The role of action research in the investigation and diffusion of innovations in health care: the PRIDE project.
In this article, the authors discuss the role of action research in relation to the investigation and practical implementation of innovations in health care. The diffusion of innovations is an essential component of the modernization of health services worldwide. However, the literature shows that it is not an easy process to research. A paradox is noted that although action research has much to offer, it has had only a limited impact in the innovation field. Drawing on an example of a project in the United Kingdom, the authors discuss whether action research is a valuable method in the study of the diffusion of innovations. They analyze its strengths and limitations as a "whole systems approach" that combines researching with developing and diffusing innovations. They argue that it is best suited to the study of innovation diffusion where there is a need for high level of adaptation in each new setting.


GABAB Receptors in the Parallel Fibre Pathway of Rat Cerebellum.
Binding studies indicate that the molecular layer of the cerebellum has a high concentration of gamma-aminobutyric acid type B (GABAB) receptors. In order to elucidate the function of these receptors we have recorded from Purkinje cells in biplanar slices of immature (14-day-old) and adult rat cerebellum using a low-noise, non-invasive, gap technique. The responses of Purkinje cells to parallel fibre stimulation in slices from both immature and adult rats contained a wave that could be inhibited by the GABAA antagonist, bicuculline. In slices from immature animals, application of 30 - 50 microM bicuculline revealed a slow (400 ms to peak) and very long-lasting (up to 1 s) hyperpolarizing wave which was inhibited by GABAB antagonists. Activation of GABAB receptors on Purkinje cells with an exogenous agonist, baclofen, also generated a hyperpolarization. Baclofen additionally inhibited the synaptic potentials generated in Purkinje cells on stimulating parallel fibres, an effect which could be reversed by GABAB antagonists. The potency of baclofen in this respect was similar in adult and immature tissue but another excitatory pathway in the cerebellar cortex, the mossy fibre to granule cell synapse, proved to be much less sensitive. We conclude that, at least in the immature rat, there are GABAB receptors on Purkinje cell dendrites and that these receptors can be activated following parallel fibre stimulation; there are also GABAB receptors on presynaptic terminals within the molecular layer of immature and adult cerebellum that, when stimulated, inhibit transmitter release.


Drug-sensitive FGFR2 mutations in endometrial carcinoma.
Oncogenic activation of tyrosine kinases is a common mechanism of carcinogenesis and, given the druggable nature of these enzymes, an attractive target for anticancer therapy. Here, we show that somatic mutations of the fibroblast growth factor receptor 2 (FGFR2) tyrosine kinase gene, FGFR2, are present in 12% of endometrial carcinomas, with additional instances found in lung squamous cell carcinoma and cervical carcinoma. These FGFR2 mutations, many of which are identical to mutations associated with congenital craniofacial developmental disorders, are constitutively activated and oncogenic when ectopically expressed in NIH 3T3 cells. Inhibition of FGFR2 kinase activity in endometrial carcinoma cell lines bearing such FGFR2 mutations inhibits transformation and survival, implicating FGFR2 as a novel therapeutic target in endometrial carcinoma.


Prevalence of influenza virus among the paediatric population in Mumbai during 2007-2009.
Influenza has a major impact on public heath, annually affecting 15-20% of the global population. Information on the activity of influenza virus in Mumbai is limited. The present study was carried out to determine the prevalence of influenza viruses causing acute respiratory infections in children by molecular methods. To study the prevalence of influenza viruses among the paediatric population in Mumbai by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). From July 2007 to July 2009, 100 respiratory samples (nasal and throat swabs) were collected from paediatric patients with acute respiratory symptoms. attending out patients department, and admitted to the paediatric wards of B. J. Wadia Hospital for Children, Mumbai. The samples were collected and processed as per World Health Organization (WHO) guidelines. Viral RNA was extracted and one-step rRT-PCR was performed to detect influenza type A (H1 and H3) and influenza type B virus. Out of 100 samples processed by rRT-PCR, a total of 11 samples (11%) were positive for influenza virus. The typing for influenza A subtypes showed 1% (1) positivity for H1 and 5% (5) positivity for H3 subtypes and 5% (5) samples tested positive for influenza type B virus. It was observed that both influenza type A and B viruses were prevalent in Mumbai during the study period. Such surveillance data are important in the early detection of any antigenic variants that may be helpful in global influenza vaccine preparation and for any pandemic preparedness activity.


Expression and structural characterization of a baculovirus ecdysteroid UDP-glucosyltransferase.
The baculovirus enzyme ecdysteroid UDP-glucosyltransferase (EGT) disrupts the hormonal balance of the insect host by catalysing the conjugation of ecdysteroids, the moulting hormones, with the sugar moiety from UDP-glucose or UDP-galactose. In this study, EGT has been overproduced using a recombinant Autographa californica nucleopolyhedrovirus and an antiserum has been raised against the purified protein. This antiserum was used to visualize the kinetics of expression of EGT by wild-type AcMNPVL-1 and by the overproducing recombinant virus. The inclusion of tunicamycin during these time-course experiments suggested that EGT is glycosylated. This was confirmed by Endo F treatment, which showed that glycosylation increased the apparent subunit molecular mass by approximately 11 kDa. These sugars do not appear to be required for enzyme activity. EGT activity invariantly elutes from gel-filtration columns as a single peak corresponding to a 260 kDa (+/-50 kDa) protein. This suggests that the enzyme is an oligomer of three to five subunits, since the subunit molecular mass is 56 kDa.


Change in subunit composition of the iron protein of nitrogenase from Rhodospirillum rubrum during activation and inactivation of iron protein.
The subunit composition of the Fe protein of nitrogenase from Rhodospirillum rubrum during activation and inactivation was investigated. It was found that the upper subunit (on gel electrophoresis) of the two-subunit Fe protein was converted into the lower subunit during activation in vitro. When the Fe protein was inactivated in vivo by the addition of NH4Cl and alpha-oxoglutarate to the cells, a phosphate-labelled upper band appeared. During activation in vitro by the activating enzyme, some of the phosphate of the upper band remained with the protein and appeared in the lower band. Activations in vitro were performed on inactive Fe protein obtained from cells grown with glutamate as the nitrogen source. Both native and oxygen-denatured Fe protein exhibited the loss of upper band during treatment with activating enzyme.


How prevalent is vitamin B(12) deficiency among vegetarians?
Vegetarians are at risk for vitamin B(12) (B12) deficiency due to suboptimal intake. The goal of the present literature review was to assess the rate of B12 depletion and deficiency among vegetarians and vegans. Using a PubMed search to identify relevant publications, 18 articles were found that reported B12 deficiency rates from studies that identified deficiency by measuring methylmalonic acid, holo-transcobalamin II, or both. The deficiency rates reported for specific populations were as follows: 62% among pregnant women, between 25% and almost 86% among children, 21-41% among adolescents, and 11-90% among the elderly. Higher rates of deficiency were reported among vegans compared with vegetarians and among individuals who had adhered to a vegetarian diet since birth compared with those who had adopted such a diet later in life. The main finding of this review is that vegetarians develop B12 depletion or deficiency regardless of demographic characteristics, place of residency, age, or type of vegetarian diet. Vegetarians should thus take preventive measures to ensure adequate intake of this vitamin, including regular consumption of supplements containing B12.


Effect of fructose 1-phosphate on the activation of liver glycogen synthase.
The activation (dephosphorylation) of glycogen synthase and the inactivation (dephosphorylation) of phosphorylase in rat liver extracts on the administration of fructose were examined. The lag in the conversion of synthase b into a was cancelled, owing to the accumulation of fructose 1-phosphate. A decrease in the rate of dephosphorylation of phosphorylase a was also observed. The latency re-appeared in gel-filtered liver extracts. Similar latency was demonstrated in extracts from glucagon-treated rats. Addition of fructose 1-phosphate to the extract was able to abolish the latency, and the activation of glycogen synthase and the inactivation of phosphorylase occurred simultaneously. Fructose 1-phosphate increased the activity of glycogen synthase b measured in the presence of 0.2-0.4 mM-glucose 6-phosphate. According to kinetic investigations, fructose 1-phosphate increased the affinity of synthase b for its substrate, UDP-glucose. The accumulation of fructose 1-phosphate resulted in glycogen synthesis in the liver by inducing the enzymic activity of glycogen synthase b in the presence of glucose 6-phosphate in vivo and by promoting the activation of glycogen synthase.


Developing and testing a tool to measure nurse/physician communication in the intensive care unit.
The purpose of this study, conducted in 3 intensive care units (ICUs) at 1 Department of Veterans Affairs Medical Center, was to develop tools and procedures to measure nurse/physician communication in future studies. We used mixed methods in a multistaged approach. Qualitative data came from 4 observations of patient care rounds and 8 interviews with nurses and physicians. Quantitative data came from anonymous surveys distributed to nurses in all 3 ICUs (n = 66). We administered the Safety Organizing Scale to measure nurses' self-reported behaviors that enable a safety culture. Analysis of variance was the main statistical test. Qualitative data were used to create an observation data collection tool and a working protocol, to measure nurse/physician communication in a future study. Analysis of variance revealed significant differences between the 3 units (f = 4.57, P = 0.02). There also were significant differences on 4 of 9 items of the Safety Organizing Scale. Using mixed methods, we gained multiple perspectives that helped us to clarify and validate the context and content of communication. Quantitative analysis showed significant differences between the 3 ICUs in nurses' perceptions of a safety culture. According to qualitative analyses, nurses from the unit which reported the weakest safety culture also were the least satisfied in their communication with physicians. Qualitative analyses corroborated quantitative findings and demonstrated the importance of contextual influences on nurse/physician communication. Through the tools and protocol we created, more realistic strategies to promote effective communication between nurses and physicians may be developed and tested in future studies.


