Separation of nanoparticles in aqueous multiphase systems through centrifugation.
This paper demonstrates the use of aqueous multiphase systems (MuPSs) as media for rate-zonal centrifugation to separate nanoparticles of different shapes and sizes. The properties of MuPSs do not change with time or during centrifugation; this stability facilitates sample collection after separation. A three-phase system demonstrates the separation of the reaction products (nanorods, nanospheres, and large particles) of a synthesis of gold nanorods, and enriches the nanorods from 48 to 99% in less than ten minutes using a benchtop centrifuge.


Quantification of extracellular and intracellular adenosine production: understanding the transmembranous concentration gradient.
Inhibitors of adenosine membrane transport cause vasodilation and enhance the plasma adenosine concentration. However, it is unclear why the plasma adenosine concentration rises rather than falls when membrane transport is inhibited. We tested the hypothesis that the cytosolic adenosine concentration exceeds the interstitial concentration under well-oxygenated conditions. In isolated, isovolumically working guinea pig hearts (n=50), the release rate of adenosine and accumulation of S-adenosylhomocysteine (after 20 minutes of 200 micromol/L homocysteine), a measure of the free cytosolic adenosine concentration, were determined in the absence and presence of specific and powerful blockers of adenosine membrane transport (nitrobenzylthioinosine 1 micromol/L), adenosine deaminase (erythro-9-hydroxy-nonyl-adenine 5 micromol/L), and adenosine kinase (iodotubericidine 10 micromol/L). Data analysis with a distributed multicompartment model revealed a total cardiac adenosine production rate of 2294 pmol. min-1. g-1, of which 8% was produced in the extracellular region. Because of a high rate of intracellular metabolism, however, 70.3% of extracellularly produced adenosine was taken up into cellular regions, an effect that was effectively eliminated by membrane transport block. The resulting approximately 2.8-fold increase of the interstitial adenosine concentration evoked near-maximal coronary dilation. We rejected the hypothesis that the cytosolic adenosine concentration exceeds the interstitial. Rather, there is significant extracellular production, and the parenchymal cell represents a sink, not a source, for adenosine under well-oxygenated conditions.


Measurement of a superconducting energy gap in a homogeneously amorphous insulator.
We present tunneling spectroscopy measurements that directly reveal the existence of a superconducting gap in the insulating state of homogenously disordered amorphous indium oxide films. Two films on both sides of the disorder induced superconductor to insulator transition show the same energy gap scale. This energy gap persists up to relatively high magnetic fields and is observed across the magnetoresistance peak typical of disordered superconductors. The results provide useful information for understanding the nature of the insulating state in the disorder induced superconductor to insulator transition.


DECLINE OF GAME BIRDS (PHASIANUS COLCHICUS AND PERDIX PERDIX) IN BAVARIA: A SURVEY ON PATHOGENIC BACTERIA, PARASITES, PESTICIDE RESIDUES, AND INFLUENCE OF SET-ASIDE LAND AND MAIZE CULTIVATION.
Due to a Europe-wide decline of grey partridge ( Perdix perdix ) and pheasant ( Phasianus colchicus ) populations, this study was conducted focusing on the county of Bavaria, south Germany. The aim was to assess the health status of game birds and identify possible causes of decline. For this purpose 203 pheasants and 11 partridges were examined during the 2011 hunting season. Pathologic examinations were conducted including examinations for parasites and bacteria. Due to public health significance, a screening for Salmonella sp., as well as real-time polymerase chain reaction examinations for Campylobacter sp. and Mycobacterium avium ssp. avium, were done. Because pesticides and land-usage can possibly influence bird numbers, the birds were screened for environmental toxin residues, including neonicotinoid insecticides, and land-usage data were correlated with the hunting bags. The result was a very-strong positive correlation of set-aside areas and a less-strong negative correlation of maize cultivation acreage. More than 90% of the birds had a good health status; only individuals showed pathologic alterations. For example, avian tuberculosis was found in two pheasants and a severe capillariosis in two partridges. A possible role of female reproductive disorders has to be confirmed in further investigations. In conclusion, results suggest the decrease of set-aside areas could be a possible reason for decline.


Effect of oral KETOPROFEN treatment in acute respiratory disease outbreaks in finishing pigs.
Infection with respiratory pathogens can influence production as well as animal welfare. There is an economical and ethical need to treat pigs that suffer from respiratory diseases. Our aim was the evaluation of the possible effects of oral NSAID medication given in feed in acute outbreaks of respiratory disease in finishing pigs. The short- and long-term impact of NSAID dosing on clinical signs, daily weight gain, blood parameters and behaviour of growing pigs in herds with acute respiratory infections were evaluated. Four finishing pig farms suffering from acute outbreaks of respiratory disease were visited thrice after outbreak onset (DAY 0, DAY 3 and DAY 30). Pigs with the most severe clinical signs (N = 160) were selected as representative pigs for the herd condition. These pigs were blood sampled, weighed, evaluated clinically and their behaviour was observed. After the first visit, half of the pens (five pigs per pen in four pens totalling 20 representative pigs per herd, altogether 80 pigs in four herds) were treated with oral ketoprofen (target dose 3 mg/kg) mixed in feed for three days and the other half (80 pigs) with a placebo. In three of the herds, some pigs were treated also with antimicrobials, and in one herd the only pharmaceutical treatment was ketoprofen or placebo. Compared to the placebo treatment, dosing of ketoprofen reduced sickness behaviour and lowered the rectal temperature of the pigs. Clinical signs, feed intake or blood parameters were not different between the treatment groups. Ketoprofen treatment was associated with somewhat reduced weight gain over the 30-day follow-up period. Concentration analysis of the S- and R-enantiomers of ketoprofen in serum samples collected on DAY 3 indicated successful oral drug administration. Ketoprofen mainly influenced the behaviour of the pigs, while it had no effect on recovery from respiratory clinical signs. However, the medication may have been started after the most severe clinical phase of the respiratory disease was over, and this delay might complicate the evaluation of treatment effects. Possible negative impact of ketoprofen on production parameters requires further evaluation.


Inhibition of breast tumor progression by systemic delivery of the maspin gene in a syngeneic tumor model.
Maspin has been shown to possess tumor-suppressing activity against breast tumor growth and metastasis. To test the therapeutic value of the maspin gene (SERPINB5) in breast cancer, we established a syngeneic breast tumor metastasis model. This model involved the implantation of mammary tumor cells orthotopically to mammary gland and allowed tumors to grow within the gland and become metastatic to other organs. The mammary tumor cells were initially isolated from MMTV-polyoma virus middle T transgenic mice and were selected in vitro for high invasiveness. Here, we demonstrate that the mammary tumor cells were highly invasive and metastatic. Overall, 100% of tumor-transplanted mice developed lung metastasis. Using nonviral liposome as a carrier, we delivered SERPINB5 to mice bearing mammary tumors. Our data showed that both primary tumor growth and metastasis were significantly inhibited in this syngeneic metastasis model. Such inhibition is mediated by SERPINB5 transgene through increased apoptosis in SERPINB5-treated tumors. Thus, SERPINB5 can be used in gene therapy against breast tumor growth and metastasis.


Effects of sensorineural hearing loss on interaural discrimination and virtual localization.
Cross-frequency binaural processing was investigated in listeners with normal hearing (NH) and with bilateral high-frequency sensorineural hearing impairment (IH). In experiment 1 just-noticeable-differences for interaural time and interaural intensity were measured using 1/3-octave narrow-band noises (NBNs) centered at 0.5 and 4 kHz. These stimuli were presented in isolation and in different cross-frequency interaural combinations. IH listeners displayed the best interaural time discrimination when the 0.5-kHz NBN was dichotic and the best intensity discrimination when both bands were dichotic. Both NH listeners (time) and IH listeners (time and intensity) displayed the poorest interaural discrimination when the NBNs were presented simultaneously with interaural differences in only the 4-kHz NBN (0.5 kHz NBN dichotic). Localization accuracy was measured in experiment 2 using the 0.5- and 4-kHz NBNs in isolation and with 0.5-kHz target/4-kHz interferer and 4-kHz target/0.5-kHz interferer conditions. Best localization of NH and IH subjects was seen for the 0.5-kHz target, with or without an interferer. Poorest localization of IH subjects was observed for the 4-kHz target and 0.5-kHz interferer. Results suggest that for these IH subjects, localization is most difficult when they are forced to rely on interaural information in a higher-frequency region with conflicting interaural information at low frequencies.


Morphometric assessment of the impact of serum thymulin immunoneutralization on pituitary cell populations in peripubertal mice.
Thymulin is a thymic hormone involved in several aspects of intra- and extrathymic T-cell differentiation. Thymulin also possesses hypophysiotropic activity which suggests that this metallopeptide may play an important role in thymus-pituitary communication, particularly during early life. The aim of the present study was to evaluate the impact of serum thymulin suppression from birth to peripuberty on the morphology of different pituitary cell populations in prepubertal C57Bl/6 mice. Animals were submitted to immunoneutralization of circulating thymulin from postnatal day 1 to the end of the study (age 32 days). From their 1st day of life, the animals were submitted to a protocol of intraperitoneal injections of rabbit anti-thymulin serum (alpha-FTS) and normal rabbit serum (NRS) in the controls. On their 33rd day of life, the animals were killed and their pituitaries were immediately dissected, fixed and immunostained using the EnVision system with primary antibodies against growth hormone, thyrotropin, corticotropin, gonadotropins and prolactin. Morphometry was performed by means of an image analysis system. The following parameters were calculated: volume density = Sigma cell area/reference area (RA); cell density (CD) = number of cells/RA, and cell size (expressed in microm2). Serum thymulin was measured by a rosette bioassay while pituitary hormones were assayed by radioimmunoassay. Serum prolactin, luteinizing hormone, follicle-stimulating hormone, growth hormone and thyroid-stimulating hormone were significantly lower in the alpha-FTS animals of either sex compared with the corresponding NRS counterparts. The somatotrope, lactotrope and corticotrope populations showed a significant decrease in CD, while cell hypertrophy was observed in some of the pituitary cell populations of the alpha-FTS group compared to the NRS group. In the alpha-FTS group, there were sex differences in the morphometric changes observed. Our results suggest that serum thymulin plays a significant role during early life in the postnatal maturation of endocrine cells of the mouse anterior pituitary gland.


