The residence time of the bound water in the hydrophobic minor groove of the carbocyclic-nucleoside analogs of Dickerson-Drew dodecamers.
The residence time of the bound water molecules in the antisense oligodeoxyribonucleotides containing 7'-alpha-methyl (TMe) carbocyclic thymidines in duplex (I), d5'(1C2G3C4G5A6A7TMc8TMe9C10G11C12G)23', and 6'-alpha-hydroxy (TOH) carbocyclic thymidines in duplex (II), d5'(1C2G3C4G5AOH6AOH7TOH8 TOH9C10G11C12G)2(3), have been investigated using a combination of NOESY and ROESY experiments. Because of the presence of 7'-alpha-methyl groups of TMe in the centre of the minor groove in duplex (I), the residence time of the bound water molecule is shorter than 0.3 ns. The dramatic reduction of the residence time of the water molecule in the minor groove in duplex (I) compared with the natural counterpart has been attributed to the replacement of second shell of hydration and disruption of hydrogen-bonding with 04' in the minor groove by hydrophobic alpha-methyl groups, as originally observed in the X-ray study. This effect could not be attributed to the change of the width of the minor groove because a comparative NMR study of the duplex (I) and its natural counterpart showed that the widths of their minor grooves are more or less unchanged (r.m.s.d change in the core part is <0.63A). For duplex (II) with polar 6'-alpha-hydroxyl groups pointed to the minor groove, the correlation time is much longer than 0.36 ns as a result of the stabilising hydrogen-bonding interaction with N3 or 02 of the neighbouring nucleotides.


Psychosocial consequences of false-positive results in screening mammography.
To evaluate the psychosocial impact of benign breast biopsies on Lebanese women after a screening mammography and the effect of these biopsies on patients' attitudes toward subsequent screening. In this retrospective study (January 2005 till April 2011), 109 consecutive patients with a history of breast biopsy without cancer were asked to answer a phone questionnaire. The response rate was 91.7% (100 women accepted to participate). A questionnaire about sociodemographic characteristics, biopsy characteristics, and patients' attitudes as measured by the negative Psychosocial Consequences Questionnaire (PCQ) and other independent questions was filled by phone call by one interviewer. The negative PCQ score was low for most women (only 9% have a negative PCQ score ≥18/36) and is statistically dependent on the result of the last mammography (P = 0.01) and the number of previous benign breast biopsies (P = 0.01). A total of 10% of women increased their medical visits after this biopsy, 8% were treated for psychiatric problems after this biopsy, and 19% self-examine their breasts more than once per week. The benign breast biopsy experience increases the willingness to adhere to the screening mammography in 71% of the patients, this reported adherence depends positively on the score of the negative PCQ (P = 0.043). The negative psychosocial effect of the biopsy is minimal in general and is positively correlated to the adherence to future mammographies. Interventions are necessary to decrease the anxiety in most susceptible women and to raise the awareness of women at risk of nonadherence to the screening mammography.


Central nervous system impairment in diabetic patients.
The aims of this study were to investigate the function of the central motor control system in interaction with the vestibular and auditory systems (measured by H-reflex changes in response to vestibular and acoustic stimulations) in diabetics without clinical data for CNS impairment, in order to establish whether the disease affects these CNS mechanisms; and to assess this approach in detecting subclinical CNS diabetic pathology. The results show the same mode of change of H-reflex amplitude in response to acoustic and vestibular stimulations in diabetics as in normal subjects. However the degree of facilitation and inhibition was significantly (p < 0.001) higher in diabetics which indicates subclinical CNS dysfunction. Therefore it was concluded that the test is useful in early diagnosis of the diabetic CNS impairment.


Extensor hallucis longus coaptation to tibialis anterior: a treatment for paralytic drop foot.
Between June 1982 and April 1983, a procedure to coapt the extensor hallucis longus (EHL) to the tibialis anterior was performed in eight post-polio patients to correct drop foot and to enable the EHL to be a more efficient dorsiflexor of ankle. Although at early follow-up, every patient was able to actively dorsiflex the ankle against gravity, at final review, (mean follow-up 7.8 years), only two patients could still do so. Three patients developed a cock-up toe deformity or dorsiflexion deformity of great toe. We have attributed the poor final results to stretching of the coaptation. Use of splints or orthosis for a longer period postoperatively and a more carefully designed physical therapy may have yielded better results. Alternatively, if the EHL is anchored to navicular bone better results may be obtained.


Silent human pancreatic glucagonoma and "A" nesidioblastosis.
Surgical fragments of healthy and tumor-bearing pancreas from a patient with pancreatic tumor were studied by electron or light microscopy, histochemistry, and immunocytochemistry (human insulin, glucagon, somatostatin, gastrin, and bovine pancreatic polypeptide). Histological results were compared to those obtained by radioimmunoassay, both in tumor and serum. The tumor was identified as a glucagonoma because reactions for Grimelius' silver impregnation and immunoreaction with an antiserum against glucagon were positive and because a very high level of glucagon in the tumor was observed. Insulin, somatostatin, and gastrin levels remained normal, both in tumor and serum, but the glucagon level was normal in serum. Associated with this silent glucagonoma, an uncommon nesidioblastosis was also diagnosed with many A cells irregularly mixed with acinar cells, isolated or clustered in small groups. Acinar "intermediate" cells of "A" type were also observed. Such associative histopathological processes evoked possible development of an endocrine tumor from nesidioblastic-like tissue. Its embryogenic origin remained uncertain.


ERK-containing microparticles from a diabetic mouse induce endothelial dysfunction.
Endothelial dysfunction is a hallmark of diabetic vascular complications. Microparticles (MPs) are small vesicles shed from the surface of blood and vascular cells that act as stimuli and during apoptosis. Circulating MPs of diabetic rats have been shown to induce endothelial dysfunction. However, the underlying mechanisms require further study. In this study, we investigated how MPs from diabetic mice affect endothelial function. MPs were collected from streptozotocin-induced diabetic mice and Institute of Cancer Research (ICR) mice as controls. The levels of MPs were assessed and characterized by flow cytometry, enzyme-linked immunosorbent assay and dot blotting. Normal mice aortas were incubated with MPs and expressions of enzymes and vascular relaxation were analyzed. We found that (1) circulating MPs level increased in diabetic mice; (2) MPs impaired endothelial-dependent relaxation in mice aorta, but diabetic mice-derived MPs (diabetes mellitus (DM) MPs) were easier to attach to the endothelial cells than were control MPs; (3) DM MPs had more extracellular signal-regulated kinase (ERK)1/2 than did control mice-derived MPs, and they induced ERK1/2 activation in mice aortas; (4) DM MPs decreased endothelial nitric oxide synthase (eNOS) in mice aortas, and eNOS was emitted from endothelial cells to blood in the shape of endothelial MPs. DM MPs significantly altered endothelial function by activation of ERK1/2, which might provide a therapeutic target for diabetic vascular complications.


[Age-associated features of the development of fibrosis and inflamaging in patients with arterial hypertension and ischemic stroke.]
The article deals with the development of fibrosis and immune inflammation in patients with arterial hypertension and acute ischemic stroke in old age. The aim of the study was to study age-associated features of the concentration of fibrosis markers (metalloproteinase-9, tissue inhibitor of matrix metalloproteinases-1, their ratio MMP-9/TIMP-1), immune inflammation (TNF-α, IL-1β, INF-γ) in patients with arterial hypertension and ischemic stroke (AI). The study included 86 patients with arterial hypertension (AH) of the 2nd degree, of which 42 were middle-aged (53±5 years) and 44 elderly (66±5 years). The control group consisted of 22 elderly patients with AH without a history of AI. The criteria for inclusion in the study are patients with hypertension who were admitted to the hospital in the acute period of the first cerebral stroke. It was found that in elderly patients with hypertension with AI, the indicators of inflamaging and fibrosis markers were significantly higher than in middle-aged people. The level of IL-1ß was 31,7% higher (p<0,01), TNF-α by 55,7% (p<0,001), INF-γ by 36,6% (p<0,01), the level of MMP-9 was 46,4% higher (p<0,01), TIMP-1 by 21,2% (p<0,01), MMP-9/TIMP-1 by 19,6% (p<0,01) in the elderly compared to middle-aged patients with hypertension and acute AI. Thus, it was found that patients with arterial hypertension and ischemic stroke have violations of the processes of inflamaging, synthesis and degradation of the extracellular matrix, especially pronounced in old age.


Connecting the disconnected: what FSM is doing?
This paper describes the effort the FSM Department of Health and Social Affairs has carried out to connect its geographically disconnected and isolated hospitals and health facilities on the same health information network. It discusses the rationale and the process for such undertaking, lists the achievements the project has made, and lays the vision for its future direction.


A review of medical airlifts by a search and rescue squadron on the east coast of England over 18 years.
This paper reviews the medical workload of a Royal Air Force Search and Rescue squadron on the East Coast of England over a period of 18 years and their association with the principal receiving hospitals in that area. It illustrates the effects of improvements in road networks on the workload of the squadron and contrasts the use of military helicopters with established U.K. civilian helicopter schemes.


Delirium in acute stroke: a review.
Delirium is a complex neuropsychiatric syndrome characterized by disturbances of consciousness, attention, cognition, and perception. It may be the presenting feature of acute stroke, but more often it complicates the clinical course in the early stage of rehabilitation. Risk factors for delirium are older age, pre-existing cognitive decline, metabolic disturbances, infections, and polypharmacy. Recognition of delirium in patients with stroke is important because of its association with a longer stay in the hospital, a poor functional outcome, and an increased risk of developing dementia. The diagnosis may be difficult because of the fluctuating course and the neurological deficits that are caused by the stroke. Nonpharmacological preventive measures, early identification, and additional medical intervention are the key measures in the management of delirium after stroke. This review describes incidence, risk factors, pathophysiology, diagnostic tools, and management of delirium in patients with a recent stroke.


Poly(9H-carbazole) as a Organic Semiconductor for Enzymatic and Non-Enzymatic Glucose Sensors.
Organic semiconductors and conducting polymers are the most promising next-generation conducting materials for electrochemical biosensors as the greener and cheaper alternative for electrodes based on transition metals or their oxides. Therefore, polycarbazole as the organic semiconducting polymer was electrochemically synthesized and deposited on working electrode. Structure and semiconducting properties of polycarbazole have theoretically and experimentally been analyzed and proved. For these electrochemical systems, a maximal sensitivity of 14 μA·cm-2·mM-1, a wide linear range of detection up to 5 mM, and a minimal limit of detection of around 0.2 mM were achieved. Moreover, Michaelis's constant of these sensors depends not only on the enzyme but on the material of electrode and applied potential. The electrocatalytic mechanism and performance of the non- and enzymatic sensors based on this material as a conducting layer have been discussed by estimating pseudocapacitive and faradaic currents and by adding glucose as an analyte at the different applied potentials. In this work, the attention was focused on the electrochemical origin and mechanism involved in the non- and enzymatic oxidation and reduction of glucose.


