NUCB-2/Nesfatin-1 promotes the proliferation of nasopharyngeal carcinoma cells.
The association of NUCB-2/Nesfatin-1 with nasopharyngeal carcinoma (NPC) remains unclear. We clarified the role of NUCB-2/Nesfatin-1 in the development, progression and diagnosis of NPC. In nasopharyngeal carcinoma cell lines (5-8 F, 6-10B, CNE1, CNE2 and NP69), western blotting, MTT, EdU and other techniques were performed to investigate the role of NUCB-2 in nasopharyngeal carcinoma. 70 tissue samples (39 NPC and 31 rhinitis) and 140 serum samples (including NPC, rhinitis, other head and neck tumors and healthy control) were included to explore the expression of NUCB-2 and its metabolite Nesfatin-1 in tissues or serum of patients with nasopharyngeal carcinoma. NUCB-2 level in NPC tissue was higher than that in rhinitis tissue (P < 0.05). Suppression of NUCB-2 in the NPC cell line CNE2 inhibited proliferation and clone formation of the cells; on the contrary, improvement of NUCB-2 in the NPC cell line CNE1 promoted cell propagation and clone development. An elevated serum level of NUCB-2 in NPC patients was detected, compared to that in patients with other head and neck tumors, rhinitis or healthy donors. Determination of nesfatin-1 combined with EA-IgA, VCA-IgA and Rta-IgG in serum samples for NPC diagnosis reached a sensitivity of 93.6% and a specificity of 94.5%, while the positive and negative predictive value of this diagnostic model was 89.8% and 96.6%, and the accuracy yielded 94.2%. This study revealed that NUCB-2 could enhance proliferation of NPC cells and NUCB-2/nesfatin-1 has the potential to be a serological marker to aid early diagnosis of nasopharyngeal carcinoma.


Ecological risks of polycyclic musk in soils irrigated with reclaimed municipal wastewater.
HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8-hexamethylcyclopenta-c-2-benzopyrane) and AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) are found in reclaimed municipal wastewater. They may accumulate in soils receiving long-term application of reclaimed water thus adversely impact the soil biota. We evaluated the extent of their accumulation in receiving soils using HYDRUS-1D based on reclaimed municipal wastewater irrigation data at a public park in Beijing. The potential for ecological harms were assessed according to tested and reported outcomes of acute toxicity tests using wheat (Triticum aetivum L), earthworm (Eisenia fetida) and springtail (Bourletiella hortensis) as target organisms. Results of comparison among EC50 values from wheat, earthworm and springtail showed the EC50 value for root elongation inhibition of wheat germination was the least. Based on the least EC50, predicted no effect concentration in soils were 290 and 320ng /g for HHCB and ATHN, respectively. Comparable results from simulation to experimental and field investigating date validated the using of HYDRUS-1D in the work. Results of risk prediction showed it would take 243 and 666 years for HHCB and AHTN accumulated in soils at current irrigation practice to reach the levels for the resulting risk characterization ratios (RCRs) to cause potential ecosystem harms.


Cognitive phenotype and psychiatric disorder in 22q11.2 deletion syndrome: A review.
The behavioural phenotype of 22q11.2 deletion syndrome syndrome (22q11DS), one of the most common human multiple anomaly syndromes, frequently includes intellectual disability (ID) together with high risk of diagnosis of psychotic disorders including schizophrenia. Candidate cognitive endophenotypes include problems with retrieval of contextual information from memory and in executive control and focussing of attention. 22q11DS may offer a model of the relationship between ID and risk of psychiatric disorder. This paper reviews research on the relationship between the cognitive phenotype and the development of psychiatric disorders in 22q11DS. Aspects of cognitive function including verbal I.Q., visual memory, and executive function, are associated with mental health outcome in people with 22q11DS. This relationship may result from a common neurobiological basis for the cognitive difficulties and psychiatric disorders. Some of the cognitive difficulties experienced by people with 22q11DS, especially in attention, memory retrieval, and face processing, may, however, in themselves constitute risk factors for development of hallucinations and paranoid delusions. Future research into factors leading to psychiatric disorder in people with 22q11DS should include assessment of social and psychological factors including life events, symptoms associated with trauma, attachment, and self-esteem, which together with cognitive risk factors may mediate mental health outcome.


Expression of toxin co-regulated pilus subunit A (TCPA) of Vibrio cholerae and its immunogenic epitopes fused to cholera toxin B subunit in transgenic tomato (Solanum lycopersicum).
For protection against cholera, it is important to develop efficient vaccine capable of inducing anti-toxin as well as anti-colonizing immunity against Vibrio cholerae infections. Earlier, expression of cholera toxin B subunit (CTB) in tomato was reported by us. In the present investigation, toxin co-regulated pilus subunit A (TCPA), earlier reported to be an antigen capable of providing anti-colonization immunity, has been expressed in tomato. Further, to generate more potent combinatorial antigens, nucleotides encoding P4 or P6 epitope of TCPA were fused to cholera toxin B subunit gene (ctxB) and expressed in tomato. Presence of transgenes in the tomato genome was confirmed by PCR and expression of genes was confirmed at transcript and protein level. TCPA, chimeric CTB-P4 and CTB-P6 proteins were also expressed in E. coli. TCPA protein expressed in E. coli was purified to generate anti-TCPA antibodies in rabbit. Immunoblot and G(M1)-ELISA verified the synthesis and assembly of pentameric chimeric proteins in fruit tissue of transgenic tomato plants. The chimeric protein CTB-P4 and CTB-P6 accumulated up to 0.17 and 0.096% of total soluble protein (TSP), respectively, in tomato fruits. Whereas expression of TCPA, CTB-P4 and CTB-P6 in E. coli can be utilized for development of conventional vaccine, expression of these antigens which can provide both anti-toxin as well as anti-colonization immunity, has been demonstrated in plants, in a form which is potentially capable of inducing immune response against cholera infection.


The science behind codes and standards for safe walkways: changes in level, stairways, stair handrails and slip resistance.
Walkway codes and standards are often created through consensus by committees based on a number of factors, including historical precedence, common practice, cost, and empirical data. The authors maintain that in the formulation of codes and standards that impact pedestrian safety, the results of pertinent scientific research should be given significant weight. This article examines many elements of common walkway codes and standards related to changes in level, stairways, stair handrails, and slip resistance. It identifies which portions are based on or supported by empirical data; and which could benefit from additional scientific research. This article identifies areas in which additional research, codes, and standards may be beneficial to enhance pedestrian safety.


Surgical treatment of pancreatic endocrine tumours in Italy: results of a prospective multicentre study of 262 cases.
Information on the treatment of pancreatic endocrine tumours (PETs) comes mostly from small, retrospective, uncontrolled studies. Newly diagnosed, histologically proven PETs, observed from June 2004 to March 2007 in 24 Italian centres, were included in a specific dataset. Three-hundred and ten patients (mean age 57.6 years, females 46.6%) were analysed. At the time of recruitment, 262 (84.5%) underwent surgery. The percentage of operated patients was 91.9% and 62.0% in surgical and non-surgical centres, respectively. A curative resection was carried out in 83.6% (n = 219) of cases, a palliative resection (debulking) in 10.7% (n = 28), an exploratory laparotomy in 4.6% (n = 12), and a bypass procedure in 1.1% (n = 3). Laparoscopy was performed in 8.0% (n = 21) of cases. Resection consisted of a pancreatoduodenectomy in 46 cases (21.0%), a distal pancreatectomy in 95 (43.4%), an enucleation in 50 (22.8%), a middle pancreatectomy in 16 (7.3%) and a total pancreatectomy in 12 (5.5%). Liver resection was associated with pancreatic resection in 26 cases (9.9%). Post-operative mortality was 1.5% and morbidity 39.7%, respectively. A curative resection was performed more frequently in asymptomatic, small, non-metastatic, benign and at uncertain behaviour tumours, with low Ki67 values. This study strongly indicates the fact that surgical resection represents the cornerstone treatment of PETs.


Understanding HIV compartments and reservoirs.
The spectrum of HIV-1 cellular reservoirs is highly diversified, and their role varies according to the milieu of the anatomical sites in which the virus replicates. In this light, mechanisms underlying HIV-1 persistence in anatomical compartments may be profoundly different from what is observed in peripheral blood. This scenario is further complicated by sub-optimal drug penetration in tissues allowing persistent and cryptic HIV-1 replication in body districts despite undetectable viremia. On this basis, this review aims at providing recent insights regarding the critical role of HIV-1 cellular reservoirs in different anatomical compartments, and their relationship with the pathogenesis of HIV-1 infection. A comprehensive definition of the complex interplay between the virus and its reservoir is critical in order to set up prophylactic and therapeutic strategies aimed at achieving the maximal virological suppression and hopefully in the near future the cure of HIV-1 infection (either functional or biological).


Ca2+/calmodulin-dependent phosphorylation of elongation factor 2.
Incubation of a ribosome-free extract of rabbit reticulocytes or rat liver with [gamma-32P]ATP and Ca2+ results in incorporation of 32P predominantly into a single polypeptide of Mr approximately 100,000. This polypeptide is identified as elongation factor 2 (EF-2). Phosphorylation of EF-2 is strictly Ca2+-dependent and can be inhibited by the calmodulin antagonist trifluoperazine. It is suggested that the Ca2+/calmodulin-dependent phosphorylation of EF-2 is involved in regulation of protein biosynthesis.


Consistent inter-individual differences in common marmosets (Callithrix jacchus) in Boldness-Shyness, Stress-Activity, and Exploration-Avoidance.
The study of animal personality, defined as consistent inter-individual differences in correlated behavioral traits stable throughout time and/or contexts, has recently become one of the fastest growing areas in animal biology, with study species ranging from insects to non-human primates. The latter have, however, only occasionally been tested with standardized experiments. Instead their personality has usually been assessed using questionnaires. Therefore, this study aimed to test 21 common marmosets (Callithrix jacchus) living in three family groups, in five different experiments, and their corresponding controls. We found that behavioral differences between our animals were not only consistent over time, but also across different contexts. Moreover, the consistent behaviors formed a construct of four major non-social personality components: Boldness-Shyness in Foraging, Boldness-Shyness in Predation, Stress-Activity, and Exploration-Avoidance. We found no sex or age differences in these components, but our results did reveal differences in Exploration-Avoidance between the three family groups. As social environment can have a large influence on behavior of individuals, our results may suggest group-level similarity in personality (i.e., "group personality") in common marmosets, a species living in highly cohesive social groups. Am. J. Primatol. 78:961-973, 2016. © 2016 Wiley Periodicals, Inc.


