a secondary operation. However, these guidelines are based on heterogeneous and retrospective studies. Therefore, the evidence does not seem to be robust, and there are still unmet needs in terms of accurate epidemiology and overall prognosis, optimal diagnostic and follow-up strategy, as well as identified risk factors that would indicate a more aggressive surgical approach at the beginning and a more intense follow-up. In this review, we are adopting a critical approach of the ENETS guidelines and published series for ANEN, focusing on the above-noted "grey areas".


Cell proliferation of human leukemia and solid tumors studied with in vivo bromodeoxyuridine and flow cytometry.
Bromodeoxyuridine (BUDR) is a thymidine analog that is incorporated into the DNA of proliferating cells. Because the dose of BUDR that is needed to label cells is not toxic, cell labeling can be accomplished in vivo by infusing the substance into patients. A monoclonal antibody against BUDR is then used to identify BUDR-labeled cells. The same cell population can also be stained for DNA content with propidium iodide (PI). Using bivariate flow cytometry (FCM) for measurements, both the percentage of BUDR-labeled cells and their total DNA content can be evaluated. This technique allows one to obtain the labeling index (LI) and the DNA synthesis time (TS). The potential doubling time (Tpot) and the fractional turnover rate (FTR) can be mathematically derived. During a 15-month period, in vivo BUDR infusion to study cell kinetics was used in 112 consecutive patients with various types of malignant tumors: acute leukemia (50), gastric cancer (42), and brain gliomas (20). The procedure took 6 to 9 h to complete and there was no immediate toxicity from BUDR administration. Successful LI and TS determinations were obtained in 89 (80%) and in 80 (72%) of the 112 patients, respectively. Proliferative activity in 34 patients with acute nonlymphoblastic leukemias who were uniformly treated for remission induction and maintenance was measured from Tpot and FTR. It was greater in responsive than in nonresponsive patients, and in those who experienced remission for over 8 months than in those who had a shorter remission. Proliferative activity was also greater in patients with advanced gastric cancers than in those with more limited disease.(ABSTRACT TRUNCATED AT 250 WORDS)


[Extrapulmonary tuberculosis in our area. Forms of presentation].
To analyse the distribution of the extrapulmonary forms of presentation of tuberculosis (EFP) in our health district. The medical records of patients diagnosed with extrapulmonary tuberculosis attending the Tuberculosis Prevention and Control Unit of the Santiago Health District were reviewed over a three years period. The classification of EFP was: extrapulmonary forms (EF), disease outside the lung; mixed forms (MF), the presence of both pulmonary and extrapulmonary tuberculosis; disseminated forms (DF), the presence of two or more extrapulmonary locations; and miliary TB, which was defined by a diffuse pulmonary radiographic pattern or diagnosis was undertaken by necropsy. A total of 921 tuberculosis infected patients were observed, of which 370 (40.2%) were extrapulmonary forms; of these, 199 were men and 171 women (mean age was 36.9 years, range 19-68). The distribution of EFP was: 307 EF (83%) of which 140 (45.6%) were pleural, 87 (28.3%) ganglionary, 16 (5.2%) intestinal, 14 (4.5%) bone and joint, 11 (3.6%) genitourinary, 11 (3.6%) cutaneous, 10 (3.3%) meningeal, and other locations 18 (5.9); MF 38 cases (10.3%); DF 8 cases (2.1%) and miliary TB 1 cases (4.6%). In HIV infected patients 17 EF (77.3%), which were mainly ganglionary (64.7%); 4 DF (18.2%); and 1 miliary TB (4.5%) cases were observed. Our findings confirm the high incidence of extrapulmonary TB, similar to the number of pulmonary forms. Our experience shows a significant modification to the classical presentation of the disease, and thus the need for sensitivity in locating the disease.


