A new simplified beading and boxing procedure for elastic impression.
Beading and Boxing of impression is taught in most dental colleges. The boxing procedure is crucial step to preserve the details of the final impression especially of the vestibular area. This article describes an alternative beading-boxing procedure that is compatible with all impression materials, is efficient, simple, inexpensive, and practicable. Use of commercially available instant adhesive around the border to act as a joining agent between elastic impressions and beading wax or bead made up of base plate wax is advocated in this technique.


A hypothesis on the most prevalent psychological type for chief residents in the field of internal medicine.
Communication is the key to good doctor-patient relations. Resident learning occurs through the process of observation and role modeling. We hypothesize that the most prevalent personality type for chief residents will be in discordance with the most prevalent type (Sensor) in the general population. We set out to determine the communication styles of a national sampling of recent chief residents in the field of medicine. The survey based on Jung's Psychological types: thinker, feeler, the intuitor and sensor. Overall self report of psychological types revealed the majority, both male and female (45.6%) to be in the 'feeler' category. Feelers are described as persons with a high need for interpersonal harmony. They value compassion and empathy and enjoy meeting other people's needs.


Minimally invasive surgery: only as good as the picture.
In minimally invasive surgery, there is increased reliance on real-time 2-dimensional images. The fibre-optic light lead is one of the most frequently damaged elements of the 'imaging chain', leading to a poor quality picture. Light leads with a honeycomb projection were connected to a light source and the resulting beam directed at a sheet of paper. Darkened sectors with diminished or absent light transmission were recorded. All suitable light leads in routine use were examined. A mean of 22.2% (SD 7.8%) of the projection had diminished or absent light transmission. Sub-optimal endoscopic equipment was in routine use.


Giant bulla mimicking pneumothorax.
It is usually thought by emergency physicians that the diagnosis of a pneumothorax is straightforward and easy to make and to treat, but the diagnosis may sometimes pose a challenge. The present report describes a case of a giant pulmonary bulla in a 40-year-old man that progressed to occupy almost the entire left hemithorax and also subsequently ruptured to produce a large left pneumothorax. The giant bulla was diagnosed only as a pneumothorax, and initially managed with a chest tube only. The differentiation between pneumothorax and a giant bulla can be very difficult, and often leads to inaccurate diagnosis and management. This case report demonstrates the clinical presentation of giant bulla and its complications such as pneumothorax and also highlights the difficulty in making this diagnosis and appropriately treating it. In this article, we emphasized how to differentiate between giant bulla and pneumothorax utilizing history, physical examination, and radiological studies including computed tomography (CT) scan.


Establishing a quantitative framework for regulatory interpretation of genetic toxicity dose-response data: Margin of exposure case study of 48 compounds with both in vivo mutagenicity and carcinogenicity dose-response data.
Quantitative relationships between carcinogenic potency and mutagenic potency have been previously examined using a benchmark dose (BMD)-based approach. We extended those analyses by using human exposure data for 48 compounds to calculate carcinogenicity-derived and genotoxicity-derived margin of exposure values (MOEs) that can be used to prioritize substances for risk management. MOEs for 16 of the 48 compounds were below 10,000, and consequently highlighted for regulatory concern. Of these, 15 were highlighted using genotoxicity-derived (micronucleus [MN] dose-response data) MOEs. A total of 13 compounds were highlighted using carcinogenicity-derived MOEs; 12 compounds were overlapping. MOEs were also calculated using transgenic rodent (TGR) mutagenicity data. For 10 of the 12 compounds examined using TGR data, the results similarly revealed that mutagenicity-derived MOEs yield regulatory decisions that correspond with those based on carcinogenicity-derived MOEs. The effect of benchmark response (BMR) on MOE determination was also examined. Reinterpretation of the analyses using a BMR of 50% indicated that four out of 15 compounds prioritized using MN-derived MOEs based on a default BMR of 5% would have been missed. The results indicate that regulatory decisions based on in vivo genotoxicity dose-response data would be consistent with those based on carcinogenicity dose-response data; in some cases, genotoxicity-based decisions would be more conservative. Going forward, and in the absence of carcinogenicity data, in vivo genotoxicity assays (MN and TGR) can be used to effectively prioritize substances for regulatory action. Routine use of the MOE approach necessitates the availability of reliable human exposure estimates, and consensus regarding appropriate BMRs for genotoxicity endpoints.


A portable device for measuring donor corneal transparency in eye banks.
To develop a portable device for measuring the donor corneal transparency and validate its efficacy for corneal evaluation in the eye-banks and for research. The transparency device (TD) has a light source, a detachable system for corneal insertion and a base for light transmission. The probe detects the transmitted light which is measured by a lux-meter. A contact lens was set as 'control' to reduce the light scattering concern, an empty petri-plate as 'blank' and the cornea as 'sample'. Two experts and non-experts (masked) observed the corneas for subjective analysis which was then compared using the TD. The parameters observed were scars, foreign-body, stromal-deformities, folds, thickness and opacity which were then converted to a relative overall percentage by the observer. Twenty corneas were evaluated for correlation, five tissues to obtain standard-deviation and twenty-four pairs for a comparative study. Experts mimicked the eye-banks with long-term experience while non-experts mimicked the emerging eye-banks. Subjective values by the experts closely resembled the measurements by TD. The average correlation between the experts and the non-experts to TD was 0.985 and 0.960 respectively. TD showed higher reproducibility than experts followed by the non-experts. The comparative study showed that increase in thickness reduces the transparency. TD is portable, easy, efficient, maintains sterility and less expensive hence the emerging eye-banks and researchers can use to raise their standards and evaluate the transparency for in vitro tests and comparative studies. The suitable transparency for the cornea deemed for clinical applications was found to be >75 %.


Preoperative, single-fraction irradiation for prophylaxis of heterotopic ossification after total hip arthroplasty.
We gave a single fraction of 750 cGy preoperatively (within 16 h of surgery) to 143 patients prior to total hip arthroplasty. The patients were evaluated for heterotopic ossification at 1, 3 and 6 months. The preoperative radiation did not affect the surgical procedure. After a median follow-up of 12 (6-24) months we encountered six patients with heterotopic ossifications of Brooker grade I-II. Potential late risks from ionising radiation should be considered when treating younger patients.


Association between depression or sleep problems and working time mismatch among Korean workers.
This study aimed to investigate the relationship between South Korean workers' working time mismatches and their depression and sleep disorders. This study used raw data from the fifth Korean Working Conditions Survey (KWCS), which sampled 50,205 workers. The risk of occurrence of sleep problems among workers was shown to be proportional to actual working time. The risk of occurrence of depression increased along with the degree of working time mismatch. To improve the health and welfare of workers, making a policy and labor culture that relieve working time mismatch is important.


Phenolic extractives from root bark of Picea abies.
Five new compounds, viz. 3,4-dimethoxyphenyl 2-O-(3-O-methyl-alpha-L-rhamnopyranosyl)-beta-D-glucopyranoside, 4'-hydroxyphenacyl beta-D-glucopyranoside, (2R,3R)-2,3-dihydro-7-hydroxy-2-(4'- hydroxy-3'-methoxyphenyl)- 3-hydroxymethyl-5-benzofuranpropanol 4'-O-(3-O-methyl-alpha-L-rhamnopyranoside), 1-(4'-hydroxy-3'-methoxyphenyl)-2-[4"-(3-hydroxypropyl)-2"-methoxyphe noxy]-1,3-propanediol 4'-O-beta-D-xylopyranoside and 3'-O-methylcatechin 7-O-beta-D-glucopyranoside, together with several known compounds were isolated from the root bark of Picea abies. The structures were elucidated on the basis of chemical and spectroscopic evidence.


Integration of pre-trained protein language models into geometric deep learning networks.
Geometric deep learning has recently achieved great success in non-Euclidean domains, and learning on 3D structures of large biomolecules is emerging as a distinct research area. However, its efficacy is largely constrained due to the limited quantity of structural data. Meanwhile, protein language models trained on substantial 1D sequences have shown burgeoning capabilities with scale in a broad range of applications. Several preceding studies consider combining these different protein modalities to promote the representation power of geometric neural networks but fail to present a comprehensive understanding of their benefits. In this work, we integrate the knowledge learned by well-trained protein language models into several state-of-the-art geometric networks and evaluate a variety of protein representation learning benchmarks, including protein-protein interface prediction, model quality assessment, protein-protein rigid-body docking, and binding affinity prediction. Our findings show an overall improvement of 20% over baselines. Strong evidence indicates that the incorporation of protein language models' knowledge enhances geometric networks' capacity by a significant margin and can be generalized to complex tasks.


Effects of repeated applications of two semi-permanent hair dyes to the skin of A and DBAf mice.
Two proprietary semi-permanent hair dyes were tested for carcinogenicity in A and DBAf mice by repeated topical applications in aqueous acetone. Mice of both strains developed lymphoid tumours but experimental differences were marked only in DBAf mice. A number of tumours of the ovary and uterus, and some skin papillomas near the penis, occured in dye-treated but not in control DBAf mice. As many hair-dye constituents are known mutagens, adequate carcinogenicity testing of these substances, and epidemiological study of exposed human populations, are needed for evaluating possible health hazard from hair dyeing.


Ultrarapid freezing: a new low-cost and effective method of embryo cryopreservation.
The authors describe a rapid freezing method (ultrarapid freezing) that has been developed for cryopreservation of early cleavage stage embryos. In the present experiments, 2-cell mouse embryos were frozen under a wide range of conditions in an attempt to optimize their survival and viability in vitro and in vivo. The experiments show that embryos exposed briefly (2 to 2.5 minutes) to relatively high concentrations of dimethyl sulfoxide (3 to 4 M) and 0.25 M sucrose survive and develop when plunged directly into liquid nitrogen and thawed in a 37 degrees C waterbath when sealed in 0.25-ml plastic pailettes. Survival and viability rates of ultrarapidly frozen embryos after thawing were comparable to those obtained with conventional slow-freezing techniques. The authors believe that this freezing technique can be further improved and that the speed, ease, and low cost of the method make it a very attractive alternative to more conventional methods for freezing early cleavage stage embryos.