Lateral lumbar interbody fusion without intraoperative neuromonitoring: a single-center consecutive series of 157 surgeries.
OBJECTIVE: Lateral lumbar interbody fusion (LLIF) is frequently used for anterior column stabilization. Many authors have reported that intraoperative neuromonitoring (IONM) of the lumbar plexus nerves is mandatory for this approach. However, even with IONM, the reported motor and sensory deficits are still considerably high. Thus, the authors' approach was to focus on the indication, trajectory, and technique instead of relying on IONM findings per se. The objective of this study therefore was to analyze the outcome of our large cohort of patients who underwent LLIF without IONM. METHODS: The authors report on 157 patients included from 2010 to 2016 who underwent LLIF as an additional stabilizing procedure following dorsal instrumentation. LLIF-related complications as well as clinical outcomes were evaluated. RESULTS: The mean follow-up was 15.9 ± 12.0 months. For 90.0% of patients, cage implantation by LLIF was the first retroperitoneal surgery. There were no cases of surgery-related hematoma, vascular injury, CSF leak, or any other visceral injury. Between 1 and 4 cages were implanted per surgery, most commonly at L2-3 and L3-4. The mean length of surgery was 92.7 ± 35 minutes, and blood loss was 63.8 ± 57 ml. At discharge, 3.8% of patients presented with a new onset of motor weakness, a new sensory deficit, or the deterioration of leg pain due to LLIF surgery. Three months after surgery, 3.5% of the followed patients still reported surgery-related motor weakness, 3.6% leg pain, and 9.6% a persistent sensory deficit due to LLIF surgery. CONCLUSIONS: The results of this series demonstrate that the complication rates for LLIF without IONM are comparable, if not superior, to those in previously reported series using IONM. Hence, the authors conclude that IONM is not mandatory for LLIF procedures if the surgical approach is tailored to the respective level and if the visualization of nerves is performed.


Unlocking green growth challenges: role of green HRM, green career adaptability, and green career success.
Multiple industries face challenges in achieving green growth that needs a fix. This research presents an alternative explanation for the acquisition of green growth using the perspective of employees of manufacturing industries. Thus, the study examines the role of green HRM, green career adaptability, and green career success in achieving green growth. Green growth drivers can construct green infrastructures for developing green aspects in economic sectors such as power generation, transportation, and the residential sector. We inquired Chinese SME employees to fill out a closed-ended online survey. PLS-SEM techniques are used to estimate how the study will turn out. According to the results, green career adaptability plays a big part in green HRM and career success. It also plays a significant role in bringing the two together. The results shown that green HRM, adapting to a green career and doing well in a green career, all help green growth in manufacturing SMEs in China. The study's results are strong in their ability to explain. This is especially true in the academic world, where people who can adapt to setbacks and have a green career are likelier to have a good career in organizations that care about the environment. By doing this, the study also helps guide the strategic development goals (SDGs) for climate action and environmental management by acquiring green growth. So, the study makes different suggestions for what to do.


Gelatinization and retrogradation phenomena in starch/montmorillonite nanocomposites plasticized with different glycerol/water ratios.
This study aims to gain insights into the intermolecular interactions present in thermoplastic starch (TPS)/montmorillonite (MMT) nanocomposites prepared using water and/or glycerol as plasticizers. Specifically, the impact of using different glycerol/water proportions on the nature of gelatinization and retrogradation processes is studied. Nanocomposites were characterized by rheometry, scanning electron microscopy (SEM) and X-rays diffraction (XRD). It is shown that clay tactoids preferentially interact with glycerol molecules rather than starch macromolecules. Consequently, the effects of MMT incorporation strongly depend on the glycerol/water ratio; when a ratio of 0.5 is used minor variations were observed on the starch gelatinization process-although stronger clays-starch interactions were evident-whereas at higher ratios the addition of clays significantly increased the gelatinization temperature, up to values over 100°C. In the gelatinization process of starch in TPS samples having only glycerol as a plasticizer, the leaching of amylose and the melting of amylopectin crystalline domains seem to occur simultaneously. This different gelatinization mechanism produces a TPS having a substantially different morphology, which exhibited reduced retrogradation characteristics.


Stem cell niche: structure and function.
Adult tissue-specific stem cells have the capacity to self-renew and generate functional differentiated cells that replenish lost cells throughout an organism's lifetime. Studies on stem cells from diverse systems have shown that stem cell function is controlled by extracellular cues from the niche and by intrinsic genetic programs within the stem cell. Here, we review the remarkable progress recently made in research regarding the stem cell niche. We compare the differences and commonalities of different stem cell niches in Drosophila ovary/testis and Caenorhabditis elegans distal tip, as well as in mammalian bone marrow, skin/hair follicle, intestine, brain, and testis. On the basis of this comparison, we summarize the common features, structure, and functions of the stem cell niche and highlight important niche signals that are conserved from Drosophila to mammals. We hope this comparative summary defines the basic elements of the stem cell niche, providing guiding principles for identification of the niche in other systems and pointing to areas for future studies.


Predictors of Biased Self-perception in Individuals with High Social Anxiety: The Effect of Self-consciousness in the Private and Public Self Domains.
"Biased self-perception," the tendency to perceive one's social performance as more negative than observers do, is characteristic of socially anxious individuals. Self-attention processes are hypothesised to underlie biased self-perception, however, different models emphasise different aspects of self-attention, with attention to the public aspects of the self being prominent. The current study aimed to investigate the relative contribution of two types of dispositional self-attention; public- and private self-consciousness to biased self-perception in a high (n = 48) versus a low (n = 48) social anxiety group undergoing an interaction task. The main finding was that private self-consciousness explained substantial and unique variance in biased negative self-perception in individuals with high social anxiety, while public self-consciousness did not. This relationship was independent of increments in state anxiety. Private self-consciousness appeared to have a specific association with bias related to overestimation of negative social performance rather than underestimation of positive social performance. The implication of this finding is that current treatment models of Social anxiety disorder might include broader aspects of self-focused attention, especially in the context of formulating self-evaluation biases.


Effectiveness of a short-structured training programme on knowledge of healthcare providers and programme managers involved in maternal and child health programmes in Odisha, India: a quality improvement study.
To evaluate the effectiveness of training programme on knowledge related to new interventions proposed under India Newborn Action Plan (INAP) and Integrated Action Plan against Pneumonia and Diarrhoea (IAPPD). Quality improvement study with pre-evaluation and post evaluation. The study was conducted in 17 districts of Odisha, India. The participants were healthcare providers and programme managers involved in maternal and child health programmes. Intervention was a short-structured (8 hours) training delivered to 127 batches with expected participation of 30 trainees in each batch. Training was divided into four modules covering new interventions related to INAP and IAPPD like causes of neonatal death, kangaroo mother care (KMC), feeding of low birthweight (LBW) infants, use of injection gentamicin, identification of possible serious bacterial infection (PSBI), identification and management of pneumonia and diarrhoea and key interventions for maternal health. Various modalities of teaching-learning method were used. Pretraining and post-training knowledge assessment was done with a pretested tool consisting of 15 items. Each item carried equal weightage in calculation of knowledge score thus maximum possible knowledge score was 15. Feedback assessment was also done after the training. The mean (SD) knowledge score significantly improved to 10.24 (2.24) after training as compared with 4.73 (1.94) before training, p<0.001 (n=982). There was significant improvement in knowledge for majority of the components namely causes of neonatal death (61.9% vs 28.1%), KMC (68.0% vs 54.6%), feeding of LBW infants (77.7% vs 6.9%), use of injection gentamicin (69.7% vs 11.2%), identification of PSBI (69.5% vs 59.5%). The improvement in knowledge score was more when healthcare providers and programme managers had provided a favourable response on feedback. Systematic pretest and post-test assessment coupled with feedback assessment can ensure the effectiveness of training programmes offered in programmatic settings.


Fine structure of cartilage canal and vascular buds in the rabbit vertebral endplate. Laboratory investigation.
The vascular terminations (vascular buds) in the bone-disc junction area are structurally very similar to cartilage. In all previous studies to date, however, the roles of cartilage canals and vascular buds were mainly discussed using histological and transparent sections but not electron microscopic sections. The purpose of this study was to clarify the ultrastructure of the vascular bud seen in the bone-disc junction in comparison to the cartilage canal. Japanese white rabbits from 2 days to 6 months of age were used in this study. The bone-disc junctions were examined by microangiogram and light and electron microscopy, and morphological changes and their association with the age of the animals were noted. The fine structure of the vascular bud was similar to that of the cartilage canal that nourished the growing cartilage. They were composed of arteries, veins, capillaries, cells resembling fibroblasts, and macrophages. The capillaries in the cartilage canal were all the fenestrated type. Vascular buds were seen over the entire bone-cartilage interface, with maximum density in the area related to the nucleus pulposus. They projected into the bone-disc junction area from the vertebral body contacting the cartilaginous endplate directly. The results of this study clarify the formation process and ultrastructure of the vascular bud seen in the bone-disc junction. The authors found a strong structural resemblance between the vascular bud and the cartilage canal and hypothesize that the immature cells seen surrounding the cartilage canal and vascular bud represent a common precursor for the 3 main types of connective tissue cells seen during early vertebral development.


The implementation of Xpert MTB/RIF assay for diagnosis of tuberculosis in Nepal: A mixed-methods analysis.
Tuberculosis (TB) is a major public health problem in low and middle-income countries. Early detection and enrolment of TB cases is a challenge for National TB Programs. To understand the performance and feasibility for scale-up of Xpert MTB/RIF assay for the TB diagnosis in Nepal. Implementation research employed mixed-method sequential explanatory design. The results of Xpert MTB/RIF assay were analysed in 26 TB diagnostic centres where Xpert machines had been installed before 2015. In-depth interviews and focus group discussions were conducted with stakeholders, purposively selected to represent experiences in centres that were functioning well, poorly or not functioning. During a one-year period in 2015/16, 23,075 Xpert MTB/RIF assays were performed in 21 diagnostic centres with 22,288 people also tested by sputum microscopy. Among these, 77% had concordant (positive or negative) results, demonstrating fair agreement (Kappa score, 0.3) between test results. Test failure and positivity rates in diagnostic centres ranged from 2.6% to 13.4% and 6.5% to 49%, respectively. The number of cartridges per positive result varied from 2.3 to 10.2. Xpert assay was positive in 3314 (15% of all cases) sputum smear microscopy negative cases. Of 4280 bacteriologically confirmed cases by Xpert assay, 355 (8%) were rifampicin resistant. Xpert machines were no longer functioning regularly throughout the year in 5 diagnostic centres. The main barriers for effective implementation of Xpert in Nepal were the lack of: timely supply of cartridges; replacement of damaged modules; maintenance of Xpert machines; and stock verification for timely procurement of cartridges. Inadequate laboratory infrastructure for maintaining functional Xpert equipment further challenges implementation and scale-up. The implementation of Xpert MTB/RIF assay has increased case-finding of TB and MDR-TB in Nepal. However, there is a need to improve laboratory performance and strengthen laboratory infrastructure for optimal utilisation and scale-up of Xpert.


