Lower breastfeeding rates persist among the Special Supplemental Nutrition Program for Women, Infants, and Children participants, 1978-2003.
We set out to compare rates of breastfeeding between women who participated in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) with those of non-WIC mothers from 1978 to 2003. The Ross Laboratories Mothers Survey is a national survey designed to determine patterns of milk feeding during infancy. Mothers were asked to recall the type of milk fed to their infant in the hospital and during each month of age. Rates of breastfeeding in the hospital and at 6 months of age were evaluated. Logistic regression analyses identified significant predictors of breastfeeding in 2003. From 1978 through 2003, rates for the initiation of breastfeeding among WIC participants lagged behind those of non-WIC mothers by an average of 23.6 +/- 4.4 percentage points. At 6 months of age, the gap between WIC participants and non-WIC mothers (mean: 16.3 +/- 3.1 percentage points) steadily increased from 1978 through 2003 and exceeded 20% by 1999. Demographic factors that were significant and positive predictors of breastfeeding initiation in 2003 included some college education, living in the western region of the United States, not participating in the WIC program, having an infant of normal birth weight, primipary, and not working outside the home. For mothers of infants 6 months of age, WIC status was the strongest determinant of breastfeeding: mothers who were not enrolled in the WIC program were more than twice as likely to breastfeed at 6 months of age than mothers who participated in the WIC program. Breastfeeding rates among WIC participants have lagged behind those of non-WIC mothers for the last 25 years. The Healthy People 2010 goals for breastfeeding will not be reached without intervention. Food package and programmatic changes are needed to make the incentives for breastfeeding greater for WIC participants.


CNS glucagon-like peptide-1 receptors mediate endocrine and anxiety responses to interoceptive and psychogenic stressors.
Responses to stressors serve to adjust physiology and behavior to increase short-term survival at the potential expense of increasing susceptibility to disease over the long term. We show that glucagon-like peptide-1 (7-36) amide (GLP-1) increases levels of the stress-activated hormones ACTH and corticosterone when administered directly into the rat brain and increases levels of anxiety as measured by the elevated plus maze. The endocrine response is preferentially activated by GLP-1 administration in the paraventricular nucleus of the hypothalamus, whereas the anxiety response is preferentially activated by administration in the central nucleus of the amygdala. Furthermore, GLP-1 antagonists block increases in stress hormones associated with the toxin LiCl and both the endocrine and anxiety responses to vertical heights. Although diverse neural circuits must necessarily process disparate stressors, the current data implicate a role for the GLP-1 system as a critical mediator of multiple stress responses.


Effects of cathepsin G pretreatment of platelets on their subsequent responses to aggregating agents.
Cathepsin G, a proteolytic enzyme from activated leukocytes, can interact with platelets during inflammation and thrombosis. Platelets that have been exposed to cathepsin G in thrombi may recirculate if they are freed during fibrinolysis. To determine whether some of the subsequent functions of such platelets would be impaired, we investigated the responses of cathepsin G-pretreated platelets to agonists that they would encounter in the circulation. Suspensions of washed human platelets were labeled with [14C]serotonin and resuspended in Tyrode-albumin solution (with 2 mM Ca2+ and apyrase). After 15 minute incubation with 400 nM cathepsin G at 37 degrees C, 52+/-3% of [14C]serotonin had been released, and glycoprotein Ib was degraded. The platelets were washed and resuspended in fresh medium to remove cathepsin G and released materials. Ristocetin-induced agglutination was abolished, indicating that the binding site for von Willebrand Factor on glycoprotein Ib had been removed. Aggregation and release of residual [14C]serotonin in response to 0.1-1.0 U/mL thrombin was blocked or greatly reduced by the cathepsin G pretreatment. This inhibition is probably largely due to cleavage by cathepsin G of some of the protease-activated receptors at the C-terminal side of Ser42 so that the tethered ligand is lost. Pretreatment with cathepsin G did not affect responses to ADP or a low concentration of platelet-activating factor in the presence of fibrinogen, indicating that receptors for these agonists were unaffected and that the function of the fibrinogen receptor, GPIIb/IIIa was unchanged. Responses to cathepsin G, the thrombin receptor-activating peptide SFLLRN, collagen, or the thromboxane A2 mimetic U46619 were partially inhibited, even in the presence of added fibrinogen. Platelet adhesion to a collagen-coated surface was 51+/-7% inhibited, which may indicate cleavage of a collagen receptor or receptors; this may partly account for strong inhibition of collagen-induced aggregation and release of granule contents; additionally, as shown by inhibition of responses to U46619, the function of the thromboxane A2 receptor may be compromised. Thus, although cathepsin G activates platelets, if they recirculate after interaction with it, their subsequent adhesion to damaged vessel walls, aggregation, and release of granule contents induced by thrombin and collagen will be diminished.


Policy entrepreneurship and policy networks in healthcare systems - the case of Israel's pediatric dentistry reform.
Can the entry of a policy entrepreneur challenge the equilibrium of a policy network and promote changes that might clash with the goals of powerful civil-servants and/or interest groups and, if so, why and how? Our goal is to examine two sides of the same coin: how does an in-depth analysis of Israel's dental care reform enrich our understanding of policy networks and policy entrepreneurship? Second, how does the literature on policy networks and policy entrepreneurship help us understand this reform? Based on a theoretical framework that appears in the literature of policy entrepreneurship and policy networks, we analyze the motivations, goals and strategies of the main actors involved in the process of reforming pediatric dental care in Israel. We demonstrate how a policy entrepreneur navigated within a policy network and managed to promote a reform that, until his appearance, no one else in that network had succeeded in enacting. Our goals are advanced through a case study of a reform in pediatric dentistry implemented in Israel in 2010. It rests on textual analyses of the literature, reports, committee minutes, parliamentary proceedings, print and online media, and updates in relevant legislation and case law between 2009 and 2015. In addition, the case study draws on the insights of one of the authors (TH), who played a role in the reform process. Historical circumstances and the Israeli public's longstanding lack of interest in changing the existing model as well as interest groups that preferred the dominance of the private sector in the dental healthcare system kept that area out of the services supplied, universally, under the National Health Insurance Law. This situation changed significantly following the publication in 2007 of a policy analysis that contributed to shifts in the motivations and balance of power within the policy network, which in turn prepared the ground for a policy change. In this environment a determined policy entrepreneur, who identified a window of opportunity, took the lead and instituted an innovative and far-reaching reform. A policy entrepreneur can leverage external factors as well as the previous activities of a policy network that has already matured to create a policy change. Such entrepreneurial activity includes maneuvering around opponents and overcoming resistance from various stakeholders.


Midtrimester abortion induced by serial intravaginal administration of prostaglandin E2 suppositories in conjunction with a contraceptive diaphragm.
Midtrimester abortion was successfully induced in 68 of 69 patients with serial intravaginal administration of prostaglandin E2 suppositories behind a contraceptive diaphragm. The mean abortion time for the successful inductions was 13.07 hours; multiparous patients aborted somewhat faster, mean 12.72 hours, as compared to nulliparous patients, mean 14.22 hours. In 36 patients the PGE2 suppositories were placed behind an intact diaphragm and the mean abortion time was 14.89 hours. In 33 patients the PGE2 suppositories were placed behind a diaphragm modified by having an opening incised in the center, the mean time in these patients was 11.96 hours. Of the 68 successful abortions 59% of the patients aborted in 12 hours or less and 88% aborted within 24 hours. The most frequently encountered side effect was temperature elevation of 2 degrees F or higher which occurred in 68% of the patients. Temperatures returned to normal levels within 4 to 6 hours after the last adminstration of PGE2. Gastrointestinal side effects occurred in 45% of patients, but these side effects were well tolerated and did not require termination of drug administration in any of the patients. Intravaginal administration of PGE2 suppositories is a very effective abortifacient technque during the midtrimester, however the use of PGE2 in conjunction with a diaphragm did not appreciabley improve the technique although the amount of drug administered and the incidence of side effects was somewhat lower than when the PGE2 suppositories are used alone. If a diaphragm is to be used, a modified diaphragm is indicated since it simplifies the clinical management of the abortion, eases administration of the suppositories and permits a more accurate estimation of cervical changes, vaginal bleeding and abortion.


Menopause and the NHS: caring for and retaining the older workforce.
Menopause is a natural transition affecting most women between the ages of 45 and 55. Three-quarters of women will experience mild to moderate menopausal symptoms and a further quarter will report them as severe. Symptoms can include night sweats, hot flushes, poor concentration, tiredness, poor memory and lowered confidence. The workplace can exacerbate these symptoms and for some women can influence their decision to stop working earlier than previously intended. The need for support and understanding from managers is crucial and can make a major difference to how a woman deals with her menopause. Many women enter the menopause at the peak of their productive lives. These women have valuable skills, knowledge and experience that employers need to retain, so they should be developing resources to help navigate this normal and natural stage of the ageing process.


Autochthonous murine models for the study of smoker and never-smoker associated lung cancers.
Lung cancer accounts for the greatest number of cancer deaths in the world. Tobacco smoke-associated cancers constitute the majority of lung cancer cases but never-smoker cancers comprise a significant and increasing fraction of cases. Recent genomic and transcriptomic sequencing efforts of lung cancers have revealed distinct sets of genetic aberrations of smoker and never-smoker lung cancers that implicate disparate biology and therapeutic strategies. Autochthonous mouse models have contributed greatly to our understanding of lung cancer biology and identified novel therapeutic targets and strategies in the era of targeted therapy. With the emergence of immuno-oncology, mouse models may continue to serve as valuable platforms for novel biological insights and therapeutic strategies. Here, we will review the variety of available autochthonous mouse models of lung cancer, their relation to human smoker and never-smoker lung cancers, and their application to immuno-oncology and immune checkpoint blockade that is revolutionizing lung cancer therapy.


Assessment of the "case-chaos" design as an adjunct to the case-control design.
In 2012, a novel case series method dubbed the "case-chaos" design was proposed as an alternative to case-control studies, whereby controls are artificially created by permutating the exposure information of the cases. Our aim in the current work was to further evaluate the case-chaos method. Using a theoretical example of 2 risk factors, we demonstrated that the case-chaos design yields risk estimations for which the odds ratios obtained for every risk factor are in the same ascending order as the risk factors' exposure prevalences in the case group. Applying the method to data from the European Study of Severe Cutaneous Adverse Reactions (EuroSCAR; 1997-2001), we were not able to obtain sensible results but instead produced results as predicted by our theoretical assessment. We therefore claim that the method is equivalent to declaring risk solely on the basis of prevalences obtained in cases. While the proposers of the case-chaos method view it as a useful adjunct, we show that it cannot produce sensible estimates.


