The social play, social skills and parent-child relationships of children with ADHD 12 months following a RCT of a play-based intervention.
There is an urgent need to investigate the long-term impact of social skill interventions for children with attention deficit hyperactivity disorder (ADHD). Interventions targeting the social skills of children with ADHD have limited short-term effectiveness and rarely investigate the long-term impact. Furthermore, these interventions are most frequently conducted in the clinic setting, without including the child's natural settings and interactants, such as their regular playmates and parents. The present study investigated the social play, social skills and parent-child relationships of children with ADHD and their playmates (n = 13/group) aged 5-13 years. A two-group before and after design with a longitudinal component was applied. Participant data compared over two time points, immediately following a randomised, controlled trial (RCT) of a play-based intervention and 12 months post-RCT. From immediately following the RCT to the 12-month follow-up, children with ADHD maintained social play skill gains in the home environment. Playmates maintained social play skill gains across the home and clinic environments. Children scored within a developmentally appropriate range, falling within 1 standard deviation of the mean for social skills and most parent-child relationship scales using norm-based assessments. Results support the long-term effectiveness of the intervention.


Outcome Following Debridement, Antibiotics, and Implant Retention in Hip Periprosthetic Joint Infection-An 18-Year Experience.
Debridement-antibiotics-and-implant-retention (DAIR) may be considered a suitable surgical option in periprosthetic joint infections (PJIs) with soundly fixed prostheses, despite chronicity. This study aims to define the long-term outcome following DAIR in hip PJI. We reviewed all hip DAIRs performed between 1997 and 2013 (n = 122) to define long-term outcome and identify factors influencing it. Data recorded included patient demographics, medical history, type of DAIR performed (+/- exchange of modular components), and organisms identified. Outcome measures included complications and/or mortality rate, implant survivorship, and functional outcome (Oxford Hip Score). Most DAIRs (67%) were of primary arthroplasties and 60% were performed within 6 weeks from the index arthroplasty. Infection eradication was achieved in 68% of the first DAIR procedure. In 32 cases, more than one DAIR was required. Infection eradication was achieved in 85% of the cases (104/122) with the (single or multiple) DAIR approach. The most common complication was PJI-persistence (15%), followed by dislocation (14%). Very good functional outcomes were obtained, especially in primary arthroplasties. All streptococcus infections were resolved with DAIR and had better outcome. Twenty-one hips have been revised (17%) to-date, 16 were for persistence of PJI. The 10-y implant survivorship was 77%. Early PJI and exchanging modular components at DAIR were independent factors for a 4-fold increased infection eradication and improved long-term implant survival. DAIR is, therefore, a valuable option in the treatment of hip PJI, especially in the early postoperative period (≤6 weeks), with good outcomes. However, DAIR is associated with increased morbidity; further surgery may be necessary and instability may occur. Where possible, exchange of modular implants should be undertaken.


[Occurrence of congenital malformations in dead fetuses and neonates autopsied between 1991 and 2001 at the Institute of Pathology and Histology in Novi Sad].
Congenital malformations are morphological developmental anomalies visible during clinical examination or autopsy (in case of death, stillborn or abortion). Their incidence in human population is estimated to be between 5-10%, and perinatal mortality rate varies from 20-25%. The research was conducted at the Department of Pathology and Histology and at the Department of Obstetrics and Gynecology in Novi Sad. We analyzed autopsy reports of newborns (under 28 days old), stillborns and miscarried fetuses in 1991 and 2001. Data on type and incidence of malformations in 1991 and 2001 were compared in order to determine statistically significant differences. Autopsy reports for 1991 revealed malformations in 21 cases, whereas autopsies were performed in 103 fetuses and newborns. The total number of deliveries at the Department of Obstetrics and Gynecology in Novi Sad was 6,160. Autopsy reports for 2001 revealed malformations in 33 cases, and autopsies were performed in 126 fetuses and newborns. The total number of deliveries at the Department of Obstetrics and Gynecology in Novi Sad was 6,101. Comparison regarding incidence of malformations in 1991 and 2001, showed no statistically significant difference. Congenital malformations are the most important cause of prenatal and perinatal mortality and morbidity. One reason for that is better treatment of other diseases, but on the other side, there are more toxic materials in human environment. It is concluded that the incidence of congenital malformations in mortality of fetuses and newborns is high (20.39% in 1991, and 26.19% in 2001). We can also point to increase of central nervous system malformations in comparison with malformations of other organ systems.


Heparanase procoagulant activity is elevated in women using oral contraceptives.
What is the effect of estrogen on heparanase procogulant activity? Estrogen increases heparanase procoagulant activity. Estrogen therapy increases the risk of thrombosis and was previously found to up-regulate heparanase expression. Heparanase is involved in angiogenesis and metastasis, and has been shown to form a complex with tissue factor (TF) and also shown to enhance the generation of factor Xa. A case-control study. Thirty-four healthy women using oral contraceptives (OC) and 41 women not using hormonal therapy and not pregnant per history were enrolled, over a 5-month period, at the Rambam Medical Center, Haifa, Israel. In vitro, estrogen receptor-positive (MCF-7) and -negative (MDA-231) cell lines were incubated with estrogen, tamoxifen and ICI-182.780 a pure estrogen receptor antagonist. The cell medium was evaluated for TF/heparanase complex activity, TF activity and heparanase procoagulant activity by chromogenic substrate. Exclusion criteria included age <18 years, post-menopausal women, concomitant medications other than supplement minerals and vitamins, acute or chronic illness. The study demonstrates increased risk of high heparanase procoagulant activity in OC users. When a cutoff level of 0.25 (absorbance 405-490 nm) was set, the odds ratio was 131 (P < 0.0001). When all results were studied by quartiles, in quartiles 3 and 4 the results were almost exclusively of the OC users (P < 0.0001). In cell cultures, estrogen and tamoxifen increased heparanase procoagulant activity in the medium of estrogen receptor-positive (MCF-7) cells. The main limitation of the current study is that the two estrogens given to the women and cell cultures, ethinyl estradiol (EE) and 17-β-estradiol (E2), respectively, may have different effects on the coagulation system, although an increase in heparanase procoagulant activity was demonstrated in both of them. Although the sample size of the study group was limited, significant differences in the activation of the extrinsic coagulation pathway were demonstrated. The clinical relevance of the heparanase procoagulant activity assay as a screening tool in thrombophilia work-up should further be elucidated.


Characterization of age-related variation in corneal biomechanical properties.
An experimental study has been conducted to determine the stress-strain behaviour of human corneal tissue and how the behaviour varies with age. Fifty-seven well-preserved ex vivo donor corneas aged between 30 and 99 years were subjected to cycles of posterior pressure up to 60 mm Hg while monitoring their behaviour. The corneas were mechanically clamped along their ring of scleral tissue and kept in physiological conditions of temperature and hydration. The tissue demonstrated hyper-elastic pressure-deformation and stress-strain behaviour that closely matched an exponential trend. Clear stiffening (increased resistance to deformation) with age was observed in all loading cycles, and the rate of stiffness growth was nonlinear with bias towards older specimens. With a strong statistical association between stiffness and age (p < 0.05), it was possible to develop generic stress-strain equations that were suitable for all ages between 30 and 99 years. These equations, which closely matched the experimental results, depicted corneal stiffening with age in a form suitable for implementation in numerical simulations of ocular biomechanical behaviour.


Success of a scholarship scheme for rural students.
Mosvold Hospital is one of 5 district hospitals providing care for 555,000 indigent people in the Umkhanyakude district, northern KwaZulu-Natal. Recruitment of professional staff is an ongoing challenge for hospital management. An innovative, locally based scholarship scheme, the Friends of Mosveld Scholarship Scheme (FOMSS), was established in 1998 to: (i) identify and fund local scholars admitted to a tertiary facility to study health science courses; (ii) support these students at university or technikon; and (iii) ensure that graduates were integrated into the workforce within the district. To determine the perceptions of FOMSS-supported graduates with regard to the factors leading to success at university/technical college. All graduates from the 1999-2002 cohort of students awarded a scholarship by the FOMSS were invited to participate. Focus group discussions or free-attitude interviews were conducted, followed by a self-administered questionnaire. Twenty-four students from Umkhanyakude district supported by the FOMSS have graduated. Eighteen are working in the district, 1 has died, 2 have completed their contract time, 1 is doing further studies and 2 are completing their internships. Factors contributing to their success include personal motivation, support at university, and holiday work experience. Despite educational challenges, students from rural areas are able to succeed at tertiary institutions and will return to work in rural districts. District hospitals can play an important role in the selection and support of students of rural origin.


Enhanced propagation in a plasmonic chain waveguide with nanoshell structures based on low- and high-order mode coupling.
We studied the performance of a plasmonic chain waveguide by employing an array of nanoshell structures. The optical properties of the proposed structures are discussed in detail with respect to the mode coupling for both low-order resonances and high-order multipolar modes. We show (a) that the choice of nanoshell particles allows an easy tuning of the structure's resonances according to given wavelength specifications and (b) that the resonances are insensitive to the chain length when high-order multipolar modes are involved. Moreover, chain waveguides that are operated on resonant multipolar modes provide propagation lengths up to 1.88 microm, which is beyond what is maximally achieved by conventional solid particle chains. This is attributed to the large field enhancement within metallic nanoshell structures, as well as to far-field effects, which play an important role in low-loss light guiding along nanoshell chains.


Heart failure with preserved ejection fraction: hypertension, diabetes, obesity/sleep apnea, and hypertrophic and infiltrative cardiomyopathy.
The detailed pathophysiology of heart failure with preserved ejection fraction (HF-PEF) remains an area of active research and controversy; however, abnormalities of diastolic function are generally believed to play an important role. Most commonly, diastolic dysfunction occurs as a consequence of myocyte hypertrophy, endomyocardial fibrosis, and abnormalities of intracellular calcium handling that are related to normal myocardial aging and accelerated by comorbidities such as hypertension, diabetes, coronary artery disease, and obesity. In this article, three fundamental risk factors are considered for "secondary" diastolic dysfunction and HF-hypertension, diabetes, and obesity-with an emphasis on the clinical epidemiology, pathophysiologic mechanisms, and treatment implications of each. The article concludes with a brief discussion of "primary" diastolic HF due to infiltrative or restrictive cardiomyopathies.