Alteration in ultrastructural morphology of bovine embryos following subzonal microinjection of bovine viral diarrhea virus (BVDV).
The aim of the present study was to evaluate the development and ultrastructure of preimplantation bovine embryos that were exposed to bovine viral diarrhea virus (BVDV) in vitro. The embryos were recovered from superovulated and fertilized Holstein-Friesian donor cows on day 6 of the estrous cycle. Compact morulae were microinjected with 20 pl of BVDV suspension (10(5.16) TCID(50)/ml viral stock diluted 1:4) under the zona pellucida (ZP), then washed in SOF medium and cultured for 24-48 h. Embryos were evaluated for developmental stages and then processed immunocytochemically for the presence of viral particles, using fluorescent anti-BVDV-FITC conjugate. Ultrastructure of cellular organelles was analysed by transmission electron microscopy (TEM).After microinjection of BVDV under the ZP, significantly more (p<0.001) embryos (83.33%) were arrested at the morula stage compared with the intact control (30.33%). Immunocytochemical analysis localized the BVDV-FITC signal inside the microinjected embryos. TEM revealed: (i) the presence of virus-like particles in the dilated endoplasmic reticulum and in cytoplasmic vacuoles of the trophoblast and embryoblast cells; (ii) the loss of microarchitecture: and (iii) abnormal disintegrated nuclei, which lacked reticular structure and the heterochromatin area. In all, the embryo nuclear structure was altered and the microarchitecture of the nucleolus had disappeared when compared with the nuclei from control embryos. Dilatation of the intercellular space and the loss of the intercellular gap junctions were often observed in bovine BVDV-exposed embryos. These findings provide evidence for the adverse effect of BVDV virus on the development of bovine embryos, which is related to irreversible changes in the ultrastructure of cell organelles.


[A case of ventricular septal perforation treated surgically with an infarction exclusion technique].
We report an 85-year-old woman with postinfarction interventricular septal perforation. She underwent successful emergent surgical treatment by a slightly modified method based on David-Komeda's procedure. Perforation in this case occurred four days after acute myocardial infarction. Preoperative Qp/Qs was 2.58, and pulmonary artery pressure was 34/25 mmHg. The area of infarction was large, and the perforation was the linear type 2.5 cm long near the apex. A probe was not able to pass through the perforation due to its complicated configuration. A double Xenomedica patch was sutured on the left side of the interventricular septum without excising the infarcted area. The suture line was placed on healthy myocardium apart from the infarcted area. The Xenomedica patch was sandwiched between the closure line of the ventriculotomy. Four days after surgery, residual shunt was observed by echocardiogram, but this subsequently disappeared on the 17th postoperative day. The patient was discharged from our hospital on the 57th postoperative day, and is now doing quite well.


Molecular pathways in placental-fetal development and disruption.
The first trimester of pregnancy ranks high in priority when minimizing harmful exposures, given the wide-ranging types of organogenesis occurring between 4- and 12-weeks' gestation. One way to quantify potential harm to the fetus in the first trimester is to measure a corollary effect on the placenta. Placental biomarkers are widely present in maternal circulation, cord blood, and placental tissue biopsied at birth or at the time of pregnancy termination. Here we evaluate ten diverse pathways involving molecules expressed in the first trimester human placenta based on their relevance to normal fetal development and to the hypothesis of placental-fetal endocrine disruption (perturbation in development that results in abnormal endocrine function in the offspring), namely: human chorionic gonadotropin (hCG), thyroid hormone regulation, peroxisome proliferator activated receptor protein gamma (PPARγ), leptin, transforming growth factor beta, epiregulin, growth differentiation factor 15, small nucleolar RNAs, serotonin, and vitamin D. Some of these are well-established as biomarkers of placental-fetal endocrine disruption, while others are not well studied and were selected based on discovery analyses of the placental transcriptome. A literature search on these biomarkers summarizes evidence of placenta-specific production and regulation of each biomarker, and their role in fetal reproductive tract, brain, and other specific domains of fetal development. In this review, we extend the theory of fetal programming to placental-fetal programming.


Preparation of new nitrogen-bridged heterocycles. 60. Syntheses and conformational analyses of bis(indolizin-1-yl) disulfides.
Some bis(indolizin-1-yl) disulfides, readily obtainable from the treatment of 1-(benzoylthio)indolizines with piperidine, were prepared and their conformations were investigated. In comparison with those of 1-(benzoylthio)indolizines, the (1)H-NMR spectra of these disulfides showed considerable high field shifts (delta 0.13-0.82 ppm) on each pyridine ring proton and the UV spectra exhibited significant bathochromic and hyperchromic shifts. These results supported strongly the participation of an intramolecular pi-pi interaction between the two indolizine rings in these molecules and, hence, of a particular gauche (cis) conformation. However, the conformational considerations and molecular calculations (Mopac PM3) for some bis(indolizin-1-yl) disulfides showed the presence of four more stable gauche forms in which two are enantiomeric, resulting in three types of gauche structures. These three types of gauche structures were confirmed by X-ray analyses.


Isolation and characterization of rice cesium transporter genes from a rice-transporter-enriched yeast expression library.
A considerable portion of agricultural land in central-east Japan has been contaminated by radioactive material, particularly radioactive Cs, due to the industrial accident at the Fukushima Daiichi nuclear power plant. Understanding the mechanism of absorption, translocation and accumulation of Cs+ in plants will greatly assist in developing approaches to help reduce the radioactive contamination of agricultural products. At present, however, little is known regarding the Cs+ transporters in rice. A transporter-enriched yeast expression library was constructed and the library was screened for Cs+ transporter genes. The 1452 full length cDNAs encoding transporter genes were obtained from the Rice Genome Resource Center and 1358 clones of these transporter genes were successively subcloned into yeast expression vectors; which were then transferred into yeast. Using this library, both positive and negative selection screens can be performed, which have not been previously possible. The constructed library is an excellent tool for the isolation of novel transporter genes. This library was screened for clones that were sensitive to Cs+ using a SD-Gal medium containing either 30 or 70 mM CsCl; resulting in the isolation of 13 Cs+ sensitive clones. 137 Cs absorption experiments were conducted and confirmed that all of the identified clones were able to absorb 137 Cs. A total of 3 potassium transporters, 2 ABC transporters and 1 NRAMP transporter were among the 13 identified clones.


The enhanced photocatalytic performance of SnS2@MoS2 QDs with highly-efficient charge transfer and visible light utilization for selective reduction of mythlen-blue.
Molybdenum disulfide (MoS2) has recently been considered as an effective material for potential photocatalytic applications; however, its photocatalytic activity was limited due to the low density of active sites. In this work, MoS2 Quantum dots (QDs) were synthesized via the ultrasonication technique to construct heterostructure with SnS2 nanosheets (SnS2@MoS2 QDs) and the prepared materials were tested for photocatalytic applications for Methylene blue (MB). Pristine SnS2 and SnS2@MoS2 QDs nanocomposite were analyzed by XRD, TEM, PL, and Uv-Vis. Both SnS2 and SnS2@MoS2 QDs exhibited a single trigonal phase with the P-3m1 space group. The TEM analysis confirmed the coupling between the pristine SnS2 and SnS2@MoS2 QDs. The results of photocatalytic activity toward MB indicated that SnS2@MoS2 QDs material exhibits much superior photocatalytic performance compared to pristine SnS2. The excellent photodegradation performance of SnS2@MoS2 QDs is due in the main to the formation of heterojunction between SnS2 and MoS2 QDs with narrow bandgap formation, which results in a facile carriers transfer and thus high photocatalytic efficiency. A representative mechanism of the photodegradation for SnS2@MoS2 QDs photocatalyst was proposed. Such an ultrasonic technique is capable of producing small metallic particle size that can be used to construct new heterostructures for water remediation applications.


[Angioplasty and stenting of the carotid artery].
Percutaneous endovascular techniques are well established procedures in the management of peripheral vascular disease and visceral arterial stenosis. They are now being adapted for use in the carotid artery as well. 8 patients with 9 extracranial carotid artery stenoses were successfully treated by percutaneous angioplasty, following which in 4 of them 5 stents were inserted. The stenotic lesions were situated in the proximal internal carotid artery and in its bifurcation and also in the common carotid artery. The indications for angioplasty in these patients were the same as for surgery. There were no major complications. 1 patient had transient hemiparesis lasting a few hours, and another had bradycardia following balloon dilation in the region of the carotid body. Percutaneous endovascular treatment of carotid artery stenosis is becoming a safe, feasible alternative to surgery.


Chronic recurrent Gorham-Stout syndrome with cutaneous involvement.
Type IV osteolysis or Gorham-Stout syndrome is a rare condition characterized by recurrent vascular tumors that disrupt normal anatomical architecture. Gorham-Stout syndrome is most commonly associated with the skeletal system with resulting replacement of bone with scar tissue following tumor regression. The loss of entire bones has given Gorham-Stout syndrome the moniker vanishing bone disease. Natural progression of Gorham-Stout syndrome is characterized by spontaneous disease resolution. However, rare variants of recurrent, progressive, and/or systemic disease have been reported. We present a patient with a history of recurrent Gorham- Stout disease refractory to all treatment options considered. In addition to skeletal disease, our patient had soft tissue and cutaneous involvement, thus reflecting the more aggressive disease variant. Previous surgical attempts to control disease had been ineffective and the patient was referred to us for radiation therapy. Treatment with external beam radiation therapy resulted in good local control and symptom palliation, but full disease resolution was never accomplished. In addition to presentation of this patient, a review of the literature on etiological hypotheses and past/future treatment options was conducted and is included.