Turkey: a further country concerned by community-acquired Escherichia coli clone O25-ST131 producing CTX-M-15.
The aim of this study was to assess the frequency and diversity of extended-spectrum beta-lactamases (ESBLs) produced by exclusively community-acquired Escherichia coli isolates in Izmir (Turkey) and to search for isolates producing CTX-M-15 and belonging to the pandemic clone E. coli O25-ST131. The patients with E. coli urinary tract infections (UTIs) and no hospitalization in the last 12 months, and no transfer from hospital, no stay in nursing home and no antimicrobial treatment in the previous 3 months were prospectively included over a 1 year period. Those E. coli detected positive for ESBL were characterized and compared with a representative of E. coli clone O25-ST131 with regard to bla genes, antibiotic resistance, phylogenetic groups, PFGE profiles and virulence factor genes (n = 17). O serotyping, multilocus sequence typing (MLST) and AmpC typing were performed to confirm that the Turkish isolate belonged to the clone O25-ST131. Among the 3108 UTIs diagnosed, 82 (2.6%) were due to community E. coli isolates and followed the strict inclusion criteria. Seventeen of them (21%) produced an ESBL, of which CTX-M-15 was predominant (53%). These ESBL-positive isolates, distributed equally into three phylogenetic groups, displayed 13 PFGE profiles and three clusters. A Turkish CTX-M-15-producing isolate as a member of the clone ST131 was suggested by a high similarity of its PFGE profile to that of the clone representative and was confirmed by O serotyping, AmpC typing and MLST. This study describes the community emergence of CTX-M-15-producing E. coli isolates, including an isolate of clone O25-ST131, in Turkey.


The physics of development 100years after D'Arcy Thompson's "On Growth and Form".
By applying methods and principles from the physical sciences to biological problems, D'Arcy Thompson's On Growth and Form demonstrated how mathematical reasoning reveals elegant, simple explanations for seemingly complex processes. This has had a profound influence on subsequent generations of developmental biologists. We discuss how this influence can be traced through twentieth century morphologists, embryologists and theoreticians to current research that explores the molecular and cellular mechanisms of tissue growth and patterning, including our own studies of the vertebrate neural tube.


A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults.
To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I. Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects. Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study. In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.


Renal hemodynamics and arterial pressure during chronic intrarenal adenosine infusion in conscious dogs.
The major aim of this study was to examine the chronic effects of increased intrarenal adenosine (ADO) levels on control of renal hemodynamics and mean arterial pressure (MAP). In six uninephrectomized conscious dogs, intrarenal ADO infusion (2 micrograms . kg-1 . min-1) for 6 days caused no significant changes in MAP, which averaged 94 +/- 3 mmHg during the control period and 91 +/- 2 mmHg during ADO infusion. ADO infusion for 6 days decreased glomerular filtration rate (GFR) and filtration fraction while causing no significant changes in effective renal plasma flow (ERPF) or sodium and water balance. To examine the role of angiotensin II (ANG II) in altering the blood pressure and renal effects of ADO, we also studied the effects of intrarenal ADO infusion in five uninephrectomized conscious dogs during continuous intrarenal infusion of ANG II (1 ng . kg-1 . min-1) to prevent renal levels of ANG II from decreasing. However, even when renal ANG II levels were maintained constant, ADO infusion at 2 micrograms . kg-1 . min-1 for 4 days and 10 micrograms . kg-1 . min-1 for 5 days failed to alter MAP, which averaged 104 +/- 6 mmHg during the control period, 106 +/- 5 mmHg during infusion of 2 micrograms . kg-1 . min-1, and 105 +/- 5 mmHg during infusion of 10 micrograms. . kg-1 . min-1 ADO. Intrarenal ANG II infusion did not prevent decreases in GFR and filtration fraction during ADO infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Diabetes in pregnancy in Mexican Americans.
Diabetes in pregnant Mexican-American women is a serious and expensive health problem. At the University of California, San Diego Medical Center, 44% of pregnant women are Mexican American. In the Diabetes in Pregnancy Clinic, only 7% of women with insulin-dependent diabetes are in this ethnic group compared with 66% of non-insulin-dependent diabetic patients and 51% of those with gestational diabetes mellitus (GDM). GDM is the most common complication of pregnancy in Mexican Americans with a prevalence approximately three times higher than that of whites (4.5 vs. 1.5%). Mexican-American obese GDM subjects had more frequent cesarean sections and were more likely to have complications of premature rupture of membranes and preterm labor (NS). Polycythemia and sepsis also occurred more often in their infants. Anthropometric measurements in infants of both lean and obese GDM subjects differed from those of infants of mothers without GDM. Infants of lean mothers with GDM were heavier and longer than those of lean mothers without GDM. In addition, they had increased waist-hip ratio and triceps and subscapular skin folds. Infants of obese mothers with GDM were heavier than those of lean mothers with GDM. Moreover, they were longer (P less than 0.04); had a higher body mass index (P less than 0.04); and larger waist and hip circumferences (P less than 0.03) and buccal (P less than 0.01), subscapular (P less than 0.01), and sum of skin-fold measurements (P less than 0.03). Our observations indicate that pregnant diabetic Mexican-American women have predominantly GDM and non-insulin-dependent diabetes. They represent a major public health problem because of increased maternal and neonatal morbidity.


Challenges in DNA motion control and sequence readout using nanopore devices.
Nanopores are being hailed as a potential next-generation DNA sequencer that could provide cheap, high-throughput DNA analysis. In this review we present a detailed summary of the various sensing techniques being investigated for use in DNA sequencing and mapping applications. A crucial impasse to the success of nanopores as a reliable DNA analysis tool is the fast and stochastic nature of DNA translocation. We discuss the incorporation of biological motors to step DNA through a pore base-by-base, as well as the many experimental modifications attempted for the purpose of slowing and controlling DNA transport.


Studies on the interaction of rheumatoid factor with monosodium urate crystals and case report of coexistent tophaceous gout and rheumatoid arthritis.
Gout and classical rheumatoid arthritis rarely coexist. We report a patient with strong evidence for both these diseases. Possible reasons for the negative correlation between these diseases are summarised. One hypothesis suggests inhibition of surface activity of monosodium urate crystals (MSU) by binding of rheumatoid factor (RF). This was studied with a purified monoclonal rheumatoid factor (mRF) with specificity for IgG. The mRF bound preferentially to MSU coated with IgG in contrast with the IgM control. Inhibition of the neutrophil chemiluminescence (CL) response to IgG-coated MSU was observed at concentrations of mRF that had no effect on the CL response to uncoated crystals. Neutrophil activation was not altered by coating crystals with an IgM control at the same concentration. These data suggest that RF may bind to antigenic determinants on exposed Fc of adsorbed IgG and block the interaction of crystal-bound IgG with Fc receptors. Although crystal coating by RF may modify the expression of gouty arthritis, it is unlikely to be the sole explanation for the dissociation between gout and RA.


Effect of alloxan diabetes on a Ca2+-activated proteinase in rat skeletal muscle.
The effect of making rats diabetic by alloxan injection on activity of the muscle Ca2+-activated proteinase (CAF) was investigated. Groups of four to seven control or alloxan-injected rats were killed 10 min (0 day) and 10, 17, and 24 days after a second alloxan injection. The second alloxan injection was given 3 days after the first. CAF activity was assayed in fractions precipitated between 0 and 45% ammonium sulfate saturation (P0-45 crude CAF fractions) that had been prepared so as to remove the protein inhibitor of CAF. Gel permeation, followed by DEAE-cellulose chromatography of pooled P0-45 crude CAF fractions from each time-treatment group, demonstrated that the assays used in this study were specific for CAF activity. Muscle CAF activity was up to 50% higher in alloxan-injected rats than in control rats, regardless of whether activity was expressed per gram sarcoplasmic protein, per gram contractile protein, or per gram skeletal muscle fresh weight. Alloxan injection diminished rate of muscle mass accumulation but did not change the proportion of sarcoplasmic or contractile protein in skeletal muscle. Hence, alloxan injection decreased the rate of contractile protein deposition. The elevation of muscle CAF activity in alloxan-injected rats is consistent with the proposed role of CAF in initiating metabolic turnover of myofibrillar proteins but does not prove this role nor exclude participation of other proteinases.


Clinical Predictors for Unsafe Direct Discharge Home Patients From Intensive Care Units.
To describe factors (demographics and clinical characteristics) that predict patients who are at an increased risk of adverse events or unplanned return visits to a health-care facility following discharge direct to home (DDH) from intensive care units (ICUs). Prospective cohort study of all adult patients who survived their stay in our medical-surgical-trauma ICU between February 2016 and 2017 and were discharged directly home. Patients were followed for 8 weeks postdischarge. Univariable and multivariable logistic regression analyses were performed to identify factors associated with adverse events or unplanned return visits to a health-care facility following DDH from ICU. A total of 129 DDH patients were enrolled and completed the 8-week follow-up. We identified 39 unplanned return visits (URVs). There was 0% mortality at 8 weeks postdischarge. Eight potential predictors of hospital URVs (P < .2) were identified in the univariable analysis: prior substance abuse (odds ratio [OR] of URV of 2.50 [95% confidence interval: 1.08-5.80], hepatitis (OR: 6.92 [1.68-28.48]), sepsis (OR: 11.03 [1.19-102.29]), admission nine equivalents of nursing manpower score (NEMS) <24 (OR: 2.28 [1.03-5.04], no fixed address (OR: 22.9 [1.2-437.3]), ICU length of stay (LOS) <2 days (OR: 2.95 [1.28-6.78]), home discharge within London, Ontario (OR: 2.44 [1.00-5.92]), and left against medical advice (AMA; OR: 6.06 [2.04-17.98]). Our study identified 8 covariates that were potential predictors of URV: prior substance abuse, hepatitis, sepsis, admission NEMS <24, no fixed address, ICU LOS <2 days, home discharge within London, Ontario, and left AMA. The practice of direct discharges home from the ICU would benefit from adequately powered multicenter study in order to construct a clinical prediction model (that would require further testing and validation).