Falling: why and what to do about it.
Some 5% of all hospitalizations are due to falls--an average length of stay varies between 8 and 15 days. Some studies report the number one reason for admission to a skilled nursing facility is falls. Who is at risk and what can be done? Assessing the risk factors and introducing a "prosthetic environment" can reduce mobility limitations.


Transplantation of gene-modified haematopoietic stem cells: Application and clinical considerations.
Autologous and allogeneic haematopoietic stem cell (HSC) transplantation has been performed in patients with various malignant and non-malignant haematological disorders for more than 50 years. Ex vivo gene modification of HSCs for autologous transplantation opens up new therapeutic avenues for genetic and infectious diseases. Major advances have been made over the last three decades with respect to gene modification of HSCs and transplantation strategies, ultimately culminating in the approval of two such therapies in Europe (Strimvelis for a rare primary immune deficiency, and LentiGlobin for beta-thalassaemia). Newer gene-modifying technologies and treatment regimens have also recently come to the fore, which hold great promise for the development of safer and more effective treatments. We provide an overview of the current state of gene-modified HSC therapies, highlighting success stories, limitations and important considerations for achieving successful translation of these therapies to the clinic.


Adenosine attenuation of the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers.
Adenosine is known to have effects on electrophysiologic parameters of the sinus node, AV node and atrium and to antagonize isoproterenol-induced increased inotropy in the ventricle. However, the effects on cardiac Purkinje fibers are not well established. Therefore, the purpose of the present experiments was to examine the effects of adenosine alone and adenosine on isoproterenol-treated canine cardiac Purkinje fibers. Microelectrode techniques were used to record transmembrane action potentials. Adenosine alone (10(-7) to 10(-4) M) produced no effects on action potential characteristics of paced fibers. Adenosine in concentrations of 10(-7), 10(-6), 10(-5) and 10(-4) M produced a 15, 24, 44* and 72*% attenuation of isoproterenol (10(-6) M)-induced action potential duration shortening, respectively (*P less than .001). In 7 of 7 fibers depolarized with 22 mM K+, adenosine (10(-4) M) ablated calcium-dependent action potentials restored with isoproterenol (10(-6) M). These effects were antagonized by theophylline (5 X 10(-5) M) and adenosine deaminase (1 U/ml). Action potential shortening due to superfusion of high calcium Tyrode's solution and calcium-dependent action potentials generated in Na+ free-high Ca++ Tyrode's solution were not antagonized by adenosine. Adenosine (10(-5) M) produced a negative chronotropic effect, increasing escape intervals from 2669 +/- 647 to 3702 +/- 717** msec in control fibers and from 1864 +/- 329 to 2658 +/- 399** msec in tyramine (10(-4) M)-treated fibers (**P less than .05), but failed to produce a negative chronotropic response in fibers pretreated with propranolol (10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)


Gender-Related Challenges in Educational Interventions with Syrian Refugee Parents of Trauma-Affected Children in Turkey.
Since 2012, more than three million Syrian refugees have fled to Turkey. While these refugees vary in socioeconomic background, it is notable that 50% of Syrian refugee children in Turkey display symptoms of post-traumatic stress and that more than 663,138 of these children between the ages of six and seventeen are not enrolled in school. For those children who are in school, high levels of trauma have significant implications for the education system as trauma alters the brain and affects the way children learn. A Global Voice for Autism is an international non-governmental relief and development organization that exists to equip teachers and families in conflict-affected communities. Its intent is to support the development and success of children with autism and trauma-related behavioral challenges in their classrooms, home, and communities. The instabilities inherent in the Syrian refugee experience pose a number of challenges to the organization's effective implementation of programming. The experiences of refugees in Turkey are highly gendered. Therefore, a qualitative gender analysis was conducted to address and better understand the challenges faced when carrying out these educational interventions. The article examines domestic violence, sexual violence, and masculinity as gender-driven constructs that influence how refugees experience trauma. In addition, structural issues in existing support systems all present significant challenges to Syrian refugee parents that impede effective program implementation. It is imperative to assess structural issues in existing support services to address these challenges and to successfully carry out meaningful and impactful programming. This Brief Report provides a series of recommendations in order to ameliorate these challenges and increase the efficacy of educational interventions with Syrian refugee parents of trauma-affected and vulnerable children in Turkey. It concludes with a call for policy changes that protect refugees from deportation when accessing support services and a network of services that do not require residency permits. It calls for increased integration of parent trauma support in educational intervention trainings and the creation of safe spaces where mothers and fathers can discuss their own trauma and challenges in the hope of significantly enhancing program efficacy.


Lack of prognostic value of mean corpuscular volume with capecitabine therapy in metastatic breast cancer.
Capecitabine is an oral fluoropyrimidine derivative which is frequently used alone or in combination regimens for the treatment of metastatic breast cancer. Although overall and progression free survivals have increased in recent years with the use of new generation drugs, predictive factors that would further improve the outcomes are needed. Previous studies have demonstrated the relation between post-treatment increase in mean corpuscular volume (MCV) and predicting therapy response as well as survival. The present study investigated the clinical impact of MCV elevation in metastatic breast cancer patients treated with capecitabine. The data of a total of 82 patients from three centers followed between June 2005 and June 2013 were retrospectively analyzed. The demographic data and hormone receptor status of the patients, as well as initial examination before and after treatment and data concerning progression were recorded. MCV ≥ 100 fl was considered as macrocytosis. Capecitabine was given at a dose of 2500 mg/m2 daily for 14 days every three weeks. Pre-treatment and post-treatment MCV and other parameters of complete blood count were recorded. Post-treatment initial evaluation was performed after 2 cycles of therapy. The median age of the patients was 46.5 years (range 26-72 years) and 54% were premenopausal. Performance status was ECOG 0 and 1 in 81 (99%) patients. The median number of cycles for capecitabine therapy was 5 (min-max: 2-18). The median ΔMCV level (post-treatment values at sixth week - baseline) was 6.4. Whilst ΔMCV was ≥ 6.4 in 42 patients, it was <6.4 in 40 patients. Clinical benefit (complete response+partial response+stable disease) was observed in 37 (88%) of 42 patients with a median ΔMCV ≥ 6.4 and in 30 (75%) of 40 patients with ΔMCV <6.4 with no statistically significant difference (p=0.158). No significant difference was determined between the group with ΔMCV ≥ 6.4 and the group with ΔMCV <6.4 in terms of progression-free survival (11 vs 12 months) (p=0.55) and overall survival (20 months vs. 24 months) (p=0.11). The identification of new predictive markers in metastatic breast cancer is very important. In some recent studies, increase in MCV has been suggested as a marker in tumor response. In the present study, however, no significant difference was determined between tumor response and increase in MCV. Further studies including higher numbers of patients are needed to determine whether increase in MCV is a predictive marker or not.


Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease.
The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from randomized human clinical trials is very limited. We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease (CAD) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease. In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial, 75 stable-CAD patients received 350 mg/day of placebo, resveratrol-containing grape extract (grape phenolics plus 8 mg resveratrol) or conventional grape extract lacking resveratrol during 6 months, and a double dose for the following 6 months. Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed. Moreover, the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells (PBMCs) was explored using microarrays and functional gene expression analysis. After 1 year, in contrast to the placebo and conventional grape extract groups, the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin (9.6 %, p = 0.01) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 (PAI-1) (-18.6 %, p = 0.05). In addition, 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited, with 27 extracellular-space acting genes involved in inflammation, cell migration and T-cell interaction signals presenting downregulation (p < 0.05) in PBMCs. No adverse effects were detected in relation to the study products. Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence-based standards, by increasing serum adiponectin, preventing PAI-1 increase and inhibiting atherothrombotic signals in PBMCs.


Beneficial effects of voluntary wheel running on activity rhythms, metabolic state, and affect in a diurnal model of circadian disruption.
Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). Physical exercise synchronizes the circadian system and has ameliorating effects on the depression- and anxiety-like phenotype induced by circadian disruption in mice and sand rats. We explored the beneficial effects of voluntary wheel running on daily rhythms, and the development of depression, T2DM, and CVD in a diurnal animal model, the fat sand rat (Psammomys obesus). Voluntary exercise strengthened general activity rhythms, improved memory and lowered anxiety- and depressive-like behaviors, enhanced oral glucose tolerance, and decreased plasma insulin levels and liver weight. Animals with access to a running wheel had larger heart weight and heart/body weight ratio, and thicker left ventricular wall. Our results demonstrate that exercising ameliorates pathological-like daily rhythms in activity and blood glucose levels, glucose tolerance and depressive- and anxiety-like behaviors in the sand rat model, supporting the important role of physical activity in modulating the "circadian syndrome" and circadian rhythm-related diseases. We suggest that the utilization of a diurnal rodent animal model may offer an effective way to further explore metabolic, cardiovascular, and affective-like behavioral changes related to chronodisruption and their underlying mechanisms.


MR of the eye with retrobulbar anesthesia.
MR imaging with retrobulbar anesthesia was performed in eight patients with uveal melanoma. Injection of 2 mL prilocain hydrochloride in 2% epinephrin into the eye muscle cone resulted in improved image quality in seven patients, without side effects. Ocular MR imaging can be indicated to clarify indeterminate sonographic findings in cases of extrascleral growth or to exclude optic nerve invasion in patients with tumors located at the posterior pole of the globe.


