Differential regulation in the heart of mitochondrial carnitine palmitoyltransferase-I muscle and liver isoforms.
Carnitine palmitoyltransferase-I (CPT-I) plays a crucial role in regulating cardiac fatty acid oxidation which provides the primary source of energy for cardiac muscle contraction. CPT-I catalyzes the transfer of long chain fatty acids into mitochondria and is recognized as the primary rate controlling step in fatty acid oxidation. Molecular cloning techniques have demonstrated that two CPT-I isoforms exist as genes encoding the 'muscle' and 'liver' enzymes. Regulation of fatty acid oxidation rates depends on both short-term regulation of enzyme activity and long-term regulation of enzyme synthesis. Most early investigations into metabolic control of fatty acid oxidation at the CPT-I step concentrated on the hepatic enzyme which can be inhibited by malonyl-CoA and can undergo dramatic amplification or reduction of its sensitivity to inhibition by malonyl-CoA. The muscle CPT-I is inherently more sensitive to malonyl-CoA inhibition but has not been found to undergo any alteration of its sensitivity. Short-term control of activity of muscle CPT-I is apparently regulated by malonyl-CoA concentration in response to fuel supply (glucose, lactate, pyruvate and ketone bodies). The liver isoform is the only CPT-I enzyme present in the mitochondria of liver, kidney, brain and most other tissues while muscle CPT-I is the sole isoform expressed in skeletal muscle as well as white and brown adipocytes. The heart is unique in that it contains both muscle and liver isoforms. Liver CPT-I is highly expressed in the fetal heart, but at birth its activity begins to decline whereas the muscle isoform, which is very low at birth, becomes the predominant enzyme during postnatal development. In this paper, the differential regulation of the two CPT-I isoforms at the protein and the gene level will be discussed.


Genetic Variation in Insect Vectors: Death of Typology?
The issue of typological versus population thinking in biology is briefly introduced and defined. It is then emphasized how population thinking is most relevant and useful in vector biology. Three points are made: (1) Vectors, as they exist in nature, are genetically very heterogeneous. (2) Four examples of how this is relevant in vector biology research are presented: Understanding variation in vector competence, GWAS, identifying the origin of new introductions of invasive species, and resistance to inbreeding. (3) The existence of high levels of vector genetic heterogeneity can lead to failure of some approaches to vector control, e.g., use of insecticides and release of sterile males (SIT). On the other hand, vector genetic heterogeneity can be harnessed in a vector control program based on selection for refractoriness.


Characterization of serum biomarkers for detection of early stage ovarian cancer.
We have previously reported the identification of three ovarian cancer biomarker panels comprised of SELDI-TOF-MS peaks representing 14 differentially expressed serum proteins for the diagnosis of ovarian cancer. Using micro-LC-MS/MS, we identified five m/z peaks as transthyretin (TTR 13.9 kDa, TTR fragment 12.9 kDa), beta-hemoglobin (Hb, 15.9 kDa), apolipoprotein AI (ApoAI, 28 kDa) and transferrin (TF, 79 kDa). Western and/or ELISA methods confirmed the differential expression of TTR, Hb, and TF, and multivariate analyses resulted in improving the detection of early stage ovarian tumors (low malignant potential and malignant; receiver operating characteristic, ROC 0.933) as compared to cancer antigen CA125 alone (ROC 0.833). Interestingly, when CA125 was included with our markers in the multivariate analysis, the ROC increased to 0.959. Furthermore, multivariate analysis with only the mucinous subtype of early stage ovarian tumors, showed our markers to greatly improve the detection of disease (ROC 0.959) as compared to CA125 alone (ROC 0.613). Interestingly, the combination of CA125 with our markers did not seem to further improve the detection of mucinous tumors (ROC 0.955). We conclude that TTR, Hb, ApoAI and TF, when combined with CA125 should significantly improve the detection of early stage ovarian cancer.


Comparing audiological test results obtained from a sound processor attached to a Softband with direct and magnetic passive bone conduction hearing implant systems.
The aim of this study was to compare audiological test results obtained from a sound processor (SP) attached to a Softband with those obtained from direct (abutment connection) bone conduction implant systems and magnetic passive bone conduction implant systems with different magnet strengths on patients implanted at our clinic. Twenty-four patients who were implanted with either an abutment or magnetic bone conduction implant system between January 2012 and December 2014 were analyzed for hearing results, such as free-field hearing thresholds, direct bone conduction hearing thresholds, and speech discrimination scores with aided and unaided conditions Both magnetic and direct osseointegrated bone conduction implant systems, as well as the Softband system, provide good hearing outcomes when compared with unaided performance; however, the abutment connection system gives better hearing thresholds in the higher frequencies. No significant difference in hearing gain was found between the Softband system, magnet 5, and magnet used by the patient. Magnetic and direct bone conduction hearing implant systems are both effective for rehabilitation of conductive and mixed hearing loss when conventional hearing aids cannot be used. However, patients with high-frequency hearing loss may be better suited to an abutment connection system if they are not satisfied with high-frequency hearing gains provided via the trial Softband system preoperatively and should be counseled accordingly.


Drug-drug interactions: antiretroviral drugs and recreational drugs.
With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.


The impact of dreams of the deceased on bereavement: a survey of hospice caregivers.
Many recently bereaved persons experience vivid and deeply meaningful dreams featuring the presence of the deceased that may reflect and impact the process of mourning. The present study surveyed 278 bereaved persons regarding their own perspective of the relationship between dreams and the mourning process. Fifty eight percent of respondents reported dreams of their deceased loved ones, with varying levels of frequency. Most participants reported that their dreams were either pleasant or both pleasant and disturbing, and few reported purely disturbing dreams. Prevalent dream themes included pleasant past memories or experiences, the deceased free of illness, memories of the deceased's illness or time of death, the deceased in the afterlife appearing comfortable and at peace, and the deceased communicating a message. These themes overlap significantly with previous models of bereavement dream content. Sixty percent of participants felt that their dreams impacted their bereavement process. Specific effects of the dreams on bereavement processes included increased acceptance of the loved one's death, comfort, spirituality, sadness, and quality of life, among others. These results support the theory that dreams of the deceased are highly prevalent among and often deeply meaningful for the bereaved. While many counselors are uncomfortable working with dreams in psychotherapy, the present study demonstrates their therapeutic relevance to the bereaved population and emphasizes the importance for grief counselors to increase their awareness, knowledge, and skills with regards to working with dreams.


Schwann cells depleted of galactocerebroside express myelin-associated glycoprotein and initiate but do not continue the process of myelination.
Two peripheral myelin components, galactocerebroside (GalC) and myelin-associated glycoprotein (MAG), are known to be expressed early in Schwann cell differentiation, prior to the formation of definitive myelin segments containing compacted membrane. To discern the relative roles of these myelin components, cultures of Schwann cells and dorsal root ganglion neurons were treated with antigalactocerebroside mAbs in order to remove GalC from the Schwann cell surface (Ranscht et al., 1987). In the continuous presence of anti-GalC antibodies and in a medium containing serum plus ascorbic acid, Schwann cells assemble a basal lamina and progress to the one:one stage of Schwann cell:axon interaction but do not differentiate further. Immunostaining with anti-MAG antibodies revealed that GalC-depleted Schwann cells expressed high levels of MAG. Double staining with anti-MAG and anti-P0 antibodies showed that there was essentially no P0 immunoreactivity in the same cells. In those Schwann cells that had attained a one:one association with large-diameter axons, the inner-axon-related cytoplasmic process had passed under the outer mesaxon but had not completed a full turn around the axon. The expression of MAG on the single cytoplasmic process apposed to the axon in Schwann cells depleted of GalC further implicates MAG in the initial envelopment of the axon during myelination.


Nitric oxide stimulates a large-conductance Ca-activated K+ channel in human skin fibroblasts through protein kinase G pathway.
In order to investigate the large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel and determine the effects of nitric oxide (NO) on the channel in human skin fibroblasts, we performed electrophysiological patch clamp recordings on 5th-passage cells of human genital skin cultures. The whole-cell outward K(+) current was increased with depolarization, and proved to be sensitive to NS1619 (a selective BK(Ca) channel activator) and iberiotoxin (a specific BK(Ca )channel inhibitor). The single-channel currents showed 226 pS of mean conductance in symmetrical K(+). Sodium nitroprusside (SNP; an NO donor) significantly increased the K(+) current amplitude in the whole-cell mode, and open probability of the channel (NPo) in the cell-attached mode, but not in the inside-out mode. S-nitroso-N-acetylpenicillamine (an NO donor) and 8-Br-cGMP (a membrane-permeant cGMP analogue) also increased the BK(Ca )channel activity. The stimulatory effect of SNP on BK(Ca) channels was inhibited by pretreatment with 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor), or KT5823 [a specific protein kinase G (PKG) inhibitor]. Cytoplasmic PKG also increased the channel activity in inside-out patches. In conclusion, the present data indicate that BK(Ca) channels constitute a significant fraction of K(+) current in human skin fibroblasts, and that NO increases NPo of BK(Ca) channels, which are mediated via the cGMP/PKG pathway, without direct effects on the channel.


Glomerular charge and size selectivity assessed by changes in salt intake in type 2 diabetic patients.
To evaluate glomerular charge selectivity in patients with type 2 diabetes, we studied changes in fractional clearance of proteins with different sizes and charges when patients were placed on two diets with different salt contents. Nineteen patients with type 2 diabetes and normoalbuminuria (< 20 micrograms/min, n = 8), microalbuminuria (20-100 micrograms/min, n = 7), or advanced albuminuria (> 100 micrograms/min, n = 4) were placed on a low-salt diet (85 mEq of sodium daily) or a high-salt diet (255 mEq of sodium daily) for 1 week, and then on the other diet, in random order. Fractional clearances of albumin and immunoglobulin G (IgG) were calculated on the last 3 days of each diet. In patients with normoalbuminuria, the high-salt diet increased the fractional clearance of IgG, which is electrically neutral, but the fractional clearance of albumin, which is anionic, was unaltered, suggesting that the pore charge of the glomerular barrier was unaffected. However, in patients with microalbuminuria, the high-salt diet increased the fractional clearances of IgG and albumin equally, indicating some neutralization of the pore charge. Fractional clearance of IgG in these first two groups was similar when salt intake was low, so pore size was the same in these groups. In patients with advanced albuminuria, fractional clearance of IgG was higher than in the other groups, indicating that size selectivity had worsened. In type 2 diabetic patients, charge selectivity is lost before size selectivity as diabetic nephropathy progresses.


