4-Demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548), a novel anticancer agent active against tumor cell lines with different resistance mechanisms.
The activity of 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyl-daunorubicin (PNU-159548), a new alkycycline with high antitumor activity against a broad range of cancer cells, was evaluated in vitro and in vivo in cells selected for resistance to different anticancer agents. Both in vitro and in vivo, PNU-159548 did retain its activity in cells expressing the multidrug resistance (MDR) phenotype, associated to MIDR-1 gene overexpression or with an alteration in the topoisomerase II gene (altered MDR), independently on the drug used for the selection of the resistant cell line. According to these data, the intracellular uptake of PNU-159548 is not influenced by the presence of MDR-1. PNU-159548 was also active, both in vitro and in vivo, against cells showing resistance to various alkylating agents iincluding cisplatin, cyclophosphamide, and melphalan) and topoisomerase I-inhibitors. Cells defective in nucleotide excision repair, which did show hypersensitivity to treatment with UV irradiation and alkylating agents, showed only a marginally increased sensitivity to PNU-159548. Similarly, the activity of the drug was not influenced by the mismatch repair system, as assessed in two different cellular systems deficient in hMLH1 expression and in which hMLH1 activity was restored by chromosome 3 transfer. The results obtained clearly indicate that the new anticancer agent PNU-159548 is able to overcome the classical mechanisms of resistance emerging after treatment with the most clinically used anticancer agents, and it could represent an alternate choice in the treatment of those tumors refractory to conventional therapy.


Reaction of cytochrome bo3 with oxygen: extra redox center(s) are present in the protein.
The reaction of oxygen with cytochrome bo3, a quinol oxidase from Escherichia coli, has been studied by resonance Raman scattering after initiation of the reaction by CO photolysis in a continuous flow apparatus and by directly mixing the enzyme with oxygen. The high-frequency region of the spectrum was monitored to determine the time evolution of the spin, oxidation, and coordination states of heme O and the oxidation state of heme B by using newly established marker lines for each heme. Three phases of the reaction were detected. In phase I, complete in 75 microseconds, O2 reacted with heme O and formed a low-spin ferric or ferryl adduct without significant oxidation of heme B. In phase II, between 75 and 120 microseconds, a small fraction of heme B was oxidized. In phase III, at approximately 1 s, the majority of heme B was oxidized and heme O reverted to a high-spin ferric state. The high rate of oxygen reduction at heme O to the three- or four-electron reduced level, despite a very low rate of heme B oxidation, indicates that there are electron donors active in the enzyme other than the metal centers. Assays of our enzyme preparations rule out a quinol in the tight binding (QH) site as a possible donor but instead suggest electron donation from the protein matrix, such as from tryptophans or tyrosine.(ABSTRACT TRUNCATED AT 250 WORDS)


Preliminary Evidence of Endotoxin Tolerance in Dairy Cows during the Transition Period.
The blastogenic response of bovine peripheral blood mononuclear cells (PBMCs) to lipopolysaccharides (LPS) has been investigated for a long time in our laboratories. In particular, a possible correlation between the blastogenic response to LPS and the disease resistance of dairy cows has been suggested in previous studies. Isolated PBMCs from eight cows at three different time points during the transition period (T0 = 15 days before calving; T1 = 7 days post-calving; T2 = 21 days post-calving) were cultured in the presence or absence of LPS, and the blastogenic response was assayed 72 h after in vitro stimulation. Moreover, the gene expression of proinflammatory cytokines and kynurenine pathway molecules was investigated by real-time RT-PCR on both unstimulated and stimulated PBMCs. The cows were retrospectively divided into healthy and diseased, based on the development of peripartum diseases (subclinical ketosis and placenta retention). The comparison between healthy and diseased cows suggested that healthy animals seemed to better control the response to LPS. On the contrary, diseased animals showed a much higher inflammatory response to LPS. Moreover, cows were retrospectively classified as high and low responders based on the in vitro proliferative response of PBMCs to LPS, using the median value as a threshold. Unstimulated PBMCs of low responders showed higher expression of the proinflammatory cytokines Interleukin 1-β (IL-1β), Interleukin 6 (IL-6) and Tumor Necrosis Factor-α (TNF-α), compared to high responders. Our preliminary data suggest that, during the peripartum period, high responders seem to be more tolerant to endotoxins and develop a lower inflammatory response to different stressors. Instead, low responders could be more prone to the development of unwanted inflammatory conditions in response to mild/moderate stressors.


Angle closure glaucoma following pupillary block in an aphakic perfluoropropane gas-filled eye.
We report the case of a 35-year-old aphakic patient who developed an intractable secondary glaucoma due to angle closure after pupillary block following the use of perfluoropropane (C3F8) gas at a nonexpansile concentration of 14%.


General Synthetic Strategy for Hollow Hybrid Microspheres through a Progressive Inward Crystallization Process.
Hollow hybrid microspheres have found great potential in different areas, such as drug delivery, nanoreactors, photonics, and lithium-ion batteries. Here, we report a simple and scalable approach to construct high-quality hollow hybrid microspheres through a previously unexplored growth mechanism. Starting from uniform solid microspheres with low crystallinity, we identified that a hollowing process can happen through the progressive inward crystallization process initiated on the particle surface: the gradual encroachment of the crystallization frontline toward the core leads to the depletion of the center and forms the central cavity. We showed that such a synthetic platform was versatile and can be applicable for a large variety of materials. By using the production of Li4Ti5O12-carbon hollow hybrid microspheres as an example, we demonstrated that high-performance anode materials could be achieved through synthesis and structure control. We expect that our findings offer new perspectives in different areas ranging from materials chemistry, energy storage devices, catalysis, to drug delivery.


C-reactive protein elevation can be caused by conditions other than inflammation and may reflect biologic aging.
Epidemiologic studies have revealed that minimal acute-phase changes predict poor prognoses in many conditions and predict disability and mortality in the elderly. These findings have usually been interpreted to indicate that inflammatory processes of some kind play a role in these situations. In fact, a minimal acute-phase response does not necessarily establish the existence of an inflammatory process but may also reflect a variety of noninflammatory states, including obesity, sleep disturbance, depression, chronic fatigue, and low levels of physical activity. I propose that a minimal acute-phase response may also be a marker of biologic aging, a condition known to predispose to poor prognoses and to death.


Separate-type scanner and wideband high-voltage amplifier for atomic-resolution and high-speed atomic force microscopy.
We have developed a liquid-environment atomic force microscope with a wideband and low-noise scanning system for atomic-scale imaging of dynamic processes at solid/liquid interfaces. The developed scanning system consists of a separate-type scanner and a wideband high-voltage amplifier (HVA). By separating an XY-sample scanner from a Z-tip scanner, we have enabled to use a relatively large sample without compromising the high resonance frequency. We compared various cantilever- and sample-holding mechanisms by experiments and finite element analyses for optimizing the balance between the usability and frequency response characteristics. We specifically designed the HVA to drive the developed scanners, which enabled to achieve the positioning accuracy of 5.7 and 0.53 pm in the XY and Z axes, respectively. Such an excellent noise performance allowed us to perform atomic-resolution imaging of mica and calcite in liquid. Furthermore, we demonstrate in situ and atomic-resolution imaging of the calcite crystal growth process in water.


Early-Onset Developmental and Epileptic Encephalopathies of Infancy: An Overview of the Genetic Basis and Clinical Features.
Our current knowledge of genetically determined forms of epilepsy has shortened the diagnostic pathway usually experienced by the families of infants diagnosed with early-onset developmental and epileptic encephalopathies. Genetic causes can be found in up to 80% of infants presenting with early-onset developmental and epileptic encephalopathies, often in the context of an uneventful perinatal history and with no clear underlying brain abnormalities. Although current disease-specific therapies remain limited and patient outcomes are often guarded, a genetic diagnosis may lead to early therapeutic intervention using new and/or repurposed therapies. In this review, an overview of epilepsy genetics, the indications for genetic testing in infants, the advantages and limitations of each test, and the challenges and ethical implications of genetic testing are discussed. In addition, the following causative genes associated with early-onset developmental and epileptic encephalopathies are discussed in detail: KCNT1, KCNQ2, KCNA2, SCN2A, SCN8A, STXBP1, CDKL5, PIGA, SPTAN1, and GNAO1. The epilepsy phenotypes, comorbidities, electroencephalgraphic findings, neuroimaging findings, and potential targeted therapies for each gene are reviewed.


Detection of cytomegalovirus from blood leukocytes separated by sepracell-MN and Ficoll-Paque/Macrodex methods.
Two density gradient separation techniques for separation of blood leukocytes were compared for the laboratory diagnosis of cytomegalovirus (CMV) viremia. Of 510 blood specimens processed by both methods, 76 (14.9%) yielded CMV. Of the 76 positive specimens, 66 (87%) and 65 (86%) were processed by the Ficoll-Paque/Macrodex (F-P/M; Macrodex is dextran 70 in normal saline; Pharmacia, Pisataway, N.J.) and Sepracell-MN methods, respectively. Of the 76 CMV-positive blood specimens, 72 (95%) were detected in shell vial cell cultures, whereas only 42 (55%) were detected in conventional tube cell cultures. The time for recognition of specific cytopathic effects due to CMV in tube cell cultures (8.0 versus 7.1 days), the number of fluorescent foci in each positive shell vial culture (19.3 versus 20.1), and the costs of the reagents ($3.50 versus $2.80) were similar and independent of the leukocyte separation method (F-P/M versus Sepracell-MN). Recovery of CMV from heparinized blood (F-P/M method) was similar to that from EDTA-anticoagulated blood (Sepracell-MN method). The Sepracell-MN method is a rapid and sensitive method for detection of CMV from blood specimens and is recommended as a replacement for the more tedious and time-consuming F-P/M procedure.