[Percentages and functions of natural killer cell subsets in peripheral blood of patients with severe aplastic anemia].
To analyze the percentage and functional changes of natural killer (NK) cell subsets in peripheral blood of severe aplastic anemia (SAA) patients before and after immunosuppressive therapy (IST) so as to evaluate the relationships between these changes and hematopoietic functions and explore the role of NK cells in the pathogenesis of SAA. By flow cytometry, the percentages of NK cells (CD3(-)CD56(+)CD16(+)) and its subsets [CD3(-)CD56(bright)CD16(-)(CD56(bright)), CD3(-)CD56(dim) CD16(+)(CD56(dim)), CD3(-)CD56(-)CD16(+)] in peripheral blood lymphocytes were detected in 12 untreated patients, 30 recovered patients and 13 normal controls respectively from April 2010 to December 2010 in our hospital. NK cells activating receptors (NKG2D and NKp46), perforin and granzyme-β of patients and normal controls were also detected. The correlation between these changes and hematopoietic functions, including the percentages of neutrophil granulocyte (ANC%), lymphocyte and reticulocyte absolute value in peripheral blood, and hyperplasia degree, percentage of granulocytes, erythrocytes, lymphocytes and megakaryocytes absolute value in bone marrow were evaluated. (1) The percentages of NK cells (10.30% ± 6.08%) and CD56 bright cells (0.11%) in untreated patients were significantly lower than those of recovered patients (16.47% ± 8.29%, 0.68%, both P < 0.05) or normal controls (19.45% ± 6.88%, 0.53%, both P < 0.05). The percentage of CD56(dim) cells in untreated patients was significantly lower than that of normal controls (9.62% ± 6.04% vs 18.21% ± 7.16%, P < 0.05). The percentage of CD3(-)CD56(-)CD16(+) cells was significantly higher in recovered patients than that of untreated patients or normal controls (0.79% vs 0.37%, 0.41%, both P < 0.05). (2) The expression of NKp46 and perforin of NK cells in untreated (88.23%, 64.97% ± 21.61%) and recovered patients (82.97%, 66.14% ± 20.73%) were significantly higher than those of healthy controls (40.99%, 42.11% ± 27.25%, all P < 0.05). (3) The percentage of NK CD56(bright) and CD3(-)CD56(-)CD16(+) cells of patients was positively correlated with ANC% (r = 0.423, 0.609, 0.468 respectively, all P < 0.05) and the percentage of granulocytes in bone marrow (r = 0.357, 0.517, 0.434 respectively, all P < 0.05). The percentages of NK, CD56(bright), CD56(dim) and CD3(-)CD56(-)CD16(+) cells were positively correlated with the hyperplasic degree of bone marrow (r = 0.455, 0.412, 0.404, 0.451 respectively, all P < 0.05), but they were negatively correlated with the percentage of lymphocytes in bone marrow (r = -0.522, -0.435, -0.411, -0.547 respectively, all P < 0.05). The expression of NKG2D, NKp46, perforin and granzyme-β of NK cells had no correlation with hematopoiesis (all P > 0.05). The lowered percentage of NK CD56(bright), CD56(dim) cells and a higher expression of perforin may cause the over-function of T lymphocytes and thus lead to hematopoietic failure in SAA.


Abrogation of Fv-1 restriction by genome-deficient virions produced by a retrovirus packaging cell line.
The Fv-1b-mediated restriction of N-tropic retrovirus vector infection of BALB/3T3 cells was partially abrogated by prior infection with N-tropic murine leukemia virus. Likewise, abrogation of the Fv-1b restriction of N-tropic murine leukemia virus replication was accomplished by prior infection with genome-deficient virions produced by an N-tropic murine leukemia virus packaging cell line. The latter observation suggests that the Fv-1 target in genome-deficient virions abrogates Fv-1 restriction in the absence of any viral genome-directed processes.


Time to pediatric epilepsy surgery is related to disease severity and nonclinical factors.
To identify clinical and nonclinical factors associated with time from epilepsy onset to surgical evaluation and treatment among a cohort of children having epilepsy surgery. Data were abstracted from records of 430 children (younger than 18 years) who had epilepsy neurosurgery at the University of California, Los Angeles from 1986 to 2010. Multivariable Cox proportional hazards models were used to analyze unique associations of clinical severity, pre-referral brain MRI, and sociodemographic characteristics with time to surgery. Shorter time to surgery was associated with active (hazard ratio [HR] 5.67, 95% confidence interval [CI] 3.74-8.70) and successfully treated infantile spasms (HR 2.20, 95% CI 1.63-2.96); daily or more seizures (HR 2.09, 95% CI 1.58-2.76); MRI before referral regardless of imaging findings (HR 1.95, 95% CI 1.47-2.58); private insurance (HR 1.54, 95% CI 1.14-2.09); and Hispanic ethnicity (HR 1.38, 95% CI 1.01-1.87). There were race/ethnicity by insurance interactions (log-rank p = 0.049) with shortest time to surgery for Hispanic children with private insurance. Shorter intervals to surgical treatment were associated with greater epilepsy severity and insurance type, consistent with existing literature. However, associations of shorter times to treatment with having a brain MRI before referral and Hispanic ethnicity were unexpected and warrant further investigation. More knowledgeable referring providers and parents with greater help-seeking capability may explain obtaining an MRI before referral. Shorter intervals to surgery among Hispanic children may relate to the same factors yielding an increased volume of Hispanic children receiving surgery at the University of California, Los Angeles since 2000.


The spin glass delafossite CuFe(0.5)V(0.5)O(2): a dipolar glass?
The ferroelectric and spin glass properties of CuFe(0.5)V(0.5)O(2) have been studied. Magnetization, ac magnetic susceptibility and specific heat measurements reveal a spin glass behavior (T(f) = 20.5 K) for this delafossite. In CuFeO(2), substitution of trivalent diamagnetic cations for Fe(3 + ) is known to change the antiferromagnetic state and induce ferroelectricity. But partial occupation of the Fe(3 + ) site by V(3 + ) is responsible for disordered magnetism in CuFe(0.5)V(0.5)O(2). The dielectric permittivity shows a frequency dependence reminiscent of relaxor ferroelectrics in which different cations occupy the same crystallographic site. Polarization measurements show the existence of a ferroelectric state below T(f) with P(5 K)≈1.3 µC m( - 2). These results point towards a relaxor-type ferroelectricity originating from a disordered array of magnetic cations. A clear coupling between electronic charges and spins is evidenced by the magnetodielectric effect.


Students with disabilities: a national survey of participation in school activities.
The policies of integration and full inclusion in school activities have been enacted to promote the independence and social participation of students with disabilities. This study examined the nature and extent of participation in schools by students with disabilities in the context of the physical, social and psychological features of the school environment. A national survey was completed by 1180 teachers of students with disabilities in the US describing student participation in school activities encompassing involvement in social activities, sports, academic and artistic/creative endeavours. Multivariate analysis revealed that school life in elementary, middle and high school could be defined by six distinct factors describing individual and group roles. Structural equation modelling yielded a second order latent variable that captured the complex and multi-dimensional aspect of participation, accounting for availability, eligibility, student characteristics/status, and student choice within a larger framework of participation.


Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas.
Within tumours, many non-neoplastic cells such as fibroblasts, endothelial cells, and macrophages assist tumour growth by producing various growth factors and pro-angiogenic cytokines. Various tumour-derived molecules drive tumour-associated macrophages towards an anti-inflammatory phenotype (M2) and thus promoting tumour growth. Here we investigated microglia/macrophage differentiation in glioma tissues by means of immunostaining of paraffin-embedded glioma samples. The number of microglia/macrophages with positive staining for CD163 and CD204, which are believed to be markers for M2 macrophages, was correlated with the histological grade of the gliomas. The ratio of M2 macrophages in the tumour-associated microglia/macrophages was also associated with the histological grade. Culture supernatant from the glioma cell line can stimulate macrophages to develop into the M2 phenotype in vitro. Macrophage colony-stimulating factor (M-CSF), which strongly induces M2 polarization of macrophages, was significantly correlated with histological malignancy and with the proportion of M2 microglia/macrophages in vivo. In addition, the proportion of M2 microglia/macrophages and M-CSF expression in tumour cells correlated well with proliferation of glioblastoma cells. These results suggest that tumour-derived M-CSF induces a shift of microglia/macrophages towards the M2 phenotype, which influences tumour growth. Evaluation of the proportion of M2 microglia/macrophages and M-CSF expression in tumour tissue would be useful for assessment of microglia/macrophage proliferative activity and the prognosis of patients with gliomas.


Disease manifestations of canine distemper virus infection in ferrets are modulated by vitamin A status.
The measles virus (MV) causes half a million childhood deaths annually. Vitamin A supplements significantly reduce measles-associated mortality and morbidity. The mechanisms whereby vitamin A acts against MV are not understood and currently there is no satisfactory small animal model for MV infection. We report on the development of a ferret model to study antiviral activity of vitamin A against canine distemper virus (CDV). CDV is closely related to MV at the molecular level and distemper in ferrets mimics measles in humans. We infected vitamin A-replete (control) and vitamin A-depleted ferrets with CDV and assessed the ability of high-dose vitamin A supplements to influence CDV disease. In control ferrets, CDV infection caused fever, rash, conjunctivitis, cough, coryza, and diarrhea. In contrast, control ferrets that were given 30 mg of vitamin A did not develop typical distemper after infection and exhibited only a mild rash. The supplement did not negatively affect ferret health and resulted in a 100% increase in serum and liver vitamin A concentrations. We also found that profound vitamin A deficiency is inducible in ferrets and can be rapidly reversed upon high-dose vitamin A supplementation. Vitamin A deficiency caused anorexia, diarrhea, cataracts, behavioral abnormalities, and ultimately death, with or without CDV infection. All ferrets that received vitamin A supplements, however, recovered uneventfully from CDV infection. These results replicate many aspects of the observations of vitamin A therapy in humans with measles and suggest that CDV infection in ferrets is an appropriate model for the study of the antiviral mechanism of vitamin A.