The influence of methylene blue light treatment and methylene blue removal filter on fibrinogen activity states and fibrin polymerisation indices.
Methylene blue light treatment (MBLT) is efficient in inactivating viruses in plasma. However, it may cause alterations in clotting factors, especially fibrinogen (Fg). The true mechanism of such a selective alteration is poorly understood, The effects of MBLT and MB removal filters (MBRF) on Fg concentration, functional activity and fibrin polymerisation were studied. Apheresis plasma collected by Haemonetic MCS Plus (n=10) was split into two equal aliquots. Both were leukofiltered and virally inactivated in a standardized fashion, using Theraflex MB-Plasma Photodynamic viral inactivation Macopharma method. One of the pair was subsequently processed, using Blueflex MBRF to remove residual MB and its by-products. Control plasma samples were obtained after filtration but before MBLT. Samples were also obtained after MBLT and MBRF. All samples were analyzed for the Fg activity, Fg antigen, thrombin clotting time (TT), and alterations fibrin polymerisation indices. After MBLT, mean Fg concentration increased slightly (2%) whereas functional activity decreased by 31%, as compared to control samples. Mean TT prolonged by 6s after MBLT, with no further changes after MBRF. A similar trend was observed using RT. Both thrombin and reptilase triggered fibrin polymerisation were delayed and the polymerisation curves slopes were decreased slightly, with concomitant changes in fibrin opacity in samples from MBLT and MBRF as compared to control. Comparison is made for the first time with a similar changes observed in dysfibrinogenemia. MBLT resulted in about 30% decrease in Fg activity but a slight modification in fibrin polymerisation indices, with no additional alteration subsequent to MBRF. These in vitro changes are similar to those seen in plasma from patients with dysfibrinogenemia, which are usually without clinical significance.


Endoscopic biliary prostheses as treatment for benign postoperative bile duct strictures.
We evaluated the efficacy of endoscopically placed biliary stents as treatment for 32 benign postoperative biliary strictures in 29 patients. Five patients also had bile fistulas. Stents were inserted for a mean of 162 days and then removed. ERCPs were obtained before stent insertion and again after removal. Responses were followed and categorized as excellent, good, or poor. Stent insertion was successful in 25 patients (86%), 23 of which have a mean follow-up of 19 months (range, 2 to 42 months) after stent removal. Seventy-four percent had an excellent (48%) or good (26%) response. Early postoperative strictures and fistulas responded favorably. We conclude that benign postoperative biliary strictures can be treated successfully by endoscopic prostheses.


Identification of inhibitors against SARS-CoV-2 variants of concern using virtual screening and metadynamics-based enhanced sampling.
Among the variants of SARS-CoV-2, some are more infectious than the Wild-type. Interestingly, these mutations enable the virus to evade the therapeutic efforts. Hence, there is a need for candidate drug molecules that can potently bind with all the variants. We have adopted a strategy combining virtual screening, molecular docking followed by rigorous sampling by metadynamics simulations to find candidate molecules. From our results we found four highly potent drug candidates that can bind to the Spike-RBD of all the variants of the virus. Additionally, we also found that certain signature residues on the RBM region commonly bind to each of these inhibitors. Thus, our study not only gives information on the chemical compounds, but also residues on the proteins which could be targeted for future drug and vaccine development studies.


Mitochondrial [4Fe-4S] protein assembly involves reductive [2Fe-2S] cluster fusion on ISCA1-ISCA2 by electron flow from ferredoxin FDX2.
The essential process of iron-sulfur (Fe/S) cluster assembly (ISC) in mitochondria occurs in three major phases. First, [2Fe-2S] clusters are synthesized on the scaffold protein ISCU2; second, these clusters are transferred to the monothiol glutaredoxin GLRX5 by an Hsp70 system followed by insertion into [2Fe-2S] apoproteins; third, [4Fe-4S] clusters are formed involving the ISC proteins ISCA1-ISCA2-IBA57 followed by target-specific apoprotein insertion. The third phase is poorly characterized biochemically, because previous in vitro assembly reactions involved artificial reductants and lacked at least one of the in vivo-identified ISC components. Here, we reconstituted the maturation of mitochondrial [4Fe-4S] aconitase without artificial reductants and verified the [2Fe-2S]-containing GLRX5 as cluster donor. The process required all components known from in vivo studies (i.e., ISCA1-ISCA2-IBA57), yet surprisingly also depended on mitochondrial ferredoxin FDX2 and its NADPH-coupled reductase FDXR. Electrons from FDX2 catalyze the reductive [2Fe-2S] cluster fusion on ISCA1-ISCA2 in an IBA57-dependent fashion. This previously unidentified electron transfer was occluded during previous in vivo studies due to the earlier FDX2 requirement for [2Fe-2S] cluster synthesis on ISCU2. The FDX2 function is specific, because neither FDX1, a mitochondrial ferredoxin involved in steroid production, nor other cellular reducing systems, supported maturation. In contrast to ISC factor-assisted [4Fe-4S] protein assembly, [2Fe-2S] cluster transfer from GLRX5 to [2Fe-2S] apoproteins occurred spontaneously within seconds, clearly distinguishing the mechanisms of [2Fe-2S] and [4Fe-4S] protein maturation. Our study defines the physiologically relevant mechanistic action of late-acting ISC factors in mitochondrial [4Fe-4S] cluster synthesis, trafficking, and apoprotein insertion.


Smooth muscle differentiation of coronary intima in autopsy tissues after sirolimus-eluting stent implantation.
In coronary atherosclerotic disease, the proliferation of intimal smooth muscle cells (SMCs) is regarded as beneficial with respect to stable and unstable plaques, but is thought detrimental in discussions on coronary stent restenosis. To resolve this discrepancy, we focused on the quality, not quantity, of intimal SMCs in coronary atherosclerotic disease. Autopsied coronary artery specimens from seven patients implanted with bare metal stents (BMS), three with paclitaxel-eluting stents (PES), and 10 with sirolimus (rapamycin)-eluting stents (SES) were immunostained for SMC markers. Cultured human coronary artery SMCs were also treated with sirolimus and paclitaxel. Intimal SMC differentiation, estimated by the ratio of h-caldesmon+ cells to α-smooth muscle actin+ (α-SMA+) cells, was significantly increased whereas dedifferentiation, estimated from the ratio of fibroblast activation protein alpha (FAPα)+ cells to α-SMA+ cells, was significantly decreased, in tissues of SES compared with BMS cases. No difference in the degree of differentiation was found between PES and BMS cases or between the three groups in nonstented arteries used as controls. Correlation analyses for each field of view revealed a significant positive correlation between h-caldesmon and calponin staining but significant negative correlations with FAPα staining in α-SMA+ cells. Cultured SMCs were shorter (dedifferentiated) and showed an increased FAPα/α-SMA protein when treated with paclitaxel, whereas they became elongated (differentiated) and showed increased calponin/α-SMA proteins with sirolimus. The SMCs of the coronary intima may differentiate after SES implantation. SMC differentiation may explain both the plaque stabilization and reduced risk of reintervention associated with SES.


Gluteal muscle fibrosis with abduction contracture of the hip.
Gluteal muscle fibrosis with hip contracture is a rare condition and causes major disability; literature reports are sparse. The aim of this study is to present, for the first time in Iraq and the region, a case series of gluteal fibrosis and the results of surgical treatment. Seven children--six boys and one girl--diagnosed as having gluteal muscle fibrosis with hip contracture, were investigated and treated by open surgical release of fibrotic bands and physiotherapy. All patients improved dramatically over the subsequent weeks, and were able to sit and squat in the normal position. Gluteal muscle fibrosis with hip contracture is present in Iraq and more awareness is needed for early diagnosis. Surgical treatment provided excellent results. More studies are needed to delineate the aetiology of the condition.


Changes in eating behavior during the aging process.
The changing demographics of the world population necessitate a review of normative eating behavior in order to better differentiate eating pathologies from age-associated changes. This review examines the psychological, social, and physiological changes in aging as they affect eating behavior. Neurochemical and neurophysiological bases of appetite, psychobehavioral models of eating, and concomitant variables of depression, bereavement, and social interactions are examined. As many sensory systems decline with aging, these declines influence food choice and acceptability and may manifest conditions such as geriatric anorexia. Special circumstances of centenarians are discussed to provide further insights into pathological, normative, and superlative aging.


Concurrent Immunohistochemical Localization and Western Blot Analysis of the MIF Receptor, CD74, in Formalin-Fixed, Paraffin-Embedded Tissue.
Archived, formalin-fixed, paraffin-embedded tissue provides a robust resource for assessing protein expression in a variety of complex tissue types. Immunohistochemical localization techniques allow one to identify proteins of interest in the different cell populations which compose these tissues, but quantitative comparison within and between samples is semiquantitative. In contrast, Western blot analysis provides a more quantitative assessment but without the ability to identify the cellular sources of expressed protein. Here we describe a dual approach using human endometrium to assess both the localization and quantitation of the macrophage migration inhibitory factor (MIF) receptor CD74 by immunohistochemical techniques and Western blotting.


Discovery of the cyclotide caripe 11 as a ligand of the cholecystokinin-2 receptor.
The cholecystokinin-2 receptor (CCK2R) is a G protein-coupled receptor (GPCR) that is expressed in peripheral tissues and the central nervous system and constitutes a promising target for drug development in several diseases, such as gastrointestinal cancer. The search for ligands of this receptor over the past years mainly resulted in the discovery of a set of distinct synthetic small molecule chemicals. Here, we carried out a pharmacological screening of cyclotide-containing plant extracts using HEK293 cells transiently-expressing mouse CCK2R, and inositol phosphate (IP1) production as a readout. Our data demonstrated that cyclotide-enriched plant extracts from Oldenlandia affinis, Viola tricolor and Carapichea ipecacuanha activate the CCK2R as measured by the production of IP1. These findings prompted the isolation of a representative cyclotide, namely caripe 11 from C. ipecacuanha for detailed pharmacological analysis. Caripe 11 is a partial agonist of the CCK2R (Emax = 71%) with a moderate potency of 8.5 µM, in comparison to the endogenous full agonist cholecystokinin-8 (CCK-8; EC50 = 11.5 nM). The partial agonism of caripe 11 is further characterized by an increase on basal activity (at low concentrations) and a dextral-shift of the potency of CCK-8 (at higher concentrations) following its co-incubation with the cyclotide. Therefore, cyclotides such as caripe 11 may be explored in the future for the design and development of cyclotide-based ligands or imaging probes targeting the CCK2R and related peptide GPCRs.


On the accessibility and localisation of cerebrosides in central nervous system myelin.
Cerebrosides are concentrated in the myelin sheath where they account for about 20% of the total lipid of the membrane. The present paper is concerned with the role and localisation of these glycolipids in the myelin lamellae. Isolated central nerve myelin preparations have been treated with two probes to investigate cerebroside accessibility in the membrane. The action of galactose oxidase on the galactose headgroups of cerebrosides is followed and quantitated by recovery of the modified glycolipid and resolution of either the 6-aldehydo sugar or galactose remaining by gas-liquid chromatography. With isolated myelin preparations only some 40--50% of the cerebroside galactose is attacked by galactose oxidase at 20 degrees C. With periodate at 20 degrees C over 90% of the galactose headgroups are oxidised in 3 h while the figure is 50--55% over the same time period at 4 degrees C rising to 85% after 22 h. With multilamellar liposomes of mixed myelin lipids only some 20--25% of the available cerebroside is oxidised at 4 degrees C, the reaction being complete in 2 h. The results are discussed in relation to the dispositon of cerebroside in the myelin lamellae. A major location on the external face of the membrane system (intraperiod dense line) is favoured. A role for cerebroside in myelin in terms of increasing the stability and resistance of the lipid phase to ion movement is suggested.