Vigorous physical activity: A potential ally in adolescent obesity management.
Individual variability may contribute to the modest and inconsistent results reported in obesity-management interventions. This study aimed to investigate the impact of non-modifiable as well as modifiable factors on body mass index (BMI) and body fat variance in adolescents with obesity followed in a clinical obesity-management programme, in order to better understand individual variability. Non-modifiable factors (i.e. socio-economic status, pregnancy BMI, weight progression across pregnancy, BMI at time of delivery, way of delivery, birth weight, breastfeeding duration, age at overweight onset, overweight duration, and FTO rs9939609 polymorphism) and modifiable factors data (i.e. self-determination level, self-efficacy and perception of importance to lose weight, energy intake, physical activity, and sedentary behaviours) from 63 adolescents (93.7% Caucasian, 55.6% girls), with a median age of 15.0 (2.5) years, and a median BMI z-score of 2.88 (0.70), followed for 6 months were analyzed. BMI z-score variance was predicted by vigorous physical activity (VPA) (F(1,57) = 4.55, p = .039), overweight duration (F(1,59) = 5.61, p = .022), way of delivery (F(2,58) = 6.55, p = .003) and self-determination level (F(1,59) = 4.75, p = .034). VPA further predicted body fat mass (%) (F(1,57) = 9.99, p = .003) as well as trunk fat mass variance (F(1,57) = 8.94, p = .006). This study suggests that although both non-modifiable and modifiable factors influence BMI and body fat variance to some extent, in adolescents with obesity, VPA (modifiable factor) stands out as the factor with the best association with both outcomes. VPA may be a potential ally in the success of clinical obesity management in adolescents, and so should be emphasised in this population.HighlightsThere is a huge individual variability within studies in response to adolescent obesity-management interventions.Both non-modifiable and modifiable factors may influence body mass index (BMI) and body fat variance, influencing interventions' outcomes.The predictive value of both non-modifiable and modifiable factors largely overlaps, making lighter the burden of the former and highlighting the value of lifestyle changes.Among modifiable factors, vigorous physical activity standouts as the factor with the best (negative) association with BMI and body fat variance.


An investigation of women's attitudes towards fertility and China's family planning policy.
Reducing China's population has formerly been considered a good thing because of the perceived environmental and social risks of overpopulation, but it has recently become apparent that the resulting population decline may create problems that will become increasingly serious in the future. The results of a survey of 4600 women in nineteen Chinese provinces in 2005 indicated that young age, high income, high education level, urban location and good employment all decreased a woman's willingness to bear children. The risks created by declining fertility in these groups have been intensified by China's 'one child' family planning policy. However, as a result of current trends and China's policies, the country's population will continue to age, leading to social problems and difficulties for sustainable development both in China and around the world. Therefore, China's policy-makers must begin planning to adjust their policy by encouraging women to give birth to more than one child.


A novel test of planning ability: great apes can plan step-by-step but not in advance of action.
The ability to identify an appropriate sequence of actions or to consider alternative possible action sequences might be particularly useful during problem solving in the physical domain. We developed a new 'paddle-box' task to test the ability of different ape species to plan an appropriate sequence of physical actions (rotating paddles) to retrieve a reward from a goal location. The task had an adjustable difficulty level and was not dependent on species-specific behaviours (e.g. complex tool use). We investigated the planning abilities of captive orangutans (Pongo pygmaeus) and bonobos (Pan paniscus) using the paddle-box. In experiment 1, subjects had to rotate one or two paddles before rotating the paddle with the reward on. Subjects of both species performed poorly, though orangutans rotated more non-food paddles, which may be related to their greater exploratory tendencies and bolder temperament compared with bonobos. In experiment 2 subjects could always rotate the paddle with the reward on first and still succeed, and most subjects of both species performed appropriate sequences of up to three paddle rotations to retrieve the reward. Poor performance in experiment 1 may have been related to subjects' difficulty in inhibiting the prepotent response to act on the reward immediately.


Moderators of physical activity and healthy eating in an integrated community-based intervention for older adults.
An integrated community-based intervention was developed to stimulate physical activity (PA) and healthy eating in older adults in a socioeconomically disadvantaged area. This study aims to assess whether its short-term effects among older adults vary by sociodemographic, psychosocial and health-related variables. The study was a controlled pre-post quasi-experimental design (intervention condition n = 430; control condition n = 213), with a baseline measurement and a 9-month follow-up measurement. The intervention consisted of a local media campaign and environmental approaches. Changes in PA and fruit and vegetable consumption (FVC) were dependent variables assessed at 9-month follow-up. Sociodemographic, psychosocial and health-related variables at baseline were tested as potential moderators of the effects of the conditions. We found different types of moderators in particular for transport-related PA and FVC. Regarding sociodemographic characteristics, gender was a moderator for household-related PA, and educational level for transport-related PA and FVC. Self-efficacy, as a psychosocial variable, was a moderator of transport-related PA and vegetable consumption. Concerning health-related outcomes, baseline levels of transport-related PA and fruit consumption were moderators for transport-related PA and fruit consumption. If adjusted for multiple testing, only three moderators persisted: educational level regarding vegetable consumption, and baseline levels regarding transport-related PA and fruit consumption. The effects of the community intervention vary somewhat by sociodemographic, psychosocial and health-related variables. The intervention seems to be especially beneficial to those who are most in need of more PA and healthy eating.


PLK1 promotes epithelial-mesenchymal transition and metastasis of gastric carcinoma cells.
Cancer cell epithelial-mesenchymal transition (EMT) is the crucial event for cancer progression and plays a vital role in the metastasis of cancer cells. Activation of Polo-like kinase 1 (PLK1) signaling has been implicated as the critical event in several tumor metastasis and EMT, however, whether PLK1 participates in gastric carcinoma metastasis and EMT still remains unclear. For this study, we elucidated the potential physiological function of PLK1 in the metastasis of gastric tumors, as well its distinct role in cells EMT and subsequently determined the mechanism involved in PLK1 regulated. Immunoblotting assay and Oncomine data mining analysis indicated that PLK1 expression was highly up-regulated in gastric carcinoma. Kaplan-Meier survival analysis for the relationship between survival outcomes and PLK1 expression in gastric carcinoma was performed with an online Kaplan-Meier plotter (http://kmplot.com/analysis/). Over-expression of PLK1 in gastric cancer cells SGC-7901 and MKN-28 significantly promoted cells profound morphological changes and enhanced metastatic ability of tumor cells. On the contrary, silencing of PLK1 induced mesenchymal epithelial transition (MET)-like morphological and inhibited the metastatic process. Furthermore, we found that the metastatic characters promoting effects of PLK1 in gastric carcinoma was related to the activation of protein kinase B (AKT). Our mechanistic investigations revealed that AKT inhibition reversed PLK1-induced EMT, blocked gastric carcinoma cells invasiveness and metastasis. Additionally, over-expression of AKT promoted the migratory and invasion ability of the two cell lines, which was disrupted by PLK1 down-regulation. To conclude, our findings demonstrate that PLK1 accelerates the metastasis and epithelial-mesenchyme transition of gastric cancer cells through regulating the AKT pathway.


A rational approach to sternal wound complications.
A large prospective study of over 350 sternal wound problems is used to help establish evaluation and treatment options to successfully treat this complication. The initial evaluation includes history, physical examination, CT scans, and intraoperative evaluations. Reconstructive options include conservative local therapies (125 patients), rewiring (30 patients), and muscle flap reconstructions (205 patients). The patients were collected over a 9-year period (1990-1999) and treated by a single reconstructive surgeon. Follow-ups for all patients has been at least 2 years (range 2-11 years), and greater than 90% obtained a healed wound at 3 months. Of the patients treated with muscle flap reconstructions, 95% are alive and healed at a 2-year follow-up.


Lack of Correlation Between Subjective and Objective Measures of Gastroesophageal Reflux Disease: Call for a Novel Validated Assessment Tool.
Background. Objective measures including the DeMeester score, lower esophageal sphincter (LES) pressure, acid exposure time, and body mass index (BMI) are used to determine gastroesophageal reflux disease (GERD) severity and eligibility for various antireflux surgical procedures. The GERD Health-Related Quality of Life (GERD-HRQL) survey is widely used to evaluate patients' subjective severity of symptoms and GERD-related quality of life. The purpose of this project was to identify whether or not the subjective measure (GERD-HRQL) correlated with objective measures (DeMeester score, LES, acid exposure time, and BMI) of GERD severity. Methods. A retrospective review of the medical records of patients who underwent antireflux surgery from 2013-2018 was completed. Patients' GERD severity was measured preoperatively and postoperatively using the GERD-HRQL. Statistical analysis included the calculation of Spearman correlation coefficients, Wilcoxon rank sum, sign, and chi-square tests. Results. 151 patients were included in the study; 64% were female. The mean age and BMI were 54.6 ± 14.6 years and 30.1 ± 4.1 kg/m2, respectively. The mean preoperative DeMeester score was 43.1 ± 36.1, LES pressure was 19.9 ± 18.4 mmHg, and acid exposure time was 11.4 ± 9.6. Mean GERD-HRQL scores decreased from 27.3 ± 9.2 preoperative to 5.3 ± 4.5 postoperative; P < .0001. Preoperative GERD-HRQL scores were not correlated with the DeMeester score (r = .11; P = .389), LES pressure (r = -.20; P = .089), acid exposure time (r = .05; P = .755), BMI (r = .10; P = .329), or age (r = -.16; P = .118). Conclusions. Total GERD-HRQL scores significantly decreased from pre- to postoperative. There was no correlation between subjective and objective GERD scoring. These data indicate the need for both physiologic evaluation and subjective assessment of patient symptoms during preoperative workup. There is a need for a contemporary, validated GERD questionnaire that correlates with objective pH testing.


