[The potential use of serum HBV RNA to guide the functional cure of chronic hepatitis B].
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in infected hepatocytes is the main cause of off-therapy viral rebound. The half-life of cccDNA is only 33-50 days, so the conversion of newly synthesized rcDNA to cccDNA in the nucleus is essential for the maintenance of cccDNA pool in infected hepatocytes. Though not directly targeting the existing cccDNA, current nucleos(t)ide analogues (NAs) may exhaust the cccDNA reservoir by blocking the rcDNA formation. Indeed, a prolonged consolidation therapy post loss of serum HBV DNA can achieve sustained remission and thus safe drug discontinuation in a small proportion of chronic hepatitis B (CHB) patients. In recent studies, we and others have demonstrated that it is the serum HBV RNA that reflects the cccDNA activity in infected hepatocytes, particularly among the patients on NAs. Here we suggest that instead of measuring serum HBV DNA only, simultaneous measurement of both viral DNA and RNA would improve the accuracy to reflect the cccDNA activity; therefore, the virological response should be redefined as consistent loss (less than the lower limit of detection) of both serum HBV DNA and RNA, which indicates the safety of drug discontinuation. Accumulating evidence has suggested that for the CHB patients with lower serum HBsAg, switch-to or add-on pegylated interferon (Peg-IFN) treatment would result in loss of serum HBsAg in a relatively large proportion of CHB patients. Since serum HBV RNA is an ideal biomarker to reflect the intrahepatic cccDNA activity, for the patients with a serum HBsAg level lower than 1 500 IU/ml after long-term NAs treatment, the serum HBV RNA should be measured. If serum HBV RNA is detected, peg-IFN should be added on; if serum HBV RNA is not detected, NAs treatment should be switched to peg-IFN treatment. We believe the therapy based on serum HBV RNA would make the functional cure of CHB (serum HBsAg loss or even conversion to anti-HBs) more efficient.


Optimization of a Digestion Method to Determine Total Mercury in Fish Tissue by Cold Vapor Atomic Fluorescence Spectrophotometry.
Several microwave-assisted digestion methods were tested at the Centro de Estudios Aplicados en Química laboratory in Quito, Ecuador, to determine the accuracy and performance efficiency of the mineralization process for the determination of total mercury in fish tissue by cold vapor atomic fluorescence spectrophotometry. The use of MARSEasyPrep high-pressure vessels, low amounts of reagents (1 cm3 HNO3, 1 cm3 H2O2, and 1 cm3 HClO4), an irradiation temperature of 210 °C, and 35 min of mineralization time resulted in accurate performance, with recoveries of certified reference material DORM-4 between 90.1% and 105.8%. This is better than the Association of Official Analytical Chemists 2015.01 method, which has a reported accuracy of 81%. The repeatability precision and intermediate precision were established at three concentration levels (0.167, 0.500, and 0.833 mg·kg-1) and expressed as the percentage of the relative standard deviation ranging from 1.5% to 3.0% and 1.7% to 4.2%, respectively. Further, the method was satisfactorily applied to analyze fortified samples of tilapia (Oreochromis niloticus), with recoveries ranging from 98.3% to 104.3%. The instrumental limits of detection and quantification were 0.118 µg·dm-3 and 0.394 µg·dm-3, respectively.


Multiple cerebral arteriovenous malformations associated to rostral hypoplasia of the superior sagittal sinus: a case report.
Multiple cerebral arteriovenous malformations (AVMs) are a rare occurrence usually associated with defined genetic disorders or a family history of cerebrovascular disease. The remaining cases cannot be associated to a genetic pathogenesis and are considered idiopathic. We report an extremely unusual case nor genetic neither idiopathic, but linked to an anatomical intracranial venous variation. The patient presented two independent frontal AVMs associated with rostral hypoplasia of the superior sagittal sinus. This anatomical variation may have induced frontal venous hypertension (VHT) triggering the development of the two AVMs. Throughout this intriguing case, we discuss the role of VHT in AVM development.


Efficient (3S)-Acetoin and (2S,3S)-2,3-Butanediol Production from meso-2,3-Butanediol Using Whole-Cell Biocatalysis.
(3S)-Acetoin and (2S,3S)-2,3-butanediol are important platform chemicals widely applied in the asymmetric synthesis of valuable chiral chemicals. However, their production by fermentative methods is difficult to perform. This study aimed to develop a whole-cell biocatalysis strategy for the production of (3S)-acetoin and (2S,3S)-2,3-butanediol from meso-2,3-butanediol. First, E. coli co-expressing (2R,3R)-2,3-butanediol dehydrogenase, NADH oxidase and Vitreoscilla hemoglobin was developed for (3S)-acetoin production from meso-2,3-butanediol. Maximum (3S)-acetoin concentration of 72.38 g/L with the stereoisomeric purity of 94.65% was achieved at 24 h under optimal conditions. Subsequently, we developed another biocatalyst co-expressing (2S,3S)-2,3-butanediol dehydrogenase and formate dehydrogenase for (2S,3S)-2,3-butanediol production from (3S)-acetoin. Synchronous catalysis together with two biocatalysts afforded 38.41 g/L of (2S,3S)-butanediol with stereoisomeric purity of 98.03% from 40 g/L meso-2,3-butanediol. These results exhibited the potential for (3S)-acetoin and (2S,3S)-butanediol production from meso-2,3-butanediol as a substrate via whole-cell biocatalysis.


Factors affecting growth from heat-treated spores of non-proteolytic Clostridium botulinum.
Heat treatment of spores of non-proteolytic Clostridium botulinum at 85°C for 120 min followed by enumeration of survivors on a medium containing lysozyme resulted in a 4.1 and 4.8 decimal reduction in numbers of spores of strains 17B (type B) and Beluga (type E), respectively. Only a small proportion of heated spores formed colonies on medium containing lysozyme; this proportion could be increased by treatments designed to increase the permeability of heated spores. The results indicate that the germination system in spores of non-proteolytic Cl. botulinum was destroyed by heating, that lysozyme could replace this germination system, and that treatments that increased the permeability of the spore coat could increase the proportion of heated spores that germinated on medium containing lysozyme. These results are important in relation to the assessment of heat-treatments required to reduce the risk of survival and growth of non-proteolytic Clostridium botulinum in processed (pasteurized) refrigerated foods for extended storage.


Syntheses and structures of new phases AeMxIn(4-x) (Ae = Sr, Ba; M = Mg, Zn): size effects and site preferences in BaAl4-type structures.
The title phases were synthesized via high-temperature solid-state methods and structurally characterized by single-crystal X-ray diffraction. The phase widths of both SrMg(x)In(4-x) (0.85 <or= x <or= 1.53) and BaMg(x)In(4-x) (0 <or= x <or= 1.79) are consistent with size matches between Ae and the encapsulating M-In cages. All compounds crystallize in body-centered tetragonal BaAl(4)-type structure (I4/mmm, Z = 2) except that SrMg(x)In(4-x), 0.85 <or= x <or= 1.24, occurs in the lower-symmetry space group (I4m2, Z = 2) and the atoms are all ordered at the composition SrMgIn(3). The substitution of the effectively smaller Mg or Zn atoms into the indium sublattice of the monoclinic SrIn(4) (C2/m) dramatically changes the structure into the tetragonal BaAl(4)-type structure. Compared with the Mg compounds in which all Mg occupy the basal 4d crystallographic site, Zn occupies the other 4e (apical) site in both BaZn(0.79(2))In(3.21) and SrZn(1.00(4))In(3.00). These differences are related to the interplay of size and electronic factors. The latter may be expressed by not only electronegativities but also total energies according to linear muffin-tin-orbital calculations.


Vitamin D fails to prevent serum starvation- or staurosporine-induced apoptosis in human and rat osteosarcoma-derived cell lines.
Previous studies have suggested that 1,25(OH)2D3, the active form of vitamin D3, may increase the survival of bone-forming osteoblasts through an inhibition of apoptosis. On the other hand, vitamin D3 has also been shown to trigger apoptosis in human cancer cells, including osteosarcoma-derived cell lines. In the present study, we show that 1,25(OH)2D3 induces a time- and dose-dependent loss of cell viability in the rat osteosarcoma cell line, UMR-106, and the human osteosarcoma cell line, TE-85. We were unable, however, to detect nuclear condensation, phosphatidylserine externalization, or other typical signs of apoptosis in this model. Moreover, 1,25(OH)2D3 failed to protect against apoptosis induced by serum starvation or incubation with the protein kinase inhibitor, staurosporine. These in vitro findings are thus at variance with several previous reports in the literature and suggest that induction of or protection against apoptosis of bone-derived cells may not be a primary function of vitamin D3.


A simple, selective, and sensitive gas chromatography-mass spectrometry method for the analysis of five process-related impurities in atenolol bulk drug and capsule formulations.
An extremely sensitive and simple gas chromatography with mass spectrometry method was developed and completely validated for the analysis of five process-related impurities, viz., 4-hydroxy-l-phenylglycine, 4-hydroxyphenylacetonitrile, 4-hydroxyphenylacetic acid, methyl-4-hydroxyphenylacetate, and 2-[4-{(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy}phenyl]acetonitrile, in atenolol. The separation of impurities was accomplished on a BPX-5 column with dimensions of 50 m × 0.25 mm i.d. and 0.25 μm film thickness. The method validation was performed following International Conference on Harmonisation guidelines in which the method was capable to quantitate 4-hydroxy-l-phenylglycine, 4-hydroxyphenylacetonitrile, and 4-hydroxyphenylacetic acid at 0.3 ppm, and methyl-4-hydroxyphenylacetate and 2-[4-{(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy}phenyl]acetonitrile at 0.35 ppm with respect to 10 mg/mL of atenolol. The method was linear over the concentration range of 0.3-10 ppm for 4-hydroxy-l-phenylglycine, 4-hydroxyphenylacetonitrile, and 4-hydroxyphenylacetic acid, and 0.35-10 ppm for methyl-4-hydroxyphenylacetate and 2-[4-{(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy}phenyl]acetonitrile. The correlation coefficient in each case was found ≥0.998. The repeatability and recovery values were acceptable, and found between 89.38% and 105.60% for all five impurities under optimized operating conditions. The method developed here is simple, selective, and sensitive with apparently better resolution than the reported methods. Hence, the method is a straightforward and good quality control tool for the quantitation of selected impurities at trace concentrations in atenolol.