Production of Human Cu,Zn SOD with Higher Activity and Lower Toxicity in E. coli via Mutation of Free Cysteine Residues.
Although, as an antioxidant enzyme, human Cu,Zn superoxide dismutase 1 (hSOD1) can mitigate damage to cell components caused by free radicals generated by aerobic metabolism, large-scale manufacturing and clinical use of hSOD1 are still limited by the challenge of rapid and inexpensive production of high-quality eukaryotic hSOD1 in recombinant forms. We have demonstrated previously that it is a promising strategy to increase the expression levels of soluble hSOD1 so as to increase hSOD1 yields in E. coli. In this study, a wild-type hSOD1 (wtSOD1) and three mutant SOD1s (mhSOD1s), in which free cysteines were substituted with serine, were constructed and their expression in soluble form was measured. Results show that the substitution of Cys111 (mhSOD1/C111S) increased the expression of soluble hSOD1 in E. coli whereas substitution of the internal Cys6 (mhSOD1/C6S) decreased it. Besides, raised levels of soluble expression led to an increase in hSOD1 yields. In addition, mhSOD1/C111S expressed at a higher soluble level showed lower toxicity and stronger whitening and antiradiation activities than those of wtSOD1. Taken together, our data demonstrate that C111S mutation in hSOD1 is an effective strategy to develop new SOD1-associated reagents and that mhSOD1/C111S is a satisfactory candidate for large-scale production.


Fifteen years' experience with the use of artificial chords for valve reconstruction in children.
To retrospectively review our experience with artificial chords in mitral and tricuspid reconstructive surgery in children. All consecutive paediatric (<18 years) patients who underwent mitral or tricuspid valve reconstruction with the use of artificial chords in our centre in the past 15 years were retrospectively analysed. Thirty-nine patients (age 3 days to 17 years) underwent reconstruction of the mitral (n = 27) or tricuspid (n = 12) valve using artificial chords. Mean number of chords was 3.5 ± 1.7. In 26 of 27 mitral valve patients, chords were placed on the anterior leaflet, in one on the posterior leaflet. In 10 of the 12 tricupid valve, patients chords were placed on the anterior leaflet and in 2 on the septal leaflet. All mitral patients underwent annuloplasty (10 bilateral Wooler-Kay and 17 rigid ring annuloplasty). Ten of the 12 tricuspid patients underwent annuloplasty (1 rigid ring and 9 commissural plication). Follow-up was after 8.7 ± 5.5 years. There was no early or late mortality. The actuarial freedom from reoperation rates at 1, 5 and 10 years were 95%, 91% and 81%, respectively. No reoperations occurred in the tricuspid group. In the mitral group, there were 2 early failures and 3 late reoperations due to mitral stenosis. Restricted leaflet motion probably caused by the artificial chords was seen in only 1 patient. Our data show that long-term durability of mitral and tricuspid valve reconstruction using artificial chords in children is good. Despite patient growth, restricted leaflet motion by the artificial chords does not seem to form a major problem.


Ethical issues and problems in clinical research.
In the paper some documents on clinical research have been presented. Declaration of Helsinki WHO documents are suggested as a basic papers in this field. Some "delicate" problems are pointed and discussed in question about placebo and "moral obligations".


Correlation of cerebral Near-infrared spectroscopy (cNIRS) and neurological markers in critically ill children.
To correlate regional brain saturations (RSO(2)) measured by cerebral Near-infrared spectroscopy (cNIRS) with serological markers indicative of neurological injury (neuron-specific enolase (NSE) and S100beta). Children with at least one organ failure who were undergoing cNIRS monitoring were eligible for enrollment, while children with hyperbilirubinemia and cyanotic heart disease were excluded. Children were further analyzed based on the presence of an acute neurological injury (defined as hypoxic/ischemic injury after cardiac arrest, status epilepticus, meningitis, encephalopathy) as well as survival. RSO(2) was measured continuously (every 30 s) and averages were obtained at 6 h and 24 h epochs prior to serum collection (E6 and E24, respectively). Serum was collected for NSE and S100beta, which were both determined by ELISA. Serum from children undergoing evaluation for fever in the Emergency department served as serological controls. Correlations were determined using the Pearson Product Moment Correlations. A total of 26 children underwent cNIRS monitoring for a total of 47 days. Overall NSE was greater in critically ill children compared to controls, as well as in all subsets of children analyzed (acute CNS injuries, no acute CNS injuries, survivors and non-survivors). S100beta tended to be greater in critically ill children, but this did not reach statistical significance. Average RSO(2) in E6 and E24 was 68.0% +/- 1.5 and 68.6% +/- 1.6, respectively, in a total of 131,036 measurements and E6 RSO(2) was strongly, negatively correlated with S100beta in children with acute neurological injuries. This is the first study to correlate averaged RSO(2) measured by cNIRS with neurological injury markers in critically ill children. We believe that this data can be used to establish thresholds for RSO(2) that can be tested in future trials to determine if this technology is predictive of long-term neurological outcome.


A survey of management practices that influence performance and welfare of dairy calves reared in southern Brazil.
Here we report dairy calf management practices used by 242 smallholder family farmers in the South of Brazil. Data were collected via a semi-structured questionnaire with farmers, inspection of the production environment and an in-depth interview with a sample of 26 farmers. Herds had an average of 22.3 lactating cows and an average milk production of 12.7 L/cow/day. Calves were dehorned in 98% of the farms, with a hot iron in 95%. Male calves were castrated in 71% of the farms; methods were surgery (68%), emasculator (29%), or rubber rings (3%). No pain control was used for these interventions. In 51% of the farms all newborn male calves were reared, sold or donated to others; in 35% all newborn males were killed on the farm. Calves were separated from the dam up to 12 h after birth in 78% of the farms, and left to nurse colostrum from the dam without intervention in 55% of the farms. The typical amount of milk fed to calves was 4 L/day until a median age of 75 days. In 40% of the farms milk was provided in a bucket, in 49% with bottles, and in 11% calves suckled from a cow. Solid feeding in the milk-feeding period started at a median age of 10 days. Calves were housed individually in 70% of the farms; in 81% of the farms calves were housed in indoor pens, in 6% in outdoor hutches and in 13% they were kept on pasture. Diarrhoea was reported as the main cause of calf mortality in 71% of the farms. Farmers kept no records of calf disease, mortality, or use of medicines. Changing the scenario identified in this survey is essential to support the sustainable development of dairy production, an activity of great economic and social relevance for the region.


Treatment of patients with unexplained infertility: gamete intrafallopian transfer (GIFT) versus tubal embryo transfer (TET).
This study compares the results of 65 cycles of gamete intrafallopian transfer (GIFT), and 19 cycles of tubal embryo transfer (TET) in couples with unexplained infertility (UI). Oocyte retrievals were carried out by laparoscopy in GIFT and transvaginally in TET, in which the embryos were transferred by laparoscopy into the fallopian tubes 48 hours later. The mean age, duration of infertility, serum estradiol levels on the day of human chorionic gonadotropin administration, number of large follicles (mean diameter greater than 10 mm) and the number of oocytes recovered were similar between these two groups. From the 65 GIFT cycles, 20 clinical pregnancies resulted (30.8%). From the 19 cycles of TET, 10 conceptions occurred (52.6%). The implantation and pregnancy rates after TET were higher than that after GIFT, but the differences were not statistically significant. The data suggest that GIFT has a similar success rate to TET in couples with UI.


[Prioritizing prescriptions in a ambulatory care setting: a tool to achieve appropriateness of care in public health management].
Waiting lists are one of the main Public Health issues within developed countries. To promote appropriateness about General Practitioners' (GPs) prescriptions, during 2009 the project "Priority setting in outpatient prescriptions" in Latium Region has been approved. Regional referees, Latium Public Health Agency managers and advisors, managers and advisors of three Local Public Health Units (LPHUs) within the Latium region and some voluntarily recruited General Practitioners (each one with more than 800 patients enrolled) were included in a team work with the duty to develop the project. During two selected months of 2010, 46 GPs have forwarded overall 2.229 medical prescriptions. The six most numerous prescriptions were picked out and analyzed by the team work. 42% of these prescriptions were identified as belonging to category D of the priority level--"standard", while 42% and 41% of prescriptions bore the expressions of "control" and "diagnostic purpose" respectively. Among these ones, 75% were represented by bilateral mammography, prescribed to women aged between 50 and 69 years: but for those people bilateral mammography is already provided free of charge within the regional program of breast cancer screening, making the routine prescription by their physician a useless duplication, unacceptable in a healthcare system of good quality. Therefore at the conclusion of the project, the team work suggests proper standards be applied by healthcare professionals and GPs to achieve a significant objective: mammography appropriateness prescriptions.


[Review of 105 cases of isolation of Rhodococcus equi in humans].
Rhodococcus equi (formerly Corynebacterium) has been long considered an exclusively zoopathogenic microbe causing mainly granulomatous pneumonias and lung abscesses in young foals. The aim of this paper was to analyse substantial features of R, equi infections hitherto reported in man. MEDLINE database was searched for relevant reports. When the original source was not obtained the data from reviews were employed. Together, 105 cases of R, equi infection in man were reported. Median age was 35 years with a range from 9 months to 83 years. The male: female ratio was 3.3. Lungs were involved in 72 cases (69%), extrapulmonary abscesses as the only symptom of infection were described in 9 cases, septic state in 7 cases. Clinical outcome was known in 98 cases, being fatal in 41 (42%). Therapy was mentioned in 70 reports, the most often used drugs being erythromycin (30 cases, 12 deaths), rifampicin (19 cases, 7 deaths) and vancomycin (18 cases, 6 deaths). R. equi was isolated from the sputum of 69% patients with the pulmonary involvement. Blood cultures were positive in 35% of cases. Out of total, 49% persons were HIV positive. Median age for HIV positive patients was 32 years with a range from 18 to 71 years, for HIV negative patients 52 years with a range from 9 months to 83 years. There were 97% males in the HIV positive group in contrast to 59% in the HIV negative group (p < 0.01). Lungs were involved in 90% of HIV positive and 48% of HIV negative cases (p < 0.01). Extrapulmonary abscesses as the only sign of infection were seen in 2% of HIV positive persons and in 15% of HIV negative ones (p < 0.05). Outcome was fatal for 60% of the HIV positive hosts and for 28% of the HIV negative individuals (p < 0.01). R. equi was isolated from the sputum of 80% pneumonic HIV positive patients and of 50% of pneumonic patients without HIV infection (p < 0.05). R. equi was detected in the blood of 67% of HIV positive patients and of 33% of HIV negative ones (p < 0.01). The analysis of published reports shows that whereas R. equi causes mainly pneumonia in persons with HIV infection, in HIV negative individuals extrapulmonary manifestations slightly prevail, most often abscesses, sepsis, eye involvement and wound infections.