High levels of Mn²⁺ inhibit secretory pathway Ca²⁺/Mn²⁺-ATPase (SPCA) activity and cause Golgi fragmentation in neurons and glia.
Excess Mn(2+) in humans causes a neurological disorder known as manganism, which shares symptoms with Parkinson's disease. However, the cellular mechanisms underlying Mn(2+) -neurotoxicity and the involvement of Mn(2+) -transporters in cellular homeostasis and repair are poorly understood and require further investigation. In this work, we have analyzed the effect of Mn(2+) on neurons and glia from mice in primary cultures. Mn(2+) overload compromised survival of both cell types, specifically affecting cellular integrity and Golgi organization, where the secretory pathway Ca(2+) /Mn(2+) -ATPase is localized. This ATP-driven Mn(2+) transporter might take part in Mn(2+) accumulation/detoxification at low loads of Mn(2+) , but its ATPase activity is inhibited at high concentration of Mn(2+) . Glial cells appear to be significantly more resistant to this toxicity than neurons and their presence in cocultures provided some protection to neurons against degeneration induced by Mn(2+) . Interestingly, the Mn(2+) toxicity was partially reversed upon Mn(2+) removal by wash out or by the addition of EDTA as a chelating agent, in particular in glial cells. These studies provide data on Mn(2+) neurotoxicity and may contribute to explore new therapeutic approaches for reducing Mn(2+) poisoning.


Cerebellar syndrome as a complication of COVID-19 disease.
COVID-19 disease is caused by the new coronavirus SARS-CoV-2. The disease first appeared in China in 2019 and quickly spread throughout the world. It primarily affects the respiratory tract, manifested by fever, cough and the development of dyspnoea, but the symptoms and complications can affect any organ system. Neurological symptoms include headaches, muscle and joint pain, taste and smell disorders. Complications include inflammatory diseases of the central nervous system, ataxia, peripheral nerve and muscle diseases, worsening of extrapyramidal diseases, and neuropsychiatric disorders. This paper presents a case report of a 62-year-old man with cerebellar syndrome, ataxia, intentional tremor and hypermetria when dealing with COVID-19 disease.


Impact of corporal punishment on victims' future violent behavior in extracurricular sports.
Over 500 cases of school-based corporal punishment (CP) are reported annually in Japan. A major feature of CP in Japanese schools is its high prevalence during extracurricular sports activities. The purpose of this study was to examine the influence of having suffered a CP-related injury on victims' later use of CP in an athletics environment. Participants were 704 undergraduate students of a sports instructor training course who were recruited as volunteers during classes. A questionnaire on past experiences of CP and later perpetration of CP was administered to the participants. It was found that 31.3% of the students had experienced CP and 2.3% had perpetrated CP on others. We conducted logistic regression analyses with CP as an objective dependent variable and gender, grade and past CP experience (elementary, junior high school, or high school) as explanatory variables. The results of the analysis revealed that having experienced CP had a significant relationship with the victims' perpetration of CP. Elementary school was the only life stage for which there was a significant correlation between having been a victim of CP and practicing it in the future. Many studies have explored the use of CP in families, while others have demonstrated that physical education students who received CP themselves are more likely to find CP an acceptable method of maintaining discipline. This is the first study that investigates whether students who experienced CP show a higher prevalence of CP perpetration. The findings indicate that experiencing CP in childhood is a risk factor for future use of CP. Proper care is required for children who have experienced CP at a young age.


Cell cycle synchrony in Giardia intestinalis cultures achieved by using nocodazole and aphidicolin.
Giardia intestinalis is a ubiquitous intestinal protozoan parasite and has been proposed to represent the earliest diverging lineage of extant eukaryotes. Despite the importance of Giardia as a model organism, research on Giardia has been hampered by an inability to achieve cell cycle synchrony for in vitro cultures. This report details successful methods for attaining cell cycle synchrony in Giardia cultures. The research presented here demonstrates reversible cell cycle arrest in G(1)/S and G(2)/M with aphidicolin and nocodazole, respectively. Following synchronization, cells were able to recover completely from drug treatment and remained viable and maintained synchronous growth for 6 h. These techniques were used to synchronize Giardia cultures to increase the percentages of mitotic spindles in the cultures. This method of synchronization will enhance our ability to study cell cycle-dependent processes in G. intestinalis.


Audiologist-Supported Internet-Based Cognitive Behavioral Therapy for Tinnitus in the United States: A Pilot Trial.
Background Patients often report that living with a condition such as tinnitus can be debilitating, worrying, and frustrating. Efficient ways to foster management strategies for individuals with tinnitus and promoting tinnitus self-efficacy are needed. Internet-based cognitive behavioral therapy (ICBT) for tinnitus shows promise as an evidence-based intervention in Europe, but is not available in the United States. The aim of this pilot study was to evaluate the feasibility of an ICBT intervention for tinnitus in the United States. Method This study reports the Phase 1 trial intended to support implementation of a larger randomized clinical trial (RCT) comparing ICBT to a weekly monitoring group. As a pilot study, a single-group pretest-posttest design was used to determine outcome potential, recruitment strategy, retention, and adherence rates of ICBT for tinnitus. The primary outcome was a change in tinnitus distress. Secondary outcome measures included measures of anxiety, depression, insomnia, tinnitus cognitions, hearing-related difficulties, and quality of life. Results Of the 42 screened participants, nine did not meet the inclusion criteria and six withdrew. There were 27 participants who completed the intervention, with a mean age of 55.48 (± 9.9) years. Feasibility was established, as a large pretest-posttest effect size of d = 1.6 was found for tinnitus severity. Large pretest-posttest effect sizes were also found for tinnitus cognitions and hearing-related effects, and a medium effect was found for insomnia and quality of life. Treatment adherence varied with a retention rate of 85% (n = 23) at post-intervention assessment and 67% (n = 18) for the follow-up assessment. Conclusions This pilot study supported the feasibility of ICBT for tinnitus in the United States. Ways of improving intervention retention and recruitment rates need to be explored in future ICBT studies. Protocol refinements that were identified will be implemented prior to further RCTs to investigate the efficacy of ICBT for tinnitus in the United States. Supplemental Material https://doi.org/10.23641/asha.15501135.


Bladder metastases of appendiceal mucinous adenocarcinoma: a case presentation.
Appendiceal adenocarcinoma is rare with a frequency of 0.08% of all surgically removed appendices. Few cases of appendiceal carcinoma infiltrating the bladder wall for spatial contiguity have been documented. A case is reported of a 45-years old woman with mucinous cystadenocarcinoma of the appendix with bladder metastasis. Although ultrasonography and voided urinary cytology were negative, abdomen computed tomography (CT) scan and cystoscopy and subsequent pathological examination revealed a mass exclusively located in the anterior wall of the bladder. Histopathology of the transurethral bladder resection revealed a bladder adenocarcinoma [6 cm (at the maximum diameter) x 2,5 cm; approximate weight: 10 gr] with focal mucinous aspects penetrating the muscle and perivisceral fat. Laparotomy evidenced the presence of a solid mass of the appendix (2,5 cm x 3 cm x 2 cm) extending to the loco-regional lymph nodes. Appendectomy and right hemicolectomy, linfoadenectomy and partial cystectomy were performed. The subsequent pathological examination revealed a mucinous cystadenocarcinoma of the appendix with metastatic cells colonising the anterior bladder wall and several colic lymph nodes. The rarity of the appendiceal carcinoma invading the urinary bladder and its usual involvement of nearest organs and the posterior bladder wall, led us to describe this case which demonstrates the ability of the appendiceal cancer to metastasize different regions of urinary bladder.


Oxidative stress and histopathological changes induced by methylthiophanate, a systemic fungicide, in blood, liver and kidney of adult rats.
Methyl-thiophanate (MT), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. Oxidative stress has been proposed as a possible mechanism involved in MT toxicity on non-target organism. In the present study, the effect of MT injected intraperitoneally to adult rats at 300 or 500 mg/kg of body weight was studied on blood, liver and kidney. Our results showed 3 days after MT injection, a significant decrease in hemoglobin and hematocrit values. A disruption in total white blood cells and platelets also occurred. Accordingly, an increased in malondialdehyde, H2O2 and advanced oxidation protein levels in liver and kidney were noted with the two doses. A significant change in plasma biomarkers and organ enzymatic and non-enzymatic activities were observed after MT treatment. The modifications in biochemical parameters were substantiated by histopathological data. These data confirmed the pro-oxidant effects of this fungicide. Accordingly, care must be taken to avoid mammalian and human exposure to MT.


Bird conservation would complement landslide prevention in the Central Andes of Colombia.
Conservation and restoration priorities often focus on separate ecosystem problems. Inspired by the November 11th (2011) landslide event near Manizales, and the current poor results of Colombia's Article 111 of Law 99 of 1993 as a conservation measure in this country, we set out to prioritize conservation and restoration areas where landslide prevention would complement bird conservation in the Central Andes. This area is one of the most biodiverse places on Earth, but also one of the most threatened. Using the case of the Rio Blanco Reserve, near Manizales, we identified areas for conservation where endemic and small-range bird diversity was high, and where landslide risk was also high. We further prioritized restoration areas by overlapping these conservation priorities with a forest cover map. Restoring forests in bare areas of high landslide risk and important bird diversity yields benefits for both biodiversity and people. We developed a simple landslide susceptibility model using slope, forest cover, aspect, and stream proximity. Using publicly available bird range maps, refined by elevation, we mapped concentrations of endemic and small-range bird species. We identified 1.54 km(2) of potential restoration areas in the Rio Blanco Reserve, and 886 km(2) in the Central Andes region. By prioritizing these areas, we facilitate the application of Article 111 which requires local and regional governments to invest in land purchases for the conservation of watersheds.