Antibody-based therapies for idiopathic pulmonary fibrosis.
Pirfenidone and nintedanib have been the first agents demonstrating to slow down the progressive functional decline in patients with Idiopathic Pulmonary Fibrosis (IPF). Antibody-based therapies with precise molecular targets have been largely investigated over the last decade in IPF as alternative or complementary treatments, in the hope to ameliorate the relentless fibrotic process of IPF. In this review, we summarize the available evidence on two groups of monoclonal antibodies tested in IPF: those directed against known fibrogenic factors and matrix components, and those developed to antagonize the inflammation and immunity pathways. While the latter have failed to demonstrate any clinical efficacy in IPF so far, the anti-CTGF pamrevlumab has been recently proved to be capable of slowing down functional decline as compared to placebo, prompting further investigation. Despite most trials on antibody-based therapies in IPF provided so far unsatisfying results, the therapeutic development in this field should continue to be pursued to deliver a more personalized treatment approach in the future, which is not currently offered by available treatment options. A more careful trial designing and the use of valid predictive markers of response to treatment are required to enhance effectiveness of future trials.


Homogeneity tests of covariance matrices with high-dimensional longitudinal data.
This paper deals with the detection and identification of changepoints among covariances of high-dimensional longitudinal data, where the number of features is greater than both the sample size and the number of repeated measurements. The proposed methods are applicable under general temporal-spatial dependence. A new test statistic is introduced for changepoint detection, and its asymptotic distribution is established. If a changepoint is detected, an estimate of the location is provided. The rate of convergence of the estimator is shown to depend on the data dimension, sample size, and signal-to-noise ratio. Binary segmentation is used to estimate the locations of possibly multiple changepoints, and the corresponding estimator is shown to be consistent under mild conditions. Simulation studies provide the empirical size and power of the proposed test and the accuracy of the changepoint estimator. An application to a time-course microarray dataset identifies gene sets with significant gene interaction changes over time.


Are blood stream infections associated with an increased risk of hemorrhagic stroke in patients with a left ventricular assist device?
Blood stream infections (BSIs) are an important cause of morbidity and mortality in patients with left ventricular assist devices (LVADs). The aim of this study was to examine the correlation between hemorrhagic cerebrovascular accident (CVA) and BSI after implantation of LVAD for advanced heart failure (HF). This was a retrospective descriptive review of 87 patients with end-stage HF, who underwent implantation of HeartMate II continuous-flow LVAD over a 4 year period. Blood stream infections were diagnosed by serial blood cultures, and suspected neurological complications including CVAs were confirmed by neuroimaging. Extensive patient chart review was performed, and descriptive characteristics were analyzed using SPSS statistical software. The mean age of our study population was 62.3 ± 12.8 years, and the majority of our patients were males (n = 75, 86.2%). The baseline characteristics were comparable in the patients with and without CVAs. Patients with BSI had a much greater incidence of CVA compared to patients without BSI (n = 13, 43.3% vs. n = 5, 10.0%; p < 0.0001). There was an increased mortality in patients with BSI than those without (n = 57, 65.5% vs. n = 30, 34.5%; p = 0.003). The risk of all CVAs (hemorrhagic/ischemic) was eightfold (odds ratio [OR] = 7.9; 95% confidence interval [CI] = 2.4-25.5; p = 0.001] in patients with BSI. Patients with BSI had a >20-fold risk of hemorrhagic CVA (OR = 24; 95% CI = 2.8-201.1; p = 0.03). Advanced HF patients with LVAD support who developed BSI need urgent evaluation and close monitoring for suspected neurological complications, particularly hemorrhagic CVA.


