Visual-perceptual impairment in a random sample of children with cerebral palsy.
Several studies have tried to establish the prevalence of visual-perceptual impairment in children with physical disabilities, particularly in those with cerebral palsy (CP), but failed to take into account the selective impairment of non-verbal intelligence that is frequent in these children. This has resulted in the confounding of visual-perceptual and non-verbal intelligence impairment. In the present study we aimed to determine how widespread visual-perceptual impairment is in children with CP by evaluating perceptual ability together with the performance level on non-verbal intelligence subtests. All children (n=96; 44 females, 52 males) who attended an institute for children with physical disabilities were included (age ranged from 4 years 11 months to 21 years 5 months) who had a non-verbal mental age between 3 and 7 years; Total IQ was <85 in 91% of participants. They were given a grating acuity task and the visual-perceptual battery L94, comprising six visual object recognition and two visuoconstruction tasks. Relative to their performance level on non-verbal intelligence subtests, 37.5% of the children were impaired on at least one task, and 18.7% on two or more tasks. No child was impaired on the visuoconstruction tasks. Visual-perceptual impairment was highest among six children with brain malformation (67%), followed by spastic CP (40%), and brain damage acquired after the first year of life (38%). There was no difference in visual-perceptual impairment between the subtypes of spastic CP. Results are not secondary to visual acuity deficits, as only one L94 task was significantly correlated with acuity impairment. We conclude that visual-perceptual impairment is frequent in children with physical disabilities, and not restricted to children with CP of hypoxic-ischaemic origin.


Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease.
The pathogenic mechanism of homocysteine's effect on cardiovascular risk is poorly understood. Recent studies show that DNA hypomethylation induced by increases in S-adenosylhomocysteine (AdoHcy), an intermediate of Hcy metabolism and a potent inhibitor of methyltransferases, may be involved in homocysteine-related pathology. We measured fasting plasma total Hcy (tHcy), AdoHcy, and S-adenosylmethionine (AdoMet) and methylation in leukocytes in 17 patients with vascular disease and in 15 healthy, age- and sex-matched controls. Patient with vascular disease had significantly higher plasma tHcy and AdoHcy concentrations and significantly lower plasma AdoMet/AdoHcy ratios and genomic DNA methylation. AdoMet concentrations were not significantly different between the two groups. More than 50% of the patients fell into the highest quartiles of plasma tHcy, AdoHcy, and [(3)H]dCTP incorporation/ micro g of DNA (meaning the lowest quartile of DNA methylation status) and into the lowest quartile of the AdoMet/AdoHcy ratios of the control group. Plasma tHcy was significantly correlated with plasma AdoHcy and AdoMet/AdoHcy ratios (n = 32; P < 0.001). DNA methylation status was significantly correlated with plasma tHcy and AdoHcy (n = 32; P < 0.01) but not with plasma AdoMet/AdoHcy ratios. Global DNA methylation may be altered in vascular disease, with a concomitant increase in plasma tHcy and AdoHcy.


Localization of mRNA for fatty acid transport protein in developing and mature brain of rats.
Gene expression for rat fatty acid transport protein (FATP) and fatty acid translocase (FAT) were examined by Northern and in situ hybridization analysis. In Northern blot analysis of developing brain, FATP mRNA was detected weakly throughout all developing stages without any changes in the expression level, while no gene expression for FAT mRNA was detected at any stages. By in situ hybridization histochemistry, intense expression was seen in the ventricular germinal zone on pre- and perinatal stages, whereas distinct expression was observed in the cerebellar Purkinje and granule cell during postpostnatal development. No expression was detected in the cerebellar external granule cell layer. Because of the high expression of FATP mRNA in the embryonic ventricular zone and the postnatal cerebellar cortical neurons in parallel to the gene expression for fatty acid binding protein (FABP) which we have recently reported, co-operated involvement of FATP and FABP in the active uptake of long-chain fatty acids is plausible in these cells.


Genome Editing in Zebrafish by ScCas9 Recognizing NNG PAM.
The CRISPR/Cas9 system has been widely used for gene editing in zebrafish. However, the required NGG protospacer adjacent motif (PAM) of Streptococcus pyogenes Cas9 (SpCas9) notably restricts the editable range of the zebrafish genome. Recently, Cas9 from S. canis (ScCas9), which has a more relaxed 5'-NNG-3' PAM, was reported to have activities in human cells and plants. However, the editing ability of ScCas9 has not been tested in zebrafish. Here we characterized and optimized the activity of ScCas9 in zebrafish. Delivered as a ribonucleoprotein complex, ScCas9 can induce mutations in zebrafish. Using the synthetic modified crRNA:tracrRNA duplex instead of in vitro-transcribed single guide RNA, the low activity at some loci were dramatically improved in zebrafish. As far as we know, our work is the first report on the evaluation of ScCas9 in animals. Our work optimized ScCas9 as a new nuclease for targeting relaxed NNG PAMs for zebrafish genome editing, which will further improve genome editing in zebrafish.


A case-control study of the effectiveness of BCG vaccine for preventing leprosy in Yangon, Myanmar.
Five randomized trials, a follow-up study, and six case-control investigations of BCG vaccine's effectiveness (VE) for preventing leprosy have been conducted internationally, with widely varying estimates of VE. Because of the difficulty of generalizing from disparate results, local estimates of VE are needed for health planning purposes and are currently particularly relevant, given the World Health Organization's (WHO) goal to eliminate leprosy by the year 2000. We conducted a case-control study in Yangon, Myanmar. Residents of Yangon between the ages of 6 years and 24 years who were listed in the National Leprosy Registry as being on active treatment for leprosy between December 1992 and April 1993 were eligible to participate in the study as cases. Control subjects were matched to the cases on age, sex, and neighbourhood. One or more doses of BCG were associated with a VE of 66%. The results show a significant trend of increasing VE with increasing number of BCG doses (one dose, VE = 55%; two doses, VE = 68%; three doses, VE = 87%). One dose of BCG vaccine appeared to provide protection substantially higher than that found in an earlier vaccine trial in Myanmar, but consistent with results from case-control studies in other countries. These data suggest that BCG reduces the risk of leprosy in Myanmar, and that BCG vaccination of infants, along with early case-finding and treatment, should be considered an important part of the leprosy intervention strategy.


The molecular basis of lactose intolerance.
A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.


Gradient band gap engineered alloyed quaternary/ternary CdZnSeS/ZnSeS quantum dots: an ultrasensitive fluorescence reporter in a conjugated molecular beacon system for the biosensing of influenza virus RNA.
Controlling and engineering the particle composition of semiconductor alloys is one of the topmost targets in the field of semiconductor materials science and technology. Quantum dot (QD) nanocrystals offer an unmatched opportunity to obtain a wide range of composition-controlled alloys and have captivated a great deal of interest recently. Herein, we report on band gap engineering via tuning and controlling the sulphur molar fraction (ternary shell layer) of quaternary/ternary core/shell alloyed CdZnSeS/ZnSeS QDs. Varying optical properties were exhibited by the alloyed QDs but a uniform particle size distribution was maintained across all the compositions. The alloyed QDs displayed bright emission colours under UV irradiation, whereas the photoluminescence quantum yields (PL QY) were in a remarkable range of 36-98%. Non-linearity of the lattice parameter was an indication of gradient alloying of the nanocrystals, whereas the kinetics of the optical properties unravelled the effect of intrinsic optical bowing. Displacement of bond length and anion mismatch influenced the optical properties of the QDs with respect to the variation in the PL QY. Alloyed CdZnSeS/ZnSe1.0S1.3 QDs with a spectacular PL QY were exploited as an ultrasensitive fluorescence reporter in a conjugated molecular beacon (MB) assay to detect influenza virus H1N1 RNA. Our detection system was rapid and highly sensitive for detecting extremely low concentrations of H1N1 RNA (down to 2 copies per mL), specific and versatile (detects H1N1 RNA in human serum). For proof of concept, the alloyed CdZnSeS/ZnSe1.0S1.3 QD-MB bioprobe exhibited a superior 12-fold sensitivity over an alloyed CdZnSeS-MB probe, while a conventional CdSe/ZnS-MB probe could not detect extremely low concentrations of influenza virus H1N1 RNA.


Influence of apolipoprotein E epsilon4 genotype on brain tissue integrity in relapsing-remitting multiple sclerosis.
Recent clinical and imaging studies have raised the hypothesis that patients with multiple sclerosis (MS) and the apolipoprotein E (ApoE) epsilon4 allele may have a more severe disease course than those without the ApoE epsilon4 allele. This seems to be related to more extensive tissue destruction and less efficient neuronal maintenance and repair in ApoE epsilon4 carriers. To evaluate the influence of different ApoE genotypes on brain tissue integrity in patients with relapsing-remitting MS (RRMS). We determined the ApoE genotype in 76 RRMS patients. Conventional T1-, T2-, and proton density-weighted magnetic resonance (MR) images were obtained for each patient and in a group of demographically matched healthy control subjects. On conventional T1-weighted MR images, an automated analysis tool was used to obtain total brain volumes normalized for head size (NBVs). Total brain lesion load was estimated on proton density- and T2-weighted MR images. From the whole group of RRMS patients, we identified 18 with and 58 without the epsilon4 allele. Both patient groups were not significantly different in age, age of disease onset, clinical disability, and disease duration. Carriers of the epsilon4 allele showed significantly (P =.01) lower NBVs than controls and non-epsilon4 allele carriers. When a similar analysis was performed on only those patients with both very short disease duration and absence of clinical disability, NBV values were still significantly lower in RRMS patients with the epsilon4 allele than in those without it (P =.02) and in controls (P =.007). In contrast, RRMS patients with different ApoE genotypes did not show significant differences in values of total brain T2-weighted lesion volumes. The presence of significant NBV decreases only in the group of RRMS patients with the ApoE epsilon4 genotype provides new evidence that links ApoE epsilon4-related impaired mechanisms of cell repair and severe tissue destruction in MS. Results of the present study suggest that this negative influence of the ApoE epsilon4 genotype might be active from the earliest disease stages.


