Market model fails: linkages between health policy and performance outcomes in western industrial countries.
In recent years, political discourse has sung the merits of the market model as a panacea for escalating health expenditures. While selected market mechanisms may be useful to control spending, there are reasons to question full-scale use of this model to shape health policy. Using the experiences of seven western industrialized countries, the argument developed in this article is that the market model's own assumptions cannot be upheld because ethical, sociological, and political factors underlying health policy make its application impossible. Specifically, a competitive equilibrium does not exist; sale of health care goods and services do not conform to the rules of marketability; and non-increasing returns are not demonstrable. A discussion of health outcome performance and spending data points out the need to attend to equity distributional concerns, state commitment to the health care access, and the extent and breadth of input into health care decision-making as other factors that should be considered.


Photoluminescent polyphosphazene nanoparticles for in situ simvastatin delivery for improving the osteocompatibility of BMSCs.
Nanomedicines have found promising applications in regulating the biological behaviors of cells because of the cell endocytosis effect. To enhance the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs), which is one of the key issues in relation to bone regeneration, a biodegradable simvastatin-bearing polyphosphazene prodrug was synthesized and made into nanoparticles (NPs). At the same time, photoluminescent tryptophan ethyl ester and hydrolyzable glycine ethyl ester were introduced as co-substituted side groups onto the polyphosphazene backbone. The resultant polymer, poly(simvastatin-co-ethyl tryptophanato-co-ethyl glycinato)phosphazene (PTGP-SIM), displayed the expected features of photoluminescence, degradability and sustained SIM release. Endocytosis of PTGP-SIM NPs by BMSCs and the location of internalized NPs, were visualized via the inherent photoluminescence features of PTGP-SIM. Thus, simvastatin was released inside the cells directly along with polymer degradation and could play a role in promoting osteogenic differentiation efficiently at quite a low local concentration. From the results, the present study suggested a very promising biomaterial for use as a flexible and functional carrier for bioactive components, which could find wide applications in relation to tissue regeneration.


Risk factors for cerebrovascular events: end-diastolic flow velocity.
There are very few studies analysing blood flow velocity parameters of common carotid arteries (CCA), obtained with color Doppler examination as a predictor in cerebrovascular events (CVE). In everyday clinical practice there are number of patients (pts) without carotid stenosis or occlusion but with decreased blood flow velocities. We performed this study to compare data of velocity parameters with type of cerebrovascular events (CVE) and multiple risk factors in patients without stenotic or occlusive extracranial disease. We included total of 127 consecutive patients who experienced various subtypes of cerebrovascular events, 68 females, 59 males, mean age 70.2 +/- SD 12.4 years, out of them 48 pts. had transients ischemic attacs (TIAs), 31 pts. had recurrent TIAs (recTIAs), 32 pts. developed ischemic stroke (IS), and 16 recurrent IS (recIS). All patients were without hemodynamically significant carotid stenosis or occlusion. As a control group we took 50 patients with comparable mean age and gender distribution, all without cerebrovascular events, but with at least 1 multiple risk factor. We included the following clinical variables: age, gender, hypertension, tobacco smoking, hyperlipidemia, obesity, diabetes mellitus. Velocity parameters were: peak-systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility index (PI), resistive index (RI). Examination was performed on distal portion of CCA, and we took the mean of both CCA. Hemodynamic parameters in CVE pts were: PSV 83.5 cm/sec, EDV 19.5 cm/sec, PI 1.54, and RI 0.77, and in Controls values were: PSV 87.5 cm/sec, EDV 28.5 cm/sec, PI 1.42, RI 0.67, respectively. No sign. diff. in PSV and PI were found between CVE (n=127) and Controls (n=50), p = 0.2, while difference in EDV was significant, p < 0.01. We found significance for the following variables: age, tobacco smoking, hypertension, hyperlipidemia and obesity. The best single predictors for CVE were: age (70.1%, p < 0.01), tobacco smoking (63%, p < 0.01, hypertension (52.8%, p < 0.01) and obesity (51.2%, p < 0.01). and among hemodynamic parameters, end-diastolic velocity less than 18 cm/sec (p < 0.05). Decreased EDV (below 18 cm/sec) revealed a significant association with CVE. (a) we found significantly lower EDV in pts with IS and recIS, (b) EDV below 18 cm/sec was the best single predictor of IS, and recIS, (c) in our CVE pts--age, tobacco smoking, hypertension, obesity, were the best single predictors for CVE.


Light scattering by a reentrant fractal surface.
Recently, rigorous numerical techniques for treating light scattering problems with one-dimensional rough surfaces have been developed. In their usual formulation, these techniques are based on the solution of two coupled integral equations and are applicable only to surfaces whose profiles can be described by single-valued functions of a coordinate in the mean plane of the surface. In this paper we extend the applicability of the integral equation method to surfaces with multivalued profiles. A procedure for finding a parametric description of a given profile is described, and the scattering equations are established within the framework of this formalism. We then present some results of light scattering from a sequence of one-dimensional flat surfaces with defects in the form of triadic Koch curves. Beyond a certain order of the prefractal, the scattering patterns become stationary (within the numerical accuracy of the method). It can then be argued that the results obtained correspond to a surface with a fractal structure. These constitute, to our knowledge, the first rigorous calculations of light scattering from a reentrant fractal surface.


Self-regulatory depletion increases emotional reactivity in the amygdala.
The ability to self-regulate can become impaired when people are required to engage in successive acts of effortful self-control, even when self-control occurs in different domains. Here, we used functional neuroimaging to test whether engaging in effortful inhibition in the cognitive domain would lead to putative dysfunction in the emotional domain. Forty-eight participants viewed images of emotional scenes during functional magnetic resonance imaging in two sessions that were separated by a challenging attention control task that required effortful inhibition (depletion group) or not (control group). Compared to the control group, depleted participants showed increased activity in the left amygdala to negative but not to positive or neutral scenes. Moreover, whereas the control group showed reduced amygdala activity to all scene types (i.e. habituation), the depletion group showed increased amygdala activity relative to their pre-depletion baseline; however this was only significant for negative scenes. Finally, depleted participants showed reduced functional connectivity between the left amygdala and ventromedial prefrontal cortex during negative scene processing. These findings demonstrate that consuming self-regulatory resources leads to an exaggerated neural response to emotional material that appears specific to negatively valenced stimuli and further suggests a failure to recruit top-down prefrontal regions involved in emotion regulation.


[Nucleolar organizer as a marker of malignancy grade and prognosis of non-Hodgkin's malignant lymphoma].
There were 51 cases of non-Hodgkin's malignant lymphoma (NHL) and 9 cases of reactive follicular hyperplasia among 60 cases of lymphoproliferative conditions. According to the Kiel classification, lymphomas of a low grade of malignancy (17 cases) and lymphomas of a high grade of malignancy (34 cases) were distinguished among NML. Significantly higher activity of the nucleolar organizers (NO) was observed in lymphomas of a high malignancy grade, particularly in lymphomas formed of cells of early differentiation stages, and enhancement of NO activity with development of lymphoma aggression. "Anomalies" of NO activity expression reflecting clinical lymphoma presentation were noted among NML of various malignancy grade. NML with a high NO activity are described as having less favourable prognosis compared to lymphomas with low NO activity. No significant difference in NO activity was found between reactive follicular hyperplasia and follicular centroblast-centrocytic lymphoma. Thus, NO activity can be considered as an additional diagnostic marker of NML grade of malignancy and prognosis.


Factors associated with dizygotic twinning after IVF treatment with double embryo transfer.
Dizygotic twin pregnancies after IVF treatment are the result of multiple embryos transferred into the uterine cavity, followed by successful double implantation. Factors that increase the chance of multiple implantation after IVF are relatively unknown. The present study aimed to investigate whether features of body composition, such as maternal height, weight and body mass index (BMI) are associated with an increased chance of dizygotic twinning after IVF with double embryo transfer (DET). This study was conducted using data from a large Dutch nationwide cohort that comprised 19 861 women who had IVF or ICSI treatment between 1983 and 1995 (OMEGA study). First 'fresh' IVF and ICSI cycles with DET resulting in a delivery of a singleton or twin (living as well as stillborn) were selected. A multivariable logistic regression analysis was performed, with the delivery of a singleton or twin as the dependent variable and height, weight, BMI, maternal age, number of retrieved oocytes, use of alcohol, smoking, highest level of education and parity as independent variables. Of the 6598 women who completed their first IVF or ICSI cycle, 2375 had DET, resulting in 496 deliveries of 371 singletons and 125 twins. Multivariable regression analysis revealed that tall women (>1.74 cm) and women with a high number of retrieved oocytes (>8) had an increased chance of dizygotic twinning [OR: 1.8 (95% CI: 1.0-3.4) and OR: 2.2 (95% CI: 1.3-3.8), respectively]. Our data demonstrate that tall stature and increased number of retrieved oocytes independently increase the chance of dizygotic twinning after IVF with DET.


Vascular access choice in incident hemodialysis patients: a decision analysis.
Hemodialysis vascular access recommendations promote arteriovenous (AV) fistulas first; however, it may not be the best approach for all hemodialysis patients, because likelihood of successful fistula placement, procedure-related and subsequent costs, and patient survival modify the optimal access choice. We performed a decision analysis evaluating AV fistula, AV graft, and central venous catheter (CVC) strategies for patients initiating hemodialysis with a CVC, a scenario occurring in over 70% of United States dialysis patients. A decision tree model was constructed to reflect progression from hemodialysis initiation. Patients were classified into one of three vascular access choices: maintain CVC, attempt fistula, or attempt graft. We explicitly modeled probabilities of primary and secondary patency for each access type, with success modified by age, sex, and diabetes. Access-specific mortality was incorporated using preexisting cohort data, including terms for age, sex, and diabetes. Costs were ascertained from the 2010 USRDS report and Medicare for procedure costs. An AV fistula attempt strategy was found to be superior to AV grafts and CVCs in regard to mortality and cost for the majority of patient characteristic combinations, especially younger men without diabetes. Women with diabetes and elderly men with diabetes had similar outcomes, regardless of access type. Overall, the advantages of an AV fistula attempt strategy lessened considerably among older patients, particularly women with diabetes, reflecting the effect of lower AV fistula success rates and lower life expectancy. These results suggest that vascular access-related outcomes may be optimized by considering individual patient characteristics.