Protective effects of scutellarin and breviscapine on brain and heart ischemia in rats.
Scutellarin is an active molecule existing in Erigeron breviscapus (vant.) Hand-Mazz. The present work was designed to study the antiischemic effects of scutellarin and its mixture with another substance, breviscapine, in male Sprague-Dawley (SD) rats. Ligature of left anterior descending arteries was performed to induce acute myocardial infarction (MI), and the middle cerebral artery occlusion was created to induce focal cerebral ischemia. The MI size was significantly reduced by scutellarin (15 and 50 mg/kg) but not by breviscapine (5 to 50 mg/kg); the effect of scutellarin on the anti-MI was dose-dependent. Compared with control group, scutellarin (50 mg/kg) reduced the myocardium cell apoptosis in MI rats. The two drugs together (5 to 50 mg/kg) significantly reduced infarction size in focal brain ischemic rats (P < 0.05). There were no significant differences among the 3 dosages in breviscapine-treated rats, and the effect of scutellarin on the anticerebral ischemia was dose-dependent. The results demonstrate that the protective effects of scutellarin on cardiovascular and cerebrovascular ischemia were better than its mixture, breviscapine, in rats.


Monitoring changes in fat-free mass in HIV-positive men with hypotestosteronemia and AIDS wasting syndrome treated with gonadal hormone replacement therapy.
To compare methods for assessing changes in body composition during gonadal hormone replacement therapy in a group of HIV-positive men with AIDS wasting syndrome. The study included a 21-day, double-blind, randomized, placebo-controlled inpatient intervention and a 12-week open-label intervention. The inpatient intervention included 18 men who were confined to a metabolic ward. Days 1-7 comprised weight stabilization and body composition measures followed by 14 days of nandrolone decanoate at either 65 or 195 mg weekly, or placebo, and repeat testing. The open-label intervention comprised 12 weeks of 200 mg nandrolone decanoate fortnightly with measurements of fat-free mass at 6 and 12 weeks. The inpatient intervention measured nitrogen balance from 24 h urine and fecal collections and fat-free mass by dual energy x-ray absorptiometry (DEXA), bioimpedance spectroscopy (BIS) and D2O dilution. Nitrogen balance was calculated as the difference between dietary intake and urinary and fecal nitrogen excretion. Nitrogen was converted to fat-free mass using the constant of 32.5 g. Repeated measures analysis of variance was used to determine which methods were significantly different from the reference nitrogen balance technique. Nitrogen accretion of lean tissue was 0.55 and 0.85 kg weekly for low and high-dose groups, respectively. Estimated nitrogen retention during the open-label study was 0.42 kg weekly. Body weight increased with the estimated lean tissue accretion. DEXA, BIS and D2O methods demonstrated improvements in fat-free mass, although the BIS estimate of fat-free mass most closely matched the results of the nitrogen retention method. DEXA, BIS and D2O techniques demonstrated increases in fat-free mass. The BIS method is less costly, more convenient to use, and had results that more closely matched those from nitrogen balance and retention methods. BIS may be the preferred method to monitor changes in fat-free mass in AIDS patients and patients with malnutrition.


Mineral, fiber, and total phenolic retention in eight fruits and vegetables: a comparison of refrigerated and frozen storage.
Minerals, total phenolics, and fiber were analyzed in several fruit and vegetable commodities to evaluate the differences between fresh and frozen produce. Magnesium, calcium, iron, zinc, and copper were evaluated in corn, carrots, broccoli, spinach, peas, green beans, strawberries, and blueberries. Each commodity was harvested fresh and split into two batches. Half of each commodity was kept fresh, and the other half was frozen. The nutrient content was analyzed over three storage times per treatment. The retention of nutrients was highly dependent on the commodity, but the majority of the commodities showed no significant difference between fresh and frozen for all analytes (p ≤ 0.05).


Solution-Processed Small-Molecule Bulk Heterojunctions: Leakage Currents and the Dewetting Issue for Inverted Solar Cells.
In organic photovoltaic (PV) devices based on solution-processed small molecules, we report here that the physicochemical properties of the substrate are critical for achieving high-performances organic solar cells. Three different substrates were tested: ITO coated with PSS, ZnO sol-gel, and ZnO nanoparticles. PV performances are found to be low when the ZnO nanoparticles layer is used. This performance loss is attributed to the formation of many dewetting points in the active layer, because of a relatively high roughness of the ZnO nanoparticles layer, compared to the other layers. We successfully circumvented this phenomenon by adding a small quantity of polystyrene (PS) in the active layer. The introduction of PS improves the quality of film forming and reduces the dark currents of solar cells. Using this method, high-efficiency devices were achieved, even in the case of substrates with higher roughness.


A Novel Rat Model of Orthodontic Tooth Movement Using Temporary Skeletal Anchorage Devices: 3D Finite Element Analysis and In Vivo Validation.
The aim of this animal study was to develop a model of orthodontic tooth movement using a microimplant as a TSAD in rodents. A finite element model of the TSAD in alveolar bone was built using μCT images of rat maxilla to determine the von Mises stresses and displacement in the alveolar bone surrounding the TSAD. For in vivo validation of the FE model, Sprague-Dawley rats (n = 25) were used and a Stryker 1.2 × 3 mm microimplant was inserted in the right maxilla and used to protract the right first permanent molar using a NiTi closed coil spring. Tooth movement measurements were taken at baseline, 4 and 8 weeks. At 8 weeks, animals were euthanized and tissues were analyzed by histology and EPMA. FE modeling showed maximum von Mises stress of 45 Mpa near the apex of TSAD but the average von Mises stress was under 25 Mpa. Appreciable tooth movement of 0.62 ± 0.04 mm at 4 weeks and 1.99 ± 0.14 mm at 8 weeks was obtained. Histological and EPMA results demonstrated no active bone remodeling around the TSAD at 8 weeks depicting good secondary stability. This study provided evidence that protracted tooth movement is achieved in small animals using TSADs.


Surface-enhanced Raman scattering chip for femtomolar detection of mercuric ion (II) by ligand exchange.
The chemical sensing for the convenient detection of mercuric ion (II) (Hg(2+)) have been widely explored with the use of various sensing materials and techniques. It still remains a challenge to achieve ultrasensitive but simple, rapid, and inexpensive detection to metal ions. Here we report a surface-enhanced Raman scattering (SERS) chip for the femtomolar (fM) detection of Hg(2+) by employing silver-coated gold nanoparticles (Au@Ag NPs) together with an organic ligand. 4,4'-Dipyridyl (Dpy) can control the aggregation of Au@Ag NPs via its dual interacting sites to Ag nanoshells to generate strong Raman hot spots and SERS readouts. However, the presence of Hg(2+) can inhibit the aggregation of Au@Ag NPs by the coordination with Dpy, and as a result the SERS signals of Dpy are quenched. On the basis of these findings, a SERS chip has been fabricated by the assembly of Au@Ag NPs on a piece of silicon wafer and the further modification with Dpy. The exchange of Dpy from the chip into the aqueous Hg(2+) droplet results in the quenching of Raman signals of Dpy, responding to 10 fM Hg(2+) that is about 6 orders of magnitude lower than the limit defined by the U.S. Environmental Protection Agency in drinkable water. Each test using the SERS chip only needs a droplet of 20 μL sample and is accomplished within ∼4 min. The SERS chip has also been applied to the quantification of Hg(2+) in milk, juice, and lake water.


UV radiation facilitates methotrexate resistance and amplification of the dihydrofolate reductase gene in cultured 3T6 mouse cells.
Pretreatment of 3T6 murine cells with the carcinogen UV radiation or N-acetoxy-N-acetylaminofluorene increased the number of methotrexate-resistant colonies. This carcinogen-induced enhancement was seen only at low toxicities. The enhancement was transient and was observed at its maximum when cells were subjected to methotrexate selection 12 to 24 h after treatment. The addition of a tumor-promoting agent, 12-O-tetradecanoylphorbol-13-acetate, during or after carcinogen treatment further enhanced this effect. A large proportion of the resistant colonies had an increase in the dihydrofolate reductase gene copy number and the relative proportions of colonies with amplified genes were similar, regardless of whether selected cells were untreated, treated with carcinogen, or treated with carcinogen plus promoter. We discuss some of the variables which both enhance the generation and improve the detection of methotrexate-resistant colonies, as well as certain implications of our results for the generation and mechanism of gene amplification.


GnRH antagonist in older IVF patients. Retrieval rates and clinical outcome.
To determine if the use of a midcycle GnRH antagonist provides better clinical outcomes and lower cancellation rates in in vitro fertilization (IVF). We examined all patients older than 40 years undergoing IVF-embryo transfer cycles between January 1999 and December 2000. Prior to June 2000, controlled ovarian stimulation in women > or = 40 years was performed with follicle stimulating hormone (FSH)/human menopausal gonadotropin (hMG) only and no GnRH agonist or antagonist (group I). After June 2000, following the release of Ganirelix in the U.S., all women > or = 40 years were stimulated with FSH/hMG + Ganirelix (group II). Outcomes of IVF cycles prior to Ganirelix were compared to results after its introduction. Cancellation rates were significantly lower in group II (16%) as compared to group I (67%) (P < .05). In patients with oocytes retrieved, group II had a significantly higher number of recovered oocytes (7.7 +/- 0.8 vs. 5.3 +/- 0.7, P < .05). However, the number of embryos transferred, cumulative embryo scores, implantation rates and ongoing pregnancy rates did not differ significantly between groups. Although our results are preliminary, the addition of GnRH antagonist avoids ovarian suppression at the start of controlled ovarian hyperstimulation and prevents the premature LH surge at midcycle. Thus, more patients attempting IVF undergo oocyte retrieval, although clinical outcomes may not necessarily be improved.


