Myocardial Disease and Long-Distance Space Travel: Solving the Radiation Problem.
Radiation-induced cardiovascular disease is a well-known complication of radiation exposure. Over the last few years, planning for deep space missions has increased interest in the effects of space radiation on the cardiovascular system, as an increasing number of astronauts will be exposed to space radiation for longer periods of time. Research has shown that exposure to different types of particles found in space radiation can lead to the development of diverse cardiovascular disease via fibrotic myocardial remodeling, accelerated atherosclerosis and microvascular damage. Several underlying mechanisms for radiation-induced cardiovascular disease have been identified, but many aspects of the pathophysiology remain unclear. Existing pharmacological compounds have been evaluated to protect the cardiovascular system from space radiation-induced damage, but currently no radioprotective compounds have been approved. This review critically analyzes the effects of space radiation on the cardiovascular system, the underlying mechanisms and potential countermeasures to space radiation-induced cardiovascular disease.


Contribution of the kidney to metabolic clearance of atrial natriuretic peptide.
To quantify the role of the kidney in whole body metabolic clearance rate (MCR) from plasma of atrial natriuretic peptide (ANP), synthetic alpha-human ANP-(1-28) was infused at 200 ng/min to steady-state conditions in chronically instrumented one-kidney conscious dogs. Clearances were measured in dogs with a normally filtering kidney and they were also measured after the glomerular filtration rate (GFR) was reduced to close to zero by acutely inflating a cuff around the renal artery (RAC), which resulted in minimal urine production and renal blood flow reduction to 59% of the resting level. In normal dogs, MCR was 1,090 +/- 134 ml/min with renal clearance rate (RCR) contributing only 13.9%. After RAC, MCR fell to 864 +/- 151 ml/min, due in part to a fall in RCR (-41.5 +/- 12.9 ml/min), but mostly due to a fall in "rest of the body" (total renal) clearance of ANP. The reduced GFR accounted for virtually all the fall in RCR. Normal plasma ANP half-life was 59.6 +/- 7.9 s. In conclusion, MCR of ANP was very high, approaching the cardiac output, suggesting that most of ANP is cleared in one circulation through peripheral tissues. GFR contributed significantly to RCR (approximately 30%) but the contribution of the kidney to whole body MCR was small relative to rest of the body clearance of ANP.


Schwann cells and fetal tectal tissue cografted to the midbrain of newborn rats: fate of Schwann cells and their influence on host retinal innervation of grafts.
Schwann cells transplanted into the adult central nervous system (CNS) can exert powerful growth-promoting effects on damaged axons. An important issue is whether central axons induced to regrow by Schwann cells retain the capacity to recognize and selectively innervate their appropriate target cells. To examine how Schwann cells may influence the specificity of neuron-neuron interactions in CNS neuropil, we cultured neonatal rat Schwann cells and mixed them with dissociated fetal tectal cells. In some instances, Schwann cells were prelabeled with Hoechst dye 33342. Schwann cells comprised between 2.5 and 15% of the combined cell population. After reaggregation, cografts were injected onto the midbrain of newborn rats. One to 6 months later, grafts were examined for the presence of Schwann cells and the pattern and density of host retinal innervation of the cografts was assessed. Immunohistochemical studies showed that areas of the transplants containing large numbers of surviving Hoechst-labeled Schwann cells were strongly immunoreactive for the low-affinity nerve growth factor receptor (p75), S-100, GFAP, and laminin. Very little peripheral (Po positive) myelin was seen. As in pure fetal tectal grafts, host retinal axons were sometimes observed to innervate superficial, localized areas in the cografts known to be homologous to the retinorecipient layers of the superior colliculus. Unlike pure tectal grafts, however, optic axons were not confined to these regions and fibers were often dispersed within the cograft neuropil. Dense growth was seen in association with Hoechst-labeled Schwann cells and, in some cases, optic axons were observed to grow toward Schwann cells and away from nearby target areas. These observations suggest that, under certain circumstances, Schwann cells can stimulate retinal axons to grow into inappropriate (nontarget) regions in the CNS, presumably by producing growth promoting factors which mask or compete with signals released from the target neurons themselves.


Breast cancer knowledge and screening practices: a survey of 1,000 Asian women.
The incidence of breast cancer in Asia is rapidly rising. Knowledge and perception often influence attendance at screening programmes. However, there has not been any survey to assess the level of knowledge of breast cancer in an Asian population. Singapore has a multiracial population and is the only Asian country with a national screening programme. We conducted a survey on 1,000 women to assess their level of knowledge and screening practices. A self-administered questionnaire was used, where one point was given for a correct answer and zero for an incorrect / "not sure" response. The maximum knowledge score was 19. The women were also surveyed for their screening practices. Points were not assigned to questions on practice. The response rate was 100 percent. The mean score was 11.4 and the median was 12 (range 0-19). The scores were high for general knowledge and disease progression, but poor for risk factors, screening, symptoms and treatment. Several myths and misconceptions were prevalent. Only 53 percent did regular breast self-examination (BSE), while 57 percent of women aged 40 years and above had gone for a screening mammogram. Increasing age, Malay race, lower educational level, lower socioeconomic class and not knowing anyone with breast cancer were significant independent predictors of poor knowledge. Higher educational level and knowledge scores were significant independent predictors of BSE practice and screening mammogram attendance. Knowledge affects practice. Public education is required to correct misconceptions and focus on women with poor knowledge. This would help to improve screening attendance rates.


The rapid antidepressant effect of acupuncture on two animal models of depression by inhibiting M1-Ach receptors regulates synaptic plasticity in the prefrontal cortex.
It is unclear whether acupuncture has a rapid antidepressant effect and what is the main mechanism. In this study, forced swimming stress test (FST) in mice were divided into five groups: control group, acupuncture group, scopolamine group, arecoline group, and acupuncture + arecoline group. Chronic unpredictable mild stress (CUMS) model rats were divided into six groups: naïve (non-CUMS) group, CUMS group, acupuncture group, scopolamine group, arecoline group, and acupuncture + arecoline group. Twenty-four hours after the end of treatment, FST was conducted in mice and rats. The expression of M1-AchR, AMPA receptors (GluR1 and GluR2), BDNF, mTOR, p-mTOR, synapsin I, and PSD95 in the prefrontal cortex was determined by western blot. The spine density of neurons in the prefrontal cortex was detected by golgi staining. The results showed that acupuncture reduced the immobility time of FST in two depression models. Acupuncture inhibited the expression of M1-AchR and promoted the expression of GluR1, GluR2, BDNF, p-mTOR, synapsin I, PSD95, and increased the density of neuron dendritic spine in the prefrontal cortex. The rapid antidepressant effect of acupuncture may be activating the "glutamate tide" - AMPA receptor activation - BDNF release - mTORC1 pathway activation through inhibiting the expression of M1-AchR in the prefrontal cortex, thereby increasing the expression of synaptic proteins and regulating synaptic plasticity.


Assisted reproductive techniques in Latin America: the Latin American Registry 2016.
What was the utilization, effectiveness and perinatal outcome of assisted reproductive technologies (ART) performed in Latin America during 2016? Retrospective collection of multinational data on ART performed in 178 institutions from 15 Latin American countries. This paper reports on 85,474 initiated cycles, 15,070 deliveries and 18,182 babies born in this period. Of all fresh autologous IVF/intracytoplasmic sperm injection (ICSI) cycles, 40.9% were performed in women aged 35-39 years, and 31.1% in women aged ≥40 years. After removing freeze-all cycles, delivery rate per oocyte retrieval was 20.31% for ICSI and 21.85% for IVF. Fresh single embryo transfer including all age categories represented 22.96%, with a 15.35% delivery rate per transfer. Double embryo transfer represented 61.58% of transfers, with a 27.62% delivery rate per transfer. Multiple births included 18.12% twins and 0.55% triplets and higher. In oocyte donation, delivery rate per transfer was 32.89%, with a twin and triplet rate of 23.48% and 0.73%, respectively. Overall, preterm deliveries reached 17.11% in singletons, 65.69% in twins and 95.51% in triplets. Perinatal mortality was 8.0‰ in singletons, 19.0‰ in twins, and 62.3‰ in high-order multiples. The number of initiated cycles continues to increase. Compared with previous years, the number of embryos transferred decreased while the proportion of single embryo transfers increased with a drop in multiple births. It is vital to motivate health care providers and consumers to continue this trend.


A 500-kiloton airburst over Chelyabinsk and an enhanced hazard from small impactors.
Most large (over a kilometre in diameter) near-Earth asteroids are now known, but recognition that airbursts (or fireballs resulting from nuclear-weapon-sized detonations of meteoroids in the atmosphere) have the potential to do greater damage than previously thought has shifted an increasing portion of the residual impact risk (the risk of impact from an unknown object) to smaller objects. Above the threshold size of impactor at which the atmosphere absorbs sufficient energy to prevent a ground impact, most of the damage is thought to be caused by the airburst shock wave, but owing to lack of observations this is uncertain. Here we report an analysis of the damage from the airburst of an asteroid about 19 metres (17 to 20 metres) in diameter southeast of Chelyabinsk, Russia, on 15 February 2013, estimated to have an energy equivalent of approximately 500 (±100) kilotons of trinitrotoluene (TNT, where 1 kiloton of TNT = 4.185×10(12) joules). We show that a widely referenced technique of estimating airburst damage does not reproduce the observations, and that the mathematical relations based on the effects of nuclear weapons--almost always used with this technique--overestimate blast damage. This suggests that earlier damage estimates near the threshold impactor size are too high. We performed a global survey of airbursts of a kiloton or more (including Chelyabinsk), and find that the number of impactors with diameters of tens of metres may be an order of magnitude higher than estimates based on other techniques. This suggests a non-equilibrium (if the population were in a long-term collisional steady state the size-frequency distribution would either follow a single power law or there must be a size-dependent bias in other surveys) in the near-Earth asteroid population for objects 10 to 50 metres in diameter, and shifts more of the residual impact risk to these sizes.