A hedonic story has a transmission advantage over a eudaimonic story.
We examined (a) whether a hedonic story (story full of hedonic activities) is better remembered and transmitted compared with a eudaimonic story (story full of eudaimonic activities), and (b) whether the hedonic story's memory and transmission advantage varies depending on contextual cues, as indexed by the day of the week. Study 1 showed that college students are surrounded with more party announcements on Wednesdays through Fridays than on Mondays and Tuesdays. Study 2 showed that the hedonic story and the eudaimonic story we created were equally interesting, rich in plot, surprising, and arousing, yet the hedonic story was rated as more disturbing, real, and newsworthy. In Studies 3 and 4, we used a serial reproduction method and found that the hedonic story was better recalled and transmitted to others than was the eudaimonic story, and that this effect was particularly strong when participants completed the study later in the week. Our findings suggest that a hedonic story is more communicable than a eudaimonic story, particularly when supported by environmental cues.


Household dampness and microbial exposure related to allergy and respiratory health in Danish adults.
Background: Indoor dampness has consistently been associated with respiratory symptoms and exacerbations. The causal mechanisms may involve increased microbial exposures. However, the evidence regarding the influence of indoor microbial exposures under damp- and non-damp conditions on the risk of asthma and allergy has been inconclusive. Objective: The aim of this study was to investigate the association between dampness and microbial exposure with allergy and respiratory health in Danish adults using a cross-sectional design. Methods: From 1,866 participants of the Health2006 cohort, we selected three non-overlapping groups: 196 at random, 107 with confirmed atopy, and 99 without atopy. Bedroom dust was sampled using electrostatic dust fall collectors and analysed for endotoxin, β-(1,3)-D-glucan, 19 microbial species or groups, and total fungal load. Household moisture-related problems and asthma were self-reported by questionnaire. Atopy was determined by skin-prick-testing and lung function was measured by spirometry. Results: Household moisture damage was positively associated with asthma outcomes, although this was statistically significant only in atopics for self-reported asthma (odds ratio (OR) 3.52; 95%CI 1.01-12.7). Mould odor was positively associated with wheezing (OR 6.05; 95%CI 1.19-30.7) in atopics. Inconsistent associations were found for individual microbial exposures and health outcomes. Inverse associations were observed between microbial diversity and rhinitis in the random sample and both doctor-diagnosed and self-reported asthma in non-atopics. Conclusions: In conclusion, our findings suggest that household moisture damage may increase the risk of asthma and wheeze with mould odor in atopics. In addition, asthma and allergy may be affected by the indoor microbial composition in urban domestic environments. Further studies are needed to identify and understand the causal agents and underlying mechanisms behind the potential effects of environmental microbial exposure on human health.


Comparative trial of influenza vaccines. I. Immunogenicity of whole virus and split product vaccines in man.
Groups of about 100 persons aged 6 to 88 years were given 1 of 6 commercially prepared whole virus or split-product bivalent (A/England-B/Mass) influenza vaccines and 6 weeks later were given 1 of 5 monovalent (B/Hong Kong) vaccines. Hemagglutination-inhibiting (HI) antibody titers in serum specimens taken 6 and 12 weeks after inoculation were compared to those obtained before immunization. Overall antibody responses in all groups were adequate, yielding HI titers that are associated with relatively good levels of protection from infection. No differences were noted among the vaccines in their ability to boost pre-existing antibody. The tributyl phosphate (TBP) split-product vaccine, however, induced significantly lower homologous seroconversion and geometric mean antibody titers (GMT) to A/England and heterologous antibody titers to A/Aichi in persons without pre-existing antibody than did equivalent whole virus vaccines. Both the TBP and the ether-treated monovalent B/Hong Kong vaccines also induced lower heterologous GMT's to B/Mass in initially seronegative individuals. These data agree with previous observations that the primary response to influenza and other viral vaccines prepared from disrupted virions results in lower levels of antibody than does that to equivalent whole virus preparations. Studies are underway to determine whether the lesser immune response induced by these vaccines in seronegative persons is the result of smaller amounts of antigen in such preparations or because the antigen may be processed less efficiently by humoral or cellular immune mechanisms.


An ultrastructural and a cytochemical study of candidal invasion of reconstituted human oral epithelium.
Opportunistic yeast, Candida albicans causes superficial and systemic mycoses in compromised patients. Adhesion to host tissues, morphogenesis and extracellular phospholipases (PL) are thought to contribute to its virulence. The nature of numerous host-parasite interactions at the invasive phase of oral candidiasis is not fully understood. Hence in this study, we explore the ultrastructural features of oral candidiasis using a tissue culture model based on reconstituted human oral epithelium (RHOE). Reconstituted human oral epithelium (Skinethic Laboratory, Nice, France) was inoculated with C. albicans SC5314 and incubated up to 48 h. The infected tissue was harvested at 12, 24 and 48 h and examined using light, scanning (SEM) and transmission electron microscopy (TEM). Localized activity of PLs of C. albicans during tissue invasion was also examined using a cytochemical method. Over a period of 48 h C. albicans invaded the RHOE, and histological examination revealed characteristic hallmarks of pathological tissue invasion. Hyphal penetration into the superficial epithelium, particularly at cell junctions, together with features of cellular internalization of yeasts was noted. Phospholipase activity was visible at the tips of hyphae and initial sites of bud formation. Further, SEM studies revealed cavitations on the surface epithelial cells particularly pronounced at the sites of hyphal invasion. Hyphal invasion was seen both at cell surfaces and intercellular cell junctions of the epithelium, the latter resembling thigmotropic behaviour. Our findings confirm that multiple cellular interactions such as internalization, thigmotropism and extracellular PLs contribute to invasive candidiasis. The RHOE model, described here, appears to be a satisfactory model for the investigation of ultrastructural and histochemical features of invasive candidiasis in humans.


Marine natural products with P-glycoprotein inhibitor properties.
P-glycoprotein (P-gp) is a protein belonging to the ATP-binding cassette (ABC) transporters superfamily that has clinical relevance due to its role in drug metabolism and multi-drug resistance (MDR) in several human pathogens and diseases. P-gp is a major cause of drug resistance in cancer, parasitic diseases, epilepsy and other disorders. This review article aims to summarize the research findings on the marine natural products with P-glycoprotein inhibitor properties. Natural compounds that modulate P-gp offer great possibilities for semi-synthetic modification to create new drugs and are valuable research tools to understand the function of complex ABC transporters.


Percutaneous transhepatic pancreatic vein catheterization in localization of insulinoma.
Localization of pancreatic insulinomas can present considerable operative difficulty. Blind pancreatic resections are likely to miss the tumor and are associated with the concomitant morbidity and mortality of repeated explorations and resections. While arteriography is often very helpful in locating the tumor preoperatively, there are some patients in whom a tumor blush cannot be seen. The use of percutaneous transhepatic pancreatic vein sampling for radioimmune insulin assay is reviewed, with particular emphasis on its usefulness in locating a small insulinoma. The technique is readily adaptable to other endocrine-secreting tumors of the pancreas.


[Auto-dermal monophilic plastic surgery of ventral hernia].
To improve the results of surgical management of postoperative ventral hernias, the authors applied their suggested variant of autodermic plasty of the hernial openings. The method consists in using for the plasty a band or graft of autologous skin armored with a monophilic thread. To reduce lymphorrhea the autodermic graft was covered with a hernial sac on a pedicle. The method was applied in 93 patients with good late-term results. The number of postoperative complications reduced to 3.5% and mortality to 1%, recurrences were not encountered.


Ear for recovery: protocol for a prospective study on parent-child communication and psychological recovery after paediatric injury.
One in six children who have been admitted to hospital with an injury develop persistent stress symptoms that put their development at risk. Parents play a crucial role in children's psychological recovery, however, it is unknown how specific parenting behaviours can help or hinder. We aim to describe the nature and quantity of parent-child communication after a child has been injured, and to examine how these interactions are related to children's psychological recovery. We are conducting a prospective observational study among children aged 3-16 years, who have been admitted to a tertiary children's hospital with a serious injury. Data collection involves a naturalistic observation of spontaneous, everyday parent-child communication at home, shortly after discharge, and an assessment of children's psychological recovery at 6 weeks and 3 months post-injury. Main analyses comprise descriptive statistics, cluster analysis and analyses of variance. This study has been approved by the Human Research Ethics Committee of the Royal Children's Hospital Melbourne (33103) and Monash University Human Research Ethics Committee (CF13/2515-2013001322). We aim to disseminate the findings through international peer-reviewed journals, international conferences and social media. Participants will be sent a summary of the overall study findings.


Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the Lateral Prefrontal Cortex.
There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, by comparing event-related potentials (ERPs) to attended and ignored sounds with ERPs to these same sounds when attention was equally distributed to all sounds. In control subjects, we observed 2 late frontally distributed ERP components: a transient facilitatory component occurring from 150 to 250 ms after sound onset; and an inhibitory component onsetting at 250 ms. Only the facilitatory component was affected in patients with LPFC damage: this component was absent when attending to sounds delivered in the ear contralateral to the lesion, with the most prominent decreases observed over the damaged brain regions. These findings have 2 important implications: (i) they provide evidence for functionally distinct facilitatory and inhibitory mechanisms supporting late auditory selective attention; (ii) they show that the LPFC is involved in the control of the facilitatory mechanisms of auditory attention.


Estimation of parasitic infection dynamics when detectability is imperfect.
The simultaneous estimation of infection rate, cure rate and detectability of parasitic infections is considered. A new method for this estimation based on a simple statistical model assuming constant transition rates between parasite states is proposed. Repeated observations on the infection status of the same individuals is required for this method. A maximum likelihood approach is used for parameter estimation and the calculation of standard errors of the estimates. The method is illustrated by a longitudinal study of the presence of Giardia lamblia infection in Kenyan children.


Adherence of forensic odontologists to the ABFO guidelines for victim evidence collection.
Certifying boards for different professions have the duty to help establish standards and guidelines for methodologies routinely performed within the discipline. For forensic dentists, this responsibility is placed upon the American Board of Forensic Odontology (ABFO). The purpose of this study was to examine whether board certified and noncertified forensic odontologists adhere to the ABFO Guidelines outlined in the collection of victim bitemark evidence. A questionnaire was developed to assess the compliance and attitudes towards the typical evidence collected, the photographic documentation, and the handling of the bite site injury. The results indicate the majority of the respondents in both representative groups routinely follow the guidelines set forth by the ABFO. The lack of personally photographing the bite injury on a consistent basis is an area of concern for all examiners. The photographic evidence is an instrumental part of the investigation and often cannot be utilized due to improper procedures being followed. The film type utilized, bite site impression techniques, and excision of any tissue samples remain an individual choice and vary significantly among each forensic odontologist.