Induced sputum cell and fluid-phase indices of inflammation: comparison of treatment with dithiothreitol vs phosphate-buffered saline.
Treatment of sputum with dithiothreitol (DTT) gives reliable measurements of cellular and fluid-phase markers of airway inflammation. We investigated the extent to which DTT treatment influences these measurements as compared with phosphate-buffered saline (PBS). Hypertonic saline-induced sputum, collected from 20 asthmatic subjects, was examined within 2 h. All portions which looked more solid (less fluid) than saliva were collected from the expectorate. The selected sputum was then divided into two portions: one treated with one volume of DTT and one volume of PBS, the other with two volumes of PBS. The filtrates were assessed blind for total and differential cell count, viability, and fluid-phase eosinophil cationic protein (ECP), fibrinogen, interleukin (IL)-5 and IL-8. Sputum treated with DTT compared with PBS had lower proportions of viable cells (median 66 versus 74%; p=0.003). In contrast, DTT-treated sputum had higher total cell counts (median 8.8 vs 2.8 x 10(6) mL(-1); p<0.001) and levels of ECP (median 1340 vs 584 mg x L(-1); p<0.001) The measurements were similar with respect to the proportion of eosinophils, neutrophils, lymphocytes, macrophages, and fluid-phase fibrinogen, IL-5 and IL-8. We conclude that dithiothreitol disperses cells more effectively and that this might account for the higher levels of eosinophil cationic protein. Dithiothreitol may affect cell viability, but the changes are not relevant with respect to cell counts. Additionally, dithiothreitol does not seem to influence the other measurements performed.


Calibration and validation of solar radiation-based equations to estimate crop evapotranspiration in a semi-arid climate.
The Abtew and Jensen-Haise solar radiation-based equations were used to estimate evapotranspiration, considering the limited climatic data in many locations. Both equations were proven to successfully predict the potential evapotranspiration (ETO) compared with the standard Penman-Monteith (PM) method in two Mediterranean countries. Calibration of the constant coefficient k of the Abtew equation showed substantial differences compared to recommended values (1.22 vs. 0.53), with the highest values observed during September (1.46). Validation of ETO measurements using calibrated Abtew equation against the PM method indicated a high correlation coefficient (r2 = 0.97, RMSE = 0.61). Further, evapotranspiration requirements, using the calibrated empirical equation, were calculated for olives (449 mm) and citrus (807 mm) showing a good agreement with recommended values for dry climate regions. Therefore, the tested equations could be safely used to predict frequencies and doses of irrigation in semi-arid climates, considering limited climatic data availability.


Exclusive measurement of the pp --> pppi(+)pi(-) reaction near threshold.
The pp-->pp pi(+) pi(-) reaction has been measured exclusively near threshold at CELSIUS. The total cross sections are nearly an order of magnitude lower than expected from previous inclusive measurements. The differential cross sections reveal pp-->pp(*)(1440)-->pp sigma = pp(pi(+)pi(-))(I = l = 0) as the dominant process as well as significant contributions from p(*)-->Delta(++)pi(-)-->psigma. The observed anisotropy in the proton angular dependence is consistent with heavy-meson exchange. In the invariant mass spectra, no narrow structures of statistical relevance (3sigma) are found.


Gut flora in health and disease: potential role of probiotics.
In a young evolving science, there are always more questions than answers. That is also the situation in the emerging field of Probiotics, and this was made very clear at the International Probiotics Workshop in Amsterdam. In the report of this workshop, we present a selection of the most urgent questions in the field of probiotics. In addition, we propose a few strategies for the future of probiotics research. During the workshop, 120 experts--from disciplines including Human Nutrition, Gastroenterology, Nutritional Therapy, Cell Biology, Microbiology and Immunology--discussed new views on microbe-host interactions and the role of probiotics in prevention and alleviation of gastro-intestinal, atopic and auto-immune diseases. There is a general consensus among the experts that administering defined strains can help in preventing and curing gut flora related diseases: the first clinical trials show a promising role for probiotics. But the system is very complex, and most underlying mechanisms are still unclear. Rapid progress in this field will depend largely on the collaboration between fundamental researchers from different disciplines and medical specialists. Besides, more clinical studies are required to convince authorities and the public of the value of microbial therapies.


Purification of an EH domain-binding protein from rat brain that modulates the gating of the rat ether-à-go-go channel.
Mutations in the gene encoding ether-à-go-go (EAG) potassium channel impair the function of several classes of potassium currents, synaptic transmission, and learning in Drosophila. Absence of EAG abolishes the modulation of a broad group of potassium currents. EAG has been proposed to be a regulatory subunit of different potassium channels. To further explore this regulatory role we searched for signaling molecules that associate with EAG protein. We have purified a approximately 95-kDa protein from rat brain membranes that binds to EAG. When co-expressed in mammalian cells this protein coimmunoprecipites with EAG and alters the gating of EAG channels. Expression of this protein is regulated during neuronal differentiation. The protein is identical to the recently reported rat protein epsin, which is an EH domain-binding protein similar to the Xenopus mitotic phosphoprotein MP90. These results show that proteins of the epsin family are modulators of channel activity that may link signaling pathways, or the cell cycle, to EAG and thus to various potassium channel functions.


Gender-specific regulation of tyrosine hydroxylase in thymocyte differentiation antigen-1 knockout mice.
Thymocyte differentiation antigen-1 (Thy-1) is a cell surface glycoprotein found on T cells and neurons and is involved in cell-to-cell interactions. In addition, Thy-1 knockouts (KO) are a potential mouse model of restless legs syndrome (RLS) based on clinical observations and the role of dopamine in the disease. In this study, we analyzed the activity and quantity of tyrosine hydroxylase (TH; the rate-limiting enzyme in dopamine production) and determined phosphorylation levels for the enzyme phosphoserine-40 (pSer-40). There was no significant difference in the total TH activity and pSer-40 TH levels between Thy-1 KO and control groups; however, TH specific activity was significantly lower (by 26%) in Thy-1 KO mice. This difference is due in part to increased TH protein levels in this group (increased by 29%). When analyzed by gender, Thy-1 KO female mouse striata contained less TH specific activity compared with control females (decreased by 41%) and male control or Thy-1 KO animals (decreased by 30%). TH specific activity and pSer-40 TH levels in male Thy-1 KO and control displayed no differences. However, pSer-40 TH was significantly higher in control females (38%) compared with control or Thy-1 KO males. The Thy-1 KO females exhibited significantly lower (28%) pSer-40 TH (normalized to GAPDH or TH) than control females. Indeed, the Thy-1 KO females had 50% of the pSer-40 TH found in controls. Our results suggest a gender effect on TH specific activity, TH protein levels, and serine-40 phosphorylation of TH in Thy-1 KO female mice.


The engineering of biomaterials exhibiting recognition and specificity.
Although synthetic materials are now widely used in implanted medical devices, they are not engineered for recognition and specificity. This article considers the design of polymer surfaces that might be specifically recognized and trigger normal healing pathways. The technological advances that will contribute to biorecognition biomaterials include surfaces to inhibit non-specific interactions, self-assembly to create ordered surface structures and strategies to place recognition sites on surfaces by random arrays of groups and by templates.


Distribution, number, and certain neurochemical identities of infracortical white matter neurons in the brains of three megachiropteran bat species.
A large population of infracortical white matter neurons, or white matter interstitial cells (WMICs), are found within the subcortical white matter of the mammalian telencephalon. We examined WMICs in three species of megachiropterans, Megaloglossus woermanni, Casinycteris argynnis, and Rousettus aegyptiacus, using immunohistochemical and stereological techniques. Immunostaining for neuronal nuclear marker (NeuN) revealed substantial numbers of WMICs in each species-M. woermanni 124,496 WMICs, C. argynnis 138,458 WMICs, and the larger brained R. aegyptiacus having an estimated WMIC population of 360,503. To examine the range of inhibitory neurochemical types we used antibodies against parvalbumin, calbindin, calretinin, and neural nitric oxide synthase (nNOS). The calbindin and nNOS immunostained neurons were the most commonly observed, while those immunoreactive for calretinin and parvalbumin were sparse. The proportion of WMICs exhibiting inhibitory neurochemical profiles was ~26%, similar to that observed in previously studied primates. While for the most part the WMIC population in the megachiropterans studied was similar to that observed in other mammals, the one feature that differed was the high proportion of WMICs immunoreactive to calbindin, whereas in primates (macaque monkey, lar gibbon and human) the highest proportion of inhibitory WMICs contain calretinin. Interestingly, there appears to be an allometric scaling of WMIC numbers with brain mass. Further quantitative comparative work across more mammalian species will reveal the developmental and evolutionary trends associated with this infrequently studied neuronal population.


Perioperative management of antithrombotic therapy.
The management of patients who require temporary interruption of warfarin therapy because of elective surgery or another invasive procedures is clinically important because of the increasing prevalence of patients who are receiving warfarin and the availability of low-molecular-weight heparins, which facilitate out-of-hospital perioperative anticoagulation. The two main issues that need to be considered in perioperative anticoagulant management is the patient's risk of a thromboembolic event when warfarin therapy is interrupted and the risk of bleeding that is associated with the surgery or procedure. An assessment of these factors will determine the optimal perioperative anticoagulant management approach. The overall objective of this review is to provide a practical approach relating to perioperative anticoagulation which can be used in everyday clinical practice.


First analysis of the secretome of the canine heartworm, Dirofilaria immitis.
The characterization of proteins released from filariae is an important step in addressing many of the needs in the diagnosis and treatment of these clinically important parasites, as well as contributing to a clearer understanding of their biology. This report describes findings on the proteins released during in vitro cultivation of adult Dirofilaria immitis , the causative agent of canine and feline heartworm disease. Differences in protein secretion among nematodes in vivo may relate to the ecological niche of each parasite and the pathological changes that they induce. The proteins in the secretions of cultured adult worms were run on Tris-Glycine gels, bands separated and peptides from each band analysed by ultra mass spectrometry and compared with a FastA dataset of predicted tryptic peptides derived from a genome sequence of D. immitis. This study identified 110 proteins. Of these proteins, 52 were unique to D. immitis. A total of 23 (44%) were recognized as proteins likely to be secreted. Although these proteins were unique, the motifs were conserved compared with proteins secreted by other nematodes. The present data indicate that D. immitis secretes proteins that are unique to this species, when compared with Brugia malayi. The two major functional groups of molecules represented were those representing cellular and of metabolic processes. Unique proteins might be important for maintaining an infection in the host environment, intimately involved in the pathogenesis of disease and may also provide new tools for the diagnosis of heartworm infection.