Genome-Wide Identification and Expression Analysis of MAPK Gene Family in Lettuce (Lactuca sativa L.) and Functional Analysis of LsMAPK4 in High- Temperature-Induced Bolting.
The mitogen-activated protein kinase (MAPK) pathway is a widely distributed signaling cascade in eukaryotes and is involved in regulating plant growth, development, and stress responses. High temperature, a frequently occurring environmental stressor, causes premature bolting in lettuce with quality decline and yield loss. However, whether MAPKs play roles in thermally induced bolting remains poorly understood. In this study, 17 LsMAPK family members were identified from the lettuce genome. The physical and chemical properties, subcellular localization, chromosome localization, phylogeny, gene structure, family evolution, cis-acting elements, and phosphorylation sites of the LsMAPK gene family were evaluated via in silico analysis. According to phylogenetic relationships, LsMAPKs can be divided into four groups, A, B, C, and D, which is supported by analyses of gene structure and conserved domains. The collinearity analysis showed that there were 5 collinearity pairs among LsMAPKs, 8 with AtMAPKs, and 13 with SlMAPKs. The predicted cis-acting elements and potential phosphorylation sites were closely associated with hormones, stress resistance, growth, and development. Expression analysis showed that most LsMAPKs respond to high temperatures, among which LsMAPK4 is significantly and continuously upregulated upon heat treatments. Under heat stress, the stem length of the LsMAPK4-knockdown lines was significantly shorter than that of the control plants, and the microscope observations demonstrated that the differentiation time of flower buds at the stem apex was delayed accordingly. Therefore, silencing of LsMAPK4 significantly inhibited the high- temperature-accelerated bolting in lettuce, indicating that LsMPAK4 might be a potential regulator of lettuce bolting. This study provides a theoretical basis for a better understanding of the molecular mechanisms underlying the MAPK genes in high-temperature-induced bolting.


[The effect of bromantane on the cardiovascular and sympathetic-adrenal systems in animals].
Bromantan administration markedly increases the stroke and minute blood volume at a reduced heart rate and peripheral resistance in anaesthetized rats, while the systemic arterial pressure exhibits an insignificant short-time increase. Bromantan also weakly increases the pressor effects of adrenaline and noradrenaline. In anaesthetized cats, bromantan modifies the shape of the amplitude-frequency characteristic of EEG measured in the upper cervical ganglion, reducing (against the initial level) the induced potential in the frequency range of the preganglionic fiber stimulation (1-10 and 25-30 Hz). In freely moving rats, capable of well-learnt Sidman's [correction of Seedman's] operant activity, bromantan showed a reliable tendency to decrease the rate of noradrenaline and adrenaline excretion with urine.


[Age-related changes in the relationship between learning progress and auditory working memory characteristics].
In order to explore the relationship between learning progress and working memory characteristics, the psychoacoustic testing of 42 persons (20-65 years old) of medical staff taught a novel science (informatics) was carried out. The subjects were divided into three age groups: 20-35, 36-50, and 51-65-year-olds. Acoustical test consisted of a set of 12 target words (professional informatics terms) presented through headphones and subsequent presentation of a random succession of 12 target and 12 masking words (all of them being professional informatics terms). Listeners had to recognize the target words. The stepwise linear regression analysis revealed a link between the progress in acquisition of the new material and characteristics of acoustical working memory, whose role in learning progress increased with age. Because the memory efficiency reduction was found in subjects older than 35 years, it was supposed that age-related changes in characteristics of the acoustical working memory were responsible for the decline in ability to learn novel material.


Arrays of quasi-hexagonally ordered silica nanopillars with independently controlled areal density, diameter and height gradients.
A consecutive fabrication approach of independently tailored gradients of the topographical parameters distance, diameter and height in arrays of well-ordered nanopillars on smooth SiO2-Si-wafers is presented. For this purpose, previously reported preparation techniques are further developed and combined. First, self-assembly of Au-salt loaded micelles by dip-coating with computer-controlled pulling-out velocities and subsequent hydrogen plasma treatment produce quasi-hexagonally ordered, 2-dimensional arrays of Au nanoparticles (NPs) with unidirectional variations of the interparticle distances along the pulling direction between 50-120 nm. Second, the distance (or areal density) gradient profile received in this way is superimposed with a diameter-controlled gradient profile of the NPs applying a selective photochemical growth technique. For demonstration, a 1D shutter is used for locally defined UV exposure times to prepare Au NP size gradients varying between 12 and 30 nm. Third, these double-gradient NP arrangements serve as etching masks in a following reactive ion etching step delivering arrays of nanopillars. For height gradient generation, the etching time is locally controlled by applying a shutter made from Si wafer piece. Due to the high flexibility of the etching process, the preparation route works on various materials such as cover slips, silicon, silicon oxide, silicon nitride and silicon carbide.