Chromatographic detection of lignin-carbohydrate complexes in annual plants by derivatization in ionic liquid.
The opportunity for detecting the presence and the amount of lignin-carbohydrate complexes (LCCs) in renewable feedstocks is a major issue for the complete utilization of biomass. Indeed, LCCs are known to shield cellulose from enzymatic hydrolysis, reducing the efficiency of the digestion processes needed for the production of biobased products. This study is focused on the chromatographic characterization of lignocellulose from agricultural residues (rice husk, wheat straw) and herbaceous energy crops ( Arundo donax , Miscanthus sinesis ) and their fractionation products (hemicellulose, cellulose, and lignin). Exploiting alternative chemical derivatizations on the aforementioned samples, it was possible to discern the connectivity among the various lignocellulosic components. The complete acetylation and benzoylation of the milled native substrates in ionic liquid media, and the systematic comparison between their GPC-UV chromatograms collected at different wavelengths has revealed itself as a straightforward technique in the detection of LCCs. This novel approach proved an extensive connectivity between the lignin and the hemicellulosic for all the analyzed specimens, whereas the cellulosic fraction was conceived as a substantially unbound moiety, accounting for the sample composition at higher molecular weights. Moreover, the collected lignin fractions were extensively characterized by means of (31)P NMR and 2D-HSQC techniques.


Activation of endothelial cell phospholipase D by hydrogen peroxide and fatty acid hydroperoxide.
We have investigated oxidant-mediated stimulation of phospholipase D (PLD) activity in bovine pulmonary artery endothelial cells (BPAEC), prelabeled with [32P]orthophosphate or [32P]lysophospholipids. Treatment of cells incubated in Hanks' balanced salt solution (HBSS) containing 0.5% ethanol with hydrogen peroxide (H2O2) or linoleic acid hydroperoxide (18:2-OOH) enhanced the formation of 32P-labeled phosphatidylethanol (PEt) and phosphatidic acid (PA) in a dose- and time-dependent manner, indicating the activation of PLD. The H2O2- and 18:2-OOH-mediated PLD activation was not associated with cytotoxicity as determined by [3H]deoxyglucose release. The addition of ferrous chloride (50 microM) augmented H2O2-induced formation of [32P]PEt and [32P]PA about 2-fold, whereas the addition of the iron chelator desferoxamine blocked the potentiating effect of ferrous chloride. Replacement of the HBSS medium with Medium 199 containing 20% calf serum also potentiated the effect of H2O2-induced PLD activation. In addition to phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) were readily hydrolyzed by PLD in response to H2O2 and 18:2-OOH treatment. The substrate specificity for oxidant-stimulated PLD activity differed from that observed in the presence of bradykinin or exhibited by agonist stimulation with 12-O-tetradecanoylphorbol 13-acetate (TPA) where PC was the major phospholipid hydrolyzed by PLD. The formation of PEt in the presence of H2O2 and 18:2-OOH was not abolished by chelation of either extracellular Ca2+ with EGTA (5 mM) or intracellular Ca2+ with 1,2-bis-(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) (25 microM, 30 min). Furthermore, pretreatment of BPAEC with the protein kinase C (PKC) inhibitor staurosporine and down-regulation of PKC by chronic TPA treatment (100 nM, 18 hr) had no effect on H2O2-induced PLD activation, suggesting that PLD activation by H2O2 is independent of PKC activity. It is possible that H2O2- and 18:2-OOH-induced activation of PLD represents an important mechanism to produce PA and diacylglycerol in endothelial cells.


Effect of Joint National Committee VII report on hospitalizations for hypertensive emergencies in the United States.
Approximately 1% to 2% of patients with hypertension will have a hypertensive emergency at some time in their life. However, no data are available on the frequency of hospitalizations for a hypertensive emergency after the publication of the Seventh Joint National Committee (JNC7) on the prevention, detection, evaluation, and treatment of high blood pressure. We sought to explore the changes in the frequency of hospitalizations and in-hospital mortality for hypertensive emergencies before and after the JNC7 report. Using the Nationwide Inpatient Sample from 2000 to 2007, adult patients (aged ≥18 years) who were hospitalized with a diagnosis of a hypertensive emergency were identified through appropriate "International Classification of Diseases, 9th revision, Clinical Modification" codes. A total of 456,259 hospitalizations with the diagnosis of hypertensive emergency occurred from the start of calendar year 2000 to the end of calendar year 2007. After adjusting for the United States census for 2000 and American Community Survey estimates for 2007 for adults, the frequency of hospitalizations with a hypertensive emergency increased in United States adults from 101/100,000 in 2000 to 111/100,000 in 2007, an average increase of about 1.11%. Despite the increase in hospitalizations, the all-cause in-hospital mortality rate decreased from 2.8% in the pre-JNC7 era to 2.6% in the post-JNC7 era (odds ratio 0.91, 95% confidence interval 0.86 to 0.96). In conclusion, the results of the present study have shown that although the number of patients with hypertensive emergency increased from 2000 to 2007, the mortality rates decreased significantly after the JNC7 guidelines.


Routine colonoscopy service.
We report our experience of 50 paediatric colonoscopies in a relatively unselected group of patients. Collaboration between an experienced colonoscopist and a paediatrician has provided a smooth, routine service and the examination has proved extremely useful for the diagnosis and management of children with colonic symptoms.


Improvements in Diabetic Neuropathy and Nephropathy After Bariatric Surgery: a Prospective Cohort Study.
There are limited data on the impact of bariatric surgery on microvascular complications of type 2 diabetes (T2D), particularly diabetic neuropathy. We assessed microvascular complications (especially neuropathy) in obese patients with T2D before and 12 months after bariatric surgery. This was a prospective observational cohort study. Measurements of neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration (VPT), cold (CPT) and warm (WPT) perception thresholds, nerve conduction studies (NCS) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL); urinary albumin/creatinine ratio (uACR), estimated glomerular filtration rate (eGFRcyst-creat) and retinal grading were taken. Twenty-six (62% female; median age 52 years) obese patients with T2D were recruited. Body mass index (BMI) (47.2 to 34.5 kg/m2; p < 0.001) decreased post-operatively. There were improvements in CNFD (27.1 to 29.2/mm2; p = 0.005), CNBD (63.4 to 77.8/mm2; p = 0.008), CNFL (20.0 to 20.2/mm2; p = 0.001), NSP (3 to 0/38; p < 0.001) and eGFRcyst-creat (128 to 120 ml/min; p = 0.015) post-bariatric surgery. Changes in (Δ) triglycerides were independently associated with ΔCNFL (β = - 0.53; p = 0.024) and Δsystolic blood pressure (β = 0.62;p = 0.017), and %excess BMI loss (β = - 0.004; p = 0.018) were associated with ΔeGFRcyst-creat. There was no significant change in NDS, VPT, CPT, WPT, NCS, uACR or retinopathy status. Glomerular hyperfiltration resolved in 42% of the 12 patients with this condition pre-operatively. Bariatric surgery results in improvements in small nerve fibres and glomerular hyperfiltration in obese people with T2D, which were associated with weight loss, triglycerides and systolic blood pressure, but with no change in retinopathy or uACR at 12 months.


Objective triage in the disaster setting: will children and expecting mothers be treated like others?
The study of disaster triage is made difficult by the complex emotional response of potentially lifesaving intervention that a triage officer must make basing decisions on a succinct and efficient algorithm. A survey of triage professionals in international settings was designed to identify possible emotionally led bias that affects objective decision making in identifying victims most likely to benefit from immediate life support intervention. This survey suggests a lack of correlation between triage priority and predictable clinical outcomes as predicted by the Revised Trauma Score tool. Among the subjects, it was observed that a pediatric victim is uniformly overtriaged when compared to less injured victims.


The storage of household long guns: the situation in Quebec.
This survey on the storage of household firearms in Quebec was conducted in 1994. At that time, 35% (175/504) of survey participants who kept long guns in their homes had failed to comply with Canadian firearm storage regulations. In most cases (85%; n=149), this was because at least one stored long gun was found to be both operable and accessible. Thirty-seven per cent of participants stated that no one, including themselves, had used their firearm(s) in the 12 months preceding the survey. These findings point to two possible ways of dealing with long guns kept in the home: render these weapons inoperable or inaccessible, which would increase the level of compliance with the regulations, and dispose of those no longer in use. The results of this survey have never been published before, and constitute the only information of this kind with respect to Quebec.


Allele frequencies of polymorphisms of TNFA, IL-6, IL-10 and IFNG in an Italian Caucasian population.
Polymorphisms in the regulatory and intronic regions of several cytokines have been associated with differential cytokine production. In this paper we genotyped, using the polymerase chain reaction-sequence-specific primers (PCR-SSP) method, a series of 363 healthy Italian Caucasians with the aim of obtaining a reference population for further studies on the role of cytokines in the inflammatory and immune responses. We also compared the results to those for other populations. The polymorphisms analysed were those of tumour necrosis factor alpha (TNFA), interleukin 6 (IL-6), interleukin 10 (IL-10) and interferon gamma (IFNG). We found that the frequency of allele TNFA*1 at position -380 was 87.7% and that of TNFA*2 was 12.4%, significantly different from those of the UK and Japanese populations but not different from that of a population in Gambia. For IL-10 the frequencies of alleles -1082A and -1082G were 63.0% and 37.0% and those of alleles -819C, - 819T, -592C and -592A were 70.8, 29.2, 70.8 and 29.2%, respectively, significantly different from those observed in south-east England, in Manchester and in an Oriental population from southern China. The frequencies of IL-6 alleles - 174C and -174G were 29.0 and 71.0%, respectively; for IFNG polymorphisms at position -874, in the population under evaluation, the alleles -874T and -874A were present in 44.7 and 55.3% of the subjects, respectively. Genotype frequencies of IL-6 were significantly different from those observed in populations from Germany and from the UK. The analysis carried out by our group indicates that there is heterogeneity in the frequencies of the cytokine polymorphisms among the different Caucasian populations, and this underlines the importance of a 'local' reference population when evaluating the clinical relevance of cytokine gene polymorphisms.


Peripheral circulatory response in cardiac failure.
Derangements of the peripheral circulation play a major role in the pathophysiology of congestive heart failure. Their appearance coincides with that of the symptoms and signs that characterize the full-blown clinical syndrome. Long-term therapy with ACE inhibitors partially reverses these abnormalities, but the pathologic mechanisms are still poorly understood.