Compensated second-order recoupling: application to third spin assisted recoupling.
We consider the effect of phase shifts in the context of second-order recoupling techniques in solid-state NMR. Notably we highlight conditions leading to significant improvements for the Third Spin Assisted Recoupling (TSAR) mechanism and demonstrate the benefits of resulting techniques for detecting long-distance transfer in biomolecular systems. The modified pulse sequences of PAR and PAIN-CP, Phase-Shifted Proton Assisted Recoupling (AH-PS-PAR) and Phase-Shifted Proton-Assisted Insensitive Nuclei Cross Polarization (ABH-PS-PAIN-CP), still rely on cross terms between heteronuclear dipolar couplings involving assisting protons that mediate zero-quantum polarization transfer between low-γ nuclei ((13)C-(13)C, (15)N-(15)N, (15)N-(13)C polarization transfer). Using Average Hamiltonian Theory we show that phase inversion compensates off-resonance contributions and yields improved polarization transfer as well as substantial broadening of the matching conditions. PS-TSAR greatly improves on the standard TSAR based methods because it alleviates their sensitivity to precise RF settings which significantly enhances robustness of the experiments. We demonstrate these new methods on a 19.6 kDa protein (U-[(15)N, (13)C]-YajG) at high magnetic fields (up to 900 MHz (1)H frequency) and fast sample spinning (up to 65 kHz MAS frequency).


A phase III extension trial with a 1-arm crossover from leuprolide to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancer.
We investigated the efficacy and safety of degarelix treatment and the effects of switching from leuprolide to degarelix in an ongoing extension study with a median 27.5-month followup of a pivotal 1-year prostate cancer trial. Patients who completed a 1-year pivotal phase III trial continued on the same monthly degarelix maintenance dose (160 or 80 mg in 125 each), or were re-randomized from leuprolide 7.5 mg to degarelix 240/80 mg (69) or 240/160 mg (65). Data are shown on the approved degarelix 240/80 mg dose. The primary end point was safety/tolerability and the secondary end points were testosterone, prostate specific antigen, luteinizing hormone and follicle-stimulating hormone responses, and prostate specific antigen failure and progression-free survival. During followup testosterone and prostate specific antigen suppression were similar to those in the 1-year trial in patients who continued on degarelix or switched from leuprolide. The prostate specific antigen progression-free survival hazard rate was decreased significantly after the switch in the leuprolide/degarelix group while the rate in those who continued on degarelix was consistent with the rate in treatment year 1. The same hazard rate change pattern occurred in the group with baseline prostate specific antigen greater than 20 ng/ml. Adverse event frequency was similar between the groups and decreased with time. Data support the statistically significant prostate specific antigen progression-free survival benefit for degarelix over leuprolide seen during year 1 and the use of degarelix as first line androgen deprivation therapy as an alternative to a gonadotropin-releasing hormone agonist.


Factors associated with enrollment of African Americans into a clinical trial: results from the African American study of kidney disease and hypertension.
Recruitment of diverse populations into clinical trials remains challenging but is needed to fully understand disease processes and benefit the general public. Greater knowledge of key factors among ethnic and racial minority populations associated with the decision to participate in clinical research studies may facilitate recruitment and enhance the generalizibility of study results. Therefore, during the recruitment phase of the African American Study of Kidney Disease and Hypertension (AASK) trial, we conducted a telephone survey, using validated questions, to explore potential facilitators and barriers of research participation among eligible candidates residing in seven U.S. locations. Survey responses included a range of characteristics and perceptions among participants and non-participants and were compared using bivariate and step-wise logistic regression analyses. One-hundred forty-one respondents in the one-hundred forty (70 trial participants and 71 non-participants) completed the survey. Trial participants and non-participants were similar in multiple demographic characteristics and shared similar views on discrimination, physician mistrust, and research integrity. Key group differences were related to their perceptions of the impact of their research participation. Participants associated enrollment with personal and societal health benefits, while non-participants were influenced by the health risks. In a step-wise linear regression analysis, the most powerful significant positive predictors of participation were acknowledgement of health status as important in the enrollment decision (OR=4.54, p=0.006), employment (OR=3.12, p = 0.05) and healthcare satisfaction (OR=2.12, p<0.01). Racially-based mistrust did not emerge as a negative predictor and subjects' decisions were not influenced by the race of the research staff. In conclusion, these results suggest that health-related factors, and not psychosocial perceptions, have predominant influence on research participation among African Americans.


Implementing trachoma control programmes in marginalised populations in Tanzania: A qualitative study exploring the experiences and perspectives of key stakeholders.
Despite aspects of the SAFE strategy for reducing trachoma in Tanzania have been somewhat successful, the disease still persists in marginalised communities even with repeated trachoma control interventions. This study aims to understand the facilitators and barriers associated with implementing trachoma control programmes in these communities, from the perspective of non-governmental organisations (NGOs). Participants were the representatives of NGOs who had knowledge and experience in the implementation of trachoma control programmes. Data was collected using in-depth, semi-structured interviews guided by a topic guide, which was updated after each interview using a constant comparative method. Interviews were audio-recorded and then transcribed verbatim. Thematic analysis was done inductively. Codes were generated from the transcripts and then clustered into themes. The context within marginalised communities often acted as a perceived barrier to successful implementation of control programmes. This included poor environmental cleanliness, lack of trust, poor disease knowledge and traditional lifestyles. Community values could either be a facilitator or a barrier, depending on the scenario. The anatomical location of the disease and the poor understanding of the disease progression also served as barriers. Considerations affecting decision-making among NGO's include financial feasibility, community needs and whether the quality of the intervention could be improved. NGOs felt that the collaboration and the opportunity to learn from other organisations were beneficial aspects of having different actors. However, this also resulted in variability in the effectiveness of interventions between districts. NGOs should focus on behaviour change and health education that is tailored to marginalised communities and seek innovative ways to implement trachoma intervention programmes whilst being minimally intrusive to the traditional way of life. Partners should also implement ways to ensure high quality programmes are being provided, by increasing staff accountability and compensating volunteers fairly.


Realization of entry-to-practice milestones by Canadians who studied medicine abroad and other international medical graduates: a retrospective cohort study.
International medical graduates must realize a series of milestones to obtain full licensure. We examined the realization of milestones by Canadian and non-Canadian graduates of Western or Caribbean medical schools, and Canadian and non-Canadian graduates from other medical schools. Using the National IMG Database (data available for 2005-2011), we created 2 cohorts: 1) international medical graduates who had passed the Medical Council of Canada Qualifying Examination Part I between 2005 and 2010 and 2) those who had first entered a family medicine postgraduate program between 2005 and 2009, or had first entered a specialty postgraduate program in 2005 or 2006. We examined 3 entry-to-practice milestones; obtaining a postgraduate position, passing the Medical Council of Canada Qualifying Examination Part II and obtaining a specialty designation. Of the 6925 eligible graduates in cohort 1, 2144 (31.0%) had obtained a postgraduate position. Of the 1214 eligible graduates in cohort 2, 1126 (92.8%) had passed the Qualifying Examination Part II, and 889 (73.2%) had obtained a specialty designation. In multivariate analyses, Canadian graduates of Western or Caribbean medical schools (odds ratio [OR] 4.69, 95% confidence interval [CI] 3.82-5.71) and Canadian graduates of other medical schools (OR 1.49, 95% CI 1.31-1.70) were more likely to obtain a postgraduate position than non-Canadian graduates of other (not Western or Caribbean) medical schools. There was no difference among the groups in passing the Qualifying Examination Part II or obtaining a specialty designation. Canadians who studied abroad were more likely than other international medical graduates to obtain a postgraduate position; there were no differences among the groups in realizing milestones once in a postgraduate program. These findings support policies that do not distinguish postgraduate applicants by citizenship or permanent residency status before medical school.


APOE region molecular signatures of Alzheimer's disease across races/ethnicities.
The role of even the strongest genetic risk factor for Alzheimer's disease (AD), the apolipoprotein E (APOE) ε4 allele, in its etiology remains poorly understood. We examined molecular signatures of AD defined as differences in linkage disequilibrium patterns between AD-affected and -unaffected whites (2673/16,246), Hispanics (392/867), and African Americans (285/1789), separately. We focused on 29 polymorphisms from 5 genes in the APOE region emphasizing beneficial and adverse effects of the APOE ε2- and ε4-coding single-nucleotide polymorphisms, respectively, and the differences in the linkage disequilibrium structures involving these alleles between AD-affected and -unaffected subjects. Susceptibility to AD is likely the result of complex interactions of the ε2 and ε4 alleles with other polymorphisms in the APOE region, and these interactions differ across races/ethnicities corroborating differences in the adverse and beneficial effects of the ε4 and ε2 alleles. Our findings support complex race/ethnicity-specific haplotypes promoting and protecting against AD in this region. They contribute to better understanding of polygenic and resilient mechanisms, which can explain why even homozygous ε4 carriers may not develop AD.


In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools.
Eugenol shows both antibacterial and antiparasitic activities, suggesting that it might be evaluated as an option for the treatment of praziquantel-resistant schistosome. The in vitro activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from Schistosoma mansoni were examined by fluorescence and scanning electron microscopy to analyze effects on the excretory system and integument damage, respectively. Biochemical tests with verapamil (a calcium channel antagonist) and ouabain (a Na+/K+-ATPase pump inhibitor) were used to characterize eugenol derivative interactions with calcium channels and the Na+/K+-ATPase, while in silico analysis identified potential Na+/K+-ATPase binding sites. The compounds showed effective doses (ED50) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED50, ED90 and ED100 (p < 0.05), caused the most damage to the excretory system and integument, according to both fluorescence and scanning electron microscopy analysis. The death of adult worms was delayed by ouabain treatment plus FB1 (192 versus 72 hours) and FB9 (192 versus 168 hours), but the response to FB4 was the same in the presence or absence of ouabain. Besides, no changes were noted when all of the eugenol derivatives were combined with verapamil. Moreover, FB1 and FB9 inhibited Na+/K+-ATPase activity according to in silico analysis but FB4 did not show a time-dependent relationship and may act on targets other than the parasite Na+/K+-ATPase. Eugenol derivatives, mainly FB4 when compared to FB1 and FB9, seem to act more effectively on the integument of adult S. mansoni worms.