Effect of verapamil on portal and splanchnic hemodynamics in patients with advanced posthepatitic cirrhosis using duplex Doppler ultrasound.
To assess the effect of verapamil (80 mg) oral administration on portal and splanchnic hemodynamics in patients with advanced posthepatitic cirrhosis using duplex Doppler ultrasound (US). Fourteen patients with post-hepatitic liver cirrhosis were included in the study. Duplex Doppler sonographic examinations were performed before, and 2-3 h after, 80 mg verapamil oral administration. Portal and splanchnic hemodynamics including vessel diameters (mm), mean flow velocities (cm/s), blood flows (ml/min), Doppler indices such as pulsatility and resistive indices (PI and RI), were investigated before and after verapamil administration. After verapamil administration; diameter of portal vein, splenic vein, and superior mesenteric artery (SMA) showed increase of 8%, 10%, and 7% (P < 0.05 to < 0.001), respectively. Increases of 20%, 38%, and 47% were found in blood flows (P < 0.05 to < 0.0001) with respect to the above vessels. Decreases of 17%, 10%, 11%, and 7% were found in SMA PI, SMA RI, splenic artery (SA) PI, and SA RI, respectively (P < 0.05 to < 0.0001). Verapamil appears to have splanchnic, portal, splenic, portocollateral and probably intrahepatic vasodilator effects in patients with advanced posthepatitic liver cirrhosis. Verapamil should be further investigated in the treatment of patients with advanced liver cirrhosis with prospective studies measuring portal and wedged hepatic pressure.


Searching for Solvents with an Increased Carbon Dioxide Solubility Using Multivariate Statistics.
Ionic liquids (ILs) are used in various fields of chemistry. One of them is CO2 capture, a process that is quite well described. The solubility of CO2 in ILs can be used as a model to investigate gas absorption processes. The aim is to find the relationships between the solubility of CO2 and other variables-physicochemical properties and parameters related to greenness. In this study, 12 variables are used to describe a dataset consisting of 26 ILs and 16 molecular solvents. We used a cluster analysis, a principal component analysis, and a K-means hierarchical clustering to find the patterns in the dataset and the discriminators between the clusters of compounds. The results showed that ILs and molecular solvents form two well-separated groups, and the variables were well separated into greenness-related and physicochemical properties. Such patterns suggest that the modeling of greenness properties and of the solubility of CO2 on physicochemical properties can be difficult.


Catastrophic Out-of-Pocket Health Expenditure Among Rural Households in the Semi-Pastoral Community, Western Ethiopia: A Community-Based Cross-Sectional Study.
Every year, 808 million people face catastrophic health expenditure (CHE), and 122 million people were pushed into poverty. It aggravates healthcare inequalities, incurs double burden opportunity costs, and pushes households to sit in a deep poverty trap. A few studies have been done so far; however, it is not enough to inform policy decisions. Therefore, this study aimed to assess the catastrophic out-of-pocket health expenditure and associated factors among rural households in Mandura District, Western Ethiopia. We conducted a community-based cross-sectional study among the Mandura district's 488 rural households from April to May 2017. We used a multistage systematic sampling technique to select the participants. We fitted a binary logistic regression model to identify the factors associated with catastrophic out-of-pocket health expenditure. We used the adjusted odds ratio (AOR) with 95% CI and the p-value <0.05 to determine the variables associated with catastrophic out-of-pocket health expenditure. Catastrophic health expenditure (CHE) with a 40% capacity to pay (CTP) households in the study area was 22.5%. Female household head (AOR = 2.92; 95% CI: 1.44, 5.93) and household with chronic illnesses (AOR = 3.93; 95% CI: 1.78, 9.14) were positively associated with CHE and, while households who had adult household members (AOR = 0.32; 95% CI: 0.16, 0.63) were negatively associated. The overall CHE, with a 40% CTP threshold, was high. Prevention of chronic illness might help to reduce the burden of the expenditure. Strengthening financial risk protection mechanisms, such as community-based health insurance, could help bring healthcare services equity.


Variation of enhancement of photosynthesis with conditions of algal growth.
The Emerson effect was observed as an enhancement of photosynthesis in long-wavelength red light when beams of shorter wavelength were added. Two light beams of wavelengths 650 and 694 mmicro, respectively, when presented together, gave a photosynthetic rate higher than the sum of the rates obtained separately. The amount of enhancement of photosynthesis depends upon the growth conditions of algal cells, and specifically on their phosphate metabolism.


Design of a novel apparatus to study nitric oxide (NO) inhibition of platelet adhesion.
Nitric oxide (NO) is a simple biological molecule which inhibits adhesion and aggregation of platelets. A novel NO delivery device has been developed to quantitatively study the effects of NO concentration and flux on the adhesion of platelets to a surface. The slit-flow device is lined with a protein-coated membrane through which NO gas permeates into a perfusing platelet suspension. A model predicting spatial NO concentrations and fluxes within the flow slit was validated. At a wall shear rate of 250 s(-1), platelet adhesion was inhibited 87% relative to controls for exposures as low as 0.1 ppm NO. Corresponding model predictions of the aqueous NO concentration and fluxes at the surface were 0.15 nM, and between 0.5 and 1.1 nanomoles cm(-2) s(-1), respectively. Endothelial cells, which release NO to inhibit platelet adhesion in vivo, generate NO at an estimated flux similar to the above values. At a NO exposure of 0.02 ppm, platelet inhibition was only 10%. The delivery device is useful for other studies in which a knowledge of the spatial NO fluxes or concentrations is desired. Knowledge of these fluxes or concentrations is beneficial towards the design of biomaterials incorporating NO to inhibit platelet adhesion.


Sociocultural and health system factors associated with mortality among febrile inpatients in Tanzania: a prospective social biopsy cohort study.
Communicable diseases are the leading causes of death in Tanzania despite the existence of effective treatment tools. We aimed to assess the sociocultural and health system factors associated with mortality from febrile illness in northern Tanzania. We interviewed febrile inpatients to determine prevalence of barriers in seeking or receiving care and grouped these barriers using the Three Delays model (delays at home, in transport and at healthcare facilities). We assessed 6-week mortality and, after matching on age, gender and severity of illness, measured the association between delays and mortality using conditional logistic regression. We enrolled 475 children, of whom 18 (3.8%) died, and 260 adults, of whom 34 (13.0%) died. For children, home delays were not associated with mortality. Among adults, a delay in care-seeking due to not recognising severe symptoms was associated with mortality (OR: 3.01; 95% CI 1.24 to 7.32). For transport delays, taking >1 hour to reach a facility increased odds of death in children (OR: 3.27; 95% CI 1.11 to 9.66) and adults (OR: 3.03; 95% CI 1.32 to 6.99). For health system delays, each additional facility visited was associated with mortality for children (OR: 1.59; 95% CI 1.06 to 2.38) and adults (OR: 2.00; 95% CI 1.17 to 3.41), as was spending >4 days between the first facility visit and reaching tertiary care (OR: 4.39; 95% CI 1.49 to 12.93). Our findings suggest that delays at home, in transport and in accessing tertiary care are risk factors for mortality from febrile illness in northern Tanzania. Interventions that may reduce mortality include community education regarding severe symptoms, expanding transportation infrastructure and streamlining referrals to tertiary care for the sickest patients.


Sedative effect of galphimine B, a nor-seco-triterpenoid from Galphimia glauca.
Galphimia glauca Cav. (Malpighiaceae) is used in Mexican traditional medicine as a sedative in the treatment of mental disorders. Sedative properties of a methanolic extract of the aerial parts of this plant have been established in animal trials and an active compound, named galphimine B, has already been isolated. This compound was submitted to neuropharmacological testing, where it was shown that galphimine B had no significant effect as an anticonvulsant, while it exhibited a strong depressant activity on the nervous system.


Relationship between the in vivo localization and the immunoblotting pattern of anti-basement membrane zone antibodies in patients with bullous pemphigoid.
To compare the localization of anti-basement membrane zone (BMZ) antibodies bound in vivo with the antigenic specificities of circulating anti-BMZ antibodies in patients with bullous pemphigoid (BP). Comparison of the results of an examination of the skin specimens of the patients using direct immunoelectron microscopy and direct immunofluorescence on 1-mol/L sodium chloride-split skin with the results of an analysis of the corresponding serum samples using the immunoblot technique. Immunodermatology department in a teaching hospital. Thirty-six patients with typical BP and circulating anti-BMZ antibodies. Serum samples from 22 patients with BP indicated only BP antigen 1 in the results of immunoblot analysis. Using direct immunofluorescence, an analysis of the peribullous skin samples obtained from these 22 patients showed deposits of IgG exclusively located along the epidermal side of sodium chloride-split skin; the results of direct immunoelectron microscopic examination showed deposits of IgG located on the intracellular portion of hemidesmosomes in 18 (82%) of these 22 specimens, whereas 4 biopsy specimens had linear IgG deposits located both intracellularly and extracellularly along the keratinocyte plasma membrane. The results of immunoblot analysis of the serum samples from 5 patients with BP indicated BP antigen 2 alone; the results of direct immunoelectron microscopic examination of peribullous skin samples from these 5 patients showed linear intracellular and extracellular deposits along the keratinocyte membrane, corresponding to an epidermal fluorescence labeling pattern of peribullous sodium chloride-split skin in 2 patients and a combined (dermal and epidermal) pattern in 3 patients. The 2 different patterns of reactivity of anti-BMZ antibody deposits bound in vivo closely corresponded to the antigenic specificities indicated in the corresponding serum samples of the patients. These results are in accordance with those previously obtained in vitro and argue for identical binding profiles of circulating antibodies that are bound in vivo in BP.


