Next-generation dengue vaccines: novel strategies currently under development.
Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.


Suspected predatory bites on a snorkeler by an oceanic whitetip shark Carcharhinus longimanus off Moorea island (French Polynesia).
Understanding why sharks bite humans is essential for developing strategies to prevent these incidents. Here, we use bite wound characteristics and eye witness descriptions of shark behavior to determine the likely motivation for several bites perpetrated by an oceanic whitetip (OWT) shark Carcharhinus longimanus on an adult female snorkeler off Moorea island (French Polynesia) in October 2019. The victim was snorkeling with others in pelagic waters as part of an organized whale-watching tour when the shark-without any warning behavior-bit her at least three times resulting in severe injuries with substantial loss of soft tissue from the chest and both forearms. The victim survived these injuries thanks to rapid and effective first aid provided by her companions. The sudden, unprovoked and repeated bites with substantial tissue removal are consistent with predatory behavior although the dominance hypothesis cannot be fully ruled out. This would be the first case of a predatory shark bite ever documented in French Polynesia in over 70 years of data collection. Given the routine association of OWT sharks with cetaceans, in-water whale watching activities should adopt appropriate risk management strategies in regions hosting this species of shark.


The negative self-perceived health of migrants with precarious status in Montreal, Canada: A cross-sectional study.
Knowledge about the health impacts of the absence of health insurance for migrants with precarious status (MPS) in Canada is scarce. MPS refer to immigrants with authorized but temporary legal status (i.e. temporary foreign workers, visitors, international students) and/or unauthorized status (out of legal status, i.e. undocumented). This is the first large empirical study that examines the social determinants of self-perceived health of MPS who are uninsured and residing in Montreal. Between June 2016 and September 2017, we performed a cross-sectional survey of uninsured migrants in Montreal, Quebec. Migrants without health insurance (18+) were sampled through venue-based recruitment, snowball strategy and media announcements. A questionnaire focusing on sociodemographic, socioeconomic and psychosocial characteristics, social determinants, health needs and access to health care, and health self-perception was administered to 806 individuals: 54.1% were recruited in urban spaces and 45.9% in a health clinic. 53.9% were categorized as having temporary legal status in Canada and 46% were without authorized status. Regions of birth were: Asia (5.2%), Caribbean (13.8%), Europe (7.3%), Latin America (35.8%), Middle East (21%), Sub-Saharan Africa (15.8%) and the United States (1.1%). The median age was 37 years (range:18-87). The proportion of respondents reporting negative (bad/fair) self-perception of health was 44.8%: 36.1% among migrants with authorized legal status and 54.4% among those with unauthorized status (statistically significant difference; p<0.001). Factors associated with negative self-perceived health were assessed using logistic regression. Those who were more likely to perceive their health as negative were those: with no diploma/primary/secondary education (age-adjusted odds ratio [AOR]: 2.49 [95% CI 1.53-4.07, p<0.001] or with a college diploma (AOR: 2.41 [95% CI 1.38-4.20, p = 0.002); whose family income met their needs not at all/a little (AOR: 6.22 [95% CI 1.62-23.85], p = 0.008) or met their needs fairly (AOR: 4.70 [95% CI 1.21-18.27], p = 0.025); with no one whom they could ask for money (AOR: 1.60 [95% CI 1.05-2.46], p = 0.03); with perception of racism (AOR: 1.58 [95% CI 1.01-2.48], p = 0.045); with a feeling of psychological distress (AOR: 2.17 [95% CI 1.36-3.45], p = 0.001); with unmet health care needs (AOR: 3.45 [95% CI 2.05-5.82], p<0.001); or with a health issue in the past 12 months (AOR: 3.44 [95% CI 1.79-6.61], p<0.001). Some variables that are associated with negative self-perceived health varied according to gender: region of birth, lower formal education, having a family income that does not meet needs perfectly /very well, insalubrious housing, not knowing someone who could be asked for money, and having ever received a medical diagnosis. In our study, almost half of immigrants without health insurance perceived their health as negative, much higher than reports of negative self-perceived health in previous Canadian studies (8.5% among recent immigrants, 19.8% among long-term immigrants, and 10.6% among Canadian-born). Our study also suggests a high rate of unmet health care needs among migrants with precarious status, a situation that is correlated with poor self-perceived health. There is a need to put social policies in place to secure access to resources, health care and social services for all migrants, with or without authorized status.


[Leber's hereditary optic neuropathy and its possible relation to a recent epidemic in Cuba].
This century, the greatest epidemic affecting the nervous system was notified in Cuba seven years ago. At the present time the epidemic continues although to a lesser extent. The clinical findings of the illness were mainly bilateral optic neuropathy sometimes accompanied by other symptoms and peripheral neuropathy. The similarity of the optic form of the illness with Leber's hereditary optic neuropathy, and their common risk factors, were obvious from the beginning. Statistics from the national reference department of neuro-ophthalmology of the Instituto de Neurologia de Cuba were reviewed. From these it was evident that the number of cases of Leber's hereditary optic neuropathy had increased in recent years, coinciding with the period of epidemic and endemic Cuban neuropathy. Many of these patients had previously been diagnosed as having epidemic optic neuropathy. We describe the characteristics of a group of these patients and discuss the differences and possible relationship between the two conditions. In the case of epidemic optic neuropathy, there is strikingly simultaneous loss of vision, less visual changes with much smaller cecocentral scotomas, loss of ganglion fibres of the retina around the papillomacular bundle, a good response to multivitamin treatment, and increased frequency of association with peripheral sensory neuropathy. This analysis reinforces the hypothesis that many patients with Leber's hereditary optic neuropathy, which started at the time of the epidemic, were incorrectly classified as suffering from this, and also perhaps their condition worsened due to the toxic nutritional features common to both conditions.


Owner-perceived, weighted quality-of-life assessments in dogs with spinal cord injuries.
To evaluate changes over time in owner-perceived, weighted quality-of-life assessments in dogs with spinal cord injuries and determine whether scores were associated with underlying etiology or with veterinarian-assigned scores for severity of neurologic dysfunction. Cohort study. 100 dogs with spinal cord injury. Duration of dysfunction, modified Frankel neurologic injury score, and etiology were recorded. At initial and recheck (4- to 6-week) evaluations, owners were asked to identify 5 areas or activities they believed had the most influence on their dogs' quality of life, assess their dogs' current status in each area, and provide a weighting for the importance of each area; results were used to construct a weighted quality-of-life score. Owners were also asked to provide a quality-of-life score with a visual analog scale (VAS). At initial and recheck evaluations, weighted quality-of-life scores were higher for ambulatory than for nonambulatory dogs. However, scores did not differ among groups when dogs were grouped on the basis of underlying etiology or duration of injury. Dogs with an increase in Frankel score between the initial and recheck evaluations had a significant increase in weighted quality-of-life score, whereas for dogs that did not have any change in Frankel score, initial and recheck weighted quality-of-life scores were not significantly different. Results suggested that owner-assigned, weighted quality-of-life scores for dogs with spinal cord injuries did not vary significantly on the basis of underlying etiology or duration of injury but were higher for ambulatory than for nonambulatory dogs.


Finger dexterity and hand function: effect of three commercial wrist extensor orthoses on patients with rheumatoid arthritis.
To investigate the effect of 3 commercial wrist orthoses on finger dexterity and hand function of patients with rheumatoid arthritis (RA). Forty-two patients with definite RA participated in the cross-over study comparing 3 styles of commercial wrist orthoses. Finger dexterity and hand function of the dominant hand were assessed while splinted and unsplinted, at the initial session and after 1 week of intermittent orthosis use. Finger dexterity was assessed using two subtests from the Purdue Pegboard Test (Purdue) and hand function was assessed using the Jebsen-Taylor Hand Function Test (Jebsen-Taylor). Both finger dexterity and hand function were reduced by splinting; men and women were affected similarly. There was no difference in finger dexterity or hand function afforded by the 3 orthoses. Results on both the Purdue and Jebsen-Taylor tests showed a significant learning effect across time. The 3 commercial wrist orthoses studied reduce dexterity similarly and significantly. When commercial wrist orthoses are to be used during tasks that require maximum dexterity, this reduction should be weighed against the known benefits of splinting.


Anastomoses between the cervical branch of the facial nerve and the transverse cervical cutaneous nerve.
Head and neck surgeons must possess a thorough knowledge of facial nerve anatomy to avoid inducing iatrogenic injury during surgery. Anastomoses of the cervical branch (CB) of the facial nerve and the transverse cervical cutaneous nerve (TCCN) are poorly documented in our field. Knowledge of these anastomoses and their positions allows for (1) preservation of high CBs that contribute to lower lip depressor function, and (2) identification of the facial nerve in retrograde dissections. Our objective was to improve understanding of facial nerve anatomy by describing these anastomoses. The communicating branch between the TCCN and the CB was evaluated in 22 adult neck halves (11 cadavers). The facial nerve was exposed, and the CB was traced anteriorly. The TCCN was identified and traced superiorly to its anastomosis(es) with the CB. The distance from each anastomosis to the selected landmarks was recorded. Between the CB and the TCCN, 33 anastomoses were identified, with at least 1 anastomosis per hemineck and 2 anastomoses in 11 heminecks. Anastomoses were identified along the inferior border of the submandibular gland (SMG; 20 specimens) or posterior to the SMG (12 specimens). Five specimens had both anastomoses near the inferior border of the SMG, and 6 specimens had 1 anastomosis near the inferior border and 1 posterior to the SMG. Communication between the TCCN and the CB is regularly present. Its anatomic locations are either posterior to the SMG, often within the parenchyma of the parotid gland, or near the inferior border of the SMG. Awareness of these anastomoses allows a method for identification and preservation of the CB of the facial nerve as well as a starting point for retrograde facial nerve dissections.