New insights into the photodissociation of methyl iodide at 193 nm: stereodynamics and product branching ratios.
The stereodynamics of methyl iodide photodissociation after excitation at 193 nm has been studied using a combination of slice imaging and resonance enhanced multiphoton ionization (REMPI) detection of the methyl and iodine products. A weak anisotropic ring appearing in the image corresponding to vibrationally excited CH3(ν1 = 1) confirms the production of ground state I((2)P3/2) atoms at this excitation wavelength as a signature of the predissociation channel reported previously [M. G. González et al., J. Chem. Phys., 2011, 135, 021102] tentatively assigned to the coupling between the B-band (3)R1 Rydberg state and the A-band (1)Q1 repulsive state. Direct REMPI detection of ground state iodine atoms indicates that most of the I((2)P3/2) species are produced in correlation with highly internally excited methyl radicals, in excellent agreement with the recent results of Xu and Pratt [Xu et al., J. Chem. Phys., 2013, 139, 214310; Xu et al., J. Phys. Chem. A, 2015, 119, 7548]. From the comparison between the CH3(ν) second order Dixon's bipolar moments β(2)(0)(20), β(0)(0)(22), β(2)(0)(02) and β(2)(0)(22) measured in this work and those reported previously for the B-band origin and the A-band, a general picture of the CH3I photodissociation stereodynamics in terms of different effects, such as the breakdown of the unique recoil direction (URD) approximation, the non-adiabatic curve crossings and the depolarization induced by the parent molecule rotation, is drawn.


Complex temporal response patterns with a simple retinal circuit.
The retina can respond to a wide array of features in the visual input. It was recently reported that the retina can even recognize complicated temporal input patterns and signal violations in the patterns. When a sequence of flashes was presented, ganglion cells exhibited a variety of firing profiles and many cells showed an "omitted stimulus response" (OSR), in which they fired strongly if a flash in the sequence was omitted. We examined the synaptic origins of the OSR by recording excitatory synaptic currents from ganglion cells in the salamander retina in response to periodic flash sequences. Consistent with previous spike recordings, ganglion cells exhibited an OSR in their current response and the OSR shifted in time with a change in flash frequency such that it could predict when the next flash should have occurred. Although the behavior may seem sophisticated, we show that a simple linear-nonlinear model with a spike threshold can account for the OSR in on ganglion cells and that the variety of complex firing profiles seen in other ganglion cells can be explained by adding contributions from the off pathway. We discuss the physiological and simulation results and their implications for understanding retinal mechanisms of visual information processing.


Large amplitude quantum mechanics in polyatomic hydrides. I. A particles-on-a-sphere model for XH(n).
A framework is presented for converged quantum mechanical calculations on large amplitude dynamics in polyatomic hydrides (XH(n)) based on a relatively simple, but computationally tractable, "particles-on-a-sphere" (POS) model for the intramolecular motion of the light atoms. The model assumes independent two-dimensional (2D) angular motion of H atoms imbedded on the surface of a sphere with an arbitrary interatomic angular potential. This assumption permits systematic evolution from "free rotor" to "tunneling" to "quasi-rigid" polyatomic molecule behavior for small, but finite, values of total angular momentum J. This work focuses on simple triatom (n=2) and tetratom (n=3) systems as a function of interatomic potential stiffness, with explicit consideration of H2O, NH3, and H3O+ as limiting test cases. The POS model also establishes the necessary mathematical groundwork for calculations on dynamically much more challenging XH(n) species with n>3 (e.g., models of CH5+) where such a reduced dimensionality approach offers prospects for being quantum mechanically tractable at low J values (i.e., J=0, 1, 2) characteristic of supersonic jet expansion conditions.


The SPIDER Embolic Protection Device performance evaluation in the carotid artery during percutaneous transluminal angioplasty and or stenting.
Recently completed studies have compared carotid endarterectomy with carotid artery stenting, a nonsurgical method of improving blood flow in the carotid arteries. Embolic protection devices can prevent particles dislodged during carotid artery stenting from causing stroke or death. An ev3 Inc.-sponsored trial (PROTECT) evaluated the performance requirements of the SPIDER Embolic Protection Device in the carotid artery for CE Marking. Patients who were candidates for percutaneous transluminal angioplasty (PTA) and or stenting were enrolled. Performance was assessed by determining the incidence of major adverse neurological events (MANE) through 30 days post-procedure in 74 patients, along with the successful placement and recovery rates of the filter. MANE was defined as stroke or death. There were a total of 5 MANE events reported in 5 patients, 1 major stroke and 4 minor strokes. There were no deaths. The total MANE event rate was 6.8% (5 of 73). The overall SAE rate was 8.2% (6 of 73). An SAE was defined as an event that resulted in the hospitalization or prolongation of hospitalization due to potential disability, or due to danger of life that resulted in an intervention or that was terminal. Technical success of the SPIDER device was defined as placement of the filter at the distal edge of the lesion in the carotid artery, placement of the recovery catheter and successful retrieval of the filter with the recovery catheter. An inability to place or retrieve the filter was concluded to be a system failure. The SPIDER device was successfully placed in the carotid artery and retrieved with an overall successful placement rate of 88.1% (74 of 84), and a retrieval rate of 98.6% (73 of 74). In conclusion, the PROTECT Trial demonstrated that the performance of the SPIDER device in the carotid artery complied with the relevant Product Directives for CE Marking. The incidence of MANE was low and comparable to what has been reported in recently published literature.


Scarring Airway Stenosis in Chinese Adults: Characteristics and Interventional Bronchoscopy Treatment.
Scarring airway stenosis is commonly seen in China as compared to other developed countries, due to the high prevalence of tuberculosis. Nowadays, interventional bronchoscopy treatment has been widely used to treat this disease in China. This study demonstrated the characteristics of scarring airway stenosis in Chinese adults and retrospectively evaluated the efficacy of interventional bronchoscopy treatment of this disease. Patients with scarring airway stenosis from 18 tertiary hospitals were enrolled between January 2013 and June 2016. The causes, site, and length of scarring airway stenosis were analyzed, and the efficacy of the interventional bronchoscopy treatment was evaluated. The final study cohort consisted of 392 patients. Endotracheobronchial tuberculosis (EBTB) was the most common cause of scarring airway stenosis (305/392, 77.8%) in Chinese adults with a high rate of incidence in young women. The left main bronchus was most susceptible to EBTB, and most posttuberculosis airway scarring stenosis length was 1.1-2.0 cm. The average clinical success rate of interventional bronchoscopy treatment for scarring airway stenosis in Chinese patients is 60.5%. The stent was inserted in 8.7% scarring airway stenosis in China. Scarring airway stenosis exhibits specific characteristics in Chinese patients. Interventional bronchoscopy is a useful and safe treatment method for the disease.


The effect of quadriceps contraction during weight-bearing on four patellar height indices.
The effect of weight-bearing on the height of the patellar using four radiological indices was studied in 25 healthy men using lateral radiographs of the knee in 30 degrees of flexion non-weight-bearing and weight-bearing. The position of the patella was quantified using the Insall-Salvati, the modified Insall-Salvati, the Blackburne-Peel and the Caton indices. The contraction of the quadriceps on weight-bearing resulted in statistically significant proximal displacement of the patella with all four indices studied. The mean Insall-Salvati index was 0.919 (SD 0.063) before and 1.109 (SD 0.042) after weight-bearing (p = 0.001), while the mean modified Insall-Salvati index was 0.734 (SD 0.039) before and 0.896 (SD 0.029) after weight-bearing (p = 0.041). Similarly, the Blackburne-Peel index was 0.691 (SD 0.09) before and 0.807 (SD 0.137) after weight-bearing (p = 0.012). The mean Caton index was 0.861 (SD 0.09) before and 0.976 (SD 0.144) after weight-bearing (p = 0.023). The effect of quadriceps contraction should be considered in clinical studies where the patellar position indices are reported.


In vitro assessment of the acid resistance of demineralized enamel irradiated with Er, Cr:YSGG and Nd:YAG lasers.
This study's purpose was to evaluate the acid resistance of demineralized enamel irradiated with high-intensity lasers. Enamel fragments were demineralized and treated as follows (N=10): Group 1-no treatment; Group 2-five percent sodium fluoride (NaF) varnish; Group 3-Er, Cr:YSGG laser (8.92 J/cm2, 0.5 W, 20 Hz, 30 seconds); Group 4-NaF and Er, Cr:YSGG laser; Group 5-Er, Cr:YSGG laser and NaF; Group 6-Nd:YAG laser (84.9 J/cm2, 0.5 W, 10 Hz, 30 seconds); Group 7-NaF and Nd:YAG laser; and Group 8-Nd:YAG laser and NaF. The samples were subjected to pH-cycling and assessed by microhardness (analysis of variance; α equals five percent) at different depths from the outer enamel surface. Samples were observed using polarized light microscopy (PLM) and scanning electron microscopy (SEM). There were no significant differences among the experimental groups in any of the subsurface layers evaluated. PLM observation revealed that the extent of demineralization of the irradiated samples was similar to the samples for Group 1 (control). SEM observation showed that irradiated surfaces were ablated and presented areas of melting. Laser irradiation, with or without applying five percent sodium fluoride, was not capable of increasing the enamel white spot lesions' acid resistance.


NMR solution structure of the RED subdomain of the Sleeping Beauty transposase.
DNA transposons can be employed for stable gene transfer in vertebrates. The Sleeping Beauty (SB) DNA transposon has been recently adapted for human application and is being evaluated in clinical trials, however its molecular mechanism is not clear. SB transposition is catalyzed by the transposase enzyme, which is a multi-domain protein containing the catalytic and the DNA-binding domains. The DNA-binding domain of the SB transposase contains two structurally independent subdomains, PAI and RED. Recently, the structures of the catalytic domain and the PAI subdomain have been determined, however no structural information on the RED subdomain and its interactions with DNA has been available. Here, we used NMR spectroscopy to determine the solution structure of the RED subdomain and characterize its interactions with the transposon DNA.


Corticotropin-releasing factor in humans. II. CRF stimulation in patients with diseases of the hypothalamo-pituitary-adrenal axis.
A stimulation test with 100 micrograms ovine or human corticotropin-releasing factor (CRF) is a useful diagnostic tool in diseases of the hypothalamo-pituitary-adrenal axis. No serious side effects were observed during the test procedure. The results showed that the CRF test is useful in making the differential diagnosis of established Cushing's syndrome (n = 42). The CRF test was also repeated after transsphenoidal surgery in 25 patients with Cushing's disease. Successfully operated patients exhibit no, blunted or normal adrenocorticotropic hormone (ACTH) responses to CRF (n = 15), whereas patients who did not show remission remained hyperresponsive (n = 10). In patients with autonomous adrenal cortisol secretion, the ACTH response to CRF was suppressed (n = 10). After surgery the ACTH response to CRF can already be demonstrated when cortisol levels are still undetectable. Pulsatile administration of CRF in one patient after unilateral adrenalectomy and another patient under corticoid therapy revealed that ACTH responses to CRF normalize rapidly but cannot be sustained if CRF administration is withdrawn, suggesting that the cause of adrenal failure after unilateral adrenalectomy for Cushing's syndrome or long-term corticoid therapy is due to hypothalamic CRF deficiency. The decrease of the ACTH responses to CRF in glucocorticoid-treated patients correlated directly to the daily corticoid dosage. Since the ACTH hyperresponse to CRF in 6 patients with Cushing's disease was also suppressed by short-term dexamethasone treatment, the pituitary level as target site for the acute feedback inhibition is also demonstrated. The evaluation of the CRF-induced ACTH response in patients with secondary adrenal failure without detectable pathology in the sella and suprasellar region (n = 6) enables the differentiation between hypothalamic and pituitary adrenal insufficiency. In patients with hypothalamic lesions the ACTH response to CRF was normal whereas insulin hypoglycemia failed to induce an ACTH rise.