Influence of Shared Decision Making on Decisional Conflict and Regret in Postpartum Mother-Infant Care: A Randomized Controlled Trial.
Although postpartum rooming-in is encouraged by the World Health Organization, independent separated nursery care is still widely adopted in Eastern countries. Our aim is to evaluate the effect of shared decision making (SDM) assisted by patient decision aids on subjective decisional conflict and regret among women who are required to make choices regarding postpartum infant care. A total of 196 pregnant women who came for routine checkups 1 month before delivery were randomly assigned to the SDM group or the classic group. Before the mothers were discharged after delivery, their decision-making difficulties were evaluated. The primary outcome was the decisional conflict, which was assessed using the SURE (Sure of myself; Understand information; Risk-benefit ratio; Encouragement) scale. The secondary outcome was the decisional regret, which was measured using the Decision Regret scale. Compared with the classic group, SDM group had surer feelings about the choice (P<.001), felt more confident about knowing the benefits and risks of each option (P<.001), had a clearer understanding of the benefits and risks (P<.001), and felt sufficiently supported with enough advice to make a suitable choice (P<.001). No significant difference was noted in the Decision Regret scores between groups. The choice of 24-hour rooming-in, 12-hour rooming-in, and separated nursery care was not significantly different between groups. SDM reduced the decisional conflict and uncertainty of the mothers. Available choices of postpartum mother-infant care should be provided to mothers through SDM that includes individual values, health goals, and clear knowledge and transparency.


Design and manufacture of combinatorial calcium phosphate bone scaffolds.
It is well known that pore design is an important determinant of both the quantity and distribution of regenerated bone in artificial bone tissue scaffolds. A requisite feature is that scaffolds must contain pore interconnections on the order of 100-1000 μm (termed macroporosity). Within this range, there is not a definitive optimal interconnection size. Recent results suggest that pore interconnections permeating the scaffold build material on the order of 2-20 μm (termed microporosity) drive bone growth into the macropore space at a faster rate and also provide a new space for bone growth, proliferating throughout the interconnected microporous network. The effects of microstructural features on bone growth has yet to be fully understood. This work presents the manufacture and characterization of novel combinatorial test scaffolds, scaffolds that test multiple microporosity and macroporosity designs within a single scaffold. Scaffolds such as this can efficiently evaluate multiple mechanical designs, with the advantage of having the designs colocated within a single defect site and therefore less susceptible to experimental variation. This paper provides the manufacturing platform, manufacturing control method, and demonstrates the manufacturing capabilities with three representative scaffolds.


Salvage Options for the Failed Total Knee Arthroplasty.
Total knee arthroplasty (TKA) is one of the most popular and successful procedures of the past century. However, as the number of TKAs continues to increase, the volume of revision surgeries also will increase. Although revision TKAs are often successful, adult reconstruction surgeons will likely continue to see patients with limited arthroplasty options after multiple failed revision TKAs. This raises the question of limb salvage versus transfemoral amputation as the final procedure option. It is important to review modern techniques for the patient who has undergone multiple revision TKAs with significant bone loss or chronic infection. These techniques include distal femur replacement, total femur arthroplasty, knee arthrodesis, and transfemoral amputation.


A multi-institutional, observational study of outcomes after catheter placement for peritoneal dialysis in Japan.
This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications. Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest. Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines. PD catheter placement in Japan was proven to be safe and appropriate.


[Optic disk drusen].
Optic disk drusen (ODD) is a much more prevalent condition than it is usually considered. It is important to recognize ODD in order to escape serious neurosurgical interventions and rule out the development of optic neuropathy leading to grave visual dysfunction. Three cases with ODD are described. The authors conclude that it is an acquired disease, which can be bi- and unilateral. Initial diagnosis "suspected congestive optic disk of both eyes" was erroneous in all cases and it was replaced by "pseudocongestion" because of ODD. A characteristic symptom of ODD is narrowing of visual field borders and presence of scotomas in the lower half of central visual field. Since ODD are a manifestation of progressive optic neuropathy leading to disorders in the central visual field, dedystrophic and (if necessary) ophthalmo-hypotensive therapy is to be carried out.


Extensive spatial genetic structure revealed by AFLP but not SSR molecular markers in the wind-pollinated tree, Fagus sylvatica.
Studies of fine-scale spatial genetic structure (SGS) in wind-pollinated trees have shown that SGS is generally weak and extends over relatively short distances (less than 30-40 m) from individual trees. However, recent simulations have shown that detection of SGS is heavily dependent on both the choice of molecular markers and the strategy used to sample the studied population. Published studies may not always have used sufficient markers and/or individuals for the accurate estimation of SGS. To assess the extent of SGS within a population of the wind-pollinated tree Fagus sylvatica, we genotyped 200 trees at six microsatellite or simple sequence repeat (SSR) loci and 250 amplified fragment length polymorphisms (AFLP) and conducted spatial analyses of pairwise kinship coefficients. We re-sampled our data set over individuals and over loci to determine the effect of reducing the sample size and number of loci used for SGS estimation. We found that SGS estimated from AFLP markers extended nearly four times further than has been estimated before using other molecular markers in this species, indicating a persistent effect of restricted gene flow at small spatial scales. However, our SSR-based estimate was in agreement with other published studies. Spatial genetic structure in F. sylvatica and similar wind-pollinated trees may therefore be substantially larger than has been estimated previously. Although 100-150 AFLP loci and 150-200 individuals appear sufficient for adequately estimating SGS in our analysis, 150-200 individuals and six SSR loci may still be too few to provide a good estimation of SGS in this species.


Inhaled nedocromil sodium as additional treatment to high dose inhaled corticosteroids in the management of bronchial asthma.
Thirty five asthmatic patients were included in a randomized, double-blind, placebo-controlled, parallel group study of inhaled nedocromil sodium (4 x 4 mg daily) as an additional treatment to high dose (greater than or equal to 1,000 micrograms) inhaled corticosteroids in the management of bronchial asthma. Following a four week baseline, patients received nedocromil sodium (17) or placebo treatment (18) for eight weeks. Five patients (four in the group subsequently randomized to nedocromil sodium) used short course oral corticosteroid therapy during the baseline and four placebo treated patients used oral steroid therapy during treatment. Fifteen patients (11 nedocromil sodium) reported unusual symptoms. Two nedocromil sodium treated patients were withdrawn owing to treatment taste and vomiting. Statistically significant treatment differences in favour of nedocromil sodium were seen for daytime symptoms (p = 0.03) and morning peak expiratory flow (PEF) (p = 0.012) during weeks 5-8, and for clinician opinion (p = 0.02). Patient opinion (p = 0.053) and evening PEF (p = 0.08) failed to reach statistical significance. Eight out of fifteen and three out of seventeen patients considered nedocromil sodium and placebo, respectively, to be very or moderately effective. The results indicate that the addition of nedocromil sodium (4 mg four times daily) to moderate to severe asthmatics not fully controlled on a regimen of greater than or equal to 1,000 micrograms inhaled corticosteroids and inhaled bronchodilators can produce improvements in symptoms and pulmonary function.


Aortic valve replacement in elderly women with small aortic roots: comparing sorin pericardial and St. Jude Medical mechanical valves.
After implanting 19mm and 21mm Sorin pericardial aortic valves (AVR) in 35 women over the age of 60 years, it was our clinical impression that these patients had an unduly high incidence of residual valve stenosis. A retrospective comparison of our experience with this valve and the 19mm St. Jude mechanical AVR in a similar group of 26 patients, operated during the same period (October 1987 to July 1994), was carried out. In comparison to the 19mm St. Jude valve, the 19 mm Sorin Pericardial valve was associated with significant residual stenosis in elderly women despite similar body surface areas. This prosthesis/patient mismatch was not eliminated by the use of a 21 mm Sorin pericardial valve. Although the Sorin pericardial valves was associated with a reduced incidence of thromboembolism and anticoagulation related hemorrhage, it had a significantly increased risk of permanent valve related morbidity and mortality. As a result if this experience we have discontinued our use of the Sorin pericardial valve.


[Immunochemical and molecular biological characteristics of dysentery phages].
Molecular organization of DNA of six dysentery phages was studied for their classification. The pattern of glucosilation of their DNA was determined by an immunochemical method and the test of competitive hybridization established the degree of homology of these DNA in relation to T4 phage DNA. Four of the phages (DDVI, Zonne "Gorkyi" Zonne "Czechoslovakia", Zonne "Poland") were shown to belong to the group of T-even phages by their pattern of DNA glucosilation and by their capacity to inhibit DNA T4X3H DNA T4 hybridization. According to these criteria, two other phages (Zonne "Ufa" and Zonne "Khabarovsk") do not belong to the group of T-even phages.


Attenuated hemispheric asymmetry in metaphor processing among adults with ADHD.
To characterize the hemispheric processing of metaphors in adults with ADHD compared to controls. We investigated the hemispheric processing of metaphors in 24 adult participants diagnosed with ADHD and 24 control participants. The hemispheric processing was examined using a divided visual field paradigm, in which different kinds of metaphors as well as literal word pairs and unrelated word pairs were presented either to the right visual field/left hemisphere (RVF/LH) or to the left visual field/right hemisphere (LVF/RH). Control participants processed metaphors more efficiently when presented in the LVF/RH than when presented in the RVF/LH, whereas participants with ADHD demonstrated attenuated asymmetry of hemispheric processing. Furthermore, asymmetry of hemispheric processing, together with sustained attention, contributed significantly to the prediction of self-report of ADHD symptoms. Our results suggest that the hemispheric processing of adults with ADHD is less lateralized than the hemispheric processing of control participants. Moreover, the diminished lateralization of metaphor processing along with deficient sustained attention may reflect distinct cognitive mechanisms underlying ADHD and as such our results support multiple pathway models of ADHD. (PsycINFO Database Record


First record of second-generation facultative parthenogenesis in a vertebrate species, the whitespotted bambooshark Chiloscyllium plagiosum.
In this study, two parthenogenetic events within a family of the whitespotted bambooshark Chiloscyllium plagiosum are reported. A captive female produced multiple parthenogens. Unexpectedly, a single specimen of a total of nine parthenogens displayed external claspers characterizing the male sex in chondrichthyans. Upon dissection, internal sexual organs of this specimen were malformed or absent; however, the presence of claspers in this study challenges the as yet assumed sex determination system in this shark species. Even more remarkable was that one of the female parthenogens reproduced asexually again producing viable offspring. As far as is known, this is the first genetically confirmed evidence for second-generation facultative parthenogenesis in vertebrates. These results support the evolutionary significance of parthenogenesis as an alternative to sexual reproduction.