Efficacy and Safety of an Etofenamate Medicated Plaster for Acute Ankle Sprain: A Randomized Controlled Trial.
The favorable benefit-risk profile of topical nonsteroidal anti-inflammatory drugs (NSAIDs) makes them a preferred treatment for pain relief in soft tissue injuries. To assess the efficacy and safety of a novel etofenamate 70-mg medicated plaster in patients with acute uncomplicated ankle sprain. Randomized controlled trial; Level of evidence, 1. Patients with grade 1 or 2 ankle sprain of recent onset were randomized to etofenamate or placebo plasters (1:1) applied twice daily for 7 days. Clinical assessments, including ankle pain on movement (POM) in mm on a 100-mm visual analog scale (VAS), were made at predefined intervals during the treatment period. In total, 156 male or female adult patients (mean age, 35.3 ± 11.8 years) were enrolled. The fall in VAS values for POM from baseline to 72 hours was markedly in favor of the etofenamate plaster, with respective reductions of 52.7% and 24.0% for active and placebo plasters (least squares mean treatment difference, 22.1 mm; P value for analysis of covariance < .0001). Similar clinically relevant differences between etofenamate and placebo were seen for POM at the 48-, 96-, and 168-hour visits (P < .0001). These differences between etofenamate and placebo plasters were reflected in area under the curve for POM, pain at rest, and ankle swelling measured at various time points during the 7 days. Time taken to achieve a meaningful (30%) and optimal (50%) reduction of POM was significantly shorter in the etofenamate group. The responder rate (proportion of patients with at least 50% pain reduction at 72 hours) was 52.5% for the etofenamate plaster and 7.7% for the placebo. A significantly greater proportion of patients randomized to etofenamate rated their progress and/or the treatment as "good" or "very good." The medicated plasters adhered well over the 12-hour dosing period and were very well-tolerated. With respect to the investigated indication, uncomplicated ankle sprain, the etofenamate plaster has therapeutic efficacy that is similar to that for the best available topical NSAID formulations. 2016-000252-99 (EudraCT number).


Forced degradation studies of lansoprazole using LC-ESI HRMS and 1 H-NMR experiments: in vitro toxicity evaluation of major degradation products.
Regulatory agencies from all over the world have set up stringent guidelines with regard to drug degradation products due to their toxic effects or carcinogenicity. Lansoprazole, a proton-pump inhibitor, was subjected to forced degradation studies as per ICH guidelines Q1A (R2). The drug was found to degrade under acidic, basic, neutral hydrolysis and oxidative stress conditions, whereas it was found to be stable under thermal and photolytic conditions. The chromatographic separation of the drug and its degradation products were achieved on a Hiber Purospher, C18 (250 × 4.6 mm, 5 μ) column using 10 mM ammonium acetate and acetonitrile as a mobile phase in a gradient elution mode at a flow rate of 1.0 ml/min. The eight degradation products (DP1-8) were identified and characterized by UPLC/ESI/HRMS with in-source CID experiments combined with accurate mass measurements. DP-1, DP-2 and DP-3 were formed in acidic, DP-4 in basic, DP-5 in neutral and DP-1, DP-6, DP-7 and DP-8 were in oxidation stress condition Among eight degradation products, five were hitherto unknown degradation products. In addition, one of the major degradation products, DP-2, was isolated by using semi preparative HPLC and other two, DP-6 and DP-7 were synthesized. The cytotoxic effect of these degradation products (DP-2, DP-6 and DP-7) were tested on normal human cells such as HEK 293 (embryonic kidney cells) and RWPE-1(normal prostate epithelial cells) by MTT assay. From the results of cytotoxicity, it was found that lansoprazole as well as its degradation products (DP-2, DP-6 and DP-7) were nontoxic up to 50-μM concentrations, and the latter showed slightly higher cytotoxicity when compared with that of lansoprazole. DNA binding studies using spectroscopic techniques indicate that DP-2, DP-6 and DP-7 molecules interact with ctDNA and may bind to its surface. Copyright © 2017 John Wiley & Sons, Ltd.


Women's Views on Factors that Influence Utilisation of Postnatal Follow-Up in Oman: A descriptive, qualitative study.
Postnatal follow-up care (PNFC) is critical for promoting maternal and newborn health and well-being. In Oman, women's utilisation of postnatal follow-up services has declined, with rates as low as 0.29 (mean visits) in some governorates, and fails to meet the recommendation of postnatal follow-up visits at two and six weeks for assessment of the mother and her newborn. The reasons for this low utilisation are not well understood. This study aimed to explore women's views on and identify factors that influence their utilisation of postnatal follow-up services. Purposive sampling was employed and semi-structured telephone interviews were conducted with 15 women aged 20-39 years at six to eight weeks post-childbirth between May and August 2021. The data were analysed using Erlingsson and Brysiewicz's content analysis approach. The following six categories were identified as influencing PNFC utilisation: 1) need for information; 2) experiences and expectations; 3) family support, expectations and customs; 4) sociocultural beliefs and practice; 5) impact of the COVID-19 pandemic; and 6) the healthcare environment. Influencing factors derived from each category include the need to empower women, provide individualised care, address family and community expectations, offer alternatives to face-to-face clinic visits and provide organised and scheduled appointments. Women in Oman identified the need for consistent information from healthcare providers and a more organised postnatal follow-up service that includes scheduled appointments and a woman-centred approach to PNFC.


The scientific basis of recent US guidance on sugars intake.
Most fruits and dairy products are high in sugars, and thus naturally occurring sugars are consumed as part of a healthy diet. Sugars are also added to foods during processing or preparation, primarily to enhance taste. Monosaccharides and disaccharides added to foods are chemically indistinguishable from naturally occurring forms. However, concern has been expressed about the apparent increasing consumption of added sugars and their possible role in displacing or diluting nutrients in the diet and contributing to the epidemic of obesity in developed countries. One of the 2000 Dietary Guidelines for Americans states, "Choose beverages and foods to moderate your intake of sugars." The Dietary Guidelines Advisory Committee discussed whether to specify added sugars rather than the broader term sugars but decided that it was not possible to conclude that added sugars per se play a negative role in the public's health. The Dietary Guidelines Advisory Committee issued a call for more definitive studies of the role of sugars in current diets and the potential effect of a reduction in added sugars on both dietary quality and energy intake. The American Heart Association recently released a statement advising consumers to limit sugars consumption. The macronutrient report for the dietary reference intakes addresses many of these same issues; the expert panel concluded that it was not appropriate to set a tolerable upper intake level for added sugars but suggested a maximal intake level of 25% of energy from added sugars because of concerns about reduced intakes of essential micronutrients.


A Context-Driven Model for the Flat Roofs Construction Process through Sensing Systems, Internet-of-Things and Last Planner System.
The main causes of building defects are errors in the design and the construction phases. These causes related to construction are mainly due to the general lack of control of construction work and represent approximately 75% of the anomalies. In particular, one of the main causes of such anomalies, which end in building defects, is the lack of control over the physical variables of the work environment during the execution of tasks. Therefore, the high percentage of defects detected in buildings that have the root cause in the construction phase could be avoidable with a more accurate and efficient control of the process. The present work proposes a novel integration model based on information and communications technologies for the automation of both construction work and its management at the execution phase, specifically focused on the flat roof construction process. Roofs represent the second area where more defects are claimed. The proposed model is based on a Web system, supported by a service oriented architecture, for the integral management of tasks through the Last Planner System methodology, but incorporating the management of task restrictions from the physical environment variables by designing specific sensing systems. Likewise, all workers are integrated into the management process by Internet-of-Things solutions that guide them throughout the execution process in a non-intrusive and transparent way.


Mouse sperm genotype and the rate of egg penetration in vitro.
(C57BL/10 X CBA)F1 mouse eggs were incubated in vitro with either F1 or outbred TO sperm for 15 minutes-6 hours. Upon removal from the sperm suspensions some eggs were treated with pronase to remove zonae and then cultured, while the remainder were simply cultured to allow a comparison of the fertilization rates in the two groups. Although a brief incubation was sufficient for a high rate of fertilization when the zonae remained intact, results from the zona-free eggs indicated that penetration, i.e., sperm fusion with the vitellus, had not been achieved in all eggs during the shorter incubations. Results from the latter groups of eggs indicated that a 1 hour incubation with TO sperm and a 2 hour incubation with F1 sperm were needed to obtain a mean fertilization rate of 50%. Fertilization was complete within 1.5 hours using TO sperm and 2.5 hours using F1 sperm, thus indicating that under similar environmental conditions sperm genotype can significantly affect the rate of penetration.


A preliminary investigation of the relationship between early maladaptive schemas and compulsive sexual behaviors in a substance-dependent population.
Past research has consistently demonstrated high co-occurrence between substance use disorders (SUDs) and compulsive sexual behaviors (CSBs). Numerous studies have also indicated that maladaptive core beliefs and early maladaptive schemas (EMS) are prevalent among individuals with SUDs and CSBs. However, research has yet to examine the relationship between EMS and CSBs among substance-dependent populations. Thus, the purpose of the current study was to examine this relationship in a sample of 198 men and 62 women in residential treatment for SUDs. Findings demonstrated that the five EMS domains were positively associated with CSBs. Results further demonstrated that patients meeting the cutoff score for CSBs scored significantly higher than patients not meeting the cutoff score for CSBs on the EMS domains of disconnection/rejection, impaired autonomy, and impaired limit. These findings suggest that there is an important and significant relationship between EMS and CSBs among adults in substance use treatment. Results from the current study indicate that EMS may provide a potentially important focus for treatment, particularly among individuals with co-morbid CSBs and SUDs. Given the preliminary nature of this study, continued research is needed to replicate and extend the findings from the current study.


A structural and spectrophotometric study on the complexation of Am(III) with TMOGA in comparison with the extracted complex of DMDOOGA.
Complexation of Am(iii) with tetramethyl-3-oxa-glutaramide (TMOGA, L(I)) is studied by spectrophotometric titrations and single crystal X-ray diffraction. Three successive complex species, [AmL(I)](3+), [AmL](3+), and [AmL](3+), have been identified and their stability constants are calculated to be 3.71 ± 0.012, 5.95 ± 0.021, and 6.93 ± 0.034 respectively, from the absorption spectra collected from the titrations of Am(iii) with L(I) at 25 °C in 1 M NaNO3. Single crystals of AmL(ClO4)3 have been grown from a HClO4 solution containing Am(3+) and L(I). The crystal structure of AmL(ClO4)3 shows that Am(iii) is coordinated by nine oxygen atoms from three L(I) ligands. The deconvoluted UV-Vis absorption spectrum of [AmL](3+) in aqueous solution is nearly identical to the diffusion reflectance spectrum of AmL(ClO4)3 in the solid state, indicating that the coordination geometry of the complexes is nearly the same. In addition, to provide parallels to solvent exaction, the extracted Am(iii) complex with N,N'-dimethyl-N,N'-dioctyl-3-oxa-glutaramide (DMDOOGA, L(II)) is also prepared and studied using spectrophotometry. The similarity in UV-Vis absorption of the extracted complex of Am(iii) with L(II) and [AmL](3+) suggests that the Am(iii) ion is also coordinated by three tridentate L(II) ligands existing as [AmL](3+) in the organic phase of solvent extraction.