Effects of a short messaging service-based skin cancer prevention campaign in adolescents.
Skin cancer prevention emphasizes early adoption and practice of sun protection behaviors. Adolescence represents a high-risk period for ultraviolet radiation exposure, presenting an opportunity for intervention. The ubiquity of mobile phones among teens offers an engaging medium through which to communicate prevention messages. To evaluate a skin cancer prevention intervention using short messaging service (SMS, or text messages) to impact sun-related knowledge, beliefs, and behaviors among adolescents. The intervention was conducted in middle school youth (N=113) recruited in April or October 2012. Participants were English speakers, 11-14 years old, routinely carried a mobile phone, and completed a 55-minute sun safety education program. Participants were sent three sun safety-themed SMS messages each week for 12 weeks. Skin and sun protective knowledge, beliefs, behaviors, and post-intervention program satisfaction were collected and analyzed at baseline and end of intervention (April/June 2012; October 2012/January 2013). Paired responses were tested for equality using Wilcoxon signed-rank tests. Ninety-six students (85%) completed the study. At 12 weeks, significant positive changes were reported for sun avoidance during peak ultraviolet radiation, sunscreen application, wearing hats and sunglasses, and knowledge about skin cancer risk. Participants expressed moderately high satisfaction with the program, and 15% shared messages with family or friends. A brief, SMS-based intervention affected youth skin cancer prevention behaviors and knowledge. Future research will determine whether program effects were sustained at 24 weeks and explore how sun safety parenting practices inform these effects.


Interactions and survival of enteric viruses in soil materials.
There were marked differences in the abilities of eight different soil materials to remove and retain viruses from settled sewage, but for each soil material the behavior of two different viruses, poliovirus type 1 and reovirus type 3, was often similar. Virus adsorption to soil materials was rapid, the majority occurring within 15 min. Clayey materials efficiently adsorbed both viruses from wastewater over a range of pH and total dissolved solids levels. Sands and organic soil materials were comparatively poor adsorbents, but in some cases their ability to adsorb viruses increased at low pH and with the addition of total dissolved solids or divalent cations. Viruses in suspensions of soil material in settled sewage survived for considerable time periods, despite microbial activity. In some cases virus survival was prolonged in suspensions of soil materials compared to soil-free controls. Although sandy and organic soil materials were poor virus adsorbents when suspended in wastewater, they gave >/=95% virus removal from intermittently applied wastewater as unsaturated, 10-cm-deep columns. However, considerable quantities of the retained viruses were washed from the columns by simulated rainfall. Under the same conditions, clayey soil material removed >/=99.9995% of the viruses from applied wastewater, and none were washed from the columns by simulated rainfall.


Metabolomic Profiling in the Characterization of Degenerative Bone and Joint Diseases.
Osteoarthritis and inflammatory arthropathies are a cause of significant morbidity globally. New research elucidating the metabolic derangements associated with a variety of bone and joint disorders implicates various local and systemic metabolites, which further elucidate the underlying molecular mechanisms associated with these destructive disease processes. In osteoarthritis, atty acid metabolism has been implicated in disease development, both locally and systemically. Several series of rheumatoid arthritis patients have demonstrated overlapping trends related to histidine and glyceric acid, while other series showed similar results of increased cholesterol and glutamic acid. Studies comparing osteoarthritis and rheumatoid arthritis reported elevated gluconic acid and glycolytic- and tricarboxylic acid-related substrates in patients with osteoarthritis, while lysosphingolipids and cardiolipins were elevated only in patients with rheumatoid arthritis. Other bone and joint disorders, including osteonecrosis, intervertebral disc degeneration, and osteoporosis, also showed significant alterations in metabolic processes. The identification of the molecular mechanisms of osteoarthritis and inflammatory arthropathies via metabolomics-based workflows may allow for the development of new therapeutic targets to improve the quality of life in these patient populations.


[Cardiac tamponade associated with umbilical venous catheter (UVC) placed in inappropriate position].
Umbilical venous catheter (UVC) is widely used in neonatal intensive care units. Pericardial effusion is an uncommon but life-threatening complication; and tamponade have been reported in 3% of neonates having such catheters. We present a case of cardiac tamponade as a complication of venous catheter in a neonate. The patient was diagnosed at the appropriate time by echocardiography and the pericardiocentesis was performed, and after removal of the complete pericardial effusion,an improvement of the critical condition was achieved. It is important to document the optimal positioning of UVC before the start of infusions.


Phage resistance evolution in vitro is not reflective of in vivo outcome in a plant-bacteria-phage system.
The evolution of resistance to parasites is fundamentally important to disease ecology, yet we remain unable to predict when and how resistance will evolve. This is largely due to the context-dependent nature of host-parasite interactions, as the benefit of resistance will depend on the abiotic and biotic environment. Through experimental evolution of the plant pathogenic bacterium Pseudomonas syringae and two lytic bacteriophages across two different environments (high-nutrient media and the tomato leaf apoplast), we demonstrate that de novo evolution of resistance is negligible in planta despite high levels of resistance evolution in vitro. We find no evidence supporting the evolution of phage-selected resistance in planta despite multiple passaging experiments, multiple assays for resistance, and high multiplicities of infection. Additionally, we find that phage-resistant mutants (evolved in vitro) did not realize a fitness benefit over phage-sensitive cells when grown in planta in the presence of phage, despite reduced growth of sensitive cells, evidence of phage replication in planta, and a large fitness benefit in the presence of phage observed in vitro. Thus, this context-dependent benefit of phage resistance led to different evolutionary outcomes across environments. These results underscore the importance of studying the evolution of parasite resistance in ecologically relevant environments.


Phase I study of a herpes simplex virus type 2 (HSV-2) DNA vaccine administered to healthy, HSV-2-seronegative adults by a needle-free injection system.
We conducted a double-blind, vehicle-controlled, dose escalation safety and immunogenicity trial of a candidate herpes simplex virus type 2 (HSV-2) surface glycoprotein D2 (gD2) DNA vaccine administered by use of a needle-free device. Sixty-two healthy adults were randomized using a 4:1 vaccine-to-placebo ratio. Half of the participants were HSV-1 seronegative, and all were HSV-2 seronegative. Vaccine doses included 100 microg, 300 microg, 1,000 microg or 3,000 microg of a plasmid expressing the gD2 protein. Subjects received vaccine at 0, 4, 8, and 24 weeks. Some subjects received an additional 1,000-microg boost at 52 weeks. We found that the vaccine was safe and well tolerated, with most adverse events being local site reactions. No dose-limiting toxicities were observed. gD2-specific cytotoxic T-lymphocyte and lymphoproliferation responses were detected 2 weeks after the third vaccine injection in one of four HSV-1-seronegative, HSV-2-seronegative participants who received 3,000 microg of vaccine. A DNA-based vaccination strategy against HSV-2 appears to be safe and may generate a vaccine-specific cellular immune response, but high vaccine doses are likely needed to elicit an immune response in most vaccinees.


A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group.
The efficacy and safety of donepezil as a treatment for patients with mild to moderate Alzheimer's disease (AD) was investigated in a multicenter, double-blind study. Patients were randomly assigned to treatment with placebo (n = 162), 5 mg/d donepezil (n = 154), or 10 mg/d donepezil (n = 157) for 24 weeks followed by a 6-week, single-blind placebo washout. The primary efficacy measures were the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Clinician's Interview Based Assessment of Change-Plus (CIBIC plus), with the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB), and patient rated Quality of Life (QoL) used as secondary measures. Cognitive function, as measured by the ADAS-cog, was significantly improved in the 5- and 10-mg/d donepezil groups as compared with the placebo group at weeks 12, 18, and 24. Clinician's global ratings on the CIBIC plus also improved in both the 5- and 10-mg/d donepezil groups relative to placebo. At the end of the 6-week placebo washout phase, ADAS-cog scores and CIBIC plus ratings were not significantly different for the three groups. Significant treatment benefits were also observed consistently in both the 5- and 10-mg/d groups on the MMSE and the CDR-SB, but there was no consistent effect on the patient-rated QoL. Cholinergic side effects (primarily diarrhea, nausea, and vomiting) were reported more often in the 10-mg/d group than either the 5-mg/d or placebo groups. Side effects were transient and generally mild in severity. These data indicate that donepezil is a well-tolerated drug that improves cognition and global function in patients with mild to moderate AD.


Antiobesity effect of Kochujang (Korean fermented red pepper paste) extract in 3T3-L1 adipocytes.
Kochujang (Korean fermented red pepper paste) is a mixture of fermented soybeans, wheat, and red pepper powder. Kochujang has been reported to reduce body fat gain and lipid levels of adipose tissues and serum in rats. We studied the inhibitory effect of Kochujang on lipid accumulation and investigated the molecular mechanism of the action in 3T3-L1 adipocytes by measuring the expression levels of adipocyte-specific genes by real-time reverse transcription-polymerase chain reaction. When 3T3-L1 adipocytes were treated with Kochujang extract (KE), the sizes of adipocytes and leptin secretion were decreased. Hormone-sensitive lipase (HSL) was transcriptionally up-regulated at 4 hours, and glycerol secretion was increased at both 4 hours and 24 hours. Moreover, mRNA expression levels of both sterol regulatory element-binding protein 1-c (SREBP-1c) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which are critical transcription factors for adipogenesis, were markedly down-regulated. Tumor necrosis factor-alpha (TNF-alpha) is reported to impair pre-adipocyte differentiation and induce lipolysis and apoptosis. KE treatment of 3T3-L1 adipocytes decreased TNF-alpha mRNA levels, but had no apparent affect on apoptosis. Taken together, our study shows that Kochujang decreased lipid accumulation in 3T3-L1 adipocytes by inhibiting adipogenesis through down-regulation of SREBP-1c and PPAR-gamma and by stimulation of lipolysis due to increased HSL activity. TNF-alpha might not be involved in the reduction of lipid accumulation by KE.