Bioactive Triterpenes from the Root of Salvia miltiorrhiza Bunge.
Danshen (Salvia miltiorrhiza) is a well-known medicinal herb in the oriental medicine. The current study on bioactive triterpenoid in the root of S. miltiorrhiza led to the isolation of a new highly hydroxylated ursane-type triterpene, urs-12-ene-2α,3β,7β,16α-tetraol (1) and five known ones including 2β-hydroxypomolic acid (2), maslinic acid (3), asiatic acid (4), ursolic acid (5), and oleanolic acid (6). Their structures were elucidated on the basis of extensive spectroscopic analyses and comparison with literature data. The antiproliferative testing against HL-60 cells revealed that the new compound 1 and ursolic acid (5) showed weak and moderate activities with IC50 values of 42.2 and 11.7 μM. In addition, compounds 1-3 showed inhibitory effect on ghrelin activity. Copyright © 2017 John Wiley & Sons, Ltd.


Active surveillance and surgery in localized prostate cancer.
Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer and also the second leading cause of cancer deaths among men. Concerns about overdiagnosis and overtreatment of PCa have been growing, leading to more conservative approaches, especially in the treatment of low-risk disease. As PCa is a relatively slow-growing tumor, complications of unnecessary curative management in low-risk PCa can be prevented by active surveillance (AS). AS helps to improve quality of life after deferred treatment. Several AS criteria have been suggested for delayed treatment. Although upgrading and/or upstaging of cancer is a limitation of AS, many reports have shown low rates of cancer-specific mortality up to now. Radical prostatectomy (RP) has been considered as standard treatment for prostate cancer to provide good oncologic outcomes. The increasing use of minimally invasive laparoscopic surgery, including robot-assisted laparoscopic prostatectomy, has contributed to better functional outcomes. So far, long-term randomized studies have not conclusively proven the superiority of either AS or RP. Well-designed long-term randomized studies will be required to compare the benefits of AS and immediate RP. Here, we review recent reports on the current status of AS and RP, including delayed RP, and discuss their merits in the management of localized PCa.


Physical activity in children measured by accelerometry: stability over time.
The aim of this study was to examine the stability of objectively measured physical activity in Swedish children and to study variables that predicted physical activity and body mass index standard deviation score (BMI SDS) at follow-up. A total of 97 children provided valid repeated measurements of physical activity between 2002 and 2005. The children were on average 7.5 years at baseline (SD+/-0.92) and 9 years at follow-up (SD+/-0.92). The mean follow-up time was approximately 1.5 years (mean 558 days, SD+/-224). An accelerometer (Actiwatch, Cambridge Neurotechnology Ltd., Cambridge, UK) was used to measure physical activity during 7 consecutive days. Yearly weight and height were examined and BMI SDS was calculated. Baseline physical activity was significantly correlated with physical activity at follow-up (r=0.59) with a stronger correlation for boys (r=0.72) than for girls (r=0.51). High physical activity levels were more stable (r=0.74) than low physical activity levels (r=0.55). Physical activity at follow-up was explained by physical activity at baseline and season (R(2)=0.46) whereas BMI SDS at follow-up was explained by BMI SDS at baseline and age (R(2)=0.90). The results of this study suggest that physical activity levels are fairly stable in 6-10-year-old children.


Carbapenemases of Chryseobacterium (Flavobacterium) meningosepticum: distribution of blaB and characterization of a novel metallo-beta-lactamase gene, blaB3, in the type strain, NCTC 10016.
Genes encoding carbapenemases in 15 reference strains of Chryseobacterium (Flavobacterium) meningosepticum from the United Kingdom National Collection of Type Cultures and in one recent clinical isolate were investigated. All the strains hydrolyzed imipenem, but their levels of resistance to carbapenems varied, with imipenem and meropenem MICs ranging from 2 to >32 microg/ml. The blaB gene, which encodes a molecular-class B carbapenemase, was detected in only six reference strains and in clinical isolate 97/P/5448. The gene from 97/P/5448 had 98% nucleotide identity with the published sequence of blaB (from strain NCTC 10585) and was designated blaB2. A distinct carbapenemase gene, designated blaB3, was cloned from the type strain of C. meningosepticum, NCTC 10016. blaB3 had an open reading frame of 750 bp with 82% nucleotide identity to blaB and blaB2 and encoded a beta-lactamase of 249 amino acids, including the putative signal peptide. This beta-lactamase showed 87.6 and 86.7% amino acid homology with BlaB and BlaB2, respectively. blaB3 was detected in one other reference strain besides NCTC 10016, but the genetic basis of the carbapenemase activity detected in the other seven reference strains was not defined. Thus, neither blaB nor blaB3 was ubiquitous in the strains of C. meningosepticum studied, indicating that the reference strains may represent more than one bacterial species, each with its own intrinsic metallo-beta-lactamase. Further taxonomic studies of C. meningosepticum are necessary to resolve this topic. Chryseobacterium spp. are environmental organisms and occasional opportunist pathogens. They apparently represent a reservoir of diverse metallo-beta-lactamases, which potentially spread to gram-negative bacteria of greater clinical significance.


Health reform through tax reform: a primer.
Tax incentives for employer-sponsored insurance and other medical spending cost about $200 billion annually and have pervasive effects on coverage and costs. This paper surveys a range of proposals to reform health care, either by adding new tax incentives or by limiting or replacing the existing tax incentives. Replacing the current tax preference for insurance with an income-related, refundable tax credit has the potential to expand coverage and reduce inefficient spending at no net federal cost. But such an approach by itself would entail substantial risks, so complementary reforms to the insurance market are essential to ensure success.


The "Outcome Reporting in Brief Intervention Trials: Alcohol" (ORBITAL) Core Outcome Set: International Consensus on Outcomes to Measure in Efficacy and Effectiveness Trials of Alcohol Brief Interventions.
The purpose of this study was to report the "Outcome Reporting in Brief Intervention Trials: Alcohol" (ORBITAL) recommended core outcome set (COS) to improve efficacy and effectiveness trials/evaluations for alcohol brief interventions (ABIs). A systematic review identified 2,641 outcomes in 401 ABI articles measured by 1,560 different approaches. These outcomes were classified into outcome categories, and 150 participants from 19 countries participated in a two-round e-Delphi outcome prioritization exercise. This process prioritized 15 of 93 outcome categories for discussion at a consensus meeting of key stakeholders to decide the COS. A psychometric evaluation determined how to measure the outcomes. Ten outcomes were voted into the COS at the consensus meeting: (a) typical frequency, (b) typical quantity, (c) frequency of heavy episodic drinking, (d) combined consumption measure summarizing alcohol use, (e) hazardous or harmful drinking (average consumption), (f) standard drinks consumed in the past week (recent, current consumption), (g) alcohol-related consequences, (h) alcohol-related injury, (i) use of emergency health care services (impact of alcohol use), and (j) quality of life. The ORBITAL COS is an international consensus standard for future ABI trials and evaluations. It can improve the synthesis of new findings, reduce redundant/selective reporting (i.e., reporting only some, usually significant outcomes), improve between-study comparisons, and enhance the relevance of trial and evaluation findings to decision makers. The COS is the recommended minimum and does not exclude other, additional outcomes.


Long-distance twin-field quantum key distribution with entangled sources.
Twin-field quantum key distribution (TFQKD), using single-photon-type interference, offers a way to exceed the rate-distance limit without quantum repeaters. However, it still suffers from photon losses and dark counts, which impose an ultimate limit on its transmission distance. In this Letter, we propose a scheme to implement TFQKD with an entangled coherent state source in the middle to increase its range, as well as comparing its performance under coherent attacks with that of TFQKD variants. Simulations show that our protocol has a theoretical distance advantage of 400 km. Moreover, the scheme has great robustness against the misalignment error and finite-size effects. Our work is a promising step toward long-distance secure communication and is greatly compatible with future global quantum networks.


Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial.
To identify predictors of response to methotrexate (MTX) in early rheumatoid arthritis (RA). In the SWEFOT trial, patients with RA with symptom duration <1 year started MTX monotherapy (20 mg/weekly) and 405/487 continued until the 3-4- month visit. The primary outcome measure was the DAS28-based European League against Rheumatism (EULAR) response criteria. Multivariate logistic regression was used to study the association between response and the following baseline characteristics: gender, age, symptom duration, cigarette smoking habits, autoantibody status, Health Assessment Questionnaire (HAQ) score, concurrent prednisolone and treatment with non-steroidal anti-inflammatory drugs. Secondary response and remission measures were the American College of Rheumatology and the Simple Disease Activity Index and Clinical Disease Activity Index (SDAI/CDAI)-derived criteria. After 3-4 months of MTX treatment, the frequency of EULAR good/moderate/no response was 34%/41%/25%, respectively. Parameters associated with a decreased likelihood of EULAR response were female gender (adjusted OR (adj OR) 0.50, 95% CI 0.31 to 0.81), symptom duration (adj OR per month increase 0.93, 95% CI 0.88 to 0.99), current smoking (adj OR 0.35, 95% CI 0.20 to 0.63) and higher HAQ (adj OR 0.56, 95% CI 0.40 to 0.80). Parameters associated with an increased likelihood of EULAR response were higher age (adj OR per 10-year increase 1.30, 95% CI 1.11 to 1.51) and prednisolone treatment (adj OR 2.84, 95% CI 1.43 to 5.63). The findings were similar when patients on prednisolone were excluded and other response criteria tested, although current smoking was the only significant predictor using all response criteria, while HAQ was the only significant predictor of all the remission criteria used. A matrix showed up to ninefold differences between subgroups stratified by the main predictors. Current smoking, female sex, longer symptom duration and younger age predict a worse response to MTX in patients with new-onset RA. TrialRegNo NCT00764725.