Mesoglycan: clinical evidences for use in vascular diseases.
Vascular glycosaminoglycans (GAG) are essential components of the endothelium and vessel wall and have been shown to be involved in several biologic functions. Mesoglycan, a natural GAG preparation, is a polysaccharide complex rich in sulphur radicals with strong negative electric charge. It is extracted from porcine intestinal mucosa and is composed of heparan sulfate, dermatan sulfate, electrophoretically slow-moving heparin, and variable and minimal quantities of chondroitin sulfate. Data on antithrombotic and profibrinolytic activities of the drug show that mesoglycan, although not indicated in the treatment of acute arterial or venous thrombosis because of the low antithrombotic effect, may be useful in the management of vascular diseases, when combined with antithrombotics in the case of disease of cerebral vasculature, and with antithrombotics and vasodilator drugs in the case of chronic peripheral arterial disease. The protective effect of mesoglycan in patients with venous thrombosis and the absence of side effects, support the use of GAG in patients with chronic venous insufficiency and persistent venous ulcers, in association with compression therapy (zinc bandages, multiple layer bandages, etc.), elastic compression stockings, and local care, and in the prevention of recurrences in patients with previous DVT following the standard course of oral anticoagulation treatment.


Health Promotion Effects of Soy Isoflavones.
Soybeans contain several physiologically active ingredients, such as soy phytosterol, soyasaponin, soy protein, and lecithin, and are therefore expected to express the functionalities of said ingredients. Among them, soy isoflavones have been studied in recent years for their various functions, including their obesity-preventing effect, blood glucose level reducing effect, osteoporosis and breast cancer risk reduction, and anti-oxidative effect, and several health promoting effects and disease preventing effects are expected. For example, it has been determined that soy isoflavones reduce body and fat weight in experiments in which mice were fed a diet containing soy isoflavones in studies on anti-obesity. Epidemiologic studies with humans have also shown that women who consume more soybeans have lower BMI than those who consume less. We previously found that soy isoflavones may have anti-obesity effects in myoblasts through the activation of transcriptional coactivator PGC-1β, which increases energy expenditure. In recent studies, a decrease in blood glucose level due to soy isoflavone was seen in an experiment in which diabetic model mice were fed a diet containing soy isoflavone. It has also been suggested that soy isoflavone intake may increase bone mineral density in postmenopausal women and reduce the risk of breast cancer. This review focuses on the actions of soy isoflavones known to date, including their anti-obesity and anti-diabetic effects, bone loss preventing effects, and cancer risk reduction effects, and introduces reports on the health promotion and disease prevention effects of soy isoflavones.


Surface transport and stable trapping of particles and cells by an optical waveguide loop.
Waveguide trapping has emerged as a useful technique for parallel and planar transport of particles and biological cells and can be integrated with lab-on-a-chip applications. However, particles trapped on waveguides are continuously propelled forward along the surface of the waveguide. This limits the practical usability of the waveguide trapping technique with other functions (e.g. analysis, imaging) that require particles to be stationary during diagnosis. In this paper, an optical waveguide loop with an intentional gap at the centre is proposed to hold propelled particles and cells. The waveguide acts as a conveyor belt to transport and deliver the particles/cells towards the gap. At the gap, the diverging light fields hold the particles at a fixed position. The proposed waveguide design is numerically studied and experimentally implemented. The optical forces on the particle at the gap are calculated using the finite element method. Experimentally, the method is used to transport and trap micro-particles and red blood cells at the gap with varying separations. The waveguides are only 180 nm thick and thus could be integrated with other functions on the chip, e.g. microfluidics or optical detection, to make an on-chip system for single cell analysis and to study the interaction between cells.


Comparative evaluation and effect of organic and inorganic fluoride dentifrices on enamel microhardness: An in vitro study.
To compare and evaluate the microhardness of enamel surface after the application of organic fluoride and inorganic fluoride dentifrices. Twenty freshly extracted premolars were collected and decoronation of all the teeth was done at cementoenamel junction. The crowns were sectioned mesiodistally into two halves with the help of diamond disc, and then the subsequent forty samples kept in 1% citric acid for the demineralization and divided into two groups by simple randomization, that is, Group A (inorganic sodium fluoride dentifrice) and Group B (organic amine fluoride dentifrice). They were treated using same protocol for 3 min, daily twice for 7 days. Those samples preserved in artificial saliva in between treatment. The enamel surface microhardness evaluated using Vickers hardness test at base level, after demineralization, as well as after remineralization. Statistical analysis of surface microhardness obtained at different stages done by Student's t-test and P < 0.05 was considered statistically significant. The samples which were treated with sodium fluoride (Group A) could not restore the mean microhardness after treatment to that of preoperative level whereas amine fluoride (Group B) treated samples showed a statistically significant increase in mean surface microhardness from baseline. Organic fluoride (amine fluoride) remineralization was more effective in restoring enamel microhardness than inorganic fluoride (sodium fluoride) remineralization.


[Fluctuation of intracerebral pressure in various types of neurosurgical pathology].
During surgery and in the post-operative period fluctuations of the intracerebral pressure and in the dynamics of the local cerebral circulation were investigated in patients with a severe cerebro-cranial injury, acute apoplectic stroke and occlusive hydrocephalia. This was done by using a combined pressure sensor that simultaneously recorded the intracerebral pressure by the volemic method and the local cerebral blood flow-through hydrogen clearance. In patients exhibiting different degrees of hypertension three types of the intracerebral pressure fluctuations were recognized, differing both in their frequency and the amplitude. In some cases the local cerebral blood flow proved inversely proportional to the intracranial pressure.


Factors associated with surgical site infection in myocardial revascularization: a retrospective longitudinal study.
to analyze the influence of sociodemographic and clinical variables, as well as the surgical checklist adherence score, on the occurrence of surgical site infection among patients undergoing myocardial revascularization. an observational, longitudinal, retrospective study was conducted at a university hospital, involving 266 medical records of patients who underwent myocardial revascularization surgery. Instruments containing sociodemographic, clinical, and infection-related variables were used, along with the Perioperative Surgical Safety Checklist. Descriptive, bivariate, and logistic regression analyses were employed. surgical site infection occurred in 89 (33.5%) patients. There was a statistically significant association between body temperature outside the range of 36 degrees Celsius to 36.5 degrees Celsius (p=0.01), the presence of invasive devices (p=0.05), surgical procedures with the anticipation of critical events (p<0.001), and the occurrence of infection. body temperature, the presence of invasive devices, and surgical procedures with the anticipation of critical events were significant factors contributing to an increased risk of infection.


Intestinal malrotation as an incidental finding on CT in adults.
Intestinal malrotation in adults is usually an incidental finding on computed tomography (CT). We present the CT findings of 18 adult patients with malrotation and discuss the clinical implications. Abdominal scans of 18 patients (12 women, six men; age range = 15-79 years) with intestinal malrotation were reviewed. Special attention was directed to the location of the superior mesenteric vessels, the location of the small and large bowels, the size of the uncinate process, the situs definition, and additional anomalies. The malrotation was an incidental finding in all but one patient. The malrotation was type Ia in 17 patients and IIc in the one symptomatic patient. The superior mesenteric vessels were vertically oriented in 10, inverted in two, normally positioned in four, and mirror imaged in two cases with situs ambiguus. All patients had aplasia of the pancreatic uncinate process, five had a short pancreas, and two had a preduodenal portal vein. Fourteen patients had a normal situs and four had heterotaxia. Seven patients had polysplenia, six of which with associated inferior vena cava anomalies. Intestinal malrotation can be diagnosed on CT by the anatomic location of a right-sided small bowel, left-sided colon, an abnormal relationship of the superior mesenteric vessels, and aplasia of the uncinate process. Awareness of these abnormalities is necessary to diagnose this anomaly. It should be sought in patients with a situs problem, inferior vena cava anomalies, polysplenia, or preduodenal portal vein. Although usually an incidental finding, it is important to diagnose such a malrotation because it may cause abdominal symptoms. Also, knowledge of associated vascular anomalies is important when abdominal surgery is planned.


Abnormal vitamin D metabolism in patients with psoriasis.
To elucidate if psoriatic skin involvement induces changes in vitamin D metabolism, the serum concentrations of the major vitamin D metabolites (25-hydroxy-vitamin D(2+3) (25OHD), 1,25-dihydroxyvitamin D(2+3) (1,25(OH)2D), and 24,25-dihydroxyvitamin D(2+3) (24,25(OH)2D)) were studied in a group of patients with psoriasis, who had not been exposed to ultraviolet radiation at least three months before the investigation. Serum concentrations of 1,25(OH)2D were significantly reduced in 17 patients with disseminated psoriasis compared to healthy age and sex matched controls (22.3 pg/ml versus 35.0 pg/ml (p less than 0.001)) and compared to 15 patients with moderate extended psoriasis (22.3 pg/ml versus 38.3 pg/ml (p less than 0.005)). Serum concentrations of the two other metabolites were not significantly decreased. In patients with moderate psoriatic skin manifestations, the values of the three vitamin D metabolites were normal. It is concluded that patients with disseminated psoriasis demonstrate decreased serum concentrations of the vitamin D metabolite 1,25(OH)2D. Since 1,25(OH)2D plays a role in differentiation and proliferation of epidermal cells, the abnormal low serum level of 1,25(OH)2D might be of importance for the abnormalities in cell maturation and proliferation found in psoriatic skin.


"I just want to be skinny.": A content analysis of tweets expressing eating disorder symptoms.
There is increasing concern about online communities that promote eating disorder (ED) behaviors through messages and/or images that encourage a "thin ideal" (i.e., promotion of thinness as attractive) and harmful weight loss/weight control practices. The purpose of this paper is to assess the content of body image and ED-related content on Twitter and provide a deeper understanding of EDs that may be used for future studies and online-based interventions. Tweets containing ED or body image-related keywords were collected from January 1-January 31, 2015 (N = 28,642). A random sample (n = 3000) was assessed for expressions of behaviors that align with subscales of the Eating Disorder Examination (EDE) 16.0. Demographic characteristics were inferred using a social media analytics company. The comprehensive research that we conducted indicated that 2,584 of the 3,000 tweets were ED-related; 65% expressed a preoccupation with body shape, 13% displayed issues related to food/eating/calories, and 4% expressed placing a high level of importance on body weight. Most tweets were sent by girls (90%) who were ≤19 years old (77%). Our findings stress a need to better understand if and how ED-related content on social media can be used for targeting prevention and intervention messages towards those who are in-need and could potentially benefit from these efforts.