Effect of aging on myocardial perfusion reserve.
Myocardial perfusion reserve (hyperemic divided by basal myocardial blood flow) describes vasodilator responsiveness of coronary-resistive vessels. The effect of aging and gender on myocardial perfusion reserve remains controversial. We studied 56 normal volunteers (21 women, 35 men; aged 50 +/- 20 yr, range 21-86 yr) with 15O-water PET to measure myocardial blood flow during basal and hyperemic states with intravenous dipyridamole (0.56 mg/kg, n = 46) or adenosine (140 micrograms/kg/min, n = 10). For comparative analysis, patients were grouped according to age: < 30 yr (n = 11), 30-49 yr (n = 18), 50-69 yr (n = 15) and > or = 70 yr (n = 12). Overall, basal flow was 1.00 +/- 0.26 ml/min/g and hyperemic flow was 3.31 +/- 1.38 ml/min/g, resulting in a myocardial perfusion reserve of 3.38 +/- 1.35. There was an increase in basal flow with age (r = 0.45, p < 0.025), although hyperemic flow was only lower in patients > or = 70 yr, causing a significant reduction in myocardial perfusion reserve: 3.54 +/- 0.96 in < 30 yr, 4.23 +/- 1.35 in 30-49 yr, 3.51 +/- 1.21 in 50-69 yr and 1.94 +/- 0.46 in > or = 70 yr (p < 0.05 versus all groups < 70 yr). Myocardial blood flow during basal and hyperemia conditions are roughly comparable up to 60 yr of age. Above this age, there is significant increase in basal flow associated with an increase in systolic blood pressure. Above 70 yr, there is a significant reduction in hyperemic flow, and thus myocardial perfusion reserve independent of hemodynamic response to vasodilator stress.


Tracking COVID-19: There's an App for That.
In March 2020, before COVID-19 laid claim to the United States, Vice President Mike Pence briefed the press about the coronavirus outbreak, which at the time was a threat to passengers aboard the Grand Princess cruise ship moored off the coast of California [1]. At the time, cases had spiked in Iran, Italy, and Spain, but the disease was still an abstraction to most Americans. When asked about a potential outbreak in Washington, D.C., Pence called on Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease, and a member of the U.S. Task Force, to address the question. Fauci replied that any individual who tested positive for the disease would undergo contact tracing, which he deemed "the public health weapon" for catching outbreaks before they start. Not long after, the World Health Organization declared a global pandemic, and the virus began spreading across the country.


Histologic grading of adenoid cystic carcinoma of the salivary glands.
Seventy-nine patients with adenoid cystic carcinoma arising in salivary glands were studied to determine whether a correlation existed between the morphologic features of the tumor and the prognosis. Three histologic grades were established: Grade I, tumors with tubular and cribriform areas but without solid components; Grade II, cribriform tumors that were either pure or mixed with less than 30% of solid areas; and Grade III, tumors with a predominantly solid pattern. Cumulative survival rates at 15 years were 39%, 26%, and 5%, for Grades I, II, and III, respectively. Grade III tumors were larger, recurred frequently, and killed the patients within 4 years. Grade I lesions were smaller, were amenable to complete surgical excision, and had a protracted clinical course. Grade II tumors lay between the other two forms both clinically and pathologically. Other important prognostic features of the adenoid cystic carcinoma were its primary site, its presence or absence at surgical margins, and the anatomic structures it involved.


Giardia cyst wall protein 1 is a lectin that binds to curled fibrils of the GalNAc homopolymer.
The infectious and diagnostic stage of Giardia lamblia (also known as G. intestinalis or G. duodenalis) is the cyst. The Giardia cyst wall contains fibrils of a unique beta-1,3-linked N-acetylgalactosamine (GalNAc) homopolymer and at least three cyst wall proteins (CWPs) composed of Leu-rich repeats (CWP(LRR)) and a C-terminal conserved Cys-rich region (CWP(CRR)). Our goals were to dissect the structure of the cyst wall and determine how it is disrupted during excystation. The intact Giardia cyst wall is thin (approximately 400 nm), easily fractured by sonication, and impermeable to small molecules. Curled fibrils of the GalNAc homopolymer are restricted to a narrow plane and are coated with linear arrays of oval-shaped protein complex. In contrast, cyst walls of Giardia treated with hot alkali to deproteinate fibrils of the GalNAc homopolymer are thick (approximately 1.2 microm), resistant to sonication, and permeable. The deproteinated GalNAc homopolymer, which forms a loose lattice of curled fibrils, is bound by native CWP1 and CWP2, as well as by maltose-binding protein (MBP)-fusions containing the full-length CWP1 or CWP1(LRR). In contrast, neither MBP alone nor MBP fused to CWP1(CRR) bind to the GalNAc homopolymer. Recombinant CWP1 binds to the GalNAc homopolymer within secretory vesicles of Giardia encysting in vitro. Fibrils of the GalNAc homopolymer are exposed during excystation or by treatment of heat-killed cysts with chymotrypsin, while deproteinated fibrils of the GalNAc homopolymer are degraded by extracts of Giardia cysts but not trophozoites. These results show the Leu-rich repeat domain of CWP1 is a lectin that binds to curled fibrils of the GalNAc homopolymer. During excystation, host and Giardia proteases appear to degrade bound CWPs, exposing fibrils of the GalNAc homopolymer that are digested by a stage-specific glycohydrolase.


Sorption of fenamiphos to different soils: the influence of soil properties.
Fenamiphos (0-ethyl-0(3-methyl-4-methylthiophenyl)-isopropylamido-phosphate) is a widely used nematicide and insecticide in bowling greens and agriculture, but information on its sorption including its metabolites is limited. Hence, the sorption of fenamiphos (nematicide) and its major degradation products fenamiphos sulfoxide (FSO) and fenamiphos sulfone (FSO2) were determined in thirteen contrasting soils collected from Australia and Ecuador. The sorption coefficients (Kd) exhibited a wide range of variation from 2.48 to 14.94 L/Kg for fenamiphos; from 0 to 7.42 L/Kg for FSO and from 0 to 9.49 L/Kg for FSO2. The sorption affinity of the three compounds for all soils tested was as follows: fenamiphos > fenamiphos sulfone > fenamiphos sulfoxide. The results showed that the sorption of fenamiphos and its metabolites in some soils is very low, and in one case is nonexistant for the metabolites. This is of particular concern as due to its low sorption coefficient, the compound could easily migrate and contaminate water bodies. Fenamiphos and its oxidation products have been reported to be highly toxic to aquatic invertebrates and therefore, the information generated in this study assumes great importance in the risk assessment of fenamiphos and its metabolites in the environment.


[Pharmacokinetics and local availability of mitomycin. The influence of vasoconstriction and chemoembolization].
The influence of the vasopressin-pro-drug glycylpressine (GP) and of a chemoembolisation with Spherex starch-particles (SP) on the availability of mitomycin (CAS 50-07-7, mitomycin C, MMC) was investigated in 30 patients with liver metastases, MMC administration was performed after blocking of the common hepatic artery by different concentrations of SP and after different time-intervals of GP. The comparison of plasma-levels after bolus injection without GP and after administration of MMC after 2, 5 and 15 min of vasoconstriction and after chemoembolisation with 450 mg or 900 mg SP, respectively, showed a remarkable reduction in the systemic circulation of MMC in the blood vessel system at about 40% (GP) and 45% (SP). A statistically significant influence on the pharmacokinetics of MMC with regard to CO, Vd, T 1/2zp, AUC and Cl(tot) was found, but not in t1/2el, t1/2biol and Vl. Both methods cause a distinctly accelerated diffusion of MMC into the tissue of the tumor region by change of the hemodynamics, leading to lowered side-effects. Thus the clinical picture was improved by MMC.


The impact of parenthood on environmental attitudes and behaviour: a longitudinal investigation of the legacy hypothesis.
Willingness to engage in sustainable actions may be limited by the psychological distance of climate change. In this study, we test the legacy hypothesis, which holds that having children leads parents to consider the legacy left to offspring in respect of environmental quality. Using the Understanding Society dataset, a longitudinal survey representative of the UK population (n = 18,176), we assess how having children may change people's individual environmental attitudes and behaviour. Results indicate that having a new child is associated with a small decrease in the frequency of a few environmental behaviours. Only parents with already high environmental concern show a small increase in the desire to act more sustainably after the birth of their first child. Overall, the results do not provide evidence in support of the legacy hypothesis in terms of individual-level environmental attitudes and behaviours. We argue that the transition to parenthood is a time where concern is prioritised on the immediate wellbeing of the child and not on the future environmental threats.


Modeling and validation of polyurethane based passive underwater acoustic absorber.
The acoustic behavior of an acoustically transparent polyurethane and an interpenetrating polymer network of polyurethane with polydimethyl siloxane were studied using dynamic mechanical analysis, finite element modeling, and experimental evaluation of acoustic properties in a water-filled pulse tube setup. Dynamic mechanical measurements in the temperature range -50 °C to +70 °C were carried out, and the data were used for time temperature superposition to generate material behavior at high frequencies. These inputs were used for modeling the acoustic behavior of these materials using ATILA, which is a commercial finite element code, capable of computing transmission and reflection characteristics of materials. From this data, absorption characteristics were computed. The results were compared with the experimental results obtained using a water-filled pulse tube facility.


Characterization of a CK II protein kinase from etiolated oat seedlings.
Protein kinases play a central role in controlling the cellular metabolism of living organisms. A protein kinase was purified from etiolated oat seedlings by several steps of ion-exchange and affinity chromatographies. The kinase was a 150-kDa tetrameric protein and composed of three subunits of 34, 37, and 40 kDa proteins. The 34 and 40 kDa proteins had ATP binding sites, suggesting that they are catalytic subunits and that the 37-kDa protein is a regulatory subunit. In the in vitro phosphorylation of a crude oat cell extract, it intensively phosphorylated a serine residue of a 110-kDa protein. The 110-kDa protein was tentatively identified as a DNA topoisomerase I, based on an amino acid sequence homology. Phosphorylation of the 110-kDa protein by the kinase required ATP or GTP as a phosphoryl group donor. The kinase activity was inhibited by 50% at a concentration of 0.05 microg/ml heparin. These results, therefore, indicate that the purified kinase is a CK II protein kinase and may be involved in the regulation of DNA topoisomerase I activity.