Peripheral nerve damage in patients with nontraumatic rhabdomyolysis.
Four patients with rhabdomyolysis due to drug intoxication were found to have peripheral nerve damage. Three patients were comatose and one was lethargic. The diagnosis of rhabdomyolysis was made by marked elevation in blood levels of creatine phosphokinase and strongly positive orthotoluidine test without RBCs in the urine. Acute renal failure developed in three patients and one had mild renal insufficiency. Electromyography showed damage to the brachial plexus in three of the patients and there was involvement of the musculocutaneous, radial, ulnar, and peroneal nerves in the fourth patient. The neurologic abnormalities disappeared completely within six weeks in two patients and considerably improved within four weeks in another patient after discharge from the hospital.


A Case of Pre-Existing Pregnancy During an In-Vitro Fertilization Cycle.
Serum progesterone levels performed prior to oocyte pick-up is commonly used to guide embryo transfer in in-vitro fertilization (IVF) cycles, as elevated levels can negatively influence pregnancy outcomes. However, levels associated with normal pregnancies should trigger clinicians to consider alternative causes such as a pre-existing pregnancy. We report a case of a 37-year-old patient who underwent controlled ovarian hyperstimulation in a gonadotrophin-releasing hormone antagonist cycle while having an undetected early pregnancy. No oocytes were retrieved at oocyte retrieval despite adequate follicular responses. Her serum progesterone level on the day of her trigger injection was 57.8 nmol/L. She was found to have a pregnancy of unknown location, detected 3 weeks after her oocyte retrieval and was subsequently treated with systemic methotrexate.


Synergistic impact of arbutin and kaempferol-7-O-α-L-rhamnopyranoside from Nephelium lappaceum L. on whitening efficacy and stability of cosmetic formulations.
Four flavonoid glycosides, namely quercetin-3-O-rhamnoside (1), kaempferol-3-O-β-D-glucopyranosyl (2), kaempferol-7-O-α-L-rhamnopyranoside (3), and kaempferol-3-O-β-D-glucopyranosyl-7-O-α-L-rhamnopyranoside (4), from Nephelium lappaceum L. seeds were evaluated for their efficacy against melanin inhibition in B16F10 melanoma cells and tyrosinase inhibition. Among them, kaempferol-7-O-α-L-rhamnopyranoside (3) displayed the highest potency in both activities without any significant cytotoxicity. The combination of compound 3 and arbutin in specific proportions demonstrated a synergistic effect (CI < 1) in inhibiting melanin production in B16F10 cells and tyrosinase inhibition. Additionally, a cosmetic formulation containing compound 3 and arbutin as active ingredients exhibited favorable stability under accelerated storage conditions. Quantitative analysis indicated that compound 3 and arbutin levels in the formulation were above 90% after one month of storage. Determination of the formulation's shelf life using the Q10 method, estimating it to be around 5.2 months from the date of manufacture. The synergy between arbutin and kaempferol-7-O-α-L-rhamnopyranoside (3) extracted from N. lappaceum substantially enhances both the whitening effectiveness and the stability of cosmetic formulations.


Single versus multi-dose vaccine vials: an economic computational model.
Single-dose vaccine formats can prevent clinic-level vaccine wastage but may incur higher production, medical waste disposal, and storage costs than multi-dose formats. To help guide vaccine developers, manufacturers, distributors, and purchasers, we developed a computational model to predict the potential economic impact of various single-dose versus multi-dose measles (MEA), hemophilus influenzae type B (Hib), Bacille Calmette-Guérin (BCG), yellow fever (YF), and pentavalent (DTP-HepB-Hib) vaccine formats. Lower patient demand favors fewer dose formats. The mean daily patient arrival thresholds for each vaccine format are as follows: for the MEA vaccine, 2 patients/day (below which the single-dose vial and above which the 10-dose vial are least costly); BCG vaccine, 6 patients/day (below, 10-dose vial; above, 20-dose vial); Hib vaccine, 5 patients/day (below, single-dose vial; above, 10-dose vial); YF vaccine, 33 patients/day (below, 5-dose vials; above 50-dose vial); and DTP-HepB-Hib vaccine, 5 patients/day (below, single-dose vial; above, 10-dose vial).


Candidate gene study of HOXB1 in autism spectrum disorder.
HOXB1 plays a major role in brainstem morphogenesis and could partly determine the cranial circumference in conjunction with HOXA1. In our sample, HOXA1 alleles significantly influence head growth rates both in autistic patients and in population controls. An initial report, suggesting that HOXB1 could confer autism vulnerability in interaction with HOXA1, was not confirmed by five small association studies. Our sample includes 269 autistic individuals, belonging to 219 simplex and 28 multiplex families. A mutational analysis of the two exons and flanking intronic sequences of the HOXB1 gene was carried out in 84 autistic patients by denaturing high performance liquid chromatography, followed by DNA sequencing. Identified rare variants were then searched by a restriction analysis in 236 autistic patients and 325-345 controls. Case-control and family-based association studies were performed on two common variants in 169 Italian patients versus 184 Italian controls and in 247 trios. We identified three common polymorphisms, rs72338773 [c.82insACAGCGCCC (INS/nINS)], rs12939811 [c.309A>T (Q103H)], and rs7207109 [c.450G>A (A150A)] and three rare variants, namely IVS1+63G>A, rs35115415 [c.702G>A (V234V)] and c.872_873delinsAA (S291N). SNPs rs72338773 and rs12939811 were not associated with autism, using either a case-control (alleles, exact P = 0.13) or a family-based design [transmission/disequilibrium test (TDT)chi2 = 1.774, P = 0.183]. The rare variants, all inherited from one of the parents, were present in two Italian and in two Caucasian-American families. Autistic probands in two families surprisingly inherited a distinct rare variant from each parent. The IVS1+63A allele was present in 3/690 control chromosomes, whereas rare alleles at rs35115415 and c.872_873delinsAA (S291N) were not found in 662 and 650 control chromosomes, respectively. The INS-T309 allele influenced head size, but its effect appears more modest and shows no interaction with HOXA1 alleles. The INS-T309 allele is also associated with more severe stereotypic behaviours, according to ADI-R scores (N = 60 patients, P < 0.01). HOXB1 mutations do not represent a common cause of autism, nor do HOXB1 common variants play important roles in autism vulnerability. HOXB1 provides minor, albeit detectable contributions to head circumference in autistic patients, with HOXA1 displaying more prominent effects. HOXB1 variants may modulate the clinical phenotype, especially in the area of stereotypic behaviours.


Light and dark smooth muscle cells in estrogen-stimulated rat myometrium.
Smooth muscle cells of different densities to transmission of electrons (termed light and dark cells) were found in rat myometrium examined in the electron microscope following fixation by immersion in glutaraldehyde. Light cells accounted for about 4% of the total population of cells. No light cells were found in tissues fixed in situ by intraarterial perfusion with glutaraldehyde. In addition to staining differences, light cells were distinguished from most dark cells by differences in nuclear, mitochondrial, endoplasmic reticular, and surface structures. The relative number of light and dark cells after in vitro fixation was not changed in tissues relaxed with adrenaline or contracted with oxytocin. Mechanical injury resulted in increased numbers of light cells. Similarly, chemical injury with metabolic inhibitors resulted in ATP depletion, followed by increased numbers of light cells and gain in water content. We concluded that light cells were produced by mechanical or metabolic damage, leading to loss of volume control mechanisms, swelling, and leakage of protein. Light cells found after fixation in vitro in numerous prior studies represent cells damaged during isolation, and not a physiological variant among smooth muscle cells.


Discovery of α7-nicotinic receptor ligands by virtual screening of the chemical universe database GDB-13.
The chemical universe database GDB-13 enumerates 977 million organic molecules up to 13 atoms of C, N, O, Cl, and S that are virtually possible following simple rules for chemical stability and synthetic feasibility. Analogs of nicotine were identified in GDB-13 using the city-block distance in MQN-space (CBD(MQN)) as a similarity measure, combined with a restriction eliminating problematic structural elements. The search was carried out with a Web browser available at www.gdb.unibe.ch . This virtual screening procedure selected 31 504 analogs of nicotine from GDB-13, from which 48 were known nicotinic ligands reported in Chembl. An additional 60 virtual screening hits were purchased and tested for modulation of the acetylcholine signal at the human α7 nAChR expressed in Xenopus oocytes, which led to the identification of three previously unknown inhibitors. These experiments demonstrate for the first time the use of GDB-13 for ligand discovery.


Antimicrobial resistance: consideration as an adverse drug event.
Antimicrobial resistance has increased dramatically in the past 15 to 20 yrs and presents a patient safety concern unlike any other in the intensive care unit. Antimicrobial resistance in critically ill patients increases morbidity, mortality, length of hospital stay, and healthcare costs. Some organisms may have intrinsically high levels of resistance or may be spread between patients by poor infection control practices. However, a major driver of antimicrobial resistance is antibiotic use. As such, the development of antimicrobial resistance can often be thought of as an adverse drug event. This article explores the link between drug use, drug dosing, other selective pressures and resistance, and describes concepts to minimize the negative impact of antimicrobial therapy. Two broad themes of these concepts are minimizing the use of antibiotics whenever possible and optimizing antibiotic usage when they are needed. Strategies for minimizing the use of antimicrobials include using optimal diagnostic procedures to ensure the need for antimicrobials, streamlining or discontinuing therapy when possible based on culture results, and using the shortest duration of therapy needed for documented infections. Strategies for optimizing antimicrobial use include using optimal dosing based on the manufacturer's instructions and current pharmacodynamic data, guiding better prescribing based on local susceptibility patterns and formulary restriction, and avoiding drugs with more propensity to foster resistance.


Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT.
Ipriflavone is a synthetic flavonoid that has been shown to exert a direct inhibitory effect on osteoclastic activity and possibly stimulate the osteoblast activity in different experimental models. The aim of the present study was to evaluate the effects of either ipriflavone alone or ipriflavone plus low dose hormone replacement therapy (HRT) in the prevention of postmenopausal bone loss. Patients were randomly allocated to different treatment groups receiving calcium (500 mg/day, control group), continuous HRT (25 or 50 micrograms/day of transdermal 17 beta-estradiol) plus medrogestone 5 mg/day for 12 days/month, ipriflavone at the standard dose of 600 mg/day, or finally ipriflavone 600 mg/day plus 17 beta-estradiol 25 micrograms/day plus medrogestone 5 mg/day for 12 days/month. No significant differences in basal levels of biochemical markers of bone turnover or in basal bone mineral density (BMD) values were evident in the different groups. In the control group after 12 months, spine BMD showed a significant (p < 0.05) 3.41% decrease. The pattern of BMD modification was significantly different from controls in the high dose HRT group (+1.84%), the ipriflavone group (+0.11%), and the combined ipriflavone/HRT group (-0.22%). Conversely, the BMD pattern in the low dose HRT group (-0.55%) was similar to that observed in controls. Thus, present results confirm that ipriflavone and 50 micrograms/day of transdermal 17 beta-estradiol are effective measures in the prevention of postmenopausal osteopenia. A lower transdermal estrogen dose is unable to increase the antiresorptive effect of ipriflavone and did not exert any further action in the prevention of postmenopausal osteopenia.