BAEP dynamic estimation in case of endocochlear pathologies using a time delay correction method.
Extraction of Brainstem Auditory Evoked Potentials (BAEPs) from the electroencephalogram (EEG) is generally difficult when both BAEP and EEG are non-stationary. In this paper we focus on the problem of BAEP non-stationarities, in particular those observed in some endocochlear pathologies assumed causing random delays of BAEPs due to an abnormal behaviour of the cochlea. The technique developed in this paper, called the Time Delay Correction (TDC) method, allows us to estimate the averaged BAEP by an optimal alignment of responses based on a correlation criterion. We demonstrate that the TDC method avoids wave smoothness, generally produced with the classical ensemble averaging method, especially in the case when the hypothesis of the time delay non-stationarity is verified. The TDC method is performed using simulated annealing (SA) algorithm, since the criterion to be optimized is nonlinear. Real signals recorded from pathological subjects are used to validate the model of non-stationarity.


Design of ultraviolet neutral density filters using metal-insulator inhomogeneous layers.
We propose the use of metal-insulator films as neutral density filters for spectrophotometric calibration in the UV and visible ranges. We present a theoretical approach to the design of such filters and show that the correct selection of starting metallic material as well as filling fraction and filter thickness is important in obtaining the required profile. A comparison between theoretical and experimental Ni/SiO(2) films show the suitability of this approach to designing neutral density filters for the 200-800-nm wavelength range and beyond.


LINC00630 as a miR-409-3p sponge promotes apoptosis and glycolysis of colon carcinoma cells via regulating HK2.
Long-chain non-coding RNAs (lncRNAs) belong to the family of non-coding RNAs and contain more than 200 nucleotides. They are involved in the growth, apoptosis, and glycolysis of carcinoma cells. A newly discovered lncRNA, LINC00630, has been reported in colon carcinoma. In this study, we found that the expression of LINC00630 was remarkably upregulated in colon carcinoma tissues and cell lines compared with that in adjacent tissues and the NCM-460 cell lines. Knocking out LINC00630 resulted in inhibition of proliferation and glycolysis but increase in apoptosis. In addition, we confirmed the direct interaction between LINC00630 and miR-409-3p in colon carcinoma cells using bioinformatics methods and dual luciferase reporter gene assay. Finally, we demonstrated that LINC00630 could promote cell growth and glycolysis and inhibit apoptosis by functioning as a miR-409-3p sponge, and further regulate hexokinase 2 (HK2) in colon carcinoma cells. Our results confirmed that LINC00630 regulates proliferation, glycolysis, and apoptosis mainly through targeting the miR-409-3p/HK2 axis, which may explain the progression of colon carcinoma and provide a potential target for the treatment of colon carcinoma.


Cultural attitudes and caregiver service use: lessons from focus groups with racially and ethnically diverse family caregivers.
Focus groups were conducted with caregivers from eight racial-specific or ethnic-specific populations (African Americans, Chinese, Filipinos, Hispanics, Koreans, Native Americans, Russians, and Vietnamese), to examine cultural variations in caregiving experiences, care-related values and beliefs, care practices, and factors contributing to decisions about the use of caregiver support services. Analysis of focus group transcripts revealed three cross-cutting constructs: familism, group identity, and attitudinal and structural barriers to service use. We discuss these findings in terms of their implications for existing knowledge regarding family responsibility, resource utilization, and program development for racially and ethnically diverse family caregivers.


UVB-induced cyclobutane pyrimidine dimer frequency correlates with skin cancer mutational hotspots in p53.
Ultraviolet light has been identified as the major carcinogen in skin cancer and the p53 tumor suppressor gene is a major target for UV-induced mutations. The mutations are probably caused by unrepaired UV-induced cyclobutane pyrimidine dimers (CPD) and possibly by the less frequent pyrimidine (6-4) pyrimidone photoproducts. While hot spots for p53 mutations in human nonmelanoma skin tumors correspond quite well to slow spots for CPD repair in cultured cells irradiated with the model mutagen 254 nm UVC (which is not present in terrestrial sunlight), they do not all coincide with sequences that are initially frequently damaged by 254 nm UVC. Using LMPCR (ligation-mediated polymerase chain reaction), we show that environmentally relevant UVB light induces CPD at CC and Pyr(m)C positions much more frequently than does UVC light, and that all eight skin cancer hot spots in p53 are also hot spots for UVB-induced CPD. Our results show that methylation of dipyrimidine sites (Pyr(m)CpG) is associated with an increase rate of CPD formation upon UVB irradiation. Consequently, DNA methylation may increase the mutagenic potential of UVB and explains that several p53 mutation hot spots are found at Pyr(m)CpG. The distribution patterns of CPD formation and the photofootprint patterns found along exons 5 and 6 of p53 gene are suggestive of DNA folding into nucleosomes.


Effect of oxygen on photosynthesis by spinach leaf protoplasts.
The photosynthetic CO(2) fixation by spinach leaf (Spinacia oleracea L. var. Kyoho) protoplasts was inhibited by substituting an atmosphere of N(2) with one of either air (21% O(2)) or 100% O(2). The inhibitory effect of 100% O(2) was greater than that of air. The mode of inhibition by 100% O(2) and air was competitive with respect to CO(2); Ki(O(2)) value was 0.32 mM at pH 7 and 0.28 mM at pH 8.5 The labeling patterns of compounds in protoplasts exposed to (14)CO(2) in light after transferring them from N(2) to O(2) atmospheres were examined. There was no detectable (14)CO(2) incorporation into glycolate under anaerobic and O(2) atmospheres; a more marked labeling of glycine occurred under an oxidative environment compared to that under the anaerobic condition, presumably because of a rapid transformation of glycolate to glycine in the protoplasts.


Wavefront investigation of a fourier transform lens with the fan trace interferometer.
The performance of a Fourier transform lens is analyzed with the help of a new interferometric device that records the aberration function along any selected section of the wavefront. These interferometric plots, which carry an automatic calibration, are analogous to the familiar geometric-optical fan ray traces and thus provide the means to compare the performance of completed lens systems with the design criteria. The interferometer is particularly well suited to test Fourier transform lenses; however, it is readily modified to investigate imaging systems as well. Therefore, photographic objectives or microscopes may also be analyzed with this interferometer, which also provides considerable freedom from alignment requirements.


Selective inhibition of COX-2 improves cutaneous wound healing of pressure ulcers in mice through reduction of iNOS expression.
Cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) are involved in chronic inflammation observed in chronic lesions. Nonetheless, neither study demonstrated if decreased COX-2 activation could promote the wound healing of pressure ulcers. Therefore, this study investigated the effect of the administration of celecoxib (a selective COX-2 inhibitor) in wound healing of pressure ulcers. Male mice were treated daily with celecoxib until euthanasia. One day after the beginning of treatment, two cycles of ischemia-reperfusion by external application of two magnetic plates were performed in skin to induce pressure ulcer formation. Celecoxib administration reduced the protein expression of inducible nitric oxide synthase (iNOS), COX-2 and PGE2. The hydroperoxide levels, neutrophil and macrophage number, and protein elastase and matrix metalloproteinase-1 levels were reduced in celecoxib-treated group when compared to control group. Celecoxib administration increased myofibroblastic differentiation, re-epithelialization and wound contraction, and decreased the skin necrosis and angiogenesis. Celecoxib administration also stimulated the formation of a more organized and mature scar increasing collagen deposition and reducing tenascin-C expression. Celecoxib administration improves the wound healing of pressure ulcers through decreased expression of iNOS and COX-2, which reduces wound inflammation and promotes dermal reconstruction and scar formation.


Chromosome-wide co-fluctuation of stochastic gene expression in mammalian cells.
Gene expression is subject to stochastic noise, but to what extent and by which means such stochastic variations are coordinated among different genes are unclear. We hypothesize that neighboring genes on the same chromosome co-fluctuate in expression because of their common chromatin dynamics, and verify it at the genomic scale using allele-specific single-cell RNA-sequencing data of mouse cells. Unexpectedly, the co-fluctuation extends to genes that are over 60 million bases apart. We provide evidence that this long-range effect arises in part from chromatin co-accessibilities of linked loci attributable to three-dimensional proximity, which is much closer intra-chromosomally than inter-chromosomally. We further show that genes encoding components of the same protein complex tend to be chromosomally linked, likely resulting from natural selection for intracellular among-component dosage balance. These findings have implications for both the evolution of genome organization and optimal design of synthetic genomes in the face of gene expression noise.


Single Drosophila ommatidium dissection and imaging.
The fruit fly Drosophila melanogaster has made invaluable contributions to neuroscience research and has been used widely as a model for neurodegenerative diseases because of its powerful genetics(1). The fly eye in particular has been the organ of choice for neurodegeneration research, being the most accessible and life-dispensable part of the Drosophila nervous system. However the major caveat of intact eyes is the difficulty, because of the intense autofluorescence of the pigment, in imaging intracellular events, such as autophagy dynamics(2), which are paramount to understanding of neurodegeneration. We have recently used the dissection and culture of single ommatidia(3) that has been essential for our understanding of autophagic dysfunctions in a fly model of Dentatorubro-Pallidoluysian Atrophy (DRPLA)(3, 4). We now report a comprehensive description of this technique (Fig. 1), adapted from electrophysiological studies(5), which is likely to expand dramatically the possibility of fly models for neurodegeneration. This method can be adapted to image live subcellular events and to monitor effective drug administration onto photoreceptor cells (Fig. 2). If used in combination with mosaic techniques(6-8), the responses of genetically different cells can be assayed in parallel (Fig. 2).


Effect of the oral administration of monosodium glutamate during pregnancy and breast-feeding in the offspring of pregnant Wistar rats.
Determine the effects of the MSG (monosodium glutamate) in the offspring of pregnant rats through the comparison of the weight, NAL (nasal-anal length) and IL (Index of Lee) at birth and with 21 days of life. Pregnant Wistar rats and their offspring were divided into 3 groups: GC, G10 and G20. Each of the groups received 0%, 10% and 20% of MSG, respectively from coupling until the end of the weaning period. Neither weight nor NAL were different among the groups at birth. The group G20 at birth had an IL lower than the group GC (p<0,05) and with 21 days of life presented weight and NAL lower than the groups G10 and this lower than the GC (p<0,01). Otherwise the G20 at 21 days of life had the IL similar to the other two groups. The weight profit percentage from birth to the 21st day of life was lower in the G20 regarding the other two groups (p<0,01). The G20 had a NAL increase percentage from birth to the 21st day of life lower than the G10 and this lower than the GC (p<0,01). MSG presented a dose-dependent relation in the variables weight and NAL. It caused a decrease in the growth pattern as well as in the weight gain pattern until the 21st day of life. The IL of the group 20% had an increased in relation to the control group after 3 weeks of follow up.