Comparative effect of disopyramide and ethmozine in suppressing complex ventricular arrhythmias by use of a double-blind, placebo-controlled, longitudinal crossover design.
This placebo-controlled, double-blind, longitudinal crossover study compares the efficacy of disopyramide and ethmozine, a new investigational drug, in suppressing frequent (40 or more per hour) ventricular premature depolarizations (VPDs) in 27 patients completing a 37 day protocol. Although both drugs significantly reduced VPDs relative to placebo, ethmozine was a superior antiarrhythmic drug in ach9eving near-total abolition of VPDs (30% of patients), which was never observed during disopyramide dosing (p less than .05). At the 80% VPD reduction level, ethmozine was effective in 56% of all patients compared with an effectiveness in only 22% of patients during disopyramide therapy (p less than .05). The mean peak plasma level of ethmozine was 0.66 +/- 0.8 micrograms/ml, which significantly fell to a trough level of 0.1 +/- 0.08 micrograms/ml (p less than .001). Mean peak and trough plasma levels of disopyramide exhibited less fluctuation (2.6 +/- 0.9 micrograms/ml vs 2.2 +/- 0.9 micrograms/ml). Ethmozine had no effect on the QT interval, whereas disopyramide prolonged it significantly. Importantly, while disopyramide produced serious side effects in 30% of patients, ethmozine was well tolerated with no statistically significant side effects compared with placebo.


Spontaneous showering of tumor emboli in a patient with advanced primary lung cancer: a case report.
Extension of primary lung tumors into the left atrium via pulmonary veins is a well-documented phenomenon. Peripheral arterial embolism and cerebral embolism originating from a primary lung neoplasm are rare events. We report a case of simultaneous acute bilateral lower limb ischemia, bilateral renal infarction, splenic infarction and cerebral infarction as a result of multiple emboli originating from primary lung malignancy invasion of the left atrium. An emergent embolectomy revealed pathologic features of the extracted thrombus that were identical to the pulmonary neoplasm.


Rapid Communication: The relationship of enterocyte proliferation with intestinal morphology and nutrient digestibility in weaning piglets.
Understanding the regulatory mechanisms of intestinal morphology and function is essential for improving postweaning growth in pigs. The objective of this study was to identify the relationships of enterocyte proliferation with intestinal villus height, crypt depth, and nutrient digestibility in piglets. Sixty-four 21-d-old weaned piglets were used. Gastrointestinal cell proliferation was evaluated via Ki-67 immunohistochemistry. Villus height and crypt depth were measured using hematoxylin and eosin (H&E)-stained sections. The apparent total tract digestibility (ATTD) of CP and GE was determined by chemical analysis. The activities of lactase and sucrase were determined with commercial kits. Western blot was carried out to assess the expression of nutrient transporters. The number of Ki-67 positive cells was associated with villus height (r = 0.548, P < 0.001) and crypt depth (r = 0.759, P < 0.001) in the jejunum. The number of Ki-67 positive cells was also associated with the ATTD of CP (r = 0.715, P = 0.001). Furthermore, a positive relationship between Ki-67 positive cell populations and lactase activity (r = 0.559, P < 0.001) was observed. Additionally, the number of Ki-67 positive cells was associated with the protein expression levels of nutrient transporters PEPT1 (r = 0.511, P = 0.030) and SGLT1 (r = 0.601, P = 0.014). Weak relationships were found between Ki-67 positive cell numbers and the ATTD of GE (r = 0.401, P = 0.099) and the activity of sucrase (r = 0.313, P = 0.087). In conclusion, enterocyte proliferation was positively associated with intestinal villus height, crypt depth, and nutrient digestibility in weaning piglets. Our findings suggested that intestinal morphology and function can be improved by regulating epithelial cell proliferation in piglets.


Ancient DNA Reveals Late Pleistocene Existence of Ostriches in Indian Sub-Continent.
Ancient DNA (aDNA) analysis of extinct ratite species is of considerable interest as it provides important insights into their origin, evolution, paleogeographical distribution and vicariant speciation in congruence with continental drift theory. In this study, DNA hotspots were detected in fossilized eggshell fragments of ratites (dated ≥25000 years B.P. by radiocarbon dating) using confocal laser scanning microscopy (CLSM). DNA was isolated from five eggshell fragments and a 43 base pair (bp) sequence of a 16S rRNA mitochondrial-conserved region was successfully amplified and sequenced from one of the samples. Phylogenetic analysis of the DNA sequence revealed a 92% identity of the fossil eggshells to Struthio camelus and their position basal to other palaeognaths, consistent with the vicariant speciation model. Our study provides the first molecular evidence for the presence of ostriches in India, complementing the continental drift theory of biogeographical movement of ostriches in India, and opening up a new window into the evolutionary history of ratites.


Identification and analysis of the stigma and embryo sac-preferential/specific genes in rice pistils.
In rice, the pistil is the female reproductive organ, and it consists of two stigmas and an ovary. The stigma is capable of receiving pollen grains and guiding pollen tube growth. The ovary holds the embryo sac, which is fertilized with male gametes to produce seed. However, little is known about the gene function and regulatory networks during these processes in rice. Here, using the RNA-Seq technique, we identified 3531 stigma-preferential genes and 703 stigma-specific genes within the rice pistils, and we verified 13 stigma-specific genes via qRT-PCR and in situ hybridization. The GO analysis showed that the transport-, localization-, membrane-, communication-, and pollination-related genes were significantly enriched in the stigma. Additionally, to identify the embryo sac-preferential/specific genes within the pistils, we compared a wild-type ovary with a mutant dst (defective stigma) ovary and found that 385 genes were down-regulated in dst. Among these genes, 122 exhibited an ovary-specific expression pattern and are thought to be embryo sac-preferential/specific genes within the pistils. Most of them were preferentially expressed, while 14 of them were specifically expressed in the pistil. Moreover, the rice homologs of some Arabidopsis embryo sac-specific genes, which played essential roles during sexual reproduction, were down-regulated in dst. Additionally, we identified 102 novel protein-coding genes, and 6 of them exhibited differences between the stigma and ovary in rice as determined using RT-PCR. According to these rice ovary comparisons, numerous genes were preferentially or specifically expressed in the stigma, suggesting that they were involved in stigma development or pollination. The GO analysis indicated that a dry rice stigma might primarily perform its function through the cell membrane, which was different from the wet stigma of other species. Moreover, many embryo sac-preferential/specific genes within the pistils were identified and may be expressed in female rice gametophytes, implying that these genes might participate in the process of female gametophyte specialization and fertilization. Therefore, we provide the gene information for investigating the gene function and regulatory networks during female gametophyte development and fertilization. In addition, these novel genes are valuable for the supplementation and perfection of the existing transcriptome in rice, which provides an effective method of detecting novel rice genes.


Organochlorine pesticide residues in breastmilk: difficulties in sample collection and in assessing intakes.
Organochlorine pesticides are highly lipophilic and stable resulting both in their persistence in the environment and their tendency to pass up the food chain. Residues of these compounds are detectable in breastmilk and have been monitored since the 1950s. Samples can be collected using non-invasive techniques and the results are frequently used to assess degradation in the environment as well as risks to recipient infants. As a food, breastmilk is unique. It is manufactured entirely for an individual consumer with some of its constituents driven by its recipient. It can form the sole source of nutrition for a considerable period of an infant's life. Standard calculations of exposure to residues rely on consumption of 750-850 ml breastmilk day(-1) containing 3.5% fat for a 5-kg infant. The fat content of breastmilk, however, is highly variable, which means that that using fixed breastmilk volumes and fat can lead to an imprecise calculation of individual risk. The fat concentration of breastmilk changes throughout a single feed, between feeds and as lactation progresses. This variation therefore raises the methodological problem of how to secure a representative sample of breastmilk. Furthermore, maternal factors such as age and parity also affect concentrations because of the persistence of organochlorine pesticide residues in maternal fat stores. It is therefore critical that samples are collected in a systematic manner taking account of these variables, particularly if the results not only are to be used for risk assessment, but also in comparing changes in environmental concentrations. Reviews of the literature have shown that these variables have often been disregarded in drawing up sampling strategies and methodologies are poorly reported in publications. The paper discusses the literature currently available on monitoring organochlorine pesticide residues in breastmilk and presents an overview of some of the factors that need to be taken into account when collecting samples and assessing infant exposure.


Selective expression of asialo GM1 on maturational subsets of lymphocytes in normal and athymic mice.
In an attempt to clarify the restriction of asialo GM1 expression, the presence of asialo GM1 positive cells in the lymphoid tissues of normal and athymic mice was examined using affinity-purified monospecific anti-asialo GM1 antibodies and a FACS-II. The results presented herein demonstrate that a significant frequency of asialo GM1-positive cells can be detected in the primary lymphoid tissues (bone marrow and thymus) as well as in the secondary lymphoid tissues (spleen and lymph nodes). The observed expression of asialo GM1 within the T-cell lineage is, in general, consistent with the previously proposed restriction of asialo GM1 expression to mature T cells. However, the demonstration that a significant frequency of asialo GM1-positive cells is detectable in bone marrow of normal mice, as well as in spleen and bone marrow of athymic mice, establishes that a substantial number of lymphocytes not committed to the T-cell lineage and/or pre-T cells also express the asialo Gm1 antigen. These results indicate that the asialo GM1 marker may be an important tool for following T differentiation from the multipotential stem cell to the functionally mature T cell.