[The risk of general anesthesia in surgery of the veins of the lower limbs].
Venous surgery on the lower limbs does not involve specific problems for the anaesthetist. General anaesthetic is still indicated in particular cases, even though techniques of locoregional anaesthetic are being more and more widely used in venous surgery of the lower limbs. Certain authors have found that the indications for general anaesthetic are limited to the counterindications or failures of local anaesthetic; others give general anaesthetic a wider application when surgery is to be carried out on a patient in the ventral decubitus position. The aim of general anaesthetic for venous surgery of the lower limbs is simply to facilitate a purely functional surgery. In this context, injury or fatality directly connected with the anaesthetic seems unacceptable. However, the accident rate is far from being low, as various inquiries have revealed. In France, the inquiry set up by INSERM found that serious accident related wholly or partially to the anaesthetic occurs once in every 3,000 operations. Of course, the accident rate increases with age and depends on the previous pathological condition. But, quite apart from cardio-vascular accidents, which have multiple causes and usually involve high-risk patients, these studies show that respiratory accidents involve every type of patient, whatever their medical history. Moreover, the majority of such accidents could have been avoided had there been adequate monitoring to detect any anomaly before the occurrence of the accident. It is thus appropriate to recall the recommendations of the American Society of Anesthiologists for standard pre-operative monitoring: monitoring of ventilation (spirometry, capnometry, debrancher alarm), monitoring of oxygenation, circulation (continuous ECG and pulse assessment) and monitoring of temperature.(ABSTRACT TRUNCATED AT 250 WORDS)


Non-invasive functional and biochemical assessment of mitoxantrone cardiotoxicity in patients with multiple sclerosis.
As mitoxantrone is a recently approved immunosuppressant for managing multiple sclerosis, the number of patients treated with this effective but potentially cardiotoxic anthracenedione derivative will increase substantially. To detect subclinical mitoxantrone-induced cardiotoxicity, sensitive non-invasive diagnostic tools are required. Assuming that changes in myocardial high-energy phosphate metabolism and alterations in left ventricular (LV) diastolic performance might be early markers of mitoxantrone-induced cardiotoxicity we examined fifteen MS patients treated with mitoxantrone up to 100 mg/m2 compared with 15 matched control MS patients. 31P-magnetic resonance (MR) spectroscopy was employed to measure myocardial high-energy phosphate metabolism, MR imaging for morphometric evaluation of changes in LV geometry. Indices of diastolic performance were assessed by Doppler echocardiography. In this exploratory study, phosphocreatine/ATP ratios were comparable between mitoxantrone-treated and control patients (1.48 +/- 0.23 and 1.43 +/- 0.41). LV mass, LV end-diastolic and systolic volumes, wall motion score, EF and cardiac output did not differ between both groups. All parameters of diastolic performance (E/A-ratio, isovolumic relaxation time, and E-wave deceleration time) were not different and within normal limits.In conclusion, using advanced diagnostic methodology, including functional, morphometric, and biochemical measurements no cardiotoxic effect of mitoxantrone up to a cumulative dose range of 100 mg/m2 could be detected.


Lack of functional influence by prenalterol through alpha 1-adrenoceptors in rat myocardium.
Some of the cardiac properties of the partial beta-agonist prenalterol may indicate a contribution from alpha 1-adrenergic stimulation. We therefore studied whether prenalterol interacted with alpha 1-adrenoceptors in rat myocardium. Combination with propranolol did not reveal an alpha 1-adrenergic inotropic effect of prenalterol in papillary muscles. Neither did prenalterol block the alpha 1-adrenergic response to phenylephrine. In myocardial cells, prenalterol inhibited 3H-prazosin binding to alpha 1-adrenoceptors only at very high concentrations. Prenalterol thus exhibited no functionally important interactions with alpha 1-adrenoceptors in myocardium, and its properties cannot be accounted for in terms of contribution from alpha 1-adrenergic effects.


Mesenchymal stem cells from tumor microenvironment favour breast cancer stem cell proliferation, cancerogenic and metastatic potential, via ionotropic purinergic signalling.
Interaction between tumor cells and the microenvironment is key in initiation, progression, and invasiveness of cancer. In particular, mesenchymal stem cells (MSCs) are recruited to the sites of developing tumors, thus promoting metastasis formation. Although it is well known that MSCs migrate and integrate in the tumor microenvironment (TME), their fate and function inside the tumor is still not clear. In this study, we analyzed the role played by MSCs in breast cancer oncogenesis. Data indicate that interaction of breast cancer cells with MSCs results in an increased proliferation and metabolic activity of breast cancer cells, partially due to MSC-derived microvesicles that are shed in the TME. Moreover, we addressed the question of whether we could modulate such interaction by acting on P2X-mediated intercellular communication. By inhibiting P2X-mediated purinergic signaling, we succeeded in reducing both the cancerogenic as well as the metastatic potential of breast cancer cells co-cultured with MSCs, in 2D as well as in 3D in vitro models. Data obtained demonstrate for the first time that the trophic effect of MSCs on breast cancer cell growth is exerted via ionotropic purinergic signaling, thus suggesting the inhibition of the purinergic signaling system as a potential target for therapeutic intervention.


Synaptic plasticity deficits and mild memory impairments in mouse models of chronic granulomatous disease.
Reactive oxygen species (ROS) are required in a number of critical cellular signaling events, including those underlying hippocampal synaptic plasticity and hippocampus-dependent memory; however, the source of ROS is unknown. We previously have shown that NADPH oxidase is required for N-methyl-D-aspartate (NMDA) receptor-dependent signal transduction in the hippocampus, suggesting that NADPH oxidase may be required for NMDA receptor-dependent long-term potentiation (LTP) and hippocampus-dependent memory. Herein we present the first evidence that NADPH oxidase is involved in hippocampal synaptic plasticity and memory. We have found that pharmacological inhibitors of NADPH oxidase block LTP. Moreover, mice that lack the NADPH oxidase proteins gp91(phox) and p47(phox), both of which are mouse models of human chronic granulomatous disease (CGD), also lack LTP. We also found that the gp91(phox) and p47(phox) mutant mice have mild impairments in hippocampus-dependent memory. The gp91(phox) mutant mice exhibited a spatial memory deficit in the Morris water maze, and the p47(phox) mutant mice exhibited impaired context-dependent fear memory. Taken together, our results are consistent with NADPH oxidase being required for hippocampal synaptic plasticity and memory and are consistent with reports of cognitive dysfunction in patients with CGD.


[Fundamental ophthalmology: the role of electrophysiological studies].
Studying of functional aspects of eye disease pathogenesis by electrophysiological methods is widely demanded in fundamental ophthalmology. Introduction of modern methods of functional assessment into experimental and clinical projects significantly broadens knowledge of normal and pathological functioning of the visual system and is the basis for further development of new strategies of pathogenetic treatment, diagnostics and expert evaluation. Some problems of ophthalmology, including those that concern age-related macular degeneration, glaucoma, diabetic retinopathy, and other diseases, are considered in the context of how much electrophysiology contributes to their solution. The role of functional examinations of the retina in studying pathophysiology of neurodegenerative brain diseases, such as Alzheimer's and Parkinson's, is also discussed.


Is breast feeding associated with offspring IQ at age 5? Findings from prospective cohort: Lifestyle During Pregnancy Study.
Breast feeding is associated with health benefits for both mother and child, but many studies focusing on neurodevelopment have lacked information on important confounders and few randomised trials exist. Our objective was to examine the influence of breast feeding on child IQ at 5 years of age while taking maternal IQ and other relevant factors into account. Prospective observational study. Population-based birth cohort in Denmark. We used data from The Lifestyle During Pregnancy Study 1782 mother-child pairs sampled from the Danish National Birth Cohort (n=101 042). Child IQ was assessed at age 5 years by the Wechsler Primary and Preschool Scales of Intelligence-Revised. On the same occasion maternal intelligence was assessed by Wechsler Adult Intelligence Scale and Raven's Standard Progressive Matrices. Exposure data on duration of breast feeding (n=1385) were extracted from telephone interviews conducted when the child was 6 and 18 months, and analyses were weighted by relevant sampling fractions. In multivariable linear regression analyses adjusted for potential confounders breast feeding was associated with child IQ at 5 years (categorical χ2 test for overall association p=0.03). Compared with children who were breast fed ≤1 month, children breast fed for 2-3, 4-6, 7-9 and 10 or more months had 3.06 (95% CI 0.39 to 5.72), 2.03 (95% CI -0.38 to 4.44), 3.53 (95% CI 1.18 to 5.87) and 3.28 (95% CI 0.88 to 5.67) points higher IQ after adjustment for core confounders, respectively. There was no dose-response relation and further analyses indicated that the main difference in IQ was between breast feeding ≤1 month versus >1 month. Breastfeeding duration of 1 month or shorter compared with longer periods was associated with approximately three points lower IQ, but there was no evidence of a dose-response relation in this prospective birth cohort, where we were able to adjust for some of the most critical confounders, including maternal intelligence.


Endotoxin increases superoxide dismutase in cultured bovine pulmonary endothelial cells.
Manganous (Mn) and copper zinc (CuZn) superoxide dismutase (SOD) concentrations and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured in cultured bovine pulmonary endothelial cells with and without exposure to Escherichia coli endotoxin (10(-1) micrograms/ml) over intervals of 0.5-24 h. The activities of two mitochondrial marker enzymes, fumarase and cytochrome-c oxidase, were also measured. Endotoxin exposure caused a marked increase (9-fold) in endothelial cell Mn SOD content without significant effects on GSH-Px, CAT, fumarase, or cytochrome-c oxidase activities. Endotoxin induced a slight decrease in CuZn SOD content over 24 h. This is the first report of a selective effect of endotoxin on Mn SOD in pulmonary endothelial cells. The response appears to be independent of an increase in mitochondrial activity (no change was observed in cytochrome-c oxidase or fumarase activities). These findings support the notion that endotoxin increases generation of toxic oxygen metabolites within pulmonary endothelial cells. An endotoxin-induced increase in Mn SOD could contribute to the reported protective effect of endotoxin against oxygen toxicity in these cells.