Assessing Integrative Psychiatry Curriculum Needs.
Research on incorporating integrative medicine (IM) into medical training is increasing. Programs and organizations around IM have been established, but there has not previously been a needs assessment focused on integrating IM into psychiatry training. The results of a needs assessment of training directors and faculty, focused on interest and priorities for developing an IM curriculum for psychiatry training programs, are described. Psychiatry Training Directors and faculty were invited to participate in a detailed electronic survey. Areas of inquiry included (a) IM content areas to include in training; (b) IM approaches to specific medical conditions; (c) existing IM content; (d) importance, interest, and strategies for IM training; and (e) availability of wellness programs for trainees. Thirty-six respondents from psychiatry training programs completed the survey. Of the training programs represented by the respondents, 50% indicated that they currently had IM content in their curriculum; only 11.8% of them rated their programs' existing IM content as sufficient. Content areas rated most highly for inclusion in a psychiatry IM curriculum included sleep health, motivational interviewing, and self-care. Respondents indicated incorporating IM into the psychiatry training curriculum (47%) or as an elective (44%) as the desired implementation strategy, with experiential onsite activities demonstrating IM topics (67%) and online modules supplemented by local faculty (58%) as the 2 most desirable learning formats. Significant barriers identified were time constraints, lack of faculty expertise in IM, current lack of curricular requirements for IM competencies, and budgetary limitations. Responses to the survey suggest that faculty need support and additional education in implementing IM training. A standardized, online curriculum could help meet that need. Our results also indicate that wellness programs for residents are currently inadequate; bolstering them could help address burnout and increase the knowledge psychiatrists have of IM modalities. The types of institutions represented by faculty interested in further developing IM offerings vary considerably, as do their current efforts to integrate IM into training programs.


Phase transitions in nanostructured water confined in carbon nanotubes by external electric and magnetic fields: a molecular dynamics investigation.
Applying electric and magnetic fields on water molecules confined in carbon nanotubes (CNTs) has important applications in cell biology and nanotechnology-based fields. In this work, molecular dynamics (MD) simulations were carried out to examine the probable phase transitions in confined water molecules confined in (14,0) CNTs at 300 K by applying different electric and magnetic fields in the axial direction. We have also studied some thermodynamics and structural properties of the confined water molecules in the different fields. Our results showed that the confined water molecules experience. Some phase (shape) transitions from the pentagonal to twisted pentagonal, spiral and circle-like shapes by increasing the electric field from 104 (V m-1) to 107 (V m-1). Also, applying the magnetic field with different intensities has small effects on the pentagonal shape of confined water molecules but applying the highest magnetic field (300 T) makes the pentagonal shape more ordered. These phase transitions have not been reported before. Our results also indicated that the ring-like shapes obtained in the presence of the electric field form more hydrogen bonds (HBs) than the other structures. The phase transitions of confined water molecules have been also proved by radial distribution function (RDF) and angle distribution function (ADF) analyses.


Zinc in Cellular Regulation: The Nature and Significance of "Zinc Signals".
In the last decade, we witnessed discoveries that established Zn2+ as a second major signalling metal ion in the transmission of information within cells and in communication between cells. Together with Ca2+ and Mg2+, Zn2+ covers biological regulation with redox-inert metal ions over many orders of magnitude in concentrations. The regulatory functions of zinc ions, together with their functions as a cofactor in about three thousand zinc metalloproteins, impact virtually all aspects of cell biology. This article attempts to define the regulatory functions of zinc ions, and focuses on the nature of zinc signals and zinc signalling in pathways where zinc ions are either extracellular stimuli or intracellular messengers. These pathways interact with Ca2+, redox, and phosphorylation signalling. The regulatory functions of zinc require a complex system of precise homeostatic control for transients, subcellular distribution and traffic, organellar homeostasis, and vesicular storage and exocytosis of zinc ions.


Impact of Helicobacter pylori on the clinical course of recurrent aphthous stomatitis.
Recurrent aphthous stomatitis is one of the most common lesions of oral mucosa. Helicobacter pylori is suggested as one of the etiological agents of recurrent aphthous stomatitis. Here, we conduct a study for evaluating the impact of H. pylori eradication on clinical course of recurrent aphthous stomatitis. Forty-six patients with minor aphthous lesions were enrolled. The number of RAS lesions at last 6 months and vitamin B(12) levels were recorded. All patients were detected for H. pylori with endoscopic biopsy. H. pylori was positive in 30 patients and negative in 16 patients. H. pylori-positive 30 patients received eradication therapy. Three months after therapy, patients were re-evaluated with urea breath test; 18 patients were negative (eradicated), and the remainders (12 patients) were positive (non-eradicated) for H. pylori. 6 months after eradication, vitamin B(12) levels and number of aphthous lesions at 6 months were recorded. Vitamin B(12) levels were significantly increased in H. pylori-eradicated group (P = 0.001), whereas no significant change was found in non-eradicated group (P = 0.638). Mean number of aphthous lesions (per 6 months) of H. pylori-eradicated group was significantly decreased after eradication (P = 0.0001); in the non-eradicated group, no significant change was found (P = 0.677). In Hp-positive group, number of RAS lesions and vitamin B(12) levels were negatively correlated when evaluated both before and after eradication. This study provides evidence to support the beneficial effect of H. pylori eradication in patients with recurrent aphthous stomatitis. The underlying mechanism might be the increase in vitamin B(12) levels after eradication.


Nanostructured chromium-based broadband absorbers and emitters to realize thermally stable solar thermophotovoltaic systems.
The efficiency of traditional solar cells is constrained due to the Shockley-Queisser limit, to circumvent this theoretical limit, the concept of solar thermophotovoltaics (STPVs) has been introduced. The typical design of an STPV system consists of a wideband absorber with its front side facing the sun. The back of this absorber is physically attached to the back of a selective emitter facing a low-bandgap photovoltaic (PV) cell. We demonstrate an STPV system consisting of a wideband absorber and emitter pair achieving a high absorptance of solar radiation within the range of 400-1500 nm (covering the visible and infrared regions), whereas the emitter achieves an emittance of >95% at a wavelength of 2.3 μm. This wavelength corresponds to the bandgap energy of InGaAsSb (0.54 eV), which is the targeted PV cell technology for our STPV system design. The material used for both the absorber and the emitter is chromium due to its high melting temperature of 2200 K. An absorber and emitter pair is also fabricated and the measured results are in agreement with the simulated results. The design achieves an overall solar-to-electrical simulated efficiency of 21% at a moderate temperature of 1573 K with a solar concentration of 3000 suns. Furthermore, an efficiency of 15% can be achieved at a low temperature of 873 K with a solar concentration of 500 suns. The designs are also insensitive to polarization and show negligible degradation in solar absorptance and thermal emittance with a change in the angle of incidence.


Single-Arm Non-Blinded Multicenter Clinical Trial on T-Cell-Replete Haploidentical Stem Cell Transplantation Using Low-Dose Antithymocyte Globulin for Relapsed and Refractory Pediatric Acute Leukemia.
Although approximately 70% of pediatric hematological malignancies are curable, approximately 30% remain fatal. No standard treatment is available in patients showing relapse and those with refractory disease. Although different methods are adopted in different hospitals, its efficacy is extremely limited. In recent years, haploidentical stem cell transplantation, involving high-dose cyclophosphamide administration post-transplanta tion, has been used, mainly in adults; however, its application is limited to removal of alloreactive T cells. Multicenter single-arm clinical trials of T-cell replete haploidentical stem cell transplantation (TCR-haplo-SCT) will be conducted in children with relapsed and refractory acute leukemia. After myeloablative conditioning using total body irradiation or busulfan, intensive graft versus host disease prophylaxis is administered, consisting of low-dose rabbit anti-human thymocyte globulin, tacrolimus, methotrexate, and prednisolone. An external control group is set up for the study. The treatment period is around 3 months, and the follow-up period is 2 years from transplantation completion.The aim of this study is to verify the efficacy and safety of TCR-haplo-SCT and present it as a new immune cell therapy for improving survival rate in children with relapsed and refractory acute leukemia.


Rapid and high-throughput colorimetric screening for anti-aggregation reagents of protein conformational diseases by using gold nanoplasmonic particles.
Cellular deposition of destabilized proteins and their aggregates is considered one of the most indisputable factors implicated in protein conformational diseases. Here, we report an innovative high-throughput screening method for discovering anti-aggregation reagents out of numerous potential candidates by using gold nanoplasmonic particles. In our method, nanoparticles act as catalytic activators to accelerate protein aggregation and simultaneously exhibit a colorimetric response according to their embedded shape on the protein aggregates. Using this principle, we observed the colorimetric response to the anti-aggregation effect of amyloid β (Aβ) with the naked eye within a few minutes. Investigation of the anti-aggregation effects of select candidates under three different protein aggregation stages showed that the anti-aggregation efficiency could relate to disease progression. Finally, results obtained with spiked samples in cerebrospinal fluid as well as under various denaturation conditions and different Aβ compositions show the feasibility of future personalized medicine considering individual patient's disease progression.