Cell-specific inhibition of retinoic acid receptor-alpha silencing by the AF2/tau c activation domain can be overcome by the corepressor SMRT, but not by N-CoR.
The human retinoic acid receptor alpha (hRAR alpha) exhibits cell-specific transcriptional activity. Previously, it was shown that in the absence of hormone the wild-type receptor is a transcriptional silencer in L cells, whereas it lacks silencing function and is a weak activator in CV1 cells. Addition of hormone leads to a further increase in transactivation in CV1 cells. Thus, the retinoic acid response mediated by RAR alpha is weak in these cells. It was shown that the CV1-specific effect is due to the receptor C terminus. We show, that the failure of silencing by RAR is not due to a general lack of corepressors in CV1 cells, since the silencing domain of RAR is functionally active and exhibits active repression in these cells. Furthermore, we show that the conserved AF2/tau c activation function of RAR is responsible for the cell-specific inhibition of silencing. Thereby, the CV1 cell specificity was abolished by replacing AF2/tau c of RAR with the corresponding sequence of the thyroid hormone receptor. Thus, we find a new role of the C-terminal conserved activation function AF2/tau c in that, specifically, the RAR AF2/tau c-sequence is able to prevent silencing of RAR in a cell-specific manner. In addition, we show that the inhibitory effect of AF2/tau c in CV1 cells can be overcome by expression of the corepressor SMRT (silencing mediator of retinoic acid and thyroid hormone receptor), but not by that of N-CoR (nuclear receptor corepressor). The expression of these two corepressors, however, had no measurable effect on RAR-mediated silencing in L cells. Thus, the expression of a corepressor can lead to a dramatic increase of hormonal response in a cell-specific manner.


Hepatocellular carcinoma subtypes based on metabolic pathways reveals potential therapeutic targets.
Hepatocellular carcinoma (HCC) is an aggressive malignancy with steadily increasing incidence rates worldwide and poor therapeutic outcomes. Studies show that metabolic reprogramming plays a key role in tumor genesis and progression. In this study, we analyzed the metabolic heterogeneity of epithelial cells in the HCC and screened for potential biomarkers. The hepatic single-cell RNA sequencing (scRNA-seq) datasets of HCC patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Based on data intergration and measurement of differences among groups, the metabolic epithelial cell subpopulations were identified. The single-cell metabolic pathway was analyzed and the myeloid subpopulations were identified. Cell-cell interaction analysis and single-cell proliferation analysis were performed. The gene expression profiles of HCC patients were obtained from the GSE14520 dataset of GEO and TCGA-LIHC cohort of the UCSC Xena website. Immune analysis was performed. The differentially expressed genes (DEGs) were identified and functionally annotated. Tumor tissues from HCC patients were probed with anti-ALDOA, anti-CD68, anti-CD163, anti-CD4 and anti-FOXP3 antibodies. Results We analyzed the scRNA-seq data from 48 HCC patients and 14 healthy controls. The epithelial cells were significantly enriched in HCC patients compared to the controls (p = 0.011). The epithelial cells from HCC patients were classified into two metabolism-related subpopulations (MRSs) - pertaining to amino acid metabolism (MRS1) and glycolysis (MRS2). Depending on the abundance of these metabolic subpopulations, the HCC patients were also classified into the MRS1 and MRS2 subtype distinct prognoses and immune infiltration. The MRS2 group had significantly worse clinical outcomes and more inflamed tumor microenvironment (TME), as well as a stronger crosstalk between MRS2 cells and immune subpopulations that resulted in an immunosuppressive TME. We also detected high expression levels of ALDOA in the MRS2 cells and HCC tissues. In the clinical cohort, HCC patients with higher ALDOA expression showed greater enrichment of immunosuppressive cells including M2 macrophages and T regulatory cells. The glycolytic subtype of HCC cells with high ALDOA expression is associated with an immunosuppressive TME and predicts worse clinical outcomes, providing new insights into the metabolism and prognosis of HCC.


Obstetric characteristics and neonatal performance in a four-year small for gestational age population.
Obstetric and neonatal performance were analyzed in an ultrasound-dated small for gestational age (SGA) population from 1982-1985. Eighty-three percent of 160 SGA infants were identified antenatally by means of intrauterine growth retardation (IUGR) risk scoring, and the pregnancies were supervised at a high-risk clinic. Fifty percent were delivered electively, predominantly in gestational weeks 38-39. Thirty percent were born preterm. The cesarean section rate was 40%. Perinatal mortality was 6%, or 4% when lethal malformations were excluded, ten times higher than the corresponding total population figures. Eleven percent of the fetuses had severe malformations. In the remaining SGA population, one infant died after experiencing severe perinatal asphyxia and another developed cerebral palsy; no other major sequelae were found before the age of 18 months. Hypoglycemia and hypothermia occurred frequently, but these problems were managed satisfactorily. The mean hospital stay for term infants was twice that of appropriate for gestational age infants. We conclude that the extra attention paid to the SGA population is well motivated. Future efforts should be directed toward improving the diagnostic techniques for IUGR, as most of the perinatal mortality occurred among SGA infants not identified before birth.


Lactoferrin quantification in cattle faeces by ELISA.
Promoting and maintaining health is critical to ruminant welfare and productivity. Within human medicine, faecal lactoferrin is quantified for routine assessment of various gastrointestinal illnesses avoiding the need for blood sampling. This approach might also be adapted and applied for non-invasive health assessments in animals. In this proof-of-concept study, a bovine lactoferrin enzyme-linked immunosorbent assays (ELISA), designed for serum and milk, was applied to a faecal supernatant to assess its potential for quantifying lactoferrin in the faeces of cattle. Faecal lactoferrin concentrations were compared to background levels to assess the viability of the technique. A comparison was then made against serum lactoferrin levels to determine if they were or were not reflective of one another. The optical densities of faecal samples were significantly greater than background readings, supporting the hypothesis that the assay was effective in quantifying faecal lactoferrin (T 13, 115 = 11.99, p < 0.0005). The mean faecal lactoferrin concentration was 0.269 µg mL-1 (S.E. 0.031) and the mean serum concentration 0.074 µg mL-1 (S.E. 0.005). Lactoferrin concentrations of faecal and serum samples, taken from the same animals on the same day, were significantly different (T 21 = 2.20, p = 0.039) and did not correlate (r = 0.2699, p = 0.238). Results support the hypothesis that lactoferrin can be quantified in cattle faeces by ELISA. Whilst further research is required to determine the physiological source of the lactoferrin, this highlights the potential of the method for non-invasive assessment of cattle immunology and pathology.


Intramedullary fixation of humeral shaft fractures.
In this paper we document seventy fractures of the humeral shaft that were treated by intramedullary fixation between 1970 and 1981. Complications developed in forty-seven (67 per cent) of the fractures, and forty-five (64 per cent) required at least one additional operative procedure. Of the sixty fractures that were internally fixed within six weeks after injury, nine (15 per cent) had a delayed union and five (8.3 per cent) had a non-union, two of which persisted despite subsequent surgery. Three of the ten fractures that were internally fixed more than six weeks after injury never united despite additional procedures that were done to secure union. Delayed union and non-union were more common in open fractures (33 per cent) than in closed fractures (21 per cent), and with open reduction (39 per cent) than with closed or so-called semi-open reduction (9 per cent). Deep infection occurred in three (5 per cent) of the fractures and was more common in open (17 per cent) than in closed fractures (2 per cent). One of the three open fractures that were treated by immediate fixation became infected, as compared with only one of the nine open fractures treated by delayed fixation. Painful adhesive capsulitis of the shoulder developed in thirty-four (56 per cent) of the patients who had fractures treated with distally directed pins, but motion of the elbow was not restricted in the nine patients with fractures treated with proximally directed pins.


[Radiological findings of gastric scirrhous cancer].
Gastric scirrhous cancer was classified from the radiological findings into three phases (typical, latent and early phases) by cancerous involvement in the gastric wall. Radiological findings in the typical phase were divided into a giant-fold type and a no giant-fold type. We made a differential diagnosis for scirrhous cancer and other diseases. Radiological findings in the typical phase of scirrhous cancer were characteristic stiffness and rigidity of the gastric wall; in the latent phase, they were swelling and winding of mucosal folds in appropriate distended stomach; and in the early phase, interrupted folds around barium fleck. The effect of chemotherapy against a gastric scirrhous cancer is decided by distensibility of the gastric wall in radiological findings.


Intestinal absorption of carboxyfluorescein entrapped in liposomes in comparison with its administration with lipid-surfactant mixed micelles.
The absorption of carboxyfluorescein (CF) entrapped in liposomes from the small intestine was investigated in vivo using bile fistula rats. Within the intestine CF was not metabolized, but 32% of the entrapped CF was released for 3 h from the liposomes when incubated with luminal incubation solution. The data of CF disappearance from the intestinal lumen and of CF plasma concentration showed that no apparent difference was observed between administration of the liposomal CF and that of free dye. Especially in initial 60 min after administration of liposomal CF, the plasma concentration was obviously lower than that in free CF administration. On the contrary, the coadministration of 40 mM lipid-surfactant mixed micelles induced a remarkable promotive effect on the absorption of free CF already in the early periods of the initial 60 min. When liposomal CF was administered into the intestinal lumen of thoracic duct-cannulated rats, the concentration in lymph was lower than that in plasma. Intramural injection of liposomal CF into intestinal wall, however, showed a much higher concentration in lymph than that in plasma. These findings suggest that liposomal entrapment of CF has rather difficulty to be absorbed through the intestinal mucosa, while lipid-surfactant mixed micelles exert a remarkable promotive effect on the absorption of CF.