Medical physics aspects of cancer care in the Asia Pacific region.
Medical physics plays an essential role in modern medicine. This is particularly evident in cancer care where medical physicists are involved in radiotherapy treatment planning and quality assurance as well as in imaging and radiation protection. Due to the large variety of tasks and interests, medical physics is often subdivided into specialties such as radiology, nuclear medicine and radiation oncology medical physics. However, even within their specialty, the role of radiation oncology medical physicists (ROMPs) is diverse and varies between different societies. Therefore, a questionnaire was sent to leading medical physicists in most countries/areas in the Asia/Pacific region to determine the education, role and status of medical physicists.Answers were received from 17 countries/areas representing nearly 2800 radiation oncology medical physicists. There was general agreement that medical physicists should have both academic (typically at MSc level) and clinical (typically at least 2 years) training. ROMPs spent most of their time working in radiotherapy treatment planning (average 17 hours per week); however radiation protection and engineering tasks were also common. Typically, only physicists in large centres are involved in research and teaching. Most respondents thought that the workload of physicists was high, with more than 500 patients per year per physicist, less than one ROMP per two oncologists being the norm, and on average, one megavoltage treatment unit per medical physicist.There was also a clear indication of increased complexity of technology in the region with many countries/areas reporting to have installed helical tomotherapy, IMRT (Intensity Modulated Radiation Therapy), IGRT (Image Guided Radiation Therapy), Gamma-knife and Cyber-knife units. This and the continued workload from brachytherapy will require growing expertise and numbers in the medical physics workforce. Addressing these needs will be an important challenge for the future.


Fibromyalgia subgroups: profiling distinct subgroups using the Fibromyalgia Impact Questionnaire. A preliminary study.
The main goal of this project was to identify the presence of fibromyalgia (FM) subgroups using a simple and frequently used clinical tool, the Fibromyalgia Impact Questionnaire (FIQ). A total of 61 women diagnosed with FM participated in this study. FM subgroups were created by applying a hierarchical cluster analysis on selected items of the FIQ (pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms). We also tested for group differences on experimental pain, psychosocial functioning and demographic characteristics. Two cluster profiles best fit our data. FM-Type I was characterized by the lowest levels of anxiety, depressive and morning tiredness symptoms, while FM-Type II was characterized by elevated levels of pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms. Both FM subgroups showed hyperalgesic responses to experimental pain. These results suggest that pain and stiffness are universal symptoms of the disorder but that psychological distress is a feature present only in some patients.


Natural suppressor activity in graft-vs-host spleen and normal bone marrow is augmented by IL 2 and interferon-gamma.
Natural suppressor (NS) cells isolated from the spleens of mice 34 or more days after induction of chronic graft-vs-host disease showed potent suppressor activity that was dependent on the presence of lymphokines such as those found in lectin-free Con A supernatant (CAS). Both IL 2 and IFN-gamma were found to enhance NS activity, with IFN-gamma being the most active molecule. To generalize these findings, normal adult bone marrow (BM), a second environment where NS activity has been reported, was examined. Normal adult BM cells nonspecifically suppressed both B and T cell mitogen responses. BM suppression could also be enhanced by the addition of CAS to the cultures. Removal of plastic-adherent cells, Thy-1.2-positive cells, or B cells did not significantly diminish suppression or remove the ability to enhance suppression with CAS. When isolated on discontinuous Percoll gradients, BM suppressor cells banded in the less dense fractions, and the suppression in these bands was also enhanced by lymphokines. The suppressive activity of these cells was greatly enhanced by the addition of CAS, IFN-gamma, or IL 2. However, IFN-gamma appears to be a more potent enhancing molecule, being active at levels between 1 and 10 U/ml.


Wavelength multiplexing in multimode optical fibers.
The capacity of optical fiber transmission systems could be increased by multiplexing several signals at different wavelengths on each fiber. This paper considers various multiplex system designs that might be used with multimode fiber transmission systems. In each case, the required multiplexer size and material properties are calculated as functions of the basic parameters of the fiber system. For fiber systems of the type currently being tested, a compact (~2 mm in diameter x 1 cm long), rugged, three-channel multiplexer could be constructed using a blazed plane reflection grating and graded-refractive-index (GRIN) optics; and it appears that such devices could be produced using available materials and technology. Multiplexers using thick gratings or multilayer dielectric filters are larger, more complicated, and require materials at the very edge of available technology. Multiplexers using a multiple thick grating or hologram could be even smaller than the blazed-grating devices, but materials having the quired characteristics have not been demonstrated.


Estimating intracellular calcium concentrations and buffering without wavelength ratioing.
We describe a method for determining intracellular free calcium concentration ([Ca(2+)]) from single-wavelength fluorescence signals. In contrast to previous single-wavelength calibration methods, the proposed method does not require independent estimates of resting [Ca(2+)] but relies on the measurement of fluorescence close to indicator saturation during an experiment. Consequently, it is well suited to [Ca(2+)] indicators for which saturation can be achieved under physiological conditions. In addition, the method requires that the indicators have large dynamic ranges. Popular indicators such as Calcium Green-1 or Fluo-3 fulfill these conditions. As a test of the method, we measured [Ca(2+)] in CA1 pyramidal neurons in rat hippocampal slices using Oregon Green BAPTA-1 and 2-photon laser scanning microscopy (BAPTA: 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid). Resting [Ca(2+)] was 32-59 nM in the proximal apical dendrite. Monitoring action potential-evoked [Ca(2+)] transients as a function of indicator loading yielded estimates of endogenous buffering capacity (44-80) and peak [Ca(2+)] changes at zero added buffer (178-312 nM). In young animals (postnatal days 14-17) our results were comparable to previous estimates obtained by ratiometric methods (, Biophys. J. 70:1069-1081), and no significant differences were seen in older animals (P24-28). We expect our method to be widely applicable to measurements of [Ca(2+)] and [Ca(2+)]-dependent processes in small neuronal compartments, particularly in the many situations that do not permit wavelength ratio imaging.


Attention-training with children from socioeconomically disadvantaged backgrounds in Cape Town.
Attention is a core process underlying competence in higher-order cognitive abilities. Previous research suggests that healthy children from low socioeconomic status (SES) backgrounds perform poorly, relative to those from higher SES backgrounds, on tasks assessing attentional abilities. In this pilot study, we investigated the effects of an attention-training intervention on task performance in low-SES children. We conducted a quasi-controlled trial with stratified randomisation, using a pre-test/ post-test design. Participants were low-SES children aged 7-13 years. Each was assigned to either an intervention group, a play control group, or a test-only control group (n = 5 per group). We implemented a ten-week manualised cognitive rehabilitation program, Pay Attention!, administering standardised tests of attention, working memory, and inhibition before and after the intervention. Between- and within-group analyses and Reliable Change Index statistics evaluated differences in scores from pre- to post-intervention. Analyses detected no notable between-group differences at either pre- or post-intervention testing. However, on tests of selective attention, attentional control, and inhibition, there were significant within-group and positive individual reliable changes exclusive to the intervention-group participants. Given the variability in our findings, more research needs be conducted with a larger sample to determine, with greater rigour, the efficacy of the intervention within samples of healthy children from low-SES backgrounds.


Pial arteriovenous fistulas associated with multiple aneurysms presenting as intracerebral hemorrhage: a case report.
Intracranial pial arteriovenous fistulas (AVFs) associated with multiple aneurysms of the main feeding arteries are very rare cerebrovascular lesions. We report a unique case of pial AVFs associated with four aneurysms of the feeding anterior cerebral artery (ACA) which presented as intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH) and spontaneous subarachnoid hemorrhage (SAH). CT angiography (CTA) and digital subtraction angiography (DSA) images demonstrated clearly the direct connection without nidus between the first and second segment of right ACA accompanied by four irregular aneurysms and an abnormally dilated draining vein into the superior sagittal sinus (SSS). Owing to the superficial-seated fistulas, the morphology of feeding arteries and associated four aneurysms and intracranial hemorrhage, the lesions were surgically treated. Postoperative cerebral angiography certified closure of the fistulas and exclusion of the four aneurysms as well as disappearance of early venous drainage. However, subsequent precontrast brain CT showed hydrocephalus underwent left ventriculoperitoneal shunt placement.


A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus.
Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II. This protein displayed a broader spectrum of receptor activities than any mammalian chemokine as it bound with high affinity to a number of both CC and CXC chemokine receptors. Binding of vMIP-II, however, was not associated with the normal, rapid mobilization of calcium from intracellular stores; instead, it blocked calcium mobilization induced by endogenous chemokines. In freshly isolated human monocytes the virally encoded vMIP-II acted as a potent and efficient antagonist of chemotaxis induced by chemokines. Because vMIP-II could inhibit cell entry of human immunodeficiency virus (HIV) mediated through CCR3 and CCR5 as well as CXCR4, this protein may serve as a lead for development of broad-spectrum anti-HIV agents.


Spontaneous surface adsorption of aqueous graphene oxide by synergy with surfactants.
The spontaneous adsorption of graphene oxide (GO) sheets at the air-water interface is explored using X-ray reflectivity (XRR) measurements. As a pure aqueous dispersion, GO sheets do not spontaneously adsorb at the air-water interface due to their high negative surface potential (-60 mV) and hydrophilic functionality. However, when incorporated with surfactant molecules at optimal ratios and loadings, GO sheets can spontaneously be driven to the surface. It is hypothesised that surfactant molecules experience favourable attractive interactions with the surfaces of GO sheets, resulting in co-assembly that serves to render the sheets surface active. The GO/surfactant composites then collectively adsorb at the air-water interface, with XRR analysis suggesting an interfacial structure comprising surfactant tailgroups in air and GO/surfactant headgroups in water for a combined thickness of 30-40 Å, depending on the surfactant used. Addition of too much surfactant appears to inhibit GO surface adsorption by saturating the interface, and low loadings of GO/surfactant composites (even at optimal ratios) do not show significant adsorption indicating a partitioning effect. Lastly, surfactant chemistry is also a key factor dictating adsorption capacity of GO. The zwitterionic surfactant oleyl amidopropyl betaine causes marked increases in GO surface activity even at very low concentrations (≤0.2 mM), whereas non-ionic surfactants such as Triton X-100 and hexaethyleneglycol monododecyl ether require higher concentrations (ca. 1 mM) in order to impart spontaneous adsorption of the sheets. Anionic surfactants do not enhance GO surface activity presumably due to like-charge repulsions that prevent co-assembly. This work provides useful insight into the synergy between GO sheets and molecular amphiphiles in aqueous systems for enhancing the surface activity of GO, and can be used to inform system formulation for developing water-friendly, surface active composites based around atomically thin materials.