Perovskite nickelates as bio-electronic interfaces.
Functional interfaces between electronics and biological matter are essential to diverse fields including health sciences and bio-engineering. Here, we report the discovery of spontaneous (no external energy input) hydrogen transfer from biological glucose reactions into SmNiO3, an archetypal perovskite quantum material. The enzymatic oxidation of glucose is monitored down to ~5 × 10-16 M concentration via hydrogen transfer to the nickelate lattice. The hydrogen atoms donate electrons to the Ni d orbital and induce electron localization through strong electron correlations. By enzyme specific modification, spontaneous transfer of hydrogen from the neurotransmitter dopamine can be monitored in physiological media. We then directly interface an acute mouse brain slice onto the nickelate devices and demonstrate measurement of neurotransmitter release upon electrical stimulation of the striatum region. These results open up avenues for use of emergent physics present in quantum materials in trace detection and conveyance of bio-matter, bio-chemical sciences, and brain-machine interfaces.


Molecular diagnostics of Salmonella and Campylobacter in human/animal fecal samples remain feasible after long-term sample storage without specific requirements.
Rapid advances in the development of sequencing technologies, numbers of commercial providers and diminishing costs have made DNA-based identification and diagnostics increasingly accessible to doctors and laboratories, eliminating the need for local investments in expensive technology and training or hiring of skilled technicians. However, reliable and comparable molecular analyses of bacteria in stool samples are dependent on storage and workflow conditions that do not introduce post-sampling bias, the most important factor being the need to keep the DNA at a stable detectable level. For that reason, there may remain other prohibitively costly requirements for cooling or freezing equipment or special chemical additives. This study investigates the diagnostic detectability of Salmonella and Campylobacter DNA in human, pig and chicken stool samples, stored at different temperatures and with different preservation methods. Stool samples were spiked with 106 CFU/mL of both Salmonella and Campylobacter strains stored at -20 °C, 5 °C and 20 °C (Room temperature, RT) and treated with either RNAlater, EDTA or Silica/ethanol. DNA was extracted at 9 different time points within 30 days and quantified by Qubit (total DNA) and qPCR (Salmonella and Campylobacter DNA). We found no statistically significant differences among the different preservation methods, and DNA from both species was easily detected at all time points and at all temperatures, both with and without preservation. This suggests that infections by these bacteria can be diagnosed and possibly also analysed in further detail simply by taking a stool sample in any suitable sealed container that can be transported to laboratory analysis without special storage or preservation requirements. We briefly discuss how this finding can benefit infection control in both developed and developing countries.


High expression of Ran binding protein 1 predicts poor outcomes in hepatocellular carcinoma patients: a Cancer Genome Atlas database analysis.
Ran-specific binding protein 1 (RANBP1) is involved in the regulation of the cell cycle, while its role in hepatocellular carcinoma (HCC) is unknown. Therefore, we aimed to demonstrate the association of RANBP1 with clinicopathologic features and potential biological functions in HCC based on The Cancer Genome Atlas (TCGA) data. We assessed RANBP1 expression and its correlation with clinicopathologic features and evaluated the prognostic value of RANBP1 with Kaplan-Meier survival analysis and the MethSurv database. Univariate and multivariate Cox regression analyses were conducted to elucidate the factors responsible for prognosis. The identification of a co-expression network and the analysis of related biological events with RANBP1 in HCC were assessed using LinkedOmics. Moreover, gene set enrichment analysis (GSEA) was employed to annotate the biological function of RANBP1. We also explored the correlation between RANBP1 and tumor immune infiltrates using a single sample GSEA (ssGSEA). The expression of RANBP1 was found significantly elevated in HCC and linked to advanced T stage and histopathological grade. Up-regulated RANBP1 expression was linked to poor prognosis. High DNA methylation levels of RANBP1 were significantly linked to very poor overall survival (OS). Co-expression network analysis revealed that RANBP1 was involved in ribosome, spliceosome, deoxyribonucleic acid (DNA) replication, ribonucleic acid (RNA) transport, and cell cycle. GSEA showed enrichment of G2M-checkpoint, Wingless and Int-1 (Wnt) cell signaling, and DNA repair in the RANBP1 high-expression phenotype. By using ssGSEA analysis, the increased RANBP1 expression was positively linked to the immune infiltration level of T helper cell type-1 (Th1) and negatively linked to the immune infiltration levels of T helper cell type-17 (Th17). Findings suggest that RANBP1 may play a pivotal role in HCC prognosis and can potentially serve as a candidate biosignature and as a therapeutic target for HCC.


Novel insights on thyroid-stimulating hormone receptor signal transduction.
The TSH receptor (TSHR) is a member of the glycoprotein hormone receptors, a subfamily of family A G protein-coupled receptors. The TSHR is of great importance for the growth and function of the thyroid gland. The TSHR and its endogenous ligand TSH are pivotal proteins with respect to a variety of physiological functions and malfunctions. The molecular events of TSHR regulation can be summarized as a process of signal transduction, including signal reception, conversion, and amplification. The steps during signal transduction from the extra- to the intracellular sites of the cell are not yet comprehensively understood. However, essential new insights have been achieved in recent years on the interrelated mechanisms at the extracellular region, the transmembrane domain, and intracellular components. This review contains a critical summary of available knowledge of the molecular mechanisms of signal transduction at the TSHR, for example, the key amino acids involved in hormone binding or in the structural conformational changes that lead to G protein activation or signaling regulation. Aspects of TSHR oligomerization, signaling promiscuity, signaling selectivity, phenotypes of genetic variations, and potential extrathyroidal receptor activity are also considered, because these are relevant to an understanding of the overall function of the TSHR, including physiological, pathophysiological, and pharmacological perspectives. Directions for future research are discussed.


Visco-Hyperelastic Model with Damage for Simulating Cyclic Thermoplastic Elastomers Behavior Applied to an Industrial Component.
In this work a nonlinear phenomenological visco-hyperelastic model including damage consideration is developed to simulate the behavior of Santoprene 101-73 material. This type of elastomeric material is widely used in the automotive and aeronautic sectors, as it has multiple advantages. However, there are still challenges in properly analyzing the mechanical phenomena that these materials exhibit. To simulate this kind of material a lot of theories have been exposed, but none of them have been endorsed unanimously. In this paper, a new model is presented based on the literature, and on experimental data. The test samples were extracted from an air intake duct component of an automotive engine. Inelastic phenomena such as hyperelasticity, viscoelasticity and damage are considered singularly in this model, thus modifying and improving some relevant models found in the literature. Optimization algorithms were used to find out the model parameter values that lead to the best fit of the experimental curves from the tests. An adequate fitting was obtained for the experimental results of a cyclic uniaxial loading of Santoprene 101-73.


A history of adolescent binge drinking in humans is associated with impaired self-movement cue processing on manipulatory scale navigation tasks.
A binge drinking pattern of alcohol consumption has been shown to have an impact on brain structures that continue to develop into late adolescence. These same brain structures have been implicated in processing self-movement cues. The current study applies an array of existing and novel kinematic analysis techniques to characterize performance on manipulatory scale tasks to assess spatial orientation deficits associated with a history of adolescent binge drinking. Using kinematic analysis techniques, a history of adolescent binge drinking in university students was associated with disruptions in outward segment movement organization and less accurate direction and distance estimation in a dead reckoning task. Similar disruptions in performance were found in the bead maze task in the first training block; however, no group differences were observed on subsequent blocks of place training. This is the first study to demonstrate a relationship between adolescent binge drinking in humans and impaired processing of self-movement cues. This pattern of results demonstrates the potential of manipulatory-scale spatial tasks to detect differences in information processing associated with factors known to disrupt normal central nervous system development.


Temperature Effects on Kinetic Parameters and Substrate Affinity of Cel7A Cellobiohydrolases.
We measured hydrolytic rates of four purified cellulases in small increments of temperature (10-50 °C) and substrate loads (0-100 g/liter) and analyzed the data by a steady state kinetic model that accounts for the processive mechanism. We used wild type cellobiohydrolases (Cel7A) from mesophilic Hypocrea jecorina and thermophilic Rasamsonia emersonii and two variants of these enzymes designed to elucidate the role of the carbohydrate binding module (CBM). We consistently found that the maximal rate increased strongly with temperature, whereas the affinity for the insoluble substrate decreased, and as a result, the effect of temperature depended strongly on the substrate load. Thus, temperature had little or no effect on the hydrolytic rate in dilute substrate suspensions, whereas strong temperature activation (Q10 values up to 2.6) was observed at saturating substrate loads. The CBM had a dual effect on the activity. On one hand, it diminished the tendency of heat-induced desorption, but on the other hand, it had a pronounced negative effect on the maximal rate, which was 2-fold larger in variants without CBM throughout the investigated temperature range. We conclude that although the CBM is beneficial for affinity it slows down the catalytic process. Cel7A from the thermophilic organism was moderately more activated by temperature than the mesophilic analog. This is in accord with general theories on enzyme temperature adaptation and possibly relevant information for the selection of technical cellulases.


Polymerase chain reaction method to detect canis materials by amplification of species-specific DNA fragment.
Rapid identification of mammal materials in feeding stuffs and food is essential for effective control of a potential source of pathogens, such as those that cause bovine spongiform encephalopathy. A convenient polymerase chain reaction (PCR)-based assay was developed for detection and identification of a canis-specific mitochondrial DNA sequence in foodstuffs and food. The amplified canis-specific PCR product was a 213 base pair band from the D-loop DNA fragment of mitochondria, a high copy gene which should improve the possibility of amplifying template molecules of adequate size among the degraded DNA fragments brought about by heat denaturation. The specificity of this method was confirmed by 8 canis blood DNA samples (from different breeds of dog) and 9 noncanis animal blood DNA samples (bovine, sheep, porcine, chicken, fish, donkey, rabbit, deer, horse). This method was able to detect the presence of canis material in foodstuffs and in food mixtures even when the concentration of canis-derived meat was reduced to 0.05%. Furthermore, it did not appear to be affected by prolonged heat treatment. This method was developed for detection of canis materials in feeding stuffs, and occasionally for medical jurisprudence detection of canis-derived materials.