[Prevalence of headache in an emergency department in Colombia].
To determine the headache prevalence like main reason of consultation, primary and secondary headaches and alarm signs in Emergency Service. It was carried out a serial sampling in the Emergency Service of the Clinica Los Comuneros in Bucaramanga, since the 6th to 15th December of 2002, including all patients older than 18 years old, were excluded pregnant women and patient with mental retardation, psychotic disorders or dementia. 100 patients out of 1,054 consulted for headache (9.49%); 25% corresponded to primary and 75% to secondary headaches. Thirty four patients had fever, headache began after the 50 years in 7, signs and focal symptoms in 4, cancer antecedent in 4, mental changes in 3, antecedent of trauma cranial in 2, thunderclap headache, headache persistently unilateral, antecedent of AIDS and signs meningeal in a patient respectively. The headache is a reason of frequent consultation in the Service of Emergency; the proportion of secondary headaches is high.


Clinical and electrophysiological characterization of myokymia and neuromyotonia in Jack Russell Terriers.
Generalized myokymia and neuromyotonia (M/NM) in Jack Russell Terriers (JRTs) is related to peripheral nerve hyperexcitability syndrome in humans, a symptom complex resulting from diverse etiologies. Clinical and electrodiagnostic evaluation is used to narrow the list of possible etiological diagnoses in JRTs with M/NM. Nine healthy JRTs and 8 affected JRTs. A prospective study was conducted comparing clinical and electrophysiological characteristics in 8 JRTs affected by M/NM with 9 healthy JRT controls. All affected dogs except 1 had clinical signs typical of hereditary ataxia (HA). In 6 dogs, neuromyotonic discharges were recorded during electromyogram. Motor nerve conduction studies showed an axonal neuropathy in only 1 affected dog. Compared with controls, brainstem auditory-evoked potentials (BAEP) showed prolonged latencies (P<.05) accompanied by the disappearance of wave components in 3 dogs. Onset latencies of tibial sensory-evoked potentials (SEP) recorded at the lumbar intervertebral level were delayed in the affected group (P<.001). The BAEP and SEP results of the only neuromyotonic dog without ataxia were normal. The BAEP and spinal SEP abnormalities observed in JRTs with M/NM were associated with the presence of HA. Therefore, these electrophysiological findings presumably arise from the neurodegenerative changes characterizing HA and do not directly elucidate the pathogenesis of M/NM. An underlying neuronal ion channel dysfunction is thought to be the cause of M/NM in JRTs.


A Prospective, Open-Label Study Evaluating Adjunctive Calcipotriene 0.005%/Betamethasone Dipropionate 0.064% Foam in Psoriasis Patients With Inadequate Response to Biologic Therapy.
To assess the effectiveness and safety of combining calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam with biologic therapies for patients with plaque psoriasis who have not obtained an adequate response with biologic therapy. This was a prospective, open-label, single-arm study of patients with chronic plaque-type psoriasis (body surface area [BSA] ≤5%) who were being treated with biologic agents for ≥24 weeks. All patients received once-daily Cal/BD foam for 4 weeks, followed by twice-weekly use on consecutive days for 12 weeks (maintenance regimen). The end points were assessed at weeks 4 and 16, and included the Physician's Global Assessment (PGA), BSA, PGA×BSA, Dermatology Life Quality Index (DLQI), and Treatment Satisfaction Questionnaire for Medication (TSQM)-9. Safety evaluations included assessments of local skin reactions and adverse events (AEs). Enrolled were 25 patients (18 men and 7 women; mean age, 53 ± 11 years). Patients had significant disease activity despite being on stable biologic therapy (median values: BSA, 3%; PGA, 3; PGA×BSA, 8). At weeks 4 and 16 versus baseline, adjunctive therapy with Cal/BD foam significantly improved PGA score (1 vs 1 vs 3; P less than .01), BSA involvement (1% vs 1% vs 3%; P less than .01), and PGA×BSA measure (1 vs 1 vs 8; P less than .01). Most patients achieved treat-to-target criteria for BSA ≤1% and PGA ≤1 at week 4 (both 76%) and week 16 (both 68%) versus 12% and 4%, respectively, at baseline. Quality of life was improved at both weeks 4 and 16, with high treatment satisfaction. Overall, adjunctive Cal/BD foam was safe and well-tolerated, with no serious AEs. Adjunctive therapy with Cal/BD foam was associated with an improvement of every measure of disease activity in patients with inadequate response to biologics, an effect that was maintained throughout the study. The majority of patients achieved treat-to-target goals. J Drugs Dermatol. 2018;17(8):845-850.


The identification of specific Rhesus-polypeptide-blood-group-ABH-active-glycoprotein complexes in the human red-cell membrane.
1. RhD,c and E immune complexes isolated from 3H- and 125I-surface-radiolabelled and unlabelled intact human red cells were analysed by SDS/polyacrylamide-gel electrophoresis. 2. Apparent Mr values of 31,900 for RhD polypeptide and 33,100 for Rhc,E polypeptide were obtained under both reducing and non-reducing conditions. Glycosylation of RhD,c and E polypeptides was not detected. 3. RhD,c and E immune complexes also contain a glycoprotein component. RhD glycoprotein (apparent Mr 45,000-100,000) is distinct from Rhc,E glycoprotein(s) (apparent Mr 35,000-65,000). Rh (Rhesus) glycoprotein carbohydrate moieties are susceptible to endo-beta-galactosidase digestion and carry blood-group-ABH determinants. This suggests the presence of polylactosaminoglycan-type structures. 4. Rh glycoproteins are not present in Rh immune complexes as a result of non-specific adsorption of membrane glycoproteins during the membrane-solubilization phase of immune-complex isolation because RhD immune complexes isolated from a 1:1 (v/v) mixture of Acde/cde and OcDE/cDE red cells do not contain blood-group-A-active glycoprotein. 5. Blood-group-A immune complexes isolated from group-A red cells of the appropriate Rh phenotypes contain the 31,900- and 33,100-apparent-Mr Rh polypeptides. 6. It was concluded from the above evidence that non-covalent Rh-glycoprotein-Rh-polypeptide complexes exist in the native red-cell membrane. 7. The 31,900- and 33,100-apparent-Mr Rh polypeptides are absent from blood-group-A immune complexes isolated from regulator type Rhnull cells (donor A.L.), but are replaced by a 33,800-apparent-Mr Rhnull-specific polypeptide (Rhnull polypeptide). It is suggested that Rhnull polypeptide is an aberrant product of the Rh gene complex.


Trauma-induced aneurysmal bone cysts in two psittacine species (Cacatua alba and Nymphicus hollandicus).
An umbrella cockatoo (Cacatua alba) and two cockatiels (Nymphicus hollandicus) were presented with rapidly enlarging masses of the head or wing joints. Historic trauma to these areas was confirmed in two cases. All birds were >2 yr of age, and two were female. Cytologic examination of fluid aspirated from masses in two cases was described as serosanguineous cytologically but failed to reveal inflammation, neoplasia, or microorganisms. Radiographic evaluation of these masses included proliferation and lysis of bone, suggestive of a neoplastic process. Histopathologic examination of surgically excised tissues revealed proliferative new bone and an absence of neoplastic tissue in all cases, consistent with aneurysmal bone cyst formation. Despite the guarded prognosis reported for other companion animals, these case results suggest a good prognosis for aneurysmal bone cyst in psittaciformes. Complete surgical excision and histopathologic examination is recommended for definitive diagnoses of aneurysmal bone cyst. Postoperative bandaging and rational antibiotic use are indicated to prevent excessive motion and secondary infection of affected sites, respectively.


Effect of norgestomet treatment after insemination on the calving rate of postpartum suckled beef cows.
Two experiments were conducted on postpartum suckled beef cows synchronized with Syncro-Mate B and artificially inseminated approximately 48 h after implant removal. In Exp. 1, cows (> or = 42 d postpartum at the timed AI) were randomly assigned to treated (n = 101) and control (n = 85) groups on d 12 after the timed AI. Treated cows received norgestomet/silicone implants that were left in situ for 9 d. Norgestomet treatment had no effect (P > .25) on the calving rates from the initial timed AI or from the return estrus. Nonpregnant norgestomet-treated cows returned to estrus in a more (P < .05) synchronized manner than the nonpregnant control cows. In Exp. 2, early postpartum cows (< 42 d postpartum at the first AI; n = 30) were included and all 118 cows (88 cows were > or = 42 d postpartum) received norgestomet/silicone implants as in Exp. 1. Of the 30 early postpartum cows, eight (19 to 41 d postpartum at the time of the first AI; mean = 29.3 d) calved to the first AI and nine calved to the second synchronized estrus. The calving dates at the next calving season for these 17 cows (57% of the cows in this group) was advanced an average of 46 d (319-d calving interval). The calving rates for the two timed insemination periods were similar (P > .25) for early and later (> or = 42 d postpartum) postpartum cows. Treatment with norgestomet implants on d 12 through 21 had no detrimental effects on established or subsequent pregnancy, synchronized the return estrus of nonpregnant cows, and was efficacious in establishing pregnancy early postpartum.


Celecoxib acts in a cyclooxygenase-2-independent manner and in synergy with emodin to suppress rat cholangiocarcinoma growth in vitro through a mechanism involving enhanced Akt inactivation and increased activation of caspases-9 and -3.
Emodin, a tyrosine kinase inhibitor, effectively blocked tyrosine phosphorylation of p185(neu) overexpressed in cultured rat C611B cholangiocarcinoma (ChC) cells and in neu-transformed WB-F344 rat-liver epithelial stem-like cells (WBneu cells). Celecoxib, a cyclooxygenase-2 inhibitor, markedly decreased prostaglandin (PG) levels overproduced by these respective neoplastically transformed liver cell types but was without effect in inhibiting PG production by untransformed WB-F344 cells that do not express detectable cyclooxygenase-2 protein. Notably, in combination, emodin (30 micro M) and celecoxib (35 micro M) acted synergistically to significantly suppress anchorage-dependent and -independent growth of C611B ChC cells and of WBneu cells over treatments with either agent alone. This prominent suppression of cell growth correlated with significant increases in the activation of caspases-9 and -3 and induction of apoptosis in the combination-treated cells, which was associated with an enhanced suppression of Akt activation. Here it is important to note that the concentration of celecoxib needed to suppress growth and induce apoptosis in the C611B and WBneu cells was markedly higher than that needed to effectively inhibit PG production by these malignant cell types. Thus, our data indicate that celecoxib is acting independently of its ability to inhibit cyclooxygenase-2 activity in suppressing growth of C611B and WBneu cells in vitro. Furthermore, our findings strongly suggest that increased inhibition of the antiapoptotic kinase Akt activation produced by the emodin/celecoxib combination treatment plays a key role in the mechanism by which this drug combination acts to enhance cell growth suppression and apoptosis in cultured C611B ChC cells and WBneu cells.