The Benefit of Microskin in Combination With Autologous Keratinocyte Suspension to Treat Full Skin Loss In Vivo.
Patients with extensive deep burns often lack enough autologous skin to cover the wounds. This study explores a new method using microskin in combination with autologous keratinocytes in the treatment of extensive deep burn. Wounds in the combination group were treated with automicroskin at an area expansion ratio of 20:1 (wound area to automicroskin area) and autologous keratinocyte suspension, which were compared with the following treatments: no autotransplant, only allografts (control group); autologous keratinocyte suspension only (keratinocyte only group); automicroskin at an area expansion ratio of 20:1 (20:1 group); and automicroskin at an area expansion ratio of 10:1 (10:1 group, positive control). The authors used epithelialization rate (epithelialized area on day 21 divided by original wound area), hematoxylin and eosin staining, laminin, and type IV collagen immunohistochemistry to assess wound healing. The epithelialization rate of combination group (74.2% ± 8.0%) was similar to that of 10: 1 group (84.3% ± 11.9%, P = .085) and significantly (P < .05) higher than that of 20:1 group (59.2% ± 10.8%), keratinocyte only group (53.8% ± 11.5%), and control group (22.7% ± 5.5%). The hematoxylin and eosin staining and immunohistochemistry showed the epithelialization in the combination group was better than that in the keratinocyte only group and control group. Microskin in combination with autologous keratinocyte suspension can promote the reepithelialization of full-thickness wounds and reduce the requirements for automircoskin, and it is a useful option in the treatment of extensive deep burns.


Ultrasound Assessment of the Abdominal Muscles at Rest and During the ASLR Test Among Adolescents With Scoliosis.
Observational study. Are there deviations in the thickness of abdominal muscles at rest in individuals with adolescent idiopathic scoliosis (AIS)? Are there deviations in abdominal muscular activity in people with AIS during the active straight leg raise (ASLR) test? Ultrasound imaging can be used to assess the lateral abdominal muscle. Some authors suggest that scoliosis develops through a weakness or improper functioning of the abdominal muscles that cannot provide adequate support to the spinal segments. However, the literature lacks studies on the functioning of the abdominal muscles in individuals with spinal deviations. This study focuses on the evaluation of the thickness of the external oblique (EO), internal oblique (IO), and transversus abdominalis (TrA) muscles of individuals with AIS. Seventy-one healthy adolescents and 71 patients with AIS, all aged 10-16 years, were studied. The thickness of the muscles at rest was measured at the end of normal exhalation in millimeters. Muscular activity during the ASLR test was measured in the final position, and the standards were normalized with the thickness produced at rest. Muscular activity during the ASLR test was represented as a percentage change in the muscle thickness. The AIS group demonstrated a smaller resting thickness of all tested muscles of both sides (P<0.01). All the muscles on the right side of the body showed higher activity in the AIS group during the ASLR test (P<0.01). Patients with AIS had thinner EO, IO, and TrA at rest in the supine position. During the ASLR test, the AIS patients displayed higher activity of the EO, IO, and TrA muscles on the right side.


Simultaneous silence organizes structured higher-order interactions in neural populations.
Activity patterns of neural population are constrained by underlying biological mechanisms. These patterns are characterized not only by individual activity rates and pairwise correlations but also by statistical dependencies among groups of neurons larger than two, known as higher-order interactions (HOIs). While HOIs are ubiquitous in neural activity, primary characteristics of HOIs remain unknown. Here, we report that simultaneous silence (SS) of neurons concisely summarizes neural HOIs. Spontaneously active neurons in cultured hippocampal slices express SS that is more frequent than predicted by their individual activity rates and pairwise correlations. The SS explains structured HOIs seen in the data, namely, alternating signs at successive interaction orders. Inhibitory neurons are necessary to maintain significant SS. The structured HOIs predicted by SS were observed in a simple neural population model characterized by spiking nonlinearity and correlated input. These results suggest that SS is a ubiquitous feature of HOIs that constrain neural activity patterns and can influence information processing.


[A case of Leber's neuroretinitis].
Described in 1916 by Theodore Leber, this rare syndrome characterized by low visual acuity, papillary edema, and a macular star (dry exsudates) occurs classically in the 30 to 40 year age range but also as frequently in children. The visual prognosis is excellent. An infectious cause is found in almost all cases. Case report A 34-year-old man consulted for declining visual acuity of the right eye which began suddenly without pain and was preceded by a flu-like syndrome lasting two weeks. Visual acuity on the right side was 2/10 P6, there was optic disk edema associated with dry macular exsudate (macular star) and a paleness of the posterior pole progressing to the periphery and readily visualized on the angiography, and a central scotome, but no dyschromatopsy. The left eye was strictly normal. Laboratory tests showed an erythrocyte sedimentation rate at 45, C reactive protein at 61, normal red cell count and minimal transaminase elevation. Spinal tap showed: 3 elements/mm(3), protein 0.28g/l, 18% gammaglobulins. Serology tests were negative. Brain imaging was normal. Corticosteroid flashes for three days were initiated and the patient was seen again two weeks later with clear clinical improvement. Visual acuity was 6/10 P2 with considerable resorption of the edema. This case is a typical illustration of acute Leber's neuroretinititis, probably caused by viral infection. The cerebrospinal fluid tests and brain imaging ruled out multiple sclerosis, and serology tests for syphilis, tuberculosis, Lyme disease and possible parasite infection were negative. Acute lever's neuroretinitis is an uncommon condition which must be distinguished from inflammatory optic neuropathy, particularly in multiple sclerosis which has a very different prognosis and clinical course.


[Ectopic gastric mucosa in the proximal esophagus].
Gastric mucosa is not found often in the proximal and medial esophagus. Hematemesis and dysphagia are the most frequent symptoms. We report a six year-old child who complained of difficulty in swallowing. A filling defect was detect in the esophagogram. We biopsied the suspected area, through an endoscopy and the pathological examination informed of ectopic gastric mucosa. We performed a 99Tc isotopic study. The child is on ambulatory controls and at the moment is asymptomatic.


[Cytochemical research on the state of the histone component and of chromatin matrix activity in neurocytes of the rat sympathetic ganglion at different times after dissection of the pre- and postganglionic nerves].
Chromatin template activity and histones were studied in the rat superior cervical ganglion neurons of the 2nd, 10th and 60th days after bilateral pre- or postganglionic nerve division using the Moore method and the Black and Ansley ammoniacal silver staining technique. Alterations in chromatin template activity were found on the 2nd, and 10th days after operation when specific function of neurons was switched off. The dynamics of template activity was different for nucleolar and nucleoplasmic chromatins to be dependent on the type of operation. At the same periods after pre- and postganglionic nerve section the pattern of ammoniacal silver staining in neuron nuclei in the superior cervical ganglion became similar to that in nondifferentiated neurons. These alterations in transcription and histones disappeared by the 60th day after both the variants of operation. Changes in histone staining were absent after the false operation without nerve division. A conclusion is made on the existing of some connection between histone transformation during differentiation and specific functioning of nerve cells.


Supercritical fluid extraction of isoflavones from biological samples with ultra-fast high-performance liquid chromatography/mass spectrometry.
An efficient method of modifier addition for supercritical fluid extraction (SFE) of polar isoflavones was developed and yielded extraordinarily high recoveries. To find the optimal extraction conditions, a temperature and pressure optimization and modifier impact study was performed in naturally contaminated and spiked samples. Ultra-fast high-performance liquid chromatography/mass spectrometry (HPLC/MS) was used for the determination of isoflavones on an Atlantis dC18 high-speed reversed phase chromatographic column (20 x 2.1 mm, 3 microm particle size). A newly elaborated supercritical fluid extraction (SFE) procedure allowed more accurate (< 5%) and precise (< 4-7%) determination of isoflavones in biological materials. The HPLC/MS method significantly reduced analysis time with simultaneous improvement of sensitivity and detection limits. The on-column limits of detection LOD (S/N = 3) for isoflavone glycosides (daidzin, genistin, glycitin, ononin, and sissotrin) were 1.3-3.6 fmol and 0.2-1.0 fmol for aglycones (daidzein, glycitein, genistein, formononetin, and biochanin A), respectively.


[Vascular surgery preventing ischemic stroke: is it possible?].
Experience with 1057 surgeries performed in patients with carotid stenosis is analyzed. It is demonstrated that for the last 10 years angiography has not been performed for diagnosis confirmation, indications for surgery are based on duplex scanning results. Thirty-five percent of operated patients had no clinical symptoms, but the majority of the patients (44%) were referred to surgeons late, after stroke. Techniques of classic and eversion endarterectomies are described in details. Postoperative lethality ranged from 0.9 to 1.2%, rate of postoperative stroke--from 1.1 to 1.4%. Long-term results were studied up to 196 months after surgery. High prophylactic efficacy of carotid endarterectomy was demonstrated. There were no progression of ipsilateral neurological symptoms in 94.3% patients.


Influence of Biologic Subtype of Inflammatory Breast Cancer on Response to Neoadjuvant Therapy and Cancer Outcomes.
Few data exist on the influence of tumor biologic subtype on treatment response and outcomes for inflammatory breast cancer (IBC). We examined a contemporary cohort of IBC patients treated with current targeted systemic therapies, selected on the basis of tumor biologic subtype, to evaluate pathologic treatment response and cancer outcomes across biologic subtypes. We studied 57 clinical stage T4dM0 IBC patients operated on at our institution from October 2008 to July 2015. Comparisons across biologic subtypes were performed by Wilcoxon rank-sum or chi-square tests; Kaplan-Meier and log-rank tests were used to analyze survival outcomes. All patients received neoadjuvant systemic therapy; 54 (95%) completed postmastectomy radiation. Ninety-one percent (52/57) had clinically node-positive disease at presentation. Pathologic complete response (pCR) rates in the breast and axilla differed significantly by approximated biologic subtype, defined as estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER-2) negative; and HER-2 positive and ER negative/HER-2 negative (all P < .001). After 50 months' median follow-up, 20 patients experienced disease recurrence. Site of first relapse was distant in 80% (16/20). Disease-free survival (DFS) and breast cancer-specific survival (BCSS) differed significantly by biologic subtype. Five-year DFS was 46% for patients with ER-positive/HER-2-negative tumors, 82% for HER-2-positive tumors, and 33% for ER-negative/HER-2-negative tumors (P < .001), while 5-year BCSS was 76%, 100%, and 57%, respectively (P = .02)-notably better than historic reports. Our data show that both treatment response and outcomes vary significantly across IBC biologic subtypes. Multimodal treatment and modern systemic therapies have markedly improved DFS and BCSS. These data provide further evidence to suggest that IBC is not a distinct biologic entity transcending standard breast tumor marker subclassification.