Validation of an Algorithm to Identify Patients at Risk for Colorectal Cancer Based on Laboratory Test and Demographic Data in Diverse, Community-Based Population.
Approximately 30%-40% of screening-eligible adults in the United States are not up to date with colorectal cancer (CRC) screening. We aimed to validate a predictive score, generated by a machine learning algorithm with common laboratory test data, to identify patients at high risk for CRC in a large, community-based, ethnically diverse cohort. We performed a nested case-control study using data from members of Kaiser Permanente Northern California (1996-2015). Cases were cohort members who received a complete blood cell count at ages 50-75 y, did not have a prior or current diagnosis of CRC diagnosis at the time of the blood cell count, and were subsequently diagnosed with CRC. We used data from the cohort to validate the ability of an algorithm that uses laboratory and demographic information to identify patients at increased risk for CRC. Test performance was evaluated using area under the receiver operating characteristic curve (AUROC) and odds ratios (OR) with 95% CI values to compare high (defined as 97% specificity or more) vs low scores. A high score from the algorithm identified patients with a CRC diagnosis within the next 6 months with 35.4% sensitivity (95% CI, 33.8-36.7) and an AUROC of 0.78 (95% CI, 0.77-0.78). Patients with a high score had an increased risk of diagnosis with early-stage CRC (OR, 13.1; 95% CI, 11.8-14.3) and advanced stage CRC (OR, 24.8; 95% CI, 22.4-27.3) within the next 6 months. In patients with high scores, the ORs for proximal and distal cancers were 34.7 (95% CI, 31.5-37.7) and 12.1 (95% CI, 10.1-13.9), respectively. The algorithm's accuracy decreased with the time interval between blood test result and CRC diagnosis; performance did not differ by sex or race. We validated a predictive model that uses complete blood cell count and demographic data to identify patients at high risk of CRC. The algorithm identified 3% of the population who require an investigation and identified 35% of patients who received a diagnosis of CRC within the next 6 months.


Memory trace dependence on number of stimuli in magnetic mismatch negativity.
Mismatch negativity (MMN) reflects a comparison process between a deviant stimulus and the memory trace of standard stimuli. Although this memory mechanism has been investigated by many research studies, the development of memory representation still remains unclear. In this study, we focused on the development of sound trace underlying the MMN response. We measured the magnetic counterpart of MMN (MMNm) in detail, when the neural trace of the standard sound was developed in accordance with the number of standard stimuli. When the number of standard stimuli increased, MMNm latency significantly shortened and the MMNm amplitude showed no significant change. Thus, the developmental effects on memory trace may differ between MMNm amplitude and MMNm latency.


Complete Freund's adjuvant suppresses the development and progression of pristane-induced arthritis in rats.
The present study produced the novel finding that treatment with a nonarthritogenic dose of Complete Freund's adjuvant (CFA) before the onset of pristane-induced arthritis (PIA) could prevent the development of PIA. Surprisingly, treatment with nonarthritogenic and arthritogenic doses of CFA could almost cure the ongoing PIA. CFA treatment also suppressed pathological changes, such as inflammatory cell infiltration, pannus formation, bone destruction, and new bone formation. The lymph node cells of rats with PIA suppressed by CFA showed significantly increased mRNA expression of IFN-gamma but no significant changes in mRNA expression of IL-2, TNF-alpha, IL-4, and IL-5 compared with those of rats in the control groups. The possible mechanisms of the suppressive effect of CFA on the development and progression of PIA were discussed in terms of the anti-inflammatory roles of IFN-gamma, nitric oxide, and heat-shock protein-specific T cell responses. The present study found a new therapeutic implication for the treatment of rheumatoid arthritis.


Biological Traits of the Pincer Wasp Gonatopus Flavifemur (Esaki & Hashimoto) Associated with Different Stages of Its Host, the Brown Planthopper, Nilaparvata Lugens (Stål).
Gonatopus flavifemur (Esaki & Hashimoto) is a common parasitoid of the most important rice pest, the brown planthopper (BPH) Nilaparvata lugens (Stål), in eastern and southeastern Asia. We investigated the parasitism rates, feeding rates, and offspring development of G. flavifemur in association with five instars of BPH nymphs and male and female adults under laboratory conditions (27 ± 1 °C and 70 ± 5% Relative Humidity). The results showed that the life stage of the host significantly affects parasitism, host feeding, and offspring development by G. flavifemur. The parasitism rate was highest on 4th instar nymphs, and the feeding rate was highest on 1st instar nymphs. The cocooning rate on male adult BPHs was significantly lower than that on other stages; however, emergence rates did not significantly differ among the BPH stages. The rate of female offspring upon emergence from 5th instars was higher than other stages. Both the parasitism and host-feeding functional responses of G. flavifemur to different BPH stages fit well with Holling type II models, supporting the results of parasitism and feeding rates and indicating that G. flavifemur would be a good agent for BPH control. In conclusion, G. flavifemur prefers to feed on young nymphs but prefers to parasitize older nymphs. In addition, 5th instar nymphs are favorable to female offspring of the pincer wasp.


[The short-term efficacy of nucleoside analogue on the treatment of acute-on-chronic liver failure].
To discuss the short-term efficacy of nucleoside analogue on the treatment of hepatitis B virus induced acute-on-chronic liver failure (HBV-ACLF). 348 patients with HBV-ACLF in our hospital from January 2006 to June 2008 were selected. According to the stages of patient's condition and whether or not with nucleoside analogue administration, The patients were divided into early stage therapy group, early stage control group, middle stage therapy group and middle stage control group. Groups were compared on the basis of stages. The clinical data were analyzed using chisquare test and independent-Samples T Test. After 2 weeks of therapy no significant difference found between the therapy group and the control group. the total bilirubin (TBil) and alanine transaminase (ALT) showed no significant difference between the middle stage therapy group and the control group in 4 weeks of therapy. However significant differences existed in the HBV DNA negative rate, PTA, the model for end-stage liver disease (MELD) score and the improvement rate between the two groups (P<0.05, P<0.01). Only the 4 week survival rate and HBV DNA negative rate showed significant difference in patients who received anti-virus therapy on the early stage as compared to the control group. Anti-virus therapy with nucleoside analogue is an effective way for the treatment of those patients with HBV-ACLF and can increase the survival rate.


Scale-up and manufacturing of clinical-grade self-inactivating γ-retroviral vectors by transient transfection.
The need for γ-retroviral (gRV) vectors with a self-inactivating (SIN) design for clinical application has prompted a shift in methodology of vector manufacturing from the traditional use of stable producer lines to transient transfection-based techniques. Herein, we set out to define and optimize a scalable manufacturing process for the production of gRV vectors using transfection in a closed-system bioreactor in compliance with current good manufacturing practices (cGMP). The process was based on transient transfection of 293T cells on Fibra-Cel disks in the Wave Bioreactor. Cells were harvested from tissue culture flasks and transferred to the bioreactor containing Fibra-Cel in the presence of vector plasmid, packaging plasmids and calcium-phosphate in Dulbecco's modified Eagle's medium and 10% fetal bovine serum. Virus supernatant was harvested at 10-14 h intervals. Using optimized procedures, a total of five ecotropic cGMP-grade gRV vectors were produced (9 liters each) with titers up to 3.6 × 10(7) infectious units per milliliter on 3T3 cells. One GMP preparation of vector-like particles was also produced. These results describe an optimized process for the generation of SIN viral vectors by transfection using a disposable platform that allows for the generation of clinical-grade viral vectors without the need for cleaning validation in a cost-effective manner.


Condition-specific Quality of Life Assessment at Each Stage of Class III Surgical Orthodontic Treatment -A Prospective Study.
Surgical orthodontic treatment has been reported to improve oral health-related quality of life (OHRQL). Such treatment comprises three stages: pre-surgical orthodontic treatment; orthognathic surgery; and post-surgical orthodontic treatment. Most studies have focused on change in OHRQL between before and after surgery. However, it is also necessary to evaluate OHRQL at the pre-surgical orthodontic treatment stage, as it may be negatively affected by dental decompensation compared with at pre-treatment. The purpose of this prospective study was to investigate the influence of surgical orthodontic treatment on QOL by assessing change in condition-specific QOL at each stage of treatment in skeletal class III cases. Twenty skeletal class III patients requiring surgical orthodontic treatment were enrolled in the study. Each patient completed the Orthognathic Quality of Life Questionnaire (OQLQ), which was developed for patients with dentofacial deformity. Its items are grouped into 4 domains: "social aspects of dentofacial deformity"; "facial esthetics"; "oral function"; and "awareness of dentofacial esthetics". The questionnaire was completed at the pre-treatment, pre-surgical orthodontic treatment, and post-surgical orthodontic treatment stages. The results revealed a significant worsening in scores between at pre-treatment and pre-surgical orthodontic treatment in the domains of facial esthetics and oral function (p<0.01), and between at pre-surgical orthodontic and post-surgical orthodontic treatment in all domains except awareness of dentofacial esthetics (p<0.05, p<0.01). A significant correlation was observed between a negative change in overjet and worsening OQLQ scores at the pre-surgical orthodontic treatment stage. Significant correlations were also observed between improvement in upper and lower lip difference, soft tissue pogonion protrusion, and ANB angle and improvement in OQLQ scores at the post-surgical orthodontic treatment stage. These results indicate that morphologic change influences OHRQL in patients undergoing surgical orthodontic treatment not only after surgery, but also during pre-surgical orthodontic treatment.


Treating Multidimensional Presenting Problems with a Mutually Integrative Approach Using the Genogram.
The present article introduces a case study and describes a mutually integrative approach to treating a complex presenting problem. This article examines the specific issues surrounding integration when a supervisor and supervisee hold different theoretical perspectives. On occasion, such a relationship demands that the supervisee adhere to the model being taught by the supervisor. Examining integration in this format presents many advantages for both treatment and training. The key to the mutual integration is that two schools of psychotherapy can be combined in a way that creates a synergy; in that, together they are more powerful than either may be in isolation. A genogram with symbols from each model is incorporated to focus the treatment and create a format for the mutual integration.