Infarct-related artery occlusion, tissue markers of ischaemia, and increased apoptosis in the peri-infarct viable myocardium.
Unfavourable cardiac remodelling often complicates acute myocardial infarction (AMI) as a result of increased cardiomyocyte apoptosis. It is currently unclear whether ongoing or recurrent ischaemia is an independent determinant for increased apoptosis in peri-infarct viable myocardium. In order to assess the link between infarct-related artery (IRA) occlusion, ischaemia, and apoptosis, 30 subjects dying 7-120 days after AMI (16 with IRA occlusion and 14 with patent IRA) and five control subjects were selected at autopsy. Cardiomyocytes were defined as apoptotic if co-expressing TUNEL and activated caspase-3. Expression of both hypoxia-inducible factor-1 and cyclo-oxygenase-2 was assessed in the peri-infarct myocardium and considered as tissue markers of ischaemia. Evidence of ischaemia was significantly more frequent in cases with IRA occlusion (53%) than in cases with patent IRA (15%) or control hearts (0%, P=0.026). The finding of IRA occlusion and markers of ischaemia identified cases with higher apoptotic rates (ARs) in the peri-infarct viable myocardium [12.2% (8.2-14.0), P<0.001 vs. others], whereas IRA occlusion without ischaemia was associated with lower AR, not significantly different from patent IRA [3.0% (1.0-7.9) vs. 2.2% (1.0-5.8), respectively, P=0.42] Ischaemia in the peri-infarct viable myocardium is present in over 50% of subjects dying late after AMI with IRA occlusion, and it is associated with increased apoptosis. Relief of ischaemia after AMI may prove of benefit in preventing apoptosis and its consequences.


Lower Limb Ground Reaction Force and Center of Pressure Asymmetry During Bodyweight Squats.
Performance asymmetries between the lower limbs have been reported across a variety of variables and for numerous motor tasks including double leg squats. Additionally, the degree of symmetry is often used as a recovery metric during rehabilitation programs. The purpose of this investigation was to examine leg asymmetry during a bodyweight double leg squat task and assess the effects of squat speed in a physically active population. Cross-over Study Design. Eighteen healthy individuals completed two sets of 20 squats at two tempos (preferred tempo and 60 bpm) while ground reaction force and center of pressure data were recorded using dual force plates. Peak vertical ground reaction force, force impulse, and center of pressure (COP) standard deviation in the anterior-posterior (AP) and mediolateral (ML) direction were calculated and analyzed to identify any differences between legs, tempo, and as a function of repetitions. Significance was set at ρ ≤ .05. The subjects exhibited greater ground reaction forces during the self-paced tempo compared to the metronome-paced tempo (F 1,79 = 14.48, p < .001) with the preferred leg generating larger values than the non-preferred leg during the self-paced condition. There was also a significant tempo x leg interaction for force impulse (F 1,79 = 5.927, p = 0.015). A greater amount of COP variability was found in the preferred leg compared to the non-preferred leg in both the AP (F 1,79 = 30.147, p < 0.001) and ML (F 1,79 = 41.204, p < 0.001) directions. These findings highlight the importance of considering multiple levels of analysis when assessing lower limb symmetry as separate variables may provide differential evidence for asymmetry. Practically, these results emphasize the need for coaches and practitioners to consider different degrees of lower limb asymmetries that may impact the development and design of strength and rehabilitation programs. 3.


PCR and single-strand conformational polymorphism for recognition of medically important opportunistic fungi.
The application of PCR technology to molecular diagnostics holds great promise for the early identification of medically important pathogens. PCR has been shown to be useful for the detection of the presence of fungal DNA in both laboratory and clinical samples. Considerable interest has been focused on the utility of selecting universal primers, those that recognize constant regions among most, if not all, medically important fungi. Once an amplicon, or piece of amplified DNA determined by the unique pair of oligonucleotide primers, has been generated, several different methods may be used to distinguish between genera and between species. The two major approaches have utilized differences in restriction enzyme digestion patterns or hybridization with specific probe. We report the application of single-strand conformational polymorphism (SSCP) as a technique to delineate the differences between fungal species and/or genera. Minor sequence variations in small single-stranded DNA cause subtle changes in conformation, allowing these strands to be separated on polyacrylamide gels by SSCP. We used a 197-bp fragment amplified from the 18S rRNA gene, common to all medically important fungi. After amplification, the fragments were denatured and run on an acrylamide-glycerol gel at room temperature or 4 degrees C for 4.5 or 4 h, respectively. Under room temperature conditions, the SSCP patterns for Candida albicans, Candida tropicalis, and Candida parapsilosis were identical and all strains within each species demonstrated the same pattern. These patterns differed markedly from those of the genus Aspergillus. The SSCP patterns of major and minor bands at room temperature permitted distinction between strains of Aspergillus fumigatus and Aspergillus flavus. There also was consistency of the SSCP banding pattern among different strains of the same Aspergillus species. The SSCP patterns for other medically important opportunistic fungi, such as Cryptococcus neoformans, Pseudallescheria boydii, and Rhizopus arrhizus, were sufficiently unique to permit distinction from those of C. albicans and A. fumigatus. We conclude that the technique of PCR-SSCP provides a novel method by which to recognize and distinguish medically important opportunistic fungi and which has potential applications to molecular diagnosis, taxonomic classification, molecular epidemiology, and elucidation of mechanisms of antifungal drug resistance.


The effects of trypsin-degradation products of albumin on the activity of the central nervous system.
The investigations deal with the pharmacological activity of albumin degradation products. The peptides which resulted from 30 min trypsin digestion of human albumin exhibited some kinin-like effects. The peptides given intraperitoneally and intraventricularly revealed a central inhibitory action, the strength of which was similar to kinin effects.


Factors involved in long-term efficacy of deep brain stimulation of the thalamus for essential tremor.
Although nucleus ventralis intermedius stimulation has been shown to be safe and efficacious in the treatment of essential tremor, there is a subset of patients who eventually lose benefit from their stimulation. Proposed causes for this phenomenon include tolerance, disease progression, and suboptimal location. The goal of this study was to assess the factors that may lead to both stimulation failure, defined as loss of meaningful tremor relief, and less satisfactory outcomes, defined as leads requiring voltages>3.6 V for effective tremor control. The authors present their clinical outcomes from 31 leads in 27 patients who had effective tremor control for >1 year following nucleus ventralis intermedius stimulation. All patients postoperatively had a mean decrease in both the writing and drawing subscales of the Fahn-Tolosa-Marin Tremor Rating Scale (p<0.001). After a mean follow-up of 40 months, 22 patients continued to have tremor control with stimulation. Four patients eventually lost efficacy of their stimulation at a mean of 39 months. There was no difference in age, duration of disease, or disease severity between the groups. Examination of perioperative factors revealed that suboptimal anteroposterior positioning as evidenced on intraoperative fluoroscopy occurred significantly more frequently in patients with stimulation failure (p=0.018). In patients with less satisfactory outcomes, no difference was seen between group demographics. Fluoroscopy again revealed suboptimal positioning more frequently in these patients (p=0.005). This study provides further evidence that suboptimal lead position in combination with disease progression or tolerance may result in less satisfactory long-term outcomes.


Expression of the cancer stem cell marker OCT4 is associated with worse prognosis and survival in cutaneous melanoma.
Cutaneous melanoma has an aggressive clinical presentation, showing rapid rate of growth and metastatic dissemination due to the permanence of cancer stem cells. The present study was to evaluate the expression of the self-renewal regulatory factor and the clinical significance of the transcription factor OCT4 in melanoma. Melanoma tissues were stained by immunohistochemistry and the correlation between the expression of this marker was determined through clinical-pathological variables and survival outcomes. Positive expression of nuclear and cytoplasmic OCT4 was observed in 49% and 41.2% of cases, respectively. The positive expression of nuclear OCT4 in melanoma was significantly associated with prognostic factors, such as Breslow depth, Clark's level, ulceration and metastasis. Survival of patients was 56% compared to positive nuclear OCT4 expression and 94.2% when compared to the low expression of the gene. Nuclear OCT4 positive genotype indicated aggressive tumor behavior with a worse clinical outcome, which indicates OCT4 as a useful biomarker in the prognosis of melanoma.


Tobacco smoking, occupational exposure and bladder cancer in Argentina.
The highest rate for bladder cancer in Latin America has been reported from La Plata, Argentina. A case-control study was carried out to investigate the reasons for this high rate. A total of 117 cases, 117 hospital controls and 117 neighbourhood sex- and age-matched controls were interviewed regarding their smoking and drinking habits and occupational exposures. Cigarette smoking and coffee drinking were identified as the major risk factors, and a significant association was also found for truck and railway drivers and for oil refinery workers. The relative risks for male smokers who ever smoked cigarettes vs. non-smokers was 4.3 (95% Cl: 1.9-10.3). The risk associated with black tobacco cigarettes was 2-3 times higher than that of blond cigarettes. For male ex-smokers the risk after 5 years of no smoking is less than one third of that of current smokers. The RR for drinking coffee was 2.4 (95% Cl: 1.4-4.4) after adjusting for the effects of tobacco smoking, and the risk increased with the number of cups per day. No association was found with the use of saccharin.