Loss of ARID1A-associated protein expression is a frequent event in clear cell and endometrioid ovarian cancers.
Inactivating somatic mutations in the ARID1A gene are described in a significant fraction of clear cell and endometrioid ovarian cancers leading to loss of the corresponding protein (BAF250a). Expression of BAF250a was examined in clear cell and endometrioid cancers accrued as part of the North Carolina Ovarian Cancer Study, a population-based case-control study, to determine whether loss of expression is associated with clinical and epidemiological features. Immunostaining for BAF250a was performed using 212 clear cell and endometrioid ovarian cancers. Associations between loss of BAF250a and clinical and epidemiological features were examined. Variables were analyzed by logistic regression. Loss of BAF250a expression was noted in 96 (45%) of 212 cancers: 34 (41%) of 82 clear cell cases and 62 (48%) of 130 endometrioid cases. There was no relationship between the loss of BAF250a and stage, grade, survival, or epidemiological variables. These data confirm that loss of the ARID1A-encoded protein BAF250a is a frequent event in the genesis of clear cell and endometrioid ovarian cancers. Loss of BAF250a was not associated with clinical or epidemiologic characteristics. One explanation for these findings is that inactivation of the chromatin remodeling pathway may be a requisite event in the development of these cancers.


Staphylococcus aureus-derived staphopain B, a potent cysteine protease activator of plasma chemerin.
Chemerin is an attractant for cells that express the serpentine receptor CMKLR1, which include immature plasmacytoid dendritic cells (pDC) and macrophages. Chemerin circulates in the blood where it exhibits low biological activity, but upon proteolytic cleavage of its C terminus, it is converted to a potent chemoattractant. Enzymes that contribute to this conversion include host serine proteases of the coagulation, fibrinolytic, and inflammatory cascades, and it has been postulated that recruitment of pDC and macrophages by chemerin may serve to balance local tissue immune and inflammatory responses. In this work, we describe a potent, pathogen-derived proteolytic activity capable of chemerin activation. This activity is mediated by staphopain B (SspB), a cysteine protease secreted by Staphylococcus aureus. Chemerin activation is triggered by growth medium of clinical isolates of SspB-positive S. aureus, but not by that of a SspB(null) mutant. C-terminal processing by SspB generates a chemerin isoform identical with the active endogenous attractant isolated from human ascites fluid. Interestingly, SspB is a potent trigger of chemerin even in the presence of plasma inhibitors. SspB may help direct the recruitment of specialized host cells, including immunoregulatory pDC and/or macrophages, contributing to the ability of S. aureus to elicit and maintain a chronic inflammatory state.


Andersen-Tawil Syndrome Is Associated With Impaired PIP2 Regulation of the Potassium Channel Kir2.1.
Andersen-Tawil syndrome (ATS) type-1 is associated with loss-of-function mutations in KCNJ2 gene. KCNJ2 encodes the tetrameric inward-rectifier potassium channel Kir2.1, important to the resting phase of the cardiac action potential. Kir-channels' activity requires interaction with the agonist phosphatidylinositol-4,5-bisphosphate (PIP2). Two mutations were identified in ATS patients, V77E in the cytosolic N-terminal "slide helix" and M307V in the C-terminal cytoplasmic gate structure "G-loop." Current recordings in Kir2.1-expressing HEK cells showed that each of the two mutations caused Kir2.1 loss-of-function. Biotinylation and immunostaining showed that protein expression and trafficking of Kir2.1 to the plasma membrane were not affected by the mutations. To test the functional effect of the mutants in a heterozygote set, Kir2.1 dimers were prepared. Each dimer was composed of two Kir2.1 subunits joined with a flexible linker (i.e. WT-WT, WT dimer; WT-V77E and WT-M307V, mutant dimer). A tetrameric assembly of Kir2.1 is expected to include two dimers. The protein expression and the current density of WT dimer were equally reduced to ~25% of the WT monomer. Measurements from HEK cells and Xenopus oocytes showed that the expression of either WT-V77E or WT-M307V yielded currents of only about 20% compared to the WT dimer, supporting a dominant-negative effect of the mutants. Kir2.1 sensitivity to PIP2 was examined by activating the PIP2 specific voltage-sensitive phosphatase (VSP) that induced PIP2 depletion during current recordings, in HEK cells and Xenopus oocytes. PIP2 depletion induced a stronger and faster decay in Kir2.1 mutant dimers current compared to the WT dimer. BGP-15, a drug that has been demonstrated to have an anti-arrhythmic effect in mice, stabilized the Kir2.1 current amplitude following VSP-induced PIP2 depletion in cells expressing WT or mutant dimers. This study underlines the implication of mutations in cytoplasmic regions of Kir2.1. A newly developed calibrated VSP activation protocol enabled a quantitative assessment of changes in PIP2 regulation caused by the mutations. The results suggest an impaired function and a dominant-negative effect of the Kir2.1 variants that involve an impaired regulation by PIP2. This study also demonstrates that BGP-15 may be beneficial in restoring impaired Kir2.1 function and possibly in treating ATS symptoms.