Effects of an invertebrate grazer on the spatial arrangement of a benthic microhabitat.
We demonstrated the effect of an aquatic herbivore on the spatial arrangement of benthic algal biomass within artificial stream channels. Transects of ceramic tiles were exposed to a gradient of snail (Physella) densities in a 30 d experiment. We observed positive effects of snails on the mean abundance of "overstory" algae (the filamentous chlorophyte Cladophora and associated epiphytes), an important benthic microhabitat in streams. Snails altered several aspects of the spatial arrangement of overstory algae. Snails reduced the strength of downstream gradients in overstory biomass, as well as residual variability around these gradients. Geostatistical analysis revealed that snails also reduced the strength of spatial dependence, and so reduced spatial heterogeneity of the overstory, at small scales (<40 cm). As a result, organisms inhabiting the overstory might experience a more fragmented habitat landscape at high snail densities. In addition, snails increased the scale of spatial dependence in understory algal biomass (algae remaining on tiles after overstory was removed) from 10 cm to 40 cm. Consumer effects on the spatial arrangement of a microhabitat argue for the inclusion of feedbacks between the biota and the environment in spatially-explicit models.


Pinacolyl methylphosphonochloridate: in vitro covalent binding to DNA and mutagenicity in the Ames test.
In the present study, in vitro binding of 14C-labeled pinacolyl methylphosphonochloridate (PiCl) to calf-thymus DNA has been investigated. The data reveal that, at PiCl concentrations of 0.038-0.26 mM, the binding is rapid and saturable at the extent of modification of 1 PiCl molecule per 2000 nucleotides. A similar range of PiCl concentrations was toxic, but did not produce a significant increase in mutagenicity in Salmonella typhimurium TA100 and TA98. Our results are of relevance with regard to the in vitro assessment of Soman-like organophosphates and the mutagenic risk of these agents and related pesticides.


The release of tumor necrosis factor-alpha, interleukin-1, interleukin-6 and prostaglandin E2 in bovine Kupffer cells stimulated with bacterial lipopolysaccharide.
Kupffer cells, in response to gut-derived bacteria, viruses and endogenous endotoxins, are thought to be a major source of proinflammatory cytokines and other mediators. In the present study, we investigated the mode of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) production by bovine Kupffer cells in response to LPS in vitro. By semi-quantitative reverse transcription-polymerase chain reaction, both TNF-alpha and IL-1beta mRNAs were expressed between 3 and 12 h after stimulation with 1 microg/ml of LPS. The IL-1alpha transcript also increased at 3 h, and then disappeared at 6 h. Although IL-6 mRNA was slightly expressed without stimulation, it increased and reached a peak after 6 h, and then decreased to normal levels by 24 h. The secretion of TNF-alpha and IL-1 was detected after 3 h and increased until 12 and 24 h, respectively, as detected by bioassay. IL-6 was secreted at a low level without stimulation, peaked 6 h after stimulation and remained elevated until 24 h. The secretion of prostaglandin E2 continued to increase for 24 h. These results suggest that several inflammatory cytokines released from bovine Kupffer cells are regulated in different modes.


Mitochondrial DNA variation and substructure among the tribal populations of Andhra Pradesh, India.
We analyzed mtDNA HVR-I variation among six tribal populations-Andh, Pardan, Gond, Naikpod, Kolam and Chenchu--from Andhra Pradesh. These tribes belong to the Dravidian and Indo-European linguistic group. Except for Chenchu, the rest of the tribal samples were collected from two or more than two locations. The analysis of molecular variance (AMOVA) of the sequences yields a significant F(ST) value (0.045), suggesting a fair degree of genetic differentiation among these tribes. When the tribal samples collected from different locations were considered as subpopulations in AMOVA, it is found that the variation among the subunits within the tribal groups is smaller than among the tribes. However, when Chenchu is removed from the analysis, the magnitude of within and between groups diversity becomes similar. In the multidimensional scaling plot based on F(ST) distances the Chenchu is found to be the extreme outlier. Exclusion of Chenchu from AMOVA analysis and multidimensional scaling plot does not result in any specific pattern of population clustering. Mismatch distribution suggest that Chenchu might have undergone a bottleneck effect and does not show evidence of past demographic expansion as shown by the other five tribal groups. A comparison of AP tribes with some other caste and tribal populations of India suggests common maternal genetic heritage.


In vivo measurement of glycine with short echo-time 1H MRS in human brain at 7 T.
To determine whether glycine can be measured at 7 T in human brain with (1)H magnetic resonance spectroscopy (MRS). The glycine singlet is overlapped by the larger signal of myo-inositol. Density matrix simulations were performed to determine the TE at which the myo-inositol signal was reduced the most, following a single spin-echo excitation. (1)H MRS was performed on an actively shielded 7 T scanner, in five healthy volunteers. At the TE of 30 ms, the myo-inositol signal intensity was substantially reduced. Quantification using LCModel yielded a glycine-to-creatine ratio of 0.14 +/- 0.01, with a Cramér-Rao lower bound (CRLB) of 7 +/- 1%. Furthermore, quantification of metabolites other than glycine was possible as well, with a CRLB mostly below 10%. It is possible to detect glycine at 7 T in human brain, at the short TE of 30 ms with a single spin-echo excitation scheme.


Abdominal aortic aneurysm healed with calcification in a female patient with Behçet's syndrome: A case report with a 2-decade follow-up.
Abdominal aortic aneurysms (AAA) are rare in Behçet syndrome (BS) but may result in life-threatening complications. AAA are generally treated with surgical intervention following aggressive immunosuppressive therapy. Healing with wall calcification and mural thrombus for AAA is scarcely reported in the literature. Herein, we present a female patient who developed a large saccular aneurysm in the infra-renal abdominal aorta 6 months after the diagnosis. Endovascular intervention was not found to be possible because of the dimensions of the aneurysm and the patient did not consent for open surgery. Therefore, she received only immunosuppressive treatment. By the second year of follow-up, we detected reduction in the size of AAA, along with circumferential wall calcification and mural thrombus. The patient was followed-up for 20 years without rupture and currently doing well. This case demonstrates that calcified large saccular AAA might not necessitate surgical intervention and be followed-up for many years without any complication.


Microvascular decompression by interposition method for treatment of trigeminal neuralgia due to vertebrobasilar dolichoectasia: a retrospective single-center study.
Trigeminal neuralgia (TN) due to vertebrobasilar dolichoectasia (VBD) is a rare disease that can be challenging to treat. The objectives of this study are to investigate the characteristics of patients with TN due to VBD and to analyze the efficacy of microvascular decompression (MVD) by the interposition method for treatment of the condition. From 2010 until 2020, the data of 30 patients with TN due to VBD who were treated with MVD by the interposition method were analyzed retrospectively. The characteristics of the patients were compared with those of patients with non-VBD TN (n = 815). Kaplan-Meier survival analysis was performed to determine pain-free survival. The 30 patients (21 males, 9 females; mean age, 63.03 years) accounted for 3.55% of all patients with TN during the study period. In 30 patients, the offending vessel was the basilar artery (BA) in 1 patient, the vertebral artery (VA) in 6 patients, the VA plus the superior cerebellar artery (SCA) in 6 patients, the VA plus the anterior inferior cerebellar artery (AICA) in 12 patients, and the VA + SCA + AICA in 5 patients. Compared to non-VBD TN patients, those with TN due to VBD were significantly more likely to be male, to have TN of the left side, and to have hypertension (all P < 0.001). Mean age at surgery (P = 0.057) and symptom duration (P = 0.308) were comparable between the two groups. All 30 patients had immediate relief of facial pain after MVD and could stop medication. There were no postoperative complications. Over mean follow-up of 76.67 months, 3 patients had recurrence. The mean duration of pain-free survival was 70.77 months. In conclusions, TN due to VBD appears to be more likely in males, in those with hypertension, and to involve the left side. The interposition method performed by experienced and skilled neurosurgeons is a safe and effective treatment for TN due to VBD. Further studies are needed to analyze the associated long-term results and the pain recurrence rate among this special population.


Enzymatic systems of inorganic pyrophosphate bioenergetics in photosynthetic and heterotrophic protists: remnants or metabolic cornerstones?
An increasing body of biochemical and genetic evidence suggests that inorganic pyrophosphate (PPi) plays an important role in protist bioenergetics. In these organisms, two types of inorganic pyrophosphatases [EC 18.104.22.168, namely soluble PPases (sPPases) and proton-translocating PPases (H+-PPases)] that hydrolyse the PPi generated by cell anabolism, thereby replenishing the orthophosphate pool needed for phosphorylation reactions, are present in different cellular compartments. Photosynthetic and heterotrophic protists possess sPPases located in cellular organelles (plastids and mitochondria), where many anabolic and biosynthetic reactions take place, in addition to H+-PPases, which are integral membrane proteins of the vacuolysosomal membranes and use the chemical energy of PPi to generate an electrochemical proton gradient useful in cell bioenergetics. This last category of proton pumps was considered to be restricted to higher plants and some primitive photosynthetic bacteria, but it has been found recently in many protists (microalgae and protozoa) and bacteria, thus indicating that H+-PPases are much more widespread than previously thought. No cytosolic sPPase (in bacteria, fungi and animal cells) has been shown to occur in these lower eukaryotes. The widespread occurrence of these key enzymes of PPi metabolism among evolutionarily divergent protists strongly supports the ancestral character of the bioenergetics based on this simple energy-rich compound, which may play an important role in survival under different biotic and abiotic stress conditions.