A Multimodal Imaging Protocol, (123)I/(99)Tc-Sestamibi, SPECT, and SPECT/CT, in Primary Hyperparathyroidism Adds Limited Benefit for Preoperative Localization.
Focused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown. Patients with 1°HPT, who underwent parathyroidectomy in 2012-2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of (123)I/(99)Tc-sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed. Of 360 patients who were identified, a curative operation was performed in 96%, using pre-operative imaging and IOPTH. Imaging analysis showed that (123)I/(99)Tc-sestamibi had a sensitivity of 86% (95% CI 82-90%), positive predictive value (PPV) 93%, and accuracy 81%, based on correct lateralization. SPECT had a sensitivity of 77% (95% CI 72-82%), PPV 92% and accuracy 72%. SPECT/CT had a sensitivity of 75% (95% CI 70-80%), PPV of 94%, and accuracy 71%. There were 3 of 45 (7%) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87%) with positive uptake on sestamibi (93% true positive, 7% false positive), concordant findings were present in 86% SPECT and 84% SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true-positive, (123)I/(99)Tc-sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4-fold. (123)I/(99)Tc-sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with (123)I/(99)Tc-sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high-volume setting.


Congenital adrenal hyperplasia clinical characteristics and genotype in newborn, childhood and adolescence.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder which can adopt three clinical expressions: two classical forms -salt-wasting (SW), with residual enzymatic activity (EA) < or = 1% and simple virilizing (SV), with EA 1-2%- and a mild late onset or nonclassical (NC) form, with EA 10-60%. Our objective is to describe clinical characteristics, growth, and bone mass in a group of patients affected by 21-hydroxylase deficiency. Besides, molecular genetics studies were performed in patients, and also when available in their parents and siblings. Nine patients with neonatal diagnosis and 8 with pre or postpubertal diagnosis were studied. Analyses of 10-point mutations in the CYP21A2 gene were performed. We found that all the patients with the classical expression, except one with a de novo mutation R356W in one allele, were fully genotyped with predictive < 2% EA mutations. Signs of hyperandrogenism were present in 5/6 NC patients; one was diagnosed by searching for mutations in asymptomatic siblings. All the NC patients were compound heterozygotes carrying V281L mutation in one allele and a predictive low EA in the other, except for one not yet determined. In patients with neonatal diagnosis, mean height was low at one year of age, though it showed a significant increase before the onset of puberty. We conclude that neonatal diagnosis of classical CAH allows an adequate follow up enhancing growth. Molecular analyses of all members of an affected family may disclose asymptomatic patients. The presence of de novo mutations, as well as, the presence of mutations with low predicted EA in NC patients reinforces the importance of genotyping for appropriate genetic counseling. In fully genotyped NC patients, the lowest value of ACTH-stimulated 17OHP was 14 ng/ml. Lower cut-off values might overestimate the diagnosis of the NC form.


Cryptococcosis: a diagnostic challenge.
Human cryptococcosis is an exogenous human infection of increasing frequency and growing importance. Early diagnosis is essential for the clinical outcome, no matter whether the infection is primary or secondary to underlying disease. Reliable and quick diagnostic methods are outlined and some pitfalls are discussed. Direct microscopy is essential, followed by cultivation procedures and serologic tests.


Knee Injury and Osteoarthritis Outcome Score (KOOS): systematic review and meta-analysis of measurement properties.
To conduct a systematic review and meta-analysis to synthesize evidence regarding measurement properties of the Knee injury and Osteoarthritis Outcome Score (KOOS). A comprehensive literature search identified 37 eligible papers evaluating KOOS measurement properties in participants with knee injuries and/or osteoarthritis (OA). Methodological quality was evaluated using the COSMIN checklist. Where possible, meta-analysis of extracted data was conducted for all studies and stratified by age and knee condition; otherwise narrative synthesis was performed. KOOS has adequate internal consistency, test-retest reliability and construct validity in young and old adults with knee injuries and/or OA. The ADL subscale has better content validity for older patients and Sport/Rec for younger patients with knee injuries, while the Pain subscale is more relevant for painful knee conditions. The five-factor structure of the original KOOS is unclear. There is some evidence that the KOOS subscales demonstrate sufficient unidimensionality, but this requires confirmation. Although measurement error requires further evaluation, the minimal detectable change for KOOS subscales ranges from 14.3 to 19.6 for younger individuals, and ≥20 for older individuals. Evidence of responsiveness comes from larger effect sizes following surgical (especially total knee replacement) than non-surgical interventions. KOOS demonstrates adequate content validity, internal consistency, test-retest reliability, construct validity and responsiveness for age- and condition-relevant subscales. Structural validity, cross-cultural validity and measurement error require further evaluation, as well as construct validity of KOOS Physical function Short form. Suggested order of subscales for different knee conditions can be applied in hierarchical testing of endpoints in clinical trials. PROSPERO (CRD42011001603).


Uncoupling Sae2 Functions in Downregulation of Tel1 and Rad53 Signaling Activities.
The Mre11-Rad50-Xrs2 (MRX) complex acts together with the Sae2 protein to initiate resection of DNA double-strand breaks (DSBs) and to regulate a checkpoint response that couples cell cycle progression with DSB repair. Sae2 supports resistance to DNA damage and downregulates the signaling activities of MRX, Tel1, and Rad53 checkpoint proteins at the sites of damage. How these functions are connected to each other is not known. Here, we describe the separation-of-function sae2-ms mutant that, similar to SAE2 deletion, upregulates MRX and Tel1 signaling activities at DSBs by reducing Mre11 endonuclease activity. However, unlike SAE2 deletion, Sae2-ms causes neither DNA damage sensitivity nor enhanced Rad53 activation, indicating that DNA damage resistance depends mainly on Sae2-mediated Rad53 inhibition. The lack of Sae2, but not the presence of Sae2-ms, impairs long-range resection and increases both Rad9 accumulation at DSBs and Rad53-Rad9 interaction independently of Mre11 nuclease activity. Altogether, these data lead to a model whereby Sae2 plays distinct functions in limiting MRX-Tel1 and Rad9 abundance at DSBs, with the control on Rad9 association playing the major role in supporting DNA damage resistance and in regulating long-range resection and checkpoint activation.


A heretical view: rather than a solely placental protective function, placental 11β hydroxysteroid dehydrogenase 2 also provides substrate for fetal peripheral cortisol synthesis in obese pregnant ewes.
Exposure to glucocorticoid levels higher than appropriate for current developmental stages induces offspring metabolic dysfunction. Overfed/obese (OB) ewes and their fetuses display elevated blood cortisol, while fetal Adrenocorticotropic hormone (ACTH) remains unchanged. We hypothesized that OB pregnancies would show increased placental 11β hydroxysteroid dehydrogenase 2 (11β-HSD2) that converts maternal cortisol to fetal cortisone as it crosses the placenta and increased 11β-HSD system components responsible for peripheral tissue cortisol production, providing a mechanism for ACTH-independent increase in circulating fetal cortisol. Control ewes ate 100% National Research Council recommendations (CON) and OB ewes ate 150% CON diet from 60 days before conception until necropsy at day 135 gestation. At necropsy, maternal jugular and umbilical venous blood, fetal liver, perirenal fat, and cotyledonary tissues were harvested. Maternal plasma cortisol and fetal cortisol and cortisone were measured. Fetal liver, perirenal fat, cotyledonary 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PD), and 11β-HSD2 protein abundance were determined by Western blot. Maternal plasma cortisol, fetal plasma cortisol, and cortisone were higher in OB vs. CON (p < 0.01). 11β-HSD2 protein was greater (p < 0.05) in OB cotyledonary tissue than CON. 11β-HSD1 abundance increased (p < 0.05) in OB vs. CON fetal liver and perirenal fat. Fetal H6PD, an 11β-HSD1 cofactor, also increased (p < 0.05) in OB vs. CON perirenal fat and tended to be elevated in OB liver (p < 0.10). Our data provide evidence for increased 11β-HSD system components responsible for peripheral tissue cortisol production in fetal liver and adipose tissue, thereby providing a mechanism for an ACTH-independent increase in circulating fetal cortisol in OB fetuses.


Dietary magnesium intake in a national sample of US adults.
Despite the role of magnesium in maintaining health, much of the U.S. population has historically not consumed adequate amounts of magnesium. Furthermore, significant racial or ethnic disparities in magnesium intake exist. Our objective was to provide more recent data about magnesium intake in the U.S. population. We analyzed the 24-h dietary recall data from 4257 participants aged >or=20 y from the National Health and Nutrition Examination Survey 1999-2000. The median intake of magnesium was 326 mg/d (mean 352 mg/d) among Caucasian men, 237 mg/d (mean 278 mg/d) among African American men, 297 mg/d (330 mg/d) among Mexican American men, 237 mg/d (mean 256 mg/d) among Caucasian women, 177 mg/d (mean 202 mg/d) among African American women, and 221 mg/d (mean 242 mg/d) among Mexican American women. Among men and women, Caucasians had significantly higher mean intakes of dietary magnesium than African Americans but not Mexican Americans. Magnesium intake decreased with increasing age (P for linear trend = 0.035 for Caucasians; P for linear trend <0.001 for African Americans and Mexican Americans). Men had higher intakes of magnesium than women for each of the three race or ethnic groups (P < 0.001 in each group). Caucasian men, African American men and Caucasian women who used vitamin, mineral or dietary supplements consumed significantly more magnesium in their diets than did those who did not. Substantial numbers of U.S. adults fail to consume adequate magnesium in their diets. Furthermore, racial or ethnic differences in magnesium persist and may contribute to some health disparities.


Quantitative analysis of conjugated and free estrogens in swine manure: solutions to overcome analytical problems due to matrix effects.
Although animal manure is an important source for environmental estrogens, quantitative analysis of estrogens in manure is complicated due to matrix interference. In the present study, chromatographic methods have been developed for quantification of conjugated and free estrogens in manure samples collected from pig farms. The whole manure samples, immediately after collection, were stored at 4°C, acidified (pH≈2.0) and spiked with (i) (13)C-labeled internal standards to account for possible storage related degradation and (ii) deuterium labeled internal standards for calibration and quantitative analysis. The liquid samples were extracted with ethyl acetate for separating conjugated and free estrogens. The solid samples were eluted with water for desorbing conjugated hormones followed by methanol for desorbing free hormones. The water and extracts were further purified using hydrophilic-lipophilic balance and/or aminopropyl cartridges. The conjugated estrogens were analyzed using high-performance liquid chromatograph-mass spectrometer, while the free estrogens were analyzed using gas chromatograph-mass spectrometer. The extraction and calibration methods used in the present study yielded excellent sensitivity, reproducibility and >85% recovery of both free and conjugated estrogens that was independent of the manure matrix. In general, the total estrogen loads in liquid and solid samples were 5.1mg/l and 4.93mg/kg, respectively. This may represent the hormonal load of approximately 2.3tons estrogen per day.


Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis.
To compare the effect of donor breast milk with infant formula in preterm infants. Separate comparisons with formula were made for donor breast milk that was: (1) given as a sole diet; (2) given as a supplement to mother's own breast milk; and (3) fortified with macronutrients and micronutrients. The main outcomes were death, necrotising enterocolitis (NEC), infection, growth and development. Electronic databases-Cochrane, CENTRAL, MEDLINE, EMBASE, CINAHL, and HMIC: DH. Systematic review and meta-analysis of trials and observational studies of preterm or low birthweight infants. Seven studies (including five randomised controlled trials), all from the 1970s and 1980s, fulfilled the inclusion criteria. All studies compared the effect of sole donor breast milk with formula (combined n = 471). One of these also compared the effect of donor breast milk with formula given as a supplement to mother's own milk (n = 343). No studies examined fortified donor breast milk. A meta-analysis based on three studies found a lower risk of NEC in infants receiving donor breast milk compared with formula (combined RR 0.21, 95% CI 0.06 to 0.76). Donor breast milk was associated with slower growth in the early postnatal period, but its long-term effect is unclear. Donor breast milk is associated with a lower risk of NEC and slower growth in the early postnatal period, but the quality of the evidence is limited. Further research is needed to confirm these findings and measure the effect of fortified or supplemented donor breast milk.


Health problems and psychosocial work environment as predictors of long term sickness absence in employees who visited the occupational physician and/or general practitioner in relation to work: a prospective study.
To determine whether psychosocial work environment and indicators of health problems are prospectively related to incident long term sickness absence in employees who visited the occupational physician (OP) and/or general practitioner (GP) in relation to work. The baseline measurement (May 1998) of the Maastricht Cohort Study, a prospective cohort study among 45 companies and organisations, was used to select employees at work who indicated having visited the OP and/or GP in relation to work. Self report questionnaires were used to measure indicators of health problems (presence of at least one long term disease, likeliness of having a mental illness, fatigue) and psychosocial work environment (job demands, decision latitude, social support, job satisfaction) as predictors of subsequent sickness absence. Sickness absence data regarding total numbers of sickness absence days were obtained from the companies and occupational health services during an 18 month period (between 1 July 1998 and 31 December 1999). Complete data were available from 1271 employees. After adjustment for demographics and the other predictors, presence of at least one long term disease (OR 2.36; 95% CI 1.29 to 4.29) and lower level of decision latitude (OR 1.69; 95% CI 1.22 to 2.38) were the strongest predictors for sickness absence of at least one month. A higher likelihood of having a mental illness, a higher level of fatigue, a lower level of social support at work, and low job satisfaction were also significant predictors for long term sickness absence, but their effect was less strong. In detecting employees at work but at risk for long term sickness absence, OPs and GPs should take into account not only influence of the psychosocial work environment in general and level of decision latitude in particular, but also influence of indicators of health problems, especially in the form of long term diseases.


Simultaneous structural replacement of the sphingoid long-chain base and sterol in budding yeast.
The basic structures of membrane lipids that compose biomembranes differ among species; i.e., in mammals, the primary structure of long-chain base (LCB), the common backbone of ceramides and complex sphingolipids, is sphingosine, whereas, in yeast Saccharomyces cerevisiae, it is phytosphingosine, and S. cerevisiae does not have sphingosine. In addition, the sterol, which is coordinately involved in various functions with complex sphingolipids, is cholesterol in mammals, while in yeast it is ergosterol. Previously, it was found that yeast cells are viable when the structure of LCBs is replaced by sphingosine by supplying an exogenous LCB to cells lacking LCB biosynthesis. Here, we characterized yeast cells having sphingosine instead of phytosphingosine (sphingosine cells). Sphingosine cells exhibited a strong growth defect when biosynthesis of ceramides or complex sphingolipids was inhibited, indicating that, in the sphingosine cells, exogenously added sphingosine is required to be further metabolized. The sphingosine cells exhibited hypersensitivity to various environmental stresses and had abnormal plasma membrane and cell wall properties. Furthermore, we also established a method for simultaneous replacement of both LCB and sterol structures with those of mammals (sphingosine/cholesterol cells). The multiple stress hypersensitivity and abnormal plasma membrane and cell wall properties observed in sphingosine cells were also observed in sphingosine/cholesterol cells, suggesting that simultaneous replacement of both LCB and sterol structures with those of mammals cannot prevent these abnormal phenotypes. This is the first study to our knowledge showing that S. cerevisiae can grow even if LCB and sterol structures are simultaneously replaced with mammalian types.


A transcriptional response to Wnt protein in human embryonic carcinoma cells.
Wnt signaling is implicated in many developmental decisions, including stem cell control, as well as in cancer. There are relatively few target genes known of the Wnt pathway. We have identified target genes of Wnt signaling using microarray technology and human embryonic carcinoma cells stimulated with active Wnt protein. The ~50 genes upregulated early after Wnt addition include the previously known Wnt targets Cyclin D1, MYC, ID2 and betaTRCP. The newly identified targets, which include MSX1, MSX2, Nucleophosmin, Follistatin, TLE/Groucho, Ubc4/5E2, CBP/P300, Frizzled and REST/NRSF, have important implications for understanding the roles of Wnts in development and cancer. The protein synthesis inhibitor cycloheximide blocks induction by Wnt, consistent with a requirement for newly synthesized beta-catenin protein prior to target gene activation. The promoters of nearly all the target genes we identified have putative TCF binding sites, and we show that the TCF binding site is required for induction of Follistatin. Several of the target genes have a cooperative response to a combination of Wnt and BMP. Wnt signaling activates genes that promote stem cell fate and inhibit cellular differentiation and regulates a remarkable number of genes involved in its own signaling system.


Growth of bacteria in 3-d colonies.
The dynamics of growth of bacterial populations has been extensively studied for planktonic cells in well-agitated liquid culture, in which all cells have equal access to nutrients. In the real world, bacteria are more likely to live in physically structured habitats as colonies, within which individual cells vary in their access to nutrients. The dynamics of bacterial growth in such conditions is poorly understood, and, unlike that for liquid culture, there is not a standard broadly used mathematical model for bacterial populations growing in colonies in three dimensions (3-d). By extending the classic Monod model of resource-limited population growth to allow for spatial heterogeneity in the bacterial access to nutrients, we develop a 3-d model of colonies, in which bacteria consume diffusing nutrients in their vicinity. By following the changes in density of E. coli in liquid and embedded in glucose-limited soft agar, we evaluate the fit of this model to experimental data. The model accounts for the experimentally observed presence of a sub-exponential, diffusion-limited growth regime in colonies, which is absent in liquid cultures. The model predicts and our experiments confirm that, as a consequence of inter-colony competition for the diffusing nutrients and of cell death, there is a non-monotonic relationship between total number of colonies within the habitat and the total number of individual cells in all of these colonies. This combined theoretical-experimental study reveals that, within 3-d colonies, E. coli cells are loosely packed, and colonies produce about 2.5 times as many cells as the liquid culture from the same amount of nutrients. We verify that this is because cells in liquid culture are larger than in colonies. Our model provides a baseline description of bacterial growth in 3-d, deviations from which can be used to identify phenotypic heterogeneities and inter-cellular interactions that further contribute to the structure of bacterial communities.


Concurrent discrimination learning of monkeys after hippocampal, entorhinal, or fornix lesions.
Ablations of anterior inferotemporal cortex in monkeys are known to impair learning when discriminations between members of several pairs of objects are taught concurrently. This deficit has been attributed to a loss of visual mnemonic functions. But ablations of hippocampus have also been shown to impair retention, and this impairment transcends the visual modality. Therefore, in the first of two experiments, we compared the behavioral effects of inferotemporal cortical lesions with those of either hippocampus, entorhinal area, or fornix, using a visual concurrent discrimination task. Monkeys with either hippocampal or entorhinal ablations were impaired, while those with fornix sections were not. However, ablations of hippocampus included inadvertent damage of the inferotemporal cortex. Therefore, in the second experiment, behavioral effects of inferotemporal lesions were compared with those of hippocampus (without additional inferotemporal damage) on the concurrent task in both visual and tactual modalities. In the visual mode, monkeys with hippocampal removals were as impaired as those with inferotemporal ablations. In the tactual mode, however, hippocampal, but no inferotemporal, ablations were followed by a deficit. Our results, taken together with other existing evidence, emphasize the role of the hippocampus in mediating associative learning in more than one modality. These results, obtained with non-human primates, are in line with clinical findings.


The first framework solid composed of vanadosilicate clusters.
In this Communication, we report the first example of a network structure composed of vanadosilicate clusters. We utilized hydrothermal conditions to synthesize a polyoxovanadogermanate (POVG): (C4H14N2)4[V14O44(GeOH)8].6H2O. By substituting SiO2 for GeO2 in the synthesis, a framework solid, H4V18O46(SiO)8C4H12N2)4.(H2O)] .4H2O, is formed in which isostructural vanadosilicate clusters are linked by five-coordinate vanadium with a (VO)O2N2 environment. The charge-compensating organic amine, 1,4-diaminobutane, in the POVG is covalently bonded to the linking vanadium polyhedra in the framework solid.