Clinical correlates of schizotypy in patients with epilepsy.
Clinical correlates of schizotypy were evaluated in 89 adult consecutive outpatients with epilepsy, using the Beck Depression Inventory, the State and Trait Anxiety Inventory, and the Schizotypal Personality Questionnaire (SPQ). Age at onset of the epilepsy significantly correlated with the constricted affect subscale of the SPQ, while a diagnosis of temporal lobe epilepsy correlated with the total SPQ score, the cognitive-perceptual factor of the SPQ, and the suspiciousness subscale of the SPQ. Schizotypal symptoms correlated with early onset of the seizures and a diagnosis of temporal lobe epilepsy, further confirming an association between psychoses and epilepsy.


Health Behavior Theory in Physical Activity Game Apps: A Content Analysis.
Physical activity games developed for a mobile phone platform are becoming increasingly popular, yet little is known about their content or inclusion of health behavior theory (HBT). The objective of our study was to quantify elements of HBT in physical activity games developed for mobile phones and to assess the relationship between theoretical constructs and various app features. We conducted an analysis of exercise and physical activity game apps in the Apple App Store in the fall of 2014. A total of 52 apps were identified and rated for inclusion of health behavior theoretical constructs using an established theory-based rubric. Each app was coded for 100 theoretical items, containing 5 questions for 20 different constructs. Possible total theory scores ranged from 0 to 100. Descriptive statistics and Spearman correlations were used to describe the HBT score and association with selected app features, respectively. The average HBT score in the sample was 14.98 out of 100. One outlier, SuperBetter, scored higher than the other apps with a score of 76. Goal setting, self-monitoring, and self-reward were the most-reported constructs found in the sample. There was no association between either app price and theory score (P=.5074), or number of gamification elements and theory score (P=.5010). However, Superbetter, with the highest HBT score, was also the most expensive app. There are few content analyses of serious games for health, but a comparison between these findings and previous content analyses of non-game health apps indicates that physical activity mobile phone games demonstrate higher levels of behavior theory. The most common theoretical constructs found in this sample are known to be efficacious elements in physical activity interventions. It is unclear, however, whether app designers consciously design physical activity mobile phone games with specific constructs in mind; it may be that games lend themselves well to inclusion of theory and any constructs found in significant levels are coincidental. Health games developed for mobile phones could be potentially used in health interventions, but collaboration between app designers and behavioral specialists is crucial. Additionally, further research is needed to better characterize mobile phone health games and the relative importance of educational elements versus gamification elements in long-term behavior change.


Cost to the patient or cost to the healthcare system? Which one matters the most for GP prescribing decisions? A UK-Italy comparison.
Charges for health services help contain healthcare costs. Despite showing that medicine consumption decreases when charges are increased there is little research that illuminates how doctors 'manage' the charge system to help patients who cannot afford treatment. This paper describes how the charge system influences the prescribing decisions of Italian and UK physicians. The data are from the qualitative stage of a multi-stage study exploring cost related influences on GP and patient decision-making regarding medicine use. The analysis presented is based on transcripts of focus groups conducted with general practitioners. To help patients who have difficulties affording their medication Italian GPs rely on a smaller number of cost reduction strategies compared to their UK counterparts. They use 'samples' left by pharmaceutical companies, or diagnose patients with pathologies that allow exemption. Occasionally they recommend some delay or change therapy to a cheaper but less effective alternative. Italian and UK GPs have firm views about preventing patients abusing the NHS and believe costs to the system are as important as costs to the individual patient. Prescribing budgets were not viewed in a positive light by Italian GPs. Due to the nature of the charge system in Italy GPs there are able to choose a reimbursable product for patients, so have less need than UK doctors to look for other means of reducing costs. Conversely, the UK GPs have developed a large number of cost reduction strategies, probably because of the charge system itself and the relatively high charges incurred by patients.


Hyperuricemic nephropathies.
This review explores the relationship between uric acid or urate and the pathogenesis of renal impairment. The following points and conclusions are emphasized: (1) uric acid is an end product of purine degradation in humans and normally depends upon renal excretion for the majority of its elimination from the body; (2) massive urate overproduction - usually occurring acutely because of tumor lysis, rhabdomyolysis, or some other cause of rapid nucleic acid turnover or tissue destruction - tends to cause acute renal failure because of an increase of intratubular uric acid precipitation and obstruction; (3) chronic urate overproduction (with increased urate excretion) is more likely to be associated with stones or gout than with acute renal failure; (4) chronic asymptomatic hyperuricemia is unlikely to cause renal disease, gout, or stones, but is associated with cardiovascular impairment over the long term, and (5) asymptomatic hyperuricemia may serve as an indicator of renal vascular disease, or, to the extent that it may reflect insulin-induced acceleration of renal tubule urate reabsorption, hyperuricemia may serve as an indicator of insulin resistance. Therefore chronic asymptomatic hyperuricemia may predict the adverse cardiovascular consequences of insulin resistance.


Rapid and selective updating of the target template in visual search.
Frequent target stimuli are detected more rapidly than infrequent ones. Here, we examined whether the frequency effect reflected durable attentional biases toward frequent target features, and whether the effect was confined to featural properties that defined the target. Participants searched for two specific target colors among distractors of heterogeneous colors and reported the line orientation of the target. The target was more often in one specific feature (e.g., a specific color or a specific orientation) than another in a training phase. This frequency difference was removed or reversed in a testing phase. Experiments 1 and 2 showed that when frequency differences were introduced to the target's defining feature, participants more rapidly found the high-frequency target than the low-frequency target. However, changes in attention were not durable-the search advantage vanished immediately when the frequency differences were removed. Experiments 3-5 showed that only featural properties that defined the target facilitated search of the more frequent feature. Features that did not define the target, such as the target feature that participants reported, sped up response but did not facilitate search. These data showed that when searching for multiple targets in a feature search task, people selectively and rapidly adapt to the frequency in the target's defining feature.


[Gastroenterology. II: Acid research and ulcer therapy].
Three discoveries of the last thirty years have revolutionized acid research and ulcer therapy: H2-receptors and their competitive inhibition, the acid pump and its blockade and, finally, Helicobacter pylori and its central role in ulcer disease. Today the problem of ulcer treatment is more or less solved by the correct use of antibiotics, while the cure of reflux disease is still problematic: pump blockers accelerate the healing of mucosal breaks and prevent, when given at long term, recurrences but they cannot change the natural history of reflux disease. These facts form the basis for future research.


Carotid Artery Dissection.
Dissection of the carotid artery in the neck is a relatively common condition. Most dissections are spontaneous, likely related to activities that cause sudden stretch of the pharyngeal portion of the carotid artery. Many patients do not develop brain ischemia but have a triad of neck and head pain, Horner's syndrome, and pulsatile tinnitus. Others present with transient or persistent brain ischemia. Strokes are due to the embolization of thrombus material from the lumen of the dissected artery to the intracranial arteries, most often the middle cerebral artery. Although there have been no randomized therapeutic trials in patients with carotid artery dissection, experience shows that standard anticoagulants in the form of heparin followed by Coumadin (Du Pont Pharma, Wilmington, DE) are effective in preventing further artery-to-artery emboli.


[Early caries diagnosis].
Early detection of carious lesions enables the dental professional to interfere in caries development. Visual inspection in combination with bitewing radiographs performed better than new quantitative methods in detecting early non-cavitated carious lesions. Once a lesion has been detected assessment of activity (diagnosis) is important in order to distinguish between an active process and a scar developed in the past. The clinical gaze, an intellectual interpretation of the dental condition, whereby the caries experience of the recent past is used as an important caries predictor, is better able to produce a correct estimate of the caries risk than prediction models based on risk factors. A correct diagnosis of lesion activity in combination with the caries risk of the patient gives us a tool to predict caries development in the future. Subsequently caries activity can be influenced by addressing the factors which cause caries (causal therapy).


Total serum cholesterol by isotope dilution/mass spectrometry: a candidate definitive method.
We describe a highly accurate and precise method for determination of total cholesterol in serum by isotope dilution/mass spectrometry. The method was developed for a Study Group of the Committee on Standards of the American Association for Clinical Chemistry, for use in establishing the accuracy of a candidate reference method for total cholesterol, and fulfills their criteria for a definitive method. Cholesterol-d7 is added to serum, with the weight ratio of cholesterol-d7 to total serum cholesterol kept near to 1:1. The esters are hydrolyzed and the cholesterol is separated and converted into the trimethylsilyl ether derivative for measurement by combined gas chromatography/mass spectrometry. The intensity ratio of the molecular ions at m/z 465 and 458 is measured for each sample and for two calibration mixtures, according to a prescribed bracketing protocol. A weight ratio for the sample is obtained by linear interpolation of the ion-intensity ratios, and the total cholesterol is then calculated. The method was applied four times over several weeks to each of five serum pools. Statistical analysis involving consideration of both replication error and variability between weeks gave a coefficient of variation for a single measurement of 0.36%. The absence of interferences in the method was demonstrated by measurements at several other masses.