Balneola vulgaris gen. nov., sp. nov., a member of the phylum Bacteroidetes from the north-western Mediterranean Sea.
A novel aerobic, Gram-negative bacterium, named 13IX/A01/164(T), was isolated from surface waters in the coastal north-western Mediterranean Sea. Cells were motile, straight rods, 2.5 mum long and 0.2 mum wide, and formed orange colonies on marine agar medium. The G+C content of the genomic DNA of strain 13IX/A01/164(T) was 42 mol%. Phylogenetic analysis of the 16S rRNA gene sequence placed the strain in the phylum Bacteroidetes within the family Crenotrichaceae. On the basis of 16S rRNA gene sequence comparison and physiological and biochemical characteristics, this isolate represents a novel species of a new genus, for which the name Balneola vulgaris gen. nov., sp. nov. is proposed. The type strain of Balneola vulgaris is 13IX/A01/164(T) (=DSM 17893(T)=CIP 109092(T)=OOB 256(T)).


Direct Formation of Large-Area 2D Nanosheets from Fluorescent Semiconducting Homopolymer with Orthorhombic Crystalline Orientation.
Semiconducting polymers have been widely investigated due to their intriguing optoelectronic properties and their high crystallinity that provides a strong driving force for self-assembly. Although there are various reports of successful self-assembly of nanostructures using semiconducting polymers, direct in situ self-assembly of these polymers into two-dimensional (2D) nanostructures has proven difficult, despite their importance for optoelectronics applications. Here, we report the synthesis of a simple conjugated homopolymer by living cyclopolymerization of a 1,6-heptadiyne (having a fluorene moiety) and its efficient in situ formation of large-area 2D fluorescent semiconducting nanostructures. Using high-resolution imaging tools such as atomic force microscopy and transmission electron microscopy, we observed the solvent-dependent self-assembly behaviors of this homopolymer; the identical starting polymer formed 2D nanosheets with different shapes, such as rectangle, raft, and leaf, when dissolved in different solvents. Furthermore, super-resolution optical microscopy enabled the real-time imaging of the fluorescent 2D nanosheets, revealing their stable and uniform shapes, fluorescence, and solution dynamics. Notably, we propose an orthorhombic crystalline packing model to explain the direct formation of 2D nanostructures based on various diffraction patterns, providing important insight for their shape modulation during the self-assembly.


Sex, sex role identification, and college students' projective drawings.
A study of 109 undergraduates found that sex and sex role identification, as assessed by the Bem Sex Role Inventory (BSRI), were related significantly to sex sequence, sexual differences, and quality of drawing on the Draw-A-Person (DAP). Specifically, males and masculine persons tended to draw males first, female and feminine persons tended to draw females first, and androgynous persons were equally likely to draw a male or a female first. The greater the sexual differentiation of the female human figure drawing, the lower the subject's degree of masculinity. The single best predictor for identifying a female subject was the quality of the female figure drawing. Results were consistent with Machover's hypothesis that drawings of the human figure reveal facets of the subject's self-image.


Applications of Tissue Decellularization Techniques in Ventricular Myocardial Biofabrication.
Ischemic heart disease is the leading cause of death around the world, and though the advent of coronary revascularization has revolutionized its treatment, many patients who sustain ischemic injury to the heart will go on to develop heart failure. Biofabrication of ventricular myocardium for replacement of irreversibly damaged ischemic myocardium is sought after as a potential therapy for ischemic heart failure, though challenges in reliably producing this biomaterial have limited its clinical application. One method that shows promise for generation of functional myocardium is the use of tissue decellularization to serve as a scaffold for biofabrication. This review outlines the methods, materials, challenges, and prospects of tissue decellularization techniques for ventricular myocardium biofabrication. Decellularization aims to preserve the architecture and composition of the extracellular matrix of the tissue it is applied to, allowing for the subsequent implantation of stem cells of the desired cell type. Decellularization can be achieved with multiple reagents, most of which have detergent properties. A variety of cell types can be implanted in the resulting scaffold, including cardiac progenitor cells, and embryonic or induced pluripotent stem cells to generate a range of tissue, from patches to beating myocardium. The future of this biofabrication method will likely emphasize patient specific tissue engineering to generate complex 3-dimensional constructs that can replace dysfunctional cardiac structures.


Assessment of Bone Mineral Density in Male Patients with Chronic Obstructive Pulmonary Disease by DXA and Quantitative Computed Tomography.
The purpose of this study is to identify the prevalence of osteoporosis in male patients with chronic obstructive pulmonary disease (COPD) by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and to compare the diagnostic abilities of the above methods. Thirty-seven male patients with established COPD were examined with DXA and standard QCT in lumbar spine, including L1, L2, and L3 vertebrae. T-scores and bone mineral density values were calculated by DXA and QCT method, respectively. Comparative assessment of the findings was performed and statistical analysis was applied. QCT measurements found more COPD patients with impaired bone mineral density compared to DXA, namely, 13 (35.1%) versus 12 (32.4%) patients with osteopenia and 16 (43.2%) versus 9 (16.2%) patients with osteoporosis (p = 0.04). More vertebrae were found with osteoporosis by QCT compared to DXA (p = 0.03). The prevalence of osteoporosis among male patients with COPD is increased and DXA may underestimate this risk. QCT measurements have an improved discriminating ability to identify low BMD compared to DXA measurements because QCT is able to overcome diagnostic pitfalls including aortic calcifications and degenerative spinal osteophytes.


Effects of aloe, aloesin, or propolis on the pharmacokinetics of benzo[a]pyrene and 3-OH-benzo[a]pyrene in rats.
This study was conducted to examine the effects of aloe and aloesin on the weight gain and blood chemistry as well as the pharmacokinetics of benzo[a]pyrene (BaP) and 3-OH-BaP in rats. The rats treated with multiple doses of aloe and aloesin (100 mg/kg every 12 h for 14-19 d) did not show any significant changes in the weight gain and blood biochemical parameters. In addition, the effects of oral treatment with aloe, aloesin, and propolis on the absorption and pharmacokinetics of benzo[a]pyrene (BaP) and its metabolite, 3-OH-BaP, were studied in rats. The treatment with a single oral dose (200 mg/kg) of aloe, aloesin, and propolis did not alter the concentration-time profiles of BaP and 3-OH-BaP after iv and oral administration of BaP. At higher oral doses (500 mg/kg), the biliary excretion of BaP and the urinary excretion of 3-OH-BaP were significantly increased, but the urinary excretion of BaP and the fecal excretion of 3-OH-BaP remained unaltered. Whether high doses of aloe increase the overall elimination of BaP deserves further investigation.


Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells.
MicroRNAs (miRNAs) control gene expression by binding to their target mRNAs for degradation and/or translation repression and are implicated in many aspects of cellular physiology. Our previous study shows that miR-29b acts as a biological repressor of intestinal mucosal growth, but its exact downstream targets remain largely unknown. In the present study, we found that mRNAs, encoding Wnt co-receptor LRP6 (low-density lipoprotein-receptor-related protein 6) and RNA-binding protein (RBP) HuR, are novel targets of miR-29b in intestinal epithelial cells (IECs) and that expression of LRP6 and HuR is tightly regulated by miR-29b at the post-transcriptional level. miR-29b interacted with both Lrp6 and HuR mRNAs via their 3'-UTRs and inhibited LRP6 and HuR expression by destabilizing Lrp6 and HuR mRNAs and repressing their translation. Studies using heterologous reporter constructs revealed a greater repressive effect of miR-29b through a single binding site in the Lrp6 or HuR 3'-UTR, whereas deletion mutation of this site prevented miR-29b-induced repression of LRP6 and HuR expression. Repression of HuR by miR-29b in turn also contributed to miR-29b-induced LRP6 inhibition, since ectopic overexpression of HuR in cells overexpressing miR-29b restored LRP6 expression to near normal levels. Taken together, our results suggest that miR-29b inhibits expression of LRP6 and HuR post-transcriptionally, thus playing a role in the regulation of IEC proliferation and intestinal epithelial homoeostasis.


Hydroxypropyltrimethyl Ammonium Chloride Chitosan Functionalized-PLGA Electrospun Fibrous Membranes as Antibacterial Wound Dressing: In Vitro and In Vivo Evaluation.
A novel poly(lactic-co-glycolic acid) (PLGA)-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) composite nanofiber wound dressing was prepared through electrospinning and the entrapment-graft technique as an antibacterial dressing for cutaneous wound healing. HACC with 30% degrees of substitution (DS) was immobilized onto the surface of PLGA membranes via the reaction between carboxyl groups in PLGA after alkali treatment and the reactive groups (⁻NH₂) in HACC molecules. The naked PLGA and chitosan graft PLGA (PLGA-CS) membranes served as controls. The surface immobilization was characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR), thermogravimetric analysis (TGA) and energy dispersive X-ray spectrometry (EDX). The morphology studies showed that the membranes remain uniform after the immobilization process. The effects of the surface modification by HACC and CS on the biological properties of the membranes were also investigated. Compared with PLGA and PLGA-CS, PLGA-HACC exhibited more effective antibacterial activity towards both Gram-positive (S. aureus) and Gram-negative (P. aeruginosa) bacteria. The newly developed fibrous membranes were evaluated in vitro for their cytotoxicity using human dermal fibroblasts (HDFs) and human keratinocytes (HaCaTs) and in vivo using a wound healing mice model. It was revealed that PLGA-HACC fibrous membranes exhibited favorable cytocompatibility and significantly stimulated adhesion, spreading and proliferation of HDFs and HaCaTs. PLGA-HACC exhibited excellent wound healing efficacy, which was confirmed using a full thickness excision wound model in S. aureus-infected mice. The experimental results in this work suggest that PLGA-HACC is a strong candidate for use as a therapeutic biomaterial in the treatment of infected wounds.


[GENDER IN THE BRAIN: BETWEEN SCIENCE AND IDEOLOGY].
Despite tremendous advances in neurosciences, the idea that biology is a major determinant for gender differences in cognition and behavior, is still alive. Media and internet continue to feed the public with old clichés that claim that women are naturally good for empathy but unable to read a map, while men have a brain suited for maths and competition. These discourses suggest that at birth the intellectual abilities are wired differently in the brains of girls and boys. Such a view is in total contradiction with today's knowledge on cerebral plasticity, and on the role of the environment in re-shaping the brain through learning and expe-riences. The plasticity concept allows new insight to the question of the origin of brain differences and similarities between the sexes. Experience in the sociocultural context involves gender learning processes which interact with the biological processes. A major challenge is that of building an interdisciplinary dialogue across the biological, social, and human sciences to develop new approaches linking sex, gender and the brain.