Prevalence and risk factors for delayed adrenal insufficiency after liver transplantation.
Liver transplantation (LT) recipients are at risk for early and delayed adrenal insufficiency for multiple reasons. Although early adrenal insufficiency is known to occur in a high proportion of recipients maintained on steroid-free immunosuppressive regimens, the prevalence and risk factors associated with delayed functional adrenal gland atrophy (FAGA) are unknown because routine evaluation for this condition is not standard practice among LT centers. We investigated a group of 87 patients (64 males) transplanted for end-stage liver disease related to different etiologies. All underwent a standard corticotropin stimulation test (CST) when, after gradual steroid tapering, they had been maintained for at least 1 week on oral prednisone at a daily dose of 5 mg. FAGA, defined by a serum cortisol concentration that, 60 minutes after corticotropin administration, did not double the baseline level and remained <20 mug/dL, was diagnosed in 23/87 patients (26.4%). Stepwise logistic regression analysis selected as significant predictors of FAGA the cumulative dosage of corticosteroids administered (P < 0.01), the increase in the body mass index after LT (P < 0.01), a low serum cholesterol concentration (P = 0.005), and a high adrenocorticotropin hormone (ACTH) serum level (P < 0.05) at the time CST was performed. In conclusion, FAGA is a common condition among LT recipients who are maintained on prolonged corticosteroid immunosuppressive treatment. Factors associated with FAGA include the cumulative steroid dose, weight changes after LT, and ACTH and cholesterol levels at the time of steroid withdrawal.


Electrochemical nutrient recovery enables ammonia toxicity control and biogas desulfurization in anaerobic digestion.
Organic waste streams can be valorized and reduced in volume with anaerobic digestion (AD). An often-encountered key issue however is the high ammonium (NH4(+)) content of certain waste streams. Ammonia (NH3), in equilibrium with NH4(+), is a toxic compound to the methanogenic community, which limits the organic loading rate and endangers process stability. An electrochemical system (ES) linked to a digester could, besides recovering this nutrient, decrease NH3 toxicity through electrochemical extraction. Therefore, two digesters with and without ES attached in the recirculation loop were operated to test whether the ES could control NH3 toxicity. During periods of high ammonium loading rates, the methane (CH4) production of the ES-coupled reactor was up to 4.5 times higher compared to the control, which could be explained through simultaneous NH4(+) extraction and electrochemical pH control. A nitrogen flux of 47 g N m(–2) membrane d(–1) could be obtained in the ES-coupled reactor, resulting in a current and removal efficiency of 38 ± 5% and 28 ± 2%, respectively, at an electrochemical power input of 17 ± 2 kWh kg(–1) N. The anode also oxidized sulfide, resulting in a significantly lower H2S emission via the biogas. Lastly, limited methanogenic community dynamics pointed to a nonselective influence of the different operational conditions.


Wire-directed localization biopsy of the breast: an audit of results and analysis of factors influencing therapeutic value in the treatment of breast cancer.
Fine-wire localization biopsy is an accurate technique for diagnosis of mammographically-detected breast abnormalities, and may also be therapeutic in the management of impalpable malignant lesions. A number of factors were therefore examined regarding their influence upon therapeutic success in a consecutive series of 129 localization biopsies. Factors included type of radiological abnormality, method and accuracy of wire localization and pre-operative cytology. Primary malignancy was detected at initial localization in 64 cases (malignant:benign ratio, 1.11:1); 26 (41%) achieving adequate local tumour excision margins without further surgery, and 38 undergoing further surgery to clear margins (mastectomy in 23, further wide excision in 15). Therapeutic success was related to the accuracy of pre-operative needle localization (needle hook within 1 cm of target lesion in 26/26 (100%) therapeutic biopsies, compared to 29/38 (76%) non-therapeutic biopsies (P<0.01, Fisher's exact test)); and to pre-operative cytology (suspicious/malignant cytology in 15/24 therapeutic, compared with only 9/29 non-therapeutic biopsies (P=0.013, chi-squared)). Localization biopsy has a high diagnostic success rate and a therapeutic value dependent upon accurate pre-operative cytological diagnosis, supplemented by precise needle localization of the target lesion.


Renalase regulates peripheral and central dopaminergic activities.
Renalase is a recently identified FAD/NADH-dependent amine oxidase mainly expressed in kidney that is secreted into blood and urine where it was suggested to metabolize catecholamines. The present study evaluated central and peripheral dopaminergic activities in the renalase knockout (KO) mouse model and examined the changes induced by recombinant renalase (RR) administration on plasma and urine catecholamine levels. Compared with wild-type (WT) mice, KO mice presented increased plasma levels of epinephrine (Epi), norepinephrine (NE), and dopamine (DA) that were accompanied by increases in the urinary excretion of Epi, NE, DA. In addition, the KO mice presented an increase in urinary DA-to-l-3,4-dihydroxyphenylalanine (l-DOPA) ratios without changes in renal tubular aromatic-l-amino acid decarboxylase (AADC) activity. By contrast, the in vivo administration of RR (1.5 mg/kg sc) to KO mice was accompanied by significant decreases in plasma levels of Epi, DA, and l-DOPA as well as in urinary excretion of Epi, DA, and DA-to-l-DOPA ratios notwithstanding the accompanied increase in renal AADC activity. In addition, the increase in renal DA output observed in renalase KO mice was accompanied by an increase in the expression of the L-type amino acid transporter like (LAT) 1 that is reversed by the administration of RR in these animals. These results suggest that the overexpression of LAT1 in the renal cortex of the renalase KO mice might contribute to the enhanced l-DOPA availability/uptake and consequently to the activation of the renal dopaminergic system in the presence of renalase deficiency.


Critical role of ethics in clinical management and public health response to the West Africa Ebola epidemic.
The devastation caused by the Ebola virus disease (EVD) outbreak in West Africa has brought to the fore a number of important ethical debates about how best to respond to a health crisis. These debates include issues related to prevention and containment, management of the health care workforce, clinical care, and research design, all of which are situated within the overarching moral problem of severe transnational disadvantage, which has very real and specific impacts upon the ability of citizens of EVD-affected countries to respond to a disease outbreak. Ethical issues related to prevention and containment include the appropriateness and scope of quarantine and isolation within and outside affected countries. The possibility of infection in health care workers impelled consideration of whether there is an obligation to provide health services where personal protection equipment is inadequate, alongside the issue of whether the health care workforce should have special access to experimental treatment and care interventions under development. In clinical care, ethical issues include the standards of care owed to people who comply with quarantine and isolation restrictions. Ethical issues in research include appropriate study design related to experimental vaccines and treatment interventions, and the sharing of data and biospecimens between research groups. The compassionate use of experimental drugs intersects both with research ethics and clinical care. The role of developed countries also came under scrutiny, and we concluded that developed countries have an obligation to contribute to the containment of EVD infection by contributing to the strengthening of local health care systems and infrastructure in an effort to provide fair benefits to communities engaged in research, ensuring that affected countries have ready and affordable access to any therapeutic or preventative interventions developed, and supporting affected countries on their way to recovery from the impact of EVD on their social and economic lives.


Embryotoxicity of arsenite and arsenate: distribution in pregnant mice and monkeys and effects on embryonic cells in vitro.
The distribution of 74As-labelled arsenate and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the 74As-arsenic appeared to pass the mouse placenta relatively free and approximately to the same extent. The retention time in maternal tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution picture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10 microM), while arsenate seemed to be without effect at concentrations up to 200 microM (highest tested). Arsenate, however, showed a potentiation of the arsenite toxicity.


Immunodiagnosis of clonorchiasis by enzyme-linked immunosorbent assay.
The present study applied the indirect enzyme-linked immunosorbent assay (ELISA) technique in the immunodiagnosis of clonorchiasis. Antigen used in this study was extracted from adult worms of Clonorchis sinensis obtained from cats. 132 patients with clonorchiasis, 100 healthy persons and 14 patients with other parasitic infections were studied. Mean O.D. ratio with standard deviation of clonorchiasis was 1.41 +/- 0.21 with 0.95 +/- 0.13 of healthy persons. Results revealed 90.2% to 95.5% of sensitivity and 84% to 99% specificity dependent on the two cut off values of O.D. ratio, i.e. 1.10 and 1.20. Antibody titers derived from O.D. ratio highly correlated with direct titration (Y = 0.0303 +/- 1.1766 X, r = 0.8945). Cross reactions of other parasite infections to clonorchiasis were observed in patients with angiostrongyliasis and schistosomiasis.


Keratin filaments restrict organelle migration into the forming spindle of newt pneumocytes.
When viewed by light microscopy the mitotic spindle of newt pneumocytes appears to assemble in an optically clear area of cytoplasm, virtually devoid of mitochondria and other organelles, which is often much larger than the spindle. This clear area is also frequently larger than the region previously occupied by the nucleus. It forms even in prometaphase cells depleted of microtubules prior to nuclear envelope breakdown by colchicine treatment. Time-lapse video microscopy reveals that as prometaphase proceeds this clear area slowly and progressively collapses around the forming spindle so that it is greatly diminished or nonexistent by the onset of anaphase. The sharply defined nature of the boundary between the clear area and the remaining cytoplasm and the fact that organelles accumulate at its periphery suggest that a structural barrier is present at the boundary that limits organelle migration into the forming spindle. Immunofluorescence and electron microscopy, of cells previously followed in the living state, reveal that the periphery of the clear area contains prominent bundles of keratin filaments but lacks microtubules and actin. From our observations we conclude that keratin filaments form a loosely organized cage that surrounds the forming newt pneumocyte spindle. We propose that this cage functions, in part, to restrict the dispersion of chromosomes during nuclear envelope breakdown and to impede the bulk migration of organelles into the forming spindle.