Designing AAC Research and Intervention to Improve Outcomes for Individuals with Complex Communication Needs.
There is a rapidly growing body of research that demonstrates the positive effects of augmentative and alternative communication (AAC) intervention on the communication of children and adults with complex communication needs. Despite the positive impact of many AAC interventions, however, many individuals with complex communication needs continue to experience serious challenges participating in educational, vocational, healthcare, and community environments. In this paper, we apply the framework proposed by the International Classification of Functioning, Disability and Health (ICF) to illustrate the need to re-think AAC intervention to improve outcomes for individuals with complex communication needs, and to foster a new generation of intervention research that will provide a solid foundation for improved services. Specifically, the paper emphasizes the need to take a more holistic view of communication intervention and highlights the following key principles to guide AAC intervention and research: (a) build on the individual's strengths and focus on the integration of skills to maximize communication, (b) focus on the individual's participation in real-world contexts,


Autoregulation of histamine synthesis through H3 receptors in isolated fundic mucosal cells.
Histamine plays an important role in the control of gastric acid secretion by activating H2 receptors located on parietal cells. In gastric mucosa, histamine is stored both in mast cells and in enterochromaffin-like cells, especially in rodents. It has been proposed that histamine may regulate its own synthesis and/or release through receptors pharmacologically distinct from H1- and H2-receptor subtypes. In this article, we studied the regulation by histamine of histidine decarboxylase (HDC) activity (enzyme responsible for the formation of histamine by decarboxylation of L-histidine) in a fraction of isolated rabbit gastric mucosal cells enriched in mucous and endocrine cells. Histamine and (R)-alpha-methylhistamine (H3 receptor agonist) dose dependently inhibited HDC activity with the same potency (mean effective concn: 32.2 +/- 0.7 and 50.5 +/- 3.1 pM, respectively) and efficacy (35 and 36% inhibition, respectively). In contrast, the H2 agonist dimaprit was devoid of effect. The H3 antagonist thioperamide was found to decrease the histamine- or (R)-alpha-methylhistamine-induced inhibition of HDC activity (mean ineffective concn = 28.3 +/- 1.8 and 9.87 +/- 0.8 nM, respectively), whereas H1 (promethazine) and H2 (ranitidine) antagonists were unable to affect HDC activity. Moreover, high concentrations of thioperamide (1-10 microns) increased histamine release from these cells. All these results allowed us to conclude that, in gastric mucosa, histamine downregulates its own synthesis (and perhaps release) through the stimulation of autoreceptors with pharmacological characteristics of H3 receptors. However, the relationship between histamine synthesis and release remains unclear and needs further investigation.


Modeling charge separation in charged nanochannels for single-molecule electrometry.
We model the transport of electrically charged solute molecules by a laminar flow within a nanoslit microfluidic channel with electrostatic surface potential. We derive the governing convection-diffusion equation, solve it numerically, and compare it with a Taylor-Aris-like approximation, which gives excellent results for small Péclet numbers. We discuss our results in light of designing an assay that can measure simultaneously the hydrodynamic size and electric charge of single molecules by tracking their motion in such nanoslit channels with electrostatic surface potential.


The effect of Russian Maternity Home routines on breastfeeding and neonatal weight loss with special reference to swaddling.
Few investigations have considered evaluating the effects of certain combinations of ward routines like swaddling of the baby and separation of mother and baby on infant variables such as neonatal weight loss. To study the effect of different ward routines in respect to proximity to mother and type of infant apparel, on breastfeeding parameters (amount of ingested milk, volume of supplements, number of breastfeeds, total duration of breastfeeding time) day 4 after birth as well as recovery from neonatal weight loss and infant's weight on day 5. In a randomized trial with factorial design four treatment groups including 176 mother-infant dyads were studied 25-120 min after birth. Randomized treatments focused on care routines administered to the infants after delivery and later in the maternity ward as well as to the type of clothing the infants received. Group 1 infants were placed skin-to-skin with their mothers after delivery, and had rooming-in while in the maternity ward. Group 2 infants were dressed and placed in their mothers' arms after delivery, and roomed-in with mothers in the maternity ward. Group 3 infants were kept in the nursery both after birth and while their mothers were in the maternity ward. Group 4 infants were kept in the nursery after birth, but roomed-in with their mothers in the maternity ward. Equal numbers of infants were either swaddled or clothed in baby attire. Breastfeeding parameters were documented during day 4 after birth. Infant's weight was measured daily. Babies who were kept in the nursery received significantly more formula and significantly less breast-milk, than did babies who roomed-in with their mothers. Swaddling did not influence the breastfeeding parameters measured. However, swaddled babies who had experienced a 2-h separation period after birth and then were reunited with their mothers tended to have a delayed recovery of weight loss compared to those infants who were exposed to the same treatment but dressed in clothes. Furthermore, swaddled babies who were kept in the nursery and received breast-milk supplements had a significantly delayed recovery of weight loss after birth when compared to those infants ingesting only breast-milk. On day 5, regression analyses of predicted weight gain in the exclusively breastfed infants indicated a significant increase per 100 ml breast-milk (59 g), compared to the predicted weight gain on day 5 per 100 ml supplements in the swaddled babies (14 g) (P=0.001). Supplements given to the infants in the nursery had a negative influence on the amount of milk ingested. In addition, supplement feeding or a short separation after birth when combined with swaddling was shown to have a negative consequence to infant weight gain.


Wide antral circumferential vs. ostial pulmonary vein isolation using pulsed field ablation-the butterfly effect.
Wide antral circumferential ablation (WACA) in comparison to ostial pulmonary vein (PV) isolation (PVI) has been attributed with improved rhythm outcome. We investigated the feasibility, lesion formation, and rhythm outcome of WACA-PVI in comparison to ostial-PVI using pulsed field ablation (PFA). Symptomatic atrial fibrillation (AF) patients (69 years, 67% male; 67% paroxysmal AF) were prospectively enrolled into our single-center registry and underwent first-time ostial-PFA or WACA-PFA, N = 15 each. In all patients, eight pulse trains (2 kV/2.5 s, bipolar, biphasic, 4× basket/flower configuration each) were delivered to each PV. In WACA-PFA, two extra pulse trains in a flower configuration were added to the anterior and posterior antrum of the PVs. For comparison of PFA lesion size, pre- and post-ablation left atrial (LA) voltage maps were acquired using a multipolar spiral catheter together with a three-dimensional electroanatomic mapping system. WACA-PFA resulted in a significant larger lesion formation than ostial-PFA (45.5 vs. 35.1 cm2, p = 0.001) with bilateral overlapping butterfly shape-like lesions and concomitant posterior LA wall isolation in 73% of patients. This was not associated with increased procedure time, sedation dosage, or exposure to radiation. One-year freedom from AF recurrence was numerically higher after WACA-PFA than ostial-PFA (94% vs. 87%) but not statistically significant (p = 0.68). No organized atrial tachycardias (ATs) were observed. Ostial-PFA patients more often underwent re-ablation due to recurrent AF episodes. WACA-PFA is feasible and resulted in significantly wider lesion sets than ostial-PFA. Concomitant posterior LA wall isolation occurred as an epiphenomenon in the majority of patients. The WACA approach was associated with neither increased procedure and fluoroscopy times nor statistically significant differences in 1-year rhythm outcome. ATs were absent.


Life is back to normal and yet not - partners' and patient's experiences of life of the first year after colorectal cancer surgery.
To describe the experience of life the first year after surgery from the perspective of persons treated for colorectal cancer and their partners. Colorectal cancer is a common cancer form, and treatment can cause unpleasant side effects such as sexual dysfunction and bowel problems. Partners struggle to keep family life normal and provide support. Little is known about couples' experiences a year after treatment for colorectal cancer. Qualitative descriptive. Individual semi-structured interviews with 13 persons treated for colorectal cancer and their partners, a total of 26 participants. One theme was identified in the study; 'Life is back to normal and yet not': participants described living a normal but different life than before. Three subthemes were identified; 'Life has a shadow of death', 'The treated body sets the rules' and 'To share or not share the illness'. Findings showed that both the patients' and their partners' lives were influenced by uncertainty and the condition of the patient. Attitudes varied towards sharing the illness. It was found that information needs varied both within and between couples. A future challenge to healthcare personnel is the obligation to meet the needs of both patients and their partners on the illness trajectory and recovery after treatment for colorectal cancer. Findings enhance the understanding of the impact of colorectal cancer on both patients and partners. Healthcare personnel need to assess both the patient's and partner's need for information, support and assistance. Support groups could be an effective tool for providing information, communication and support. Future studies are needed to evaluate such groups.


Update of the Xylella spp. host plant database - systematic literature search up to 30 June 2019.
Following a request from the European Commission, EFSA was asked to create and regularly update a database of host plant species of Xylella spp. In 2018, EFSA released a new Xylella spp. host plant database that was now updated with informative data extracted from 76 recent publications retrieved through an extensive literature search. This report is related to the third version of the database published in Zenodo in the EFSA Knowledge Junction community, covering articles selected from: a systematic literature review conducted up of 30 June 2019; Europhyt database up to 15 October 2019; and relevant articles identified by EFSA Horizon scanning and personal communications from experts. Some data on Xylella fastidiosa strains and geographical coordinates included in the already published database were updated or modified with the purpose of increasing the accuracy and consistency of the database itself. Thirty-seven new host plant species of X. fastidiosa, identified through the data extracted from the selected publications, have been added to the database. Those plant species were reported as naturally infected, artificially infected or infected under unspecified conditions by subsp. multiplex, pauca or unknown (i.e. not reported in the publication) subspecies of X. fastidiosa. No additional data were retrieved for Xylella taiwanensis. Six new Sequence Types (STs) have been identified in Brazil, Italy and the USA. Information on the tolerant/resistant response of plant species or varieties to X. fastidiosa infection are also reported in the database. The overall number of Xylella spp. host plants reaches now 343 plant species, 163 genera and 64 families determined with two different detection methods, till 595 plant species, 275 genera and 85 families regardless the detection method applied. The EFSA database on Xylella spp. host plants is updated regularly with the aim to provide information and scientific support to risk assessors, risk managers and researchers dealing with Xylella spp.