Correction to: "A Temple of God": A Qualitative Analysis of the connection Between Spiritual/Religious Beliefs and Health Among Mormons.
The original version of the article was inadvertently published with textual error.


Effect of adrenal medullectomy on responses in heat production, plasma catecholamines and body temperature of burned rats to changes in the temperature of the hypothalamus.
Burn (B) and control (C) rats with and without adrenal medullectomy (Adx) 9-11 days postburn underwent warning and cooling of the preoptic anterior hypothalamus (POAH) during calorimetry at 22 degrees and 28 degrees C ambient. Blood was drawn for catecholamine assay during each displacement of the POAH temperature (Thy). The heat production (Hp) for the AdxB group at 22 degrees and 28 degrees C was not different from the Hp for the sham AdxB group (80 +/- 4 vs 86 +/- 8 at 22 degrees C, 58 +/- 8 vs 64 +/- 7 W/m2 at 28 degrees C) in spite of there being no detectable circulating epinephrine (E) for the AdxB groups. Cooling of the POAH of the AdxB 22 degrees C group, however, did not induce a further increment in Hp, in contrast to all other groups. Thy demonstrated good significant negative linear correlation with Hp for all groups. The resulting slopes were not significantly different from one another, indicating no difference in thermal sensitivity of the POAH between the groups. In four of eight groups plasma norepinephrine (NE) demonstrated positive correlation with Hp and in five of eight groups negative correlation with Thy, Plasma E values did not correlate with Hp and demonstrated negative correlation with Thy in two of four possible groups. These data show that postburn hypermetabolism is not dependent on E in the rat and suggest that NE may be calorigenic in burned rats.


Biological Impacts in Fathead Minnow Larvae Following a 7-Day Exposure to Agricultural Runoff: A Microcosm Study.
The objective of this study was to investigate the impact of agricultural runoff on growth and development in fathead minnow larvae. Identifying these impacts in the field is difficult due to the complexity of pulsatile events and the challenge of maintaining larval fish under environmental conditions. This paper presents evidence of sublethal impacts on minnow larvae, maintained in microcosms, following a 7-day exposure to agricultural runoff. Fathead minnow larvae (5-12 dph) were exposed to agricultural runoff in the Elkhorn River, NE, USA. At 28 dph, 16 days after the field exposure, river exposed larvae showed reductions in body mass and length compared to controls. Female larvae exposed to river water also showed a reduction in the expression of cyp19a compared to controls. Further research will be necessary to separate the impact of agrichemicals from that of other stressors, such as suspended sediment and daily oscillation in water temperature.


A cell-based assay for rapid assessment of ACE2 catalytic function.
Angiotensin-converting enzyme II (ACE2) is a monocarboxypeptidase expressed throughout multiple tissues and its catalysis of bioactive peptides regulates the renin-angiotensin system mediating blood pressure homeostasis. ACE2 is implicated in a variety of diseases, including obesity, diabetes, and cardiovascular diseases, and is the obligate entry receptor for SARS-CoV-2 infection. Disease-associated genetic variants of ACE2 are increasingly being identified but are poorly characterized. To aid this problem, we introduce a fluorometric cell-based assay for evaluating surface-expressed ACE2 catalytic activity that preserves the native glycosylation of the host environment and is amenable to high-throughput analysis of ACE2 variants in multi-well plates. We demonstrate sensitivity to detecting catalysis of the key ACE2 substrates, Angiotensin II, Apelin-13, and des-Arg9-bradykinin, and impact of a catalytically-deficient ACE2 variant. Normalizing catalytic measures to surface ACE2 expression accounts for variability in ACE2 variant transfection, surface delivery or stability. This assay provides a convenient and powerful approach for investigating the catalytic characteristics of ACE2 variants involved in cardiovascular peptide cascades and homeostasis of multiple organs.


The use of fresh embryos in stem cell research: ethical and policy issues.
Fresh embryos resulting from in vitro fertilization, including many of poor quality, can provide sources of human embryonic stem cell lines. We consider why some donate such embryos for this research, address relevant ethical and policy issues, and present core guidelines for fresh embryo donation based on those of Canada.


Interactions between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine.
The effect of cognition-enhancing agents oxiracetam and aniracetam on scopolamine-induced amnesia and brain acetylcholine decrease was investigated in the rat. Acetylcholine levels were measured by means of a gas-chromatographic method. Scopolamine (0.63 mg/kg IP 60 min before training) prevented the acquisition of a passive avoidance conditioned response ("step through": retest 30 min after training) and brought about a 64, 56 and 42% decrease in acetylcholine level in the cortex, hippocampus and striatum respectively. Oxiracetam (50 and 100 mg/kg IP) administered 30 min before scopolamine reduced the scopolamine-induced amnesic effect and decrease in acetylcholine level in the cortex and hippocampus, but not in the striatum. Lower and higher doses of oxiracetam were ineffective. Aniracetam (100 mg/kg PO) also prevented scopolamine-induced amnesia but attenuated acetylcholine decrease in the hippocampus only. Aniracetam (300 mg PO) reduced acetylcholine decrease in the hippocampus but did not prevent scopolamine-amnesia. In conclusion, oxiracetam and aniracetam exert a stimulatory effect on specific central cholinergic pathways. However, a direct relationship between cognition-enhancing properties and cholinergic activation needs further confirmation.


Characterization and genomic analysis of a broad-spectrum lytic phage HZ2201 and its antibiofilm efficacy against Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a clinically common conditionally pathogenic bacterium, and the abuse of antibiotics has exacerbated its drug resistance in recent years. This has resulted in extensive reports about the usage of Pseudomonas aeruginosa phage as a novel antibacterial drug. In this study, we isolated a novel phage HZ2201 with a broad lytic spectrum. The lytic rate of this phage against Pseudomonas aeruginosa reached 78.38% (29/37), including 25 multi-drug- and carbapenem-resistant Pseudomonas aeruginosa strains. Transmission electron microscopy revealed that phage HZ2201 belongs to the class Caudoviricetes. Biological characterization showed that phage HZ2201 had an latent period of 40 min, a lytic period of 20 min, and a burst size of 440 PFU/cell, with improved tolerance to temperature and pH. Considering genomic analysis, the HZ2201 genome was a circular double-stranded DNA with a size of 45,431 bp and a guanine-cytosine (G + C) content of 52.16%, and contained 3 tRNAs. 27 of the 74 open reading frames (ORFs) annotated by the Rapid Annotation using Subsystem Technology (RAST) tool could be matched to the genomes of known functions, and no genes related to virulence and antibiotic resistance were found. The phylogenetic tree suggests that phage HZ2201 is highly related to the phage ZCPS1 and PaP3, and ORF57 and ORF17 are predicted to encode a holin and an endolysin, respectively. Cell lysis by HZ2201 proceeds through the holin-endolysin system, suggesting that it is a novel phage. Additionally, we demonstrated that phage HZ2201 has a high inhibitory capacity against Pseudomonas aeruginosa biofilms. The results of our study suggest that phage HZ2201 is a novel potential antimicrobial agent for treating drug-resistant Pseudomonas aeruginosa infection.


Coordinate changes in levels of human serum low and high density lipoprotein subclasses in healthy men.
Measurement of serum lipoproteins by analytic ultracentrifugation revealed significant correlations involving subfractions of low density (LDL) and high density (HDL) lipoproteins in 81 men studied cross-sectionally at baseline and longitudinally during a 1-year exercise trial. One-year changes in lipoprotein levels in 38 exercising men and in 30 sedentary controls showed correlations that paralleled those observed at baseline. Positive correlations observed between plasma levels of larger, more buoyant LDL of flotation rate (Sof) 7 to 10 (LDL-I) and HDL2 may be due to processes that also coregulate changes in levels of these lipoprotein subclasses. Similarly, positive correlations among smaller, more dense LDL of Sof 2 to 6 (LDL-III), IDL, and HDL3 suggest that levels of these lipoprotein species are also coordinately regulated. An inverse correlation of change in LDL-I with change in LDL-III raises the possibility of precursor-product relationships between LDL in these categories. Thus, changes in lipoproteins which are related to coronary disease risk are not independent of one another, and the development of coronary disease may be influenced by processes linking the metabolism of individual IDL, LDL, and HDL components.


Role of dexamethasone and insulin on the development of the five urea-cycle enzymes in cultured rat foetal hepatocytes.
The activity changes of the urea-cycle enzymes were monitored in cultured foetal hepatocytes after dexamethasone and insulin treatments. Addition of dexamethasone induced the development of carbamoyl-phosphate synthetase, argininosuccinate synthetase, argininosuccinase and arginase activities as soon as day 16.5 of gestation. When insulin was added together with dexamethasone, it markedly inhibited the steroid-induced increase in carbamoyl-phosphate synthetase, argininosuccinate synthetase and argininosuccinase activities.


Susceptibility genes for schizophrenia: mutant models, endophenotypes and psychobiology.
Schizophrenia is characterised by a multifactorial aetiology that involves genetic liability interacting with epigenetic and environmental factors to increase risk for developing the disorder. A consensus view is that the genetic component involves several common risk alleles of small effect and/or rare but penetrant copy number variations. Furthermore, there is increasing evidence for broader, overlapping genetic-phenotypic relationships in psychosis; for example, the same susceptibility genes also confer risk for bipolar disorder. Phenotypic characterisation of genetic models of candidate risk genes and/or putative pathophysiological processes implicated in schizophrenia, as well as examination of epidemiologically relevant gene × environment interactions in these models, can illuminate molecular and pathobiological mechanisms involved in schizophrenia. The present chapter outlines both the evidence from phenotypic studies in mutant mouse models related to schizophrenia and recently described mutant models addressing such gene × environment interactions. Emphasis is placed on evaluating the extent to which mutant phenotypes recapitulate the totality of the disease phenotype or model selective endophenotypes. We also discuss new developments and trends in relation to the functional genomics of psychosis which might help to inform on the construct validity of mutant models of schizophrenia and highlight methodological challenges in phenotypic evaluation that relate to such models.