Remotely sensed between-individual functional trait variation in a temperate forest.
Trait-based ecology holds the promise to explain how plant communities work, for example, how functional diversity may support community productivity. However, so far it has been difficult to combine field-based approaches assessing traits at the level of plant individuals with limited spatial coverage and approaches using remote sensing (RS) with complete spatial coverage but assessing traits at the level of vegetation pixels rather than individuals. By delineating all individual-tree crowns within a temperate forest site and then assigning RS-derived trait measures to these trees, we combine the two approaches, allowing us to use general linear models to estimate the influence of taxonomic or environmental variation on between- and within-species variation across contiguous space.We used airborne imaging spectroscopy and laser scanning to collect individual-tree RS data from a mixed conifer-angiosperm forest on a mountain slope extending over 5.5 ha and covering large environmental gradients in elevation as well as light and soil conditions. We derived three biochemical (leaf chlorophyll, carotenoids, and water content) and three architectural traits (plant area index, foliage-height diversity, and canopy height), which had previously been used to characterize plant function, from the RS data. We then quantified the contributions of taxonomic and environmental variation and their interaction to trait variation and partitioned the remaining within-species trait variation into smaller-scale spatial and residual variation. We also investigated the correlation between functional trait and phylogenetic distances at the between-species level. The forest consisted of 13 tree species of which eight occurred in sufficient abundance for quantitative analysis.On average, taxonomic variation between species accounted for more than 15% of trait variation in biochemical traits but only around 5% (still highly significant) in architectural traits. Biochemical trait distances among species also showed a stronger correlation with phylogenetic distances than did architectural trait distances. Light and soil conditions together with elevation explained slightly more variation than taxonomy across all traits, but in particular increased plant area index (light) and reduced canopy height (elevation). Except for foliage-height diversity, all traits were affected by significant interactions between taxonomic and environmental variation, the different responses of the eight species to the within-site environmental gradients potentially contributing to the coexistence of the eight abundant species.We conclude that with high-resolution RS data it is possible to delineate individual-tree crowns within a forest and thus assess functional traits derived from RS data at individual level. With this precondition fulfilled, it is then possible to apply tools commonly used in field-based trait ecology to partition trait variation among individuals into taxonomic and potentially even genetic variation, environmental variation, and interactions between the two. The method proposed here presents a promising way of assessing individual-based trait information with complete spatial coverage and thus allowing analysis of functional diversity at different scales. This information can help to better understand processes shaping community structure, productivity, and stability of forests.


Cranioplasties following craniectomies in children-a multicenter, retrospective cohort study.
Complications following pediatric cranioplasty after craniectomy with either autologous bone flaps or cranial implants are reported to be common, particularly bone flap resorption. However, only sparse data are available regarding cranioplasty strategies, complications, and outcomes. This manuscript describes a Canadian-Dutch multicenter pediatric cohort study with autografts and cranial implant cranioplasties following craniectomies for a variety of indications. The study included all children (< 18 years) who underwent craniectomy and subsequent cranioplasty surgeries from 2008 to 2014 (with a minimum of 1-year follow-up) at four academic hospitals with a dedicated pediatric neurosurgical service. Data were collected regarding initial diagnosis, age, time interval between craniectomy and cranioplasty, bone flap storage method, type of cranioplasty for initial procedure (and redo if applicable), and the postoperative outcome including surgical site infection, wound breakdowns, bone flap resorption, and inadequate fit/disfigurement. Sixty-four patients (46 males, average age 9.7 ± 5.5 years) were eligible for inclusion, with mean follow-up of 82.3 ± 31.2 months after craniectomy. Forty cranioplasties (62.5%) used autologous bone re-implant, 23 (57.5%) of which showed resorption. On average, resorption was documented at 434 days (range 62-2796 days) after reimplantation. In 20 cases, a revision cranioplasty was needed. In 24 of the post-craniectomy cases (37.5%), a cranial implant was used with one of ten different implant types. Implant loosening prompted a complete revision cranioplasty in 2 cases (8.3%). Cranial implants were associated with low morbidity and lower reoperation dates compared to the autologous cranioplasties. The most prominent finding in this multicenter cohort study was that bone flap resorption in children remains a common and widespread problem following craniectomy. Cranioplasty strategies varied between centers and evolved over time within centers. Cranial implants were associated with low morbidity and low reoperation rates. Still, longer term and prospective multicenter cohort studies are needed to optimize cranioplasty strategies in children after craniectomies.


[Spatiotemporal variation patterns of potential evapotranspiration in five provinces of Northwest China in 1960-2011].
By using Penman-Monteith model and Hurst index model, this paper analyzed the spatiotemporal variation patterns of potential evapotranspiration (ET0) in the five provinces of Northwest China in 1960-2011. In the meantime, the dominant factors driving the variations of the ET0 were quantitatively analyzed by using sensitivity analysis method. In 1960-2011, the ET0 in the five provinces presented an overall decreasing trend, with a drop rate of -0.72 mm x a(-1), but the ET0 increased gradually after 1993. An obvious spatial difference was shown in the annual average ET0. The average ET0 in the five provinces was 1158 mm (675-2282 mm), wit the maximum (2282 mm) in Qijiaojing of Xinjiang and the low values (>800 mm) in Qinba Mountains in south Shaanxi. Except in spring, the ET0 in other seasons showed a decreasing trend. In the analysis of future trend, the ET0 in most areas (81.4%) of Northwest China would present a trend from decrease to increase. Therefore, under the background of global warming, the warm and wet degree in Northwest China would be somewhat weakened, but the ET0 in the middle part of Xinjiang would be decreased continuously. Wind speed was the main factor affecting the ET0 in Northwest China at both annual and monthly scales, but the affecting extent of wind speed differed with seasons and areas. The spatial extent affected by the wind speed in winter expanded across the entire five provinces of Northwest China, while the spatial extent affected by the wind speed in summer included the entire Xinjiang and the northwest of Gansu and Qinghai.


Dietary equol and bone metabolism in postmenopausal Japanese women and osteoporotic mice.
Equol binds to the estrogen receptor with greater affinity than its precursor, daidzein, an isoflavone found in soybeans. Inter-individual differences in the ability to produce equol may lead to differential effects of isoflavone intervention on human health. Here, we review previously published work from our laboratory on equol producer status and bone health in humans and in a mouse model of osteoporosis. We performed a 1-y, double-blind, randomized trial to compare the effects of isoflavone (75 mg of isoflavone conjugates/d; equivalent to 47 mg/d of the aglycone form) with those of placebo on bone mineral density (BMD), fat mass, and serum isoflavone concentrations in 54 early postmenopausal Japanese women classified by their equol-producer phenotype. Isoflavone intervention increased the serum equol concentration in equol producers but not in nonproducers (P < 0.04). The annualized changes in BMD in the total hip and intertrochanteric regions in the isoflavone-treated equol producers (-0.46 and -0.04%, respectively) were less than in the nonproducers (-2.28 and -2.61%, respectively). The annualized change in fat mass was lower in the equol producers compared with the nonproducers in the isoflavone group. The annualized changes in BMD and fat mass did not differ between the equol producers and nonproducers in the placebo group. Equol also inhibited bone loss and fat accumulation in estrogen-deficient osteoporotic mice. Our data suggest that prevention of bone loss and fat accumulation in early postmenopausal women by isoflavones may depend on an individual's equol-producing capacity.


[Effect of light deprivation on homeostasis, life span and development of spontaneous tumors in HER-2/neu transgenic mice].
Twenty five female HER-2/neu transgenic mice (FVB/N), aged 2 months, were surgically deprived of lighting; 30 intact transgenic mice, kept under standard conditions, were in control. Light deprivation was followed by inhibited intake of feed, decreased body mass and delayed age-associated estral disorders, as compared with control. Mean survival rate among experimental mice was higher by 13.5% than in control (p 0.001). Mean life span among the last surviving 10% of the experimental mice was longer than in control by 21.5% while maximum life span--by 21%. Although the number of tumor bearers under 7 months in the study group was twice that in control (p<0.05), they had almost equalized by the end of the experiment. The number of multiple malignancies and the size of tumor and metastases to the lung increased too.


[Autonomy and dementia].
In the course of centuries, the value of autonomy has been greatly emphasized, though the content of the concept has varied. Between various meanings it has taken, which one does allow to retain it amongst the care objectives as long as possible during the dementia process? A critical examination of the philosophical and medico-social literature shows that the different meanings of autonomy can be organized according to two poles. The first one, the canonical one, is the most usual, and regards autonomy as a matter of internal competences of the subject (such as rationality, reflexivity, memory). Subjects with dementia are therefore more or less rapidly excluded from the access to autonomy. The second one is relational and refers to external conditions. Do the relationships, the institutions in which the demented person is included, and the policies on which he depends allow him the opportunity to act autonomously? In this meaning, others people are considered as a potential resource to identify the goals and means appropriate for the subject. Therefore, this relational pole recognises the possibility for the demented subject to be longer autonomous than according to the canonical pole because his autonomy does not depend only on himself but on all those who care for him directly or indirectly. In this meaning, he can exercise his autonomy in more domains.