Comparison of real-time PCR assays for detection of pathogenic Leptospira spp. in blood and identification of variations in target sequences.
Leptospirosis is considered an underdiagnosed disease. Although several PCR-based methods are currently in use, there is little information on their comparability. In this study, four quantitative real-time PCR (qPCR) assays (SYBR green and TaqMan chemistries) targeting the secY, lfb1, and lipL32 genes were evaluated as diagnostic assays. In our hands, these assays can detect between 10(2) and 10(3) bacteria/ml of pure culture, whole-blood, plasma, and serum samples. In three independent experiments, we found a slightly higher sensitivity of the PCR assays in plasma than in whole blood and serum. We also evaluated the specificity of the PCR assays on reference Leptospira strains, including newly described Leptospira species, and clinical isolates. No amplification was detected for DNA obtained from saprophytic or intermediate Leptospira species. However, among the pathogens, we identified sequence polymorphisms in target genes that result in primer and probe mismatches and affect qPCR assay performance. In conclusion, most of these assays are sensitive and specific tools for routine diagnosis of leptospirosis. However, it is important to continually evaluate and, if necessary, modify the primers and/or probes used to ensure effective detection of the circulating Leptospira isolates.


Multidrug resistance gene (MDR1) expression in human brain tumors.
Multidrug resistance for many types of cancer outside the central nervous system (CNS) has been found to be due to the overexpression of the multidrug resistance gene MDR1, of which the gene-product P-glycoprotein acts as a membrane-bound efflux pump for many anticancer drugs. To examine whether brain tumors overexpress the MDR1 gene, 25 brain-tumor specimens were subjected to Northern blot analysis: 10 gliomas, eight meningiomas, three schwannomas, one malignant lymphoma, and three tumors metastatic to the brain. Ten fresh-frozen autopsy specimens of various parts of normal brain were also analyzed. Blots were hybridized with 32P-labeled Chinese hamster complementary deoxyribonucleic acid (cDNA) and 32P-labeled human MDR1 cDNA. The MDR1 gene messenger ribonucleic acid (mRNA) was detected in two tumors using the Chinese hamster probe (one sphenoid wing meningioma and one metastatic prostate tumor) and in one CNS lymphoma using the human probe. Intact mRNA could not be extracted from the fresh-frozen autopsy specimens of normal brain. Seventeen tumors were examined for P-glycoprotein by immunohistochemical staining using murine monoclonal antibody C219: eight gliomas, eight meningiomas, and one craniopharyngioma. The neoplastic cells from two gliomas and three meningiomas and the blood vessels within six gliomas and two meningiomas stained positively for P-glycoprotein. Seven of 10 normal brain specimens stained positively for P-glycoprotein in blood vessels but no specimen demonstrated staining of parenchymal cells. This study demonstrates that the MDR1 gene can be detected in normal brain, and in malignant, benign, and metastatic lesions. P-glycoprotein can be present in tumor blood vessels even when it is not seen in neoplastic cells. Although the role of P-glycoprotein in tumor blood vessels needs to be further examined and more clearly defined, drug resistance in malignant primary brain tumors may result from characteristics not solely of neoplastic cells but also tumor vasculature.


The role of parietal cortex in overimitation: a study with fNIRS.
Previous studies have shown right parietal activation in response to observing irrational actions. Behavioral studies show that people sometimes imitate irrational actions, a phenomenon called overimitation. However, limitations on movement in functional magnetic resonance imaging (fMRI) mean that the neural basis of overimitation has not been studied. To address this, our study employed a less restrictive neuroimaging technique, functional near-infrared spectroscopy (fNIRS). Measurements were taken while participants observed either rational or irrational movements before performing movements on a computerized puzzle task. Observing irrational actions produced greater activation in right anterior inferior parietal lobule (aIPL), replicating results from the fMRI literature. This is a proof of principle that fNIRS can be used as an alternative to fMRI in social cognition experiments, and that parietal cortex has a core role in responding to irrational actions.


Responses of plant growth rate to nitrogen supply: a comparison of relative addition and N interruption treatments.
This paper investigates the effects of uptake of nitrate and the availability of internal N reserves on growth rate in times of restricted supply, and examines the extent to which the response is mediated by the different pools of N (nitrate N, organic N and total N) in the plant. Hydroponic experiments were carried out with young lettuce plants (Lactuca sativa L.) to compare responses to either an interruption in external N supply or the imposition of different relative N addition rate (RAR) treatments. The resulting relationships between whole plant relative growth rate (RGR) and N concentration varied between linear and curvilinear (or possibly bi-linear) forms depending on the treatment conditions. The relationship was curvilinear when the external N supply was interrupted, but linear when N was supplied by either RAR methods or as a supra-optimal external N supply. These differences resulted from the ability of the plant to use external sources of N more readily than their internal N reserves. These results show that when sub-optimal sources of external N were available, RGR was maintained at a rate which was dependent on the rate of nitrate uptake by the roots. Newly acquired N was channelled directly to the sites of highest demand, where it was assimilated rapidly. As a result, nitrate only tended to accumulate in plant tissues when its supply was essentially adequate. By comparison, plants forced to rely solely on their internal reserves were never able to mobilize and redistribute N between tissues quickly enough to prevent reductions in growth rate as their tissue N reserves declined. Evidence is presented to show that the rate of remobilization of N depends on the size and type of the N pools within the plant, and that changes in their rates of remobilization and/or transfer between pools are the main factors influencing the form of the relationship between RGR and N concentration.


Angiosome-Based Allografts: Vascularized Composite Allotransplantation for Tailored Subunit Reconstruction with Volkmann Ischemic Contracture as a Case in Point.
As we enter an age with new approaches to tissue reconstruction, the emphasis on the adage "like for like" has become even more relevant. This study illustrates the potential for several tailored vascularized composite allotransplantation reconstructive techniques and, in particular, for the management of Volkmann contracture. Twenty fresh cadaver dissections and 30 archival lead oxide radiographic studies were examined to (1) identify potential upper limb vascularized composite allotransplantation donor sites (i.e., elbow, forearm, and flexor tendon complex) and (2) demonstrate a "mock transplant" of the vascularized volar forearm allograft for a severe Volkmann ischemia defect. They were designed without skin to reduce antigenicity. The elbow joint was supplied within the brachial angiosome and the flexor tendon complex of the flexor digitorum superficialis and flexor digitorum profundus by the superficial palmar arch of the ulnar angiosome. The forearm allograft of flexor muscles, median, ulnar, and anterior interosseous nerves, when harvested on the brachial vessels, was supplied within the radial, ulnar, and anterior interosseous angiosomes but could be based on the ulnar artery alone because of intramuscular connections with the other territories. A mock transplant was performed with a distal-to-proximal dissection of the allograft, facilitating the best and fastest technique. This application of the angiosome concept highlights the anatomical feasibility of the volar forearm vascularized composite allotransplantation donor site focusing on a complex subunit problem in the upper limb-severe Volkmann ischemic contracture. It demonstrates the potential use and immunologic advantage of subdivided and modified nonskin variations of vascularized composite allotransplantation in reconstructive transplantation surgery. Therapeutic, V.


Differential expression of CD73, CD86 and CD304 in normal vs. leukemic B-cell precursors and their utility as stable minimal residual disease markers in childhood B-cell precursor acute lymphoblastic leukemia.
Optimal discrimination between leukemic blasts and normal B-cell precursors (BCP) is critical for treatment monitoring in BCP acute lymphoblastic leukemia (ALL); thus identification of markers differentially expressed on normal BCP and leukemic blasts is required. Multicenter analysis of CD73, CD86 and CD304 expression levels was performed in 282 pediatric BCP-ALL patients vs. normal bone marrow BCP, using normalized median fluorescence intensity (nMFI) values. CD73 was expressed at abnormally higher levels (vs. pooled normal BCP) at diagnosis in 71/108 BCP-ALL patients (66%), whereas CD304 and CD86 in 119/202 (59%) and 58/100 (58%) patients, respectively. Expression of CD304 was detected at similar percentages in common-ALL and pre-B-ALL, while found at significantly lower frequencies in pro-B-ALL. A significant association (p = 0.009) was found between CD304 expression and the presence of the ETV6-RUNX1 fusion gene. In contrast, CD304 showed an inverse association with MLL gene rearrangements (p = 0.01). The expression levels of CD73, CD86 and CD304 at day 15 after starting therapy (MRD15) were stable or higher than at diagnosis in 35/37 (95%), 40/56 (71%) and 19/41 (46%) cases investigated, respectively. This was also associated with an increased mean nMFI at MRD15 vs. diagnosis of +24 and +3 nMFI units for CD73 and CD86, respectively. In addition, gain of expression of CD73 and CD86 at MRD15 for cases that were originally negative for these markers at diagnosis was observed in 16% and 18% of cases, respectively. Of note, CD304 remained aberrantly positive in 63% of patients, despite its levels of expression decreased at follow-up in 54% of cases. Here we show that CD73, CD86 and CD304 are aberrantly (over)expressed in a substantial percentage of BCP-ALL patients and that their expression profile remains relatively stable early after starting therapy, supporting their potential contribution to improved MRD analysis by flow cytometry.


Doxorubicin-Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake.
Doxorubicin (DOX) is an effective anthracycline antibiotic drug which is commonly used in a broad range cancer therapy. However, due to dose depending side effects and toxicity to non-cancerous tissues, its clinical applications are restricted. To overcome these limitations, human serum albumin (HSA) has been investigated as a biocompatible drug delivery vehicle. In this study, human serum albumin submicron particles (HSA-MPs) were fabricated by using the Co-precipitation-Crosslinking-Dissolution technique (CCD technique) and DOX was loaded into the protein particles by absorption. DOX-HSA-MPs showed uniform peanut-like shape, submicron size and negative zeta-potential (-13 mV). The DOX entrapment efficiency was 25% of the initial amount. The in vitro release in phosphate buffered saline pH 7.4 was less than 1% within 5 h. In contrast, up to 40% of the entrapped DOX was released in presence of a protein digesting enzyme mixture (Pronase®) within the same time. In addition, in vitro cytotoxicity and cellular uptake of DOX-HSA-MPs were evaluated using the lung carcinoma cell line A549. The results demonstrated that DOX-HSA-MPs reduced the cell metabolic activities after 72 h. Interestingly, DOX-HSA-MPs were taken up by A549 cells up to 98% and localized in the cell lysosomal compartment. This study suggests that DOX-HSA-MPs which was fabricated by CCD technique is seen as a promising biopolymer particle as well as a viable alternative for drug delivery application to use for cancer therapy.