Gambling related family coping and the impact of problem gambling on families in Hong Kong.
Despite substantial evidence that problem gambling is associated with a wide range of family difficulties, limited effort has been devoted to studying the negative impacts on family members as a result of problem gambling and how they cope and function under the impacts of problem gambling in Chinese communities. Among the very few Chinese-specific gambling-related family impact studies, none have examined how gambling-related family coping responses are related to gambling-related family impacts. Based on a sample of treatment-seeking Chinese family members of problem gamblers, this study aimed to explore: (1) the demographic characteristics and health and psychological well-being of the family members; (2) the gambling-related family member impacts (active disturbance, worrying behavior); (3) the family coping strategies (engaged, tolerant-inactive and withdrawal coping); (4) the relationship between gambling-related family member impacts, psychological distress and family coping strategies. It was hypothesized that positive significant relationships would be found between family member impacts, psychological distress and family coping strategies. From March 2011 to February 2012, a total of 103 family members of problem gamblers who sought help from Tung Wah Group of Hospitals Even Centre in Hong Kong were interviewed. Results showed that a majority of family members were partners or ex-partners of the gambler with low or no income. A large proportion of participants reported moderate to high psychological distress (72.6 %), poor to fair general health (60.2 %), and poor to neither good nor bad quality of life (61.1 %). Family member impacts were positively significantly correlated to all family coping strategies and psychological distress. Tolerant-inactive coping had the strongest relationships with family member impacts and psychological distress. Strong relationships between family member impacts and psychological distress were also found. The results provide preliminary support for aspects of the stress-strain-coping-support model in the Chinese culture. It is suggested that family member-specific treatment groups targeting family coping are required to alleviate the level of negative impacts of gambling disorder on family members.


Transcranial approach for spontaneous CSF rhinorrhea due to Sternberg's canal intrasphenoidal meningoencephalocele: case report and review of the literature.
One type of congenital intrasphenoidal meningoencephalocele is remnant of lateral craniopharyngeal (Sternberg's) canal. We present a case of a 23-year girl with 10-month history of right side CSF rhinorrhea. CT scan, MRI revealed congenital meningoencephalocele and CSF leak from middle fossa to right side of sphenoid sinus, and there were bony defects at the floor of the anterior aspect of the right middle fossa. Transcranial repair was performed with right side pterional craniotomy. Careful preoperative evaluation and localization of the sphenoid defect are essential for selection of the best possible surgical approach and skull base reconstruction for repair of sphenoid sinus CSF leaks and meningoencephaloceles. In this case, an endoscopic technique was not successful so, transcranial repair was performed with right side pterional craniotomy.


Relationship of NDVI and oak (Quercus) pollen including a predictive model in the SW Mediterranean region.
Techniques of remote sensing are being used to develop phenological studies. Our goal is to study the correlation among the Normalized Difference Vegetation Index (NDVI) related with oak trees included in three set data polygons (15, 25 and 50 km to aerobiological sampling point as NDVI-15, 25 and 50), and oak (Quercus) daily average pollen counts from 1994 to 2013. The study was developed in the SW Mediterranean region with continuous pollen recording within the mean pollen season of each studied year. These pollen concentrations were compared with NDVI values in the locations containing the vegetation under a study based on two cartographic sources: the Extremadura Forest Map (MFEx) of Spain and the Fifth National Forest Inventory (IFN5) from Portugal. The importance of this work is to propose the relationship among data related in space and time by Spearman and Granger causality tests. 9 out of 20 studied years have shown significant results with the Granger causality test between NDVI and pollen concentration, and in 12 years, significant values were obtained by Spearman test. The distances of influence on the contribution of Quercus pollen to the sampler showed statistically significant results depending on the year. Moreover, a predictive model by using Artificial Neural Network (ANN) was applied with better results in NDVI25 than for NDVI15 or NDVI50. The addition of NDVI25 with the lag of 5 days and some weather parameters in the model was applied with a RMSE of 4.26 (Spearman coefficient r = 0.77) between observed and predicted values. Based on these results, NDVI seems to be a useful parameter to predict airborne pollen.


Antipsychotic medication treatment for mild hallucinations in Parkinson's disease: Positive impact on long-term worsening.
To test if antipsychotic medication treatment of Parkinson's disease (PD) patients with mild hallucinations and retained insight delays deterioration to delusions or hallucinations without insight. We identified subjects at the time they developed their first hallucination, based on documented progression in their UPDRS thought disorder (TD) score from <2 to 2 ("benign" hallucinations with insight retained). We registered TD scores at follow-up visits and their hallucination treatment: antipsychotic medication, PD medication reduction, or observation. The primary outcome measure was the time from the first TD = 2 until the TD score worsened to 3 (hallucinations with loss of insight) or 4 (delusions, psychosis). The effect of antipsychotic medication treatment on transition hazard rate was modeled by proportional hazards regression (Cox model) with antipsychotic medication use as a time-dependent covariate. Of 64 patients, 31 received antipsychotic medication during the study (mean group follow-up 31 months). Of the 38 subjects who reached endpoint, eight subjects had been treated with antipsychotic medication compared to 30/33 in those not treated with antipsychotic medication. Antipsychotic medication treatment reduced the risk of deterioration [hazard ratio = 0.156, CI = (0.067-0.363), P < 0.0001] compared to treatment without antipsychotic medications. The median time from the introduction of antipsychotic medication to the conversion from TD = 2 to TD > 2 was 39 months in subjects on antipsychotic medication compared to 12 months in patients treated otherwise. Until randomized treatment trials provide definitive information, early antipsychotic medication treatment for mild hallucinations should be considered with the combined goal of improving current hallucinations and reducing risks of later deterioration.


Bone marrow transplantation. III. Major problems and future directions.
In parts I and II, the applications of bone marrow transplantation to the treatment of neoplastic and non-neoplastic disorders have been discussed. In addition, problems which are unique to each of these areas have been presented. This final section addresses the problems that are common to both areas which include the problems of graft-versus-host disease and infection. Both experimental and clinical approaches to these areas will be presented and some of the newer approaches for controlling these problems will be discussed. Finally, the major challenges for the future will be presented.


Factors influencing full breastfeeding in a southwestern ontario community: assessments at 1 week and at 6 months postpartum.
Factors associated with full breastfeeding (FBF) at 1 week and at 6 months postpartum were examined in a cohort of 856 mother-infant dyads. Questionnaires were mailed at 4 time points over the first 6 months postpartum. At 1 week, 68% of infants were FBF; at 6 months, 23% were FBF. Factors significantly associated with FBF at 1 week were hospital of delivery, residing with a smoker, maternal shiftwork during pregnancy, and having no prior breast-feeding experience. Cox proportional hazards regression analysis showed that residing with a smoker, having consumed caffeine during pregnancy, reporting elevated maternal trait anxiety at 1 week postpartum, having been employed full-time outside the home prior to delivery, and having received anesthesia/analgesia during labor/delivery were associated with earlier cessation of FBF, whereas not having previous breastfeeding experience predicted its continuation. Although most mothers are breastfeeding early on, a number of factors adversely affect its successful continuation.


A distance-field based automatic neuron tracing method.
Automatic 3D digital reconstruction (tracing) of neurons embedded in noisy microscopic images is challenging, especially when the cell morphology is complex. We have developed a novel approach, named DF-Tracing, to tackle this challenge. This method first extracts the neurite signal (foreground) from a noisy image by using anisotropic filtering and automated thresholding. Then, DF-Tracing executes a coupled distance-field (DF) algorithm on the extracted foreground neurite signal and reconstructs the neuron morphology automatically. Two distance-transform based "force" fields are used: one for "pressure", which is the distance transform field of foreground pixels (voxels) to the background, and another for "thrust", which is the distance transform field of the foreground pixels to an automatically determined seed point. The coupling of these two force fields can "push" a "rolling ball" quickly along the skeleton of a neuron, reconstructing the 3D cell morphology. We have used DF-Tracing to reconstruct the intricate neuron structures found in noisy image stacks, obtained with 3D laser microscopy, of dragonfly thoracic ganglia. Compared to several previous methods, DF-Tracing produces better reconstructions.


[Can diagnostic errors be avoided?]
Errors in the diagnostic process contribute substantially to medical errors and adverse events in the health care system. Research into ways to reduce diagnostic errors is still in its infancy. In this article, it is argued that checklists and time-outs for a brief moment of diagnostic reflection may be advisable.


Renal angiomyolipoma: a clinicopathologic, immunohistochemical, and follow-up study of 46 cases.
We reviewed 46 cases of renal angiomyolipoma covering the period from 1977 to 1997. Eight cases were associated with tuberous sclerosis and one with lymphangiomyomatosis. Histologically, the lesions were most often classic with the three usual components, i.e., mature adipose tissue, thick-walled blood vessels, and smooth muscle. Seven cases were particularly misleading: three cases were entirely adipose mimicking liposarcoma: two cases had an exclusively smooth-muscle component, one mimicking lymphangiomyomatosis and one with epithelioid cells; another case had a monophasic epithelioid pleomorphic component ("REON": renal epithelioid oxyphilic neoplasm) and proved to be fatal; and another case was associated with collecting duct carcinoma. The immunohistochemical profile showed the coexpression of alpha-smooth-muscle actin and HMB45. Our study is the first to show positivity of estrogen and progesteron receptors or both in more than 25% of cases. Of 35 cases with follow-up information, only one patient died of malignant spread of angiomyolipoma.