Intracranial pressure waves: characterization of a pulsation absorber with notch filter properties using systems analysis: laboratory investigation.
The relationship between the waveform of intracranial pressure (ICP) and arterial blood pressure can be quantitatively characterized using a newly developed technique in systems analysis, the time-varying transfer function. This technique considers the arterial blood pressure as an input signal composed of multiple frequencies represented in the output ICP according to the transfer function imposed by the intracranial system on the input signal. The transfer function can change with time and with physiological manipulations. The authors examined data obtained from canine experiments involving manipulations of ICP. The authors analyzed 11 experiments from 3 normal mongrel dogs under conditions of normal ICP and with changes in ICP made by bolus injection, infusion, or withdrawal of cerebrospinal fluid by using time-varying transfer function. During normal ICP periods, the gain of the transfer function displayed a deep notch (> or = 1 log unit) centered at or near the cardiac frequency. In systems terms, the intracranial compartment under normal conditions appears to act as a notch filter attenuating the cardiac frequency input relative to other frequencies. Epochs of ICP elevation showed suppression of the notch, and the notch was restored when ICP returned to normal. The intracranial system in these animals could be considered to include a pulsation absorber for which the target frequency appears to be close to the cardiac frequency. One possible source for such an absorber mechanism might be the free movement of cerebrospinal fluid, implying that impairment of this motion may have important clinical implications in various neurological conditions such as hydrocephalus.


Increased erythrocyte catalase activity in patients with hyperthyroidism.
Levels of human erythrocyte catalase activity were determined in 38 patients with thyroidal dysfunction. In patients with hyperthyroidism, erythrocyte catalase activities were found to be higher than the levels of normal subjects (P less than 0.001). In hypothyroidism, erythrocyte catalase activities were of the same order as those of normal subjects. Significantly high positive correlation was found between erythrocytes catalase activity and the levels of thyroxine (r = 0.5794, n = 36, P less than 0.001), and slight positive correlation was detected between catalase activity and the levels of triiodothyronine (r = 0.3978, n = 33, P less than 0.05). A decreased erythrocyte catalase activity was observed when erythrocytes lysate was incubated with thyroid hormones. It was suggested that erythrocyte catalase activity had close relationship with thyroid state, however, direct effect of thyroid hormones were not observed on erythrocyte catalase assay system in vitro.


Integration of phosphoinositide- and calmodulin-mediated regulation of TRPC6.
Multiple TRP channels are regulated by phosphoinositides (PIs). However, it is not known whether PIs bind directly to TRP channels. Furthermore, the mechanisms through which PIs regulate TRP channels are obscure. To analyze the role of PI/TRP interactions, we used a biochemical approach, focusing on TRPC6. TRPC6 bound directly to PIs, and with highest potency to phosphatidylinositol 3,4,5-trisphosphate (PIP(3)). We found that PIP(3) binding disrupted the association of calmodulin (CaM) with TRPC6. We identified the PIP(3)-binding site and found that mutations that increased or decreased the affinity of the PIP(3)/TRPC6 interaction enhanced or reduced the TRPC6-dependent current, respectively. PI-mediated disruption of CaM binding appears to be a theme that applies to other TRP channels, such as TRPV1, as well as to the voltage-gated channels KCNQ1 and Ca(v)1.2. We propose that regulation of CaM binding by PIs provides a mode for integration of channel regulation by Ca(2+) and PIs.


[Proliferation of the myoctes of the left atrium and ventricle after different kinds of myocardial injuries in adult rats].
Myocardial infarction of the left ventricle was induced in adult rats weighing 120-160 g by ligation of the left coronary artery at various levels: in the area of the auricle, of the first third of the left ventricle, and in the middle of it. The left auricle was injured in the other experimental series: the ligature was applied to its anterior wall or to the auricular appendage. Sham-operated animals served as control; only pericardium was removed in them. The left half of the heart was examined on the 5th postoperative day. Mitosis of myocytes was found in the auricle or in the auricular appendage of the animals in those experimental series in which these sections of the heart were injured directly and had a thickened epicardium (in 35 of 49 cases); mitotic index varied from 0.9 to 10%. No mitoses were found in the myocytes of the auricle and the auricular appendage after ligation of the coronary artery in the middle of the ventricle. Mitoses in the myocytes of the ventricle were rare (in 7 of 49 cases) and were located far from the site of infarction, in the subepicardial region; mitotic index here varied from 1 to 2%.


Gastroesophageal reflux disease in children: how reliable is the gold standard?
To investigate the causes and degree of interobserver variability in esophageal pH monitoring for the diagnosis of gastroesophageal reflux. This retrospective study included all children (n = 72) who underwent pH monitoring during 1 year at Maxima Medical Centre in Veldhoven, the Netherlands. An interobserver variability of 18% was found. Variability was caused by differences in opinion about the duration of registration, doubts about probe position, artifacts and drift of baseline pH. Most of these problems can be eliminated by posttest calibration and assessment of the pH electrode position. However, a clear definition of monitoring artifacts is lacking. This study shows that mutual agreement in the interpretation of pH studies was fair (kappa coefficient of 0.70).


Regional and global left ventricular function following a simulated 5 km race in sports-trained adolescents.
The effects of a short, high-intensity bout of exercise on cardiac systolic and diastolic function are not well understood in adolescent athletes. Consequently, the aims of the study were to evaluate global left ventricular (LV) systolic and diastolic function, as well as segmental wall motion responses (cardiac strain), prior to as well as 45 and 225 min following a simulated 5 km cross-country race. Twenty trained, adolescent males (age: 15.2 ± 0.7 years) volunteered for exercise testing. LV fractional shortening and the ratio of early (E) and late (A) peak flow velocities reflected global systolic and diastolic function, respectively. Peak longitudinal mitral annular septal tissue velocities were also determined during systole and diastole. Longitudinal strain (ε) and strain rates were determined across the LV. LV fractional shortening was significantly (P < 0.05) higher at 225 min post-race (37.6 ± 5.8%) compared to pre-race (34.5 ± 4.7%) and 45 min post-race (34.9 ± 5.4 %). This difference was abolished after adjusting for post-race heart rates. There was a significant (P < 0.05) decrease in the E:A ratio at both 45 min (2.04 ± 0.57) and 225 min post-race (2.20 ± 0.66) compared to the pre-race value (2.80 ± 0.68). When these data were adjusted for post-race heart rates, these pre-post-race differences in E:A ratio were abolished. There were no significant alterations in either tissue Doppler velocities or longitudinal ε. The evidence suggests that a 5 km race does not lead to any significant post-exercise attenuation in global or regional LV systolic and diastolic function in trained adolescents.


Interaction of Shiga toxins with human brain microvascular endothelial cells: cytokines as sensitizing agents.
Neurologic abnormalities are among the most serious extraintestinal complications of infection with Shiga toxin (Stx)-producing bacteria. Histopathologic examination of tissues from patients with extraintestinal sequelae suggested that Stxs damage endothelial cells. It is shown here that human brain microvascular endothelial cells (HBMECs) are relatively resistant to purified Stxs (50% cytotoxic doses [CD50s] >/=10 microgram/mL). Pretreatment of HBMECs with tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, n-butyric acid, or a cAMP analogue resulted in a 103- to 104-fold decrease in CD50 values and a 2- to 4-fold increase in fluoresceinated Stx binding to HBMECs. Treatment of HBMECs with lipopolysaccharides did not significantly alter cytotoxicity or toxin binding. TNF-alpha and IL-1beta treatment was associated with the increased HBMEC expression of the toxin-binding glycolipid globotriaosylceramide. HBMECs did not produce IL-1beta and produced only trace amounts of TNF-alpha when stimulated with purified Stx1 in vitro.


Dermatologic manifestations of fluoride exposure.
The dermatologic manifestations of fluoride/fluorine exposure have not been established definitively. There is no evidence of allergic dermatologic reactions to fluorides, and the most reproducible toxic reactions are those to inorganic gaseous fluorines and solutions of hydrogen fluoride, which produce burns. Anecdotal associations have included papulondular and pustular eruptions secondary to topical fluoride-containing preparations, telangiectases and Chizzola maculae in the setting of airborne inorganic fluorides. Carefully controlled studies are needed to identify fluoride as the primary cause of these dermatoses, as well as to correlate the gross pathology, specific histopathology, and plasma levels of fluorine.


Supplement 2008-2010 (no. 48) to the White-Kauffmann-Le Minor scheme.
This supplement (no. 48) of the White-Kauffmann-Le Minor scheme reports on the characterization of 63 new Salmonella serovars and 25 new variants of previously described Salmonella serovars recognized by the WHO Collaborating Centre for Reference and Research on Salmonella between 2008 and 2010. Forty-four new serovars were assigned to Salmonella enterica subspecies enterica, 12 to subspecies salamae, two to subspecies arizonae, two to subspecies diarizonae and three to subspecies houtenae. All these new serovars or new variants are described with their multilocus sequence type.


The experience of loneliness among young people with depression: a qualitative meta-synthesis of the literature.
Young people have a higher prevalence of loneliness than other age groups, and they are also at risk of depression. Quantitative studies describe a bidirectional association between loneliness and depression, but there is limited understanding of how these influence each other. Little is known about the experience of loneliness among young people with depression. Qualitative approaches may help understand the relationship between loneliness and depression among young people, and how to intervene to improve outcomes. We aimed to conduct a meta-synthesis to understand the complex inter-relationship between loneliness and depression among young depressed people by synthesising evidence from a systematic review of qualitative studies. We conducted a meta-synthesis of qualitative studies capturing experiences of loneliness among young people with depression. We systematically searched six electronic databases for selected search terms, critically appraised eligible studies, and analysed the data from included studies using the approach of thematic synthesis. We used feedback from an inter-disciplinary research workshop to improve reflexivity. Our inclusion criteria identified fourteen studies. Our analysis identified four themes: (1) social withdrawal due to poor mental health, (2) non-disclosure of depression contributing to social distance, (3) the desire to connect, and (4) paradoxes of loneliness and depression. These themes illustrated a range of pathways between depression and loneliness, and a sense of how these might be mutually reinforcing. Our findings suggest that where depressed individuals engage in certain behaviours (withdrawing; not confiding) for a range of reasons, this can lead to feelings of loneliness, an awareness of which worsens their mood, thus perpetuating their depression. Young people with depression experience loneliness as an insurmountable distance between themselves and others. Our findings identified non-disclosure of depression, and the debilitating nature of the depressive symptomatology, as factors perpetuating a vicious cycle of loneliness and depression. They suggest that approaches to tackling the problem might include helping young people communicate about their depression to trusted friends and educating their social networks in how to support them. The wider research literature suggests that cognitive interventions may have a role in shifting maladaptive cognitions about their social world.