Microbiology of otitis media in Costa Rican children, 1999 through 2001.
Because of the increasing number of resistant middle ear pathogens and the impact of the new conjugate Streptococcus pneumoniae vaccine, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required. To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media (AOM), recurrent otitis media (ROM) and therapeutic failure otitis media (FOM). Between 1999 and 2001 middle ear fluid (MEF) was collected from 276 Costa Rican patients. S. pneumoniae serotyping and pulsed field gel electrophoresis analysis was done on available strains. Among the total study population, 102 were AOM patients, 98 were ROM patients and 76 were FOM patients. Overall S. pneumoniae (88 strains) was the most common pathogen isolated followed by Haemophilus influenzae (41 strains) and Streptococcus pyogenes (10 strains). H. influenzae was the most common agent in FOM patients (P = 0.015). Beta-lactamase production was observed in 3 of 41 (7%) H. influenzae strains and 3 of 3 (100%) Moraxella catarrhalis strains. Penicillin-nonsusceptible S. pneumoniae strains were more common in FOM (64%) and ROM (63%) patients than in AOM (42%) patients (P = 0.05). S. pneumoniae serotype 19F was the most prevalent serotype, mainly within one distinct clone. Overall S. pneumoniae serotype 19F was the most common isolate from the middle ear fluid of Costa Rican children. Beta-lactamase-negative H. influenzae was the most prevalent in the subpopulation of patients with FOM. S. pyogenes was the third most common isolate and M. catarrhalis was uncommon.


Long-term exposure to fine particulate matter and incidence of diabetes in the Danish Nurse Cohort.
It has been suggested that air pollution may increase the risk of type 2 diabetes but data on particulate matter with diameter <2.5μm (PM2.5) are inconsistent. We examined the association between long-term exposure to PM2.5 and diabetes incidence. We used the Danish Nurse Cohort with 28,731 female nurses who at recruitment in 1993 or 1999 reported information on diabetes prevalence and risk factors, and obtained data on incidence of diabetes from National Diabetes Register until 2013. We estimated annual mean concentrations of PM2.5, particulate matter with diameter <10μm (PM10), nitrogen oxides (NOx) and nitrogen dioxide (NO2) at their residence since 1990 using a dispersion model and examined the association between the 5-year running mean of pollutants and diabetes incidence using a time-varying Cox regression. Of 24,174 nurses 1137 (4.7%) developed diabetes. We detected a significant positive association between PM2.5 and diabetes incidence (hazard ratio; 95% confidence interval: 1.11; 1.02-1.22 per interquartile range of 3.1μg/m(3)), and weaker associations for PM10 (1.06; 0.98-1.14 per 2.8μg/m(3)), NO2 (1.05; 0.99-1.12 per 7.5μg/m(3)), and NOx (1.01; 0.98-1.05 per 10.2μg/m(3)) in fully adjusted models. Associations with PM2.5 persisted in two-pollutant models. Associations with PM2.5 were significantly enhanced in never smokers (1.24; 1.09-1.42), and augmented in obese (1.25; 1.06-1.47) and subjects with myocardial infarction (1.32; 0.86-2.02), but without significant interaction. Fine particulate matter may the most relevant pollutant for diabetes development among women, and non-smokers, obese women, and heart disease patients may be most susceptible.


Evaluation of magnetic resonance diffusion and spectroscopy measurements as predictive biomarkers in stage 1 cervical cancer.
To establish whether ADC and total choline were significantly different between cervical tumors with different histological characteristics (type, degree of differentiation, presence or absence of lymphovascular invasion, lymph-node involvement) in order to establish their role as predictive biomarkers. 62 patients with stage 1 cervical cancer were scanned at 1.5 T. T2-weighted imaging (TR/TE=4500/80 ms), to identify tumor and normal cervix, was followed by diffusion-weighted imaging (TR/TE=2500/69 ms; 5 b-values 0, 100, 300, 500 and 800 s/mm(2)) and MR spectroscopic imaging (15 mm slice, 7.5 mm in-plane resolution, TR=888 ms). Regions of interest in normal cervix and tumor were drawn on apparent diffusion coefficient (ADC) maps by an expert observer with reference to the T2-weighted images. ADCs were calculated using a monoexponential fit of data from all b-values. MR spectra in voxels designated as tumor (>30% tumor) or non-tumor were quantified using LCModel and referenced to tissue water. There was a statistically significant difference between the ADC of tumor regions (1117+/-183x10(-6) mm(2)/s) and of selected normal regions (1724+/-198x10(-6) mm(2)/s; p<0.001), and between tumors that were well/moderately differentiated (1196+/-181x10(-6) mm(2)/s) compared with those that were poorly differentiated (1038+/-153x10(-6) mm(2)/s; p=0.016). There was no significant difference between the ADCs of the tumors when separated by other characteristics (tumor type, lymphovascular invasion, lymph-node metastases), or between measured total choline in any of the groups. ADCs are lower in cancer compared to normal cervical tissue, with degree of tumor differentiation contributing to this difference.


Characteristics of Specialty Mental Health Provider Networks in Oregon Medicaid.
Provider networks for mental health are narrower than for other medical specialties. Providers' influence on access to care is potentially greater in Medicaid because enrollees are generally limited to contracted providers, without out-of-network options for nonemergency mental health care. The authors used claims-based metrics to examine variation in specialty mental health provider networks. In a cross-sectional analysis of 2018 Oregon Medicaid claims data, claims from adults ages 18-64 years (N=100,515) with a psychiatric diagnosis were identified. In-network providers were identified as those associated with any medical claims filed for at least five unique Medicaid beneficiaries enrolled in a health plan (coordinated care organization [CCO]) during the study period. Specialty mental health providers were categorized as prescribers (psychiatrists and mental health nurse practitioners) and nonprescribers (therapists, counselors, clinical nurse specialists, psychologists, and social workers). Measures of network composition, provider-to-population ratio, continuity, and concentration of care were calculated at the CCO level; the correlation between these measures was estimated to describe the degree to which they capture unique dimensions of provider networks. Across 15 CCOs, the number of prescribing providers per 1,000 patients was relatively stable. CCOs that expanded their networks did so by increasing the number of nonprescribing providers. Moderately negative correlations were found between the nonprescriber provider-to-population ratio and proportions of visits with prescribers as well as with usual provider continuity. This analysis advances future research and policy applications by offering a more nuanced view of provider network measurement and describing empirical variation across networks.


Malnutrition, tube feeding and pressure sores: data are incomplete.
To review data about the relationship between pressure sores and (1) nutritional status, (2) nutrient intake, and (3) tube feeding. Medline search of terms associated with "decubitus ulcer" combined with terms associated with "pressure sore" from 1985 through August 1994. Hand review of all issues of the journal Decubitus (now Advances in Wound Care) through June 1994 and the Journal of Parenteral and Enteral Nutrition from January 1987 through May-June 1994. Review of bibliography of pertinent articles. A small survey of experts. Articles where the title, Me SH terms, or abstract suggested an examination of the relationship between nutrition and pressure sores, and those suggested by the experts, were reviewed. Study designs were disparate. Results were simply tabulated. In seven studies, low serum albumin was associated with development or presence of pressure sores; in five it was not. Most measures of nutritional status were not associated with pressure sore outcomes. Poor nutritional intake was associated with poor pressure sore outcome in four of seven studies. Tube feeding was positively associated with presence of pressure sores in one study. Special nutrition support was ineffective in improving pressure sore outcome in a second. Two studies showed better healing in patients receiving high-protein formula: in one, all patients were tube fed; in the other, route of feeding was not stated. Data about the relationship between malnutrition and pressure sores are incomplete and contradictory. No randomized trials of tube feeding as prevention or treatment of pressure sores has been done. Routine use of tube feeding to prevent or treat pressure sores is not clearly supported by data.


Differential Interaction of Cannabidiol with Biomembranes Dependent on Cholesterol Concentration.
Cannabidiol (CBD), the major nonpsychoactive component of plant-derived cannabinoids, has been reported to have a broad range of potential beneficial pharmacological effects on the central nervous system (CNS). In this study, the droplet interface bilayer, a model cell membrane, is used to examine the effects of CBD on passive water permeability, a fundamental membrane biophysical property. The presence of CBD decreases the water permeability of model lipid membranes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and at low concentrations of cholesterol (Chol) (20 mol %) in DOPC, whereas when higher concentrations of Chol are present (33 mol %), CBD has an opposing effect, increasing water permeability. The diametric effect in water permeability change upon addition of CBD to Chol-low and Chol-high bilayers signifies a variant interaction of CBD, depending on the initial state of bilayer packing and fluidity. Additionally, differential scanning calorimetry studies provide evidence that there are selective changes in thermotropic behavior for CBD with DOPC and with DOPC/Chol membranes, respectively, supportive of these varying membrane interactions of CBD dependent upon cholesterol. The intriguing ability of CBD to sensitively respond to membrane Chol concentrations in modifying physical properties highlights the significant impact that CBD can have on heterogeneous biomembranes including those of the CNS, the neurons of which are enriched in Chol to a point where up to a quarter of the body's total Chol is in the brain, and defective brain Chol homeostasis is implicated in neurodegenerative diseases.


Evaluation of single pixel step sizes in visual acuity assessment.
Adaptive thresholding procedures (e.g., ZEST) benefit from testing near the current estimate of threshold. Therefore, small increments may improve precision of these techniques. We evaluated the validity of visual acuity assessment when letters are not constrained to a multiple of 5 pixels high. Snellen letters were presented over a ±5 pixel range spanning the final threshold estimate. Sizes that were a multiple of 5 pixels (e.g., 20 and 25) were presented 160 times, and other sizes were presented 40 times. This resulted in 320 letter presentations at multiples of 5 and at non-multiples of 5. Post hoc ZEST procedures were used to compute acuity threshold estimates based on testing at those two sets of sizes. Two subjects participated: subject 1 for the right and left eyes and subject 2 in two sessions with binocular viewing. Psychometric functions were fit to the data and were used to model simulated observers. Simulations were run for each data set, and the number of presentations at each size matched the number presented to the subject. Ninety percent limits for proportion correct at each letter size were determined from the simulation data, and these limits were used as criteria for identifying outliers in the subject's data. No significant difference in acuity thresholds were found when letters were rendered in multiples of 5 pixel heights vs. letters without this constraint. Empirical data fell within the bounds defined by simulations, with no idiosyncratic results found for either set of letter sizes. Letter sizes that do not conform to a multiple of 5 pixel letter height yield valid acuity scores. This facilitates adaptive psychometric procedures for acuity testing, such as ZEST and QUEST, in which letter sizes are selected to be as close to the current estimate of threshold size as possible.