Hypothalamic-pituitary-adrenal axis function in the Zucker obese rat.
The development of many endocrine, metabolic, and behavioral abnormalities characteristic of genetically obese Zucker rats is dependent upon the presence of glucocorticoids, the secretion of which is regulated by a neuroendocrine cascade initiated by hypothalamic release of CRF. Recent reports have inferred alterations in central CRF tone as a putative factor contributing to dysregulation of the pituitary-adrenal axis and of metabolic processes in this phenotype. In the current study the hypothalamic CRF system in Zucker lean (FA/?) and obese (fa/fa) phenotypes was functionally evaluated. Neither the stalk median eminence content of CRF or arginine vasopressin (AVP) nor hypothalamic levels of CRF or AVP mRNA differed in the lean and obese phenotypes. No phenotypic differences were observed in either basal or stimulated CRF release from hypothalamic tissue obtained from lean and obese rats. Furthermore, in intact rats the magnitude of pituitary-adrenal responses to various stressors was also similar between phenotypes. However, secretion of CRF and AVP into the hypophysial-portal circulation of obese rats was, respectively, 73% and 35% lower than that of the lean rats. Adrenalectomy was associated with a 3-fold elevation of hypophysial-portal CRF levels in obese rats compared to intact controls. Corticosterone infusion was more effective in suppressing portal CRF levels in adrenalectomized obese compared to adrenalectomized lean rats. Finally, neither CRF receptor number and affinity nor the magnitude of pituitary-adrenal responses to rat CRF challenge (1 micrograms, iv) differed between Zucker phenotypes. These observations lead us to infer that rats of the obese phenotype exhibit reduced hypothalamic CRF tone due to dysregulation of the HPA axis at a site proximal to the hypophysiotropic CRF system that mediates glucocorticoid feedback regulation.


Generation in vitro of EBV-induced specific cytotoxic T cells in autologous serum avoids complications due to self-preferred foetal calf serum-specific T-cell cytotoxicity.
A previous report has established that in cultures of human mononuclear leukocytes, foetal calf serum (FCS) is capable of generating high levels of T cells preferentially cytotoxic for the autologous lymphoblastoid cell line (LCL). The present study compared the capacity of Epstein-Barr virus (EBV) to generate cytotoxic T cells in cultures of mononuclear cells grown in FCS in this system. Five EBV-seropositive and three seronegative donors were used and cultures were harvested at 14 days. With cultures from seropositive donors, whether grown in FCS or in autologous serum, EBV infection generated T cells cytotoxic for the autologous LCL; the response in uninfected control cultures was markedly lower. With seronegative donor cultures grown in FCS, there was virtually no difference in the capacity of T cells generated in infected or uninfected cultures to lyse the autologous LCL. Moreover, cells from seronegative donors cultured in human serum gave no detectable lysis of autologous LCL in either infected or uninfected cultures, clearly showing the absence of a response to EBV. This evidence shows that it is possible to distinguish the generation of specific cytotoxic T cells by FCS from generation by EBV, and with certain donors the apparently EBV-induced response may actually include a significant component induced by FCS in the medium. The cytotoxicity patterns of EBV-induced and FCS-induced T cells for autologous and allogeneic LCL targets showed a degree of parallelism, stressing the need for caution in interpretation of data obtained from cultures using FCS.


Individual Differences in Face Identity Processing with Fast Periodic Visual Stimulation.
A growing body of literature suggests that human individuals differ in their ability to process face identity. These findings mainly stem from explicit behavioral tasks, such as the Cambridge Face Memory Test (CFMT). However, it remains an open question whether such individual differences can be found in the absence of an explicit face identity task and when faces have to be individualized at a single glance. In the current study, we tested 49 participants with a recently developed fast periodic visual stimulation (FPVS) paradigm [Liu-Shuang, J., Norcia, A. M., & Rossion, B. An objective index of individual face discrimination in the right occipitotemporal cortex by means of fast periodic oddball stimulation. Neuropsychologia, 52, 57-72, 2014] in EEG to rapidly, objectively, and implicitly quantify face identity processing. In the FPVS paradigm, one face identity (A) was presented at the frequency of 6 Hz, allowing only one gaze fixation, with different face identities (B, C, D) presented every fifth face (1.2 Hz; i.e., AAAABAAAACAAAAD…). Results showed a face individuation response at 1.2 Hz and its harmonics, peaking over occipitotemporal locations. The magnitude of this response showed high reliability across different recording sequences and was significant in all but two participants, with the magnitude and lateralization differing widely across participants. There was a modest but significant correlation between the individuation response amplitude and the performance of the behavioral CFMT task, despite the fact that CFMT and FPVS measured different aspects of face identity processing. Taken together, the current study highlights the FPVS approach as a promising means for studying individual differences in face identity processing.


REM-Enriched Naps Are Associated with Memory Consolidation for Sad Stories and Enhance Mood-Related Reactivity.
Emerging evidence suggests that emotion and affect modulate the relation between sleep and cognition. In the present study, we investigated the role of rapid-eye movement (REM) sleep in mood regulation and memory consolidation for sad stories. In a counterbalanced design, participants (n = 24) listened to either a neutral or a sad story during two sessions, spaced one week apart. After listening to the story, half of the participants had a short (45 min) morning nap. The other half had a long (90 min) morning nap, richer in REM and N2 sleep. Story recall, mood evolution and changes in emotional response to the re-exposure to the story were assessed after the nap. Although recall performance was similar for sad and neutral stories irrespective of nap duration, sleep measures were correlated with recall performance in the sad story condition only. After the long nap, REM sleep density positively correlated with retrieval performance, while re-exposure to the sad story led to diminished mood and increased skin conductance levels. Our results suggest that REM sleep may not only be associated with the consolidation of intrinsically sad material, but also enhances mood reactivity, at least on the short term.


[Study of immunoglobulin E in sera and bronchoalveolar fluid of patients with pulmonary tuberculosis].
A highly sensitive sandwich-variety of EIA was used to measure the content of IgE in 144 sera and 59 samples of the bronchoalveolar fluid (BAF) of patients with pulmonary tuberculosis. As compared to normal persons, the content of serum IgE in the patients was significantly increased; the content of IgE in tuberculosis patients appeared as high as that in patients suffering from atopic allergy (pollenosis, bronchial asthma). The highest content of IgE was detected in patients with disseminated pulmonary tuberculosis, in the active disease phase, including those with bacterial isolation. The content of IgE was much higher in a group of patients with delayed process involution and inadequate treatment results than in a group with beneficial treatment results. The findings of the clinicoimmunological analysis permit the high content of serum IgE to be estimated as an unfavourable prognostic sign. In the BAF of patients with pulmonary tuberculosis, IgE was discovered in 30% of cases. A good correlation was noted between the IgE content in the serum and the frequency of IgE demonstration in the BAF.


Cytotoxic effect of protic ionic liquids in HepG2 and HaCat human cells: in vitro and in silico studies.
Protic ionic liquids (PILs) are innovative chemical compounds, which due to their peculiar nature and amazing physico-chemical properties, have been studied as potential sustainable solvents in many areas of modern science, such as in the industrial fields of textile dyeing, pharmaceuticals, biotechnology, energy and many others. Due to their more than probable large-scale use in a short space of time, a wider analysis in terms of ecotoxicity and biological safety to humans has been attracting significant attention, once many ionic liquids were found to be "a little less than green compounds" towards cells and living organisms. The aim of this study is to investigate the cytotoxicity of 13 recently synthesized PILs, as well as to reinforce knowledge in terms of key thermodynamic magnitudes. All the studied compounds were tested for their in vitro toxic activities on two human cell lines (normal keratinocytes HaCaT and hepatocytes HepG2). In addition, due to the enormous number of possible combinations of anions and cations that can form ionic liquids, a group contribution QSAR model has been tested in order to predict their cytotoxicity. The estimated and experimental values were adequately correlated (correlation coefficient R 2 = 0.9260). The experimental obtained results showed their remarkable low toxicity for the studied in vitro systems.


Molecular, morphometric and functional analyses demonstrate that the growth hormone deficient little mouse is not hypomyelinated.
To study the effects of naturally occurring growth hormone deficiency type I on CNS myelination, we compared the myelination of brains from little and wild-type littermate mice using molecular, histological, morphometric, and functional analyses. The little mouse produces only 6-8% of normal levels of growth hormone (GH) and approximately 20% of normal circulating levels of insulin-like growth factor 1 (IGF-1). Our data show that the expression of myelin basic protein (MBP) and proteolipid protein (PLP) of the little brain exhibit the same temporal pattern and amount as that of the wild-type brain. Furthermore, the density and size of myelinated axons and the myelin sheath thickness in the corpus callosum, anterior commissure and the optic nerve are comparable in the little and wild-type brains. These regions are reduced in size in the little mouse brain proportionate to the overall reduction in brain size implying a reduction in the total number of neurons. Therefore, it follows that the total myelin content is reduced, but when normalized to brain size, the myelin concentration is unchanged. Myelin staining patterns of whole brains were identical. Moreover, functional analysis of the visual pathway indicated no difference between the little and control mice. These results are inconsistent with previous reports of hypomyelination in the little mouse and suggest that this form of GH deficiency does not adversely affect the myelination process except possibly through neuronal proliferation. However, since axon size and density are maintained, the neuronal growth may conversely be inherently limited by other restricted brain growth.


What must I do to succeed?: narratives from the US premedical experience.
How does a lay person become a doctor? How is a physician made? These questions have been central to work of medical sociologists for well over a half-century. Despite this abiding focus on socialization, nearly all of the literature on this process in the US is informed by studies of the medical school and residency years, with almost no empirical attention paid to the premedical years. Our study addresses this gap in knowledge. To better understand the premedical years we conducted 49 in-depth interviews with premedical students at a selective, public Midwestern university. We found that students understand and explain decisions made during the premedical years with narratives that emphasize the qualities of achievement-orientation, perseverance, and individualism. We also find that these qualities are also emphasized in narratives employed to account for the choice to collaborate with, or compete against, premedical peers. Examination of premedical narratives, and the qualities they emphasize, enriches our understanding of how premedical education shapes a physician's moral development, and underscores the need to include the premedical years in our accounts of "becoming a doctor."