The role of dioleoylphosphatidylethanolamine (DOPE) in targeted gene delivery with mannosylated cationic liposomes via intravenous route.
We have previously reported that mannosylated cationic liposome consisting with the mannosylated cationic cholesterol derivative Man-C4-Chol (Man) and dioleoylphosphatidylethanolamine (DOPE) (Man/DOPE) could deliver DNA to the liver by intravenous administration via mannose receptor-mediated endocytosis, however, rapid degradation in lysosomes might be a rate-limiting step in its gene transfection. In this study, we tried to evaluate the role of DOPE in in vivo gene transfer by comparing its transfection efficacy with mannosylated liposomes composed of Man and dioleoylphosphatidylcholine (DOPC) (Man/DOPC). In vitro studies showed that the cellular association of both liposome/pCMV-Luc complexes was almost the same, although Man/DOPE complex showed about 10-fold higher transfection activity than Man/DOPC complex. After intraportal administration into mice, Man/DOPE complex showed higher gene expression than Man/DOPC complex, suggesting that DOPE improves intracellular trafficking in target cells under in vivo conditions. An intravenous administration study demonstrated that Man/DOPE complex was accumulated in the liver more efficiently and achieved a higher gene expression in the liver than Man/DOPC complex. Thus, we conclude that the property of DOPE in mannosylated liposomes contributes to the efficient gene expression in the target site through enhanced distribution to the target site and intracellular sorting in the target cells under in vivo conditions.


Effects of daily static stretch training over 6 weeks on maximal strength, muscle thickness, contraction properties, and flexibility.
Static stretch training (SST) with long stretching durations seems to be sufficient to increase flexibility, maximum strength (MSt) and muscle thickness (MTh). However, changes in contraction properties and effects on muscle damage remain unclear. Consequently, the objective of the study was to investigate the effects of a 6-week self-performed SST on MSt, MTh, contractile properties, flexibility, and acute response of creatine kinase (CK) 3 days after SST. Forty-four participants were divided into a control (CG, n = 22) and an intervention group (IG, n = 22), who performed a daily SST for 5 min for the lower limb muscle group. While isometric MSt was measured in leg press, MTh was examined via sonography and flexibility by functional tests. Muscle stiffness and contraction time were measured by tensiomyography on the rectus femoris. Additionally, capillary blood samples were taken in the pretest and in the first 3 days after starting SST to measure CK. A significant increase was found for MSt (p < 0.001, η 2 = 0.195) and flexibility in all functional tests (p < 0.001, η 2 > 0.310). Scheffé post hoc test did not show significant differences between the rectus femoris muscle inter- and intragroup comparisons for MTh nor for muscle stiffness and contraction time (p > 0.05, η 2 < 0.100). Moreover, CK was not significantly different between IG and CG with p > 0.05, η 2 = 0.032. In conclusion, the increase in MSt cannot be exclusively explained by muscular hypertrophy or the increased CK-related repair mechanism after acute stretching. Rather, neuronal adaptations have to be considered. Furthermore, daily 5-min SST over 6 weeks does not seem sufficient to change muscle stiffness or contraction time. Increases in flexibility tests could be attributed to a stretch-induced change in the muscle-tendon complex.


Treatment of refractory lymphoproliferative diseases with daily, low-dose vincristine, continuous infusion of bleomycin, and high-dose prednisone.
Vincristine 0.25 mg/m2 by IV push and bleomycin 5 units daily by continuous infusion were given on days 1, 2, 3 and 4, together with prednisone 1,000 mg/m2 po in 4 divided doses either on days 1, 3, 5, and 7 (6 patients) or on days 1 and 3 (11 patients) to 17 patients with various lymphoproliferative diseases who had failed their previous treatment program. Fourteen were leukopenic and/or thrombocytopenic. Of 10 patients with non-Hodgkin's lymphoma 2 achieved complete remission and 5 a partial response. Both patients with Hodgkin's disease achieved partial response. A decrease in plasma M protein (median decrease 51%) was observed in 3/3 patients with multiple myeloma and 2/2 with Waldenstrom's macroglobulinemia. Decrease in tumor cell infiltration by 48%, 58% and 100% was observed in 3 patients (2 with macroglobulinemia and 1 with myeloma) in the bone marrow. Leukopenia of less than 3,600/mm3 and thrombocytopenia of less than 70,000/mm3 reverted to normal in 5/7 and 7/10 patients, respectively. Remission duration ranged from 4 to 35+ weeks (median 17 weeks). Three patients had severe GI bleeding. Psychosis controlled by phenothiazines was observed in one, and bleomycin toxicity (anaphylaxis, skin rash, and lung toxicity, one each) was observed in 3 patients. No severe neurotoxicity was observed.


Epidemiological evidence for causal relationship between Epstein-Barr virus and Burkitt's lymphoma from Ugandan prospective study.
Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma. These findings strongly support a causal relationship between the Epstein-Barr virus and Burkitt's lymphoma but suggest that the oncogenic potential of the virus is realised only in exceptional circumstances.


Content Analysis of Feedback Journals for New Nurses From Preceptor Nurses Using Text Network Analysis.
This study aimed to identify keywords, core topic areas, and subthemes by analyzing feedback journals written by preceptor nurses to new nurses during the preceptorship period and to derive implications through word clustering. A total of 143 preceptor nurses' feedback journals for new nurses from March 2020 to January 2021 were converted into a database using Microsoft Office Excel. Text network analysis was performed using the NetMiner 4.4.3 program. After data preprocessing, simple frequency, degree centrality, closeness centrality, betweenness centrality, and community modularity were analyzed. In the feedback journals, the most central words were "study," "medication," "practice," "nursing," "method," "need," and "effort," whereas frustration, "new nurses" had low centrality. Five subthemes were derived: (1) learning necessity to strengthen new nurses' competency, (2) independence of new nurses, (3) emphasis on accuracy in nursing skills, (4) difficulties in understanding the nursing tasks expected of new nurses, and (5) basic competency of new nurses. The results of this study highlighted the experiences of new nurses and allowed for an assessment of journal feedback content provided by preceptor nurses. As such, the study provides basic data to develop a standardized education and competency empowerment program for preceptor nurses.


Kinetic studies for sorption of amino acids using a strong anion-exchange resin. Effect of ionic strength.
This work deals with the influence of the ionic strength on the sorption of L-phenylalanine and L-tyrosine by a strong basic anion-exchange resin, converted to the hydroxide form with sodium hydroxide. Equilibrium uptake isotherms were obtained for phenylalanine and tyrosine by carrying out batch experiments at different ionic strength values of the solution. The model used to correlate these results is the modified Langmuir equation which has been applied with success to biological systems. Batch kinetic experiments were performed using a packed bed of differential length inserted in a liquid circulation loop and in which the ionic strength of the solution was varied. Moreover, an experiment at variable pH for tyrosine was also performed. Experimental transient concentration profiles were compared to those predicted by the pore diffusion model and enabled the estimation of the intraparticle diffusivities for phenylalanine and tyrosine.


The effects of differential and variable training on the quality parameters of a handball throw.
The aim of this study was to undertake a comprehensive temporal, effective, and practical training study (variable and differential learning) that would offer athletes the opportunity to increase their performance, and to analyse the effects by measuring kinematics and quality parameters. Two participants of differing standards--a player of the first Austrian League and an Olympic and World Champion--but of similar anthropometric characteristics were recruited. One of the participants (Austrian League) was tested on five different occasions (pre-test and four retests) to measure the effects of four different training phases using kinematic analysis. The results of the study indicate an increase in ball velocity within the differential training phases (first, second, and fourth phases), different proximal-to-distal sequences of the participants, and a change of movement pattern during training measured by the segment velocities and the angle-time courses.


Removal of an intra-renal migrated ureteral stent through a percutaneous nephroscopy in a 2-year-old child.
Ureteral stents are widely used to facilitate ureteral patency in the postoperative period of pyeloplasty and they are usually removed using forceps under cystoscopic guidance. Proximal migration of the ureteric stent is a rare but known complication and it is even less common in the pediatric age group. We present a case of antegrade retrieval of ureteral stent through a nephroscopic approach in a 2-year-old boy after unsuccessful cystoscopic, ureteroscopic and fluoroscopic attempt of removal due to intra-renal migration.


Tabletability Flip - Role of Bonding Area and Bonding Strength Interplay.
Predicting tableting performance of mixtures from that of individual components is of practical importance for achieving efficient and robust tablet design. It has been commonly assumed that a solid form exhibiting better tabletability will result in better tabletability when formulated. However, we show that the rank order of tabletability between two powders can flip when mixed with another powder, a phenomenon termed tabletability flip. Using three examples, we show that the tabletability flip upon mixing with microcrystalline cellulose is activated by the switch of the dominating factor in the bonding area (BA) and bonding strength (BS) interplay that determines tablet tensile strength. A mechanistic understanding of this phenomenon can significantly improve the accuracy of predicted tableting performance of mixtures from that of individual powders.


Meta-Analysis of the Relationship between XRCC1-Arg399Gln and Arg280His Polymorphisms and the Risk of Prostate Cancer.
Prostate cancer is one of the most common noncutaneous malignancies in Western countries. Because there has been a debate regarding the relationship between the XRCC1-Arg399Gln and Arg280His polymorphisms and prostate cancer risk, we therefore performed this meta-analysis. The electronic databases PubMed, EMBASE, and Medline were searched prior to October 1, 2014. An odds ratio and 95% confidence interval were used to calculate association. Heterogeneity was tested by both a chi-square test and I statistic. Funnel plots and Egger's test were used to assess publication bias. All statistical analyses were performed using STATA 12.0 software. A significant association between the XRCC1-Arg399Gln polymorphism and prostate cancer risk was found under a homozygote model and a recessive model. A significant association between XRCC1-Arg280His and prostate cancer risk was found under a heterozygote model and a dominant model [corrected]. Overall, the results of this meta-analysis show that the XRCC1-Arg399Gln polymorphism may be associated with an increased risk for prostate cancer under the homozygote model and the recessive model. And XRCC1-Arg280His polymorphism is likely to be related with prostate cancer risk under the heterozygote model and the dominant model. Additional larger well-designed studies are needed to validate our results.


Mercury (II) reduction and co-precipitation of metallic mercury on hydrous ferric oxide in contaminated groundwater.
Mercury (Hg) speciation and sorption analyses in contaminated aquifers are useful for understanding transformation, retention, and mobility of Hg in groundwater. In most aquifers hydrous ferric oxides (HFOs) are among the most important sorbents for trace metals; however, their role in sorption or mobilization of Hg in aquifers has been rarely analyzed. In this study, we investigated Hg chemistry and Hg sorption to HFO under changing redox conditions in a highly HgCl2-contaminated aquifer (up to 870μgL(-1) Hg). Results from aqueous and solid phase Hg measurements were compared to modeled (PHREEQC) data. Speciation analyses of dissolved mercury indicated that Hg(II) forms were reduced to Hg(0) under anoxic conditions, and adsorbed to or co-precipitated with HFO. Solid phase Hg thermo-desorption measurements revealed that between 55 and 93% of Hg bound to HFO was elemental Hg (Hg(0)). Hg concentrations in precipitates reached more than 4 weight %, up to 7000 times higher than predicted by geochemical models that do not consider unspecific sorption to and co-precipitation of elemental Hg with HFO. The observed process of Hg(II) reduction and Hg(0) formation, and its retention and co-precipitation by HFO is thought to be crucial in HgCl2-contaminated aquifers with variable redox-conditions regarding the related decrease in Hg solubility (factor of ~10(6)), and retention of Hg in the aquifer.