SmartSurfACE transepithelial photorefractive keratectomy with mitomycin C enhancement after small incision lenticule extraction.
To evaluate predictability, stability, efficacy, and safety of transepithelial photorefractive keratectomy (TPRK) using smart pulse technology (SPT) (SmartSurface procedure) of Schwind Amaris with mitomycin C for correction of post small incision lenticule extraction (SMILE) myopic residual refractive errors. This study is a prospective, non-comparative case series conducted at a private eye centre in Ismailia, Egypt, on eyes with post-SMILE myopic residual refractive errors because of undercorrection or suction loss (suction loss occurred after the posterior lenticular cut and the creation of side-cuts; redocking was attempted, and the treatment was completed in the same session with the same parameters) with myopia or myopic astigmatism. The patients were followed up post-SMILE for six months before the SmartSurface procedure, and then they were followed up for one year after that. TPRK were performed using Amaris excimer laser at 500 kHz. The main outcomes included refractive predictability, stability, efficacy, safety and any reported complications. This study included 68 eyes of 40 patients out of 1920 total eyes (3.5%) with post-SMILE technique myopic residual refractive errors. The average duration between the SMILE surgery and TPRK was 6.7 ± 0.4 months (range 6 to 8 months). The mean refractive spherical equivalent (SE) was within ± 0.50 D of plano correction in 100% of the eyes at 12 months post-TPRK. Astigmatism of < 0.50 D was achieved in 100% of the eyes. The mean of the residual SE error showed statistically significant improvement from preoperative - 1.42 ± 0.52 D to 0.23 ± 0.10 D (P < 0.0001). Uncorrected distance visual acuity (UDVA) (measured by Snellen's chart and averaged in logMAR units) was improved significantly to 0.1 ± 0.07 (P < 0.0001). UDVA was 0.2 logMAR or better in 100% of the eyes, 0.1 logMAR or better in 91.2% of the eyes, and 0.0 logMAR in 20.6% of the eyes. Corrected distance visual acuity (CDVA) remained unchanged in 79.4% of eyes. 14.7% of eyes gained one line of CDVA (Snellen). 5.9% of eyes gained two lines of CDVA (Snellen). Transepithelial photorefractive keratectomy using smart pulse technology with mitomycin C enhancement after SMILE is a safe, predictable, stable, and effective technique.


The long-term interaction of diet and dopamine D2 gene expression on brain microglial activation.
Dopamine D2 receptors are expressed on microglial in the central nervous system and promote anti-inflammatory responses. Little work has been done on the interaction between the dopamine D2 receptors and diet on activated microglial expression in the brain. To assess this, the current study uses in vitro autoradiography to look at microglial activation in the brain as a marker for neuroinflammation. Mice with different levels of expression of the DA D2 gene were given a chronic diet of either normal diet chow or high fat diet chow for 30 weeks. Mice were then euthanized and their brains were processed for [3H]PK11195 autoradiography. Mice with reductions or lack of the D2 gene showed higher [3H]PK11195 binding in a diet-specific manner within somatosensory and striatal regions, as well as the piriform, frontal, insular, and entorhinal regions compared to mice with normal D2 gene levels. These brain regions are important for sensory processing, habit formation, as well as cognitive function tasks related to learning, motivation, and memory. These results suggest that decreased D2R levels may increase vulnerability to specific inflammatory markers. Future studies will need to examine the implications of these inflammatory changes on brain function and behavior.


Contrast-Enhanced Ultrasound and High Sensitive Doppler for Monitoring Outcomes of Uterine Artery Embolization.
To monitor fibroid microvascularity using contrast-enhanced ultrasound (CEUS) and a new high-sensitive Doppler mode (SMI) for assessment of uterine artery embolization (UAE) outcomes. Forty women with symptomatic uterine fibroids scheduled for UAE were enrolled in this Institutional Review Board-approved study. Subjects underwent three examinations (day 0, 15, and 90 post-UAE) with Color Doppler (CDI), power Doppler (PDI), color and monochrome SMI (cSMI and mSMI), and CEUS imaging of the fibroids. Clips were assessed by two radiologists classifying fibroids based on their vascularity. Fibroid fractional vascularity (FV; % of enhanced pixels within the fibroid) and flow intensity (as mean brightness level of the enhanced pixels) were quantified. Results were analyzed using repeated measures ANOVA and nonparametric Wilcoxon sign rank tests. Inter-reader agreement was assessed with κ-values. There was overall agreement between readers for all imaging modalities and examination times (P = .25; κ = 0.70). The FV analysis showed statistically significant differences between CEUS and the Doppler imaging modes (CDI, PDI, cSMI, and mSMI) for the three examination times were compared (P < .0001). The comparison using CDI, PDI, and cSMI showed no statistically significant difference (P = .53). The flow intensity analysis comparison between the Doppler imaging modes (CDI, PDI, cSMI and mSMI) and examination times showed statistically significant differences between all the Doppler imaging modalities (P = .02), except for the 90days post-UAE (P = .34). When the comparison was made for CDI, PDI, and cSMI there was no statistically significant differences (P < .47). CEUS and SMI can accurately evaluate fibroid microvascularity, and therefore, can be a noninvasive and accurate method for monitoring outcomes following UAE treatment.


New adaptive method for phase I trials in oncology.
Assessment of the maximum tolerated dose for a small sample of patients is the objective of phase I trials in oncology. We propose a new adaptive approach performing differentiation of each type of toxicity and their grades, definition of the dose-limiting toxicity as a logical combination of toxicity events, modeling of the risk of toxic events as a function of the drug dose, and integration of individual covariates. An application study with retrospective data from a phase I Taxol pediatric trial revealed age as an influential covariate, allowing individualization of a patient's maximum tolerated dose. A simulation study illustrates the practice of sequential inclusion of patients, of constraints in the dose-finding process and of trial stopping rules. The approach presented here allows quick maximum tolerated dose assessment with a small sample of patients and assists the design of phase I trials in oncology.


Monitoring During Vascular Surgery.
Vascular surgical patients present unique challenges for anesthesiologists, because of their medical vulnerabilities as well as their tendency for rapid intraoperative hemodynamic changes. Intraoperative monitors have been used for decades to reduce adverse outcomes, improve mortality, and create optimal surgical conditions. Understanding the indications and appropriate management of monitoring modalities is essential for optimizing patient care, and preventing harm associated with misinterpretation. We aim to review monitoring technologies used in complex vascular procedures, as well as the current guidelines, clinical trial outcomes, and basic mechanisms of each monitoring modality.


Myosin light chain 2a and 2v identifies the embryonic outflow tract myocardium in the developing rodent heart.
The embryonic heart consists of five segments comprising the fast-conducting atrial and ventricular segments flanked by slow-conducting segments, i.e. inflow tract, atrioventricular canal and outflow tract. Although the incorporation of the flanking segments into the definitive atrial and ventricular chambers with development is generally accepted now, the contribution of the outflow tract myocardium to the definitive ventricles remained controversial mainly due to the lack of appropriate markers. For that reason we performed a detailed study of the pattern of expression of myosin light chain (MLC) 2a and 2v by in situ hybridization and immunohistochemistry during rat and mouse heart development. Expression of MLC2a mRNA displays a postero-anterior gradient in the tubular heart. In the embryonic heart it is down-regulated in the ventricular compartment and remains high in the outflow tract, atrioventricular canal, atria and inflow tract myocardium. MLC2v is strongly expressed in the ventricular myocardium and distinctly lower in the outflow tract and atrioventricular canal. The co-expression of MLC2a and MLC2v in the outflow tract and atrioventricular canal, together with the single expression in the atrial (MLC2a) and ventricular (MLC2v) myocardium, permits the delineation of their boundaries. With development, myocardial cells are observed in the lower endocardial ridges that share MLC2a and MLC2v expression with the myocardial cells of the outflow tract. In neonates, MLC2a continues to be expressed around both right and left semilunar valves, the outlet septum and the non-trabeculated right ventricular outlet. These findings demonstrate the contribution of the outflow tract to the definitive ventricles and demonstrate that the outlet septum is derived from outflow tract myocardium.


Influence of Ag Photodeposition Conditions over SERS Intensity of Ag/ZnO Microspheres for Nanomolar Detection of Methylene Blue.
Surface enhanced Raman spectroscopy (SERS) is considered a versatile and multifunctional technique with the ability to detect molecules of different species at very low molar concentration. In this work, hierarchical ZnO microspheres (ZnO MSs) and Ag/ZnO MSs were fabricated and decorated by hydrothermal and photodeposition methods, respectively. For Ag deposition, precursor molar concentration (1.9 and 9.8 mM) and UV irradiation time (5, 15, and 30 min) were evaluated by SEM, TEM, X-ray diffraction and Raman spectroscopy. X-ray diffraction showed a peak at 37.9° corresponding to the (111) plane of Ag, whose intensity increases as precursor concentration and UV irradiation time increases. SEM images confirmed the formation of ZnO MSs (from 2.5 to 4.5 µm) building by radially aligned two-dimensional ZnO nanosheets with thicknesses below 30 nm. The Raman spectra of Ag/ZnO MSs exhibited a vibration mode at 486 cm-1 which can be directly associated to Ag deposition on ZnO MSs surface. The performance of SERS substrate was evaluated using rhodamine 6G. The SERS substrate grown at 9.8 mM during 30 min showed the best SERS activity and the ability to detect methylene blue at 10-9 M.


Detection of paradoxical carbon dioxide gas embolism with opening of patent foramen ovale by perioperative transesophageal echocardiography during laparoscopic hepatectomy - A case report.
Due to its various advantages, laparoscopic surgery is preferred over laparotomy in patients who require hepatic resection. Carbon dioxide embolism -which occurs approximately ten times more often in laparoscopic hepatectomy than in general laparoscopic surgery-presents with insignificant symptoms and may be overlooked. A 70-year-old male with hepatic cell carcinoma underwent laparoscopic hepatectomy. Though his vital signs were stable during the initiation of surgery, they became unstable during the procedure. The surgeon detected portal vein rupture, and transesophageal echocardiography was subsequently performed. A large amount of gas in the heart chamber and paradoxical embolism through a patent foramen ovale due to a right-to-left shunt were observed. We treated the symptoms, and the surgery was completed without any further issues. Active use of transesophageal echocardiography to identify and monitor heart functions during a suspected carbon dioxide embolism can significantly reduce morbidity and mortality associated with that embolism.


Differences between induction effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene and phenobarbitone.
The inductive effects of phenobarbitone (PB) and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) were compared in C57BL/6J mice. Induction parameters included six substrates: ethylmorphine (EM), benzphetamine (Bph), biphenyl, ethoxycoumarin (EtoC), pentoxyresorufin and dichloro-p-nitroanisole (DPNA). In order to validate this descriptive approach the comparison was extended to diazepam, rifampicin, warfarin, and pregnenolone-16 alpha-carbonitrile (PCN). All inducers were clearly distinguishable from each other. Warfarin was similar to PB, rifampicin was similar to PCN. TCPOBOP differed significantly from PB in relative liver weight, cytochrome P-450 content of liver microsomes, EM-, Bph- and DPNA-demethylations, biphenyl-hydroxylations, EtoC de-ethylation and absorption maximum of reduced CO-cytochrome P-450. TCPOBOP, as an inducer, was less "specific" than PB: total metabolic rates were excessively increased due to microsomal protein (1.5 times) and cytochrome P-450 (4 times) augmentation, whereas cytochrome P-450-related metabolic rates were less increased than those after PB. Thus TCPOBOP does not seem to be as similar to PB as was suggested in the first description of its inducing potency.