XRCC4 controls nuclear import and distribution of Ligase IV and exchanges faster at damaged DNA in complex with Ligase IV.
Non-homologous end-joining (NHEJ) is one major pathway for the repair of double-stranded DNA breaks in mammals. Following break recognition, alignment and processing, broken DNA ends are finally rejoined by the essential DNA Ligase IV. In the cell, Ligase IV is unable to function without its constitutive interaction partner XRCC4 and becomes unstable when it is missing, and it has been assumed that XRCC4 may also be required for recruitment of Ligase IV to repair sites. To investigate the function of complex formation between both proteins directly in the living cell, we stably expressed them as bio-fluorescent fusion proteins in human HT-1080 cell clones. Ligase IV or XRCC4 were expressed either alone or both were co-expressed at a roughly equimolar ratio. Labelled proteins were overexpressed manifold in comparison to endogenously expressed proteins. We show that over-expressed Ligase IV was only partially imported into the nucleus and showed a diffuse distribution there, whereas XRCC4 expressed alone was entirely nuclear with a distinct exclusion from nucleoli. When Ligase IV was co-expressed with XRCC4, both proteins formed the natural complex, and Ligase IV was not only efficiently imported but also resembled the sub-nuclear distribution of XRCC4. In addition, Ligase IV, when in complex with XRCC4, acquired a delayed nuclear reimport after mitotic cell division of XRCC4. We further determined by photobleaching the kinetics with which the proteins exchange at UVA laser-irradiated nuclear sites between damage-bound and diffusing states. We found that the dynamic exchange rate of the Ligase IV/XRCC4 complex at micro-irradiated sites was faster than that of XRCC4 expressed alone. In summary, our findings demonstrate a novel function of XRCC4 in controlling nuclear import and sub-nuclear distribution of Ligase IV, and they suggest that XRCC4 modulates the dynamic interaction of the Ligase IV/XRCC4 complex with the NHEJ machinery at double-stranded DNA breaks.


Naltrexone: a clinical perspective.
The narcotic antagonist naltrexone was studied in over 300 opiate addicts. Patient selection was a major factor in determining retention and treatment outcome. Treatment time ranged from 1 week to over a year (mean = 2 months). A quarter of the study patients had multiple treatment episodes. Stabilized patients had few side effects, except for occasional nausea and abdominal cramps. Almost half the subjects tested naltrexone by using opiates at least once; all reported satisfactory narcotic blockade. Very few subjects switched to nonopiates to get high, although several did increase their alcohol consumption during the first weeks of therapy. One-third of subjects contacted in a follow-up study were opiate-free 6 months after stopping naltrexone, indicating a successful short-term treatment modality.


Maternal serum human placental growth hormone (hPGH) at 11 to 13 weeks of gestation in preeclampsia.
Human placental growth hormone (hPGH) is produced by human placenta and plays a central role in the maternal metabolic adjustments to pregnancy. The objective of this study was to investigate the maternal serum concentration of hPGH at 11-13 weeks of gestation in pregnancies that subsequently developed preeclampsia (PE), and to examine the possible association with uterine artery pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A (PAPP-A). The maternal serum concentration of hPGH at 11-13 weeks was measured in a case-control study from 60 cases that developed PE and 120 unaffected controls. The measured hPGH concentration was converted into a multiple of the expected median (MoM) in unaffected pregnancies. Regression analysis was used to determine the significance of association between hPGH MoM with uterine artery PI MoM and PAPP-A MoM. In the pregnancies that subsequently developed PE the median serum hPGH concentration was not significantly different from that in the unaffected group (0.92 versus 1.00 MoM), whereas uterine artery PI was increased (1.31 versus 1.01 MoM) and serum PAPP-A was decreased (0.76 versus 1.01 MoM). In the group that developed PE there was no significant association between serum hPGH MoM and gestational age at delivery, uterine artery PI MoM, or serum PAPP-A MoM. The finding that in the PE group serum hPGH level during the first trimester is normal suggests that it is unlikely that this hormone plays a role in the pathogenesis of PE.


Glomerular tip lesion in minimal change nephropathy: a study of autopsies before 1950.
The clinical significance of the glomerular tip lesion, characterized by podocyte prominence, capsular adhesion, and/or intracapillary foam cells at or adjacent to the urinary pole, remains unclear. It has been postulated that this lesion simply represents a response to heavy proteinuria, and cases of nephrotic syndrome with tip lesions, but no other histological abnormalities, may represent a form of minimal change nephropathy (MCN). However, others have reported that such lesions have a clinical course similar to that of primary focal segmental glomerulosclerosis (FSGS), and the tip lesion often is included among histological variants of FSGS. To determine whether tip lesions may be seen in MCN, we examined histological slides of kidneys from pre-1950 autopsies of patients with a diagnosis of lipoid nephrosis, a term that at that time comprised MCN and FSGS. Before the introduction of antibiotics and corticosteroid therapy, patients with nephrotic syndrome frequently died of sepsis. Eight such cases, with autopsies performed from 1924 to 1943, were identified in which no glomeruli had changes typical of classic FSGS or membranous nephropathy. More than 400 glomeruli were present in each case. Patient ages ranged from 3 to 45 years (six patients <11 years), all had marked edema (duration, 2 weeks to 21 months) and heavy proteinuria, and each died of sepsis and/or pneumonia (pneumococcal in six patients). Glomerular tip lesions were found in five of these eight cases (range, 3 to 26 lesions per case; 0.3% to 4.4% of total glomeruli present), with no predilection for the deep, middle, or superficial cortex. No tip lesions were seen in kidneys from autopsies of age-matched patients without a history of glomerular disease. These findings suggest that the glomerular tip lesion can occur in MCN and most likely represents a response to heavy proteinuria that is not disease specific.


Everyday life with rheumatoid arthritis and implications for patient education and clinical practice: a focus group study.
This study aimed to explore how everyday life is affected by rheumatoid arthritis (RA), in order to inform patient education and clinical practice and generate further research. Six focus group interviews were conducted with, in total, 32 participants. Interview data were analysed using content analysis methods. The study showed that RA affected almost every aspect of participants' everyday lives, particularly self-identity, social relationships, work and relationships with health and social care professionals. A small number of the participants did not have these experiences, due to receiving fast diagnosis and effective medical treatment. The findings point to a need to increase knowledge about RA, support symptom management and reduce the physical, social and psychological challenges posed by RA in everyday life. An individualized and engaged approach to patient education, taking the individual experiences as the point of departure, is suggested. The results indicate directions for further research. The general implications for patient education that emerge from this study might not address the support needs of those who did not experience significant changes in everyday life. A more detailed and in-depth understanding about living with RA in the first years after diagnosis would provide a valuable supplement to the many retrospective studies, and useful knowledge in the design of patient education tailored to those who are newly diagnosed with RA.


Urgent care centre in Sweden-the integration of teams and perceived effects.
An urgent care centre (UCC) is an upcoming trend in Swedish health care. Although UCCs have been established in other countries, their effectiveness and value have not yet been studied in Sweden. The aim of this study was to investigate the interaction between the UCC and emergency department (ED) by using validated evaluation models. One adult ED (AED) and one child ED (CED), together with a newly established UCC nearby, were included in this study. The interaction between the UCC team and the ED teams was studied by using two evaluation models: one for evaluation of integration and the other one for the evaluation of the effects, in terms of perceived relief of the ED after the establishment of the UCC. It was evident that integration was achieved early on in the course of the follow-up. However, the perception of integration varied between low (EDs) and high collaboration (UCC). All respondents of the EDs indicated relief, in terms of pace and pressure on the ED since the UCC was established. This study indicates that the grade of integration and collaboration between UCC and ED can be achieved automatically and very early during the establishment. It also shows that UCCs can be a competent complement to EDs and alleviate some of the heavy pressure placed on EDs due to ED overcrowding.


The efficacy of diagnostic imaging.
The authors discuss the assessment of the contribution of diagnostic imaging to the patient management process. A hierarchical model of efficacy is presented as an organizing structure for appraisal of the literature on efficacy of imaging. Demonstration of efficacy at each lower level in this hierarchy is logically necessary, but not sufficient, to assure efficacy at higher levels. Level 1 concerns technical quality of the images; Level 2 addresses diagnostic accuracy, sensitivity, and specificity associated with interpretation of the images. Next, Level 3 focuses on whether the information produces change in the referring physician's diagnostic thinking. Such a change is a logical prerequisite for Level 4 efficacy, which concerns effect on the patient management plan. Level 5 efficacy studies measure (or compute) effect of the information on patient outcomes. Finally, at Level 6, analyses examine societal costs and benefits of a diagnostic imaging technology. The pioneering contributions of Dr. Lee B. Lusted in the study of diagnostic imaging efficacy are highlighted.


Avatars and emotional engagement in asynchronous online communication.
The notion that an avatar can elicit a sense of emotional involvement or connection on the part of a user in asynchronous online communication was explored through a pair of content analyses of a popular online question-and-answer bulletin board. In the first study, questions accompanied by an avatar not only received more answers than questions without an avatar, but the answers were more likely to be characterized by expressions of empathy. In the second study, a preference for answering questions accompanied by an avatar was found to be associated with interpersonal, altruistic motives for answering questions. Results are discussed in terms of presence and alternative explanations, as well as practical implications.


Exosome-Mediated Insulin Delivery for the Potential Treatment of Diabetes Mellitus.
Exosomes are extracellular nanovesicles between 30 and 150 nm that serve as essential messengers for different biological signaling and pathological processes. After their discovery, a wide range of applications have been developed, especially in therapeutic drug delivery. In this context, the aim of this work was to test the efficiency of exosome-mediated human insulin delivery using exosomes extracted from three different cell lines: hepatocellular carcinoma (HepG2); primary dermal fibroblasts (HDFa) and pancreatic β cells (RIN-m); all are related to the production and/or the ability to sense insulin and to consequently regulate glucose levels in the extracellular medium. The obtained results revealed that the optimal insulin loading efficiency was achieved by a 200 V electroporation, in comparison with incubation at room temperature. Moreover, the maximum in vitro exosome uptake was reached after incubation for 6 h, which slightly decreased 24 h after adding the exosomes. Glucose quantification assays revealed that exosome-mediated incorporation of insulin presented significant differences in HDFa and HepG2 cells, enhancing the transport in HDFa, in comparison with free human insulin effects in the regulation of extracellular glucose levels. No significant differences were found between the treatments in RIN-m cells. Hence, the results suggest that exosomes could potentially become a valuable tool for stable and biocompatible insulin delivery in diabetes mellitus treatment alternatives.