Altered expression of glutamate transporters in experimental autoimmune encephalomyelitis.
Amelioration of experimental autoimmune encephalomyelitis (EAE) by blockade of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), has been recently demonstrated [Nat. Med. 6 (2000) 67; Nat. Med. 6 (2000) 62]. However, the mechanisms underlying regulation of the extracellular glutamate concentration in EAE are unclear. To address this, we examined the expression of three distinct Na(+)-dependent glutamate transporters (GLT-1, GLAST and EAAC1) in the spinal cord of the Lewis rat EAE. EAE induced a dramatic increase in EAAC1 protein and mRNA levels, which corresponded closely with the course of neurological symptoms. In contrast, the levels of GLT-1 and GLAST protein were down-regulated in the spinal cord at the peak of disease symptoms, and no recovery was observed after remission. Furthermore, these changes in GLT-1, GLAST and EAAC1 expression were suppressed by treatment with NBQX. These results suggest that AMPA receptor activation precedes the altered expression of glutamate transporters, and that the dysregulation of extracellular glutamate concentration might play a critical role in pathological changes and neuronal dysfunction in EAE.


Research progress on the structural characterization, biological activity and product application of polysaccharides from Crataegus pinnatifida.
Crataegus pinnatifida is a plant of the Crataegus genus in the Rosaceae family and is commonly used as a food and medicinal resource. Crataegus pinnatifida polysaccharide, as one of the main active ingredients of Crataegus pinnatifida, has a variety of beneficial biological activities, such as antioxidant, hypoglycemic activity, lipid-lowering, intestinal flora regulation, promotion immune regulation, and antitumor activities. However, the extraction methods of Crataegus pinnatifida polysaccharides lack innovation, the primary structure is relatively limited, and the biological activity mechanism needs to be further explored. Therefore, this review summarizes the research status of the extraction, purification, structural characterization, biological activity, and product application of Crataegus pinnatifida polysaccharides. The purpose of this study is to generate support for further development and application of polysaccharides from Crataegus pinnatifida.


Impact of a continuous enhanced cardio-respiratory monitoring pathway on cardio-respiratory complications after bariatric surgery: A retrospective cohort study.
To determine the impact of an enhanced monitoring pathway consisting of continuous postoperative cardio-respiratory monitoring on adverse outcomes after bariatric. Single-center, retrospective cohort study. Adult patients who underwent bariatric surgeries between 2009 and 2016. We evaluated the use of an enhanced monitoring pathway consisting of a distant, continuous, non-invasive respiratory monitoring system on postoperative cardio-respiratory complications in patients undergoing bariatric surgery. Treating physicians had the option to assign patients to enhanced monitoring (intervention group) in the postoperative period for suspected or diagnosed OSA or other clinical concerns. The control group had intermittent vital sign checks as per institutional standards. The primary outcome was a composite of cardio-respiratory complications (rapid response team activation, intensive care admission, respiratory complications), major adverse cardiac events, and all-cause mortality. The secondary outcome was length of stay (LOS). Of 1450 patients, 752 patients received enhanced monitoring (intervention) and 698 patients received standard monitoring (control). Univariate analysis showed that, compared to control, enhanced monitoring was associated with lower odds of composite cardio-respiratory complications (OR: 0.41, 95%CI: 0.32-0.53, p < 0.001) and lower odds of prolonged LOS > 2 days (OR: 0.37, 95% CI: 0.28-0.49, p < 0.001. After adjusting for potential confounders, enhanced monitoring remained associated with a reduction in composite cardio-respiratory complications (OR: 0.64, 95% CI: 0.46-0.88, p = 0.005). Our study demonstrates that postoperative enhanced monitoring pathway was associated with a lower incidence of cardio-respiratory composite events, compared to a standard of care, in patients undergoing bariatric surgery. As our results show association rather than causation, future prospective randomized trials are needed to confirm the benefit of enhanced monitoring. Findings of our study add to the existing literature involved in clinical management pathways to reduce the incidence of adverse postoperative outcomes in high-risk patients undergoing inpatient surgeries.


Cannabinoid use in psychotic patients impacts inflammatory levels and their association with psychosis severity.
Inflammatory abnormalities are well-documented in individuals with chronic psychotic disorders. Particular attention has focused on interleukin-6 (IL-6) and its correlation with psychotic symptom severity. Cannabis use is associated with an increased risk of psychosis and also has immunomodulating properties. It has been hypothesized that inflammatory disturbances are a common underlying pathology between cannabis use and psychosis. We measured inflammatory markers in individuals admitted to a psychiatric unit with acute psychosis who had toxicology positive for natural and/or synthetic cannabinoids (n = 59) compared to patients with negative cannabinoid toxicology (n = 60). Psychosis severity was assessed using the Positive and Negative Syndrome Scale (PANSS). While PANSS scores were similar between groups, cannabinoid-positive participants were more likely to receive pro re nata (PRN or as-needed) medications for agitation in the psychiatric emergency room, particularly synthetic cannabinoid-positive participants. In unadjusted models, cannabinoid-positive participants had lower interferon-γ (IFN-γ) levels (p = 0.046), but this finding was not significant after adjusting for covariates and multiple comparisons. Among cannabinoid-positive participants, IL-6 levels negatively correlated with PANSS total score (p = 0.040), as well as positive (p = 0.035) and negative (p = 0.024) subscales. Results suggest inflammatory alterations among psychotic individuals with comorbid cannabinoid use.


Comparison of physiological responses to morning and evening submaximal running.
The aim of this study was to assess the effect of time of day on physiological responses to running at the speed at the lactate threshold. After determination of the lactate threshold, using a standard incremental protocol, nine male runners (age 26.3 +/- 5.7 years, height 1.77 +/- 0.07 m, mass 73.1 +/- 6.5 kg, lactate threshold speed 13.6 +/- 1.6 km x h(-1); mean +/- s) completed a standardized 30 min run at lactate threshold speed, twice within 24 h (07:00-09:00 h and 18:00-21:00 h). Core body temperature, heart rate, minute ventilation, oxygen uptake, carbon dioxide expired, respiratory exchange ratio and capillary blood lactate were measured at rest, after a warm-up and at 10, 20 and 30 min during the run. In addition, the rating of perceived exertion was reported every 10 min during the run. Significant diurnal variation was observed only for body temperature (36.9 +/- 0.9 degrees C vs 37.3 +/- 0.3 degrees C) and respiratory exchange ratio at rest (0.86 +/- 0.01 vs 0.89 +/- 0.07) (P < 0.05). Diurnal variation persisted for body temperature throughout the warm-up (37.1 +/- 0.2 degrees C vs 37.5 +/- 0.3 degrees C) and during exercise (36.2 +/- 0.6 degrees C vs 38.6 +/- 0.4 degrees C), but only during the warm-up for the respiratory exchange ratio (0.85 +/- 0.05 vs 0.87 +/- 0.02) (P < 0.05). The rating of perceived exertion was significantly elevated during the morning trial (12.7 +/- 0.9 vs 11.9 +/- 1.2) (P < 0.05). These findings suggest that, despite the diurnal variation in body temperature, other physiological responses to running at lactate threshold speed are largely unaffected. However, a longer warm-up may be required in morning trials because of a slower increase in body temperature, which could have an impact on ventilation responses and ratings of perceived exertion.


Hematopoietic prostaglandin D synthase-derived prostaglandin D2 ameliorates adjuvant-induced joint inflammation in mice.
Although prostaglandins (PGs) are known to be involved in the progression of arthritis, the role of PGD2 remains unclear. In this study, we evaluated the role of PGD2 in joint inflammation using genetically modified mice. Injection of complete Freund's adjuvant (CFA) increased the production of PGD2 and induced paw swelling and cartilage erosion in wild-type (WT) mice. These phenomena were accompanied with an increase in the mRNA levels of TNF-α, IL-6, IL-1β, and matrix-degrading metalloproteinase-9. Knockdown of hematopoietic PGD synthase (H-PGDS) abolished the PGD2 production and exacerbated all of the arthritic manifestations in the inflamed paw. Immunostaining revealed that infiltrating macrophages strongly expressed H-PGDS in the CFA-injected paw. Morphologic studies revealed vascular hyperpermeability and angiogenesis in the inflamed WT paw. H-PGDS deficiency was accelerated, whereas daily administration of a PGD2 receptor D prostanoid (DP) agonist attenuated the CFA-induced hyperpermeability and angiogenesis. We further confirmed that DP deficiency exacerbated, whereas the administration of the DP agonist improved, the CFA-induced arthritic manifestations. The findings demonstrate that H-PGDS-derived PGD2 ameliorates joint inflammation by attenuating vascular permeability and subsequent angiogenesis and indicates the therapeutic potential of a DP agonist for arthritis.-Tsubosaka, Y., Maehara, T., Imai, D., Nakamura, T., Kobayashi, K., Nagata, N., Fujii, W., Murata, T. Hematopoietic prostaglandin D synthase-derived prostaglandin D2 ameliorates adjuvant-induced joint inflammation in mice.


Positive distraction for children during burn wound care in Australia - An evaluation of the 'Captains on Call' pilot.
Burn wound care procedures can cause severe pain to the child, and distress for both the child and caregivers. We evaluated a new Starlight Children's Foundation program, 'Captains on Call', which aims to provide positive distraction during burn wound care procedures to reduce the child's anxiety and pain. This paper presents a preliminary evaluation, using a qualitative design, of Captains on Call at the Women's and Children's Hospital, Australia. We conducted interviews with caregivers (n = 18), patients (n = 6), nurses (n = 5) and Captain Starlights (n = 3). Interviews focused on program impact and recommendations for how to improve the program. We identified seven themes: (1) positive distraction from pain and boredom, (2) benefit of additional support, (3) creating positive memories of the hospital, (4) catering for unique needs of each patient and family, (5) general appreciation, (6) importance of regular visits, and (7) a desire to expand the program. All caregivers, nurses and patients reported that they were likely to recommend the program to others. This study provides early evidence to support the benefit of the Captains on Call program to families and health professionals, as well as the feasibility in providing this integrated care.