Incidence of rhegmatogenous retinal detachment in myopic phakic eyes.
Rhegmatogenous retinal detachment (RRD) is a potentially blinding disease, more common in the myopic population. This systematic review aimed to collect the existing literature on the incidence of RRD in myopic phakic eyes. MEDLINE, Embase, and the Cochrane Library were searched to identify eligible studies published until February 2020. In total 2715 publications were identified, of which only 3 were considered eligible and 2 as eligible with major limitations. Because of substantial differences between the included studies, a pooled analysis was not conducted. Summarizing the results and considering several limitations, an annual RRD incidence per 100 000 of 15 to 34 for mild myopia, 15 to 73 for moderate myopia, 102 to 128 for high myopia, and 287 in very highly myopic eyes was shown. Large well-designed studies are needed, including precise information on the refractive status or axial eye length, lens status, traumatic injuries, and intraocular surgeries during follow-up.


Regulation of milk protein synthesis by progesterone in cultured mouse mammary gland.
The effect of progesterone on the synthesis of milk proteins, casein and alpha-lactalbumin was investigated by culturing mammary explants from mid-pregnant mice in serum-free medium. The addition of progesterone at concentrations above 10 ng/ml inhibited both the casein and alpha-lactalbumin accumulation that were induced by the synergistic actions of insulin, prolactin and cortisol. The maximal inhibition was attained at a progesterone concentration of 100 ng/ml. The maximal level of inhibition of the alpha-lactalbumin accumulation was about 90% in the presence of insulin and prolactin or insulin, prolactin and 0.01 microgram/ml of cortisol. The inhibition of the casein accumulation by progesterone was about 80% in the presence of insulin and prolactin, and about 40% in the presence of insulin, prolactin and 1 microgram/ml of cortisol, indicating that cortisol partially antagonized the action of progesterone on the casein synthesis. When the inhibitory effect of progesterone on the accumulation of both alpha-lactalbumin and casein was examined in cultured mammary tissues from virgin, early pregnant, mid-pregnant and late pregnant mice, the degree of inhibition was markedly reduced in tissue from late pregnant mice. This indicates that the susceptibility of mammary gland to the inhibitory action of progesterone varies with the developmental stage of the tissue.


Advantages of the population-based approach to pregnancy dating: results from 23,020 ultrasound examinations.
To confirm the results from two previous evaluations of term prediction models, including two sample-based models and one population-based model, in a third population. In a study population of 23,020 second-trimester ultrasound examinations, data were prospectively collected and registered over the period 1988-2009. Three different models for ultrasonically estimated date of delivery were applied to the measurements of fetal biparietal diameter (BPD) and two models were applied to the femur length (FL) measurements; the resulting term estimations were compared with the actual time of delivery. The difference between the actual and the predicted dates of delivery (the median bias) was calculated for each of the models, for three BPD/FL-measurement subgroups and for the study population as a whole. For the population-based model, the median bias was + 0.4 days for the BPD-based predictions and - 0.4 days for the FL-based predictions, and the biases were stable over the inclusion ranges. The biases of the two traditional models varied with the size of the fetus at examination; median biases were - 0.87 and + 2.2 days, respectively, with extremes - 4.2 and + 4.8 days for the BPD-based predictions, and the median bias was + 1.72 days with range - 0.8 to + 4.5 days for FL-based predictions. The disagreement between the two sample-based models was never less than 2 days for the BPD-based predictions. This study confirms the results from previous studies; median biases were negligible with term predictions from the population-based model, while those from the traditional models varied substantially. The biases, which have clinical implications, seem inevitable with the sample-based models, which, even if overall biases were removed, will perform unsatisfactorily.


Detection of mutagenic activity in textiles with Salmonella typhimurium.
A hundred and ninety-six textile samples were tested in a modified version of the Salmonella/microsome assay for release of mutagenic contaminants. As heat sterilization of the samples can result in reduction of mutagenic activity, tests were performed with streptomycin resistant derivatives of Salmonella tester strains TA98 and TA100. Textile samples were preincubated in buffered saline (PBS), DMSO or ethanol. Subsequently, the fabrics were placed on streptomycin supplemented selective agar plates. In total, 18 samples (9.2%) exerted mutagenic activity. DMSO was the most effective solvent (15 positives) followed by ethanol (9 positive samples) and PBS (7 positives). Most fabrics (16) caused mutagenic effects only upon metabolic activation with liver S9 mix. Chemical analysis indicates that the positive results obtained with PBS are not due to release of histidine or formaldehyde. Three directly active samples gave negative results in strain TA98NR which is devoid of classical nitroreductase. With one exception all other textiles were negative in strain TA98/1,8-DNP6 (which lacks O-acetyltransferase). These findings indicate that nitroaromatics and amines might be responsible for the mutagenic effects of the textiles.


Solvent extraction of organic molecules of exobiological interest for in situ analysis of the Martian soil.
A solid-liquid extraction method able to perform in situ extraction of organic compounds on Mars is proposed. The extraction efficiency of various organic solvents was tested and compared to that of water. The selected key compounds are molecules of exobiological interest: glycine, alanine, serine, glutamic acid, oxalic acid, benzoic acid, phthalic acid, isophthalic acid, terephthalic acid and 1,3,5-benzenetricarboxylic acid. Among the organic solvents, propanol gives the highest yield of extraction for all the targeted compounds except for benzoic acid. A mixture of propanol and ethyl acetate increases significantly the extraction yield of benzoic acid. The extraction time was considerably reduced (140 h to 15 min) by using sonication. The method is discussed for an easy automation with coupling to an in situ GC-MS space instrument.


Pheophorbide A isolated from Gelidium amansii inhibits adipogenesis by regulating adipogenic transcription factors and AMPK in 3T3-L1 adipocytes.
Adipocyte lipid accumulation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. As part of our efforts to isolate antiobesity agents from natural products, we first isolated the active compound from the extract of Gelidium amansii through bioassay-guided fractionation. We then hypothesized that pheophorbide A isolated from G amansii inhibits adipogenesis by downregulating adipogenic transcription factors; therefore, the antiadipogenic effects of pheophorbide A were investigated in 3T3-L1 adipocytes. On differentiation of 3T3-L1 preadipocytes into adipocytes, they were treated with pheophorbide A (0-83 µM). Pheophorbide A inhibited triglyceride accumulation (half maximal inhibitory concentration = 114.2 µM) and stimulated glycerol release in a dose-dependent manner in 3T3-L1 adipocytes. In addition, pheophorbide A significantly decreased leptin concentrations in 3T3-L1 adipocytes. Pheophorbide A inhibited adipogenesis by suppressing the expression of adipogenic transcriptional factors including peroxisome proliferator-activated receptor γ, CCATT/enhancer binding protein α, sterol regulatory element binding protein 1c, and fatty acid synthase. It also induced the expression of phosphorylation of AMP-activated protein kinase. Therefore, these results suggest that pheophorbide A may be useful for preventing or treating obesity because of its inhibitory effect on adipogenesis.


TROP2 Down-regulated DSG2 to Promote Gastric Cancer Cell Invasion and Migration by EGFR/AKT and DSG2/PG/β-Catenin Pathways.
Gastric cancer (GC) is the fourth most commonly found cancer and the second- highest cause of cancer-related death worldwide. TROP2 overexpression is closely related to many cancers, including gastrointestinal tumors. DSG2 is an important protein in cell adhesion, and its loss affects cell migration. This study aimed to explore the specific mechanism of TROP2 in promoting gastric cancer and provide a basis for the prevention and treatment of gastric cancer. DSG2 was identified as an interacting protein of TROP2 in GC cells by coimmunoprecipitation and mass spectrometry. The regulated behavior of TROP2 on DSG2 expression was investigated with TROP2 over-expressure or knockdown. Cell-cell adhesion capacity mediated by DSG2 was evaluated by adhesion-related assays. Electron microscope observation was made for accessing GC tumor desmosome assembly. Proteins in EGFR/AKT and DSG2/PG/β-catenin pathways were evaluated by western blotting. This study suggests that abundant expression of TROP2 in GC cells lessened DSG2 levels as well as desmosome adhesion, increased cell invasion and migration, and promoted malignant progression through EGFR/AKT and DSG2/PG/β-catenin pathways. TROP2 promotes cell invasion and migration in gastric cancer by decreasing DSG2 expression through EGFR/AKT and DSG2/PG/β-catenin pathways.


Hyperuricemia is independently associated with left ventricular hypertrophy in post-menopausal women but not in pre-menopausal women in rural Northeast China.
The aim of this article is to estimate the relationship between hyperuricemia and left ventricular hypertrophy (LVH) and to investigate whether menopause was associated with the relationship between hyperuricemia and LVH. This survey was conducted from July 2012 to August 2013. A total of 6029 women (3508, 58.2% were post-menopause) from the rural Northeast China were randomly selected and examined. LVH was defined using the 2007 Guidelines for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Age, body mass index, glucose, estimated glomerular filtration rate and lipid level were significantly correlated with serum uric acid level. LVH showed a gradual increase in accordance with the serum uric acid level in entire study population (<4.0 mg/dL, 11.4%; 4 to <5 mg/dL, 14.9%; 5 to <6 mg/dL, 18.9%; ≥6 mg/dL, 27.4%; p < 0.001). Multivariate analysis revealed that hyperuricemia was a significantly independent risk factor for LVH in post-menopausal women [OR (95% CI): 1.367 (1.026, 1.821)], but not in pre-menopausal women [OR (95% CI): 1.290 (0.669, 2.486)]. These findings suggested that hyperuricemia can be used as a risk marker of LVH in a female population and, in particular, as an independent risk factor in post-menopausal women but not in pre-menopausal women.


Non-communicable diseases in low- and middle-income countries: context, determinants and health policy.
The rise of non-communicable diseases and their impact in low- and middle-income countries has gained increased attention in recent years. However, the explanation for this rise is mostly an extrapolation from the history of high-income countries whose experience differed from the development processes affecting today's low- and middle-income countries. This review appraises these differences in context to gain a better understanding of the epidemic of non-communicable diseases in low- and middle-income countries. Theories of developmental and degenerative determinants of non-communicable diseases are discussed to provide strong evidence for a causally informed approach to prevention. Health policies for non-communicable diseases are considered in terms of interventions to reduce population risk and individual susceptibility and the research needs for low- and middle-income countries are discussed. Finally, the need for health system reform to strengthen primary care is highlighted as a major policy to reduce the toll of this rising epidemic.