Early antithymocyte globulin therapy improves survival in patients with steroid-resistant acute graft-versus-host disease.
Second-line therapies for steroid-resistant acute GVHD have been used with limited success. We have reviewed the responses of 79 hematopoetic stem cell transplant (HSCT) patients uniformly treated from 1990-1998 with equine antithymocyte globulin (ATG) for steroid-resistant acute GVHD, defined as progression of acute GVHD after 4 days of treatment with prednisone or no improvement of acute GVHD after 7 days of treatment with prednisone. Patients received HSCT from 34 related (32 matched sibling/2 partially matched) and 45 unrelated (14 HLA-A, -B, -DRB1 matched/31 partially matched) donors. Prior to ATG therapy, severe (grade III-IV) GVHD was observed in 34 patients (43%). Organs involved included skin in 81% of patients, lower GI tract in 52%, upper GI tract in 28%, and liver in 11%. Treatment consisted of 1-5 courses (median, 2 courses) of ATG (15 mg/kg per dose bid x 5 days) given for a median of 16 days (range, 5 to 44 days) after the onset of GVHD. All patients continued to receive prednisone, 60 mg/m2 per day (or methylprednisolone IV equivalent), plus CSA (75%) or tacrolimus (4%). At day 28 of treatment, overall improvement was observed in 54% of patients; durable (> or = 28 days) complete response was observed in 20% of patients, and partial response was observed in 34% of patients. In multivariate analysis, patients with CML or a malignant disease other than acute leukemia had a greater likelihood of overall response than did those with nonmalignant diseases. Patients with acute skin GVHD (with or without other organ involvement) responded most frequently. Chronic GVHD developed in 51% of patients by 1 year after HSCT. One patient developed EBV lymphoproliferative disease. For the entire cohort, the probability of survival at 1 year was 32% (95% CI, 22%-42%). In multivariate analysis, factors associated with better survival included earlier onset of acute GVHD, shorter time from initial treatment for GVHD to treatment with ATG, and the use of non-T-cell-depleted stem cell grafts. These data suggest that treatment with ATG can be an active therapy, especially in patients with skin GVHD and early signs of steroid resistance.


Extracellular vesicles and anti-cancer drug resistance.
Extracellular vesicles (EVs) including exosomes, microvesicles, oncosomes, and microparticles have been associated with communicating anti-cancer drug-resistance. The in vitro, pre-clinical in vivo and patients' data linking EVs to drug-resistance (and the specific drugs involved) in breast cancer, prostate cancer, lung cancer, ovarian cancer, haematological malignancies, colorectal cancer, gastric cancer, pancreatic cancer, glioblastoma, neuroblastoma, melanoma, kidney cancer and osteosarcoma. Details of the mechanisms by which the resistance seems to be occurring (e.g. EVs transferring drug-efflux pumps from drug-resistant cancer cells, EVs binding monoclonal antibodies in the peripheral circulation and so reducing their bioavailability, EVs from tumour microenvironment cells, etc.) are outlined, as are efforts to try to block such resistance. Research to date strongly supports EVs as playing a key role in drug-resistance. Further studies including tailored clinical studies are now warranted to determine how best to prevent this occurring, in the interest of patients and also for economic benefit. Furthermore, efforts to exploit safe (non-cancer origin) EVs as anti-cancer drug delivery vehicles that may achieve efficacy with more limited side-effects than free drug, deserve further investigation.


Diversity of intestinal Escherichia coli populations in Nicaraguan children with and without diarrhoea.
Escherichia coli remains an important aetiological agent of infantile diarrhoea in Nicaragua. However, little is known about whether there is a high prevalence of endemic strains or whether infection is due to the epidemic spread of virulent clones. This study was undertaken to determine the diversity and distribution of clonal groups in a population of intestinal E. coli isolated from the faeces of children from León, Nicaragua, with (n=381) and without (n=145) diarrhoea, between March 2005 and September 2006. All samples had been screened previously for the presence of diarrhoeagenic E. coli (DEC) markers by multiplex PCR. From each sample, 8 E. coli colonies (where available) were analysed by biochemical fingerprinting (PhP-RE system), yielding a total of 4009 tested isolates. On average, three different biochemical phenotypes (BPTs) were found among the eight colonies analysed from each sample. The total diversity, measured as Simpson's diversity index (Di), was 0.97 among all 4009 isolates studied. Cluster analysis of data from all 4009 isolates revealed 24 common BPTs (identified in at least 1 % of the isolates) and 234 less common BPTs. Similar Di values were obtained among isolates from infants with and without diarrhoea, indicating that no widespread outbreak of DEC had occurred. Moreover, among samples that were positive for the DEC types enteroaggregative E. coli, enteropathogenic E. coli and enterotoxigenic E. coli (ETEC) carrying the eltB gene, the diversities were almost as high as among non-DEC samples, whereas samples positive for ETEC carrying estA, enteroinvasive E. coli and enterohaemorrhagic E. coli showed lower diversities, indicating the prevalence of virulent clonal groups among these samples. The PhenePlate patterns of the 24 common BPTs identified here were compared with those obtained from E. coli isolated in a cohort infant study performed in 1991-1992 in the same area. Only 4 % of the isolates from the 1990s were similar to any of the common BPTs found in the present study.


Dilated intercavernous sinuses: an MR sign of carotid-cavernous and carotid-dural fistulas.
Dilated venous channels traversing the sella and connecting the two cavernous sinuses were seen on contrast-enhanced MR images in four patients with angiographically proved carotid fistulas. The anatomy and variations of these so-called intercavernous sinuses are discussed and are demonstrated in Latex-injected anatomic specimens. Direct visualization of the intercavernous sinuses on contrast-enhanced MR images may serve as an ancillary sign for the diagnosis of carotid-cavernous or carotid-dural fistulas near the sella.


More skin, more sun, more tan, more melanoma.
Although personal melanoma risk factors are well established, the contribution of socioeconomic factors, including clothing styles, social norms, medical paradigms, perceptions of tanned skin, economic trends, and travel patterns, to melanoma incidence has not been fully explored. We analyzed artwork, advertisements, fashion trends, and data regarding leisure-time activities to estimate historical changes in UV skin exposure. We used data from national cancer registries to compare melanoma incidence rates with estimated skin exposure and found that they rose in parallel. Although firm conclusions about melanoma causation cannot be made in an analysis such as this, we provide a cross-disciplinary, historical framework in which to consider public health and educational measures that may ultimately help reverse melanoma incidence trends.


Incidence of bacteremia and antimicrobial resistance, and associated factors among patients transferred from long-term care hospital.
To evaluate the prevalence of bacteremia and antimicrobial resistance, and associated factors among infectious patients transferred from long-term care hospitals (LTCHs). Consecutive adult patients who were transferred for suspected infection from affiliated LTCH's to study hospital emergency department (ED) over a 12 month period from January to December 2016 were included retrospectively. Patients with positive blood cultures (excluding contaminants as clinically determined) were defined as primary measure and subjected to further analysis according to antimicrobial resistance pattern. The latter was categorized into 4 subgroups based on groups of antimicrobial choices for empiric choices of suspected bloodstream infections. R-Group 0: bacteria susceptible to penicillin and amoxicillin; R-Group 1: bacteria resistant to penicillin/amoxicillin, first, second, or third generation cephalosporins. R-Group 2: ESBL-producing bacteria or bacteria resistant methicillin, fourth generation cephalosporin, or fluoroquinolone. R-Group 3: highly resistant pathogens including vancomycin resistant enterococci, carbapenem or colistin resistant Gram negatives. Blood culture isolate could therefore be included in >1 group. Among 756 patients who were transferred from LTCHs, we excluded 278 patients who were not suspicious of infection and 65 patients who were not checked blood culture at ED. In total, 422 patients were enrolled. The incidence of bacteremia was 20.4% (n = 86). The most frequent pathogen was E. coli (n = 25) followed by S. aureus (n = 10), S. epidermidis (n = 8), and K. pneumonia (n = 6). The incidences of the R-Group 1, 2, and 3 groups were 16.8% (n = 71), 14.4% (n = 61), and 1.4% (n = 6), respectively. Of the Gram-positive pathogens (n = 44), the R-Group 1, 2, and 3 groups were 84.1% (n = 37), 75.0% (n = 33), and 9.1% (n = 4), respectively. Of the Gram-negative pathogens (n = 46), the R-Group 1, 2, and 3 groups were 82.6% (n = 38), 69.6% (n = 32), and 4.3% (n = 2), respectively. Among tested variables, initial serum procalcitonin level was significantly associated with the presence of bacteremia (AOR 1.03, 95% confidence interval 1.00-1.05), R-Group 1 (1.04, 1.01-1.07) and the R-Group 2 (1.04, 1.00-1.06). The prevalence of bloodstream infections in patients admitted from LTCH was high (20.4%) with majority of these infections from resistant bacteria. Procalcitonin levels were significantly higher in bacteremic patients with an increasing trend towards bacteria in the antimicrobial resistant groups.


Emotion, regulation, and moral development.
Research and theory on the role of emotion and regulation in morality have received considerable attention in the last decade. Much relevant work has concerned the role of moral emotions in moral behavior. Research on differences between embarrassment, guilt, and shame and their relations to moral behavior is reviewed, as is research on the association of these emotions with negative emotionality and regulation. Recent issues concerning the role of such empathy-related responses as sympathy and personal distress to prosocial and antisocial behavior are discussed, as is the relation of empathy-related responding to situational and dispositional emotionality and regulation. The development and socialization of guilt, shame, and empathy also are discussed briefly. In addition, the role of nonmoral emotions (e.g. anger and sadness), including moods and dispositional differences in negative emotionality and its regulation, in morally relevant behavior, is reviewed.