Olive-Oil-Derived Polyphenols Effectively Attenuate Inflammatory Responses of Human Keratinocytes by Interfering with the NF-κB Pathway.
Extra virgin olive oil (EVOO) is rich in phenolic compounds, including hydroxytyrosol (HTy) and hydroxytyrosyl acetate (HTy-Ac), which have presented multiple beneficial properties. Their impact on inflammatory responses in human keratinocytes and modes of action have not been addressed yet. Primary human keratinocytes are pretreated with HTy-Ac or HTy for 30 min and stimulated with IL-1β or Toll-like receptor 3 ligand (TLR3-l). Thymic stromal lymphopoietin (TSLP), measured by ELISA, is attenuated by both polyphenols in a dose-dependent manner. The expression of several inflammation-related genes, including distinct TSLP isoforms and IL-8, are assessed by quantitative RT-PCR and likewise inhibited by HTy-Ac/HTy. Mechanistically, EVOO phenols counteracts IκB degradation and translocation of NF-κB to the nucleus, a transcription factor of essential significance to TSLP and IL-8 transcriptional activity; this is evidenced by immunoblotting. Accordingly, NF-κB recruitment to critical binding sites in the TSLP and IL-8 promoter is impeded in the presence of HTy-Ac/HTy, as demonstrated by chromatin immunoprecipitation. Promoter reporter assays finally reveal that the neutralizing effect on NF-κB induction has functional consequences, resulting in reduced NF-κB-directed transcription. EVOO phenols afford protection from inflammation in human keratinocytes by interference with the NF-κB pathway.


Incidental genetic findings in randomized clinical trials: recommendations from the Genomics and Randomized Trials Network (GARNET).
Recommendations and guidance on how to handle the return of genetic results to patients have offered limited insight into how to approach incidental genetic findings in the context of clinical trials. This paper provides the Genomics and Randomized Trials Network (GARNET) recommendations on incidental genetic findings in the context of clinical trials, and discusses the ethical and practical issues considered in formulating our recommendations. There are arguments in support of as well as against returning incidental genetic findings in clinical trials. For instance, reporting incidental findings in clinical trials may improve the investigator-participant relationship and the satisfaction of participation, but it may also blur the line between clinical care and research. The issues of whether and how to return incidental genetic findings, including the costs of doing so, should be considered when developing clinical trial protocols. Once decided, plans related to sharing individual results from the aim(s) of the trial, as well as incidental findings, should be discussed explicitly in the consent form. Institutional Review Boards (IRBs) and other study-specific governing bodies should be part of the decision as to if, when, and how to return incidental findings, including when plans in this regard are being reconsidered.


Progressive increase in telomerase activity from benign melanocytic conditions to malignant melanoma.
The expression of telomerase activity and the in situ localization of the human telomerase RNA component (hTR) in melanocytic skin lesions was evaluated in specimens from sixty-three patients. Specimens of melanocytic nevi, primary melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight patients, whereas metastasized lymph nodes were obtained from five patients. Telomerase activity was determined in these specimens by using a Polymerase Chain Reaction-based assay (TRAP). High relative mean telomerase activity levels were detected in metastatic melanoma (subcutaneous metastases = 54.5, lymph node metastases = 56.5). Much lower levels were detected in primary melanomas, which increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark III = 1.1, and Clark IV = 1.9). Twenty-six formalin-fixed, paraffin-embedded melanocytic lesions were sectioned and analyzed for telomerase RNA with a radioactive in situ hybridization assay. In situ hybridization studies with a probe to the template RNA component of telomerase confirmed that expression was almost exclusively confined to tumor cells and not infiltrating lymphocytes. These results indicate that levels of telomerase activity and telomerase RNA in melanocytic lesions correlate well with clinical stage and could potentially assist in the diagnosis of borderline lesions.


[Minor promoters of phage phi X174 are controlled by CRP-cAMP, lexA, glnG and several other common common regulatory systems of the host cell].
It was found that CRP-cAMP-recognized sequences in DNA being suggested as GTGN7-11CAC (with variability both in domain's structures and in spacer's length) are located non-randomly in promoters. In CRP-cAMP-stimulated promoters they lie upstream the "-35" box and are separated from it by a whole number of DNA turns, whereas in CRP-cAMP-repressed ones they are located downstream "-35" in a half-whole-turn-number distance. Several CRP-, SOS- and NR1-sites in the phi X174 DNA sequence were found and a few new promoters were deduced from it. PCRP1 lies within gene F and has both CRR and ntrC sites and one SOS-operator, PCRP3 (in gene A) has a CRP site which overlaps with the SOS-operator, PA and PCRP2 (in gene G) have sCRP and PD has a stringent discriminator. Four promotors, PCRP1, PCRP2, PA and PB are cloned in the pBR322 plasmid. For cloned PCRP1 the activation by exogenous cAMP and the SOS-induction by the mitomycin C were observed in vivo in pVYB215-containing cells by increasing the levels of beta-lactamase up to 27-fold. The new gene L of the phi X174 is deduced from the DNA sequence. It has two start points, overlaps the gene F inside it and codes for peptides 23 or 19 amino acids in length. These lethal peptides have strong homology in sequence to the cellular protein sulA(sfiA) of E. coli, and L* can cause observed filamentation and death of pVYB215- bearing cells after PCRP1 induction. In the A and A* protein sequences two domains "helix-turn-helix" were found that are homologous to those in CRP and repressors; this makes possible the competition between A* and CRT for its DNA sites that also have some homology. The model of the phi X174 infection cycle control and mechanisms of DNA recognition by CRP-CAMP are discussed. PCRP1 is the first promotor controlled by both three global regulons of E. coli cell.


Coronary artery bypass graft surgery versus percutaneous coronary intervention with drug-eluting stents for left main coronary artery disease: A meta-analysis of randomized trials.
Despite several clinical studies, efficacy of coronary artery bypass grafting (CABG) surgery versus percutaneous coronary intervention (PCI) in patients with left main (LM) disease remains controversial. The objective of this meta-analysis of randomized trials was to evaluate the clinical outcome of CABG versus PCI with drug-eluting stents in LM coronary disease. We systematically searched online databases up to March 2017 for randomized trials comparing CABG to PCI with drug-eluting stents. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). We included data from 5 randomized trials and 4595 patients. At 30days, CABG was associated with higher stroke (OR 2.54 [95% CI, 1.02-6.31]) and periprocedural myocardial infarction (OR 1.45 [95% CI, 1.00-2.10]), with no other significant differences compared to PCI. At 1year, CABG reduced repeat revascularization (OR 0.56 [95% CI, 0.40-0.77]), but increased stroke (OR 5.11 [95% CI, 1.62-16.12]). At 3-5years, CABG reduced repeat revascularization (OR 0.55 [95% CI, 0.45-0.67]) and non-periprocedural myocardial infarction (OR 0.45 [95% CI, 0.29-0.70]), without significant differences on other outcomes. From the present updated meta-analysis of available studies on LM coronary disease treatment, there were no differences in mortality, myocardial infarction, and stroke rate at 3-5years follow-up after CABG or PCI, but CABG decreased the rate of repeat revascularization and non-periprocedural infarction. However, at short-term follow-up, CABG showed higher rate of stroke and periprocedural myocardial infarction, but these effects attenuated over time. These findings merit further investigation at longer follow-up.


Lack of cross-resistance to a novel succinate dehydrogenase inhibitor, fluopyram, in highly boscalid-resistant isolates of Corynespora cassiicola and Podosphaera xanthii.
Recently in Japan, isolates resistant to boscalid, a succinate dehydrogenase inhibitor (SDHI), have been detected in Corynespora cassiicola (Burk. & Curt.) Wei and Podosphaera xanthii (Castaggne) Braun & Shishkoff, the pathogens causing Corynespora leaf spot and powdery mildew disease on cucumber, respectively. Resistant isolates of C. cassiicola are widely distributed and represent a serious problem in disease control at present. Novel SDHI fungicides, including fluopyram, are now under development. The growth of very highly boscalid-resistant, highly resistant and sensitive isolates of C. cassiicola was strongly suppressed on fluopyram-amended YBA agar medium. Although boscalid and another SDHI, penthiopyrad, hardly controlled Corynespora leaf spot and powdery mildew on cucumber plants when very highly or highly boscalid-resistant isolates were employed for inoculation, fluopyram still exhibited excellent control efficacy against these resistant isolates as well as sensitive isolates of C. cassiicola and P. xanthii. Differential sensitivity to boscalid, penthiopyrad and fluopyram, clearly found in these two important pathogens of cucumber, may indicate involvement of a slightly distinct site of action for fluopyram from the two other SDHIs. This finding may lead to the discovery of unique SDHIs in the future.


Secretory PAF-acetylhydrolase of the rat hepatobiliary system: characterization and partial purification.
Hepatocytes and Kupffer cells in primary culture both secrete plasma-type platelet-activating factor-acetylhydrolase (pPAF-AH) into serum-free culture medium. The rate of secretion of pPAF-AH by Kupffer cells was 20 to 25 times higher than from hepatocytes, and Kupffer cells expressed a higher level of pPAF-AH mRNA than did hepatocytes. Purified liver cell-secreted pPAF-AH exhibited a major protein band of 65-67 kDa on SDS-PAGE; this was the band predominantly labeled when the enzyme catalytic center was reacted with [3H]diisopropylfluorophosphate ([3H]DFP). Rat bile collected from cannulated bile ducts contained significant PAF-AH activity, and bile samples possessed a prominent band at 30-32 kDa, which was the exclusive target for [3H]DFP. Experiments using tunicamycin, an inhibitor of N-linked glycosylation, and endoglycosidase H suggested that pPAF-AH secreted constitutively by cultured hepatocytes and Kupffer cells is glycosylated. The present study supports the notion that hepatic secretion of pPAF-AH into the blood contributes to the regulation of PAF and oxidized phospholipid levels in the circulation, whereas secretion of PAF-AH into the bile may allow hepatic control of these phospholipid signaling molecules in the gastrointestinal tract.


Correction of superior sulcus defects after enucleation.
Anophthalmic patients can develop a deep recess or sulcus in the upper lid, usually associated with enophthalmos. If due to an absence or loss of a socket implant, a secondary one can be implanted. In those cases with a socket implant, one method of treatment is directed at adding a silicone block to the inferior orbit to cause a forward movement of fat to fill out the upper eyelid as well as reducing the enophthalmos. Another approach, particularly if enophthalmos is minimal, is to directly implant a dermis-fat graft into the upper eyelid. The graft is taken from above the iliac crest and the amount implanted should create a slight overcorrection, allowing for some fat absorption.