A patient of severe cervicofacial subcutaneous emphysema associated with Munchausen's syndrome.
Subcutaneous cervicofacial emphysema is an entity with the presence of air within the fascial planes of the head and neck, which results from various causes. A case of severe subcutaneous cervicofacial emphysema associated with Munchausen's syndrome is presented. Detailed diagnostic investigations to find out the organic cause of the condition were failed. Episodes of facial swelling were prevented by psychiatric support. Munchausen's syndrome should be kept in mind among the etiological factors of subcutaneous cervicofacial emphysema cases, in whom no organic causes can be found out.


Cystic Appearance on Imaging Methods (Bosniak III-IV) in Histologically Confirmed Papillary Renal Cell Carcinoma is Mainly Characteristic of Papillary Renal Cell Carcinoma Type 1 and Might Predict a Relatively Indolent Behavior of Papillary Renal Cell Carcinoma.
The aim of this study was to determine the proportion of cystic tumors according to preoperative CT (Bosniak III, IV) among surgically treated patients with histologically confirmed papillary renal cell carcinoma (pRCC) and to assess progression rates among patients with and without cystic appearance on imaging. A total of 138 patients with pRCC histology surgically treated in the period of January 2007-March 2017 were included. Clinical and radiological characteristics, type of surgery, histopathology results, and follow-up data were recorded and statistically evaluated. Forty-one cases (29.7%) of cystic lesions (10× BIIF, 14× BIII, 17× BIV) were detected by CT. Patients with pRCC1 significantly more frequently presented with cystic appearance on CT (33/78; 42.3%) in comparison to other papillary types (8/60; 13.3%; p = 0.0002). During a median follow-up time of 49.4 months, only 2 patients with cystic lesions progressed after surgery. Cystic appearance on imaging methods is mainly a characteristic of pRCC1 (42.3%). Cystic morphology on imaging might predict a relatively indolent behavior of all pRCC types. Preoperative scoring systems including tumor growth patterns (cystic vs. solid) are needed for further classification.


MiR-29 regulates the function of goat granulosa cell by targeting PTX3 via the PI3K/AKT/mTOR and Erk1/2 signaling pathways.
PTX3, a member of the pentraxin protein family, plays important roles in ovulation as a marker of cumulus cell-oocyte complex expansion. However, the expression and function of PTX3 in goat ovarian GCs remain unclear. We isolated GCs from small and large follicles and found that PTX3 expression was significantly decreased and miR-29 mRNA expression was significantly increased during the growth of antral follicles. MiR-29 decreased PTX3 expression by targeting its 3' untranslated. Furthermore, miR-29 promoted GC proliferation, suppressed steroidogenesis and apoptosis by targeting PTX3 via the activation of the PI3K/AKT/mTOR and Erk1/2 signaling pathways. Treatment with inhibitors also verified these results. Meanwhile, we found that PI3K/AKT/mTOR and Erk1/2 signaling pathways had different role in secretion of E2 and P4 by regulating differently various steroidogenic enzyme (CYP19A1, CYP11A1, StAR and HSD3B) expression. These outcomes indicate the potential role of PTX3 in goat follicular growth and atresia.


Layer-Specific BTX-A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement.
The rising incidence of health-endangering obesity constantly calls for more effective treatments. Gastric intramural injection of botulinum neurotoxin A (BTX-A) as a new modality carries great promise yet inconsistent therapeutic efficacy. A layer-specific delivery strategy enabled by dissolving microneedles is hence pioneered to investigate the working site of BTX-A and the resulting therapeutic effects. The drug-loaded tips of the layer-specific gastric paralysis microneedles (LGP-MN) rapidly release and achieve uniform distribution of BTX-A within the designated gastric wall layers. In an obesity rat model, the LGP-MNs not only prove safer than conventional injection, but also demonstrate consistently better therapeutic effects with muscular layer delivery, including 16.23% weight loss (3.06-fold enhancement from conventional injection), 55.20% slower gastric emptying rate, improved liver steatosis, lowered blood lipids, and healthier gut microbiota. Further hormonal study reveals that the elevated production of stomach-derived glucagon-like peptide-1 due to the muscularis-targeting LGP-MN treatment is an important contributor to its unique glucose tolerance-improving effect. This study provides clear indication of the gastric muscularis as the most favorable working site of BTX-A for weight loss and metabolic improvement purposes, and meanwhile suggests that the LGP-MNs could serve as a novel clinical approach to treat obesity and metabolic syndromes.


No Association Between -159C/T Polymorphism of the CD14 Gene and Asthma Risk: a Meta-Analysis of 36 Case-Control Studies.
Numerous studies have evaluated the association between -159C/T polymorphism of the CD14 gene and asthma risk; however, these studies have yielded inconsistent results. We performed meta-analyses to investigate the association between CD14-159C/T polymorphism and asthma risk. Studies were identified from PubMed, Embase, and two Chinese databases. Odds ratios (ORs) with 95 % confidence interval (CI) were used to evaluate the strength of association. Thirty-six studies were collected for meta-analysis, which involved 6954 cases and 7525 controls. In the overall populations, no significant association between the CD14-159C/T polymorphism and asthma risk was found for the dominant (OR = 0.90, 95 % CI = 0.81-1.01, P = 0.08) or other models; stratified analyses indicated that the CD14-159C/T polymorphism was not associated with asthma risk in Caucasians or Asians or adults or children. Among the atopic asthma populations, no significant results were observed in the all-combined or subgroup analyses. This meta-analysis demonstrates that the CD14-159C/T polymorphism may not be a risk factor for asthma.


Stem and leaf rust-induced miRNAome in bread wheat near-isogenic lines and their comparative analysis.
Wheat rusts remain a major threat to global wheat production and food security. The R-gene-mediated resistance has been employed as an efficient approach to develop rust-resistant varieties. However, evolution of new fungal races and infection strategies put forward the urgency of unravelling novel molecular players, including non-coding RNAs for plant response. This study identified microRNAs associated with Sr36 and Lr45 disease resistance genes in response to stem and leaf rust, respectively. Here, small RNA sequencing was performed on susceptible and resistant wheat near-isogenic lines inoculated with stem and leaf rust pathotypes. microRNA mining in stem rust-inoculated cultivars revealed a total of distinct 26 known and 7 novel miRNAs, and leaf rust libraries culminated with 22 known and 4 novel miRNAs. The comparative analysis between two disease sets provides a better understanding of altered miRNA profiles associated with respective R-genes and infections. Temporal differential expression pattern of miRNAs pinpoints their role during the progress of infection. Differential expression pattern of miRNAs among various treatments as well as time-course expression of miRNAs revealed stem and leaf rust-responsive miRNAs and their possible role in balancing disease resistance/susceptibility. Disclosure of guide strand, passenger strand and a variant of novel-Tae-miR02 from different subgenome origins might serve as a potential link between stem and leaf rust defence mechanisms downstream to respective R-genes. The outcome from the analysis of microRNA dynamics among two rust diseases and further characterization of identified microRNAs can contribute to significant novel insights on wheat-rust interactions and rust management. KEY POINTS: • Identification and comparative analysis of stem and leaf rust-responsive miRNAs. • Chromosomal location and functional prediction of miRNAs. • Time-course expression analysis of pathogen-responsive miRNAs.


Cyclodextrin complexation: influence on the solubility, stability, and cytotoxicity of camptothecin, an antineoplastic agent.
The solubility of camptothecin (CPT), a highly potent antineoplastic agent, as a function of different concentrations of cyclodextrins (alpha-cyclodextrin, alpha-CD; beta-cyclodextrin, beta-CD; and gamma-cyclodextrin, gamma-CD; hydroxypropyl-beta-cyclodextrin, HP-beta-CD; and randomly substituted dimethyl-beta-cyclodextrin, RDM-beta-CD, and dimethyl-gamma-cyclodextrin, RDM-beta-CD) in 0.02 N HCl solution at 25 degrees C was investigated. The results showed a linear increase in the solubility of CPT with increasing concentration of CDs. The apparent stability constants (K(c)) for the CPT complexes with alpha-CD, beta-CD, gamma-CD, HP-beta-CD, RDM-beta-CD, and RDM-gamma-CD were 188, 266, 73, 160, 910, and 40.6 M(-1), respectively, suggesting that RDM-beta-CD afforded the most stable complex. At a 25% w/v concentration of RDM-beta-CD, the solubility of CPT was 228.45 +/- 8.45 microg/ml, about 171 times higher than that in 0.02 N HCl. The stability of CPT in pH 7.4 buffer at 25 degrees C also increased linearly with an increase in the concentration of RDM-beta-CD. The observed pseudo-first-order hydrolysis rate constants (k(obs)) for the free and complexed CPT were 11.8 x 10(-3) and 1.18 x 10(-3) min(-1), corresponding to an increase in half-life of CPT from 58.7 to 587.3 min, respectively. The preliminary cytotoxicity study against the human-derived myeloid THP-1 leukemia cell line showed RDM-beta-CD/CPT and HP-beta-CD/CPT complexes to be about two-fold more active than free CPT. In conclusion, the results showed that CDs, in general, and RDM-beta-CD, in particular, are effective complexing agents and can be used to improve the solubility and stability of CPT. The increase in cytotoxicity of CPT in the presence of CD is likely due to an increase in its stability.


Response inhibition is impaired by developmental methylmercury exposure: acquisition of low-rate lever-pressing.
Developmental methylmercury (MeHg) exposure produces response perseveration on discrimination reversal procedures, disrupts sensitivity to reinforcement, and enhances sensitivity to dopamine agonists - a profile suggesting a deficit in behavioral inhibition. To examine inhibition, we examined MeHg's effects on the acquisition and persistence of low-rate lever-pressing following a history of high-rate responding. Additionally, we examined whether chronic exposure to selenium protects against MeHg's developmental neurotoxicity. Female rats were exposed in utero via maternal exposure to drinking water containing 0ppm, 0.5ppm or 5ppm of Hg as MeHg, producing approximately 0μg/kg/day, 40μg/kg/day, or 400μg/kg/day of Hg. The mothers (during gestation) and the offspring (throughout life) consumed a purified diet containing 0.06ppm or 0.6ppm of Se (as sodium selenite), forming a 2 (lifespan diet)×3 (developmental MeHg) factorial design. Adult offspring lever-pressed under two schedules of reinforcement. A differential reinforcement of high-rate (DRH) schedule imposed rigid response requirements that remained constant through the study. A high-rate percentile schedule (PCNT-H) incorporated a flexible criterion that reinforced short interresponse times using an adjusting criterion that was sensitive to recent performance. After high-rate responding stabilized, the PCNT-H schedule was abruptly inverted by reinforcing long interresponse times. Acquisition of low-rate responding was impaired in the MeHg-exposed rats because of intrusions of high-rate response bursts. DRH response rates did not change. Dietary selenium did not influence MeHg's effects. High-rate operant behavior perseverated, suggesting that gestational MeHg exposure impairs response inhibition - an effect that extends results previously reported using choice procedures or spatial and visual discrimination reversals.