Changes in ocular astigmatism with age: A longitudinal study.
To investigate changes in astigmatism with age. Are changes from with-the-rule (WTR) in younger ages to against-the-rule (ATR) in older patients mediated through oblique astigmatic axes or spherical prescriptions, and at what ages do these changes occur? Prescription data were gathered retrospectively from one optical practice belonging to a large multiple group in the UK. Longitudinal assessments were made of the changes in astigmatism for 326 patients (mean age at first prescription 46 years, range 28-69 years) and 640 eyes through their recorded prescription history (median 20 years of prescription data per participant, IQR 19-22 years, range 18-29 years). Changes in small degrees of astigmatism (0.25 or 0.50 DC) from WTR to ATR were more than three times more likely to pass through an oblique cylinder axis as through a spherical prescription (56 vs. 16, χ 1 2 = 22.2, p < 0.0001). For patients aged 28-40 years at their first recorded eye examination, 55% (92/167) of eyes had an onset of astigmatic changes at a mean of 44 years (SD 6.2) and 41% (68/167) of eyes had no change until after a mean of 54 years (SD 4.6). Compared with a measured prevalence of oblique astigmatism in the literature of 11%-19%, 36% (232/640) of the eyes in this study had an oblique cylinder prescribed at least once in their refraction history and of these oblique cylinders, 78% were transient in nature. The change in ocular astigmatism with age, from WTR to ATR, was more than three times more likely (56 vs. 16) to pass through oblique cylinder axes as through a spherical prescription. Changes in oblique astigmatism have been implicated in complaints with new spectacles, so given this prevalence of oblique cylinder axes (232/640, 36%), continuing professional development is needed regarding reconciling these oblique changes with previous prescriptions.


Mechanisms for the Risk of Acute Coronary Syndrome and Arrhythmia Associated With Phytogenic and Synthetic Cannabinoid Use.
Phytogenic cannabinoids from Cannabis sativa and synthetic cannabinoids are commonly used substances for their recreational and medicinal properties. There are increasing reports of cardiotoxicity in close temporal association with cannabinoid use in patients with structurally normal hearts and absence of coronary arterial disease. Associated adverse events include myocardial ischemia, conduction abnormalities, arrhythmias, and sudden death. This review details the effects of phytogenic and synthetic cannabinoids on diverse receptors based on evidence from in vitro, human, and animal studies to establish a molecular basis for these deleterious clinical effects. The synergism between endocannabinoid dysregulation, cannabinoid receptor, and noncannabinoid receptor binding, and impact on cellular ion flux and coronary microvascular circulation is delineated. Pharmacogenetic factors placing certain patients at higher risk for cardiotoxicity are also correlated with the diverse effects of cannabinoids.


Molecular structure of the Brucella abortus metalloprotein RicA, a Rab2-binding virulence effector.
The Gram-negative intracellular pathogen Brucella abortus is the causative agent of brucellosis, which is among the most common zoonoses globally. The B. abortus RicA protein binds the host-expressed guanosine nucleotide-binding protein, Rab2, and modulates B. abortus infection biology. We have solved the first X-ray crystal structure of RicA to 2.7 Å resolution and have quantified the affinity of RicA binding to human Rab2 in its GDP-bound and nucleotide-free forms. RicA adopts a classic γ-carbonic anhydrase (γ-CA) fold containing a left-handed β-helix followed by a C-terminal α-helix. Two homotrimers of RicA occupy the crystallographic asymmetric unit. Though no zinc was included in the purification or crystallization buffers, zinc is contained within the RicA crystals, as demonstrated by X-ray fluorescence spectroscopy. Electron density for a Zn(2+) ion coordinated by three histidine residues is evident in the putative active site of RicA. However, purified RicA preparations do not exhibit carbonic anhydrase activity, suggesting that Zn(2+) may not be the physiologically relevant metal cofactor or that RicA is not a bona fide carbonic anhydrase enzyme. Isothermal titration calorimetry (ITC) measurements of purified RicA binding to purified human Rab2 and GDP-Rab2 revealed similar equilibrium affinities (Kd ≈ 35 and 40 μM, respectively). This study thus defines RicA as a Zn(2+)-binding γ-carbonic anhydrase-like protein that binds the human membrane fusion/trafficking protein Rab2 with low micromolar affinity in vitro. These results support a model in which γ-CA family proteins may evolve unique cellular functions while retaining many of the structural hallmarks of archetypal γ-CA enzymes.


PEGylated and CD47-conjugated nanoellipsoidal artificial antigen-presenting cells minimize phagocytosis and augment anti-tumor T-cell responses.
Antigen-presenting cells (APCs) are powerful tools to expand antigen-specific T cells ex vivo and in vivo for tumor immunotherapy, but suffer from time-consuming generation and biosafety concerns raised by live cells. Alternatively, the cell-free artificial antigen-presenting cells (aAPCs) have been rapidly developed. Nanoscale aAPCs are recently proposed owing to their superior biodistribution and reduced embolism than conventional cell-sized aAPCs, but pose the challenges: easier cellular uptake and smaller contact surface area with T cells than the cell-sized counterparts. This study aimed to fabricate a new "stealth" nano-aAPCs with microscale contact surface area to minimize cellular uptake and activate antigen-specific T cells by combination uses of ellipsoidal stretch, PEGylation, and self-marker CD47-Fc conjugation. The spherical polylactic-co-glycolic acid nanoparticles were fabricated using a double-emulsion method, and then stretched twofold using film-stretching procedure followed by PEGylation and co-coupling with CD47-Fc, H-2Kb/TRP2180-188-Ig dimers, and anti-CD28. The resulting PEGylated and CD47-conjugated nanoellipsoidal aAPCs (EaAPCPEG/CD47) were co-cultured with macrophages or spleen lymphocytes and also infused into melanoma-bearing mice. The in vitro and in vivo effects were evaluated and compared with the nanospherical aAPCs (SaAPC), nanoellipsoidal aAPCs (EaAPC), or PEGylated nanoellipsoidal aAPC (EaAPCPEG). EaAPCPEG/CD47 markedly reduced cellular uptake in vitro and in vivo, as compared with EaAPCPEG, EaAPC, SaAPC, and Blank-NPs and expanded naïve TRP2180-188-specific CD8+ T cells in the co-cultures with spleen lymphocytes. After three infusions, the EaAPCPEG/CD47 showed much stronger effects on facilitating TRP2180-188-specific CD8+ T-cell proliferation, local infiltration, and tumor necrosis in the melanoma-bearing mice and on inhibiting tumor growth than the control aAPCs. The superimposed or synergistic effects of ellipsoidal stretch, PEGylation, and CD47-Fc conjugation minimized cellular uptake of nano-aAPCs and enhanced their functionality to expand antigen-specific T cells and inhibit tumor growth, thus suggesting a more valuable strategy to design "stealth" nanoscale aAPCs suitable for tumor active immunotherapy.


Multivariate optimization of dispersive liquid-liquid microextraction for the determination of paclobutrazol and triflumizole in water by GC-MS.
A new analytical method based on dispersive liquid-liquid microextraction with gas chromatography mass spectrometry has been optimized for the simultaneous determination of paclobutrazol and triflumizole in tap water and wastewater samples. A two-level, full-factorial design that allowed the study of main effects and factor interactions was applied to analyze the influence on microextraction process by chloroform, ethanol, potassium iodide and hand shaking period. The extraction conditions selected were 200 μL of chloroform, 3.0 mL of ethanol, 2.0 g of potassium iodide and 15 s of hand shaking. The limits of detection obtained for triflumizole and paclobutrazol under optimum conditions were 0.97 and 0.29 ng/mL, respectively. Calibration plots of both analytes were linear over a wide concentration range, and good precision was observed for replicate measurements. Applicability and accuracy of the method were determined by performing spiked recovery tests. Appreciable recovery results were obtained for municipal wastewater and matrix matching was used to obtain close to 100% recovery for tap water.


A study of the Va-1 group of pseudomonads and its relationship to Pseudomonas pickettii.
The Va-1 group of denitrifying pseudomonads was characterized and compared with Pseudomonas pickettii (Va-2). They share many features but differ in their production of acid from cellobiose, lactose and maltose and in their denitrification (gas from nitrate) at 35 degrees C. DNA-DNA hybridizations between a strain of Va-1 and the type strain of P. pickettii disclosed 84% homology and hence indicated that Va-1 is a biovar of this species. Since both are potential human pathogens, features are presented that distinguish these and other phenotypically similar species that are recovered from clinical specimens.


Endogenous nitric oxide in Pseudomonas fluorescens ZY2 as mediator against the combined exposure to zinc and cefradine.
A better understanding on the mechanism involved in bacterial resistance to combined exposure to antibiotics and heavy metals is helpful in implementing practices to mitigate their ecological risk and spread of resistance genes in microbial population. Pseudomonas fluorescens ZY2, a strain isolated from swine wastewater, was chosen to study its growth (bacterial density OD600), the formation of reactive oxygen species (ROS), nitric oxide (NO) and NO synthases (NOS) under Zn, cefradine or Zn + cefradine treatments. Using Zn and cefradine as representative heavy metal and antibiotic in this investigation, respectively, the resistance of P. fluorescens ZY2 to toxic chemical exposure was investigated. Bacterial densities of treatment groups significantly increased over the time of incubation, but less than the control. ROS, NO and NOS initially increased, but then decreased after the initial 8 h of culturing, and were positively related to Zn concentrations. Moreover, the formation of ROS, NOS, and NO was activated by cefradine at Zn of up to 160 mg/L, but inhibited at Zn of 200 mg/L whether cefradine was added or not. Zn concentration affected ROS and NO concentrations between treatments and also was closely related to the variation of the relative bacterial density. For P. fluorescens ZY2, the mediation of endogenous NO to overcome ROS in response to the combined exposure of Zn and cefradine was suggested as a co-resistance mechanism, which would be beneficial to evaluate the ecological risk of heavy metals and antibiotics.


Expression of SR-BI and LXRα in Macrophage Origin Foam Cells of Mouse RAW264.7 Up-regulated by Astragalus Polysaccharide.
To investigate the influences of Astragalus polysaccharides (APS) on the expressions of SR-BI(Scavenger receptor-BI) and LXR α in RAW264.7 macrophage origin foam cells. Mouse RAW264.7 cells were induced in foam cells and identification of the foamed by oil-red O staining. The RAW264.7 macrophage origin foam cells were dealt with APS with distinct contents (0, 10, 20, 50, or 100 mg/L). The mRNA and protein expressions of SR-BI and LXRα were measured by RT-PCR as well as ELISA, respectively. Macrophages were differentiated into foam cells 48 h after ox-LDL induction. In contrast to the control part, the mRNA and protein expressions of SR-BI and LXRα in RAW264.7 macrophage origin foam cells were up-regulated dosage-dependently after being treated with different concentrations of APS (P < 0.05). APS could promote intracellular cholesterol efflux by up-regulating the expressions of SR-BI and LXR α of RAW264.7 cells.