CDC Grand Rounds: Newborn Screening for Hearing Loss and Critical Congenital Heart Disease.
Newborn screening is a public health program that benefits 4 million U.S. infants every year by enabling early detection of serious conditions, thus affording the opportunity for timely intervention to optimize outcomes (1). States and other U.S. jurisdictions decide whether and how to regulate newborn screening practices. Most newborn screening is done through laboratory analyses of dried bloodspot specimens collected from newborns. Point-of-care newborn screening is typically performed before discharge from the birthing facility. The Recommended Uniform Screening Panel includes two point-of-care conditions for newborn screening: hearing loss and critical congenital heart disease (CCHD). The objectives of point-of-care screening for these two conditions are early identification and intervention to improve neurodevelopment, most notably language and related skills among infants with permanent hearing loss, and to prevent death or severe disability resulting from delayed diagnosis of CCHD. Universal screening for hearing loss using otoacoustic emissions or automated auditory brainstem response was endorsed by the Joint Committee on Infant Hearing in 2000 and 2007* and was incorporated in the first Recommended Uniform Screening Panel in 2005. Screening for CCHD using pulse oximetry was recommended by the Advisory Committee on Heritable Disorders in Newborns and Children in 2010 based on an evidence review† and was added to the Recommended Uniform Screening Panel in 2011.§.


Comparative investigation of the desensitizing efficacy of a new dentifrice: a 14-day clinical study.
The effect on dentinal hypersensitivity from the use of a new formulation dentifrice containing 5.0% potassium nitrate and 0.454% stannous fluoride in a silica base (Colgate Sensitive Maximum Strength Toothpaste, Colgate-Palmolive Co.) over a 14-day period was compared to a commercially available, nondesensitizing control dentifrice (Colgate Winterfresh Gel, Colgate-Palmolive Co.). A total of 66 subjects were entered into and completed the study. They were stratified into two balanced groups according to their baseline mean tactile (Yeaple Probe) sensitivity scores and air blast (thermal) sensitivity scores. The two groups were randomly assigned to use either the new formulation dentifrice or the commercially available control dentifrice. Participants were instructed to brush their teeth twice daily (morning and evening) for 1 minute with their assigned dentifrice and a commercially available soft-bristled toothbrush. Dentinal hypersensitivity examinations (tactile and air blast sensitivity) were conducted at baseline and after 3, 7, 10, and 14 days' use of the products. All examinations were conducted by the same examiner. Participants who used the new formulation dentifrice containing potassium nitrate/stannous fluoride/silica demonstrated a statistically significant improvement in both tactile sensitivity and air blast sensitivity after 10 and 14 days' use of the dentifrice (p < 0.05), as compared to a commercially available control dentifrice. It was concluded that a new dentifrice formulation containing 5.0% potassium nitrate and 0.454% stannous fluoride in a silica base provided a statistically significant reduction in dentinal hypersensitivity after only 10 days, as compared to a commercially available nondesensitizing control dentifrice.


Predictors of mortality for patients with COVID-19 and large vessel occlusion.
This study evaluates the mortality risk of patients with emergent large vessel occlusion (ELVO) and COVID-19 during the pandemic. We performed a retrospective cohort study of two cohorts of consecutive patients with ELVO admitted to a quaternary hospital from March 1 to April 17, 2020. We abstracted data from electronic health records on baseline, biomarker profiles, key time points, quality measures and radiographic data. Of 179 patients admitted with ischemic stroke, 36 had ELVO. Patients with COVID-19 and ELVO had a higher risk of mortality during the pandemic versus patients without COVID-19 (OR 16.63, p = 0.004). An age-based sub-analysis showed in-hospital mortality in 60% of COVID-19 positive patients between 61-70 years-old, 66.7% in between 51-60 years-old, 50% in between 41-50 years-old and 33.3% in between 31-40 years old. Patients that presented with pulmonary symptoms at time of stroke presentation had 71.4% mortality rate. 27.3% of COVID-19 patients presenting with ELVO had a good outcome at discharge (mRS 0-2). Patients with a history of cigarette smoking (p = 0.003), elevated d-dimer (p = 0.007), failure to recanalize (p = 0.007), and elevated ferritin levels (p = 0.006) had an increased risk of mortality. Patients with COVID-19 and ELVO had a significantly higher risk for mortality compared to COVID-19 negative patients with ELVO. A small percentage of COVID-19 ELVO patients had good outcomes. Age greater than 60 and pulmonary symptoms at presentation have higher risk for mortality. Other risk factors for mortality were a history of cigarette smoking, elevated, failure to recanalize, elevated d-dimer and ferritin levels.


Note: amplification characteristics of all-normal-dispersion mode-locked Yb-doped fiber laser: influence of input pulse shape.
The amplification properties of the pulses at and after the nonlinear polarization rejection (NPR) port of an all-normal-dispersion Yb-doped mode-locked fiber laser are studied. The experimental results show that the spectra of the output pulses after the NPR port are considerably resistant to distortions on amplification and can be compressed in the femtosecond regime without any significant side-lobes and hence can serve as an excellent seed source for further power amplification. The experimental results are substantiated by numerical analysis of the amplifier setup.


The effects of supervisors' supportive role, job stress, and work-family conflicts on the nurses' attitudes.
This study developed and tested a research model that examined the effects of supervisor support (SUPPORT), work-family conflict (W-FCON), family-work conflict (F-WCON), and job stress (JSTRESS) on a number of selected consequences using data collected from nurses and nurse axillaries in Shiraz University of Medical Sciences hospitals in Fars province (south of Iran). The results demonstrated that W-FCON and F-WCON exerted a significant positive influence on JSTRESS. Contrary to the study hypothesis, the results did not provide any empirical support for the significant negative relationship between W-FCON, F-WCON, and JSTRESS with family satisfaction (FSAT). The findings further revealed that higher JSTRESS led to lower life satisfaction (LSAT). As expected, high levels of FSAT resulted in increased LSAT. However, this study failed to find significant negative relationships between conflicts in the work-family interface and LSAT. The results also revealed that JSTRESS was not significantly associated with LSAT. Consonant with the study hypotheses, W-FCON, F-WCON, and JSTRESS were found to be significant for turnover intentions, whereas LSAT did not. Implications for managers and future research directions are presented.


Mapping and modification of an antibody hapten binding site: a site-directed mutagenesis study of McPC603.
The quantitative contributions of various amino acid residues to hapten binding in the Fv fragment of the antibody McPC603 were investigated by site-directed mutagenesis. The three-dimensional structure of the Fab' fragment of McPC603 is known to atomic resolution. The haptens phosphocholine, choline sulfate, 3-(trimethylammonium)propane-1-sulfonate, 4-(trimethylammonium)butyric acid, and 4-(trimethyl-ammonium)butyric acid methyl ester were tested for binding. It was found that the phosphate group but not the sulfate and sulfonate groups, interacts with the hydroxyl group of Tyr33(h). The required positive charge for the binding of the phosphate must be contributed by Arg52(h); a lysine at this position or an additional positive charge at position 33(h) abolishes the binding to a phosphocholine affinity column. The interaction between Tyr100(l) and Glu35(h) was found to be essential and could not be functionally replaced by any other pair of residues tested. Binding of the quaternary ammonium ion needs a negative charge; it can reside in either Asp97(l) or Asp101(h), but both together prevent binding to the affinity column. These data may serve as the basis for the development of quantitative treatments of antigen-antibody interactions.


Medicare program; legislative changes concerning payment to hospitals for federal fiscal year 1990--HCFA. Notice of legislative changes.
This notice describes those portions of sections 6001, 6002, 6003(a), (b), and (d), 6004(a) and (b), 6021, 6101, 6110, and 6205(b) of the Omnibus Budget Reconciliation Act of 1989 that affect Federal fiscal year 1990 payments to prospective payment hospitals and hospitals excluded from the prospective payment system and that are self-implementing. The changes required by these sections affect the prospective payment rates, rural referral centers, payments for capital-related costs, periodic interim payments, cancer hospitals, and payments for nursing and allied health education.


[Effects of simulated grazing disturbance on soil water infiltration of biocrust slope in the hilly Loess Pla-teau, China].
Water is the key factor for vegetation restoration in the Loess Plateau region. Biological soil crust (biocrust), a widely distributed soil surface cover, significantly affects soil infiltration. Disturbance would affect soil water infiltration of biocrust. The effects of different intensities of disturbance on soil water infiltration of biocrust are still unclear. By simulating the trampling disturbance of sheep, we examined the effects of disturbance intensity (10%, 20%, 30%, and 40%) estimated by the coverage of broken biocrust on the surface cover of biocrust slope in the Hegou catchment of Wuqi County, Shaanxi Province. Soil water infiltration under different intensities were measured by the linear source infiltration method. The influence mechanisms of disturbance on soil water infiltration of biocrust slope were investigated with a structural equation model and correlation analysis. Results showed that compared to that without disturbance, the coverage of cyanobacterial crust was increased by 33.6% at 10% of disturbance intensity, no difference at 20% of disturbance intensity, and decreased by 36.1% and 75.0% at 30% and 40% of disturbance intensities, respectively. Litter coverage was increased by 34.3% under 40% of disturbance intensity, while that of other treatments were not changed. Surface roughness was decreased by 22.3%, 11.1%, and 5.6% at 10%, 20%, and 30% of disturbance intensities, respectively, but increased by 8.2% at the 40% of disturbance intensity. The initial infiltration rate at 40% of disturbance intensity was 77.1% higher than that without disturbance, while other treatments had no significant difference at the initial infiltration rate. Furthermore, distur-bance did not affect the stable and average infiltration rate. Our results confirmed that disturbance mainly promoted the initial infiltration by reducing the coverage of cyanobacterial crust, increasing the coverage of litter, and changing soil roughness. This study would provide scientific basis for the management of biocrust of rehabilitated lands in the Loess Plateau region.