Novel Lipids to Regulate Obesity and Brain Function: Comparing Available Evidence and Insights from QSAR In Silico Models.
Lipid molecules, such as policosanol, ergosterol, sphingomyelin, omega 3 rich phosphatidylcholine, α-tocopherol, and sodium butyrate, have emerged as novel additions to the portfolio of bioactive lipids. In this state-of-the-art review, we discuss these lipids, and their activity against obesity and mental or neurological disorders, with a focus on their proposed cellular targets and the ways in which they produce their beneficial effects. Furthermore, this available information is compared with that provided by in silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) models in order to understand the usefulness of these tools for the discovery of new bioactive compounds. Accordingly, it was possible to highlight how these lipids interact with various cellular targets related to the molecule transportation and absorption (e.g., α-tocopherol transfer protein for α-Tocopherol, ATP-binding cassette ABC transporters or Apolipoprotein E for sphingomyelins and phospholipids) or other processes, such as the regulation of gene expression (involving Sterol Regulatory Element-Binding Proteins for ergosterol or Peroxisome Proliferator-Activated Receptors in the case of policosanol) and inflammation (the regulation of interleukins by sodium butyrate). When comparing the literature with in silico Quantitative Structure-Activity Relationship (QSAR) models, it was observed that although they are useful for selecting bioactive molecules when compared in batch, the information they provide does not coincide when assessed individually. Our review highlights the importance of considering a broad range of lipids as potential bioactives and the need for accurate prediction of ADMET parameters in the discovery of new biomolecules. The information presented here provides a useful resource for researchers interested in developing new strategies for the treatment of obesity and mental or neurological disorders.


Histidine utilisation operon (hut) is upregulated at low temperature in the antarctic psychrotrophic bacterium Pseudomonas syringae.
The antarctic psychrotrophic bacterium Pseudomonas syringae was mutagenised using a transposon Tn5-OT182 which facilitates identification of promoter fusions expressing the reporter gene (lacZ) for beta-galactosidase. Most mutants expressed beta-galactosidase both at optimal growth temperature (20-22 degrees C) and at low temperature (4 degrees C). But a small percentage of the mutants (approximately 5%) were unique in that they expressed beta-galactosidase activity predominantly at low temperature. One such mutant was found to have an insertion in the gene for urocanase (hutU) of the histidine utilisation (hut) operon. Direct assay of urocanase and histidase activity in wild-type cells of various antarctic psychrotrophic strains including P. syringae, P. fluorescens and P. putida also suggested that the hut operon is expressed at an elevated level at low temperature.


Rooting the domain archaea by phylogenomic analysis supports the foundation of the new kingdom Proteoarchaeota.
The first 16S rRNA-based phylogenies of the Archaea showed a deep division between two groups, the kingdoms Euryarchaeota and Crenarchaeota. This bipartite classification has been challenged by the recent discovery of new deeply branching lineages (e.g., Thaumarchaeota, Aigarchaeota, Nanoarchaeota, Korarchaeota, Parvarchaeota, Aenigmarchaeota, Diapherotrites, and Nanohaloarchaeota) which have also been given the same taxonomic status of kingdoms. However, the phylogenetic position of some of these lineages is controversial. In addition, phylogenetic analyses of the Archaea have often been carried out without outgroup sequences, making it difficult to determine if these taxa actually define lineages at the same level as the Euryarchaeota and Crenarchaeota. We have addressed the question of the position of the root of the Archaea by reconstructing rooted archaeal phylogenetic trees using bacterial sequences as outgroup. These trees were based on commonly used conserved protein markers (32 ribosomal proteins) as well as on 38 new markers identified through phylogenomic analysis. We thus gathered a total of 70 conserved markers that we analyzed as a concatenated data set. In contrast with previous analyses, our trees consistently placed the root of the archaeal tree between the Euryarchaeota (including the Nanoarchaeota and other fast-evolving lineages) and the rest of archaeal species, which we propose to class within the new kingdom Proteoarchaeota. This implies the relegation of several groups previously classified as kingdoms (e.g., Crenarchaeota, Thaumarchaeota, Aigarchaeota, and Korarchaeota) to a lower taxonomic rank. In addition to taxonomic implications, this profound reorganization of the archaeal phylogeny has also consequences on our appraisal of the nature of the last archaeal ancestor, which most likely was a complex organism with a gene-rich genome.


We stop for no storm: coping with an environmental disaster and public health research.
Coping with natural disasters is part of the public nurses' role, and the public health nursing (PHN) researcher is doubly challenged with continuing to conduct community-based research in the midst of the disaster. The PHN may provide service along with attempting to continue the research. The challenges faced by public/community health nurse researchers as a result of hurricane Ike are discussed to provide lessons for other public/community health researchers who may be affected by natural disasters in the future. It is important to consider challenges for recruitment and retention of research subjects after a disaster, impact of natural disasters on ongoing research, and opportunities for research to be found in coping with natural disasters. A community-based study that was in progress at the time of hurricane Ike will be used as an example for coping with a natural disaster. We will present "lessons learned" in the hope of helping researchers consider what can go wrong with research studies in the midst of natural disasters and how to proactively plan for keeping research reliable and valid when natural disasters occur. We will also discuss the opportunities for collaborations between researchers and the community following any disaster.


Conversion of an amplified fragment length polymorphism marker into a co-dominant marker in the mapping of the Rph15 gene conferring resistance to barley leaf rust, Puccinia hordei Otth.
Leaf rust, caused by Puccinia hordei, is an important disease afflicting barley ( Hordeum vulgare) in many production regions of the world. The leaf rust resistance gene Rph15 was identified in an accession of wild barley ( Hordeum vulgare subsp. spontaneum) and is one of the most broadly effective resistance genes known. Using amplified fragment length polymorphism (AFLP) and simple sequence repeat markers, Rph15 was mapped to chromosome 2HS in an F(2) population derived from a cross between Bowman ( Rph15), a Bowman backcross-derived line carrying Rph15, and the susceptible cultivar Bowman. AFLP marker P13M40 co-segregated with Rph15 in this mapping population and two others involving Bowman ( Rph15) and cultivars Proctor and Nudinka. The dominant AFLP marker P13M40 was converted to a co-dominant PCR-based marker that may be useful in breeding programs employing marker-assisted selection. The allelic relationship between Rph15 and the gene Rph16, also mapping to chromosome 2HS, was studied. The lack of segregation in F(2) progeny derived from the two resistance sources indicates that Rph15 and Rph16 are alleles of the same locus.


Videolaryngoscopy versus direct laryngoscopy for tracheal intubation in children (excluding neonates).
Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta-analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers (www.clinicaltrials.gov and www.controlledtrials) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of 'Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta-analysis. We identified three studies that are awaiting classification and two ongoing studies.Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I2 = 90%; very low-quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I2 = 67%; low-quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I2 = 0%; low-quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low-quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group.Two studies (n = 100) reported other haemodynamic responses to intubation (very low-quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low-quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group.Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low-quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome.


Oral contraceptives and breast cancer: what has 20 years of research shown?
This article reviews 20 years of research to determine if oral contraceptive usage increases the risk of breast cancer. Studies using animal models, epidemiology, and human tissues are presented. Results suggest oral contraceptives do not initiate breast cancer, but may act as tumor promoters, stimulating the growth of already transformed cells. The answers are not all in, and the need for continued research is emphasized.


Hypovolemic shock induced by laparoscopic cholecystectomy--a case report.
Since its introduction and development in the 1960s, laparoscopic cholecystectomy has become widely accepted by the medical community and the public as the treatment of choice for various gallbladder disorders. We present a 46-year-old male who underwent laparoscopic cholecystectomy, during which inadvertent penetration of the first trocar resulted in injury of the abdominal aorta and then hypovolemic shock ensured. The time from notification of shock by the anesthesiologist to switch of procedure to exploratory laparotomy for stanching hemorrhage was twenty minutes. During the intervention, blood loss was over 3,000 ml and despite rapid infusion of plasma expander, blood pressure could only be maintained between 40/18 to 60/20 mmHg. After the patient became stabilized and blood pressure was elevated to acceptable levels, conventional cholecystectomy was performed instead. Perioperative blood loss of 7,300 ml was estimated. In total, the patient received 24 units of packed red blood cells, 12 units of fresh frozen plasma, and 12 units of platelets. After the operation, the patient was transferred to the surgical ICU for further observation. For 24 h at the ICU, blood pressure remained unstable, urine output decreased gradually, and scrotal and leg edema developed. Forty-four h after admission to the surgical ICU, arrhythmia and profound hypotension were noted and cardiac arrest ensued. After resuscitation for 2 h, the patient could not be revived and succumbed to cardiovascular decompensation secondary to acute renal shutdown and continuous retroperitoneal hemorrhage.


Weight loss in patients with diabetes treated with a metformin-sulfonylurea combination in comparison with twice-daily mixed insulin.
To investigate whether patients previously treated with insulin or sulfonylureas alone can be transferred to a combination of sulfonylureas and metformin therapy and realize a prolonged weight loss. We conducted a retrospective review of medical records to identify three groups of patients with type 2 diabetes: group 1, those requiring insulin who had remained on a daily regimen of two injections of mixed insulin; group 2, patients whose regimen had been changed from sulfonylureas alone to a combination of a sulfonylurea and metformin; and group 3, patients whose regimen had been converted from twice-daily mixed insulin alone to a sulfonylurea-metformin combination. Results relative to loss of weight in these three groups were analyzed. For a 12-month period, no significant weight loss was noted in group 1, and group 2 showed a small nonsignificant weight loss in 6 months. Only group 3 had a significant weight loss at 3, 6, 9, and 12 months, maximizing at a mean weight loss of 22 lb (10 kg) at 12 months. In addition, in those patients in whom data were available, a significant weight loss was found at 18 and 21 months. At 21 months, however, weight began to increase. Percentage weight loss followed a pattern similar to that seen with total weight loss. The proportion of patients losing weight did not differ significantly in groups 1 and 2; however, in group 3, after 3 and 12 months a significant proportion of patients (79% and 86%, respectively) had lost weight. Race, gender, or baseline body weight had no effect on weight loss. From this retrospective study of patients with type 2 diabetes, we conclude that conversion from insulin to combination oral therapy with sulfonylureas and metformin results in a significant weight loss for up to 21 months.