[Hemagglutination tests with insect viruses].
Nucleopolyhedrosis viruses isolated from larvae of Mamestra brassicae L. and larvae of Ocneria dispar L. as well as granulosis virus isolated from Apamea anceps Shiff. were found to agglutinate red blood cells from a variety of animal species. Chicken and goose erythrocytes proved to be most sensitive. The haemagglutination-inhibition test with the virus of Mamestra brassicae and with specific mouse immune ascitic fluid (IAF) was positive. The titer of IAF was 1:160.


Fibulin-5 protects the extracellular matrix of chondrocytes by inhibiting the Wnt/β-catenin signaling pathway and relieves osteoarthritis.
Osteoarthritis (OA) is a common disease in the elderly and seriously affects the quality of life of patients. The purpose of this study was to explore the protective effect of Fibulin-5 on articular chondrocytes and its mechanism of action. Articular cartilage tissues from patients with OA and normal people were selected and tested for differences in Fibulin-5 expression. In addition, human chondrocytes were cultured, and the effects of Fibulin-5 on the extracellular matrix (ECM) of chondrocytes and the level of inflammation were examined by means of cell transfection and cytokine intervention. SKL2001, an agonist of the Wnt/β-catenin signaling pathway, was used to validate the mechanism of action of Fibulin-5 to protect chondrocytes. Fibulin-5 was lowly expressed in the cartilage tissue of patients with OA. Overexpression of Fibulin-5 significantly increased the expressions of ECM collagen II and aggrecan in chondrocytes, while decreasing the expressions of MMP-3 and MMP-13. In addition, Fibulin-5 reduced IL-1β-induced inflammation of chondrocytes, as well as expressions of IL-6, IL-8, and TNF-α. Overexpression of Fibulin-5 also reduced the activity of Wnt/β-catenin signaling pathway, and activation of Wnt/β-catenin signaling pathway attenuated the protective effects of Fibulin-5 on the ECM of chondrocytes. Fibulin-5 can protect the ECM of chondrocytes and reduce the inflammatory response of chondrocytes by inhibiting the Wnt/β-catenin signaling pathway.


Kinetic modelling of the effect of alpha subunit phosphorylation on the activity of the protein synthesis initiation factor eIF-2.
The ability of eIF-2.GDP in which the alpha subunit of eIF-2 is phosphorylated (eIF-2(alpha P).GDP) to act as a competitive inhibitor of eIF-2B-catalysed exchange of eIF-2-bound GDP has been investigated by modelling data provided by Rowlands et al. (J. Biol. Chem. 263, 5526-5533:1988). Some revision of previously determined dissociation and rate constants proved to be necessary. Under the conditions employed it was not possible to demonstrate significant inhibition of GDP exchange by eIF-2 (alpha P).GDP without substantial increase in its affinity for eIF-2B over that of eIF-2.GDP. Classic double reciprocal plots for competitive inhibition were found only when [eIF-2B] was low in relation to [eIF-2 (alpha P).GDP]. Relatively high cellular [eIF-2B] lessens the inhibitory effect of eIF-2(alpha P).GDP and suggests the possibility of other potential controls of initiation.