Platelet-activating factor antagonists protect amyloid-beta damaged neurons from microglia-mediated death.
Neurons treated with sub-lethal concentrations of amyloid-beta1-42 developed phenotypic changes and selectively bound a CD14-IgG chimera; in co-cultures, microglia recognised and killed these amyloid-beta1-42 -damaged neurons. Pre-treatment with the platelet-activating factor (PAF) antagonists (Hexa-PAF, CV6209 or ginkgolide B) reduced CD14-IgG binding to amyloid-beta1-42 -damaged neurons, and the presence of PAF antagonists in co-cultures increased neuronal survival in a dose-dependant manner. PAF antagonists also protected neurons treated with HuPrP82-146, a peptide found in prion diseases. Second messenger studies demonstrated that the addition of PAF mimicked some of the effects of amyloid-beta1-42 on neurons. PAF-damaged neurons bound CD14-IgG, and PAF-damaged neurons were killed by microglia in a CD14-dependent process. Neuronal death was inversely related to both the concentration of PAF, and the number of microglia added. The effects of PAF were reduced by an antagonist of the prostanoid D receptor (BWA868C) indicating that neuronal damage induced by PAF is partly mediated by prostaglandins. These observations are compatible with the hypothesis that sub-lethal concentrations of amyloid-beta1-42 stimulate a cascade of second messengers including PAF and the prostaglandins. At nanomolar concentrations PAF induces a change in neuronal phenotype that activates microglia via the CD14 molecule, these activated microglia then kill the amyloid-beta1-42 damaged neurons.


Monoclonal antibody F1 binds to the kringle domain of factor XII and induces enhanced susceptibility for cleavage by kallikrein.
In a previous study we have shown that monoclonal antibody F1 (MoAb F1), directed against an epitope on the heavy chain of factor XII distinct from the binding site for anionic surfaces, is able to activate factor XII in plasma (Nuijens JH, et al: J Biol Chem 264; 12941, 1989). Here, we studied in detail the mechanism underlying the activation of factor XII by MoAb F1 using purified proteins. Formation of factor XIIa was assessed by measuring its amidolytic activity towards the chromogenic substrate H-D-Pro-Phe-Arg-pNA (S-2302) in the presence of soybean trypsin inhibitor and by assessing cleavage on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Upon incubation with MoAb F1 alone, factor XII was auto-activated in a time-dependent fashion, activation being maximal after 30 hours. Factor XII incubated in the absence of MoAb F1 was hardly activated by kallikrein, whereas in the presence of MoAb F1, but not in that of a control MoAb, the rate of factor XII activation by kallikrein was promoted at least 60-fold. Maximal activation of factor XII with kallikrein in the presence of MoAb F1 was reached within 1 hour. This effect of kallikrein on the cleavage of factor XII bound to MoAb F1 was specific because the fibrinolytic enzymes plasmin, urokinase, and tissue-type plasminogen activator could not substitute for kallikrein. Also, trypsin could easily activate factor XII, but in contrast to kallikrein, this activation was independent of MoAb F1. SDS-PAGE analysis showed that the appearance of amidolytic activity correlated well with cleavage of factor XII. MoAb F1-induced activation of factor XII in this purified system was not dependent on the presence of high-molecular-weight kininogen (HK), in contrast to the activation of the contact system in plasma by MoAb F1. Experiments with deletion mutants revealed that the epitopic region for MoAb F1 on factor XII is located on the kringle domain. Thus, this study shows that binding of ligands to the kringle domain, which does not contribute to the proposed binding site for negatively charged surfaces, may induce activation of factor XII. Therefore, these findings point to the existence of multiple mechanisms of activation of factor XII.


Nutrition assessment in patients undergoing liver transplant.
Liver transplantation (LT) is a major surgery performed on patients with end stage liver disease. Nutrition is an integral part of patient care, and protein-energy malnutrition is almost universally present in patients suffering from liver disease undergoing LT. Nutrition assessment of preliver transplant phase helps to make a good nutrition care plan for the patients. Nutrition status has been associated with various factors which are related to the success of liver transplant such as morbidity, mortality, and length of hospital stay. To assess the nutritional status of preliver transplant patients, combinations of nutrition assessment methods should be used like subjective global assessment, Anthropometry mid arm-muscle circumference, Bioelectrical impedance analysis (BIA) and handgrip strength.


Bronchial blood flow reduction with positive end-expiratory pressure after acute lung injury in sheep.
Smoke inhalation increases bronchial blood flow (Qbr) and produces edema of the airway system. This study investigates whether the increased Qbr seen 24 h after inhalation injury can be affected by mechanical ventilation with PEEP (5, 10, 15 cm H2O). Sheep (n = 8) previously prepared with cardiopulmonary catheters and ultrasonic transit time flow probes mounted around their bronchial arteries were insufflated with four sets of 12 breaths each of cotton smoke. Different levels of PEEP were added to the mechanical ventilation 24 h after injury; each PEEP level was applied for 45 min. There were significant increases in Qbr and lung lymph flow (QL) associated with a marked decrease in bronchial vascular resistance (BVR) 24 h after injury. However, no change was observed in mean arterial pressure (MAP) or cardiac index (CI). There was a substantial reduction in PaO2/FIO2 (P/F), which indicated a deterioration in arterial oxygenation. The application of varying levels of PEEP decreased Qbr (p less than .05) while BVR increased (p less than .05), but QL and P/F did not. CI and MAP were recorded. After removal of PEEP, none of the cardiopulmonary variables were significantly different from their postsmoke control values. These findings suggest that mechanical ventilation with PEEP markedly decreases the smoke-induced hyperemia edema frequently seen after inhalation injury without any significant alterations in MAP or CI.


Platelets: A possible glance into brain biological processes in schizophrenia.
Schizophrenia is a severe mental disorder, characterized by behavioral, emotional and cognitive disturbances, which commonly follows a chronic course. Diagnostic accuracy, management plans, treatment evaluation and prognosis are dependent on relatively subjective assessments. Despite extensive research and improvement in imaging technology, as well as modern genetic and molecular methodologies, the biological basis of this disease is still unclear. Therefore, there is a need for objective and valid biological markers. Platelets have often been used as a model in neurobiological research. The accessibility of platelets and their similarities with neurons turns them into an attractive candidate to search for biological markers for diagnosis and for unraveling pathophysiological processes relevant to the etiology of brain disorders, including schizophrenia. The present review addresses the main changes in platelet physiology observed in schizophrenia and its response to antipsychotic medication. We summarize numerous studies demonstrating impaired metabolism, uptake and receptor kinetics of schizophrenia-relevant neurotransmitters, abnormalities in membrane derived phospholipids and polyunsaturated fatty acids, as well as dysfunctions in the mitochondria. These changes fit with the various hypotheses raised for the etiology of schizophrenia, including the dopamine-glutamate hypothesis, the autoimmune hypothesis, the polyunsaturated fatty acid hypothesis and the impaired energy metabolism hypothesis. Despite extensive research in platelets, no conclusive reliable biomarker has been identified yet. This review suggests that the clinical heterogeneity and the biological complexity of schizophrenia lead to the inevitable conclusion that biomarkers will be identified only for subgroups characterized according to the different diagnostic criteria. Moreover, any biomarker would have to be an array of interrelated factors or even a set of several such arrays.


Morphogenesis of the glomerular filter: the synchronous assembly and maturation of two distinct extracellular matrices.
The morphogenesis of the glomerular filtration apparatus during pre- and postnatal development in the rodent involves the coordinated assembly of two closely apposed but morphologically different extracellular matrices, the glomerular capillary basement membrane and the mesangial matrix. The cellular origin of these matrices is known to be distinct and complex; however, the mechanisms by which these matrices are assembled during morphogenesis are not entirely understood. It has been shown that in the earliest stages of glomerular morphogenesis the nascent glomerular basement membrane exists as a four-layered structure, the product of both the visceral epithelium and capillary endothelium. During the latter stages of glomerular development, the quadrilaminar structure becomes a trilaminar basement membrane, the event thought to occur by fusion of closely apposed basement membrane layers. In subsequent stages of maturation and throughout the life of the animal, the visceral epithelial cells, which line the periphery of the glomerular capillary, are the primary source of newly synthesized basement membrane material. The mesangial matrix, which lacks the specific organization of a basement membrane, first occurs in the developing glomerulus as a diffuse matrix central to the developing glomerular capillaries. During glomerular maturation the mesangial matrix undergoes a compaction/arborization coincident with the ramification of the vascular histoarchitecture of the glomerular tuft. Recent advances in the cell biology of basement membrane now demonstrate that there is a divergence in isoforms of the molecules that comprise the glomerular capillary basement membrane and mesangial matrices during development, possibly coincidental with functional specialization during the process of glomerular maturation.


Dyslipidemia in obese cats.
Obesity is an important endocrine disorder in cats and is a risk factor for diabetes similar to humans. The goal of this study was to examine the effect of long-term obesity and different diets (high protein, and high carbohydrate supplemented with saturated fatty acids or n-3 polyunsaturated fatty acids) on plasma lipids in the fasted and fed states in 12 lean (LEAN) and 12 obese (OBESE) cats with ultracentrifugation, and nuclear magnetic resonance spectroscopy. OBESE had higher plasma non-esterified fatty acids and triglycerides, as well as very-low-density-lipoproteins (VLDL) consisting primarily of medium-sized particles. The concentration of low-density-lipoproteins (LDL) was comparable between the groups, although OBESE had mostly very small, whereas LEAN had mostly large particles. The concentration of high-density-lipoproteins (HDL) was lower in OBESE and consisted primarily of small particles. Plasma triglycerides, and triglycerides and cholesterol in all lipoproteins increased postprandially. Different diets had little effect on lipids. Our results show that long-term obese cats develop similar lipoprotein changes to humans, yet, hypertension and atherosclerosis have not been described in obese cats. This suggests that dyslipidemia alone is not sufficient to induce hypertension and atherosclerosis. Other anti-atherogenic factors may be present in the obese, dyslipidemic cat.


Organometallic clusters as precursors for metallic nanoparticles: effect of cluster size, ligand set, and decomposition method.
The pyrolysis of organometallic clusters containing osmium and/or ruthenium on a silica support leads to metallic nanoparticles in the 1 to 10 nm size range. The particle size obtained is correlated to the ligand set, and there are also indications that the shape of the cluster may have some effect on the shape of the nanoparticles obtained. In comparison, the size of nanoparticles obtained through thermolysis in a coordinating solvent are fairly independent of the nature of the organometallic precursor and tends to lead to aggregation of smaller, spherical nanoparticles into larger particles.