A proteolytic nanobiocatalyst with built-in disulphide reducing properties.
We report a method to equip proteolytic nanobiocatalysts with intrinsic disulphide bond reducing properties. After immobilisation onto silica particles, selected protease enzymes are partially shielded in a nanometre-thick mercaptosilica layer acting not only as a protective system but also as a substrate reducing agent. The biocatalysts produced efficiently perform simultaneous disulphide bond reduction and protein digestion. Besides a significant simplification of the proteolysis process, this strategy allows for a drastic increase of the enzyme stability.


A conserved motif in the yeast nucleolar protein Nop2p contains an essential cysteine residue.
Nop2p is an essential nucleolar protein in Saccharomyces cerevisiae that is involved in large ribosomal subunit assembly. It has substantial homology with human p120, the proliferation-associated nucleolar antigen that is overexpressed in many human cancers. A motif containing an invariant Pro-Cys dipeptide is found in Nop2p, p120 and the bacterial Fmu proteins. A total of nine conserved residues, including Pro423 and Cys424, were individually altered in Nop2p by site-directed mutagenesis. Nop2p function was abolished by conversion of Cys424 into either alanine or serine. All of the other Nop2p mutations tested sustained yeast viability, including glycine replacement of Pro423 and the conversion of a second conserved cysteine into alanine. The crucial role of Cys424 in Nop2p is intriguing, due to the critical roles that cysteine residues adjacent to a proline have in a number of nucleotide-modifying enzymes.


Uptake of the Influenza Vaccination in Pregnancy.
Influenza is caused by a highly infectious RNA virus, which usually occurs in a seasonal pattern with epidemics in the winter months. The objective of this study was to determine the uptake of the influenza vaccine in a pregnant population and ascertain the reasons why some women did not receive it. A prospective cohort study was conducted over a two-week period in January 2016 in the National Maternity Hospital Dublin, a tertiary referral maternity hospital delivering over 9000 infants per year. There were 504 women studied over the 2-week period. Overall, 197(39.1%) women received the vaccine at a mean gestational age 20.9 weeks (SD 7.0). Given the increased rates of influenza in the community and the associated implications for mother and infant, it is important that pregnant women are educated regarding the risks of influenza in pregnancy and encourage this cohort to be vaccinated.


SES and correlated factors do not explain the association between periodontal disease, edentulism, and cancer risk.
Severe periodontal disease and edentulism have been previously reported to be significantly associated with cancer risk and mortality, including in the Atherosclerosis Risk in Communities study (2018); however, complex sources of confounding by socioeconomic status (SES), and characteristics correlated with SES, could have been present in earlier analyses. To capture life course SES and its correlates, we generated a propensity score and included it, along with other potential confounders such as smoking and obesity, into a Cox regression model to examine the association between periodontal disease and cancer risk. In addition, we stratified the model with the propensity score by low and high SES. All statistical tests were two-sided. Compared with our previous study, the associations for severe periodontitis and cancer incidence remained comparable after weighting by the propensity score (e.g., for total cancer: before weighting, hazard ratio = 1.24, 95% confidence interval = 1.07-1.42 vs. after weighting, hazard ratio = 1.23, 95% confidence interval = 1.05-1.44 when comparing severe periodontitis to no or mild periodontitis). Associations were comparable in low and high SES strata and statistically significant among participants with high SES. Complex sources of confounding by SES and its correlates are unlikely to fully account for the positive associations observed for periodontal disease and edentulism and cancer risk.


Water Splitting with Series-Connected Polymer Solar Cells.
We investigate light-driven electrochemical water splitting with series-connected polymer solar cells using a combined experimental and modeling approach. The expected maximum solar-to-hydrogen conversion efficiency (ηSTH) for light-driven water splitting is modeled for two, three, and four series-connected polymer solar cells. In the modeling, we assume an electrochemical water splitting potential of 1.50 V and a polymer solar cell for which the external quantum efficiency and fill factor are both 0.65. The minimum photon energy loss (Eloss), defined as the energy difference between the optical band gap (Eg) and the open-circuit voltage (Voc), is set to 0.8 eV, which we consider a realistic value for polymer solar cells. Within these approximations, two series-connected single junction cells with Eg = 1.73 eV or three series-connected cells with Eg = 1.44 eV are both expected to give an ηSTH of 6.9%. For four series-connected cells, the maximum ηSTH is slightly less at 6.2% at an optimal Eg = 1.33 eV. Water splitting was performed with series-connected polymer solar cells using polymers with different band gaps. PTPTIBDT-OD (Eg = 1.89 eV), PTB7-Th (Eg = 1.56 eV), and PDPP5T-2 (Eg = 1.44 eV) were blended with [70]PCBM as absorber layer for two, three, and four series-connected configurations, respectively, and provide ηSTH values of 4.1, 6.1, and 4.9% when using a retroreflective foil on top of the cell to enhance light absorption. The reasons for deviations with experiments are analyzed and found to be due to differences in Eg and Eloss. Light-driven electrochemical water splitting was also modeled for multijunction polymer solar cells with vertically stacked photoactive layers. Under identical assumptions, an ηSTH of 10.0% is predicted for multijunction cells.


Protective effect of punicalagin, the main polyphenol compound of pomegranate, against acrylamide-induced neurotoxicity and hepatotoxicity in rats.
Acrylamide (ACR) is widely used in industries. Oxidative stress and apoptosis pathways are important mechanisms behind ACR-induced hepatotoxicity and neurotoxicity. Regarding to antioxidant and antiapoptotic properties of punicalagin (PUN), the protective effect of this agent on ACR-induced toxicity in rat was evaluated. Rats were divided into seven groups: control, ACR (50 mg/kg/day, i.p.), PUN (10, 20, and 40 mg/kg/day, i.p.) plus ACR, vitamin E (200 mg/kg, i.p.) plus ACR, and PUN groups. After 11 days, the gait score test was evaluated. Then, the animals were sacrificed and the malondialdehyde (MDA) and glutathione (GSH) contents were determined in the brain and liver tissues. Apoptosis-involved factors and myelin basic protein (MBP) were determined by western blotting. Severe movement disorder, MDA enhancement, and GSH reduction in the brain and liver tissues were observed in ACR-treated animals. The Bax/Bcl2 ratio and caspase-3 levels were enhanced in the tested tissues. ACR elevated the level of aspartate aminotransferases and decreased serum protein and albumin concentration. PUN recovered movement disorders, changed the level of markers which are important in oxidative stress and reduced apoptosis. Also, PUN increased the MBP level which was reduced due to ACR toxicity. PUN can protect against ACR-induced toxicity through antioxidant and antiapoptotic properties.


Tufts academic health information network: concept and scenario.
Tufts University School of Medicine's new health sciences education building, the Arthur M. Sackler Center for Health Communications, will house a modern medical library and computer center, classrooms, auditoria, and media facilities. The building will also serve as the center for an information and communication network linking the medical school and adjacent New England Medical Center, Tufts' primary teaching hospital, with Tufts Associated Teaching Hospitals throughout New England. Ultimately, the Tufts network will join other gateway networks, information resource facilities, health care institutions, and medical schools throughout the world. The center and the network are intended to facilitate and improve the education of health professionals, the delivery of health care to patients, the conduct of research, and the implementation of administrative management approaches that should provide more efficient utilization of resources and save dollars. A model and scenario show how health care delivery and health care education are integrated through better use of information transfer technologies by health information specialists, practitioners, and educators.


pH/redox dual stimuli-responsive sheddable nanodaisies for efficient intracellular tumour-triggered drug delivery.
A series of dual stimuli-responsive poly(l-histidine)n-S-S-polyurethane-S-S-poly(l-histidine)n [p(His)n-SS-PU-SS-p(His)n; n = 25, 35, 50, and 75] triblock copolymers that bear two pH-responsive p(His)n end-blocks and PU middle-blocks tethered by a redox-responsive disulphide linker have been synthesized. The resulting triblock copolymers self-assemble to form micelles, nanodaisies (NDs), of uniform size (∼100 nm) and efficiently encapsulate the anticancer drug doxorubicin (Dox) with a high drug loading content (∼19%). The in vitro release profile shows an enhanced release of Dox in an acidic environment in the presence of 10 mM glutathione. The in vitro cell viability assays performed in various cell lines show that the NDs have no acute or intrinsic toxicity. Confocal microscopy images and flow cytometry results show the pH-responsive cellular uptake of Dox-loaded NDs, accelerated at pH ≤ 5.0. The tumour accumulation and in vivo bio-distribution studies of near-infrared dye (IR-820)-labeled NDs show higher tumour accumulation in CT26 tumour-bearing mice within 72 h. Furthermore, the Dox-loaded NDs effectively inhibit the CT26 tumours, suggesting that they are promising nanocarriers for cancer therapy.


Modification of the expression of two NPR1 suppressors, SNC1 and SNI1, in soybean confers partial resistance to the soybean cyst nematode, Heterodera glycines.
Systemic acquired resistance (SAR) is an enhanced defence response triggered when plants detect a pathogen. The response is extended to uninfected organs to protect against future attack. NPR1 is a nuclear leucine-rich repeat protein with a key role in SAR. It binds specifically to salicylic acid, and acts as a transcriptional coregulator of SAR activators and an inhibitor of transcriptional repressors. The proteins encoded by Suppressor of NPR1, Constitutive (SNC1) and Suppressor of NPR1, Inducible (SNI1) interact with NPR1 to regulate the expression of pathogenesis-related genes. The Arabidopsis thaliana (L.) Heynh. snc1 mutant exhibits a constitutive resistance response, but in the sni1 mutant, the SNI1 protein is rendered incapable of suppressing pathogen resistance genes. To study the influence of SNC1 and SNI1 on resistance to the soybean cyst nematode (Heterodera glycines), soybean (Glycine max (L.) Merr.) roots were separately transformed with four constructs designed to: (i) overexpress GmSNC1, the soybean orthologue of AtSNC1; (ii) overexpress AtSNI1; (iii) silence GmSNC1 and (iv) silence GmSNI1. A significant reduction of the female nematode population was observed in Treatments (i) and (iv). The expression of SAR marker genes was analysed in these treatments. The unusual pattern of expression of pathogen resistance genes shows there are differences in the effect resistance genes have on soybean and A. thaliana. Although NPR1 is involved in the cross-talk between the salicylic acid, jasmonic acid and ethylene pathways, understanding the nematode resistance mechanism in plants is still imprecise. These results provide further insights into the soybean defence response.