Neuroleptics and the natural course of schizophrenia.
To determine if neuroleptic treatment changes the natural course of schizophrenia, 22 studies were reviewed in which relatively similar patients were or were not given neuroleptics at specific times during the course of their illness. Nineteen of the studies were from first- or predominantly first-break populations. While there was little consensus among the authors of the studies reviewed, a reanalysis of the data indicates that early intervention with neuroleptics in first-break schizophrenic patients increases the likelihood of an improved long-term course. This finding is similar to that of earlier investigators who indicated there was a decrease in patients with the more severe forms of the illness following the introduction of convulsive therapies. Furthermore, there is evidence that stable schizophrenic patients whose neuroleptics are discontinued and have relapses may have a difficult time returning to their previous level of function. The findings describe in this paper have implications for both the treatment of schizophrenia and for understanding the pathophysiological processes that determine the course of the disorder.


A new monoclonal antibody (CH-F42) recognizes a CD7- subset of normal T lymphocytes and circulating malignant cells in adult T-cell lymphoma-leukemia and Sézary syndrome.
We describe a new rat immunoglobulin M monoclonal antibody (CH-F42) that recognizes a subset (1.5% to 8%) of normal peripheral blood T lymphocytes. The phenotype of these cells was determined, using dual-color immunofluorescence, to be CD2+, CD3+, CD4+, CD5+, CD7-, CD8-. They do not express T-cell activation markers, and are positive for UCHL1 (CD45RO), but negative for 2H4 (CD45RA). The antigen was expressed on circulating malignant cells in Sézary syndrome (four of four cases) and adult T-cell lymphoma-leukemia (ATLL) (four of six cases) and negative in a variety of other hematologic malignancies tested. These included chronic and acute lymphoid leukemias of B and T lineage, together with chronic and acute myeloid leukemias. However, normal CH-F42+ cells do not display any of the ultrastructural features associated with Sézary or ATLL cells. The marked similarities between these conditions together with the shared expression of an otherwise very restricted surface antigen (CH-F42) provide strong evidence for the existence of a common normal counterpart. Preliminary characterization studies of the antigen, which is also expressed by K562 and Jurkat cells, suggest the CH-F42 antigen is an O-linked, sialated glycan on a glycoprotein.


[The scientometric analysis of dissertation studies in the field of specialty public health and health care concerning children population].
The article considers trends and priority directions of research studies of the field of public health and health care of children population. The interpretative content analysis was applied to study dissertations in the field of public health and health care in 1991-2012. The sampling included 4194 units of information. The first stage of study established that problems of children population are considered in 14.8% dissertations defended on the mentioned specialty. The next stage the categories of content-analysis were examined. They were divided on the following axes: axis I "Main problem of study", axis II "Localization of study", axis III "Examined age groups", axis IV "Distribution of studies on gender of examined contingent", axis V "Examined contingent", axis VI "Additional medical specialty". It is established that in dissertations on public health and health care of children population on axis I prevails organizational subject matter (27.2%). The health condition of various contingents of children population (16.8%), preventive aspects of pediatrics (12.2%), examination of particular conditions/diseases/classes of diseases (10.8%) are fixed as priority directions. In the most dissertations the regional character of studies is presented (98.2%). The prevailing age group in studies is the adolescent group (19.9%). The inter-disciplinary relationships of dissertations on problems of public health and health care of children population are revealed with such specialties as "Pediatrics" (16.2%), "Obstetrics and gynecology" (3.8%) and "Hygiene" (3.4%). With consideration for recognition of health promotion and optimization of health care of children population as priority directions of public health policy amount of research studies in this field is to be admitted as inadequate. With purpose of optimization of scientific knowledge and development of system of medical social care to children population it is needed to promote research studies of problems of public health and health care of children and adolescents.