Pancreatic fibrosis in patients with chronic alcohol abuse: correlation with alcoholic pancreatitis.
To investigate the incidence and histological features of pancreatic fibrosis, including chronic alcoholic pancreatitis, in patients with a history of chronic alcohol abuse. Forty-six autopsy cases of alcoholic dependence syndrome, 53 cases of chronic alcoholism, and 30 cases of chronic alcoholic pancreatitis were studied histopathologically. Fibrosis was seen in 33 of 46 cases of alcoholic dependence syndrome, 20 of 53 cases of chronic alcoholism, and all 30 cases of chronic alcoholic pancreatitis. Fibrosis was categorized into three types: intralobular, perilobular, and mixed intralobular and perilobular sclerosis. In chronic alcoholic pancreatitis, fibrosis was found mainly in perilobular, or interlobular, areas, and in some advanced cases extended into intralobular areas, so that the pancreatic tissue was completely replaced by fibrosis. Hence, interlobular fibrosis was found in all cases of chronic alcoholic pancreatitis. In contrast, in cases that had predominantly intralobular fibrosis, which were usually cases of alcoholic dependence syndrome, the pancreatic tissue had not completely disappeared, even at an advanced stage, and some parenchymal regeneration similar to that seen in hemochromatosis was observed. Interlobular and intralobular pancreatic fibrosis associated with alcohol abuse appears in distinct pathological patterns with differing mechanisms.


Philosophy of care. A pilot study comparing certified nurse-midwives and physicians.
Certified nurse-midwives (CNMs) and physicians (MDs) are thought to differ in philosophy of pregnancy care and childbirth. However, these differences have not been documented quantitatively. This article describes and compares the beliefs and care philosophies of CNMs and MDs toward aspects of antepartum and intrapartum care of low-risk women. The sample included seven CNMs and 10 obstetricians at a large tertiary-care hospital. Using stringent statistical criteria for testing differences between the two groups, significantly more teaching was done by the CNMs than by the MDs. Other differences were all in expected directions.


Maturation dependence of the turnover of phosphatidylinositides in rabbit red blood cells.
"Pulse-chase" experiments with erythrocytes and reticulocytes prelabelled with 32P-Pi revealed a high turnover of the monoester phosphate groups of PIP2 in reticulocytes, which declines strongly during maturation [Maretzki et al., Biomed. Biochim. Acta 45, 1227-1236 (1986)]. The 3H-inositol uptake exhibits a strong maturational loss. A carrier-mediated uptake of inositol in reticulocytes is suggested. In reticulocytes PI, PIP and PIP2 incorporated 3H-inositol in the relative distribution of 86; 5 and 9%, respectively, but only PI to a minor extent in erythrocytes. A small release of 3H-labelled inositol phosphates was found in reticulocytes, which was not stimulated by extracellular calcium during incubation. Determination of the 32P/3H-ratio in double-labelled phosphatidylinositides in reticulocytes demonstrated a very slow turnover of the diester phosphate bonds compared with that of the inositol phosphate ester groups.


[Severe infections due to Streptococcus milleri in children].
Streptococcus milleri (S. milleri) is found in healthy individuals in the mouth, nasopharynx, throat, vagina and in feces, and has been reported to be isolated from several infectious diseases in man, particularly from abscess in various parts of the body. We report two cases of severe infections due to S. milleri isolated from subdural abscess and pleural empyema. [Case 1] 13 year old boy who had been healthy until he was noticed to have meningeal signs and was diagnosed as left subdural abscess with siagonantritis by cranial CT scans. S. milleri was isolated from subdural abscess and maxillary sinus. [Case 2] 10 year old boy who had encephalitis and severe mental retardation after measles at 6 months of age. He had a fever, dyspnea and chest X-ray abnormalities and was diagnosed as right pleural empyema. Three strains of organism, S milleri, Bacteroides spp. and Fusobacterium nucleatum were isolated from the pleural effusion.


[Preliminary safety and stability assessment of orthodontic miniscrew implantation guided by surgical template based on cone-beam CT images].
To develop surgical templates for orthodontic miniscrew implantation based on cone-beam CT(CBCT)three-dimensional(3D)images and to evaluate the safety and stability of implantation guided by the templates. DICOM data obtained in patients who had CBCT scans taken were processed using Mimics software, and 3D images of teeth and maxillary bone were acquired. Meanwhile, 3D images of miniscrews were acquired using Solidworks software and processed with Mimics software. Virtual position of miniscrews was determined based on 3D images of teeth, bone, and miniscrews. 3D virtual templates were designed according to the virtual implantation plans. STL files were output and the real templates were fabricated with stereolithographic appliance(SLA). Postoperative CBCT scans were used to evaluate the implantation safety and the stability of miniscrews were investigated. All the templates were positioned accurately and kept stable throughout the implantation process. No root damage was found. The deviations were(1.73±0.65)mm at the corona, and(1.28±0.82)mm at the apex, respectively. The stability of miniscrews was fairly well. Surgical templates for miniscrew implantation could be acquired based on 3D CBCT images and fabricated with SLA. Implantation guided by these templates was safe and stable.


Factors influencing maternal mental health and family functioning during the low birthweight infant's first year of life.
The care of the low birthweight (LBW) infant poses a considerable challenge to the entire family, especially to the infant's mother, who is typically the primary caregiver. The purpose of this study was to determine the effects of the infant's medical vulnerability and the psychosocial context of caregiving on the mental health of mothers who care for these infants and the functioning of their families. Results indicate that the degree to which an infant was unresponsive and the severity of the baby's physical health problems during the first year were associated with more mental health problems for the mother. Lack of infant responsiveness was also related to less cohesion and adaptability for the family as a whole. Family cohesion, presence of a partner, emotional support, and a mother's satisfaction with her family all contributed to her better mental health. In contrast, her life stress and the family's use of internally focused coping strategies contributed to worse mental health outcomes. Findings indicate the need for nursing interventions to support the mother and family in developing effective approaches to care for their LBW infant and for one another.


Chromosome aberrations induced by an ultrasonic fetal pulse detector.
Human blood cultures were exposed to ultrasound from an ultrasonic fetal heart detector for periods of one and two hours. Considerable increases in the number of chromosome aberrations over control values were found.


A novel DAX1 gene mutation in a Turkish infant with X-linked adrenal hypoplasia congenita.
Adrenal hypoplasia congenita (AHC) is a rare inherited disorder of the adrenal cortex commonly manifested as an early onset adrenal insufficiency syndrome. A novel DAX1 (NR0B1) gene mutation was detected in a Turkish newborn boy presenting with primary adrenal insufficiency. He was from a family with a history of unexplained death of three male siblings in the neonatal period. This report highlights the value of mutational analysis of the DAX1 gene for definitive diagnosis of AHC as well as for genetic counselling because this disorder shows an X-linked genetic pattern of transmission, providing the possibility of finding new cases even in presymptomatic individuals.


Preservation of B-cell-associated surface antigens by chemical fixation.
Usual methods of chemical fixation preclude examination of cells with most monoclonal antibodies due to alteration or destruction of the surface antigen itself. A method of chemical stabilization and preservation of human B-cell-associated surface antigens is described which facilitates retrospective flow cytometric analysis. This method involves pretreatment of the cells with protease enzyme inhibitors, followed by chemical cross-linking of surface proteins with 2% formalin, and finally blockade of non-specific reactive groups with excess glycine. Once prepared, the expression of pertinent cellular antigens is stable on the cell surface for as long as 4 years. Such methodology could conceivably be used for preparation of cells for longitudinal quality control of monoclonal antibodies or archival storage of patient specimens for retrospective flow cytometric analysis.


The Amplification of Common Somatic Symptoms by Posttraumatic Stress Disorder in Firefighters.
Posttraumatic stress disorder (PTSD) in emergency service personnel and other trauma-exposed populations is known to be associated with a variety of physical health problems. However, little attention has been paid to the health of ageing emergency service personnel, who may be forced into early medical retirement because of a combination of these issues. Currently employed (N = 274) Australian firefighters completed a cross-sectional survey using validated, self-report measures of PTSD and somatic symptoms. Analyses examined the association between probable PTSD and a range of common somatic symptoms, and whether any association differed depending on the age of the firefighters. Firefighters with PTSD reported greater levels of neurological (p = .024), gastrointestinal (p = .015), and cardiorespiratory (p = .027) symptoms compared to those without PTSD. After adjusting for sex, age, and rank, linear regression analysis demonstrated that PTSD was significantly associated with increased total somatic symptom severity (p = .024), with PTSD accounting for 9.8% of the variance in levels of somatic symptoms. There was no interaction between age and the association between PTSD and somatic symptom severity. These results suggest that PTSD is associated with a significant increase in a wide range of somatic symptoms among firefighters, regardless of age. The implications for the identification and treatment of PTSD are discussed.


Reduction of long-term potentiation at Schaffer collateral-CA1 synapses in the rat hippocampus at the acute stage of vestibular compensation.
Vestibular compensation is a recovery process from vestibular symptoms over time after unilateral loss of peripheral vestibular end organs. The aim of the present study was to observe time-dependent changes in long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in the CA1 area of the hippocampus during vestibular compensation. The input-output (I/O) relationships of fEPSP amplitudes and LTP induced by theta burst stimulation to Schaffer's collateral commissural fibers were evaluated from the CA1 area of hippocampal slices at 1 day, 1 week, and 1 month after unilateral labyrinthectomy (UL). The I/O relationships of fEPSPs in the CA1 area was significantly reduced within 1 week post-op and then showed a non-significant reduction at 1 month after UL. Compared with sham-operated animals, there was a significant reduction of LTP induction in the hippocampus at 1 day and 1 week after UL. However, LTP induction levels in the CA1 area of the hippocampus also returned to those of sham-operated animals 1 month following UL. These data suggest that unilateral injury of the peripheral vestibular end organs results in a transient deficit in synaptic plasticity in the CA1 hippocampal area at acute stages of vestibular compensation.