Mortality of workers potentially exposed to organic and inorganic brominated chemicals, DBCP, TRIS, PBB, and DDT.
A historical prospective mortality study was conducted on 3579 white male workers employed between 1935 and 1976 with potential exposures to brominated compounds including 1,2-dibromo-3-chloropropane (DBCP), Tris (2,3-dibromopropyl) phosphate, polybrominated biphenyls (PBB), various organic and inorganic bromides, and DDT. The vital status as of 31 December 1976 was determined for 3384 (95%) of these workers: 2806 (79%) were still living and 578 (16%) had died. Death certificates were obtained for 541 deaths (94% of all deaths). The mortality experience of the entire cohort and several subcohorts was compared with that of United States white men adjusted for age and calendar time. The comparison statistic was the commonly used standardised mortality ratio (SMR). Historical industrial hygiene data were not available, and the workers were classified by their work areas or departments in order to estimate their potential exposures. Overall mortality for the entire cohort and several subgroups was significantly lower than expected. For the entire cohort, significant mortality deficits were observed in diseases of the circulatory system, non-malignant respiratory disease, and diseases of the digestive system. On the other hand, mortality from diabetes mellitus was significantly raised for the cohort. No significant overall or cause-specific mortality excess was detected among employees potentially exposed to either TRIS or DDT. A significant mortality excess due to diseases of the circulatory system was observed among workers potentially exposed to DBCP. Mortality from testicular cancer was significantly higher than expected among those potentially exposed to other organic bromides. The common potential exposure of those who had died of testicular cancer was methyl bromide. Owing to the lack of accurate historical exposure information and the fact that many workers were potentially exposed to a multitude of chemicals, it is difficult to draw definitive statements on the causations of the observed mortality excesses.


Characteristics of individuals infected with the human immunodeficiency virus and provider interaction in the predominantly rural Southeast.
This detailed study describes the demographic characteristics, behavioral characteristics, care-seeking behavior, and barriers to health care and social services for patients infected with the human immunodeficiency virus (HIV) in the Southeast. We conducted a cross-sectional study of Medicaid-eligible HIV-positive individuals (chart abstractions [N = 679], patient surveys [N = 487]) and care providers (N = 101) in North Carolina. Relative risks compare blacks, women, and respondents reporting substance abuse with their reference groups. Results are compared with those of a larger sample including persons from Alabama and South Carolina. Forty-one percent of respondents did not receive care locally, and 69% of female respondents had young children at home. In the 12 months before the survey, 66% reported substance abuse; 49% reported multiple living situations; 11% had entered drug treatment; and 10% had difficulty with the law. The findings in North Carolina did not differ from those in Alabama and South Carolina. Mean indices from care provider surveys revealed low interagency knowledge and referrals. Patients have complex needs for both social services and health care. However, providers are not working together.


Effects of labeling and interpersonal contact upon attitudes towards schizophrenia: implications for reducing mental illness stigma in urban China.
As mental illness stigma contributes to poor outcomes for schizophrenia in China, locating strategies to reduce public stigma is imperative. It is currently unknown whether diagnostic labeling and contact with different help-seeking sources increase or decrease public stigma in China. Further, it remains unresolved whether prior personal contact acts to reduce stigma in this context. Advancing understanding of these processes may facilitate stigma-reduction strategies. We administered an experimental vignette randomly assigning one of four labeling conditions to respondents to assess social distance towards a psychotic vignette individual in a sample of 160 Northern, urban Chinese community respondents. As expected, respondents given a "non-psychiatric, indigenous label" + "lay help-seeking" condition endorsed the least social distance. Unexpectedly, the labeling condition with a "psychiatric diagnostic label" + "lay help-seeking" condition elicited the greatest social distance. Unlike Western studies, personal contact did not independently decrease community stigma. However, prior contact reduced social distance to a greater extent in the labeling condition with a "non-psychiatric, indigenous label" + "lay help-seeking" condition when compared with all other labeling conditions. The results indicate that cultural idioms do provide some protection from stigma, but only among respondents who are already familiar with what mental illness is. Our finding that the condition that depicted untreated psychosis elicited the greatest amount of stigma, while the "treated psychosis" condition was viewed relatively benignly in China, suggests that improved access to mental health services in urban China has the potential to decrease public stigma via labeling mechanisms.


Delay in the Diagnosis of APECED: A Case Report and Review of Literature from Iran.
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is a rare monogenic autosomal recessive disorder caused by biallelic mutations in the AIRE (autoimmune regulator) gene. Patients with APECED present with heterogeneous endocrine and non-endocrine manifestations. In this study, we report an Iranian patient who presented with Addison disease, chronic mucocutaneous candidiasis, alopecia totalis, keratopathy and asplenia treated as an isolated endocrinopathy for 25 years. In the adulthood, the diagnosis of APECED was made by genetic analysis which demonstrated homozygous nonsense p.R257* (c.769C>T) mutation of AIRE. APECED has been shown to be frequent in some ethnicities including Iranian Jews. Therefore, we reviewed 39 Iranian APECED patients published in the literature. We found that most of the Iranian patients were of Jewish ethnic background and presented hypoparathyroidism, adrenal insufficiency, and candidiasis as the main clinical manifestation.


Translational and transcriptional inhibitors block serotonergic phase advances of the suprachiasmatic nucleus circadian pacemaker in vitro.
The mammalian circadian pacemaker is located in the suprachiasmatic nucleus (SCN). Various inputs modulate pacemaker phase, including the serotonergic (5HTergic) input from the midbrain raphe. 5HT phase-advances the SCN pacemaker when applied during mid subjective day. In vitro studies indicate that 5HT advances the mammalian circadian pacemaker through a process that includes stimulating 5HT7 receptors, activating protein kinase A, and opening K+ channels. How these cytoplasmic and membrane events translate into a shift in the molecular core of the circadian oscillator is not known. To further understand this process, the authors investigated whether 5HTergic phase advances require transcription or translation. Using two reversible translational inhibitors, anisomycin and cycloheximide, the authors show that inhibiting protein synthesis blocks 5HTergic phase shifts. The authors further show that the transcriptional inhibitor 5,6-dichloro-1-beta-ribobenzimidazole also blocks 5HTergic phase shifts. These results are similar to those found previously with respect to 5HTergic modulation of the Aplysia ocular circadian clock, and suggest that 5HT may phase-shift the SCN pacemaker through increasing transcription and translation of specific proteins.


[Reconstructive reoperations on abdominal aorta and main arteries of extremities in the synthetic prosthesis thrombosis].
The results of surgical treatment of 176 patients aging from 42 to 75 years, to whom earlier the reconstruction operation on abdominal aorta and the lower extremities main arteries was performed, were analyzed. The causes of the synthetic prosthesis thrombosis occurrence were studied, individualized surgical tactics, depending on the hip arteries inflow and outflow, was substantiated. There was proposed an access to a. femoris profunda and the profundoplasty method. The immediate and late follow-up results of their application are satisfactory.


The effects of different initial restrictive pressures used to reduce blood flow and thigh composition on tissue oxygenation of the quadriceps.
Blood flow restriction training technique can be affected by several factors resulting in changes in responses to training; therefore it is necessary to investigate and reveal detailed information about this novel training technique. Participants had their thigh size, thickness of subcutaneous fat, and regional bone free muscle mass measured prior to testing. A Near-Infrared Spectrometer was used to measure tissue oxygenation and a cardiovascular profiling system was utilised to measure stroke volume and heart rate. Initial restrictive pressure of 30, 50, and 70 mmHg were set in random order on three separate days, and then six target pressures were sequentially applied. Tissue oxygenation decreased significantly as both initial restrictive pressure and target pressures increased, but the magnitude of decreases was stronger with higher initial restrictive pressure. There were significant negative correlations between tissue oxygenation and leg lean body mass, total lean body mass, and thigh circumference when initial restrictive pressure was set at 30 mmHg. The findings indicated that changes in initial restrictive pressure affected the amount of venous return verified by the decreases in tissue oxygenation and stroke volume. In addition, thigh composition and size had a significant impact on the effects of initial restrictive pressure.


Identification of base substitutions in the promoter regions of the A gamma- and G gamma-globin genes in A gamma- (or G gamma-) beta+-HPFH heterozygotes using the DNA-amplification-synthetic oligonucleotide procedure.
DNA amplification combined with hybridization with 32P-labeled synthetic oligonucleotide probes has been used to identify base substitutions in the 5' promoter region of the A gamma globin gene in members of eleven families from China, Sardinia, Canada, and the United States who had a heterozygosity for the A gamma-beta+-hereditary persistence of fetal hemoglobin (HPFH), and in members of six black families with a possible G gamma-beta+-HPFH heterozygosity. All three known A gamma types were observed, ie, the British type (-198, T----C), the Chinese type (-196, C----T), and the Green type (-117, G----A); the latter has been found in a black family. Of the six families with G gamma-beta+-HPFH, three had C----G at -202 and none T----C -175. Conditions for hybridization of amplified DNA with the specific probes are provided and the usefulness of the technique is discussed. The increase in numbers of A gamma(G gamma)-beta+-HPFH heterozygotes with specific base substitutions greatly enhances the probability of a direct correlation between these substitutions and the increase in the production of a specific gamma chain.