A study of the analytical behaviour of selected synthetic and naturally occurring quinolines using electrospray ionisation ion trap mass spectrometry, liquid chromatography and gas chromatography and the construction of an appropriate database for quinoline characterisation.
Mass spectral fragmentation of quinoline alkaloids of significance in plants has been investigated using electrospray ionisation ion trap mass spectrometry (ESI-MS(n)) with a view to characterisation of molecules of unknown structure isolated from these natural sources. This investigation has led to the generation of an appropriate database incorporating data from ESI-MS(n) and also from gas liquid chromatography (GLC) and liquid chromatography (HPLC) for these low molecular mass quinolines. This has been put to practical application in the identification of quinoline alkaloids in a plant extract. Thus, an acid extraction of the leaves of Choisya ternata containing such tertiary alkaloids was analysed by liquid chromatography-electrospray ionisation mass spectrometry (HPLC-ESI-MS) and the resulting behaviour of the quinolines was compared with that of the quinoline alkaloids in the database.


Initial experience with hypothermic machine perfusion of kidneys from deceased donors in the Uppsala region in Sweden.
Simple cold storage (CS) is the gold standard for organ preservation. Recently, evidence has been presented suggesting compared with CS hypothermic machine perfusion (HMP) improves the quality and outcome of kidneys for transplantation. Uppsala has used the LifePort Kidney Transporter to preserve deceased donor kidneys. We evaluated our first single-center 52 cases retrospectively. Deceased donor kidneys preserved with HMP between July 2010 and July 2012 (n = 52) were compared with a matched historical cohort of organs preserved by CS between January 2009 and July 2012 (n = 87). We evaluated delayed graft function (DGF), creatinine level at hospital discharge, length of hospital stay, incidence of acute rejection episodes during the first year after transplantation, and graft survival. Both groups included approximately 69% expanded criteria donors (ECD). Median cold ischemia time (CIT) was 12.8 hours in the HMP group and 11.7 hours in the CS group. The incidence of DGF was 11.5% with HMP and 20.7% with CS. Compared with CS, HMP significantly reduced the occurrence of DGF from 21.4% to 0% using standard criteria kidneys (P = .046), whereas the use of HMP did not impact the occurrence of DGF with ECD kidneys. The creatinine level at hospital discharge was lower after HMP than after CS (P = .047). No difference in graft survival was observed between the groups. Machine perfusion resulted in a lower occurrence of DGF using kidneys from standard criteria donors with a lower creatinine at hospital discharge among the cohort with reasonably low CIT. Using machine perfusion seems to be safe; no adverse surgical events occurred during the study period.


MEG response to median nerve stimulation correlates with recovery of sensory and motor function after stroke.
Hemiparesis due to damage by stroke in primary motor cortex (MI) or its underlying projections presents a problem for functional neuroimaging technologies that attempt to evaluate the neurophysiological basis for restoration of motor function. Traditional assessments of MI function require patients to move their fingers, hands, or limbs, which can be either impossible or markedly compromised after stroke. We recently demonstrated in normal subjects that magnetoencephalography (MEG), a non-invasive neuromagnetic functional imaging technique, detects neuronal response elicited by electrical median nerve stimulation in MI, as well as primary somatosensory cortex (SI). In the present study, we used the MEG response from median nerve stimulation to investigate the recovery of primary motor and somatosensory in acute ischemic stroke patients. Twelve patients with unilateral ischemic strokes that affected sensorimotor functions of their hand were studied in the acute stage (4.4+/-1.2 days, mean+/-SD) and during a 1-month follow-up (38.6+/-5.6 days, except for one patient's follow-up done 6 month after stroke). Among the multiple cortical sources localized after median nerve stimulation, one source localized to SI and another localized to the vicinity of MI. Changes in the source strengths of the first component post-stimulus of MI and SI correlated with the extent of recovery of sensorimotor functions as determined by neurological exams. This study provides a novel way of indirectly assessing MI function using MEG during the acute stroke phase, when many patients often cannot perform motor tasks due to paralysis.


Blood Pressure Control Targets and Risk of Cardiovascular and Cerebrovascular Events After Intracerebral Hemorrhage.
Intracerebral hemorrhage (ICH) survivors are at high risk for recurrent stroke and cardiovascular events. Blood pressure (BP) control represents the most potent intervention to lower these risks, but optimal treatment targets in this patient population remain unknown. We sought to determine whether survivors of ICH achieving more intensive BP control than current guideline recommendations (systolic BP <130 mmHg and diastolic BP <80 mmHg) were at lower risk of major adverse cardiovascular and cerebrovascular events and mortality. We analyzed data for 1828 survivors of spontaneous ICH from 2 cohort studies. Follow-up BP measurements were recorded 3 and 6 months after ICH, and every 6 months thereafter. Outcomes of interest were major adverse cardiovascular and cerebrovascular events (recurrent ICH, incident ischemic stroke, myocardial infarction), vascular mortality (defined as mortality attributed to recurrent ICH, ischemic stroke, or myocardial infarction), and all-cause mortality. During a median follow-up of 46.2 months, we observed 166 recurrent ICH, 68 ischemic strokes, 69 myocardial infarction, and 429 deaths. Compared with survivors of ICH with systolic BP 120 to 129 mmHg, participants who achieved systolic BP <120 mmHg displayed reduced risk of recurrent ICH (adjusted hazard ratio [AHR], 0.74 [95% CI, 0.59-0.94]) and major adverse cardiovascular and cerebrovascular events (AHR, 0.69 [95% CI, 0.53-0.92]). All-cause mortality (AHR, 0.76 [95% CI, 0.57-1.03]) and vascular mortality (AHR, 0.68 [95% CI, 0.45-1.01]) did not differ significantly. Among participants aged >75 years or with modified Rankin Scale score 4 to 5, systolic BP <120 mmHg was associated with increased all-cause mortality (AHR, 1.38 [95% CI, 1.02-1.85] and AHR, 1.36 [95% CI, 1.03-1.78], respectively), but not vascular mortality. We found no differences in outcome rates between survivors of ICH with diastolic BP <70 versus 70 to 79 mmHg. Targeting systolic BP <120 mmHg in select groups of survivors of ICH could result in decreased major adverse cardiovascular and cerebrovascular events risk without increasing mortality. Our findings warrant investigation in dedicated randomized controlled trials.


Intermittent levosimendan treatment in patients with severe congestive heart failure.
Levosimendan (LS) is a novel inodilator for the treatment of severe congestive heart failure (CHF). In this study, we investigated the potential long-term effects of intermittent LS treatment on the pathophysiology of heart failure. Thirteen patients with modest to severe CHF received three 24-h intravenous infusions of LS at 3-week intervals. Exercise capacity was determined by bicycle ergospirometry, well-being assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ) and laboratory parameters of interest measured before and after each treatment. One patient experienced non-sustained periods of ventricular tachycardia (VT) during the first infusion and had to discontinue the study. Otherwise the LS infusions were well tolerated. Exercise capacity (VO2max) did not improve significantly during the study although symptoms decreased (P < 0.0001). Levels of plasma NT-proANP, NT-proBNP and NT-proXNP decreased 30-50% during each infusion (P < 0.001 for all), but the changes disappeared within 3 weeks. Although norepinephrine (NE) appeared to increase during the first treatment (P = 0.019), no long-term changes were observed. Intermittent LS treatments decreased effectively and repetitively plasma vasoactive peptide levels, but no carryover effects were observed. Patients' symptoms decreased for the whole study period although there was no objective improvement of their exercise capacity. The prognostic significance of these effects needs to be further studied.


Facile syntheses of the disaccharide repeating unit of the O-antigenic polysaccharide of Burkholderia pseudomallei strain 304b and its dimer and trimer.
A highly efficient strategy for the preparation of a disaccharide-repeating unit of the O-antigenic polysaccharide of Burkholderia pseudomallei strain 304b, and its dimer and trimer, has been developed through a regio- and stereoselective manner using p-methoxylphenyl 2,4,6-tri-O-benzoyl-α-D-glucopyranoside and 3-O-allyloxycarbonyl-2,4-di-O-benzoyl-6-deoxy-α-L-talopyranosyl trichloroacetimidate as the key synthons. The target molecules were equipped with a p-methoxylphenyl handle at the reducing terminus to allow for their further functionalization and attachment to a carrier protein.


Complete dissection of the lymph nodes located along and at the roots of the left gastroepiploic vessels during distal gastrectomy.
Achieving complete dissection of the lymph nodes located at the roots of the left gastroepiploic vessels is difficult when distal gastrectomy is the surgical goal; firstly, because the short gastric vessels must be preserved to supply blood to the remnant stomach; and also, because the roots of the left gastroepiploic vessels at the splenic hilus are obscured intraoperatively by adipose tissues. We describe herein a technique which enables complete and easy dissection of the lymph nodes located along and at the roots of the left gastroepiploic vessels.


Frequency of thrombolytic targets in stroke patients presenting in an extended time window.
The objective of this study was to determine the proportion of stroke patients presenting in an extended time window who have a thrombolytic treatment target. Patients presenting up to 24 h after stroke onset have been found to have penumbral tissue on multimodal imaging. Stroke patients presenting in this extended time window without a large vessel occlusion (LVO) may benefit from reperfusion therapy using thrombolysis. Patients seen at our institutions from 2011 through 2015 were reviewed to identify those who presented >4 h and <24 h from last seen normal (LSN) and did not receive acute treatment. Magnetic resonance imaging (MRI) scans were used to dichotomize patients using a diffusion-perfusion mismatch ratio of 1.2. During the study period, 3469 patients were evaluated by our stroke service, with 893 seen 4-24 h from LSN who were not treated. MRI was performed with diffusion and perfusion imaging in 439 patients, of whom 26 were excluded due to hemorrhage and 37 were excluded due to LVO. This left 376 patients who potentially could have been treated with thrombolysis in an extended time window and were included in the analysis. Of these, 156 (42%) demonstrated a mismatch ratio >1.2. Patients with a mismatch presented earlier (P = 0.012), were more likely to be female (P = 0.03), and had higher National Institutes of Health Stroke Scale (P < 0.001). Almost half of the patients presenting 4-24 h from LSN had a target for thrombolysis in our study. Multimodal imaging may be able to expand the population of treatable stroke patients given the results of recent clinical trials.


Corrigendum to "Effects of trigonal deformation on electronic structure and thermoelectric properties of bismuth" [2018 J Phys Condens Matter 30 285504].
In the mentioned paper [1], the cohesive energy E (eV/atom) as the function of the c/a in Table 3 should be corrected as follows.