Changes in surface glycosylation and glycocalyx shedding in Trichobilharzia regenti (Schistosomatidae) during the transformation of cercaria to schistosomulum.
The invasive larvae (cercariae) of schistosomes penetrate the skin of their definitive hosts. During the invasion, they undergo dramatic ultrastructural and physiological transitions. These changes result in the development of the subsequent stage, schistosomulum, which migrates through host tissues in close contact with host's immune system. One of the striking changes in the transforming cercariae is the shedding of their thick tegumental glycocalyx, which represents an immunoattractive structure; therefore its removal helps cercariae to avoid immune attack. A set of commercial fluorescently labeled lectin probes, their saccharide inhibitors and monoclonal antibodies against the trisaccharide Lewis-X antigen (LeX, CD15) were used to characterize changes in the surface saccharide composition of the neuropathogenic avian schistosome Trichobilharzia regenti during the transformation of cercariae to schistosomula, both in vitro and in vivo. The effect of various lectins on glycocalyx shedding was evaluated microscopically. The involvement of peptidases and their inhibitors on the shedding of glycocalyx was investigated using T. regenti recombinant cathepsin B2 and a set of peptidase inhibitors. The surface glycocalyx of T. regenti cercariae was rich in fucose and mannose/glucose residues. After the transformation of cercariae in vitro or in vivo within their specific duck host, reduction and vanishing of these epitopes was observed, and galactose/N-acetylgalactosamine emerged. The presence of LeX was not observed on the cercariae, but the antigen was gradually expressed from the anterior part of the body in the developing schistosomula. Some lectins which bind to the cercarial surface also induced secretion from the acetabular penetration glands. Seven lectins induced the shedding of glycocalyx by cercariae, among which five bound strongly to cercarial surface; the effect could be blocked by saccharide inhibitors. Mannose-binding protein, part of the lectin pathway of the complement system, also bound to cercariae and schistosomula, but had little effect on glycocalyx shedding. Our study did not confirm the involvement of proteolysis in glycocalyx shedding.


Anti-interferon globulin inhibits the development of glomerulonephritis in mice infected at birth with lymphocytic choriomeningitis virus.
Swiss mice infected at birth with lymphocytic choriomeningitis virus develop glomerulonephritis. Injection of potent anti-mouse interferon globulin at the time of viral infection inhibited the development of these renal lesions. We conclude that the production of endogenous interferon by this virus in the first few days of life plays an important role in the pathogenesis of this glomerulonephritis.


[The cardiorenal syndrome and erythropoietin].
The pathophysiological condition, in which combined cardiac and renal dysfunction amplifies a progression in the failure of the individual organ, has been denoted as severe cardiorenal syndrome (SCRS). An interactive network of cardiorenal connectors, i.e., the renin-angiotensin system (RAS), nitric oxide (NO) and reactive oxygen species (ROS) balance, the sympathetic nervous system (SNS), and inflammation, has been proposed as the cornerstones of the pathophysiology of SCRS. Because erythropoietin (Epo) production declinesin chronic renal failure (CRF) and Epo sensitivity might decrease by the cardiorenalconnectors in patients with the SCRS, it is not surprising thatanaemia is a commonly occurring state coinciding with CRF and chronic heart failure (CHF). Epo treatment in patients with SCRS acts via haematopoietic effects, but also may intervenes in the vicious circle of cardiorenal connectors with subsequent deteriorating effects on cardiac, renal, and vascular function. It appears that regular Epo treatment in anaemic patients with diminished renal function improves cardiac performance, delays the progression of kidney disease, and may be of clinical benefit even to patients suffering from CHF with relatively mild anaemia. Despite growing evidence about Epo having positive effects on both renal and cardiac function, little is known about the underlying mechanisms of action.


How to Avoid and Deal with Pelvic Mesh Litigation.
Medical malpractice as it relates to transvaginal mesh implantation adds another level of responsibility when deciding on surgical options to repair stress urinary incontinence or pelvic organ prolapse. As mesh is a viable option for repair, the informed consent process must involve a time commitment to discuss thoroughly the knowns and unknowns about mesh, and potentially must cover other aspects related to surgery: FDA classification of mesh, experience, potential off label usage, and conflicts of interest. A therapeutic alliance must be developed between physician and patient to allay possible fears about the intrinsic uncertainty of surgery. Proper risk assessment of the patient and pre-operative judgment as to when and if mesh implantation is appropriate are decisions that must be documented. Resolution of a conflict from a complication can be dealt with formally or informally. Above all, sharp skills, good communication, broad knowledge base of mesh surgeries, complication management, knowledge of guidelines, along with methodical documentation can mitigate or avert mesh-related litigation.


FK778 attenuates lymphocyte-endothelium interaction after cardiac transplantation: in vivo and in vitro studies.
The malononitrilamide FK778 is a novel derivate of leflunomide and interacts with T- and B-cell function by inhibiting de novo pyrimidine synthesis. We investigated the effects of FK778 upon acute cardiac allograft rejection and upon adhesion molecule upregulation in experimental transplantation and by using in vitro cell culture. Heterotopic, abdominal cardiac transplantations were performed in the Brown Norway (BN) to Lewis (Lew) rat model. The study groups received daily low- or high-dose FK778 immunosuppression. FK778 plasma levels were quantified by HPLC. Grafts were harvested on the fifth postoperative day for histologic and immunohistologic examinations using computerized morphometry. Purified BN aortic endothelial cell cultures were pretreated with low- or high-dose FK778 according to FK778 plasma levels and were stimulated with tumor necrosis factor (TNF)-alpha. Adhesion molecule expression was quantified by immunofluorescence, FACS analysis, and Western blotting. Lymphocyte-endothelium adhesion assays were performed using purified Lew lymphocytes and radiolabeled TNF-alpha was used for receptor binding assays. FK778 treatment dose-dependently reduced graft mononuclear infiltration of CD4(+), CD8(+), and ED1(+) cells, but only high-dose FK778 treatment significantly reduced early upregulation of ICAM-1 and VCAM-1 in vivo. FK778 also dose-dependently reduced TNF-alpha-stimulated endothelial adhesion molecule upregulation in vitro, whereas the effect on VCAM-1 was more dominant. We did not find evidence that FK778 interferes with surface receptor binding of TNF-alpha. Lymphocyte adhesion to endothelial cell monolayers was significantly attenuated by FK778. Besides its inhibitory effect on pyrimidine synthesis, FK778 directly reduces endothelial adhesion molecule upregulation and attenuates lymphocyte-endothelium interaction, which is a critical step in graft rejection.


An algorithm for direct causal learning of influences on patient outcomes.
This study aims at developing and introducing a new algorithm, called direct causal learner (DCL), for learning the direct causal influences of a single target. We applied it to both simulated and real clinical and genome wide association study (GWAS) datasets and compared its performance to classic causal learning algorithms. The DCL algorithm learns the causes of a single target from passive data using Bayesian-scoring, instead of using independence checks, and a novel deletion algorithm. We generate 14,400 simulated datasets and measure the number of datasets for which DCL correctly and partially predicts the direct causes. We then compare its performance with the constraint-based path consistency (PC) and conservative PC (CPC) algorithms, the Bayesian-score based fast greedy search (FGS) algorithm, and the partial ancestral graphs algorithm fast causal inference (FCI). In addition, we extend our comparison of all five algorithms to both a real GWAS dataset and real breast cancer datasets over various time-points in order to observe how effective they are at predicting the causal influences of Alzheimer's disease and breast cancer survival. DCL consistently outperforms FGS, PC, CPC, and FCI in discovering the parents of the target for the datasets simulated using a simple network. Overall, DCL predicts significantly more datasets correctly (McNemar's test significance: p<<0.0001) than any of the other algorithms for these network types. For example, when assessing overall performance (simple and complex network results combined), DCL correctly predicts approximately 1400 more datasets than the top FGS method, 1600 more datasets than the top CPC method, 4500 more datasets than the top PC method, and 5600 more datasets than the top FCI method. Although FGS did correctly predict more datasets than DCL for the complex networks, and DCL correctly predicted only a few more datasets than CPC for these networks, there is no significant difference in performance between these three algorithms for this network type. However, when we use a more continuous measure of accuracy, we find that all the DCL methods are able to better partially predict more direct causes than FGS and CPC for the complex networks. In addition, DCL consistently had faster runtimes than the other algorithms. In the application to the real datasets, DCL identified rs6784615, located on the NISCH gene, and rs10824310, located on the PRKG1 gene, as direct causes of late onset Alzheimer's disease (LOAD) development. In addition, DCL identified ER category as a direct predictor of breast cancer mortality within 5 years, and HER2 status as a direct predictor of 10-year breast cancer mortality. These predictors have been identified in previous studies to have a direct causal relationship with their respective phenotypes, supporting the predictive power of DCL. When the other algorithms discovered predictors from the real datasets, these predictors were either also found by DCL or could not be supported by previous studies. Our results show that DCL outperforms FGS, PC, CPC, and FCI in almost every case, demonstrating its potential to advance causal learning. Furthermore, our DCL algorithm effectively identifies direct causes in the LOAD and Metabric GWAS datasets, which indicates its potential for clinical applications.


Establishment of a new scirrhous gastric carcinoma cell line with microsatellite instability.
We report on the establishment of a new scirrhous gastric cancer cell line with microsatellite instability (MSI), designated OCUM-7. This cell line was derived from a primary scirrhous gastric carcinoma. The cells were floating and round shape in culture. Histologic findings of xenografted tumor obtained from OCUM-7 cells showed a poorly differentiated adenocarcinoma with medullary growth. DNA histograms of OCUM-7 cells showed an aneuploid pattern. MSI status of OCUM-7 was analyzed using 8 microsatellite markers. Five of 8 microsatellite loci showed a novel band shift, which demonstrated that OCUM-7 cells were MSI-high. MSI-positive cell lines established from a primary scirrhous gastric carcinoma have not been reported, while several reports of the establishment of a scirrhous gastric cancer cell line are available. OCUM-7 might be beneficial for analyzing the mechanisms of MSI in scirrhous gastric carcinoma.


A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles.
A new heterogeneous catalytic system consisting of cobalt nanoparticles (CoNPs) supported on MgO and tert-butyl hydroperoxide (TBHP) as oxidant is presented. This CoNPs@MgO/t-BuOOH catalytic combination allowed the epoxidation of a variety of olefins with good to excellent yield and high selectivity. The catalyst preparation is simple and straightforward from commercially available starting materials and it could be recovered and reused maintaining its unaltered high activity.