The left atrial appendage, a small, blind-ended structure: a review of its echocardiographic evaluation and its clinical role.
The increasing prevalence of stroke and atrial fibrillation is a stimulus for new therapeutic strategies and also warrants a review of imaging modalities of the most important source of cardiac systemic embolic events: the left atrial appendage (LAA). This blind-ended, complex structure is embryologically distinct from the body of the left atrium and is sometimes regarded as just a minor extension of the atrium. However, it should routinely be analyzed as part of a transesophageal echocardiographic (TEE) examination. A pulsed Doppler TEE analysis of LAA emptying flow should supplement a two-dimensional (2-D) analysis; these examinations have proven to be highly reproducible and to help assess thromboembolic risk. In 2-D imaging, potential thrombus and spontaneous echo contrast should be sought. In addition, LAA plays a hemodynamic role that participates in atrial function and is influenced by various hemodynamic conditions. In view of the embolic risks from a dysfunctional appendage, the LAA is often ligated during cardiac valve surgery. New devices are under evaluation for percutaneous closure of the LAA, and further studies should improve the definition, understanding, and treatment of LAA dysfunction.


Sarcoidosis in a preschooler with only skin and joint involvement.
Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. It is relatively rare in children less than 15 years of age and especially in those less than 5-6 years of age. Sarcoidosis characteristically involves the skin, eyes, and synovial tissues in patients less than 5-6 years of age. We report a 3-year-old boy with sarcoidosis who had cutaneous findings with joint symptoms. Dermatologic examination revealed lichenoid, erythematous, 2-3 mm papules, some of them grouped, all over his extremities and trunk. There were symmetric swellings on his ankles and wrists without erythema or pain which did not interfere with function. However, until now, no eye involvement had been detected in the patient.


Aberrant expression of c-met mRNA in human gastric carcinomas.
We examined mRNA expression for c-met encoding hepatocyte growth factor receptor in 8 gastric carcinoma cell lines and 31 surgically resected gastric carcinoma tissues by Northern-blot analysis. Two forms of the transcript, sized 7.0 kb and 6.0 kb, were found in gastric carcinomas. Transcripts of both sizes were detected at various levels in all the gastric carcinoma cell lines except the MKN-74 line, which expressed only the 7.0-kb form. Of the 31 gastric carcinomas, 15 (48%) over-expressed the 7.0-kb transcript when compared with non-neoplastic mucosa. The 6.0-kb transcript of the c-met gene was expressed at considerable levels in 52% of the gastric carcinoma tissues, whereas it was only slightly expressed in non-neoplastic mucosa of a small number of cases. An important finding was that expression of the 6.0-kb transcript was closely correlated with tumor staging, lymph-node metastasis and depth of tumor invasion. These results, overall, suggest that the 6.0-kb transcript of the c-met gene might participate in the development and progression of gastric carcinomas.


Neurobehavioral Effects of Cephalosporins: Assessment of Locomotors Activity, Motor and Sensory Development in Zebrafish.
Most third- and fourth-generation cephalosporins, such as cefotaxime, cefmenoxime, cefepime, and cefpirome, contain an aminothiazoyl ring at the C-7 position. Drug impurity, which may be produced either during synthesis or upon degradation, can induce adverse effects. Various reports have indicated that neurotoxicity is a side effect of cephalosporin. In this study, we developed methods for assessing the free-swimming activities and behaviors in zebrafish larvae in response to continuous darkness and stimulation of light-to-dark photoperiod transition by chemical treatments. We also performed transcriptome analysis to identify differentially expressed genes (DEGs). Gene ontology analysis revealed that various processes related to nervous system development were significantly enriched by DEGs. We integrated 16 DEGs with protein-protein interaction networks and identified that neuroactive ligand-receptor interaction [e.g., λ-aminobutyric acid and glutamate receptor, metabotropic 1a (GRM1A)] pathway was regulated by the compounds. Our findings suggested that neurobehavioral effects mainly depend on the mother nucleus structure 7-aminocephalosporanic acid and the substitution at the C-3 position. In addition, gad2, or111-4, or126-3, grm1a, opn8c, or111-5, or113-2, and or118-3 may potentially be utilized as novel biomarkers for this class of cephalosporins, which causes neurotoxicity. This study provides neurological behavior, transcriptome, and docking information that could be used in further investigations of the structures and developmental neurotoxicity relationship of chemicals.


[Study on pluripotency and cultivation of ES-like cells derived from male germ stem cells of bovine fetuses].
Male germ stem cells (mGSCs), which is in testis after sex differentiation, derive from primordial germ cells. In this study, bovine mGSCs were isolated from testis of 20 weeks fetuses. Number of CD9 positive cells of the cells through two-steps adhering plates velocity different was 95.8% by flow cytometer. The carina-type cells clones and the plane-type cells clones appeared in co-cultured system. One cells lines had been successively maintained for 4 passages, and the cells clusters showed AKP positive staining. The cells clusters showed nest-shape in third passage showed SSEA1 and Oct-4 positive staining. These cells can also spontaneously differentiate into c-kit positive staining germ cells, and the cells were directional induced to formaactin positive staining cardiac-like cells cluster and NF positive staining neuron-like cells. The conclusion showed that male germ stem cells from 20 weeks bovine fetuses could be in vitro formed like embryonic stem cells.


Ethylene glycol poisoning: toxicokinetic and analytical factors affecting laboratory diagnosis.
Ethylene glycol poisoning is an important toxicological problem in medical practice because early diagnosis and treatment can prevent considerable morbidity and mortality. When ingested in the form of antifreeze or other automotive products, ethylene glycol results in central nervous system depression, cardiopulmonary compromise, and renal insufficiency. Metabolism of ethylene glycol to organic acids is required for metabolic derangement and organ damage. Laboratory features of ethylene glycol poisoning include increased anion gap metabolic acidosis, increased osmolal gap, calcium oxalate crystalluria, and detectable ethylene glycol in serum. This Case Conference integrates discussion of the toxicokinetic and analytical variables that affect the laboratory diagnosis of ethylene glycol intoxication.


Lactoferrin from bovine milk inhibits bovine herpesvirus 1 in cell culture but suppresses development of in vitro-produced bovine embryos.
Bovine herpesvirus 1 (BoHV-1) is widely distributed among cattle populations and has been associated with cells, fluids, and tissues collected from donor animals for use in reproductive technologies. The purpose of this study was to determine if lactoferrin would inhibit BoHV-1 in cell culture and to evaluate if embryos could develop normally when cultured in vitro with lactoferrin. In Experiment 1, lactoferrin (10 mg/mL) inhibited up to 25,000 plaque forming units (PFU)/mL of BoHV-1 in Madin Darby bovine kidney (MDBK) cell culture. In Experiment 2, lactoferrin (10 mg/mL) combined with cidofovir (62.5 microg/mL) inhibited up to 100,200 PFU/mL of virus in cell culture. In Experiment 3, following fertilization, presumptive zygotes were cultured in media containing lactoferrin (10, 5, and 2.5 mg/mL). Embryonic development and quality were assessed, and embryonic viability was determined by counting the nucleated cells of developed blastocysts. While lactoferrin did not affect the nucleated cell count of the treated embryos, it did significantly decrease blastocyst development. In conclusion, lactoferrin from bovine milk can inhibit BoHV-1 in cell culture. However, supplementation of in vitro culture medium with lactoferrin inhibits blastocyst development of in vitro-produced embryos.


EXAMINING THE PREFERENCE FOR SHADE STRUCTURES IN FARMED GREEN SEA TURTLES (CHELONIA MYDAS) AND SHADE'S EFFECT ON GROWTH AND TEMPERATURES.
The Cayman Turtle Farm raises thousands of green sea turtles ( Chelonia mydas ) annually under aquaculture conditions. Historically, the turtles have been raised in tanks without routine access to a shade structure. The purpose of this study was to determine the effects of adding a shade structure on curved carapace length (CCL) and weight gain of green sea turtles. In addition, water and cloacal temperatures were compared across treatment groups and shade cover preferences observed. Ninety turtles were split equally into three treatment groups for this 8-wk study. In the first group turtles were kept in tanks in full sun, the second group in half-shaded tanks, and the third group in tanks completely covered with shade cloth. Time-lapse cameras mounted above half-shaded tanks were used to determine turtle shade structure preferences throughout the day. There were no differences in CCL among treatment groups. Significant increases in weights were noted in turtles kept in full sun and half-shaded tanks versus the fully shaded tanks. Significantly higher water and cloacal turtle temperatures were noted in the full-sun tank compared with the half-shaded or completely shaded tanks. A significantly lower number of turtles was observed in the sun in the half-shaded tanks, indicating a possible preference by turtles for a shade structure. Results suggest that providing shade structures for sea turtles results in a significant decrease in both overall water temperature as well as a reduction in maximum high daily temperatures. Results also suggest that turtles exhibit a preference for shade structures when it is provided as an option. From these results, we recommend that a shade structure be provided when housing green sea turtles in outdoor enclosures.


Reliability and validity of the Turkish version of the mini Osteoporosis Quality of Life Questionnaire.
The purpose of this study was to develop a Turkish version of the mini Osteoporosis Quality of Life Questionnaire (mini-OQLQ), and assess its reliability and validity. Sixty-four women with postmenopausal osteoporosis were included in the study. Patients who were diagnosed with secondary osteoporosis through clinical and laboratory examinations were excluded from the study. After translation process, the Turkish version of the scale was applied to each participant twice with an interval of 2 weeks. For reliability study, internal consistency (Cronbach's α) of mini-OQLQ total score and test-retest intraclass correlation coefficient (ICC) were calculated. Validation study was assessed by correlating the scale with QUALEFFO 41. The mean age at menopause and age of patients were 45.61 ± 6.04 and 59.91 ± 8.69 years, respectively. Cronbach's α of the Turkish version of the mini-OQLQ was 0.898. The test-retest reliability (ICC) of the Turkish version of the mini-OQLQ was determined as 0.81 for the total score, and ranged between 0.71 and 0.84 for individual items. In terms of validity, the Turkish version of mini-OQLQ showed significant negative correlation with QUALEFFO 41 (r= -0.756; p < 0.0001). The Turkish version of the mini-OQLQ was found to be reliable and valid in the evaluation of life quality of patients with postmenopausal osteoporosis.