Antioxidant Potentials and Xanthine Oxidase Inhibitory Effect of Two Furanocoumarins Isolated from Tamus communis L.
In this investigation, the screening of two furanocoumarins; 5,8- dimethoxypsoralen (1) and heraclinin (2), isolated from the methanol root-extracts of Tamus communis L for their antioxidant activity and xanthine oxidase inhibitory effect was carried out, using different assays such as DPPH free radical scavenging effect, β- carotene / linoleic acid, xanthine oxidase (XO) inhibition and in addition to blood total antioxidant capacity. Results revealed that the two compounds have significant DPPH radical scavenging activity and effective inhibition of linoleic acid oxidation in a dose-dependent manner; 5,8-dimethoxypsoralen exhibited the highest activity with an I% = 72.69 ± 1.88%. These results indicate that the isolated compounds inhibit xanthine oxidase activity and scavenge superoxide radicals with heraclinin (2) as the more potent xanthine oxidase inhibitor, and 5,8-dimethoxypsoralen (1) as the more effective on cytochrome c reduction, the two tested compounds can effectively protect erythrocytes against hemolytic injury induced by AAPH. These results are promising for further studies of the biological and pathological effects of these natural products.


Skeletal muscle phosphoproteins: muscle-specific basal and cAMP-dependent phosphoprotein profiles.
To determine whether or not phosphorylation of skeletal muscle proteins is related to functional specialization of individual muscles, we examined the distribution of phosphoproteins in skeletal muscles with different functional properties. Protein phosphorylation was carried out using [gamma-32P]ATP and employing endogenous protein kinases present in skeletal muscle homogenates. Phosphoprotein bands were separated by polyacrylamide gel electrophoresis. We found distinct cAMP-stimulated and basal phosphoprotein patterns in each contraction type; indicating that the phosphoprotein profile is related to functional characteristics. Muscle-specific, cAMP-dependent phosphoproteins may permit coordinate short-term alterations in twitch characteristics of skeletal muscle fibers in response to circulating hormones or other mediators.


Evolutionary anatomy of the plantar aponeurosis in primates, including humans.
The plantar aponeurosis in the human foot has been extensively studied and thoroughly described, in part, because of the incidence of plantar fasciitis in humans. It is commonly assumed that the human plantar aponeurosis is a unique adaptation to bipedalism that evolved in concert with the longitudinal arch. However, the comparative anatomy of the plantar aponeurosis is poorly known in most mammals, even among non-human primates, hindering efforts to understand its function. Here, we review previous anatomical descriptions of 40 primate species and use phylogenetic comparative methods to reconstruct the evolution of the plantar aponeurosis and its relationship to the plantaris muscle in primates. Ancestral state reconstructions suggest that the overall organization of the human plantar aponeurosis is shared with chimpanzees and that a similar anatomical configuration evolved independently in different primate clades as an adaptation to terrestrial locomotion. The presence of a plantar aponeurosis with clearly developed lateral and central bands in the African apes suggests that this structure is not prohibitive to suspensory locomotion and that these species possess versatile feet adapted for both terrestrial and arboreal locomotion. This plantar aponeurosis configuration would have been advantageous in enhancing foot stiffness for bipedal locomotion in the earliest hominins, prior to the evolution of a longitudinal arch. Hominins may have subsequently evolved thicker and stiffer plantar aponeuroses alongside the arch to enable a windlass mechanism and elastic energy storage for bipedal walking and running, although this idea requires further testing.


Should We Use Contrast-Enhanced Ultrasound (CEUS) for the Characterization of Nonpalpable Testicular Lesions? An Analysis from a Cost-Effectiveness Perspective.
Accurate characterization of testicular lesions is crucial to allow for correct treatment of malignant tumors and to avoid unnecessary procedures in benign ones. In recent years, contrast-enhanced ultrasound (CEUS) proved to be superior in specifying the dignity of small, nonpalpable testicular lesions (< 1.5 cm) compared to native B-mode and color Doppler ultrasound which were previously regarded as the primary imaging method. However, the cost-effectiveness of CEUS has not been evaluated yet. The aim of this study was to analyze the cost-effectiveness of CEUS as compared to unenhanced ultrasound for the characterization of nonpalpable testicular lesions. A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with unenhanced ultrasound and CEUS. Model input parameters were obtained from recent literature. Deterministic sensitivity analysis of diagnostic parameters and costs was performed. Also, probabilistic sensitivity analysis using Monte-Carlo Modelling was applied. The willingness-to-pay (WTP) was set to $100 000/QALY. In the base-case scenario, unenhanced ultrasound resulted in total costs of $5113.14 and an expected effectiveness of 8.29 QALYs, whereas CEUS resulted in total costs of $4397.77 with 8.35 QALYs. Therefore, the unenhanced ultrasound strategy was dominated by CEUS in the base-case scenario. Sensitivity analysis showed CEUS to be the cost-effective alternative along a broad range of costs. Contrast-enhanced ultrasound is a cost-effective imaging method for the characterization of nonpalpable testicular lesions.