Mitogenomics phylogenetic relationships of the current sloth's genera and species (Bradypodidae and Megalonychidae).
We sequenced the complete mitogenome of 39 sloths (19 Bradypus variegatus, 4 B. tridactylus, 1 B. pygmaeus, 1 B. torquatus, 4 Choloepus didactylus, and 10 C. hoffmanni). A Bayesian tree (BI) indicated a temporal split between Bradypus and Choloepus around 31 million years ago (MYA, Oligocene) and the other major splits within each genera during the Miocene and Pliocene. A haplotype network (MJN) estimated a lower temporal split between the sloth genera (around 23.5 MYA). Both methods detected the ancestor of B. torquatus as the first to diverge within Bradypus (21 for BI and 19 MJN), followed by that of the ancestor of B. tridactylus. The split of B. pygmaeus from the common ancestor with B. variegatus was around 12 MYA (BI) or 4.3 MYA (MJN). The splits among the previous populations of B. variegatus began around 8 MYA (BI) or 3.6 MYA (MJN). The trans-Andean population was the first to diverge from the remaining cis-Andean populations of B. variegatus. The genetic differentiation of the trans-Andean B. variegatus population relative to the cis-Andean B. variegatus is similar to that found for different species of sloths. The mitogenomic analysis resolved the differentiation of C. hoffmanni from the C. didactylus individuals of the Guiana Shield. However, one C. didactylus from the Colombian Amazon specimen was inside the C. hoffmanni clade. This could be the first example of possible natural hybridization in the Amazon of both Choloepus taxa or the existence of un-differentiable phenotypes of these two species in some Amazonian areas.


The effects of hydrostatic pressure on ribosome conformation in Escherichia coli: and in vivo study using differential scanning calorimetry.
Differential scanning calorimetry of whole Escherichia coil cells allowed the detection in vivo of changes in ribosome conformation. This enabled for the first time an analysis of the effects of high hydrostatic pressures on ribosomes in living cells. A correlation was observed between loss of cell viability and decrease in ribosome-associated enthalpy in cells subjected to pressures of 50-250 MPa for 20 min. Cell death and ribosome damage were therefore closely related phenomena. In pressure-treated cells, the thermogram peak temperatures decreased, suggesting that the remaining ribosomes had adopted a less stable conformation. During subsequent incubation of the cultures at 37 degrees C, peak temperatures and enthalpies gradually increased over a period of 5 h. This change in ribosome conformation had no apparent effect on cell survival, as viability continued to decrease. The addition of 5 mM MgCl2 before pressure treatment of cells prevented the reduction in stability of surviving ribosomes but had no effect on the initial loss of enthalpy or on cell viability.


Effect of particle adsorption rates on the disproportionation process in pickering stabilised bubbles.
The degree of shrinkage of particle stabilised bubbles of various sizes, in a polydisperse bubble dispersion, has been investigated in the light of the finite adsorption times for the particles and the disproportionation kinetics of the bubbles. For the case where the system contains an abundance of particles we find a threshold radius, above which bubbles are stabilised without any significant reduction in their size. Bubbles with an initial radius below this threshold on the other hand undergo a large degree of shrinkage prior to stabilisation. As the ratio of the available particles to the bubbles is reduced, it is shown that the final bubble size, for the larger bubbles in the distribution, becomes increasingly governed by the number of particles, rather than their adsorption time per se. For systems with "adsorption controlled" shrinkage ratio, the final bubble distribution is found to be wider than the initial one, while for a "particle number controlled" case it is actually narrower. Starting from a unimodal bubble size distribution, we predict that at intermediate times, prior to the full stabilisation of all bubbles, the distribution breaks up into a bimodal one. However, the effect is transient and a unimodal final bubble size distribution is recovered, when all the bubbles are stabilised by the particles.


On the melting point depression, coalescence, and chemical ordering of bimetallic nanoparticles: the miscible Ni-Pt system.
Among the properties that distinguish nanoparticles (NPs) from their bulk counterparts is their lower melting points. It is also common knowledge that relatively low melting points enhance the coalescence of (usually) nascent nanoclusters toward larger NPs. Finally, it is well established that the chemical ordering of bi- (or multi-) metallic NPs can have a profound effect on their physical and chemical properties, dictating their potential applications. With these three considerations in mind, we investigated the coalescence mechanisms for Ni and Pt NPs of various configurations using classical molecular dynamics (MD) computer simulations. Benchmarking the coalescence process, we identified a steeper melting point depression for Pt than for Ni, which indicates a reversal in the order of melting for same-size NPs of the two elements. This reversal, also evident in the nano-phase diagram thermodynamically constructed using the regular solution model, may be useful for utilising NP coalescence as a means to design and engineer non-equilibrium NPs via gas-phase synthesis. Indeed, our MD simulations revealed different coalescence mechanisms at play depending on the conditions, leading to segregated chemical orderings such as quasi-Janus core-satellite, or core-(partial) shell NPs, despite the expected theoretical tendency for elemental mixing.


Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development.
Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV ("MesoERV1-12") were identified and verified by qPCR in mouse tissues. "MesoERV1-12" expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. "MesoERV1-12" levels were significantly increased by demethylating agent 5-Aza-2'-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. "MesoERV7" promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy.


Inhibition by fluoxetine of LH-stimulated cyclic AMP synthesis in tumor Leydig cells partly involves AMPK activation.
Fluoxetine (FLX), a widely used antidepressant primarily acting as a selective serotonin reuptake inhibitor (SSRI), has been shown to exhibit other mechanisms of action in various cell types. Consequently, it might have unexpected adverse effects not related to its intended use, possibly in the endocrine regulation of reproduction. We show in the present report that after a 1-hour preincubation of MLTC-1 Leydig cells with FLX, the intracellular cyclic adenosine monophosphate (cAMP) responses to Luteinizing Hormone (LH) and forskolin (FSK) are reduced through AMPK-dependent and -independent pathways respectively. FLX at low concentrations (12.5μM and 25μM) induced this inhibition without triggering AMPK phosphorylation, while higher FLX concentrations (50μM and 100μM) induced AMPK phosphorylation and lowered ATP concentration similarly to Metformin. Pretreatment with the specific AMPK inhibitor Compound C (CpdC), significantly diminished the inhibition of cAMP synthesis caused by high concentration of FLX. Moreover, as expected FLX also caused a decline of steroidogenesis which is under the control of cAMP. Taken together, these findings demonstrate that the inhibition of cAMP synthesis by FLX is dose-dependent and occurs in MLTC-1 cells through two mechanisms, AMPK-independent and AMPK-dependent, at low and high concentrations, respectively. FLX also inhibited hormone-induced steroidogenesis in MLTC-1 cells and mouse testicular Leydig cells, suggesting similar mechanisms in both cell types.


Isolation of rabbit liver heat shock protein with molecular weight 90 kD (Hsp90) and its interaction with troponin components and calponin.
Using a modified method consisting of chromatography on phenyl-Sepharose, Q-Sepharose, and hydroxyapatite, we isolated a highly purified heat shock protein with molecular weight 90 kD (Hsp90) from rabbit liver. The isolated protein was recognized on immunoblot by commercially available monoclonal anti-Hsp90 antibodies. The chromatographic properties, interaction with actin and calmodulin, phosphorylation in the presence of Mg-ATP, and one-dimensional peptide maps of rabbit liver Hsp90 are similar to the corresponding properties of Hsp90 isolated from other sources. In the presence of soluble carbodiimide and N-hydroxysuccinimide, rabbit liver Hsp90 can be cross-linked with calmodulin, troponin C, troponin I, and calponin. The data obtained indicate that Hsp90 may participate in the assembly of regulatory proteins of the actin filament.


AI am a rheumatologist: a practical primer to large language models for rheumatologists.
Natural language processing (NLP), a subclass of artificial intelligence, large language models (LLMs), and its latest applications, such as Generative Pre-trained Transformers (GPT), ChatGPT, or LLAMA, have recently become one of the most discussed topics. Up to now, artificial intelligence and NLP ultimately impacted several areas, such as finance, economics and diagnostic/scoring systems in healthcare. Another area that artificial intelligence has affected and will continue to affect increasingly is academic life. This narrative review will define NLP, LLMs and their applications, discuss the opportunities and challenges that components of academic society will experience in rheumatology, and discuss the impact of NLP and LLMs in rheumatology healthcare.


Thinking with the living body: the biopsychosocial model and the cosmopolitics of existence.
This paper argues that the 'biopsychosocial' model of the body highlights the importance of the psychosocial dimension for a better understanding of health and illness. Most importantly, by emphasising the fundamental relevance of values in the make-up of living systems, the biopsychosocial model radically challenges the common sense operation of evidence-based biomedical operations that bifurcate the body into the subjectivities of human perceptions and the non-subjective qualities of the nature of bodies. The biopsychosocial model protests against the manner by which only non-subjective qualities gain explanatory power in analysing, diagnosing and treating somatic and mental health issues. To accentuate the explanatory importance of values in understanding embodied human life, I will introduce Émile Durkheim's seminal work about human society as a reality sui generis that introduces the scientific realm for a 'special psychology' (Durkheim) to analyse 'values' as an emergent accomplishment of human social life. Still, as important Durkheim's account is in understanding societal values, it is only partially valid for the biopsychosocial model since it iterates the common sense operation of bifurcation by dismissing individual perceptions as valid sources to gain knowledge about the realities of human social values. To avoid bifurcation and to give importance to the subjectivities of every mode of existence, I will introduce Tarde's monadology that emphasises the value-laden psychosocial processes and societal organisation in understanding all bodies and things-human and non-human alike. A monadological reading of the body universalises the 'biopolitics' of human affairs and unfolds what I call the 'cosmopolitics of existence'. With the shift from the biopolitics of human affairs to the cosmopolitics of existence this paper wishes to contribute to novel ways of thinking the biopsychosocial body beyond bifurcating mind and nature.