Inhibition of endogenous thioredoxin in the heart increases oxidative stress and cardiac hypertrophy.
Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells. However, the extent of Trx1 contribution to overall antioxidant mechanisms is unknown in any organs. We generated transgenic mice with cardiac-specific overexpression of a dominant negative (DN) mutant (C32S/C35S) of Trx1 (Tg-DN-Trx1 mice), in which the activity of endogenous Trx was diminished. Markers of oxidative stress were significantly increased in hearts from Tg-DN-Trx1 mice compared with those from nontransgenic (NTg) mice. Tg-DN-Trx1 mice exhibited cardiac hypertrophy with maintained cardiac function at baseline. Intraperitoneal injection of N-2-mercaptopropionyl glycine, an antioxidant, normalized cardiac hypertrophy in Tg-DN-Trx1 mice. Thoracic aortic banding caused greater increases in myocardial oxidative stress and enhanced hypertrophy in Tg-DN-Trx1 compared with NTg mice. In contrast, transgenic mice with cardiac-specific overexpression of wild-type Trx1 did not show cardiac hypertrophy at baseline but exhibited reduced levels of hypertrophy and oxidative stress in response to pressure overload. These results demonstrate that endogenous Trx1 is an essential component of the cellular antioxidant mechanisms and plays a critical role in regulating oxidative stress in the heart in vivo. Furthermore, inhibition of endogenous Trx1 in the heart primarily stimulates hypertrophy, both under basal conditions and in response to pressure overload through redox-sensitive mechanisms.


Using LLMs and Explainable ML to Analyze Biomarkers at Single-Cell Level for Improved Understanding of Diseases.
Single-cell RNA sequencing (scRNA-seq) technology has significantly advanced our understanding of the diversity of cells and how this diversity is implicated in diseases. Yet, translating these findings across various scRNA-seq datasets poses challenges due to technical variability and dataset-specific biases. To overcome this, we present a novel approach that employs both an LLM-based framework and explainable machine learning to facilitate generalization across single-cell datasets and identify gene signatures to capture disease-driven transcriptional changes. Our approach uses scBERT, which harnesses shared transcriptomic features among cell types to establish consistent cell-type annotations across multiple scRNA-seq datasets. Additionally, we employed a symbolic regression algorithm to pinpoint highly relevant, yet minimally redundant models and features for inferring a cell type's disease state based on its transcriptomic profile. We ascertained the versatility of these cell-specific gene signatures across datasets, showcasing their resilience as molecular markers to pinpoint and characterize disease-associated cell types. The validation was carried out using four publicly available scRNA-seq datasets from both healthy individuals and those suffering from ulcerative colitis (UC). This demonstrates our approach's efficacy in bridging disparities specific to different datasets, fostering comparative analyses. Notably, the simplicity and symbolic nature of the retrieved gene signatures facilitate their interpretability, allowing us to elucidate underlying molecular disease mechanisms using these models.


Endogenous cortisol regulates immunoglobulin E-dependent late phase reactions.
To investigate the impact that physiological variation in serum cortisol has on IgE-mediated events, 10 atopic subjects underwent cutaneous antigen challenge with measurement of the early phase wheal (EPW) at 20 min and the late phase reaction (LPR) at 6 h. All subjects were challenged during control conditions between 8:00 and 9:00 a.m. Repeat challenges were performed in five subjects at 6:00 p.m. and in eight subjects after ingestion of metyrapone, a specific inhibitor of cortisol synthesis. Compared with control values, mean serum cortisol was suppressed in the evening and after metyrapone (P less than 0.05 all time points). No effect was seen on the EPW, but mean LPR diameters at three antigen dilutions were significantly increased by cortisol suppression (P less than 0.05). Replacement doses of hydrocortisone given in the evening and with metyrapone abrogated these increases. Blinded analysis of LPR biopsies from cortisol-suppressed subjects revealed increases in leukocytoclasis (P less than or equal to 0.0001), interstitial leukocytes (P less than or equal to 0.01), and eosinophils (P less than or equal to 0.04). These results indicate that physiological levels of serum cortisol can regulate IgE-dependent cutaneous inflammation by affecting the expression of cellular events at late phase sites.


[Usefulness of chest CT in the diagnosis of pulmonary sequestration].
Pulmonary sequestration is a rare congenital anomaly, characterized by nonfunctional embryonic pulmonary tissue. Pulmonary sequestration accounts for 0.15-6.40% of all congenital pulmonary malformations. This anomaly, which is classified as intralobar or extralobar, involves the lung parenchyma and its vascularization. We report the case of a 56-year-old male presenting with hemoptysis. A chest X-ray showed an area of opacity behind the cardiac silhouette in the base of the left hemithorax. Chest CT scans with intravenous contrast revealed pulmonary sequestration. The patient underwent surgery, in which the anomalous tissue was successful resected. The postoperative evolution was favorable, and the patient was discharged to outpatient treatment.


Cervical epidural anesthesia in post stroke patients: are we safe?
The role of regional anesthetic techniques such as cervical epidural and inter-scalene brachial plexus blockade (ISB) in rehabilitated stroke patients remains uncertain. We present a case of rehabilitated stroke patient with reactive airway disease, which was managed using cervical epidural anesthesia for an above the elbow amputation. We further discuss the implications of the performance of cervical epidural anesthesia in post stroke patients.


The impact of no-fault compensation on health care expenditures: an empirical study of OECD countries.
Around the world, governments are faced with spiralling health care expenditures. This raises the need for further insight in the determinants of these expenditures. Existing literature focuses primarily on income, ageing, health care financing and supply variables. This paper includes medical malpractice system characteristics as determinants of health spending in OECD countries. Estimates from our regression models suggest that no-fault schemes for medical injuries with decoupling of deterrence and compensation reduce health expenditures per capita by 0.11%. Furthermore, countries that introduced a no-fault system without decoupling of deterrence and compensation are found to have higher (+0.06%) health care spending.


Using an Image Fusion Methodology to Improve Efficiency and Traceability of Posterior Pole Vessel Analysis by ROPtool.
The diagnosis of plus disease in retinopathy of prematurity (ROP) largely determines the need for treatment; however, this diagnosis is subjective. To make the diagnosis of plus disease more objective, semi-automated computer programs (e.g. ROPtool) have been created to quantify vascular dilation and tortuosity. ROPtool can accurately analyze blood vessels only in images with very good quality, but many still images captured by indirect ophthalmoscopy have insufficient image quality for ROPtool analysis. To evaluate the ability of an image fusion methodology (robust mosaicing) to increase the efficiency and traceability of posterior pole vessel analysis by ROPtool. We retrospectively reviewed video indirect ophthalmoscopy images acquired during routine ROP examinations and selected the best unenhanced still image from the video for each infant. Robust mosaicing was used to create an enhanced mosaic image from the same video for each eye. We evaluated the time required for ROPtool analysis as well as ROPtool's ability to analyze vessels in enhanced vs. unenhanced images. We included 39 eyes of 39 infants. ROPtool analysis was faster (125 vs. 152 seconds; p=0.02) in enhanced vs. unenhanced images, respectively. ROPtool was able to trace retinal vessels in more quadrants (143/156, 92% vs 115/156, 74%; p=0.16) in enhanced mosaic vs. unenhanced still images, respectively and in more overall (38/39, 97% vs. 34/39, 87%; p=0.07) enhanced mosaic vs. unenhanced still images, respectively. Retinal image enhancement using robust mosaicing advances efforts to automate grading of posterior pole disease in ROP.


Back-gated spray-deposited carbon nanotube thin film transistors operated in electrolytic solutions: an assessment towards future biosensing applications.
We report on back-gated carbon nanotube (CNT) thin-film transistors (CNTFETs) and their performance in electrolytic solutions to assess their suitability for future application as biosensors. Spray-deposited CNT networks were used as the sensitive active layer which offers the opportunity for integration on flexible sensing platforms at low-cost. We characterized the transistors' behavior in electrolytes by analyzing the response to different KCl solutions and buffers over a wide pH range. We observed a linear response of the drain current upon changing the pH in low molarity buffers and obtained an exponential dependence on the salt concentration of the electrolyte. These responses can be attributed to electrostatic gating effects that go along with shifts in the threshold voltage. Even though a lot of effort has been put into understanding the biosensing mechanism a detailed theory is still missing. Back-gated CNTFETs operated in electrolytic solutions can be a further tool to investigate and clarify the existing unsolved phenomena.


Only as happy as the least happy child: multiple grown children's problems and successes and middle-aged parents' well-being.
Middle-aged parents' well-being may be tied to successes and failures of grown children. Moreover, most parents have more than one child, but studies have not considered how different children's successes and failures may be associated with parental well-being. Middle-aged adults (aged 40-60; N = 633) reported on each of their grown children (n = 1,384) and rated their own well-being. Participants indicated problems each child had experienced in the past two years, rated their children's successes, as well as positive and negative relationship qualities. Analyses compared an exposure model (i.e., having one grown child with a problem or deemed successful) and a cumulative model (i.e., total problems or successes in the family). Consistent with the exposure and cumulative models, having one child with problems predicted poorer parental well-being and the more problems in the family, the worse parental well-being. Having one successful child did not predict well-being, but multiple grown children with higher total success in the family predicted enhanced parental well-being. Relationship qualities partially explained associations between children's successes and parental well-being. Discussion focuses on benefits and detriments parents derive from how grown progeny turn out and particularly the implications of grown children's problems.


Carbon nanotube-copper exhibiting metal-like thermal conductivity and silicon-like thermal expansion for efficient cooling of electronics.
Increasing functional complexity and dimensional compactness of electronic devices have led to progressively higher power dissipation, mainly in the form of heat. Overheating of semiconductor-based electronics has been the primary reason for their failure. Such failures originate at the interface of the heat sink (commonly Cu and Al) and the substrate (silicon) due to the large mismatch in thermal expansion coefficients (∼300%) of metals and silicon. Therefore, the effective cooling of such electronics demands a material with both high thermal conductivity and a similar coefficient of thermal expansion (CTE) to silicon. Addressing this demand, we have developed a carbon nanotube-copper (CNT-Cu) composite with high metallic thermal conductivity (395 W m(-1) K(-1)) and a low, silicon-like CTE (5.0 ppm K(-1)). The thermal conductivity was identical to that of Cu (400 W m(-1) K(-1)) and higher than those of most metals (Ti, Al, Au). Importantly, the CTE mismatch between CNT-Cu and silicon was only ∼10%, meaning an excellent compatibility. The seamless integration of CNTs and Cu was achieved through a unique two-stage electrodeposition approach to create an extensive and continuous interface between the Cu and CNTs. This allowed for thermal contributions from both Cu and CNTs, resulting in high thermal conductivity. Simultaneously, the high volume fraction of CNTs balanced the thermal expansion of Cu, accounting for the low CTE of the CNT-Cu composite. The experimental observations were in good quantitative concurrence with the theoretically described 'matrix-bubble' model. Further, we demonstrated identical in-situ thermal strain behaviour of the CNT-Cu composite to Si-based dielectrics, thereby generating the least interfacial thermal strain. This unique combination of properties places CNT-Cu as an isolated spot in an Ashby map of thermal conductivity and CTE. Finally, the CNT-Cu composite exhibited the greatest stability to temperature as indicated by its low thermal distortion parameter (TDP). Thus, this material presents a viable and efficient alternative to existing materials for thermal management in electronics.


Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
Neuroblastomas are characterized by chromosomal alterations with biological and clinical significance. We analyzed paired blood and primary tumor samples from 22 children with high-risk neuroblastoma for loss of heterozygosity (LOH) and DNA copy number change using the Affymetrix 10K single nucleotide polymorphism (SNP) array. Multiple areas of LOH and copy number gain were seen. The most commonly observed area of LOH was on chromosome arm 11q (15/22 samples; 68%). Chromosome 11q LOH was highly associated with occurrence of chromosome 3p LOH: 9 of the 15 samples with 11q LOH had concomitant 3p LOH (P = 0.016). Chromosome 1p LOH was seen in one-third of cases. LOH events on chromosomes 11q and 1p were generally accompanied by copy number loss, indicating hemizygous deletion within these regions. The one exception was on chromosome 11p, where LOH in all four cases was accompanied by normal copy number or diploidy, implying uniparental disomy. Gain of copy number was most frequently observed on chromosome arm 17q (21/22 samples; 95%) and was associated with allelic imbalance in six samples. Amplification of MYCN was also noted, and also amplification of a second gene, ALK, in a single case. This analysis demonstrates the power of SNP arrays for high-resolution determination of LOH and DNA copy number change in neuroblastoma, a tumor in which specific allelic changes drive clinical outcome and selection of therapy.


[Ulcers of the colon in association with nonsteroidal anti-inflammatory drugs (NSAID)--a rare cause of gastrointestinal bleeding? Report of 3 cases].
Although adverse side effects of nonsteroidal anti-inflammatory drugs (NSAID) can affect the whole gastrointestinal tract, most reports refer to upper gastrointestinal tract complications. We report on 3 patients with lower gastrointestinal bleeding (patient 1 and 2) respectively detectable fecal blood loss (patient 3) after the use of NSAID. Patient 1 and 3 were taking NSAID over at least 6 months for the treatment of rheumatic diseases while patient 2 reported a single use of 2 g acetylsalicylic acid. Colonoscopy showed a single ulcer of the colon in patients 1 and 2. Due to acute bleeding patient 1 required interventional endoscopic treatment. Colonoscopy of patient 3 revealed multiple colonic ulcerations. Gastroduodenoscopy also detected adverse NSAID-effects on the upper gastrointestinal tract in patient 1 and 3 (ulcers of the stomach, erosive duodenitis). NSAID-medication was discontinued in all patients and, additionally, mesalazine was administered to patient 3. Consecutively, symptoms and lesions disappeared. Our cases stress the clinical importance of NSAID-toxicity distal to the small intestine which may exist concomitantly to lesions of the upper gastrointestinal tract and is not obligatory dose-dependent.


Measuring the impact of headache in children: a critical review of the literature.
Headache is the most frequent neurological symptom and commonest manifestation of pain in childhood. Measuring the impact of headache in terms of health status, functioning and quality of life can inform the prioritization of competing resource claims, screen for unmet need, improve communication between patient and physician and monitor response to treatment. We undertook a critical review of the literature measuring the impact of headache in children and identified 33 papers that contained relevant information. Findings reflected a wide range of settings, age groups, methodologies and outcome measures. Considerable methodological limitations affected all studies, including inadequate description of study design, methodology and data analysis. Nevertheless, although we found the existing literature to be of inconsistent quality, the impact of headache in children and adolescents is substantial. Rigorous studies are required to quantify this burden using measures that are valid and reliable and whose development has been informed by both theoretical and practical perspectives.


Optical fiber nanotips coated with molecular beacons for DNA detection.
Optical fiber sensors, thanks to their compactness, fast response and real-time measurements, have a large impact in the fields of life science research, drug discovery and medical diagnostics. In recent years, advances in nanotechnology have resulted in the development of nanotools, capable of entering the single cell, resulting in new nanobiosensors useful for the detection of biomolecules inside living cells. In this paper, we provide an application of a nanotip coupled with molecular beacons (MBs) for the detection of DNA. The MBs were characterized by hybridization studies with a complementary target to prove their functionality both free in solution and immobilized onto a solid support. The solid support chosen as substrate for the immobilization of the MBs was a 30 nm tapered tip of an optical fiber, fabricated by chemical etching. With this set-up promising results were obtained and a limit of detection (LOD) of 0.57 nM was reached, opening up the possibility of using the proposed nanotip to detect mRNAs inside the cytoplasm of living cells.


Biodegradation characteristics of environmental endocrine disruptor di-n-butyl phthalate.
The biodegradation characteristics of di-n-butyl phthalate (DBP), an environmental endocrine disruptor, were studied by the method of dominant bacteria and immobilized microorganisms. Taking DBP as the only carbon source to acclimatize the collected activated sludge, the concentration of DBP increased progressively in the process of acclimatization. Plate streaking was used to separate 1 strain of the degradation dominant bacteria after acclimatization. Better conditions to degrade DBP by the bacterium could be obtained through orthogonal experiments and the bacterium was identified. Then the acclimated activated sludge was made to immobilize the microorganism using polyvinyl alcohol as entrapment agent. The immobilized microorganism degraded DBP at different conditions. The appropriate conditions to degrade DBP by the dominant bacteria were: degradation time, 32 h; DBP concentration, 200 mg/L; rate of shaking incubator, 100 r/min; pH, 7 and temperature, 30 degrees C. DBP could be degraded by more than 95% under such conditions. The bacteria were identified as Pseudomonas. The proliferated immobilized microorganisms degraded DBP more effectively and more adapted to temperature and pH than the free acclimated activated sludge. One strain of DBP degradation dominant bacteria was separated from the acclimatized activated sludge. It could grow with DBP as the only carbon source and energy, and degraded DBP effectively. After having been immobilized and proliferated, the dominant bacteria could keep a higher biological activity and degrade DBP more effectively than activated sludge.


Standardisation of cell lines.
Standardisation of cell-based assays is significantly enhanced through the preparation and quality control of master and working cell banks. Validation of the cell substrate for use in an assay must address not only the assay conditions but also aspects such as culture passage level, pre-assay preparation and seeding of cells and pre-use validation of "critical reagents".


Recipes for Inducing Cold Denaturation in an Otherwise Stable Protein.
Although cold denaturation is a fundamental phenomenon common to all proteins, it can only be observed in a handful of cases where it occurs at temperatures above the freezing point of water. Understanding the mechanisms that determine cold denaturation and the rules that permit its observation is an important challenge. A way to approach them is to be able to induce cold denaturation in an otherwise stable protein by means of mutations. Here, we studied CyaY, a relatively stable bacterial protein with no detectable cold denaturation and a high melting temperature of 54 °C. We have characterized for years the yeast orthologue of CyaY, Yfh1, a protein that undergoes cold and heat denaturation at 5 and 35 °C, respectively. We demonstrate that, by transferring to CyaY the lessons learnt from Yfh1, we can induce cold denaturation by introducing a restricted number of carefully designed mutations aimed at destabilizing the overall fold and inducing electrostatic frustration. We used molecular dynamics simulations to rationalize our findings and demonstrate the individual effects observed experimentally with the various mutants. Our results constitute the first example of rationally designed cold denaturation and demonstrate the importance of electrostatic frustration on the mechanism of cold denaturation.


Circadian rhythms and mood disorders: Time to see the light.
The importance of time is ever prevalent in our world, and disruptions to the normal light/dark and sleep/wake cycle have now become the norm rather than the exception for a large part of it. All mood disorders, including seasonal affective disorder (SAD), major depressive disorder (MDD), and bipolar disorder (BD), are strongly associated with abnormal sleep and circadian rhythms in a variety of physiological processes. Environmental disruptions to normal sleep/wake patterns, light/dark changes, and seasonal changes can precipitate episodes. Moreover, treatments that target the circadian system have proven to be therapeutic in certain cases. This review will summarize much of our current knowledge of how these disorders associate with specific circadian phenotypes, as well as the neuronal mechanisms that link the circadian clock with mood regulation. We also discuss what has been learned from therapies that target circadian rhythms and how we may use current knowledge to develop more individually designed treatments.


Aam assessment instrument for disease activity in Aamavata: Scope and challenges.
Development and validation of instruments based on concepts and clinical features described in Ayurveda is a constructive step towards translational research in Ayurveda. The clinical decisions in traditional medical practices often depend on clinical features. Such attempts from Ayurveda experts also contribute to strengthen an endeavour of integrative medicine. A recently published article in J-AIM on development and validation of Aam Assessment Instrument (AAI) to assess the disease activity in amavata is a landmark study. This study is undertaken in patients with rheumatoid arthritis (RA), a prototype of inflammatory arthritis. We suggest that the specificity and reliability of AAI in RA and amavata would increase if complemented with joint count as described in Ayurveda texts. These joint counts can be further sub-classified for different types of inflammatory arthritides. Similarly, this AAI can also be validated and used for constitutional features in other ama-dominant non-rheumatic systemic diseases. This may need development of more comprehensive ama-specific features. We also need to consider the limitations of patient-reported outcome measures (PROMs) during further development and validation of AAI. Collective, multicentric, organized efforts by Ayurveda clinicians will lead to the development of reliable, sensitive, specific, and reproducible instruments for clinical assessments in various diseases.