ISOMAP and machine learning algorithms for the construction of embedded functional connectivity networks of anatomically separated brain regions from resting state fMRI data of patients with Schizophrenia.
We construct Functional Connectivity Networks (FCN) from resting state fMRI (rsfMRI) recordings towards the classification of brain activity between healthy and schizophrenic subjects using a publicly available dataset (the COBRE dataset) of 145 subjects (74 healthy controls and 71 schizophrenic subjects). First, we match the anatomy of the brain of each individual to the Desikan-Killiany brain atlas. Then, we use the conventional approach of correlating the parcellated time series to construct FCN and ISOMAP, a nonlinear manifold learning algorithm to produce low-dimensional embeddings of the correlation matrices. For the classification analysis, we computed five key local graph-theoretic measures of the FCN and used the LASSO and Random Forest (RF) algorithms for feature selection. For the classification we used standard linear Support Vector Machines. The classification performance is tested by a double cross-validation scheme (consisting of an outer and an inner loop of "Leave one out" cross-validation (LOOCV)). The standard cross-correlation methodology produced a classification rate of 73.1%, while ISOMAP resulted in 79.3%, thus providing a simpler model with a smaller number of features as chosen from LASSO and RF, namely the participation coefficient of the right thalamus and the strength of the right lingual gyrus.


Assessment of Halogen Off-Center Point-Charge Models Using Explicit Solvent Simulations.
Compounds containing halogens can form halogen bonds (XBs) with biological targets such as proteins and membranes due to their anisotropic electrostatic potential. To accurately describe this anisotropy, off-center point-charge (EP) models are commonly used in force field methods, allowing the description of XBs at the molecular mechanics and molecular dynamics level. Various EP implementations have been documented in the literature, and despite being efficient in reproducing protein-ligand geometries and sampling of XBs, it is unclear how well these EP models predict experimental properties such as hydration free energies (ΔGhyd), which are often used to validate force field performance. In this work, we report the first assessment of three EP models using alchemical free energy calculations to predict ΔGhyd values. We show that describing the halogen anisotropy using some EP models can lead to a slight improvement in the prediction of the ΔGhyd when compared with the models without EP, especially for the chlorinated compounds; however, this improvement is not related to the establishment of XBs but is most likely due to the improvement of the sampling of hydrogen bonds. We also highlight the importance of the choice of the EP model, especially for the iodinated molecules, since a slight tendency to improve the prediction is observed for compounds with a larger σ-hole but significantly worse results were obtained for compounds that are weaker XB donors.


1-, 2-, and 4-ethynylpyrenes in the structure of twisted intercalating nucleic acids: structure, thermal stability, and fluorescence relationship.
A postsynthetic, on-column Sonogashira reaction was applied on DNA molecules modified by 2- or 4-iodophenylmethylglycerol in the middle of the sequence, to give the corresponding ortho- and para-twisted intercalating nucleic acids (TINA) with 1-, 2-, and 4-ethynylpyrene residues. The convenient synthesis of 2- and 4-ethynylpyrenes started from the hydrogenolysis of pyrene that has had the sulfur removed and separation of 4,5,9,10-tetrahydropyrene and 1,2,3,6,7,8-hexahydropyrene, which were later converted to the final compounds by successive Friedel-Crafts acetylation, aromatization by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, and a Vilsmeier-Haack-Arnold transformation followed by a Bodendorf fragmentation. Significant alterations in thermal stability of parallel triplexes and antiparallel duplexes were observed upon changing the attachment of ethynylpyrenes from para to ortho in homopyrimidine TINAs. Thus, for para-TINAs the bulge insertion of an intercalator led to high thermal stability of Hoogsteen-type parallel triplexes and duplexes, whereas Watson-Crick-type duplexes were destabilized. In the case of ortho-TINA, both Hoogsteen and Watson-Crick-type complexes were stabilized. Alterations in the thermal stability were highly influenced by the ethynylpyrene isomers used. This also led to TINAs with different changes in fluorescence spectra depending on the secondary structures formed. Stokes shift of approximately 100 nm was detected for pyren-2-ylethynylphenyl derivatives, whereas values for 1- and 4-ethynylpyrenylphenyl conjugates were 10 and 40 nm, respectively. In contrast with para-TINAs, insertion of two ortho-TINAs opposite each other in the duplex as a pseudo-pair resulted in formation of an excimer band at 505 nm for both 1- and 4-ethynylpyrene analogues, which was also accompanied with higher thermal stability.


Athletes with a concussion history in the last two years have impairments in dynamic balance performance.
The purpose of this study was to determine if National Collegiate Athletics Association Division 1 American Football and Ice Hockey athletes with a history of concussion have impaired dynamic balance control when compared to healthy control athletes. This cross-sectional observational study recruited 146 athletes; 90 control athletes and 56 athletes with a history of concussion. Athletes were tested during a pre-season evaluation using the inertial-sensor instrumented Y Balance Test. Independent variables were normalized reach distance, gyroscope magnitude sample entropy, and jerk magnitude root mean square. Kruskal-Wallis H test and Dunn-Bonferroni analysis demonstrated that individuals with a concussion history within the last 2 years have statistically significantly lower jerk magnitude root mean square in the posteromedial (Z = 23.22, P = .015) and posterolateral (Z = 24.64, P = .010) reach directions, when compared to the control group. There was no significant difference between those who sustained a concussion longer than two years ago and the control group for the posteromedial (Z = -1.25; P = .889) and posterolateral (Z = 6.44; P = .469) directions. These findings show that athletes with a concussion history within the last two years possess dynamic balance deficits, when compared to healthy control athletes. Conversely, athletes whose injury occurred greater than 2 years ago possessed comparable performance to the healthy controls. This suggests that sensorimotor control deficits may persist beyond clinical recovery, for up to 2 years. Therefore, clinicians should integrate balance training interventions into the return-to-play process to accelerate sensorimotor recovery and mitigate the risk of future injury.


The characteristics and clinical outcome of drug-induced liver injury: a single-center experience.
The aim of this cohort study was to determine the characteristics and clinical outcome of 170 patients with drug-induced liver injury (DILI) in a single center. Between January 2001 and June 2007, a total of 170 individuals who were diagnosed with DILI were retrospectively analyzed. The median follow-up period was 110.0 days. During the study period, a total of 5471 new patients were assessed for liver test abnormalities. Of those, 170 patients (3.1%) fulfilled the criteria of DILI. A total of 83 different drugs were considered to be related to the hepatotoxicity; a single drug was suspected in 57.6% of individuals. The median interval between the suspicious drug intake and DILI recognition was 15.0 days. Hepatocellular pattern was observed in 50.0% of patients with a mean alanine aminotransferase level of 952.2+/-907.0 U/L. The main causative group of drugs was antibiotics. Sixty-two patients required hospitalization; acute liver failure developed in 14 (8.2%), chronicity was observed in 19 (11.2%), and 7 died (4.1%). Overall, complete recovery occurred in 82% of patients. The presence of jaundice on admission and shorter interval period between drug intake and DILI recognition were identified as risk factors for the development of acute liver failure. DILI is an important cause of liver test abnormalities in outpatient clinics, and antibiotics represent the most common drug group. Overall, complete recovery after the withdrawal of the suspicious drug occurred in the majority of patients, but DILI may progress to acute liver failure, chronicity, and death.


Developmental multi-trajectory of irritability, anxiety, and hyperactivity as psychological markers of heterogeneity in childhood aggression.
A growing body of evidence suggests that child aggression is likely to be driven by multiple developmental pathways. However, little is known about the complex interactions between developmental trajectories of child psychological factors (such as anxiety, irritability, and hyperactivity/impulsivity dimensions) and their associations with aggression from childhood to adolescence. Therefore, the current study aimed to identify clusters of individuals with different developmental multi-trajectory, investigate their early risk factors, and describe their longitudinal associations with physical aggression. The sample comprised 4898 children derived from the Fragile Families and Child Wellbeing Study. A parallel process growth mixture model was used to identify developmental multi-trajectory groups at 5, 9 and 15 years old. Associations between multi-trajectory group membership and physical aggression were examined with Generalized Estimating Equations models. Finally, multinomial logistic regression was performed to assess perinatal and early risk factors for multi-trajectory groups. Multi-trajectory groups differed in the magnitude of risk for exhibiting physical aggression, compared to typically developing children. The risk for physical aggression was the most prominent in children who were hyperactive/impulsive and irritable [odds ratio (OR) 6.47; 95% confidence interval (CI) 5.44-7.70] and hyperactive/impulsive, irritable, and anxious (OR 7.68; CI 6.62-8.91). Furthermore, maternal cigarette and alcohol use during pregnancy and maternal depression consistently predicted multi-trajectory groups characterized by problematic levels of at least two co-occurrent psychological symptoms. Identified combinations of developmental trajectories of psychological characteristics were associated with different magnitude in risk for exhibiting physical aggression. These results may highlight the heterogeneity of developmental trajectories associated with childhood aggression.