Long-Term Prevalence and Risk Factors of Musculoskeletal Disorders among the Schoolteachers in Hail, Saudi Arabia: A Cross-Sectional Study.
Musculoskeletal disorders (MSDs) are affecting up to 95% of teachers and are considered a primary occupational health hazard leading to absenteeism, early retirement, and lower quality of life and teaching quality. The current study is aimed at exploring the prevalence and risk factors of MSDs among the schoolteachers in Hail, Saudi Arabia. A cross-sectional study was conducted online among the teachers in Hail City using the Nordic Musculoskeletal Questionnaire. Teachers were randomly selected from randomly selected high schools. Teachers with at least 1 year experience were recruited for the study. Descriptive statistics, Cochran's Q test, and binominal regression were used to investigate the prevalence of MSDs among such teachers and to determine if the percentage of MSDs differed by anatomical region and risk factor (one hundred forty-five males and 106 females filled out the questionnaires). The prevalence of MSDs in the last 12 months was 93.63% (235 of 251 teachers). Interestingly, 91% of the affected participants (214 of 235 teachers) complained of MSDs in more than one anatomical region. The most affected site was the lower back (183 of 251 teachers, 72.91%), followed by the shoulders (168 of 251 teachers, 66.93%), and the least affected sites were the elbows (45 of 251 teachers, 17.93%). The females showed a higher prevalence of MSDs than the males. Only gender was a significant risk factor for shoulder and neck MSDs (p < 0.02). Overall, the findings of the current study suggest a high prevalence of MSDs among teachers, especially in the lower back and shoulders. The affected teachers should learn more about biomechanics and ergonomics and should engage in exercise to improve their health. Future studies should focus on identifying the biomechanical and ergonomic risk factors of MSDs and on designing MSD prevention programmes to reduce the burden of MSDs.


Assessment of chronic effects of tebuconazole on survival, reproduction and growth of Daphnia magna after different exposure times.
The effect of the fungicide tebuconazole (0.41, 0.52, 0.71 and 1.14mg/L) on survival, reproduction and growth of Daphnia magna organisms was monitored using 14 and 21 days exposure tests. A third experiment was performed by exposing D. magna to the fungicide for 14 days followed by 7 days of recovery (14+7). In order to test fungicide effects on D. magna, parameters as survival, mean whole body length, mean total number of neonates per female, mean number of broods per female, mean brood size per female, time to first brood/reproduction and intrinsic rate of natural increase (r) were used. Reproduction was seriously affected by tebuconazole. All tebuconazole concentrations tested affected the number of broods per female and day to first brood. At 14-days test, number of neonates per female and body size decreased by concentrations of tebuconazole higher than 0.52mg/L, whereas at 21-days test both parameters were affected at all the concentrations tested. Survival of the daphnids after 14 days fungicide exposure did not exhibited differences among experimental and control groups. In this experiment r value was reduced (in a 22%) when animals were exposed to concentrations of 0.71mg/L and 1.14mg/L. Survival of daphnids exposed during 21 days to 1.14mg/L declined, and the intrinsic rate of natural increase (r) decreased in a 30 % for tebuconazole concentrations higher than 0.41mg/L. Longevity of daphnids pre-exposed to tebuconazole for 14 days and 7 days in clean water did not show differences from control values and all of them survived the 21 days of the test. However, after 7 days in fungicide free medium animals were unable to restore control values for reproductive parameters and length. The maximum acceptable toxicant concentration (MATC) was calculated using the r values as parameter of evaluation. MATC estimations were 0.61mg/L and 0.46mg/L for 14 and 21 days, respectively. Results showed that the number of neonates per female was the highest sensitive parameter to the effects of tebuconazole on D. magna. On the other hand, a recovery period of 7 days in a free toxicant medium would not be longer enough to reestablish normal reproduction parameters in pre-exposed tebuconazole daphnids.


Theoretical study of phase transition, surface tension, and nucleation rate predictions for argon.
In this work, a weighted density functional theory has been used to study the equilibrium and metastable processes for argon. In the theoretical approach, the two- and three-body interactions of the fluid molecules are considered simultaneously, and the renormalization group transformation is applied to address the long-range fluctuations inside the critical region. The global phase equilibria, planar and curvature-dependent surface tensions, critical radius, and nucleation rates of argon are investigated systematically. The results are in good agreement with the experimental data. Meanwhile, this work applies a methodology for calculating the curved surface tension in local supersaturated environments, showing that the Tolman length is negligible far from the critical region. Near the critical point, however, the Tolman length becomes positive and appears to diverge.


Perfluorooctanoic acid binds to peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation in 3T3-L1 adipocytes.
We examined the effect of perfluorooctanoic acid (PFOA) on adipose cells using 3T3-L1 adipocytes and found that PFOA increased adipocyte differentiation, triglyceride accumulation, and the mRNA level of factors related to adipocyte differentiation. In addition, PFOA bound to peroxisome proliferator-activated receptor γ (PPAR γ). These results suggest that PFOA promotes adipocyte differentiation as a PPAR γ ligand.


Cloning and characterization of an Arabidopsis thaliana Nudix hydrolase homologous to the mammalian GFG protein.
In a search for a plant antimutator MutT protein, an Arabidopsis thaliana Nudix hydrolase with homology to the mammalian GFG protein was expressed as a hexahistidine fusion polypeptide in Escherichia coli and purified to homogeneity. Unlike the GFG protein, the A. thaliana homolog could not complement the mutT mutation in a MutT-deficient E. coli strain nor was it able to hydrolyze 8-oxo-dGTP, the main substrate of the MutT protein. Instead the recombinant protein hydrolyzed a variety of nucleoside diphosphate derivatives showing a preference for ADP-ribose, with Km and k(cat) values of 1.2 mM and 2.7 s(-1) respectively. The products of ADP-ribose hydrolysis were AMP and ribose-5-phosphate. The optimal activity was at alkaline pH (8.5) with Mg2+ (5 mM) ions as the cofactor. The protein exists as a dimmer in solution.


Antagonism of mmu-mir-106a attenuates asthma features in allergic murine model.
MicroRNAs (miRs) regulate immunological pathways in health and disease, and a number of miRs have been shown to be altered in mouse models of asthma. The secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine, has been shown to be defective in many inflammatory diseases including asthma. We recently demonstrated that miR-106a inhibits IL-10 in a post-transcriptional manner. In this study, we investigated the effect of inhibition of mmu-miR106a in asthmatic condition to find its possible role as a therapeutic target. Our in vitro experiments with mouse macrophage, RAW264.7, revealed that mmu-miR-106a potentially decreased IL-10 along with increase in proinflammatory cytokine. Furthermore, administration of mmu-miR-106a to naive mice reduced IL-10 levels in lungs in a dose-dependent manner without altering lung histology. Most interestingly, knockdown of mmu-miR-106a in an established allergic airway inflammation has significantly alleviated most of the features of asthma such as airway hyperresponsiveness, airway inflammation, increased Th2 response, goblet cell metaplasia, and subepithelial fibrosis along with increase in IL-10 levels in lung. This represents the first in vivo proof of a miRNA-mediated regulation of IL-10 with a potential to reverse an established asthmatic condition.


Anxiety-related attentional biases and their regulation by attentional control.
This study examined the role of self-reported attentional control in regulating attentional biases related to trait anxiety. Simple detection targets were preceded by cues labeling potential target locations as threatening (likely to result in negative feedback) or safe (likely to result in positive feedback). Trait anxious participants showed an early attentional bias favoring the threatening location 250 ms after the cue and a late bias favoring the safe location 500 ms after the cue. The anxiety-related threat bias was moderated by attentional control at the 500-ms delay: Anxious participants with poor attentional control still showed the threat bias, whereas those with good control were better able to shift from the threatening location. Thus, skilled control of voluntary attention may allow anxious persons to limit the impact of threatening information.


Nationwide surveillance of AIDS-defining illnesses among HIV patients in Japan from 1995 to 2017.
The accurate prevalence of acquired immunodeficiency syndrome (AIDS)-defining illnesses (ADIs) in human immunodeficiency virus (HIV)-infected patients has not been well investigated. Hence, a longitudinal nationwide surveillance study analyzing the current status and national trend of opportunistic complications in HIV-infected patients in Japan is warranted. A nationwide surveillance of opportunistic complications in HIV-infected patients from 1995 to 2017 in Japan was conducted. An annual questionnaire was sent to 383 HIV/AIDS referral hospitals across Japan to collect information (CD4+ lymphocyte count, time of onset, outcome, and antiretroviral therapy [ART] status) of patients diagnosed with any of 23 ADIs between 1995 and 2017. The response and case capture rates of the questionnaires in 2017 were 53% and 76%, respectively. The number of reported cases of opportunistic complications peaked in 2011 and subsequently declined. Pneumocystis pneumonia (38.7%), cytomegalovirus infection (13.6%), and candidiasis (12.8%) were associated with the cumulative incidence of ADIs between 1995 and 2017. The mortality rate in HIV-infected patients with opportunistic complications substantially decreased to 3.6% in 2017. The mortality rate was significantly higher in HIV patients who received ART within 14 days of diagnosis of complications than in those who received ART 15 days after diagnosis (13.0% vs. 3.2%, p < 0.01). We have demonstrated a 23-year trend of a newly diagnosed AIDS status in Japan with high accuracy. The current data reveal the importance of Pneumocystis pneumonia as a first-onset illness and that early initiation of ART results in poor outcomes in HIV patients in Japan.