[Effects of halogen derivative hydrocarbons on radiation damage of biological membranes].
Sharp increase of radiation-induced damages of isolated erythrocyte membrane lipids and proteins upon irradiation in presence of some halogen derivative hydrocarbon are shown. On chloroform and CCl4 examples it is shown that marked effects displayed under relatively low (submillimoles) concentrations and radiation doses that induced only insignificant oxidative membrane damages in absence of modifiers. The data are received which evidenced in favour of decisive role in these processes of halogenated organic radicals forming under one-electron reduction of halogen derivative hydrocarbons by hydrated electrons.


A study of post exercise hypotension in normotensive offspring of hypertensives after acute exercise.
Post exercise hypotension (PEH) is a well-known entity in hypertensive and borderline hypertensive patients. Since the results are inconsistent in normotensives and there is a genetic predisposition of the individuals to hypertension, we hypothesized that PEH is expected to occur in those normotensives who are offspring of hypertensive parents. In this study, we therefore aimed to compare the magnitude of PEH after an acute bout of moderate intensity continuous exercise (MICE) in the offspring of hypertensives vs. offspring of normotensives. Sixty normotensive participants of both genders (male and female in equal proportion), aged 18-40 yr, were divided into two groups based on their family history of hypertension. The cases (Group 1, n=30) consisted of the normotensives who were offspring of hypertensive parents while the normotensives who were offspring of normotensive parents were taken as the controls (Group 2, n=30). The hypertensive patients were excluded from the study. The individuals underwent a control session (sitting at rest for 5-10 min), followed by a single acute bout of MICE based on the target heart rate (60-70% of maximum heart rate) on a treadmill at the same time of the day (in the morning). The pre- and post-exercise measurements (after 10 min post exercise) of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) were taken in all the participants using mercury sphygmomanometer in sitting position on the left arm. The intergroup and intragroup net effects of exercise on BP were compared with P<0.05 considered significant. The mean SBP was reduced by 5 mmHg than the baseline in the offspring of hypertensives (cases) as compared to the controls after exercise (P=0.01). The fall in mean DBP and MAP was insignificant across both the groups, but the magnitude of PEH measured as delta changes (BP before and after exercise) in SBP (~5 mmHg) and MAP (~4 mmHg) were significantly higher for the cases as compared to the controls (P=0.01). PEH occurs in higher magnitude in normotensives who are genetically predisposed to hypertension, such as offspring of hypertensive parents, and may find regular exercise-induced PEH as an important primary preventive tool to prevent or delay the development of hypertension.


Shoulder injuries in ice hockey.
Financial support for this study was provided by: the Hubbard Foundation, St. Paul, MN; Institute for Athletic Medicine, Fairview Community Hospitals, Minneapolis, MN; Institute for Athletic Medicine of John C. Lincoln Hospital. Phoenix, AZ; The Mendon Schutt Foundation, Minneapolis; Minnesota State High School League, Anoka, MN; University of Minnesota Computer Center; multiple private donations. A study of shoulder injuries incurred by high school ice hockey players was conducted for the 1982-1983 and 1983-1984 competitive seasons. Data from 480 players (73%), who competed on 12 teams within a 30 mile radius, were included in the analysis. Among these players, shoulder injuries accounted for a rate of 9.4 injuries per 100 players; separation of the acromioclavicular joint was the most common injury. Although 39% of the reported injuries were of mild severity, 44% were moderate in severity, and 18% were major in severity; moreover, 59% of the injured players reported residual persistent symptoms. Of the total injuries, 88% occurred in games or under game-type conditions. The greatest proportion of injuries occurred to players engaged in play in the forward position while in the offensive zone. Over 54% of the injuries were caused by contact with the boards surrounding the ice surface and, reportedly, 43% of the injuries were associated with illegal activities. Based on the study findings, strategies for injury prevention include the following: consideration of techniques of coaching and of play; enforcement of the current rules to decrease the number of injuries related to illegal activities; research relevant to board design and materials to determine if a more yielding barrier can be placed around the playing surface; and utilization of the latest equipment, incorporating unique design and materials, that facilitates dissipation of forces. In addition, there is a need for further comprehensive research efforts relevant to ice hockey injuries that can enable the identification of other risk factors so that prevention and control of injuries can be managed more readily.J Orthop Sports Phys Ther 1988;10(2):54-58.


Strength of pulmonary vascular response to regional alveolar hypoxia.
Regional alveolar hypoxia in the lung induces regional pulmonary vasoconstriction which diverts blood flow from the hypoxic area. However, the predominant determinant of the distribution of perfusion in the normal erect lung is gravity so that more perfusion occurs at the base than at the apex. To determine the strength of the regional alveolar hypoxic response in diverting flow with or against the gravity gradient a divided tracheal cannula was placed in anesthetized dogs and unilateral alveolar hypoxia created by venilating one lung with nitrogen while ventilating the other lung with oxygen to preserve normal systemic oxygentation. Scintigrams of the distribution of perfusion obtained with intravenous 13-N and the MGH positron camera revealed a 34 and 32 per cent decrease in perfusion to the hypoxic lung in the supine and erect positions and a 26 per cent decrease in the decubitus position with the hypoxic lung dependent (P equal to 0.94 from supine shift), indicating nearly equal vasoconstriction with shift of perfusion away from the hypoxic lung in all positions. Analysis of regional shifts in perfusion revealed an equal vasoconstrictor response from apex to base in the supine position but a greater response in the lower lung zones in the erect position where perfusion was also greatest.


Analgesic effect of ethyl alcohol.
The analgesic properties of ethyl alcohol administered i.v. were investigated, using elevation of the pain threshold for applied somatic stimuli as an index. Alcohol proved markedly superior to saline in this respect and produced an effect equivalent to that of i.v. morphine.


The effect of H3K79 dimethylation and H4K20 trimethylation on nucleosome and chromatin structure.
Histone methylation regulates chromatin function dependent on the site and degree of the modification. In addition to creating binding sites for proteins, methylated lysine residues are likely to influence chromatin structure directly. Here we present crystal structures of nucleosomes reconstituted with methylated histones and investigate the folding behavior of resulting arrays. We demonstrate that dimethylation of histone H3 at lysine residue 79 locally alters the nucleosomal surface, whereas trimethylation of H4 at lysine residue 20 affects higher-order structure.


Frizzled-7-targeted delivery of zinc oxide nanoparticles to drug-resistant breast cancer cells.
There is a need for novel strategies to treat aggressive breast cancer subtypes and overcome drug resistance. ZnO nanoparticles (NPs) have potential in cancer therapy due to their ability to potently and selectively induce cancer cell apoptosis. Here, we tested the in vitro chemotherapeutic efficacy of ZnONPs loaded via a mesoporous silica nanolayer (MSN) towards drug-sensitive breast cancer cells (MCF-7: estrogen receptor-positive, CAL51: triple-negative) and their drug-resistant counterparts (MCF-7TX, CALDOX). ZnO-MSNs were coated on to gold nanostars (AuNSs) for future imaging capabilities in the NIR-II range. Electron and confocal microscopy showed that MSN-ZnO-AuNSs accumulated close to the plasma membrane and were internalized by cells. High-resolution electron microscopy showed that MSN coating degraded outside the cells, releasing ZnONPs that interacted with cell membranes. MSN-ZnO-AuNSs efficiently reduced the viability of all cell lines, and CAL51/CALDOX cells were more susceptible than MCF7/MCF-7-TX cells. MSN-ZnO-AuNSs were then conjugated with the antibody to Frizzled-7 (FZD-7), the receptor upregulated by several breast cancer cells. We used the disulphide (S-S) linker that could be cleaved with a high concentration of glutathione normally observed within cancer cells, releasing Zn2+ into the cytoplasm. FZD-7 targeting resulted in approximately three-fold amplified toxicity of MSN-ZnO-AuNSs towards the MCF-7TX drug-resistant cell line with the highest FZD-7 expression. This study shows that ZnO-MSs are promising tools to treat triple-negative and drug-resistant breast cancers and highlights the potential clinical utility of FZD-7 for delivery of nanomedicines and imaging probes specifically to these cancer types.


Resting-state connectivity alterations during transient global amnesia.
While the pathophysiology of transient global amnesia (TGA) is not understood, due to the specific nature of the clinical deficits, transient dysfunction in the medial temporal lobe, especially in the hippocampus, is assumed; however, concomitant disturbances in other brain regions and in executive function have been postulated. In this study, a cohort of 16 patients was prospectively recruited from the emergency department for resting-state functional MRI (fMRI) during the acute stage of TGA, as confirmed by a standardized neuropsychological assessment. Twenty age- and sex-matched controls, as well as twenty patients with a history of TGA, were recruited for comparison. Functional data were processed using independent component analysis (ICA), allowing the complete automatic (data-driven) identification of spontaneous network dynamics. We documented a severe disturbance in anterograde episodic long-term memory in all patients. Group-based ICA of resting-state data in acute TGA patients versus that of controls and patients with a past TGA episode demonstrated reduced FC mainly of structures belonging to the executive network (EN), but also the hippocampus, confirming its pathophysiological involvement in the disorder, as well as areas belonging to the salience network and other subcortical regions. No significant differences were found when comparing connectivity in patients with a history of TGA and controls. Our findings strengthen previous empirical and theoretical accounts of hippocampal and executive dysfunction in TGA. The disruption of frontal, parietal and insular control regions, together with disruption in the hippocampus, provides a new interpretation for the pathophysiology and neuropsychological profile of this neurological disorder on a large-scale network level.


Penile carcinoma: a twenty-five-year experience.
The treatment of 34 patients with carcinoma of the penis was reviewed during a twenty-five-year period (1958-1983). There were 26 patients with Stage I disease, 7 patients with Stage II, and 1 patient with Stage III disease. Among the Stage I group, 12 patients underwent partial/total penectomy and immediate ilioinguinal lymphadenectomy; 14 patients were treated with partial/total penectomy and observation of clinically nonpalpable nodes. Within the observation period, 10 of the 26 patients died, with a mean survival time of one hundred thirty-three months (standard error = 20.4), and a median of one hundred twenty months. Both the Mantel-Cox and Breslow test statistics showed the survival distribution of these groups of patients not to be significantly different from each other. All 7 patients with Stage II penile cancer died, with a mean survival time of 10.6 months (standard error = 2.1) which is significantly different from the Stage I group and the reported survival of 30-60 percent in the literature. A plan of management for the primary lesion and the role of ilioinguinal lymphadenectomy are presented.