Aquaporin-2 and -3: representatives of two subgroups of the aquaporin family colocalized in the kidney collecting duct.
Since the molecular identification of the first aquaporin in 1992, the number of proteins known to belong to this family has been rapidly increasing. These members may be separated into two subgroups based on gene structure, sequence homology, and function. Regulation of the water permeability of the collecting ducts of the kidney is essential for urinary concentration. Aquaporin-2 and -3, which are representative of these subgroups, are colocalized in the collecting ducts. Understanding these subgroups will elucidate the differences between aquaporin-2 and -3. Aquaporin-2 is a vasopressin-regulated water channel located in the apical membrane, and aquaporin-3 is a constitutive water channel located in the basolateral membrane. In contrast to aquaporin-3, which appears to be less well regulated, many studies have now identified multiple regulational mechanisms at the gene, protein, and cell levels for aquaporin-2, thus reflecting its physiological importance. Evidence of the participation of aquaporin-2 in the pathophysiology of water-balance disorders is accumulating.


[Statistical study regarding anemia in patients admitted with epistaxis. Importance of its control and the associated risk factors].
To emphasize the importance of hemodinamic control and risk factors in the patients hospitalized due to epistaxis. Retrospective study of 200 consecutive patients admitted by such cause between 1997 and 2004 of whom 46 (23%) developed some degree of anemia. Among other clinical variables we analyze the present risk factors, age, sex, levels of hematocrit and hemoglobin, origin of the nasal hemorrhage, number of transfusions that were required and type of nasal packing used. We prove a significant statistical association (p<0,01)) between epistaxis with anemia and risk factors. About 39% of the anemizing epistaxis needed a transfusion, generally red cell concentrates. Every admitted epistaxis needs a good hemodinamic study and control of the patient and the treatment of the base pathology associated.


Oxidative stress in leukemia and antioxidant treatment.
Oxidative stress is caused by the imbalance between the generation of free radicals/reactive oxygen species (ROS) and the antioxidant defense systems, which can activate various transcription factors and affect their transcriptional pathways. Oxidative stress plays an important role in the occurrence and development of leukemia and is closely related to the treatment and prognosis of leukemia. The standard chemotherapy strategies for the pre-treatment of leukemia have many drawbacks. Hence, the usage of antioxidants and oxidants in the treatment of leukemia is being explored and has been preliminarily applied. This article reviews the research progress of oxidative stress and leukemia. In addition, the application of antioxidants treatment in leukemia has been summarized.


Advances in nanomedicine for head and neck cancer.
The quality of life of patients with head and neck squamous cell carcinoma (HNSCC) has been improved because of advances in surgical and radiotherapeutic techniques as well as organ-preservation methods. Despite such progresses, survival rates are dismal because of frequent recurrences, distant metastases and the development of secondary primary tumors. Nanoparticles have distinct characteristics such as a high surface/volume ratio and surface charge and size that can be easily modified. Because of such inherent features, nanoparticles are used in imaging, adjuvant radiotherapy, and drug- or gene-delivery. Thus, nanomedicine holds great promise in the diagnosis and treatment of cancer. In the present review, we summarize recent advances in nanomedicine in the diagnosis and treatment of head and neck cancer. We first review the application of inorganic nanoparticles to photo-thermal and magneto-thermal radiotherapy. We also discuss the use of organic nanoparticles in drug- or gene-delivery during chemotherapy. We then review the application of inorganic nanoparticles as radiotherapy enhancers. Finally, we address the factors that influence the biodistribution of nanoparticles in vivo.


Nuclear Matter Effects on Jet Production at Electron-Ion Colliders.
Jet production and jet substructure in reactions with nuclei at future electron-ion colliders will play a preeminent role in the exploration of nuclear structure and the evolution of parton showers in strongly interacting matter. In the framework of soft-collinear effective theory, generalized to include in-medium interactions, we present the first theoretical study of inclusive jet cross sections and the jet charge at the electron-ion collider. Predictions for the modification of these observables in electron-gold relative to electron-proton collisions reveal how the flexible center-of-mass energies and kinematic coverage at this new facility can be used to enhance the signal and maximize the impact of the electron-nucleus program. Importantly, we demonstrate theoretically how to disentangle the effects from nuclear parton distribution functions and the ones that arise from strong final-state interactions between the jet and the nuclear medium.


Ergodicity of the generalized lemon billiards.
In this paper, we study a two-parameter family of convex billiard tables, by taking the intersection of two round disks (with different radii) in the plane. These tables give a generalization of the one-parameter family of lemon-shaped billiards. Initially, there is only one ergodic table among all lemon tables. In our generalized family, we observe numerically the prevalence of ergodicity among the some perturbations of that table. Moreover, numerical estimates of the mixing rate of the billiard dynamics on some ergodic tables are also provided.


Ultrastructure of the secretory epithelium, nerve fibers, and capillaries in the mouse sweat gland.
The ultrastructure of the mouse sweat gland was examined, in support of neurological studies of sweat glands and their relationships to the autonomic nervous system. It was found that the mouse sweat gland is similar to that of the rat and has only one type of secretory cell. Many nerve fibers are entwined with the secretory tubule and contain accumulations of round, clear vesicles, some microtubules, but apparently no neurofilaments. Cholinesterase is found in the clefts between nerve fibers and their ensheathing Schwann cells. The nerve fibers tend to run parallel with capillaries, but have no close association with either the capillaries or the secretory epithelium. Capillaries provide an abundant blood supply to the sweat gland and are fenestrated. The relationships between cellular elements of the sweat gland provide no direct evidence of the mechanisms involved in neurogenic sweating, although it seems likely that effector substances are diffusely distributed.


[Application status and prospect of single-cone obturation technique with bioceramic sealers].
Compared with cold lateral condensation and continuous wave of condensation which are classically used in clinical, newly emerging single-cone obturation technique is easy-to-operate as well as time-saving. Especially when combined with bioceramic root canal sealers of improved physicochemical and biological properties, single-cone obturation technique showed satisfactory short-term outcomes in clinical observations. However, difficulties still exist in avoiding the root canal overfilling and in operating the retreatment. Besides, the long-term effects of single-cone obturation with bioceramic sealers still remain unclear. This article makes an overview on the history and development of single-cone obturation ,and provides analysis of its pros and corns. Furthermore, we would also like to summarize its clinical application and look into its future improvements.


Frailty in younger adults in hospital.
Even though frailty has been extensively measured in the acute care setting, relatively little is known about the frailty of younger adult inpatients. This study aimed to measure frailty in a sample of hospitalized adults aged 18 years and over and to examine how frailty in younger adult inpatients differs from middle-aged and older adult inpatients. Secondary analyses of prospectively collected cohort data. Research nurses assessed 910 patients at admission to four Australian hospitals using the interRAI Acute Care instrument. Comparison of frailty index (FI) scores and domains was conducted across three age groups: younger (18-49 years), middle-aged (50-69 years) and older adults (≥70 years). Multivariable logistic regression examined risk of prolonged length of stay and unfavourable discharge destination. Younger adults (n = 214; 23.5%) had a mean (SD) FI of 0.19 (0.10). Approximately 27% (n = 57) of younger adults were frail (FI > 0.25). Mood and behaviour, health symptoms and syndromes, nutrition and pain were the most frequently affected domains in younger adults and 50% had ≥3 comorbidities. Frailty increased the risk of long length of stay (odds ratio (OR) = 1.77, P < 0.001) but not the risk of an unfavourable discharge (OR = 1.40, P = 0.20) in younger adults. This study showed that frailty is prevalent in younger patients admitted to acute care and is associated with adverse outcomes. This study was a critical first step towards establishing an understanding of frailty in younger hospitalized adults.


Evidence of a General Acid-Base Catalysis Mechanism in the 8-17 DNAzyme.
DNAzymes are catalytic DNA molecules that can perform a variety of reactions. Although advances have been made in obtaining DNAzymes via in vitro selection and many of them have been developed into sensors and imaging agents for metal ions, bacteria, and other molecules, the structural features responsible for these enzymatic reactions are still not well understood. Previous studies of the 8-17 DNAzyme have suggested conserved guanines close to the phosphodiester transfer site may play a role in the catalytic reaction. To identify the specific guanine and functional group of the guanine responsible for the reaction, we herein report the effects of replacing G1.1 and G14 (G; p Ka,N1 = 9.4) with analogues with a different p Ka at the N1 position, such as inosine (G14I; p Ka,N1 = 8.7), 2,6-diaminopurine (G14diAP; p Ka,N1 = 5.6), and 2-aminopurine (G14AP; p Ka,N1 = 3.8) on pH-dependent reaction rates. A comparison of the pH dependence of the reaction rates of these DNAzymes demonstrated that G14 in the bulge loop next to the cleavage site, is involved in proton transfer at the catalytic site. In contrast, we did not find any evidence of G1.1 being involved in acid-base catalysis. These results support general acid-base catalysis as a feasible strategy used in DNA catalysis, as in RNA and protein enzymes.


[Corneal donation : Dilemma between growing demand and declining donor rate].
One of the most important requirements for successful corneal transplantation is the availability of donor tissue and thus the approval for postmortem corneal tissue donation. The aim of this study was to investigate donor willingness compared to the continuously increasing demand in recent years. Archives of the local eye bank at the Department of Ophthalmology, University of Cologne, Germany in the time period between 1 July 2011 and 31 December 2015 were examined regarding the willingness for corneal donations in deceased patients from the University Hospital of Cologne. Absolute numbers of deceased, exclusion criteria for donation as well as the rate of negative and affirmative decisions were evaluated. In 235 (5.1 %) out of 4593 deceased at the University Hospital of Cologne, corneal donation was accomplished during the observation period. Of the patients 2923 (63.6 %) were excluded because of absolute contraindications for corneal donation and the rate of absolute contraindications increased from 46.6 % in 2011 to 68.9 % in 2015. Willingness for corneal donation in potentially suitable deceased patients diminished from 34.9 % in 2011, to 34.3 % in 2012, 35.5 % in 2013, 28.4 % in 2014 and to 24.1 % in 2015. In relation to the total number of deceased, the number of corneal tissue donations decreased from 11.5 % in 2011 to 3.5 % in 2015. Despite a rising demand, data from Cologne seem to indicate that the number of corneal donations has declined to some extent. In order to increase the number of corneal donors in the future, further educational work as well as standardization and optimization of the tissue donation process seem to be urgently needed.