Cocaine hepatotoxicity: influence of hepatic enzyme inducing and inhibiting agents on the site of necrosis.
Cocaine-induced hepatotoxicity has been reported in human beings and is well documented in mice. One interesting feature of this toxicity that appears to be common to both species is an apparent shift in the intraacinar site of necrosis under circumstances known to alter cocaine metabolism. However, the evidence in human subjects is limited, and studies elucidating the mechanism of this phenomenon cannot be performed in human beings. Although future studies in mice may define the basis of this mechanism, the current evidence is a somewhat fragmented composite of studies using different mouse strains and enzyme-inducing agents. Therefore a comprehensive pathologic investigation was initiated for the purpose of identifying and establishing an animal model suitable for studying this phenomenon. In naive ICR mice a single 60 mg/kg dose of cocaine was found to produce midzonal (zone 2) coagulative necrosis. In mice whose oxidative metabolism had been increased with beta-ionone or in which esterase metabolism had been inhibited by diazinon, the severity of the toxicity was increased but the intraacinar origin of the lesion did not change. However, when the oxidative microsomal metabolism of ICR mice was induced by phenobarbital or beta-naphthoflavone, the acinar zone affected was dramatically different. Phenobarbital induction produced zone 1 necrosis, whereas beta-napthoflavone induction caused necrosis in zone 3. The site of necrosis corresponded with the distribution of cocaine, and its metabolites were identified with colloidal gold-conjugated antibody probes. The results of this study suggest that the agents shifting the location of cocaine-induced hepatic necrosis alter the intraacinar site of protein binding of cocaine and its metabolites.


Contrasting patterns of phenotypic variation linked to chromosomal inversions in native and colonizing populations of Drosophila subobscura.
In fewer than two decades after invading the Americas, the fly Drosophila subobscura evolved latitudinal clines for chromosomal inversion frequencies and wing size that are parallel to the long-standing ones in native Palearctic populations. By sharp contrast, wing shape clines also evolved in the New World, but the relationship with latitude was opposite to that in the Old World. Previous work has suggested that wing trait differences among individuals are partially due to the association between chromosomal inversions and particular alleles which influence the trait under consideration. Furthermore, it is well documented that a few number of effective individuals founded the New World populations, which might have modified the biometrical effect of inversions on quantitative traits. Here we evaluate the relative contribution of chromosomal inversion clines in shaping the parallel clines in wing size and contrasting clines in wing shape in native and colonizing populations of the species. Our results reveal that inversion-size and inversion-shape associations in native and colonizing (South America) populations are generally different, probably due to the bottleneck effect. Contingent, unpredictable evolution was suggested as an explanation for the different details involved in the otherwise parallel wing size clines between Old and New World populations of D. subobscura. We challenge this assertion and conclude that contrasting wing shape clines came out as a correlated response of inversion clines that might have been predicted considering the genetic background of colonizers.


Bleaching and restoring endodontically treated teeth.
Internal, or "walking," bleaching has been successfully used in dentistry for many years to reverse stains associated with nonvital teeth. The procedure is predictable for color change but is not without problems. Current research has identified the cause of cervical resorption, which has been associated with internal bleaching. Second-generation esthetic bonding materials theoretically should provide an improved seal at the tooth-restorative interface, but the limited current research does not support this contention. A suggested method for internal bleaching and restoring the access cavity is presented.


Emerging Role of Myeloperoxidase in the Prognosis of Nephrotic Syndrome Patients Before and After Steroid Therapy.
Myeloperoxidase (MPO) is a myelocyte derived iron containing enzyme particularly involved in host defense by destroying foreign micro organisms invading the body. Numerous evidences suggest that MPO is involved in the pathogenesis of many inflammatory diseases, especially atherosclerosis. Present study deals with the role of MPO in the renal function and progression of disease in Nephrotic syndrome patients. Case- Control Study carried out in Kasturba Medical College Hospital, Mangalore, India. Forty newly diagnosed Nephrotic syndrome cases, 40 age and sex matched healthy controls and 15 subjects in Nephrotic syndrome remission, were included in the study. Myeloperoxidase enzyme was assayed by 4 amino antipyrine methods in all the subjects. Other renal parameters like urea, creatinine, Blood Urea Nitrogen (BUN), BUN- Creatinine ratio (BUN/Cr) total protein, albumin, globulin, albumin - globulin ratio (A/G ratio) and estimated Glomerular Filtration Rate (eGFR) were also analysed. 24 hour urine protein-creatinine ratio was estimated in Nephrotic syndrome cases and remission group by turbidimetric assay. Students paired t-test and Wilcoxon Signed Rank test were used for the comparison of the data. Pearson and Spearman analyses were used for correlation of the parameters. MPO levels were found to be high in Nephrotic syndrome cases when compared to healthy controls. Urea, creatinine, BUN, BUN/Cr ratio and eGFR were high in Nephrotic syndrome cases while total protein, albumin, globulin and A/G ratio showed decreased levels. MPO had a positive correlation with creatinine and urine protein-creatinine ratio in Nephrotic syndrome. During remission, MPO levels decreased significantly while total protein and albumin levels increased. Myeloperoxidase enzyme is found to be elevated and it strongly correlated with the severity of disease in Nephrotic syndrome. Further studies can be done to use MPO as a therapeutic target in Nephrotic syndrome to ameliorate the symptoms.


Diaper Slit Perineal Bag Urine Sampling.
Many indications justifiably drive the pediatrician to request a urine sample in order to assess the health status of the incontinent baby or infant. Urine collection by means of an adhesive perineal bag is the most widely used in children who do not control urine emission, despite its inaccurate reflection of bacteriuria. We suggest a novel technique to immediately visualize the micturition event upon occurrence, in attempt to shorten waiting times and exhausting checking and rechecking opaque diapers in order to determine whether the desired sample has finally been delivered. The perineal urine collection bag is pulled through a vertical slit created in the front of the disposable diaper. The bag is now visible at all times. In general, waiting times appear shortened since the implementation of this practice. Since the adoption of this technique at a number of our clinics, we have not experienced bag displacement as was previously experienced. Forgoing the need to manipulate the diaper and repeatedly awakening irritable infants was gladly welcomed by parents. Widespread adoption of the diaper slit technique seems a promising procedure enhancing comfort and facilitating the process of obtaining a urine sample in the incontinent child. Assumptions that this procedure actually shortens waiting times and raises the success rates of sample retrieval remain to be proven by formal comparative trials.


Vasoconstrictor and corticosteroid responsive components of allergic nasal mucosal swelling.
This study evaluated the relative contributions of vascular engorgement and less reversible components of inflammation (edema, cellular infiltration) to production of allergic nasal congestion. We established the minimum nasal airway resistance (NAR) inducible by oxymetazoline spray in 29 asymptomatic patients. During ragweed season, we restudied them with the same decongestant regimen before and after 1 week of treatment with oral methylprednisolone (Medrol tablets, Upjohn) or a matched placebo. It was not possible, in the conditions of this study, to decongest symptomatic patients to baseline using only the topical vasoconstrictor. This could be accomplished in those receiving methylprednisolone. Corticoid therapy relieved a non-vascular component of congestion or rendered vasoconstrictor therapy more effective.


Communicating PNPLA3 genetic risk status for NAFLD among Mexican-origin men.
The burden of non-alcoholic fatty liver disease (NAFLD) continues to disproportionately impact under-resourced communities in the U.S., particularly Mexican-origin populations. Genetic polymorphisms such as the rs738409 C/G variant in patatin-like phospholipase domain-containing 3 (PNPLA3) have been associated with higher prevalence of and progression along the NAFLD spectrum. This qualitative study conducted in the U.S. Southwest aimed to assess Mexican-origin men's experience receiving genetic testing for PNPLA3 risk carrier status. Semi-structured interviews were conducted with 17 Mexican-origin men whose NAFLD status and genetic predisposition were determined as part of a previous cross-sectional study. The interview guide included questions exploring participants' insights on how genetic risk status was delivered, how the information influenced their motivation for lifestyle modification to reduce NAFLD risk, and any knowledge sharing that occurred with family members after learning of their PNPLA3 risk status. Interviews were conducted and audio recorded in English (n = 6) and Spanish (n = 11) and uploaded into NVivo software for data analysis and interpretation. Guided by the Health Belief Model, a thematic analysis approach was used to identify primary themes. Results highlighted men's preference for receiving this type of genetic risk information through a letter sent to their homes. General comprehension of PNPLA3 risk status was deemed high and most men stated sharing their genetic predisposition to NAFLD with their immediate family members. Participants also indicated that family and awareness of this genetic risk acted as primary motivators for implementing behavior changes (e.g., diet, physical activity) toward the prevention of more severe liver conditions. Findings from this qualitative study suggest the feasibility of communicating genetic risk for NAFLD among Mexican-origin men. Future strategies for the dissemination of genetic risk results among Mexican-origin individuals should consider familial and cultural appropriate strategies.


STAIR Group Treatment for Veterans with PTSD: Efficacy and Impact of Gender on Outcome.
Group Skills Training in Affective and Interpersonal Regulation (STAIR) is an evidence-based, manualized treatment for individuals with post-traumatic stress symptoms, that focuses on improving functioning through mood management (e.g., emotion regulation) and relationship skills development. To date, no study has evaluated the potential benefit of group STAIR among Veterans. Feasibility of delivering STAIR in a mixed-gender group format and the potential impact of gender on outcome were examined. Participants (n = 39) were Veterans enrolled in a post-traumatic stress disorder (PTSD) Clinic at a large VA Medical Center. Veterans participated in one of four mixed-gender STAIR groups and completed self-report questionnaires of PTSD symptoms and general psychological distress at pre-treatment and post-treatment. Institutional review board approval was obtained for this study. There was significant pre-treatment to post-treatment improvements in PTSD symptoms as measured by the Post-traumatic Stress Checklist (PCL) (Cohen's d = 0.91), as well as in general psychological distress as measured by the Brief Symptom Inventory (BSI) (Cohen's d = 0.90). Change in PTSD symptoms from pre-treatment to post-treatment did not differ across gender. However, the interaction between gender and time on change in (BSI) was significant, where change in general psychological distress significantly decreased from pre-treatment to post-treatment for male Veterans but not for female Veterans. The results from this study demonstrate the feasibility and initial effectiveness of STAIR delivered in a mixed-gender group format for Veterans with PTSD. It should be noted, however, that male Veterans benefited more from this approach than female Veterans. The findings suggest the value of investigating Veterans' attitudes and beliefs about the benefits and drawbacks of mixed-gender group therapy for trauma-related difficulties.