Understanding chaperone specificity: evidence for a 'client code'.
The interactions of molecular chaperones with clients can be regulated by chaperone post-translational modification (PTMs) collectively known as the 'chaperone code'. What is less understood is how PTMs on client proteins may impact chaperone-client interactions. In this forum, we discuss the possibility of a 'client code'.


Early results of direct coronary stenting in consecutive patients when multivessel, complex, long lesions, and small vessels are included.
Direct coronary stenting is the dominant technique for coronary stent implantation, but previous randomized studies have strongly selected lesions to treat. To evaluate whether the results can be generalized to routine clinical practice, all consecutive patients with direct stenting in 15 hospitals were entered into a prospective registry. Single vessels and simple lesions, but also multivessel, complex and long lesions, and small vessels size (< or =2.5 mm) were included. Immediately results as well as clinical events within 30 days after the procedure were evaluated. Between April and November 2002, direct coronary stenting was performed in 452 consecutive patients (559 lesions) at 15 sites. Stents edge-protected by "sleeves" (SOX technology, NIR Stent, Boston Scientific) or with short transitional edge protection (STEP technology, Multilink Stents, Guidant) were selected to minimize vessel injury outside the stent edges during balloon inflation/deployment. Stents were successfully implanted in 96% of lesions. Lesions were multivessel in 27%, type B2-C in 40%, very angulated in 28%, calcified in 18%, and longer than 20 mm in 10% of patients. Vessels were smaller than < or =2.5 mm in 27% of patients. Direct coronary stenting was unsuccessful in 25 lesions (24 patients) characterized by more unstable angina (p=0.07), more treated lesions (p<0.01), and more distal locations (p=0.001). Dissection occurred in 6% of patients, and one stent embolised. The 30-day follow-up period included 1 death (due to subacute occlusion), 11 (2.4%) acute myocardial infarctions (8 non-Q wave), and one stroke (following carotid surgery). Direct coronary stenting yielded excellent results at 30 days although some expanded indications will be included.


[The probiotic yogurt Activia shortens intestinal transit, but has not been shown to promote defecation].
Activia is a yogurt product containing the probiotic bacterium Bifidobacterium animalis DN-173 010. Five clinical trials have been carried out. Four of these show that dairy products containing this bacterium shorten intestinal transit in volunteers. However, except in a subgroup of 19 out of 267 patients in one study, no significant effect of Activia was reported on the frequency, quantity or consistency of stools. In its marketing in the Netherlands, the company that produces Activia, Danone, claims that Activia promotes defecation. There is insufficient scientific evidence to support this claim.


Soluble beta-amyloid leads to mitochondrial defects in amyloid precursor protein and tau transgenic mice.
Mitochondrial dysfunction has been identified in neurodegenerative disorders including Alzheimer's disease, where accumulation of beta-amyloid (Abeta) and oxidative stress seem to play central roles in the pathogenesis, by probably directly leading to mitochondrial dysfunction. In order to study the in vivo effect of Abeta load during aging, we evaluated the mitochondrial function of brain cells from transgenic mice bearing either mutant amyloid precursor protein (tgAPP) or mutant amyloid precursor protein and mutant PS1 (tgAPP/PS1) as well as from nontransgenic wild-type littermates. tgAPP mice exhibit onset of Abeta plaques at an age of 6 months, but the intracellular soluble Abeta load is already increased at 3 months of age. In contrast, onset of Abeta plaques starts at an age of 3 months in tgAPP/PS1 mice. In addition, we investigated the effects of different Abeta preparations on mitochondrial function of brain cells from tau transgenic mice. Of note, mitochondrial damage such as reduced mitochondrial membrane potential and ATP levels can already be detected in the brains from these mice before the onset of plaques. In agreement with our findings in tgAPP mice, soluble Abeta induced mitochondrial dysfunction in brain cells from tau transgenic mice. Our results indicate that mitochondrial dysfunction is exacerbated by the presence of soluble Abeta species as a very early event during pathogenesis.


Molecular cloning of four cDNAs encoding prepro-crustacean hyperglycemic hormone (CHH) from the eyestalk of the red rock crab Cancer productus: identification of two genetically encoded CHH isoforms and two putative post-translationally derived CHH variants.
Recently, we demonstrated that the four known sinus gland (SG) isoforms of Cancer productus crustacean hyperglycemic hormone precursor-related peptide (Capr-CPRP I-IV) are differentially distributed in conserved patterns among individual crabs. This finding strongly supported the presence of multiple prepro-crustacean hyperglycemic hormone (chh) transcripts in each crab, as well as the translation and processing of the encoded prepro-hormones. Whether these transcripts contained common or distinct isoforms of CHH remained unknown. To address this question, molecular analyses of the C. productus eyestalk prepro-chhs were undertaken. Using a PCR-based cloning strategy, four prepro-chh cDNAs were characterized: one encoding CPRP I, one encoding CPRP III (found to possess Ile(26) rather than Leu(26) as reported previously), and two encoding CPRP II. No cDNA encoding CPRP IV was identified. The deduced CHH present in the prepro-hormones containing CPRP I and III were identical (Capr-CHH I) and differed from that (Capr-CHH II) present in the two prepro-hormones containing Capr-CPRP II at a single residue, a Thr(5) for Ser(5) substitution. As both CHH isoforms possess Glu at position 1, a cyclization of this residue to pyroglutamine is likely as the peptides mature, as has been seen for the CHHs of other brachyuran species. Likewise, homology to other CHHs suggests all C. productus isoforms are C-terminally amidated. These post-translational modifications would result in four SG isoforms of CHH: Capr-CHH I, Capr-pyro-CHH I, Capr-CHH II, and Capr-pyro-CHH II. Southern blotting supported the hypothesis that at least three prepro-chh transcripts are present in each crab, while dual in situ hybridization-immunohistochemistry localized the transcripts to previously mapped CHH immunopositive somata in the X-organ, the major source of innervation to the SG.


Influence of Religion on Attitude Towards Suicide: An Indian Perspective.
This cross-sectional survey was aimed to compare attitudes towards suicide and suicidal behaviour among randomly selected sample (N = 172) belonged to Hindu and Muslim religions. Data were collected through face-to-face interview. Hindus differed from Muslims regarding suicidal attempts among family (χ (2) = 12.356, p < .002) and community members (χ (2) = 20.425, p < .000). Our study also showed that suicidal behaviours were comparatively low among Muslim participants than Hindus. Further, Muslims hold more negative attitudes towards suicide than Hindus. An enhanced understanding of attitudes towards suicide among general population may be crucial to plan educational, intervention and prevention programs.


Genetic study of infantile spasm with hypsarrhythmia.
Infantile spasms (IS) appear to be a distinct syndrome complicated by heterogeneous etiology. Family data support a multifactorial model involving a polygenic determination of susceptibility to IS but requiring environmental factors such as anoxia, birth trauma, or immunization to precipitate seizures. The empiric recurrence risk among siblings was estimated to be 15 +/- 3 and for all first degree relatives as 7 +/- 5 per 1,000. These risks should be interpreted with caution since possible heterogeneity of IS may result in the occurrence of families in which cases are presumably totally environmental, and other rare families which may be segregating for an autosomal recessive disorder. Careful review of involved medical and family histories and a thorough physical examination should permit discrimination among these possibilities.


Fosfomycin increases chromosome instability in lymphocytes from Fanconi Anemia patients.
Fanconi Anemia (FA) is a chromosome instability (CI) syndrome, clinically characterized by progressive bone marrow failure and increased cancer predisposition. Lymphocytes from FA patients have hypersensitivity to alkylating agents, particularly to diepoxybutane (DEB). The antibiotic fosfomycin (FOM) is an alkylating agent. FOM is used as a large spectrum antibiotic and also as a prophylactic pre-surgery agent. FOM has been considered non-genotoxic. However, no specific genotoxic evaluation directed to patients with hypersensitivity to alkylating agents was performed. As FA patients are very susceptible to infections and may be submitted to several surgeries, FOM can eventually be prescribed to them during their lifetime. In the present study we evaluated the putative genotoxic effect of FOM in cultured lymphocytes from FA patients, compared to cultured lymphocytes from healthy donors (HD). Cultures from FA patients and HD were treated with 0.5mM FOM or with 0.6mM DEB and CI was evaluated. Results showed that FOM significantly increases CI in cultured lymphocytes from FA patients, compared to lymphocytes from HD, in which no effect was found. Additionally, a direct correlation between DEB and FOM toxicity was observed in lymphocytes from FA patients, indicating similar susceptibility to both agents.


The performance of electrode ultrafiltration membrane bioreactor in treating cosmetics wastewater and its anti-fouling properties.
The membrane fouling problem of the membrane bioreactor (MBR) for wastewater treatment reduces the membrane flux and the pollutants removal efficiencies, which is the major obstacle limiting its application and should be properly solved. The combination of membrane and electricity can effectively slow down the membrane fouling rate due to electric repulsion between the pollutants and the membrane. In this study, the performance and the membrane fouling features of an electrode ultrafiltration membrane bioreactor (EMBR) fed with cosmetics wastewater were compared with a conventional ultrafiltration membrane bioreactor (UMBR). The results showed the COD removal efficiency increased by 4.43% and the transmembrane pressure (TMP) reduced by 50% in the EMBR as compared with the UMBR. The specific surface areas of electrode ultrafiltration membrane and conventional ultrafiltration membrane declined by 56.9% and 78.8% after 90 days of operation, respectively. The Protein (PN), polysaccharide (PS) and humic acids (HA) in the cake layer of EMBR were only 61.27%, 78.37% and 34.85% of that of UMBR, which contributed to its loose and porous structure and thus decreased the growth rate of TMP and extended the operation cycle. Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory calculation proved that the energy barrier between the electrode ultrafiltration membrane and the pollutants was 50% higher than that between the conventional ultrafiltration membrane and the pollutants. Therefore, the strong anti-fouling property of the electrode ultrafiltration membrane could reduce the chemicals dosage and manpower consumption for membrane cleaning and could be preferred for the treatment of cosmetics or alike wastewater containing high concentrations of surfactants and fatty acids.