The potential of Festuca rubra and Calamagrostis epigejos for the revegetation of fly ash deposits.
Two grass species, Festuca rubra (sown) and Calamagrostis epigejos (naturally recolonised), were studied at two fly ash deposit lagoons, weathered 5 (L1) and 13 years (L2). Both species were assessed in terms of their invasive ability, photosynthetic efficiency, trace elements accumulation, and damage symptoms, while the characteristics of the habitat were assessed in terms of trace element content, and the pH and EC of the ash. In the ash weathered for 5 and 13 years, B and Mn concentrations fell within the normal range for soils, while there was an As, Mo and Cu excess, and Se and Zn deficit. There was no difference in the photosynthetic efficiency (ns) of the C. epigejos populations at the different-aged ash lagoons, but differences were found between the populations of F. rubra (P<0.001). F. rubra displayed damage symptoms, in the form of leaf tip chlorosis and necrosis, and wilting seedlings--a result of B accumulation in toxic concentrations and a Cu and Mn deficit. After 13 years the sown F. rubra remained over 9.5% of the ash lagoon's area (L2), while over the same period the naturally recolonised C. epigejos had overgrown 87.5% of the area. The greater colonisation and survival potential of C. epigejos is a result of multiple tolerance to the conditions at ash deposits and of the competitive ability of this species to dominate the colonised habitat. Therefore, characteristics of naturally colonised species can be used for modelling future actions of biological restoration of fly ash deposits aimed at binding the ash with minimal investment (the short-term aim), and for providing conditions for revegetation, and shortening the successive phases in the revegetation of ash deposits after the closure of thermal plants (the long-term aim).


Thiol exchange reactions involving selenotrisulfides.
The occurrence of in vitro thiol exchange reactions involving selenotrisulfides has been documented by HPLC analyses of reaction solutions. Asymmetric selenotrisulfide (RSSeSR') (R,R' = penicillamine, cysteine, glutathione) was formed by the reactions between (i) a mixture of thiols and selenite, (ii) thiol (R'SH) and symmetric selenotrisulfide (RSSeSR), and (iii) symmetric selenotrisulfides (RSSeSR and R'SSeSR'). Further reaction of an asymmetric selenotrisulfide with thiol (R'SH) produced another symmetric selenotrisulfide (R'SSeSR'). These thiol exchange reactions may offer significant information to elucidate intake and metabolism of selenium in vivo.


Monomethyl Phthalate Causes Early Embryo Development Delay, Apoptosis, and Energy Metabolism Disruptions Through Inducing Redox Imbalance.
Phthalates are a class of environmental endocrine disrupting chemicals which can cause reproductive system damages. However, data about reproductive toxicity spectrum of phthalate metabolites among Chinese women undergoing in vitro fertilization (IVF) treatments are scarce yet. Previous studies regarding underlying embryo toxicities focused on oxidative stress and apoptosis, while energy metabolism abnormality might be another key cause for embryo developmental disruptions. Here, we found that among the measured eight phthalate metabolites, monomethyl phthalate (MMP) had the second highest urinary concentration in women receiving IVF. Compare to the lowest exposure level group, MMP in tertile 3 was associated with fewer counts of oocyte retrieved and good-quality embryos, and MMP in tertile 2 was correlated with reduced good-quality embryo rate. The direct embryo toxicities of MMP were studied using mouse 2-cell embryos. Consistent to results found in human populations, exposure to MMP induced mouse early embryo developmental delay. Furthermore, MMP exposure led to excessive reactive oxygen species production in early embryos, and antioxidant can partially rescue the early embryo development slow down. Embryo apoptosis could also be caused by oxidative stress. To be noted, elevated apoptosis level was not found in live "slow" embryos but dead embryos, which suggested that apoptosis was not related to early embryo developmental delay. Additionally, MMP exposure depleted adenosine triphosphate (ATP) synthesis of early embryos, which could be reversed by antioxidant. In conclusion, MMP, as the newly found embryonic toxicant in Chinese women, resulted in early embryo development delay, apoptosis, and energy metabolism disruptions via inducing redox imbalance.


Inequality factors in access to early-phase clinical trials in oncology in France: results of the EGALICAN-2 study.
Investigation of the disparities in the access to experimental treatment in early-phase clinical trials is lacking. The objective of the EGALICAN-2 study was to identify the factors underpinning such inequalities. A national prospective survey was conducted in 11 early-phase clinical trial centers (CLIP2) certified by the French National Cancer Institute. Sociodemographic, socioeconomic and medical data were collected. Univariate logistic regression models were carried out to estimate odds ratios and 90% confidence intervals associated with the effect of each study variable. A multivariate logistic regression model was built to explore the independent factors associated with the administration of the experimental treatment (C1D1). A post hoc analysis was carried out excluding female cancer patients. Between 2015 and 2016, 1355 patients referred from 11 CLIP2 centers in France were included in the study. Eight hundred and forty-eight patients received C1D1 (73%) and 320 patients (27%) were screening failure. Median age was 58 years (range 17-97 years) and 667 patients (54%) were female. Most patients had a metastatic disease (n = 751, 87%). In the multivariate logistic regression analysis, the significant independent factors associated with C1D1 were male sex, initial care received in a hospital with an early-phase unit and living in wealthy metropolitan areas (P values <0.05). In the post hoc analysis, the sex factor was no longer significant [odds ratio = 1.21 (95% confidence interval 0.86-1.70), P value = 0.271]. This study investigated the factors producing social inequalities in the context of early-phase clinical trials in oncology. Our research highlights factors of sex, care pathway and geographic location. Gynecological cancer was found to impact C1D1 significantly, unlike breast cancer. The results of this study should contribute to improve patient access to early-phase clinical trials.


Possibility as an anti-cancer drug of astemizole: Evaluation of arrhythmogenicity by the chronic atrioventricular block canine model.
Since astemizole in an oral dose of 50 mg/kg/day was recently reported to exert anti-cancer effect in mice, we evaluated its proarrhythmic potential using the atrioventricular block dogs in order to clarify its cardiac safety profile. An oral dose of 3 mg/kg prolonged the QT interval without affecting the QTc (n = 4), whereas that of 30 mg/kg increased the short-term variability of repolarization and induced premature ventricular contractions in each animal, resulting in the onset of torsade de pointes in 1 animal (n = 4). Thus, proarrhythmic dose of astemizole would be lower than anti-cancer one, limiting its re-profiling as an anti-cancer drug.


Influence of plant genotype on the cultivable fungi associated to tomato rhizosphere and roots in different soils.
Rhizosphere and root-associated microbiota are crucial in determining plant health and in increasing productivity of agricultural crops. To date, research has mainly focused on the bacterial dimension of the microbiota. However, interest in the mycobiota is increasing, since fungi play a key role in soil ecosystems. We examined the effect of plant genotype, soil, and of Fusarium oxysporum f. sp. lycopersici (Fol) on the cultivable component of rhizosphere and root-associated mycobiota of tomato. Resistant and susceptible varieties were cultivated on two different soils (A and B), under glasshouse conditions. Isolated fungi were identified by morphological and molecular approaches. Differences were found between the rhizosphere and the roots, which in general displayed a lower number of species. The structure of the mycobiota was significantly affected by the soil type in the rhizosphere as well as by the plant genotype within the roots (NPERMANOVA, p < 0.05). The addition of Fol changed the community structure, particularly in soil A, where Penicillium spp. and Fusarium spp. were the dominant responding fungi. Overall, the results indicated that i) soil type and plant genotype affect the fungal communities; ii) plant roots select few species from the rhizosphere; and iii) the fungal community structure is influenced by Fol.


Altered developmental timing in early life stages of Antarctic krill (Euphausia superba) exposed to p,p'-DDE.
Persistent organic pollutants (POPs) are persistent, toxic and bioaccumulative anthropogenic organic chemicals, capable of undergoing long range environmental transport to remote areas including the Antarctic. p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) has been identified as a dominant POP accumulating in Antarctic krill (Euphausia superba), which is a key Southern Ocean species. This study examined the developmental toxicity of p,p'-DDE via aqueous exposure to Antarctic krill larvae. p,p'-DDE exposure was found to stimulate developmental timing in the first three larval stages of Antarctic krill, while extended monitoring of larvae after a five day exposure period had ended, revealed delayed inhibitory responses during development to the fourth larval stage. Stimulatory responses were observed from the lowest p,p'-DDE body residue tested of 10.1±3.0 μmol/kg (3.2±0.95 mg/kg) preserved wet weight, which is comparable to findings for temperate species and an order of magnitude lower than the exposure level found to cause sublethal behavioural effects in Antarctic krill. The delayed responses included increased mortality, which had doubled in the highest p,p'-DDE treatment (95±8.9% mortality at 20 μg/L p,p'-DDE) compared to the solvent control (44±11% mortality) 2 weeks after end of exposure. Development of surviving metanauplius larvae to calyptopis 1 larvae was delayed by 2 days in p,p'-DDE exposed larvae compared with untreated larvae. Finally, the developmental success of surviving p,p'-DDE exposed larvae was reduced by 50 to 75% compared to the solvent control (100% developmental success). The lowest observed effect concentration for all delayed effects was 1 μg/L, the lowest exposure concentration tested. These findings demonstrate the importance of delayed and indirect effects of toxicant exposure. Further, the findings of this study are important for environmental risk assessment of POPs in the Southern Ocean ecosystem and strongly highlight the significance of developmental endpoints for ecotoxicological testing.


Suppressed expression of granulocyte macrophage colony-stimulating factor in oviduct ampullae of obese cows.
Obese heifers have been found to produce fewer excellent-grade embryos than lean and normal heifers due to unknown mechanisms. Oviducts synthesize granulocyte macrophage colony-stimulating factor (GMCSF) to promote embryogenesis, and GMCSF expression may be down-regulated in the oviducts of obese cows. The present study evaluated the relationship between the degree of obesity and GMCSF expression in the ampullary or isthmic section of oviducts in lean [n=5; body condition score (BCS) on a 5-point scale, 2.5], normal (n=6; BCS, 3.0), and obese (n=5; BCS, 4.0) Japanese Black cows. GMCSF mRNA and protein expression in the ampulla, measured by real-time PCR and western blotting, respectively, were less (P<0.05) in the obese group than in the normal group. mRNA and GMCSF protein did not differ significantly in the isthmus among the three groups. The obese group had less GMCSF immuno-reactivity in the tunica mucosa, the primary site of GMCSF gene expression, of the ampulla than the normal and lean groups. In conclusion, unlike normal and lean cows, obese cows had suppressed GMCSF gene expression in the ampulla.