[The participation of the delta opioid receptors in immunomodulation].
The delta-receptors agonist DSLET inhibited immune responses in the CBA mice. The immunosuppression was shown to be due to an interaction with the serotoninergic system. No immunostimulating effect of the delta-opioid receptors antagonist ICI 174,864 occurred in the animals with dissection of the pituitary stalk. The immunostimulation was shown to be realised via the thymus and prevented by a preliminary haloperidol blockade of the D-2 dopaminergic receptors. The cerebral delta-opioid receptors seem to participate in neuro-immunomodulation through the interaction with the serotonin and dopamine neurotransmitter systems.


Kinematic and kinetic parameters to identify water polo players' eggbeater kick techniques.
This study aimed to clarify the kinematic and kinetic parameters that identify the technical differences in the eggbeater kick. Twelve water polo players performed the eggbeater kick, and its kinematics were recorded by a motion capture system. Pressure distributions around the feet were measured by sixteen pressure sensors attached to the dorsal and plantar surfaces of the feet, from which the resultant fluid force acting on the feet and the vertical component of the force (i.e., propulsive force) were estimated. Repeated-measures analysis of variance (including post hoc test) results showed that the pressure difference, due to negative pressure on the dorsal side of the foot, around the first toe was significantly larger than the other foot segments (difference of up to 7 kN/m2, P < 0.01). Moreover, cluster analysis (including Fisher information) results showed that the kinetic (fluid force and pressure) data had a major influence on clustering; the highest Fisher information was 10.42 for the mean propulsive force. Among the kinematic foot parameters, the influence of the foot angle data on clustering was large, suggesting its importance as a technical parameter of the eggbeater kick in relation to the kinetic data.


Tramadol for the management of acute pain.
This paper reviews the use of tramadol in the management of acute pain. Tramadol is a weak opioid analgesic with a potency comparable to that of pethidine. While it is not recommended as a supplement to general anaesthesia because of its insufficient sedative activity, tramadol has been successful in the treatment of postoperative pain. Several studies have demonstrated its analgesic efficacy after intramuscular and intravenous application, both in adults and children. Moreover, negligible respiratory depressant activity and only minor side effects have consistently been shown. Patient-controlled analgesia with tramadol has been frequently employed and was well accepted by the patients. There have been only a few studies of oral or spinal application of tramadol in acute pain states. Tramadol has also been used for the control of pain associated with labour and acute myocardial infarction, as well as for the management of trauma pain. In summary, tramadol can be recommended as a basic analgesic for the treatment of patients with moderate to severe pain.


American Society of Hematology--40th annual meeting. 4-8 December 1998, Miami Beach, FL, USA.
The annual meeting of the American Society of Hematology was attended by over 30,000 researchers, nurses, hematologists and physicians. The work presented covered a spectrum from basic science, drugs in development and reports of clinical trials. Over 4600 abstracts were submitted with 3000 presented mainly in poster form. Overviews of clinical progress were presented in satellite symposia hosted by various pharmaceutical companies. An education program, including 23 sessions intending to summarize the 'state of the art' in various clinical fields, was also presented. The sessions are available in a book distributed for the first time to all members of the society. Forty 'meet-the-expert' breakfast sessions allowed free interchange between basic and clinical researchers and interested practitioners. The aim of this meeting was the dissemination of the results of research efforts to practising hematologists, who would then take home the newest information to apply to their daily clinical decisions. Because of the large size of the meeting and the many simultaneous sessions, this meeting report is confined to those areas of greatest interest to the reporter, although some mention will be made of other topics of general interest.


Energy consumption and its measurement in physical activity.
The low daily energy consumption of the average adult in the developed countries may be increased in certain individuals either because of the occupation or by voluntary activity in leisure. Jogging is one example of this. However, we have little objective information on activity within the population and epidemiologically this is a serious deficiency. There is a need for not only quantitative data on duration of activity but also its level of strenuousness. On the other hand, depending on the purpose of the measurement, it may not often be necessary actually to measure energy expenditure--heart rate measurement or energy values taken from published tables may be adequate. Indeed, energy expenditure or VO2 may not only be unnecessary but even misleading in some cases. When knowledge of energy consumption is required, (for example, in specialized biochemical or in nutritional studies) heart rates will not usually give an accurate enough prediction and oxygen uptake has to be measured. This has to be converted to energy units either by using the RQ or Weir's (1949) formula. Errors of up to +/- 10% may be common here, especially in short-term measurements in exercise. Weir's formula is more likely to lead to larger error and perhaps should be superceded.


The Implications of Drug-Polymer Interactions on the Physical Stability of Amorphous Solid Dispersions.
Amorphous solid dispersions (ASDs) are a formulation and development strategy that can be used to increase the apparent aqueous solubility of poorly water-soluble drugs. Their implementation, however, can be hindered by destabilization of the amorphous form, as the drug recrystallizes from its metastable state. Factors such as the drug-polymer solubility, miscibility, mobility, and nucleation/crystal growth rates are all known to impact the physical stability of an ASD. Non-covalent interactions (NCI) between the drug and polymer have also been widely reported to influence product shelf-life. In this review, the relationship between thermodynamic/kinetic factors and adhesive NCI is assessed. Various types of NCIs reported to stabilize ASDs are described, and their role in affecting physical stability is examined. Finally, NCIs that have not yet been widely explored in ASD formulations, but may potentially impact their physical stability are also briefly described. This review aims to stimulate further theoretical and practical exploration of various NCIs and their applications in ASD formulations in the future.


Fishmeal supplementation during ovine pregnancy and lactation protects against maternal stress-induced programming of the offspring immune system.
Prenatally stressed offspring exhibit increased susceptibility to inflammatory disorders due to in utero programming. Research into the effects of n-3 PUFAs shows promising results for the treatment and prevention of these disorders. The purpose of this study was to investigate whether maternal fishmeal supplementation during pregnancy and lactation protects against programming of the offspring's immune response following simulated maternal infection. In order to accomplish this, 53 ewes were fed a diet supplemented with fishmeal (FM; rich in n-3 PUFA) or soybean meal (SM; rich in n-6 PUFAs) from day 100 of gestation (gd 100) through lactation. On gd135, half the ewes from each dietary group were challenged with either 1.2 μg/kg Escherichia coli lipopolysaccharide (LPS) endotoxin to simulate a bacterial infection, or saline as the control. At 4.5 months of age the offspring's dermal immune response was assessed by cutaneous hypersensitivity testing with ovalbumin (OVA) and candida albicans (CAA) 21 days after sensitization. Skinfold measurements were taken and serum blood samples were also collected to assess the primary and secondary antibody immune response. Offspring born to SM + LPS mothers had a significantly greater change in skinfold thickness in response to both antigens as well as a greater secondary antibody response to OVA compared to all treatments. Supplementation during pregnancy with FM appears to protect against adverse fetal programming that may occur during maternal infection and this may reduce the risk of atopic disease later in life.


Congenital Chagas Disease in the United States: Cost Savings through Maternal Screening.
Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors through transfusions, transplants, insect feces in food, and from mother to child during gestation. Congenital infection could perpetuate Chagas disease indefinitely, even in countries without vector transmission. An estimated 30% of infected persons will develop lifelong, potentially fatal, cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment of Chagas disease in the United States. We constructed a decision-analytic model to find the lower cost option, comparing costs of testing and treatment, as needed, for mothers and infants with the lifetime societal costs without testing and the consequent morbidity and mortality due to lack of treatment or late treatment. We found that maternal screening, infant testing, and treatment of Chagas disease in the United States are cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence above 0.06% compared with no screening program. Newly approved diagnostics make universal screening cost saving with maternal prevalence as low as 0.008%. The present value of lifetime societal savings due to screening and treatment is about $634 million saved for every birth year cohort. The benefits of universal screening for T. cruzi as part of routine prenatal testing far outweigh the program costs for all U.S. births.


Metabolism of carbovir, a potent inhibitor of human immunodeficiency virus type 1, and its effects on cellular metabolism.
Carbovir (CBV) [the (--)-enantiomer of the carbocyclic analog of 2',3'-dideoxy-2',3'-didehydroguanosine] is a potent inhibitor of human immunodeficiency virus type 1 (HIV) replication in vitro. We have characterized the metabolism of CBV and its effect on cellular metabolism in an effort to better understand its mechanism of action. CBV was primarily metabolized to the 5'-triphosphate of CBV (CBV-TP) to concentrations sufficient to inhibit HIV reverse transcriptase. Infection of CEM cells with HIV did not affect the metabolism of CBV. In CEM cells, there was no evidence of the degradation of CBV by purine nucleoside phosphorylase. The half-life of CBV-TP in CEM cells was 2.5 h, similar to that of the 5'-triphosphate of zidovudine (AZT). However, unlike the levels of the 5'-triphosphate of AZT, CBV-TP levels declined without evidence of a plateau. CBV did not affect the metabolism of AZT, and AZT did not affect the metabolism of CBV. A small amount of CBV was incorporated into DNA in intact CEM cells, and this incorporation was increased by incubation with mycophenolic acid, an inhibitor of IMP dehydrogenase. CBV specifically inhibited the incorporation of nucleic acid precursors into DNA but had no effect on the incorporation of radiolabeled precursors into RNA or protein. CBV did not decrease the level of TTP, dGTP, dCTP, or dATP. These results suggested that the cytotoxicity of CBV was due to the inhibition of DNA synthesis. Further studies are necessary to identify the target(s) responsible for growth inhibition.