Ionic Liquids: An Ideal Solvent for Tuning the UCST Phase Behavior of Polymer Gels.
Liquid-liquid phase separation (LLPS) is a common stimulus-responsive phenomenon widely studied and applied in constructing intelligent systems such as microfluidic valves, smart windows, and biosensors. However, LLPS in an aqueous solution has limited applicability confined to a narrow temperature range within 0-100 °C. In addition, for easy exploitation of thermoresponsive behavior, phase separation must be stable and accurately predictable under varying conditions. This study proposes a gel system exhibiting UCST phase behavior using ionic liquids (ILs) and hydrophilic polymers, whose phase transition temperature can be linearly tuned within a wide range (from subzero to over 100 °C) by varying the mixing ratio of ILs in their blends. Similar to the mixing of ILs with structurally similar cations, mixing ILs containing different anions proved to be an effective ideal random mixing method based on experimental results and molecular dynamics simulations. This mixing mechanism of ILs accounts for the linear regulation of the UCST of the ionogels when the mixing ratio of ILs in their blends varies. Moreover, the unique feature of ILs was further demonstrated using other hydrophilic polymer networks and multiple combinations of ILs, suggesting the generality of this strategy for UCST regulation in the ionogels.


Hypertension in women: progress and unsolved problems.
Hypertension is the most common cause of increased risk for heart and vascular disease in the adult population. Both men and women are at risk for hypertension and both benefit from anti-hypertensive therapy. However, hypertension tends to be less prevalent in women and is better tolerated; hypertensive women have fewer strokes and heart attacks than do hypertensive men. Women may develop reversible hypertension due to use of birth control pills. Another form of curable secondary hypertension, renal artery stenosis caused by fibromuscular dysplasia, is much more frequent in young women than men. Antihypertensive drug treatment for severe hypertension benefits both sexes, although clinical trials establishing this have been conducted only in men. There is no proof that white women with mild hypertension benefit from antihypertensive drug therapy. Non-drug approaches including weight reduction, change in diet, and exercise may be equally beneficial.


A probabilistic assessment of the contribution of wastewater-irrigated lettuce to Escherichia coli O157:H7 infection risk and disease burden in Kumasi, Ghana.
Wastewater use for vegetable production is widespread across the cities of many developing countries. Studies on the microbial health risks associated with the practice have largely depended on faecal indicator organisms with potential underestimation or overestimation of the microbial health risks and disease burdens. This study assessed the Escherichia coli O157:H7 infection risk and diarrhoeal disease burden measured in disability-adjusted life years (DALYs) associated with the consumption of wastewater-irrigated lettuce in Kumasi, Ghana using data on E. coli O157:H7 in ready-to-harvest, wastewater-irrigated lettuce. Two exposure scenarios - best case and worst case - associated with a single consumption of wastewater-irrigated lettuce were assessed. The assessment revealed wastewater-irrigated lettuce is contributing to the transmission of E. coli O157:H7 in Kumasi, Ghana. The mean E. coli O157:H7 infection risk and DALYs in the wet and dry seasons, irrespective of the exposure scenario, were above the World Health Organization tolerable daily infection risk of 2.7 × 10⁻⁷ per person per day and 10⁻⁶ DALYs per person per year. It is recommended that legislation with clear monitoring indicators and penalties is implemented to ensure that farmers and food sellers fully implement risk mitigating measures.


[A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs].
The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique antithrombin product developed by Japanese researchers in 1990, and is used for vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits platelet aggregation and prevents myocardial infraction, projects for developing antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in France, was introduced in 1981 and prevailed widely in Japan for reducing the risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an antithrombotic drug in 1988, and was also approved by Japanese authorities in 2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs; alprostadil alfadex for injection (1979), and limaprost alfadex for oral use (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992. Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are the notable drugs in this field. Ethyl icosapentate, from fish oil, is available for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen activators are useful for thromboembolism. The streptokinase from bacterial origin developed in the USA and Europe was not introduced, and urokinase (1965) was the first plasminogen activator developed in Japan. Then tissue plasminogen activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical recombination, 1991), nateplase (genetical recombination, 1996), monteplase (1998) and pamiteplase (1998) were developed and approved for acute myocardial infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for the same indication. While the development of the hemostatic drugs ceased in the 1960s, avid project studies for antithrombotic drugs including fibrinolytics began in the 1980s and are progressing now towards new molecular targets. This may be due to the increasing tendency of cardiovascular thromboembolic diathesis in Japan. (The figures in parentheses are the years approved by the Japanese Ministry of Health, Labor and Welfare.)


Molecular characterization of a distinct bipartite begomovirus species infecting tomato in India.
A distinct bipartite begomovirus was found associated with tomato plants showing yellowing, curling, and crumpling of the leaves, in a sub-temperate region in India. The complete DNA-A and DNA-B components were amplified through rolling circle amplification (RCA) using Phi-29 DNA polymerase and characterized. The DNA-A of the isolate was comprised of 2,756 nucleotides, encoding six open reading frames (ORFs) and DNA-B that of 2,725 nucleotides, encoding two ORFs. Genome organization of the isolate was typical of an old world bipartite begomovirus. Comparisons showed that DNA-A and its intergenic region (IR) have the highest sequence identity (86% and 84%, respectively) with the Tomato leaf curl New Delhi virus (ToLCNDV; DQ116885) and some other begomoviruses (>84%) reported from cucurbits and tomato. This data suggested that the isolate is a distinct begomovirus species for which a name Tomato leaf curl Palampur virus (ToLCPMV) is proposed. DNA-B showed the maximum sequence identity (73%) with Tomato leaf curl New Delhi virus-India-[Pakistan:Dargai:T5/6:2001] (AY150305). The common region (CR) of DNA-A and DNA-B showed 94% sequence similarity with each other. In the present study, phylogenetic relationship of this new species was also established with different begomoviruses reported from tomato and other begomoviruses showing highest homologies with complete DNA-A and DNA-B sequences. ToLCPMV is being reported from a sub-temperate region in India which was previously unaffected by begomoviruses and its whitefly vector.


Astatine-211-labeled radiotherapeutics: an emerging approach to targeted alpha-particle radiotherapy.
Targeted radiotherapy or endoradiotherapy is an appealing approach to cancer treatment because of the potential for delivering curative doses of radiation to tumor while sparing normal tissues. Radionuclides that decay by the emission of alpha-particles such as the heavy halogen astatine-211 (211At) offer the exciting prospect of combining cell-specific molecular targets with radiation having a range in tissue of only a few cell diameters. Herein, the radiobiological advantages of alpha-particle targeted radiotherapy will be reviewed, and the rationale for using 211At for this purpose will be described. The chemistry of astatine is similar to that of iodine; however, there are important differences which make the synthesis and evaluation of 211At-labeled compounds more challenging. Perhaps the most successful approach that has been developed involves the astatodemetallation of tin, silicon or mercury precursors. Astatine-211 labeled agents that have been investigated for targeted radiotherapy include [211At]astatide, 211At- labeled particulates, 211At-labeled naphthoquinone derivatives, 211At-labeled methylene blue, 211At-labeled DNA precursors, meta-[211At]astatobenzylguanidine, 211At-labeled biotin conjugates, 211At-labeled bisphosphonates, and 211At-labeled antibodies and antibody fragments. The status of these 211At-labeled compounds will be discussed in terms of their labeling chemistry, cytotoxicity in cell culture, as well as their tissue distribution and therapeutic efficacy in animal models of human cancers. Finally, an update on the status of the first clinical trial with an 211At-labeled targeted therapeutic, 211At-labeled chimeric anti-tenascin antibody 81C6, will be provided.


Closed-chest electrode-catheter technique for His bundle ablation in dogs.
A modified quadripolar electrode catheter that had two-thirds of the distal surface insulated with high-voltage plastic was inserted in 10 dogs. After a His bundle potential had been recorded, a synchronized direct-current electrical discharge was delivered between the electrodes showing the largest His bundle deflection using a standard direct-current defibrillator, and a metallic plate was positioned over the dog's back. Complete atrioventricular (AV) block was induced in 9 of 10 dogs, which were followed for 3 mo before being killed. During AV block, the QRS complex was broad and not preceded by a His bundle deflection. The mean control cycle length during AV block was 1,441 +/- 223 ms and decreased to 1,151 +/- 181 ms after exercise, a response that was usually abolished by beta-blockade. Overdrive pacing resulted in pacemaker suppression with gradual rate stabilization after 10-20 beats. There was no evidence of myocardial or valvular damage. This technique provides for a stable model of complete AV block and is suitable for experiments in which heart rate control is required. In addition, this technique may be of value for patients with tachycardia requiring His bundle section.


The case for comparability in financial reporting.
Government-owned organizations are accountable to citizens and their elected representatives. These organizations must provide financial information that will help in determining whether they are effectively pursuing their primary goal, which is to promote the general welfare. Regardless of the kind of service provided by a government-owned organization, the information needs of citizens and their elected representatives must be considered when developing accounting rules. If these needs are ignored or compromised in favor of the needs of other users, such as investors or creditors (the primary users of business financial reports), then financial reporting by government-owned organizations will not meet its objectives.


Hypoxia inducible factors 1alpha and 2alpha are associated with VEGF expression and angiogenesis in gallbladder carcinomas.
To investigate the significance of the hypoxia inducible factors HIF-1alpha and HIF-2alpha in gallbladder adenocarcinomas and their relation to angiogenesis and to the expression of VEGF, an angiogenic factor transcriptionally regulated by HIFalphas. HIF-1alpha and 2alpha expression was assessed immunohistochemically in 60 patients with early gallbladder adenocarcinomas, treated with surgery alone. In addition, the vascular density (VD) and the expression of the angiogenic factors VEGF and thymidine phosphorylase (TP) were examined. The results were correlated with clinico-pathological features and prognosis. Overexpression of HIF-1alpha and 2alpha was significantly associated with increased tumor angiogenesis and VEGF expression, while HIF-2alpha was linked with upregulation of TP. None of these factors were associated with T-stage and tumor grade. Although HIFs did not relate significantly with prognosis, patients with HIF-1/2 expression who failed to switch-on VEGF or intratumoral angiogenesis had a favorable outcome. Hypoxia inducible factors are upregulated in a large proportion of gallbladder adenocarcinomas, a feature strongly related to increased expression of VEGF and intensified angiogenesis.