Inhaled lysophosphatidylcholine provokes bronchoconstriction in guinea pigs in vivo.
Lysophosphatidylcholine is increased in the airway of bronchial asthma, but its role is not clear. We investigated the role of lysophosphatidylcholine in asthma in anaesthetized, mechanically ventilated guinea pigs. Pressure at the airway opening was measured as an index of bronchial response. Increasing doses of lysophosphatidylcholine (1--10 mg/ml) were inhaled and then bronchoalveolar lavage was carried out. 100 and 200 microg/ml methacholine were inhaled 10 min after inhalation of 2.5 mg/ml lysophosphatidylcholine, 10 mg/ml dipalmitoyl phosphatidylcholine and 10 mg/ml glycerophosphocholine, all of which per se did not change the pressure at the airway opening. Effect of 1.0 microg/kg salbutamol, or 60 mg/kg diphenhydramine on the lysophosphatidylcholine-induced increase in the pressure at the airway opening was investigated. Inhalation of lysophosphatidylcholine dose-dependently increased the pressure at the airway opening and increased bronchial responsiveness to methacholine. On the other hand, inhalation of dipalmitoyl phosphatidylcholine decreased the pressure at the airway opening and decreased bronchial responsiveness to methacholine. Intravenously administered salbutamol, but not diphenhydramine, prevented the lysophosphatidylcholine-induced increase in the pressure at the airway opening. The percentage of leukocytes in bronchoalveolar lavage fluid did not change significantly at least within 20 min after the lysophosphatidylcholine inhalation. Lysophosphatidylcholine causes bronchoconstriction and enhances bronchial responsiveness without inducing leukocyte infiltration in the airway, suggesting that lysophosphatidylcholine may be a new bronchoconstrictor mediator in bronchial asthma.


Interactions of cisplatin with non-DNA targets and their influence on anticancer activity and drug toxicity: the complex world of the platinum complex.
Since the discovery of its anticancer activity in 1970s, cisplatin and its analogs have become widely used in clinical practice, being administered to 40-80% of patients undergoing chemotherapy for solid tumors. The fascinating story of this drug continues to evolve presently, which includes advances in our understanding of complexity of molecular mechanisms involved in its anticancer activity and drug toxicity. While genomic DNA has been generally recognized as the most critical pharmacological target of cisplatin, the results reported across multiple disciplines suggest that other targets and molecular interactions are likely involved in the anticancer mode of action, drug toxicity and resistance of cancer cells to this remarkable anticancer drug. This article reviews interactions of cisplatin with non-DNA targets, including RNAs, proteins, phospholipids and carbohydrates in the context of its pharmacological activity and drug toxicity. Some of these non-DNA targets and associated mechanisms likely act in a highly concerted manner towards the biological outcome in cisplatin-treated tumors; therefore, the understanding of complexity of cisplatin interactome may open new avenues for modulation of its clinical efficacy or for designing more efficient platinum-based anticancer drugs to reproduce the success of cisplatin in the treatment of highly curable testicular germ cell tumors in its therapeutic applications to other cancers.


Configuration optimization of bionic piezoelectric hair sensor for acoustic/tactile detection.
Specialized sensory hairs are important biological sensors for arthropods to detect and recognize environmental conditions including acoustic, pressure and airflow signals. However, the present design methodology of such biomimic micro devices are mainly depending on shape mimicking, which greatly restricts their performance. In this paper, a novel genetic algorithm based optimization model for design of piezoelectric functional hair is developed for improving its acoustic pressure or tactile sensitivity. Furthermore, the sensing mechanism of axially polarized piezoelectric hair is explored and the main influencing factors on sensitivity including hair configuration and axial strain distribution are determined. Then, a series of optimized hair configurations are obtained in a specific frequency band from 1 Hz to 500 Hz, whose average sensitivity of 2.21 × 10-3 V Pa-1 is 10 times greater than that of the straight hair of 2.15 × 10-4 V Pa-1 with the same size. For tactile load detection, the output voltage of the optimized hair is about 1.5 times as much as that of the straight hair. The obtained hairs are similar with the spider's trichobothria and tactile hair, which presents an explanation of biological hairs sensitive to dynamic and static loads.


Preparation and characterization of a novel monoclonal antibody specific to human NOB1 protein.
The human NOB1 gene is located at chromosome 16q22.1, encoding a protein consisting of one zinc ribbon domain. Here we aimed to efficiently generate a monoclonal antibody against NOB1 protein. We synthesized the peptide APVEHVVADAGAFLRH based on published NOB1 cDNA sequences. The peptide was chemically linked with the carrier protein keyhole limpet hemocyanin and then injected into Balb/c mice. Hybridomas were screened by indirect enzyme-linked immunosorbent assay (ELISA) using either purified 6xHis-NOB1 fusion protein or the peptide. One MAb named H11 (IgG1), effective in detecting the native NOB1 protein, was characterized by ELISA and Western immunoblotting. By using the MAb, we found NOB1 protein was expressed in human lung, liver, spleen, and kidney tissues. Taken together, the MAb H11 would be helpful for understanding the distribution and functions of NOB1.


Four cases of hepatitis B virus-related fibrosing cholestatic hepatitis treated with lamivudine.
Fibrosing cholestatic hepatitis (FCH) is a rare and extremely severe form of hepatitis B virus (HBV) infection. This condition was originally described in HBV-infected recipients after a liver transplantation. Recently, FCH has been reported not only in liver transplant recipients, but also in other immunosuppressed patients. It is characterized clinically by cholestatic hepatic dysfunction, and pathologically by severe periportal fibrosis, cholestasis, widespread balloon degeneration of hepatocytes, and only a mild infiltration of inflammatory cells. Without treatment, FCH is universally fatal within a few months of diagnosis. There have been only two isolated case reports of FCH with long-term patient survival, and one case report with treatment failure after lamivudine therapy. Because of the rarity of this clinical entity, the therapeutic efficacy of lamivudine in patients with FCH cannot be evaluated systematically. Here, we present four patients with HBV-related FCH treated with lamivudine. One received antineoplastic therapy for acute lymphoblastic leukemia, and the other three were renal graft recipients. Two patients who developed FCH after a renal transplantation survived with an improvement in liver function and were followed up for 20 and 30 months, respectively, and were found to be in good health. However, the other two patients died of sepsis, possibly as a consequence of the immunosuppression with hepatic failure despite lamivudine treatment. Our experience suggests that lamivudine can alter the grave natural history of FCH.


Preparation of cadmium sulfide nanoparticles and their application for improving the properties of the electrochemical sensor for the determination of enrofloxacin in real samples.
An advanced electrochemical sensor for the detection of enrofloxacin (ENR) based on the use of a modified electrode containing cadmium sulfide (CdS) nanoparticles (NPs) is reported. The CdS NPs were synthesized and characterized and then coated onto the electrode to fabricate a modified electrode that exhibited a lower limit of detection of 9.5 × 10-8 mol·L-1 . This detection limit compares with a traditional electrode that exhibited a concentration detection range of 1.0 × 10-2 to 1.0 × 10-7 mol·L-1 . This modified electrode demonstrated good selectivity, reproducibility, response time (<40 s), lifetime (up to 12 wk), and pH range (3.3-7.2) for the determination of ENR in real samples (eg, pig urine).


Structural Key Bit Occurrence Frequencies and Dependencies in PubChem and Their Effect on Similarity Searches.
Little published literature exists on the 881 bit structural keys used by PubChem for categorizing and comparing the compounds present in its database. We characterized these structural keys by examining their frequencies of occurrence within the PubChem compound database. In addition, bit dependencies, defined as the universal presence of a bit given the presence of another, were determined. We show that the vast majority of bits are rarely set and that substantial numbers of dependencies exist. A comparison of similarity searches with five United States Food and Drug Administration approved drugs as reference compounds using the full structural keys versus a variant in which all dependent bits were removed was performed using the Tanimoto coefficient. These bit dependencies not only affect similarity scores, but also alter the compounds returned in similarity searching. Judicious selection of bits is needed to maintain sufficient ability to differentiate related compounds.


Identification of vascular patients at very high risk for recurrent cardiovascular events: validation of the current ACC/AHA very high risk criteria.
To validate and assess performance of the current ACC/AHA very high risk criteria in patients with clinically manifest arterial disease. Data were used from the SMART study (n = 7216) and REACH Registry (n = 48 322), two prospective cohorts of patients with manifest atherosclerotic arterial disease. Prevalence and incidence rates of recurrent major adverse cardiovascular events (MACE) were calculated, according to the ACC/AHA VHR criteria (cardiovascular disease combined with diabetes, smoking, dyslipidaemia, and/or recent recurrent coronary events). Performance of the ACC/AHA criteria was compared with single very high risk factors in terms of C-statistics and Net Reclassification Index. All patients were at VHR according to the ESC guidelines (incidence of recurrent MACE in SMART was 2.4/100PY, with 95% CI 2.3-2.5/100PY and in REACH 5.1/100PY with 95% CI 5.0-5.3/100PY). In SMART 57% of the patients were at VHR according to the ACC/AHA criteria (incidence of recurrent MACE 2.7/100PY, 95% CI 2.5-2.9/100PY) and in REACH this was 64% (5.9/100PY, 95% CI 5.7-6.1/100PY). The C-statistic for the ACC/AHA VHR criteria was 0.53 in REACH and 0.54 in SMART. Very high risk factors with comparable or slightly better performance were eGFR < 45, polyvascular disease and age >70 years. Around two third of the patients meeting the ACC/AHA VHR criteria had a predicted 10-year risk of recurrent MACE <30%. The ACC/AHA VHR criteria have limited discriminative power. Identifying patients with clinically manifest arterial disease at VHR for recurrent vascular events using eGFR <45, polyvascular disease, or age >70 years performs as well as the ACC/AHA VHR criteria.


Hypothalamic neuropeptide expression following chronic food restriction in sedentary and wheel-running rats.
When rats are given access to a running-wheel in combination with food restriction, they will become hyperactive and decrease their food intake, a paradoxical phenomenon known as activity-based anorexia (ABA). Little is known about the regulation of the hypothalamic neuropeptides that are involved in the regulation of food intake and energy balance during the development of ABA. Therefore, rats were killed during the development of ABA, before they entered a state of severe starvation. Neuropeptide mRNA expression levels were analysed using quantitative real-time PCR on punches of separate hypothalamic nuclei. As is expected in a state of negative energy balance, expression levels of agouti-related protein (AgRP) and neuropeptide Y (NPY) were increased 5-fold in the arcuate nucleus (ARC) of food-restricted running ABA rats vs 2-fold in sedentary food-restricted controls. The co-regulated expression of AgRP and NPY strongly correlated with relative body weight and white adipose tissue mass. Arcuate expression of pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) was reduced 2-fold in the ABA group. In second-order neurons of the lateral hypothalamic area (LHA), melanin-concentrating hormone (MCH) mRNA expression was upregulated 2-fold in food-restricted running rats, but not in food-restricted sedentary controls. Prepro-orexin, CART and corticotropin-releasing hormone expression levels in the LHA and the paraventricular nucleus (PVN) were unchanged in both food-restricted groups. From this study it was concluded that during the development of ABA, neuropeptides in first-order neurons in the ARC and MCH in the LHA are regulated in an adequate response to negative energy balance, whereas expression levels of the other studied neuropeptides in secondary neurons of the LHA and PVN are unchanged and are probably regulated by factors other than energy status alone.