Religion, social support, fat intake and physical activity.
Most research on diet and exercise has focused on these health behaviours as proximate causes of disease, rather than examine the context of how diet and exercise are developed and maintained. This study examined religion and social support in relationship to fat intake and physical activity. Data from surveys of 546 adults aged 17-91 years, residing in one upstate New York county, were analysed. Most relationships between the multiple facets of religion, fat intake and physical activity were not statistically significant. After controlling for demographics and social support, Conservative Protestant women and women specifying an "Other" religious affiliation reported higher fat intakes than did Catholic women. There were no relationships between religion and fat intake in men. In women, religious commitment was associated with greater moderate and vigorous physical activity, whereas in men, divine social support was associated with greater moderate physical activity. Social support did not substantially change the magnitude of the relationships between religion, diet and physical activity. Overall, there were few relationships between religion, fat intake and physical activity, suggesting that in contemporary US society religion may play a small role in the context of how diet and exercise are developed and maintained. The limited range of religiosity in the sample, however, may have underestimated the role of religion. Significant relationships between religion and physical activity in women suggest that further research is needed to more clearly delineate religion's relationship with health behaviours.


Insights into the innate immunome of actiniarians using a comparative genomic approach.
Innate immune genes tend to be highly conserved in metazoans, even in early divergent lineages such as Cnidaria (jellyfish, corals, hydroids and sea anemones) and Porifera (sponges). However, constant and diverse selection pressures on the immune system have driven the expansion and diversification of different immune gene families in a lineage-specific manner. To investigate how the innate immune system has evolved in a subset of sea anemone species (Order: Actiniaria), we performed a comprehensive and comparative study using 10 newly sequenced transcriptomes, as well as three publically available transcriptomes, to identify the origins, expansions and contractions of candidate and novel immune gene families. We characterised five conserved genes and gene families, as well as multiple novel innate immune genes, including the newly recognised putative pattern recognition receptor CniFL. Single copies of TLR, MyD88 and NF-κB were found in most species, and several copies of IL-1R-like, NLR and CniFL were found in almost all species. Multiple novel immune genes were identified with domain architectures including the Toll/interleukin-1 receptor (TIR) homology domain, which is well documented as functioning in protein-protein interactions and signal transduction in immune pathways. We hypothesise that these genes may interact as novel proteins in immune pathways of cnidarian species. Novelty in the actiniarian immunome is not restricted to only TIR-domain-containing proteins, as we identify a subset of NLRs which have undergone neofunctionalisation and contain 3-5 N-terminal transmembrane domains, which have so far only been identified in two anthozoan species. This research has significance in understanding the evolution and origin of the core eumetazoan gene set, including how novel innate immune genes evolve. For example, the evolution of transmembrane domain containing NLRs indicates that these NLRs may be membrane-bound, while all other metazoan and plant NLRs are exclusively cytosolic receptors. This is one example of how species without an adaptive immune system may evolve innovative solutions to detect pathogens or interact with native microbiota. Overall, these results provide an insight into the evolution of the innate immune system, and show that early divergent lineages, such as actiniarians, have a diverse repertoire of conserved and novel innate immune genes.


Reproducibility of diurnal variation of heart rate.
Heart rate variation has been utilized as a parameter for validating autonomic nerve and sinus node function. However, few reports are available on the reproducibility of such data. In the present study, we studied the reproducibility of the diurnal variation of heart rate in 15 patients, and the effect of age differences on the variation in 30 normal men using a Holter ECG monitoring method. For investigating reproducibility, Holter ECG monitoring was performed twice, the two measurements being separated by a short interval. A moving average method applied on heart rate of every 3h exhibited essentially the same diurnal pattern of heart rate between two records in each patient. Excellent reproducibility of the pattern was also demonstrated by a lag correlation analysis. Variability of heart rate in normal men was independent of age. These results suggest that heart rate variation was essentially constant in each subject, at least within a short period.


Tolazoline decreases survival time during microwave-induced lethal heat stress in anesthetized rats.
Effects of alpha-adrenergic antagonists have been studied during environmental heating but not during microwave-induced heating. Tolazoline may exert some of its effects via alpha-adrenegic blockade. In the present study, ketamine-anesthetized Sprague-Dawley rats were exposed to 2450-MHz microwaves at an average power density of 60 mW/cm2 (whole-body specific absorption rate of approximately 14 W/kg) until lethal temperatures were attained. The effects of tolazoline (10 mg/kg body weight) on physiological responses (including changes in body temperature, heart rate, blood pressure, and respiratory rate) were examined. Survival time was significantly shorter in the tolazoline group than in saline-treated animals. In general, heart rate and blood pressure responses were similar to those that occur during environmental heat stress. Heart rate, however, was significantly elevated in animals that received tolazoline, both before and during terminal microwave exposure. It is possible that changes associated with the elevated heart rate (e.g., less cardiac filling) in tolazoline-treated animals resulted in greater susceptibility to microwave-induced heating and the lower survival time.


Primary neuroendocrine carcinoma of the brain.
Neuroendocrine neoplasms (NENs) are malignancies with rare reports of central nervous system development. A 34-year-old woman was found to have a primary NEN of the brain, and she had recurrence with identical histology 10 years later. Extracranial NENs were excluded. She had routine surveillance for the first 5 years with MRIs and positron emission tomography/CTs after the initial presentation which was treated with radiation followed by cisplatin and etoposide. This case highlights the difference in primary NENs versus NEN metastases to the brain, and that longer periods of surveillance are likely required for primary NENs. This is important because the prognosis between primary NENs and metastatic NENs to the brain are vastly different and should not be treated as equal diseases. The patient eventually died of her recurrence secondary to complications of a ventriculoperitoneal shunt placed for treatment of hydrocephalus from the disease.


Production of Herbicide-Sensitive Strain to Prevent Volunteer Rice Infestation Using a CRISPR-Cas9 Cytidine Deaminase Fusion.
When cultivated rice seed fall into fields, they may overwinter and spontaneously germinate the next spring. Such germinated plants are termed "volunteer rice." Volunteer grains originating from feed rice varieties may differ in certain traits, such as quality and taste, as compared with those of rice cultivated for human consumption, which may reduce the overall quality of the final harvested grain. Many rice varieties show resistance to benzobicyclon (BBC), a beta-triketone herbicide (bTH) that inhibits 4-hydroxyphenylpyruvate dioxygenase (HPPD). Recently, the rice gene HIS1 (HPPD INHIBITOR SENSITIVE 1) conferring resistance to BBC and other bTHs was identified. In this study, to suppress the occurrence of volunteer rice infestation, we attempted to generate a BBC-sensitive rice strain via the knockout of the HIS1 gene using genome editing techniques. The production of a his1 knockout line was carried out by the start-codon substitution or stop-codon creation using CRISPR-Cas9 cytidine deaminase fusion, which is useful as a novel amino acid sequence is not generated due to the shifting of the reading frame. The mutation frequencies of independent transgenic plants were 3.6, 13.5, 13.8, and 21.2% at four gRNAs for start-codon substitution and three stop-codon creations. The his1 knockout lines were conferred with sensitivity to BBC, re-confirming by genome editing that this is indeed the gene responsible for BBC resistance/sensitivity. The his1 knockout lines also exhibited a sensitive phenotype to other bTHs, including sulcotrione, mesotrione, tembotrione, and tefuryltrione, compared with the wild-type variety 'Nipponbare.' These results demonstrate the potential of herbicide-sensitive rice produced by genome editing technology as a material to control volunteer feed rice using pre-labeled herbicides for varieties consumed by humans.


Placenta hominis protects osteoporosis in ovariectomized rats.
In China, Japan, and Korea, placenta hominis extracts (PHEs) are used clinically for the treatment of osteoporosis. The anti-osteoporotic effect of PHEs was studied. The trabecular bone area and thickness in OVX rats decreased by 50% from those in sham-operated rats; these decreases were completely inhibited by administration of PHEs for 7 weeks. Osteoclast numbers and the osteoblast surface were enhanced in OVX rats, but PHEs had no effect on these phenomena. Serum phosphorus and alkaline phosphatase in OVX rats increased compared to those in sham-operated rats, but the increases were not affected by the administration of PHEs. Thyroxine (T4) level was stimulated in OVX rats. The extracts inhibited the T4 level in the OVX rats. These results strongly suggest that PHEs be effective in preventing the development of bone loss induced by OVX in rats.


Effects of Exposure to Welding Fume on Lung Function: Results from the German WELDOX Study.
The association between exposure to welding fume and chronic obstructive pulmonary disease (COPD) has been insufficiently clarified. In this study we assessed the influence of exposure to welding fume on lung function parameters. We investigated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and expiratory flow rates in 219 welders. We measured current exposure to respirable particles and estimated a worker's lifetime exposure considering welding techniques, working conditions and protective measures at current and former workplaces. Multiple regression models were applied to estimate the influence of exposure to welding fume, age, and smoking on lung function. We additionally investigated the duration of working as a welder and the predominant welding technique. The findings were that age- and smoking-adjusted lung function parameters showed no decline with increasing duration, current exposure level, and lifetime exposure to welding fume. However, 15% of the welders had FEV1/FVC below the lower limit of normal, but we could not substantiate the presence of an association with the measures of exposure. Adverse effects of cigarette smoking were confirmed. In conclusion, the study did not support the notion of a possible detrimental effect of exposure to welding fume on lung function in welders.


Spinal mechanisms of antinociceptive effect caused by oral administration of bis-selenide in mice.
The present study was designed to investigate further the mechanisms involved in the antinociception caused by bis-selenide in behavioral model of pain in mice. Bis-selenide (5-50 mg/kg), given orally, produced significant inhibition of the antinociceptive behavior induced by intrathecal (i.t.) injection of glutamate (175 nmol/site), kainate (110 pmol/site) and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 50 nmol/site) and the maximal inhibitions observed were 57+/-5, 46+/-7 and 73+/-3%, respectively. Bis-selenide failed to affect the nociception induced by alpha-amino-3-hydroxy-5-mehtyl-4-isoxazolepropionic acid (AMPA; 135 pmol/site) and N-methyl-d-aspartate (NMDA; 450 pmol/site). This compound also reduced the nociceptive response induced by tumor necrosis factor-alpha (TNF-alpha; 0.1 pg/site), interleukin-1beta (IL-1beta; 1 pg/site), substance P (SP) (135 ng/site, i.t.) and capsaicin (30 ng/site) and the inhibitions observed were 81+/-3%, 88+/-1%, 77+/-3 and 67+/-3, respectively. The oral administration of bis-selenide (25-50 mg/kg) in mice caused a significant increase in the reaction time to thermal stimuli in the hot plate test and the mean ID(50) value (and the 95% confidence limits) was 20.37 (15.00-25.74) mg/kg. The antinociceptive effect caused by bis-selenide (50 mg/kg, p.o.) on the hot plate test in mice was reversed by intrathecal (i.t.) injection of some K(+) channel blockers such as tetraethylammonium (TEA, non-selective voltage-dependent K(+) channel inhibitor) and glibenclamide (ATP-sensitive K(+) channel inhibitor), but not apamin and charybdotoxin (large- and small-conductance Ca(2+)-activated K(+) channel inhibitors, respectively). Together, these results indicate that bis-selenide produces antinociception at spinal sites through the activation of ATP-sensitive and voltage-gated K(+) channels and interaction with kainate and trans-ACDP receptors as well as vanilloid and neuropeptide receptors and pro-inflammatory cytokines.