Association between the Rating Perceived Exertion, Heart Rate and Blood Lactate in Successive Judo Fights (Randori).
This study aims to investigate the association between the rating of perceived exertion (RPE), heart rate (HR) and the blood lactate concentration ([La]) in successive judo fight simulations (randori). TEN ATHLETES PARTICIPATED IN THE STUDY (AGE: 25.6±2.1 years; stature: 1.75±0.07 m; body mass: 75.6±14.9kg; %BF: 11.5±7.8%; practice: 14.5±6.2 years) and completed 4 judo fight simulations (T1 to T4) with duration of 5 min separated by 5 min passive recovery periods. Before each randori, [La] and HR were collected, and after each randori, the same measures and the RPE (CR-10 scale) were collected. SIGNIFICANT CORRELATIONS WERE OBSERVED BETWEEN: (1) CR-10 and HR (T2: r =0.70; T3: r =0.64; both, P<0.05); (2) ΔCR-10 and Δ[La] (T1-T2: r = .71, P< 0.05; T2-T3: r =0.92, P<0.01; T3-T4: r =0.73, P<0.05). Moreover, significant differences were noted in the behavior of the HR between the 2(nd) (T2) and 3(rd) (T3) judo fight simulations (P<0.05). The use of CR-10 in the evaluation process, as well as in deciding the load of training in judo, should be done with caution.


Applicability of RAD-tag genotyping for interfamilial comparisons: empirical data from two cetaceans.
Restriction-site-associated DNA tag (RAD-tag) sequencing has become a popular approach to generate thousands of SNPs used to address diverse questions in population genomics. Comparatively, the suitability of RAD-tag genotyping to address evolutionary questions across divergent species has been the subject of only a few recent studies. Here, we evaluate the applicability of this approach to conduct genome-wide scans for polymorphisms across two cetacean species belonging to distinct families: the short-beaked common dolphin (Delphinus delphis; n = 5 individuals) and the harbour porpoise (Phocoena phocoena; n = 1 individual). Additionally, we explore the effects of varying two parameters in the Stacks analysis pipeline on the number of loci and level of divergence obtained. We observed a 34% drop in the total number of loci that were present in all individuals when analysing individuals from the distinct families compared with analyses restricted to intraspecific comparisons (i.e. within D. delphis). Despite relatively stringent quality filters, 3595 polymorphic loci were retrieved from our interfamilial comparison. Cetaceans have undergone rapid diversification, and the estimated divergence time between the two families is relatively recent (14-19 Ma). Thus, our results showed that, for this level of divergence, a large number of orthologous loci can still be genotyped using this approach, which is on par with two recent in silico studies. Our findings constitute one of the first empirical investigations using RAD-tag sequencing at this level of divergence and highlights the great potential of this approach in comparative studies and to address evolutionary questions.


Effects of chemicals on delayed matching behavior in pigeons. III. Effects of triethyltin.
The effects of triethyltin (TET) on delayed matching-to-sample performance were studied in male White Carneaux pigeons. Pigeons were trained to peck a red or green center key 15 times to turn it off. After a 2- or 5-sec delay, one side key was illuminated by a red color and the other by a green color. One peck on the side key whose color matched the color that the center key had been, produced food. After performance had stabilized, TET was administered intramuscularly at 3 different dosages (1.75, 3.0 and 5.6 mg/kg) to 3 different groups of birds. Birds received 4 injections of the same dose 2 weeks apart. Responding was totally suppressed in all animals 3 hours after each TET administration at all dosage levels. At 27 and 51 hrs after TET administration, dose-dependent decreases in both matching accuracy and rate of responding were observed. These behavioral changes disappeared in 2 to 3 days.


A CORRECTION.
IN a recently published volume on "The Origin of Submarine Canyons" the writer inadvertently credited to A. C. Veatch an excerpt from a submarine chart actually contoured by P. A. Smith, of the U. S. Coast and Geodetic Survey. The chart in question is Chart IVB of Special Paper No. 7 of the Geological Society of America entitled "Atlantic Submarine Valleys of the United States and the Congo Submarine Valley, by A. C. Veatch and P. A. Smith," and the excerpt appears as Plate III of the volume fist cited above. In view of the heavy labor involved in contouring the charts accompanying the paper by Veatch and Smith and the beauty of the finished product, it would be unfair to Mr. Smith to permit the error to go uncorrected. Excerpts from two other charts are correctly ascribed to Dr. Veatch.


Excitation of 1S and 3S metastable helium atoms to doubly excited states.
We present spectra of triplet and singlet metastable helium atoms resonantly photoexcited to doubly excited states. The first members of three dipole-allowed ;{1,3}P;{o} series have been observed and their relative photoionization cross sections determined, both in the triplet (from 1s2s ;{3}S;{e}) and singlet (from 1s2s ;{1}S;{e}) manifolds. The intensity ratios are drastically different with respect to transitions from the ground state. When radiation damping is included the results for the singlets are in agreement with theory, while for triplets spin-orbit interaction must also be taken into account.


Principles of surgical management of ovarian carcinomas.
Nearly 80% of the approximately 20,000 women who develop ovarian carcinoma each year in the United States are diagnosed at stages II, III, or IV. The main goals of surgery in these patients are confirmation of diagnosis, accurate staging of the tumor, and reduction of tumor bulk. Among the topics discussed are intraoperative management, differential diagnosis by frozen section, pediatric tumors, ovarian carcinoma during pregnancy, second-look operations, and laparoscopic surgery.


Altered Brain Connectivity and Network Topological Organization in a Non-ordinary State of Consciousness Induced by Hypnosis.
Hypnosis has been shown to be of clinical utility; however, its underlying neural mechanisms remain unclear. This study aims to investigate altered brain dynamics during the non-ordinary state of consciousness induced by hypnosis. We studied high-density EEG in 9 healthy participants during eyes-closed wakefulness and during hypnosis, induced by a muscle relaxation and eyes fixation procedure. Using hypotheses based on internal and external awareness brain networks, we assessed region-wise brain connectivity between six ROIs (right and left frontal, right and left parietal, upper and lower midline regions) at the scalp level and compared across conditions. Data-driven, graph-theory analyses were also carried out to characterize brain network topology in terms of brain network segregation and integration. During hypnosis, we observed (1) increased delta connectivity between left and right frontal, as well as between right frontal and parietal regions; (2) decreased connectivity for alpha (between right frontal and parietal and between upper and lower midline regions) and beta-2 bands (between upper midline and right frontal, frontal and parietal, also between upper and lower midline regions); and (3) increased network segregation (short-range connections) in delta and alpha bands, and increased integration (long-range connections) in beta-2 band. This higher network integration and segregation was measured bilaterally in frontal and right parietal electrodes, which were identified as central hub regions during hypnosis. This modified connectivity and increased network integration-segregation properties suggest a modification of the internal and external awareness brain networks that may reflect efficient cognitive-processing and lower incidences of mind-wandering during hypnosis.


Animal models of infectious arthritis.
The results from animal studies of bacterial joint infection have demonstrated pathogenic changes in synovium, cartilage, and bone which lead to joint destruction. Mechanisms responsible for the changes in these articular components remain to be more completely defined in order to develop methods to prevent articular destruction. Eradication of the active infectious process with early institution of antibiotics and adequate drainage is required but is not sufficient to prevent chronic destructive processes initiated by the acute bacterial infection. Biochemical effects of changes in the anabolic and catabolic functions of the cells in bone, cartilage, and synovium and the control mechanisms for these functions undoubtedly hold the key to prevention of destruction in infectious arthritis. Much less is understood about the pathogenic changes and mechanisms in infections caused by anaerobic bacteria, mycobacteria, fungi or viruses. Application of advances in immunological, morphological and biochemical techniques to animal models of infectious arthritis provides the opportunity to increase understanding of pathogenic mechanisms and to develop innovative methods of treatment.


Impact of the 1998 UK National Allocation Scheme for deceased heartbeating donor kidneys.
National and regional strategies for allocating deceased heartbeating (DHB) donor kidneys to patients awaiting transplant are of great importance and have major implications for patients and healthcare systems. We describe the rationale for the 1998 National Kidney Allocation Scheme (1998 NKAS) and its impact on renal transplantation in the United Kingdom over 5 years. The 1998 NKAS was based on three tiers of patients defined by human leukocyte antigen (HLA) mismatch. This involved national allocation of well-matched kidneys in tiers 1 and 2, with regional allocation for less well-matched patients in tier 3. Pediatric patients (younger than 18 years) and regional patients were prioritized in tiers 1 and 2, with a points score based on six factors determining the specific priority order for allocation. The 1998 NKAS allocated approximately half the kidneys from DHB donors to the national transplant list and resulted in significantly improved HLA matching, more than doubling the proportion of transplants that were 000 HLA-A, -B, and -DR mismatched from 7% to 16% for adults. Pediatric patients achieved comparable levels of HLA matching to adult patients for the first time in the United Kingdom through improved access to adult donor organs. The scheme also benefited highly sensitized patients and improved equity with regard to patient blood group, rareness of HLA type, and HLA homozygosity. The 1998 NKAS represented a significant advance for the allocation of DHB donor kidneys in the United Kingdom and, while not addressing inequities in access to transplant, it did largely achieve the principal goal of improving HLA matching.


Medical School Experiences Shape Women Students' Interest in Orthopaedic Surgery.
Orthopaedic surgery now has the lowest percentage of women in residency programs of any surgical specialty. Understanding factors, particularly those related to the medical school experience, that contribute to the specialty's inability to draw from the best women students is crucial to improving diversity in the profession. (1) Does required medical school exposure to orthopaedic surgery increase the proportion of women choosing the specialty? (2) Do negative perceptions deter women from choosing orthopaedic surgery? (3) What proportion of orthopaedic faculty members are women, and what proportion of residents are women? (4) To what degree has gender bias been identified in the application/interview process? Two PubMed searches of articles between 2005 and 2015 were performed using a combination of medical subject headings. The first search combined "Orthopaedics" with "Physicians, women" and phrases "women surgeons" or "female surgeons" and the second combined "Orthopedics" with "Internship & Residency" or "exp Education, Medical" and "Sex Ratio" or "Sex Factors", resulting in 46 publications of which all abstracts were reviewed resulting in 11 manuscripts that were related to the research questions. The Google Scholar search of "women in orthopaedic surgery" identified one additional publication. These 12 manuscripts were read and bibliographies of each reviewed with two additional publications identified and included. Required exposure to orthopaedics was found to be positively associated with the number of women applicants to the field, whereas negative perceptions have been reported to deter women from choosing orthopaedic surgery. Orthopaedics has the lowest percentage of women faculty and women residents (14%) compared with other specialties; this suggests that same gender mentorship opportunities are limited. For women applying to orthopaedics, gender bias is most evident through illegal interview questions, in which women are asked such questions more often than men (such as family planning questions, asked to 61% of women versus 8% of men). Successful recruitment of women to orthopaedic surgery may be improved by early exposure and access to role models, both of which will help women students' perceptions of their role in field of orthopaedic surgery.