Evidence of the validity of the Multidimensional Scale of Perceived Social Support (MSPSS) in university students.
Social support refers to the social resources that a person perceives to be available and has been strongly associated with physical and mental health outcomes. The present study aimed to evaluate the internal consistency, construct validity, and test-retest reliability of the Perceived Social Support Multidimensional Scale (PSSMS) in university students in the Midwest of Brazil. Exploratory and confirmatory factor analyses were performed with two independent random samples, both consisting of 1,147 students. The test-retest study was carried out with a sample of 347 medical students. Data were collected in two separate moments with a 14-day interval. The solution with the best fit was the three-factor model: family, friends, and significant others. The factor loadings of the scale items ranged between 0.767 and 0.950 and each factor showed high internal consistency (Cronbach's alpha=0.96, 0.97, and 0.97, respectively). The model also attained adequate fit: χ2(d.f.)=380 (49), p<0.0001; SRMR=0.023; RMSEA=0.077; CFI=0.993; TLI=0.990. Test-retest reliability was moderate (weighted kappa ranging from 0.36 to 0.52). The results suggest that the PSSMS has acceptable psychometric properties for use with university students.


Tomoxetine (Eli Lilly & Co).
Eli Lilly is developing tomoxetine, a norepinephrine reuptake inhibitor, for the potential treatment of attention deficit hyperactivity disorder (ADHD) and depression. As of May 2000, tomoxetine was undergoing phase III trials in the US [368128]. An NDA was filed with the FDA in October 2001, with a launch expected in the second half of 2002 [426786]. Tomoxetine was first investigated by Lilly in the 1980s as a potential treatment for depressive illness. The compound was selected from a series of potent inhibitors of norepinephrine reuptake, and reached large-scale phase II clinical trials for depression in 1990. Development for this indication appeared to stop at that time, despite some evidence that tomoxetine wasfairly effective [273943]. In 1996, Lilly apparently restarted preclinical development of tomoxetine as a potential therapyfor ADHD, and submitted EP-00721777 claiming tomoxetine's utility for this disorder in July of that year [273956]. In June 2001, ABN AMRO predicted sales of $121 million in 2002, rising to $4,064 million in 2012 [422762]. In October 2001, analysts at Salomon Smith Barney predicted that the product would make sales of $24 million in 2002, rising to $305 million in 2005 [427501].


The biogenesis of mitochondria in Saccharomyces cerevisiae. A comparison between cytoplasmic respiratory-deficient mutant yeast and chlormaphenicol-inhibited wild type cells.
The effects of chloramphenicol on S. cerevisiae and on a cytoplasmic respiratory-deficient mutant derived from the same strain are compared. In the normal yeast, high concentrations of chloramphenicol in the growth medium completely inhibit the formation of cytochromes a, a(3), b, and c(1) and partially inhibit succinate dehydrogenase formation, whereas they do not affect cytochrome c synthesis. This has been correlated with the marked reduction of mitochondrial cristae formation in the presence of the drug. In glucose-repressed normal yeast, chloramphenicol has little effect on the formation of outer mitochondrial membrane, or on the synthesis of malate dehydrogenase and fumarase. However, both these enzymes, as well as the number of mitochondrial profiles, are markedly decreased when glucose de-repressed yeast is grown in the presence of chloramphenicol. The antibiotic did not appear to affect the cytoplasmic respiratory-deficient mutant. The results have been interpreted to indicate that chloramphenicol inhibits the protein-synthesizing system characteristic of the mitochondria. Since the drug does not prevent the formation of cytochrome c, of several readily solubilized mitochondrial enzymes, or of outer mitochondrial membrane, it is suggested that these are synthesized by nonmitochondrial systems.


Comparative efficacy of cephalexin and ampicillin for shigellosis and other types of acute diarrhea in infants and children.
Most ampicillin-resistant Shigella are susceptible to cephalexin. Randomized treatment with cephalexin or ampicillin was given to 154 infants and children with acute diarrhea. Rectal swab cultures revealed Shigella in 42%, Salmonella in 6%, enteropathogenic Escherichia coli in 2%, and no pathogen in 50%. Cephalexin failed to eradicate Shigella after 5 days of treatment in 76% of patients as contrasted with 28% of ampicillin-treated patients with susceptible organisms. Shigella persisted in 78% of ampicillin-treated patients with resistant organisms. Diarrhea lasted more than 5 days in 43% of cephalexin-treated patients, in 56% of the ampicillin group with resistant organisms, but in only 9% of ampicillin-treated patients with susceptible organisms. The failure of cephalexin was due to the relatively high minimal inhibitory concentrations and minimal bacterial concentrations of 5 or 10 mug/ml and, although serum concentrations were twice the minimal bacterial concentration, they were not sufficient to demonstrate killing by the serum dilution method. In vitro susceptibility or resistance of Shigella to ampicillin correlated with clinical success or failure. Cephalexin is not a suitable drug for treatment of shigellosis in patients with ampicillin-resistant organisms.


Interactive Effects of UV-B Light with Abiotic Factors on Plant Growth and Chemistry, and Their Consequences for Defense against Arthropod Herbivores.
Ultraviolet-B (UV-B) light plays a crucial role in plant-herbivorous arthropods interactions by inducing changes in constitutive and inducible plant defenses. In particular, constitutive defenses can be modulated by UV-B-induced photomorphogenic responses and changes in the plant metabolome. In accordance, the prospective use of UV-B light as a tool to increase plant protection in agricultural practice has gained increasing interest. Changes in the environmental conditions might, however, modulate the UV-B -induced plant responses. While in some cases plant responses to UV-B can increase adaptation to changes in certain abiotic factors, UV-B-induced responses might be also antagonized by the changing environment. The outcome of these interactions might have a great influence on how plants interact with their enemies, e.g., herbivorous arthropods. Here, we provide a review on the interactive effects of UV-B and light quantity and quality, increased temperature and drought stress on plant biochemistry, and we discuss the implications of the outcome of these interactions for plant resistance to arthropod pests.


Evidence for a Role of Prolactin in Mediating Effects of Photoperiod during the Dry Period.
Photoperiod manipulation during the lactation cycle alters milk yield, with long days (LDPP) increasing yield in lactation and short days (SDPP) in the dry period improving subsequent yield. Circulating prolactin (PRL) is directly related to day length, with LDPP increasing and SDPP decreasing PRL, respectively. Two blocks of 24 multiparous Holstein cows were used during two consecutive years to test the hypothesis that the mammary response to SDPP is the result of decreased concentrations of PRL in the circulation relative to LDPP. Cows were randomly assigned to one of three treatment groups during the dry period: SDPP, LDPP, or SDPP+PRL. Cows were returned to ambient photoperiod at calving and milk yield and DMI recorded for 120 d and 42 d, respectively. Mammary biopsies were obtained to determine rates of [³H]-thymidine incorporation into DNA in vitro. Treatment of SDPP cows with PRL caused a rapid increase in systemic PRL that reached concentrations similar to cows under LDPP. The periparturient PRL surge was similar for LDPP and SDPP+PRL cows, but those groups had greater surge concentrations versus SDPP. Cows exposed to SDPP produced more milk than LDPP cows, and there was a trend for SDPP+PRL cows to produce more milk than LDPP cows. Milk production was inversely related to the periparturient PRL surge. There was a trend for a treatment effect on mammary cell proliferation with greater proliferation in mammary tissue of SDPP cows relative to LDPP or SDPP+PRL on day -20 relative to parturition. Replacement of PRL to cows on SDPP when dry resulted in milk yield intermediate to cows on SDPP or LDPP, supporting the concept of a link between dry period PRL and yield.


[Effects on blood coagulation-fibrinolytic system after transcatheter hepatic arterial therapy in cases of hepatocellular carcinoma analyzed by plasma levels of plasmin-alpha 2-PI complex, D dimer and thrombin-ATIII complex].
To clarify the effects on blood coagulation-fibrinolytic system after transcatheter hepatic arterial therapy for cases of hepatocellular carcinoma (HCC), plasma levels of Plasmin-alpha 2PI complex (PIC), Ddimer and Thrombin-ATIII (TAT) before and after therapy were measured by EIA, in addition to other conventional coagulofibrinolytic parameters. In the group (9 cases) treated with intra-arterial injection of adriamycin, there were no significant changes of coagulofibrinolytic parameters except for Ddimer (P less than 0.05) which was elevated 1-2 days after therapy. However, only two cases in whom plasma PIC, Ddimer and TAT levels were clearly elevated before therapy, showed further marked elevation of those parameters after therapy. In the group (29 cases) treated with intra-arterial injection of adriamycin-lipiodol suspension, whether or not embolized with gelfoam, plasma PIC, Ddimer and TAT levels were significantly elevated (P less than 0.01) after therapy, as well as other conventional coagulofibrinolytic parameters. These results indicate that hypercoagulable and hyperfibrinolytic states were induced by treatment. Moreover, the secondary hyperfibrinolytic state tended to persist longer than the hypercoagulable state. The 14 cases embolized with gelfoam seemed to have more apparent effects on blood coagulation-fibrinolytic system than cases not treated with gelfoam. Therefore, we conclude that caution and prophylaxis for the occurrence of disseminated intravascular coagulation are necessary for transcatheter arterial therapy for cases of HCC.


Bayesian framework for THz-TDS plasma diagnostics.
Terahertz time-domain spectroscopy (THz-TDS) is an optical diagnostic used to noninvasively measure plasma electron density and collision frequency. Conventional methods for analyzing THz-TDS plasma diagnostic data often do not account for measurement artifacts and do not quantify parameter uncertainties. We introduce a novel Bayesian framework that overcomes these deficiencies. The framework enables computation of both the density and collision frequency, compensates for artifacts produced by refraction and delay line errors, and quantifies parameter uncertainties caused by noise and imprecise knowledge of unmeasured plasma properties. We demonstrate the framework with sample measurements of a radio frequency inductively-coupled plasma discharge.