Donating in good faith or getting into trouble Religion and organ donation revisited.
There is worldwide shortage of organs for solid-organ transplantation. Many obstacles to deceased and live donation have been described and addressed, such as lack of understanding of the medical process, the issue of the definition of brain death, public awareness of the need for transplants, and many others. However, it is clear that the striking differences in deceased and live donation rates between different countries are only partly explained by these factors and many cultural and social reasons have been invoked to explain these observations. We believe that one obstacle to both deceased and live donation that is less well appreciated is that of religious concerns. Looking at the major faiths and religions worldwide, it is reassuring to see that most of them encourage donation. However, there is also scepticism amongst some of them, often relating to the concept of brain death and/or the processes surrounding death itself. It is worthwhile for transplant teams to be broadly aware of the issues and also to be mindful of resources for counselling. We believe that increased awareness of these issues within the transplant community will enable us to discuss these openly with patients, if they so wish.


[Matrix metalloproteinase-3 genotype distribution and its relation with blood pressure profiles in Guangzhou rural population].
To analyze the distribution of matrix metalloproteinase-3 (MMP-3) genotype and its association with the blood pressure profiles in Guangzhou rural population. This study was conducted among 680 rural residents aged 40-70 years (including 314 men and 366 women) from 3 villages in an rural area of Guangzhou. The blood pressures of the subjects were measured and blood samples were collected for genotype analysis using polymerase chain reaction and direct sequencing of the MMP-3 gene promoter region to detect the 5 adenines (5A)/6 adenines (6A) polymorphisms. The frequencies of MMP-3 genotypes 6A/6A, 5A/5A, and 5A/6A were 82.6%, 1.8% and 15.6% among these residents, respectively. The distribution of MMP-3 genotypes and allele frequencies showed no significant gender- or age-related variations. The men with different genotypes (6A/6A vs 5A/6A+5A/5A) did not show significant differences in blood pressure levels, whereas the women with 5A/6A+5A/5A genotypes had higher systolic and diastolic blood pressures than those with a 6A/6A genotype. The allele 5A was highly frequent in the hypertensive residents as compared with the normotensive residents. The 6A homozygote is the predominant genotype of MMP-3 in Guangzhou rural population, which has a significantly lower proportion of 5A homozygote than the Western populations. The 5A allele is associated with a high risk of hypertension especially in women and may affect both systolic and diastolic blood pressures.


Towards Transparent Deep Image Aesthetics Assessment with Tag-based Content Descriptors.
Deep learning approaches for Image Aesthetics Assessment (IAA) have shown promising results in recent years, but the internal mechanisms of these models remain unclear. Previous studies have demonstrated that image aesthetics can be predicted using semantic features, such as pre-trained object classification features. However, these semantic features are learned implicitly, and therefore, previous works have not elucidated what the semantic features are representing. In this work, we aim to create a more transparent deep learning framework for IAA by introducing explainable semantic features. To achieve this, we propose Tag-based Content Descriptors (TCDs), where each value in a TCD describes the relevance of an image to a human-readable tag that refers to a specific type of image content. This allows us to build IAA models from explicit descriptions of image contents. We first propose the explicit matching process to produce TCDs that adopt predefined tags to describe image contents. We show that a simple MLP-based IAA model with TCDs only based on predefined tags can achieve an SRCC of 0.767, which is comparable to most state-of-the-art methods. However, predefined tags may not be sufficient to describe all possible image contents that the model may encounter. Therefore, we further propose the implicit matching process to describe image contents that cannot be described by predefined tags. By integrating components obtained from the implicit matching process into TCDs, the IAA model further achieves an SRCC of 0.817, which significantly outperforms existing IAA methods. Both the explicit matching process and the implicit matching process are realized by the proposed TCD generator. To evaluate the performance of the proposed TCD generator in matching images with predefined tags, we also labeled 5101 images with photography-related tags to form a validation set. And experimental results show that the proposed TCD generator can meaningfully assign photography-related tags to images.


Prevalence and patient characteristics of Mayer-Rokitansky-Küster-Hauser syndrome: a nationwide registry-based study.
What is the prevalence of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome? The prevalence of MRKH syndrome in Denmark is 1 in 4982 (95% confidence interval (CI): 4216-5887) live female births. The prevalence of MRKH syndrome has been estimated to be around 1 in 4000-5000 females. However, population-based prevalence studies of MRKH syndrome are sparse. Moreover, population-based data on patient characteristics are lacking. This retrospective cohort study used the Danish National Patient Registry (DNPR) to identify a nationwide population-based cohort of patients with MRKH syndrome. Subsequently, patients were linked to the Danish Cytogenetic Central Registry (DCCR) and patient medical records in order to validate the diagnoses. Hospitalizations and outpatient visits from 1994 to April 2015 at all public hospitals in Denmark were searched for patients assigned with a diagnosis code indicative of MRKH syndrome. The diagnoses were validated by diagnostic history in the DNPR and DCCR data, and by review of patient medical records. The prevalence was estimated considering the identified patients born from 1974 to 1996. Patient characteristics were described using data collected from DNPR, DCCR and patient medical records. The diagnosis was validated in 304 of 314 patients (96.8%) suspected with MRKH syndrome by review of diagnostic histories, DCCR data, and medical records and in 168 patients, the diagnosis of MRKH syndrome was confirmed (positive predictive value = 55.3% (95% CI: 49.5-60.9%)). The prevalence was 1 in 4982 (95% CI: 4216-5887) live female births based on 138 patients born from 1974 to 1996. Typical MRKH syndrome and atypical MRKH syndrome/Müllerian duct aplasia, Renal aplasia, and Cervicothoracic Somite dysplasia association were present in 56.5% and 43.5% of the patients, respectively. Kidney malformations were the most prevalent extragenital malformations, described in 38 of 111 patients (34.2%). However, in 57 patients (33.9%) no urinary tract imaging was performed. Three familial cases of MRKH syndrome were identified. We identified all patients with MRKH syndrome diagnosed at public hospitals in Denmark. When interpreting the prevalence estimate, caution must be taken due to limitations such as patients not diagnosed in public hospitals, other diagnosis codes not used in the study and the unknown impact of a net positive migration rate in Denmark. The prevalence estimate around 1 in 5000 is in accordance with a previous nationwide study. We consider the prevalence generalizable to other Caucasian populations. Prevalence studies of non-Caucasian populations are needed to investigate whether inter-ethnic differences in prevalence exist. Finally, the results of this study emphasize the need for sufficient basic examinations of patients with MRKH syndrome, including the importance of family medical history. None.


[Application of single stapler combined with prolapsing technique in anterior resection of ultra-low rectal cancer].
Evaluation of single stapler combined with prolapsing technique for anus-preserving of ultra-low rectal cancer and its indication as well as surgical procedure. Forty-three patients with ultra-low low rectal cancer suitable for anterior resection were divided into two groups, single stapler combined with prolapsing technique was applied for experiment group, conventional double stapler technique was applied for control group. To compare the distal margin, local recurrence rate, complications, anal continence function and expenses. The distal margin of experimental group is significantly longer than that of control group (2.2 cm +/- 0.2 cm VS 1.9 cm +/- 0.4 cm, P = 0.006). The distance between dentate line and distal incision line of control group is much longer than experimental group (1.9 cm +/- 0.5 cm VS 1.3 cm +/- 0.3 cm, P < 0.001). There is no recurrence in experimental group but 3 cases recurrence within 1 year in control group. The anastomose fistula rate, instrument expenses of experimental group are less than those of control group. There is no distinct in anal continence between two groups. Occasional minor soiling is present in 1 case of experimental group. Single stapler combined with prolapsing technique is superior to double stapler technique for anus-preserving of ultra-low rectal cancer.


Neurological manifestations in three German children with AIDS.
We report the neurological findings in two children with AIDS and one child with lesser AIDS. The first patient developed acute encephalopathy 37 months after having received a blood transfusion from a HTLV-III positive donor. CCT showed ring-enhancement and hypodense lesions with homogenous enhancement. Autopsy revealed CNS toxoplasmosis. The second child with AIDS, born to an iv drug-addicted mother, had one seizure at four months of age, but other neurologic signs were absent. She died of pneumonia due to Pneumocystis carinii at seven months of age. Postmortem examination of the brain revealed extensive nerve cell damage in the cerebral cortex and cerebellum, probably due to terminal hypoxemia and not AIDS-related. In both children clinical features of childhood AIDS like failure to thrive, lymphadenopathy, oral thrush and chronic pulmonary infiltrates were absent. The hallmark of the third child's clinical course was a progressive loss of psychomotor abilities with onset of the neurological symptoms nine months before other signs of AIDS occurred. AIDS should be suspected or excluded in children at increased risk for AIDS presenting with either acquired atypical CNS infection or unexplained developmental regression, even in the absence of other clinical symptoms of pediatric AIDS.


In vitro angiogenic potency in human microvascular endothelial cells derived from myocardium, lung and skin.
Human microvascular endothelial cells derived from myocardium (HCMEC), lung (HPMEC) and foreskin (HDMEC) showed different angiogenic potency when cultivated in their original growth media provided by the distributors. In order to standardize microenvironmental conditions in an all-in-one assay of angiogenesis the aim of this study was to find one optimal growth medium for the endothelial cells derived from the different organs. Therefore each endothelial cell type was cultivated under identical conditions in the different original growth media as well as in several media formulations of the original growth media. Results reveal that even if cultivated in the same growth medium under exactly the same cultivation conditions--over a prolonged time period of 60 days--the endothelial cells still showed different angiogenic potency. This is due to a combination of extrinsic factors, i.e. the isolation procedure and in particular the growth medium, as well as to intrinsic differences between cells of diverse origin.