Photo-pollution disrupts reproductive homeostasis in female rats: The duration-dependent role of selenium administrations.
Although selenium is known to be essential for reproductive function, studies have indicated the adverse effect with its prolonged use. The present study investigated the duration-related effect of selenium administrations on reproductive hormones and estrous cycle indices in adult female Wistar rats exposed to a model of light pollution using altered photoperiod (AP). Ninety-six cyclic female Wistar rats displaying 4-5 days' estrous cycle length (ECL) and weighing 148-152 g were randomly divided into short and long experimental cohorts consisting of six groups each and spanning for 1 and 8 weeks, respectively. Each consisted of control, high selenium dose (HSE), low selenium dose (LSE), AP, AP + HSE, and AP + LSE. The rats were orally administered high dose (150 μg/kg) and low dose (100 μg/kg) of sodium selenite once per day. The estrous cycle indices were monitored. Plasma levels of follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E), progesterone (P), prolactin, E/P ratio, and histology of ovary and uterine horn were evaluated. The statistical analysis was performed using Statistical Package for the Social Sciences. In AP rats, HSE and LSE caused no significant effect on LH, E, P, and E/P ratio, ECL, estrus interval (EI), and estrous cycle ratio (ECR). The effect of HSE and LSE on LH, E, P, E/P ratio, and ECL showed no duration-dependent increase, but there was a duration-dependent increase in EI and ECR at low dose. The study indicated that administration of HSE of selenium improved reproductive function in photo-pollution-exposed rats irrespective of the duration of treatment.


Efficient diode-pumped mid-infrared emission from acetylene-filled hollow-core fiber.
We report 3.1-3.2 μm mid-infrared emission from acetylene-filled low loss antiresonant hollow-core fiber pumped with an amplified, modulated, narrowband, tunable 1.5 μm diode laser. The maximum power conversion efficiency of ~30%, with respect to the absorbed pump power, is obtained with a 10.5 m length of fiber at 0.7 mbar. The maximum efficiency with respect to the total incident pump power (~20%) and the minimum pump laser energy required (<50 nJ) are both improved compared to similar work reported previously using an optical parametric oscillator as a pump source. This paper provides an effective route to obtain compact mid-infrared fiber lasers.


Development of a monoclonal antibody, anti-6C2, which is involved in the interaction of CD4 T helper cells and activated B cells.
We have developed a mAb anti-6C2, by immunizing mice with T cell line derived from the Callithrix jacchus (common marmoset). Anti-6C2 is reactive with approximately 50% of unfractionated T cells, 50% of CD4+ cells, and 40% of CD8+ cells. Regarding CD4+ cells, anti-6C2-reactive cells substantially overlap with the CD29+CD45RO+ Th cell population. Moreover, anti-6C2 can divide these T cells into 6C2+ and 6C2- subpopulations. The CD4+CD45RO+6C2+ cells maximally respond to soluble Ag such as tetanus toxoid and provide strong helper function for PWM-driven B cell IgG synthesis. Most interestingly, anti-6C2 was also reactive against activated B cells but not resting B cells; furthermore, this epitope was inducible through activation of resting B cells or B cell line. Biochemical characterization showed that anti-6C2 precipitated two glycoproteins with the relative molecular weights of 180,000 and 95,000 from 125I-surface labeled cell lysate. Sequential immunoprecipitation studies demonstrated that these two glycoproteins were the lymphocyte function-associated antigen (LFA-1) Ag complex (CD11a/18). Significantly, although this antibody did not inhibit cytotoxic killer T cell responses and Ag-induced T cell proliferation as did conventional anti-LFA-1, it did inhibit PWM-driven B cell IgG synthesis. Because 6C2 expression was induced after B cell activation, the above results strongly suggest that the 6C2 molecule may play a role in the interaction of CD4 helper cells and activated B lymphocytes.


Editorial: taking FIT to the people: out of the office and into the mail.
Colorectal cancer (CRC) screening is most commonly performed in the United States using an opportunistic approach: patients coming to a physician's office for other unrelated reasons are offered screening with either fecal occult blood tests or, more commonly, a referral for colonoscopy. This approach has been effective to a point. CRC screening rates are increasing, but are still suboptimal and vary across different regions of the United States. Mailed fecal immunochemical test (FIT) outreach has the potential to allow more consistent CRC screening, by moving beyond opportunistic, office visit-based screening, to an organized approach. The study by van Roon et al. in this issue of the American Journal of Gastroenterology demonstrates that mailing FIT collection devices will not result in decreased sensitivity for 10-14 days following the specimen collection.


Psychological distress in patients with pancreatic cancer--an understudied group.
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, unsuccessful in significantly improving 5-year survival. A diagnosis of pancreatic cancer may be associated with increased psychological distress, yet remarkably little is known about the degree of psychological distress experienced by these patients at the time of diagnosis and treatment. In a cross-sectional study, 304 patients with pancreatic cancer and 7749 patients with other cancer diagnoses completed the Brief Symptom Inventory (BSI) or the Brief Symptom Inventory-Shortened Version (BSI-18) and the Problem Common Checklist (PCL) during outpatient registration. Sociodemographic characteristics were collected from patients' clinical files. A higher percentage of pancreatic cancer patients reported elevated distress across each subscale of the BSI and BSI-18 when compared with those diagnosed with other cancer diagnoses as a group. The most notable difference was established on the depression subscale, with 28.8% of pancreatic patients reporting elevated depression compared with 18.5% of other cancer diagnoses. In pancreatic patients, a significant difference was also found in the percentage of males endorsing high depression levels when compared with females (34.0 vs 22.6%, p<0.05). Pancreatic cancer patients demonstrate elevated levels of psychological distress. This should alert providers to be vigilant in evaluating patients for distress and to provide appropriate referrals. The endorsement of fatigue and pain, along with the observed gender differences, suggest that early distress management interventions may need to include components targeted to these issues.


Kindergarten-aged children's reactions to an emotionally charged naturalistic event: relations between cognitions, self-reported emotions, and emotional behaviour.
Relations between kindergarten-aged children's cognitions, self-reported emotions, and expressive behaviour regarding an emotion-eliciting event were examined by investigating 32 Dutch children's reactions to meeting "Sinterklaas", who they think brings presents for children, but who might also punish them. Measures included cognitions about Sinterklaas, emotion self-reports, and expressive behaviour when meeting Sinterklaas. Girls', but not boys', self-reports were related to their expressive behaviour. Boys' cognitions were not related to their emotions, whereas girls' cognitions and emotions were related inversely. That is, girls who reported the most positive cognitions about Sinterklaas showed the most, rather than the least, fear.


Morphine elimination and hepatic blood flow--a study in patients with portal hypertension.
To investigate the influence of changes in portal venous blood flow on the clearance of morphine, the elimination of a single intravenous dose of morphine sulphate was studied in twelve patients with periportal fibrosis undergoing distal splenorenal shunt for portal hypertension. All patients had almost normal preoperative liver function. Six patients (Group A) received morphine after induction of anesthesia but before surgery; a further six patients (Group B) received morphine after completion of the splenorenal shunt and removal of all vascular clamps. Blood was sampled for 24 hours after morphine administration and analysed for plasma morphine concentration using high performance liquid chromatography. The maximum concentration of morphine was significantly greater in those patients in Group B who received morphine after the shunt (P < .002). Clearance of morphine during the operation was also significantly reduced in these patients compared with the initial clearance (before release of the clamps) in Group A (P < .004). As a consequence of these changes the AUC was greater in this group (P < 0.004). However, there were no differences with the elimination rates after surgery had finished. The results suggest that in individuals with normal liver function, the clearance of morphine is dependent on hepatic blood flow.


Renin-angiotensin system inhibition improves coronary flow reserve in hypertension.
Angiotensin II not only elevates arterial pressure, it adversely alters hemodynamics and cardiovascular structure and exacerbates the course of hypertensive disease. Alterations in coronary hemodynamics, including reductions in coronary blood flow and flow reserve, reflect the pathophysiology of arteriolar disease and associated endothelial dysfunction thereby promoting coronary insufficiency and increasing overall cardiovascular risk. In spontaneously hypertensive rats, coronary flow reserve, the difference between basal coronary blood flow and the flow achieved during maximal coronary vasodilation achieved by physiological or pharmacological interventions, is drastically impaired at rest; however, it can be improved significantly by pharmacological agents that inhibit the renin-angiotensin system, alone or in combination. The combination of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin-II (type 1) receptor blocker, in equidepressor doses, markedly improved coronary flow reserve to levels seen in normotensive Wistar Kyoto rats after 12 weeks of treatment, while diminishing cardiovascular mass and improving systemic hemodynamics and ventricular metabolic demands. These findings suggest the potential merits for clinical studies employing the combination of ACE inhibitor and angiotensin receptor blocker therapy in patients with hypertension and hypertensive heart disease.


[Cytokeratin expression in fetal lung--immunohistochemical studies].
This paper is to give information about the pattern of expression of cytokeratin in bronchial mucosa, alveolar epithelium, lung stroma and pleura during the prenatal development of the lung. Our immunohistochemical investigations occurred in the lung of a 6 week old embryo and in 21 lungs of intrauterine died fetuses from the 12th to the 36th week of gestation according to the modified avidin-biotin-method. Findings of investigations will be compared with expression patterns in tumors and normal lungs of adults. In summary the investigations showed the following results: 1. Immunohistochemically in fetal lungs proteins are demonstrable that are used in the pathology of adults as markers for the histogenetic differentiation of various cell forms. 2. An expression of cytokeratins we could constantly prove in epithelial cells of fetal lungs after the 6th week of gestation. 3. Cytokeratins are mostly found at the cell membranes. 4. With increasing differentiation in direction to alveolar epithelium changes the composition of cytokeratin in the cells. 5. Cells of the pleura mesothelium are expressing cytokeratins in a pattern similar to that of bronchiolar epithelium. All in all the pattern of antigenic expression in fetal lungs considerably assimilates to that in adult lungs during the fetal lung development.


Clinical use of the autism diagnostic observation schedule-second edition with children who are deaf.
The Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was administered to eight children who are deaf and who are native American Sign Language (ASL) users with previous autism spectrum disorder (ASD) diagnosis. Classification on two different module selection criteria was compared based on: (1) standardized administration rules (signs not counted as equivalent to words) and (2) commonly utilized clinical administration (sign language complexity treated equivalently to spoken language complexity). Differential module selection resulted in discrepant classification in five of the eight cases (63%) and suggests that ADOS-2 via standardized test administration may result in a failure to identify autism among children who are deaf with primary communication in ASL. Two of the eight children (25%) did not exceed the cutoff for an ASD classification on either module administered despite previous ASD diagnosis. Overall results suggest that caution should be used when utilizing the ADOS-2 with children who are deaf who primarily communicate using ASL.