Population versus hospital controls for case-control studies on cancers in Chinese hospitals.
Correct control selection is crucial to the internal validity of case-control studies. Little information exists on differences between population and hospital controls in case-control studies on cancers in Chinese hospital setting. We conducted three parallel case-control studies on leukemia, breast and colorectal cancers in China between 2009 and 2010, using population and hospital controls to separately match 540 incident cases by age, gender and residency at a 1:1 ratio. Demographic and lifestyle factors were measured using a validated questionnaire in face-to-face interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using conditional logistic regression analyses. The two control groups had closely similar exposure distributions of 15 out of 16 factors, with the only exception being that hospital controls were less likely to have a BMI ≥ 25 (OR = 0.71, 95% CI: 0.54, 0.93). For exposure of green tea drinking, the adjusted ORs (95% CIs) comparing green tealeaves intake ≥ 1000 grams annually with non-drinkers were 0.51 (0.31, 0.83) and 0.21 (0.27, 0.74) for three cancers combined, 0.06 (0.01, 0.61) and 0.07 (0.01, 0.47) for breast cancer, 0.52 (0.29, 0.94) and 0.45 (0.25, 0.82) for colorectal cancer, 0.65 (0.08, 5.63) and 0.57 (0.07, 4.79) for leukemia using hospital and population controls respectively. The study found that hospital controls were comparable with population controls for most demographic characteristics and lifestyle factors measured, but there was a slight difference between the two control groups. Hospital outpatients provide a satisfactory control group in hospital-based case-control study in the Chinese hospital setting.


Phage Selection of Cyclic Peptides for Application in Research and Drug Development.
Cyclic peptides can bind to protein targets with high affinities and selectivities, which makes them an attractive modality for the development of research reagents and therapeutics. Additional properties, including low inherent toxicity, efficient chemical synthesis, and facile modification with labels or immobilization reagents, increase their attractiveness. Cyclic peptide ligands against a wide range of protein targets have been isolated from natural sources such as bacteria, fungi, plants, and animals. Many of them are currently used as research tools, and several have found application as therapeutics, such as the peptide hormones oxytocin and vasopressin and the antibiotics vancomycin and daptomycin, proving the utility of cyclic peptides in research and medicine. With the advent of phage display and other in vitro evolution techniques, it has become possible to generate cyclic peptide binders to diverse protein targets for which no natural peptides have been discovered. A highly robust and widely applied approach is based on the cyclization of peptides displayed on phage via a disulfide bridge. Disulfide-cyclized peptide ligands to more than a hundred different proteins have been reported in the literature. Technology advances achieved over the last three decades, including methods for generating larger phage display libraries, improved phage panning protocols, new cyclic peptide formats, and high-throughput sequencing, have enabled the generation of cyclic peptides with ever better binding affinities to more challenging targets. A relatively new cyclic peptide format developed using phage display involves bicyclic peptides. These molecules consist of two macrocyclic peptide rings cyclized through a chemical linker. Compared to monocyclic peptides of comparable molecular mass, bicyclic peptides are more constrained in their conformation. As a result, they can bind to their targets with a higher affinity and are more resistant to proteolytic degradation. Phage-encoded bicyclic peptides are generated by chemically cyclizing random peptide libraries on phage. Binders are identified by conventional phage panning and DNA sequencing. Next-generation sequencing and new sequence alignment tools have enabled the rapid identification of bicyclic peptides. Bicyclic peptide ligands were developed against a range of diverse target classes including enzymes, receptors, and cytokines. Most ligands bind with nanomolar affinities, with some reaching the picomolar range. To date, several bicyclic peptides have been positively evaluated in preclinical studies, and the first clinical tests are in sight. While bicyclic peptide phage display was developed with therapeutic applications in mind, these peptides are increasingly used as research tools for target evaluation or as basic research probes as well. Given the efficient development method, the ease of synthesis and handling, and the favorable binding and biophysical properties, bicyclic peptides are being developed against more and more targets, ever increasing their potential applications in research and medicine.


Flipping the script: The effects of opioid prescription monitoring on specialty-specific provider behavior.
Mandatory access Prescription Drug Monitoring Programs (MA-PDMPs) aim to curb the epidemic at a common point of initiation of use, the prescription. However, there is recent concern about whether opioid policies have been too restrictive and reduced appropriate access to patients with the most need for opioid pharmaceuticals. We assess MA-PDMP's effect on specialty-specific opioid prescribing behavior of Medicare providers. Our findings suggest that requiring providers to query a PDMP differentially affects opioid prescribing across provider specialties. We find a three to four percent decrease in prescribing for Primary Care and Internal Medicine providers. This result is driven by healthcare providers at the lower end of the prescribing distribution. There is also suggestive evidence of an increase in opioid use disorder treatment drugs prescribed by these same providers. We also find no evidence for the hypothesis that MA-PDMPs restrict prescribing by providers who treat patients with potentially high levels of pain, few drug substitutes, or urgency for pain treatment (e.g., Oncology/Palliative care). This result is not dependent on whether a state provides exemptions for these providers. Our results indicate that MA-PDMPs may help close provider-patient informational gaps while retaining a provider's ability to supply these drugs to patients with a need for opioids.


Policy, evidence and practice for post-birth care plans: a scoping review.
Postnatal care continually attracts less attention than other parts of the childbirth year. Many regions consistently report poor maternal satisfaction with care in the post-birth period. Despite policy recommending post-birth planning be part of maternity services there remains a paucity of empirical evidence and reported experience using post-birth care plans. There is a need to report on post-birth care plans, identify policy and guideline recommendations and gaps in the current empirical research, as well as experiences creating and using post-birth care plans. This scoping review accessed empirical literature and government and professional documents from 2005 to present day to build a picture of current understanding of policy imperatives and existent published empirical evidence. The review was informed by the Arksey and O'Malley approach employing five stages. The review revealed that post-birth care planning is promoted extensively in health policy and there is emergent evidence for its implementation. Yet there is a paucity of practice examples and only one evaluation in the UK. The review identified four overarching themes: 'Positioning of post-birth care planning in policy; 'Content and approach'; 'Personalised care and relational continuity'; Feasibility and acceptability in practice'. Empirical evidence supports post-birth care planning, but evidence is limited leaving many unanswered questions. Health care policy reflects evidence and recommends implementation of post-birth care plans, however, there remains a paucity of information in relation to post-birth care planning experience and implementation in practice. Women need consistent information and advice and value personalised care. Models of care that facilitate these needs are focused on relational continuity and lead to greater satisfaction. It remains unclear if a combination of post-birth care planning and continuity of carer interventions would improve post-birth outcomes and satisfaction. Gaps in research knowledge and practice experience are identified and implications for practice and further research suggested.


[From conduct disorder in childhood to psychopathy in adult life].
Mental health professionals seldom recognize psychopathy in their daily practice. Usually forensic psychiatrists and psychologists are involved because individuals with psychopathic personality are involved in serious criminal behavior and implicated with the law. Most of the times the profiles of children who evolve in adult psychopaths have components from other disorders, especially conduct disorder. The term psychopathy originates from the Greek words "psyche" (soul) and "pathos" (passion) and was used to identify initially every mental illness. Although in the bibliography the terms Antisocial Personality Disorder, Psychopathic Personality, Psychopathy and Sociopathy are used as synonyms, it has not been clarified if the Antisocial Personality Disorder and Psychopathic Personality constitute two different entities or if the latter constitutes the more serious and hard core subtype of the first. The prevalence of Psychopathic Personality in the general population is estimated as 1%, with the proportion of men: women to be 3:1. The adult male psychopaths are responsible for almost 50% of the serious criminal behavior. Diagnosis of Psychopathic Personality is completed with the use of specific psychometric tools: Psychopathy Checklist-Revised (PCL-R) and Psychopathy Checklist: Screening Version (PCL: SV). The most recognizable elements of psychopathy are the non-existence of conscience and their shallow emotional relations. They are individuals with persuasion, that use the suitable phraseology in order to approach, impress and charm their prey. Nuclear characteristic is the inability to feel guilt, remorse and the nonexistence of moral rules. They lose their temper easily and present aggressiveness without obvious or insignificant reason. They develop various antisocial behaviors that are repeated with success, the gravity of violent behavior tends to increase and they have problems with the law. Nevertheless, people with Psychopathic Personality at one point were children, without diagnosis of Psychopathic Personality, as such a diagnosis is not appropriate at early childhood or adolescence. Psychopathic or/and antisocial tendencies sometimes are recognized in children and early adolescent age. Such behaviors lead usually to the diagnosis of Conduct Disorder or Oppositional Defiant Disorder or Attention Deficit and Hyperactivity Disorder in early years of life and increase the possibility to have a diagnosis of Antisocial Personality Disorder and Psychopathic Personality as an adult. There are many studies on the underlying risk factors for Psychopathic Personality, focusing in genetic, neurobiological, developmental, environmental, social and other factors. There is no effective treatment for Psychopathic Personality in adult life. Children with a specific neurobiological profile or behavioral disturbances that increase the risk of developing a Psychopathic Personality in adult life, have better chances to respond in exceptionally individualized interventions, depending on the character of the child. The parents are educated to supervise their children, to overlook annoying behaviors and to encourage the positive ones. It appears that the punishment does not attribute, on the contrary it strengthens undesirable behaviors. Use of reward appears to have better results. Programs of early highly focused therapeutic interventions in vulnerable members of the population are our best hope for the reduction of fully blown psychopaths in the general adult population.