Circadian rhythms of hormone secretion and obesity.
The adipose tissue homeostasis is profoundly affected by circadian rhythms of corticosteroid secretion and chronic loss of hormonal oscillations is associated with obesity. How adipose tissue differentially responds to pulsatile vs continuous presence of glucocorticoids is poorly defined. To address this question, Bahrami-Nejad et al studied differentiation of pre-adipocytes, containing endogenously tagged CCAAT/enhancer binding protein and peroxisome proliferator-activated receptor (PPAR) γ (key regulators of adipocyte differentiation), in response to corticosteroids that were delivered either in an oscillatory fashion or continuously. The authors show that the bi-stable state of differentiation of pre-adipocytes and adipocytes was regulated by a combination of fast and slow positive feedback networks, that determined unique threshold of PPARγ in these cells. Evidently, pre-adipocytes used the fast feedback loop to reject differentiation cues of oscillating pulses of glucocorticoids and failed to differentiate into fat cells. In contrast, when glucocorticoids were delivered continuously, precursor cells exploited the slow feedback loop to embark on a path of maximal differentiation. This differential differentiation response of pre-adipocytes to pulsatile vs continuous exposure to glucocorticoids was corroborated in vivo. Thus, mice receiving non-oscillating doses of exogenous glucocorticoids, for 21 d, elicited excessive accumulation of visceral and subcutaneous fat. These data shed new light on the mechanisms of obesity caused by putative misalignment of circadian secretion of glucocorticoids or their persistently high levels due to chronic stress or Cushing's disease.


Why must the debate continue on Krabbe disease newborn screening?
Since the early 2000s, many families impacted by Krabbe disease have tried to implement newborn screening for this rare fatal neurological disorder in their home state. However, despite grassroots efforts, states have been unable to agree to newborn screening for Krabbe disease due to poor testing mechanisms, lack of understanding of the developmental outcomes of transplantation, low incidence rate, and more. Over the past five years, many organizations and experts have made significant strides to help Krabbe disease meet the eligibility requirements for state panels and the Recommended Uniform Screening Panel (RUSP). Nevertheless, ethicists and newborn screening advisory committees continue to disregard the progress our community has made in the treatment and screening of Krabbe disease.


Review article: the pharmacodynamics and pharmacokinetics of proton pump inhibitors--overview and clinical implications.
During the past two decades, enormous changes occurred in the management of gastric acid-related diseases. First, the histamine2-receptor antagonists were introduced, offering patients the first single-agent therapy that effectively reduced gastric acid secretion. Proton pump inhibitors became widely available in the early 1990s, and they generally appeared to be superior to the histamine2-receptor antagonists in acid-suppressing activity, symptom control and healing. Most physicians now use proton pump inhibitors as first-line treatment for many patients with acid-peptic disorders, including erosive gastro-oesophageal reflux disease (GERD), nonerosive reflux disease (NERD) and duodenal and gastric ulcers. Although proton pump inhibitors are often thought to be interchangeable, some differences have emerged in their pharmacological properties, which may be reflected in some aspects of clinical efficacy. Such differences include potency, speed of onset and duration of pH 'holding times'. Helicobacter pylori has now been recognized as an important factor in the pathogenesis of acid-peptic disorders. It is clear that H. pylori eradication can dramatically reduce the chronicity of gastric and duodenal ulcers, and accepted therapeutic regimens for H. pylori eradication now include proton pump inhibitors and two or more antibiotics. Although all accepted proton pump inhibitor-based 'triple therapies' are roughly equivalent in efficacy, there is now a shortened regimen available that will potentially enhance compliance and decrease cost. This review examines the relative advantages of proton pump inhibitors vs. histamine2-receptor antagonists in the context of acid suppression and in various gastric acid-related diseases. A brief overview presents the pharmacodynamics and pharmacokinetics of the proton pump inhibitors with particular attention paid to rabeprazole, one of the newer drugs in its class.


Heparin-Regulated Prodrug-Type Macromolecular Theranostic Systems for Cancer Therapy.
Heparin is a kind of naturally occurring polymer with excellent biocompatibility and solubility. It is characterized by dense of negative charge, higher than any endogenous components. Heparin can bind with various cationic peptides and proteins, thereby providing a useful noncovalent linkage for building a drug delivery system. As a case in point, heparin/cell-penetrating peptides (CPP) interaction is strong, and remains stable in vivo. They can be used to modify different proteins, respectively, and subsequently, by simply mixing the modified proteins, a protein-protein conjugate can be form via the stable heparin/CPP linkage. This linkage could not be broken unless addition of protamine that bears higher cationic charge density than CPP, and CPP thus can be substituted and released. Of note, heparin is a potent antagonist of CPP, and their binding naturally inhibits CPP-mediated drug cell penetration. Based on this method, we developed a heparin-regulated macromolecular prodrug-type system, termed ATTEMPTS, for drug targeting delivery. In this review article, we mainly summary the application of ATTEMPTS in delivery of various macromolecular drugs for cancer therapy, and also introduce the heparin-regulated nanoprobes for tumor imaging.


Diet composition and body mass index in Tehranian adults.
Human studies investigating the relationship between macronutrients intake and obesity, have failed to achieve consistent findings. This study was undertaken to assess the relationship between macronutrients intake and body mass index in a group of Tehranians. From 15,005 participants of the Tehran Lipid and Glucose Study, 1290 subjects aged over 10 years (565 males and 725 females) were selected randomly for dietary survey. Anthropometric indices were measured according to standard protocols and BMI was calculated. Dietary data were collected by trained interviewers using two non-consecutive 24-hour dietary recalls. Data on smoking habits, educational level and physical activity were compiled. Under- and over-reporting of energy intake were defined as EI: BMR < 1.35 and > or = 2.4, respectively. Calorie-adjusted amounts of macronutrients were calculated by the residual method, following which energy intakes from all calorie-adjusted macronutrients were simultaneously included in the multiple regression models controlling for age, physical activity, educational level and smoking and mutual effects of macronutrients. Total energy intake was not included to avoid collinearity. BMI increased with age in either gender. Controlling for confounding variables, energy intake from fat was positively associated with BMI in males in the 10-18, 19-24, 25-50 and 51+ year age categories (beta = 0.06, 0.13, 0.33, 0.48, P<0.05 for all, respectively) and females in the 19-24, 25-50 and 51+ age categories (beta = 0.17, 0.43, 0.52, P<0.05 for all, respectively). This relationship remained after excluding misreporters (beta = 0.06, 0.15, 0.36, 0.50 for males and beta = 0.21, 0.46, 0.54 for females in the corresponding age categories, respectively). The correlation of fat intake to BMI was not significant in younger females (10-18 year). No association was seen between energy intake from protein and carbohydrate with BMI in subjects before and after exclusion of misreporters. In conclusion, energy from fat was found to be independently and positively associated with obesity in adults. No other association was observed between energy from protein and carbohydrate with BMI.


Blending administrative and community organization practice: the case of community residential facilities.
The authors discuss the management of community programs serving deinstitutionalized populations. They make a case for the concept of "community integration" (re-entry into society), arguing that translating the concept into meaningful practice requires clearer specification of the relevant client communities and calls for a blending of traditional administrative and community organizations skills, with resultant implications for social work education. Illustrations are drawn from the field of mental health and the needs of the chronically mentally ill.


Enhanced Low-Temperature Thermoelectric Performance in (PbSe)1+δ(VSe2)1 Heterostructures due to Highly Correlated Electrons in Charge Density Waves.
We explore the effect of charge density wave (CDW) on the in-plane thermoelectric transport properties of (PbSe)1+δ(VSe2)1 and (PbSe)1+δ(VSe2)2 heterostructures. In (PbSe)1+δ(VSe2)1 we observe an abrupt 86% increase in the Seebeck coefficient, 245% increase in the power factor, and a slight decrease in resistivity over the CDW transition. This behavior is not observed in (PbSe)1+δ(VSe2)2 and is rather unusual compared to the general trend observed in other materials. The abrupt transition causes a deviation from the Mott relationship through correlated electron states. Raman spectra of the (PbSe)1+δ(VSe2)1 material show the emergence of additional peaks below the CDW transition temperature associated with VSe2 material. Temperature-dependent in-plane X-ray diffraction (XRD) spectra show a change in the in-plane thermal expansion of VSe2 in (PbSe)1+δ(VSe2)1 due to lattice distortion. The increase in the power factor and decrease in the resistivity due to CDW suggest a potential mechanism for enhancing the thermoelectric performance at the low temperature region.


Genome-Wide Analysis of the Apple CBL Family Reveals That Mdcbl10.1 Functions Positively in Modulating Apple Salt Tolerance.
Abiotic stresses are increasingly harmful to crop yield and quality. Calcium and its signaling pathway play an important role in modulating plant stress tolerance. As specific Ca2+ sensors, calcineurin B-like (CBL) proteins play vital roles in plant stress response and calcium signaling. The CBL family has been identified in many plant species; however, the characterization of the CBL family and the functional study of apple MdCBL proteins in salt response have yet to be conducted in apple. In this study, 11 MdCBL genes were identified from the apple genome. The coding sequences of these MdCBL genes were cloned, and the gene structure and conserved motifs were analyzed in detail. The phylogenetic analysis indicated that these MdCBL proteins could be divided into four groups. The functional identification in Na+-sensitive yeast mutant showed that the overexpression of seven MdCBL genes could confer enhanced salt stress resistance in transgenic yeast. The function of MdCBL10.1 in regulating salt tolerance was also verified in cisgenic apple calli and apple plants. These results provided valuable insights for future research examining the function and mechanism of CBL proteins in regulating apple salt tolerance.


Multiple nodules of intermediate trophoblast following hydatidiform moles.
After removal of a complete hydatidiform mole, seven patients developed an unusual complication characterized by a proliferation of intermediate trophoblast-forming nodules in the endometrium or myometrium. The patients were examined because of vaginal bleeding or mildly elevated human chorionic gonadotrophin (HCG) titers. Three patients were cured by hysterectomy, one by endometrial curettage, one by endometrial curettage plus chemotherapy, and one (who also had choriocarcinoma) by multiple doses of chemotherapy after hysterectomy; the seventh patient was lost to follow-up. These nodules probably represent a mild form of postmolar trophoblastic disease.