Roles of potential plant hormones and transcription factors in controlling leaf senescence and drought tolerance.
Plant leaves offer an exclusive windowpane to uncover the changes in organs, tissues, and cells as they advance towards the process of senescence and death. Drought-induced leaf senescence is an intricate process with remarkably coordinated phases of onset, progression, and completion implicated in an extensive reprogramming of gene expression. Advancing leaf senescence remobilizes nutrients to younger leaves thereby contributing to plant fitness. However, numerous mysteries remain unraveled concerning leaf senescence. We are not still able to correlate leaf senescence and drought stress to endogenous and exogenous environments. Furthermore, we need to decipher how molecular mechanisms of the leaf senescence and levels of drought tolerance are advanced and how is the involvement of SAGs in drought tolerance and plant fitness. This review provides the perspicacity indispensable for facilitating our coordinated point of view pertaining to leaf senescence together with inferences on progression of whole plant aging. The main segments discussed in the review include coordination between hormonal signaling, leaf senescence, drought tolerance, and crosstalk between hormones in leaf senescence regulation.


[Observations on the maturity of stillborn calves].
Organ weight and trace element analyses were performed on 75 stillborn calves from the same dairy cow herd. The elements Fe, Mn, Zn and Cu were measured in the livers of 66 of the calves. The calves ranged in age from 259 to 299 days of gestation, and in weight from 18 to 58 kg. Based on the quotients of organ and other body parts, stage of growth of the humerus and age, the animals were grouped as either preterm (P), term but light (TL), and term with appropriate weight (TA) calves. In P group calves the heart, lungs, liver, kidneys, thymus, spleen and thyroid glands were relatively heavy. In the TL group calves the brain, heart, lungs and thyroid glands were relatively heavy whereas the spleen and thymus were comparatively light. The liver Fe and Zn values were lower in this group than in the other 2 groups.


Gas-permeable contact lenses can protect against ocular trauma: two cases.
To report two cases of rigid gas-permeable contact lens wearers who were protected from serious foreign body-related injury through the wearing of their contact lenses. Two case reports. Rigid gas-permeable contact lenses appear to have protected the eyes of two patients from probable serious injury. Rigid gas-permeable contact lenses can have a protective effect against some types of trauma, although they are not recommended to be used for protective purposes.


Limitations of P-Values and R-squared for Stepwise Regression Building: A Fairness Demonstration in Health Policy Risk Adjustment.
Stepwise regression building procedures are commonly used applied statistical tools, despite their well-known drawbacks. While many of their limitations have been widely discussed in the literature, other aspects of the use of individual statistical fit measures, especially in high-dimensional stepwise regression settings, have not. Giving primacy to individual fit, as is done with p-values and R2, when group fit may be the larger concern, can lead to misguided decision making. One of the most consequential uses of stepwise regression is in health care, where these tools allocate hundreds of billions of dollars to health plans enrolling individuals with different predicted health care costs. The main goal of this "risk adjustment" system is to convey incentives to health plans such that they provide health care services fairly, a component of which is not to discriminate in access or care for persons or groups likely to be expensive. We address some specific limitations of p-values and R2 for high-dimensional stepwise regression in this policy problem through an illustrated example by additionally considering a group-level fairness metric.


In vitro study of ultrasound radiation force-driven twinkling sign using PVA-H gel and glass beads tissue-mimicking phantom.
The twinkling sign observed in ultrasound coded-excitation imaging (e.g., GE B-Flow) has been reported in previous research as a potential phenomenon to detect micro calcification in soft tissue. However, the mechanism of the twinkling sign has not been clearly understood yet. We conducted an in vitro experiment to clarify the mechanism of the twinkling sign by measuring a soft tissue-mimicking phantom with ultrasonic and optical devices. A soft tissue-mimicking phantom was made of poly(vinyl alcohol) hydro (PVA-H) gel and 200-μm-diameter glass beads. We applied ultrasound to the phantom using medical ultrasound diagnostic equipment to observe the twinkling sign of glass beads. Optical imaging with a laser sheet and a high-speed camera was performed to capture the scatter lights of the glass beads with and without ultrasound radiation. The scatter lights from the glass beads were quantified and analyzed to evaluate their oscillations driven by the ultrasound radiation force. The twinkling sign from the glass beads embedded in the PVA-H gel soft tissue phantom was observed in ultrasound B-Flow color imaging. The intensity and oscillation of the scattered lights from the glass beads showed significant difference between the cases with and without ultrasound radiation. The results showed a close relationship between the occurrence of the twinkling sign and the variations of the scatter lights of glass beads, indicating that ultrasound radiation force-driven micro oscillation causes the twinkling sign of micro calcification in soft tissue.


Public Health Policy Strategies to Address the Opioid Epidemic.
Public health policy responses to the opioid epidemic require addressing both opioid supply and opioid demand. The growth in prescriptions of opioid analgesics, for example, is associated with escalating opioid overdose fatalities.1 Enhanced access to opioid agonist treatment, conversely, is required to curb demands driven by opioid use disorders. Oregon's multidimensional approaches toward opioid misuse and abuse achieved 20% reductions in opioid prescribing and a 30% reduction in the opioid overdose fatality rate.


Diverse types of junctions containing tight junction proteins in stratified mammalian epithelia.
Molecular compositions and functions of tight junctions (TJs), that is, continuous, cell-cell-connecting zonulae occludentes serving as barrier structures for the paracellular transport of molecules and particles, have hitherto been determined for simple epithelia and for endothelia. In 2002, special TJ structures with barrier functions were identified in the stratum granulosum of mammalian epidermis. In addition, using biochemical and immunocytochemical methods, various types of TJ-type junctions have also been described that also contain claudins and/or occludin as well as typical TJ plaque proteins, in cell layers of all stratified squamous epithelia (e.g., various types of epidermis, gingiva, lingual, and other kinds of oral mucosa, pharynx, esophagus, trachea, vagina, and exocervix), including tissues without a lumen, such as the reticulum and Hassall corpuscles of the thymus, and tumors derived from such epithelia, notably squamous cell carcinomas. Biological and pathological aspects of TJ-related structures in such tissues are discussed.


Antifungal effect of essential oil components against Aspergillus niger when loaded into silica mesoporous supports.
Essential oil components (EOCs) are known for their antifungal properties; however, their high volatility limits their application as antimicrobial agents. Strategies used for controlling the volatility of EOCs include encapsulation or loading into porous materials. This study evaluated the in vitro antifungal activity of selected EOCs (carvacrol, cinnamaldehyde, eugenol and thymol) against the fungus Aspergillus niger when loaded into MCM-41 and β-cyclodextrin (β-CD). Carvacrol and thymol in Mobil Composition of Matter No. 41 (MCM-41) displayed remarkable enhanced antifungal properties in comparison to the pure or β-CD-encapsulated EOCs. In fact, carvacrol and thymol were able to maintain antifungal activity and inhibit fungal growth for 30 days, suggesting better applicability of these EOCs as natural preservatives. The sustained antifungal effect of EOCs encapsulated into silica mesoporous supports was described.


Cancer risks in twins and singletons from twin and non-twin families.
The unique intrauterine environment has been proposed to put twins at increased risk of certain cancers compared to singletons, still large population comparisons have generally indicated lower risks in twins. To improve the understanding of potential twin influence on cancer we compared twins to their singletons siblings, to target a unique twinning influence. Singletons from twin families were contrasted to singletons from non-twin families to further capture potential twin family influence on risk of cancer. Family relations were identified using the Swedish Multi-Generation Register. Among individuals born between 1932 and 1958, 49,156 twins and N = 35,227 singletons were identified from 18,098 unique twin families. All incident cases of specific cancer types were identified in the National Cancer Register up to the end of 2007. Standardized survival functions were estimated using weighted Cox proportional hazard regression and the corresponding cumulative risks plotted against age. Overall, primary cancers were identified in 9% and 18% of all male and female twins, compared to 11% and 19% of their male and female singleton siblings. When specific cancer sites were compared using standardized cumulative risk plots, no consistent statistically significant differences were noted either between twins and singletons of twin families or between singletons of twin and non-twin families. Despite a different intrauterine experience, twinning does not seem to have any greater negative influence on life-time risks of cancer. The findings also indicate that twin family membership has no substantial influence on cancer risks.


The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma.
Interleukin (IL)-31A binds to an heterodimer composed of IL-31 receptor A (IL-31RA) and Oncostatin M Receptor (OSMR). The IL-31/IL-31R complex is involved in the pathogenesis of various skin diseases, including cutaneous T-cell lymphoma. No information is available on the relations between the IL-31/IL-31R complex and B-cell lymphoma. Here we have addressed this issue in follicular lymphoma (FL), a prototypic germinal center(GC)-derived B-cell malignancy. IL-31 enhanced primary FL cell proliferation through IL-31R-driven signal transducer and activator of transcription factor 1/3 (STAT1/3), extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation. In contrast, GC B cells did not signal to IL-31 in spite of IL-31R expression. GC B cells expressed predominantly the inhibitory short IL-31RA isoform, whereas FL cells expressed predominantly the long signaling isoform. Moreover, GC B cells lacked expression of other IL-31RA isoforms potentially involved in the signaling pathway. IL-31 protein expression was significantly higher in surface membrane than in cytosol of both FL and GC B cells. IL-31 was detected in plasma membrane microvesicles from both cell types but not released in soluble form in culture supernatants. IL-31 and IL-31RA expression was higher in lymph nodes from FL patients with grade IIIa compared with grade I/II, suggesting a paracrine and/or autocrine role of IL-31/IL-31RA complex in tumor progression through microvesicle shedding.


Acute appendicitis presenting as pneumoperitoneum in a teenage boy undergoing chemotherapy.
Chemotherapy of paediatric haematological malignancies can induce infectious complications of the gastrointestinal tract, with predilection of the ileocaecal region. Common causes of right lower abdominal pain in the febrile patient with neutropaenia include acute appendicitis, typhlitis, ileus and intussusception. In this case report, we describe a teenage boy with acute appendicitis presenting with pneumoperitoneum during his course of chemotherapy. The incidence, aetiology, diagnosis, investigations and management of this uncommon presentation in a common disease are discussed. The controversial topic of the management of acute appendicitis in a febrile patient with neutropaenia is also reviewed and discussed.