Social and land use composition determinants of health: variability in health indicators.
Previous studies have shown that a community's socioeconomic status has a significant impact on its residents' health, and that vulnerability in deprived populations expresses itself as variability in health outcomes. The current study adds to this ecological research approach the notion that underlying community vulnerabilities are also related to the physical environment and population growth of a locality. The paper explores the variability in various health indicators in 252 localities in Israel as a function of the localities' socioeconomic status, population growth, and land use composition measures. The results indicate that a locality's socioeconomic status and its land use composition are both strongly associated with various health outcomes and their variability. These findings are of particular interest in light of the fact that the results were obtained from a country with a universal healthcare system.


Piezoelectric Mechanism and a Compliant Film to Effectively Suppress Dendrite Growth.
We show a piezoelectric mechanism that effectively suppresses dendrite growth using a compliant piezoelectric film as a separator or coating. When an electrode surface starts to lose stability upon lithium deposition, any protrusion causes film stretching, generating a local piezoelectric overpotential that suppresses deposition on the protrusion. Lithium ions thus spontaneously deposit to a flat surface. By proposing a theory that couples electrochemistry and piezoelectricity, we quantify the suppression effect and growth morphology. We find that the dendrite-suppression capability is over 5 × 105 stronger than the limit of mechanical blocking by any separators or solid-state electrolytes. Surprisingly, the mechanism ensures deposition to form a flat surface even if the initial substrate surface has significant protrusions, suggesting its robustness and effectiveness against manufacturing defects. We show that the mechanism is so strong that even a weak piezoelectric material is highly effective, opening up a wide range of materials.


The use of mebendazole in the treatment of filariases due to Loa loa and Mansonella perstans.
Patients harbouring Loa loa and/or Mansonella perstans infections, or presenting typical filarial symptomatology, were treated with mebendazole, a drug shown to be efficient in other parasitoses. Of the patients who took the drug during 21 days and provided regular blood samples, 84% showed a significant decrease in their L. loa microfilaraemia and 100% in their M. perstans microfilaraemia, with a concomitant improvement in the clinical manifestations and no side reaction to drug administration. Additionally, the long-lasting effect of the drug (up to day 200 in some cases) may suggest a positive action on the adult worm. Mebendazole may consequently be regarded as a safer alternative to diethylcarbamazine for the treatment of these two parasitoses.


The lines are open: An artist's experience of working with dementia research.
This paper offers a first-hand account from a visual artist working with people living with a rare dementia. It explores the processes and motivations involved in situating an individual artistic practice in the field of dementia research. The paper discusses the potential role of creative art-making for neuropsychological testing and some of the complexities of interpretation that this involves. This account also highlights the ways in which working with people with dementia can be personally and artistically transformative.


Crossbow suicide: mechanisms of injury and neuropathologic findings.
Crossbow injuries are rarely reported events in modern times. Two cases of death due to self-inflicted crossbow injuries to the head are reported in 2 men aged 18 and 27 years, respectively. Despite relatively low velocity and concussive force, the sharpness and propulsion force of crossbow bolts may be sufficient to enable penetration of the skull at short range. Due to the relatively low concussive force of the crossbow bolt, however, death may not be instantaneous but may occur from intraparenchymal cerebral damage sometime thereafter. Detailed neuropathologic evaluation of such cases may therefore demonstrate "red cell" hypoxic injury, as well as axonal injury, not limited to the region of the missile tract, but widely distributed, even to the point of extensive brain stem involvement. These changes may result from primary mechanical deformation at the time of injury, from secondary hypoxic damage, or from a combination of both factors. Immunohistochemical staining of brains for amyloid precursor protein to delineate more clearly the pattern of axonal damage may assist in determining the extent of injury in such cases.


Complementary therapy for induction of labour.
Midwives at West Middlesex hospital (WMUH) offer complementary therapies as part of antenatal care. Aromatherapy and reflex zone therapy (also known as 'reflexology', a system of using touch on areas of the feet that stimulate parts of the body) are offered to induce spontaneous labour for women with low risk pregnancies once post dates, reducing the need for medical induction of labour (IOL) and intervention and reducing the cost to the NHS. This paper discusses how this service was implemented and developed, and the audit results and feedback from women and midwives.


CO2 sensing by connexin26 and its role in the control of breathing.
Breathing is essential to provide the O2 required for metabolism and to remove its inevitable CO2 by-product. The rate and depth of breathing is controlled to regulate the excretion of CO2 to maintain the pH of arterial blood at physiological values. A widespread consensus is that chemosensory cells in the carotid body and brainstem measure blood and tissue pH and adjust the rate of breathing to ensure its homeostatic regulation. In this review, I shall consider the evidence that underlies this consensus and highlight historical data indicating that direct sensing of CO2 also plays a significant role in the regulation of breathing. I shall then review work from my laboratory that provides a molecular mechanism for the direct detection of CO2 via the gap junction protein connexin26 (Cx26) and demonstrates the contribution of this mechanism to the chemosensory regulation of breathing. As there are many pathological mutations of Cx26 in humans, I shall discuss which of these alter the CO2 sensitivity of Cx26 and the extent to which these mutations could affect human breathing. I finish by discussing the evolution of the CO2 sensitivity of Cx26 and its link to the evolution of amniotes.


Postmenopausal Chinese-Singaporean Women Have a Higher Ratio of Visceral to Subcutaneous Adipose Tissue Volume than Caucasian Women of the Same Age and BMI.
Central fat accumulation is a significant determinant of cardio-metabolic health risk, known to differ between ethnically distinct human populations. Despite evidence for preferential central adiposity in Asian populations, the proportional distribution between the subcutaneous and visceral compartments in Chinese postmenopausal women has not been thoroughly investigated. For this analysis, volumetrically quantified subcutaneous and visceral adipose tissue (SAT, VAT) in the pelvic and abdominal regions of postmenopausal Asian (Chinese-Singaporean) and Caucasian (German) women matched for age and Body Mass Index (BMI) was undertaken, to examine such differences between the two groups. Volumes were calculated from segmentations of magnetic resonance imaging datasets of the abdomen and pelvis. Despite SAT, VAT, and the corresponding total adipose tissue (TAT) being similar between the groups, VAT/SAT and VAT/TAT were higher in the Asian group (by 24.5% and 18.2%, respectively, each p = 0.02). Further, VAT/SAT and VAT/TAT were positively correlated with BMI in the Caucasian group only (p = 0.02 and p = 0.01, respectively). We concluded that VAT is proportionally higher in the non-obese Asian women, compared to the Caucasian women of matched age and BMI. This conclusion is in agreement with existing literature showing higher abdominal adiposity in Asian populations. Additionally, in the Asian group, BMI did not correlate with visceral adiposity on a significant level. Further analysis is required to examine the extent to which this increased VAT may impact cardio-metabolic health. There is, however, a need to emphasize healthy lifestyle behaviors in non-obese post-menopausal women of Chinese ancestry.


Amino Acid Cross-Linked Graphene Oxide Membranes for Metal Ions Permeation, Insertion and Antibacterial Properties.
Graphene oxide (GO) and its composite membranes have exhibited great potential for application in water purification and desalination. This article reports that a novel graphene oxide membrane (GOM) of ~5 µm thickness was fabricated onto a nylon membrane by vacuum filtration and cross-linked by amino acids (L-alanine, L-phenylalanine, and serine). The GOM cross-linked by amino acids (GOM-A) exhibits excellent stability, high water flux, and high rejection to metal ions. The rejection coefficients to alkali and alkaline earth metal ions through GOM-A were over 94% and 96%, respectively. The rejection coefficients decreased with an increasing H+ concentration. Metal ions (K+, Ca2+, and Fe3+) can be inserted into GOM-A layers, which enlarges the interlayer spacing of GOM-A and neutralizes the electronegativity of the membrane, resulting in the decease in the rejection coefficients to metal ions. Meanwhile, GOM-A showed quite high antibacterial efficiency against E. coli. With the excellent performance as described above, GOM-A could be used to purify and desalt water.


ADHD: a psychological response to an evolving concept. (Report of a Working Party of the British Psychological Society).
The British Psychological Society is the only national organization of psychologists within the United Kingdom representing all aspects of psychology and all subspecialisms within psychology. It is both a learned scientific society and a professional association. To address the concept of attention-deficit/hyperactivity disorder (ADHD), the Professional Affairs Board of the Society convened a Working Party, consisting of individuals nominated by subsystems of the Society because of their recognized professional and academic expertise. They covered a range of specialisms, including educational, clinical, criminological, neurological, and cognitive psychology. A report by the Working Party was published in September 1996. It had two main aims: first, to outline the research that was relevant to current understanding of the notion of ADHD from an historical, psychological, and biological perspective, and, second, to consider implications for practice in the light of the information obtained. The focus was predominantly on children, although it was recognized that problems could persist into adulthood. The intention was to write a report for professionals that also would be accessible to a wider audience. This article is a highly abridged version of the report. It omits the references to research reviews and research studies contained in the full account. Selected extracts are included in order to justify the conclusions and the recommendations that are made and to inform a North American audience of developments in the United Kingdom.


[The evolution of teaching education in the health area].
To evaluate the performance through time of the Centro de Investigación Educativa y Formación Docente (Educational Research and Teaching Education Center) at the Instituto Mexicano del Seguro Social (Mexican Institute of Social Security), Nuevo León Office using as an indicator the ability for critical reading of theoretical texts of education. A comparative cross-sectional study was made among professors with and without teaching education, as well as among the several generations of professors that took teaching education courses at the Centro de Investigación Educativa y Formación Docente. A previously validated instrument was used to measure the ability for critical reading. It was applied to 358 professors, 107 with teaching education at the Centro de Investigación Educativa y Formación Docente in Monterrey and 251 without teaching education, at the IMSS Nuevo León Office. It was found that the previous teaching education constitutes a "positive risk" with an odds ratio of 17.66 (CI 9.02-34.12). Statistically significant differences were also found between not educated professors (median of 15) and educated professors (median of 35). In the scale, the grades at random and very low predominated in not educated professors, while the educated ones were located in the low and average. Professors at the Centro de Investigación Educativa y Formación Docente are improving their teaching labor using research as a means of self-criticism.