Effectiveness of multidisciplinary rehabilitation services in postacute care: state-of-the-science. A review.
To summarize the efficacy of postacute rehabilitation and to outline future research strategies for increasing knowledge of its effectiveness. English-language systematic reviews that examined multidisciplinary therapy-based rehabilitation services for adults, published in the last 25 years and available through Cochrane, Medline, or CINAHL databases. We excluded multidisciplinary biopsychosocial rehabilitation programs and mental health services. Using the search term rehabilitation, 167 records were identified in the Cochrane database, 1163 meta-analyses and reviews were identified in Medline, and 226 in CINAHL. The Medline and CINAHL search was further refined with 3 additional search terms: therapy, multidisciplinary, and interdisciplinary. In summary, we used 12 reviews to summarize the efficacy of multidisciplinary, therapy-based postacute rehabilitation; the 12 covered only 5 populations. Two reviewers extracted information about study populations, sample sizes, study designs, the settings and timing of rehabilitation, interventions, and findings. Based on systematic reviews, the evidence for efficacy of postacute rehabilitation services across the continuum was strongest for stroke. There was also strong evidence supporting multidisciplinary inpatient rehabilitation for patients with rheumatoid arthritis, moderate to severe acquired brain injury, including traumatic etiologies, and for older adults. Heterogeneity limited our ability to conclude a benefit or a lack of a benefit for rehabilitation in other postacute settings for the other conditions in which systematic reviews had been completed. The efficacy of multidisciplinary rehabilitation services has not been systematically reviewed for many of the diagnostic conditions treated in rehabilitation. We did not complete a summary of findings from individual studies. Given the limitations and paucity of systematic reviews, information from carefully designed nonrandomized studies could be used to complement randomized controlled trials in the study of the effectiveness of postacute rehabilitation. Consequently, a stronger evidence base would become available with which to inform policy decisions, guide the use of services, and improve patient access and outcomes.


Impact of Soil Composition and Electrochemistry on Corrosion of Rock-cut Slope Nets along Railway Lines in China.
Taking the slope of Suiyu Railway to study, the research separately studied soil resistivity, soil electrochemistry (corrosion potential, oxidization reduction potential, electric potential gradient and pH), soil anions (total soluble salt, Cl(-), SO4(2-) and ), and soil nutrition (moisture content, organic matter, total nitrogen, alkali-hydrolysable nitrogen, available phosphorus, and available potassium) at different slope levels, and conducted corrosion grade evaluation on artificial soil according to its single index and comprehensive indexes. Compared with other factors, water has the biggest impact on the corrosion of slope protection net, followed by anion content. Total soluble salt has the moderate impact on the corrosion of slope protection net, and stray current has the moderate impact on the corrosion of mid-slope protection net. Comprehensive evaluation on the corrosive degree of soil samples indicates that the corrosion of upper slope is moderate, and the corrosion of mid-slope and lower slope is strong. Organic matter in soil is remarkably relevant to electric potential gradient. Available nitrogen, available potassium and available phosphorus are remarkably relevant to anions. The distribution of soil nutrient is indirectly relevant to slope type.


Bronchus compression relieved by patent ductus arteriosus stenting.
Patent ductus arteriosus (PDA) stenting is evolving as an alternative to surgical aorto-pulmonary shunts for infants with ductal-dependent pulmonary blood flow. Given anatomical proximity, the PDA can compress the ipsilateral bronchus. We report a case series of four patients with bronchial compression by a tortuous PDA who underwent PDA stenting. Our four patients received PDA stents for ductal-dependent pulmonary blood flow despite preprocedure imaging evidence of bronchial compression. We reviewed the cross-sectional chest imaging to assess the degree of bronchial compression and the variables that affect it, namely PDA size, PDA tortuosity, and the anatomical relationship between the compressed bronchus and the PDA. Three out of the four patients had postprocedure imaging, and all showed relief of the previously seen bronchial compression. Post-PDA stenting patients had a smaller and straight PDA with significant lateralization away from the compressed bronchus. None of the four patients developed symptoms of bronchial compression poststenting. Our study suggests that pre-existing bronchial compression does not preclude PDA stenting. Stent placement in an engorged and tortuous PDA led to significant improvement in pre-existing bronchial compression. Improvement may be attributed to PDA shrinkage, straightening, and lateralization. Further studies are needed to confirm our findings.


Expression of the methyl-CpG-binding protein MeCP2 in rat brain. An ontogenetic study.
Rett syndrome (RS) is caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2) and is characterized by arrested postnatal neurodevelopment. We followed the expression of MeCP2 protein in various brain structures of normal rat from birth to 2 years of age. By measuring the amount of protein using the Western blot technique, or by determining the percentage of immunoreactive cells, significant heterogeneity in MeCP2 distribution among various brain areas was observed. Highest expression was found in olfactory bulb and in frontal cortex. In contrast, little expression was detected in caudate-putamen, septum and hippocampus. Except in the olfactive nuclei, very few cells showed detectable MeCP2 protein at birth. The number increased during the first week of age, especially in cortex and nucleus accumbens. Rather than playing a global role in gene transcription, the heterogeneous distribution of MeCP2 transcription factor favors the idea that it has a specialized function in neurons.


A virtual frame system for stereotactic radiosurgery planning.
We describe a computerized (or virtual) model of a stereotactic head frame to enable planning prior to the day of radiosurgery. The location of the virtual frame acts as a guide to frame placement on the day of the procedure. The software consists of a triangular mesh representation of the essential frame hardware that can be overlaid with any MR scan of the patient and manipulated in three dimensions. The software calculates regions of the head that will actually be accessible for treatment, subject to the geometric constraints of the Leksell Gamma Knife hardware. DICOM-compliant MR images with virtual fiducial markers overlaid onto the image can then be generated for recognition by the treatment planning system. Retrospective evaluation of the software on 24 previously treated patients shows a mean deviation of the position of the virtual frame from the actual frame position of 1.6 +/- 1.3 mm. Initial clinical use on five patients indicates an average discrepancy of the virtual frame location and the actual frame location of <1 mm. MR images with virtual fiducial markers can be imported into radiosurgical treatment planning software and used to generate an initial treatment plan. The virtual frame provides a tool for prospective determination of lesion accessibility, optimization of the frame placement, and treatment planning before the day of the procedure. This promises to shorten overall treatment times, improve patient comfort, and reduce the need for repeat treatments due to suboptimally placed frames.


Point prevalence of SARS-CoV-2 infection in Sweden at six time points during 2020.
In order to estimate the prevalence and understand the spread of SARS-CoV-2 in Sweden, the Public Health Agency of Sweden, with support from the Swedish Armed Forces, conducted a series of point prevalence surveys between March and December 2020. Sampling material and instructions on how to perform self-sampling of the upper respiratory tract were delivered to the homes of the participants. Samples were analysed by real-time PCR, and the participants completed questionnaires regarding symptoms. The first survey in the Stockholm region in March 2020 included 707 participants and showed a SARS-CoV-2 prevalence of 2.5%. The following five surveys, performed on a national level, with between 2461 and 2983 participants, showed SARS-CoV-2 prevalences of 0.9% (April), 0.3% (May), 0.0% (August), 0.0% (September), and 0.7% (December). All positive cases who responded to questionnaires reported experiencing symptoms that occurred from 2 weeks before the date of sampling up to and including the date of sampling. None of the individuals shown to be PCR-positive were asymptomatic at the time of sampling or in the 14 days prior to sampling. This is in contrast to many other surveys in which a substantial proportion of positive cases have been reported to be asymptomatic. Our surveys demonstrate a decreasing ratio between notified cases and the observed prevalence throughout the year, in line with increasing testing capacity and the consecutive inclusion of all symptomatic individuals in the case definition for testing.


Variations of microbiota in three types of typical military contaminated sites: Diversities, structures, influence factors, and co-occurrence patterns.
Contamination with energetic compounds (ECs) is common in military sites and poses a great risk to the environment and human health. However, its effects on the soil bacterial communities remain unclear. This study assessed the variations of bacterial communities, co-occurrence patterns, and their influence factors in three types of typical military-contaminated sites (artillery range, military-industrial site, and ammunition destruction site). The results showed that the most polluted sites were ammunition destruction sites, followed by military-industrial sites, whereas pollution in the artillery ranges was minimal. The average concentrations of ECs including 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) in the study sites ranged 120-1.67 × 105, 20-7.20 × 104, and 180-2.38 × 105 μg/kg, respectively. Bacterial diversity and community structure in military-industrial and ammunition destruction sites were significantly changed, but not in artillery ranges. TNT, pH, and soil moisture are the critical factors affecting bacterial communities in contaminated military sites. Co-occurrence network analysis indicated that the pressure of ECs affected bacterial interactions and microbiota function. Our findings provide new insights into the variations in bacterial communities in EC-contaminated military sites and references for the bioremediation of ECs.


Association between statin therapy dose intensity and radiation cardiotoxicity in non-small cell lung cancer: Results from the NI-HEART study.
Radiation cardiotoxicity is a dose-limiting toxicity and major survivorship issue for patients with non-small cell lung cancer (NSCLC) completing curative-intent radiotherapy, however patients' cardiovascular baseline is not routinely optimised prior to treatment. In this study we examined the impact of statin therapy on overall survival and post-radiotherapy cardiac events. Patients treated between 2015-2020 at a regional center were identified. Clinical notes were interrogated for baseline patient, tumor and cardiac details, and both follow-up cancer control and cardiac events. Three cardiologists verified cardiac events. Radiotherapy planning scans were retrieved for application of validated deep learning-based autosegmentation. Pre-specified Cox regression analyses were generated with varying degrees of adjustment for overall survival. Fine and Gray regression for the risk of cardiac events, accounting for the competing risk of death and cardiac covariables was undertaken. Statin therapy was prescribed to 59% of the 478 included patients. The majority (88%) of patients not prescribed a statin had at least one indication for statin therapy according to cardiovascular guidelines. In total, 340 patients (71%) died and 79 patients (17%) experienced a cardiac event. High-intensity (HR 0.68, 95%CI 0.50-0.91, p = 0.012) and medium-intensity (HR 0.70, 95%CI 0.51-0.97, p = 0.033) statin therapy were associated with improved overall survival after adjustment for patient, cancer, treatment, response and cardiovascular clinical factors. There were no consistent differences in the rate or grade of cardiac events according to statin intensity. Statin therapy is associated with improved overall survival in patients receiving curative-intent radiotherapy for NSCLC, and there is evidence of a dose-response relationship. This study highlights the importance of a pre-treatment cardiovascular risk assessment in this cohort. Further studies are needed to examine if statin therapy is cardioprotective in patients undergoing treatment for NSCLC with considerable incidental cardiac radiation dose and a low baseline cardiac risk.