Basal cell carcinoma: importance of histologic discontinuities in the evaluation of resection margins.
Pathologists frequently need to judge whether basal cell carcinomas have been excised adequately. Traditionally, excision adequacy is assessed by looking for the presence of tumor at the margins of resection. This time-honored activity has questionable value, since it has been demonstrated that the majority of tumors with positive margins do not recur, and a substantial minority of tumors with negative margins do recur. It is proposed that excision adequacy can be evaluated by considering the pattern of tumor growth. Tumors composed of widely dispersed nests need wider margins than tumors that grow as tight clusters of tumor nests, and this assertion can be evaluated statistically. A morphometric study of 28 basal cell carcinomas (BCCs) was performed, in which the distribution of tumor cell nests seen in cross-section was analyzed. The average distance from the center varied greatly (272 to 2273 microns) among these tumors. Standard deviations were calculated from distances between the tumor center to each nest within the tumor, and one-tailed Student's t tests were used to obtain 90%, 95%, and 99% confidence limits for distances beyond which no additional tumor nests are expected. These distances, in tumor radii, ranged from 0.8 to 1.9 and from 1.03 to 4.89, for 90% and 99% confidence limits, respectively. Conventional methods used to determine margin adequacy do not account for the discontinuous appearance of BCC in histologic sections. This theoretical model demonstrates that an alternate way of assessing excision adequacy can be achieved with a statistical analysis of the pattern of tumor growth, rather than looking for absence of tumor at the resection margin.(ABSTRACT TRUNCATED AT 250 WORDS)


Amino acids and cancer: potential for therapies?
Cancer patients may have a variety of disorders associated with systemic inflammation caused by disease progression. Consequently, we have protein hypercatabolism. In view of this, protein and amino acid adequacy should be considered in relation to nutritional behavior. Therefore, this review aims to evaluate the influence of protein and amino acids in the nutritional therapy of cancer. Diets with adequate protein levels appear to be beneficial in the treatment of cancer; guidelines suggest consumption of greater than 1.0-1.5 g/kg body weight/day. In patients diagnosed with malnutrition, sarcopenia, or cachexia, it is recommended to use the maximum amount of protein (1.5 g/kg of weight/day) to adapt the diet. In addition, based on the evidence found, there is no consensus on the dose and effects in cancer patients of amino acids such as branched-chain amino acids, glutamine, arginine, and creatine. When evaluating the components of the diet of cancer patients, the protein recommendation should be greater than 1.0-1.5 g/kg of weight/day, with a distribution between animal and vegetable proteins. We found little evidence demonstrating clinical benefits regarding individual or combined amino acid supplementation. Still, it is unclear how the use, dose, and specificity for different types of cancer should be prescribed or at what stage of treatment amino acids should be prescribed.


Diabetes and preimplantation events of embryogenesis.
From animal and human studies is it clear that mammalian embryos are vulnerable to injury during the earliest preimplantation stages of development. Exposure to some agents during this brief period has resulted not only in fetal loss but also in malformations. Thus, the potential for maternal induced embryotoxicity exists earlier than previously expected. This period is marked by a drastic change in metabolic needs at the late morula stage. Glucose becomes the predominant exogenous energy substrate and enters the blastocyst via one of three facilitative glucose transporters, GLUT1, GLUT2, and GLUT3. It has been shown that maternal diabetes adversely affects the preimplantation embryo. Recent work has revealed that hyperglycemia leads to a downregulation of the GLUTs at the blastocyst stage in the mouse. This downregulation results in decreased glucose transport into the blastocyst of diabetic mice and thus lower intraembryonic free glucose levels. The embryos are starving themselves of the key substrate necessary for survival. Maternal diabetes also causes a decrease in the number of cells in rat blastocyst and recently hyperglycemia has been shown to induce apoptosis in the mouse blastocyst via cell death effector pathways involving BAX and caspases. Significant loss of key progenitor cells from the blastocyst may predispose these diabetic embryos to later developmental deficiencies manifesting as dysmorphogenesis, fetal loss or early growth delay. The hypothesis that the hyperglycemia-induced decrease in glucose transport triggers apoptosis is presented and discussed as a novel mechanism to explain preimplantation diabetic embryopathy.


Baker's asthma: still among the most frequent occupational respiratory disorders.
Baker's asthma and rhinitis are among the most frequent occupational respiratory disorders. The aim of the study was to evaluate the frequency of work-related symptoms and the clinical relevance of sensitization to allergens in screened and symptomatic bakers. Eighty-nine bakers participating in a screening study and 104 bakers filing a claim for compensation were examined with regard to occupational and clinical case history, lung function parameters, and sensitization to bakery allergens by skin prick tests, specific IgE analyses, and inhalative challenge tests. A high prevalence of respiratory disorders, abnormal lung function parameters, and sensitization to bakery allergens exists. Most frequently, bakers with workplace-related respiratory symptoms showed sensitization to wheat flour (64%), rye flour (52%), soy bean flour (25%), and alpha-amylase (21%). The correlation between these sensitizations and asthma case history and inhalative challenge test responses was significant. However, approximately 29% of the bakers with respiratory symptoms showed no sensitization to these bakery allergens, whereas 32% of the sensitized bakers in the screening group had no workplace-related symptoms. Atopic status defined by skin prick test sensitization to common allergens or elevated total IgE levels was found to be a risk factor for the development of sensitization to bakery allergens and respiratory symptoms. On the other hand, there is evidence for an increased frequency of elevated total IgE as the result of occupational allergen exposure because respective findings were observed in bakers without symptoms. Sensitization to bakery allergens seems to be the main cause of baker's asthma and rhinitis but cannot explain the asthma case history in each case. Further methods are required to objectively assume irritative pathomechanisms. Our findings indicate the necessity for an improved primary prevention of exposure to inhalative noxae in bakeries.


beta-Amyloid (A beta) deposition in the medial temporal lobe of patients with dementia with Lewy bodies.
The distribution and density of diffuse, primitive and classic beta-amyloid (A beta) deposits in the medial temporal lobe (MTL) was studied in cases of dementia with Lewy bodies (DLB) with and without associated Alzheimer's disease (AD) and 15 cases of sporadic AD. In the 'pure' DLB cases, virtually no A beta deposits were observed in the CA regions of the hippocampus or dentate gyrus whereas deposits were distributed throughout the MTL in DLB/AD and AD cases. Densities of diffuse and primitive A beta deposits were similar in AD and DLB/AD cases but density was significantly reduced in the 'pure' DLB cases. The density of the classic deposits was significantly reduced in DLB cases with or without associated AD compared with AD cases. These results suggest that A beta deposition in the MTL in 'pure' DLB cases is similar to that of elderly non-demented patients while, with the exception of the classic deposits, A beta deposition in DLB/AD cases is similar to that in cases of AD alone.


Health and well-being promotion strategies for 'hard to reach' older people in England: a mapping exercise.
Older people from deprived areas, the oldest old and those from ethnic minorities engage less in health promotion interventions and related research, potentially generating inequities. Aim To explore and map the extent to which such 'hard to reach' groups of older people, are the focus of local health and well-being strategies in England. Document analysis of current health and well-being promotion strategies in a purposive sample of 10 localities in England with high proportions of some or all of the three hard to reach groups. Documents were analysed using an interpretive approach. Findings A total of 254 documents were retrieved and reviewed. Much of the content of the documents was descriptive and reported the implications for resources/services of population ageing rather than actual initiatives. All localities had an Older People's Strategy. Strategies to counter deprivation included redistribution of winter fuel payments, income maximisation, debt reduction and social inclusion initiatives, a focus on older owner occupiers and recruitment of village 'agents' to counter rural deprivation. The needs of the oldest old were served by integrated services for older people, a community alarm service with total coverage of the 85+ population, and dietary advice. The needs of black and minority ethnic (BME) older people were discussed in all localities and responses included community work with BME groups, attention to housing needs and monitoring of service use by BME older people. Three other themes that emerged were: use of telecare technologies; a challenge to the idea of 'hard to reach' groups; and outreach services to those at most risk. Document analysis revealed a range of policy statements that may indicate tailoring of policy and practice to local conditions, the salience of national priorities, some innovative local responses to policy challenges and even dissenting views that seek to redefine the policy problem.


Local conduction at the BiFeO(3)-CoFe(2)O(4) tubular oxide interface.
In strongly correlated oxides, heterointerfaces, manipulating the interaction, frustration, and discontinuity of lattice, charge, orbital, and spin degrees of freedom, generate new possibilities for next generation devices. In this study, existing oxide heterostructures are examined and local conduction at the BiFeO(3)-CoFe(2)O(4) vertical interface is found. In such hetero-nanostructures the interface cannot only be the medium for the coupling between phases, but also a new state of the matter. This study demonstrates a novel concept on for oxide interface design and opens an alternative pathway for the exploration of diverse functionalities in complex oxide interfaces.


Do skill-based conditioning games offer a specific training stimulus for junior elite volleyball players?
This study investigated the specificity of skill-based conditioning games and compared the effectiveness of skill-based conditioning games and instructional training for improving physical fitness and skill in junior elite volleyball players. Twenty-five junior volleyball players (mean age +/- SE, 15.6 +/- 0.1 years) participated in this study. Heart rate data were collected on all players during the Australian Junior Volleyball Championships. After the competition, players were randomly allocated into a skill-based conditioning games group (n = 12) or an instructional training group (n = 13). Each player participated in a 12-week training program that included 3 organized court training sessions per week. No significant differences (P > 0.05) were detected between competition and skill-based conditioning games for the percentage of time spent in low-intensity, moderate-intensity, and high-intensity activities. Skill-based conditioning games induced improvements in vertical jump, spike jump, speed, agility, upper-body muscular power, and estimated maximal aerobic power, whereas technical instruction improved only spike jump and speed. Conversely, instructional training induced meaningful improvements in all measurements of skill, whereas improvements in technical skill after skill-based conditioning games were uncommon and typically small. The results of this study show that skill-based conditioning games offer a specific training stimulus to simulate the physiological demands of competition in junior elite volleyball players. Although the improvements in physical fitness after training were greater with skill-based conditioning games, instructional training resulted in greater improvements in technical skill in these athletes. These findings suggest that a combination of instructional training and skill-based conditioning games is likely to confer the greatest improvements in fitness and skill in junior elite volleyball players.