Subsequent pregnancy in mothers of infants with congenital heart disease.
Pregnancy rates for mothers of infants with conotruncal cardiac malformations and mothers of healthy control infants were compared for a 3-year period. Mothers of infants who died of congenital heart disease had the highest pregnancy rates, followed by control mothers, and then by mothers of surviving infants with congenital heart disease. Comparison in relation to the number of living children showed similar subsequent pregnancy rates for mothers of deceased infants with congenital heart disease and mothers of control infants, but lower rates for mothers of surviving infants with congenital heart disease. "Replacement" of a deceased infant occurs frequently, apparently in order to achieve a desired family size, whereas decreased reproduction in families of living infants with congenital heart disease may reflect the psychosocial and economic impact of the continuing care of a child with severe heart disease.


Macrophages in rheumatoid arthritis.
In rheumatoid arthritis (RA) tissue macrophages release growth factors, matrix metalloproteinases, cytokines, and chemokines. While in normal joints there is a balance between proinflammatory and anti-inflammatory cytokines, an imbalance between these inducers and inhibitors of inflammation occurs in RA, where macrophages are responsible for inducing inflammation, matrix destruction and angiogenesis.


A census of mammal populations in Punta Leona Private Wildlife Refuge, Costa Rica.
Population sizes of six mammal species were estimated using the King method during the late dry season (March) of 1996 in the Punta Leona Private Wildlife Refuge, Costa Rica. The white-faced monkey (Cebus capucinus), coati (Nasua narica) and nine-banded armadillo (Dasypus novemcinctus) with 148, 46, and 8 sighted individuals, respectively, demonstrated the largest populations in the refuge. The Central American spider monkey (Ateles geoffroyi), tamandua anteater (Tamandua mexicana), and variegated squirrel (Sciurus variegatoides) were also included in the census. Population densities are calculated, habitat types are described, and habitat use and activity periods are discussed.


Role of Ga-68 DOTANOC Positron Emission Tomography/ Computed Tomography Scan in Clinical Management of Patients with Neuroendocrine Tumors and its Correlation with Conventional Imaging- Experience in a Tertiary Care Center in India.
Aim of the study was to evaluate the role of 68Gallium-DOTANOC positron emission tomography/computed tomography (68Ga-DOTANOC PET/CT), a pan somatostatin receptor (SSTR) analog in the clinical management of patients with neuroendocrine tumors (NETs) and its correlation with conventional imaging. We retrospectively evaluated 69 patients of known/suspected NETs who underwent 68Ga-DOTANOC PET/CT scan for tumor localization (n = 15), stage modification (primary staging, n = 26 and restaging, n = 25) and therapy monitoring (n = 3). We also compared PET scan with conventional imaging as reference standard and evaluated the impact of PET/CT in the clinical management of patients. The concordant findings on 68Ga-DOTANOC PET/CT and conventional imaging seen in 33 and discordant in 36 patients. Among discordant group, disease was upstaged in 32 patients; down staged in 3 patients; no stage change in one patient. PET/CT localized primary tumor in 4 patients. Among patients with raised tumor markers (39/69), PET was positive in 29 and negative in 10 patients. Patients were followed for mean duration of 27 months to assess management. We found strong agreement between positive PET and raised tumor markers (Kappa value = 0.8). Sensitivity and specificity of PET/CT for primary tumor localization, stage modification, and therapy monitoring was >90% (P < 0.05). Study shows that DOTANOC, a broad spectrum SSTRs binding peptide labeled with Ga-68 in PET/CT scan is an excellent modality in the management of NETs patients.