Pseudo-turbulence in two-dimensional buoyancy-driven bubbly flows: A DNS study.
We present a direct numerical simulation (DNS) study of buoyancy-driven bubbly flows in two dimensions. We employ the volume of fluid (VOF) method to track the bubble interface. To investigate the spectral properties of the flow, we derive the scale-by-scale energy budget equation. We show that the Galilei number (Ga) controls different scaling regimes in the energy spectrum. For high Galilei numbers, we find the presence of an inverse energy cascade. Our study indicates that the density ratio of the bubble with the ambient fluid or the presence of coalescence between the bubbles does not alter the scaling behaviour.


Changes in blood levels of zinc, copper, selenium, glutathione peroxidase, vitamin B12 and total and free thyroxine in sheep removed from pasture and held without food for 50 hours.
Blood was collected from a group of ten sheep immediately after removal from pasture and thereafter at regular intervals for 50 hours whilst maintaining them without food but with adequate water. The samples were analysed for parameters normally examined as an aid to the diagnosis of zinc, copper, selenium, cobalt and iodine status. Serum vitamin B12 levels increased with time. Mean plasma zinc concentrations and mean serum concentrations of both T4 and fT4 followed significant parabolic trends. Maximum mean zinc levels (50 +/- 10% higher than initial values) were recorded after 30 hours. T4 and fT4 levels peaked at approximately 26 hours. Zinc levels at two hours were 20 +/- 5% lower than the initial values. Whole blood copper, selenium and glutathione peroxidase levels did not change significantly with time the largest differences were 11 +/- 6%, 5 +/- 4% and 10 +/- 8% respectively.


Intraperitoneal cisplatin and regional hyperthermia for ovarian carcinoma.
To review the theoretical basis and results of a Phase I study of concurrent intraperitoneal cisplatin and hyperthermia in the treatment of ovarian carcinoma. Previously treated patients with epithelial ovarian carcinoma received intraperitoneal instillation of cisplatin and 60 minutes of regional hyperthermia, with a goal temperature of 41.5 degrees C. Cisplatin dose started at 20 mg/m2 with escalation to the maximally tolerated dose. Six such cycles given every 3 weeks were planned. Pharmacokinetic studies with and without hyperthermia were performed. Fifteen patients receiving 17 courses of treatment were evaluable. The maximally tolerated dose of cisplatin was between 80 and 120 mg/m2. The dose limiting toxicity was nephrotoxicity in all but one course. The median intraperitoneal temperature was 40.7 degrees C; the majority of treatments in which the goal temperature was not reached had power limited by patient discomfort. No major toxicities attributable to hyperthermia were noted. Pharmacokinetic studies noted no significant differences between treatments with vs. without hyperthermia, with intraperitoneal to plasma area under the curve ratios being 30-35. Ten patients had a decline in their CA-125 count during treatment, although in only two patients did this response persist beyond their course of treatment. Intraperitoneal cisplatin and regional hyperthermia can be performed with reasonable toxicity. The maximally tolerated dose of 80-120 mg/m2 in pretreated patients (which is similar to those reported with cisplatin alone) and median intraperitoneal temperatures of 40.7 degrees C, however, are felt to be too low to be efficacious in a significant percentage of women with bulky recurrent disease. Further study using intravenous thiosulfate and controlled analgesia is being performed.


The palmar abduction-pronation osteotomy of the first metacarpal bone combined with tendon transfer for lateral thenar muscle paralysis.
The authors describe a palmar abduction-pronation osteotomy of the first metacarpal bone combined with a tendon transfer for treatment of palsy of the lateral thenar muscles. The results of fourteen cases are reported.


Complete resection is not required in patients with neuroblastoma under 1 year of age.
The prognosis of neuroblastoma (NB) patients when detected before 1 year of age is excellent, particularly in patients whose disease is detected by screening. In some institutions patients with stage I or II NB detected by screening have been observed closely without any treatment. Most showed tumor regression or maturation and are surviving without tumor resection. Resection of infantile NB sometimes is complicated by vascular accidents resulting in vanishing kidney or intestinal infarction. The role of surgery in the treatment of infantile NB therefore is becoming controversial. The authors have treated infants who have easily resectable primary tumors with resection and sampling for lymph node metastases. If the resection of the primary tumor seemed difficult, only biopsy was performed initially followed by chemotherapy with or without resection. The authors analyzed the clinical outcome of the infantile NB in their institution to elucidate the role of surgery in this particular group of patients. Thirty-six patients less than 12 months of age were treated between 1982 and 1997. Twenty-five patients who showed no symptoms had NB detected by screening at 6 months. Five patients had stage IVS disease in early infancy. No patients had bone or remote lymph node metastases. N-mycamplification was not detected in any of the 28 tumors examined. There were four diploid and 12 near-triploid tumors. Complete resection was possible in 13 stage I and II patients without any complications. Obvious lymph node metastases were not resected in 13 patients with stage II or III NB. Partial resection leaving gross residual disease was accomplished in three patients with stage III NB. Surgical resection was not attempted in four patients because of unresectability in three patients with stage III or IVS disease and because of marked tumor shrinkage after a short course of chemotherapy in one patient with stage III NB involving the celiac axis. A neonatal cervicomediastinal stage III NB recurred very rapidly after partial resection but started to regress spontaneously 2 months postoperatively. Another neonatal stage II cervical NB progressed to stage IVS with hepatomegaly causing respiratory distress but regressed spontaneously. All the patients are alive and disease free without surgical morbidity. All of the 21 patients who underwent partial tumor resection with or without chemotherapy are alive and doing well without tumor, indicating that complete resection is not required in this particular group of patients.


Rodent models for mania: practical approaches.
The scarcity of good animal models for bipolar disorder (BPD) and especially for mania is repeatedly mentioned as one of the rate-limiting factors in the process of gaining a better understanding into its pathophysiology and of developing better treatments. Standard models of BPD have some value but usually represent only one facet of the disease and have partial validity. A number of new approaches for modeling BPD and specifically mania have been suggested in the last few years and can be combined to improve models. These approaches include targeted mutation models representing reverse translation, the identification of advantageous strains for components of the disorder, a search for the most homologous species to address specific human pathology, and the exploration of individual differences of response including the separation between susceptible and resilient animals. Additionally, recent efforts have identified and developed new tests to distinguish between "normal" and "BPD-like" animals including the different utilization of known tests and novel tests such as the female-urine-sniffing test and behavior pattern monitor analysis. Additional tests relating to further domains of BPD are still needed. An ideal model for BPD that will encompass the entire disease and be useful for every demand will probably not become available until we have a full understanding of the pathophysiology of the disorder. However, the current advances in modeling should lead to better comprehension of the disorder and therefore to the gradual development of increasingly improved models.


Development of a humidity pretreatment method for the measurement of ozone in ambient air.
A frost filter (FRF) was developed as a humidity pretreatment device (HPD) to improve the measurement of ambient ozone (O3). The FRF was produced in a tube, which was supercooled by a thermoelectric cooling device based on the Peltier effect. The relative humidity (RH) of the air samples varied from 30% to 80% at 25 °C, and the O3 concentration was set as 100 ppbv. Besides O3, SO2 at 150 ppbv was used for comparison. The density of the FRF was evaluated. Comparison studies on the humidity removal efficiencies and loss ratios of analytes among a FRF HPD, a short Nafion™ tube (NS), and a long Nafion™ tube (NL) HPDs were conducted. As results, the density of the FRF was dependent on the temperature at a fixed sampling flow rate. The outlet humidity of both the FRF and the NL HPDs were less than 8% RH at 25 °C. The mean concentrations of O3 and SO2 after the FRF HPD were similar to the initial concentrations at all humidity levels, whereas they were significantly different for both the NS and NL HPDs at higher humidity. This suggests that the FRF HPD is a reliable humidity pretreatment for O3 measurements.


Epidemiology of dancers fracture.
Dancer's fracture is a spiral, oblique fracture of the diaphysis of the fifth metatarsal. Although it is a well-known fracture in high performance athletes, it is less studied in a general population. The article investigates the epidemiology within an adult population consulting a regional trauma and orthopedic center in the United Kingdom. Study population included all patients older than 16 years presenting with a dancer's fracture. Recorded data were age, sex, side and energy of trauma mechanism, applied treatment and time of healing. Of all fifth metatarsal fractures, 25% was found to have a dancer's fracture. About 80% were women, and about 80% was older than 40 years. In the +40 y age group, all patients had a low energy trauma mechanism, where in the -40y age group this was only 27%. All patients were treated conservatively and no correlation was found between type of treatment (walker boot, stiff soled shoe) and time of healing. The time of healing was similar in both age groups and in general 1 out of 3 patients needed longer than 6 weeks to heal. There is an increased incidence of dancer's fracture observed in the female general population +40y age. A strong correlation was found between the +40y age group and low-energy trauma mechanism. This shows the importance of treating dancer's fracture as a fragility fracture. Retrospective cohort study: level 3.


Growth hormone secretion during long-term thiopental anesthesia in the immature rat.
The secretory pattern of growth hormone (GH) in 29 to 31 day old immature rats during long-term thiopental anesthesia was studied. Individual GH secretory profiles were determined by sequential blood sampling at 10 min intervals for 6.0 hr starting from about 1.0-1.5 hr after the onset of thiopental administration. EEG was concurrently monitored throughout the experimental period, and the animals were maintained in stable patterns. GH levels in whole blood samples were determined by radioimmunoassay and were subjected to analysis by power spectrum and least-squares methods. The results showed that all 25 immature rats exhibited episodic secretion of GH. Twenty-four of them (96%) showed GH surges occurring with periodicities within the mean +/- 2SD range for the results from unanesthetized, sham-operated animals. The mean periodicity for the 25 animals was 3.25 +/- 0.12 (SE) hr. The results suggest that the rhythmicity of GH secretion observed in the freely-moving condition is maintained during anesthesia.


The preparation, formation, fermentability, and applications of resistant starch.
Resistant starch (RS) cannot be digested in the small intestine but can be fermented by microflora in the colon. To meet the demand for RS, effective methods and advanced equipment for preparing RS have emerged, but further development is needed. RS contents are affected by different prepared methods, starch source and certain nutrients such as protein, phenols, and hydrocolloids interacted with RS. As a beneficial fermentation substrate, RS modifies and stabilizes the intestinal flora to balance the intestinal environment and improve intestinal tract health and function. RS is also a kind of ingredient with potential physiological function, even better than that dietary fiber, but also in terms of providing various health benefits. RS has good food-processing characteristics as well and can thus be widely used in the food industry.