The diagnosis and management of acute bacterial meningitis in resource-poor settings.
Acute bacterial meningitis is more common in resource-poor than resource-rich settings. Survival is dependent on rapid diagnosis and early treatment, both of which are difficult to achieve when laboratory support and antibiotics are scarce. Diagnostic algorithms that use basic clinic and laboratory features to distinguish bacterial meningitis from other diseases can be useful. Analysis of the CSF is essential, and simple techniques can enhance the yield of diagnostic microbiology. Penicillin-resistant and chloramphenicol-resistant bacteria are a considerable threat in resource-poor settings that go undetected if CSF and blood can not be cultured. Generic formulations of ceftriaxone are becoming more affordable and available, and are effective against meningitis caused by penicillin-resistant or chloramphenicol-resistant bacteria. However, infection with Streptococcus pneumoniae with reduced susceptibility to ceftriaxone is reported increasingly, and alternatives are either too expensive (eg, vancomycin) or can not be widely recommended (eg, rifampicin, which is the key drug to treat tuberculosis) in resource-poor settings. Additionally, improved access to affordable antibiotics will not overcome the problems of poor access to hospitals and the fatal consequences of delayed treatment. The future rests with the provision of effective conjugate vaccines against S pneumoniae, Haemophilus influenzae, and Neisseria meningitides to children in the poorest regions of the world.


[Cytology of peritoneal exudate as the criterion for phases of inflammation in diffuse purulent peritonitis].
A cytological study was made of the exudation from the abdominal cavity in 131 patient with diffuse peritonitis to determine the time-related course of the inflammatory process in the peritoneum against the background of the therapy conducted. The exudation from the abdominal cavity was assayed at hospital admission, at surgery, and in the postoperative period, the planned ointment assanations having been performed. Used in the cytological study was the M. P. Pokrovsky and M. S. Makarov method in modification of D. M. Steinberg (1948) who suggested ways for the amounts of the microflora and those cell types occurring in the exudate to be determined in smears-impressions with the relevant cytogrammes made up. The most significant characteristics of the maiden, second, and third phases of inflammation of the peritoneum were revealed. On the basis of the above characteristics (cytologic signs) we have developed criteria for phases of inflammation of the peritoneum that permit the assessment of efficiency of the therapy treatments administered to be carried out.


The first step of gibberellin biosynthesis in pumpkin is catalyzed by at least two copalyl diphosphate synthases encoded by differentially regulated genes.
The first step in gibberellin biosynthesis is catalyzed by copalyl diphosphate synthase (CPS) and ent-kaurene synthase. We have cloned from pumpkin (Cucurbita maxima L.) two cDNAs, CmCPS1 and CmCPS2, that each encode a CPS. Both recombinant fusion CmCPS proteins were active in vitro. CPS are translocated into plastids and processed by cleavage of transit peptides. For CmCPS1 and CmCPS2, the putative transit peptides cannot exceed the first 99 and 107 amino acids, respectively, because longer N-terminal deletions abolished activity. Levels of both CmCPS transcripts were strictly regulated in an organ-specific and developmental manner. Both transcripts were almost undetectable in leaves and were abundant in petioles. CmCPS1 transcript levels were high in young cotyledons and low in roots. In contrast, CmCPS2 transcripts were undetectable in cotyledons but present at significant levels in roots. In hypocotyls, apices, and petioles, CmCPS1 transcript levels decreased with age much more rapidly than those of CmCPS2. We speculate that CmCPS1 expression is correlated with the early stages of organ development, whereas CmCPS2 expression is correlated with subsequent growth. In contrast, C. maxima ent-kaurene synthase transcripts were detected in every organ at almost constant levels. Thus, ent-kaurene biosynthesis may be regulated through control of CPS expression.


Contribution to the aetiology of synovitis in chickens, with special reference to non-infective factors. V. Extractability of glucosaminoglycans/mucoproteins from tendon tissue.
A comparative study was undertaken regarding the extractability of glucosaminoglycans and mucoproteins in the tendon tissue of birds highly susceptible to synovitis, viz.broiler breed cocks (BB cocks), and of birds highly resistant to synovitis. viz. White Leghorn hens (WL hens). It was shown that in ;the case of WL hens this extractability decreased in accordance with ageing. In the case of BB cocks such a decrease was not observed. This observation is in support of a working hypothesis which supposes a relatively high degree of interaction between the several components of tendon components of tendon tissue (e.g. collagen and glucosaminoglycans/mucoproteins) in the case of WL hens, and a relatively low degree of this interaction in the case of BB cocks. Moreover the results of this study account for the observation that the tendon tissue of WL hens is more resistant to tensile stress than that of BB cocks, and they indicate that the above interaction is a determinant in the aetiology of synovitis.


Effect of water temperature and density of juvenile salmonids on growth of young-of-the-year Atlantic salmon Salmo salar.
A von Bertalanffy growth model for young-of the-year Atlantic salmon Salmo salar in a small French coastal stream was fitted using water temperatures and densities of juvenile salmonids (S. salar and brown trout Salmo trutta) as covariates influencing daily growth rate. The Bayesian framework was used as a template to integrate prior information from external data sets. The relative influence of the covariates on parr growth was quantified and results showed that growth of S. salar juveniles depended on both water temperatures and densities, but that most of the spatiotemporal variability of growth resulted from local spatiotemporal variations of 0+ age salmonid (S. salar and S. trutta) densities. Further analysis revealed that the fluctuations in young-of-the-year salmonid densities are likely to dominate the effects of potential future warming of water temperature due to climate change. It is concluded that factors that could affect salmonid densities might well have a greater effect on S. salar population dynamics than factors influencing water temperatures.


Sedation and delirium in the intensive care unit: an Australian and New Zealand perspective.
A survey was conducted to determine sedation and delirium practices in Australian and New Zealand intensive care units. The survey was in two parts, comprising an online survey of reported sedation and delirium management (unit survey) and a collection of de-identified data about each patient in a unit at a given time on a specified day (patient snapshot survey). All intensive care units throughout Australia and New Zealand were invited by email to participate in the survey. Twenty-three predominantly metropolitan, level III Australian and New Zealand intensive care units treating adult patients participated. Written sedation policies were in place in 48% of units, while an additional 44% of units reported having informal sedation policies. Seventy percent of units routinely used a sedation scale. In contrast, only 9% of units routinely used a delirium scale. Continuous intravenous infusion is the primary means of patient sedation (74% of units). While 30% of units reported routinely interrupting sedation, only 10% of sedated patients in the snapshot survey had had their sedation interrupted in the preceding 12 hours. Oversedation appears to be common (46% of patients with completed sedation scales). Use of neuromuscular blockade is low (10%) compared to other published studies. Midazolam and propofol were the most frequently used sedatives. The proportion of patients developing delirium was 21% of assessable patients. Failed and self-extubation rates were low: 3.2% and 0.5% respectively. In Australian and New Zealand intensive care units, routine use of sedation scales is common but not universal, while routine delirium assessment is rare. The use of a sedation protocol is valuable and should be encouraged.


Paediatric physician-researchers: coping with tensions in dual accountability.
Potential conflicts between the roles of physicians and researchers have been described at the theoretical level in the bioethics literature (Czoli, et al., 2011). Physicians and researchers are generally in mutually distinct roles, responsible for patients and participants respectively. With increasing emphasis on integration of research into clinical settings, however, the role divide is sometimes unclear. Consequently, physician-researchers must consider and negotiate salient ethical differences between clinical- and research-based obligations (Miller et al, 1998). This paper explores the subjective experiences and perspectives of 30 physician-researchers working in three Canadian paediatric settings. Drawing on qualitative interviews, it identifies ethical challenges and strategies used by physician-researchers in managing dual roles. It considers whether competing obligations could have both positive and adverse consequences for both physician-researchers and patients. Finally, we discuss how empirical work, which explores the perspectives of those engaged in research and clinical practice, can lead the way to understanding and promoting best practice.


PROMETHAZINE-INDUCED THROMBOPHLEBITIS IN A NIGERIAN MAN: A CASE REPORT.
Promethazine is a phenothiazine derivative that possesses antihistamine, anti-dopaminergic and anticholinergic properties. It is commonly used to treat motion sickness, allergic conditions, nausea and vomiting, in addition to its use as a sedative. Promethazine has vesicant properties and is highly caustic to the intima of blood vessels and surrounding tissues. Intravenous administration may result in thrombophlebitis, unintentional intra-arterial administration, perivascular extravasation and tissue necrosis. To the best of our knowledge there is no previous published report of promethazine-induced thrombophlebitis from sub- Saharan Africa. A 29-year-old Nigerian male was admitted at our hospital on account of malaria with acute gastroenteritis. Due to persistent vomiting, he was administered 25 mg of promethazine injection via a size 22G intravenous cannula which was inserted the previous day on the anteromedial aspect of his right forearm and maintained with continuous intravenous crystalloid infusion. Upon administration of promethazine, he experienced intense burning and erythema. The cannula was removed immediately, another cannula was inserted on the contralateral arm, and promethazine was replaced with ondansetron. Subsequently, he developed a tender, subcutaneous cord-like swelling extending from the middle-third of the anteromedial aspect of his right forearm, corresponding with the site of previous venous cannulation. Ultrasonography revealed a hypoechoic, non-compressible basilic vein, with no flow on colour Doppler interrogation, in keeping with superficial thrombophlebitis. He was treated with a topical anti-inflammatory agent, and the pain and redness subsided after four weeks. The preferred parenteral route of administration of promethazine is deep intramuscular injection. Recommendations to prevent promethazine-induced thrombophlebitis include: use of large and patent veins, use of lower doses, drug dilution and slow administration, use of alternative therapies, and patient education. Promethazine-induced tissue injury is under-reported in this part of the world. Creating awareness through this case report would help reduce the morbidity following promethazine administration.


Comparison of biorelevant simulated media mimicking the intestinal environment to assess the solubility profiles of poorly soluble drugs.
During the discovery stage in lead identification/optimization, compounds are characterized for their solubilities in biorelevant media and these data are often used to model the in vivo behavior of the compounds and predict the fraction absorbed. These media are selected to closely approximate the composition of human intestinal fluid. Owing to the complexity and variability in human intestinal fluid composition, it is essential that the chosen simulated media mimic the in vivo condition as closely as possible. Several recipes have been developed and are routinely used in assessing the solubilities of compounds. It is necessary to revisit these recipes and modify them as the understanding of the human GI tract increases. In the present work, we have evaluated the solubilities of six model compounds in several media and have proposed slight modifications to the currently used recipes based on our own data and that reported in the literature.