Allyl-isatin suppresses cell viability, induces cell cycle arrest, and promotes cell apoptosis in hepatocellular carcinoma HepG2 cells.
The anticancer effect of the newly synthesized isatin derivative, N-allyl-isatin (Allyl-I), was evaluated in vitro with human hepatocellular carcinoma HepG2 cells. Cell viability was detected by cell counting kit-8 (CCK8) assay. Acridine orange (AO)/ethidium bromide (EB) double staining was used to observe the cell morphology. Flow cytometry was used to assess the effects of Allyl-I on the cell cycle, apoptosis rate, and mitochondrial membrane potential (MMP). Western blot analysis was performed to detect the influence of Ally1-I on the expression of cytochrome c (cyt c), Bax, Bcl-2, and cleaved caspase-3. Allyl-I significantly inhibited HepG2 cell viability in a time- and dose-dependent manner. Allyl-I can induce cell cycle arrest in HepG2 cells at the G2/M phase. Apoptotic nuclear morphological changes were observed after AO/EB double staining. Fluorescein isothiocyanate-conjugated Annexin V (Annexin V-FITC) and propidium iodide (PI) double staining showed that the apoptotic rates significantly increased in the presence of Allyl-I. Rhodamine 123 staining indicated that Allyl-I can decrease the MMP. Allyl-I also altered the expression of mitochondrial apoptosis-related proteins. Protein levels of cyt c and cleaved caspase-3 were upregulated following Allyl-I treatment. By contrast, the Bcl-2/Bax ratio decreased. Results suggest that Allyl-I suppresses cell viability, induces cell cycle arrest, and promotes cell apoptosis in HepG2 cells. Furthermore, the induction of apoptosis might be correlated with the mitochondrial pathway.


Immunohistochemical localization of c-erbB-2 in human breast carcinomas.
This study was carried out to assess the utility of antibodies raised to synthetic peptides of the predicted sequence of the c-erbB-2 gene product to identify immunocytochemically those tumours overexpressing this putative transmembrane receptor. Staining with rabbit antiserum 21N gave the best correlation with gene amplification and did not stain the membrane of any of the normal tissues at the dilution which strongly stained the membrane of any of the normal tissues at the dilution which strongly stained the amplified tumours. No significant correlation was found with lymph node involvement, epidermal growth factor receptor status or with oestrogen receptor levels. Of the 12 out of 34 cases which demonstrated c-erbB-2 gene amplification in the primary tumour, two had lymph node metastases which were also positive immunocytochemically. Fourteen other cases which had lymph node metastases were negative in the primary tumour and in the metastases. These tumours all showed strong membrane positivity. A comparison of modified methacarn and formol saline fixation demonstrated an increased sensitivity with the former, but the staining pattern was unaltered. This small but extensively studied group of cases has indicated that increased c-erbB-2 protein can be identified routinely in fixed tissue sections, making it possible to carry out extensive studies to look for clinical correlates, but also to assess the stage in tumour progression at which the increased expression occurs and whether it correlates with any potentially premalignant condition.


An in vivo mouse model of intraosseous spinal cancer causing evolving paraplegia.
The spine is the commonest site of skeletal metastatic disease and uncontrolled growth of cancer in the spine will inevitably cause pain and neurologic compromise. Improved understanding of the pathobiology behind this devastating condition is urgently needed. For this reason, the aim of this study was to establish a clinically relevant, animal model of spinal cancer. A percutaneous orthotopic injection of human breast (MDA-MB-231) or human prostate (PC-3) cancer cells was administered into the upper lumbar spine of nude mice (n = 6). Animals were monitored twice daily for general welfare, gait asymmetry or disturbance, and hindlimb weakness. After sacrifice, plain radiographs, micro-CT imaging and histological analysis of the spines were performed on each mouse. All mice recovered fully from the inoculation procedure and displayed normal gait and behaviour patterns for at least 3 weeks post-inoculation. Subsequently, between 3 and 5 weeks post-inoculation, each mouse developed evolving paralysis in their hindlimbs over 48-72 h. All followed the same pattern of decline following onset of neurological dysfunction; from gait asymmetry and unilateral hindlimb weakness, to complete unilateral hindlimb paralysis and finally to complete bilateral hindlimb paralysis. Plain radiographs, micro-CT scanning and histological analysis confirmed local tumour growth and destruction of the spine in all six mice. An in vivo mouse model of human intraosseous spinal cancer has been established forming cancers that grow within the spine and cause epidural spinal cord compression, resulting in a reproducible, evolving neurological deficit and paralysis that closely resembles the human condition.


Immunopotentiation against internal parasites.
The economic importance of livestock losses attributed to internal parasites has led to the need of developing and successfully employing effective antiparasitic vaccines. An increasingly important strategy in the development of more effective vaccines is the preparation and use of immunopotentiators or adjuvants. Immunopotentiators or adjuvants have been used effectively in combination with antigen(s) or alone to protect animals against internal parasites. The use of immunopotentiators for specific and nonspecific stimulation of protective immunity against internal parasites is reviewed.


Increased incorporation of fatty acids into phospholipids of lungs and livers of rabbits under the influence of bromhexine and ambroxol.
The incorporation of lauric acid, palmitic acid and oleic acid into phospholipids of lung and liver has been studied in tissue slices of control rabbits and of rabbits treated with bromhexine or ambroxol in doses of 10 mg/kg. A marked increase (up to 200% of the controls) of palmitic acid incorporation into phosphatidylcholine (lecithin) and phosphatidylethanolamine of the lung was found whereas the incorporation rate of palmitic acid into lecithin and phosphatidylethanolamine of the liver displayed no significant change. The incorporation of lauric acid and oleic acid into lung phospholipids was not accelerated. The observed effects were more marked in short time experiments (analysis 2 h after drug injection) than after treatements for 7 days. It is concluded that the phospholipid synthesis is stimulated by the drugs especially in the lungs. This seems to be of particular interest with respect to the surfactant system of the lung and might have some therapeutic relevance.


Lhermitte's sign in thoracic spinal tumour. Personal observation.
In a case of midthoracic spinal metastasis with a partial transverse cord lesion a typical Lhermitte's sign was elicited by flexion of the head. This is a very rare phenomenon with thoracic spinal tumours.


Childhood tuberculosis: epidemiology, diagnosis, treatment, and vaccination.
Despite the existence of a government-run tuberculosis (TB) control program, the current nationwide burden of TB continues to be a public health problem in Taiwan. Intense current and previous efforts into diagnostic, therapeutic, and preventive interventions have focused on TB in adults, but childhood TB has been relatively neglected. Children are particularly vulnerable to severe disease and death following infection, and children with latent infections become reservoirs for future transmission following disease reactivation in adulthood, thus fueling future epidemics. Additional research, understanding, and prevention of childhood TB are urgently needed. This review assesses the epidemiology, diagnosis, treatment, and relevant principles of TB vaccine development and presents efficacy data for the currently licensed vaccines.


Identification of altered metabolic pathways of γ-irradiated rice mutant via network-based transcriptome analysis.
In order to develop rice mutants for crop improvement, we applied γ-irradiation mutagenesis and selected a rice seed color mutant (MT) in the M14 targeting-induced local lesions in genome lines. This mutant exhibited differences in germination rate, plant height, and root length in seedlings compared to the wild-type plants. We found 1645 different expressed probes of MT by microarray hybridization. To identify the modified metabolic pathways, we conducted integrated genomic analysis such as weighted correlation network analysis with a module detection method of differentially expressed genes (DEGs) in MT on the basis of large-scale microarray transcriptional profiling. These modules are largely divided into three subnetworks and mainly exhibit overrepresented gene ontology functions such as oxidation-related function, ion-binding, and kinase activity (phosphorylation), and the expressional coherences of module genes mainly exhibited in vegetative and maturation stages. Through a metabolic pathway analysis, we detected the significant DEGs involved in the major carbohydrate metabolism (starch degradation), protein degradation (aspartate protease), and signaling in sugars and nutrients. Furthermore, the accumulation of amino acids (asparagine and glutamic acid), sucrose, and starch in MT were affected by gamma rays. Our results provide an effective approach for identification of metabolic pathways associated with useful agronomic traits in mutation breeding.


Validity of the Timed Up and Go Test as a Measure of Functional Mobility in Persons With Multiple Sclerosis.
To examine the validity of the timed Up and Go (TUG) test as a measure of functional mobility in persons with multiple sclerosis (MS) by using a comprehensive framework based on construct validity (ie, convergent and divergent validity). Cross-sectional study. Hospital setting. Community-residing persons with MS (N=47). Not applicable. Main outcome measures included the TUG test, timed 25-foot walk test, 6-minute walk test, Multiple Sclerosis Walking Scale-12, Late-Life Function and Disability Instrument, posturography evaluation, Activities-specific Balance Confidence scale, Symbol Digits Modalities Test, Expanded Disability Status Scale, and the number of steps taken per day. The TUG test was strongly associated with other valid outcome measures of ambulatory mobility (Spearman rank correlation, rs=.71-.90) and disability status (rs=.80), moderately to strongly associated with balance confidence (rs=.66), and weakly associated with postural control (ie, balance) (rs=.31). The TUG test was moderately associated with cognitive processing speed (rs=.59), but not associated with other nonambulatory measures (ie, Late-Life Function and Disability Instrument-upper extremity function). Our findings support the validity of the TUG test as a measure of functional mobility. This warrants its inclusion in patients' assessment alongside other valid measures of functional mobility in both clinical and research practice in persons with MS.


Liver transplantation for a patient with homocystinuria.
A 24-yr-old man was diagnosed with HCU during neonatal screening and remained on a pyridoxine, vitamin B12, folic acid, and betaine regimen with dietary methionine restriction for more than 10 yr. He had normal mental development, marfanoid appearance, myopia because of lens dislocation, and recurrent ankle subluxation during adolescence. Thereafter, he was a poor adherent to the conventional diet-restrictive therapy, and LT was considered when he developed hypertension and multiple infarctions over the right cerebellum early in the second decade of his life despite taking aspirin as a prophylaxis from 17 yr of age. In November 2009, he received a deceased whole LT from a blood group compatible donor. Along with the success of the transplantation, he was completely disease free without dietary or nutritional control. To the best of our knowledge, this is the first case of LT intended to cure HCU, and with promising results. This case provides an insight into the role of LT for this congenital metabolic disease, for which the decision should be made by judging between the severity of the disease and the risk of the operation, as well as the life quality of the patient.


Group size and structure in western lowland gorillas (Gorilla gorilla gorilla) at Mbeli Bai, Republic of Congo.
This paper describes the size and structure of western lowland gorilla groups visiting Mbeli Bai, a swampy forest clearing in northern Congo. An observation platform at the edge of the clearing was used over a 3-yr period, with gorillas visible for 1,681 hr. Data are presented on 14 groups and seven solitary males. Mean group size (excluding solitary males) was 8.4 +/- SD 4.3, and did not differ significantly from most other gorilla studies. All groups at Mbeli contained only one fully mature male and did not show evidence of fission-fusion or regular subgrouping. All emigrating males that remained in the population became solitary, and "bachelor" groups were not observed. Methodological issues are raised, including the classification of multi-male groups, and the demographic profiles of other populations are discussed in the light of results from Mbeli.