Assessment of diabetes continuing medical education.
A diabetes professional education program was conducted and evaluated with 31 physicians from a rural/suburban community. Treatment guidelines were established by diabetes experts and community practitioners. To document effectiveness, medical record and survey data on 397 patients of the physicians were collected before and after the program. Each participant received a profile of their baseline performance as compared with peers as part of the educational program. A syllabus was designed to complement both the treatment guidelines and the findings from the baseline data. A telephone conference call with a diabetes consultant also occurred. A comparison between data collected before and after the program showed no significant differences in blood glucose levels or hospitalization rates. Physicians were more likely to recommend self-monitoring of blood glucose (SMBG) (7% versus 20%, P less than 0.05) and to examine their patients' feet (47% versus 73%, P less than 0.05) after the program. More patient education was available in the office (53% versus 73%). Patients using insulin were more likely to test urine for ketones (48% versus 61%, P less than 0.05) and know that decreased sensation in the feet could lead to injury (42% versus 53%, P less than 0.05). However, no improvements were noted in monitoring other complications, regulating diet, or in most aspects of patient education after the program. The results indicated the need for increased emphasis on the value of brief appropriate examinations for monitoring complications of diabetes and the need for physicians to learn techniques for counseling patients in self-management as well as to refer their patients to educational resources.


Achilles Tendinosis Stopping the Progression to Disability.
The purpose of this article is to differentiate between acute Achilles tendinitis and chronic Achilles tendinosis and to highlight a specific treatment protocol for mid-portion Achilles tendinosis. Tendinosis (degeneration of the tendon) results from chronic tissue injury and has long-term implications for a dancer's career. An eccentric heavy-load exercise protocol has been used successfully to treat tendinosis in athletes. A modified eccentric exercise protocol is proposed as one component of an effective rehabilitation program for dancers. This protocol facilitates tissue remodeling to build strength, flexibility, and adaptability of the Achilles tendon tissue, so that dancers can continue to dance without further complications of the injury.


[Seven means of measuring fear of treatment: reliability and convergent validity].
Fear of dental treatment sometimes already begins during childhood. Different kinds of diagnostic instruments can measure children's dental anxiety. In this study the reliability and convergent validity of 7 instruments are compared. Results show that there is no 'gold standard' with which convergent validity can be established unambiguously. Furthermore, self report measures are investigated more often than observational measures even though the latter are more commonly used. Generally, the compared measures are satisfactory in respect to their reliability. Nevertheless, sufficient interest coherence is sometimes lacking. This could be explained by the multidimensional character of the construct 'fear' and, in some cases, the type of measuring-method. In almost none of the compared studies were norms defined prior to the study by means of which statistical indicators could be unambiguously interpreted. In the present study, such norms were established.


Income Inequality and Population Health: A Global Gradient?
Cross-national empirical research about the link between income inequality and population health produces conflicting conclusions. We address these mixed findings by examining the degree to which the income inequality and health relationship varies with economic development. We estimate fixed-effects models with different measures of income inequality and population health. Results suggest that development moderates the association between inequality and two measures of population health. Our findings produce two generalizations. First, we observe a global gradient in the relationship between income inequality and population health. Second, our results are consistent with income inequality as a proximate or conditional cause of lower population health. Income inequality has a 139.7% to 374.3% more harmful effect on health in poorer than richer countries and a significantly harmful effect in 2.1% to 53.3% of countries in our sample and 6.6% to 67.6% of the world's population but no significantly harmful effect in richer countries.


[Preconception care in patients with diabetes].
In patients with diabetes, pregnancy is associated with high maternal and fetal risks, especially in unplanned pregnancies. Current evidence confirms that timely family planning and interdisciplinary care and management starting at the preconceptional period can optimize metabolic control and significantly reduce these risks. The purpose of this article is to summarize the different aspects to consider as well as provide tools to use when preparing patients with diabetes for a pregnancy.


Number of sexual partners and health lifestyle of adolescents. Use of the AMA Guidelines for Adolescent Preventive Services to address a basic research question.
To expand understanding of the behavioral epidemiology of an important sexually transmitted disease risk factor within a clinical framework of the AMA Guidelines for Adolescent Preventive Services (GAPS): Recommendations and Rationale. Cross-sectional analysis of the fourth year of a longitudinal study of adolescent health behavior. High schools in a single major urban school district. Nine hundred and forty-six white, African American, and Hispanic sexually active adolescents. Number of sexual partners in previous year and other health-risk and health-protective behaviors. Measures are operationalized according to guidelines for adolescent preventive services recommendations. Adolescents with 3 or more sexual partners annually were more involved with potentially health-harming behaviors such as illicit substance use and less involved with potentially health-protective behaviors such as seat belt use. These relationships were independent of sex, ethnic group, or socioeconomic status. The number of sexual partners may be considered part of a larger pattern of adolescent health-risk and health-protective behaviors. The guidelines may provide a useful framework for clinical assessment of these patterns as part of a routine health care visit of adolescent patients.


Proximal Humerus Fractures: How to Achieve Best Outcomes.
The treatment of proximal humerus fractures remains controversial. Although treatment modalities may vary, the goal of obtaining the best outcomes for patients remains the same. Most proximal humerus fractures can be treated nonsurgically but should still be managed actively. Deciding on surgical management requires a good understanding of indications and options. Indications for open reduction and internal fixation include younger or active patients with displaced two-, three-, and four-part fractures as well as fracture-dislocations with head-split patterns. Obtaining ideal outcomes requires anatomic reduction with restoration of the medial calcar as well as optimal position of implants to favor biomechanical stability. Reverse total shoulder arthroplasty is indicated for patients with severe and displaced fractures in older or low-demand patients. Obtaining the best functional outcomes depends on implant position, tuberosity healing, and early surgical intervention. Regardless of the treatment modality, these fractures can be challenging, and proper patient rehabilitation must be implemented. Future research will focus on patient selection and improving surgical techniques to maximize outcomes.


Lymphoid cell infiltration into Epstein-Barr virus-positive nasopharyngeal carcinomas.
A pilot study was designed to analyze lymphoid cell infiltration in Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinomas (NPCs) and to determine whether this pattern of infiltration is consistent with non-EBV+ head and neck carcinomas or with solid EBV+ tumors in other locations. We performed a retrospective analysis of archived NPCs and oral cavity carcinomas. Immunohistochemical staining of the archive material for various markers (CD3, CD8, UCHL-1, S-100, and intercellular adhesion molecule) was performed. Polymerase chain reaction techniques to establish the presence of the EBV genome were used. Cells in different locations were counted under a light microscope by 2 of the authors. The infiltration pattern of NPCs was different from that of oral cavity carcinomas. Stromal infiltration was significantly denser in oral cavity carcinomas. Tumor nest infiltration was more pronounced in NPCs. The pattern of infiltration was comparable with what has been described for other solid EBV+ tumors. The immune response to NPCs is likely to be strongly influenced by the presence of the EBV genome. The pattern of infiltration is similar to that of other non-head and neck EBV+ solid tumors and different from that of EBV- head and neck carcinomas.


Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case-Control Study.
Atypical femur fractures (AFFs) are well-established serious complication of long-term bisphosphonate and denosumab therapy in patients with osteopenia or osteoporosis. To elucidate underlying mechanism(s) for the development of AFF, we performed a nested case-control study to investigate bone tissue nanomechanical properties and prevailing bone microstructure and tissue-level remodeling status as assessed by bone histomorphometry. We hypothesized that there would be differences in nanomechanical properties between patients with and without AFF and that bone microstructure and remodeling would be related to nanomechanical properties. Thirty-two full-thickness transiliac bone biopsies were obtained from age- and sex-matched patients on long-term bisphosphonate therapy with (n = 16) and without an AFF (n = 16). Standard histomorphometric measurements were made in each sample on three different bone envelopes (cancellous, intracortical, and endosteal). Iliac bone wall thickness was significantly lower on all three bone surfaces in patients with AFF than in those without AFF. Surface-based bone formation rate was suppressed similarly in both groups in comparison to healthy premenopausal and postmenopausal women, with no significant difference between the two groups. Nanoindentation was used to assess material properties of cortical and cancellous bone separately. Elastic modulus was higher in cortical than in cancellous bone in patients with AFF as well as compared to the elastic modulus of cortical bone from non-AFF patients. However, the elastic modulus of the cancellous bone was not different between AFF and non-AFF groups or between cortical and cancellous bone of non-AFF patients. Resistance to plastic deformation was decreased in cortical bone in both AFF and non-AFF groups compared to cancellous bone, but to a greater extent in AFF patients. We conclude that long-term bisphosphonate therapy is associated with prolonged suppression of bone turnover resulting in altered cortical remodeling and tissue nanomechanical properties leading to AFF. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


Gene conversion and intragenic recombination at the SUP6 locus and the surrounding region in Saccharomyces cerevisiae.
Spontaneous secondary mutations of the ochre suppressor SUP6 were selected in a haploid strain of Saccharomyces cerevisiae. Unselected tetrads were dissected from crosses heterozygous for one of three allleles of SUP6 and for three other loci in this region which span a length of 14 map units (his2, cdc14 and met10). The study showed that all of these markers were characterized by high frequency of meiotic gene conversion and long conversion lengths which frequently extended into adjacent marked loci. Despite the high conversion frequency of SUP6, recombination between alleles of this locus reached a maximum frequency of only 2 x 10(-3) protrophs/spore. Although the allelic recombination frequencies were not distance dependent and consequently could not be used to order the alleles, the inequality between the two recombinant outside marker combinations among selected intragenic recombinants produced an internally consistent map of the suppressor locus. Recombination at SUP6 (whether detected as conversion in tetrads or the production of recombinants among random spores) was accompanied by significantly less than 50% outside marker recombination.


Is the startle reaction an emotion?
In this study, we examined startle reactions in which the subjects did and did not know when a blank pistol would be fired. In addition, we asked subjects to suppress their startle response and to simulate a startle when there was no gunshot. Detailed measurement of facial muscular actions supported most of the findings reported by Landis and Hunt (1939), but our findings suggested that startle be considered a reflex not an emotion. The findings are considered in terms of current disagreements about exactly what constitutes an emotion, including the argument between Zajonc (1980) and Lazarus (1984) about the role of appraisal.