A Comparative Study of Serum Ferritin Levels Among Unfit and Fit Blood Donors.
Cheap methodologies are being utilized by low-resource countries to determine blood donors' fitness. Important hematological biomarkers might have to be evaluated to enhance the use of these methods. The study evaluated the pattern of serum ferritin in 18-24 fit and unfit prospective blood donors (PDBs) and the prevalence of iron store deficiency. This study was a cross-sectional, comparative study which was conducted at the blood donor clinic of the Lagos University Teaching Hospital. Blood samples were collected by venipuncture into sodium-ethylenediaminetetraacetic acid and plain bottles. The latter was centrifuged and used for ferritin determination via human ferritin enzyme-linked immunosorbent assay test kit, while the former was used for red cell indices analysis using an autoanalyzer. Data were analyzed using SPSS version 20, values were presented as mean ± standard deviation, and P ≤ 0.05 was considered statistically significant. A total of 263 PDB were recruited into the study consisting of 210 (79%) males and 53 (21%) females, with a mean age of 32.88 ± 8.22. Only 110 (41.8%) of the participants were considered fit, while 153 (58.2%) were unfit using copper sulfate specific gravity. There was no statistically significant difference (P = 0.301) in the mean level of serum ferritin in unfit blood donors (74.5 ± 90.8 μg/L) compared to that of the fit blood donors (61.5 ± 54.5 μg/L). The prevalence of iron store depletion among blood donors in Lagos state was 11.8% (31 of 263) with a higher proportion (7.6%) occurring among unfit donors. However, low levels of serum ferritin (<15 μg/L) were significantly associated with the occurrence of anemia (hemoglobin < 12.5 g/gl) among unit donors (19%; P = 0.05). Although serum ferritin depletion appears to be higher in the unfit blood donors, the use of serum ferritin as an index for the screening and determination of PDBs' fitness requires further evaluation.


Fitting contraceptive diaphragms: can laywomen provide quality training for doctors?
To test the feasibility of training laywomen as professional patients to teach doctors to fit the contraceptive diaphragm. Semi-structured interviews with instructing doctors and questionnaires to DFFP trainees. These documented current teaching practice and the acceptability of professional patients. The Delphi technique was used to establish a curriculum for the professional patients' training programme. The results show that there is currently a lack of standardisation in teaching methods and content with respect to diaphragm fitting. All instructing doctors and DFFP trainees involved had experienced difficulties in recruiting women for training, and the majority would be happy to work with professional patients. After three rounds of the Delphi procedure, consensus was reached and a curriculum developed. Five women were recruited on to a training programme, and four successfully completed it. Lack of standardisation and difficulty recruiting patients are current problems when training doctors to fit diaphragms. Our study shows that the use of professional patients would be acceptable to both DFFP trainees and instructing doctors, and that it is possible to recruit and train women for this purpose.


Simultaneous determination of curvature, plane of curvature, and temperature by use of a miniaturized sensing head based on fiber Bragg gratings.
We present what we believe to be a novel miniaturized sensor configuration based on fiber Bragg gratings for simultaneous measurement of curvature and temperature in smart structures and composite materials. Because of the particular geometry of the sensing head, it is possible not only to measure the radius of curvature but also to determine the plane of curvature. We arrange three Bragg gratings in the vertices of the smallest equilateral triangle that can be defined by the cross sections of the fibers. The set is then inserted into a glue-filled capillary stainless-steel tube to provide both suitable protection for the Bragg sensors and rotational symmetry to the sensing head. This tube also ensures isolation from axial strain, allowing for the additional determination of temperature. The proposed sensing head is particularly well suited for applications in smart structures because it can be embedded along any layer of a composite material (including the neutral line) without special concern for the relative orientation of the Bragg gratings and the composite layers. We can also use this sensing configuration to implement more-sophisticated sensors dedicated, for example, to the measurement of multiaxial acceleration or flow and temperature.


IGF gene polymorphisms and breast cancer in African-American and Hispanic women.
Previous studies from our group and others have shown that increased circulatory levels of the ligand insulin-like growth factor 1 (IGF-1) and decreased levels of the predominant IGF-1 binding protein 3 (IGFBP-3) are associated with an increased incidence of breast cancer and poor outcome. Some studies suggest that, in addition to the influence of environmental factors on the levels of IGF-1 and IGFBP-3, alterations in their gene polymorphisms may play a significant role in the risk of cancer. In this study, we investigated the association between gene polymorphisms along the IGF axis and breast cancer, including the IGF-1 (CA) dinucleotide repeat, IGFBP-3 A-202C single nucleotide polymorphism, and the 2-bp deletion and (AGG)n repeat polymorphisms in the IGF type 1 receptor (IGF-IR). A total of 654 subjects, including both African-American and Hispanic/Latino subjects, were screened for various gene polymorphisms. IGF gene polymorphism genotyping was performed by PCR-GeneScan and PCR-RFLP methods. Our results demonstrated a significant association between the non-19/non-19 IGF-1 (CA)n polymorphism and breast cancer (OR = 1.75; 95% CI = 1.07-2.88; P = 0.027). Furthermore, absence of the wild-type-19 allele and alleles <(CA)19 were strongly associated with breast cancer (OR = 1.82; 95% CI = 1.20-2.77; P = 0.005 and OR = 1.70; 95% CI = 1.19-2.43; P = 0.003, respectively). The association of the non-19/non-19 polymorphism with breast cancer was also more significant in premenopausal women (P = 0.04). We did not find any significant association of the IGFBP-3 polymorphism with breast cancer. In the case of IGF-1R polymorphisms, the only significant trend was in the (AGG)5 allele; however, the frequency of this allele was very rare. In summary, our study demonstrated a significant association of IGF-1 polymorphisms and breast cancer. Future studies are necessary to understand the mechanistic value of these polymorphisms in breast cancer risk.


Fibronectin-DNA-apatite composite layer for highly efficient and area-specific gene transfer.
In 2004, Shen et al. developed a safe and efficient gene transfer system using a DNA-apatite composite layer. We have recently succeeded in improving further the gene transfer efficiency by immobilizing a cell adhesion molecule laminin, in a DNA-apatite composite layer. In this study, we showed that not only laminin but fibronectin immobilized in a DNA-apatite composite layer enhances cell adhesion and cell spreading on the layer, thereby markedly improving the gene transfer efficiency. Therefore, the immobilization of a cell adhesion molecule in a DNA-apatite composite layer is crucial for improving the gene transfer efficiency. By using fibronectin instead of laminin and optimizing the condition to prepare the fibronectin-DNA-apatite composite layer, the amount (weight) of cell adhesion molecule required was reduced to approximately one-fourth while retaining the relatively high gene transfer efficiency. It was also shown that the resulting fibronectin-DNA-apatite composite layer prepared under the optimized condition mediated the area-specific gene transfer on its surface, that is, DNA was preferentially transferred to the cells adhering to the surface of the fibronectin-DNA-apatite composite layer. The present gene transfer system with potential for area-specific transfection and advantages of safety and relatively high efficiency would be useful in tissue engineering applications, gene therapy, and production of transfection microarrays.


[Meaning, phonological, orthography and kinestic route of reading and writing: a case with alexia and agraphia due to the left parietal lesion].
Abstract A 69-year-old right-handed man developed alexia with agraphia after resection of a brain tumor in the left parietal lobe. After the operation, neurological examination revealed right lower quadrantanopia, mild paresis and sensory disturbance on the right side. He showed marked alexia with agraphia, very mild aphasia, acalculia, and constructional disability. In reading tasks, he was able to read kanji word and kana words but not a single kana character or nonword. After he traced a single kana character or kana nonword, he was able to read it. In writing tasks, he could write kana but not kanji characters, except simple kanji characters that involved less than 4 strokes. These findings indicated that kinesthetic traces may enable such patients to read and write. We propose that processes of reading and writing may include kinesthetic route in addition to the meaning, phonological, and orthographical routes.


Assessing the primary data hosted by the Spanish node of the Global Biodiversity Information Facility (GBIF).
In order to effectively understand and cope with the current 'biodiversity crisis', having large-enough sets of qualified data is necessary. Information facilitators such as the Global Biodiversity Information Facility (GBIF) are ensuring increasing availability of primary biodiversity records by linking data collections spread over several institutions that have agreed to publish their data in a common access schema. We have assessed the primary records that one such publisher, the Spanish node of GBIF (GBIF.ES), hosts on behalf of a number of institutions, considered to be a highly representative sample of the total mass of available data for a country in order to know the quantity and quality of the information made available. Our results may provide an indication of the overall fitness-for-use in these data. We have found a number of patterns in the availability and accrual of data that seem to arise naturally from the digitization processes. Knowing these patterns and features may help deciding when and how these data can be used. Broadly, the error level seems low. The available data may be of capital importance for the development of biodiversity research, both locally and globally. However, wide swaths of records lack data elements such as georeferencing or taxonomical levels. Although the remaining information is ample and fit for many uses, improving the completeness of the records would likely increase the usability span for these data.


Comparing the priorities of parents and young people with cerebral palsy.
Adolescence is a period of change and transition that may pose unique challenges for young people with cerebral palsy (CP). We compared statements of priorities, i.e. what adolescents (13-17) and youth (18-21) and their parents would like to be able to do to enable greater activity and participation. Participants were 198 parents and 135 young people with CP (45% males) from seven Children's Hospitals in the United States. The interviews were structured using The Canadian Occupational Performance Measure. Priority statements were categorised as Adult Tasks, Biology, Self-Identity or Physical Activity. All parents identified more priorities for Biology and Adult Tasks (p < 0.001). Adolescents identified the fewest priorities for Self-Identity (p < 0.01). Youth identified, in descending order of frequency, priorities in Adult Tasks, Biology, Self-Identity and Physical Activity (p < 0.05). In the parent-young people dyads when disagreements occurred, Self-Identity issues were identified more often by parents (p < 0.05) and priorities for Physical Activity were identified more often by young people (p < 0.01). The shared and differing priorities of parents and young people with CP may reflect different roles, perceptions and experiences. The findings have implications for healthcare professionals, providing a framework to compare and contrast the priorities of young people and their parents.