Establishment of a rat liver transplantation model with prolonged biliary warm ischemia time.
To investigate the impact of different time points of secondary warm ischemia on bile duct in a rat autologous liver transplantation model with external bile drainage. One hundred and thirty-six male inbred SD rats were randomly assigned to one of four groups (I-IV) according to the secondary warm ischemia time of 0, 10, 20 and 40 min. A rat model of autologous liver transplantation with continuous external biliary drainage under ether anesthesia was established. Ten rats in each group were used to evaluate the one-week survival rate. At 6 h, 24 h, 3 d and 7 d after reperfusion of the hepatic artery, 6 rats were killed in each group to collect the blood sample via the infrahepatic vena cava and the median lobe of liver for assay. Warm ischemia time of liver, cold perfusion time, anhepatic phase, operative duration for biliary external drainage and survival rates in the four groups were analyzed for the establishment of models. No significant difference was shown in warm ischemia time, anhepatic phase and operative duration for biliary external drainage among the four groups. Five of the 40 rats in this study evaluated for the one-week survival rate died, including three deaths of severe pulmonary infection in group IV. A significant decrease of one-week survival rate in group IV was noted compared with the other three groups. With the prolongation of the biliary warm ischemia time, the indexes of the liver function assessment were significantly elevated, and biliary epithelial cell apoptosis index also increased. Pathological examinations showed significantly aggravated inflammation in the portal area and bile duct epithelial cell injury with the prolonged secondary warm ischemia time. Microthrombi were found in the micrangium around the biliary tract in some sections from groups III and IV. The relationship between secondary warm ischemia time and the bile duct injury degree is time-dependent, and 20 min of secondary warm ischemia time is feasible for the study of bile duct injury.


Evaluation of a laparoscopically assisted ovariectomy technique in cats.
To describe a laparoscopically assisted ovariectomy (LAO) technique in the cat with a bipolar vessel sealing device (BVSD) or suture ligation and to compare the outcomes to open ovariohysterectomy (OO). Randomized prospective study ANIMALS: Healthy, adult, sexually intact female cats (n = 30). Ten cats were assigned to each group: LAO with BVSD (group A), LAO with ligation (group B), and OO with ligation (group C). Surgical times and complications were assessed. Serum glucose and cortisol were measured prior to surgery and at 1, 2, 4, 6, 12, and 24 hours after surgery. Pain was scored by using an interactive visual analog scale (IVAS) at 0, 1, 2, 4, 6, 8, 12, 18, 24, 36, and 48 hours after surgery. Rescue analgesia was provided when IVAS score was 4 or more. Physiological and serum values and IVAS scores were compared among groups with area under the curve (AUC) by using a 1-way ANOVA. Surgical time was shortest for group C (19.1 ± 5.2 minutes; P < .0002); there was no significant difference between groups A (27.7 ± 6.6 minutes) and B (33.2 ± 8.2 minutes). All procedures were completed successfully. No significant differences among groups were found in IVAS scores (P = .36), rescue analgesia (P = .22), glucose AUC (P = .53), or cortisol AUC (P = .27). The LAO technique was accomplished as described in all cats with no complications or failures. Pain scores were not different from cats undergoing OO. LAO can be performed efficiently to maximize the benefits of minimally invasive surgery and is amenable to clinical practice.


[Clinical observation on effect of tongfu xiere recipe in treating surgical abdominal diseases accompanied with systemic inflammatory response syndrome].
To observe the effect of Tongfu Xiere Recipe (TXR) on surgical abdominal diseases accompanied with systemic inflammatory response syndrome (SIRS). Forty-six patients in the post-operational stage were treated by basic therapy, including conventional treatment and antibiotics applying, and combined use of TXR, and compared with the 43 patients treated by basic therapy alone as the control group. Compared with the control group, the incidence of complications in the treatment group was significantly lower (P<0.01). The incidence of multiple organ dysfunction syndrome (MODS) and the mortality in the treatment group showed an decreasing tendency. Moreover, levels of plasma endotoxin, TNF-alpha, IL-6 and IL-8 in the treatment group after treatment decreased significantly, while IL-2 level increased (P < 0.01), and showed a significant difference (P < 0.01) as compared with those in the control group. The combined therapy can decrease the levels of blood endotoxin and inflammation promoting cytokine and increase the level of cytokine that directly related with immune function to regulate immunity and inhibit the inflammatory reaction, and furthermore, to prevent MODS and decrease the mortality of patients with surgical abdominal diseases accompanied SIRS.


Preparation and Study of Folate Modified Albumin Targeting Microspheres.
In this study, folate modified bovine serum albumin was successfully synthesized, while preparation of Nintedanib albumin microspheres (ND-FSA NPs) as a carrier was carried out via electrospinning technology. Folate modified albumin was used to enhance the targeting potential of the prepared microspheres. The prepared microspheres had spherical appearance and smooth outer surface. The diameters of microspheres (764.68 ± 88.46 nm) and zeta potential (- 18.38 ± 0.41 mV) were acceptable. The prepared ND-FSA NPs demonstrated a good degree of modification, wherein the modification rate was 28.1%. In vitro release was significantly increased in three different media (double deionized water-DDW, HCl-pH 1.2, and phosphate buffered solution containing 0.5% Tween 80). It is worth noting that incorporation of Nintedanib into folic acid modified albumin microspheres resulted in an enhanced uptake of the drug into MCF-7 breast cancer cells coupled with higher inhibition rate. Altogether, incorporation of Nintedanib into folate modified albumin microspheres is a new approach to improve water solubility and targeting effect of the drug.


Salvage lung resection after definitive radiation (>59 Gy) for non-small cell lung cancer: surgical and oncologic outcomes.
Isolated local relapse occurs in 24% to 35% of patients after definitive chemoradiation for locally advanced non-small cell lung cancer. Although originally considered inoperable, select patients are referred for surgical salvage. We describe a series of salvage lung resection after curative-intent radiation. Twenty-four consecutive patients from 1997 to 2005 were identified retrospectively. Medical records reviewed. Patients were grouped by surgical indication: A, obvious relapse by computed tomography (CT), 7 patients; B, abnormal fluorodeoxyglucose-positron emission tomography (FDG-PET), 12; C, delayed conversion to trimodality, 4; and D, chronic bronchopleural fistula, 1. All patients received definitive radiation (median, 63.9 Gray), 22 with concurrent chemotherapy. Original staging included cardiothoracic surgical consultation in 4. Median time from radiation to resection was 21 weeks. Twenty-four patients underwent 25 resections: one wedge, 10 lobectomies, 4 bilobectomies, and 10 pneumonectomies. Nineteen flaps were performed, 16 omental. Fourteen had complications, including one death from adult respiratory distress syndrome. Viable tumor was found in 19 patients. Median overall survival was 30 months (12 months, group A; 43 months, group B). Estimated 3-year survival was 47%. The Kaplan-Meier survival curve for group B was superior to that for group A (p = 0.019). Salvage lung resection after definitive chemoradiation is feasible, with encouraging survival. Surgical indication is predictive, with higher survival among patients undergoing resection for abnormal FDG-PET than for obvious relapse by CT. FDG-PET should be studied prospectively in selecting patients for salvage lung resection. Systematic staging may have increased primary incorporation of surgery, minimizing the need for late salvage.


Plasmapheresis as rescue therapy for systemic lupus erthyematosus-associated diffuse alveolar haemorrhage.
Diffuse alveolar haemorrhage (DAH) is a rare complication of systemic lupus erythematosus (SLE), which can have a potentially lethal outcome. Conventional treatments of the condition include cyclophosphamide and intravenous immunoglobulins. Successful treatment with rituximab and plasmapheresis has also been described. The authors report the case of a woman recently diagnosed with SLE who developed DAH refractory to conventional treatment while on immunosuppressive treatment for class III lupus nephritis whose DAH responded to plasmapheresis.


Immunofluorescence detection of drugs in postmortem tissues: a new technique with potential for assessment of drug influence in cause of death.
This report describes a new technique, immunofluorescence, for the detection and possible characterization of drug content in postmortem tissues. By using antisera generated against a drug-protein conjugate, the stabilization of tissue-sequestered drug is accomplished by incubation of fresh frozen sections of tissue with dilute solutions of rabbit anti-drug antibodies. Secondary incubation with a fluorescence-labeled anti-rabbit immunoglobulin labels these points of sequestration. Tissue sections so stained are examined by fluorescence microscopy. In studies with rats given graded doses of morphine sulfate, there were discernible differences in tissue binding of morphine in brain sections from animals treated "therapeutically," fatally, and chronically. Extension of these studies to human autopsy material is anticipated and potential problems are discussed. This technique offers the forensic toxicologist the potential for evaluating the drug content of tissues in situ.


Management Effectiveness of a Secondary Coniferous Forest for Landscape Appreciation and Psychological Restoration.
We investigated the influence of forest management on landscape appreciation and psychological restoration in on-site settings by exposing respondents to an unmanaged, dense coniferous (crowding) forest and a managed (thinned) coniferous forest; we set the two experimental settings in the forests of the Fuji Iyashinomoroi Woodland Study Center. The respondents were individually exposed to both settings while sitting for 15 min and were required to answer three questionnaires to analyze the psychological restorative effects before and after the experiment (feeling (the Profile of Mood States), affect (the Positive and Negative Affect Schedule), and subjective restorativeness (the Restorative Outcome Scale). To compare landscape appreciation, they were required to answer another two questionnaires only after the experiment, for scene appreciation (the semantic differential scale) and for the restorative properties of each environment (the Perceived Restorativeness Scale). Finally, we obtained these findings: (1) the respondents evaluated each forest environment highly differently and evaluated the thinned forest setting more positively; (2) the respondents' impressions of the two physical environments did not appear to be accurately reflected in their evaluations; (3) forest environments have potential restorative effects whether or not they are managed, but these effects can be partially enhanced by managing the forests.


Pott's puffy tumour mimicking preseptal cellulitis.
Periorbital swelling can be secondary to local infections (for example, hordeolum) or reflective of an adjacent infection (for example, dental disease). Rarely, periorbital swelling can indicate underlying sinus disease; Pott's puffy tumour is a unique and serious form of this process. This paper presents an unusual way in which a smouldering sinusitis can erode through bone and result in orbital cellulitis or intracranial infection.