[Quantitative blood flow measurements with the c. w.-Doppler ultrasound procedure. An animal experiment study].
The qualification of the c.w.-ultrasound-doppler method for quantitative blood flow measurement was investigated in an animal experimental study in dogs. The simultaneous measurements by means of the electromagnetic flow measurement showed a correlation coefficient from 0.865 to 0.942 in dependence on the exposure angle to ultrasonic waves. The c.w.-ultrasound-doppler method appears suitable for quantitative blood flow measurements after these results. The exactness of the definition of the perpendicular as reference angle for deriving the exposure angle for ultrasonic waves has proved true.


The fluorescence properties of tiara like structural thiolated palladium clusters.
A series of tiara like structural Pdn(SR)2n (5 ≤n≤ 20) nanoclusters were synthesized by using a modified Brust-Schiffrin route and isolated via thin layer chromatography, and further measured using MALDI-MS. A new crystal structure of tiara like structural Pd6(SC2H4Ph)12 was determined by single-crystal X-ray crystallography. The atomic distance of PdPd increased and the Pd-S bond length decreased with the increase in the n value in the optimized structure of Pdn(SR)2n (5 ≤n≤ 10), which were optimized by density functional theory at the B3LYP level. All these 16 Pdn(SR)2n nanoclusters exhibit weak emission at 620 nm with single band excitation at around 268 nm. The origin of emission of this series of clusters could be illustrated by using a ligand to metal charge transfer model.


Testing the generalist-specialist dilemma: the role of pyrrolizidine alkaloids in resistance to invertebrate herbivores in Jacobaea species.
Plants produce a diversity of secondary metabolites (SMs) to protect them from generalist herbivores. On the other hand, specialist herbivores use SMs for host plant recognition, feeding and oviposition cues, and even sequester SMs for their own defense. Therefore, plants are assumed to face an evolutionary dilemma stemming from the contrasting effects of generalist and specialist herbivores on SMs. To test this hypothesis, bioassays were performed with F2 hybrids from Jacobaea species segregating for their pyrrolizidine alkaloids (PAs), using a specialist flea beetle (Longitarsus jacobaeae) and a generalist slug (Deroceras invadens). Our study demonstrated that while slug feeding damage was negatively correlated with the concentration of total PAs and that of senecionine-like PAs, flea beetle feeding damage was not affected by PAs. It was positively correlated though, with leaf fresh weight. The generalist slug was deterred by senecionine-like PAs but the specialist flea beetle was adapted to PAs in its host plant. Testing other herbivores in the same plant system, it was observed that the egg number of the specialist cinnabar moth was positively correlated with jacobine-like PAs, while the silver damage of generalist thrips was negatively correlated with senecionine- and jacobine-like PAs, and the pupae number of generalist leaf miner was negatively correlated with otosenine-like PAs. Therefore, while the specialist herbivores showed no correlation whatsoever with PA concentration, the generalist herbivores all showed a negative correlation with at least one type of PA. We concluded that the generalist herbivores were deterred by different structural groups of PAs while the specialist herbivores were attracted or adapted to PAs in its host plants.


Pleural liquid pressure.
The knowledge of pleural liquid pressure (Pliq) is essential for understanding the mechanical coupling between lung and chest wall and the liquid exchanges of the pleural space. In the last decade, research in this field contributed new ideas and stimulating controversies but also caused some confusion. These aspects, along with the older contributions, are considered in this review, which is divided into three sections. The topics of the first section are 1) measurements of Pliq with different techniques in various mammals and various regions of the pleural space, 2) comparison of Pliq with the pressure exerted by the lung recoil (Ppl), and 3) vertical gradient of Pliq and downward flow of pleural liquid. In the second section the mechanisms absorbing liquid from the pleural space are analyzed: 1) Starling forces of the visceral pleura, 2) lymphatic drainage through the stomata of the parietal pleura, and 3) active transport of solutes. The third section deals with 1) measurements of pleural liquid thickness with two approaches in the costal region of various mammals and 2) mechanisms preventing a complete removal of pleural liquid and, thus, ensuring the lubrication.


Evolutionary dynamics of the leaf phenological cycle in an oak metapopulation along an elevation gradient.
It has been predicted that environmental changes will radically alter the selective pressures on phenological traits. Long-lived species, such as trees, will be particularly affected, as they may need to undergo major adaptive change over only one or a few generations. The traits describing the annual life cycle of trees are generally highly evolvable, but nothing is known about the strength of their genetic correlations. Tight correlations can impose strong evolutionary constraints, potentially hampering the adaptation of multivariate phenological phenotypes. In this study, we investigated the evolutionary, genetic and environmental components of the timing of leaf unfolding and senescence within an oak metapopulation along an elevation gradient. Population divergence, estimated from in situ and common-garden data, was compared to expectations under neutral evolution, based on microsatellite markers. This approach made it possible (1) to evaluate the influence of genetic correlation on multivariate local adaptation to elevation and (2) to identify traits probably exposed to past selective pressures due to the colder climate at high elevation. The genetic correlation was positive but very weak, indicating that genetic constraints did not shape the local adaptation pattern for leaf phenology. Both spring and fall (leaf unfolding and senescence, respectively) phenology timings were involved in local adaptation, but leaf unfolding was probably the trait most exposed to climate change-induced selection. Our data indicated that genetic variation makes a much smaller contribution to adaptation than the considerable plastic variation displayed by a tree during its lifetime. The evolutionary potential of leaf phenology is, therefore, probably not the most critical aspect for short-term population survival in a changing climate.


[Pulmonary Chlamydia infections in children].
In the last decades chlamydial infection of the respiratory tract have been described in children. Chlamydia trachomatis, the most common identifiable cause of neonatal infections conjunctivitis is also a recognised cause of pneumonia in newborns and is responsible for about one third of sexually transmitted disease. Chlamydia psittaci is mainly pathogenic for birds and occasionally for human. More recently Chlamydia pneumoniae has been found associated with pulmonary abnormalities, nasopharynx and pulmonary oropharynx infections. Microbiologic diagnosis can be difficult. Several non culture methods are now available such as the direct fluorescent antibody test and enzyme immuno-assays. X ray chest show a reticulated and (or) nodular pattern. Treatment is mainly macrolide based with erythromycin.


The precedence effect.
In a reverberant environment, sounds reach the ears through several paths. Although the direct sound is followed by multiple reflections, which would be audible in isolation, the first-arriving wavefront dominates many aspects of perception. The "precedence effect" refers to a group of phenomena that are thought to be involved in resolving competition for perception and localization between a direct sound and a reflection. This article is divided into five major sections. First, it begins with a review of recent work on psychoacoustics, which divides the phenomena into measurements of fusion, localization dominance, and discrimination suppression. Second, buildup of precedence and breakdown of precedence are discussed. Third measurements in several animal species, developmental changes in humans, and animal studies are described. Fourth, recent physiological measurements that might be helpful in providing a fuller understanding of precedence effects are reviewed. Fifth, a number of psychophysical models are described which illustrate fundamentally different approaches and have distinct advantages and disadvantages. The purpose of this review is to provide a framework within which to describe the effects of precedence and to help in the integration of data from both psychophysical and physiological experiments. It is probably only through the combined efforts of these fields that a full theory of precedence will evolve and useful models will be developed.


ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1.
ATM has a central role in controlling the cellular responses to DNA damage. It and other phosphoinositide 3-kinase-related kinases (PIKKs) have giant helical HEAT repeat domains in their amino-terminal regions. The functions of these domains in PIKKs are not well understood. ATM activation in response to DNA damage appears to be regulated by the Mre11-Rad50-Nbs1 (MRN) complex, although the exact functional relationship between the MRN complex and ATM is uncertain. Here we show that two pairs of HEAT repeats in fission yeast ATM (Tel1) interact with an FXF/Y motif at the C terminus of Nbs1. This interaction resembles nucleoporin FXFG motif binding to HEAT repeats in importin-beta. Budding yeast Nbs1 (Xrs2) appears to have two FXF/Y motifs that interact with Tel1 (ATM). In Xenopus egg extracts, the C terminus of Nbs1 recruits ATM to damaged DNA, where it is subsequently autophosphorylated. This interaction is essential for ATM activation. A C-terminal 147-amino-acid fragment of Nbs1 that has the Mre11- and ATM-binding domains can restore ATM activation in an Nbs1-depleted extract. We conclude that an interaction between specific HEAT repeats in ATM and the C-terminal FXF/Y domain of Nbs1 is essential for ATM activation. We propose that conformational changes in the MRN complex that occur upon binding to damaged DNA are transmitted through the FXF/Y-HEAT interface to activate ATM. This interaction also retains active ATM at sites of DNA damage.


Manual therapy with steroid injections in low-back pain. Improvement of quality of life in a controlled trial with four months' follow-up.
To compare prospectively the effect of manual treatment such as manipulation, specific mobilization, muscle stretching, auto-traction, and cortisone injections with standardized conventional but optimized activating treatment by primary health care teams. Prospective controlled multicentre trial with four months' follow-up. Kopparberg County, Sweden. Six primary health care or occupational health care centres, representing a catchment area of 56000 residents participated. 101 outpatients with acute or subacute low-back pain were, during the period February 1988 to April 1989, randomly allocated to one of two treatment groups. Quality of life was assessed at baseline and at four months by means of visual analogue scales (VAS). The occurrence of 27 different symptoms of a psychosomatic character was surveyed initially and at four months by questions answered by "yes" or "no" in a questionnaire. There were significant differences concerning quality of life and presence of general symptoms in favour of the group receiving manual treatment with steroid injections. Manual treatment with steroid injections was superior to conventional treatment in minimizing mental and somatic symptoms and increasing quality of life, in parallel with other measures of improvement.