The Influence of Heat and Cryogenic Treatment on Microstructure Evolution and Mechanical Properties of Laser-Welded AZ31B.
The pores and coarse lamellar Mg17Al12 that inevitably occur in the weld zone are the major challenge for laser-welded magnesium (Mg) alloys including AZ31B. In order to improve microstructure uniformity and eliminate welding defects, a new process assisted with combination of heat and cryogenic treatment was applied in this study. The results showed that after solution treatment, the number and size of precipitates decreased and the uniformity of the microstructure improved. After cryogenic treatment, the lamellar Mg17Al12 was cracked into particles, and the grain size was refined. After solution + cryogenic treatment, Al8Mn5 substituted the lamellar Mg17Al12. Through studying the changes in microhardness, precipitates, and microstructure under different treatments, it was found that the conversation of Mg17Al12 from lamellar state into particle-like state as well as the appearance of dispersed Al8Mn5 particles played a second-phase strengthening role in improving the mechanical properties of Mg alloy laser-welded joint, and the tensile strength (258.60 MPa) and elongation (10.90%) of the sample were 4.4% and 32.6% higher than those of the as-welded joint.


A fluoride-selective PCT chemosensor based on formation of a static pyrene excimer.
[reaction: see text] Calixarene-based fluorescent chemosensor 1 with two fluorogenic pyrene units conjugated to amide groups as guest recognition sites is synthesized. Complexation of F(-) by 1 causes a red shift of its absorption band to 400 nm (Deltalambda = 54 nm) and a blue shift of the excimer emission to 470 nm (Deltalambda = 12 nm) together with enhanced fluorescence intensity. The blue-shifted excimer emission is attributed to a pyrene dimer formed in the ground state, a so-called static excimer.


A Case of Extranodal Metastasis of Primary Bone Lymphoma in the Lower Extremity.
Primary bone lymphoma is a rare disease, accounting for less than 5% of all extranodal lymphoma. Although the femur is cited as being the most common site, primary bone lymphoma is rare, accounting for less than 1% of all non-Hodgkin's lymphoma. Herein we present a case of diffuse B-cell-type malignant lymphoma manifested as a large soft-tissue mass of the leg, via metastasis of primary non-Hodgkin's lymphoma of the femur, which went untreated. We highlight the advantages of various imaging modalities used throughout the process of diagnosis and treatment because accurate and early diagnosis are essential. This case gives us a unique opportunity to witness the rapid progression of metastasis and an atypical location.


Human saturated steroid 6alpha-hydroxylase.
This study was conducted to evaluate further the reaction catalyzed by the saturated steroid 6alpha-hydroxylase of extrahepatic human tissues. Progesterone and 5alpha-dihydroprogesterone (5alpha-DHP) are plasma-borne precursors of 5alpha-pregnan-3alpha-ol-20-one, an anxiolytic/anesthetic steroid, and 5alpha-pregnan-3beta-ol-20-one in extrahepatic human tissues. These two steroids are metabolized further by a saturated steroid 6alpha-hydroxylase enzyme(s) that is distinct from the cytochrome P450 6alpha-hydroxylase that catalyzes the 6alpha-hydroxylation of delta4-3-ketosteroids such as progesterone, cortisol, and testosterone. Products of this saturated steroid 6alpha-hydroxylase, viz. 3beta/alpha,6alpha-dihydroxy-5alpha-pregnan-20-ones, are major radiolabeled urinary metabolites (excreted as glucuronosides) of i.v. administered tritium-labeled 5alpha-DHP in women and men. T47-D human breast cancer cells, which are rich in saturated steroid 6alpha-hydroxylase activity, were used as the enzyme source in this study. The greatest total and the highest specific activity of saturated steroid 6alpha-hydroxylase were localized in microsome-enriched preparations; enzyme activity was linear with incubation time up to 30 min and with microsome-enriched tissue protein concentrations between 0.05-0.5 mg/mL incubation mixture. The velocity of the reaction was similar in incubations in which the pH was varied from 6.0-8.0, and NADH and NADPH were equally effective in supporting the 6alpha-hydroxylation of 5alpha-pregnan-3beta-ol-20-one and 5alpha-pregnan-3alpha-ol-20-one. The more efficient substrates for this enzyme were 5alpha-pregnan-3beta-ol-20-one and 5alpha-pregnan-3alpha-ol-20-one, and the apparent Km (approximately 3.5 micromol/L) and maximum velocity (approximately 150 pmol/min x mg microsome-enriched protein) for these two substrates were indistinguishable. 5alpha-Androstane-3beta,17beta-diol was less efficiently 6alpha-hydroxylated, and 5alpha-androstane-3alpha,17beta-diol was an inefficient substrate. The addition of a variety of inhibitors of cytochrome P450 monooxygenases to the incubation mixtures did not diminish significantly the 6alpha-hydroxylation of 5alpha-pregnan-3beta-ol-20-one, findings consistent with those of other investigators who suggested that human saturated steroid 6alpha-hydroxylase (of human prostate) is not a cytochrome P450.


How Can Transcranial Magnetic Stimulation Be Used to Modulate Episodic Memory?: A Systematic Review and Meta-Analysis.
A systematic review and meta-analysis were conducted to synthesize the existing literature on how transcranial magnetic stimulation (TMS) has been used to modulate episodic memory. Given the numerous parameters of TMS protocols and experimental design characteristics that can be manipulated, a mechanistic understanding of how changes in the combination of parameters (e.g., frequency, timing, intensity, targeted brain region, memory task) modulate episodic memory is needed. To address this, we reviewed 59 studies and conducted a meta-analysis on 245 effect sizes from 37 articles on healthy younger adults (N = 1,061). Analyses revealed generally more beneficial effects of 1-Hz rTMS vs. other frequencies on episodic memory. Moderation analyses revealed complex interactions as online 20-Hz rTMS protocols led to negative effects, while offline 20-Hz rTMS led to enhancing effects. There was also an interaction between stimulation intensity and frequency as 20-Hz rTMS had more negative effects when applied below- vs. at-motor threshold. Conversely, 1-Hz rTMS had more beneficial effects than other frequencies when applied below- vs. at- or above-motor threshold. No reliable aggregate or hypothesized interactions were found when assessing stimulation site (frontal vs. parietal cortex, left vs. right hemisphere), stimulated memory process (during encoding vs. retrieval), the type of retrieval (associative/recollection vs. item/familiarity), or the type of control comparison (active vs. sham or no TMS) on episodic memory. However, there is insufficient data to make strong inference based on the lack of aggregate or two-way interactions between these factors, or to assess more complex (e.g., 3-way) interactions. We reviewed the effects on other populations (healthy older adults and clinical populations), but systematic comparison of parameters was also prevented due to insufficient data. A database of parameters and effects sizes is available as an open source repository so that data from studies can be continuously accumulated in order to facilitate future meta-analysis. In conclusion, modulating episodic memory relies on complex interactions among the numerous moderator variables that can be manipulated. Therefore, rigorous, systematic comparisons need to be further investigated as the body of literature grows in order to fully understand the combination of parameters that lead to enhancing, detrimental or null effects on episodic memory.


Miller-Dieker Syndrome due to a 5.5-Mb 17p Deletion in a 17;Y Pseudodicentric Chromosome.
Miller-Dieker syndrome (MDS) is a contiguous gene deletion syndrome in which almost all patients present de novo 17p13.3 deletions. We report on a male infant with MDS and an unusual unbalanced translocation involving chromosomes Y and 17 that resulted in a large 5.5-Mb 17pterp13.2 deletion and a karyotype with 45 chromosomes. Apart from the deletion of the MDS critical region, the deletion of additional distal genes seemed to have no major influence on the patient's phenotype, since he did not show any unusual clinical findings that are not commonly described in MDS patients.


Predictors for hematopoietic growth factors use in HIV/HCV-coinfected patients treated with peginterferon alfa 2b and ribavirin.
HIV/hepatitis C virus (HCV)-coinfected individuals have accelerated liver disease, increased drug toxicities, and modest responses to peginterferon and ribavirin. Hematologic toxicities necessitating dose reduction or discontinuation are limiting factors to HCV treatment in the coinfected patient. This study aimed to identify predictors for the need of filgrastim and darbepoetin to manage hematologic toxicities so as to maintain patients on full doses of study drugs for the duration of study. The primary study was a single-center, open-label, prospective study to evaluate the safety, efficacy, and viral kinetics of 48-week peginterferon alfa 2b and ribavirin in HIV/HCV-coinfected patients. Complete blood count was monitored at baseline, days 3, 7, 10, 14, and then weekly for the first month, fortnightly until week 8, then monthly from week 12 to 48. Filgrastim was initiated when absolute neutrophil count (ANC) fell below 750 cells/mm(3) and darbepoetin was used when hemoglobin dropped to less than 10 g/dL. All patients experienced decrease in ANC and hemoglobin. Twenty of 30 (66.6%) of patients required hematopoeitic growth factors, 15 (50%) received filgrastim, and 12 (40%) received darbepoetin. Seven (23.3%) required both. Baseline ANC of less than 2250 cells per millimeter and negative rate of change of hemoglobin on day 3 of therapy were excellent predictors for filgrastim and darbepoetin use, respectively. Supplemental growth factors were associated with substantial increase in overall cost for HCV treatment. Larger clinical trials will be needed to address the cost effectiveness of supplemental growth factor use in the HIV/HCV-coinfected patients.


Light-chain 3A autophagic activity and prognostic significance in non-small cell lung carcinomas.
Lung carcinoma has a poor prognosis that is mainly predicted by the stage of the disease. Despite evaluation of various prognostic factors, the role of autophagy, a self-degradative process involved in the turnover of cytoplasmic material, remains unexplored in lung malignancy. Autophagic activity was investigated in 115 patients with non-small cell lung carcinoma treated with surgery (64 squamous cell carcinomas, 24 adenocarcinomas of mixed subtype, 18 large cell carcinomas, 9 uncommon types). The median overall survival was 32 months (range, 2-102 months). We used the MAP1LC3A antibody and a standard immunohistochemical technique. Autophagic activity was correlated with clinical and pathologic parameters. Immunohistochemical examination revealed three patterns of autophagic activity: diffuse cytoplasmic, cytoplasmic perinuclear, and "stone-like" structures (SLSs), which are dense, rounded cytosolic structures typically enclosed within light-chain 3 (LC3) A-positive vacuoles. A high SLS count was associated with a reduction of the overall median survival from 88 to 15 months and constituted the strongest independent variable in multivariate analysis. Interestingly, a high presence of SLS defined significantly poor prognosis within stage I and II, whereas a similar trend was noted within stage III. The other two patterns of LC3A reactivity were not correlated with prognosis. Exaggerated autophagy, as indicated by the intense presence of SLSs, is strongly correlated with a poor outcome in non-small cell lung carcinoma, suggesting possibly that autophagy functions as a survival tool in cancer cells.